bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of the pharmacology and clinical applications of levetiracetam in dogs and cats
Authors: Mastrocco Alicia , Prittie Jennifer , West Chad , Clark Melissa
Published: November 2023

Objective

To review and summarize the pharmacology of the antiepileptic drug (AED), levetiracetam (LEV), and to discuss its clinical utility in dogs and cats.

Data Sources

Veterinary and human peer‐reviewed medical literature and the authors’ clinical experience.

LEV is an AED with mechanisms of action distinct from those of other AEDs. In people and small animals, LEV exhibits linear kinetics, excellent oral bioavailability, and minimal drug–drug interactions. Serious side effects are rarely reported in any species. LEV use is gaining favor for treating epilepsy in small animals and may have wider clinical applications in patients with portosystemic shunts, neuroglycopenia, and traumatic brain injury. In people, LEV may improve cognitive function in patients with dementia.

Conclusion

LEV is a well‐tolerated AED with well‐documented efficacy in human patients. Although its use is becoming more common in veterinary medicine, its role as a first‐line monotherapy in small animal epileptics remains to be determined. This review of the human and animal literature regarding LEV describes its role in epileptic people and animals as well as in other disease states and provides recommendations for clinical usage.
Slopes in eigenvarieties for definite unitary groups
Authors: Ye Lynnelle
Published: November 2023

We generalize bounds of Liu–Wan–Xiao for slopes in eigencurves for definite unitary groups of rank $2$ to slopes in eigenvarieties for definite unitary groups of any rank. We show that for a definite unitary group of rank $n$, the Newton polygon of the characteristic power series of the $U_p$ Hecke operator has exact growth rate $x^{1+2/{n(n-1)}}$, times a constant proportional to the distance of the weight from the boundary of weight space. The proof goes through the classification of forms associated to principal series representations. We also give a consequence for the geometry of these eigenvarieties over the boundary of weight space.
Comments on and illustrations of the WFUMB CEUS liver guidelines: Rare malignant mesenchymal liver lesions
Authors: Zadeh Ehsan Safai , Schreiber Nicole , Görg Christian , Huber Katharina Paulina , Möller Kathleen , Berzigotti Analisa , Thomsen Thomas , Jenssen Christian , Jung Ernst-Michael , Lim Adrian , Kitano Masayuki , Shimizu Ryo , Dong Yi , Cui Xin Wu , Srivastava David , Dietrich Christoph F.
Published: November 2023

The diagnosis or rare mesenchymal malignant lesions of the liver may be a challenge owing to the rarity of the disease and is usually made by histological confirmation. An ultrasound examination with, if required, color Doppler sonography and contrast-enhanced ultrasound, taking into account the clinical background of the patient, may help to focus the differential diagnosis. In this review, we describe the pathological and ultrasound features of several rare mesenchymal malignant liver lesions which include undifferentiated sarcoma of the liver, leiomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, and epithelioid hemangioendothelioma.
Effects of Breaking Up Sedentary Behavior With Short Bouts of Yoga and Tai-Chi on Glycemia, Concentration, and Well-Being
Authors: Colvin Alexander , Murray Lynne , Noble Jillian , Chastin Sebastien
Published: November 2023

Background: Investigating the effects of breaking up sedentary behavior with short bouts of Yoga and Tai-Chi on glycemic control, concentration, and well-being in healthy individuals. Methods: In this randomized balanced incomplete block study, 15 adults (age = 26 [2.50] y, 8 females) completed 2 of 3 protocols: uninterrupted sitting (Control), sitting interrupted with 3 minutes of Yoga every 30 minutes, or with 3 minutes of Tai-Chi every 30 minutes. Protocols lasted 7.5 hours and included a standardized diet. Glucose was measured every 30 minutes with a glucometer (Abbott FreeStyle Libre). Concentration and well-being were recorded with self-reported ecological momentary assessment. Area under the curve was calculated for glucose data. Statistical analyses were performed as a hierarchical repeated-measures model. Results: Glucose area under the curve for the Yoga intervention (34.55 [3.12] mmol/L) was significantly lower than the Control (38.14 [3.18] mmol/L; P < .05). There was a trend toward lower glucose in the Tai-Chi group compared with the Control, but no significant differences were found (AUCTai-Chi = 36.64 [3.11] mmol/L; P = .57). Mean concentration in all groups decreased throughout the day, with the largest decrease in the Control. Well-being for the Yoga and Control groups decreased but increased with Tai-Chi. Concentration and well-being responses were not statistically significant between intervention groups. Conclusions: Breaking up sedentary behavior using 3-minute bouts of Yoga significantly lowers blood glucose in healthy individuals without compromising concentration or well-being. Tai-Chi did not provide the same significant effect on glucose levels but allowed better maintenance of concentration and well-being. These interventions provide effective ways to combat the deleterious effects of prolonged sedentary time while maintaining concentration and well-being.
Macrophage activation drives ovarian failure and masculinization in zebrafish
Authors: Bravo Paloma , Liu Yulong , Draper Bruce W. , Marlow Florence L.
Published: November 2023

