bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis of genome-wide association studies of gestational duration and spontaneous preterm birth identifies new maternal risk loci
Authors: Pasanen Anu , Karjalainen Minna K. ,   FinnGen, Zhang Ge , Tiensuu Heli , Haapalainen Antti M. , Ojaniemi Marja , Feenstra Bjarke , Jacobsson Bo , Palotie Aarno , Laivuori Hannele , Muglia Louis J. , Rämet Mika , Hallman Mikko
Published: October 2023

Background

Preterm birth (<37 weeks of gestation) is a major cause of neonatal death and morbidity. Up to 40% of the variation in timing of birth results from genetic factors, mostly due to the maternal genome.

Methods

We conducted a genome-wide meta-analysis of gestational duration and spontaneous preterm birth in 68,732 and 98,370 European mothers, respectively.

Results

The meta-analysis detected 15 loci associated with gestational duration, and four loci associated with preterm birth. Seven of the associated loci were novel. The loci mapped to several biologically plausible genes, for example HAND2 whose expression was previously shown to decrease during gestation, associated with gestational duration, and GC (Vitamin D-binding protein), associated with preterm birth. Downstream in silico-analysis suggested regulatory roles as underlying mechanisms for the associated loci. LD score regression found birth weight measures as the most strongly correlated traits, highlighting the unique nature of spontaneous preterm birth phenotype. Tissue expression and colocalization analysis revealed reproductive tissues and immune cell types as the most relevant sites of action.

Conclusion

We report novel genetic risk loci that associate with preterm birth or gestational duration, and reproduce findings from previous genome-wide association studies. Altogether, our findings provide new insight into the genetic background of preterm birth. Better characterization of the causal genetic mechanisms will be important to public health as it could suggest new strategies to treat and prevent preterm birth.
A novel proneural function of Asense is integrated with the sequential actions of Delta-Notch, L’sc and Su(H) to promote the neuroepithelial to neuroblast transition
Authors: Martin Mercedes , Gutierrez-Avino Francisco , Shaikh Mirja N. , Tejedor Francisco J.
Published: October 2023

In order for neural progenitors (NPs) to generate distinct populations of neurons at the right time and place during CNS development, they must switch from undergoing purely proliferative, self-renewing divisions to neurogenic, asymmetric divisions in a tightly regulated manner. In the developingDrosophilaoptic lobe, neuroepithelial (NE) cells of the outer proliferation center (OPC) are progressively transformed into neurogenic NPs called neuroblasts (NBs) in a medial to lateral proneural wave. The cells undergoing this transition express Lethal of Scute (L’sc), a proneural transcription factor (TF) of the Acheate Scute Complex (AS-C). Here we show that there is also a peak of expression of Asense (Ase), another AS-C TF, in the cells neighboring those with transient L’sc expression. These peak of Ase cells help to identify a new transitional stage as they have lost NE markers and L’sc, they receive a strong Notch signal and barely exhibit NB markers. This expression of Ase is necessary and sufficient to promote the NE to NB transition in a more robust and rapid manner than that ofl’scgain of function orNotchloss of function. Thus, to our knowledge, these data provide the first direct evidence of a proneural role for Ase in CNS neurogenesis. Strikingly, we found that strong Delta-Notch signaling at the lateral border of the NE triggersl’scexpression, which in turn inducesaseexpression in the adjacent cells through the activation of Delta-Notch signaling. These results reveal two novel non-conventional actions of Notch signaling in driving the expression of proneural factors, in contrast to the repression that Notch signaling exerts on them during classical lateral inhibition. Finally, Suppressor of Hairless (Su(H)), which seems to be upregulated late in the transitioning cells and in NBs, repressesl’scandase, ensuring their expression is transient. Thus, our data identify a key proneural role of Ase that is integrated with the sequential activities of Delta-Notch signaling, L’sc, and Su(H), driving the progressive transformation of NE cells into NBs.
Physical activity and its correlates among school teachers in a semi-urban district of Nepal
Authors: Shrestha Rajan , Pahari Durga Prasad , Adhikari Santoshi , Khatri Bijay , Majhi Sangita , Adhikari Tara Ballav , Neupane Dinesh , Kallestrup Per , Vaidya Abhinav
Published: October 2023

Regular physical activity (PA) is one of the effective strategies for mitigating non-communicable diseases, promoting healthy ageing, and preventing premature mortality. In South Asia, up to 34.0% of adults are insufficiently active, and up to 44.1% of adults in Nepal. We sought to assess self-reported PA status and its correlates among teachers in the semi-urban district of Nepal. A cross-sectional descriptive study was conducted among teachers at randomly selected public secondary schools in Bhaktapur, Nepal, from November 2018-April 2019. PA status was assessed in Metabolic Equivalent to task minutes per week using the International Physical Activity Questionnaire (IPAQ)–Long Form. Point estimates and odds ratios were calculated at a 95% confidence interval, and a p-value <0.05 was considered statistically significant. Among the 360 participants, the mean (SD) age was 40.3 (10.2) years, with 52.5% female participation. A low level of PA was seen among 11.9% (95% CI: 8.4–15.2) of teachers, and more than half (56.0%) of the activity was only moderate intensity. Domestic and garden work was the main contributor (43.0%) of total PA, while leisure time was the least (14.0%). Among the socio-demographic factors, only sex was significantly associated (p = 0.005) with PA. Participants living in locations with walkable areas were 3.4 times (95% CI: 1.6–7.3) more likely to be engaged in moderate-to-high level PA than those without. In our study, the point prevalence of insufficient PA among teachers working at public secondary schools was higher than the national point prevalence. PA promotion programs targeting sedentary populations like school teachers should be developed to reduce the point prevalence of insufficient PA.
Co-constructing collaboration: An evidence-based approach to advance and evaluate equitable global public health research partnerships
Authors: Amos Vanessa , LeBaron Virginia , Chuong Tuyet , Elmore Catherine E. , Hamal Pawan Kumar , Paudel Bishnu D. , Steen Amber , Chapagain Sandhya
Published: October 2023

