bluuebunny/crossref_metadata_2025 huggingface dataset:
ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency
Authors: Zhou Mo , Yang Tao , Yuan Ming , Li Xinyu , Deng Jieyi , Wu Shiyu , Zhong Zhihan , Lin Yingtong , Zhang Wanying , Xia Baijin , Wu Yating , Wang Lilin , Chen Tao , Liu Ruxin , Pan Ting , Ma Xiancai , Li Linghua , Liu Bingfeng , Zhang Hui
Published: July 2024

The human immunodeficiency virus type 1 (HIV-1) reservoir consists of latently infected cells which present a major obstacle to achieving a functional cure for HIV-1. The formation and maintenance of HIV-1 latency have been extensively studied, and latency-reversing agents (LRAs) that can reactivate latent HIV-1 by targeting the involved host factors are developed; however, their clinical efficacies remain unsatisfactory. Therefore, it is imperative to identify novel targets for more potential candidates or better combinations for LRAs. In this study, we utilized CRISPR affinity purification
in situ
of regulatory elements system to screen for host factors associated with the HIV-1 long terminal repeat region that could potentially be involved in HIV-1 latency. We successfully identified that origin recognition complex 1 (ORC1), the largest subunit of the origin recognition complex, contributes to HIV-1 latency in addition to its function in DNA replication initiation. Notably, ORC1 is enriched on the HIV-1 promoter and recruits a series of repressive epigenetic elements, including DNMT1 and HDAC1/2, and histone modifiers, such as H3K9me3 and H3K27me3, thereby facilitating the establishment and maintenance of HIV-1 latency. Moreover, the reactivation of latent HIV-1 through ORC1 depletion has been confirmed across various latency cell models and primary CD4
+
T cells from people living with HIV-1. Additionally, we comprehensively validated the properties of liquid-liquid phase separation (LLPS) of ORC1 from multiple perspectives and identified the key regions that promote the formation of LLPS. This property is important for the recruitment of ORC1 to the HIV-1 promoter. Collectively, these findings highlight ORC1 as a potential novel target implicated in HIV-1 latency and position it as a promising candidate for the development of novel LRAs.

IMPORTANCE

Identifying host factors involved in maintaining human immunodeficiency virus type 1 (HIV-1) latency and understanding their mechanisms prepares the groundwork to discover novel targets for HIV-1 latent infection and provides further options for the selection of latency-reversing agents in the “shock” strategy. In this study, we identified a novel role of the DNA replication factor origin recognition complex 1 (ORC1) in maintaining repressive chromatin structures surrounding the HIV-1 promoter region, thereby contributing to HIV-1 latency. This discovery expands our understanding of the non-replicative functions of the ORC complex and provides a potential therapeutic strategy for HIV-1 cure.
Sub-genomic flaviviral RNA elements increase the stability and abundance of recombinant AAV vector transcripts
Authors: Meganck Rita M. , Ogurlu Roza , Liu Jiacheng , Moller-Tank Sven , Tse Victor , Blondel Leo O. , Rosales Alan , Hall Aaron C. , Vincent Heather A. , Moorman Nathaniel J. , Marzluff William F. , Asokan Aravind
Published: July 2024

Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE). Further dissection of engineered transcripts revealed that sfRNA elements (i) require incorporation in
cis
within the 3′ untranslated region (UTR) of AAV genomes, (ii) require minimal dumbbell structures to exert the observed effects, and (iii) can stabilize AAV transcripts independent of 5′−3′ exoribonuclease 1 (XRN1)-mediated decay. Additionally, preliminary
in vivo
assessment of AAV vectors bearing sfRNA elements in mice achieved increased transcript abundance and expression in cardiac tissue. Leveraging the functional versatility of engineered viral RNA elements may help improve the potency of AAV vector-based gene therapies.

IMPORTANCE

Viral RNA elements can hijack host cell machinery to control stability of transcripts and consequently, infection. Studies that help better understand such viral elements can provide insights into antiviral strategies and also potentially leverage these features for therapeutic applications. In this study, by incorporating structured flaviviral RNA elements into recombinant adeno-associated viral (AAV) vector genomes, we show improved AAV transcript stability and transgene expression can be achieved, with implications for gene transfer.
Bis-benzylisoquinoline alkaloids inhibit African swine fever virus internalization and replication by impairing late endosomal/lysosomal function
Authors: Zhu Junhai , Chen Huahan , Gao Fei , Jian Weijun , Huang Guangyu , Sunkang Yongjie , Chen Xiaona , Liao Ming , Zhang Kehui , Qi Wenbao , Huang Lihong
Published: July 2024

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a highly infectious disease afflicting domestic pigs and wild boars. It exhibits an alarming acute infection fatality rate of up to 100%. Regrettably, no commercial vaccines or specific drugs for combating this disease are currently available. This study evaluated the anti-ASFV activities in porcine alveolar macrophages, 3D4/21 cells, and PK-15 cells of four bis-benzylisoquinoline alkaloids (BBAs): cepharanthine (CEP), tetrandrine, fangchinoline, and iso-tetrandrine. Furthermore, we demonstrated that CEP, which exhibited the highest selectivity index (SI = 81.31), alkalized late endosomes/lysosomes, hindered ASFV endosomal transport, disrupted virus uncoating signals, and thereby inhibited ASFV internalization. Additionally, CEP disrupted ASFV DNA synthesis, leading to the inhibition of viral replication. Moreover, berbamine was labeled with NBD to synthesize a fluorescent probe to study the cellular location of these BBAs. By co-staining with Lyso-Tracker and lysosome-associated membrane protein 1, we demonstrated that BBAs target the endolysosomal compartments for the first time. Our data together indicated that BBAs are a class of natural products with significant inhibitory effects against ASFV infection. These findings suggest their potential efficacy as agents for the prevention and control of ASF, offering valuable references for the identification of potential drug targets.

