bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of WHSC1/NSD2 and T-cell infiltration with prostate cancer metastasis and prognosis
Authors: Li Qiheng , Zhu Jiang , Zhang Yang , Pan Yun , Li Zhengjin , Wang Min , Gao Yixuan , Feng Dongmei , He Xiaoyong , Zhang Chunmei
Published: December 2023

Progress in immunotherapy for prostate cancer (PCa) lags that for other cancers, mainly because of limited immune infiltration in PCa. This study aimed to assess the feasibility of NSD2 as an immunotherapeutic target in PCa. Immunohistochemistry was performed to evaluate the expression pattern of NSD2 in 34 cases of benign prostatic hyperplasia (BPH), 36 cases of prostatic intraepithelial neoplasia (PIN), and 57 cases of PCa, including 19 cases of metastatic castration-resistant prostatic cancer (mCRPC). Single-cell RNA sequencing and gene set enrichment analysis (GSEA) were used to correlate NSD2 with certain downstream pathways. Furthermore, the Immuno-Oncology-Biological-Research (IOBR) software package was used to analyze the potential roles of NSD2 in the tumor microenvironment. We found that the positive expression rate of NSD2 increased progressively in BPH, PIN and PCa. mCRPC had the highest staining intensity for NSD2. High NSD2 expression was positively correlated with the infiltration level of CD4+ tumor-infiltrating lymphocytes (TILs) and negatively correlated with that of CD8+ TILs. Importantly, a new immune classification based on NSD2 expression and CD4+ TILs and CD8+ TILs was successfully used to stratify PCa patients based on OS.PSA and CD4+ TILs are independent risk factors for PCa bone metastasis. This study demonstrates a novel role for NSD2 in defining immune infiltrate on in PCa and highlights the great potential for its application in immunotherapy response evaluation for prostate malignancies.
Optimizing the thermophysical qualities of innovative clay–rGO composite bricks for sustainable applications
Authors: Soliman Wafaa , Shahat M. Abdelhamid
Published: December 2023

This work concerned the development of a unique reduced graphene oxide (rGO) nano-filler to provide innovative opportunities in enhancing the thermophysical performance of clay composite bricks. Whereas, a series of clay–rGO composite bricks were produced, doped with various levels of rGO nanosheets (i.e., 0, 1, 2, 4, and 6 wt% clay). Each clay–rGO composite’s microstructure, shrinkage, morphology, density, porosity, and thermophysical characteristics were carefully investigated, and the thermal conductivity performance was optimized. Incorporation of different levels of rGO NPs to the clay matrix allowed all the peaks intensity to rise relative to the untreated one in the XRD pattern. Meanwhile, the inclusion of these doping resulted in a grew in the crystallite sizes and apparent porosity within the compositions. In this vein, shrinkage fracture of fabricated brick composites varied depending on dopants type and levels during the drying and firing processes. Moreover, there are some changes in chemical compositions, as well as wave shifts, suggesting that functional groups of rGO may have contributed to partially introduce carbonyl groups in clay–rGO composites. Besides, the porous topography and bulk density improved rapidly with respect to the plane of the rGO nanosheets within the composites. The differ-dense microstructure displayed in the SEM micrographs supports these outcomes. Remarkably, clay–(4%)rGO compound not only has an optimum thermal conductivity value (0.43 W/mK), but it also has a high heat capacity (1.94 MJ/m3K). These results revealed the exceptional features of rGO sheets such as large surface area with high porosity within the modified clay composites.
Klinische Neurophysiologie im Wandel, eine neue Schriftleitung
Authors: Grimm Alexander , Marquetand Justus
Published: December 2023

Klinische Neurophysiologie im Wandel, eine neue Schriftleitung

Liebe Leserinnen und
Leser,

auch die Klinische Neurophysiologie ist stets im Wandel der Zeit: Nachdem
Prof. Dr. Buchner zuletzt die Schriftleitung der Klinischen Neurophysiologie inne
hatte und die ihm damit übertragenen Aufgaben vorbildlich erfüllte,
wird der Staffelstab an zwei Vertreter der nächsten Generation
übergeben.
Neurologische Ultraschalldiagnostik – ein
Update
Authors: Allendörfer Jens , Gröschel Klaus , Harrer-Haag Judith U. , Walter Uwe , Schminke Ulf
Published: December 2023

Das Ausbildungscurriculum der neurologischen Ultraschalldiagnostik beinhaltet
nicht nur die fächerübergreifenden Ausbildungsinhalte im
Anwendungsbereich der extra- und intrakraniellen hirnzuführenden
Arterien, sondern umfasst zusätzlich die erweiterte Diagnostik
intrakranieller Gefäße mittels transkranieller Duplexsonografie,
die Untersuchung der Hirnvenen, die funktionelle transkranielle
Doppler-Sonografie inklusive Monitoringverfahren sowie die Hirnparenchym- und
Orbitasonografie.
Erwachsenwerden mit CED
Authors: Schardt Vivien , Holtz Sandra , Fley Gabriele , Schuster Susanne
Published: December 2023

