bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of Disk Friction Loss by Applying a Fin to the Back of a Centrifugal Impeller
Authors: Maeda Satoshi , Sano Takeshi , Miyagawa Kazuyoshi , Sakai Kento
Published: March 2024

It is well known that the ratio of disk friction loss of low specific speed pumps is large. When the specific speed is 100 min−1, m3/min, m or less, the disk friction loss increases remarkably. In this study, focusing on the clearance flow from the diffuser outlet to the impeller outlet (This is called the outward flow) behind the centrifugal pump, a fin was installed on outer diameter side of the rotating wall on the back side of a centrifugal pump as a countermeasure, and the influence of changes in velocity distribution near the wall on disk friction loss was investigated by torque measurements, velocity measurement, and computational fluid dynamics (CFD) analysis. As a result, it was clarified that disk friction loss is decreasing by installing the fin in both torque measurements and CFD results, because the clearance flow is separated by fin and circumferential velocity is increased in the wake region of the fin in both measurements and CFD. In addition, it was clarified that disk friction coefficient (normalized torque) can be expressed as a function of the inlet swirl ratio and Reynolds number. Also, prediction equation is derived for each shape (with and without fin). According to the equation, it was found that disk friction loss reduction effect by installing a fin becomes larger when Reynolds number and the inlet swirl ratio are small.
Progress toward ultra-cold Sr for the AION project—A red MOT and an optical-heterodyne diagnostic tool for injection-locked laser diodes
Authors: Pasatembou E. , Baynham C. F. A. , Buchmüller O. , Evans D. , Hobson R. , Iannizzotto Venezze L. , Josset A.
Published: March 2024

Long-baseline atom interferometers, such as the one to be built by the AION collaboration, require ultra-cold atomic clouds. These are produced by trapping the atoms in magneto-optical traps (MOTs) using high-power, narrow-linewidth lasers. We report on the laser and optical master–slave injection-locked system used to address the 1S0–3P1 strontium transition at 689 nm and on the trapping of strontium atoms in a narrowband MOT. We demonstrate the quality of the injection through the characterization of the injection lock using an easy-to-assemble method that uses a double-pass acousto-optic modulator to generate and detect a heterodyne beatnote. The reported system is used to produce an atomic cloud at a temperature of 812(43) nK in a narrowband red MOT.
A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection
Authors: Yu Yang , Chen Si , Zhang Haonan , Duan Yuanyuan , Li Zhuogang , Jiang Lefang , Cao Weihua , Peng Qun , Chen Xulin
Published: March 2024

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets
in vitro
. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection
in vitro
. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the
in vivo
therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.

IMPORTANCE

Antivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection
in vitro
. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.
Complete genome sequence of
Gluconobacter frateurii
ML.ISBL3, an endophytic strain isolated from aerial roots of
Syngonium podophyllum
Authors: Lam M. , Leung K. M. , Lai G. K. K. , Leung F. C. C. , Griffin S. D. J.
Published: March 2024

The endophytic strain
Gluconobacter frateurii
ML.ISBL3 was isolated from aerial roots of
Syngonium podophyllum
in Hong Kong. Its complete genome, established through hybrid assembly, comprises a single chromosome of 3,309,710 bp (56.30% G+C).
Comprehensive virulence profiling and evolutionary analysis of specificity determinants in
Staphylococcus aureus
two-component systems
Authors: Ahator Stephen Dela , Wenzl Karoline , Hegstad Kristin , Lentz Christian S. , Johannessen Mona
Published: March 2024

In the
Staphylococcus aureus
genome, a set of highly conserved two-component systems (TCSs) composed of histidine kinases (HKs) and their cognate response regulators (RRs) sense and respond to environmental stimuli, which drive the adaptation of the bacteria. This study investigates the complex interplay between TCSs in
S. aureus
USA300, a predominant methicillin-resistant
S. aureus
strain, revealing shared and unique virulence regulatory pathways and genetic variations mediating signal specificity within TCSs. Using TCS-related mutants from the Nebraska Transposon Mutant Library, we analyzed the effects of inactivated TCS HKs and RRs on the production of various virulence factors,
in vitro
infection abilities, and adhesion assays. We found that the TCSs’ influence on virulence determinants was not associated with their phylogenetic relationship, indicating divergent functional evolution. Using the co-crystallized structure of the DesK-DesR from
Bacillus subtilis
and the modeled structures of the four NarL TCSs in
S. aureus
, we identified interacting residues, revealing specificity determinants and conservation within the same TCS, even from different strain backgrounds. The interacting residues were highly conserved within strains but varied between species due to selection pressures and the coevolution of cognate pairs. This study unveils the complex interplay and divergent functional evolution of TCSs, highlighting their potential for future experimental exploration of phosphotransfer between cognate and non-cognate recombinant HK and RRs.

