bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions for expectant and new parents who are at increased risk for perpetrating child abuse and neglect: protocol for a systematic review and meta-analysis
Authors: Tamon Hiroki , Suto Maiko , Ogawa Kunio , Takehara Kenji , Tachibana Yoshiyuki
Published: November 2022

Introduction

The prevention of child abuse and neglect is an urgent matter given the serious effects persisting into adulthood, and the increased risk of the offspring of abused children being abusive themselves. Intervening as early as possible may prevent abuse that can begin in infancy. Although several systematic reviews have investigated the effects of interventions on populations who are at increased risk for perpetrating child abuse and neglect, few studies have focused on women or interventions that start during perinatal periods. This study aims to describe a systematic review to examine the effects of interventions to prevent child abuse and neglect that begin during pregnancy and immediately after childbirth (less than 1 year). The study will involve performing a systematic review and meta-analysis based on the latest research articles and a broader literature search.

Methods and analysis

The protocol was prepared using the 2015 statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The literature search will be performed using the MEDLINE, PsycINFO, Embase and Cochrane Central Register of Controlled Trials databases from inception onward. Randomised controlled trials of interventions that begin during pregnancy or the first year postpartum, designed to prevent child abuse and neglect in families who are at increased risk for these issues, will be included. Data collection, quality assessment and statistical syntheses will be conducted by following the methods in the protocol that are predefined. Any index of child maltreatment will be included as a primary outcome. A meta-analysis and sub-group analyses will be considered based on the characteristics of interventions.

Ethics and dissemination

This study does not require ethical approval. The findings will be presented at conferences and will be submitted to a peer-reviewed journal.

PROSPERO registration number

CRD42021266462.
Using set visualisation to find and explain patterns of missing values: a case study with NHS hospital episode statistics data
Authors: Ruddle Roy A , Adnan Muhammad , Hall Marlous
Published: November 2022

Objectives

Missing data is the most common data quality issue in electronic health records (EHRs). Missing data checks implemented in common analytical software are typically limited to counting the number of missing values in individual fields, but researchers and organisations also need to understand multifield missing data patterns to better inform advanced missing data strategies for which counts or numerical summaries are poorly suited. This study shows how set-based visualisation enables multifield missing data patterns to be discovered and investigated.

Design

Development and evaluation of interactive set visualisation techniques to find patterns of missing data and generate actionable insights. The visualisations comprised easily interpretable bar charts for sets, heatmaps for set intersections and histograms for distributions of both sets and intersections.

Setting and participants

Anonymised admitted patient care health records for National Health Service (NHS) hospitals and independent sector providers in England. The visualisation and data mining software was run over 16 million records and 86 fields in the dataset.

Results

The dataset contained 960 million missing values. Set visualisation bar charts showed how those values were distributed across the fields, including several fields that, unexpectedly, were not complete. Set intersection heatmaps revealed unexpected gaps in diagnosis, operation and date fields because diagnosis and operation fields were not filled up sequentially and some operations did not have corresponding dates. Information gain ratio and entropy calculations allowed us to identify the origin of each unexpected pattern, in terms of the values of other fields.

Conclusions

Our findings show how set visualisation reveals important insights about multifield missing data patterns in large EHR datasets. The study revealed both rare and widespread data quality issues that were previously unknown, and allowed a particular part of a specific hospital to be pinpointed as the origin of rare issues that NHS Digital did not know exist.
Respiratory diseases in survivors of adult cancer compared with the general population: a systematic review protocol
Authors: Andresen Kirsty , Carreira Helena , Quint Jennifer K , Bhaskaran Krishnan
Published: November 2022

Introduction

There is concern that survivors of adult cancers may be at increased risk of respiratory infections and of exacerbations of pre-existing respiratory conditions. Considering the high prevalence of respiratory disease in the general population, increased respiratory disease risk in survivors of adult cancers could translate into an important impact on morbidity and mortality. The aim of this systematic review is to summarise and assess the quality of all studies comparing respiratory outcomes between adult cancer survivors and individuals with no history of cancer.

Methods and analysis

This systematic literature review will be conducted using Medline, EMBASE and Cochrane. We will include cohort or case–control studies that provide a comparative estimate of the risk of a respiratory disease of interest in survivors of adult cancer against a comparator cohort of cancer-free individuals. No geographic, time or language restrictions will be applied. We will assess the risk of bias using the Scottish Intercollegiate Guidelines Network methodology checklists. Results will be summarised by type of respiratory outcome, cancer type and cancer survivorship definition. If sufficient numbers of homogeneous studies are found, summary measures of association will be calculated using random effects meta-analysis models.

Ethics and dissemination

Ethical approval is not applicable to our study. The results will be used to identify evidence gaps and priorities for future research to understand respiratory morbidity in survivors of adult cancers and identify possible mitigation strategies. Results from this review will be disseminated to clinical audiences and submitted to a peer-reviewed journal when completed.

