bluuebunny/crossref_metadata_2025 huggingface dataset:
The natural pattern of birth timing and gestational age in the U.S. compared to England, and the Netherlands
Authors: Declercq Eugene , Wolterink Anneke , Rowe Rachel , de Jonge Ank , De Vries Raymond , Nieuwenhuijze Marianne , Verhoeven Corine , Shah Neel
Published: January 2023

Objective

To examine cross-national differences in gestational age over time in the U.S. and across three wealthy countries in 2020 as well as examine patterns of birth timing by hour of the day in home and spontaneous vaginal hospital births in the three countries.

Methods

We did a comparative cohort analysis with data on gestational age and the timing of birth from the United States, England and the Netherlands, comparing hospital and home births. For overall gestational age comparisons, we drew on national birth cohorts from the U.S. (1990, 2014 & 2020), the Netherlands (2014 & 2020) and England (2020). Birth timing data was drawn from national data from the U.S. (2014 & 2020), the Netherlands (2014) and from a large representative sample from England (2008–10). We compared timing of births by hour of the day in hospital and home births in all three countries.

Results

The U.S. overall mean gestational age distribution, based on last menstrual period, decreased by more than half a week between 1990 (39.1 weeks) and 2020 (38.5 weeks). The 2020 U.S. gestational age distribution (76% births prior to 40 weeks) was distinct from England (60%) and the Netherlands (56%). The gestational age distribution and timing of home births was comparable in the three countries. Home births peaked in early morning between 2:00 am and 5:00 am. In England and the Netherlands, hospital spontaneous vaginal births showed a generally similar timing pattern to home births. In the U.S., the pattern was reversed with a prolonged peak of spontaneous vaginal hospital births between 8:00 am to 5:00 pm.

Conclusions

The findings suggest organizational priorities can potentially disturb natural patterns of gestation and birth timing with a potential to improve U.S. perinatal outcomes with organizational models that more closely resemble those of England and the Netherlands.
Satellite monitoring of terrestrial plastic waste
Authors: Kruse Caleb , Boyda Edward , Chen Sully , Karra Krishna , Bou-Nahra Tristan , Hammer Dan , Mathis Jennifer , Maddalene Taylor , Jambeck Jenna , Laurier Fabien
Published: January 2023

Plastic waste is a significant environmental pollutant that is difficult to monitor. We created a system of neural networks to analyze spectral, spatial, and temporal components of Sentinel-2 satellite data to identify terrestrial aggregations of waste. The system works at wide geographic scale, finding waste sites in twelve countries across Southeast Asia. We evaluated performance in Indonesia and detected 374 waste aggregations, more than double the number of sites found in public databases. The same system deployed in Southeast Asia identifies 996 subsequently confirmed waste sites. For each detected site, we algorithmically monitor waste site footprints through time and cross-reference other datasets to generate physical and social metadata. 19% of detected waste sites are located within 200 m of a waterway. Numerous sites sit directly on riverbanks, with high risk of ocean leakage.
Effects of riboflavin/ultraviolet-A scleral collagen cross-linking on regional scleral thickness and expression of MMP-2 and MT1-MMP in myopic guinea pigs
Authors: Lv Xiaotong , Lai Lingbo , Xu Yushan , Sun Mingshen , Li Yu , Song Yanzheng , Wang Ningli , Zhang Fengju
Published: January 2023

Objective

To investigate the effects of scleral collagen cross-linking (SXL) using riboflavin and ultraviolet A (UVA) light on the scleral thickness of different regions and expression of matrix metalloproteinase 2 (MMP-2) and membrane-type MMP-1 (MT1-MMP) in guinea pigs with lens-induced myopia.

Methods

Forty-eight 4-week-old guinea pigs were assigned to three groups (n = 16 per group): SXL group, lens-induced myopia (LIM) group, and control group. The sclera of the right eye of the guinea pig in the SXL group was surgically exposed, riboflavin was dropped on the treatment area for 10 minutes before the 30-minute UVA irradiation. The same surgical procedure was performed in the LIM group without UVA irradiation. The -10.00 D lenses were then placed on the right eyes of guinea pigs in the SXL and LIM groups for six weeks. The control group received no treatment. The left eyes were untreated in all groups. The ocular axial length (AXL) and refraction were measured at 4 weeks and 10 weeks of age. 10-week-old guinea pigs were sacrificed, and the right eyes were enucleated and evenly divided for preparation of hematoxylin and eosin (HE) stained sections, quantitative real-time polymerase chain reaction (qPCR) and western blotting. The scleral thickness of different regions was measured on HE stained sections. The temporal half of the sclera was harvested to measure the expression of MMP-2 and MT1-MMP by qPCR and western blotting.

Results

The AXL was significantly shorter, and the degree of myopic refraction was significantly lower in the SXL group than those in the LIM group at 10 weeks of age. The scleral thickness of the cross-linked area was significantly greater in the SXL group than that of the corresponding area in the LIM group, while the scleral thickness of the untreated nasal side was not significantly different between the SXL group and the LIM group. The expression of MMP-2 and MT1-MMP of the cross-linked sclera was significantly downregulated compared with that of the corresponding area in the LIM group.

