bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatigue performance of fiber laser fusion cut edges on thick plates
Authors: Lipiäinen Kalle , Ahola Antti , Afkhami Shahriar , Skriko Tuomas
Published: December 2023

Fatigue performance of cut edges is an important factor in structural design, especially when geometrical stress concentration factors (SCFs) are present. High power laser cutting systems have enabled efficient and fast fusion cutting with nitrogen as an assistant gas. The fusion cutting induces recast layer, which features crack-like defects close to cut edge. In this study, plates with thickness 16 ≤ t ≤ 30 mm have been fatigue-tested. A 10 kW fiber laser cutting system was used to cut plates with nitrogen as an assistant gas. High strength steel (HSS) S690 specimens included unnotched coupon specimens and welded T-profile with longitudinal gusset in post-weld treated conditions, where laser cut edge was found critical. Fatigue performance of S690 cut edges were found close to 170 MPa m = 3 when SCFs of welded specimens were included on analysis. Local properties at the cut edge including hardness measurements and scanning electron microscope (SEM) fractography. Fractography obtained local quality use with theory of critical distances -based fatigue strength assessment was demonstrated.
Effects of machining parameters on Ni-Mn-Ga-based alloys for fabrication of multifunctional micro devices using femtosecond pulse width laser
Authors: Kumthekar Aditya , Laitinen Ville , Ullakko Kari
Published: December 2023

Ni-Mn-Ga-based magnetic shape memory (MSM) alloy single crystals are known for their large magnetic-field-induced strain (MFIS). This quality makes them a promising material for use in micro actuators and devices. However, the manufacturing of single-crystal-based Ni-Mn-Ga micro actuators is challenging due to their high brittleness and other material properties – numerous machining techniques that are successfully used for the deep engraving of conventional engineering materials cannot be directly applied to Ni-Mn-Ga-based alloys. Nevertheless, previous studies have shown that a femtosecond pulse width laser (FPWL) can be successfully utilized for the defect-free micromachining various materials. This work studies the effects of different engraving parameters and introduces a novel scanning-based method for the deep micromachining of Ni-Mn-Ga-based MSM alloys with maximum surface quality. Results show that a 4-layer strategy with a 0.01 mm hatch distance provides excellent machining in terms of surface quality and dimensional accuracy. This study can be utilized within design stages to estimate minimum margin based on required machined depth and avoid defects that occur in the sample preparation stage. Additionally, evolution of structures generated by FPWL machining are characterized. The results highlight how FPWL can be considered a highly capable process for the micromachining and surface structuring of Ni-Mn-Ga-based single crystals for manufacturing multifunctional MSM microdevices.
Evaluation of a hybrid protocol using continuous glucose monitoring and point-of-care testing in non–critically ill patients in a community hospital
Authors: Baker Matt , Lauterwasser Sara , Valenti Catherine , Kallenberger Michael , Stolte Haleigh
Published: December 2023

Purpose

Inpatient glycemic management typically involves use of point-of-care (POC) glucose measurements to inform insulin dosing decisions. This study evaluated a hybrid monitoring protocol using real-time continuous glucose monitoring (rtCGM) supplemented with POC testing at a community hospital.

Methods

Adult inpatients receiving POC glucose testing were monitored using rtCGM in a telemetry unit. The hybrid monitoring protocol required a once-daily POC test but otherwise primarily relied on rtCGM values for insulin dosing decisions. Outcomes assessment included surveillance error grid (SEG) and Clarke Error Grid (CEG) analysis results, the mean absolute relative difference (MARD) for available rtCGM-POC value pairs before and after study protocol application, the number of POC tests avoided, and the number of hypoglycemic events involving a blood glucose value of <70 mg/dL identified by rtCGM and POC values.

Results

Data were collected from 30 inpatients (the mean age was 69.4 years, 77% were female, 80% had type 2 diabetes, and 37% were at-home insulin users). With the protocol applied, a total of 202 rtCGM-POC pairs produced a MARD of 12.5%. SEG analysis showed 2 pairs in the “moderate” risk category, with all other pairs in the “none” or “slight” risk categories. CEG analysis showed 99% of paired values to be in the clinically acceptable range. Six hypoglycemic events in 5 patients were resolved without incident. Three hundred three POC tests were avoided, a 60% reduction for the study duration.