Trial registration number

This study has been registered on PROSPERO (registration number: CRD42022311557).
Protocol for national mental health guidelines for community sport in Australia
Authors: Liddelow Caitlin , Schweickle Matthew J , Sutcliffe Jordan T , Swann Christian , Keegan Richard , Rice Simon , Okely Anthony David , Vella Stewart A
Published: November 2022

Organised sports are the most common settings for sports participation. Despite a range of documented benefits from participation, these positive outcomes are not always guaranteed. Emotional distress from pressure and injuries can mean some participants experience negative outcomes. To ensure organised sports are well equipped to promote the mental health of their members, evidence-based guidelines for them are required. Using a Community-Based Participatory Research framework, mental health guidelines for community sport will be developed. In Phase One, community sport stakeholders will participate in focus groups. The aim is to understand their preferences of the content, purpose and scope of the guidelines. In Phase Two, an e-Delphi study will be conducted with experts in mental health and sport in Australia to gather recommendations on the purpose and scope of the guidelines. In Phase Three, a national consensus meeting with an Expert Guideline Development Committee will be held to draft the guidelines. In Phase Four, follow-up focus groups will be held with community sport stakeholders to understand the usability and acceptability of the draft guidelines. In Phase Five, a second e-Delphi study will be conducted to provide feedback on the revised guidelines after community stakeholder review. In Phase Six, implementation case studies will assess the implementation of the guidelines in community sport clubs. These mental health guidelines will answer an urgent call for action by experts. The guidelines will be based on sector needs and preferences, be acceptable and useable, and be able to be implemented by community sport clubs globally by 2025.
UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes:RAD51C,RAD51D,BRIP1andPALB2
Authors: Hanson Helen , Kulkarni Anjana , Loong Lucy , Kavanaugh Grace , Torr Bethany , Allen Sophie , Ahmed Munaza , Antoniou Antonis C , Cleaver Ruth , Dabir Tabib , Evans D Gareth , Golightly Ellen , Jewell Rosalyn , Kohut Kelly , Manchanda Ranjit , Murray Alex , Murray Jennie , Ong Kai-Ren , Rosenthal Adam N , Woodward Emma Roisin , Eccles Diana M , Turnbull Clare , Tischkowitz Marc ,   On behalf of Consensus meeting attendees, Lalloo Fiona
Published: November 2022

Germline pathogenic variants (GPVs) in the cancer predisposition genesBRCA1,BRCA2,MLH1,MSH2,MSH6,BRIP1,PALB2,RAD51DandRAD51Care identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV inBRCA1,BRCA2,MLH1,MSH2andMSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV inBRIP1,PALB2,RAD51DandRAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition ofRAD51Cand RAD51Das OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management ofBRIP1,PALB2,RAD51DandRAD51Ccarriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.
Blaming, naming and a just culture
Authors: Tasker Adam
Published: November 2022

BackgroundProblematic cultures within NHS trusts are repeatedly cited as contributing to failures in patient safety and care. The NHS has attempted to address this through promotion of a Just Culture having recognised the improvements made by other safety critical sectors, including aviation, following its adoption. Changing the culture of an organisation is a significant leadership challenge that goes far beyond the revision of management processes.

Story of selfI served as a Helicopter Warfare Officer in the Royal Navy prior to commencing medical training. In this article, I reflect on a near miss incident that I was involved in during my previous career and examine the attitudes of myself and my colleagues, and the practices and behaviours of the squadron’s leaders.

ConclusionThis article compares my experience within aviation to that of my medical training. Lessons are identified that are relevant to medical training, professional expectations, and the management of clinical incidents to support the implementation of a Just Culture within the NHS.
Gaming for Adherence to Medication using Ehealth in Rheumatoid arthritis (GAMER) study: a randomised controlled trial
Authors: Pouls Bart P H , Bekker Charlotte L , Gundogan Fatma , Hebing Renske CF , van Onzenoort Hein AW , van de Ven Liesbeth I , Vonkeman Harald E , Tieben Rob , Vriezekolk Johanna E , van Dulmen Sandra , Van den Bemt Bart
Published: November 2022

Objective

To examine the effect on adherence to disease modifying anti-rheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) of a serious game that targeted implicit attitudes toward medication.

Methods

A multicentre randomised controlled trial (RCT) was performed with adults with RA that used DMARDs and possessed a smartphone/tablet. Control and intervention groups received care as usual. The intervention group played the serious game at will during 3 months. Game play data and online questionnaires Compliance Questionnaire on Rheumatology (CQR), Beliefs about Medicine Questionnaire (BMQ), Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI) were collected. Primary outcome was DMARD implementation adherence operationalised as the difference in proportion of non-adherent participants (<80% taking adherence) between intervention and control group after 3 months using a Chi-squared test. Two sample t-tests and Wilcoxon rank-sum test were performed to test for differences on secondary outcomes.

Results

Of the 110 intervention participants that started the study, 87 participants (79%) installed the game and had a median playtime of 9.7 hours at 3 months. Overall, 186 participants completed the study. Adherence in intervention group (63%) and control group (54%) did not differ significantly (p=0.13) at 3 months. Neither were there differences oberved in CQR continuous score, beliefs about medication (BMQ) or clinical outcomes (HAQ and RADAI).

Conclusion

A serious game aimed at reinterpreting attitudes toward medication failed to show an effect on adherence to DMARDs or clinical outcomes in patients with RA. The game was played frequently indicating that it can be an effective channel for reaching patients.

