bluuebunny/crossref_metadata_2025 huggingface dataset:
Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation
Authors: Cao Yanyan , Sun Tao , Sun Bo , Zhang Guilin , Liu Jiayun , Liang Bin , Zheng Chuansheng , Kan Xuefeng
Published: November 2023

Objective

To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism.

Materials and Methods

The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo.

Results

LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-β in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor.

Conclusion

The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.
Implementing harm reduction kits in an office-based addiction treatment program
Authors: Shang Margaret , Thiel Brent , Liebschutz Jane M. , Kraemer Kevin L. , Freund Ariana , Jawa Raagini
Published: November 2023

Background

The rising rates of drug use-related complications call for a paradigm shift in the care for people who use drugs. While addiction treatment and harm reduction have historically been siloed in the US, co-location of these services in office-based addiction treatment (OBAT) settings offers a more realistic and patient-centered approach. We describe a quality improvement program on integrating harm reduction kits into an urban OBAT clinic.

Methods

After engaging appropriate stakeholders and delivering clinician and staff trainings on safer use best practices, we developed a clinical workflow for universal offering and distribution of pre-packaged kits coupled with patient-facing educational handouts. We assessed: (1) kit uptake with kit number and types distributed; and (2) implementation outcomes of feasibility, acceptability, appropriateness, and patient perceptions.

Results

One-month post-implementation, 28% (40/141) of completed in-person visits had at least one kit request, and a total of 121 kits were distributed. Staff and clinicians found the program to be highly feasible, acceptable, and appropriate, and patient perceptions were positive.

Conclusions

Incorporating kits in OBAT settings is an important step toward increasing patient access and utilization of life-saving services. Our program uncovered a significant unmet need among our patients, suggesting that kit integration within addiction treatment can improve the standard of care for people who use drugs.
Connections between health research systems and decision-making spaces: lessons from the COVID-19 pandemic in the province of Québec, Canada
Authors: Smits Pernelle , Cambourieu Caroline , Ouimet Mathieu
Published: November 2023

The coronavirus 2019 (COVID-19) pandemic allowed for exceptional decision-making power to be placed in the hands of public health departments. Data and information were widely disseminated in the media and on websites. While the improvement of pandemic management is still a learning curve, the ecosystem perspective – that is, the interconnection of academic health research systems and decision-making spaces – has received little attention. In this commentary, we look at the mechanisms in place, or not, in Canada for ensuring decision-making spheres can “speak” to academic research systems. We look at the thick walls that are still in place between health research systems and decision-making spaces. More precisely, we discuss three organizational flaws that we identified in the evidence-informed decision-making ecosystem of Québec and, more broadly, Canada. We introduce some inspiring measures that other countries have implemented to better link evidence and public health decision-making during health crises. The observed flaws and options are related to the vitality of early information sharing relays, the cross-sectional capacity to issue opinions, and the collection and integration of hard and soft data.
Estimating the cost-effectiveness threshold of advanced non-small cell lung cancer in China using mean opportunity cost and contingent valuation method
Authors: Peng Qian , Yin Yue , Liang Min , Zhao Mingye , Shao Taihang , Tang Yaqian , Mei Zhiqing , Li Hao , Tang Wenxi
Published: November 2023

Objectives

Monetizing health has sparked controversy and has implications for pricing strategies of emerging health technologies. Medical insurance payers typically set up thresholds for quality-adjusted life years (QALY) gains based on health productivity and budget affordability, but they rarely consider patient willingness-to-pay (WTP). Our study aims to compare Chinese payer threshold and patient WTP toward QALY gain of advanced non-small cell lung cancer (NSCLC) and to inform a potential inclusion of patient WTP under more complex decision-making scenarios.

Methods

A regression model was constructed with cost as the independent variable and QALY as the dependent variable, where the regression coefficients reflect mean opportunity cost, and by transforming these coefficients, the payer threshold can be obtained. Patient WTP was elicited through a contingent valuation method survey. The robustness of the findings was examined through sensitivity analyses of model parameters and patient heterogeneity.