Conclusion

Use of a hybrid monitoring protocol of rtCGM and POC testing in a community hospital demonstrated sustained rtCGM accuracy and was found to reduce the frequency of POC testing to manage inpatient glycemia.
THItoGene: a deep learning method for predicting spatial transcriptomics from histological images
Authors: Jia Yuran , Liu Junliang , Chen Li , Zhao Tianyi , Wang Yadong
Published: December 2023

Spatial transcriptomics unveils the complex dynamics of cell regulation and transcriptomes, but it is typically cost-prohibitive. Predicting spatial gene expression from histological images via artificial intelligence offers a more affordable option, yet existing methods fall short in extracting deep-level information from pathological images. In this paper, we present THItoGene, a hybrid neural network that utilizes dynamic convolutional and capsule networks to adaptively sense potential molecular signals in histological images for exploring the relationship between high-resolution pathology image phenotypes and regulation of gene expression. A comprehensive benchmark evaluation using datasets from human breast cancer and cutaneous squamous cell carcinoma has demonstrated the superior performance of THItoGene in spatial gene expression prediction. Moreover, THItoGene has demonstrated its capacity to decipher both the spatial context and enrichment signals within specific tissue regions. THItoGene can be freely accessed at https://github.com/yrjia1015/THItoGene.
RNet: a network strategy to predict RNA binding preferences
Authors: Liu Haoquan , Jian Yiren , Hou Jinxuan , Zeng Chen , Zhao Yunjie
Published: December 2023

Determining the RNA binding preferences remains challenging because of the bottleneck of the binding interactions accompanied by subtle RNA flexibility. Typically, designing RNA inhibitors involves screening thousands of potential candidates for binding. Accurate binding site information can increase the number of successful hits even with few candidates. There are two main issues regarding RNA binding preference: binding site prediction and binding dynamical behavior prediction. Here, we propose one interpretable network-based approach, RNet, to acquire precise binding site and binding dynamical behavior information. RNetsite employs a machine learning-based network decomposition algorithm to predict RNA binding sites by analyzing the local and global network properties. Our research focuses on large RNAs with 3D structures without considering smaller regulatory RNAs, which are too small and dynamic. Our study shows that RNetsite outperforms existing methods, achieving precision values as high as 0.701 on TE18 and 0.788 on RB9 tests. In addition, RNetsite demonstrates remarkable robustness regarding perturbations in RNA structures. We also developed RNetdyn, a distance-based dynamical graph algorithm, to characterize the interface dynamical behavior consequences upon inhibitor binding. The simulation testing of competitive inhibitors indicates that RNetdyn outperforms the traditional method by 30%. The benchmark testing results demonstrate that RNet is highly accurate and robust. Our interpretable network algorithms can assist in predicting RNA binding preferences and accelerating RNA inhibitor design, providing valuable insights to the RNA research community.
Genetic structure of southern populations of Hydrochoerus hydrochaeris (Rodentia: Caviidae)
Authors: González-Barboza Matías , Bou Nadia , Byrne Soledad , Ignacio Túnez Juan , Barbanti Duarte José Mauricio , Cosse Mariana
Published: December 2023

The capybara (Hydrochoerus hydrochaeris) is a large semi-aquatic rodent with a broad distribution across South America. Although it is a relatively common and well-known species, there are few studies on its evolutionary history. Consequently, we decided to investigate the genetic diversity, population structure, and demographic history of capybaras, including new populations from its southern distribution range, by using a 226 bp fragment of the mitochondrial D-loop region. We found 16 haplotypes and populations, with moderate levels of haplotype and nucleotide diversity. In addition, the genetic structure analyses suggested high genetic divergence among populations, mainly among Pampean and Chacoan populations. We also found a consistent phylogeographical pattern with the distribution of main rivers. In agreement with palaeontological data, we propose two colonization pathways towards the south driven by main basins: Paraná–Paraguay and Uruguay–Atlantic.
Prognostic role of discordance between quantitative flow ratio and visual estimation in revascularization guidance
Authors: Terentes-Printzios Dimitrios , Oikonomou Dimitrios , Gkini Konstantia-Paraskevi , Gardikioti Vasiliki , Aznaouridis Konstantinos , Dima Ioanna , Tsioufis Konstantinos , Vlachopoulos Charalambos
Published: December 2023

Aims

Revascularization guided by functional severity has presented improved outcomes compared with visual angiographic guidance. Quantitative flow ratio (QFR) is a reliable angiography-based method for functional assessment. We sought to investigate the prognostic value of discordance between QFR and visual estimation in coronary revascularization guidance.

Methods and results

We performed offline QFR analysis on all-comers undergoing coronary angiography. Vessels with calculated QFR were divided into four groups based on the decision to perform or defer percutaneous coronary intervention (PCI) and on the QFR result, i.e.: Group A (PCI−, QFR > 0.8); Group B (PCI+, QFR ≤ 0.8); Group C (PCI+, QFR > 0.8); Group D (PCI−, QFR ≤ 0.8). Patients with at least one vessel falling within the disagreement groups formed the discordance group, whereas the remaining patients formed the concordance group. The primary endpoint was the composite endpoint of cardiovascular death, myocardial infarction, and ischaemia-driven revascularization. Overall, 546 patients were included in the study. Discordance between QFR and visual estimation was found in 26.2% of patients. After a median follow-up period of 2.5 years, the discordance group had a significantly higher rate of the composite outcome (hazard ratio: 3.34, 95% confidence interval 1.99–5.60, P < 0.001). Both disagreement vessel Groups C and D were associated with increased cardiovascular risk compared with agreement Groups A and B.