IMPORTANCE

Given the widespread conservation of two-component systems (TCSs) in bacteria and their pivotal role in regulating metabolic and virulence pathways, they present a compelling target for anti-microbial agents, especially in the face of rising multi-drug-resistant infections. Harnessing TCSs therapeutically necessitates a profound understanding of their evolutionary trajectory in signal transduction, as this underlies their unique or shared virulence regulatory pathways. Such insights are critical for effectively targeting TCS components, ensuring an optimized impact on bacterial virulence, and mitigating the risk of resistance emergence via the evolution of alternative pathways. Our research offers an in-depth exploration of virulence determinants controlled by TCSs in
S. aureus
, shedding light on the evolving specificity determinants that orchestrate interactions between their cognate pairs.
Combined transcriptomic and ChIPseq analyses of the
Bordetella pertussis
RisA regulon
Authors: Coutte Loïc , Antoine Rudy , Slupek Stephanie , Locht Camille
Published: March 2024

The regulation of
Bordetella pertussis
virulence is mediated by the two-component system BvgA/S, which activates the transcription of virulence-activated genes (
vag
s). In the avirulent phase, the
vag
s are not expressed, but instead, virulence-repressed genes (
vrg
s) are expressed, under the control of another two-component system, RisA/K. Here, we combined transcriptomic and chromatin immunoprecipitation sequencing (ChIPseq) data to examine the RisA/K regulon. We performed RNAseq analyses of RisA-deficient and RisA-phosphoablative
B. pertussis
mutants cultivated in virulent and avirulent conditions. We confirmed that the expression of most
vrg
s is regulated by phosphorylated RisA. However, the expression of some, including those involved in flagellum biosynthesis and chemotaxis, requires RisA independently of phosphorylation. Many RisA-regulated genes encode proteins with regulatory functions, suggesting multiple RisA regulation cascades. By ChIPseq analyses, we identified 430 RisA-binding sites, 208 within promoter regions, 201 within open reading frames, and 21 in non-coding regions. RisA binding was demonstrated in the promoter regions of most
vrg
s and, surprisingly, of some
vag
s, as well as for other genes not identified as
vag
s or
vrg
s. Unexpectedly, many genes, including some
vag
s, like
prn
,
brpL
,
bipA,
and
cyaA
, contain a BvgA-binding site and a RisA-binding site, which increases the complexity of the RisAK/BvgAS network in
B. pertussis
virulence regulation.

IMPORTANCE

The expression of virulence-activated genes (
vag
s) of
Bordetella pertussis
, the etiological agent of whooping cough, is under the transcriptional control of the two-component system BvgA/S, which allows the bacterium to switch between virulent and avirulent phases. In addition, the more recently identified two-component system RisA/K is required for the expression of
B. pertussis
genes, collectively named
vrg
s, that are repressed during the virulent phase but activated during the avirulent phase. We have characterized the RisA/K regulon by combined transcriptomic and chromatin immunoprecipitation sequencing analyses. We identified more than 400 RisA-binding sites. Many of them are localized in promoter regions, especially
vrg
s, but some were found within open reading frames and in non-coding regions. Surprisingly, RisA-binding sites were also found in promoter regions of some
vag
s, illustrating the previously underappreciated complexity of virulence regulation in
B. pertussis
.
Nemertodermatida—Endosymbionts of Deep-Sea Acorn Worms (Hemichordata, Torquaratoridae)
Authors: Ezhova O. V. , Lukinykh A. I. , Malakhov V. V.
Published: March 2024

Worm-like endosymbionts were found in the hepatic region of the digestive tract of the deep-sea acorn worm Quatuoralisia malakhovi Ezhova et Lukinykh, 2022 (family Torquaratoridae) from the Bering Sea. The symbionts were assigned to the taxon Nemertodermatida on the basis of histological examination. Torquaratoridae are similar in feeding type to holothuroids, which have also been found to have Xenacoelomorpha endosymbionts.
Masquerading fungal bowel mass in an adolescent: a clinicopathological challenge
Authors: Sarngadharan C Meera Anitha K Viswambharan , DCunha Aureen Ruby , Rai Sandeep B , Prasad Kishan , Ail Divya
Published: March 2024

Abdominal masses clubbed with weight loss in the paediatric age group can raise hairs, especially since malignancy is a differential. We present the case of an early adolescent male who presented with abdominal pain and was found to have a mass mimicking a malignancy. The resected surgical specimen revealed entomophthoromycosis of the jejunum and he made a complete recovery following surgery and adjuvant itraconazole. The diagnosis of a fungal aetiology in these cases requires a high index of suspicion and background knowledge of the risk factors, disease occurrence and mode of presentation. Gastrointestinal entomophthoromycosis has an impressive potential for cure if promptly diagnosed and treated.
HIV-associated nemaline myopathy manifesting as bent spine syndrome
Authors: Nasir Ali Zagham , Jameson Andrew
Published: March 2024

