bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-induced TMTC3 expression in esophageal squamous cell carcinoma potentiates tumor angiogenesis through Rho GTPase/STAT3/VEGFA pathway
Authors: Yuan Hongyu , Zhao Zitong , Xu Jing , Zhang Ruiping , Ma Liying , Han Jing , Zhao Weihong , Guo Mingzhou , Song Yongmei 
Published: September 2023

Abstract
Background
Hypoxia is one of most typical features in the tumor microenvironment of solid tumor and an inducer of endoplasmic reticulum (ER) stress, and HIF-1α functions as a key transcription factor regulator to promote tumor angiogenesis in the adaptive response to hypoxia. Increasing evidence has suggested that hypoxia plays an important regulatory role of ER homeostasis. We previously identified TMTC3 as an ER stress mediator under nutrient-deficiency condition in esophageal squamous cell carcinoma (ESCC), but the molecular mechanism in hypoxia is still unclear.

Methods
RNA sequencing data of TMTC3 knockdown cells and TCGA database were analyzed to determine the association of TMTC3 and hypoxia. Moreover, ChIP assay and dual-luciferase reporter assay were performed to detect the interaction of HIF-1α and TMTC3 promoter. In vitro and in vivo assays were used to investigate the function of TMTC3 in tumor angiogenesis. The molecular mechanism was determined using co-immunoprecipitation assays, immunofluorescence assays and western blot. The TMTC3 inhibitor was identified by high-throughput screening of FDA-approved drugs. The combination of TMTC3 inhibitor and cisplatin was conducted to confirm the efficiency in vitro and in vivo.

Results
The expression of TMTC3 was remarkably increased under hypoxia and regulated by HIF-1α. Knockdown of TMTC3 inhibited the capability of tumor angiogenesis and ROS production in ESCC. Mechanistically, TMTC3 promoted the production of GTP through interacting with IMPDH2 Bateman domain. The activity of Rho GTPase/STAT3, regulated by cellular GTP levels, decreased in TMTC3 knockdown cells, whereas reversed by IMPDH2 overexpression. Additionally, TMTC3 regulated the expression of VEGFA through Rho GTPase/STAT3 pathway. Allopurinol inhibited the expression of TMTC3 and further reduced the phosphorylation and activation of STAT3 signaling pathway in a dose-dependent manner in ESCC. Additionally, the combination of allopurinol and cisplatin significantly inhibited the cell viability in vitro and tumor growth in vivo, comparing with single drug treatment, respectively.

Conclusions
Collectively, our study clarified the molecular mechanism of TMTC3 in regulating tumor angiogenesis and highlighted the potential therapeutic combination of TMTC3 inhibitor and cisplatin, which proposed a promising strategy for the treatment of ESCC.
Brain tissue oxygen monitoring in traumatic brain injury—part II: isolated and combined insults in relation to outcome
Authors: Svedung Wettervik Teodor , Beqiri Erta , Hånell Anders , Bögli Stefan Yu , Placek Michal , Guilfoyle Mathew R. , Helmy Adel , Lavinio Andrea , O’Leary Ronan , Hutchinson Peter J. , Smielewski Peter 
Published: September 2023

Abstract
Background
The primary aim was to explore the concept of isolated and combined threshold-insults for brain tissue oxygenation (pbtO2) in relation to outcome in traumatic brain injury (TBI).

Methods
A total of 239 TBI patients with data on clinical outcome (GOS) and intracranial pressure (ICP) and pbtO2 monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke’s Hospital, Cambridge, UK, between 2002 and 2022 were included. Outcome was dichotomised into favourable/unfavourable (GOS 4–5/1–3) and survival/mortality (GOS 2–5/1). PbtO2 was studied over the entire monitoring period. Thresholds were analysed in relation to outcome based on median and mean values, percentage of time and dose per hour below critical values and visualised as the combined insult intensity and duration.