Conclusion

Discordance between QFR and visual estimation in revascularization guidance was associated with a worse long-term prognosis. Our results highlight the importance of proper patient selection for intervention and the need to avoid improper stent implantations when not dictated by a comprehensive functional assessment.
Long-term results after the réparation à l'étage ventriculaire procedure for transposition of the great arteries and double-outlet right ventricle with pulmonary stenosis
Authors: Pontailler Margaux , Moiroux-Sahraoui Alexander , Bernheim Ségolène , Gaudin Régis , Houyel Lucile , Bonnet Damien , Vouhé Pascal , Raisky Olivier
Published: December 2023

OBJECTIVES

The purpose of this study is to describe the long-term results of the ‘réparation à l’étage ventriculaire’ (REV) technique for double-outlet right ventricle and transposition of the great arteries (TGA) with pulmonary stenosis (PS).

METHODS

Between 1980 and 2021, 157 patients underwent a REV procedure (median age and weight: 20.8 months and 7.7 kg). The most frequent anatomical presentation was the association between TGA, ventricular septal defect and PS (n = 116, 73.9%).

RESULTS

Sixty-seven patients (42.7%) underwent a Rashkind procedure, and 67 patients (42.7%) a prior surgical palliation (including 62 systemic-to-pulmonary artery shunts). Resection of the conal septum and/or ventricular septal defect enlargement was performed in 109 patients (69.4%). Thirteen patients (8.3%) died, including 4 during the first postoperative month and 2 after heart transplant. Overall survival at 40 years was 89.3%. Thirty-seven patients (23.6%) required 68 reinterventions on the right ventricular outflow tract (RVOT), including 49 reoperations, with a median delay of 9 years after the REV (8 months to 27 years). Twenty patients (12.7%) underwent RVOT valvulation (16 surgical and 4 interventional). Freedom from RVOT reintervention and reoperation at 40 years were 60.3% and 62.6%, respectively. Four patients (2.5%) required reoperation for left ventricular outflow tract obstruction, with a median delay of 4.8 years.

CONCLUSIONS

The REV procedure is a good alternative for TGA and double-outlet right ventricle with PS patients. Only a quarter of the patients required redo surgery on the RVOT. Reoperations for left ventricular outflow tract obstruction are scarce.
Patient decision aids for aortic stenosis and chronic coronary artery disease: a systematic review and meta-analysis
Authors: Harris Emma , Benham Alex , Stephenson John , Conway Dwayne , Chong Aun-Yeong , Curtis Helen , Astin Felicity
Published: December 2023

Aims

Shared decision-making is recommended for patients considering treatment options for severe aortic stenosis (AS) and chronic coronary artery disease (CAD). This review aims to systematically identify and assess patient decision aids (PtDAs) for chronic CAD and AS and evaluate the international evidence on their effectiveness for improving the quality of decision-making.

Methods and results

Five databases (Cochrane, CINAHL, Embase, MEDLINE, and PsycInfo), clinical trial registers, and 30 PtDA repositories/websites were searched from 2006 to March 2023. Screening, data extraction, and quality assessments were completed independently by multiple reviewers. Meta-analyses were conducted using Stata statistical software. Eleven AS and 10 CAD PtDAs were identified; seven were less than 5 years old. Over half of the PtDAs were web based and the remainder paper based. One AS and two CAD PtDAs fully/partially achieved international PtDA quality criteria. Ten studies were included in the review; four reported on the development/evaluation of AS PtDAs and six on CAD PtDAs. Most studies were conducted in the USA with White, well-educated, English-speaking participants. No studies fulfilled all quality criteria for reporting PtDA development and evaluation. Meta-analyses found that PtDAs significantly increased patient knowledge compared with ‘usual care’ (mean difference: 0.620; 95% confidence interval 0.396–0.845, P < 0.001) but did not change decisional conflict.

Conclusion

Patients who use PtDAs when considering treatments for AS or chronic CAD are likely to be better informed than those who do not. Existing PtDAs may not meet the needs of people with low health literacy levels as they are rarely involved in their development.

Registration

PROSPERO: CRD42021264700.
Exploring Rural–Urban Differences in the Association Between Internet Use and Cognitive Functioning Among Older Adults in China
Authors: Yu Xinfang , Ang Shannon , Zhang Yang
Published: December 2023

Objectives

We examine rural–urban differences between internet use and cognitive functioning among older Chinese adults and the mediating role of perceived social support networks across rural and urban areas.

Methods

Data were from the 2016 and 2018 waves of the Chinese Longitudinal Aging Social Survey (N = 9,591). Ordinary least squares regression and mediation analyses were used to examine the specific hypotheses.

Results

General internet use was significantly associated with improved cognitive functioning among older adults in the overall sample. Social support networks mediated the relationship between general internet use and cognitive functioning, but only for older adults living in rural areas. After disaggregating internet use into specific online activities, watching shows was associated with better cognitive functioning for older adults living in urban areas. For those in rural areas, chatting was positively associated with cognitive functioning, while playing games was negatively associated with cognitive functioning.

