bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Best Prepare Pharmacy Students for Disaster Management: A Qualitative Study
Authors: Wiedyaningsih Chairun , Nugroho Akhmad Kharis , Widyakusuma Niken Nur , Prasetyo Septimawanto Dwi
Published: February 2023

Objective:

This study explores the opinions of academic and practicing pharmacists about ways to prepare pharmacy students for disaster management to enable them to optimize their role in disaster health management.

Methods:

Semi-structured individual interviews were conducted for data collection from April through June 2021. The research participants were 9 pharmacists who were involved in disaster management. The interview guide was developed following a comprehensive literature review on disaster management. Data were analyzed using thematic analysis.

Results:

The main themes identified are knowledge of health and disaster management, specific skills in disaster management, positive attitudes toward involvement in disaster management, and appropriate behavior in the face of a disaster, as well as personal readiness and training to achieve competence and readiness. Participants mentioned that special training in soft skills, especially communication and problem-solving, is essential for students.

Conclusion:

Disaster-specific competencies and personal readiness through training can prepare pharmacy students for disaster management. Soft skills such as communication and problem-solving must be the highest priority.
Anxiety in a Specialist Perinatal Mental Health Service: patient characteristics, management, and outcomes
Authors: McKenna F. , Gibbons M. , Imcha M. , Duffy R. M. , Mohamad M. M.
Published: February 2023

Objectives:

To outline characteristics of patients with anxiety diagnoses attending a Specialist Perinatal Mental Health Service (SPMHS) in Ireland, the mental health care received by those patients, mental health and obstetric outcomes for those patients, and immediate neonatal outcomes for their babies.

Methods:

A retrospective chart review was conducted of patients with antenatal anxiety diagnoses who attended the SPMHS in University Maternity Hospital Limerick, from initiation of the service to the end of its first year.

Results:

Data were collected on 100 patients, 81 with a mental health diagnosis prior to attending the SPMHS, 32 with prior engagement with psychiatry, and 23 with a previous perinatal diagnosis. The mean age of patients was 32.4 (19–47, std 6.158). Beyond initial assessment, the Mental Health Midwife was involved in the care of 61% of patients, more than any other specialty including psychiatry. Twenty-seven patients had psychiatric medication either started or altered by the SPMHS. The most common reason for eventual discharge was that patients were well. Two patients presented in mental-health-related crisis to emergency services and one patient was admitted to an acute psychiatric ward.

Conclusions:

Patients attending the SPMHS for anxiety spanned a broad spectrum of demographics and diagnoses and received varied set of interventions. A significant proportion of patients had a primary diagnosis of Pregnancy-related anxiety. The Mental Health Midwife played a key role in management of these patients. Though rates of mental health crises and admissions were low, the absence of a Mother and Baby Unit in Ireland was highlighted.
Evaporating Rayleigh–Bénard convection: prediction of interface temperature and global heat transfer modulation
Authors: Scapin Nicolò , Demou Andreas D. , Brandt Luca
Published: February 2023

We propose an analytical model to estimate the interface temperature

$\varTheta _{\varGamma }$

and the Nusselt number

$Nu$

for an evaporating two-layer Rayleigh–Bénard configuration in statistically stationary conditions. The model is based on three assumptions: (i) the Oberbeck–Boussinesq approximation can be applied to the liquid phase, while the gas thermophysical properties are generic functions of thermodynamic pressure, local temperature and vapour composition, (ii) the Grossmann–Lohse theory for thermal convection can be applied to the liquid and gas layers separately and (iii) the vapour content in the gas can be taken as the mean value at the gas–liquid interface. We validate this setting using direct numerical simulations in a parameter space composed of the Rayleigh number (

$10^6\leq Ra\leq 10^8$

) and the temperature differential (

$0.05\leq \varepsilon \leq 0.20$

), which modulates the variation of state variables in the gas layer. To better disentangle the variable property effects on

$\varTheta _\varGamma$

and

$Nu$

, simulations are performed in two conditions. First, we consider the case of uniform gas properties except for the gas density and gas–liquid diffusion coefficient. Second, we include the variation of specific heat capacity, dynamic viscosity and thermal conductivity using realistic equations of state. Irrespective of the employed setting, the proposed model agrees very well with the numerical simulations over the entire range of

$Ra$

–

$\varepsilon$

investigated.
Effective slip length for transverse shear flow over partially invaded grooves
Authors: Yariv E.
Published: February 2023

We consider transverse shear flow over a

$2L$

-periodic array of air-filled grooves, which are separated by solid slats. We address the scenario where the liquid partially invades the grooves. Following Crowdy's solution of the longitudinal problem (J. Fluid Mech. vol. 925, 2021, R2), we focus upon the simplified geometry of infinitely narrow slats. For flat menisci, the ratio