Trial registration number

NL7217.
The Paleoproterozoic Amer supergroup, Amer Fold Belt, Nunavut: stratigraphy, structure, correlations, and uranium metallogeny
Authors: Jefferson C.W. , Rainbird R.H. , Young Grant M. , White J.C. , Tschirhart V. , Creaser R.A.
Published: November 2022

The Amer Belt, hosting eleven informal formations of the Amer supergroup, is proposed as type area for four regional Paleoproterozoic sequences (Ps1–Ps4) in central Rae Craton, western Churchill Province. The ca. 1.9–1.865 Ga Snowbird orogeny (DP1) affected only Ps1–Ps3, whereas the ca. 1.87–1.81 Ga Hudsonian orogeny (DP2) affected all four. Sequence Ps1 Ayagaq Lake formation (<2.3 Ga quartzite) initiates as schistose basal polymict orthoconglomerate unconformably overlying paleoweathered Neoarchean rocks. It transitions upward to lower Ps2 Resort Lake formation: gossanous, recessive, graphitic, pyritic-metalliferous phyllite (Re–Os age: 2126 ± 24 Ma). Ps2 conductors beneath the <1.74 Ga Thelon formation have been drilled for unconformity-related uranium. Gradationally overlying siliceous dolomitic marble (Aluminium River formation) completes Ps2. The gradationally overlying lower Ps3 is either foliated calcareous tholeiitic basalt (Five Mile Lake formation) or grey phyllite (Three Lakes formation). These lateral equivalents host strong linear aeromagnetic markers. The Oora Lake formation foliated feldspathic calcareous sandstone gradationally overlies only the Three Lakes formation and underlies the upper Ps3 Showing Lake formation (interbedded phyllite and foliated calcareous arkose) whose two arkose members host laterally continuous disseminated uraninite + magnetite forming linear aeromagnetic markers. Pristine sequence Ps4 molasse, deposited and weakly deformed during DP2, comprises four formations of rhythmically interbedded, deep maroon to pink and green, feldspathic-lithic arenite, conglomerate, and mudstone that unconformably overlie and include clasts of DP1-deformed Ps1–Ps3 + Neoarchean basement. Ps4 detrital zircon (3.05–1.90 Ga) suggests local + distal provenance from south Rae and Slave Cratons, and Taltson–Thelon magmatic zone.
Renormalization of supersymmetric chiral theories in rational spacetime dimensions
Authors: Gracey J. A.
Published: November 2022

We renormalize models with scalar chiral superfields with an odd superpotential to several orders in perturbation theory. These extensions of the cubic Wess–Zumino model are renormalizable in spacetime dimensions which are rational. When endowed with an O(N) symmetry it is shown that they share the same property as their non-supersymmetric counterparts in that at a particular fixed point there is an emergent $$OSp(1|n-1)$$

O
S
p
(
1
|
n
-
1
)

symmetry, where n is the power of the superpotential. This is shown at a loop order beyond that for which it was established in the parallel non-supersymmetric theory.
Bound states of the isotonic Mathews–Lakshmanan oscillator system within the Dunkl formalism
Authors: Schulze-Halberg Axel
Published: November 2022

We construct a quantum Hamiltonian for the isotonic Mathews–Lakshmanan oscillator system within the Dunkl formalism. It is shown that the Dunkl Hamiltonian does not admit bound states if the isotonic term is present. If the isotonic term is not present, then the Dunkl Hamiltonian admits bound states of even parity only. These results are in contrast to the findings for the conventional Mathews–Lakshmanan oscillator system.
Nonlinear system stabilization in an anisotropic porous medium with Oldroyd-B fluid based on an actuator and sensor array
Authors: Surendar R. , Muthtamilselvan M.
Published: November 2022

In this research, the authors precisely focus on the analysis of the chaotic behavior in an Oldroyd-B fluid saturated anisotropic porous medium via a feedback control technique. A four-dimensional (4D) weakly nonlinear system emerging from a Galerkin method of the constitutive and preservation equations is developed to accord with a convective stabilization with various Darcy numbers (Da) and feedback control gain value [Formula: see text]. The chaotic dynamic convection is governed by the Darcy–Rayleigh number ([Formula: see text]) and feedback control, while the Da has a significant impact on system stabilization. Their results reveal the effects of the feedback gain parameter [Formula: see text], stress relaxation parameter ([Formula: see text]), strain retardation parameter ([Formula: see text]), Darcy number (Da), mechanical ([Formula: see text]) and thermal ([Formula: see text]) anisotropy parameter on the stability and destabilization of thermal convection. Stabilization of thermal convection are important in cooling, nuclear power, and a range of technical, biological and engineering processes. In particular, feedback control gain values are discovered to be the preferred mode for the controlled onset of oscillatory convection. Finally, a graphical representation is presented to demonstrate that the feedback control approach is more effective in regulating the entire system when aperiodic external disturbances occur.
The impact of slip mechanisms on the flow of hybrid nanofluid past a wedge subjected to thermal and solutal stratification
Authors: Baby Riya , Puneeth V. , Narayan S. S. , Khan M. Ijaz , Anwar M. Shoaib , Bafakeeh Omar T. , Oreijah Mowffaq , Geudri Kamel
Published: November 2022