BMP15 is a conserved regulator of ovarian development and maintenance in vertebrates. In humans, premature ovarian insufficiency is caused by autoimmunity and genetic factors, including mutation of BMP15. The cellular mechanisms underlying ovarian failure caused by BMP15 mutation and immune contributions are not understood. Using zebrafish, we established a causal link between macrophage activation and ovarian failure, which, in zebrafish, causes sex reversal. We define a germline-soma signaling axis that activates macrophages and drives ovarian failure and female-to-male sex reversal. Germline loss of zebrafish Bmp15 impairs oogenesis and initiates this cascade. Single-cell RNA sequencing and genetic analyses implicate ovarian somatic cells that express conserved macrophage-activating ligands as mediators of ovarian failure and sex reversal. Genetic ablation of macrophages or elimination of Csf1Rb ligands, Il34 or Csf1a, delays or blocks premature oocyte loss and sex reversal. The axis identified here provides insight into the cells and pathways governing oocyte and ovary maintenance and potential therapeutic targets to preserve female fertility.
HILPS
, a long noncoding RNA essential for global oxygen sensing in humans
Authors: Chen Zhi , Chen Chan , Xiao Lei , Tu Rongfu , Yu Miaomiao , Wang Donghai , Kang Wenqian , Han Meng , Huang Hao , Liu Hudan , Zhao Bing , Qing Guoliang
Published: November 2023

Adaptation to low levels of oxygen (hypoxia) is a universal biological feature across metazoans. However, the unique mechanisms how different species sense oxygen deprivation remain unresolved. Here, we functionally characterize a novel long noncoding RNA (lncRNA),
LOC105369301
, which we termed hypoxia-induced lncRNA for polo-like kinase 1 (PLK1) stabilization (
HILPS
).
HILPS
exhibits appreciable basal expression exclusively in a wide variety of human normal and cancer cells and is robustly induced by hypoxia-inducible factor 1α (HIF1α).
HILPS
binds to PLK1 and sequesters it from proteasomal degradation. Stabilized PLK1 directly phosphorylates HIF1α and enhances its stability, constituting a positive feed-forward circuit that reinforces oxygen sensing by HIF1α.
HILPS
depletion triggers catastrophic adaptation defect during hypoxia in both normal and cancer cells. These findings introduce a mechanism that underlies the HIF1α identity deeply interconnected with PLK1 integrity and identify the
HILPS
-PLK1-HIF1α pathway as a unique oxygen-sensing axis in the regulation of human physiological and pathogenic processes.
Obesity and lifespan, a complex tango
Authors: Diaz-Ruiz Alberto , Price Nathan L. , Ferrucci Luigi , de Cabo Rafael
Published: November 2023

Obesity and aging share comorbidities, phenotypes, and deleterious effects on health that are associated with chronic diseases. However, distinct features set them apart, with underlying biology that should be explored and exploited, especially given the demographic shifts and the obesity epidemic that the world is facing.
Shared sequence characteristics identified in non-canonical rearrangements of HSV-1 genomes
Authors: Shitrit Alina , Nisnevich Valerya , Rozenshtein Nofar , Kobo Hila , Phan Hoang Van , Tay Savaş , Szpara Moriah , Weitzman Matthew D. , Drayman Nir , Kobiler Oren
Published: November 2023

Genomic rearrangements contribute to the enhancement of genetic diversity in populations. However, non-canonical rearrangements (NCRs) such as deletions, insertions, and inversions have the potential to trigger genomic instability. In the case of DNA viruses, NCRs can lead to generation of defective viral genomes (DVGs). To study NCRs in herpes simplex virus type 1 (HSV-1) genomes, we enriched DVGs formation by undiluted serial passaging on various cell types. We found that viral passaging on cell type that enables more viral genomes to initiate replication induces higher amplitude and frequency of cyclic patterns associated with DVGs formation. Despite differences in the rates of DVG accumulation, cell lines displayed comparable quantities of distinct NCRs, indicating that fluctuations caused by DVGs may impose bottlenecks on population genetic diversity. These findings propose additional roles for DVGs in modulating viral genetic diversity. Each cell type exhibited a unique population of NCRs, suggesting that NCRs accumulate in a cell type-specific manner. Interestingly, we identified a higher prevalence of short homologies and short reverse complementary in the parental sequences of NCR junction sites across all cell types. These shared sequence characteristics were also observed in NCRs identified in sequences obtained from clinical samples. The fundamental properties of HSV-1 NCR formation uncovered in this study may have broader implications for other DNA viruses.

