bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic Effects of Germination and Ultrasonication on Nutritional and Structural Characteristics of Kodo (Paspalum scrobiculatum) and Little (Panicum sumatrense) Millet
Authors: Dey Swarnima , Saxena Alok , Kumar Yogesh , Maity Tanushree , Tarafdar Ayon
Published: August 2024

This study aimed to investigate the nutritional and structural properties of kodo (Paspalum scrobiculatum) and little (Panicum sumatrense) millets on administering ultrasonication and germination treatments. Significant changes in the treated samples were recorded, including lower levels of antinutrients such as tannin and phytates, and higher antioxidant activity, improving their nutritional value. The treated kodo and little millets showed significantly improved nutritional bio‐accessibility, with an impressive in vitro protein digestibility of >82%. The modified structure of the starch granules in the treated millets showed pseudoplastic flow characteristics and a polyhedron/spherical morphology which was a novel finding. DSC thermogram revealed that the treated millets may be processed at higher temperatures while exhibiting a lower enthalpy, which could expand their uses in a range of food products. FTIR spectra indicated the presence of phenolic groups in both millet samples studied, at approximately 2817 cm⁻1 frequency. The results obtained offer insightful information about the benefits of ultrasonication and germination for processing kodo and little millets in terms of altered starch characteristics, enhanced bio‐accessibility of nutrients, and better nutritional profiles, which qualify millets for the development of functional food products.
Evaluation of Vertical Human‐Structure Interaction on a Pedestrian Bridge Using a Predictive Human Gait Model
Authors: Aux Juan D. , Castillo Bryan , Riascos Carlos , Marulanda Johannio , Thomson Peter
Published: August 2024

Many modern pedestrian bridges exhibit flexibility and susceptibility to vibrations due to the use of lightweight and high‐strength materials, which can cause discomfort for pedestrians and affect their serviceability. Although gait biomechanics have been extensively studied and optimisation techniques for gait prediction on rigid surfaces have been previously employed, there is a paucity of studies investigating the effects of human‐structure interaction on pedestrian crossings over flexible structures. In this study, inverse dynamics and optimisation techniques were employed to predict human gait on a flexible structure in the sagittal plane. Gait was formulated as an optimal motor task subject to multiple constraints, with the performance criterion being the minimization of mechanical energy expenditure throughout a complete gait cycle. Segmental movements, pedestrian‐applied forces, and bridge vibrations were predicted based on parameters describing gait (such as gait speed, gait frequency, and double support duration), as well as physical and dynamic parameters characterizing the pedestrian bridge (including natural frequency, damping coefficient, and bridge length).
Supplementary Table S3 from Characterizing Relationships between T-cell Inflammation and Outcomes in Patients with High-Risk Neuroblastoma According to Mesenchymal and Adrenergic Signatures
Authors: Kaufman Maria E. , Vayani Omar R. , Moore Kelley , Chlenski Alexandre , Wu Tong , Lee Sang Mee , Desai Ami V. , He Chuan , Cohn Susan L. , Applebaum Mark A.
Published: August 2024

Table comparing our novel adrenergic and mesenchymal gene signatures with previously published signatures by Van Gronigen et al and Boeva et al.
Data from Characterizing Relationships between T-cell Inflammation and Outcomes in Patients with High-Risk Neuroblastoma According to Mesenchymal and Adrenergic Signatures
Authors: Kaufman Maria E. , Vayani Omar R. , Moore Kelley , Chlenski Alexandre , Wu Tong , Lee Sang Mee , Desai Ami V. , He Chuan , Cohn Susan L. , Applebaum Mark A.
Published: August 2024

Abstract
Recent insights have identified adrenergic (ADRN) and mesenchymal (MES) cell lineages as distinct biologic cell types and T-cell inflammation as a prognostic marker in neuroblastoma. We hypothesized that elucidating unique and overlapping aspects of these biologic features could serve as novel biomarkers for informing ongoing efforts to improve therapeutic approaches for children with high-risk neuroblastoma. We identified lineage-specific, single-stranded super-enhancers to define ADRN and MES specific genes. Publicly available RNA-seq of diagnostic tumor biopsies was used in Discovery and Validation cohorts. Each tumor was assigned a relative MES score and T-cell inflammation (TCI) score. Survival was assessed using the Kaplan–Meier method, and differences were assessed by the log-rank test. Inflammation scores were correlated with MES scores and anticorrelated with MYCN-amplification in both cohorts. Among patients with high-risk, ADRN tumors, those with TCI tumors had superior overall survival to those with non-inflamed tumors. A similar, but nonsignificant, trend was observed in the Validation cohort. Conversely, there was no difference according to TCI status in the MES cohort in either the Discover or Validation cohorts. High-inflammation scores were correlated with improved survival in some patients with high-risk, ADRN but not MES neuroblastoma. Our findings bolster support for further developing T-cell-based and immunotherapy-based approaches for children with high-risk neuroblastoma of varying MES and ADRN expression.
Significance:
Adrenergic (ADRN) and mesenchymal (MES) lineages are distinct biologic cell types in neuroblastoma. We defined ADRN and MES specific genes and found that high-risk, ADRN tumors harboring elevated T-cell inflammation signatures had superior overall survival. Our findings bolster support for further developing immunotherapy-based approaches for children with high-risk neuroblastoma.
Particle Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study, Systematic Review and Meta-Analysis
Authors: Mizumoto Masashi , Shibuya Kei , Terashima Kazuki , Murakami Masao , Murakami Motohiro , Shioyama Yoshiyuki , Matsuo Yoshiro , Ogino Takashi , Ohno Tatsuya , Waki Takahiro , Ogino Hiroyuki , Tamamura Hiroyasu , Katoh Norio , Wakatsuki Masaru , Okimoto Tomoaki , Suzuki Motohisa , Saito Takashi , Toyama Shingo , Hashimoto Takayuki , Ohba Hisateru , Kubo Shoji , Hasegawa Kiyoshi , Maruo Kazushi , Sakurai Hideyuki
Published: August 2024