HIV-associated myopathies include HIV-associated polymyositis, inclusion body myositis, diffuse infiltrative lymphocytosis syndrome and sporadic late-onset nemaline myopathy (HIV-NM). HIV-NM typically manifests as a painless, progressive proximal and axial muscle weakness with characteristic histological findings of intracytoplasmic rods, or nemaline bodies, seen in atrophic muscle fibres. HIV-NM presents prior to or shortly after initiation of antiretroviral therapy (ART) and is treated with intravenous immunoglobulin, glucocorticoids or immunosuppression. We present a case of HIV-NM in a patient with well-controlled HIV on decades-long ART with progressive bent spine syndrome, or camptocormia. This case highlights the importance of considering HIV-associated myopathies such as HIV-NM in patients with HIV who present with musculoskeletal complaints.
Codesign of health technology interventions to support best-practice perioperative care and surgical waitlist management
Authors: Aitken Sarah Joy , James Sophie , Lawrence Amy , Glover Anthony , Pleass Henry , Thillianadesan Janani , Monaro Sue , Hitos Kerry , Naganathan Vasi
Published: March 2024

Objectives

This project aimed to determine where health technology can support best-practice perioperative care for patients waiting for surgery.

Methods

An exploratory codesign process used personas and journey mapping in three interprofessional workshops to identify key challenges in perioperative care across four health districts in Sydney, Australia. Through participatory methodology, the research inquiry directly involved perioperative clinicians. In three facilitated workshops, clinician and patient participants codesigned potential digital interventions to support perioperative pathways. Workshop output was coded and thematically analysed, using design principles.

Results

Codesign workshops, involving 51 participants, were conducted October to November 2022. Participants designed seven patient personas, with consumer representatives confirming acceptability and diversity. Interprofessional team members and consumers mapped key clinical moments, feelings and barriers for each persona during a hypothetical perioperative journey. Six key themes were identified: ‘preventative care’, ‘personalised care’, ‘integrated communication’, ‘shared decision-making’, ‘care transitions’ and ‘partnership’. Twenty potential solutions were proposed, with top priorities a digital dashboard and virtual care coordination.

Discussion

Our findings emphasise the importance of interprofessional collaboration, patient and family engagement and supporting health technology infrastructure. Through user-based codesign, participants identified potential opportunities where health technology could improve system efficiencies and enhance care quality for patients waiting for surgical procedures. The codesign approach embedded users in the development of locally-driven, contextually oriented policies to address current perioperative service challenges, such as prolonged waiting times and care fragmentation.

Conclusion

Health technology innovation provides opportunities to improve perioperative care and integrate clinical information. Future research will prototype priority solutions for further implementation and evaluation.
Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement
Authors: Lacombe Didier , Bloch-Zupan Agnès , Bredrup Cecilie , Cooper Edward B , Houge Sofia Douzgou , García-Miñaúr Sixto , Kayserili Hülya , Larizza Lidia , Lopez Gonzalez Vanesa , Menke Leonie A , Milani Donatella , Saettini Francesco , Stevens Cathy A , Tooke Lloyd , Van der Zee Jill A , Van Genderen Maria M , Van-Gils Julien , Waite Jane , Adrien Jean-Louis , Bartsch Oliver , Bitoun Pierre , Bouts Antonia H M , Cueto-González Anna M , Dominguez-Garrido Elena , Duijkers Floor A , Fergelot Patricia , Halstead Elizabeth , Huisman Sylvia A , Meossi Camilla , Mullins Jo , Nikkel Sarah M , Oliver Chris , Prada Elisabetta , Rei Alessandra , Riddle Ilka , Rodriguez-Fonseca Cristina , Rodríguez Pena Rebecca , Russell Janet , Saba Alicia , Santos-Simarro Fernando , Simpson Brittany N , Smith David F , Stevens Markus F , Szakszon Katalin , Taupiac Emmanuelle , Totaro Nadia , Valenzuena Palafoll Irene , Van Der Kaay Daniëlle C M , Van Wijk Michiel P , Vyshka Klea , Wiley Susan , Hennekam Raoul C
Published: March 2024

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP,EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1:CREBBP; RTS2:EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.
High frequency dielectric study on the hydrogen bonding interaction on 1,5-pentanediol + 1,4-dioxane binary mixtures
Authors: Garad Nitin P. , Saknure Shankar H. , Dongre Daiwashala G. , Kumbharkhane Ashok C.
Published: March 2024

The complex dielectric permittivity spectra (CPS) of a binary mixture of 1,5-pentanediol (1,5-PD) with 1,4-dioxane (1,4-DX) were determined using time-domain reflectometry in the frequency range of 10 MHz to 30 GHz. The experimental CPS data were fitted to the Cole–Davidson equation using a nonlinear least squares fit method to determine the dielectric relaxation parameters. The intermolecular interactions in the binary liquids were studied through the Kirkwood correlation factor, excess parameters, thermodynamic parameters, and Bruggeman’s factor.
Range-wide contrast in management outcomes for transboundary Northeast Pacific sablefish
Authors: Kapur Maia S. , Haltuch M.A. , Connors B. , Berger A. , Holt K. , Marshall K. , Punt A. E.
Published: March 2024