This investigation aims to inspect the flow and thermal characteristics of hybrid nanoparticles under the effect of thermophoresis and Brownian motion. The hybrid nanofluid is formed by dispersing the silver nanoparticles into the base fluid composed of tungsten oxide and water. The resulting hybrid nanofluid is assumed to flow over a moving wedge. The wedge is a geometry that can be commonly seen in many manufacturing industries, moulding industries, etc., where friction creates more heat and cooling becomes a necessary process. This study currently focuses on such areas of the industries. In this regard, the flow expressions in the form of Partial Differential Equations (PDEs) are obtained by incorporating the modified Buongiorno’s model and using boundary layer approximations. The modified Buongiorno model helps us analyze the impact of volume fraction along with the slip mechanisms. Suitable transformations are used to achieve the nondimensional form of governing equations, and further, it transforms the PDE to Ordinary Differential Equation (ODE). The RKF-45 is used to solve the obtained ODE and the boundary conditions. Furthermore, graphic analysis of the solutions for fluid velocity, energy distributions and dimensionless concentration is provided. It was noted that the behavior of the Nusselt and Sherwood numbers was determined by analyzing numerous parameters. The conclusions show that they decrease with greater values of the stratification factors. Additionally, with higher values of the wedge parameter, the magnitude of the velocity field and the thermal boundary layer diminish.
Electrochemical exfoliation and characterizations of low-defect, large-scale thermally reduced graphene oxide via pencil core
Authors: Singh Pankaj Kumar , Sharma Kamal , Singh Pradeep Kumar
Published: November 2022

The most difficult aspect in electrochemical synthesis of graphene oxide (GO) is preventing graphite from disintegrating on the surface of the anode, which affects microstructural characteristics and yield. In this study, the effect of applied potential, electrolytic temperature, and types of electrolytic solution on yield, anode surface disintegration and microstructural properties of electrochemically synthesized GO has been investigated. The GO has been synthesized in an aqueous solution of 1 M piranha solution and sulfuric acid ([Formula: see text]) via electrochemical method by applying 24 V DC power source. After that, the GO was thermally reduced at around 650[Formula: see text]C in a muffle furnace, and cooled down inside the muffle furnace. The yield, pH of the electrolytic solution, and anode surface disintegration all looked to be affected by the applied voltage and electrolyte temperature. Between the temperatures of 50[Formula: see text]C and 70[Formula: see text]C, the maximum yield was observed. During UV–Vis and XRD investigation, the absorbance, crystal structure, and interplanar distance appear to be unaffected by the reduction temperature, high voltage, electrolyte temperature and hydrogen peroxide addition. As demonstrated by Raman spectra, TEM, FE-SEM, AFM, and TGA analysis, high voltage, electrolyte temperature, and hydrogen peroxide addition have an important effect on the degree of defect, microstructure, and oxygen percentage, surface roughness and thermal stability of thermally reduced graphene oxide (TRGO).
A Novel Defuzzification Approach of Ranking Parametric Fuzzy Numbers Based on the Value and Ambiguity Calculated at Decision Levels
Authors: Chutia Rituparna
Published: November 2022

Generally, in every decision-making process under the fuzzy domain, ranking of fuzzy numbers is indispensable. Although such approaches are abundant, yet a universally accepted approach is not apparent. Hence, newer methodologies have been developed since its inception. In many instances, defuzzification techniques are being criticized as these methodologies are based on intuition and the geometry of the fuzzy numbers. Furthermore, in many instances the reasonable properties that a ranking method should follow are not being verified. However, in the current study, a novel defuzzification technique is being developed with the notion of value and multiple of a ambiguity inclusion-exclusion function, [Formula: see text], with ambiguity at various decision levels. The current method perfectly obeys the intuition and the geometry of the fuzzy numbers. Adding to this, it should be emphasized that the current methodology follows all the reasonable properties of a ranking method. Furthermore, new properties are stated and proved which illustrate the novelty of the present method. Furthermore, the shortcomings and drawbacks of the existing methods are overcome by the current methodology. Noteworthy, the current method ranks the fuzzy numbers and their corresponding images consistently, which was not evident in most of the existing methods.
Arcsine and Darling–Kac laws for piecewise linear random interval maps
Authors: Hata Genji , Yano Kouji
Published: November 2022

We give examples of piecewise linear random interval maps satisfying arcsine and Darling–Kac laws, which are analogous to Thaler’s arcsine and Aaronson’s Darling–Kac laws for the Boole transformation. They are constructed by random switch of two piecewise linear maps with attracting or repelling fixed points, which behave as if they were indifferent fixed points of a deterministic map.
Knowledge Creation in International Non-Profit Organisations
Authors: Le Quang Ngoc , Tuamsuk Kulthida
Published: November 2022