Introduction: A prospective study was started in May 2016 to evaluate the efficacy and safety of particle therapy for intrahepatic cholangial carcinoma (ICC). To compare treatment modalities, we also conducted a meta-analysis of literature data and a systematic comparison using registry data. Methods: Patients who received particle therapy for ICC from May 2016 to June 2018 were registered. Nineteen manuscripts (4 particle therapy, 8 3D-CRT, 7 SBRT) were selected for the meta-analysis. Results: A total of 85 cases (proton beam therapy 59, carbon therapy 26) were registered. The median overall survival (OS) of the 85 patients was 22.1 months (95% CI: 12.9–31.3); the 1-, 2-, 3-, and 4-year OS rates were 70.9% (95% CI: 61.1–80.7%), 47.6% (36.8–58.4%), 37.7% (26.7–48.7%), and 22.7% (10.2–35.2%), respectively; and the 1-, 2-, 3-, and 4-year local recurrence rates were 8.2% (1.1–15.3%), 21.6% (9.3–33.9%), 33.4% (16.7–50.1%), and 33.4% (16.7–50.1%), respectively. In the meta-analysis and registry data, the 1-year OS for particle therapy, SBRT and 3D-CRT were 71.8% (95% CI: 64.6–77.8%), 59.2% (53.0–64.9%, p = 0.0573), and 47.2% (36.8–56.9%, p = 0.0004), respectively. The incidence of grade 3 or higher late non-hematological toxicity in the meta-analysis and registry data were 7.4–12% for particle therapy, 6.7–16.7% for SBRT, and 8.1–14.3% for 3D-CRT. Conclusions: Particle therapy achieved a good therapeutic effect for ICC, and a meta-analysis indicated that particle therapy is a better treatment modality than SBRT and 3D-CRT.
Philippe Steiner. Faire la Fête. Sociologie de la joie
Authors: Barreto Mariana
Published: August 2024

Esta reseña presenta el libro Faire la Fête - Sociologie de la joie de Philippe Steiner. En él, el autor presenta su investigación sobre las tradicionales fiestas callejeras que tienen lugar en la ciudad de Bayona, en la región vasca del suroeste de Francia. El sociólogo francés muestra que celebrar es participar de la efervescencia popular, pero también fabricarla. Para que la fiesta se lleve a cabo, es necesario prepararla, recibir a la multitud invitada, gestionarla durante su estancia en el tiempo y espacio de la fiesta. De esta manera, el significado de la celebración puede ser experimentado por la alegría de la multitud. En esta obra que vincula economía y cultura, Steiner explora el mundo de los eventos festivos e invita a la sociología a reivindicar la alegría como objeto.
A carreira acadêmica como profissão de mulheres: algumas histórias a partir da FFCL-USP
Authors: Chaguri Mariana Miggiolaro , Pires Bárbara Luisa
Published: August 2024

Este artigo explora as trajetórias de diferentes mulheres que fizeram carreira acadêmica nas primeiras décadas de funcionamento da FFCL-USP. Para tanto, traça em primeiro lugar um panorama sobre a presença de mulheres no corpo discente e docente da Faculdade entre 1934 e 1969, observando as interseções entre gênero e carreira acadêmica no período. Em segundo lugar, para aprofundar a investigação, aborda o caso de três docentes que atuaram nas Cadeiras de Sociologia I e II: Maria Isaura Pereira de Queiroz, Marialice Foracchi e Maria Sylvia de Carvalho Franco. Argumentamos que diferenças de gênero produziram impactos na distribuição de oportunidades entre homens e mulheres no interior de uma cultura acadêmica e institucional que então começava a se desenhar.
Metamorfoses de uma universidade: os estudantes da USP entre 2000 e 2020
Authors: Almeida Ana Maria F. , Serroni Perosa Graziela , Lamana Guilherme , Maia Rafael
Published: August 2024

Following the end of the authoritarian regime and the increase in elementary and secondaryeducation in the 1990s, there was a rise in demands for broader access to higher education and for public universities to become more inclusive to historically  underrepresented groups. This article explores how USP responded to them by discussing the expansion of recruitment and the adoption of affirmative actions and retention policies. Furthermore, we examine the changes in the composition of the student body. Our analysis highlights the gains, contradictions, and asymmetries that have emerged during this university’s recent  democratization process.
Description and total ontogeny of the Sonoran Tiger Mantis, Stagmomantis clauseni sp. nov., and key to the subgenus Nigralora (Mantodea: Mantidae)
Authors: GARIKIPATI LOHITASHWA
Published: August 2024