$\lambda$

of the slip length to

$L$

depends upon a single geometric parameter, namely the ratio

$H$

of the invasion depth to

$L$

. We analyse the singular limit

$H\ll 1$

using matched asymptotic expansions, with an outer region on the scale of the period and an inner region on the scale of a single slat. In the outer region, we employ the complex-variable formulation of Stokes flows, obtaining the complex velocity as a divergent series. This formal representation is transformed to an admissible closed-form expression. In the inner region, the problem is equivalent to that of Stokes flow past a finite line segment. Asymptotic matching yields

$\lambda = [\ln (2/{\rm \pi} H)-1]/{\rm \pi}$

.
The first discovery of Lochkovian (Lower Devonian) conodonts in central Guangxi, South China and its geological implications
Authors: Lu Jian-Feng , Guo Wen , Wang Yi , Xu Hong-He
Published: February 2023

The Lochkovian, Pragian, and basal part of the Emsian, which represent the post-Kwangsian Orogeny strata in the South China Block, are mainly composed of siliciclastic rocks. This lithological composition impedes investigation of Pragian and Lochkovian conodont biostratigraphy in the South China Block, which results in a persistent controversy on the age of relevant lithological units. The present study provides new evidence by reporting for the first time Lochkovian conodonts obtained from the South China Block, specifically the Gaoling Member of the Nahkaoling Formation at the Lingli section, central Guangxi. The conodont fauna, consisting of Pandorinellina exigua lingliensis Lu n. subsp., Pandorinellina exigua exigua, Zieglerodina? tuojiangensis Lu n. sp., Amydrotaxis praejohnsoni, and Eognathodus cf. E. irregularis, places the studied interval of the Gaoling Member in the lower or middle Lochkovian (contingent upon varying definitions for the base of the middle Lochkovian) to lower Pragian. Moreover, Amydrotaxis praejohnsoni, which was reported previously only in North America and eastern Australia, is herein also recorded in the South China Block, and thus may play an important role in intercontinental biostratigraphical correlation. By shedding light on the age of the upper limit of the underlying Lianhuashan Formation at the Lingli section, the present study indicates that the Kwangsian Orogeny ended before the late Lochkovian. This date is slightly earlier than the previously estimated late Lochkovian based on studies of fossil plants from the siliciclastic rocks deposited after the Kwangsian Orogeny.

UUID: http://zoobank.org/8010f983-4f6f-43dd-949f-de4653e53d9d
THE ECONOMY AND POLICY TRADE-OFFS
Authors: Tenreyro Silvana
Published: February 2023

Good evening. It is a pleasure and an honour to be here at NIESR to give the annual Dow lecture. We are very lucky in the UK to have high-quality independent institutions such as NIESR focusing on the policy landscape, and in my time on the MPC I have always valued their commentary and research.
Asymptotic profiles for positive solutions of diffusive logistic equations
Authors: Sun Jian-Wen , Fang Peng-Fei
Published: February 2023

In this paper, we study the asymptotic profiles of positive solutions for diffusive logistic equations. The aim is to study the sharp effect of linear growth and nonlinear function. Both the classical reaction-diffusion equation and nonlocal dispersal equation are investigated. Our main results reveal that the linear and nonlinear parts of reaction term play quite different roles in the study of positive solutions.
The existence of unbounded solutions of asymmetric oscillations in the degenerate resonant case
Authors: Li Min , Li Xiong
Published: February 2023

We prove the existence of unbounded solutions of the asymmetric oscillation in the case when each zero of the discriminative function is degenerate. This is the only case that has not been studied in the literature.
On stability for generalized linear differential equations and applications to impulsive systems
Authors: Gallegos Claudio A. , Robledo Gonzalo
Published: February 2023

In this paper, we are interested in investigating notions of stability for generalized linear differential equations (GLDEs). Initially, we propose and revisit several definitions of stability and provide a complete characterization of them in terms of upper bounds and asymptotic behaviour of the transition matrix. In addition, we illustrate our stability results for GLDEs to linear periodic systems and linear impulsive differential equations. Finally, we prove that the well-known definitions of uniform asymptotic stability and variational asymptotic stability are equivalent to the global uniform exponential stability introduced in this article.
Animosity, Amnesia, or Admiration? Mass Opinion Around the World Toward the Former Colonizer
Authors: Baker Andy , Cupery David
Published: February 2023

Nearly all contemporary countries were colonized at some point in their history by a foreign power, but do citizens resent their former metropoles for past colonial abuses? We exploit survey questions in which respondents were asked for their opinion of a named foreign country. Our analyses of responses from over ninety countries yield the surprising finding that today's citizens are more favourable toward their country's former colonizer – by 40 per cent of a standard deviation – than they are toward other countries. Contemporary monadic traits that make former metropoles liked around the world – especially their tendency to be democracies – as well as their relatively high volumes of trade with former colonies explain their popularity among citizens of their former colonies. We also illustrate and describe these patterns in two least-likely cases, Mexico and Zimbabwe. Our findings have important implications for understanding international soft power, an asset about which today's states care deeply.
A Critical Analysis of the Corporate Whistleblowing Provisions of the South African Companies Act
Authors: Cassim Rehana
Published: February 2023