Sablefish ( Anoplopoma fimbria) of the Northeast Pacific support a highly mobile, valuable fishery resource currently managed as three separate populations. Recent work has shown sablefish to be genetically mixed; have high movement rates; and have synchronous biomass trends, including recent declines. A management strategy evaluation was developed with stakeholders and scientists from three regions to investigate whether spatially structured management paradigms might result in better conservation and economic outcomes. The management strategy evaluation includes a transboundary operating model to represent spatial population dynamics including movement and a delay–difference estimation method with varying spatial complexities and potential stratifications, and harvest control rules. Mismatches in the spatial scale of management and the underlying biological units pose a crucial risk of localized depletion in the southern U.S. West Coast. This study presents one of the first transboundary, spatially-explicit management strategy evaluations conditioned to actual data. These results underscore the importance of spatial management strategy evaluation tools and implications when regional management is conducted in isolation. Future work should incorporate additional spatial hypotheses and investigate the drivers of recruitment patterns range-wide.
White-footed mouse (Peromyscus leucopus) response to restoration of grassland alvar
Authors: Burgess Thomas , Sukumar Smera , Thomas Melissa , Bowman Jeff
Published: March 2024

Grassland alvar is a rare plant community that occurs throughout North America and northern Europe, and may require control of encroaching vegetation to be maintained or restored. We evaluated the hypothesis that restoration techniques used to restore the alvar ecosystem do not lead to declines in small mammal abundance. More specifically, we used a Before-After Control-Impact (BACI) design to compare how two methods of vegetation control, prescribed burns and mechanical removal, affected small mammal populations. The restoration was conducted beginning in 2019 on Pelee Island, Ontario, Canada. Live trapping of small mammals and associated vegetation sampling were conducted before and after on treatment and control locations. The only small mammal species to be caught during the study was the white-footed mouse ( Peromyscus leucopus (Rafinesque, 1818)), which had an observed decrease across all treatment sites and the control site. Generalized linear mixed effects models demonstrated that the main effects of treatment and year best explained mouse abundance at the site level. Interannual variability appeared to explain more variation in mouse abundance than treatment effects. Our study did not provide strong evidence that the vegetation control measures we employed might limit white-footed mouse abundance.
Effect of Co doping on the structure and magnetic properties of Bi0.8Ba0.2FeO3 nanoparticles
Authors: Wu Zhongjin , Liu Guoqing , Lu Zeyi , Gao Kaiyang , Wang Changyang , Liu Min , Xia Yanfang
Published: March 2024

A series of Bi[Formula: see text]Ba[Formula: see text]Fe[Formula: see text]CoxO3 ([Formula: see text], 0.05, 0.10, and 0.15) samples were synthesized using the tartaric acid modified sol–gel method. The crystal structure of the prepared samples was analyzed by XRD, and the samples co-doped with Ba and Co were all rhombohedral distorted structures with the R3c space group. With an increase in the doping amount, a reduction in lattice parameters was observed along with crystallite sizes consistently being below 62[Formula: see text]nm. Mössbauer spectral analysis at room temperature reveals a good fit with two sextets and a doublet, all attributed to the Fe[Formula: see text] state. This suggests that the charge balance within the samples is maintained through the generation of oxygen vacancies in the system. The hysteresis loops of all samples revealed the weak ferromagnetic of the Co-doped Bi[Formula: see text]Ba[Formula: see text]FeO3 nanoparticles. With the increase in Co doping, the magnetic parameters such as saturation magnetization and coercive field significantly improved.
Intrinsic surface states with electron–surface optical phonon interaction influence in wurtzite Zn-IV-N2 semiconductors
Authors: Li Gen-Xiao , Yan Zu-Wei
Published: March 2024

The electronic intrinsic surface states in wurtzite Zn-IV-N2 (with group-[Formula: see text], Ge and Si) semiconductors were investigated using an intermediate-coupling variational approach considering the electron–surface optical phonon interaction influence. The intrinsic surface state energy distribution and the average penetrating depth of surface state eigen-wave function of the electron have been evaluated numerically by changing the surface potential barrier [Formula: see text] for wurtzite ZnSnN2, ZnGeN2 and ZnSiN2, respectively. The results show that the electronic intrinsic surface state energy increased linearly with increasing surface potential barrier [Formula: see text] for all the calculated materials. The result also indicated that the electronic intrinsic surface state energies variations due to the influence of electron–surface optical phonon interaction are dozens of[Formula: see text]meV. The average penetrating depth of electronic surface state eigen-wave function is independent of [Formula: see text]. Its value is no more than the corresponding material’s lattice constant. The electronic scattering by surface optical phonon should be taken into account in the study of the intrinsic surface state of electrons in the group of Zn-IV-nitrides (with [Formula: see text], Ge and Si) semiconductors, especially for materials having strong electron–phonon interaction and wide band gap.
Transition and Propagation of Epilepsy in an Improved Epileptor Model Coupled with Astrocyte
Authors: An Kangning , Du Lin , Zhang Honghui , Shen Zhuan , Sun Xiaojuan
Published: March 2024