This study empirically investigates knowledge creation (KC) in the context of the not-for-profit environment and seeks an understanding of how the dynamic of KC occurs in non-profit organisations (NPOs) in developing countries. The study, qualitative in nature, was applied in international non-profit organisations (INPOs), which is based on the 31 interviews taken at various such organisations in Thailand. The research illustrates the context of interaction dynamic that figures out the exampled NPOs, that is the creation of four types of ba, which enhances the KC process and identifies the specific knowledge types that are managed in these organisations. The investigation offers a holistic approach of the processes of organisational knowledge-creating in the NPOs. Furthermore, it is intended that the evidence presented a critical attitude regarding knowledge management (KM)-NPOs domains, especially in the KC process in the academic community. For NPO practitioners, this paper allows us to discover the organisational practices on the process-creating to enhance KM activities in their organisation.
Electrochromic properties of conductive polyporphyrin films based on 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and 5,10,15,20-tetrakis(4-pyridyl)porphyrin
Authors: Tesakova Mariya V. , Syrbu Sergey A. , Parfenyuk Vladimir I.
Published: November 2022

Polyporphyrin films based on 5,10,15,20-tetrakis(4-pyridyl)porphyrin and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin were obtained by electrochemical polymerization during the electrooxidation of the respective monomers. The polyporphyrin formation involved the side substituents, with the [Formula: see text]-conjugated porphyrin platform being preserved. The obtained polyporphyrins form uniform electroconductive coatings, tightly adhered to the electrode surface. The electrochromic properties were studied by the spectroelectrochemical method. Electronic absorption spectra of the films were recorded under the action of electric current at the stepwise potential changes within several intervals. The obtained polyporphyrin films were shown to possess electrochromic properties. The films were oxidized when exposed to anodic potentials and reduced when exposed to cathodic potentials. The electronic absorption spectra were used to calculate the optical band gap of the initial, oxidized and reduced films and to evaluate their conductivity. The highest conductivity was found in the electrochemically oxidized poly-5,10,15,20-tetrakis(4-aminophenyl)porphyrin film.
A QUANTUM LEAP? THE CASE FOR RADICAL INNOVATION
Authors: TIDD JOE
Published: November 2022

Incremental innovation has become the norm as the influence of business and management disciplines and functions have come to dominate research and practice—for example, standard processes for product development, design-thinking to improve existing user practices and superficial business model variations. Such incremental approaches to managing innovation have merit, and can result in significant cumulative changes over time. However, the way in which such incremental innovation is resourced, organised and managed is fundamentally different to that for radical innovation, which is critical to address more significant commercial and social challenges. The cases of new product development (NPD) and business model innovation (BMI) are examined to identify the challenges researchers and managers face. We argue that to acquire a deeper understanding of how radical innovation works, more ambitious cross-disciplinary research is needed, rather than the current direction of travel in the literature towards single discipline studies and standard processes that apply primarily to incremental commercial innovations.
Generation and Evaluation of Hydrogel-Facilitated 3D Tumor Microenvironments of Breast Cancer
Authors: Goklany Sheba , Brown Earl , De La Torre Lauryn , Rege Kaushal
Published: November 2022

Engineered three-dimensional (3D) cell culture models can accelerate drug discovery, and lead to new fundamental insights in cell–cell, cell–extracellular matrix (ECM), and cell–biomolecule interactions. Existing hydrogel or scaffold-based approaches for generating 3D tumor models do not possess significant tunability and possess limited scalability for high throughput drug screening. We have developed a new library of hydrogels, called Amikagels, which are derived from the crosslinking of amikacin hydrate (AH) and poly(ethylene glycol) diglycidyl ether (PEGDE). Here we describe the use of Amikagels for generating 3D tumor microenvironments (3DTMs) of breast cancer cells. Biological characteristics of these breast cancer 3DTMs, such as drug resistance and hypoxia were evaluated and compared to those of two-dimensional (2D) monolayer cultures. Estrogen receptor (ER) positive breast cancer 3DTMs formed on Amikagels were more dormant compared to their respective 2D monolayer cultures. Relative to their respective 2D cultures, breast cancer 3DTMs were resistant to cell death induced by mitoxantrone and doxorubicin, which are commonly used chemotherapeutic drugs in cancer, including breast cancer. The drug resistance seen in 3DTMs was correlated with hypoxia seen in these cultures but not in 2D monolayer cultures. Inhibition of Mucin 1 (MUC1), which is overexpressed in response to hypoxia, resulted in nearly complete cell death of 2D monolayer and 3DTMs of breast cancer. Combination of an ER stress inducer and MUC1 inhibition further enhanced cell death in 2D monolayer and 3DTMs. Taken together, this study shows that the Amikagel platform represents a novel technology for the generation of physiologically relevant 3DTMs in vitro and can serve as a platform to discover novel treatments for drug-resistant breast cancer.
A new Cambrian frondose organism: ‘Ediacaran survivor’ or convergent evolution?
Authors: Hu Shixue , Zhao Fangchen , Liu Alexander G. , Zhu Maoyan
Published: November 2022

Guangweia cheni
gen. et sp. nov. is an exceptionally preserved frond-like fossil from the early Cambrian Guanshan biota of SW China, which shares morphological similarities with some characteristic late Ediacaran frondose organisms in comprising a leaf-like frond attached via a stem to a discoidal structure resembling a holdfast. Plausible evidence for tissue differentiation and bilateral symmetry in
G. cheni
implies a eumetazoan affinity. However,
G. cheni
profoundly differs from Ediacaran frondose taxa in several morphological characters, including its possession of an unusual wedge-shaped apical structure. These observations preclude direct phylogenetic relationships with known Ediacaran forms. Instead,
G. cheni
may record convergent evolution of a frondose bodyplan: a possibility that should be entertained for other purported Cambrian frondose taxa.