Im Laufe ihres Lebens stehen Kinder und Jugendliche mit chronisch-entzündlichen Darmerkrankungen häufig vor besonderen Herausforderungen. Neben klinischen Symptomen, Beschwerden und Komplikationen gibt es eine Vielzahl an belastenden psychischen Stressfaktoren. Unterstützend für die Krankheitsbewältigung sind eine an die Bedürfnisse angepasste Versorgungsstruktur, ein spezifisches Behandlungsteam und eine patientenzentrierte Pflege.
Impfungen bei Erwachsenen mit Diabetes
Authors: Witzke Oliver
Published: December 2023

Impfungen stellen die wichtigsten Präventionsmaßnahmen in der Medizin dar, und ihre medizinische und gesellschaftliche Relevanz wurde in der zurückliegenden Pandemie deutlich. Menschen mit Diabetes besitzen aufgrund eines geschwächten Immunsystems ein erhöhtes Risiko für Infektionskrankheiten. Daher ordnet die Ständige Impfkommission (STIKO) diese Patient*innen als Risikogruppe ein und hat einige Impfempfehlungen angepasst. Die folgende Übersicht bündelt die aktuell relevanten Standard- und Indikationsvakzinierungen für Erwachsene mit Diabetes mellitus und liefert mit der RSV-Impfung auch einen Ausblick auf eine mögliche zukünftige Ergänzung.
Systematische Parodontitistherapie und
Kieferorthopädie
Authors: Hoedke Daniela , Dommisch Henrik
Published: December 2023

Die aktuelle Klassifikation parodontaler und peri-implantärer
Erkrankungen und Zustände teilt die Parodontitis in vier Schweregrade
(Stadium I-IV) und drei Progressionsgrade (Grad A-C) ein. Die erste, 2020 von
der Europäischen Föderation für Parodontologie (EFP)
verabschiedete und 2021 in Deutschland von der Deutschen Gesellschaft
für Parodontologie (DG PARO) implementierte Leitlinie zur Therapie der
Parodontitis adressiert die Stufen I-III der Parodontitis und beinhaltet deren
systematische, stufenweise Behandlung. In der 2022 verabschiedeten Leitlinie zur
Therapie der fortgeschrittenen Parodontitis (Stadium IV) werden
interdisziplinäre Behandlungskonzepte verschiedener zahnmedizinischer
Disziplinen beschrieben, deren Evidenz bewertet und daraus
Behandlungsempfehlungen abgeleitet. Dieser Artikel soll eine Übersicht
zur Klassifikation der parodontalen Erkrankungen geben und die systematische
Parodontitistherapie unter besonderer Berücksichtigung der
kieferorthopädischen Behandlung von Patienten mit Parodontitis
zusammenfassen.
The role of dynamics in heterogeneous catalysis: Surface diffusivity and N
2
decomposition on Fe(111)
Authors: Bonati Luigi , Polino Daniela , Pizzolitto Cristina , Biasi Pierdomenico , Eckert Rene , Reitmeier Stephan , Schlögl Robert , Parrinello Michele
Published: December 2023

Dynamics has long been recognized to play an important role in heterogeneous catalytic processes. However, until recently, it has been impossible to study their dynamical behavior at industry-relevant temperatures. Using a combination of machine learning potentials and advanced simulation techniques, we investigate the cleavage of the N

2

triple bond on the Fe(111) surface. We find that at low temperatures our results agree with the well-established picture. However, if we increase the temperature to reach operando conditions, the surface undergoes a global dynamical change and the step structure of the Fe(111) surface is destabilized. The catalytic sites, traditionally associated with this surface, appear and disappear continuously. Our simulations illuminate the danger of extrapolating low-temperature results to operando conditions and indicate that the catalytic activity can only be inferred from calculations that take dynamics fully into account. More than that, they show that it is the transition to this highly fluctuating interfacial environment that drives the catalytic process.
Dengue a global threat: An insight into management and control
Authors: Jamil Muhammad , Saleem Ashiq , Naz Rida , Ahmad Sajad , Ramzan Faiqah , Ali Mubarik , Jabeen Norina
Published: December 2023

Background
: Dengue, whose severe forms have the potential to be fatal, is the most prevalent and rapidly proliferating vector-borne viral disease worldwide. It is evolving as a significant public health and economic dilemma for both rural and urban communities.
Objectives
: Given the urgent need for control measures, the purpose of this study is to evaluate both traditional and contemporary preventive strategies.
Results
: Traditional dengue control measures, while somewhat effective, tend to provide only temporary relief. In contrast, biotechnological innovations such as paratransgenesis, sterile insect technology, and genetically modified vectors have increased the effectiveness of conventional methods. In addition, the novel discovery of vaccines and immunotherapies offers a promising avenue for the management of dengue.
Discussion & Conclusion:
Integration of time-tested techniques with the most recent biotechnological interventions emerges as a crucial dengue-prevention strategy. While these developments offer cause for optimism, additional research is required to determine the long-term implications and viability of these techniques.
Implications
: The findings have significant implications for theory, policymaking, and medical practice, highlighting the need for a combined approach to dengue management.
Failure of the well-rounded retract for outer space and Teichmüller space
Authors: Fortier Bourque Maxime
Published: December 2023

The well-rounded retract for

S

L
n

(

Z

)

SL_n(\mathbb {Z})

is defined as the set of flat tori of unit volume and dimension

n
n

whose systoles generate a finite-index subgroup in homology. This set forms an equivariant spine of minimal dimension for the space of flat tori.