IMPORTANCE

Mutations and genetic rearrangements are the primary driving forces of evolution. Viruses provide valuable model systems for investigating these mechanisms due to their rapid evolutionary rates and vast genetic variability. To investigate genetic rearrangements in the double-stranded DNA genome of herpes simplex virus type 1, the viral population was serially passaged in various cell types. The serial passaging led to formation of defective genomes, resulted from cell-specific non-canonical rearrangements (NCRs). Interestingly, we discovered shared sequence characteristics underlying the formation of these NCRs across all cell types. Moreover, most NCRs identified in clinical samples shared these characteristics. Based on our findings, we propose a model elucidating the formation of NCRs during viral replication within the nucleus of eukaryotic cells.
The phage fought the cells, and the phage won: a satellite symposium at the ASV 2023 annual meeting
Authors: Parent Kristin N.
Published: November 2023

This satellite symposium was focused on the molecular arms race between bacteria and their predators, the bacteriophages: who’s the friend and who’s the foe? This
Gem
recounts highlights of the talks and presents food for thought and additional reflections on the current state of the field.
HIV-2 inhibits HIV-1 gene expression via two independent mechanisms during cellular co-infection
Authors: Yapo Vincent , Majumder Kinjal , Tedbury Philip R. , Wen Xin , Ong Yee T. , Johnson Marc C. , Sarafianos Stefan G.
Published: November 2023

Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). The two main forms of HIV are HIV-1 and HIV-2; in the clinic, each is predominantly found in the context of monoinfection. However, dual infections are found in regions where HIV-1 and HIV-2 coexist, such as West Africa. Both viruses can induce AIDS; however, HIV-2 is generally less pathogenic than HIV-1 and progresses more slowly to AIDS. Additionally, there are reports that HIV-2 infection can reduce HIV-1-associated pathogenesis in dual-infected patients, and in cell culture. However, the mechanisms underlying these protective effects are not well understood. To decipher these mechanisms, we performed dual infections with HIV-1 and HIV-2 in cell culture. We demonstrated that HIV-1 and HIV-2 can co-infect individual cells. HIV-2 infection was found to inhibit HIV-1 infection when performed prior to or simultaneously with HIV-1 infection. Two distinct mechanisms were identified. First, HIV-2 induces an interferon (IFN) response that broadly inhibits gene expression. Second, in the absence of IFN production, HIV-1-specific inhibition was found to be conferred by the HIV-2 trans-activation response (TAR) element. The HIV-2 TAR (TAR-2) element appears to inhibit HIV-1 long terminal repeat (LTR) promoter activity through competition with the HIV-1 TAR element for HIV-1 Tat binding. We show that this results in suppression of HIV-1 LTR-driven transcription by stalling RNA polymerase II early transcription complexes at the HIV-1 LTR promoter region.

IMPORTANCE

Twenty-five years after the first report that HIV-2 infection can reduce HIV-1-associated pathogenesis in dual-infected patients, the mechanisms are still not well understood. We explored these mechanisms in cell culture and showed first that these viruses can co-infect individual cells. Under specific conditions, HIV-2 inhibits HIV-1 through two distinct mechanisms, a broad-spectrum interferon response and an HIV-1-specific inhibition conferred by the HIV-2 TAR. The former could play a prominent role in dually infected individuals, whereas the latter targets HIV-1 promoter activity through competition for HIV-1 Tat binding when the same target cell is dually infected. That mechanism suppresses HIV-1 transcription by stalling RNA polymerase II complexes at the promoter through a minimal inhibitory region within the HIV-2 TAR. This work delineates the sequence of appearance and the modus operandi of each mechanism.
Metagenome-assembled genomes from particle-associated microbial communities in the mesopelagic zone of the Pacific Ocean
Authors: Hollensteiner Jacqueline , Schneider Dominik , Poehlein Anja , Himmelbach Axel , Daniel Rolf
Published: November 2023

We report 10 particle-associated metagenome-assembled genomes (MAGs) from the mesopelagic zone of Pacific Ocean seawaters. MAGs comprise members of
Flavobacteria Halomonas
,
Blastomonas
,
Brevundimonas
,
Alteromonas, Shingomonas
,
Sphingopyxis
,
Tabrizicola, Proteobacteria
, and
Gammaproteobacteria
. Functional annotation suggests that these bacteria are involved in central particulate organic carbon conversion, nitrogen cycling, and phosphorus cycling.
Association between administration or recommendation of the human papillomavirus vaccine and primary care physicians’ knowledge about vaccination during proactive recommendation suspension: a nationwide cross-sectional study in Japan
Authors: Sakanishi Yuta , Takeuchi Jiro , Suganaga Rei , Nakayama Kuniko , Nishioka Yosuke , Chiba Hiroshi , Kishi Tomomi , Machino Ako , Mastumura Mami , Okada Tadao , Suzuki Tomio
Published: November 2023

Objective

The Japanese government suspended the proactive recommendation of the human papillomavirus vaccine (HPVv) in 2013, and the vaccination rate of HPVv declined to <1% during 2014–2015. Previous studies have shown that the recommendation by a physician affects a recipient’s decision to receive a vaccine, and physicians’ accurate knowledge about vaccination is important to increase vaccine administration. This study aimed to evaluate the association between physicians’ knowledge of vaccination and the administration or recommendation of HPVv by primary care physicians (PCPs) in the absence of proactive recommendations from the Japanese government.

