bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanometer-thick TiO2 channel thin film transistors as radical monitors for plasma enhanced atomic layer deposition
Authors: Yamano Kohei , Takeda Hibiki , Miyazawa Ryo , Miura Masanori , Ahmmad Bashir , Hirose Fumihiko
Published: November 2024

Nanometer-thick-TiO2-channel thin-film transistors (TFTs) are examined as oxidizing-agent monitors for room-temperature atomic layer deposition (RTALD). RTALD is a plasma-based process using plasma-excited humidified argon where OH radicals oxidize the precursor-gas adsorbed surface. In the TFT, the anatase TiO2 channel, with a thickness of 16 nm, is attached to a 300 nm thick gate capacitor of SiO2, while the channel surface is exposed to the ALD ambient. A heavily doped n-type Si substrate attached to the gate SiO2 is used as the gate electrode. The gate width and length are 1000 and 60 μm, respectively. When the TFT is installed in the RTALD chamber, the drain-current waveform is recorded in the course of the metal organic gas adsorption, evacuation of the residual gas, oxidization, and evacuation. In the present study, three kinds of metal organic (MO) precursors, tetrakis(dimethyl)amino titanium, tris(dimethyl)amino silane, and trimethyl aluminum are examined. The drain current exhibits strong responses upon the exposure of the plasma excited humidified argon. This suggests that OH radicals in the plasma might oxidize the adsorbed MO precursors to produce the OH moieties, where the surface polarization of OH moieties might enhance channel conductivity. The experimental results suggest the applicability of the present TFT as a plasma monitor in RTALD.
Photoassisted electron emission from planar-type electron source based on graphene/oxide/silicon structure
Authors: Shimawaki Hidetaka , Nagao Masayoshi , Murakami Katsuhisa
Published: November 2024

This paper reports on photoassisted electron emission from a planar-type electron emission source based on a graphene/oxide/p-Si structure under visible laser light irradiation. The electron source is expected to be useful as a photocathode with a high quantum efficiency and an ultrafast pulsed electron beam. The electron emission efficiency is found to be 12%, independent of laser light irradiation. Without a negative electron affinity surface, the emission current generated by irradiation shows an increase of several orders of magnitude compared with that in the dark, and a quantum efficiency of 0.3% is achieved. This electron source exhibits advanced photoassisted electron emission characteristics with high photosensitivity in the order of milliamps per watt. The photoassisted emission from the device shows a photoresponse with a rise and fall time of 70 μs at a wavelength of 633 nm, which is determined by the diffusion process of photoexcited electrons in the bulk. The use of a heavily doped p-type silicon substrate provides a practical route for further improvement.
Learning a Trauma-Sensitive Sport Model: Programme Implementation Experiences
Authors: Shaikh Majidullah , Culver Diane M. , Forneris Tanya
Published: November 2024

This study investigates the learning experiences of youth sport leaders as they implemented a trauma-sensitive sport model in a Canadian youth-serving organisation. Using Wenger-Trayner and Wenger-Trayner’s value-creation cycle, the study assesses the value generated through leaders’ participation in ongoing social learning opportunities and programme implementation. Two cohorts of leaders participated in this study, and data were collected through interviews, knowledge surveys, and communications on an online workspace. The qualitative thematic analysis offered insights of the diverse learning interactions and value generated in these interactions, and these findings were further complemented by the quantitative findings. The results indicated that leaders encountered various learning interactions (e.g., training workshops, applied practice, and peer discussions) and generated in immediate (e.g., enjoyment and peer relationships), applied (e.g., programme facilitation skills, supporting youth’s learning, and youths’ receptivity), realised (e.g., leaders’ knowledge and youths’ behaviour change), and transformative values (e.g., transfer of leaders’ skills and influence on club culture and practices). The study contributes valuable insights into applying trauma-sensitive models in youth sports, emphasising the importance of varied learning interactions and outcomes.
Leisure-Time Physical Activity to Reduce Risk of Long-Term Sickness Absence Across Diverse Subgroups in the Working Population—A Prospective Cohort Study of 68,000 Participants
Authors: Morera Álvaro , Calatayud Joaquín , López-Bueno Rubén , Núñez-Cortés Rodrigo , Bláfoss Rúni , Venge Skovlund Sebastian , Andersen Lars Louis
Published: November 2024

Background: There is a dearth of knowledge regarding the relationship between engaging in moderate and vigorous physical activity and long-term sickness absence (LTSA), particularly among various population subgroups such as individuals of different ages or body mass indices. We aimed to evaluate the prospective associations of moderate and vigorous leisure-time physical activity with the risk of LTSA in the general working population. Methods: A prospective cohort study with a 2-year register follow-up was conducted, where 68,222 representative workers from Denmark completed a questionnaire about work environment, lifestyle, and health. Data on LTSA (≥6 consecutive weeks of sickness absence) were obtained from the Danish Register for Evaluation of Marginalization. We used Cox regression for the statistical analysis, adjusting for relevant confounding factors. We also performed age- and BMI-stratified analyses. Results: In the fully adjusted model, 2 to 4 hours per week of moderate activity (hazard ratios [HR] = 0.87; 95% CI, 0.77 to 0.99) and ≥2 hours per week of vigorous activity reduced LTSA risk compared with no physical activity. However, 2 to 4 hours per week of vigorous activity (HR = 0.84; 95% CI, 0.76 to 0.91) provided the greatest risk reduction. In the total sample, the complete absence of vigorous activity was associated with increased risk of LTSA (HR = 1.13; 95% CI, 1.05 to 1.22). In stratified analyses, the results were consistent for workers <50 years (HR = 1.14; 95% CI, 1.03 to 1.26), ≥50 years (HR = 1.13; 95% CI, 1.02 to 1.26), and those with a BMI ≥ 25 (HR = 1.16; 95% CI, 1.06 to 1.28). The complete absence of moderate activity was not associated with LTSA. Conclusion: Vigorous leisure-time physical activity appears to be more important than moderate activity to prevent LTSA.
Saving Women’s Sport: The Case for Feminist Dialogue With the Unregulated Majority
Authors: Pape Madeleine
Published: November 2024