A recent reinvigorated effort into examining morphology and ecology of Nearctic Mantodea has led to the description of nearly 10 new species in the past decade. Expeditions to southern Arizona, combined with iNaturalist observations, suggested that S. wheelerii sensu Anderson is a complex of at least two cryptic species across its extensive range. Herein I describe one new species: Stagmomantis clauseni sp. nov., the Sonoran Tiger Mantis, from the Sonoran and Chihuahuan deserts, utilizing citizen science contributions, comparative morphology, and captive observations to describe its ontogeny and ethology. In addition, I also redescribe Stagmomantis wheelerii (Thomas 1875) and document the holotypes of Stagmomantis colorata (Hebard 1922) for the first time. The development of Stagmomantis clauseni sp. nov. also warranted the description of new hatching and signaling systems in Mantodea. For ease of both citizen and professional scientists a dichotomous key is provided for members of the subgenus Nigralora including characters in life.
First brown lacewings (Neuroptera: Hemerobiidae) from the early Eocene Green River Formation
Authors: MAKARKIN VLADIMIR N.
Published: August 2024

Pseudonotherobius kohlsi gen. et sp. nov. and Megalomus? coloradensis sp. nov. (Neuroptera: Hemerobiidae) are described from the early Eocene of the Parachute Creek Member of the Green River Formation, Colorado, U.S.A. The main diagnostic character states of Pseudonotherobius gen. nov. are the presence of a crossvein between the proximal branch of RP and RA in the forewing, and the costal space being dilated medially in the hind wing. The latter condition is unique in the family. The genus is preliminarily assigned to the subfamily Carobiinae due to the similarity of its venation to that of the extant Australian genus Notherobius New, 1988.
Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation
Authors: Chen Yuhua , He Wei , Qiu Junlin , Luo Yangyang , Jiang Chenlong , Zhao Feng , Wei Hong , Meng Jiao , Long Tianlin , Zhang Xin , Yang Lingjian , Xu Quanhua , Wang Juning , Zhang Chi
Published: August 2024

Background

Stroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke.

Methods

We administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion–reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model.

Results

We found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1β levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1β release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy.

Conclusion

The HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.
Sticking together: independent evolution of biofilm formation in different species of staphylococci has occurred multiple times via different pathways
Authors: Crossman Lisa , Sims Leanne , Dean Rachael , Felgate Heather , Calvo Teresa Diaz , Hill Claire , McNamara Iain , Webber Mark A. , Wain John
Published: August 2024

Background

Staphylococci cause a wide range of infections, including implant-associated infections which are difficult to treat due to the presence of biofilms. Whilst some proteins involved in biofilm formation are known, the differences in biofilm production between staphylococcal species remains understudied. Currently biofilm formation by Staphylococcus aureus is better understood than other members of the genus as more research has focused on this species.

Results

We assembled a panel of 385 non-aureus Staphylococcus isolates of 19 species from a combination of clinical sources and reference strains. We used a high-throughput crystal violet assay to assess the biofilm forming ability of all strains and assign distinct biofilm formation categories. We compared the prevalence of Pfam domains between the categories and used machine learning to identify amino acid 20-mers linked to biofilm formation.

This identified some domains within proteins already linked to biofilm formation and important domains not previously linked to biofilm formation in staphylococci. RT-qPCR confirmed the expression of selected genes predicted to encode important domains within biofilms in Staphylococcus epidermidis.

The prevalence and distribution of biofilm associated domains showed a link to phylogeny, suggesting different Staphylococcus species have independently evolved different mechanisms of biofilm production.

Conclusions

This work has identified different routes to biofilm formation in diverse species of Staphylococcus and suggests independent evolution of biofilm has occurred multiple times across the genus. Understanding the mechanisms of biofilm formation in any given species is likely to require detailed study of relevant strains and the ability to generalise across the genus may be limited.
Differential effects of everyday-life social support on chronic pain
Authors: Weiß Martin , Jachnik Annalena , Lampe Emilia C. , Gründahl Marthe , Harnik Michael , Sommer Claudia , Rittner Heike L. , Hein Grit
Published: August 2024

Background

Social support is a multidimensional construct encompassing emotional support as well as pain-focused care and attention, also known as solicitous support. One the one hand, social support is widely believed to positively influence pain symptoms, their intensity, and the ability to cope and influence pain. On the other hand, social support can be negative if it conflicts with the patient’s needs or even causes discomfort. How different types of social support influence pain is not very well understood especially because most of the present research originates from laboratory studies, raising uncertainties about its generalizability to the everyday life of individuals with chronic pain.

Methods

Here, we tested the effects of emotional, solicitous, and negative social support on pain intensity cross-sectionally in everyday life. We collected data from 20 patients with acute complex regional pain syndrome using a smartphone-based Ecological Momentary Assessment with up to 30 survey prompts over a period of five consecutive days.