Discussion

We showed that social support mediates the relationship between internet use and cognitive functioning differently in rural and urban areas. Cognitive benefits derived from specific types of online activities also depend on their residence. These findings suggest that efforts aimed at improving internet use among rural older adults may be more fruitful if they focus on building social opportunities for older adults.
Health literacy and breast cancer screening adherence: results from the population of Tuscany, Italy
Authors: Zanobini Patrizio , Bonaccorsi Guglielmo , Giusti Martina , Minardi Valentina , Possenti Valentina , Masocco Maria , Garofalo Giorgio , Mereu Giovanna , Cecconi Rossella , Lorini Chiara
Published: December 2023

Mammographic screening can reduce breast cancer (BC) mortality in women. In Italy, although attendance rates increased recently, they are still far from the recommended levels internationally. Inadequate health literacy (HL) may be a reason for poor awareness and/or knowledge about the importance of completing cancer screening. This study examined the relationship between HL, other sociodemographic determinants, and their influence on participation in both opportunistic and organized BC screenings among women aged 50–69 in Tuscany. The study analyzed 2017–2019 data from the Tuscan population subsample in the Italian Behavioral Risk Factor Surveillance System PASSI (Progressi delle Aziende Sanitarie per la Salute in Italia). HL was assessed using the Italian version of the six-item European Health Literacy Survey Questionnaire (HLS-EU-Q6). Among the 2250 interviewees, 75.3% underwent the organized BC screening and 9.4% on voluntary basis. Although to a different extent, HL was significantly associated to compliance rates with both opportunistic and organized screenings. Among sociodemographic factors, only occupational status was associated with opportunistic screening attendance rates. As expected, being invited by letter resulted to be strongly associated with participation to organized screening programs and the medical advice predicts for participating to both opportunistic and organized screening. This study highlights the relevant role that HL plays in BC, opportunistic and organized, screening adherence in a universal healthcare system. To increase BC screening participation rates, healthcare systems would benefit by implementing interventions for improved HL at population level or within healthcare organizations.
Aberrant monocytopoiesis drives granuloma development in sarcoidosis
Authors: Hiranuma Ryosuke , Sato Ryota , Yamaguchi Kiyoshi , Nakamizo Satoshi , Asano Kenichi , Shibata Takuma , Fukui Ryutaro , Furukawa Yoichi , Kabashima Kenji , Miyake Kensuke
Published: December 2023

In sarcoidosis, granulomas develop in multiple organs including the liver and lungs. Although mechanistic target of rapamycin complex 1 (mTORC1) activation in macrophages drives granuloma development in sarcoidosis by enhancing macrophage proliferation, little is known about the macrophage subsets that proliferate and mature into granuloma macrophages. Here, we show that aberrantly increased monocytopoiesis gives rise to granulomas in a sarcoidosis model, in which Tsc2, a negative regulator of mTORC1, is conditionally deleted in CSF1R-expressing macrophages (Tsc2csf1rΔ mice). In Tsc2csf1rΔ mice, common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), common monocyte progenitors / monocyte progenitors (cMoPs / MPs), inducible monocyte progenitors (iMoPs), and Ly6Cint CX3CR1low CD14− immature monocytes (iMOs), but not monocyte-dendritic cell progenitors (MDPs) and common dendritic cell progenitors (CDPs), accumulated and proliferated in the spleen. Consistent with this, monocytes, neutrophils, and neutrophil-like monocytes increased in the spleens of Tsc2csf1rΔ mice, whereas dendritic cells did not. The adoptive transfer of splenic iMOs into wild-type mice gave rise to granulomas in the liver and lungs. In these target organs, iMOs matured into Ly6Chi classical monocytes/macrophages (cMOs). Giant macrophages (gMAs) also accumulated in the liver and lungs, which were similar to granuloma macrophages in expression of cell surface markers such as MerTK and SLAMF7. Furthermore, the gMA-specific genes were expressed in human macrophages from sarcoidosis skin lesions. These results suggest that mTORC1 drives granuloma development by promoting the proliferation of monocyte/neutrophil progenitors and iMOs predominantly in the spleen, and that proliferating iMOs mature into cMOs and then gMAs to give rise to granuloma after migration into the liver and lungs in sarcoidosis.
Deploying a national clinical text processing infrastructure
Authors: McManus Kimberly F , Stringer Johnathon Michael , Corson Neal , Fodeh Samah , Steinhardt Steven , Levin Forrest L , Shotqara Asqar S , D’Auria Joseph , Fielstein Elliot M , Gobbel Glenn T , Scott John , Trafton Jodie A , Taddei Tamar H , Erdos Joseph , Tamang Suzanne R
Published: December 2023

Objectives

Clinical text processing offers a promising avenue for improving multiple aspects of healthcare, though operational deployment remains a substantial challenge. This case report details the implementation of a national clinical text processing infrastructure within the Department of Veterans Affairs (VA).

Methods

Two foundational use cases, cancer case management and suicide and overdose prevention, illustrate how text processing can be practically implemented at scale for diverse clinical applications using shared services.