Studies of eligibility regulation often focus on how, given inconclusive science, policymakers engage in ideological work to stabilize the women’s category. This paper considers the policy role of women athletes and particularly the “unregulated majority”: the notion that certain women are protected from eligibility regulation and benefit from a cisnormative, binary, and Global North-dominated system of sports competition. I examine a case from the 1990s, when a group of women athletes sought to reinstate gynecological exams and chromosome screening in track and field. Analyzing correspondence of the “Gender Verification Fax Club,” an influential group of experts, I consider whether meaningful dialogue was achieved. I reflect on how a feminist approach to dialogue could address the role of hegemonic femininity in eligibility regulation.
The Summer North Atlantic Oscillation, Arctic sea ice, and Arctic jet Rossby wave forcing
Authors: Folland Chris K. , Ou Tinghai , Linderholm Hans W. , Scaife Adam A. , Knight Jeff , Chen Deliang
Published: November 2024

We use Coupled Model Intercomparison Project Phase 6 (CMIP6) coupled and Atmospheric Model Intercomparison Project (AMIP) climate models, dynamical analyses, and observations to investigate interactions between summer Arctic sea ice concentration (SIC) variations and the Summer North Atlantic Oscillation (SNAO). Observations suggest that SIC-SNAO relationships mainly come from the East Siberian to Arctic Canada (ESAC) region where a weak atmospheric jet stream exists in summer. Twelve CMIP6 models with the most realistic atmospheric climatologies over the North Atlantic and Europe agree well with reanalyses on relationships between SIC and Northern Hemisphere atmospheric circulation. CMIP6 model data indicate that ESAC SIC influences the SNAO with a lead time of several weeks. However, AMIP simulations do not reproduce the observed atmospheric circulation when observed sea ice is prescribed. Rossby wave analyses do though support observed ESAC SIC influences on the SNAO. We conclude that ESAC Arctic SIC modestly influences the SNAO, and such investigations require the use of coupled models.
Symptoms after Lyme disease: What’s past is prologue
Authors: Marques Adriana
Published: November 2024

Protracted fatigue and other symptoms can occur after Lyme disease and other infections, with numerous possible drivers. Studies on posttreatment Lyme disease have been inconclusive, with no confirmed biomarker emerging. Prolonged antibiotic therapy provides no benefit. Thus, a holistic approach toward understanding and treating this complex disease is necessary.
LiaR-dependent gene expression contributes to antimicrobial responses in group A
Streptococcus
Authors: Vega Luis Alberto , Sanson-Iglesias Misú , Mukherjee Piyali , Buchan Kyle D. , Morrison Gretchen , Hohlt Anne E. , Flores Anthony R.
Published: November 2024

The ability to sense and respond to host defenses is essential for pathogen survival. Some mechanisms involve two-component systems (TCSs) that respond to host molecules, such as antimicrobial peptides (AMPs), and activate specific gene regulatory pathways to aid in survival. Alongside TCSs, bacteria coordinate cell division proteins, chaperones, cell wall sortases, and secretory translocons at discrete locations within the cytoplasmic membrane, referred to as functional membrane microdomains (FMMs). In group A
Streptococcus
(GAS), the FMM or “ExPortal” coordinates protein secretion, cell wall synthesis, and sensing of AMP-mediated cell envelope stress
via
the LiaFSR three-component system. Previously, we showed that GAS exposure to a subset of AMPs (α-defensins) activates the LiaFSR system by disrupting LiaF and LiaS co-localization in the ExPortal, leading to increased LiaR phosphorylation, expression of the transcriptional regulator SpxA2, and altered GAS virulence gene expression. The mechanisms by which LiaFSR integrates cell envelope stress with responses to AMP activity and virulence are not fully elucidated. Here, we show the LiaFSR regulon is comprised of genes encoding SpxA2 and three membrane-associated proteins: a PspC domain-containing protein (PCP), the lipoteichoic acid-modifying protein LafB, and the membrane protein insertase YidC2. Our data support that phosphorylated LiaR induces transcription of these genes
via
a conserved operator, whose disruption attenuates GAS virulence and increases susceptibility to AMPs in a manner primarily dependent on differential expression of SpxA2. Our work expands our understanding of the LiaFSR regulatory network in GAS and identifies targets for further investigation of mechanisms of cell envelope stress tolerance contributing to GAS pathogenesis.
Do white-footed mice, the main reservoir of the Lyme disease pathogen in the United States, clinically respond to the borrelial tenancy?
Authors: Rogovskyy Artem S. , Pliasas Vasilis C. , Buhrer Ryan , Lewy Keith , Wiener Dominique J. , Jung Yoonsung , Bova Jonathan , Rogovska Yuliya , Kim Sun J. , Jeon Eunhye “Grace”
Published: November 2024