Equitable global health partnerships are essential to promote innovative research and strengthen research capacity to address critical public health challenges, but how to optimally evaluate such collaborations is unclear. This was a sequential, multi-method study that utilized an electronic survey informed by the literature followed by semi-structured interviews to comprehensively evaluate the experience of participating in a global research-capacity building collaboration between Nepal and U.S. clinicians and investigators. De-identified quantitative survey were analyzed to calculate descriptive and summary statistics, along with crosstabs of each variable by group. Groups were defined based on country-of-origin and Chi Square statistics calculated to assess for statistically significant differences (p<0.05) between groups. Interviews were analyzed using a descriptive qualitative approach to develop an overall thematic map. 22 survey responses (52.4% response rate) were analyzed; 13 (59.1%) from Nepal, 9 (40.9%) from the U.S. Eight participants (4 Nepal; 4 U.S.) were interviewed. Over the course of the project, all participants reported gaining experience and confidence with research. The majority of participants “strongly agreed” there was a shared understanding of goals, priorities and strategies (Nepal, 58.3%, n = 7; U.S., 88.9%, n = 8;) and that power was shared equally (Nepal, 58.3%, n = 7; U.S., 55.6%, n = 5). The over-arching theme that emerged from the interviews was the importance of ‘establishing community’ which participants discussed within the broader context of COVID-19. Overall, team members reported strong bi-directional benefit and a greater emphasis on perceived benefits versus challenges. Our survey tool and interview guide, designed to holistically evaluate the impact of a global partnership across various levels of the Social Ecological Model, with particular attention to power dynamics and equity, can be adapted and used by others engaged in similar research capacity collaborations.
Prevalence and public health significance of rabies virus in bats in the North Region of Cameroon
Authors: Dah Isaac , Poueme Namegni Rodrigue Simonet , Mouiche Mouliom Mohamed Moctar , Dickmu Jumbo Simon , Nguena Guefack Noumedem Ranyl , Conclois Isabelle , Florian Liegeois , God-Yang Laurent , Kameni Feussom Jean Marc , Wade Abel , Missé Dorothée , Awah-Ndukum Julius
Published: October 2023

Background

Rabies is a zoonotic disease of all warm-blooded animals including humans. There is a paucity of data on the status of rabies in wild animals in Cameroon and the disease is endemic in the country with dogs being the main source of transmission. Bat habitats are widespread in Cameroon, but there is limited information on the prevalence of rabies in bats, and their role of as potential reservoirs of rabies virus.

Methods

A cross sectional study was carried out to estimate the prevalence and to assess risk factors of rabies virus in bats in the North Region of Cameroon. A total of 212 bats belonging to three families (Pteropodidae, Vespertilionidae and Molossidae) and 5 species were sampled in 7 localities in the North Region of Cameroon and were tested for rabies virus antigen using direct Immunofluorescence Test (IFA).

Results

Overall, 26.9% (57/212) of the bats collected showed an IFA positive reaction. The prevalence was significantly higher (P<0.05) in adult bats (33.3% (36/108)) compared to young individuals (20.2%; 21/104). The main risk factors identified in the study for human exposure to bats were gender (Male), religion (Christianity), localities (Babla and Lagdo), the practice of bat hunting, bat consumption, unawareness of bat rabies and cohabitation with bats in close proximity.

Conclusion

The study revealed the first evidence of Lyssavirus in bats in Cameroon. This finding showed that bat rabies are real and represents a potential public health concern in communities with bat habitats in the North Region of Cameroon. Enhancing the level of public awareness and health education on the potential of bats as reservoirs of Lyssavirus in Cameroon as well as the integration of the “One Health” approach for effective management of animal and human rabies should be emphasized.
Trichomonas vaginalis adherence phenotypes and extracellular vesicles impact parasite survival in a novel in vivo model of pathogenesis
Authors: Molgora Brenda M. , Mukherjee Sandip Kumar , Baumel-Alterzon Sharon , Santiago Fernanda M. , Muratore Katherine A. , Sisk Anthony E. , Mercer Frances , Johnson Patricia J.
Published: October 2023