Results

Insights from these use cases underline both commonalities and differences, providing a replicable model for future text processing applications.

Conclusions

This project enables more efficient initiation, testing, and future deployment of text processing models, streamlining the integration of these use cases into healthcare operations. This project implementation is in a large integrated health delivery system in the United States, but we expect the lessons learned to be relevant to any health system, including smaller local and regional health systems in the United States.
The evolutionary dynamics of local adaptations under genetic rescue is determined by mutational load and polygenicity
Authors: Zhang Yulin , Stern Aaron J , Nielsen Rasmus
Published: December 2023

Inbred populations often suffer from increased mutational load and reduced fitness due to lower efficacy of purifying selection in groups with small effective population sizes. Genetic rescue (GR) is a conservation tool that is studied and deployed with the aim of increasing the fitness of such inbred populations by assisted migration of individuals from closely related outbred populations. The success of GR depends on several factors—such as their demographic history and distribution of dominance effects of mutations—that may vary across populations. While we understand the impact of these factors on the dynamics of GR, their impact on local adaptations remains unclear. To this end, we conduct a population genetics simulation study to evaluate the impact of trait complexity (Mendelian vs. polygenic), dominance effects, and demographic history on the efficacy of GR. We find that the impact on local adaptations depends highly on the mutational load at the time of GR, which is in turn shaped dynamically by interactions between demographic history and dominance effects of deleterious variation. Over time local adaptations are generally restored post-GR, though in the short term they are often compromised in the process of purging deleterious variation. We also show that while local adaptations are almost always fully restored, the degree to which ancestral genetic variation affecting the trait is replaced by donor variation can vary drastically and is especially high for complex traits. Our results provide insights on the impact of GR on trait evolution and considerations for the practical implementation of GR.
Genomic analysis supports Cape Lion population connectivity prior to colonial eradication and extinction
Authors: de Flamingh Alida , Gnoske Thomas P , Rivera-Colón Angel G , Simeonovski Velizar A , Kerbis Peterhans Julian C , Yamaguchi Nobuyuki , Witt Kelsey E , Catchen Julian , Roca Alfred L , Malhi Ripan Singh
Published: December 2023

Cape lions (Panthera leo melanochaitus) formerly ranged throughout the grassland plains of the “Cape Flats” in what is today known as the Western Cape Province, South Africa. Cape lions were likely eradicated because of overhunting and habitat loss after European colonization. European naturalists originally described Cape lions as “black-maned lions” and claimed that they were phenotypically distinct. However, other depictions and historical descriptions of lions from the Cape report mixed or light coloration and without black or extensively developed manes. These findings suggest that, rather than forming a distinct population, Cape lions may have had phenotypic and genotypic variation similar to other African lions. Here we investigate Cape lion genome characteristics, population dynamics, and genetic distinctiveness prior to their extinction. We generated genomic data from 2 historic Cape lions to compare to 118 existing high-coverage mitogenomes, and low-coverage nuclear genomes of 53 lions from 13 African countries. We show that, before their eradication, lions from the Cape Flats had diverse mitogenomes and nuclear genomes that clustered with lions from both southern and eastern Africa. Cape lions had high genome-wide heterozygosity and low inbreeding coefficients, indicating that populations in the Cape Flats went extinct so rapidly that genomic effects associated with long-term small population size and isolation were not detectable. Our findings do not support the characterization of Cape lions as phylogeographically distinct, as originally put forth by some European naturalists, and illustrates how alternative knowledge systems, for example, Indigenous perspectives, could potentially further inform interpretations of species histories.
Determination of FRAND royalty rates: an examination of prominent SEP cases
Authors: Effraimidis Georgios , Werner Dan , Boushie Kristopher
Published: December 2023

Technology standards are critical in creating a common interface, allowing interoperability between individual components, devices and networks. Technology standards often incorporate many essential patented inventions, which are referred to as standard-essential patents (SEPs). Owners of declared SEPs provide commitments to standard setting organizations (SSOs) that they will license their SEPs on fair, reasonable and non-discriminatory (FRAND) terms to companies that practice the standards. However, it is sometimes disputed whether or not these royalty rates are FRAND; in these cases, the burden of determining a FRAND royalty falls to courts. It is important for parties involved in SEP litigation to be knowledgeable of the appropriate economic tools and models to address the various issues arising in these unique and challenging patent disputes. This article discusses how various approaches to patent valuation have been applied in prominent SEP cases over the last decade.
Outcomes in patients with high- and very high-risk localized prostate cancer treated with definitive IMRT and long-term hormone therapy
Authors: Kawamura Norihiko , Hayashi Takuji , Nagahara Akira , Nakai Yasutomo , Nakayama Masashi , Ikawa Toshiki , Kanayama Naoyuki , Morimoto Masahiro , Konishi Koji , Nishimura Kazuo
Published: December 2023

Background

The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect.

Methods

Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74–78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3–6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy.

Results

The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure.