Supplementary material:
A supplementary figure and sketch, scanning electron microscope–energy dispersive X-ray (SEM-EDX) elemental maps and spectra, and detailed images, interpretative drawings and measurements are available at
https://doi.org/10.6084/m9.figshare.c.6294893

Thematic collection:
This article is part of the Advances in the Cambrian Explosion collection available at:
https://www.lyellcollection.org/topic/collections/advances-in-the-cambrian-explosion
Hybridization Based Machine Translations for Low-Resource Language with Language Divergence
Authors: Sethi Nandini , Dev Amita , Bansal Poonam , Sharma Deepak Kumar , Gupta Deepak
Published: November 2022

A hybridised form of direct and rule-based language processing is used in this paper to present a Machine translation system from Sanskrit to Hindi. The divergence between Sanskrit and Hindi is also discussed in this paper, along with a proposition for how to handle it. Sanskrit-Hindi bilingual dictionaries, Grammatical Sanskrit corpus and a Sanskrit analyses rule base, have all been used in the projected system. The projected system's ability to access data from various data vocabularies and rule bases utilised in the system expansion has been improved by the usage of Elasticsearch technique. Additionally, a novel technique that builds a parse tree from the parsing table is presented in this paper. The system processes the input Sanskrit sentence using the parsing approach and the Context Free Grammar in normal form for Sanskrit language processing. No standard Sanskrit-Hindi Grammatical corpora available for Machine Translation which is designed and developed in the proposed work. The specific language sentence is produced using the Grammatical corpora and bilingual dictionaries. The proposed system achieved a Bilingual Evaluation Understudy (BLEU) score of 51.6 percent after being tested using Python's natural language toolkit API. The proposed system performs better than current systems when compared to cutting-edge systems, according to the comparison.
ONION: Online Semantic Autoencoder Hashing for Cross-Modal Retrieval
Authors: Zhang Donglin , Wu Xiao-Jun , Chen Guoqing
Published: November 2022

Cross-modal hashing (CMH) has recently received increasing attention with the merit of speed and storage in performing large-scale cross-media similarity search. However, most existing cross-media approaches utilize the batch-based mode to update hash functions, without the ability to efficiently handle the online streaming multimedia data. Online hashing can effectively address the preceding issue by using the online learning scheme to incrementally update the hash functions. Nevertheless, the existing online CMH approaches still suffer from several challenges, such as (1) how to efficiently and effectively utilize the supervision information, (2) how to learn more powerful hash functions, and (3) how to solve the binary constraints. To mitigate these limitations, we present a novel online hashing approach named
ONION
(
ON
line semant
I
c aut
O
encoder hashi
N
g). Specifically, it leverages the semantic autoencoder scheme to establish the correlations between binary codes and labels, delivering the power to obtain more discriminative hash codes. Besides, the proposed ONION directly utilizes the label inner product to build the connection between existing data and newly coming data. Therefore, the optimization is less sensitive to the newly arriving data. Equipping a discrete optimization scheme designed to solve the binary constraints, the quantization errors can be dramatically reduced. Furthermore, the hash functions are learned by the proposed autoencoder strategy, making the hash functions more powerful. Extensive experiments on three large-scale databases demonstrate that the performance of our ONION is superior to several recent competitive online and offline cross-media algorithms.
3D-Guided Frontal Face Generation for Pose-Invariant Recognition
Authors: Wu Hao , Gu Jianyang , Fan Xiaojin , Li He , Xie Lidong , Zhao Jian
Published: November 2022

Although deep learning techniques have achieved extraordinary accuracy in recognizing human faces, the pose variances of images captured in real-world scenarios still hinder reliable model appliance. To mitigate this gap, we propose to recognize faces via generation frontal face images with a
3D
-Guided Deep
P
ose-
I
nvariant Face Recognition
M
odel (3D-PIM) consisted of a simulator and a refiner module. The simulator employs a 3D Morphable Model (3D MM) to fit the shape and appearance features and recover primary frontal images with less training data. The refiner further enhances the image realism on both global facial structure and local details with adversarial training, while keeping the discriminative identity information consistent with original images. An Adaptive Weighting (AW) metric is then adopted to leverage the complimentary information from recovered frontal faces and original profile faces and to obtain credible similarity scores for recognition. Extended experiments verify the superiority of the proposed “recognition via generation” framework over state-of-the-art.
Effect of Flow Configurations on the Desalination Performance of Symmetrical Desalination Battery with Intercalation Electrodes
Authors: Yao Shouguang , Liu Rui , Wu Zhangtian , Luo Jianguo , Zhang Qiqi
Published: November 2022