Trichomonas vaginalis is a human infective parasite responsible for trichomoniasis–the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis resides exclusively in the urogenital tract of both men and women. In women, T. vaginalis has been found colonizing the cervix and vaginal tract while in men it has been identified in the upper and lower urogenital tract and in secreted fluids such as semen, urethral discharge, urine, and prostatic fluid. Despite the over 270 million cases of trichomoniasis annually worldwide, T. vaginalis continues to be a highly neglected organism and thus poorly studied. Here we have developed a male mouse model for studying T. vaginalis pathogenesis in vivo by delivering parasites into the murine urogenital tract (MUT) via transurethral catheterization. Parasite burden was assessed ex-vivo using a nanoluciferase-based gene expression assay which allowed quantification of parasites pre- and post-inoculation. Using this model and read-out approach, we show that T. vaginalis can be found within MUT tissue up to 72 hrs post-inoculation. Furthermore, we also demonstrate that parasites that exhibit increased parasite adherence in vitro also have higher parasite burden in mice in vivo. These data provide evidence that parasite adherence to host cells aids in parasite persistence in vivo and molecular determinants found to correlate with host cell adherence in vitro are applicable to infection in vivo. Finally, we show that co-inoculation of T. vaginalis extracellular vesicles (TvEVs) and parasites results in higher parasite burden in vivo. These findings confirm our previous in vitro-based predictions that TvEVs assist the parasite in colonizing the host. The establishment of this pathogenesis model for T. vaginalis sets the stage for identifying and examining parasite factors that contribute to and influence infection outcomes.
Quantitative analysis of chest computed tomography of COVID-19 pneumonia using a software widely used in Japan
Authors: Suzuki Minako , Fujii Yoshimi , Nishimura Yurie , Yasui Kazuma , Fujisawa Hidefumi
Published: October 2023

This study aimed to determine the optimal conditions to measure the percentage of the area considered as pneumonia (pneumonia volume ratio [PVR]) and the computed tomography (CT) score due to coronavirus disease 2019 (COVID-19) using the Ziostation2 image analysis software (Z2; Ziosoft, Tokyo, Japan), which is popular in Japan, and to evaluate its usefulness for assessing the clinical severity. We included 53 patients (41 men and 12 women, mean age: 61.3 years) diagnosed with COVID-19 using polymerase chain reaction who had undergone chest CT and were hospitalized between January 2020 and January 2021. Based on the COVID-19 infection severity, the patients were classified as mild (n = 38) or severe (n = 15). For 10 randomly selected samples, the PVR and CT scores by Z2 under different conditions and the visual simple PVR and CT scores were compared. The conditions with the highest statistical agreement were determined. The usefulness of the clinical severity assessment based on the PVR and CT scores using Z2 under the determined conditions was statistically evaluated. The best agreement with the visual measurement was achieved by the Z2 measurement condition of ≥–600 HU. The areas under the receiver operating characteristic curves, Youden’s index, and the sensitivity, specificity, and p-values of the PVR and CT scores by Z2 were as follows: PVR: 0.881, 18.69, 66.7, 94.7, and <0.001; CT score: 0.77, 7.5, 40, 74, and 0.002, respectively. We determined the optimal condition for assessing the PVR of COVID-19 pneumonia using Z2 and demonstrated that the AUC of the PVR was higher than that of CT scores in the assessment of clinical severity. The introduction of new technologies is time-consuming and expensive; our method has high clinical utility and can be promptly used in any facility where Z2 has been introduced.
Assessment of treatment-specific tethering survival bias for the juvenile blue crab Callinectes sapidus in a simulated salt marsh
Authors: Miller Cole R. , Hyman A. Challen , Shi Daniel H. , Lipcius Romuald N.
Published: October 2023

The blue crab (Callinectes sapidus) is ecologically and economically important in Chesapeake Bay. Nursery habitats, such as seagrass beds, disproportionately contribute individuals to the adult segment of populations. Salt marshes dominated by smooth cordgrass Spartina alterniflora are intertidal nursery habitats which may serve as a refuge from predation for juvenile blue crabs. However, the effects of various characteristics of salt marshes on nursery metrics, such as survival, have not been quantified. Comparisons of juvenile survival between salt marshes and other habitats often employ tethering to assess survival. Although experimental bias when tethering juvenile prey is well recognized, the potential for habitat-specific bias in salt marshes has not been experimentally tested. Using short-term mesocosm predation experiments, we tested if tethering in simulated salt marsh habitats produces a habitat-specific bias. Juvenile crabs were tethered or un-tethered and randomly allocated to mesocosms at varying simulated shoot densities and unstructured sand. Tethering reduced survival, and its effect was not habitat specific, irrespective of shoot density, as evidenced by a non-significant interaction effect between tethering treatment and habitat. Thus, tethering juvenile blue crabs in salt marsh habitat did not produce treatment-specific bias relative to unvegetated habitat across a range of shoot densities; survival of tethered and un-tethered crabs was positively related to shoot density. These findings indicate that tethering is a useful method for assessing survival in salt marshes, as with other nursery habitats including seagrass beds, algae and unstructured sand.
Evaluation of the water-equivalent characteristics of the SP34 plastic phantom for film dosimetry in a clinical linear accelerator
Authors: Kim Kyo-Tae , Choi Yona , Cho Gyu-Seok , Jang Won-Il , Yang Kwang-Mo , Lee Soon-Sung , Bahng Jungbae
Published: October 2023