IMPORTANCE

The urgency and severity of African swine fever (ASF) underscore the critical need for effective interventions against this highly infectious disease, which poses a grave threat to domestic pigs and wild boars. Our study reveals the potent anti-African swine fever virus (ASFV) efficacy of bis-benzylisoquinoline alkaloids (BBAs), particularly evident in the absence of progeny virus production under a 5 µM concentration treatment. The structural similarity among cepharanthine, tetrandrine, fangchinoline, and iso-tetrandrine, coupled with their analogous inhibitory stages and comparable selectivity indexes, strongly suggests a shared antiviral mechanism within this drug category. Further investigation revealed that BBAs localize to lysosomes and inhibit the internalization and replication of ASFV by disrupting the endosomal/lysosomal function. These collective results have profound implications for ASF prevention and control, suggesting the potential of the investigated agents as prophylactic and therapeutic measures. Furthermore, our study offers crucial insights into identifying drug targets and laying the groundwork for innovative interventions.
Draft genome for
Pseudomonas alkylphenolica
IMGN1, isolated from soil
Authors: Lee Jaeyeon , Ku Bon-Jin , Kim Yeongjun , Han Jeong A. , Kim Eun Yu , Lee Ho-Seok
Published: July 2024

Biocontrol using organisms like
Pseudomonas alkylphenolica
offers a viable alternative to chemical pesticides, enhancing plant growth and reducing environmental impact. This study details the genome of
Pseudomonas alkylphenolica
IMGN1, a strain known for promoting plant growth, advancing our understanding of biocontrol mechanisms.
Draft genome sequences of four
Corynebacterium amycolatum
strains isolated from female urine samples
Authors: Kula Alex , Chilton Grace , Damaso James , Golzar Yusef , Rushnaiwala Fatima , Appleberry Helen , Wolfe Alan J. , Putonti Catherine
Published: July 2024

Corynebacterium amycolatum
is an emerging pathogen of the urinary tract. Here, we present the draft genomes for four strains isolated from urine collected from symptomatic and asymptomatic female participants.
Impact of host species on assembly, composition, and functional profiles of phycosphere microbiomes
Authors: Roager Line , Kempen Paul J. , Bentzon-Tilia Mikkel , Sonnenschein Eva C. , Gram Lone
Published: July 2024

Microalgal microbiomes play vital roles in the growth and health of their host, however, their composition and functions remain only partially characterized, especially across microalgal phyla. In this study, a natural seawater microbiome was introduced to three distinct, axenic species of microalgae, the haptophyte
Isochrysis galbana,
the chlorophyte
Tetraselmis suecica,
and the diatom
Conticribra weissflogii
(previously
Thalassiosira
), and its divergence and assembly under constant illumination was monitored over 49 days using 16S rRNA amplicon and metagenomic analyses. The microbiomes had a high degree of host specificity in terms of taxonomic composition and potential functions, including CAZymes profiles. Rhodobacteraceae and Flavobacteriaceae families were abundant across all microalgal hosts, but
I. galbana
microbiomes diverged further from
T. suecica
and
C. weissflogii
microbiomes.
I. galbana
microbiomes had a much higher relative abundance of Flavobacteriaceae, whereas the two other algal microbiomes had higher relative abundances of Rhodobacteraceae. This could be due to the bacterivorous mixotrophic nature of
I. galbana
affecting the carbohydrate composition available to the microbiomes, which was supported by the CAZymes profile of
I. galbana
microbiomes diverging further from those of
T. suecica
and
C. weissflogii
microbiomes. Finally, the presence of denitrification and other anaerobic pathways was found exclusively in the microbiomes of
C. weissflogii,
which we speculate could be a result of anoxic microenvironments forming in aggregates formed by this diatom during the experiment. These results underline the significant role of the microalgal host species on microbiome composition and functional profiles along with other factors, such as the trophic mode of the microalgal host.

IMPORTANCE

As the main primary producers of the oceans, microalgae serve as cornerstones of the ecosystems they are part of. Additionally, they are increasingly used for biotechnological purposes such as the production of nutraceuticals, pigments, and antioxidants. Since the bacterial microbiomes of microalgae can affect their hosts in beneficial and detrimental ways, understanding these microbiomes is crucial to both the ecological and applied roles of microalgae. The present study advances the understanding of microalgal microbiome assembly, composition, and functionality across microalgal phyla, which may inform the modeling and engineering of microalgal microbiomes for biotechnological purposes.
Central Afar: An analogue for oceanic plateau development
Authors: Rime Valentin , Keir Derek , Phethean Jordan , Kidane Tesfaye , Foubert Anneleen
Published: July 2024