Design

Cross-sectional study analysed data obtained through a web-based, self-administered questionnaire survey.

Setting

The questionnaire was distributed to Japan Primary Care Association (JPCA) members.

Participants

JPCA members who were physicians and on the official JPCA mailing list (n=5395) were included.

Primary and secondary outcome measures

The primary and secondary outcomes were the administration and recommendation of HPVv, respectively, by PCPs. The association between PCPs’ knowledge regarding vaccination and each outcome was determined based on their background and vaccination quiz scores and a logistic regression analysis to estimate the adjusted ORs (AORs).

Results

We received responses from 1084 PCPs and included 981 of them in the analysis. PCPs with a higher score on the vaccination quiz were significantly more likely to administer the HPVv for routine and voluntary vaccination (AOR 2.28, 95% CI 1.58 to 3.28; AOR 2.71, 95% CI 1.81 to 4.04, respectively) and recommend the HPVv for routine and voluntary vaccination than PCPs with a lower score (AOR 2.17, 95% CI 1.62 to 2.92; AOR 1.88, 95% CI 1.32 to 2.67, respectively).

Conclusions

These results suggest that providing accurate knowledge regarding vaccination to PCPs may improve their administration and recommendation of HPVv, even in the absence of active government recommendations.
Clinical staging across eating disorders: a scoping review protocol
Authors: Hyam Lucy Elizabeth , Phillips Matthew , Gracie Lara , Allen Karina , Schmidt Ulrike
Published: November 2023

Introduction

Clinical staging models in psychiatry assert that there are earlier, less severe or more malleable forms of illness that are distinguishable from later, more chronic forms of illness, and that these stages may have different prognostic and treatment implications. Previous reviews on clinical staging in eating disorders (EDs) suggest a staging heuristic could be useful for anorexia nervosa, but less research is available on how this applies to other EDs. An up-to-date review is required to synthesise new and heterogenous avenues of research. This scoping review aims to explore the extent and types of evidence in relation to illness staging for EDs and how these concepts are associated with treatment response and outcomes.

Methods and analysis

This protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension for Scoping Reviews checklist and the Joanna Briggs Institute Reviewer’s Manual. We will consider any documents providing evidence for clinical staging such as those which describe full or partial staging models, for all EDs, across various domains of assessment and functioning. Participants will include clinical or non-clinical population samples with full-syndrome EDs or disordered eating behaviour. PubMed, PsycINFO, MEDLINE and Web of Science databases will be systematically searched for relevant literature. Two authors will export documents and screen titles, abstracts and full texts. Data will be extracted into a charting form drafted by the authors. A narrative summary of the documents will be conducted in line with the study aims. Finally, clinical and research recommendations will be outlined.

Ethics and dissemination

Ethical approval will not be required to synthesise published and unpublished literature. The study will be published in a peer-reviewed journal and shared at conferences, via social media, and in other communications.
Protocol of a randomised trial of teriparatide followed by zoledronic acid to reduce fracture risk in adults with osteogenesis imperfecta
Authors: Hald Jannie D , Keerie Catriona , Weir Christopher J , Javaid Muhammad K , Lam Wayne , Osborne Patricia , Walsh Jennifer , Langdahl Bente L , Ralston Stuart H
Published: November 2023

Introduction

Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI.

Methods and analysis

Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL.

Ethics and dissemination

The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care.

Trial registration number

ISRCTN15313991.
Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial
Authors: Zhu Jiaying , Sun Chuqing , Li Min , Hu Guoru , Zhao Xing-Ming , Chen Wei-Hua
Published: November 2023

Objective

We aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.

Design

Healthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences between the PPI and H2RA groups.

Results

Both interventions disrupted the gut microbiota, with PPIs demonstrating more pronounced effects. PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut. This led to a significant increase in both the number and total abundance of oral species present in the gut, including the identification of known disease-associated species like
Fusobacterium nucleatum
and
Streptococcus anginosus
. Overall, gut microbiome-based machine learning classifiers could accurately distinguish PPI from non-PPI users, achieving an area under the receiver operating characteristic curve (AUROC) of 0.924, in contrast to an AUROC of 0.509 for H2RA versus non-H2RA users.

Conclusion

Our study provides evidence that PPIs have a greater impact on the gut microbiome and oral-to-gut transmission than H2RAs, shedding light on the mechanism underlying the higher risk of certain diseases associated with prolonged PPI use.

