bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empagliflozin ameliorates liver fibrosis in NASH rat model via targeting hepatic NF-κB/SOX9/OPN signaling and osteocalcin level
Authors: Elseweidy Mohamed M. , Ali Abd El-Monem , Hassanin Sara M. , Mahmoud Yasmin K. 
Published: November 2023

AbstractNon-alcoholic steatohepatitis (NASH) may be associated with tissue fibrotic changes and can be treated via different therapeutic tools which may however either initiate weak or long-term side effects that minimize its use. Empagliflozin (EMPA) is an oral anti-diabetic drug which has characteristic effects during hepatic steatosis regarding lipid accumulation and insulin resistance. In this study, we aimed to investigate an additional mechanism through which EMPA can exert and potentiate its anti-inflammatory and anti-fibrotic effects in NASH rat model. Male Wistar albino rats fed on high fat diet (HFD) and 20% fructose in drinking water for 18 weeks and received EMPA (30 mg/kg/day, orally) starting from week 11. Body and liver weights, homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile, liver function tests, other biochemical and histological parameters were determined. HFD joined with fructose intake significantly increased body and liver weights, HOMA-IR value, hepatic inflammatory and fibrotic markers, liver transaminases, hepatic expression of nuclear factor-kappa B (NF-κB), sex determining region Y box 9 (SOX 9), and osteopontin (OPN) with significant decrease in hepatic osteocalcin (OCN). Intense hepatic lesions with severe microsteatosis and deposition of collagen fibers were clearly observed. Effectively, EMPA restored the normal liver functions, downregulated hepatic inflammatory cytokines, NF-κB, SOX 9, OPN, and increased OCN level. These results highlight another pathway illustrated the anti-fibrotic effects of EMPA against liver fibrosis probably through downregulation of NF-κB/SOX 9/OPN signaling along with upregulation of hepatic OCN which may potentiate the valuable anti-inflammatory and anti-fibrotic effects of EMPA.
Graphical abstract
Maximizing Access and Minimizing Barriers to Research in Low- and Middle-Income Countries: Open Access and Health Equity
Authors: Saloojee Haroon , Pettifor John M. 
Published: November 2023

AbstractAccess to published research has always been difficult for researchers and clinicians in low- and middle-income countries, because of the cost of and lack of access to the relevant publications. The dramatic recent increase in electronic research publications has resulted in a marked improvement in reader access to these publications through their mainly Open Access policies, however the costs of processing of submissions and publication have now become the burden of the researchers wishing to publish, rather than the readers. For many researchers working in LMIC, the Article Processing Charges (APC) are prohibitive, hampering the publication of research being conducted in and relevant to these countries. A number of grant funding agencies and international not-for-profit organizations are trying to address these issues by including funding for article publications in their grants, or by supporting publishing entities by subsiding the cost of publication, but more needs to be done by major journal publishers through markedly reducing the APC being charged to researchers in LMIC for open access facilities.
Collaborative Expression: Transcriptomics of Conus virgo Suggests Contribution of Multiple Secretory Glands to Venom Production
Authors: Fedosov Alexander , Tucci Carmen Federica , Kantor Yuri , Farhat Sarah , Puillandre Nicolas 
Published: November 2023

AbstractVenomous marine gastropods of the family Conidae are among the most diversified predators in marine realm—in large due to their complex venoms. Besides being a valuable source of bioactive neuropeptides conotoxins, cone-snails venoms are an excellent model for molecular evolution studies, addressing origin of key innovations. However, these studies are handicapped by scarce current knowledge on the tissues involved in venom production, as it is generally assumed the sole prerogative of the venom gland (VG). The role of other secretory glands that are present in all Conus species (salivary gland, SG) or only in some species (accessory salivary gland, ASG) remains poorly understood. Here, for the first time, we carry out a detailed analysis of the VG, SG, and ASG transcriptomes in the vermivorous Conus virgo. We detect multiple transcripts clusters in both the SG and ASG, whose annotations imply venom-related functions. Despite the subsets of transcripts highly-expressed in the VG, SG, and ASG being very distinct, SG expresses an L-, and ASG—Cerm08-, and MEFRR- superfamily conotoxins, all previously considered specific for VG. We corroborate our results with the analysis of published SG and VG transcriptomes from unrelated fish-hunting C. geographus, and C. striatus, possibly fish-hunting C. rolani, and worm-hunting Conus quercinus. In spite of low expression levels of conotoxins, some other specific clusters of putative venom-related peptides are present and may be highly expressed in the SG of these species. Further functional studies are necessary to determine the role that these peptides play in envenomation. In the meantime, our results show importance of routine multi-tissue sampling both for accurate interpretation of tissue-specific venom composition in cone-snails, and for better understanding origin and evolution of venom peptides genes.
The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy
Authors: Piccardo Arnoldo , Treglia Giorgio , Fiz Francesco , Bar-Sever Zvi , Bottoni Gianluca , Biassoni Lorenzo , Borgwardt Lise , de Keizer Bart , Jehanno Nina , Lopci Egesta , Kurch Lars , Massollo Michela , Nadel Helen , Roca Bielsa Isabel , Shulkin Barry , Vali Reza , De Palma Diego , Cecchin Diego , Santos Ana Isabel , Zucchetta Pietro 
Published: November 2023