The structure, composition, and evolution of oceanic plateaus are poorly understood and strongly debated. Here, we compared the magmatic history and crustal structure of Afar with the Greenland–Iceland–Faroe Ridge and other oceanic plateaus. Key similarities indicate that Central Afar represents the early stage of development of a specific type of oceanic plateau: a rifted oceanic magmatic plateau (ROMP). These features begin their formation before continental rifting and develop into wide magmatic rift systems capable of isolating slivers of continental crust within the new igneous crust. Importantly, the anomalous magmatism continues through breakup and for several tens of millions of years afterward. The recognition of Central Afar as a precursor of this type of oceanic plateau allows us to better understand their formation. Increased melt production causes early and voluminous magmatism, ultrathick igneous crust, and repeated reorganization of the extension locus during rift/ridge jumps, which delay the onset of oceanization and Penrose-style crustal production. These factors differentiate ROMPs from many magma-rich rifted continental margins and from other types of oceanic plateaus, highlighting that Central Afar and other ROMPs should neither be considered as conventional magma-rich margins nor be considered as normal oceanic crust.
Expert CONsensus on Visual Evaluation in Retinal disease manaGEment: the CONVERGE study
Authors: Anderson Roger S , Roark Mark , Gilbert Rose , Sumodhee Dayyanah
Published: July 2024

Background/Aims

Recent decades have seen significant advances in both structural and functional testing of retinal disease. However, the current clinical value of specific testing modalities, as well as future trends, need to be clearly identified in order to highlight areas for further development in routine care and clinical trials.

Methods

We designed a modified two-round Delphi study to obtain the opinion of a multidisciplinary group of 33 international experts involved in the field of retinal disease management/research to determine the level of agreement and consensus regarding the value and performance of specific structural and functional testing methods for retinal disease. On a Likert scale, a median of 1–2 indicated disagreement with the statement, and 5–6 indicated agreement with the statement. An IQR of ≤2 indicated consensus in the responses. Several questions also allowed comments on responses.

Results

There was overall agreement that structural testing currently predominates for detection and monitoring. There was moderate agreement that functional testing remains important and will continue to do so in the future because it provides complementary information. Certain respondents considered that properly designed and applied psychophysical tests are as reliable and repeatable as structural observations and that functional changes are the most important in the long run. Respondents considered future care and research to require a combination of structural and functional testing with strong consensus that the relative importance will depend on disease type and stage.

Conclusion

The study obtained important insights from a group of international experts regarding current and future needs in the management of retinal disease using a mix of quantitative and qualitative approaches. Responses provide a rich range of opinions that will be of interest to researchers seeking to design tests for future patient care and clinical trials.
Choroidal involvement in acute retinal necrosis: case series and review of the literature
Authors: Patel Anamika , Pathengay Avinash , Pavesio Carlos , Testi Ilaria
Published: July 2024

Purpose

To show the role of multimodal imaging in identifying choroidal involvement in acute retinal necrosis (ARN).

Methods

Retrospective case series of ARN patients. Clinical data, including medical history, clinical features and multimodal imaging findings, were collected.

Results

Three patients were included. Imaging modalities, such as indocyanine green angiography and optical coherence tomography, were critical in showing choroidal involvement in ARN.

Conclusion

Choroidal involvement may occur in ARN along with the well-known retinal features.
Insomnia and other sleep disorders in adolescence
Authors: Delahoyde Mary-Kate , Tyack Charlie , Kugarajah Sarusan , Joseph Desaline
Published: July 2024

Sleep is important for our survival. Research suggests that getting ‘good’ sleep is a problem for a proportion of adolescents. The paper advocates for holistic treatment of sleep disorders incorporating expertise from a multidisciplinary team. Much of the assessment and treatment of sleep disorders in adolescents comes from research within adult populations, therefore, there is a need for further research to be completed within the adolescent population to ensure there is a robust evidence base for assessment and treatment of sleep disorders.
Differential effects of balloon pulmonary angioplasty on chronic thromboembolic pulmonary disease
Authors: Minatsuki Shun , Hatano Masaru , Hirose Kazutoshi , Saito Akihito , Yagi Hiroki , Takeda Norifumi , Komuro Issei
Published: July 2024

Background

Decreased diffusing capacity of the lungs for carbon monoxide (DLco) is associated with microvascular damage in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an effective treatment for CTEPH, but the efficacy of BPA in patients with CTEPH with low DLco remains unclear because BPA does not directly address microvascular damage. This study investigates the influence of microvasculopathy on BPA in CTEPH according to DLco.

Methods

We retrospectively analysed data from patients with inoperable CTEPH who underwent BPA at the University of Tokyo Hospital from July 2011 to August 2023. The patients were classified into two groups based on their preprocedural DLco (normal DLco (ND) and low DLco (LD) groups), with a DLco cut-off value of 80%. We compared the patient characteristics and effectiveness of BPA between the groups.

Results

Among the 75 patients, 36 were in the LD group. The LD group had a shorter 6-minute walking distance (324±91 vs 427±114 m) than the ND group but the mean pulmonary artery pressure (mPAP) was similar (38.9±7.3 vs 41.1±9.2 mm Hg) before BPA. BPA improved the haemodynamic status and exercise tolerance in both groups. The LD group exhibited a higher mPAP (25.1±7.4 vs 21.5±5.6 mm Hg) and required more sessions of BPA (median 6 vs 4). Based on the analysis of covariance adjusted for baseline values, low DLco significantly correlated with mPAP (sβ=−0.304, 95% CI −7.015 to –1.132, p=0.007) and pulmonary vascular resistance (sβ=−0.324, 95% CI −141.0 to –29.81, p=0.003).