Results

Our results showed that solicitous social support decreased pain, in particular in male patients. Emotional support was beneficial on pain in women but not in men.

Conclusions

Taken together, these findings highlight the differential effects of social support in every-day life on chronic pain.
Impact of non-pharmaceutical interventions on COVID-19 incidence and deaths: cross-national natural experiment in 32 European countries
Authors: Costa Diogo , Rohleder Sven , Bozorgmehr Kayvan
Published: August 2024

Purpose

Non-pharmaceutical interventions (NPIs) have been the cornerstone of COVID-19 pandemic control, but evidence on their effectiveness varies according to the methods and approaches taken to empirical analysis.

We analysed the impact of NPIs on incident SARS-CoV-2 across 32 European countries (March-December 2020) using two NPI trackers: the Corona Virus Pandemic Policy Monitor – COV-PPM, and the Oxford Covid-19 Government Response Tracker – OxCGRT.

Methods

NPIs were summarized through principal component analysis into three sets, stratified by two waves (C1-C3, weeks 5–25, and C4-C6, weeks 35–52). Longitudinal, multi-level mixed-effects negative binomial regression models were fitted to estimate incidence rate ratios for cases and deaths considering different time-lags and reverse causation (i.e. changing incidence causing NPIs), stratified by waves and geographical regions (Western, Eastern, Northern, Southern, Others).

Results

During the first wave, restrictions on movement/mobility, public transport, public events, and public spaces (C1) and healthcare system improvements, border closures and restrictions to public institutions (C2) were associated with a reduction in SARS-CoV-2 incidence after 28 and 35-days. Mask policies (C3) were associated with a reduction in SARS-CoV-2 incidence (except after 35-days). During wave 1, C1 and C2 were associated with a decrease in deaths after 49-days and C3 after 21, 28 and 35-days. During wave 2, restrictions on movement/mobility, public transport and healthcare system improvements (C5) were also associated with a decrease in SARS-CoV-2 cases and deaths across all countries.

Conclusion

In the absence of pre-existing immunity, vaccines or treatment options, our results suggest that the observed implementation of different categories of NPIs, showed varied associations with SARS-CoV-2 incidence and deaths across regions, and varied associations across waves. These relationships were consistent across components of NPIs derived from two policy trackers (CoV-PPM and OxCGRT).
ALLin4IPE- an international research study on interprofessional health professions education: a protocol for an ethnographic multiple-case study of practice architectures in sites of students’ interprofessional clinical placements across four universities
Authors: Lindh Falk Annika , Abrandt Dahlgren Madeleine , Dahlberg Johanna , Norbye Bente , Iversen Anita , Mansfield Kylie J. , McKinlay Eileen , Morgan Sonya , Myers Julia , Gulliver Linda
Published: August 2024

Background

The global discourse on future health care emphasises that learning to collaborate across professions is crucial to assure patient safety and meet the changing demands of health care. The research on interprofessional education (IPE) is diverse but with gaps in curricula design and how IPE is enacted in practice.

Purpose and aims

This research project will identify. 1) how IPE in clinical placements emerges, evolves, and is enacted by students when embedded in local health care practices, 2) factors critical for the design of IPE for students at clinical placements across the four countries.

Methods

A study involving four countries (Sweden, Norway, Australia and New Zealand) using the theory of practice architectures will be undertaken between 2023 and 2027. The project is designed as an international, collaborative multiple-case ethnographic study, using the theoretical framework of practice architectures (TPA). It will include four ethnographic case studies of IPE, one in each country. Data will be collected in the following sequence: (1) participant observation of students during interprofessional placements, (2) interviews with students at clinical placement and stakeholders/professionals, (3) Non-clinical documents may be used to support the analysis, and collection of photos may be use as memory aids for documenting context. An analysis of “sayings, doings and relatings” will address features of the cultural- discursive, material-economic, social-political elements making up the three key dimensions of TPA. Each of the four international cases will be analysed separately. A cross case analysis will be undertaken to establish common learning and critical IPE design elements across the four collaborating universities.

Discussion

The use of TPA framework and methodology in the analysis of data will make it possible to identify comparable dimensions across the four research sites, enabling core questions to be addressed critical for the design of IPE. The ethnographic field studies will generate detailed descriptions that take account of country-specific cultural and practice contexts. The study will also generate new knowledge as to how IPE can be collaboratively researched.
Maternal dietary patterns during pregnancy and birth weight: a prospective cohort study
Authors: Li Tongtong , He Yusa , Wang Nan , Feng Chengwu , Zhou Puchen , Qi Ye , Wang Zhengyuan , Lin Xiaojun , Mao Dou , Sun Zhuo , Sheng Aili , Su Yang , Shen Liping , Li Fengchang , Cui Xueying , Yuan Changzheng , Wang Liang , Zang Jiajie , Zong Geng
Published: August 2024

Background

Existing data on maternal dietary patterns and birth weight remains limited and inconsistent, especially in non-Western populations. We aimed to examine the relationship between maternal dietary patterns and birth weight among a cohort of Chinese.