Section 159 of the South African Companies Act 71 of 2008 regulates corporate whistleblowing in companies registered under the act. This article critically evaluates section 159 to ascertain whether it adequately protects and encourages corporate whistleblowers. It compares this section with the whistleblower provisions in the Australian Corporations Act 2001, which have strongly influenced section 159 and which were recently reformed, and argues that in the light of the distressing levels of corporate corruption, the low reporting rates of wrongdoing and the widespread victimization of whistleblowers, there is a pronounced need to protect corporate whistleblowers in South Africa. It contends that section 159 does not go far enough in protecting and encouraging corporate whistleblowers, and calls for numerous important reforms to be urgently made.
T. F. Torrance, Catholicism, and the quest for church unity
Authors: Maclean Stanley
Published: February 2023

This article examines T. F. Torrance's engagement with Catholicism. It uncovers the breadth and depth of his ecumenical spirit, while concurrently shedding light on his own theological development. The article reveals an evolution in Torrance's posture toward Catholicism, moving from fierce criticism to critical praise, with the Second Vatican Council as a watershed in his thinking. His criticism was provoked by what he considered the fundamental problem with Catholicism (namely, the ‘Latin heresy’ in its theology); while his praise was elicited by the evangelical, christocentric, and ecumenical spirit of the Council.
The importance of modeling pragmatic syntactic bootstrapping
Authors: MINTZ Toben H.
Published: February 2023

Syntactic bootstrapping is based on the premise that there are probabilistic correspondences between the syntactic structure in which a word occurs and the word’s meaning, and that such links hold, with some degree of generality, cross-linguistically. The procedure has been extensively discussed with respect to verbs, where it has been proposed as a mechanism for constraining the massive ambiguity that arises when inferring the meaning of a verb that is used to describe an event (Fisher, Hall, Rakowitz & Gleitman, 1994; Gleitman, 1990; Gleitman, Cassidy, Nappa, Papafragou & Trueswell, 2005). In her keynote paper (Hacquard, 2022), Hacquard focuses on classes of verbs for which inferences about meaning are arguably even harder, because they involve concepts that have no observable counterparts: these are attitude verbs such as think and want, and modals such as must and can. She walks us through, in meticulous detail, the limits of a purely syntactic bootstrapping mechanism, and she describes how augmenting syntactic information with pragmatic information, via pragmatic syntactic bootstrapping (Hacquard, 2022; Hacquard & Lidz, 2019), might address these limitations. The proposal is exciting, and the detail with which Hacquard works through these examples is impressive; she supports her arguments with behavioral experiments, corpus analyses, and two very targeted computational analyses. In this commentary I suggest that Hacquard’s proposal is laid out in sufficient detail such that a comprehensive computational modeling effort would be fruitful for evaluating and further developing her account.
Syntactic bootstrapping with clausal complements of adjectives
Authors: SYRETT Kristen
Published: February 2023

Like verbs, adjectives pose a challenge to the young word learner in that some – like red, round, rough, or rectangular – map onto properties that are detectable through the senses, while others – like ready, reasonable, or required – express abstract properties that have no reliable, physical correlate. Even for those adjectives whose properties are observable, how does a child know that one particular property is being highlighted above all others? The physical environment alone will not suffice. Just as with verbs, the child learning adjectives is faced with an inherent indeterminacy of meaning, which can only be resolved through the incorporation of cues originating from multiple sources.
One welfare: Linking poverty, equid ownership and equid welfare in the brick kilns of India
Authors: Kubasiewicz LM , Watson T , Norris SL , Chamberlain N , Nye C , Perumal RK , Saroja R , Raw Z , Burden FA
Published: February 2023

The brick kilns in India are associated with extremely low pay, poor working conditions and a lack of regulation. Equids, however, may provide a route out of poverty by enabling workers to access a higher income. The relatively higher financial returns from healthy equids could also motivate welfare improvements. We used a mixed-methods approach including livelihoods questionnaires, semi-structured interviews and welfare assessments to investigate the links between poverty, equid ownership and equid welfare in the brick kilns of Ahmedabad, India. Whilst equid owners earned more than non-owners during the kiln season, the opposite trend was found for these workers for work conducted outside of the kilns during the off-season. Equid ownership was, however, strongly influenced by social factors and, within certain communities, equid ownership may be the only viable escape from extreme poverty. In terms of welfare, equid behaviour was better for owners with better financial security, likely due to the availability of resources. Equid health improved with longevity of ownership, suggesting that owners who view working with their equids as a long-term partnership are more likely to ensure their equids are kept in good health. For stakeholders aiming to improve both human health and equid welfare, a ‘one welfare’ approach which values the intrinsic connections between poverty and both equid ownership and equid welfare could greatly increase success.
Scholarship on the Middle East in Political Science and International Relations: A Reassessment
Authors: Teti Andrea , Abbott Pamela
Published: February 2023