In this paper, a tripartite synapse network is constructed to examine external and internal triggering factors of epilepsy transition and propagation in neurons with the Epileptor-2 model. We first explore the external stimuli in the environment that induce epileptic activities and transition behaviors among Ictal Discharges (IDs) and Interictal Discharges (IIDs) states. The higher the strength and abruptness of the stimuli, the more severe is the occurrence of epilepsy within a reasonable range of parameters. Then for the internal triggering factors, the results of the tripartite synapse network, which is improved by combining the Epileptor-2 model with astrocyte by means of ion exchange and new connections, show that astrocytes can transmit normal physiological activity information and filter out abnormal discharge information of neurons. One of the causes for epileptic seizures is the abnormal release of glial neurotransmitters in astrocytes. The excessive release of glutamate causes the discharge state of neurons to transit from nonepileptic to IIDs, IDs and tonic, while adenosine triphosphate can alleviate epilepsy. Meanwhile, the synapse dysfunction of an astrocyte-free network can also lead to seizures, and the epilepsy propagation ability of a tripartite synapse network becomes weaker than that of an astrocyte-free network. Our research is expected to provide some theoretical basis for the therapeutic approach to curing epilepsy in the intracellular and extracellular contexts.
Study on the Development Efficiency of Leisure Agriculture in Suburban Towns: An Empirical Analysis Based on the Case of Xinkou Town, Tianjin City
Authors: ZHANG Ruiying , LI Rui , LV Xianhong
Published: March 2024

The leisure agriculture in suburban towns provides important space for citizens to carry out leisure activities. This paper takes Xinkou town in Tianjin city as an example to analyze the development efficiency of leisure agriculture in suburban towns. On the premise of establishing the indicators for evaluating the development efficiency of leisure agriculture in Xinkou town, this paper first uses the data envelopment analysis (DEA) to measure the input and output indicators of leisure agriculture in 18 natural villages in Xinkou town, and calculates the comprehensive technical efficiency, target values, redundancy and returns to scale of leisure agriculture, and then evaluates the development efficiency of leisure agriculture in Xinkou town. Furthermore, by using the high/low clustering tool under the ArcGIS spatial statistics module, this paper conducts a high/low clustering analysis of the development efficiency of leisure agriculture in 18 natural villages of Xinkou town, and figures out the reasons for the high/low clustering of natural villages in Xinkou town spatially. After the research and analysis, the following conclusions are drawn: From the input–output perspective, except for Zhengzhuangzi village, Diliubu village, Yuejiakai village, and Dangcheng village, the development efficiency of leisure agriculture in other villages is relatively low due to their poor resource foundations, or deficiencies in management experience and transportation location. The development of leisure agriculture in Xinkou town is unbalanced, showing a pattern of polarized clusters: Diliubu village and Shuigaozhuang village form the most obvious high-value cluster, while Xiaoshawo village, Bijia village and Xuanjiayuan village form the most obvious low-value cluster, where the southeast corner of Xinkou town registers the lowest development efficiency value of leisure agriculture because it is far away from the town center and the main transportation arteries, and falls short of high-quality pastoral scenery. For the future development of leisure agriculture in Xinkou town, it is supposed to optimize the land use policy, provide active support to the competitive industrial and commercial capital, non-governmental capital, rural collective economic organizations, farmers’ cooperatives, and family farms, strengthen the in-depth integration of industries, improve the support system for new-type leisure agriculture, and build leisure agriculture brands with local features.
Introduction to the Issue on Artificial Intelligence in the Public Sector: Risks and Benefits of AI for Governments
Authors: Mellouli Sehl , Janssen Marijn , Ojo Adegboyega
Published: March 2024

Artificial Intelligence (AI) is increasingly adopted by public sector organizations to provide better public services and to transform their internal processes. AI is now considered a key enabler for digital innovation and transformation in the public sector. However, AI is still relatively a new research area in the field of digital government. The term, AI, captures a wide range of technologies, techniques, and tools such as machine/deep learning, natural language processing, robotics, computer vision, and more recently Generative AI. While these AI technologies afford different applications and benefits in the government context, they also create social, ethical, and legal challenges. These challenges require solutions combining both technical (e.g., data and algorithmic solutions to minimize bias) and institutional (e.g., governance structures and processes) mechanisms. The special issue is a collection of articles that contribute to a better understanding of the issues associated with AI deployment in different areas of government operations. They cover AI applications in the areas of emergency response, policy analysis, public bids, and citizen participation. The contributions also address the challenge of realizing a legal transparency regime for AI in government and the effect of AI in bureaucratic decision-making.
Steaming Maintains Fatty Acids, Antioxidants, and Proximate Content in Snack Bar Products from Cocoa Beans
Authors: Iswari Kasma , Atman  , Marlina Leni , Riska  , Antarlina Sri Satya , Arief Ratna Wylis , Waryat  , Suwarda Rosniyati , Sjafrina Noveria , Yani Alvi , Sunarmani  , Joseph Gabriel Herald , Lintang Meivie , Layuk Payung , Arif Abdullah Bin
Published: March 2024