For both the Outer space

X
n

X_n

of metric graphs of rank

n
n

and the Teichmüller space

T

g

\mathcal {T}_g

of closed hyperbolic surfaces of genus

g
g

, we show that the literal analogue of the well-rounded retract does not contain an equivariant spine. We also prove that the sets of graphs whose systoles fill either topologically or geometrically (two analogues of a set proposed as a spine for

T

g

\mathcal {T}_g

by Thurston) are spines for

X
n

X_n

but that their dimension is larger than the virtual cohomological dimension of

O
u
t
(

F
n

)

Out(F_n)

in general.
Disparities in acute myeloid leukemia treatments and outcomes
Authors: Eisfeld Ann-Kathrin
Published: December 2023

Purpose of review

This review aims to summarize different contributors to survival disparities in acute myeloid leukemia (AML) patients. The focus is set on African-American (hereafter referred to as Black) patients, with separate consideration of self-reported race and ancestry. It aims to also highlight the interconnectivity of the different features that impact on despair survival.

Recent findings

The main themes in the literature covered in this article include the impact of social deprivation, clinical trial enrollment and biobanking, structural racism and ancestry-associated differences in genetic features on survival outcomes.

An increasing number of studies have not only shown persistent survival disparities between Black and non-Hispanic White AML patients, but uncovered a multitude of contributors that have additive adverse effects on patient outcomes. In addition to potentially modifiable features, such as socioeconomic factors and trial enrollment odds that require urgent interventions, there is emerging data on differences in disease biology with respect to genetic ancestry, including frequencies of known AML-driver mutations and their associated prognostic impact.
A modified RGB trichrome (HemRGB) for improving nuclear staining: application to colorectal cancer histopathology
Authors: Gaytán Francisco
Published: December 2023

The RGB trichrome staining method has been used to highlight two major components of the extracellular matrix, collagen and glycosaminoglycans. While the RGB trichrome efficiently stains extracellular matrix components, it lacks a nuclear stain, limiting its application in histopathology. To address this issue, a modification of the original stain, named HemRGB trichrome, has been developed. This modification incorporates iron hematoxylin for improving nuclear staining while retaining specificity for the staining of extracellular matrix. The application of HemRGB trichrome staining to samples from both normal colonic tissues and colorectal adenocarcinomas (CRC) provides a robust nuclear staining, together with a high-contrasted staining of tumor microenvironmental components, such as infiltrating immune cells, collagen and ground substance, extracellular mucins, as well as contrasted interfaces between CRC metastases and liver parenchyma. This study underscores the potential of HemRGB trichrome as a valuable tool for histopathological studies, especially for cancer evaluation, where nuclear characteristics are particularly relevant.
Internal Dynamics Interact with Proprioceptive Feedback During Movement Execution in an RNN Model of Motor Cortex
Authors: Jiang Hongru , Bu Xiangdong , Zheng Zhiyan , Pan Xiaochuan , Chen Yao
Published: December 2023

Proprioceptive feedback provides the information about the state of the body, which is critical in motor control. However, the contribution of proprioceptive feedback to motor cortical activity during voluntary movement execution is unclear. Here, we built an recurrent neural network model of motor cortex that receives proprioceptive feedback, and optimized it to control a virtual arm to perform a delayed-reach task. Simulated neural activity is similar to real data, indicating that our model captures the motor cortical dynamics. We further disrupted recurrent connectivity and proprioceptive feedback to dissect their contribution, and found that internal dynamics dominate in neural population activity, while proprioceptive feedback controls movement termination. Moreover, proprioceptive feedback improves the network’s robustness against noisy initial conditions. We further investigated the relative importance of the components in proprioceptive feedback and found that the feedback of hand velocity contributes most to the similarity between simulation and real data. Finally, we show that our motor cortex model can be implemented in the sensorimotor system, demonstrating our model’s biological plausibility. In summary, motor command may arise from the intersection between recurrent dynamics in motor cortex and proprioceptive feedback.
Vagus nerve stimulation by focused ultrasound attenuates acute myocardial ischemia/reperfusion injury predominantly through cholinergic anti-inflammatory pathway
Authors: Zhang Qian , Cai Qianyun , Zhong Shenrong , Li Qin , Qiu Weibao , Wu Juefei
Published: December 2023

Background

The invasive method using electrically stimulating vagus nerve has been demonstrated to inhibit the inflammatory response against acute myocardial ischemia/reperfusion(I/R) injury. This neuro-regulatory technique used is invasive implantation of electrical stimulators which have the risk of infection and other complications. A non-invasive method of vagus nerve stimulation applying on acute myocardial I/R injury is particularly important and desirable.

Objectives

This study aimed to test the hypothesis that focused ultrasound stimulation(FUS) of vagus nerve attenuates acute myocardial I/R injury through cholinergic anti-inflammatory pathway.

Methods

This study was completed with two parts. In the first part, ischemia was induced by left anterior descending coronary artery (LAD) occlusion for 30 minutes (min), followed by 2 hours (h) of reperfusion, FUS lasted for 50 min after reperfusion for 10 min. Infammatory markers, arrhythmia score, histopathology, infammatory markers α7 nicotinic acetylcholine receptor (α7nAchR) protein were determined. In the second part, ischemia was induced by LAD occlusion for 30 min, followed by 24h of reperfusion, FUS lasted for 50 min after reperfusion for 10 min. Myocardial fibrosis, infarct size, echocardiographic measurements, biomarkers of pro-oxidative stress, antioxidant and myocardial apoptosis were determined.