Results

The payer mean threshold in the base-case was estimated at 150,962 yuan (1.86 times per capita GDP, 95% CI 144,041–159,204). The two scenarios analysis generated by different utility inputs yielded thresholds of 112,324 yuan (1.39 times per capita GDP) and 111,824 yuan (1.38 times per capita GDP), respectively. The survey included 85 patients, with a mean WTP of 148,443 yuan (1.83 times per capita GDP, 95% CI 120,994–175,893) and median value was 106,667 yuan (1.32 times the GDP per capita). Due to the substantial degree of dispersion, the median was more representative. The payer threshold was found to have a high probability (98.5%) of falling within the range of 1–2 times per capita GDP, while the robustness of patient WTP was relatively weak.

Conclusions

In China, a country with a copayment system, payer threshold was higher than patient WTP, indicating that medical insurance holds significant decision-making authority, thus temporarily negating the need to consider patient WTP.
Deciphering the molecular and cellular atlas of immune cells in septic patients with different bacterial infections
Authors: Sun Ping , Cui Mintian , Jing Jiongjie , Kong Fanyu , Wang Shixi , Tang Lunxian , Leng Junling , Chen Kun
Published: November 2023

Background

Sepsis is a life-threatening organ dysfunction caused by abnormal immune responses to various, predominantly bacterial, infections. Different bacterial infections lead to substantial variation in disease manifestation and therapeutic strategies. However, the underlying cellular heterogeneity and mechanisms involved remain poorly understood.

Methods

Multiple bulk transcriptome datasets from septic patients with 12 types of bacterial infections were integrated to identify signature genes for each infection. Signature genes were mapped onto an integrated large single-cell RNA (scRNA) dataset from septic patients, to identify subsets of cells associated with different sepsis types, and multiple omics datasets were combined to reveal the underlying molecular mechanisms. In addition, an scRNA dataset and spatial transcriptome data were used to identify signaling pathways in sepsis-related cells. Finally, molecular screening, optimization, and de novo design were conducted to identify potential targeted drugs and compounds.

Results

We elucidated the cellular heterogeneity among septic patients with different bacterial infections. In Escherichia coli (E. coli) sepsis, 19 signature genes involved in epigenetic regulation and metabolism were identified, of which DRAM1 was demonstrated to promote autophagy and glycolysis in response to E. coli infection. DRAM1 upregulation was confirmed in an independent sepsis cohort. Further, we showed that DRAM1 could maintain survival of a pro-inflammatory monocyte subset, C10_ULK1, which induces systemic inflammation by interacting with other cell subsets via resistin and integrin signaling pathways in blood and kidney tissue, respectively. Finally, retapamulin was identified and optimized as a potential drug for treatment of E. coli sepsis targeting the signature gene, DRAM1, and inhibiting E. coli protein synthesis. Several other targeted drugs were also identified in other types of sepsis, including nystatin targeting C1QA in Neisseria sepsis and dalfopristin targeting CTSD in Streptococcus viridans sepsis.

Conclusion

Our study provides a comprehensive overview of the cellular heterogeneity and underlying mechanisms in septic patients with various bacterial infections, providing insights to inform development of stratified targeted therapies for sepsis.
Exploring the efficacy and beneficial population of preimplantation genetic testing for aneuploidy start from the oocyte retrieval cycle: a real-world study
Authors: Ma Shujuan , Liao Jingnan , Zhang Shuoping , Yang Xiaoyi , Hocher Berthold , Tan Jing , Tan Yueqiu , Hu Liang , Gong Fei , Xie Pingyuan , Lin Ge
Published: November 2023

Background

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used as an embryo selection technique in in vitro fertilization (IVF), but its effectiveness and potential beneficiary populations are unclear.

