bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated yeast cultivation control using a biosensor and flow cytometry
Authors: Foncillas Raquel Perruca , Magnusson Sara , Al-Rudainy Basel , Wallberg Ola , Gorwa-Grauslund Marie F , Carlquist Magnus
Published: October 2024

Effective microbial bioprocessing relies on maintaining ideal cultivation conditions, highlighting the necessity for tools that monitor and regulate cellular performance and robustness. This study evaluates a fed-batch cultivation control system based on at-line flow cytometry monitoring of intact yeast cells having a fluorescent transcription factor-based redox biosensor. Specifically, the biosensor assesses the response of an industrial xylose-fermenting Saccharomyces cerevisiae strain carrying the TRX2p-yEGFP biosensor for NADPH/NADP+ ratio imbalance when exposed to furfural. The developed control system successfully detected biosensor output and automatically adjusted furfural feed rate, ensuring physiological fitness at high furfural levels. Moreover, the single-cell measurements enabled the monitoring of subpopulation dynamics, enhancing control precision over traditional methods. The presented automated control system highlights the potential of combining biosensors and flow cytometry for robust microbial cultivations by leveraging intracellular properties as control inputs.

One-Sentence Summary

An automated control system using flow cytometry and biosensors enhances microbial bioprocessing by regulating cellular performance in response to the environmental stressor furfural.
Optimal timing for initiating androgen receptor signaling inhibitor therapy in patients with nonmetastatic castration-resistant prostate cancer: a multicenter collaborative study
Authors: Hara Shuhei , Urabe Fumihiko , Tashiro Kojiro , Goto Yuma , Iwamoto Yuya , Ohtsuka Takashi , Fukuokaya Wataru , Imai Yu , Iwatani Kosuke , Atsuta Mahito , Mori Keiichiro , Igarashi Taro , Aikawa Koichi , Yanagisawa Takafumi , Kimura Shoji , Murakami Masaya , Tsuzuki Shunsuke , Yanada Brendan A , Hata Kenichi , Furuta Akira , Yamada Hiroki , Miki Jun , Kimura Takahiro ,   JIKEI-YAYOI Collaborative Group, Urabe Fumihiko , Hara Shuhei
Published: October 2024

Objective

We determined the optimal timing for initiating androgen receptor signaling inhibitor (ARSI) therapy in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and assessed its impact on oncological outcomes.

Materials and methods

This retrospective study included 145 nmCRPC patients who received enzalutamide, apalutamide or darolutamide at the Jikei University Hospital or its affiliated institutions between May 2014 and November 2022. Patients were stratified based on prostate-specific antigen (PSA) doubling time (PSADT) at CRPC diagnosis and PSA levels at ARSI initiation. Oncological outcomes, including progression-free survival (PFS), metastasis-free survival (MFS), cancer-specific survival and overall survival, were assessed using the Kaplan–Meier curve and Cox regression analysis.

Results

The median age of the patients was 73 (interquartile range [IQR]: 52–88) years, and the median follow-up duration was 36 (IQR: 2–104) months. The median PSA level at ARSI initiation was 5.4 (IQR: 2.2–48) ng/ml, and 44.8% of patients had a PSADT <3 months. Multivariate analysis revealed that PSADT and PSA levels at ARSI initiation were independent MFS predictors. Patients with a PSADT ≤3 months and a PSA level ≥5.4 ng/ml experienced significantly reduced PFS and MFS. Notably, ARSI initiation at a PSA level ≥5.4 ng/ml was associated with worse outcomes, suggesting the potential benefit of earlier intervention.

Conclusions

Patients with rapid PSADT are at increased risk of early disease progression, suggesting that immediate treatment may be warranted. In addition, initiating therapy at a PSA level <5.4 ng/ml may be associated with improved patient outcomes in patients with low PSADT.
Religion, secularism, and postsecularism in Chinese internet literature
Authors: Ni Zhange
Published: October 2024

Internet literature emerged in China in the 1990s and became commercialized in the early 2000s, with readers paying an access fee, which is split between literary platforms and their contracted writers, to access popular novels. While the most popular genre is fantasy, a type of imaginative literature devoted to invoking magic beyond the limits of empirical reality and scientific rationality, the primary source of magic for Chinese fantasy is traditional Chinese cosmology and its concrete applications in everyday practices. These ideas and practices, the onto-epistemic-practical foundation of Chinese religion before the twentieth century, were considered superstitious and targeted for elimination in modernizing and secularization processes. However, they have not only survived but taken up a new life in fantasy novels, which depict them as the antecedents of, alternatives to, or more advanced forms than modern scientific endeavors at engineering natural environments and enhancing human bodies. This is why I see online fantasy literature as a palimpsest bearing the traces of Chinese religion, Chinese secularism, and the social conditions of contemporary China. In bearing such traces, this literature exemplifies the postsecular.
Immunoglobulin A nephropathy and IgA vasculitis
Authors: Cheung Chee Kay , Barratt Jonathan
Published: October 2024