Chocolate products on the market are generally in the form of chocolate bars as snacks made from cocoa powder. Fat and powder are separated first through a pressing process to obtain the cocoa powder. Cocoa powder loses most of its fat content during processing. Therefore, the study aimed to determine the effect of steaming time on the cocoa bean content of fatty acids, free fatty acids, proximate levels, and antioxidant activity of snack bar products made from steamed cocoa beans. Seven steaming time intervals for cocoa beans were studied. The results showed that a longer steaming time affects the fatty acids, saturated fatty acids, antioxidants, and proximate in cocoa beans. Steaming time treatment at 45 minutes increased oleic acid, palmitic acid, and antioxidant activity. In addition, reducing free fatty acids represents a quality improvement that meets international Codex Alimentarius standards, offering a competitive advantage in the market. The food industry can adopt this steaming technique to develop snack bars and new products that are healthier and more sustainable by using steaming as an effective processing method in maintaining and increasing the nutritional value of products.
Development and Optimization of a Multiplex Real‐Time RT‐PCR to Detect SARS‐CoV‐2 in Human Samples
Authors: Castellar-Mendoza Camilo , Calderón-Peláez María-Angélica , Castellanos Jaime E. , Velandia-Romero Myriam L. , Coronel-Ruiz Carolina , Camacho-Ortega Sigrid , Bernal-Cepeda Lilia J. , López-Ibarra Lady , Arturo Jhann A. , Delgado Félix G. , Gutierrez-Barbosa Hernando , Bohorquez-Avila Sonia , Madroñero Johanna , Corredor-Rozo Zayda L. , Perdomo-Lara Sandra J. , Fonseca-Benitez Angela , Calvo Eliana
Published: March 2024

PCR and its variants (RT‐PCR and qRT‐PCR) are valuable and innovative molecular techniques for studying nucleic acids. qPCR has proven to be highly sensitive, efficient, and reproducible, generating reliable results that are easy to analyze. During the COVID‐19 pandemic, qPCR became the gold standard technique for detecting the SARS‐CoV‐2 virus that allowed to confirm the infection event, and those asymptomatic ones, and thus save millions of lives. In‐house multiplex qPCR tests were developed worldwide to detect different viral targets and ensure results, follow the infections, and favor the containment of a pandemic. Here, we present the detailed fundamentals of the qPCR technique based on fluorogenic probes and processes to develop and optimize a successful multiplex RT‐qPCR test for detecting SARS‐CoV‐2 that could be used to diagnose COVID‐19 accurately.
Use of the Serum Level of Cholinesterase as a Prognostic Marker of Nonfatal Clinical Outcomes in Patients Hospitalized with Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Chen Zhixiang , Zha Lei , Hu Bin , Xu Bin , Zuo Lin , Yang Jun , Chu Zhuhua , Ma Lingling , Hu Fangfang
Published: March 2024

Introduction. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes to a poor prognosis. Reliable biomarkers to predict adverse outcomes during hospitalization are important. Aim. To investigate the relationship between the serum cholinesterase (ChE) level and adverse clinical outcomes, including hypoxemia severity, hypercapnia, duration of hospital stay (DoHS), and noninvasive ventilation (NIV) requirement, in patients with AECOPD. Methods. Patients hospitalized with AECOPD in the Wuhu Hospital of Traditional Chinese Medicine between January 2017 and December 2021 were included. Results. A total of 429 patients were enrolled. The serum ChE level was significantly lower in patients with hypercapnia, who required NIV during hospitalization and who had a DoHS of >10 days, with an oxygenation index < 300. The ChE level was correlated negatively with the C-reactive protein level and neutrophil-to-lymphocyte ratio and correlated positively with the serum albumin level. Multivariate logistic regression analysis indicated that a serum ChE level of ≤4116 U/L (OR = 2.857, 95% CI = 1.46–5.58, p=0.002) was associated significantly with NIV requirement. Conclusions. The serum ChE level was correlated significantly with complicating severe hypoxemia, hypercapnia, prolonged DoHS, and the need for NIV in patients hospitalized with AECOPD. The serum ChE level is a clinically important risk-stratification biomarker in patients hospitalized with AECOPD.
Data from The Regulation of AMPK β1, TSC2, and PTEN Expression by p53: Stress, Cell and Tissue Specificity, and the Role of These Gene Products in Modulating the IGF-1-AKT-mTOR Pathways
Authors: Feng Zhaohui , Hu Wenwei , de Stanchina Elisa , Teresky Angelika K. , Jin Shengkan , Lowe Scott , Levine Arnold J.
Published: March 2024