A recently published dataset of Middle East and North Africa (MENA)–focused scholarship in journals selected to represent the disciplinary “core” of political science sheds empirical light on key publishing trends, from the balance between quantitative and qualitative studies to the growth in experimental and “large-N” statistical methods. Cammett and Kendall’s (2021) analysis shows that between 2001 and 2019, MENA-focused studies declined as a share of publications but that slightly less than half of that work is qualitative. However, the definition of qualitative research that the study uses significantly overstates the number of such articles in the Cammett and Kendall dataset. Our analysis rectifies this, distinguishing among research studies that use qualitative evidence, qualitative methods, theoretical traditions, and paradigms (i.e., positivist/post-positivist). This yields a more accurate and significantly starker picture of the marginality of MENA qualitative research in core politics journals. These results raise the question of why methodologically sophisticated scholarship outside of the “top journals” has not been published there.
Internet-delivered cognitive behavioural therapy for chronic fatigue among adolescents with a chronic medical condition: a single case study
Authors: Nijhof Linde N. , Nijhof Sanne L. , van de Putte Elise M. , Houtveen Jan , van Montfrans Joris M. , Knoop Hans
Published: February 2023

Background:

Severe fatigue is a prominent symptom among adolescents with a chronic medical condition, with major impact on their well-being and daily functioning. Internet-based cognitive behavioural therapy (I-CBT) is a promising treatment for severe fatigue among adolescents with a chronic medical condition, but its effectiveness has not been studied.

Aims:

We developed an I-CBT intervention for disabling fatigue in a chronic medical condition and tested its feasibility and effectiveness in an adolescent with an immune dysregulation disorder (IDD), namely juvenile idiopathic arthritis (JIA).

Method:

The application of I-CBT is illustrated through a clinical case study of a 15-year-old girl with JIA and chronic severe fatigue. An A-B single case experimental design was used with randomization of the waiting period prior to start of the intervention. Outcomes were weekly measures of fatigue severity, physical functioning, school absence and pain severity.

Results:

Fatigue severity significantly decreased following I-CBT. Improvements were observed towards increased school attendance and improved physical functioning following the intervention, but these effects were too small to become significant.

Conclusions:

The study provides preliminary support for the feasibility and effectiveness of the application of I-CBT for severe fatigue in adolescents with a long-term medical condition.
Greater accelerometer-measured physical activity is associated with better cognition and cerebrovascular health in older adults
Authors: Bangen Katherine J. , Calcetas Amanda T. , Thomas Kelsey R. , Wierenga Christina , Smith Christine N. , Bordyug Maria , Brenner Einat K. , Wing David , Chen Conan , Liu Thomas T. , Zlatar Zvinka Z.
Published: February 2023

Objectives:

Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults.

Method:

Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week.

Results:

Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume.

Conclusions:

Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.
Ending disability segregated employment: ‘modern slavery’ law and disabled people's human right to work
Authors: Steele Linda
Published: February 2023

Disability segregated employment (also referred to as ‘sheltered workshops’) violates disabled people's human right to work and employment. This article argues that modern slavery law might serve as one part of a broader strategy to end disability segregated employment, ensure accountability for the injustices within them and ensure equal access to open employment opportunities for disabled people. This is on the basis that disability segregated employment can be understood as a form of labour exploitation under modern slavery law – specifically forced labour and servitude. Modern slavery law is a useful legal tool to unseat deeply entrenched ableist attitudes of disability segregated employment as beneficial and necessary and build corporate/charity, public and government momentum towards the transition away from disability segregated employment, even if this particular area of law cannot itself legally compel the closure of sheltered workshops and an increase in open employment opportunities for disabled people.
Multiple-herbicide-resistant waterhemp control in glyphosate/glufosinate/2,4-D-resistant soybean with one- and two-pass weed control programs
Authors: Duenk Emily , Soltani Nader , Miller Robert T. , Hooker David C. , Robinson Darren E. , Sikkema Peter H.
Published: February 2023

Waterhemp control in Ontario has increased in complexity due to the evolution of biotypes that are resistant to five herbicide modes of action (Groups 2, 5, 9, 14, and 27 as categorized by the Weed Science Society of America). Four field trials were carried out over a 2-yr period in 2021 and 2022 to assess the control of multiple-herbicide-resistant (MHR) waterhemp biotypes in glyphosate/glufosinate/2,4-D-resistant (GG2R) soybean using one- and two-pass herbicide programs. S-metolachlor/metribuzin, pyroxasulfone/sulfentrazone, pyroxasulfone/flumioxazin, and pyroxasulfone + metribuzin applied preemergence (PRE) controlled MHR waterhemp similarly by 46%, 63%, 60%, and 69%, respectively, at 8 wk after postemergence (POST) application (WAA-B). A one-pass application of 2,4-D choline/glyphosate DMA POST provided greater control of MHR waterhemp than glufosinate. Two-pass herbicide programs of a PRE herbicide followed by (fb) a POST-applied herbicide resulted in greater MHR waterhemp control compared to a single PRE or POST herbicide application. PRE herbicides fb glufosinate or 2,4-D choline/glyphosate DMA POST controlled MHR waterhemp by 74% to 91% and by 84% to 96%, respectively, at 8 WAA-B. Two-pass herbicide applications of an effective PRE residual herbicide fb 2,4-D choline/glyphosate DMA POST in GG2R soybean can effectively manage waterhemp that is resistant to herbicides in Groups 2, 5, 9, 14, and 27.
A Volume‐Conserved Approach to Estimating Sea‐Ice Production in Antarctic Polynyas
Authors: Lin Y. , Yang Q. , Shi Q. , Nakayama Y. , Chen D.
Published: February 2023