As white-footed mice,
Peromyscus leucopus
, are considered the primary animal reservoir of
Borreliella burgdorferi sensu stricto
(
Bb
), the main agent of Lyme disease (LD) in the United States, these animals represent the most relevant model to study borrelial spirochetes in the context of their natural life cycle. Previous studies have consistently demonstrated that although white-footed mice respond immunologically to the invasion of the Lyme pathogen,
P. leucopus
adults do not develop a clinically detectable disease. This tolerance, which is common for mammalian reservoirs of different pathogens, contrasts with detrimental anti-borrelial responses of C3H mice, a widely used animal model of LD, which always result in a clinical manifestation (e.g., arthritis). The current investigation is a follow-up of our recent study that already showed a relative quiescence of the spleen transcriptome for
Bb
-infected white-footed mice compared to the infected C3H mice. In an effort to identify the mechanism behind this tolerance, in this study, we have evaluated an extensive list of hematological and biochemical parameters measured in white-footed mice after their 70-day-long borrelial infection. Despite missing reference intervals for
Peromyscus
mice, our sex- and age-matched uninfected controls allowed us to assess the blood and serum parameters. In addition, for our assessment, we also utilized behavioral, immunological, and histological analyses. Collectively, by using the metrics reported herein, the present results have demonstrated clinical unresponsiveness of
P. leucopus
mice to the borrelial infection, presenting no restriction to a long-term host–pathogen co-existence.
The ribosome-associated quality control pathway supports survival in the absence of non-stop ribosome rescue factors
Authors: Callan Katrina , Prince Cassidy R. , Feaga Heather A.
Published: November 2024

In bacteria, if a ribosome translates an mRNA lacking a stop codon it becomes stalled at the 3′ end of the message. These ribosomes must be rescued by
trans
-translation or the alternative rescue factors (ArfA or ArfB). However, mounting evidence suggests that the ribosome quality control (RQC) pathway may also rescue non-stop ribosomes. Here, we surveyed the conservation of ribosome rescue pathways in >15,000 bacterial genomes. We found that
trans
-translation is conserved in >97% of bacterial genomes, while the other rescue pathways are restricted to particular phyla. We did not detect the gene encoding RqcH, the major mediator of RQC, in Proteobacteria (Pseudomonadota). In all Proteobacteria investigated to date,
trans
-translation is essential in the absence of the Arf proteins. Therefore, we tested whether expression of RQC components from
Bacillus subtilis
could rescue viability in the absence of
trans
-translation and ArfA in
Escherichia coli
. We found that the RQC pathway indeed functions in
E. coli
and rescues the well-documented synthetic lethal phenotype of ∆
ssrA
∆
arfA
. Moreover, we show that the RQC pathway in
B. subtilis
is essential in the absence of
trans
-translation and ArfA, further supporting a role for the RQC pathway in the rescue of non-stop ribosomes. Finally, we report a strong co-occurrence between RqcH and the ribosome splitting factor MutS2, but present experimental evidence that there are likely additional ribosome splitting factors beyond MutS2 in
B. subtilis
. Altogether, our work supports a role for RQC in non-stop ribosome rescue and provides a broad survey of ribosome rescue pathways in diverse bacteria.

IMPORTANCE

In bacteria, it is estimated that 2%–4% of all translation reactions terminate with the ribosome stalled on a damaged mRNA lacking a stop codon. Mechanisms that rescue these ribosomes are essential for viability. We determined the functional overlap between the ribosome quality control pathway and the classical non-stop rescue systems [alternative rescue factor (ArfA) and
trans
-translation] in a representative Firmicute and Proteobacterium, phyla that are evolutionarily distinct. Furthermore, we used a bioinformatics approach to examine the conservation and overlap of various ribosome rescue systems in >15,000 species throughout the bacterial domain. These results provide key insights into ribosome rescue in diverse phyla.
Draft genome sequence of
Aurantiochytrium
spp. strains L3W, 9LR, 8W, 10W, and 10LW, a fatty acid-producing thraustochytrids from food wastes
Authors: Suenaga Toshikazu , Mitarai Yukine , Anh Tran Nhat , Gotoh Takehiko , Nishijima Wataru , Nakai Satoshi
Published: November 2024

We report draft genome sequences of
Aurantiochytrium
spp. strains L3W, 9LR, 8W, 10W, and 10LW isolated from coastal environments. The strains were able to produce polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), confirming the metabolic pathways retained in the genomes.
Genome assembly of a potential probiotic
Bifidobacterium bifidum
BB11 strain isolated from Holstein calves
Authors: Langa Sydwell , Mamphogoro Tshifhiwa Paris
Published: November 2024

Here we report the genome sequence of
Bifidobacterium bifidum
BB11 strain, isolated from the Holstein bull calf’s rumen samples. The strain tested positive for probiotic characteristics such as bile salt tolerance, adhesion, and acid tolerance. The genome size was 2,200,000 bp with the guanine and cytosine (G+C) content of 62.5%.
Recombinant chimeric horsepox virus (TNX-801) is attenuated relative to vaccinia virus strains in both
in vitro
and
in vivo
models
Authors: Trefry Stephanie V. , Awasthi Mayanka , Raney Christy N. , Cregger Amy L. , Gonzales Chase A. , Layton Brittney L. , Enamorado Robert N. , Martinez Nelson A. , Gohegan Deborah S. , Masoud-Bahnamiri Masoudeh , Cho Jennifer Y. , Myscofski Dawn M. , Moulaei Tinoush , Ziółkowska Natasza E. , Goebel Scott J. , Lederman Seth , Bavari Sina , Nasar Farooq
Published: November 2024