Results

FUS of vagus nerve significantly decreased the level of infammatory markers in I/R+FUS group compared with the I/R group, I/R+vagotomy group and I/R+vagotomy+FUS group. FUS decreased the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF), while also reduced arrhythmia score in I/R+FUS group compared with the I/R group. These improvements were associated with the inhibition of acute inflammatory reaction through cholinergic anti-inflammatory pathway. FUS limited myocardial fibrosis and infarct size, preserved left ventricular function. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress.

Conclusions

The noninvasive method of ultrasonic neuromodulation using FUS of vagus nerve exerted protective effects on acute myocardial I/R injury. Its potential mechanisms involved the suppression of acute inflammatory reaction through cholinergic anti-inflammatory pathway.
Nonstate ownership, agency costs and corporate performance: evidence from Chinese state-owned enterprises
Authors: Chen Qi-an , Bao Anze , Chen Junpei , Lu Yi
Published: December 2023

Purpose

The primary objective of introducing nonstate ownership into state-owned enterprises (SOEs) is to enhance corporate performance. This study explores how nonstate ownership affects corporate performance, emphasizing agency costs as the primary mechanism.

Design/methodology/approach

Using data from 2010 to 2019 for listed SOEs, the authors measure nonstate ownership based on shareholding ratios, control rights and shareholding–control matching. The authors also use fixed-effects and mediation-effects models, with agency costs as the primary mechanism.

Findings

Increased nonstate shareholding ratios, stronger control rights and improved shareholding–control matching promote SOE performance. Nonstate shareholding ratios boost performance through resource effects, while control rights and shareholding–control matching promote performance by mitigating agency costs. A heterogeneity analysis indicates stronger effects in local SOEs and highly marketized regions. Moreover, control rights and shareholding–control matching reinforce the positive impact of shareholding ratios on performance.

Originality/value

The mixed-ownership reform of Chinese SOEs aims to optimize shareholding and control structures between state and nonstate shareholders. Therefore, research on the impact of nonstate shareholding ratios, control rights and shareholding–control matching on corporate performance is highly pertinent. However, existing studies have focused on the effects of single factors on performance, without exploration of the economic implications of shareholding–control matching. This study not only prioritizes the optimization of shareholding and control structures but also underscores the importance of granting nonstate shareholders control rights proportionate to their shareholding, providing critical evidence of the value of improving SOEs' ownership structure.
Construction of taxonomy of conceptualization of sustainability in improving the industrial production process
Authors: de Oliveira Neves Fábio , Salgado Eduardo Gomes , Ewbank Henrique , Sampaio Paulo
Published: December 2023

Purpose

Industrialization is a major contributor to pollution and the worsening of some social problems. A change in this context would help in a new industrial model aiming at a viable and sustainable manufacturing system. This research aims to verify the state of the art of sustainability within the industrial production process through a systematic literature review, verifying the main characteristics in relation to industrial sustainability that the literature demonstrates.

Design/methodology/approach

The development of the research took place in three stages: a survey of articles with Journal Citation Reports (JCR), the construction of the database and descriptive analysis and text mining analyses of social networks and content. The survey took place through academically endorsed research platforms, totaling a total of 352 scientific articles, which included 18 quality management tools and worked with at least one sustainability indicator (financial, social and environmental).

Findings

Lean manufacturing, integrated management system and Six Sigma were the most cited quality tools, and articles containing the three indicators were found more frequently. It was found that most authors treated sustainability only as an environmental contribution. Knowledge of the organization's structural and management issues is essential for implementing sustainability and production process improvement.

Originality/value

This work is the first to develop a systematic analysis regarding the use of sustainability implementation in the industrial production process, considering a wide scope of production process tools, guiding on the characteristics of sustainability relating to the main critical success factors (CSFs), motivations, difficulties and benefits that lead industries in different parts of the world to implement sustainability.
Synergizing organizational inclusion and IT competencies through resource orchestration: a longitudinal exploration
Authors: Masood Ayesha , Salameh Anas A. , Khalil Ashraf , Zhang Qingyu , Papa Armando
Published: December 2023

Purpose

This study investigates the integration of information technology (IT) competencies with organizational inclusion initiatives and its impact on firm performance. It examines the role of organizational inclusion in promoting knowledge management capability (KMC) and the moderating effect of approach and avoidance motivation on the relationship between KMC and operational performance.

Design/methodology/approach

The study is grounded in the resource orchestration theory (ROT), which conceptualizes the integration of IT competencies and organizational inclusion. It employs hierarchical regression analysis on data collected from 204 firms and 374 managerial respondents to test the proposed hypotheses.

Findings

The results indicate that IT competencies enhance the relationship between organizational inclusion and KMC. Additionally, the relationship between KMC and operational performance is weaker when employees exhibit higher levels of avoidance motivation.

Practical implications

This study offers theoretical and managerial insights for integrating IT competencies into organizational inclusion initiatives, providing guidance for organizations seeking to enhance their performance, with a specific focus on the relevance of China as the research context.