Conclusion

Riboflavin/UVA SXL could slow myopia progression and thicken the cross-linked sclera in guinea pigs, which might be related to the downregulation of MMP-2 and MT1-MMP expression during the scleral remodeling process.
Association of RNA-modification “writer” genes with prognosis and response to immunotherapy in patients with low-grade glioma
Authors: Zhang Lupeng , Qu Chiwen , Shi Chen , Wu Fan , Tang Yifan , Li Yue , Li Jinlong , Feng Huicong , Zhong Suye , Yang Jun , Zeng Xiaomin , Peng Xiaoning
Published: January 2023

RNA modification is a key regulatory mechanism involved in tumorigenesis, tumor progression, and the immune response. However, the potential role of RNA modification “writer” genes in the immune microenvironment of gliomas and their effect on the response to immunotherapy remains unclear. The purpose of this study was to evaluate the role of RNA modification "writer" gene in the prognosis and immunotherapy response of low-grade glioma (LGG). The consensus non-negative matrix factorization (CNMF) method was used to identify different RNA modification subtypes. We used a novel eigengene screening method, the variable neighborhood learning Harris Hawks optimizer (VNLHHO), to screen for eigengenes among the RNA modification subtypes. We constructed a principal components analysis score(PCA_score)-based prognostic prediction model and validated it using an independent cohort. We also analyzed the association between PCA_score and the immune and molecular features of LGG. The results suggested that LGG can be divided into two different RNA modification-based subtypes with distinct prognostic and molecular features. High PCA_score was significantly associated with a poor prognosis in LGG and was an independent prognostic factor. A nomogram containing PCA_score and clinical features was constructed, and it showed a significant predictive value. PCA_score was negatively correlated with tumor purity and the abundance of CD4+ T cells in LGG patients. LGG patients with high PCA_score had lower Tumor Immune Dysfunction and Exclusion scores and showed an immunotherapy response. In conclusion, we report a novel RNA modification-based prognostic model for LGG that lays the foundation for evaluating LGG prognosis and developing more effective therapeutic strategies for these tumors.
Newly discovered crocodile mummies of variable quality from an undisturbed tomb at Qubbat al-Hawā (Aswan, Egypt)
Authors: De Cupere Bea , Van Neer Wim , Barba Colmenero Vicente , Jiménez Serrano Alejandro
Published: January 2023

A description is provided of the crocodile remains that were found during an excavation carried out in 2019 at Qubbat al-Hawā (Aswan, Egypt). The material consists of five more or less complete bodies and five heads that were in varying states of preservation and completeness. The absence of resin, which was apparently not used during the preparation of the mummies, and the almost complete loss of linen bandages, due to insect damage, allowed a detailed morphological and osteometric description of the remains. Attention was focused on the general state of preservation of the crocodiles, the completeness of their skeletons and skulls, the presence of cut or other marks that could indicate the cause of death, and the processing of the carcasses. Moreover, the possible provenance of the crocodiles, the methods of capture and killing of the animals and their possible chronological attribution are discussed. It is concluded that the manner in which these specimens were prepared, as well as the variation observed in the type of ‘final product’, are unlike any other crocodile material described so far. The preparation method suggests a pre-Ptolemaic date for the deposit. The morphological and metrical features indicate that both Crocodylus niloticus and the recently resurrected species Crocodylus suchus are present among these individuals that range from 1.8 to 3.5 m in length.
How health literacy relates to venous leg ulcer healing: A scoping review
Authors: Bouguettaya Ayoub , Gethin Georgina , Probst Sebastian , Sixsmith Jane , Team Victoria , Weller Carolina
Published: January 2023

Background

The level of personal health literacy of patients with venous leg ulcers is likely to affect their ability to self-manage their condition impacting on their adherence to treatment and influences healing and recovery outcomes.

Objectives

To scope existing research that examined the level of health literacy in venous leg ulcer patients, to identify how this may link to self-management behaviours (particularly physical activity and compression adherence), and venous leg ulcer healing outcomes.

Methods

This scoping review was based on the PRISMA-ScR six-stage framework. We searched MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, Open Grey, and Google Scholar for publications examining general and specific health literacy in those with venous leg ulcers and for those examining any potential links of health literacy with self-management/healing generally, published between 2000–2020. This search was guided by a published protocol; studies that described other types of ulcers or did not examine health literacy were excluded. After applying inclusion and exclusion criteria the initial search identified 660 articles.

Results

We included five articles. Four studies used randomised controlled trials or experimental designs to test the effect of specific health literacy interventions on venous leg ulcer knowledge, compression therapy use, or healing outcomes. One study was a cross- sectional survey with qualitative elements, assessing health literacy in venous leg ulcer patients. Broadly, the research suggested that health literacy was suboptimal amongst those with venous leg ulcers, and health literacy interventions had limited effects on improving key venous leg ulcer specific outcomes.