In this study, some confusing points about electron film dosimetry using white polystyrene suggested by international protocols were verified using a clinical linear accelerator (LINAC). According to international protocol recommendations, ionometric measurements and film dosimetry were performed on an SP34 slab phantom at various electron energies. Scaling factor analysis using ionometric measurements yielded a depth scaling factor of 0.923 and a fluence scaling factor of 1.019 at an electron beam energy of <10 MeV (i.e., R50 < 4.0 g/cm2). It was confirmed that the water-equivalent characteristics were similar because they have values similar to white polystyrene (i.e., depth scaling factor of 0.922 and fluence scaling factor of 1.019) presented in international protocols. Furthermore, percentage depth dose (PDD) curve analysis using film dosimetry showed that when the density thickness of the SP34 slab phantom was assumed to be water-equivalent, it was found to be most similar to the PDD curve measured using an ionization chamber in water as a reference medium. Therefore, we proved that the international protocol recommendation that no correction for measured depth dose is required means that no scaling factor correction for the plastic phantom is necessary. This study confirmed two confusing points that could occur while determining beam characteristics using electron film dosimetry, and it is expected to be used as basic data for future research on clinical LINACs.
Design of tractor virtual test system based on high-level architecture technology
Authors: Yan Xianghai , Shang Chengyan , Zhang Junjiang , Xu Liyou
Published: October 2023

The limitations of the tractor virtual test system are evident in various aspects, including model reuse, system expansion, offsite interconnection, and virtual reality verification. To address these challenges, a distributed virtual test system for tractors based on the high-level architecture (HLA) is proposed. Involve analyzing the hardware structure and the tractor virtual test system, constructing the system federation and its members, and designing the federated object model (FOM) and simulation object model (SOM) tables. The system integrates multi-domain commercial software and enables real-time virtual testing through TCP/IP interconnection of multiple machines. To evaluate the system’s performance, a virtual test of the tractor’s reversing clutch engagement performance is conducted. The system’s simulation performance and data transmission delay are thoroughly tested and analyzed. The results indicate that when the system’s data volume reaches 5000KB, the data delay is 9.7ms, which satisfies the requirement of not exceeding 10ms for tractor virtual testing delay. The virtual test of the reversing clutch power reversal process demonstrates that it lasts 0.7s, with the vehicle speed changing from -3.5km/h to 3.5km/h, the forward gear piston oil pressure increasing from 0MPa to 5MPa, and the peak impact degree reaching 17m/s3. The slip work during the reversing process is measured to be 21kJ. Furthermore, the gray correlation method is employed to compare the virtual test results with the bench test results, confirming their consistency. The power reversal process exhibits relatively smooth speed changes overall. Therefore, the tractor power shift transmission (PST) reversing clutch virtual test model operates effectively within the HLA-based tractor virtual test system.
Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model
Authors: Otero Claire E. , Barfield Richard , Scheef Elizabeth , Nelson Cody S. , Rodgers Nicole , Wang Hsuan-Yuan , Moström Matilda J. , Manuel Tabitha D. , Sass Julian , Schmidt Kimberli , Taher Husam , Papen Courtney , Sprehe Lesli , Kendall Savannah , Davalos Angel , Barry Peter A. , Früh Klaus , Pollara Justin , Malouli Daniel , Chan Cliburn , Kaur Amitinder , Permar Sallie R.
Published: October 2023

Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity confers partial protection. However, poorly understood immune correlates of protection against placental transmission contributes to the current lack of an approved vaccine to prevent cCMV. In this study, we characterized the kinetics of maternal plasma rhesus CMV (RhCMV) viral load (VL) and RhCMV-specific antibody binding and functional responses in a group of 12 immunocompetent dams with acute, primary RhCMV infection. We defined cCMV transmission as RhCMV detection in amniotic fluid (AF) by qPCR. We then leveraged a large group of past and current primary RhCMV infection studies in late-first/early-second trimester RhCMV-seronegative rhesus macaque dams, including immunocompetent (n = 15), CD4+ T cell-depleted with (n = 6) and without (n = 6) RhCMV-specific polyclonal IgG infusion before infection to evaluate differences between RhCMV AF-positive and AF-negative dams. During the first 3 weeks after infection, the magnitude of RhCMV VL in maternal plasma was higher in AF-positive dams in the combined cohort, while RhCMV glycoprotein B (gB)- and pentamer-specific binding IgG responses were lower magnitude compared to AF-negative dams. However, these observed differences were driven by the CD4+ T cell-depleted dams, as there were no differences in plasma VL or antibody responses between immunocompetent AF-positive vs AF-negative dams. Overall, these results suggest that levels of neither maternal plasma viremia nor humoral responses are associated with cCMV following primary maternal infection in healthy individuals. We speculate that other factors related to innate immunity are more important in this context as antibody responses to acute infection likely develop too late to influence vertical transmission. Yet, pre-existing CMV glycoprotein-specific and neutralizing IgG may provide protection against cCMV following primary maternal CMV infection even in high-risk, immunocompromised settings.
Tyrosine phosphorylation of IRF3 by BLK facilitates its sufficient activation and innate antiviral response
Authors: Li Wei-Wei , Fan Xu-Xu , Zhu Zi-Xiang , Cao Xue-Jing , Zhu Zhao-Yu , Pei Dan-Shi , Wang Yi-Zhuo , Zhang Ji-Yan , Wang Yan-Yi , Zheng Hai-Xue
Published: October 2023