Immunoglobulin A nephropathy (IgAN) is the commonest pattern of glomerulonephritis identified in areas of the world where kidney biopsy is widely practised. It is defined pathologically by IgA deposition in the glomerular mesangium accompanied by a mesangial proliferative glomerulonephritis which may vary greatly in severity. Aetiology is uncertain, but abnormalities of IgA1 hinge-region O-glycosylation are consistently found. Clinical features—IgAN can present with (1) visible haematuria, typically in children and young adults, developing within a day or two of an upper respiratory tract infection (‘synpharyngitic’); (2) asymptomatic nonvisible haematuria/proteinuria; (3) nephrotic syndrome (<5% of cases); (4) acute kidney injury (uncommon); and (5) chronic kidney disease with up to 75% of patients reaching kidney failure within 20 years of diagnosis. IgA vasculitis (previously known as Henoch–Schönlein purpura (HSP)) is a small vessel systemic vasculitis characterized by small blood vessel deposition of IgA that predominantly affects the skin, joints, gut, and kidney, with nephritis that may be histologically indistinguishable from IgA nephropathy. Management—current first-line treatment options for most patients with IgAN are directed at optimizing supportive care, by controlling blood pressure and limiting proteinuria through blockade of the renin–angiotensin–aldosterone axis. With the introduction of novel disease-modifying therapies this is likely to change over the coming 5 years with a focus on treating the IgAN, rather than the downstream consequences of IgAN-induced nephron loss. In the rare patient presenting with a rapidly progressive glomerulonephritis (RPGN), a regimen such as those used for vasculitis and other forms of RPGN should be considered, for example, cyclophosphamide in combination with oral prednisolone.
Thin membrane nephropathy
Authors: Topham Peter , Gale Daniel
Published: October 2024

Thin membrane nephropathy is a common autosomal dominant glomerular disorder that results in persistent nonvisible haematuria and is pathologically characterized by the presence of diffuse and uniform thinning of the glomerular basement membrane. Recent genetic studies have identified mutations in the COL4A3 and COL4A4 genes in 40% of affected families. There is no specific treatment. Prognosis is excellent for most people, but in some cases proteinuria and progressive renal impairment occur.
Close binary fractions in accreted and in situ halo stars
Authors: Bashi Dolev , Belokurov Vasily , Hodgkin Simon
Published: October 2024

The study of binary stars in the Galactic halo provides crucial insights into the dynamical history and formation processes of the Milky Way. In this work, we aim to investigate the binary fraction in a sample of accreted and in situ halo stars, focusing on short-period binaries. Utilizing data from Gaia Data Release 3 (DR3), we analysed the radial velocity uncertainty $\sigma _{\mathrm{RV}}$ distribution of a sample of main-sequence stars. We used a novel Bayesian framework to model the dependence in $\sigma _{\mathrm{RV}}$ of single and binary systems allowing us to estimate binary fractions F in a sample of bright ($G_{\mathrm{RVS}}$ < 12) Gaia sources. We selected the samples of in situ and accreted halo stars based on estimating the 6D phase space information and affiliating the stars to the different samples on an action angle versus energy ($L_{\mathrm{z}}{\!-\!}E$) diagram. Our results indicate a higher, though not significant, binary fraction in accreted stars compared to the in situ halo sample. We further explore binary fractions using cuts in E and $L_z$, and find a higher binary fraction in both high-energy and prograde orbits that might be explained by differences in metallicity. By cross-matching our Gaia sample with APOGEE DR17 catalogue, we confirm the results of previous studies on higher binary fractions in metal-poor stars and find the fractions of accreted and in situ halo stars consistent with this trend. Our finding provides new insights into binary stars’ formation processes and dynamical evolution in the primordial Milky Way Galaxy and its accreted dwarf Galaxies.
Wide Area VISTA Extra-galactic Survey (WAVES): unsupervised star-galaxy separation on the WAVES-Wide photometric input catalogue using UMAP and hdbscan
Authors: Cook Todd L , Bandi Behnood , Philipsborn Sam , Loveday Jon , Bellstedt Sabine , Driver Simon P , Robotham Aaron S G , Bilicki Maciej , Kaur Gursharanjit , Tempel Elmo , Baldry Ivan , Gruen Daniel , Longhetti Marcella , Iovino Angela , Holwerda Benne W , Demarco Ricardo
Published: October 2024

Star-galaxy separation is a crucial step in creating target catalogues for extragalactic spectroscopic surveys. A classifier biased towards inclusivity risks including high numbers of stars, wasting fibre hours, while a more conservative classifier might overlook galaxies, compromising completeness and hence survey objectives. To avoid bias introduced by a training set in supervised methods, we employ an unsupervised machine learning approach. Using photometry from the Wide Area VISTA Extragalactic Survey (WAVES)-Wide catalogue comprising nine-band $u - K_s$ data, we create a feature space with colours, fluxes, and apparent size information extracted by ProFound. We apply the non-linear dimensionality reduction method UMAP (Uniform Manifold Approximation and Projection) combined with the classifier hdbscan (Hierarchical Density-Based Spatial Clustering of Applications with Noise) to classify stars and galaxies. Our method is verified against a baseline colour and morphological method using a truth catalogue from Gaia, SDSS (Sloan Digital Sky Survey), GAMA (Galaxy And Mass Assembly), and DESI (Dark Energy Spectroscopic Instrument). We correctly identify 99.75 per cent of galaxies within the AB magnitude limit of $Z=21.2$, with an F1 score of $0.9971 \pm 0.0018$ across the entire ground truth sample, compared to $0.9879 \pm 0.0088$ from the baseline method. Our method’s higher purity ($0.9967 \pm 0.0021$) compared to the baseline ($0.9795 \pm 0.0172$) increases efficiency, identifying 11 per cent fewer galaxy or ambiguous sources, saving approximately 70 000 fibre hours on the 4MOST (4-m Multi-Object Spectroscopic Telescope) instrument. We achieve reliable classification statistics for challenging sources including quasars, compact galaxies, and low surface brightness galaxies, retrieving 92.7 per cent, 84.6 per cent, and 99.5 per cent of them, respectively. Angular clustering analysis validates our classifications, showing consistency with expected galaxy clustering, regardless of the baseline classification.
From outskirts to core: the suppression and activation of radio AGN around galaxy clusters
Authors: de Vos K , Hatch N A , Merrifield M R
Published: October 2024