Conclusion

This review provides a synthesis of extant literature examining health literacy in patients with venous leg ulcers. We identified a dearth of literature investigating the value of general and specific health literacy interventions in this space. Most importantly, no recent research on general health literacy and venous leg ulcers was identified, despite strong theoretical utility to do so. The few studies identified largely indicated that targeting health literacy of patients with venous leg ulcers is a viable area of research and intervention, encouraging future researchers and clinicians to consider patient health literacy in venous leg ulcer management.
A framework to quantify flow through coral reefs of varying coral cover and morphology
Authors: Pomeroy Andrew W. M. , Ghisalberti Marco , Peterson Michael , Farooji Vahid Etminan
Published: January 2023

Flow velocities within coral reefs are greatly reduced relative to those at the water surface. The in-reef flow controls key processes that flush heat, cycle nutrients and transport sediment from the reef to adjacent beaches, all key considerations in assessments of reef resilience and restoration interventions. An analytical framework is proposed and tested with a suite of high-resolution numerical experiments. We demonstrate a single parameter that describes the total coral frontal area explains variation of horizontally averaged velocity within a reef canopy across morphologies, densities, and flow depths. With the integration of existing data of coral cover and geometry, this framework is a practical step towards the prediction of near-bed flows in diverse reef environments.
Adverse childhood experiences and hormonal contraception: Interactive impact on sexual reward function
Authors: Novick Andrew M. , Stoddard Joel , Johnson Rachel L. , Duffy Korrina A. , Berkowitz Lily , Costa Vincent D. , Sammel Mary D. , Epperson C. Neill
Published: January 2023

The current literature suggests that some women are uniquely vulnerable to negative effects of hormonal contraception (HC) on affective processes. However, little data exists as to which factors contribute to such vulnerability. The present study evaluated the impact of prepubertal adverse childhood experiences (ACEs) on reward processing in women taking HC (N = 541) compared to naturally cycling women (N = 488). Participants completed an online survey assessing current and past HC use and exposure to 10 different adverse childhood experiences (ACEs) before puberty (ACE Questionnaire), with participants categorized into groups of low (0–1) versus high (≥2) prepubertal ACE exposure. Participants then completed a reward task rating their expected and experienced valence for images that were either erotic, pleasant (non-erotic), or neutral. Significant interactions emerged between prepubertal ACE exposure and HC use on expected (p = 0.028) and experienced (p = 0.025) valence ratings of erotic images but not pleasant or neutral images. Importantly, follow-up analyses considering whether women experienced HC-induced decreases in sexual desire informed the significant interaction for expected valence ratings of erotic images. For current HC users, prepubertal ACEs interacted with HC-induced decreased sexual desire (p = 0.008), such that high ACE women reporting decreased sexual desire on HC showed substantially decreased ratings for anticipated erotic images compared to both high prepubertal ACE women without decreased sexual desire (p < 0.001) and low prepubertal ACE women also reporting decreased sexual desire (p = 0.010). The interaction was not significant in naturally cycling women reporting previous HC use, suggesting that current HC use could be impacting anticipatory reward processing of sexual stimuli among certain women (e.g., high prepubertal ACE women reporting HC-induced decreases in sexual desire). The study provides rationale for future randomized, controlled trials to account for prepubertal ACE exposure to promote contraceptive selection informed by behavioral evidence.
Automated measurement of inter-arytenoid distance on 4D laryngeal CT: A validation study
Authors: Ma Andrew , Desai Nandakishor , Lau Kenneth K. , Palaniswami Marimuthu , O’Brien Terence J. , Palaniswami Paari , Thyagarajan Dominic
Published: January 2023

Changes to the voice are prevalent and occur early in Parkinson’s disease. Correlates of these voice changes on four-dimensional laryngeal computed-tomography imaging, such as the inter-arytenoid distance, are promising biomarkers of the disease’s presence and severity. However, manual measurement of the inter-arytenoid distance is a laborious process, limiting its feasibility in large-scale research and clinical settings. Automated methods of measurement provide a solution. Here, we present a machine-learning module which determines the inter-arytenoid distance in an automated manner. We obtained automated inter-arytenoid distance readings on imaging from participants with Parkinson’s disease as well as healthy controls, and then validated these against manually derived estimates. On a modified Bland-Altman analysis, we found a mean bias of 1.52 mm (95% limits of agreement -1.7 to 4.7 mm) between the automated and manual techniques, which improves to a mean bias of 0.52 mm (95% limits of agreement -1.9 to 2.9 mm) when variability due to differences in slice selection between the automated and manual methods are removed. Our results demonstrate that estimates of the inter-arytenoid distance with our automated machine-learning module are accurate, and represents a promising tool to be utilized in future work studying the laryngeal changes in Parkinson’s disease.
The influence of a mineral oil cationic nanoemulsion or perfluorohexyloctane on the tear film lipid layer and higher order aberrations
Authors: Habbe Kirsten Julia , Frings Andreas , Saad Amr , Geerling Gerd
Published: January 2023

Purpose

To prospectively assess the effect of a single and regular application of either a cationic nanoemulsion of mineral oil (CN) or perfluorohexyloctane (F6H8) on the lipid layer of the tear film and higher order aberrations (HOA) in patients with Dry Eye Disease (DED).

Methods

Fifty-seven patients with a lipid layer thickness (LLT) ≤ 75 interferometric colour units (ICU) were included in the study. In group A (20 patients) the effect of a single drop of F6H8 or CN on HOA and LLT was assessed immediately after application and up to two hours later. For long term effects (Group B) 37 patients applied CN or F6H8 five times a day for 12 weeks. Measurement of LLT, HOA, non-invasive-tear-break-up-time (NIBUT) and meibography were assessed prior to as well as at 4 weeks and 12 weeks after initiation of treatment. Our study is registered in the “German Clinical Trials Register” under the trial number: DRKS00028696.