Methods

In this study, 4,184 mother-child pairs were included from the Iodine Status in Pregnancy and Offspring Health Cohort. Maternal diet during pregnancy was evaluated using a self-administered food frequency questionnaire with 69 food items. Principal component analysis was used to identify dietary patterns. Information on birth weight and gestational age was obtained through medical records. Adverse outcomes of birth weight were defined according to standard clinical cutoffs, including low birth weight, macrosomia, small for gestational age, and large for gestational age.

Results

Three maternal dietary patterns were identified: plant-based, animal-based, and processed food and beverage dietary patterns, which explained 23.7% variance in the diet. In the multivariate-adjusted model, women with higher adherence to the plant-based dietary patten had a significantly higher risk of macrosomia (middle tertile vs. low tertile: odds ratio (OR) 1.45, 95% CI 1.00-2.10; high tertile vs. low tertile: OR 1.55, 95% CI 1.03–2.34; P-trend = 0.039). For individual food groups, potato intake showed positive association with macrosomia (high tertile vs. low tertile: OR 1.72, 95% CI 1.20–2.47; P-trend = 0.002). Excluding potatoes from the plant-based dietary pattern attenuated its association with macrosomia risk. No significant associations was observed for the animal-based or processed food and beverage dietary pattern with birth weight outcomes.

Conclusions

Adherence to a plant-based diet high in carbohydrate intake was associated with higher macrosomia risk among Chinese women. Future studies are required to replicate these findings and explore the potential mechanisms involved.
Facilitators and barriers to monitoring and evaluation at syringe service programs
Authors: Healy Elise , Means Arianna Rubin , Knudtson Kelly , Frank Noah , Juarez Alexa , Prohaska Stephanie , McKnight Courtney , Des Jarlais Don , Asher Alice , Glick Sara N.
Published: August 2024

Background

Syringe services programs (SSPs) provide harm reduction supplies and services to people who use drugs and are often required by funders or partners to collect data from program participants. SSPs can use these data during monitoring and evaluation (M&E) to inform programmatic decision making, however little is known about facilitators and barriers to collecting and using data at SSPs.

Methods

Using the Consolidated Framework for Implementation Research (CFIR), we conducted 12 key informant interviews with SSP staff to describe the overall landscape of data systems at SSPs, understand facilitators and barriers to data collection and use at SSPs, and generate recommendations for best practices for data collection at SSPs. We used 30 CFIR constructs to develop individual interview guides, guide data analysis, and interpret study findings.

Results

Four main themes emerged from our analysis: SSP M&E systems are primarily designed to be responsive to perceived SSP client needs and preferences; SSP staffing capacity influences the likelihood of modifying M&E systems; external funding frequently forces changes to M&E systems; and strong M&E systems are often a necessary precursor for accessing funding.

Conclusions

Our findings highlight that SSPs are not resistant to data collection and M&E, but face substantial barriers to implementation, including lack of funding and disjointed data reporting requirements. There is a need to expand M&E-focused funding opportunities, harmonize quantitative indicators collected across funders, and minimize data collection to essential data points for SSPs.
Elevated expression of Aurora-A/AURKA in breast cancer associates with younger age and aggressive features
Authors: Ingebriktsen L. M. , Humlevik R. O. C. , Svanøe A. A. , Sæle A. K. M. , Winge I. , Toska K. , Kalvenes M. B. , Davidsen B. , Heie A. , Knutsvik G. , Askeland C. , Stefansson I. M. , Hoivik E. A. , Akslen L. A. , Wik E.
Published: August 2024

Background and objective

Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-related AURKA-associated biological processes.

Methods

Aurora kinase A immunohistochemical staining was performed on tissue microarrays of primary tumors from an in-house breast cancer cohort (n = 355) with information on clinico-pathologic data, molecular markers, and long and complete follow-up. A subset of the in-house cohort (n = 127) was studied by the NanoString Breast Cancer 360 expression panel for exploration of mRNA expression. METABRIC cohorts < 50 years at breast cancer diagnosis (n = 368) were investigated for differentially expressed genes and enriched gene sets in AURKA mRNA high tumors stratified by age. Differentially expressed genes and gene sets were investigated using network analyses and g:Profiler.

Results

High Aurora kinase A protein expression associated with aggressive clinico-pathologic features, a basal-like subtype, and high risk of recurrence score. These patterns were confirmed using mRNA data. High AURKA gene expression demonstrated independent prognostic value when adjusted for traditional clinico-pathologic features and molecular subtypes. Notably, high AURKA expression significantly associated with reduced disease-specific survival within patients below 50 years, also within the luminal A subtype. Tumors of high AURKA expression showed gene expression patterns reflecting increased DNA damage activation and higher BRCAness score.