Originality/value

This study enriches the scholarly discourse by examining the underexplored integration of IT competencies with organizational inclusion, notably in the context of China. It illuminates the moderating role of motivation in the KMC-operational performance relationship, benefiting both academia and practitioners. Furthermore, this work extends the literature by demonstrating how combining organizational inclusion and IT competencies can enhance workplace KMC, connecting it to internal knowledge resources. Theoretical implications extend beyond organizational inclusion and IT to show the broader application potential of ROT in management and information systems.
Affordability and sustainability in the human right to water
Authors: Carchi Darwin , Orellana Mercy , Martínez Andrés , Segovia Joselin
Published: December 2023

Purpose

The purpose of this study is to analyze the affordability and sustainability of residential water consumption in Ecuador, a developing country.

Design/methodology/approach

To determine affordability, the authors assess water consumption and its distribution across different income levels of the population in the three main cities: Cuenca, Guayaquil and Quito. The authors then simulate the effects of a pricing policy on sustainability by deriving demand elasticities through a quadratic almost ideal demand system (QUAIDS).

Findings

Results show that Ecuador has low water tariffs with respect to other cities in Latin America, which points to its affordability. However, sustainability might not be guaranteed since consumption is overall higher than the level suggested by the World Health Organization. From an economic point of view, this could be motivated by the low tariffs. Indeed, the simulation of a pricing policy shows that higher prices can significantly reduce demand for most of the sample. However, in low-income households this reduction may compromise vital consumption.

Research limitations/implications

This research has important implications in terms of stimulating the discussion of how water affordability and sustainability can be achieved. For the case study, Ecuador, the results indicate that sustainability may not be guaranteed and that policies need to be designed to encourage it. Another implication is that population income levels should be considered to avoid negative effects for the most vulnerable groups. The main limitations of this study are methodological. First, the QUAIDS model is based on a conditional demand model (Zhen et al., 2013), which does not take into account spending on other goods. Second, data availability is limited and prevents a deeper analysis.

Originality/value

To the best of the authors' knowledge, this is the first study to analyze these issues in Ecuador, a country that recognizes the human right to water at the constitutional level.
Evaluating the implementation of a person-centred transition programme for adolescents and young adults with long-term conditions: the role of context and organisational behaviour
Authors: Feather Julie , Kaehne Axel , Kiernan Joann
Published: December 2023

Purpose

Drawing on the experiences of healthcare professionals in one paediatric hospital, this paper explores the influence of context and organisational behaviour on the implementation of a person-centred transition programme for adolescents and young adults (AYA) with long-term conditions.

Design/methodology/approach

A single embedded qualitative case study design informed by a realist evaluation framework, was used. Participants who had experience of implementing the transition programme were recruited from across seven individual services within the healthcare organisation. The data were gathered through semi-structured interviews (n = 20) and analysed using thematic analysis.

Findings

Implementation of the transition programme was influenced by the complex interaction of macro, meso and micro processes and contexts. Features of organisational behaviour including routines and habits, culture, organisational readiness for change and professional relationships shaped professional decision-making around programme implementation.

Originality/value

There exists a significant body of research relating to the role of context and its influence on the successful implementation of complex healthcare interventions. However, within the area of healthcare transition there is little published evidence on the role that organisational behaviour and contextual factors play in influencing transition programme implementation. This paper provides an in-depth understanding of how organisational behaviour and contextual factors affect transition programme implementation.
Developing entrepreneurship skills in scientific academia: best practices from India and Japan
Authors: Tikas Gaurav
Published: December 2023

Purpose

This paper aims to identify such “entrepreneurial skills” that the scientific community can develop within themselves through training and practice to improve their academic research translation capabilities and performance.

Design/methodology/approach

From a qualitative perspective, this study currently presents a few findings from some of the best government-funded laboratories in India and Japan, where they are training their young researchers to be world-class scientists as well as entrepreneurs to help them commercialize their scientific research findings from lab to market for societal benefit.

Findings

This paper intends to focus on identifying some of the “best practices” in developing such capabilities that allow “entrepreneurial scientists” to take their science to the society through entrepreneurship. This paper presents two exemplary case studies about institutions that are trying to build innovation and entrepreneurship capabilities in their research groups through continuous training and practice in the fields of biotechnology (India) and autonomous transportation (Japan).

Originality/value

Policymakers and top management teams at academic institutions can learn from the “best practices” on envisioning, evaluation and execution skills for designing their innovation and entrepreneurship skill-building programs for their scientific community.
External validation of the Oakland Score to assess safe hospital discharge among adult patients with acute lower gastrointestinal bleeding in a single New Zealand Centre
Authors: Amer Mostafa , Haddow James Boyd
Published: December 2023

Background

Acute lower gastrointestinal bleeding (LGIB) is a common reason for hospital admission. However, the majority resolve spontaneously and only a minority require inpatient intervention. We aimed to describe the epidemiology and aetiology of acute LGIB admissions in our institution. We also aimed to validate the Oakland Score, which can identify patients at low risk of adverse outcome from LGIB, in our population and determine the proportion who could have safely avoided admission.

Methods

Using the prospective, validated Otago Clinical Audit database (DIVA), we searched for adult patients admitted to Dunedin Hospital with a primary diagnosis of LGIB between January 2013 and December 2020. We retrieved data to calculate the Oakland Score and details of inpatient treatment from the electronic patient record. We excluded patients admitted electively, admissions related to inflammatory bowel disease, and those with upper gastrointestinal bleeding.