Results

CN led to an increase of the LLT from 46.8 ± 16.9 ICU to 76.3 ± 23.5 ICU (p = 0.021) and to an increase of HOA from 0.43 ± 0.06 μm to 0.48 ± 0.08 μm immediately after application (p = 0.027). There was no correlation between the increase of LLT and HOA (r = -0.04; p = 0.90). In group B an increase of LLT was observed in the F6H8 group from 45.8 ± 8.8 ICU at baseline to 66.7 ± 19.5 ICU at 12 weeks (p = 0.002). No changes of HOA were measured throughout the observation period in group B. After 12 weeks CN increased NIBUT from 9.9 ± 5.3 seconds to 15.5 ± 5.6 seconds (p = 0.04). F6H8 increased NIBUT from 12.4 ± 5.9 seconds to 16.9 ± 4.7 seconds (p = 0.02) after 12 weeks.

Conclusion

CN leads to a short-term increase in LLT and HOA, but only immediately after application. In contrast F6H8 does lead to an increase of LLT after regular long-term use but has no effect on HOA. The regular application of lipid-based products does not seem to decrease the quality of vision as measured in HOA. Instead, CN and F6H8, both are able to stabilize the tear film after regular application.
Personality descriptions influence perceived cuteness of children and nurturing motivation toward them
Authors: Takamatsu Reina , Kusumi Takashi , Nittono Hiroshi
Published: January 2023

The current empirical evidence regarding the effects of personality on physical attractiveness is limited to adult faces. In two preregistered studies, we demonstrated that personality descriptions influenced perceived cuteness, warmth, competence of young children, and female adults’ nurturing motivation toward them. Study 1 showed that participants rated children accompanied by positive personality descriptions as cuter, friendlier, and more intelligent than their initial ratings. Negative personality descriptions reduced perceived cuteness in children, which in turn reduced nurturing motivation. Study 2 showed that negative personality descriptions consistently reduced perceived cuteness and warmth ratings after manipulation, regardless of the initial level of perceived cuteness. After one week, cuteness and warmth ratings in the positive personality condition tended to return to their initial ratings. However, the effect of negative personality descriptions on cuteness ratings persisted for all children. Together, our findings suggest that female adults’ perception of cuteness and nurturing motivation are induced not only by children’s appearance but also their personality.
Mental toll on working women during the COVID-19 pandemic: An exploratory study using Reddit data
Authors: Huang Chengyue , Bandyopadhyay Anindita , Fan Weiguo , Miller Aaron , Gilbertson-White Stephanie
Published: January 2023

COVID-19 has led to an unprecedented surge in unemployment associated with increased anxiety, stress, and loneliness impacting the well-being of various groups of people (based on gender and age). Given the increased unemployment rate, this study intends to understand if the different dimensions of well-being change across age and gender. By quantifying sentiment, stress, and loneliness with natural language processing tools and one-way, between-group multivariate analysis of variance (MANOVA) using Reddit data, we assessed the differences in well-being characteristics for age groups and gender. We see a noticeable increase in the number of mental health-related subreddits for younger women since March 2020 and the trigger words used by them indicate poor mental health caused by relationship and career challenges posed by the pandemic. The MANOVA results show that women under 30 have significantly (p = 0.05) higher negative sentiment, stress, and loneliness levels than other age and gender groups. The results suggest that younger women express their vulnerability on social media more strongly than older women or men. The huge disruption of job routines caused by COVID-19 alongside inadequate relief and benefit programs has wrecked the economy and forced millions of women and families to the edge of bankruptcy. Women had to choose between being home managers and financial providers due to the countrywide shutdown of schools and day-cares. These findings open opportunities to reconsider how policy supports women’s responsibilities.
Genetic enhancement of Trichoderma asperellum biocontrol potentials and carbendazim tolerance for chickpea dry root rot disease management
Authors: G. Ramangouda , Naik M. K. , Nitnavare Rahul B. , Yeshvekar Richa , Bhattacharya Joorie , Bhatnagar-Mathur Pooja , Sharma Mamta
Published: January 2023

Advances in biocontrol potentials and fungicide resistance are highly desirable for Trichoderma. Thus, it is profitable to use mutagenic agents to develop superior strains with enhanced biocontrol properties and fungicide tolerance in Trichoderma. This study investigates the N-methyl-n-nitro-N-nitrosoguanidine (NTG) (100 mg/L) induced mutants of Trichoderma asperellum. Six NTG (3 each from 1st & 2nd round) induced mutants were developed and evaluated their biocontrol activities and carbendazim tolerance. Among the mutant N2-3, N2-1, N1 and N2-2 gave the best antagonistic and volatile metabolite activities on inhibition of chickpea F. oxysporum f. sp. ciceri, B. cinerea and R. bataticola mycelium under in vitro condition. Mutant N2-2 (5626.40 μg/ml) showed the highest EC50 value against carbendazim followed by N2-3 (206.36 μg/ml) and N2-1 (16.41 μg/ml); and succeeded to sporulate even at 2000 μg/ml of carbendazim. The biocontrol activity of N2-2 and N2 with half-dose of carbendazim was evaluated on chickpea dry root rot under controlled environment. Disease reduction and progress of the dry root rot was extremely low in T7 (N2-2 + with half-dose of carbendazim) treatment. Further, carbendazim resistant mutants demonstrated mutation in tub2 gene of β-tubulin family which was suggested through the 37 and 183 residue changes in the superimposed protein structures encoded by tub2 gene in N2 and N2-2 with WT respectively. This study conclusively implies that the enhanced carbendazim tolerance in N2-2 mutant did not affect the mycoparasitism and plant growth activity of Trichoderma. These mutants were as good as the wild-type with respect to all inherent attributes.
A privacy-preserving and computation-efficient federated algorithm for generalized linear mixed models to analyze correlated electronic health records data
Authors: Yan Zhiyu , Zachrison Kori S. , Schwamm Lee H. , Estrada Juan J. , Duan Rui
Published: January 2023