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism.
Mutación económica-hospitalaria en el Estado señorial de los Fernández de Velasco (1380-1517)
Authors: Villagrasa-Elías Raúl
Published: October 2023

Los trabajos sobre asistencia hospitalaria en la corona de Castilla se han caracterizado, por lo general, por tratarse de análisis locales y haber sido protagonizados por la monarquía como su gran promotora a finales de la Edad Media y principios de la Modernidad. Este artículo consiste en un ejercicio comparativo del régimen económico de tres hospitales castellanos de Medina de Pomar y Briviesca, instituciones y villas bajo la influencia de la nobleza, en concreto, la familia de los Fernández de Velasco. A través del estudio de los gastos es posible medir las transformaciones económicas entre estos tres centros asistenciales, tendiendo a un desembolso mayor en profesionales especializados, medicamentos y religiosidad. El tránsito hacia la época moderna no eliminó los elementos piadosos de estos edificios, al contrario, intensificó la ritualidad y teatralidad de la caridad.
The effect of natural fillers on the mechanical properties and flammability of low-density polyethylene
Authors: Samujło Bronisław
Published: October 2023

The effect of 10-40 wt% natural fillers (pumpkin husks, bean sorting waste, pine sawdust) on the mechanical properties and flammability of LDPE was examined. As the filler content increased, the hardness slightly increased and the tensile strength and relative elongation decreased. The tensile modulus more than doubled (pumpkin husks, pine sawdust). The linear combustion rate increased unfavorably, but the assumed flammability class HB40 was achieved, except for LDPE filled with 40 wt% pine sawdust (HB75). At the same time, the temperature in the combustion area decreased in the vertical flammability test.
Initial Beliefs Uncertainty
Authors: Galimberti Jaqueson K.
Published: October 2023

This paper evaluates how initial beliefs uncertainty can affect data weighting and the estimation of models with adaptive learning. One key finding is that misspecification of initial beliefs uncertainty, particularly with the common approach of artificially inflating initials uncertainty to accelerate convergence of estimates, generates time-varying profiles of weights given to past observations in what should otherwise follow a fixed profile of decaying weights. The effect of this misspecification, denoted as diffuse initials, is shown to distort the estimation and interpretation of learning in finite samples. Simulations of a forward-looking Phillips curve model indicate that (i) diffuse initials lead to downward biased estimates of expectations relevance in the determination of actual inflation, and (ii) these biases spill over to estimates of inflation responsiveness to output gaps. An empirical application with U.S. data shows the relevance of these effects for the determination of expectational stability over decadal subsamples of data. The use of diffuse initials is also found to lead to downward biased estimates of learning gains, both estimated from an aggregate representative model and estimated to match individual expectations from survey expectations data.
Probabilistic hierarchical clustering based identification and segmentation of brain tumors in magnetic resonance imaging
Authors: Vidyarthi Ankit
Published: October 2023

The automatic segmentation of the abnormality region from the head MRI is a challenging task in the medical science domain. The abnormality in the form of the tumor comprises the uncontrolled growth of the cells. The automatic identification of the affected cells using computerized software systems is demanding in the past several years to provide a second opinion to radiologists. In this paper, a new clustering approach is introduced based on the machine learning aspect that clusters the tumor region from the input MRI using disjoint tree generation followed by tree merging. Further, the proposed algorithm is improved by introducing the theory of joint probabilities and nearest neighbors. Later, the proposed algorithm is automated to find the number of clusters required with its nearest neighbors to do semantic segmentation of the tumor cells. The proposed algorithm provides good semantic segmentation results having the DB index-0.11 and Dunn index-13.18 on the SMS dataset. While the experimentation with BRATS 2015 dataset yields Dice
complete=80.5 %, Dice
core=73.2 %, and Dice
enhanced=62.8 %. The comparative analysis of the proposed approach with benchmark models and algorithms proves the model’s significance and its applicability to do semantic segmentation of the tumor cells with the average increment in the accuracy of around ±2.5 % with machine learning algorithms.
Bioactive adrenomedullin (bio-ADM) is associated with endothelial dysfunction in infants and children with complex congenital heart disease undergoing open-heart surgery on cardiopulmonary bypass
Authors: Schaefer Maike , Stein Andreas , Ruf Bettina , Balling Gunter , Palm Jonas , Simmelbauer Andreas , Cleuziou Julie , Sander Michaela , Auer Josef , Borgmann Kristina , Struck Joachim , Hartmann Oliver , Schulte Janin , Hörer Jürgen , Tassani-Prell Peter , Ewert Peter , Holdenrieder Stefan , Wolf Cordula M.
Published: October 2023

Objectives

Children with congenital heart disease (CHD) undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at risk for systemic inflammation leading to endothelial dysfunction associated with increased morbidity. Bioactive adrenomedullin (bio-ADM) is a peptide regulating vascular tone and endothelial permeability. The aim of this study was to evaluate the dynamics of plasma bio-ADM in this patient cohort and its role in capillary leak.