Abstract
The insulin-like growth factor 1 (IGF-1)-AKT-mTOR pathways sense the availability of nutrients and mitogens and respond by signaling for cell growth and division. The p53 pathway senses a variety of stress signals which will reduce the fidelity of cell growth and division, and responds by initiating cell cycle arrest, senescence, or apoptosis. This study explores four p53-regulated gene products, the β1 and β2 subunits of the AMPK, which are shown for the first time to be regulated by the p53 protein, TSC2, PTEN, and IGF-BP3, each of which negatively regulates the IGF-1-AKT-mTOR pathways after stress. These gene products are shown to be expressed under p53 control in a cell type and tissue-specific fashion with the TSC2 and PTEN proteins being coordinately regulated in those tissues that use insulin-dependent energy metabolism (skeletal muscle, heart, white fat, liver, and kidney). In addition, these genes are regulated by p53 in a stress signal–specific fashion. The mTOR pathway also communicates with the p53 pathway. After glucose starvation of mouse embryo fibroblasts, AMPK phosphorylates the p53 protein but does not activate any of the p53 responses. Upon glucose starvation of E1A-transformed mouse embryo fibroblasts, a p53-mediated apoptosis ensues. Thus, there is a great deal of communication between the p53 pathway and the IGF-1-AKT and mTOR pathways. [Cancer Res 2007;67(7):3043–53]
Data from Osteopontin Promotes Integrin Activation through Outside-In and Inside-Out Mechanisms: OPN-CD44V Interaction Enhances Survival in Gastrointestinal Cancer Cells
Authors: Lee Jia-Lin , Wang Mei-Jung , Sudhir Putty-Reddy , Chen Gen-Der , Chi Chin-Wen , Chen Jeou-Yuan
Published: March 2024

Abstract
Osteopontin (OPN) and splice variants of CD44 (CD44V) have independently been identified as markers for tumor progression. In this study, we show that both OPN and CD44V are frequently overexpressed in human gastric cancer and that OPN-engaged CD44V ligation confers cells an increased survival mediated through integrin activation. First, we show that OPN treatment confers cells an increased resistance to UV-induced apoptosis. The OPN-mediated antiapoptosis is dependent on the expression of the variant exon 6 (V6)- or V7-containing CD44 as shown by overexpression of individual CD44V in gastric AZ521 cells that express no or very low level of endogenous CD44 and by knockdown of the constitutively expressed V6-containing CD44 isoforms in colon HT29 cells. Although OPN also interacts with RGD integrins, OPN-RGD sequence is dispensable for OPN-mediated antiapoptosis. OPN-induced antiapoptosis is mainly attributed to the engagement of CD44V isoforms and the relay of an inside-out signaling via Src activity, leading to robust integrin activation. Furthermore, OPN-elicited antiapoptosis was observed when cells were plated on fibronectin but not on poly-d-lysin, and preincubation of cells with anti-integrin β1 antibody to block integrin-extracellular matrix (ECM) interaction or ectopic expression of the dominant-negative forms of focal adhesion kinase to block ECM-derived signal abolished OPN-induced survival, suggesting that OPN-elicited antiapoptotic function is propagated from matrix transduced by integrin. Taken together, we showed that OPN-CD44V interaction promotes ECM-derived survival signal mediated through integrin activation, which may play an important role in the pathogenic development and progression of gastric cancer. [Cancer Res 2007;67(5):2089–97]
Data from Endothelial Function of von Hippel-Lindau Tumor Suppressor Gene: Control of Fibroblast Growth Factor Receptor Signaling
Authors: Champion Kristen J. , Guinea Maria , Dammai Vincent , Hsu Tien
Published: March 2024

Abstract
von Hippel-Lindau (VHL) disease results from germline and somatic mutations in the VHL tumor suppressor gene and is characterized by highly vascularized tumors. VHL mutations lead to stabilization of hypoxia-inducible factor (HIF), which up-regulates proangiogenic factors such as vascular endothelial growth factor (VEGF). This pathway is therefore believed to underlie the hypervascular phenotypes of the VHL tumors. However, recent studies have identified novel VHL functions that are independent of the HIF-VEGF pathway. In addition, a potential role of VHL in the tumor microenvironment, which carries heterozygous VHL mutations in VHL patients, has been overlooked. Here, we report a novel HIF-independent VHL function in the endothelium. VHL knockdown in primary human microvascular endothelial cells caused defective turnover of surface fibroblast growth factor (FGF) receptor, increased extracellular signal-regulated kinase signaling, and ETS1 activation, leading to increased cell motility in response to FGF and three-dimensional cord formation in vitro. HIF-α knockdown in VHL loss-of-function endothelial cells does not impede their elevated in vitro angiogenic activity. Importantly, the elevated angiogenic response to FGF is recapitulated in Vhl-heterozygous mice. Thus, partial loss of function of VHL in endothelium may be a contributing factor in tumor angiogenesis through a HIF-VEGF–independent mechanism. [Cancer Res 2008;68(12):4649–57]
Data from Bexarotene (LGD1069, Targretin), a Selective Retinoid X Receptor Agonist, Prevents and Reverses Gemcitabine Resistance in NSCLC Cells by Modulating Gene Amplification
Authors: Tooker Patricia , Yen Wan-Ching , Ng Shi-Chung , Negro-Vilar Andrès , Hermann Thomas W.
Published: March 2024