Conclusions

Our findings indicate higher AURKA expression in young breast cancer, and associations between high Aurora-A/AURKA and aggressive tumor features, including higher tumor cell proliferation, and shorter survival, in the young. Our findings point to AURKA as a marker for increased DNA damage and DNA repair deficiency and suggest AURKA as a biomarker of clinical relevance in young breast cancer.
Effectiveness and cost-effectiveness of a community intervention in enhancing access to care and improving clinical outcomes for depression: a protocol for a cluster randomised controlled trial in India
Authors: Nadkarni Abhijit , Gandhi Yashi , Fernandes Luanna , Mirchandani Kedar , Kamat Shreyas , Weiss Helen A. , Singla Daisy R. , Velleman Richard , Lu Chunling , Bhatia Urvita , Biswal Bijayalaxmi , Sequeira Miriam , D’souza Ethel , Raikar Kedar , Patel Vikram
Published: August 2024

Background

Although depression is the leading cause of disability worldwide, treatment coverage for the condition is inadequate. Supply-side barriers (e.g. shortage of specialist mental health professionals) and demand-side barriers (e.g. lack of awareness about depression) lead to limited availability of evidence-based interventions, poor demand for care, and low levels of adherence to care. The aim of our study is to examine if the addition of a community intervention delivered by community volunteers enhances the population-level impact of an evidence based psychosocial intervention (Healthy Activity Program [HAP]) in routine primary care by increasing demand for HAP and improving HAP adherence and effectiveness.

Methods

A hybrid type 2 effectiveness implementation cluster randomised controlled trial will be implemented in the state of Goa, India. Twenty-eight clusters of villages and their associated public sector health centres will be randomly allocated through restricted randomisation. Clusters will be randomly allocated to the ‘Community Model’ or ‘Facility Model’ arms. All clusters will offer the HAP and clusters in the ‘Community Model’ arm will additionally receive activities delivered by community volunteers (“Sangathis”) to increase awareness about depression and support demand for and adherence to HAP. The primary outcomes are Contact Coverage (Patient Health Questionnaire [PHQ-9] score > 4 as a proportion of those screened) and Effectiveness Coverage (mean PHQ-9 score amongst those who score ≥ 15 at baseline, i.e. those who have moderately severe to severe depression) at 3 months post-recruitment. Additional outcomes at 3 and 6 months will assess sustained effectiveness, remission, response to treatment, depression awareness, social support, treatment completion, and activation levels. Economic and disability outcomes will be assessed to estimate incremental cost-effectiveness ratios. Implementation will be evaluated through process data and qualitative data informed by the RE-AIM framework. A minimum of 79488 primary care attenders will be screened for the Contact Coverage outcome, and 588 individuals with PHQ-9 ≥ 15 will be recruited for the Effectiveness Coverage outcome.

Discussion

If effective, our community intervention will have relevance to India’s Ayushman Bharat universal healthcare programme which is scaling up care for depression in primary care, and also to other low- and middle- income countries.

Trial registration

Registered on ClincalTrials.gov (NCT05890222.) on 12/05/2023.
Multicomponent family support intervention in intensive care units: statistical analysis plan for the cluster-randomized controlled FICUS trial
Authors: von Felten Stefanie , Filipovic Miodrag , Jeitziner Marie-Madlen , Verweij Lotte , Riguzzi Marco , Naef Rahel
Published: August 2024

The FICUS trial is a cluster-randomized superiority trial to determine the effectiveness of a nurse-led, interprofessional family support intervention (FSI) on the quality of care, family management and individual mental health of family members of critically ill patients, compared to usual care. This paper describes the statistical analysis plan of the FICUS trial. The primary outcome is quality of family care, assessed by the Family Satisfaction in ICU Questionnaire (FS-ICU-24R) at patient discharge from the ICU. Several secondary outcomes are additionally assessed 3, 6, and 12 months thereafter. Sixteen clusters (ICUs) were randomly assigned 1:1 to FSI or usual care using minimization (8 per treatment). The target sample size is 56 patients per cluster (896 in total). Recruitment has been completed in January 2024. The follow-up of the last participant will be completed in early 2025. The primary and secondary outcomes will be analyzed by linear mixed-effects models (LMM). The main model for the primary outcome will include a random intercept per cluster with treatment (FSI vs. usual care) as the only explanatory variable due to the relatively small number of clusters. In addition, covariate-adjusted analyses will be conducted, including two cluster-level characteristics used in the minimization as well as participant-level characteristics. Moreover, a number of subgroup analyses by cluster- and participant-level characteristics are pre-specified.

Trial registration ClinicalTrials.gov NCT05280691. Registered on February 20, 2022.
Large-scale copy number alterations are enriched for synthetic viability in BRCA1/BRCA2 tumors
Authors: Zhu Yingjie , Pei Xin , Novaj Ardijana , Setton Jeremy , Bronder Daniel , Derakhshan Fatemeh , Selenica Pier , McDermott Niamh , Orman Mehmet , Plum Sarina , Subramanyan Shyamal , Braverman Sara H. , McMillan Biko , Sinha Sonali , Ma Jennifer , Gazzo Andrea , Khan Atif , Bakhoum Samuel , Powell Simon N. , Reis-Filho Jorge S. , Riaz Nadeem
Published: August 2024

Background

PathogenicBRCA1orBRCA2germline mutations contribute to hereditary breast, ovarian, prostate, and pancreatic cancer. Paradoxically, bi-allelic inactivation ofBRCA1orBRCA2(bBRCA1/2) is embryonically lethal and decreases cellular proliferation.The compensatory mechanisms that facilitate oncogenesis in bBRCA1/2 tumors remain unclear.