Trial registration number

ChiCTR2300072310.
Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand
Authors: Lauhasurayotin Supanun , Moonla Chatphatai , Ittiwut Rungnapa , Ittiwut Chupong , Songthawee Natsaruth , Komvilaisak Patcharee , Natesirinilkul Rungrote , Sirachainan Nongnuch , Rojnuckarin Ponlapat , Sosothikul Darintr , Suphapeetiporn Kanya
Published: November 2023

Aims

Von Willebrand disease (VWD) is an inherited haemostatic disorder with a wide range of bleeding phenotypes based on von Willebrand factor (VWF) levels. Multiple assays includingVWFgene analysis are employed to correctly diagnose VWD and its subtypes. However, data onVWFmutations among Southeast Asian populations are lacking. We, therefore, aimed to explore genetic variations in Thai patients with type 2 and type 3 VWD by whole exome sequencing (WES).

Methods

In this multicentre study, Thai patients with type 2 and type 3 VWD, according to the definitions and VWF levels recommended by the international guidelines, were recruited. WES was performed using DNA extracted from peripheral blood in all cases. The novel variants were verified by Sanger sequencing.

Results

Fifteen patients (73% females; median age at diagnosis 3.0 years) with type 2 (n=12) and type 3 VWD (n=3) from 14 families were enrolled. All patients harboured at least oneVWFvariant. Six missense (p.Arg1374Cys, p.Arg1374His, p.Arg1399Cys, p.Arg1597Trp, p.Ser1613Pro, p.Pro1648Arg) and one splice-site (c.3379+1G>A) variants in theVWFgene were formerly described. Notably, sixVWFvariants, including three missense (p.Met814Ile, p.Trp856Cys, p.Pro2032Leu), one deletion (c.2251delG) and two splice-site (c.7729+4A>C, c.8115+2delT) mutations were novelly identified. Compound heterozygosity contributed to type 2 and type 3 VWD phenotypes in two and one patients, respectively.

Conclusions

Type 2 and type 3 VWD in Thailand demonstrate the mutational variations amongVWFexons/introns with several unique variants. The WES-based approach potentially provides helpful information to verify VWD diagnosis and facilitate genetic counselling in clinical practice.
Understanding progressive tissue loss and wound burden in combat casualties: lessons learnt for future operational capability
Authors: Staruch Robert , Naumann D N , Wordsworth M , Jeffery S , Rickard R
Published: November 2023

Understanding tissue loss following injury is important due to its prevalence among the war-wounded and the impact it has on subsequent treatment and rehabilitation. Progressive tissue loss is a type of tissue loss that has complicated extremity injury in recent conflicts. It has resulted in more proximal residual limb lengths and has influenced rehabilitation. Quantifying wound burden in combat casualties remains a challenge due to poor quality of data sets that lack the capacity for detailed analysis. The aims of this article are to outline the current hurdles in attempting to quantify wound burden in combat casualties and to propose simple interventions to improve data capture for future analysis.
Outdoor light at night and mortality in the UK Biobank: a prospective cohort study
Authors: Liang Xue , Wang Zixin , Cai Honglin , Zeng Yi Qian , Chen Jinjian , Wei Xianglin , Dong Guanghui , Huang Yu , Lao Xiang Qian
Published: November 2023

Background

More than 83% of the world’s population lives under light-polluted skies while information about health effects of outdoor light at night (LAN) is limited. We examined the association of LAN with natural cause (NC) and cardiovascular disease (CVD) mortality using the UK Biobank.

Methods

We included 273 335 participants recruited between 2006 and 2010. Level of LAN was estimated at each participant’s address using time-varying satellite data for a composite of persistent night-time illumination at ~1 km2scale. Information on causes of death until 12 November 2021 was obtained through record linkage. Cox proportional hazards regression was used.

Results

In the follow-up with an average of 12.4 years, 14 864 NC and 3100 CVD deaths were identified. Compared with the participants exposed to the first quartile of LAN, participants exposed to the highest quartile showed an 8% higher risk of NC mortality (HR: 1.08, 95% CI 1.03 to 1.13) after adjusting for age, sex, social-economic status, shift work, lifestyle factors and body mass index. However, the association disappeared after further adjustment for PM2.5and evening noise, with HRs (95% CIs) of 1.02 (0.97 to 1.07), 1.01 (0.97 to 1.06) and 1.03 (0.97 to 1.08), respectively, for the participants exposed to the second, third and fourth quartiles of LAN. No significant associations were observed between LAN and CVD mortality, either.