Recombinant chimeric horsepox virus (TNX-801) is a preclinical vaccine in development against mpox and smallpox. In this report, we investigated the potential phenotypic differences in
in vitro
and
in vivo
models between TNX-801 and older vaccinia virus (VACV)-based vaccine strains (VACV-Lis and VACV-NYCBH) used in the eradication of smallpox as well as VACV-WR, VACV-IHD, and MVA. TNX-801 displayed a small plaque phenotype (~1–2 mm) in BSC-40 and Vero-E6 cells. Multi-step replication kinetics in immortalized nonhuman primate cell lines, and human primary cells from dermal and respiratory tracts yielded >10- to 100-fold lower infectious titers than the VACV strains. In addition, the infectious particle-to-genome copy ratio data suggests that TNX-801 genome packaging is ~10- to 100-fold less efficient than the VACV strains and the potential mechanism of TNX-801 attenuation is at the packaging/egress stage. Lastly, the susceptibility to VACV and TNX-801 infection of three new immunocompromised murine models (C56BL/6
Ifnar
−/−
, C56BL/6
Ifngr
−/−
, and C56BL/6
Ifnar
−/−
/
Ifngr
−/−
) was investigated. VACV strains were able to produce severe disease including decrease in body weight and temperature, as well as lethality in murine models via the intraperitoneal or intranasal routes. In contrast to VACV strains, TNX-801 was unable to produce any disease in murine models. These data demonstrate that TNX-801 is >10- to 1,000-fold more attenuated compared to older VACV-based smallpox vaccine strains in human primary cell lines and immunocompromised mice.

IMPORTANCE

Variola and monkeypox viruses are medically important pathogens that can cause fatal human disease. The two FDA-approved vaccines, ACAM-2000 and JYNNEOS, have important advantages and disadvantages. ACAM-2000 offers durable immunity; however, it has high adverse event rates. In contrast, JYNNEOS has a safer profile but requires two doses 4-weeks apart to achieve comparable immunity. Consequently, there is a need for vaccines offering durable immunity via single immunization with minimal adverse events. TNX-801 is a preclinical stage vaccine that can stimulate potent immunity via a single dose and provides protection against lethal mpox disease in the nonhuman primate model. Here, we show that TNX-801 is >10- to 1,000-fold attenuated in
in vitro
and
in vivo
models including human primary cells and immunocompromised murine models than vaccine strains utilized in smallpox eradication. The natural attenuation of TNX-801 and its ability to induce protective immunity via a single vaccination are promising and warrants further development.
Evidence for a Late Cretaceous to Paleogene basement-involved retroarc wedge in the southern U.S. Cordillera: A case study from the northern Chiricahua Mountains, Arizona
Authors: Chapman James B. , Clinkscales Christopher , Trzinski Adam , Daniel Michael
Published: November 2024

Late Cretaceous to Paleogene contractional deformation in the southern U.S. Cordillera is commonly attributed to the Laramide Orogeny, in part because of the prevalence of moderate- to high-angle, basement-involved reverse faults. However, it is unclear if the tectonic models developed for the archetypal Laramide foreland belt in the U.S. Rocky Mountain region are applicable to the southern U.S. Cordillera. New geologic mapping of the northern Chiricahua Mountains in southeast Arizona, USA, indicates the presence of an originally sub-horizontal thrust fault, the Fort Bowie fault, and a thin-skinned ramp-flat thrust system that is offset by a younger thrust fault, the Apache Pass fault, that carries basement rocks. Cross-cutting relationships and new geochronologic data indicate deformation on both faults occurred between 60 Ma and 35 Ma. A biotite 40Ar/39Ar plateau age of 48 Ma from the hanging wall of the basement-involved Apache Pass fault is interpreted to record erosion related to reverse fault movement and rock uplift. The presence of thrust faults in southeast Arizona raises the possibility of a latest Cretaceous–Eocene retroarc orogenic wedge that linked the Sevier and Mexican thrust belts to the north and south, respectively. Basement-involved deformation does not rule out the presence of a retroarc wedge, and many Cordilleran orogenic systems include basement-involved thrusting.
Supplemental Material: Formation of rare-element pegmatites in the Chinese Altai: Contribution of two-stage melting
Authors: Liu Siyu , Wang Rui , al. et
Published: November 2024

Detailed description of geological background, analytical methods and modeling approach, and geochemical data.  
Flexible ngo-donor coordination in aid interventions to strengthen resilience: the case of Lebanon’s primary healthcare system
Authors: Khodor Rawya , Bou Karroum Lama , El-Jardali Fadi
Published: November 2024

Introduction

With shifts in international aid, international donors have increasingly regarded non-governmental organisations (NGOs) as capable of providing alternative public service arrangements. As funding flows to NGOs, particularly in contexts where both actors work towards strengthening health system resilience, NGO-donor relationships evolve. However, despite calls to investigate the contribution of relationships between actors within health systems, including NGOs and their donors, to health system resilience, empirical research is limited. Understanding these relationships is crucial for comprehending their role in fostering resilient health systems. This research fills this gap, by examining how NGO-donor coordination contributes to health system resilience in Lebanon.