Results
Median pbtO2 was slightly, but not significantly, associated with outcome. A pbtO2 threshold at 25 and 20 mmHg, respectively, yielded the highest x2 when dichotomised for favourable/unfavourable outcome and mortality/survival in chi-square analyses. A higher dose and higher percentage of time spent with pbtO2 below 25 mmHg as well as lower thresholds were associated with unfavourable outcome, but not mortality. In a combined insult intensity and duration analysis, there was a transition from favourable towards unfavourable outcome when pbtO2 went below 25–30 mmHg for 30 min and similar transitions occurred for shorter durations when the intensity was higher. Although these insults were rare, pbtO2 under 15 mmHg was more strongly associated with unfavourable outcome if, concurrently, ICP was above 20 mmHg, cerebral perfusion pressure below 60 mmHg, or pressure reactivity index above 0.30 than if these variables were not deranged. In a multiple logistic regression, a higher percentage of monitoring time with pbtO2 < 15 mmHg was associated with a higher rate of unfavourable outcome.

Conclusions
Low pbtO2, under 25 mmHg and particularly below 15 mmHg, for longer durations and in combination with disturbances in global cerebral physiological variables were associated with poor outcome and may indicate detrimental ischaemic hypoxia. Prospective trials are needed to determine if pbtO2-directed therapy is beneficial, at what individualised pbtO2 threshold therapies are warranted, and how this may depend on the presence/absence of concurrent cerebral physiological disturbances.
Decreasing consumption of sugar-sweetened beverages and Raising tap water consumption through Interventions based on Nutrition and sustainability for Kids: study protocol of the “DRINK” cluster randomised controlled trial
Authors: Castetbon Katia , Assakali Wassila , Thiébaut Isabelle , Desbouys Lucille 
Published: September 2023

Abstract
Background
Effectiveness of actions to reduce sugar-sweetened beverage (SB) consumption in children still needs to be improved. Furthermore, the growing concern about sustainable food systems encourages to develop sustainability-based interventions. The objective of this cluster randomised controlled trial is to evaluate the long-term effectiveness of nutrition- and environmental sustainability-based interventions on the reduction in SB intake and on the increase in tap water consumption in 3rd to 6th grade primary school children (8 to 11 years of age).

Methods
Forty-eight French-speaking Belgian primary schools (equivalent to around 3500 pupils involved in the evaluation) are randomised using a factorial plan: (i) control, (ii) nutrition-based intervention, (iii) sustainability-based intervention, and (iv) both. The interventions (encouragement of water breaks; provision of posters, leaflets, reusable cups, and glass bottles; website; meetings at school) were undertaken from February 2022 to June 2023. Evaluation includes questionnaires for the children and their parents on various determinants of dietary behaviour, a 4-day diary to collect information on the child’s beverage consumption, and audits at schools. The first evaluation was conducted in Spring 2021 before any intervention, with the two post-intervention evaluations being held in 2022 and 2023. The main quantitative judgement criterion will be the change over time in the mean SB consumption (in ml/day) in the intervention groups compared with the control group. Given the context of the research (school), the safety of the intervention, and the content of data collection, a consent was acknowledged as unnecessary by the Ethical Committee of the Faculty of Psychology (ULB; n°073/2021), but children and parents are explicitly informed of their right to refuse to fill in the questionnaires.

Discussion
Multicomponent interventions based on nutrition and on environmental sustainability, alone or mixed, will provide an original and topical insight into health promotion at school around dietary behaviours. The dissemination plan will enable to widely inform stakeholders, school staff, and families, in addition to the scientific community through the usual medium (articles, conferences), about the research findings in 2024–2025.

Trial registration
ISRCTN Registry ISRCTN99843102. Retrospectively registered on 25 May 2021
First report of the efficacy of a fluralaner-based pour-on product (Exzolt® 5%) against ectoparasites infesting cattle in Brazil
Authors: da Costa Alvimar José , de Souza Martins João Ricardo , de Almeida Borges Fernando , Vettorato Luis Fernando , Barufi Francisco Bonomi , de Oliveira Arriero Amaral Heitor , Abujamra Luara Carolina , de Castro Rodrigues Daniel , Zanetti Lopes Welber Daniel 
Published: September 2023

Abstract
Background
This study describes the effectiveness of a novel active pharmaceutical ingredient, fluralaner (isoxazoline class), against important ectoparasites infesting cattle in Brazil.

Methods
A total of 13 studies involving a 5% fluralaner-based pour-on formulation (Exzolt 5%; further referred to as Exzolt) were conducted. Specifically, the effectiveness of this formulation was studied against Rhipicephalus microplus (6 studies), Cochliomyia hominivorax larvae (4 studies), Dermatobia hominis larvae (1 study) and Haematobia irritans flies (2 studies).