Conclusions

BPA was associated with an improvement in the haemodynamic status and exercise tolerance in patients with CTEPH even with low DLco. However, low DLco may attenuate the effect of BPA on mPAP and pulmonary vascular resistance and require more treatment sessions.
Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial
Authors: Krumholz Harlan M , de Lemos James A , Sattar Naveed , Linetzky Bruno , Sharma Palash , Mast Casey J , Ahmad Nadia N , Bunck Mathijs C , Stefanski Adam
Published: July 2024

Background

Treating obesity may be a pathway to prevent and control hypertension. In the SURMOUNT-1 trial in people with obesity or overweight with weight-related complications, 72-week tirzepatide treatment led to clinically meaningful body weight and blood pressure reduction. Post hoc analyses were conducted to further explore the effects of tirzepatide on the pattern of blood pressure reduction and whether the effects were consistent across various subgroups.

Methods

The mixed effect for repeated measure model was used to compare changes in overall blood pressure, across demographic and clinical subgroups, baseline blood pressure subgroups and hypertension categories between SURMOUNT-1 participants randomised to treatment with tirzepatide and placebo. The association between weight changes and blood pressure and adverse events associated with low blood pressure were also evaluated by mediation analysis.

Results

Tirzepatide treatment was associated with a rapid decline in systolic and diastolic blood pressure over the first 24 weeks, followed by blood pressure stabilisation until the end of the observation period, resulting in a significant net reduction by 72 weeks of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure versus placebo. Participants randomly assigned to any tirzepatide group were more likely than those assigned to placebo to have normal blood pressure at week 72 (58.0% vs 35.2%, respectively). The effects were broadly consistent across baseline blood pressure subgroups, shifting the blood pressure distribution curve to lower blood pressure levels. The mediation analysis indicated that weight loss explained 68% of the systolic and 71% of the diastolic blood pressure reduction. Low blood pressure adverse events were infrequent, but the rate was higher in the tirzepatide group.

Conclusions

In these post hoc analyses, in participants with obesity or overweight, tirzepatide was associated with reduced blood pressure consistently across participant groups primarily via weight loss, with relatively few blood pressure-related adverse events.

Trial registration number

NCT04184622.
Large-scale analysis to identify risk factors for ovarian cancer
Authors: Madakkatel Iqbal , Lumsden Amanda L , Mulugeta Anwar , Mäenpää Johanna , Oehler Martin K , Hyppönen Elina
Published: July 2024

Objective

Ovarian cancer is characterized by late-stage diagnoses and poor prognosis. We aimed to identify factors that can inform prevention and early detection of ovarian cancer.

Methods

We used a data-driven machine learning approach to identify predictors of epithelial ovarian cancer from 2920 input features measured 12.6 years (IQR 11.9 to 13.3 years) before diagnoses. Analyses included 221 732 female participants in the UK Biobank without a history of cancer. During the follow-up 1441 women developed ovarian cancer. For factors that contributed to model prediction, we used multivariate logistic regression to evaluate the association with ovarian cancer, with evidence for causality tested by Mendelian randomization (MR) analyses in the Ovarian Cancer Genetics Consortium (25 509 cases).

Results

Greater parity and ever-use of oral contraception were associated with lower ovarian cancer risk (ever vs never OR 0.74, 95% CI 0.66 to 0.84). After adjustment for established risk factors, greater height, weight, and greater red blood cell distribution width were associated with increased ovarian cancer risk, while higher aspartate aminotransferase levels and mean corpuscular volume were associated with lower risk. MR analyses confirmed observational associations with anthropometric/adiposity traits (eg, body fat percentage per standard deviation (SD); OR inverse-variance weighted (ORIVW) 1.28, 95% CI 1.13 to 1.46) and aspartate aminotransferase (ORIVW0.87, 95% CI 0.78 to 0.98). MR also provided genetic evidence for a protective association of higher total serum protein on ovarian cancer, higher lymphocyte count on serous and endometrioid ovarian cancer, and greater forced expiratory volume in 1 s on serous ovarian cancer among other findings.

Conclusions

This study shows that certain risk factors for ovarian cancer are modifiable, suggesting that weight reduction and interventions to reduce the number of ovulations may provide potential for future prevention. We also identified blood biomarkers associated with ovarian cancer years before diagnoses, warranting further investigation.
Week-to-week changes in training were not prospectively associated with injuries among Wisconsin high school cross-country runners
Authors: Joachim Mikel Renee , Heiderscheit Bryan C , Kliethermes Stephanie A
Published: July 2024

Background

Training characteristics, such as volume and duration, have been studied in relation to running-related injury (RRI) risk, with mixed findings in adult runners. There is a lack of research assessing how training characteristics relate to RRI in youth runners, despite the high RRI rates observed in this population.

Purpose

To prospectively determine associations between (1) total weekly running volume and duration and (2) week-to-week changes in running volume, duration, intensity and training stress with in-season RRI among high school cross-country runners.

Methods

Runners completed a preseason demographics and injury history survey and daily surveys regarding training distance, duration, intensity and current RRI. Values were summed weekly and change scores were calculated relative to the prior week. Runners completing ≥75% of daily surveys were analysed; sensitivity analyses for those completing ≥50% and ≥90% were conducted. Generalised estimating equations assessed associations between change in each predictor, including interactions with sex and RRI within the subsequent week, controlling for year in school, prior RRI and repeated observations.