Methods

This research focuses on Lebanon’s primary health system, primarily managed by NGOs through contracts and heavily funded by donors. It examines NGOs operating under the national primary healthcare network (PHCN). The participants, including staff from these NGOs and donor agencies funding them, were purposively selected. 31 semi-structured interviews were conducted. The analysis framework relied on a thematic analysis.

Results

The findings revealed that the flexibility in NGO-donor coordination in Lebanon depends on donors’ trust, regular coordination and donors’ willingness to listen to NGOs’ needs. In this light, they uncovered that flexible NGO-donor coordination enhances NGOs’ resilience capacities in shocks, allowing them to operate flexibly. By strengthening NGOs’ resilience, which contributes to the resilience of the broader health system, this relationship contributes to health system resilience.

Conclusion

The findings contradict the mainstream development literature on NGO-donor relationships. The latter focuses on donor funding requirements that often result in rigid NGO-donor coordination, making it difficult for NGOs to be resilient. Rather, they emphasise the donors’ role in implementing flexible development approaches, through flexible NGO-donor coordination, strengthening health system resilience. Overall, this paper contributes to the health system resilience literature by exploring how specific configurations of NGO-donor coordination strengthen health system resilience.
Catatonia in anti-NMDA receptor encephalitis: a case series and approach to improve outcomes with electroconvulsive therapy
Authors: Kraiter F. Gabriela , May Dakota T. , Slauer Ryan D. , Abburi Nandini , Eckstein Christopher , Shah Suma , Komisar Jonathan R. , Feigal Jacob P.
Published: November 2024

Background

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has been recognised to present with the syndrome of catatonia. In severe cases dysautonomia is representative of malignant catatonia. The treatment with benzodiazepines (BZDs) and electroconvulsive therapy (ECT) may decrease morbidity and mortality in patients presenting with anti-NMDA receptor encephalitis and catatonia.

Methods

This is a retrospective case series of eight patients with anti-NMDA receptor encephalitis treated with ECT. We use clinical prediction scores (Clinical Assessment Scale for Autoimmune Encephalitis [CASE] and anti-NMDAR Encephalitis One-Year Functional Status scores) to compare expected outcomes and observed outcomes.

Results

CASE scores in our group ranged between 5 and 19, with a mean score of 13.8 (median 15.5). NEOS scores ranged from 2 to 4, with a mean and median of 3. Of the eight patients, six had a favourable modified Rankin Score (0–2) at a follow-up of 8 to 12 months. Patients received an average of 29.9 ECT treatments in total.

Conclusions

Based on clinical prediction scores, this cohort had better than expected functional outcomes. We discuss the use of BZDs and ECT in these cases and propose a treatment algorithm for patients who present with catatonic syndrome in anti-NMDA receptor encephalitis.
Network-based hub biomarker discovery for glaucoma
Authors: Li Min , Liu Shunming , Ma Shuo , Shang Xianwen , Zhang Xiayin , Jason Ha , Huang Yu , Kiburg Katerina , Zhao Ke , Hu Guang , Zhang Lei , Yu Honghua , He Mingguang , Zhang Xueli
Published: November 2024

Objective

Glaucoma is an optic neuropathy and the leading cause of irreversible blindness worldwide. However, the early detection of glaucoma remains challenging, as chronic forms of glaucoma remain largely asymptomatic until considerable irreversible visual field deficits have ensued. Thus, biomarkers that facilitate early diagnosis and treatment for glaucoma patients with a high risk of progression are pressing.

Methods and analysis

Human disease–biomarker interactions network and human disease–target–drug interactions network were first constructed based on multiomics data. The greedy search algorithm was used to search for the hub biomarkers and drug targets for glaucoma. Genome-wide association studies and epidemiological data from the UK Biobank were used to verify our results. Biological network and functional analysis was conducted to find common network features and pathways.

Results

We identified 10 hub biomarkers/drug targets for the diagnosis, treatment and prognosis for glaucoma. These results were verified by text mining and genomic/epidemiology data. We also predicted the new application of BMP1 and MMP9 to diagnose glaucoma and confirm the theory of hub biomarkers with multiple clinical applications. Further, relevant pivotal pathways for these hub biomolecules were discovered, which may serve as foundations for future biomarker and drug target prediction for glaucoma.

Conclusion

We have used a network-based approach to identify hub diagnostic and therapeutic biomarkers for glaucoma and detected relationships between glaucoma and associated diseases. Several hub biomarkers were identified and verified, which may play more important roles in the diagnosis and treatment of glaucoma.
Correlation of safety and efficacy of atezolizumab therapy across indications
Authors: Durán-Pacheco Gonzalo , Chandler G Scott , Maiya Vidya , Socinski Mark A , Sonpavde Guru , Puente Javier , Essioux Laurent , Carter Corey , Cardona Jose Vicente , Mohindra Rajat , Naidoo Jarushka
Published: November 2024

Background

The association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation between severity and impact of specific organ involvement by immune-related adverse events (irAE) and cancer outcomes is poorly understood. Most irAEs are mild-to-moderate but severe irAEs may pose clinical management challenges and affect patient outcomes.