Methods

Plasma samples from 73 pediatric CHD patients were collected for bio-ADM measurement at five different timepoints (TP) in the pre-, intra-, and post-operative period. The primary endpoint was a net increase in bio-ADM levels after surgery on CPB. Secondary endpoints included association of bio-ADM levels with clinical signs for endothelial dysfunction.

Results

Bio-ADM levels increased after surgery on CPB from pre-operative median of 12 pg/mL (IQR [interquartile range] 12.0–14.8 pg/mL) to a maximum post-operative median of 48.8 pg/mL (IQR 34.5–69.6 pg/mL, p<0.001). Bio-ADM concentrations correlated positively with post-operative volume balance, (r=0.341; p=0.005), increased demand for vasoactive medication (duration: r=0.415; p<0.001; quantity: TP3: r=0.415, p<0.001; TP4: r=0.414, p<0.001), and hydrocortisone treatment for vasoplegia (bio-ADM median [IQR]:129.1 [55.4–139.2] pg/mL vs. 37.9 [25.2–64.6] pg/mL; p=0.034). Patients who required pleural effusion drainage revealed higher bio-ADM levels compared to those who did not (median [IQR]: 66.4 [55.4–90.9] pg/mL vs. 40.2 [28.2–57.0] pg/mL; p<0.001).

Conclusions

Bio-ADM is elevated in children after cardiac surgery and higher levels correlate with clinical signs of capillary leakage. The peptide should be considered as biomarker for endothelial dysfunction and as potential therapeutic target in this indication.
Innovations in HbA1c analysis: finding the balance between speed and accuracy. An investigation of a potential new Secondary Reference Measurement Procedure for the IFCC
Authors: Lenters-Westra Erna , English Emma
Published: October 2023

Objectives

The escalating prevalence of diabetes worldwide has resulted in a dramatic increase in the number of people who need testing, which in turn necessitates faster HbA1c measurement. The Tosoh GR01 addresses the need for fast turnaround times of whilst offering pragmatic steps to maintain result accuracy in a single instrument by offering two distinct operating modes: Short Mode (SM) and Long Mode (LM). The aim of this study was to evaluate all relevant aspects of the performance of the Tosoh GR01 with a view to accepting the instrument as a future Secondary Reference Measurement Procedure (SRMP) for the IFCC.

Methods

Certified Clinical & Laboratory Standards Institute (CLSI) Evaluation Protocols (EP) were used to evaluate precision (EP-5), accuracy (EP-9), linearity (EP-6), carry-over (EP-10) and the effect of hemoglobin variants and other potential interferences.

Results

Both modes demonstrated CVs <0.6 % in SI units and <0.4 % in NGSP units at 46 mmol/mol (6.4 %) and 75 mmol/mol (9.0 %) and passed both National Glycohemoglobin Standardization Program (NGSP) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) certification procedures when compared with 7 IFCC Certified Secondary Reference Measurement Procedures (SRMP). Sigma for both modes was >6 when using the results of EP-5 and EP-9 at an HbA1c concentration of 50 mmol/mol (6.7 %). Neither mode showed any interference with common Hb-variants except for HbAE when HbA1c was >65 mmol/mol. In the SM HbAS, HbAD and HbAC were recognized but no result was reported.

Conclusions

There is a good balance between speed and accuracy for determining HbA1c with the Tosoh GR01 in both analytical modes and the device is suitable for use as an IFCC SRMP.
Language maintenance and shift in a Swiss community on the Black Sea
Authors: Bichurina Natalia
Published: October 2023

This paper explores the dynamics of the linguistic situation in a Swiss colony of Shabo on the Black Sea, created in 1822. Its political belonging changed several times: from the Russian empire to the Kingdom of Romania and the USSR (today Ukraine). Metalinguistic discourse produced by various social actors in different sociopolitical settings is compared here to the use of Francoprovençal, French, and Russian as discovered in archival data. Accordingly, the study is based, on the one hand, on the narratives in manuscripts and publications (from the Archives of Odessa, Bern, and Romainmôtiers), and on the other hand, on a corpus of private letters (from family archives in Vaud), as well as early (socio)linguistic descriptions compared to linguistic data collected in Vaud. This case study aims to shed light on the complex relationship between the linguistic processes and language ideologies in changing socio-political spaces.
Locating the ‘Age of Prescriptivism’ in Late Modern periodical reviews: a corpus-assisted discourse analytic approach
Authors: Malory Beth
Published: October 2023

This paper reports the findings of a corpus-based study of prescriptive and normative discourses in Late Modern English review periodicals, using a purpose-built diachronic corpus of review articles published during the period 1750–1899. Drawing on established protocols from Corpus-Assisted Discourse Studies and systematic comparison of 15 sub-corpora, it identifies decades during which prescriptive discourses were most frequent. This distributional pattern provides empirical evidence of an ‘Age of Prescriptivism’ in periodical reviewing, during which prescriptive discourses reached their zenith. Whilst the label ‘Age of Prescriptivism’ has been applied to a number of periods of English in recent decades, the findings reported here show clearly that the eighteenth century was the locus of prescriptive activity in the review periodical genre. The innovative application of corpus-based discourse-analytic methodologies for the identification of normative trends reported in this paper also has potential implications for studying prescriptivism as a sociohistorical linguistic phenomenon in other diachronic contexts.
Tailoring full-Stokes thermal emission from twisted-gratings structures
Authors: Yang Chiyu , Cai Wenshan , Zhang Zhuomin M.
Published: October 2023