To investigate how the radio-identified active galactic nuclei (AGN) fraction varies with cluster-centric radius, we present the projected and de-projected distributions of a large sample of Low-Frequency Array-identified radio AGN out to $30R_{500}$ around galaxy clusters. The AGN fraction experiences a ${\sim} 25~{{\ \rm per\ cent}}$ increase above the field fraction in the cluster outskirts at around $10R_{500}$, a ${\sim} 20~{{\ \rm per\ cent}}$ decrease around ${\sim} 0.5R_{500}$, and an increase of over three times the field fraction value in the very cluster core. We label these three radial windows the outer, intermediate, and inner regions respectively, and investigate how these radial trends might arise due to intrinsic properties of the AGN population. The only difference seen in host galaxy stellar mass is in the inner region, where there is a much higher fraction of massive host galaxies. Analysing AGN radio luminosity, regions with a higher AGN fraction tend to have more radio luminous AGN, and vice versa. We discuss the physical mechanisms that might be responsible for these results with reference to the literature.
A novel circRNA–miRNA–mRNA regulatory axis as a sex-specific biological variable in bronchopulmonary dysplasia
Authors: Das Pragnya , Shyamal Sharmishtha , Prahaladan Varsha M , Mishra Smruti S , Takada Xander , Chandran Srinarmadha , Addya Sankar , Agarwal Beamon , Andersson Sture , Panda Amaresh C , Bhandari Vineet
Published: October 2024

Babies born prematurely with gestational age <28 weeks usually develop a severe pulmonary complication called Bronchopulmonary Dysplasia (BPD) in response to hyperoxia. BPD is a sexually dimorphic pediatric disease with no curative options. Several micro RNAs (miRNAs) are implicated in BPD and are expressed differentially in males and females. Circular (circ) RNAs serve as sponges for their dedicated miRNAs to influence transcription and translation. We tested the dimorphism of these circular RNAs in BPD to assess their biological significance and unravel a circRNA–miRNA–mRNA regulatory axis in response to hyperoxia. Our RNA-Sequencing assay identified approximately 33 000 circRNAs at the alveolar stage of development with only a handful of them being expressed differentially between males and females in the control room air (RA) and hyperoxia-treated (BPD) groups. One circRNA, i.e circNfix was found to be associated with miR204-5p that targets the downstream mRNA target Ntrk2. To prove that circNfix regulates Ntrk2, we silenced circNfix using a GapmeR and found that Ntrk2 was also suppressed, leading to an improved alveolar phenotype in BPD male pups. From the results of our study, we can propose circNfix and Ntrk2 as novel key regulators in the pathogenesis and sexual dimorphism of BPD, while simultaneously proposing the use of circNfix GapmeR towards a potential therapeutic application.
Older people predialysis care pathways and early morbidity–mortality upon start of dialysis
Authors: Hamroun Aghiles , Aymes Estelle , Couchoud Cécile , Béchade Clémence , Moranne Olivier , Beuscart Jean-Baptiste , Gauthier Victoria , Dauchet Luc , Amouyel Philippe , Stengel Bénédicte , Glowacki François
Published: October 2024

Background

The ageing of the population with advanced chronic kidney disease (CKD) increases the complexity of care pathways. Our aim was to identify subgroups of older people according to predialysis care pathways and describe their association with early morbidity–mortality after transition to dialysis.

Methods

This study included 22 128 incident dialysis patients aged ≥75 years during 2009–2017 from the French nationwide registry linked to the National Health Data System. Predialysis care pathways were identified by ascending hierarchical classification based on preselected healthcare use indicators in the previous year. Their association with a composite outcome of death or hospitalization ≥50% of the time off dialysis within the first year of dialysis was studied by multivariable logistic regression accounting for demographics, comorbidities, functional status, conditions of dialysis initiation, socioeconomic deprivation index and home-to-dialysis center travel time.

Results

Five care pathway profiles were identified, characterized by limited healthcare use (Cluster 1, 28%), non-nephrology ambulatory care (Cluster 2, 17%), nephrology ambulatory care (Cluster 3, 37%) and a high level of non-nephrology or nephrology hospitalizations (Clusters 4 and 5, both 9%). Profile subgroups did not differ according to patient age and comorbidities, but Clusters 1, 2 and 4 displayed higher levels of social deprivation. Compared with Cluster 3, the odds ratios of primary composite outcome were significantly increased for Clusters 1, 4 and 5 [odds ratio (95% confidence interval) of 1.16 (1.08–1.25), 1.17 (1.05–1.32) and 1.12 (1.01–1.25), respectively]. Moreover, prolonged hospitalizations were also more common in all groups, compared with Cluster 3.