Results
The therapeutic efficacy of Exzolt was found to exceed 98% at 4 days post treatment (DPT), while persistent efficacy (> 90% efficacy) against repeated infestations of R. microplus was observed for up to 79 DPT. In field studies, ≥ 98% therapeutic efficacy was demonstrated at all study sites by 7 DPT, and a persistent efficacy (> 90% efficacy) was observed for 42, 49 or 56 DPT. Exzolt prevented C. hominivorax eggs from developing to the larval stage, thus mitigating the development of myiasis in cattle naturally and artificially infested with this screworm. The efficacy of Exzolt against D. hominis larvae was 98% at 3 DPT, while persistent efficacy (> 90% effectiveness) was found to last for up to 70 DPT. Against H. irritans, Exzolt showed therapeutic efficacy (≥ 90%) within the first day of treatment at both study sites, while persistent efficacy (≥ 90%) was observed for 7 DPT at one site and for 21 DPT at the other site.

Conclusions
Overall, the results from these studies confirm that Exzolt is therapeutically efficacious against the most important ectoparasites infesting cattle in Brazil. The novel active pharmaceutical ingredient, fluralaner, provides a new treatment option for farmers to control cattle ectoparasites, especially where there is resistance to other chemical classes. In addition, an effective control of ectoparasites will improve overall cattle health and well-being as well as production.

Graphical Abstract
Borrelia persica infection in wild carnivores in Israel: molecular characterization and new potential reservoirs
Authors: Shwartz Dor , Nachum-Biala Yaarit , Oren Stephanie , Aharoni Kobi , Edery Nir , Moss Lior , King Roni , Lapid Roi , Straubinger Reinhard K. , Baneth Gad 
Published: September 2023

Abstract
Background
Borrelia persica causes tick-borne relapsing fever in Israel, the eastern Mediterranean basin, and Asia. Relapsing fever is associated with severe illness and potentially death in humans and animals. Since B. persica infection has rarely been described in wild animals, the aim of this study was to evaluate the prevalence of infection with B. persica in wild carnivores in Israel.

Methods
Spleen and blood clot samples from wild carnivores, which underwent necropsy, were tested for the presence of Borrelia DNA by real-time polymerase chain reaction (PCR). PCR products were sequenced, and the spirochete loads were quantified using a specific quantitative PCR (qPCR).

Results
A total of 140 samples from 74 wild carnivores were analyzed for the presence of Borrelia DNA. Six out of the 74 (8.1%) animals were found positive for B. persica by PCR and sequencing of the flagellin B gene, of which 4/74 (5.4%) were also positive by PCR for the glycerophosphodiester phosphodiesterase (glpQ) gene. Positive samples were obtained from three European badgers, and one striped hyena, golden jackal, and red fox each. All B. persica-positive animals were young males (P < 0.0001). Quantifiable results were obtained from 3/5 spleen and 4/5 blood samples. The spirochete loads in the blood were significantly higher than those found in the spleen (P = 0.034).

Conclusions
The prevalence of B. persica infection found in wild carnivores brought for necropsy was unexpectedly high, suggesting that this infection is widespread in some wild animal species in Israel. This is the first report of B. persica infection in the European badger and striped hyena. These carnivores have a wide geographical range of activity, and the results of this survey raise the possibility that they may serve as reservoir hosts for B. persica.

Graphical Abstract
Physical function and sex differences in radiographic axial spondyloarthritis: a cross-sectional analysis on Bath Ankylosing Spondylitis Functional Index
Authors: Hallström Magnus , Klingberg Eva , Deminger Anna , Rehnman Jeannette Beckman , Geijer Mats , Forsblad-d’Elia Helena 
Published: September 2023

Abstract
Background
Physical function is an important determinant of health-related quality of life in radiographic axial spondyloarthritis patients (r-axSpA). To improve the basis of effective healthcare efforts, we aimed to investigate which demographic and disease-related factors that influence Bath Ankylosing Spondylitis Functional Index (BASFI) in r-axSpA patients overall and stratified by sex. Furthermore, we sought to explore differences between sexes regarding separate BASFI questions and also to explore which factors that may contribute to these differences.

Methods
This observational cross-sectional study included patients fulfilling the modified New York criteria for Ankylosing Spondylitis. Patients were assessed with 66/68 joint count and Bath Ankylosing Spondylitis Metrology Index (BASMI) measurements. Lateral X-rays were performed for Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP), and BASFI were registered. Multivariable linear regression analyses were used to investigate which factors that associate with BASFI.