Abstract
Background
Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals.

Methods
We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA).

Results
Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5–46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies.

Conclusions
PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.
Coronary no-reflow and adverse events in patients with acute myocardial infarction after percutaneous coronary intervention with current drug-eluting stents and third-generation P2Y12 inhibitors
Authors: Ndrepepa Gjin , Cassese Salvatore , Xhepa Erion , Joner Michael , Sager Hendrik B. , Kufner Sebastian , Laugwitz Karl-Ludwig , Schunkert Heribert , Kastrati Adnan 
Published: November 2023

Abstract
Background
The frequency and prognostic value of coronary no-reflow (CNR) was investigated in studies that have used an outdated reperfusion therapy in terms of stent technology and antithrombotic drugs. We assessed the association of CNR with adverse outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and newer antithrombotic drugs, ticagrelor or prasugrel.

Methods
This study included 3100 patients with AMI who underwent PCI with current DES and third-generation P2Y12 inhibitors. CNR was defined as Thrombolysis in Myocardial Infarction (TIMI) blood flow grade ≤ 2 at the end of PCI. The primary end point was 1-year incidence of net adverse clinical and cerebral events—a composite end point of death of any cause, myocardial infarction, stroke or major bleeding.

Results
CNR was diagnosed in 130 patients (4.2%). The primary end point occurred in 28 patients in the CNR group and 354 patients in the reflow group (cumulative incidence 23.2% and 12.8%; adjusted hazard ratio = 1.53, 95% confidence interval 1.01–2.33; P = 0.049). The 1-year incidences of death or myocardial infarction (14.6% vs. 7.6%; P = 0.003), myocardial infarction (8.8% vs. 3.9%; P = 0.007) and major bleeding (10.9% vs. 5.6%; P = 0.008) were significantly higher in patients with CNR than patients with reflow. The risk of adverse events in patients with CNR was highest within the first 30 days after PCI.

Conclusion
In patients with AMI undergoing PCI with current DES and third generation P2Y12 receptor inhibitors, CNR was associated with a higher risk of adverse outcomes at 1 year.

Graphical abstract
Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation
Authors: Takeuchi Chihiro , Sato Junichi , Yamamichi Nobutake , Kageyama-Yahara Natsuko , Sasaki Akiko , Akahane Takemi , Aoki Rika , Nakajima Shigemi , Ito Masayoshi , Yamamichi Mitsue , Liu Yu-Yu , Sakuma Nobuyuki , Takahashi Yu , Sakaguchi Yoshiki , Tsuji Yosuke , Sakurai Kouhei , Tomida Shuta , Niimi Keiko , Ushijima Toshikazu , Fujishiro Mitsuhiro 
Published: November 2023

Abstract
Background
Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms.

Methods
A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression.

Results
Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach.

Conclusions
AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.
Evaluating a cutting-edge augmented reality-supported navigation system for spinal instrumentation
Authors: Schwendner Maximilian , Ille Sebastian , Wostrack Maria , Meyer Bernhard 
Published: November 2023

Abstract
Objective
Dorsal instrumentation using pedicle screws is a standard treatment for multiple spinal pathologies, such as trauma, infection, or degenerative indications. Intraoperative three-dimensional (3D) imaging and navigated pedicle screw placement are used at multiple centers. For the present study, we evaluated a new navigation system enabling augmented reality (AR)-supported pedicle screw placement while integrating navigation cameras into the reference array and drill guide. The present study aimed to evaluate its clinical application regarding safety, efficacy, and accuracy.