Large collaborative research networks provide opportunities to jointly analyze multicenter electronic health record (EHR) data, which can improve the sample size, diversity of the study population, and generalizability of the results. However, there are challenges to analyzing multicenter EHR data including privacy protection, large-scale computation resource requirements, heterogeneity across sites, and correlated observations. In this paper, we propose a federated algorithm for generalized linear mixed models (Fed-GLMM), which can flexibly model multicenter longitudinal or correlated data while accounting for site-level heterogeneity. Fed-GLMM can be applied to both federated and centralized research networks to enable privacy-preserving data integration and improve computational efficiency. By communicating a limited amount of summary statistics, Fed-GLMM can achieve nearly identical results as the gold-standard method where the GLMM is directly fitted to the pooled dataset. We demonstrate the performance of Fed-GLMM in numerical experiments and an application to longitudinal EHR data from multiple healthcare facilities.
Mortality inequalities in France since the 1920s: Evidence of a reversal of the income gradient in mortality
Authors: Bonnet Florian , d’Albis Hippolyte , Thuilliez Josselin
Published: January 2023

Many recent studies show that Europe has had a lower mortality inequality for most ages than the United States over the last thirty years. However, the evolution of the income gradient in mortality all along the twentieth century remains poorly understood. This article uses a unique dataset that gives the annual lifetables and fiscal income for the 90 administrative regions of mainland France from 1922 to 2020. The income gradients in mortality are computed across regions using a traditional method with calendar ages and, alternatively, with mortality milestones to control for the increase in life expectancy over time. The study reveals a systematic reversal of the gradient that occurred around the 1970s for both sexes and all ages or mortality groups when calculated at an aggregated level. Inequality in mortality amongst the oldest age groups has however returned to a level observed at least ten years earlier because of Covid-19, even after controlling for mortality improvements over the period.
Protocol of BEYOND trial: Clinical BEnefit of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in rhYthm cONtrol of atrial fibrillation in patients with diabetes mellitus
Authors: Lee Kyuhyun , Lee Soo Kyoung , Lee Juyeon , Jeon Bo Kyung , Kim Tae-Hoon , Yu Hee Tae , Lee Jung Myung , Park Jin-Kyu , Baek Yong-Soo , Kim Dong Hyeok , Shim Jaemin , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam , Park Junbeom
Published: January 2023

SGLT-2 inhibitor, traditionally used for glycemic control, has several beneficial effects that can help manage heart failure (HF). SGLT-2 inhibitors reduce the risk of cardiovascular mortality in patients with HF. As atrial fibrillation (AF) is closely associated with HF and diabetes mellitus (DM) is a risk factor for AF, we assume that SGLT-2 inhibitors will also show therapeutic benefits regarding AF, especially for rhythm control. This trial has a multicenter, prospective, open, blinded endpoint design. It is a 1:1 randomized and controlled study. A total of 716 patients who are newly diagnosed of AF and DM within 1 year will be enrolled from 7 tertiary medical centers. The trial is designed to compare the effects of SGLT-2 inhibitors and other oral hypoglycemic agents on atrial rhythm control in patients with AF and DM. The primary outcome is the recurrence of AF within a year (including post-antiarrhythmic drugs (AAD) or ablation). The secondary outcomes are the ablation rate within a year, change in AF burden, size of the left atrium, NT-proBNP, the AF symptom score, and the quality of life. This trial will prospectively evaluate the effect and safety of SGLT-2 inhibitors on AF rhythm control in patients with DM. It will provide an invaluable dataset on rhythm control in AF with DM for future studies and offer novel information to assist in clinical decisions. (BEYOND trial, ClinicalTrials.gov number: NCT05029115. https://clinicaltrials.gov/ct2/show/NCT05029115).
A two-gene marker for the two-tiered innate immune response in COVID-19 patients
Authors: Lei Hongxing
Published: January 2023

For coronavirus disease 2019 (COVID-19), a pandemic disease characterized by strong immune dysregulation in severe patients, convenient and efficient monitoring of the host immune response is critical. Human hosts respond to viral and bacterial infections in different ways, the former is characterized by the activation of interferon stimulated genes (ISGs) such as IFI27, while the latter is characterized by the activation of anti-bacterial associated genes (ABGs) such as S100A12. This two-tiered innate immune response has not been examined in COVID-19. In this study, the activation patterns of this two-tiered innate immune response represented by IFI27 and S100A12 were explored based on 1421 samples from 17 transcriptome datasets derived from the blood of COVID-19 patients and relevant controls. It was found that IFI27 activation occurred in most of the symptomatic patients and displayed no correlation with disease severity, while S100A12 activation was more restricted to patients under severe and critical conditions with a stepwise activation pattern. In addition, most of the S100A12 activation was accompanied by IFI27 activation. Furthermore, the activation of IFI27 was most pronounced within the first week of symptom onset, but generally waned after 2–3 weeks. On the other hand, the activation of S100A12 displayed no apparent correlation with disease duration and could last for several months in certain patients. These features of the two-tiered innate immune response can further our understanding on the disease mechanism of COVID-19 and may have implications to the clinical triage. Development of a convenient two-gene protocol for the routine serial monitoring of this two-tiered immune response will be a valuable addition to the existing laboratory tests.
Cost-utility analysis of atezolizumab with bevacizumab in untreated unresectable or advanced hepatocellular carcinoma in France
Authors: Gaugain Loïg , Cawston Hélène , Dubois de Gennes Coline , Sanchez Alvares Javier , Nahon Pierre , Mazaleyrat Benjamin , Le Dissez Clément
Published: January 2023