Methods

We assessed the association between irAE grade (G) and specific organ involvement with overall survival (OS) in 9,521 patients across 14 studies involving atezolizumab as mono (IO) or with chemo/targeted (C-IO) therapy as compared with chemo/targeted therapy (C) in advanced non-small cell lung, small-cell lung, renal cell, urothelial, and triple-negative breast cancers. We used a mixed-effect Cox proportional hazard model for time-varying covariates to address immortal-time bias; adjusted for baseline factors associated with irAEs and OS to control for confounding bias; and focused on five common irAEs (dermatologic, thyroid dysfunction, hepatitis, pneumonitis, and colitis) to avoid low statistical power for rare events.

Results

For patients treated with IO or C-IO, G1-2 irAEs were associated with improved OS (HR=0.65, p<0.01) and G3-4 irAEs showed a slight increased risk of death (HR=1.18, p=0.10) versus patients without irAEs. By specific irAE, G1-2 cutaneous irAEs, thyroid dysfunction, or pneumonitis were associated with improved OS (p<0.05), while G3-4 pneumonitis and colitis were associated with worse OS (p<0.01). There was no association between hepatitis and OS by any grade. Findings were consistent across indications.

Conclusions

This analysis demonstrates a correlation between irAEs and improved OS with atezolizumab by severity grade and the most common irAEs by organ involvement. Low-grade irAEs are significantly associated with improved OS, while specific high-grade irAEs are associated with poorer OS, underscoring the importance of early recognition and management of toxicity to optimize benefit/risk balance.
Is rheumatoid arthritis always preceded by a symptomatic at-risk phase of arthralgia?
Authors: Claassen Stijn , Boeren Anna M P , Khidir Sarah J H , van Steenbergen Hanna W , van der Helm-van Mil Annette H M
Published: November 2024

Objectives

Secondary prevention of rheumatoid arthritis (RA) is generally considered potentially impactful because the entire RA population is believed to experience a symptomatic ‘pre-RA’ phase. We wondered whether this dogma is correct. Therefore we investigated an inception cohort of patients with newly diagnosed RA and studied among them patients who did and did not present with preceding arthralgia at risk for RA.

Methods

Consecutively diagnosed patients with RA between 2012 and 2022 were studied (n=699). These patients had either directly presented with clinically apparent arthritis, or had first presented with clinically suspect arthralgia (CSA). Clinical characteristics at symptom onset and RA diagnosis were compared. Whether certain characteristics frequently occurred together was studied using a K-means algorithm after dimension reduction with partial least squares discriminant analysis. To validate that groups differed in long-term outcomes, sustained disease-modifying anti-rheumatic drug-free remission (SDFR) of the groups was studied during a median follow-up of 5.3 years.

Results

Patients with RA who had first presented with CSA were younger, more often had a gradual symptom onset and were more often anti-citrullinated protein antibodies (ACPA)-positive. Studying characteristics at symptom onset and RA diagnosis revealed four patient clusters, of which two clusters included almost all patients with a preceding CSA phase. Patients in these two clusters (55% of RA population) were younger, had a gradual symptom onset, longer symptom duration and were more frequently ACPA-positive. Patients with RA in these clusters achieved SDFR less often (HR 0.51 (95% CI 0.37 to 0.68)) than the patients with RA in the two clusters where preceding CSA was infrequent/absent.

Conclusion

These data suggest the notion that the entire RA population has an identifiable symptomatic risk stage should be refuted. This may impact on the scope of preventive interventions targeting the symptomatic risk phase.
Partial involvement of nitric oxide synthase in increased pilocarpine-induced sweating in exercise-trained men
Authors: Okamoto Yumi , Otsuka Junto , Amano Tatsuro
Published: November 2024

The physiological mechanisms involved in augmented cholinergic agonist-induced sweating in exercise-trained individuals remain unclear. This study hypothesizes that nitric oxide synthase (NOS) contributes to augmented pilocarpine-induced sweating in habitually exercise-trained individuals. Endurance-trained and untrained men ( n = 15 each) iontophoretically received 1% L-NAME, a NOS inhibitor, and saline (control) in the forearm and then administered 0.001% and 1% pilocarpine to evaluate sweat rate. L-NAME administration attenuated pilocarpine-induced sweating by 10% in the exercise-trained ( P = 0.004) but not in untrained ( P = 0.764) groups independent of pilocarpine concentrations. Results indicate that NOS partially contributes to increased cholinergic sweating in exercise-trained men.
Rural Tourist Attractions Recommendation Model Based on Multi-Feature Fusion Graph Neural Networks
Authors: Zhang Xiangrong , Wang Xueying
Published: November 2024

With the rapid growth of the rural tourism industry, traditional tourism recommendation technologies can no longer meet the necessary requirements. To address the issue of rural tourist attraction recommendations, a rural tourist attraction recommendation model is constructed based on a multi-feature fusion graph neural network. First, construct a feature map based on the relationship between tourists’ preferences and tourist attractions, and incorporate the attention mechanism to enhance the model’s learning capabilities. Second, utilize a two-part graph model to extract positive and negative preference features of tourists, and a conversation graph model to extract tourists’ transfer preference features. Finally, various features are utilized to generate suggested content by computing scores for tourists’ travel preferences. To address the problem of recommending tourist groups, suitable features for random group matching are collected and the cosine function is employed to identify users with similar random group features. Finally, the multi-features are merged, and the tourists’ interest preferences are scored to arrive at content recommendations. In the experiment on individualized attraction recommendations, data from the Chengdu area were used to test the proposed model. The accuracy of the model’s recommendations was 0.822 for five recommendations which outperformed the other models. In the experiment for group-based attraction recommendations, this experiment tested the Chengdu dataset. The proposed model achieved the highest accuracy of 0.972 when the group size was 70, outperforming the other two models. Additionally, with regards to different numbers of recommendations, the proposed model’s accuracy was 0.5241, which was the best performance among the three models when the number of recommendations was set to five. The proposed recommendation model performs optimally in suggesting tourist attractions and meets the needs of rural tourism. The research content provides crucial technical references for tourist traveling and rural tourism development.
Adadelta-CSA: Adadelta-Chameleon Swarm Algorithm for EEG-Based Epileptic Seizure Detection
Authors: Indu Salini G. , Sowmy I.
Published: November 2024