Conclusions

Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.
Quality of life but not cachexia definitions are associated with overall survival in women with cervical cancer: a STROBE-compliant cohort study
Authors: Luvián-Morales Julissa , Delgadillo-González Merari , Castro-Eguiluz Denisse , Oñate-Ocaña Luis F , Cetina-Pérez Lucely
Published: December 2023

Background

Cancer-related cachexia (CRC) has a profound impact on health-related quality of life (HRQL), and both were reported to be associated with overall survival (OS). We hypothesize that HRQL and CRC are associated with OS. This study analyzed the impact of CRC on HRQL and its prognostic value in women with cervical cancer (CC).

Methods

A cohort study including consecutive women with CC treated from October 2020 to October 2021 in a cancer center. Cox’s model defined the associations of immune, biochemical and nutritional parameters, clinical cachexia classifications and HRQL with OS.

Results

Two hundred forty-four consecutive women with CC were included. Cachexia classifications and several scales of the QLQ-C30 were associated with OS by bivariate but not by multivariate analysis. QLQ-CX24 scales were not associated with OS. The prognostic nutritional index (PNI) (hazard ratio (HR) 0.828; 95% confidence interval (CI) 0.766–0.896), Food aversion (HR 0.95; 95% CI 0.924–0.976), Eating difficulties (HR 1.041; 95% CI 1.013–1.071), Loss of control (HR 4.131; 95% CI 1.317–12.963), Forced self to eat (1.024; 95% CI 1.004–1.044) and Indigestion (HR 0.348; 95% CI 0.131–0.928) scales of the QLQ-CAX24 were independently associated with OS by multivariate analysis (p = 1.9×10−11).

Conclusion

This model permitted a clear stratification of prognostic subgroups. The PNI and several QLQ-CAX24 scales were associated with OS in women with CC. CRC, defined by several cachexia classifications, was not an independent prognostic factor. These findings require confirmation because of their possible diagnostic, therapeutic and prognostic implications.

The prognostic nutritional index and several QLQ-CAX24 scales were associated with overall survival in women with cervical cancer. Cancer-related cachexia, defined by several cachexia classifications, was not an independent prognostic factor, neither The International Federation of Gynecology and Obstetrics (FIGO) stage classifications.
Neonatal CD4+ T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response
Authors: Kempis-Calanis Linda Aimara , Rodríguez-Jorge Otoniel , Gutiérrez-Reyna Darely Yarazeth , Ventura-Martínez Carlos Jesús , Spicuglia Salvatore , Medina-Rivera Alejandra , Thieffry Denis , González Aitor , Santana María Angélica
Published: December 2023

The adaptive immune response is coordinated by CD4+ T cells, which determine the type and strength of the immune response and the effector cells involved. It has been reported that CD4+ T cells are less responsive in neonates, leading to low activation of the cellular response and poor antibody production by B cells. This low response is essential for the tolerant window that favors birth transition from the sterile environment in the womb to the outside world but leaves neonates vulnerable to infection, which is still an important health issue. Neonates have a high morbidity and mortality rate due to infections, and the molecular reasons are still understudied. We asked whether the neonatal naive CD4+ T cells have a genomic program that predisposes them to a low response. Therefore, we evaluated the transcriptome and epigenome of human neonatal and adult naive CD4+ T cells. Our results point to a gene expression profile forming a distinct regulatory network in neonatal cells, which favors proliferation and a low T-cell response. Such expression profile is supported by a characteristic epigenetic landscape of neonatal CD4+ T cells, which correlates with the characteristic transcriptome of the neonatal cells. These results were confirmed by experiments showing a low response to activation signals, higher proliferation, and lower expression of cytokines of neonatal CD4+ T cells as compared to adult cells. Understanding this network could lead to novel vaccine formulations and better deal with life-threatening diseases during this highly vulnerable period of our lives.
Responses to Real-World and Hypothetical Menthol Flavor Bans Among US Young Adults Who Smoke Menthol Cigarettes
Authors: Tam Jamie , Jimenez-Mendoza Evelyn , Buckell John , Sindelar Jody , Meza Rafael
Published: December 2023

Introduction

Menthol cigarette bans have been implemented in some US states and localities, and a federal ban is being proposed by the FDA. This study asks how young adults who use menthol cigarettes respond to changes in menthol cigarette availability.

Aims and Methods

An online survey of young adults ages 18–34 who reported smoking menthol cigarettes on ≥7 of 30 days around Thanksgiving 2019 (n = 734), oversampling Massachusetts—the first state with a menthol ban. Participants reported their tobacco use behavior following real-world menthol cigarette bans or predicted their behavior under a hypothetical federal ban.