Methods
A total of 20 patients were operated on between 06/2021 and 01/2022 using the new technique for intraoperative navigation. Intraoperative data with a focus on accuracy and patient safety, including patient outcome, were analyzed. The accuracy of pedicle screw placement was evaluated by intraoperative CT imaging.

Results
A median of 8 (4–18) pedicle screws were placed in each case. Percutaneous instrumentation was performed in 14 patients (70%). The duration of pedicle screw placement (duration scan–scan) was 56 ± 26 (30–107) min. Intraoperative screw revision was necessary for 3 of 180 pedicle screws (1.7%). Intraoperatively, no major complications occurred—one case of delay due to software issues and one case of difficult screw placement were reported.

Conclusion
The current study's results could confirm the use of the present AR-supported system for navigated pedicle screw placement for dorsal instrumentation in clinical routine. It provides a reliable and safe tool for 3D imaging-based pedicle screw placement, only requires a minimal intraoperative setup, and provides new opportunities by integrating AR.
The changing pattern of common respiratory viruses among children from 2018 to 2021 in Wuhan, China
Authors: Wan Lu , Li Liangyu , Zhang Haiyue , Liu Chan , Li Ruiyun , Wu Xiaojun , Chen Jianjun 
Published: November 2023

Abstract
Background
Acute respiratory infections in children are a global public health challenge. Owing to the coronavirus disease (COVID-19) pandemic, non-pharmaceutical interventions, including patient isolation, social distancing, hand washing, and mask wearing, have been widely implemented, impacting the transmission of common respiratory viruses. The aim of this study was to clarify the epidemiological features of respiratory viruses in children less than 14 years of age in Wuhan before and after COVID-19.

Methods
Respiratory specimens were collected from patients aged < 14 years at two hospitals in Wuhan, China, from January 2018 to December 2021. Seven respiratory viruses were identified using an immunofluorescence assay. Pathogen profiles and seasonality were analysed.

Results
The number of visits and virus detection rate decreased dramatically after February 2020. The respiratory virus detection rate peaked in January and December and decreased dramatically in February and August. The detection rate was lower in 2021 than in 2018 and 2019. Respiratory syncytial virus (RSV) was identified as the leading pathogen in children aged < 1 year and 1–4 years before and after the COVID-19 pandemic. In children aged 5–14 years, influenza virus was detected at the highest rate before, and RSV after, the COVID-19 pandemic. RSV was the most common virus in coinfections.

Conclusions
This study revealed the epidemiological patterns of common respiratory viruses from 2018 to 2021. The spectrum of pathogens involved in paediatric respiratory infections had partly changed. Non-pharmaceutical interventions resulted in fewer opportunities for the spread of common viruses but also in an “immunity debt” that could have negative consequences when the pandemic is under control in Wuhan.
Rigorous engineering of collective adaptive systems – 2nd special section
Authors: Wirsing Martin , Jähnichen Stefan , De Nicola Rocco 
Published: November 2023

AbstractAn adaptive system is able to adapt at runtime to dynamically changing environments and to new requirements. Adaptive systems can be single adaptive entities or collective ones that consist of several collaborating entities. Rigorous engineering requires appropriate methods and tools that help guaranteeing that an adaptive system lives up to its intended purpose. This paper introduces the special section on “Rigorous Engineering of Collective Adaptive Systems.” It presents the 11 contributions of the section categorizing them into five distinct research lines: correctness by design and synthesis, computing with bio-inspired communication, new system models, machine learning, and programming and analyzing ensembles.
Constructing hermeneutical relations: a postphenomenological inquiry into immersive VR memory palaces
Authors: Vindenes Joakim , Wasson Barbara 
Published: November 2023

AbstractWhile VR adaptations of the mnemonic Method of Loci (or the ‘Memory Palace’ technique) show promising results in increasing mnemonic capabilities, little to no research has explored the use and integration of Virtual Memory Palaces over time in a context of self-initiated studying. To explore the use of Virtual Memory Palaces (VMPs) contextually, we conducted an in-the-wild study where we gave ten participants a VR Head-Mounted Display through which they could access and furnish their VMP over eight weeks. We conducted go-along interviews in our participants’ VMPs at various intervals throughout the eight-week study, exploring their creations and querying them about their experience. Based on our findings, this article discusses individual and contextual factors that come into play when a VMP is approached as a personal project in the midst of an already-established study routine. We frame our study as a postphenomenological inquiry into the mediating effects of VMPs, where our primary interest lies in what relationship the students developed to the VMP.
Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy
Authors: Michaeli Daniel Tobias , Michaeli Thomas , Albers Sebastian , Boch Tobias , Michaeli Julia Caroline 
Published: November 2023

Abstract
Background
Over the past decades, US Congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations and review pathways: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.