Results

We identified 761 patients of which 501 met inclusion criteria (56% male, median age 76 years, 82% NZ European). Overall, 72% were managed with observation or diagnostic endoscopy, 32% received blood products, and 7% required haemostatic intervention to control bleeding. The area under the receiver operating characteristic curve for the Oakland Score was 0.85 (95% CI, 0.81–0.89). A cut‐off score of ≤10 predicted a 95% probability of safely avoiding admission. This equates to saving 30 bed‐days annually.

Conclusion

The majority of patients admitted with LGIB are managed conservatively. The Oakland Score could be used as a stratification tool to safely reduce the admission rate.
A Comparative Study of Microwave-Assisted and Conventional Heating Approaches for the Multicomponent Synthesis of 4,6-Diarylpyrimidines
Authors: Becerra-Rivas Christian A. , Cuervo-Prado Paola A. , Orozco-Lopez Fabian
Published: December 2023

A series of 2-amino-4,6-diarylpyrimidines were synthesized using a Biginelli-type three-component strategy optimized in conventional-heated reflux, in contrast to a non-conventional approach using a mono-mode microwave reactor. Conventional heating protocols involved organic solvents and general base catalysis, whereas a microwave-assisted method followed experimental protocols framed within the principles of green chemistry by using CaCl2 as a catalyst in solvent-free conditions. This study revealed that although conventional heating led to the main product in higher yields at longer reaction times, the microwave strategy suceeded in substantially shorter reaction times, with yields ranging from acceptable to good and efficiencies comparable to conventional heating methodology.
Modeling of Combustor Non-Uniformities Evolution Through a High-Pressure Turbine Stage
Authors: Notaristefano Andrea , Gaetani Paolo
Published: December 2023

In modern gas turbines, the reduction of pollutant emissions can be achieved by employing lean-burn combustors. At the combustion chamber outlet, the flow is non-uniform and characterized by a residual swirl superimposed to steady (hot streak) and unsteady (entropy waves) temperature disturbances. During the transport from the combustor outlet to the turbine inlet, these disturbances are weakly dissipated and persist at the turbine inlet. Therefore, the interaction between the combustor non-uniformities and the turbine has to be deeply studied. To study combustor–turbine interaction experimentally, a common practice is to install combustor simulators on non-reactive turbine test facilities. For this purpose, a combustor simulator was designed and installed at the Politecnico di Milano turbine test facility. This device can generate a combined steady/unsteady temperature disturbance and swirl profile at the turbine inlet. Using this layout, several experimental campaigns have been carried out changing the type of injected disturbance, the injection position, and the turbine operating condition. In this paper, the data collected from these experiments have been used to develop simplified models to predict the transport and dissipation of combustor perturbations through a turbine's first stage. In the open literature, few attempts are discussed regarding the modeling of combustor–turbine interaction that—in authors’ opinion—represents an important tool for preliminary turbine design.
Windage Torque Reduction in Low-Pressure Turbine Cavities Part I: Concept Design and Numerical Investigations
Authors: Li Zhihui , Christodoulou Loizos , Jefferson-Loveday Richard , Ambrose Stephen , Jackson Richard , Lock Gary D. , Sangan Carl M. , Scobie James A.
Published: December 2023

The windage torque on rotational walls has a negative effect on the performance of the low-pressure turbine. In this paper, three novel flow control concepts (FCCs) were proposed to reduce the windage torque within a turbine stator well, with upstream and downstream cavities connected by an interstage labyrinth seal. The swirl and flow pattern inside a reference turbine cavity was first investigated and the potential locations for the FCCs were identified using numerical simulations. FCC1 was a circumferential row of leaned deflectors downstream of the labyrinth seal. FCC2 was a set of deflector vanes and platform to optimize the ingress swirl at high radius in the upstream cavity. FCC3 combined the two flow concepts and the superposition resulted in a stator well windage torque reduction of 70% when compared to the baseline design. The FCCs also showed performance benefits at off-design conditions and over a range of secondary flow rates to the cavity. In Part II, the numerical analysis and performance of the FCCs are validated in an experimental rig using additively manufactured components.
A phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the pharmacokinetics, safety, and tolerability of oral ceftibuten in healthy adult subjects
Authors: Hernández-Mitre María Patricia , Wallis Steven C. , Morgan Elizabeth E. , Dudley Michael N. , Loutit Jeffery S. , Griffith David C. , Roberts Jason A.
Published: December 2023