Results

434 runners enrolled in the study; 161 (37%) completed ≥75% of daily surveys. No associations between total volume, total duration or week-to-week change in training characteristics and in-season RRI were observed (p≥0.54). Sensitivity analyses did not detect any significant associations.

Conclusion

Total weekly running volume and duration and weekly changes in training were not associated with RRI. RRI are multifactorial and assessing the interaction between training characteristics and other lifestyle factors is likely necessary for determining RRI risk in youth runners.
White matter abnormalities in healthy E200K carriers may serve as an early biomarker for genetic Creutzfeldt-Jakob disease (gCJD)
Authors: Omer Nurit , Droby Amgad , Silbak Rawan , Trablus Noa , Bar David Aya , Shiner Tamara , Alcalay Yifat , Alcalay Roy , Nathan Talya , Thaler Avner , Mirelman Anat , Gana Weisz Mali , Goldstein Orly , Glinka Tal , Orr-Urtreger Avi , Giladi Nir , Bregman Noa
Published: July 2024

Background

MRI is an important tool for disease diagnosis of Creutzfeldt-Jakob disease (CJD), yet its role in identifying preclinical stages of disease remains unclear. Here, we explored subtle white matter (WM) alterations in genetic CJD (gCJD) patients and in asymptomatic E200K mutation carriers using MRI, depending on total tau protein (t-tau) levels in CSF.

Methods

Six symptomatic gCJD patients and N=60 healthy relatives of gCJD patients were included. Participants underwent genetic testing for the E200K mutation, MRI scans at 3T and a lumbar puncture (LP) for t-tau. Diffusion tensor imaging (DTI) metrics were calculated along WM tracts.

Results

gCJD patients demonstrated higher mean diffusivity (MD), radial diffusivity (RD) and lower fractional anisotropy (FA) values compared with healthy relatives in several WM tracts (p<0.05). Out of the healthy relatives, 50% (N=30) were found to be carriers of the E200K mutation. T-tau levels in cerebrospinal fluid (CSF) were above the normal range (>290 pg/mL) in N=8 out of 23 carriers who underwent an LP. No significant differences in FA, MD, axial diffusivity (AD) and RD were detected between healthy mutation carriers (HMC) and healthy non-carriers within the WM tracts. Finally, significantly higher FA and lower MD, RD and AD along several WM tracts were found in HMC with elevated t-tau compared with HMC with normal t-tau (p<0.05).

Conclusions

DTI abnormalities along WM tracts were found in healthy E200K mutation carriers with elevated t-tau in CSF. Longer follow-up is required to determine whether these subtle WM alterations are predictive of future conversion to symptomatic gCJD.

Trial registration number

NCT05746715.
Retinal vasculopathy with cerebral leukoencephalopathy: a rare mimic of CNS vasculitis
Authors: Martin Andrew J
Published: July 2024

Retinal vasculopathy with cerebral leukoencephalopathy is a rare autosomal dominant genetic disorder due to mutation in theTREX1gene and presents with both central nervous system (CNS) and other organ dysfunction. It is often misdiagnosed as demyelination or vasculitis based on imaging features, often with potentially harmful immunotherapy given unnecessarily. This report describes two sisters with progressive hemiparesis, retinal vasculopathy and hepatic dysfunction, one of whom was initially misdiagnosed and treated for cerebral vasculitis. Imaging showed extensive and asymmetric white matter lesions with persistent diffusion restriction and contrast enhancement. Extensive autoimmune and infectious investigations were unremarkable. Both patients had a novel heterozygous variant in theTREX1gene, giving a diagnosis of retinal vasculopathy with cerebral leukoencephalopathy. Clinicians should consider this condition in atypical presentations of suspected demyelination or CNS vasculitis.
One-year opioid consumption trajectories among individuals receiving multidisciplinary postsurgical care: a single-center observational study from the Toronto General Hospital Transitional Pain Service
Authors: Pagé M Gabrielle , Katz Joel , Darville Rasheeda , Gabriel Gretchen , Ladha Karim S , Huang Alexander , Ganty Praveen , Katznelson Rita , Tamir Diana , Fiorellino Joseph , Kahn Michael , Tao Leeping , Slepian Maxwell , Wieskopf Jeffrey , Clarke Hance
Published: July 2024

Introduction

The Transitional Pain Service (TPS) is an innovative, personalized approach to postsurgical opioid consumption and pain management. The objectives of this study were to identify trajectories of opioid consumption and pain intensity within 12 months after initiating treatment through the TPS, identify biopsychosocial factors associated with trajectory membership, and examine the relationship between trajectory membership and other outcomes of interest over the same 12-month period.

Methods

Consecutive patients referred to the TPS were included in the present study (n=466). After providing informed consent, they completed self-report questionnaires at the initial visit at the TPS (either pre surgery or post surgery) and at every TPS visit until 12 months. Growth mixture modeling was used to derive trajectories and identify associated factors.

Results

Results showed three distinct opioid consumption trajectories for both presurgical opioid consumers and opioid-naïve patients. These trajectories all decreased over time and among those who were consuming opioids before surgery that returned to presurgical levels. Being man, having a substance use disorder, or reporting higher levels of pain interference were associated with higher daily opioid consumption for presurgical opioid consumers. For presurgical opioid-naïve individuals, higher opioid consumption trajectories were associated with higher levels of psychological distress. Five pain intensity trajectories were identified, and there were no significant association between opioid consumption and pain intensity trajectories.