Conclusions

We did not observe significant associations of LAN with NC and CVD mortality in this large nationwide cohort. The health effects of LAN remain unclear. Further studies are warranted to address this public health concern.
Deciphering MMP9’s dual role in regulating SOD3 through protein–protein interactions
Authors: Gawargi Flobater I. , Mishra Paras K.
Published: November 2023

Although the collagenase enzyme activity of matrix metalloproteinase-9 (MMP9) is well-documented, its non-enzymatic functions remain less understood. The interaction between intracellular superoxide dismutase-1 (SOD1) and MMP9 is known, with SOD1 suppressing MMP9. However, the mechanism by which MMP9, a secretory protein, influences the extracellular antioxidant superoxide dismutase-3 (SOD3) is not yet clear. To explore MMP9's regulatory impact on SOD3, we employed human embryonic kidney-293 cells, transfecting them with MMP9 overexpresssion and catalytic-site mutant plasmids. Additionally, MMP9 overexpressing cells were treated with an MMP9 activator and inhibitor. Analyses of both cell lysates and culture medium provided insights into MMP9's intracellular and extracellular regulatory roles. In-silico analysis and experimental approaches like proximal ligation assay and co-immunoprecipitation were utilized to delineate the protein-protein interactions between MMP9 and SOD3. Our findings indicate that activated MMP9 enhances SOD3 levels, a regulation not hindered by MMP9 inhibitors. Intriguingly, catalytically inactive MMP9 appeared to reduce SOD3 levels, likely due to MMP9's binding with SOD3, leading to their proteolytic degradation. This MMP9 influence on SOD3 was consistent in both intracellular and extracellular environments, suggesting a parallel in MMP9-SOD3 interactions across these domains. Ultimately, this study unveils a novel interaction between MMP9 and SOD3, highlighting the unique regulatory role of catalytically inactive MMP9 in diminishing SOD3 levels, contrasting its usual upregulation by active MMP9.
A proposed renormalization scheme for non-local QFTs and application to the hierarchy problem
Authors: Abu-Ajamieh Fayez , Vempati Sudhir K.
Published: November 2023

We propose a renormalization scheme for non-local Quantum Field Theories (QFTs) with infinite derivatives inspired by string theory. Our Non-locality Renormalization Scheme (NRS) is inspired by Dimensional Regularization (DR) in local QFTs and is shown to significantly improve the UV behavior of non-local QFTs. We illustrate the scheme using simple examples from the $$\phi ^{3}$$

ϕ
3

and $$\phi ^{4}$$

ϕ
4

theories, then we evaluate the viability of NRS-enhanced non-local QFTs to solve the hierarchy problem using a simplified toy model. We find that non-locality protects the mass of a light scalar from receiving large corrections from any UV sector to which it couples, as long as the non-locality scale $$\Lambda $$
Λ
is sufficiently smaller than the scale of the UV sector. We also find that NRS eliminates any large threshold corrections from the IR sector.
Demonstration of 75 km-fiber quantum clock synchronization in quantum entanglement distribution network
Authors: Tang Bang-Ying , Tian Ming , Chen Huan , Han Hui , Zhou Han , Li Si-Chen , Xu Bo , Dong Rui-Fang , Liu Bo , Yu Wan-Rong
Published: November 2023

The quantum entanglement distribution network, serviced as the communication infrastructure which distributes quantum information among remote users, enables many applications beyond the reach of classical networks. Recently, the applications such as quantum key distribution and quantum secure direct communication, have been successfully demonstrated in the quantum entanglement distribution network. In this article, we propose a multi-user round-trip quantum clock synchronization (QCS) scheme in the quantum network, which can be implemented with one single entangled photon source located at the server. The server distributes the entangled photons to remote multiple users with the wavelength division multiplexing strategy, and each user feeds partial received photons back to the server. The clock difference between the server and each user is calculated from the one-way and round-trip propagation times, which are determined according to the time correlation of entangled photons. Afterwards, the demonstration has been conducted between the server and a user over a 75-km-long fiber link, where the measured clock difference uncertainty is 4.45 ps, and the time deviation is 426 fs with an average time of 4000 s. Furthermore, the proposed QCS scheme is linearly scalable to many users, with respect to user hardware and number of deployed fibers.
Quantifying inaccuracies in vertical stress determination methods in sedimentary basins; a case study of deep coal-bearing strata in the Cooper Basin, Australia
Authors: Musolino Matthew , King Rosalind , Holford Simon , Hillis Richard
Published: November 2023

Knowledge of subsurface stresses is critical to management and prediction of fluid behaviour in the Earth's crust. However, uncertainties associated with the estimation of vertical stress magnitudes are rarely explored. In settings where the principal stresses are close, small changes of only a few MPa can have drastic effects on, stress regime prediction, fault reactivation and expected fracture behaviour. Using petroleum datasets from the Moomba Gas Field in the Cooper Basin, Australia, we assess the effects of interpolation between gaps in density wireline logs that have been filtered to remove sections of poor density tool contact in coal-bearing sequences. In addition, we compare the sonic velocity–density Nafe–Drake and Gardner transforms by comparing estimates of density from sonic velocity against density from wireline logs. The results indicate that vertical stress could be underestimated by
c.
3 MPa at
c.
3 km in well Moomba 61, using traditional methods. The Gardner transform shows a stronger correlation between sonic and density values for rocks in the Cooper Basin. However, once calibrated to the regional sonic velocity–density trend, the Nafe–Drake transform better matches the density logging tool in Moomba 61. This study delivers a more robust workflow for estimating the vertical stress in basins with deep coal-bearing strata.
Named Entity Recognition in Persian Language based on Self-attention Mechanism with Weighted Relational Position Encoding
Authors: Ganjalipour Ebrahim , Refahi Sheikhani Amir Hossein , Kordrostami Sohrab , Hosseinzadeh Ali Asghar
Published: November 2023