Accurate estimation of sea‐ice production (SIP) is crucial to understanding the formation of Antarctic Bottom Water (AABW). Existing SIP estimates depend on the heat‐budget method, using atmospheric reanalysis together with satellite‐derived sea‐ice thickness data, and make an unrealistic assumption of no ocean heat flux occurring below the ice. Here, we propose a new method to estimate SIP based on the sea‐ice volume‐conservation (VC) theory. This new method can consider cases with sea‐ice melting (negative SIP). For a latent‐heat polynya—the Ross Sea Polynya—this method captures the synoptic SIP variations affected by warm‐water intrusions, including small‐scale melting and freezing patterns. Using the new VC approach for a sensible‐heat polynya, the Maud Rise Polynya, the sub‐sea‐ice oceanic heat flux was indirectly estimated, and the sea‐ice melting rate induced by warm water uplifted by Ekman pumping was estimated to be 0.15 and 1.44 cm d−1 for 2016 and 2017, respectively.
Periodicities and Plasma Density Structure of Jupiter's Dawnside Magnetosphere
Authors: Schok A. A. , Delamere P. A. , Mino B. , Damiano P. A. , Zhang B. , Sciola A. , Sorathia K. , Wing S. , Johnson J. R. , Ma X. , Yao Z. , Brambles O.
Published: February 2023

Ability to quantify variations in magnetic field topology and density within Jupiter's magnetosphere is an important step in understanding the overall structure and dynamics. The Juno spacecraft has provided a rich data set in the dawnside magnetosphere. The recent Grid Agnostic MHD for Extended Research Applications (GAMERA) global simulation study by Zhang et al. (2021, https://doi.org/10.1126/sciadv.abd1204) showed a highly structured plasmadisc with closed magnetic field lines mapped between the outer dawn‐tail flank and the high‐latitude polar region. To test these model predictions, we examined Juno's magnetic field data and electron/energetic particle data to categorize portions of orbits 1–15 into one of three regions based on plasma confinement: the flux pileup region, the intermediate region, and the plasmadisc region. For each region we examined periodicities from magnetic field fluctuations and particle density fluctuations on the 1–10 hr time scale. Periodicities on this time scale could relate to internal (e.g., plasmadisc structure) or external processes (e.g., Kelvin‐Helmholtz vortices). Similar analysis was performed on the GAMERA simulation with the data split into two regions, an outer (150 > R > 60) region and an inner (R < 60) region. Finally, using published density moments from Huscher et al. (2021, https://doi.org/10.1029/2021JA029446), we compared the relative density variations of the Juno moments and the GAMERA simulation to further understand the overall structure and dynamics of the plasmadisc. The agreement between data and simulation supports the existence of such a highly structured plasmadisc.
Cognitive impairments correlate with increased central nervous system immune activation after allogeneic haematopoietic stem cell transplantation
Authors: Boberg Erik , Kadri Nadir , Hagey Daniel W. , Schwieler Lilly , El Andaloussi Samir , Erhardt Sophie , Iacobaeus Ellen , Le Blanc Katarina
Published: February 2023

Murine studies indicate that, after allogeneic haematopoietic stem cell transplantation (aHSCT), donor-derived macrophages replace damaged microglia and alloreactive T-cells invade the central nervous system (CNS). The clinical relevance of this is unknown. We assessed CNS immune surveillance and metabolic activity involved in neuronal survival, in relation to fatigue and cognitive dysfunction in 25 long-term survivors after aHSCT. Patients with cognitive dysfunction exhibited increased proportions of activated T-cells and CD16 + NK-cells in the cerebrospinal fluid (CSF). Immune cell activation was paralleled with reduced levels of anti-inflammatory factors involved in T-cell suppression (transforming growth factor-β, programmed death ligand-1), NK-cell regulation (poliovirus receptor, nectin-2), and macrophage and microglia activation (CD200, chemokine [C-X3-C motif] ligand-1). Additionally, the CSF mRNA expression pattern was associated with neuroinflammation and oxidative stress. Furthermore, proteomic, and transcriptomic studies demonstrated decreased levels of neuroprotective factors, and an upregulation of apoptosis pathway genes. The kynurenine pathway of tryptophan metabolism was activated in the CNS of all aHSCT patients, resulting in accumulation of neurotoxic and pro-inflammatory metabolites. Cognitive decline and fatigue are overlooked but frequent complications of aHSCT. This study links post-transplant CNS inflammation and neurotoxicity to our previously reported hypoactivation in the prefrontal cortex during cognitive testing, suggesting novel treatment targets.
Harnessing the reverse cholesterol transport pathway to favor differentiation of monocyte-derived APCs and antitumor responses
Authors: Raccosta Laura , Marinozzi Maura , Costantini Susan , Maggioni Daniela , Ferreira Lorena Maria , Corna Gianfranca , Zordan Paola , Sorice Angela , Farinello Diego , Bianchessi Silvia , Riba Michela , Lazarevic Dejan , Provero Paolo , Mack Matthias , Bondanza Attilio , Nalvarte Ivan , Gustafsson J-A , Ranzani Valeria , De Sanctis Francesco , Ugel Stefano , Baron Silvère , Lobaccaro Jean-Marc A. , Pontini Lorenzo , Pacciarini Manuela , Traversari Catia , Pagani Massimiliano , Bronte Vincenzo , Sitia Giovanni , Antonson Per , Brendolan Andrea , Budillon Alfredo , Russo Vincenzo
Published: February 2023