Conclusions

Results suggest that opioid consumption and pain intensity trajectories mostly decrease after surgery in a high-risk population enrolled in a TPS. Results also show heterogeneity in postsurgical recovery and highlight the importance of using personalized interventions to optimize individual trajectories.
Long-term explantation risk in patients with chronic pain treated with spinal cord or dorsal root ganglion stimulation
Authors: Gatzinsky Kliment , Brink Beatrice , Eyglóardóttir Kristin Lilja , Hallén Tobias
Published: July 2024

Objective

To investigate long-term explantation risks and causes for the explantation of neuromodulation devices for the treatment of chronic pain from different manufacturers.

Methods

This retrospective analysis included patients implanted with a system for spinal cord stimulation (SCS) or dorsal root ganglion (DRG) stimulation at Sahlgrenska University Hospital between January 2012 and December 2022. Patient characteristics, explantation rates and causes for explantation were obtained by reviewing medical records.

Results

In total, 400 patients were included in the study. Including all manufacturers, the cumulative explantation risk for any reason was 17%, 23% and 38% at 3, 5 and 10 years, respectively. Explantation risk due to diminished pain relief at the same intervals was 10%, 14% and 23%. A subgroup comparison of 5-year explantation risk using Kaplan-Meier analysis did not show a statistically significant difference between the manufacturers. In multivariable Cox regression analyses, there was no difference in explantation risk for any reason, but for explantation due to diminished pain relief, a higher risk was noted for Medtronic (preferably older types of SCS devices) and DRG stimulation. No other predictive factor for explantation was found.

Conclusions

Although SCS and DRG stimulation are well-established and safe treatments for chronic pain, the long-term explantation risk remains high. The difference between manufacturers highlights the importance of technological evolution for improving therapy outcomes. Increased stringency in patient selection and follow-up strategies, as well as further development of device hardware and software technology for increased longevity, could possibly reduce long-term explantation risks.
Economic evaluation of the recent French tobacco control policy: a model-based approach
Authors: Devaux Marion , Dorfmuller Ciampi Marina , Guignard Romain , Lerouge Aliénor , Aldea Alexandra , Nguyen-Thanh Viêt , Beck François , Arwidson Pierre , Cecchini Michele
Published: July 2024

Background

One in four French adults smoked daily in 2021, compared with one in six in Organisation for Economic Co-operation and Development (OECD) countries. To strengthen its tobacco control policy, in 2016, France has started implementing a policy package that includes a 3-year gradual price increase, plain packaging, an annual social marketing campaign promoting cessation and the reimbursement of nicotine replacement products. This study aims to evaluate the health and economic impact of this policy package.

Methods

The long-term policy impact on disease cases, healthcare expenditure and gains in labour participation and productivity was evaluated by using the OECD microsimulation model for Strategic Public Health Planning for Non-Communicable Diseases. The model was fed with historical and projected trends on tobacco smoking prevalence as produced by the policy package.

Results

Over the period 2023–2050, the policy package is estimated to avoid about 4.03 million (2.09–11.84 million) cases of chronic diseases, save €578 million (365–1848 million) per year in health expenditure and increase employment and workforce productivity by the equivalent to 19 800 (9100–59 900) additional full-time workers per year, compared with a scenario in which the intervention package is not implemented. The intervention cost is estimated at about €148 million per year. For each euro invested in the policy package, €4 will be returned in long-term savings in healthcare expenditure.

Conclusions

The tobacco control policy package implemented by France, targeting smoking initiation and promoting tobacco cessation is an effective intervention with an excellent return on investment.
Analysis of axisymmetric thermoelastic diffusive half-space with variable material properties using hyperbolic two-temperature model
Authors: Bajpai Ankit , Sharma P.K. , Mishra Krishna C.
Published: July 2024

The aim of the current study is to investigate the variable thermal conductivity and diffusivity impact on the transient response of an axisymmetric thermodiffusive elastic half-space under axisymmetric thermal, mechanical, and concentration loads in the light of hyperbolic two-temperature generalized fractional thermoelastic diffusion model. With the help of Kirchhoff’s transform, the governing equations are converted into linear form. The resulting equations are solved by imposing the combined Laplace–Hankel transform. In converted space, the solutions for different field quantities are presented in compact form. The copper material is considered for numerical computation. By employing a mathematical inversion procedure, the solutions are converted into the original space. Numerically computed solutions for various physical quantities are illustrated in the form of graphs to show the impact of variable thermal conductivity and diffusivity, hyperbolic two temperature, and fractional parameters. Validation of the obtained results is also presented.
Analysis of the $$\Xi _c^* {\bar{K}}$$ molecular pentaquark state by its electromagnetic properties
Authors: Özdem Ulaş
Published: July 2024

We are systematically studying the electromagnetic characteristics of multiquark systems to shed light on their internal structure, whose nature and quantum numbers are controversial. In this study, we investigate the magnetic dipole, electric quadrupole, and magnetic octupole moments of the $$\Xi _c^*{\bar{K}}$$

Ξ
c
∗

K

¯

state within the context of the QCD light-cone sum rule. During this analysis, we posit that the $$\Xi _c^*{\bar{K}}$$

Ξ
c
∗

K

¯

state assumes a molecular structure with quantum numbers $$J^P = \frac{3}{2}^-$$

J
P

=

3
2

-

. The extracted outcomes are given as $$\mu _{\Xi _c^*{\bar{K}}} = 0.15^{+0.04}_{-0.03}\,\mu _N$$

μ

Ξ
c
∗

K

¯

=
0
.