Methods

We identified recurrent genetic alterations enriched in human bBRCA1/2 tumors and experimentally validated if these improved proliferation in cellular models. We analyzed mutations and copy number alterations (CNAs) in bBRCA1/2 breast and ovarian cancer from the TCGA and ICGC. We used Fisher’s exact test to identify CNAs enriched in bBRCA1/2 tumors compared to control tumors that lacked evidence of homologous recombination deficiency. Genes located in CNA regions enriched in bBRCA1/2 tumors were further screened by gene expression and their effects on proliferation in genome-wide CRISPR/Cas9 screens. A set of candidate genes was functionally validated with in vitro clonogenic survival and functional assays to validate their influence on proliferation in the setting of bBRCA1/2 mutations.

Results

We found that bBRCA1/2 tumors harbor recurrent large-scale genomic deletions significantly more frequently than histologically matched controls (n = 238 cytobands in breast and ovarian cancers). Within the deleted regions, we identified 277 BRCA1-related genes and 218 BRCA2-related genes that had reduced expression and increased proliferation in bBRCA1/2 but not in wild-type cells in genome-wide CRISPR screens. In vitro validation of 20 candidate genes with clonogenic proliferation assays validated 9 genes, includingRIC8AandATMIN(ATM-Interacting protein). We identified loss ofRIC8A, which occurs frequently in both bBRCA1/2 tumors and is synthetically viable with loss of bothBRCA1andBRCA2. Furthermore, we found that metastatic homologous recombination deficient cancers acquire loss-of-function mutations inRIC8A. Lastly, we identified thatRIC8Adoes not rescue homologous recombination deficiency but may influence mitosis in bBRCA1/2 tumors, potentially leading to increased micronuclei formation.

Conclusions

This study provides a means to solve the tumor suppressor paradox by identifying synthetic viability interactions and causal driver genes affected by large-scale CNAs in human cancers.
Polyunsaturated fatty acids promote M2-like TAM deposition via dampening RhoA-YAP1 signaling in the ovarian cancer microenvironment
Authors: Wang Huogang , Yung Mingo MH , Xuan Yang , Chen Fushun , Chan Waisun , Siu Michelle KY , Long Runying , Jia Shuo , Liang Yonghao , Xu Dakang , Song Zhangfa , Tsui Stephen KW , Ngan Hextan YS , Chan Karen KL , Chan David W
Published: August 2024

Background

Peritoneal metastases frequently occur in epithelial ovarian cancer (EOC), resulting in poor prognosis and survival rates. Tumor-associated-macrophages (TAMs) massively infiltrate into ascites spheroids and are multi-polarized as protumoral M2-like phenotype, orchestrating the immunosuppression and promoting tumor progression. However, the impact of omental conditioned medium/ascites (OCM/AS) on TAM polarization and its function in tumor progression remains elusive.

Methods

The distribution and polarization of TAMs in primary and omental metastatic EOC patients’ tumors and ascites were examined by m-IHC, FACS analysis, and immunofluorescence. QPCR, immunofluorescence, FACS analysis, lipid staining assay, ROS assay, and Seahorse real-time cell metabolic assay characterized TAMs as being polarized in the ascites microenvironment. The oncogenic role of TAMs in tumor cells was demonstrated by co-cultured migration/invasion, proliferation, and spheroid formation assays. Mechanistic studies of the regulations of TAM polarization were performed by using RNA-Seq, GTPase pull-down, G-LISA activation assays, and other biochemical assays. A Yap1 macrophages (MФs) conditional knockout (cKO) mouse model demonstrated the roles of YAP1 in TAM polarization status and its pro-metastatic function. Finally, the anti-metastatic potential of targeting TAMs through restoring YAP1 by pharmacological agonist XMU MP1 was demonstrated in vitro and in vivo.

Results

Abundant polyunsaturated fatty acids (PUFAs) in OCM/AS suppressed RhoA-GTPase activities, which, in turn, downregulated nuclear YAP1 in MФs, leading to increased protumoral TAM polarization accompanied by elevated OXPHOS metabolism. Abolishment of YAP1 in MФs further confirmed that a higher M2/M1 ratio of TAM polarization could alleviate CD8+ T cell infiltration and cytotoxicity in vivo. Consistently, the loss of YAP1 has been observed in EOC metastatic tissues, suggesting its clinical relevance. On the contrary, restoration of YAP1 expression by pharmaceutical inhibition of MST1/2 induced conversion of M2-to-M1-like polarized MФs, elevating the infiltration of CD8+ T cells and attenuating tumor growth.