Lipid and cholesterol metabolism play a crucial role in tumor cell behavior and in shaping the tumor microenvironment. In particular, enzymatic and non-enzymatic cholesterol metabolism, and derived metabolites control dendritic cell (DC) functions, ultimately impacting tumor antigen presentation within and outside the tumor mass, dampening tumor immunity and immunotherapeutic attempts. The mechanisms accounting for such events remain largely to be defined. Here we perturbed (oxy)sterol metabolism genetically and pharmacologically and analyzed the tumor lipidome landscape in relation to the tumor-infiltrating immune cells. We report that perturbing the lipidome of tumor microenvironment by the expression of sulfotransferase 2B1b crucial in cholesterol and oxysterol sulfate synthesis, favored intratumoral representation of monocyte-derived antigen-presenting cells, including monocyte-DCs. We also found that treating mice with a newly developed antagonist of the oxysterol receptors Liver X Receptors (LXRs), promoted intratumoral monocyte-DC differentiation, delayed tumor growth and synergized with anti-PD-1 immunotherapy and adoptive T cell therapy. Of note, looking at LXR/cholesterol gene signature in melanoma patients treated with anti-PD-1-based immunotherapy predicted diverse clinical outcomes. Indeed, patients whose tumors were poorly infiltrated by monocytes/macrophages expressing LXR target genes showed improved survival over the course of therapy. Thus, our data support a role for (oxy)sterol metabolism in shaping monocyte-to-DC differentiation, and in tumor antigen presentation critical for responsiveness to immunotherapy. The identification of a new LXR antagonist opens new treatment avenues for cancer patients.
Long noncoding RNA ENST00000436340 promotes podocyte injury in diabetic kidney disease by facilitating the association of PTBP1 with RAB3B
Authors: Hu Jinxiu , Wang Qimeng , Fan Xiaoting , Zhen Junhui , Wang Cheng , Chen Huimin , Liu Yingxiao , Zhou Ping , Zhang Tingwei , Huang Tongtong , Wang Rong , Lv Zhimei
Published: February 2023

Dysfunction of podocytes has been regarded as an important early pathologic characteristic of diabetic kidney disease (DKD), but the regulatory role of long noncoding RNAs (lncRNAs) in this process remains largely unknown. Here, we performed RNA sequencing in kidney tissues isolated from DKD patients and nondiabetic renal cancer patients undergoing surgical resection and discovered that the novel lncRNA ENST00000436340 was upregulated in DKD patients and high glucose-induced podocytes, and we showed a significant correlation between ENST00000436340 and kidney injury. Gain- and loss-of-function experiments showed that silencing ENST00000436340 alleviated high glucose-induced podocyte injury and cytoskeleton rearrangement. Mechanistically, we showed that fat mass and obesity- associate gene (FTO)-mediated m6A induced the upregulation of ENST00000436340. ENST00000436340 interacted with polypyrimidine tract binding protein 1 (PTBP1) and augmented PTBP1 binding to RAB3B mRNA, promoted RAB3B mRNA degradation, and thereby caused cytoskeleton rearrangement and inhibition of GLUT4 translocation to the plasma membrane, leading to podocyte injury and DKD progression. Together, our results suggested that upregulation of ENST00000436340 could promote podocyte injury through PTBP1-dependent RAB3B regulation, thus suggesting a novel form of lncRNA-mediated epigenetic regulation of podocytes that contributes to the pathogenesis of DKD.
Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma
Authors: Li Qing , Zhang Xiao-Xin , Hu Li-Peng , Ni Bo , Li Dong-Xue , Wang Xu , Jiang Shu-Heng , Li Hui , Yang Min-Wei , Jiang Yong-Sheng , Xu Chun-Jie , Zhang Xue-Li , Zhang Yan-Li , Huang Pei-Qi , Yang Qin , Zhou Yang , Gu Jian-ren , Xiao Gary Gui-Shan , Sun Yong-wei , Li Jun , Zhang Zhi-Gang
Published: February 2023