A three-dimensional analytical model of symmetrical desalination battery (SDB) is established to investigate the effect of different flow configurations on the desalination performance of SDB from the aspects of pressure drop, salt adsorption capacity (SAC), average salt adsorption rate (ASAR) and energy consumption. In addition, the effects of flow channel width and electrode thickness on the desalination performance are also considered. The simulation results show that the pump energy consumption can be saved by increasing the area difference between the inlet and outlet of the SDB and shortening the distance between them. Reducing the outlet area or setting the inlet at corners of the SDB can obviously alleviate the uneven reaction of active material in the intercalation electrode. Compared with the basic configuration, the SAC, ASAR and energy consumption of the SDBs are increased by placing the inlet and outlet on the electrodes. The SDB with the configuration of intermediate inflow and circumferential outflow obtains the lowest dilution concentration among the five configurations. Increasing the channel width can improve the ASAR but increase the charging energy consumption. The increase of electrode thickness increases the SAC and charging energy consumption of the SDB but decreases the ASAR of the SDB.
Getting sweeter: new evidence for glucose transporters in specific cell types of the airway?
Authors: Baines Deborah L. , Vasiljevs Stanislavs , Kalsi Kameljit K.
Published: November 2022

New technologies such as single-cell RNA sequencing (scRNAseq) has enabled identification of the mRNA transcripts expressed by individual cells. This review provides insight from recent scRNAseq studies on the expression of glucose transporters in the epithelial cells of the airway epithelium from trachea to alveolus. The number of studies analyzed was limited, not all reported the full range of glucose transporters and there were differences between cells freshly isolated from the airways and those grown in vitro. Furthermore, glucose transporter mRNA transcripts were expressed at lower levels than other epithelial marker genes. Nevertheless, these studies highlighted that there were differences in cellular expression of glucose transporters. GLUT1 was the most abundant of the broadly expressed transporters that included GLUT8, 10, and 13. GLUT9 transcripts were more common in basal cells and GLUT12 in ionocytes/ciliated cells. In addition to alveolar cells, SGLT1 transcripts were present in secretory cells. GLUT3 mRNA transcripts were expressed in a cell cluster that expressed monocarboxylate (MCT2) transporters. Such distributions likely underlie cell-specific metabolic requirements to support proliferation, ion transport, mucous secretion, environment sensing, and airway glucose homeostasis. These studies have also highlighted the role of glucose transporters in the movement of dehydroascorbic acid/vitamin C/myoinositol/urate, which are factors important to the innate immune properties of the airways. Discrepancies remain between detection of mRNAs, protein, and function of glucose transporters in the lungs. However, collation of the data from further scRNAseq studies may provide a better consensus and understanding, supported by qPCR, immunohistochemistry, and functional experiments.
Hypoxia as a regulator of tumor stroma and metastasis
Authors: Lee Kyoung Eun
Published: November 2022

Metastasis is the leading cause of mortality in most patients with cancer. Despite its clinical importance, mechanistic underpinnings of metastatic progression remain poorly understood. Hypoxia, a condition of insufficient oxygen availability, frequently occurs in solid tumors because of their high oxygen/nutrient demand and abnormal tumor vasculature. In this review, we describe the roles of hypoxia and hypoxia-inducible factor (HIF) signaling in the metastatic cascade, with an emphasis on recent biological insights from in vivo studies.
Bidirectional sensitivity of CALHM1 channel to protons from both sides of plasma membrane
Authors: Kwon Jae Won , Jeon Young Keul , Kim Sung Joon
Published: November 2022

Calcium homeostasis modulator 1 (CALHM1), a newly discovered voltage-dependent nonselective ion channel, has drawn attention for its role in neuronal activity and taste sensation. Its sluggish voltage-dependent activation is facilitated by lowering extracellular Ca2+ concentration ([Ca2+]e). Here, we investigated the effects of extracellular and intracellular pH (pHe and pHi) on human CALHM1. When normalized to the amplitude of the CALHM1 current ( ICALHM1) under whole cell patch clamp at symmetrical pH 7.4, ICALHM1 decreased at acidic pHe or pHi, whereas it sharply increased at alkaline pHe or pHi. The effects of pH were preserved in the inside-out configuration. The voltage dependence of ICALHM1 showed leftward and rightward shifts at alkaline and acidic pHe and pHi, respectively. Site-directed mutagenesis of the water-accessible charged residues of the pore and nearby domains revealed that E17, K229, E233, D257, and E259 are nonadditively responsible for facilitation at alkaline pHi. Identification of the pHe-sensing residue was not possible because mutation of putative residues impaired membrane expression, resulting in undetectable ICALHM1. Alkaline pHe-dependent facilitation appeared gradually with depolarization, suggesting that the sensitivity to pHe might be due to H+ diffusion through the open-state CALHM1. At pHe 6.2, decreased [Ca2+]e could not recover the inhibited ICALHM1 but further augmented the increased ICALHM1 at pHe 8.6, suggesting that unidentified common residues might contribute to the [Ca2+]e and acidic pHe. This study is the first, to our knowledge, to demonstrate the remarkable pH sensitivity of CALHM1, which might contribute to the pH-dependent modulation of neuronal excitability or taste sensation.
Long noncoding RNA LINC01882 ameliorates aGVHD via skewing CD4+ T cell differentiation toward Treg cells
Authors: Teng Yao , Xia Linghui , Huang Zhenli , Yao Lan , Wu Qiuling
Published: November 2022