Results

Most respondents who exclusively smoked versus dual used with e-cigarettes continued smoking/using combustible tobacco following real-world bans (95.3% vs. 86.9%), accessing menthol cigarettes from other jurisdictions. Fewer who smoked exclusively responded by using e-cigarettes compared to those who dual used (3.9% vs. 43.7%). Quitting all tobacco use (ie, no smoking, vaping, or any tobacco use) was uncommon for both groups (3.6% vs. 9.0%). Under a hypothetical ban, majorities of those who exclusively smoke and who dual use predicted they would continue smoking (72.2% vs. 71.8%); fewer who smoke exclusively would use e-cigarettes compared to those who dual use (14.7% vs. 41.4%). Those who smoke exclusively were more likely to report quitting all tobacco compared to those who dual use (29.6% vs. 12.4%).

Conclusions

Under real-world and hypothetical menthol cigarette bans, most respondents continued smoking. However, more young adults continued smoking following real-world bans, reflecting the limitations of local/state restrictions when menthol cigarettes are available in other jurisdictions.

Implications

This survey asked young adults who use menthol cigarettes how they responded to real-world changes in the availability of menthol cigarettes; 89% reported continuing to smoke. Those who smoked exclusively were far less likely to respond by switching to e-cigarettes compared to people who dual used both products. Under a hypothetical federal menthol cigarette ban, 72% of young adults predicted that they would continue smoking. Quitting all tobacco was less common in the real-world scenario compared to the hypothetical ban. Access to menthol cigarettes in other jurisdictions and flavored cigars likely dampen the public health benefit of menthol cigarette bans.
Tobacco Imagery in Indian Over-the-Top (OTT) Media and Its Compliance With Existing Tobacco Laws: A Content Analysis
Authors: Pulicherla Naveen Kumar , Kodali Prakash Babu
Published: December 2023

Introduction

Over-the-top (OTT) media are internet-based content delivery systems offering media services to the viewers bypassing the traditional broadcasting platforms. The OTT media, with limited regulatory oversight, can serve as a source of exposure to tobacco-promoting content.

Aims and Methods

This study analyzed the depiction of tobacco imagery in Indian OTT programs and assessed their compliance with existing Indian tobacco control policies. We conducted a content analysis of 28 purposively sampled OTT exclusive programs (14 movies and 14 web series) in India. Breathe California method was used to code the OTT content for tobacco imagery. We assessed the prevalence of tobacco imagery, its duration per episode or program, product placements, and brand appearances. We also evaluated OTT programs adherence to existing tobacco control policies in India.

Results

Tobacco imagery was identified in all of the web series and most OTT-exclusive movies. On average the web series depicted seven incidents of tobacco imagery per episode, whereas there were close to 19 incidents of tobacco imagery per movie. Ten minutes of OTT programming (including movies and web series) had on average 8.40 s of tobacco imagery. None of the OTT programs studied fully complied with Indian tobacco control policies.

Conclusions

Depiction of tobacco imagery in OTT exclusive programs is common in India. Streaming platforms need to comply with existing tobacco control policies. Furthermore, there is a need to strengthen these policies and strictly enforce them to ensure tobacco-free mass media.

Implications

India has more than 267 million tobacco users and accounts for the largest share of smokeless tobacco use globally. OTT platforms are largely unregulated and are considered drivers for global tobacco use. This is one of the few studies examining tobacco imagery in Indian OTT content, reporting the gaps in tobacco control policies in India. This study documents the product placement of smokeless tobacco, duration of exposure to tobacco imagery, and empirically report the compliance of OTT platforms with Indian tobacco control policies. The study findings can aid in strengthening tobacco control policies in India.
The association between maternal body mass index and breast milk composition: a systematic review
Authors: Hashemi Javaheri Fatemeh Sadat , Karbin Karim , Senobari Mohammad Amin , Hakim Hakime Ghadiri , Hashemi Mohammad
Published: December 2023

Context

Breast milk composition is influenced by many factors, ranging from maternal nutritional status to infant sex. Previous studies have explored the relationship between maternal body mass index (BMI) and breast milk composition; however, the findings have been inconsistent and controversial.

Objective

To systematically review the evidence on the association of maternal weight and BMI with breast milk composition.

Data Sources

The PubMed and Scopus databases were searched up to May 3, 2023, using the following search strategy: (“maternal weight” OR “maternal BMI” OR “mother’s weight” OR “mother’s BMI”) AND (“maternal milk” OR “human milk” OR “breast milk”).

Data Extraction

A total of 83 publications, involving data from more than 11 310 lactating women, were identified. All extracted data were compiled, compared, and critically analyzed.

Data Analysis

Overall, maternal BMI was associated with higher levels of leptin and insulin, and the ratio of omega-6 to omega-3 polyunsaturated fatty acids in breast milk. However, no conclusive associations were found between maternal BMI and the levels of energy, macronutrients, micronutrients, and other components of breast milk.

Conclusions

This systematic review provides robust evidence supporting a positive correlation between maternal BMI and breast milk concentrations of leptin, insulin, and the omega-6 to omega-3 polyunsaturated fatty acid ratio. Nevertheless, disparities in findings are noticeable for other constituents of breast milk. To comprehensively grasp the influence of maternal weight and BMI on breast milk composition, further research endeavors are imperative.