To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN.
Investigating microstructure evolution of lithium metal during plating and stripping via operando X-ray tomographic microscopy
Authors: Sadd Matthew , Xiong Shizhao , Bowen Jacob R. , Marone Federica , Matic Aleksandar
Published: February 2023

Efficient lithium metal stripping and plating operation capable of maintaining electronic and ionic conductivity is crucial to develop safe lithium metal batteries. However, monitoring lithium metal microstructure evolution during cell cycling is challenging. Here, we report the development of an operando synchrotron X-ray tomographic microscopy method capable of probing in real-time the formation, growth, and dissolution of Li microstructures during the cycling of a Li||Cu cell containing a standard non-aqueous liquid electrolyte solution. The analyses of the operando X-ray tomographic microscopy measurements enable tracking the evolution of deposited Li metal as a function of time and applied current density and distinguishing the formation of electrochemically inactive Li from the active bulk of Li microstructures. Furthermore, in-depth analyses of the Li microstructures shed some light on the structural connectivity of deposited Li at different current densities as well as the formation mechanism of fast-growing fractal Li microstructures, which are ultimately responsible for cell failure.
A NPAS4–NuA4 complex couples synaptic activity to DNA repair
Authors: Pollina Elizabeth A. , Gilliam Daniel T. , Landau Andrew T. , Lin Cindy , Pajarillo Naomi , Davis Christopher P. , Harmin David A. , Yap Ee-Lynn , Vogel Ian R. , Griffith Eric C. , Nagy M. Aurel , Ling Emi , Duffy Erin E. , Sabatini Bernardo L. , Weitz Charles J. , Greenberg Michael E.
Published: February 2023

Neuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome across the long lifespan of postmitotic neurons1–5. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is unknown. Here we identify an activity-dependent DNA repair mechanism in which a new form of the NuA4–TIP60 chromatin modifier assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex from the brain and demonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By characterizing the landscape of activity-induced DNA double-strand breaks in the brain, we show that NPAS4–NuA4 binds to recurrently damaged regulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound by NPAS4–NuA4 are partially protected against age-dependent accumulation of somatic mutations. Impaired NPAS4–NuA4 signalling leads to a cascade of cellular defects, including dysregulated activity-dependent transcriptional responses, loss of control over neuronal inhibition and genome instability, which all culminate to reduce organismal lifespan. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental and autism spectrum disorders. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation, the disruption of which may contribute to developmental disorders, neurodegeneration and ageing.
Effects of Al2O3, SiO2 nanoparticles, and g-c3n4 nanosheets on biocement production from agricultural wastes
Authors: Abdelsalam Essam M. , Samer Mohamed , Seifelnasr Amira , Moselhy Mohamed A. , Ibrahim Hatem H. A. , Faried Maryam , Attia Yasser A.
Published: February 2023

Environmental issues are brought up concerning the production of Portland cement. As a result, biocement serves as a reliable substitute for Portland cement in green construction projects. This study created a brand-new technique to create high-quality biocement from agricultural wastes. The technique is based on nanomaterials that improve and accelerate the "Microbially Induced Calcite Precipitation (MICP)" process, which improves the quality of the biocement produced. The mixture was further mixed with the addition of 5 mg/l of graphitic carbon nitride nanosheets (g-C3N4 NSs), alumina nanoparticles (Al2O3 NPs), or silica nanoparticles (SiO2 NPs). The cement: sand ratio was 1:3, the ash: cement ratio was 1:9, and water: cement ratio was 1:2. Cubes molds were prepared, and then cast and compacted. Subsequent de-molding, all specimens were cured in nutrient broth-urea (NBU) media until testing at 28 days. The medium was replenished at an interval of 7 days. The results show that the addition of 5 mg/l of g-C3N4 NSs with corncob ash delivered the highest “Compressive Strength” and the highest “Flexural Strength” of biocement mortar cubes of 18 and 7.6 megapascal (MPa), respectively; and an acceptable “Water Absorption” (5.42%) compared to all other treatments. This treatment delivered a “Compressive Strength”, “Flexural Strength”, and “Water Absorption” reduction of 1.67, 1.26, and 1.21 times the control (standard Portland cement). It was concluded that adding 5 mg/l of g-C3N4 NSs to the cementitious mixture enhances its properties, where the resulting biocement is a promising substitute for conventional Portland cement. Adding nanomaterials to cement reduces its permeability to ions, increasing its strength and durability. The use of these nanomaterials can enhance the performance of concrete infrastructures. The use of nanoparticles is an effective solution to reduce the environmental impact associated with concrete production.
Generalisability of fetal ultrasound deep learning models to low-resource imaging settings in five African countries
Authors: Sendra-Balcells Carla , Campello Víctor M. , Torrents-Barrena Jordina , Ahmed Yahya Ali , Elattar Mustafa , Ohene-Botwe Benard , Nyangulu Pempho , Stones William , Ammar Mohammed , Benamer Lamya Nawal , Kisembo Harriet Nalubega , Sereke Senai Goitom , Wanyonyi Sikolia Z. , Temmerman Marleen , Gratacós Eduard , Bonet Elisenda , Eixarch Elisenda , Mikolaj Kamil , Tolsgaard Martin Grønnebæk , Lekadir Karim
Published: February 2023