Objectives
This study reviews the FDA’s five special designations for drug development regarding their safety, efficacy/clinical benefit, clinical trials, innovation, economic incentives, development timelines, and price.

Methods
We conducted a keyword search to identify studies analyzing the impact of the FDA's special designations (orphan, fast track, accelerated approval, priority review, and breakthrough therapy) on the safety, efficacy/clinical benefit, trials, innovativeness, economic incentives, development times, and pricing of new drugs. Results were summarized in a narrative overview.

Results
Expedited approval reduces new drugs’ time to market. However, faster drug development and regulatory review are associated with more unrecognized adverse events and post-marketing safety revisions. Clinical trials supporting special FDA approvals frequently use small, non-randomized, open-label designs. Required post-approval trials to monitor unknown adverse events are often delayed or not even initiated. Evidence suggests that drugs approved under special review pathways, marketed as “breakthroughs”, are more innovative and deliver a higher clinical benefit than those receiving standard FDA approval. Special designations are an economically viable strategy for investors and pharmaceutical companies to develop drugs for rare diseases with unmet medical needs, due to financial incentives, expedited development timelines, higher clinical trial success rates, alongside greater prices. Nonetheless, patients, physicians, and insurers are concerned about spending money on drugs without a proven benefit or even on drugs that turn out to be ineffective. While European countries established performance- and financial-based managed entry agreements to account for this uncertainty in clinical trial evidence and cost-effectiveness, the pricing and reimbursement of these drugs remain largely unregulated in the US.

Conclusion
Special FDA designations shorten clinical development and FDA approval times for new drugs treating rare and severe diseases with unmet medical needs. Special-designated drugs offer a greater clinical benefit to patients. However, physicians, patients, and insurers must be aware that special-designated drugs are often approved based on non-robust trials, associated with more unrecognized side effects, and sold for higher prices.
Robots for inclusive classrooms: a scoping review
Authors: Díaz-Boladeras Marta , Claver i Díaz Ada , García-Sánchez Marta 
Published: November 2023

AbstractRobot-based activities have been proven to be a valuable tool for children with learning and developmental disabilities. However, their feasibility in general educational environments needs further exploration. This scoping review provides a critical examination of robot-based learning experiences involving children with disabilities, implemented either in mainstream schools or in specialized centers in order to gain insight into their potential to support inclusion. For this purpose, a search was conducted in the multidisciplinary Scopus and WoS databases, completed with Dialnet database. Based on PRISMA guidelines for literature reviews, we limited the systematic analysis to 33 papers published after 2009 that contain information on the instructional design and details of how the activities were implemented. On the other hand, studies reporting interventions with robots for clinical purposes were excluded as well as papers focused exclusively on technical developments. Content analysis shows that most experiences lead to improvements in terms of educational goals and/or stakeholders’ satisfaction. However, the analysis also reported issues that may hinder the adoption of these practices in general classrooms and integrated education services. The reported difficulties include the lack of stability and autonomy of the robots used, the need for aids and adaptations to enable children with sensory and physical impairments to interact easily with the robots, and the requirement of technical support with system’s setup, implementation and maintenance. We conclude that robots and robotics are a powerful tool to address the needs of diverse learners who are included in mainstream classrooms. This review aims at presenting evidences of good practices and recommendations for successful implementation.
On maximal partial Latin hypercubes
Authors: Donovan Diane M. , Grannell Mike J. , Yazıcı Emine Şule 
Published: November 2023

AbstractA lower bound is presented for the minimal number of filled cells in a maximal partial Latin hypercube of dimension d and order n. The result generalises and extends previous results for $$d=2$$

d
=
2

(Latin squares) and $$d=3$$

d
=
3

(Latin cubes). Explicit constructions show that this bound is near-optimal for large $$n> d$$

n
>
d

. For $$d>n$$

d
>
n

, a connection with Hamming codes shows that this lower bound gives a related upper bound for the same quantity. The results can be interpreted in terms of independent dominating sets in certain graphs, and in terms of codes that have covering radius 1 and minimum distance at least 2.