15

-
0.03

+
0.04

μ
N

, $${\mathcal {Q}}_{\Xi _c^*{\bar{K}}} = (-0.93^{+0.22}_{-0.17})\times 10^{-3}\,\textrm{fm}^{\textrm{2}}$$

Q

Ξ
c
∗

K

¯

=

(
-
0
.

93

-
0.17

+
0.22

)

×

10

-
3

fm
2

, and $${\mathcal {O}}_{\Xi _c^*{\bar{K}}} = (-0.45^{+0.10}_{-0.09})\times 10^{-4}\,{\textrm{fm}}^{\textrm{3}}$$

O

Ξ
c
∗

K

¯

=

(
-
0
.

45

-
0.09

+
0.10

)

×

10

-
4

fm

3

. The findings of this study, when considered alongside other pertinent characteristics, may assist in elucidating the nature of this controversial phenomenon.
Nano Thermal Simulation of Graphene Field Effect Transistor Based on Ballistic Diffusive Model
Authors: Nasri Faouzi , Salama Husien , Salama Khalifa Ahmed
Published: July 2024

This paper investigates temperature evolution in graphene field-effect transistors. We present a refined Ballistic-diffusive equation model (BDE) tailored for scrutinizing the phonon transport within GNRFET transistors. Furthermore, we examine the influence of the channel length on thermal characteristics. COMSOL Multiphysics is employed to compute the phonon transport and temperature distribution in nano-GNRFET. Our results reveal that the phonon transport anticipated by the suggested BDE model closely corresponds to that derived from the Boltzmann transport equation. The proposed model proficiently gauges the thermal performance of GNRFET, with the outcomes suggesting that the characteristic length of the GNR has a negligible impact on the temperature increase.
Fabrication and Characterization of Four-State Inverter Utilizing Quantum Dot Gate Field-Effect Transistors (QDGFETS)
Authors: Khan Bilal , Mays Roman , Gudlavalleti Raja , Heller Evan , Jain Faquir
Published: July 2024

This paper presents the experimental results of nMOS quantum dot gate field-effect transistor (QDG-FET) based four-state inverter fabricated and tested with Si/SiO2 and Ge/GeO2 quantum dots. The site-specific self-assembly of SiOx-cladded Si and GeOx-cladded Ge quantum dot layers in the gate region implements both the driver and load FETs in enhancement nMOS inverters. A four-state inverter will allow the reduction of FET count in logic block in microprocessors.
8-State SRAMS Based on Cladded GE Quantum Dot Gate FETS
Authors: Saman B. , Almalki A. , Chandy J. , Heller E. , Jain F. C.
Published: July 2024

This paper describes the fabrication of quantum dot gate (QDG) [Formula: see text]-FETs using GeOx-cladded Ge quantum dot self-assembled on tunnel gate oxide. Experimental I–V characteristics exhibiting 4-states are presented. Simulations are presented for the operation of a viable 8-state SRAM using QDG-FETs.
Application of Interactive Object Model in Sports Teaching
Authors: Wang Xiangyang
Published: July 2024

Traditional physical education is just repeated training without quantitative teaching and training data results. Multimedia information analysis and retrieval technology can make repeated research on the content of competition or training, and increase the quantitative analysis of training indicators. Therefore, this paper proposes an interactive compressed domain key video object model to realize the design and production of physical education video, so as to quantify the effect of physical education. This paper discusses the interactive design and application of PE teaching video from three aspects: static, dynamic, and semantic. The interactive object model proposed in this paper can formulate corresponding strategies for different key sports video objects. The distortion rate of the complete key video object is 2.3%, which is 0.09% lower than the distortion rate of the Kim2002 scheme. From a usage perspective, through the scheme proposed in this article, coaches can obtain teaching videos with simple initial extreme values on an interactive interface, and the distortion rate of the video object is lower than that of traditional schemes.
Pinchuk scaling method on domains with non-compact automorphism groups
Authors: Thu Ninh Van , Son Nguyen Thi Kim , Dieu Nguyen Quang
Published: July 2024

In this paper, we characterize weakly pseudoconvex domains of finite type in [Formula: see text] in terms of the boundary behavior of automorphism orbits by using the scaling method.
Enumerating families of clusters in type 𝔸̃
Authors: Maresca Ray , Proskura Nikolas
Published: July 2024

In this paper, we will place clusters in type [Formula: see text] (equivalently triangulations of an annulus) into infinite families parametrized by winding numbers of certain arcs in the corresponding triangulation. We will count how many such families there are and provide an algebraic description of these families in terms of the corresponding cluster category.
Optimizing the preparation of bromo phthalonitriles and piloting them to peripherally brominated boron subphthalocyanines
Authors: Wassink Lea , Bender Timothy P.
Published: July 2024