Epilepsy is referred to as a neurological disorder, which is detected via examination and manual comprehension of Electroencephalogram (EEG) signals. In deep learning schemes, various enhancements have emerged to efficiently address complex issues by end-to-end learning. The major objective of this research is to propose a new seizure detection approach from EEG signals using a deep learning-based classification technique. The pre-processing is the initial stage, where denoising is performed using a Short-Time Fourier Transform (STFT). Subsequently, the statistical features, time-domain features and spectral features are extracted from the pre-processed signal. Finally, an efficient optimization approach, named Adadelta-Chameleon Swarm Algorithm (Adadelta-CSA), is proposed and employed to train Deep Neural Network (DNN) to carry out the precise seizure prediction. Here, the integration of the Adadelta concept in the Chameleon Swarm Algorithm (CSA) has resulted in Adadelta-CSA. At last, the performance of the Adadelta-CSA scheme-based DNN is compared with the existing techniques by considering accuracy, sensitivity and specificity, and it is found to produce better values of 0.951, 0.966, and 0.935, respectively.
Comparison of Hand Function after Single-Digit Replantation in Elderly and Younger Patients
Authors: NAKANISHI Akito , KAWAMURA Kenji , OMOKAWA Shohei , HASEGAWA Hideo , TANAKA Yasuhito
Published: November 2024

Background: With ageing of the population, there is an increasing likelihood that elderly people will seek employment, with a resultant increase in the incidence of hand injuries, including digital amputations. However, the surgical indication for replantation of an amputated digit in elderly patients is controversial. The purpose of this study was to compare functional outcomes after single-digit replantation of the thumb to long finger in older (≥65 years old) and younger (<65 years old) patients to assess the feasibility of digit replantation in the elderly population.

Methods: A retrospective cohort study was performed in 25 patients (12 elderly and 13 younger) with successful replantation of the thumb, index or long finger at our hospital. All patients were followed up for more than 1 year. Key pinch strength, Semmes–Weinstein (S–W) test, % total active motion (TAM), Purdue Pegboard Test score (hand dexterity) and Disabilities of the Arm, Shoulder and Hand (DASH) score were investigated.

Results: Elderly patients showed significantly worse results for the S–W test and Purdue Pegboard Test score. The % TAM, key-pinch strength and DASH scores were similar in the two groups.

Conclusions: Replantation surgery in elderly patients results in similar postoperative hand function (finger mobility and pinch strength) and activities of daily living to those in younger patients.

Level of Evidence: Level III (Therapeutic)
Emplacement and landscape controls on ancient submarine volcanism: 3D seismic geomorphological analysis of Cretaceous volcanic activity in the Browse Basin, Australian North West Shelf
Authors: Tsutsui K. , Holford S. , Schofield N. , Bunch M. , McClay K. , King R.
Published: November 2024

Ancient submarine volcanic systems preserved within sedimentary basins provide opportunities to investigate the time and spatial distributions of intrusive and extrusive rocks, though existing work has largely focused on the geometrical features of submarine volcanic products, with limited interrogation of their interactions with sedimentary processes. This study investigates a buried submarine volcanic system within the Browse Basin, Australian North West Shelf. Through the integration of three-dimensional seismic reflection survey with borehole data, our study reveals intricate geometric features of a submarine volcano and lava channels, and their relationship to an associated intrusive network of Early Cretaceous age that has been preserved beneath ∼3.5 km of sedimentary overburden. In planform, the volcano has a diameter >4.5 km with a preserved height reaching 650 m. Meandering lava-flow channels extend ∼20 km southward of the volcanic edifice, forming lava lobes with pressure ridges at the flow termini. Abundant sheet intrusions, identified within underlying Jurassic and older strata, indicate a magma transport from the north. The localized accumulation of sills led to variations in palaeo-seafloor topography, influencing the direction of lava flows and post-volcanic sedimentation patterns. Our findings have a broad range of implications encompassing submarine volcanism and their impacts on basin dynamics.
ATP: Achieving Throughput Peak for DNN Training via Smart GPU Memory Management
Authors: Chen Weiduo , Dong Xiaoshe , Zhang Fan , Li Bowen , Wang Yufei , Wang Qiang
Published: November 2024

Due to the limited GPU memory, the performance of large DNNs training is constrained by the unscalable batch size. Existing researches partially address the issue of GPU memory limit through tensor recomputation and swapping, but overlook the exploration of optimal performance.