Background and aims

The IMbrave150 clinical trial assessed the efficacy and safety of atezolizumab in combination with bevacizumab (ATZ+BVA) versus sorafenib in adults with advanced/unresectable hepatocellular carcinoma, who have not received prior systemic treatment. Our aim was to assess the cost-effectiveness of ATZ+BVA versus sorafenib in France based on an updated prices and considering French National real-world data, to confirm the initial recommendations from the Heath Technology Assessment submission published in 2021, and provide additional visibility to decision-makers reflecting current clinical practice.

Methods

A partition survival model was developed to project clinical outcomes, quality of life, and costs of patients with HCC treated with ATZ+BVA versus sorafenib over a lifetime horizon. Survival outcomes were extrapolated via parametric functions for both treatment strategies. Quality of life (EQ-5D-5L, French tariffs) were sourced from IMbrave150. The Guyot method was considered as a scenario analysis by integrating retrospective real-world data extracted from the French Health Insurance Database to refine long term survival extrapolations.

Results

In the reference case, ATZ+BVA was associated with 0.61 additional Quality Adjusted Life Years (QALYs) compared to sorafenib (1.95 vs 1.35), and an incremental cost of €92,704. The incremental cost-utility ratio (ICUR) was 152,974 €/QALY gained. Adjusting the survival curves with French external evidence led to a 14% ICUR reduction (131,163 €/QALY).

Conclusions

ATZ+BVA is a cost-effective strategy based on the range recently published for the value of a QALY in France and offers better chances of survival to patients.
Cadmium stress interacts with nutrient availability and light condition to affect the growth of Hydrocotyle vulgaris
Authors: Zhang Rui , Chen Zhi-Huan , Cui Wen-Tao , Qiu Shang-Yan , Qian Zi-Han , He Xue-Ge , Xin Jun-Cai , Si Chao
Published: January 2023

Heavy metal pollution is becoming a serious problem in wetland and often co-occurs with nutrient availability and light conditions variation. We hypothesized that nutrient availability and light condition can affect the growth of wetland plants under heavy metal stress. To test this hypothesis, single ramets of a common, clonal wetland plant Hydrocotyle vulgaris were grown for four weeks at three levels of cadmium with three levels of nutrient availability under 30% or 100% light conditions. High level of nutrient availability and high light condition overall promoted growth of H. vulgaris under Cd stress. Under the two light conditions, responses of H. vulgaris to Cd treatments differed among three nutrient levels. Under 30% light condition, 2 mg L-1 Cd2+ treatment decreased total mass at the low nutrient level and decreased ramet number at the medium nutrient level; 0.5 and 2 mg L-1 Cd2+ treatments decreased leaf mass ratio at the low and the medium nutrient levels. Under 100% light condition, 2 mg L-1 Cd2+ treatments significantly decreased total mass at the high level of nutrients; 2 mg L-1 Cd2+ treatment decreased ramet number at the medium and the high nutrient levels and decreased leaf mass ratio at the medium nutrient levels. Our results suggested that Cd stress can interact with nutrient availability and light condition to affect the performance of wetland plants such as H. vulgaris.
Characterizing inhibitors of human AP endonuclease 1
Authors: Pidugu Lakshmi S. , Servius Hardler W. , Sevdalis Spiridon E. , Cook Mary E. , Varney Kristen M. , Pozharski Edwin , Drohat Alexander C.
Published: January 2023

AP endonuclease 1 (APE1) processes DNA lesions including apurinic/apyrimidinic sites and 3´-blocking groups, mediating base excision repair and single strand break repair. Much effort has focused on developing specific inhibitors of APE1, which could have important applications in basic research and potentially lead to clinical anticancer agents. We used structural, biophysical, and biochemical methods to characterize several reported inhibitors, including 7-nitroindole-2-carboxylic acid (CRT0044876), given its small size, reported potency, and widespread use for studying APE1. Intriguingly, NMR chemical shift perturbation (CSP) experiments show that CRT0044876 and three similar indole-2-carboxylic acids bind a pocket distal from the APE1 active site. A crystal structure confirms these findings and defines the pose for 5-nitroindole-2-carboxylic acid. However, dynamic light scattering experiments show the indole compounds form colloidal aggregates that could bind (sequester) APE1, causing nonspecific inhibition. Endonuclease assays show the compounds lack significant APE1 inhibition under conditions (detergent) that disrupt aggregation. Thus, binding of the indole-2-carboxylic acids at the remote pocket does not inhibit APE1 repair activity. Myricetin also forms aggregates and lacks APE1 inhibition under aggregate-disrupting conditions. Two other reported compounds (MLS000552981, MLS000419194) inhibit APE1 in vitro with low micromolar IC50 and do not appear to aggregate in this concentration range. However, NMR CSP experiments indicate the compounds do not bind specifically to apo- or Mg2+-bound APE1, pointing to a non-specific mode of inhibition, possibly DNA binding. Our results highlight methods for rigorous interrogation of putative APE1 inhibitors and should facilitate future efforts to discover compounds that specifically inhibit this important repair enzyme.
Decrease in the expression of muscle-specific miRNAs, miR-133a and miR-1, in myoblasts with replicative senescence
Authors: Shintani-Ishida Kaori , Tsurumi Riko , Ikegaya Hiroshi
Published: January 2023