Conclusion

Despite a similar comorbidity profile, older people with advanced CKD experience very heterogeneous predialysis care pathways, some of which associated with higher burden of hospitalization after the transition to dialysis.
Symptom management in isocitrate dehydrogenase mutant glioma
Authors: Walbert Tobias , Avila Edward K , Boele Florien W , Hertler Caroline , Lu-Emerson Christine , van der Meer Pim B , Peters Katherine B , Rooney Alasdair G , Templer Jessica W , Koekkoek Johan A F
Published: October 2024

According to the 2021 World Health Organization classification of CNS tumors, gliomas harboring a mutation in isocitrate dehydrogenase (mIDH) are considered a distinct disease entity, typically presenting in adult patients before the age of 50 years. Given their multiyear survival, patients with mIDH glioma are affected by tumor and treatment-related symptoms that can have a large impact on the daily life of both patients and their caregivers for an extended period of time. Selective oral inhibitors of mIDH enzymes have recently joined existing anticancer treatments, including resection, radiotherapy, and chemotherapy, as an additional targeted treatment modality. With new treatments that improve progression-free and possibly overall survival, preventing and addressing daily symptoms becomes even more clinically relevant. In this review we discuss the management of the most prevalent symptoms, including tumor-related epilepsy, cognitive dysfunction, mood disorders, and fatigue, in patients with mIDH glioma, and issues regarding patient’s health-related quality of life and caregiver needs in the era of mIDH inhibitors. We provide recommendations for practicing healthcare professionals caring for patients who are eligible for treatment with mIDH inhibitors.
A novel approach to peer support for academic researchers
Authors: Khodabakhsh S , Hoffmann C , Sauchelli S , Shi G , Mitchell A
Published: October 2024

Background

Academic researchers experience high levels of stress, isolation and loneliness, which compromise their well-being. There is a particular need to address these issues amongst early career and postgraduate research staff. ‘Spaces for Listening’ is an initiative to increase active listening and provide peer support.

Aims

To assess the feasibility, acceptability and potential impacts of Spaces for Listening in an academic setting.

Methods

Early career and postgraduate researchers from a large university in the UK were invited to attend ‘Academic Spaces for Listening’ (ASfL). Five ASfL sessions (including in-person and Chinese language) were held. A mixed-methods study using online survey and in-depth interviews was conducted. Quantitative data were analysed using descriptive statistics, and qualitative data were analysed using principles of thematic analysis. The qualitative and quantitative findings were integrated at the interpretation phase.

Results

A total of 25 participants attended an ASfL session, 22 of them completed the survey and 6 participants participated in semi-structured interviews. Participants were very satisfied with the session content (68%, n = 15), organization (68%, n = 15) and delivery (68%, n = 15). Four themes were identified from qualitative analysis: (i) the ‘Academic Spaces for Listening’ (ASfL) experience; (2) impact of ASfL; (3) potential challenges of ASfL and (4) ASfL in the future. Interpersonal connectedness was an important outcome for participants during the session. Participants showed interest in the future of ASfL.

Conclusions

Implementing Spaces for Listening in an academic setting is feasible and was well received by participants. The initiative may fill a gap in the social interactions amongst academic researchers.
Correlating Climate Conditions With Pseudomonas aeruginosa Prevalence in Diabetic Foot Infections Within the United States
Authors: Winski Rebecca , Xu Jiachen , Townsend Jonathan , Chan Arthur , Wattengel Bethany A , Davis Matthew , Puckett Andrew , Huntsman Kyle , O’Leary Ashley L , Mergenhagen Kari A
Published: October 2024

Background

The 2023 “International Working Group on the Diabetic Foot/Infectious Disease Society of America Guidelines on the Diagnosis and Treatment of Diabetes-Related Foot Infections” (DFIs) provides recommendations for Pseudomonas coverage based on the climate region.

Methods

This was a retrospective national study of veterans between 1/1/2010 and 3/23/2024 with diabetes mellitus and a culture below the malleolus wound. Prevalence of Pseudomonas was categorized based on climate zones according to the International Energy Conservation Code. Multivariable logistic regression was used to determine odds ratios and 97.5% CIs.

Results

The prevalence of Pseudomonas significantly varied between US climates. Pseudomonas was most prevalent within the Hot Humid climate, where it was isolated in 11.6% of DFI cultures. Pseudomonas was least prevalent within the Very Cold climate, where it was isolated in 6.2% of cultures. In the multivariable logistic regression model, hot and humid climates were associated with an odds of P. aeruginosa of 1.92 (97.5% CI, 1.69–2.20), a hot, dry climate was associated with an odds of 1.65 (97.5% CI, 1.44–1.90), and a humid climate was associated with an odds of 1.65 (97.5% CI, 1.45–1.89). A lower Charlson Comorbidity Index, inpatient admission, recent antipseudomonal antibiotic use, and swabs were less likely to have Pseudomonas. Recent admission increased the odds of P. aeruginosa (odds ratio [OR], 1.34; 97.5% CI, 1.27–1.41). History of P. aeruginosa was associated with an increase in P. aeruginosa (OR, 8.90; 97.5% CI, 8.29–9.56).