Most artificial intelligence (AI) research and innovations have concentrated in high-income countries, where imaging data, IT infrastructures and clinical expertise are plentiful. However, slower progress has been made in limited-resource environments where medical imaging is needed. For example, in Sub-Saharan Africa, the rate of perinatal mortality is very high due to limited access to antenatal screening. In these countries, AI models could be implemented to help clinicians acquire fetal ultrasound planes for the diagnosis of fetal abnormalities. So far, deep learning models have been proposed to identify standard fetal planes, but there is no evidence of their ability to generalise in centres with low resources, i.e. with limited access to high-end ultrasound equipment and ultrasound data. This work investigates for the first time different strategies to reduce the domain-shift effect arising from a fetal plane classification model trained on one clinical centre with high-resource settings and transferred to a new centre with low-resource settings. To that end, a classifier trained with 1792 patients from Spain is first evaluated on a new centre in Denmark in optimal conditions with 1008 patients and is later optimised to reach the same performance in five African centres (Egypt, Algeria, Uganda, Ghana and Malawi) with 25 patients each. The results show that a transfer learning approach for domain adaptation can be a solution to integrate small-size African samples with existing large-scale databases in developed countries. In particular, the model can be re-aligned and optimised to boost the performance on African populations by increasing the recall to $$0.92 \pm 0.04$$

0.92
±
0.04

and at the same time maintaining a high precision across centres. This framework shows promise for building new AI models generalisable across clinical centres with limited data acquired in challenging and heterogeneous conditions and calls for further research to develop new solutions for the usability of AI in countries with fewer resources and, consequently, in higher need of clinical support.
The choice of an autocorrelation length in dark-field lung imaging
Authors: Spindler Simon , Etter Dominik , Rawlik Michał , Polikarpov Maxim , Romano Lucia , Shi Zhitian , Jefimovs Konstantins , Wang Zhentian , Stampanoni Marco
Published: February 2023

Respiratory diseases are one of the most common causes of death, and their early detection is crucial for prompt treatment. X-ray dark-field radiography (XDFR) is a promising tool to image objects with unresolved micro-structures such as lungs. Using Talbot-Lau XDFR, we imaged inflated porcine lungs together with Polymethylmethacrylat (PMMA) microspheres (in air) of diameter sizes between 20 and 500 $$\upmu \hbox {m}$$

μ
m

over an autocorrelation range of 0.8–5.2 $$\upmu \hbox {m}$$

μ
m

. The results indicate that the dark-field extinction coefficient of porcine lungs is similar to that of densely-packed PMMA spheres with diameter of $${200}\,\upmu \hbox {m}$$

200

μ
m

, which is approximately the mean alveolar structure size. We evaluated that, in our case, the autocorrelation length would have to be limited to $${0.57}\,\upmu \hbox {m}$$

0.57

μ
m

in order to image $${20}\,\hbox {cm}$$

20

cm

-thick lung tissue without critical visibility reduction (signal saturation). We identify the autocorrelation length to be the critical parameter of an interferometer that allows to avoid signal saturation in clinical lung dark-field imaging.
Multi-dimensional safety risk assessment on coal mines under the profitability dilemma
Authors: You Qi , Yao Qingguo , Song Ruixin , Yu Kai , Xu Cuicui , Cao Haiying
Published: February 2023

China is a major coal producer, with huge differences in coal production and safety situations between the South and the North. Taking province A as an example, its coal enterprises have low output, poor efficiency, backward equipment, and low-quality personnel. The output accounts for 0.08% of the country, and the number of deaths accounts for 2.2% of the country, the safety situation of coal enterprises in province A is severe. In order to study the safety risk situation of coal mines under difficult conditions, this paper screens 98 factor indexes including multiple subjects such as enterprise managers, front-line workers, government supervisors, external environment, work quality, stress factors, economic factors, and other dimensions. For different data, the indicator weights were calculated using triangular fuzzy number, entropy weight method, CRITIC method, and three rough set methods in a total of six methods. The comprehensive weights of the indicators were obtained using the proposed new comprehensive weight method. The current situation of safety work of four coal mining enterprises and three levels of government supervision departments was evaluated, and the evaluation results were compared with other existing data to verify the reliability of the evaluation system. The horizontal comparison of the evaluation results indicates the main problems of each subject; the longitudinal comparison points out the problems that need to be solved with the assistance of higher-level enterprises and the central government, and corresponding suggestions for coal mining enterprises and government departments are put forward to reduce the safety risks of troubled coal mining enterprises.