Results
A total of 353 r-axSpA patients were included, mean age 52.2 ± 12.7 years, 62.3% males. No significant sex difference was seen in BASFI scores (2.7 ± 2.0 in males vs 2.9 ± 2.1 in females). Age, body mass index, ASDAS-CRP, BASMI or mSASSS, fatigue, and tenderness were found to associate independently with BASFI in different models (R2 0.53–0.63). Investigation of separate BASFI questions revealed that the ability to look over shoulder was worse in males than females (mean 4.43 ± 3.37 vs 3.74 ± 3.06, p = 0.05) and most strongly correlated with mSASSS and BASMI among separate BASFI questions (r = 0.53, p < 0.001; r = 0.62, p < 0.001). The ability to climb stairs was worse in females than males (mean 2.49 ± 2.77 vs 1.54 ± 2.32, p < 0.001).

Conclusions
No difference between male and female r-axSpA patients was seen in BASFI despite significant sex differences in BASMI, mSASSS, and CRP levels. Our results underline the impact of fatigue and tenderness on BASFI. The ability to climb stairs without a handrail was scored worse among females compared to males. Furthermore, the ability to look over the shoulder was worse in males than females and closely related to spinal mobility and structural spinal changes.
A multi-omics study to investigate the progression of the Correa pathway in gastric mucosa in the context of cirrhosis
Authors: Ma Ruiguang , Li Qian , Yu Guoxian , Wang Jun , Li Yueyue , Xu Xinyan , Zhu Yiqing , Dong Min , Gao Yanjing , Li Lixiang , Li Zhen 
Published: September 2023

Abstract
Background
Patients with liver cirrhosis (LC) are prone to gastric mucosa damage. We investigated the alterations of gastric mucosa in LC patients and their possible mechanisms through multi-omics.

Results
We observed significant gastric mucosa microbial dysbiosis in LC subjects. Gastric mucosal microbiomes of LC patients contained a higher relative abundance of Streptococcus, Neisseria, Prevotella, Veillonella, and Porphyromonas, as well as a decreased abundance in Helicobacter and Achromobacter, than control subjects. The LC patients had higher levels of bile acids (BAs) and long-chain acylcarnitines (long-chain ACs) in serum. The gastric mucosal microbiomes were associated with serum levels of BAs and long-chain ACs. Transcriptome analyses of gastric mucosa revealed an upregulation of endothelial cell specific molecule 1, serpin family E member 1, mucin 2, caudal type homeobox 2, retinol binding protein 2, and defensin alpha 5 in LC group. Besides, the bile secretion signaling pathway was significantly upregulated in the LC group.

Conclusions
The alterations in the gastric mucosal microbiome and transcriptome of LC patients were identified. The impaired energy metabolism in gastric mucosal cells and bile acids might aggravate the inflammation of gastric mucosa and even exacerbate the Correa’s cascade process. The gastric mucosal cells might reduce bile acid toxicity by bile acid efflux and detoxification.
Trial registration: ChiCTR2100051070.
Convergent evolution and convergent loss in the grasping structures of immature earwigs and aphidlion-like larvae as demonstrated by about 100-million-year-old fossils
Authors: Haug Carolin , Haug Gideon T. , Kiesmüller Christine , Haug Joachim T. 
Published: September 2023

AbstractConvergent evolution is a common phenomenon, independently leading to similar morphologies in different evolutionary lineages. Often similar functional demands drive convergent evolution. One example is the independent evolution of grasping structures in different lineages of Euarthropoda, though the exact morphology of these grasping structures varies significantly. In this study, we investigated grasping apparatuses with two movable counteracting structures as well as some related structures, exemplified by the stylets (compound structures of mouthparts) of aphidlion-like larvae (part of Neuroptera or lacewings) and the cerci of immature earwigs (Dermaptera). For the stylets of aphidlion-like larvae, studies have pointed to a significant loss in morphological diversity in the last 100 million years. We used quantitative morphology to evaluate if a similar process has also occurred in the cerci of earwigs. The cerci of extant immature earwigs exhibit two distinct types of morphologies in the modern fauna: elongated cerci divided into several ringlets with a feeler-type function, and pincer-like stout cerci. In some fossil immature earwigs, however, the cerci are generally elongated but undivided and roughly occupy the morphospace between those of the two modern cerci types; hence this fossil cerci morphology appears to have been lost. To some extent, a comparable loss is also found in certain lacewing larvae. Outgroup comparisons suggest that the morphologies no longer present today are in fact not ancestral, but instead specialised, hence their loss is possibly resulting from disruptive evolution in earwigs as well as lacewings. We discuss the possible functions of these specialised grasping structures.
Lung aeration estimated by chest electrical impedance tomography and lung ultrasound during extubation
Authors: Joussellin Vincent , Bonny Vincent , Spadaro Savino , Clerc Sébastien , Parfait Mélodie , Ferioli Martina , Sieye Antonin , Jalil Yorschua , Janiak Vincent , Pinna Andrea , Dres Martin 
Published: September 2023