Conclusions

The prevalence of DFI organisms varies within different US climates. Utilization of local climate information may allow for more accurate and targeted empiric antibiotic selection when treating DFIs.
Detrimental effect of an early exposure to antibiotics on the outcomes of immunotherapy in a multi-tumor cohort of patients
Authors: Guerrero Patricia , Albarrán Víctor , González-Merino Carlos , García de Quevedo Coral , Sotoca Pilar , Chamorro Jesús , Rosero Diana Isabel , Barrill Ana , Alía Víctor , Calvo Juan Carlos , Moreno Jaime , Pérez de Aguado Patricia , Álvarez-Ballesteros Pablo , San Román María , Serrano Juan José , Soria Ainara , Olmedo María Eugenia , Saavedra Cristina , Cortés Alfonso , Gómez Ana , Lage Yolanda , Ruiz Álvaro , Ferreiro María Reyes , Longo Federico , Guerra Eva , Martínez-Delfrade Íñigo , Garrido Pilar , Gajate Pablo
Published: October 2024

Background

Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape of many solid tumors. Modulation of the intestinal microbiota by antibiotics (Abx) has been suggested to impact on ICI outcomes.

Methods

Retrospective analysis of 475 patients with advanced solid tumors treated with ICI from 2015 to 2022. For each patient, the use of Abx was recorded from 1 month before ICI initiation until disease progression or death. The impact of Abx on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), and overall survival (OS) was analyzed. Kaplan-Meier and log-rank tests were used to compare survival outcomes.

Results

In total 475 patients with advanced solid tumors were evaluated. Median age was 67.5 years and performance status (PS) was 0-1 in 84.6%. 66.5% of patients received Abx during treatment with ICI, mainly beta-lactams (53.8%) and quinolones (35.9%). The early exposure to Abx (from 60 days before to 42 days after the first cycle of ICI) was associated with a lower ORR (27.4% vs 39.4%; P < .01), a lower DCR (37.3% vs 57.4%; P < .001), lower PFS (16.8 m vs 27.8 m; HR 0.66; P < .001]) and lower OS (2.5 m vs 6.6 m; HR 0.68; P = .001]). The negative impact of Abx on OS and PFS was confirmed by a multivariable analysis. This effect was not observed among patients receiving Abx after 6 weeks from ICI initiation.

Conclusions

Our results validate the hypothesis of a detrimental effect of an early exposure to Abxon the efficacy of ICI in a multi-tumor cohort of patients.
Transcription factor OsMYB2 triggers amino acid transporter OsANT1 expression to regulate rice growth and salt tolerance
Authors: Nie Shengsong , Huang Weiting , He Chongchong , Wu Bowen , Duan Honglang , Ruan Jingjun , Zhao Quanzhi , Fang Zhongming
Published: October 2024

Amino acid transporters (AATs) play important roles in plant growth and stress tolerance; however, whether the abscisic acid signaling pathway regulates their transcription in rice (Oryza sativa) under salt stress remains unclear. In this study, we report that the transcription factor OsMYB2 (MYB transcription factor 2) of the abscisic acid signaling pathway mediates the expression of the gene encoding the AAT aromatic and neutral AAT 1 (OsANT1), which positively regulates growth and salt tolerance in rice. OsANT1 was mainly expressed in the leaf blade and panicle under normal conditions and transports leucine, phenylalanine, tyrosine, and proline (Pro), positively regulating tillering and yield in rice. Nevertheless, salt stress induced the accumulation of abscisic acid and strongly increased the expression level of OsANT1 in the root, resulting in enhanced salt tolerance of rice seedlings, as evidenced by higher Pro concentration and antioxidant-like enzyme activities and lower malondialdehyde and hydrogen peroxide concentrations. Moreover, we showed that OsMYB2 interacts with the promoter of OsANT1 and promotes its expression. Overexpression of OsMYB2 also improved tillering, yield, and salt tolerance in rice. In conclusion, our results suggest that the transcription factor OsMYB2 triggers OsANT1 expression and regulates growth and salt tolerance in rice, providing insights into the role of the abscisic acid signaling pathway in the regulatory mechanism of AATs in response to salt stress.
Automating body-worn camera footage review through AI: baseline attitudes from a multisite randomized control trial
Authors: Watts Seth , White Michael D , Malm Aili
Published: October 2024

Body-worn cameras (BWCs) have been widely adopted as a tool to promote police reform. However, studies have shown that most of the footage recorded by BWCs (about 95 per cent) is never reviewed or seen, which undercuts the core benefits of BWCs. Artificial Intelligence-driven analytics may overcome this problem. One example is Truleo, which uses natural language processing to analyse the audio footage and produce metrics of risk and professionalism. However, there is virtually no research examining its use and impact in policing. In the current study, we describe preliminary findings from ongoing randomized controlled trials testing the implementation and impact of Truleo in the Apache Junction and Casa Grande Police Departments. We draw on focus groups of officers, sergeants, and upper-level management and officer perceptions via surveys administered pre-deployment of the technology. We conclude with a discussion of policy implications related to the use of AI for BWC footage review, particularly with regard to how the technology may promote professionalism, intensify supervision, and increase organizational efficiency.
Nonthermal Baryogenesis from Minimal Supersymmetric Standard Model Flat Direction
Authors: Haba Naoyuki , Shimizu Yasuhiro , Tanabe Yoshihiro , Yamada Toshifumi
Published: October 2024