In response, we propose ATP, a recomputation and swapping based GPU memory management framework that aims to maximize training performance by breaking GPU memory constraints. ATP utilizes a throughput model we proposed to evaluate the theoretical peak performance achievable by DNN training on GPU, and provide the optimum memory size required for recomputation and swapping. We optimize the mechanisms for GPU memory pool and CUDA stream control, employs an optimization method to search for specific tensors requiring recomputation and swapping, thereby bringing the actual DNN training performance on ATP closer to theoretical values. Evaluations with different types of large DNN models indicate that ATP achieve throughput improvements ranging from 1.14 ∼ 1.49 ×, while support model training exceeding the GPU memory limit by up to 9.2 ×.
A Formally Integrated Adaptive Speed Management for Proactive Traffic Safety
Authors: Barhoumi Oumaima , Nour Mariam , Zaki Mohamed H. , Tahar Sofiène
Published: November 2024

The emergence of connected autonomous vehicles (CAVs) represents a key development in the quest to enhance traffic safety. CAVs hold significant promise for improving traffic safety and have great potential to contribute to transportation sustainability. However, their safety depends on the accuracy of the programmed rules and algorithms that guide their decision-making process. This article introduces an adaptive traffic management system that integrates a formal traffic safety rule defined by pre-established bounds for Traffic Conflict Techniques. This system enables dynamic speed adjustments for vehicles violating the traffic safety rule to prevent potential collisions. To evaluate the effectiveness of our approach, we study a traffic flow on the SR528 highway in Orlando, Florida, and analyze the behavior of each vehicle in traffic based on extracted traffic safety indicators such as time-to-collision and space headway. This analysis is performed by the traffic safety rule to identify violating vehicles, and the speed update is achieved through the integration of the computer algebra system Mathematica and a micro-simulation tool called SUMO. Our study aims to improve the safety and efficiency of the traffic flow by combining simulation, TCTs analysis, and semi-formal tools like Mathematica to aid in the decision-making process of vehicles during traffic events, particularly shockwaves. Preliminary results demonstrate the efficacy of our approach in mitigating the impact of shockwaves. After applying the speed update, we observe an increase in time-to-collision and space headway. This indicates improved safety and reduced likelihood of collisions. Our findings highlight the potential of adaptive traffic management systems to enhance transportation safety and efficiency.
Enhancing ID-based Recommendation with Large Language Models
Authors: Chen Lei , Gao Chen , Du Xiaoyi , Luo Hengliang , Jin Depeng , Li Yong , Wang Meng
Published: November 2024

Large Language Models (LLMs) have recently garnered significant attention in various domains, including recommendation systems. Recent research leverages the capabilities of LLMs to improve the performance and user modeling aspects of recommender systems. These studies primarily focus on utilizing LLMs to interpret textual data in recommendation tasks. However, it's worth noting that in ID-based recommendations, textual data is absent, and only ID data is available. The untapped potential of LLMs for ID data within the ID-based recommendation paradigm remains relatively unexplored. To this end, we introduce a pioneering approach called “LLM for ID-based Recommendation” (LLM4IDRec). This innovative approach integrates the capabilities of LLMs while exclusively relying on ID data, thus diverging from the previous reliance on textual data. The basic idea of LLM4IDRec is that by employing LLM to augment ID data, if augmented ID data can improve recommendation performance, it demonstrates the ability of LLM to interpret ID data effectively, exploring an innovative way for the integration of LLM in ID-based recommendation. Specifically, we first define a prompt template to enhance LLM's ability to comprehend ID data and the ID-based recommendation task. Next, during the process of generating training data using this prompt template, we develop two efficient methods to capture both the local and global structure of ID data. We feed this generated training data into the LLM and employ LoRA for fine-tuning LLM. Following the fine-tuning phase, we utilize the fine-tuned LLM to generate ID data that aligns with users’ preferences. We design two filtering strategies to eliminate invalid generated data. Thirdly, we can merge the original ID data with the generated ID data, creating augmented data. Finally, we input this augmented data into the existing ID-based recommendation models without any modifications to the recommendation model itself. We evaluate the effectiveness of our LLM4IDRec approach using three widely-used datasets. Our results demonstrate a notable improvement in recommendation performance, with our approach consistently outperforming existing methods in ID-based recommendation by solely augmenting input data.
Studies on the ssDNA-Based Biosensor Regeneration and Miniaturization for Electrochemical Detection of miRNAs
Authors: Zaras Izabela , Sokal Marta , Jarczewska Marta
Published: November 2024

One of the most significant disadvantages of biosensing systems is the limited possibility of their regeneration, which only allows for their single use for detection of most targets. The reduction of biosensor fabrication cost could thus be achieved by elaboration of protocol providing the highest recovery of sensing layer response. A further drop of production expenses could yield the biosensor miniaturization as it leads to consumption of chemicals required for receptor layer formation as well as execution of measurements. To address the above-mentioned challenges, we aimed to find the most adequate method of regeneration of single-stranded DNA-based layers specific to miRNA 141 molecule which elevated concentration might refer to progression of cancer. The studies indicated that 5 min. incubation of ssDNA-modified electrode in 4 M urea provided the highest response towards miRNA 141 among all tested regeneration procedures. Furthermore, the possibility of ssDNA immobilization on was shown. This enabled miRNA 141 detection within 0.1 nM–1 μM concentration range with high selectivity. Moreover, ssDNA layers elaborated on miniaturized transducers were distinguished with sufficient stability after 24 h storage in 20 mM PBS and could be also regenerated using 4 M urea.