Conclusion

This study revealed that PUFAs-enriched OCM/AS of EOC promotes M2-like TAM polarization through RhoA-YAP1 inhibition, where YAP1 downregulation is required for accelerating protumoral M2-like TAM polarization, thereby causing immunosuppression and enhancing tumor progression. Conversion of M2-to-M1-like polarized MФs through Yap1 activation inhibits tumor progression and contributes to developing potential TAMs-targeted immunotherapies in combating EOC peritoneal metastases.
Design, synthesis, pharmacophore modeling, and molecular docking of some novel chloroacetamide derivatives as herbicidal agents
Authors: El-Zemity Saad R. , Esmaiel Kareem E. E. , Badawy Mohamed E. I.
Published: August 2024

Background

The discovery of new lead compounds with desired properties and biological activity is an excellent challenge in pesticide chemistry. Chloroacetamide are an important class of synthetic herbicides.

Results

To explore the herbicidal activity of chloroacetamides, several new chloroacetamide derivatives have been designed, and synthesized. The compounds have been described by forming Schiff bases followed by chloroacetylation of imines. The herbicidal activity as a chlorophyll inhibition was evaluated against two broadleaf weeds (Chenopodium album and Anagallis arvensis) and two grass weeds (Lolium temulentum and Echinochloa crus-galli) in comparison with acetochlor as a standard herbicide. 1H-NMR, 13C-NMR and mass spectroscopic analyses confirmed the chemical structures of the synthesized compounds. Several compounds have demonstrated highly potent herbicidal activity compared to the standard herbicide acetochlor. Some of them have been described as the most effective against weeds tested, such as compounds 5b and 18b. Molecular docking to the active sites of Very Long Chain Fatty Acid Synthase (VLCFAS) has indicated that most compounds are low-energy binding agents and show high affinity for the active pocket.

Conclusion

Novel herbicides may be discovered by combining chloroacetamide derivatives with these existing lead structures.

Graphical Abstract
Simplified semantics for further relevant logics II
Authors: Øgaard Tore Fjetland
Published: August 2024

It is shown how to model propositional constants within the simplified Routley-Meyer semantics. Various axioms and rules allowing the definition of modal operators, implicative negations, enthymematical conditionals, and propositions expressing various infinite conjunctions and disjunctions are set forth and shown to correspond to specific frame conditions. Two propositional constants which are both often designated as “the Ackermann constant” are shown to capture two such “infinite” propositions: The conjunction of every logical law and the conjunction of every truth –what Anderson and Belnap called the “world” constant.
Clinical Spectrum, Diagnosis, and Management of TANGO2 Deficiency Disorder: A Comprehensive Review
Authors: Dołęga Marcin , Gacka Piotr , Dróżdż Olgierd , Gołda Joanna , Mężyk Julia , Snopkowska Aleksandra
Published: August 2024

TANGO2 deficiency disorder is an autosomal recessive disease caused by biallelic pathogenic variants in the TANGO2 gene. First described in 2016, the disorder is characterized by acute metabolic crises, neurological dysfunctions, developmental delays, and intellectual disabilities. Laboratory findings indicate a mitochondrial fatty acid oxidation defect, with metabolic crises often triggered by stressors such as illness or fasting. The TANGO2 protein, implicated in lipid metabolism, membrane trafficking, and cellular homeostasis, is critical for maintaining lipid droplets, regulating phospholipid levels, and facilitating protein and lipid transport between cellular compartments. Symptoms of TANGO2 deficiency are diverse, including psychomotor delays, intellectual impairments, seizures, ataxia, and episodic neurological symptoms known as TANGO2 spells. Diagnosis involves genetic testing, with several pathogenic variants identified. During metabolic crises, patients may experience severe cardiac and metabolic disturbances. No curative treatment exists; management includes B-vitamin supplementation, antiepileptic drugs, and interventions for spasticity, dystonia, thyroid dysfunction, and arrhythmias. TANGO2 deficiency disorder can co-occur with DiGeorge syndrome, complicating diagnosis due to overlapping symptoms. Improved awareness and diagnostic strategies are crucial for effective management of this underrecognized condition.
Influence of obesity on developing osteoarthritis and the recovery after knee joint replacement – a review
Authors: Pasieka Karolina , Perenc Helena , Majka Karolina , Krawczyk Kornelia , Pędras Marek , Kosar Michał , Kosiorowska Paulina , Korzonek Urszula , Kupniewski Kuba
Published: August 2024

Obesity is a chronic disease accompanied by inflammation. It is becoming more and more prevalent all around the world and so are its consequences. Osteoarthritis (OA) is a degenerative disease of the joints. The range of its risk factors is broad, but the most common is obesity. OA can be treated in a surgical and non-surgical way. The surgical method - knee replacement is the most effective way of treating OA, but unfortunately it does not solve the problem. Obesity takes a part not only in development of OA, but is also involved in developing postoperative complications and impairing the recovery in general. The influence of obesity is determined not only by the weight and increased mechanical forces affecting the organism, but also on a molecular level by the hormonal activity of the substances produced by white adipose tissue. Condition of the patient should be optimised before the surgery in order to minimize the risk of complications and increase the chances for fast and effective recovery. Obese patients after the surgery need proper nutrition and care focused on their needs, which often is a challenge to the healthcare providers. After the surgery those patients cannot be sent back to the condition that made them sick. Reduction of weight is suggested to prevent the development of postoperative complications and OA. Prehabilitation seems to improve the immediate postoperative results. Starting regular training a few weeks after the surgery seems to positively affect the process of recovery.