We study an inflection point inflation scenario where a flat direction of the minimal supersymmetric standard model (MSSM) is identified with the inflaton. We focus on the case where the flat direction (inflaton) has nonzero baryon number, and consider a nonthermal baryogenesis scenario where the decay of the inflaton at the reheating directly generates baryon asymmetry of the universe. Specifically, we consider a udd flat direction that is lifted by a superpotential operator of dimension 6, and show that inflection point inflation with the udd flat direction can be compatible with cosmological observations and can account for the baryon asymmetry of the universe.
Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein
Authors: Sun Zixuan , Wang Tangrong , Hou Xiaomei , Bai Wenhuan , Li Jiali , Li Yu , Zhang Jiaxin , Zheng Yuzhou , Wu Zhijing , Wu Peipei , Yan Lirong , Qian Hui
Published: October 2024

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.
Effects of intrauterine extracellular vesicle microRNAs on embryonic gene expression in low‐fertility cows
Authors: Ichikawa Rei , Kimura Koji , Nakamura Sho , Ohkura Satoshi , Matsuyama Shuichi
Published: October 2024

Embryo survival and pre‐implantation development depend on uterine luminal fluid, which is believed to play a role in early embryonic death and infertility in cows. Extracellular vesicles (EVs) in the uterine luminal fluid contain microRNAs (miRNAs), crucial mediators of intercellular communication. miRNAs regulate conceptus–maternal interactions and participate in embryonic development by suppressing gene expression. Therefore, we hypothesized that miRNAs in the intrauterine EVs of low‐fertility cows would hinder embryonic survival and development. EVs were collected from the bovine uterine luminal fluid of both normal‐ and low‐fertility cows 7 days post‐estrus. Small RNA‐sequencing analysis of miRNAs isolated from these EVs identified eight miRNAs that were highly expressed in normal‐fertility cows (normal‐fertility miRNAs) and eight with elevated expression in low‐fertility cows (low‐fertility miRNAs). These two sets of miRNAs were transfected into hatched blastocysts via lipofection. RNA‐seq following lipofection with low‐fertility miRNAs identified 424 differentially expressed genes (DEGs) relative to the control; in contrast, following lipofection with normal‐fertility miRNAs, seven DEGs were identified. Pathway analysis of the DEGs identified following lipofection with low‐fertility miRNAs revealed substantial enrichment of mitogen‐activated protein kinase (MAPK) signaling. Expression of activator protein 1 (AP1) and interferon‐tau (IFNT) mRNA was significantly lower in the low‐fertility miRNA transfection group than in the control. IFNT is essential for maternal pregnancy recognition. Therefore, miRNAs in intrauterine EVs from low‐fertility cows at 7 days post‐estrus may inhibit embryo development and suppress IFNT expression by altering MAPK signaling.
Predicting immune protection against outcomes of infectious disease from population-level effectiveness data with application to COVID-19
Authors: Hao Tianxiao , Ryan Gerard E. , Lydeamore Michael J. , Cromer Deborah , Wood James , McVernon Jodie , McCaw James M. , Shearer Freya M. , Golding Nick
Published: October 2024

Quantifying the extent to which previous infections and vaccinations confer protection against future infection or disease outcomes is critical to managing the transmission and consequences of infectious diseases.

We present a general statistical model for predicting the strength of protection conferred by different immunising exposures (numbers, types, and variants of both vaccines and infections), against multiple outcomes of interest, whilst accounting for immune waning. We predict immune protection against key clinical outcomes: developing symptoms, hospitalisation, and death. We also predict transmission-related outcomes: acquisition of infection and onward transmission in breakthrough infections. These enable quantification of the impact of immunity on population-level transmission dynamics. Our model calibrates the level of immune protection, drawing on both population-level data, such as vaccine effectiveness estimates, and neutralising antibody levels as a correlate of protection. This enables the model to learn realised immunity levels beyond those which can be predicted by antibody kinetics or other correlates alone.

We demonstrate an application of the model for SARS-CoV-2, and predict the individual-level protective effectiveness conferred by natural infections with the Delta and the Omicron B.1.1.529 variants, and by the BioNTech-Pfizer (BNT162b2), Oxford-AstraZeneca (ChAdOx1), and 3rd-dose mRNA booster vaccines, against outcomes for both Delta and Omicron. We also demonstrate a use case of the model in late 2021 during the emergence of Omicron, showing how the model can be rapidly updated with emerging epidemiological data on multiple variants in the same population, to infer key immunogenicity and intrinsic transmissibility characteristics of the new variant, before these can be directly observed via vaccine effectiveness data.

This model provided timely inference on rapidly evolving epidemic situations of significant concern during the early stages of the COVID-19 pandemic. The general nature of the model enables it to be used to support management of a range of infectious diseases.
EFFECTIVENESS OF A TAILORED SLEEP EDUCATION PROGRAM TO IMPROVE SLEEP AND ITS IMPACT ON ACADEMIC PERFORMANCE IN MULTISPORT YOUTH ATHLETES
Authors: Merayo Ana , Rodas Gil , Sans Oscar , Iranzo Alex , Capdevila Lluis
Published: October 2024

Objective

to evaluate the effectiveness of a sleep education program among young athletes in enhancing sleep quality and duration, as well as mood and academic performance.

Design: prospective cohort study.

Methods

We included 639 players (11% female; mean age of 13.89±3.8 years) of 5 sports disciplines in a professional club were evaluated before and after a sport season, through 4 specific instruments: 1) sleep diaries to estimate nocturnal sleep duration, 2) the Children’s Sleep Disorder Score Scale (SDSC) to assess sleep quality, 3) the Sleep Vitality Scale (SVS) to examine mood, and 4) school records of academic performance. The sleep education program included staff, family and individual sessions. It focused on the promotion of healthy sleep habits.