Muscles that are injured or atrophied by aging undergo myogenic regeneration. Although myoblasts play a pivotal role in myogenic regeneration, their function is impaired with aging. MicroRNAs (miRNAs) are also involved in myogenic regeneration. MiRNA (miR)-1 and miR-133a are muscle-specific miRNAs that control the proliferation and differentiation of myoblasts. In this study, we determined whether miR-1 and miR-133a expression in myoblasts is altered with cellular senescence and involved in senescence-impaired myogenic differentiation. C2C12 murine skeletal myoblasts were converted to a replicative senescent state by culturing to a high passage number. Although miR-1 and miR-133a expression was largely induced during myogenic differentiation, expression was suppressed in cells at high passage numbers (passage 10 and/or passage 20). Although the senescent myoblasts exhibited a deterioration of myogenic differentiation, transfection of miR-1 or miR-133a into myoblasts ameliorated cell fusion. Treatment with the glutaminase 1 inhibitor, BPTES, removed senescent cells from C2C12 myoblasts with a high passage number, whereas myotube formation and miR-133a expression was increased. In addition, primary cultured myoblasts prepared from aged C57BL/6J male mice (20 months old) exhibited a decrease in miR-1 and miR-133a levels compared with younger mice (3 months old). The results suggest that replicative senescence suppresses muscle-specific miRNA expression in myoblasts, which contributes to the senescence-related dysfunction of myogenic regeneration.
Determinants and predictors of mental health during and after COVID-19 lockdown among university students in Malaysia
Authors: Mir Imtiyaz Ali , Ng Shang Kuan , Mohd Jamali Muhammad Noh Zulfikri , Jabbar Mohammed AbdulRazzaq , Humayra Syeda
Published: January 2023

Background

Young adults, particularly university students might be at greater risk of developing psychological distress, and exhibiting symptoms of anxiety and depression during the COVID-19 pandemic. The primary objective of this study was to explore and compare the determinants and predictors of mental health (anxiety and depression) during and after the COVID-19 lockdown among university students.

Methods

This was an observational, cross-sectional study with a sample size of 417 students. An online survey utilizing International Physical Activity Questionnaire–Short Form (IPAQ-SF), General Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) was distributed to Universiti Tunku Abdul Rahman students via Google forms.

Results

During lockdown, family income [χ2 (1, n = 124) = 5.155, p = 0.023], and physical activity (PA) [χ2 (1, n = 134) = 6.366, p = 0.012] were associated with anxiety, while depression was associated with gender [χ2 (1, n = 75) = 4.655, p = 0.031]. After lockdown, family income was associated with both anxiety [χ2 (1, n = 111) = 8.089, p = 0.004], and depression [χ2 (1, n = 115) = 9.305, p = 0.002]. During lockdown, family income (OR = 1.60, p = 0.018), and PA (OR = 0.59, p = 0.011) were predictors for anxiety, while gender (OR = 0.65, p = 0.046) was a predictor for depression. After lockdown, family income was a predictor for both anxiety (OR = 1.67, p = 0.011), and depression (OR = 1.70, p = 0.009).

Conclusion

Significant negative effects attributed to the COVID-19 lockdown, and certain factors predisposed to the worsening of mental health status in university students. Low family income, PA, and female gender were the major determinants and predictors linked to anxiety and depression.
Intrinsic resistance of HIV-2 and SIV to the maturation inhibitor GSK2838232
Authors: Smith Robert A. , Raugi Dana N. , Nixon Robert S. , Song Jennifer , Seydi Moussa , Gottlieb Geoffrey S. ,   on behalf of the University of Washington-Senegal HIV-2 Study Group
Published: January 2023

GSK2838232 (GSK232) is a novel maturation inhibitor that blocks the proteolytic cleavage of HIV-1 Gag at the junction of capsid and spacer peptide 1 (CA/SP1), rendering newly-formed virions non-infectious. To our knowledge, GSK232 has not been tested against HIV-2, and there are limited data regarding the susceptibility of HIV-2 to other HIV-1 maturation inhibitors. To assess the potential utility of GSK232 as an option for HIV-2 treatment, we determined the activity of the compound against a panel of HIV-1, HIV-2, and SIV isolates in culture. GSK232 was highly active against HIV-1 isolates from group M subtypes A, B, C, D, F, and group O, with IC50 values ranging from 0.25–0.92 nM in spreading (multi-cycle) assays and 1.5–2.8 nM in a single cycle of infection. In contrast, HIV-2 isolates from groups A, B, and CRF01_AB, and SIV isolates SIVmac239, SIVmac251, and SIVagm.sab-2, were highly resistant to GSK232. To determine the role of CA/SP1 in the observed phenotypes, we constructed a mutant of HIV-2ROD9 in which the sequence of CA/SP1 was modified to match the corresponding sequence found in HIV-1. The resulting variant was fully susceptible to GSK232 in the single-cycle assay (IC50 = 1.8 nM). Collectively, our data indicate that the HIV-2 and SIV isolates tested in our study are intrinsically resistant to GSK232, and that the determinants of resistance map to CA/SP1. The molecular mechanism(s) responsible for the differential susceptibility of HIV-1 and HIV-2/SIV to GSK232 require further investigation.
Ebola virus disrupts the inner blood-retinal barrier by induction of vascular endothelial growth factor in pericytes
Authors: Gao Jiawang , Guo Zhengyuan , Li Wei , Zhang Xiaowei , Zhang Xian-En , Cui Zongqiang
Published: January 2023