Abstract
Acquired drug resistance is a major obstacle in cancer therapy. As for many other drugs, this is also the case for gemcitabine, a nucleoside analogue with activity against non–small cell lung cancer (NSCLC). Here, we evaluate the ability of bexarotene to modulate the acquisition and maintenance of gemcitabine resistance in Calu3 NSCLC models. In the prevention model, Calu3 cells treated repeatedly with gemcitabine alone gradually developed resistance. However, with inclusion of bexarotene, the cells remained chemosensitive. RNA analysis showed a strong increase of rrm1 (ribonucleotide reductase M1) expression in the resistant cells (Calu3-GemR), a gene known to be involved in gemcitabine resistance. In addition, the expression of genes surrounding the chromosomal location of rrm1 was increased, suggesting that resistance was due to gene amplification at the chr11 p15.5 locus. Analysis of genomic DNA confirmed that the rrm1 gene copy number was increased over 10-fold. Correspondingly, fluorescence in situ hybridization analysis of metaphase chromosomes showed an intrachromosomal amplification of the rrm1 locus. In the therapeutic model, bexarotene gradually resensitized Calu3-GemR cells to gemcitabine, reaching parental drug sensitivity after 10 treatment cycles. This was associated with a loss in rrm1 amplification. Corresponding with the in vitro data, xenograft tumors generated from the resistant cells did not respond to gemcitabine but were growth inhibited when bexarotene was added to the cytotoxic agent. The data indicate that bexarotene can resensitize gemcitabine-resistant tumor cells by reversing gene amplification. This suggests that bexarotene may have clinical utility in cancers where drug resistance by gene amplification is a major obstacle to successful therapy. [Cancer Res 2007;67(9):4425–33]
Data from Association Study of 69 Genes in the Ret Pathway Identifies Low-penetrance Loci in Sporadic Medullary Thyroid Carcinoma
Authors: Ruiz-Llorente Sergio , Montero-Conde Cristina , Milne Roger L. , Moya Christian M. , Cebrián Arancha , Letón Rocío , Cascón Alberto , Mercadillo Fátima , Landa Iñigo , Borrego Salud , de Nanclares Guiomar Pérez , Álvarez-Escolá Cristina , Díaz-Pérez José Ángel , Carracedo Ángel , Urioste Miguel , González-Neira Anna , Benítez Javier , Santisteban Pilar , Dopazo Joaquín , Ponder Bruce A. , Robledo Mercedes
Published: March 2024

Abstract
To date, few association studies have been done to better understand the genetic basis for the development of sporadic medullary thyroid carcinoma (sMTC). To identify additional low-penetrance genes, we have done a two-stage case-control study in two European populations using high-throughput genotyping. We selected 417 single nucleotide polymorphisms (SNP) belonging to 69 genes either related to RET signaling pathway/functions or involved in key processes for cancer development. TagSNPs and functional variants were included where possible. These SNPs were initially studied in the largest known series of sMTC cases (n = 266) and controls (n = 422), all of Spanish origin. In stage II, an independent British series of 155 sMTC patients and 531 controls was included to validate the previous results. Associations were assessed by an exhaustive analysis of individual SNPs but also considering gene- and linkage disequilibrium–based haplotypes. This strategy allowed us to identify seven low-penetrance genes, six of them (STAT1, AURKA, BCL2, CDKN2B, CDK6, and COMT) consistently associated with sMTC risk in the two case-control series and a seventh (HRAS) with individual SNPs and haplotypes associated with sMTC in the Spanish data set. The potential role of CDKN2B was confirmed by a functional assay showing a role of a SNP (rs7044859) in the promoter region in altering the binding of the transcription factor HNF1. These results highlight the utility of association studies using homogeneous series of cases for better understanding complex diseases. [Cancer Res 2007;67(19):9561–7]
Data from The p38 MAPK Pathway Mediates Aryl Propionic Acid–Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells
Authors: Quann Emily J. , Khwaja Fatima , Djakiew Daniel
Published: March 2024

Abstract
The p75NTR acts as a tumor suppressor in the prostate, but its expression is lost as prostate cancer progresses and is minimal in established prostate cancer cell lines such as PC-3, DU-145, and LNCaP. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in PC-3 and DU-145 cells leading to p75NTR-mediated decreased survival. Here, we investigate the mechanism by which these drugs induce p75NTR expression. We show that the observed increase in p75NTR protein due to R-flurbiprofen and ibuprofen treatment was accompanied by an increase in p75NTR mRNA, and this increase in mRNA was the result of increased mRNA stability and not by an up-regulation of transcription. In addition, we show that treatment with R-flurbiprofen or ibuprofen led to sustained activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Furthermore, inhibition of the p38 MAPK pathway with the p38 MAPK–specific inhibitor SB202190 or by small interfering RNA (siRNA) knockdown of p38 MAPK protein prevented induction of p75NTR by R-flurbiprofen and ibuprofen. We also observed that siRNA knockdown of MAPK-activated protein kinase (MK)-2 and MK3, the kinases downstream of p38 MAPK that are responsible for the mRNA stabilizing effects of the p38 MAPK pathway, also prevented an induction of p75NTR by R-flurbiprofen and ibuprofen. Finally, we identify the RNA stabilizing protein HuR and the posttranscriptional regulator eukaryotic translation initiation factor 4E as two possible mechanisms by which the p38 MAPK pathway may increase p75NTR expression. Collectively, the data suggest that R-flurbiprofen and ibuprofen induce p75NTR expression by increased mRNA stability that is mediated through the p38 MAPK pathway. [Cancer Res 2007;67(23):11402–10]