Abstract
Background
This study hypothesized that patients with extubation failure exhibit a loss of lung aeration and heterogeneity in air distribution, which could be monitored by chest EIT and lung ultrasound. Patients at risk of extubation failure were included after a successful spontaneous breathing trial. Lung ultrasound [with calculation of lung ultrasound score (LUS)] and chest EIT [with calculation of the global inhomogeneity index, frontback center of ventilation (CoV), regional ventilation delay (RVD) and surface available for ventilation] were performed before extubation during pressure support ventilation (H0) and two hours after extubation during spontaneous breathing (H2). EIT was then repeated 6 h (H6) after extubation. EIT derived indices and LUS were compared between patients successfully extubated and patients with extubation failure.

Results
40 patients were included, of whom 12 (30%) failed extubation. Before extubation, when compared with patients with successful extubation, patients who failed extubation had a higher LUS (19 vs 10, p = 0.003) and a smaller surface available for ventilation (352 vs 406 pixels, p = 0.042). After extubation, GI index and LUS were higher in the extubation failure group, whereas the surface available for ventilation was lower. The RVD and the CoV were not different between groups.

Conclusion
Before extubation, a loss of lung aeration was observed in patients who developed extubation failure afterwards. After extubation, this loss of lung aeration persisted and was associated with regional lung ventilation heterogeneity.
Trial registration Clinical trials, NCT04180410, Registered 27 November 2019—prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04180410.
The burden of vision loss in the Middle East and North Africa region, 1990–2019
Authors: Bahremani Erfan , Alizadeh Mahasti , Nejadghaderi Seyed Aria , Noori Maryam , Sullman Mark J M , Kolahi Ali-Asghar , Safiri Saeid 
Published: September 2023

Abstract
Background
The loss of vision is a substantial public health concern that has important implications for an individual’s quality of life. The primary objective of this research was to document the burden of vision loss in the Middle East and North Africa (MENA) region, spanning the years 1990–2019, by age group, sex, underlying cause and sociodemographic index (SDI).

Methods
Publicly available data concerning the burden of vision loss were acquired from the Global Burden of Disease study 2019. The data encompassed all 21 countries within the MENA region for the period spanning 1990 to 2019. The estimates were reported as raw counts and age-standardised rates per 100,000, accompanied by their corresponding 95% uncertainty intervals (UIs).

Results
In 2019, MENA had an age-standardised point prevalence of 7040.0 (95% UI: 6195.0, 8002.7) and an YLD rate of 314.5 (222.1, 427.6) per 100,000 for vision loss, which were 11.1% (-12.5, -9.7) and 24.3% (-27.6, -20.8) lower, respectively, than in 1990. In 2019, Afghanistan [469.6 (333.0, 632.8)] had the largest age-standardised YLD rate and Turkey [210.7 (145.3, 290.9)] had the lowest. All countries showed a decrease in the age-standardised point prevalence and YLD rate between 1990 and 2019, except for Oman, Afghanistan, and Yemen. Furthermore, in 2019 the largest number of prevalent cases and YLDs were found in the 65–69 age group. Also in 2019, the age-standardised YLD rates in MENA exceeded the global averages for most age groups, for both males and females. In 2019, refractive disorders were the most common types of vision loss among children, adolescents, and middle-age adults in MENA, while near vision loss and cataracts were the most common among older adults. Finally, the burden of vision loss had a slightly negatively association with SDI over the period 1990–2019.

Conclusion
Although the burden of vision loss has decreased over the last three decades, the prevalence remains high. These results underscore the importance of healthcare policymakers taking action to implement preventive measures, especially among the elderly and those living in low socioeconomic countries, to decrease the attributable burden in MENA.