Results

The 16t-25 years-old (y-o) group exhibited an increase in nocturnal sleep duration (p=0.002), while the 12-15 y-o group showed a decrease (p=0.01). In contrast, the 7-11y-o group exhibited no change. For sleep quality, the 12-15y-o (p < 0.001) and 16-25y-o (p<0.001) groups, while the 7-11y-o group exhibited inferior sleep quality (p 0.001). Regarding mood, the 7-11y-o group showed a significant deterioration (p=0.008), while no changes were observed in the 12-15y-o and 16-25y-o groups. Academic performance exhibited a significant improvement in the 7-11y-o (p=0.001), 12-15y-o (p<0.001), and 16-25y-o (p=0.008) groups.

Conclusions

Among athletes aged 12-25y-o, participation in a sleep education program led to improvements in sleep quality and duration, accompanied by enhanced academic performance. However, this intervention did not yield positive effects for athletes between the ages of 7 and 11 years.
Local and global mortality experience: A novel hierarchical model for regional mortality risk
Authors: Nalmpatian Asmik , Heumann Christian , Alkaya Levent , Jackson William
Published: October 2024

Accurate mortality risk assessment is critical for decision-making in life insurance, healthcare, and public policy. Regional variability in mortality, driven by diverse local factors and inconsistent data availability, presents significant modeling challenges. This study introduces a novel hierarchical mortality risk model that integrates global and local data, enhancing regional mortality estimation across diverse regions. The proposed approach employs a two-stage process: first, a global Light Gradient Boosting Machine model is trained on globally shared features; second, region-specific models are developed to incorporate local characteristics. This framework outperforms both purely local models and standard imputation techniques, particularly in data-scarce regions, by leveraging global patterns to improve generalization. The model is computationally efficient, scalable, and robust in handling missing values, making it adaptable for other domains requiring integration of multi-regional data. This method enhances predictive accuracy across various regions and provides a more reliable approach for mortality risk estimation in data-scarce environments.
Machine learning-based equations for improved body composition estimation in Indian adults
Authors: Birk Nick , Kulkarni Bharati , Bhogadi Santhi , Aggarwal Aastha , Walia Gagandeep Kaur , Gupta Vipin , Rani Usha , Mahajan Hemant , Kinra Sanjay , Mallinson Poppy AC
Published: October 2024

Bioelectrical impedance analysis (BIA) is commonly used as a lower-cost measurement of body composition as compared to dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) in large-scale epidemiological studies. However, existing equations for body composition based on BIA measures may not generalize well to all settings.

We combined BIA measurements (TANITA BC-418) with skinfold thickness, body circumferences, and grip strength to develop equations to predict six DXA-measured body composition parameters in a cohort of Indian adults using machine learning techniques. The participants were split into training (80%, 1297 males and 1133 females) and testing (20%, 318 males and 289 females) data to develop and validate the performance of equations for total body fat mass (kg), total body lean mass (kg), total body fat percentage (%), trunk fat percentage (%), L1-L4 fat percentage (%), and total appendicular lean mass (kg), separately for males and females. Our novel equations outperformed existing equations for each of these body composition parameters. For example, the mean absolute error for total body fat mass was 1.808 kg for males and 2.054 kg for females using the TANITA’s built-in estimation algorithm, 2.105 kg for males and 2.995 kg for females using Durnin-Womersley equations, and 0.935 kg for males and 0.976 kg for females using our novel equations.

These equations may provide improved estimation of body composition in research and clinical contexts conducted in India and will be made available as an online application for use in future research in these populations.
Reduction of clonal hematopoiesis mutation burden in coronary patients treated with low-dose colchicine
Authors: Tardif Jean-Claude , Busque Lambert , Geoffroy Steve , Sandoval Johanna , Perreault Louis-Philippe Lemieux , Mongrain Ian , Valois Diane , Gaulin-Marion Marie-Josée , Buscarlet Manuel , Provost Sylvie , Maggioni Aldo P. , Kouz Simon , Pinto Fausto J. , Lopez-Sendon Jose , Waters David D. , Diaz Rafael , Gamra Habib , Kiwan Ghassan S. , Berry Colin , Koenig Wolfgang , Grégoire Jean C. , L’Allier Philippe L. , Provencher Mylène , Guertin Marie-Claude , Roubille François , Oussaid Essaid , Barhdadi Amina , Dubé Marie-Pierre
Published: October 2024

Clonal hematopoiesis involves mutations in hematopoietic stem/progenitor cells, which increase the risk of cardiovascular disease, particularly under pro-inflammatory conditions. This study assessed the impact of the anti-inflammatory medication colchicine on clonal hematopoiesis in patients with recent myocardial infarction from the COLCOT trial. Participants were randomly assigned to low-dose colchicine (0.5 mg daily) or placebo, with 848 providing two DNA samples for longitudinal analysis. Targeted error-corrected sequencing was used, and 15,919 mutations were followed over a median period of 19.5 months. The results showed significantly lower variant allele fractions in the colchicine group compared to placebo (p interaction=0.03), with notable reductions inTET2(10.3%, p=0.007; p interaction=0.001),TP53(11.8%, p=0.001; p interaction=0.03), andSF3B1mutations (19.9%, p=0.006; p interaction=0.005). Thus, colchicine reduced the proportion of clonal hematopoiesis mutations in patients with coronary disease, and longer-term studies with diverse populations are needed to confirm its potential benefits in mitigating related health risks.
Estimating the serotype-specific association between the concentration of vaccine-induced serum antibodies and protection against pneumococcal colonization
Authors: Wong Anabelle , Warren Joshua L. , Fitch Laura , Perniciaro Stephanie , Dagan Ron , Weinberger Daniel M.
Published: October 2024