Named-entity Recognition (NER) is challenging for languages with low digital resources. The main difficulties arise from the scarcity of annotated corpora and the consequent problematic training of an effective NER Model. We propose a customized model based on linguistic properties to compensate for this lack of resources in low-resource languages like Persian. According to pronoun-dropping and subject-object-verb word order specifications of Persian, we propose new weighted relative positional encoding in the self-attention mechanism. Using the pointwise mutual information factor, we inject co-occurrence information into context representation. We trained and tested our model on three different datasets: Arman, Peyma, and ParsTwiNER, and our method achieved 94.16%, 93.36%, and 84.49% word-level F1 scores, respectively. The experiments showed that our proposed model performs better than other Persian NER models. Ablation Study and Case Study also showed that our method can converge faster and is less prone to overfitting.
The effect of acute and 14-day exogenous ketone supplementation on glycemic control in adults with type 2 diabetes: two randomized controlled trials
Authors: Falkenhain Kaja , Oliveira Barbara F. , Islam Hashim , Neudorf Helena , Cen Haoning H. , Johnson James D. , Madden Kenneth , Singer Joel , Walsh Jeremy J. , Little Jonathan P.
Published: November 2023

Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.
Experimental Investigations of Damage Identification for Aluminum Foam Sandwich Beams Using Two-Step Method
Authors: He Xinyu , Ge Dongsheng , An Yi
Published: November 2023

In the experiment, strain gauges and dynamic signal acquisition instruments are used to collect and record data, and the stochastic subspace algorithm is used to extract the first three strain modal parameters of each case. The damage amount identified by the second natural frequency based on the modified Timoshenko beam theory is more in line with the actual situation. The damage depth of case 2 and case 4 is 2 mm, and the identified damage amount is 10% and 9%, respectively. The damage depth of case 3 and case 5 is 4 mm, and the identified damage amount is 16% and 23%, respectively. The damage location information of case 6 is well identified by using the normalized strain modal shape difference index and the enhanced strain modal shape difference index. Taking the strain response signal of case 6 as an example, it is proved that the stochastic subspace strain modal parameter identification algorithm has strong anti-interference ability under the action of 1.5 times, 4 times, and 9 times noise. In addition, the method is verified by theoretical calculation and numerical simulation, and the damage law has a high degree of coincidence with the test. The experimental results show that this method expands the theoretical basis of foam metal damage degree information identification and improves the accuracy of damage location information identification and the anti-interference of parameter identification.
Effects and Mechanisms of Fucoxanthin from Hizikia fusiforme on Inhibiting Tongue Squamous Cell Carcinoma Proliferation via AKT/mTOR-Mediated Glycolysis
Authors: Zhang Xiu Qiang , Liu Tao Yu , Zhang Lu Tao , Hua Zheng Hao , Jin Xuan An , Xu Feng , Ji Jin Chao , Xu Bo Huai , Ding Hao Miao
Published: November 2023

Fucoxanthin, a natural carotenoid, contains special ene bonds and 5, 6-mono-epoxide compounds in its molecule, which has physiological activities such as anticancer, antioxidant, anti-inflammatory, antiobesity, and antidiabetic. However, the anticancer actions and underlying mechanisms of fucoxanthin on oral cancer remain to be assessed. In this study, we used tongue carcinoma (CAL-27) cells to examine the effects and underlying mechanisms of fucoxanthin derived from Hizikia fusiforme on CAL-27 proliferation. MTT assays were used to estimate fucoxanthin’s effect on the proliferative capacity of CAL-27 cells. Flow cytometry was used to examine how fucoxanthin affects apoptosis initiation and alters cell cycle progression in CAL-27 cells. Spectrophotometry was used to assess the impact of fucoxanthin on adenosine triphosphate (ATP) generation, glucose uptake, lactate production, and the enzymatic activities of pyruvate kinase and hexokinase in CAL-27 cells. Western blotting was used to investigate fucoxanthin’s impact on the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and glycolysis-related protein expression levels in CAL-27 cells. Fucoxanthin significantly inhibited CAL-27 cell viability time- and dose-dependently

p
 

<
 
0.01

. Administration of fucoxanthin induced CAL-27 cell apoptosis and cell cycle arrest at the G1 phase

p
 

<
 
0.05

. Furthermore, fucoxanthin significantly decreased glucose uptake, lactate production, and ATP production in CAL-27 cells

p
 

<
 
0.01

and significantly inhibited glycolysis-related enzyme activities and protein expression levels

p

 

<

 