Systematic Review Registration

PROSPERO registration no. CRD42023458667.
Ethylene inhibits photosynthesis via temporally distinct responses in tomato plants
Authors: Mohorović Petar , Geldhof Batist , Holsteens Kristof , Rinia Marilien , Daems Stijn , Reijnders Timmy , Ceusters Johan , Van den Ende Wim , Van de Poel Bram
Published: December 2023

Ethylene is a volatile plant hormone that regulates many developmental processes and responses toward (a)biotic stress. Studies have shown that high levels of ethylene repress vegetative growth in many important crops, including tomato (Solanum lycopersicum), possibly by inhibiting photosynthesis. We investigated the temporal effects of ethylene on young tomato plants using an automated ethylene gassing system to monitor the physiological, biochemical, and molecular responses through time course RNA-seq of a photosynthetically active source leaf. We found that ethylene evokes a dose-dependent inhibition of photosynthesis, which can be characterized by 3 temporally distinct phases. The earliest ethylene responses that marked the first phase and occurred a few hours after the start of the treatment were leaf epinasty and a decline in stomatal conductance, which led to lower light perception and CO2 uptake, respectively, resulting in a rapid decline of soluble sugar levels (glucose, fructose). The second phase of the ethylene effect was marked by low carbohydrate availability, which modulated plant energy metabolism to adapt by using alternative substrates (lipids and proteins) to fuel the TCA cycle. Long-term continuous exposure to ethylene led to the third phase, characterized by starch and chlorophyll breakdown, which further inhibited photosynthesis, leading to premature leaf senescence. To reveal early (3 h) ethylene-dependent regulators of photosynthesis, we performed a ChIP-seq experiment using anti-ETHYLENE INSENSITIVE 3-like 1 (EIL1) antibodies and found several candidate transcriptional regulators. Collectively, our study revealed a temporal sequence of events that led to the inhibition of photosynthesis by ethylene and identified potential transcriptional regulators responsible for this regulation.
Credit Risk Sharing and Credit Market Regulation
Authors: Subramanian Ajay
Published: December 2023

I show how aggregate risk influences credit default swap (CDS) markets and CDS regulation in an analytically tractable general equilibrium framework. For low aggregate risk, the equilibrium with unregulated CDS markets is efficient with bondholders being fully insured. A general efficient allocation can be implemented via transfers alone. For intermediate aggregate risk, a margin requirement on CDS sellers is also necessary to implement the general efficient allocation. If aggregate risk is sufficiently high, unregulated CDS markets break down. A margin requirement on CDS sellers restores equilibrium and efficiency, but it must be maximally stringent and accompanied by constraints on CDS purchases by buyers. (JEL G22, G28, D52)
The Drama of Elections: Election Plays in the Long Eighteenth Century
Authors: Packham Kendra
Published: December 2023

This article breaks new literary and historical ground by recovering a rich but forgotten dramatic genre, and its literary and political significance: the eighteenth-century election play. It examines a range of plays which took contemporary elections as a key dramatic subject and setting—including a previously unexplored manuscript work which engages with the culture and politics of Defoe’s novel Robinson Crusoe—and argues that these plays open new perspectives on the period’s literature and politics, and the vital exchanges between them. Elections fuelled dramatic creativity and culture. Popular politics afforded profitable themes and occasions for comedy, satire, and heroic representations, supplying characters, settings, plots, and spectacle. Such plays, in turn, energized political culture. Election plays were circulated and performed not only when and where elections took place, and, although subject to forms of censorship, they encouraged active political engagement across the social spectrum and across the country in terms of their authors, audiences, and performers. Engaging with popular dramatic forms as well as popular politics, these plays popularized different perspectives, shaped by particular performances and conventions. They contributed to the conceptualization and commercialization of politics, fuelling a market for entertaining representations of the ‘humours’ of elections and a culture in which contested elections were seen as a key aspect of life and debate. At a time when the right—and opportunity—to vote for MPs was highly restricted, election plays both reflected, and helped to fuel and shape, an adversarial, far-reaching culture of elections and electioneering.
Fields of Knowledge under Construction: Pedology and Medico-pedagogical Approaches in France at the Turn of the Twentieth Century
Authors: Arnaud Sabine
Published: December 2023

Examining the work of Georges Paul-Boncour and Jean Philippe, two now almost forgotten physicians active from the turn of the twentieth century on in the medical and educational field of ‘school hygiene’ for so-called abnormal children, this article exemplifies a specific current in psychiatry whose terms first kept oscillating between medico-pedagogical treatment and therapeutic hygiene. I investigate how Paul-Boncour and Philippe’s interest in abnormal children led them to challenge education as a whole. By attempting to individualise education, the two doctors were swimming against the tide of regular schooling, which evaluated children on their ability to fit in with others and fulfil preset expectations. The conflicts between these physicians and their contemporaries (teachers, psychologists, lawyers) attest the emergence of a dimension in psychiatry that was rooted in collaboration with teachers, as doctors and teachers worked together for the full development of ‘pedology’, the scientific study of children’s development.