Methods

This retrospective cohort study included patients who underwent their first oocyte retrieval cycles at CITIC-Xiangya between January 2016 and November 2019, and the associated fresh and thawed embryo transfer cycles up to November 30, 2020. PGT-A (PGT-A group) and intracytoplasmic sperm injection (ICSI)/IVF (non-PGT-A group) cycles were included. The numbers of oocytes and embryos obtained were unrestricted. In total, 60,580 patients were enrolled, and baseline data were matched between groups using 1:3 propensity score matching. Sensitivity analyses, including propensity score stratification and traditional multivariate logistic regression, were performed on the original unmatched cohort to check the robustness of the overall results. Analyses were stratified by age, body mass index, ovarian reserve/responsiveness, and potential indications to explore benefits in subgroups. The primary outcome was cumulative live birth rate (CLBR). The other outcomes included live birth rate (LBR), pregnancy loss rate, clinical pregnancy rate, pregnancy complications, low birth weight rate, and neonatal malformation rate.

Results

In total, 4195 PGT-A users were matched with 10,140 non-PGT-A users. A significant reduction in CLBR was observed in women using PGT-A (27.5% vs. 31.1%; odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.78–0.91; P < 0.001). However, women using PGT-A had higher first-transfer pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI 1.81–2.23; P < 0.001) and LBR (52.6% vs. 34.2%, OR = 2.13, 95% CI 1.92–2.36; P < 0.001) rates and lower rates of early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI 0.48–0.70; P < 0.001), preterm birth (8.6% vs 17.3%; P < 0.001), and low birth weight (4.9% vs. 19.3%; P < 0.001). Moreover, subgroup analyses revealed that women aged ≥ 38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefited from PGT-A, with a significant increase in first-transfer LBR without a decrease in CLBR.

Conclusion

PGT-A does not increase and decrease CLBR per oocyte retrieval cycle; nonetheless, it is effective in infertile populations with specific indications. PGT-A reduces complications associated with multiple gestations.
LncRNA-Gm9866 promotes liver fibrosis by activating TGFβ/Smad signaling via targeting Fam98b
Authors: Liao Xiaomin , Ruan Xianxian , Yao Peishan , Yang Dan , Wu Xianbin , Zhou Xia , Jing Jie , Wei Dafu , Liang Yaodan , Zhang Taicheng , Qin Shanyu , Jiang Haixing
Published: November 2023

Objective

The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis.

Methods

The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866.

Results

The expression of α-smooth muscle actin (α-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-β1 (TGFβ1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFβ1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferation and migration of HCs. Mechanistically, lncRNA-Gm9866 may directly bine with Fam98b. Silencing Fam98b in stably overexpressing lncRNA-Gm9866 cell lines reversed the increase of pro-fibrogenic genes and pro-apoptotic genes, fibrosis related pathway protein TGFβ1, Smad2/3, p-Smad2/3 and Notch3 induced by overexpressing lncRNA-Gm9866.

Conclusions

LncRNA-Gm9866 may regulate TGFβ/Smad and Notch pathways by targeting Fam98b to regulate liver fibrosis. LncRNA-Gm9866 may be a new target for diagnosis and treatment of liver fibrosis.
Reliability of the tunisian pediatric gait, arms, legs, and spine: toward a valid screening tool for tunisian children with musculoskeletal conditions
Authors: Hanene Lassoued Ferjani , Amdouni Narjess , Emna Rabhi , Hela Sahli , Kaouther Ben Abdelgheni , Dorra Ben Nessib , Dhia Kaffel , Kaouther Maatallah , Wafa Hamdi
Published: November 2023

Background

Pediatric musculoskeletal disorders account for 10% of first-line consultations in Tunisia. Referral delay and deficiencies in musculoskeletal screening raise a challenge to the early diagnosis and management of rheumatic conditions in children. The pGALS (Pediatric Gait Arms Legs Spine) was developed and translated into many languages to overcome these deficiencies. Our study aimed to adapt and validate pGALS to the Tunisian dialect for school-age children.

Methods

Using the Delphi method, we carried out a cross-cultural adaptation of the pGALS to the Tunisian dialect. This consensual version was validated in a cross-sectional study, in two pediatric centers.