Ebola virus (EBOV) causes severe hemorrhagic fever in humans with high mortality. In Ebola virus disease (EVD) survivors, EBOV persistence in the eyes may break through the inner blood–retinal barrier (iBRB), leading to ocular complications and EVD recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we used the in vitro iBRB model to simulate EBOV in retinal tissue and found that Ebola virus-like particles (EBO-VLPs) could disrupt the iBRB. Cytokine screening revealed that EBO-VLPs stimulate pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF downregulates claudin-1 to disrupt the iBRB. Ebola glycoprotein is crucial for VEGF stimulation and iBRB breakdown. Furthermore, EBO-VLPs caused iBRB breakdown by stimulating VEGF in rats. This study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EVD survivors.
Vissungo’s “Songs of the Earth”
Authors: Grasse Jonathon
Published: January 2023

Chapter three examines the work song tradition strongly linked to the gold rush and subsequent mining legacies known as vissungo, a genre now losing its last practitioners and which was specific to small communities surrounding the vicinities of the Serro Frio historical city of Diamantina. In considering manumission (an enslaved person's purchase or award of freedom) the narrative engages the full array of enslaved and freed populations. In presenting vissungo's musical spaces, the topic of runaway-slave communities known as quilombos is introduced. The quilombo topic brings readers into the twenty-first century with discussion of the contemporary land reform social movement, and into commercial music through the widely recognized singer Clementina de Jesus. Through examining vissungo music and textual topics, and by broadening discussion toward work song in general, the chapter continues a 300-plus-year social history of Afro-Mineiro culture initiated by the calundú chapter.
The Viola in Minas Gerais
Authors: Grasse Jonathon
Published: January 2023

“The Viola in Minas Gerais: Rural Dreams and Urban Realities,” presents a musical instrument as iconic of the rural past and as a vehicle for contemporary instrumentalism. The topic offers a window into places and times in regional development, such as the rugged interior of the sertão, and the growth of the caipira ideal of rural culture, both viewed here with a broad historical swath and their close relationships to musical genres. First person narratives offer ethnographic proximity to players and luthiers responsible for maintaining the tradition. A brief history of viola makers includes discussion of the Queluz luthiers of the nineteenth and early twentieth centuries. The importance of musicians such as Zé Coco de Riachão (multi-instrumentalist, luthier), Virgílio Lima (luthier), and Max Rosa (luthier, collector), and Tavinho Moura (performer, composer) is expanded upon. The chapter ends with an ethnographic visit to a Belo Horizonte viola festival.
Regionalist Themes in the Songs of the Corner Club
Authors: Grasse Jonathon
Published: January 2023

Chapter nine analyzes songs of the Corner Club popular music collective for regionalist themes and images. Of the primary themes found are those of bucolic rurality and the power of the natural world, the contrasting gleam of modern Belo Horizonte, poetic expressions of isolation and independence associated with Minas Gerais, and political protest punctuated with regional ideals. The chapter discusses social and political movements, the military dictatorship, revisits the viola (particularly in the work of Tavinho Moura), and ends with a return to themes of local Afro-Mineiro music culture as discovered in the early 2000s work of Corner Club leader Milton Nascimento. The chapter presents brief biographical sketches of collective members, their deep family connections to Minas Gerais, and some of their roles in the collective's discography. Through key collective members Lô Borges and Beto Guedes, rock is seen as a new strata of 1960s-70s identity in Belo Horizonte.
Introduction
Authors: Midkiff Emily
Published: January 2023

This chapter opens the book with an example of a science fiction book for children, Frank Einstein and the Antimatter Motor (2014), and an anecdote about how it was nearly not published due to the belief that children do not like science fiction with too much science. Through comparing this children's book to advanced and classic science fiction, this chapter sets the stage for examining how adult beliefs about childhood innocence and ability obscures the actual quality and possibilities of science fiction for young readers. The chapter concludes with an overview of the book's other chapters.
Snapshot of a Western Place
Authors: Marius Philippe-Richard
Published: January 2023

The first part of this chapter links the experience of a working-class unemployed mother of two to that of an upper-middle-class black couple to reveal across class lines Haitians’ aspirational turn to Western ways of being social. Between the two emerges a practical critique of the romantic longing for mythic anticolonial narratives (Scott 2004), among which the tale of the Black Republic is an alluring epic. The chapter also teases out a political liberalism that circulates among privileged blacks and among privileged mulattoes, while the sociopolitics of color preempt linkages between liberals across the boundaries of their respective formations. Through the Haitian bourgeois liberal experience, it ends with a critique of Susan Buck-Morss’s ahistorical reading of the Saint-Domingue Revolution through Hegel’s “universal.” This critical engagement sees Buck-Morss’s exercise in dehistoricization as the epitome of a global imagining of Haiti as a project of absolute liberation derailed by global forces.
Death Dice
Authors: Young Simon
Published: January 2023

This legend concerns the folklore of war, crime, and death. Soldiers sentenced to death for a crime are allowed to role dice to decide who dies: a miracle of some kind occurs to save the soldier.