Polarized thermal emission finds extensive applications in remote sensing, landmine detection, and target detection. In applications such as ellipsometry and biomedical analysis, the generation of emission with controllable polarization is preferred. It is desired to manipulate the polarization state over the full Stokes parameters. While numerous studies have demonstrated either linear or circular polarization control using metamaterials, full-Stokes thermal emission has not been explored. Here, a microstructure based on two layers of silicon carbide gratings is proposed to tailor the polarization state of thermal emission, covering the full-Stokes parameter range. The bilayer twisted-gratings structure breaks mirror symmetry. Wave interference at the interfaces and diffraction by the gratings enhance the emission dichroism, resulting in almost completely polarized emission. By adjusting the twist angle between the gratings, the polarization state can be continuously tuned from linear to circular, nearly covering the entire surface of Poincaré sphere. This study provides a design for tailoring full-Stokes emission with notable advantages over other plasmonic metasurfaces.
Single cell RNA sequencing – a valuable tool for cancer immunotherapy: a mini review
Authors: Kodous Ahmad S. , Balaiah Meenakumari , Ramanathan Priya
Published: October 2023

Single-cell RNA sequencing (scRNA-seq) technology has made great strides in research over the last decade. Data analysis has been aided by developments in bioinformatics tools and artificial intelligence, allowing biological and clinical researchers to get a deeper understanding of the different cell clusters and their dynamics within tumours. Combining conventional treatment modalities like chemotherapy and radiation with immunotherapy is a growing trend in cancer treatment. Hence, knowledge of the tumour microenvironment and the effect of each treatment modality on the TME, at a single cell level can provide treating clinicians with better clues for patient stratification and prognostication. With this knowledge, immunotherapy could become successful in treating a wide range of cancers, opening the path for the creation of even more effective treatment strategies. Despite the widespread availability of scRNA-seq technology, computational analysis and data interpretation are still challenges. Worldwide, such challenges are being addressed by various researchers, strengthening the contribution of this technology towards cancer elimination. In this mini-review, we primarily focus on the technique, its workflow, and the computational aspects of scRNA technology, along with an overview of the current challenges in the analysis and interpretation of the data generated.
Prediction of the rubberized concrete behavior: A comparison of gene expression programming and response surface method
Authors: Tufail Rana Faisal , Farooq Danish , Javed Muhammad Faisal , Mehmood Tahir , Maqsoom Ahsen , Ashraf Hassan , Deifalla Ahmed Farouk , Ahmad Jawad
Published: October 2023

The use of rubber in concrete to partially substitute mineral aggregates is an effort to decrease the global amount of scrap tires. This study investigates the behavior of rubberized concrete (RC) with various replacement ratios (0–50%) by volume and replacement type (fine, coarse, and fine-coarse) using soft computing techniques. The uniaxial compressive strength (CS), elastic modulus (EM), and ductility (D) are measured, and the effect of rubber content and the rubber aggregate type on the properties of RC is investigated. Scanning electron microscopy and X-ray diffraction analyses are made to determine its microstructural and chemical composition. This article compares the efficiency of two RC models using a recently developed artificial intelligence technique, i.e., gene expression programming (GEP) and conventional technique, i.e., response surface method (RSM). Statistical models are developed to predict the CS, TS, EM, and D. The mathematical models are validated using determination coefficient (R
2) and adjusted coefficient (R
2adj), and they are found to be significant. Furthermore, both methods (i.e., RSM and GEP) are very well correlated with the experimental data. The GEP is found to be more effective at predicting the experimental test results for RC. The projected methods can be executed for any practical value of RC.
The Burdened Body: Byzantine Enkolpia and the Weight of the Sacred
Authors: Drpić Ivan
Published: October 2023

Few products of human artistry seem as insistently concerned with self-representation as jewelry. In Georg Simmel’s classic formulation, articles of personal adornment work to enhance an individual’s social persona by magnifying their Ausstrahlung. While medieval Christian devotional jewels were well-equipped to operate in this manner, their true significance lay elsewhere. Objects such as pectoral crosses, reliquary rings, rosaries, and prayer nuts were designed not so much to mediate between self and society, but rather to stage and facilitate an encounter of the self with itself. Focusing on Byzantine devotional neck pendants, or enkolpia, this essay considers how religiously significant wearables participated in introspective spiritual practices aimed at forming and reforming the Christian subject. The essay, more specifically, attends to the enkolpion as an instrument of self-imposed discipline and explores how the corporeal experience of carrying this object and feeling its weight, however minimal, on the body contributed to the wearer’s cultivation of inner vigilance.
Marie-Antoinette and the Image of Moral Instruction
Authors: Lawrence Larkin T.
Published: October 2023