This was a phase I, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of oral ceftibuten to describe the pharmacokinetics (PK) of
cis-
ceftibuten (administered form) and
trans-
ceftibuten (metabolite), and to describe safety and tolerability at higher than licensed doses. Subjects received single 400, 600, or 800 mg doses of ceftibuten on Days 1 and 4, followed by 7 days of twice-daily dosing from Days 4 to 10. Non-compartmental methods were used to describe parent drug and metabolite PK in plasma and urine. Dose proportionality was examined using
C
max
, AUC
0–12
, and AUC
0–INF
. Accumulation was calculated as the ratio of AUC
0–12
on Days 4 and 10. Adverse events (AEs) were monitored throughout the study. Following single ascending doses, mean
cis
- and
trans-
ceftibuten
C
max
were 17.6, 24.1, and 28.1 mg/L, and 1.1, 1.5, and 2.2 mg/L, respectively;
cis
-ceftibuten urinary recovery accounted for 64.3%–86.9% of the administered dose over 48 h. Following multiple ascending doses, mean
cis
- and
trans-
ceftibuten
C
max
were 21.7, 28.1, and 38.8 mg/L, and 1.4, 1.9, and 2.8 mg/L, respectively;
cis
-ceftibuten urinary recovery accounted for 72.2%–96.4% of the administered dose at steady state. The exposure of
cis-
and
trans-
ceftibuten increased proportionally with increasing doses.
Cis
- and
trans-
ceftibuten accumulation factor was 1.14–1.19 and 1.28–1.32. The most common gastrointestinal treatment emergent AEs were mild and resolved without intervention. Ceftibuten was well tolerated. Dose proportionality and accumulation of
cis
- and
trans
-ceftibuten were observed. These results support the ongoing development of ceftibuten at doses up to 800 mg twice-daily. (The study was registered at ClinicalTrials.gov under the identifier NCT03939429.)
Development of a quadruple qRT-PCR assay for simultaneous identification of hypervirulent and carbapenem-resistant
Klebsiella pneumoniae
Authors: Xu Zhixiang , Li Baisheng , Jiang Yushan , Huang Jia , Su Lebin , Wu Weibo , Pang Qilin , Li Zhuolin , Zhang Jiaqi , Li Xiaohe , Wang Jun , Cen Fulan , Peng Ling , Liang Jinhu , Wang Fuxiang , Liu Chang , Shen Chenguang , Liu Yingxia , Yang Yang
Published: December 2023

The increasing prevalence of hypervirulent (hv) and carbapenem-resistant (CR)
Klebsiella pneumoniae
(Kp) highlights the importance of timely and accurate differential diagnosis for epidemiological investigation and clinical management. A multiplex quantitative real-time PCR (qRT-PCR) assay for the simultaneous identification of hvKp and CR-Kp was developed and validated with excellent performance in sensitivity and specificity. Generally, the
gltA
gene for Kp, the
iucA
,
rmpA
and
rmpA2
genes for hvKp, and the
Klebsiella pneumoniae
carbapenemases (KPC) gene for CR-Kp were included in the qRT-PCR assay. The detection limits for classic Kp (cKp), CR-cKp, hvKp, and CR-hvKp strains could all reach 50 genome equivalent copies and 20 CFUs per reaction with high accuracy (
R
2
> 0.99) and reliability (CV values < 3%). Detection results from 84 Kp positive clinical samples showed 31 hvKp with 8 CR-hvKp and 53 cKp with 1 CR-cKp strains. The presence of virulence-associated factors for the identified hvKp and KPC genes for CR-Kp was confirmed by previously developed conventional PCR and antimicrobial susceptibility tests, respectively. Furthermore, the qRT-PCR identified hvKp strains showed mortality rates of ≥40% in the outbred murine infection model, while no death for the identified cKp strains. These results indicated that our multiplex qRT-PCR assay could accurately identify hvKp and CR-Kp strains, which will be of great use for the rapid and accurate diagnosis in a clinical setting and the surveillance of the circulating Kp.

IMPORTANCE

Globally, the increasing number of hypervirulent
Klebsiella pneumoniae
(hvKp) and carbapenem-resistant Kp (CR-Kp) infections poses a huge public health challenge with high morbidity and mortality. Worrisomely, due to the mobility of elements carrying virulence and drug-resistance genes, the increasing prevalence of CR-hvKp has also been found with an overwhelming mortality rate in recent years. However, the current detection methods for hvKp and CR-Kp have many disadvantages, such as long turnaround time, complex operation, low sensitivity, and specificity. Herein, a more sensitive, rapid, single-reaction, and multiplex quantitative real-time PCR was developed and validated to differentiate the circulating lineages of Kp with excellent performance in sensitivity and specificity, providing a useful tool for the differential diagnosis and the surveillance of the circulating Kp.
The Thymic Hormone Thymosin-1α Reduces the Pro-Inflammatory Response of Raw 264.7 Cells Induced by Endotoxin
Authors: Novoselova E. G. , Glushkova O. V. , Khrenov M. O. , Lunin S. M. , Sharapov M. G. , Goncharov R. G. , Mubarakshina E. K. , Novoselova T. V. , Parfenyuk S. B.
Published: December 2023

Abstract—The aim of this work was to study the effects of thymosin-1 alpha (Tα1) on the anti-inflammatory response of RAW 264.7 macrophages cultured in the presence of lipopolysaccharide (LPS) from the walls of gram-negative bacteria. As well, we evaluated production of pro-inflammatory cytokines and the activity of the NF-κB and SAPK/JNK signaling pathways. In addition, the level of expression of a number of genes that regulate cell apoptosis, as well as the activity of receptors involved in the pro-inflammatory response, was determined. First, the addition of Tα1 normalized the level of cytokine production to varying degrees, with a particularly noticeable effect on IL-1β and IL-6. Second, the addition of Tα1 normalized the activity of the NF-κB and SAPK/JNK signaling cascades and the expression of the Tlr4 gene. Third, Tα1 significantly reduced p53 and the activity of the P53 gene, which is a marker of cell apoptosis. Fourth, it was shown that the increase in Ar-1 gene expression under the influence of LPS was significantly reduced using Tα1. Thus, it was found that the presence of Tα1 in the RAW 264.7 cell culture medium significantly reduced the level of the pro-inflammatory response of cells.
The Protective Action of Hsp70 and Hydrogen Sulfide Donors in THP-1 Macrophages in the Lipopolysaccharide-Induced Inflammatory Response by Modulating Endocytosis
Authors: Yurinskaya M. M. , Garbuz D. G. , Evgen’ev M. B. , Vinokurov M. G.
Published: December 2023