Acute graft-versus-host disease (aGVHD) is a severe T cell-mediated immune response after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the molecular mechanisms remain to be elucidated and novel treatments are necessary to be developed. In the present study, we found that the expression of long noncoding RNA (lncRNA) LINC01882 decreased significantly in the peripheral blood CD4+ T lymphocytes of patients with aGVHD than non-aGVHD patients. In addition, lncRNA LINC01882 overexpression promoted Treg differentiation but exhibited no effects on Th17 percentages, while its knockdown resulted in opposite effects. Mechanistically, lncRNA LINC01882 could competitively bind with let-7b-5p to prevent the degradation of its target gene smad2, which acts as a promoter in Treg differentiation. Furthermore, the mice cotransplanted with LINC01882-overexpressed CD4+ T cells with PBMCs had a lower histological GVHD score and higher survival rate compared with control mice. In conclusion, our study discloses a novel LINC01882/let-7b-5p/smad2 pathway in the modulation of aGVHD and indicates that lncRNA LINC01882 could be a promising biomarker and therapeutic target for patients with aGVHD.
Red light-green light: T-cell trafficking in cardiac and vascular inflammation
Authors: Sanders Erin , Alcaide Pilar
Published: November 2022

Extravasation of T cells from the bloodstream into inflamed tissues requires interactions between T cells and vascular endothelial cells, a necessary step that allows T cells to exert their effector function during the immune response to pathogens and to sterile insults. This cellular cross talk involves adhesion molecules on both the vascular endothelium and the T cells themselves that function as receptor-ligand pairs to slow down circulating T cells. These will eventually extravasate into sites of inflammation when they receive the correct chemokine signals. Accumulation of T cells within the vascular wall can lead to vessel thickening and vascular disease, whereas T-cell extravasation into the myocardium often leads to cardiac chronic inflammation and adverse cardiac remodeling, hallmarks of heart failure. On the flip side, T-cell trafficking is required for pathogen clearance and to promote tissue repair after injury resulting from cardiac ischemia. Thus, a better understanding of the central players mediating these interactions may help develop novel therapeutics to modulate vascular and cardiac inflammation. Here, we review the most recent literature on pathways that regulate T-cell transendothelial migration, the last step leading to T-cell infiltration into tissues and organs in the context of vascular and cardiac inflammation. We discuss new potential avenues to therapeutically modulate these pathways to enhance or prevent immune cell infiltration in cardiovascular disease.
Altered intramuscular network of lipid droplets and mitochondria in type 2 diabetes
Authors: de Almeida Martin Eisemann , Nielsen Joachim , Petersen Maria Houborg , Wentorf Emil Kleis , Pedersen Niklas Bigum , Jensen Kurt , Højlund Kurt , Ørtenblad Niels
Published: November 2022

Excessive storage of lipid droplets (LDs) in skeletal muscles is a hallmark of type 2 diabetes. However, LD morphology displays a high degree of subcellular heterogeneity and varies between single muscle fibers, which impedes the current understanding of lipid-induced insulin resistance. Using quantitative transmission electron microscopy (TEM), we conducted a comprehensive single-fiber morphological analysis to investigate the intramuscular network of LDs and mitochondria, and the effects of 8 wk of high-intensity interval training (HIIT) targeting major muscle groups, in patients with type 2 diabetes and nondiabetic obese and lean controls. We found that excessive storage of intramuscular lipids in patients with type 2 diabetes was exclusively explained by extremely large LDs situated in distinct muscle fibers with a location-specific deficiency in subsarcolemmal mitochondria. After HIIT, this intramuscular deficiency was improved by a remodeling of LD size and subcellular distribution and mitochondrial content. Analysis of LD morphology further revealed that individual organelles were better described as ellipsoids than spheres. Moreover, physical contact between LD and mitochondrial membranes indicated a dysfunctional interplay between organelles in the diabetic state. Taken together, type 2 diabetes should be recognized as a metabolic disease with high cellular heterogeneity in intramuscular lipid storage, underlining the relevance of single-cell technologies in clinical research. Furthermore, HIIT changed intramuscular LD storage toward nondiabetic characteristics.
Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis
Authors: Meadows Vik , Marakovits Corinn , Ekser Burcin , Kundu Debjyoti , Zhou Tianhao , Kyritsi Konstantina , Pham Linh , Chen Lixian , Kennedy Lindsey , Ceci Ludovica , Wu Nan , Carpino Guido , Zhang Wenjun , Isidan Abdulkadir , Meyer Alison , Owen Travis , Gaudio Eugenio , Onori Paolo , Alpini Gianfranco , Francis Heather
Published: November 2022

We evaluated knockdown of the apical sodium bile acid transporter (ASBT) using Vivo-Morpholino in Mdr2KO mice. ASBT inhibition decreases primary sclerosing cholangitis (PSC) pathogenesis by reducing hepatic mast cell infiltration, altering bile acid species/cholehepatic shunt, and regulating gut inflammation/dysbiosis. Since a large cohort of PSC patients present with IBD, this study is clinically important. We validated findings in human PSC and PSC-IBD along with studies in novel human 3-D organoids formed from human PSC livers.