Long attributed to François-Hubert Drouais or his atelier, a three-quarter length portrait of Marie-Antoinette, together with a curiously inscribed frame, displayed in the lobby of the Hôtel Le Bristol, Paris, serves as a pretext for reconstructing the queen’s practice of gifting portraits of herself to members of her chapel. This essay explores Marie-Antoinette’s tendency in the early part of her reign to entrust the production of portraits to the Cabinet des tableaux. It argues on the basis of stylistic analysis that the Le Bristol portrait was probably the work of Jean-Martial Frédou and on the basis of iconographical analysis that it accommodated the quarrel between philosophes and clerics over reform of the Catholic Church in France, which made it suited to Monsignor du Chilleau, Bishop of Chalon.
Disgust-induced avoidant processing of autobiographical memories as a transdiagnostic mechanism in the persistence of psychopathology
Authors: von Spreckelsen Paula , de Jong Peter J.
Published: October 2023

We present a model of disgust-induced avoidant processing of autobiographical memories contributing to the persistence of psychopathology. Following the model, autobiographical memory retrieval is biased toward disgust-related experiences. Critically, disgust promotes the avoidance of specific autobiographical memories by reactively aborting the processing of those memories or by strategically preventing access to them, making disgust appraisals immune to corrective information. In the context of eating disorders/body image, studies provided consistent evidence for a bias toward disgust-related memories of their own body in women with a more negative body image. Although the current research casts doubt on disgust-induced strategic avoidant retrieval of body-related memories, it provided initial evidence for reactive avoidance of such memories. Insight into the role of disgust-induced avoidant memory processing as a transdiagnostic mechanism may help in understanding the refractoriness of disgust-relevant psychopathologies (including depressive and trauma-related disorders) and point to the necessity of therapeutic strategies to address disgust-induced avoidance.
Angular Head Velocity Cells within Brainstem Nuclei Projecting to the Head Direction Circuit
Authors: Graham Jalina A. , Dumont Julie R. , Winter Shawn S. , Brown Joel E. , LaChance Patrick A. , Amon Carly C. , Farnes Kara B. , Morris Ashlyn J. , Streltzov Nicholas A. , Taube Jeffrey S.
Published: October 2023

The sense of orientation of an animal is derived from the head direction (HD) system found in several limbic structures and depends on an intact vestibular labyrinth. However, how the vestibular system influences the generation and updating of the HD signal remains poorly understood. Anatomical and lesion studies point toward three key brainstem nuclei as key components for generating the HD signal—nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nuclei. Collectively, these nuclei are situated between the vestibular nuclei and the dorsal tegmental and lateral mammillary nuclei, which are thought to serve as the origin of the HD signal. To determine the types of information these brain areas convey to the HD network, we recorded neurons from these regions while female rats actively foraged in a cylindrical enclosure or were restrained and rotated passively. During foraging, a large subset of cells in all three nuclei exhibited activity that correlated with the angular head velocity (AHV) of the rat. Two fundamental types of AHV cells were observed; (1) symmetrical AHV cells increased or decreased their firing with increases in AHV regardless of the direction of rotation, and (2) asymmetrical AHV cells responded differentially to clockwise and counterclockwise head rotations. When rats were passively rotated, some AHV cells remained sensitive to AHV, whereas firing was attenuated in other cells. In addition, a large number of AHV cells were modulated by linear head velocity. These results indicate the types of information conveyed from the vestibular nuclei that are responsible for generating the HD signal.

SIGNIFICANCE STATEMENTExtracellular recording of brainstem nuclei (nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nucleus) that project to the head direction circuit identified different types of AHV cells while rats freely foraged in a cylindrical environment. The firing of many cells was also modulated by linear velocity. When rats were restrained and passively rotated, some cells remained sensitive to AHV, whereas others had attenuated firing. These brainstem nuclei provide critical information about the rotational movement of the head of the rat in the azimuthal plane.
SIRT2 negatively regulates the cGAS‐STING pathway by deacetylating G3BP1
Authors: Li Yutong , Bie Juntao , Song Chen , Li Yunfei , Zhang Tianzhuo , Li Haishuang , Zhao Long , You Fuping , Luo Jianyuan
Published: October 2023

SIRT2, a cytoplasmic member of the Sirtuin family, has important roles in immunity and inflammation. However, its function in regulating the response to DNA virus infection remains elusive. Here, we find that SIRT2 is a unique regulator among the Sirtuin family that negatively modulates the cGAS‐STING‐signaling pathway. SIRT2 is down‐regulated after Herpes simplex virus‐1 (HSV‐1) infection, and SIRT2 deficiency markedly elevates the expression levels of type I interferon (IFN). SIRT2 inhibits the DNA binding ability and droplet formation of cGAS by interacting with and deacetylating G3BP1 at K257, K276, and K376, leading to the disassembly of the cGAS‐G3BP1 complex, which is critical for cGAS activation. Administration of AGK2, a selective SIRT2 inhibitor, protects mice from HSV‐1 infection and increases the expression of IFN and IFN‐stimulated genes. Our study shows that SIRT2 negatively regulates cGAS activation through G3BP1 deacetylation, suggesting a potential antiviral strategy by modulating SIRT2 activity.