0.05

. Fucoxanthin also substantially decreased the expression levels of phosphorylated ribosomal protein S6, phosphorylated AKT, and phosphorylated mTOR

p
 

<
 
0.05

. In conclusion, fucoxanthin inhibited CAL-27 cell proliferation, and this mechanism may be associated with the AKT/mTOR-mediated glycolysis pathway.
Application of ImageJ in Optical Coherence Tomography Angiography (OCT‐A): A Literature Review
Authors: Rahimi Masoud , Khameneh Esmaeil Asadi , Riazi-Esfahani Hamid , Mahmoudi Tahereh , Khalili Pour Elias , Kafieh Rahele
Published: November 2023

Background. This study aimed to review the literature on the application of ImageJ in optical coherence tomography angiography (OCT‐A) images. Methods. A general search was performed in PubMed, Google Scholar, and Scopus databases. The authors evaluated each of the selected articles in order to assess the implementation of ImageJ in OCT‐A images. Results. ImageJ can aid in reducing artifacts, enhancing image quality to increase the accuracy of the process and analysis, processing and analyzing images, generating comparable parameters such as the parameters that assess perfusion of the layers (vessel density (VD), skeletonized density (SD), and vessel length density (VLD)) and the parameters that evaluate the structure of the layers (fractal dimension (FD), vessel density index (VDI), and lacunarity (LAC)), and the foveal avascular zone (FAZ) that are used widely in the retinal and choroidal studies), and establishing diagnostic criteria. It can help to save time when the dataset is huge with numerous plugins and options for image processing and analysis with reliable results. Diverse studies implemented distinct binarization and thresholding techniques, resulting in disparate outcomes and incomparable parameters. Uniformity in methodology is required to acquire comparable data from studies employing diverse processing and analysis techniques that yield varied outcomes. Conclusion. Researchers and professionals might benefit from using ImageJ because of how quickly and correctly it processes and analyzes images. It is highly adaptable and potent software, allowing users to evaluate images in a variety of ways. There exists a diverse range of methodologies for analyzing OCTA images through the utilization of ImageJ. However, it is imperative to establish a standardized strategy to ensure the reliability and consistency of the method for research purposes.
PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma
Authors: Tao Hongru , Jin Chen , Zhou Liyuan , Deng Zhenzhong , Li Xiao , Dang Wenzhen , Fan Shijie , Li Bing , Ye Fei , Lu Junyan , Kong Xiangqian , Liu Chuanpeng , Luo Cheng , Zhang Yuanyuan
Published: November 2023

Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyltransferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8+ T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8+ T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA derived from endogenous retroviral elements (ERV) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of Dnmt1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8+ T cells as well as IFNγ+CD8+ T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB.

Significance:

Targeting PRMT1 stimulates interferon signaling by increasing expression of endogenous retroviral elements and double-stranded RNA through repression of DNMT1, which induces antitumor immunity and synergizes with immunotherapy to suppress tumor progression.
SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer
Authors: Zhao Yue , Chen Jiancheng , Zheng Hanhao , Luo Yuming , An Mingjie , Lin Yan , Pang Mingrui , Li Yuanlong , Kong Yao , He Wang , Lin Tianxin , Chen Changhao
Published: November 2023

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1–eIF4G1 interaction. Moreover, DHCR24 directly anchored to TBK1 mRNA 3′-untranslated region to increase its stability, thus forming a feed forward loop to elevate TBK1 expression. TBK1 activated PI3K/Akt signaling to promote VEGFC secretion, resulting in lymphangiogenesis and LN metastasis. DHCR24 silencing significantly impeded bladder cancer lymphangiogenesis and lymphatic metastasis in a patient-derived xenograft model. Collectively, these findings elucidate DHCR24-mediated translation machinery that promotes lymphatic metastasis of bladder cancer and supports the potential application of DHCR24-targeted therapy for LN-metastatic bladder cancer.

Significance:

DHCR24 is a SUMOylation regulator that controls translation initiation complex assembly and orchestrates TBK1 mRNA circularization to activate Akt/VEGFC signaling, which stimulates lymphangiogenesis and promotes lymph node metastasis in bladder cancer.
Not All Neonatal Encephalopathies Are due to Perinatal Hypoxia
Authors: Kulkarni Tushar , Dsougi Hussein Mohamed Lma , El Halik Mahmoud , Bastaki Fatma Abdulla Mohammad
Published: November 2023

A late preterm female neonate, born to a consanguineously married couple by normal vaginal delivery and unremarkable family history, was admitted to our NICU soon after birth for management of respiratory distress secondary to meconium aspiration syndrome and persistent pulmonary hypertension of newborn. She required intensive ventilatory and hemodynamic support and was encephalopathic since birth but did not fulfill the criteria for therapeutic hypothermia. Extensive metabolic workup revealed no diagnosis, but neuroimaging showed characteristic findings consistent with the diagnosis of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. This was supported by the result of whole exome sequence that identified a novel homozygous mutation, c.1191 + 11A>C, for DARS2 gene confirming the diagnosis.