Background

Pneumococcal conjugate vaccines (PCVs) offer indirect protection by reducing pneumococcal colonization in the vaccinated children and thus transmission. As higher-valency PCVs may trigger a weaker immune response, it is important to understand how differences in immunogenicity between PCVs translate to effectiveness against colonization.

Methods

We estimated the serotype-specific relationship between the concentration of vaccine-induced serum immunoglobulin G (IgG) and protection against colonization using a hierarchical Bayesian model with the longitudinal data from a randomized controlled trial in Israel. Then, we combined these estimates with the summary-level immunogenicity data (geometric mean concentration and 95% confidence intervals) from head-to-head clinical trials comparing PCV13 vs. PCV7, PCV 15 vs. PCV13, and PCV20 vs. PCV13 to infer the relative effectiveness of higher-valency PCVs against colonization.

Results

The hierarchical Bayesian model predicted that the risk of colonization increased as serum IgG decreased, and the association differed by serotype. Our approach estimated higher-valency PCVs to have lower vaccine effectiveness against colonization with some serotypes: 14 and 23F across comparisons; 4 when comparing PCV13 with PCV7 and comparing PCV20 with PCV13; 5, 6A, 6B 7F, 19A, and 19F when comparing PCV15 and PCV20 with PCV13, and additionally 1, 9V and 18C when comparing PCV20 with PCV13.

Conclusions

These findings suggest that while new PCVs might provide sufficient protection against severe disease, protection against transmission might be somewhat reduced for some serotypes. The overall impact should be evaluated in the local context and further monitoring is critical to evaluate the impact of these changes in the coming years.
Identification of Early Risk Factors for Mortality in Pediatric Veno-Arterial Extra Corporeal Membrane Oxygenation: The Patient Matters
Authors: Weinerman Bennett , Kwon Soon Bin , Alalqum Tammam , Nametz Daniel , Megjhani Murad , Clark Eunice , Varner Caleb , Cheung Eva W. , Park Soojin
Published: October 2024

Objective

Pediatric Veno-Arterial Extra Corporeal Membrane Oxygenation (VA ECMO) is a life saving technology associated with high mortality. A successful VA ECMO course requires attention to multiple aspects of patient care, including ECMO and patient parameters. Early, potentially modifiable, risk factors associated with patient mortality should be analyzed and adjusted for when assessing VA ECMO risk profiles.

Method

Retrospective single center experience of pediatric patients requiring VA ECMO from January 2021 to October 2023. Laboratory and ECMO flow parameters were extracted from the patients record and analyzed. Risk factors were analyzed using a Cox proportion hazard regression

Main Results

There were 45 patients studied. Overall survival was 51%. Upon uncorrected analysis there were no significant differences between the patients who survived and those who died. Utilizing a Cox proportion hazard regression, platelet count, fibrinogen level and creatine level were significant risk factors within the first twenty-four hours of a patient’s ECMO course.

Significance

Although we did not find a significant difference among ECMO flow parameters in this study, this work highlights that granular ECMO flow data can be incorporated to risk analysis profiles and potential modeling in pediatric VA ECMO. This study demonstrated, that when controlling for ECMO flow parameters, kidney dysfunction and clotting regulation remain key risk factors for pediatric VA ECMO mortality.
Combination of mitomycin C and low-dose metronidazole synergistically againstClostridioides difficileinfection and recurrence prevention
Authors: Gong Jun-Jia , Huang I-Hsiu , Hung Yuan-Pin , Chen Yi-Wei , Lin Yun-Chien , Chen Jenn-Wei
Published: October 2024

Clostridioides difficileis an anaerobic, spore-forming, Gram-positive pathogen responsible for various conditions from mild diarrhea to severe toxic megacolon and potentially death. Current treatments forC. difficileinfection (CDI) rely on antibiotics like vancomycin and metronidazole (MTZ); however, the high doses required often disrupt gut microbiota, leading to a high recurrence rate. Mitomycin C (MMC), a chemotherapy drug approved by the FDA, is known for inducing phage production in lysogenic bacterial strains, effectively targeting the host bacteria. Given that 70% ofC. difficilestrains harbor prophages, this study investigates MMC’s potential to enhance antibiotic efficacy against CDI. Our in vitro experiments indicate that MMC acts synergistically with MTZ to inhibit the growth ofC. difficilestrain R20291. Furthermore, this combination decreases biofilm-resident vegetative cell resistance and reduces the MTZ concentration needed to killC. difficilein stool samples ex vivo. In a CDI mouse relapse model, in vivo results show that MMC combined with a low dose of MTZ significantly improves survival rates and reduces fecal spore counts after antibiotic treatment. Overall, these findings suggest that a low-dose combination of MMC and MTZ offers enhanced therapeutic efficacy for CDI, both in vitro and in vivo, and may provide a promising new approach for treatment.