Abstract—Hsp70 and hydrogen sulfide donors reduce inflammatory processes in human and animal cells. The biological action mediated by Hsp70 and H2S donors (GYY4137 and sodium thiosulfate) depends on their protection kinetics from cell activation by lipopolysaccharides. However, the molecular mechanisms of action of Hsp70 and H2S are not well understood. We studied the effect of human recombinant Hsp70 and H2S donors on the formation of reactive oxygen species and tumor necrosis factor-alpha induced in human cells (THP-1) by lipopolysaccharides. Transcriptomic changes occurring in these cells after LPS administration in combination with GYY4137 pretreatment were investigated. The results we obtained showed that Hsp70 and hydrogen sulfide donors reduce inflammatory processes in cells activated by the action of LPS. Hsp70 and H2S donors differed in the kinetics of the protective action, while hydrogen sulfide donors turned out to be more effective. The role of endocytosis in the mechanisms of protection of cells by H2S and Hsp70 donors from the action of LPS was studied. It has been found that GYY4137 pretreatment of LPS-exposed cells reduces the LPS-induced induction of various pro-inflammatory genes and affects the expression of genes of various intracellular signaling pathways.
CoPMoV Sulfide Catalysts Supported on Natural Halloysite Nanotubes in Hydrotreating of Dibenzothiophene and Naphthalene
Authors: Vinogradov N. A. , Timoshkina V. V. , Tsilimbaeva E. A. , Zasypalov G. O. , Pimerzin A. A. , Glotov A. P.
Published: December 2023

Mixed sulfided CoMo catalysts supported on γ-Al2O3 and halloysite nanotubes (HNTs) were synthesized by incipient wetness impregnation with salt solutions of Keggin-type phosphorus- and vanadium-containing heteropolyacids. The synthesized materials were characterized by low-temperature nitrogen adsorption, energy dispersive X-ray fluorescence analysis, temperature-programmed reduction (both for the oxide and sulfide catalysts), and Raman spectroscopy, and were tested in hydrogenation of naphthalene and hydrodesulfurization of dibenzothiophene. The HNT-supported catalyst exhibited a greater activity in these reactions.
Droplet Physics and Intracellular Phase Separation
Authors: Jülicher Frank , Weber Christoph A.
Published: December 2023

Living cells are spatially organized by compartments that can nucleate, grow, and dissolve. Compartmentalization can emerge by phase separation, leading to the formation of droplets in the cell's nucleo- or cytoplasm, also called biomolecular condensates. Such droplets can organize the biochemistry of the cell by providing specific chemical environments in space and time. These compartments provide transient environments, suggesting the relevance of nonequilibrium physics of droplets as a key to unraveling the underlying physicochemical principles of biological functions in living cells. In this review, we highlight coarse-grained approaches that capture the physics of chemically active emulsions as a model for condensates orchestrating chemical processes. We also discuss the dynamics of single molecules in condensates and the material properties of biological condensates and their relevance for the cell. Finally, we propose wetting, prewetting, and surface phase transitions as a possibility for intracellular surfaces to control biological condensates, spatially organize membranes, and exert mechanical forces.
The Consequence of Short Insemination Strategy on Sperm Biological Characteristics, Embryo Morphokinetics, and Clinical Outcomes in the IVF Program
Authors: Anbari Fatemeh , Khalili Mohammad Ali , Mahaldashtian Maryam , Agha-Rahimi Azam , Nabi Ali , Izadi Mahin , Woodward Bryan , Mangoli Esmat
Published: December 2023

Overnight coincubation of the cumulus–oocyte complexes (COCs) with spermatozoa may be accompanied by overproduction of reactive oxygen species (ROS) and possible determinant effects on sperm cellular status in the in vitro fertilization (IVF) program. The COCs from 100 cases were divided into two groups of short (2 hr) and long (18 hr) inseminations. The malondialdehyde (MDA) level as by-product of ROS was assessed in the insemination medium. The sperm DNA integrity, the mitochondrial membrane potential (MMP), and acrosome reaction (AR) were evaluated using sperm chromatin dispersion (SCD), fluorescence stain of JC-1, and double staining, respectively. Normally, fertilized oocytes (n = 525) were assessed via time-lapse monitoring (TLM) for assessment of the time of fading (tPNF), 2 until 8 timing (t2-t8), s1 (t2-tPNF), s2 (t4-t3), s3 (t8-t5), and duration of cell cycles. Finally, the best embryos were transferred, and clinical outcomes were assessed. Higher rates of MDA concentration, DNA fragmentation, and AR and low rate of MMP were noticed in long compared to short insemination groups (

p
≤
0.0001

). The morphokinetic parameters showed five-cell stage (t5) and cell cycle 3 (cc3) that were significantly different between the groups (

p
=
0.04

and

p
=
0.03

, respectively). A high level of ROS observed in the long insemination group might have a detrimental effect on sperm status. Although, similar embryo quality and clinical outcomes were noticed in two insemination groups, but the trend was toward the short insemination.