Boron subphthalocyanines (BsubPcs) are versatile molecules with advantageous properties for applications. The BsubPcs are synthesized by the cyclotrimerization of a phthalonitrile and are composed of three isoindole subunits bound by three aza-/imine-bridging nitrogens. There are a variety of BsubPc derivatives shown within the literature due to the differentiation of a phthalonitrile precursor. The differentiation of a phthalonitrile enables the peripheral functional groups. The BsubPcs can be derivatized in two steps: First step is the cyclotrimerization of a phthalonitrile in the presence of a strong Lewis Acid, typically a boron trihalide (BX3) and enables a remaining axial substituent that is a B-X[Formula: see text] bond; second step is optional, the B-X[Formula: see text] bond can react with a nucleophile and results in B-X[Formula: see text]. If the starting phthalonitrile is asymmetric, it will result in a combination of isomers. For this study, our approach is to have bromine substituents and to study their physical properties to see if applicable to organic electronic applications; chlorine and fluorine have been in past studies as halogens are unique and variations may present useful tools as they are known for electronegativities. The general phthalonitrile with no substitutions is produced in industry from [Formula: see text]-xylene. There are a variety of ways to synthesize other phthalonitriles with halogens. However, phthalonitriles can also be made by a method that has the most versatility with its substituents and can start with phthalic acid and go to phthalic anhydride to phthalimide to phthalamide and final to phthalonitrile; it is also possible to synthesize a phthalimide directly from phthalic acid, and this is part of this study as we were focusing on bromination, we also wanted to optimize the synthetic pathways to brominated phthalonitriles, and we took an engineering perspective and for this study, we wish to show you.
Coordination complexes of iron(II) phthalocyanine with cationic, anionic and neutral ligands
Authors: Romanenko Nikita R. , Faraonov Maxim A. , Kuzmin Alexey V. , Khasanov Salavat S. , Konarev Dmitri V.
Published: July 2024

A series of coordination complexes of iron(II) phthalocyanine (FeIIPc) with anionic, cationic and neutral ligands has been obtained in crystalline form. The salt of FeIIPc with MDABCO[Formula: see text] cations (MDABCO[Formula: see text][FeI(Pc[Formula: see text]][Formula: see text]⋅(I[Formula: see text]⋅2TPC⋅2C6H4Cl2 (1) contains FeIIPc reduced to [FeI(Pc[Formula: see text]][Formula: see text], and the FeI ion coordinates two cationic MDABCO[Formula: see text] ligands with the Fe-N(MDABCO[Formula: see text] bond length of 2.49–2.50 Å. The I[Formula: see text] anions are introduced into the phthalocyanine layers to compensate positive charge of the second MDABCO[Formula: see text] cation and form short hydrogen bonds with Pc. Preparation of dianionic salt of FeIIPc with the Bu3MeP[Formula: see text] cations by their reduction with sodium fluorenone ketyl yields a green solution characteristic of neutral FeIIPc. The solved structure shows deprotonation of the cations and the formation of Bu3PCH2 ylide which coordinates to FeIIPc in (Bu3PCH[Formula: see text][FeII(Pc[Formula: see text]] (2). Two anionic acetylide (C[Formula: see text]CH[Formula: see text] or imidazole (Im[Formula: see text] ligands coordinate to FeIIPc by dissolving with cryptand and yielding {Cryptand(Na[Formula: see text]}2{(CCH[Formula: see text]FeII(Pc[Formula: see text]}⋅2C6H4Cl2 (3) and {Cryptand(Na[Formula: see text]}2{(Im[Formula: see text]FeII(Pc[Formula: see text]}⋅2C6H4Cl2 (4) complexes. In contrast to 1, complexes 2–4 are mainly neutral with weak charge transfer from ligands to FeII, which is accompanied by the formation of FeI in 2 and 3.
Existence, concentration and multiplicity of solutions for (p,N)-Laplacian equations with convolution term
Authors: Li Yiqing , Van Nguyen Thin , Zhang Binlin
Published: July 2024

In this paper, we concern some qualitative properties of the following [Formula: see text]-Laplacian equations with convolution term: [Formula: see text] where [Formula: see text] is a positive parameter, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] satisfies the critical exponential growth. By using the variational methods and the penalization method, we prove the existence of solutions for the above equations which concentrates at a local minimum of [Formula: see text] in the semi-classical limit as [Formula: see text]. Moreover, we obtain the multiplicity of solutions for the above equations by the Morse theory.
Multi-decomposition of complete graphs into stars and bowties of size 6
Authors: Hemalatha P. , Ramya K.
Published: July 2024

Let [Formula: see text] denote a complete graph on [Formula: see text] vertices and [Formula: see text] denote a complete bipartite graph [Formula: see text]. A Bowtie [Formula: see text] is a graph formed by the union of two cycles [Formula: see text] and [Formula: see text] intersecting at a common vertex. A decomposition of a graph [Formula: see text] is a collection of edge-disjoint subgraphs [Formula: see text], such that every edge of G belongs to exactly one [Formula: see text]. Given non-isomorphic subgraphs [Formula: see text] and [Formula: see text] of [Formula: see text], a [Formula: see text] — multi-decomposition of [Formula: see text] is the decomposition of [Formula: see text] into [Formula: see text] copies of [Formula: see text] and [Formula: see text] copies of [Formula: see text], such that [Formula: see text], for some integers [Formula: see text]. In this paper, the multi-decomposition of [Formula: see text] into [Formula: see text] and [Formula: see text] has been investigated and obtained a necessary and sufficient condition when [Formula: see text]. It is proved that for a given positive integer [Formula: see text], [Formula: see text] can be decomposed into [Formula: see text] copies of [Formula: see text] and [Formula: see text] copies of [Formula: see text] for some pair of non-negative integers [Formula: see text] if and only if [Formula: see text], for all [Formula: see text].