Results

Ninety-two patients were enrolled, 43 females (46.7%) and 49 males (53.3%), mean age was 9.4 ± 2.6 years. The mean test duration was 3.4 ± 2.3 min, and the acceptability and comprehension of the test were good. Six patients had a musculoskeletal complaint, 19 had positive pGALS, and 14 were diagnosed with musculoskeletal disease. The internal consistency score (Cronbach’s α) was 0.852. The sensitivity of the test was 92.8%, the specificity was 92.3%, the positive likelihood ratio was 2.16, and the negative likelihood ratio was 0.01.

Conclusion

The pGALS test adapted to the Tunisian dialect is a relevant, quick, and valid tool for screening musculoskeletal abnormalities in school-age children.
A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT
Authors: Yee Karen S. , Chirila Costel , Davenport Eric , Mladsi Deirdre , Barnett Christine , Kronenberger William G.
Published: November 2023

Background

Norm-based scores used to assess cognitive ability have clinical value when describing functioning of patients with neuronopathic disorders compared with unaffected, same-age peers. However, they have limitations when used to assess change in cognitive ability between two timepoints, especially in children with severe cognitive decline. Calculation of Projected Retained Ability Scores (PRAS) is a novel method developed to characterize absolute change in norm-based ability test scores. In this analysis, PRAS were calculated post hoc for children with mucopolysaccharidosis II (MPS II; Hunter syndrome) and early cognitive impairment in a 52-week phase 2/3 randomized controlled trial (RCT) and its extension study of intrathecal idursulfase (idursulfase-IT). Patients completing the first year of the extension after receiving idursulfase-IT in the RCT and extension (n = 32 of 34 enrolled) or the extension only (n = 15 of 15 enrolled) were categorized according to changes in Differential Ability Scales, Second Edition, General Conceptual Ability (DAS-II GCA) scores and PRAS at 1 and 2 years. Analyses were conducted in the overall population and a subpopulation aged < 6 years at baseline (idursulfase-IT in the RCT and extension [n = 27] and extension only [n = 12]).

Results

PRAS methodology differentiated patients with decreases in DAS-II GCA scores into three separate categories reflecting below-average cognitive growth rates, plateauing cognitive development, and deteriorating cognitive functioning. After 1 year in the RCT, 72.4% of patients who initiated idursulfase-IT had above-average or average cognitive growth rates in DAS-II GCA scores compared with 53.3% of those who did not receive idursulfase-IT; 6.9% versus 20.0% experienced deteriorating cognitive functioning. Similar results were seen in children aged < 6 years: 76% (idursulfase-IT group) versus 50% (no idursulfase-IT) had above-average or average cognitive growth rates in DAS-II GCA scores; 4% versus 17% had deteriorating cognitive functioning. The difference in the distributions of cognitive categories at 1 year in children aged < 6 years was significant (p = 0.048). At 2 years, the proportions of patients in different cognitive categories were more similar between treatment groups.

Conclusions

PRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time.

Trial Registration: ClinicalTrials.gov NCT02055118 (registration date: 4 February 2014) and NCT02412787 (registration date: 9 April 2015).
FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression
Authors: Hu Wei-Min , Li Ming , Ning Jin-Zhuo , Tang Yu-Qi , Song Tian-Bao , Li Lin-Zhi , Zou Fan , Cheng Fan , Yu Wei-Min
Published: November 2023

Background

Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear.

Methods

In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model.

Results

FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs.

Conclusions

In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.
Examining the impact of a universal social and emotional learning intervention (Passport) on internalising symptoms and other outcomes among children, compared to the usual school curriculum: study protocol for a school-based cluster randomised trial
Authors: O’Brien Annie , Hamilton Suzanne , Humphrey Neil , Qualter Pamela , Boehnke Jan R. , Santos Joao , Demkowicz Ola , Panayiotou Margarita , Thompson Alex , Lau Jennifer , Burke Lauren , Lu Yizhuo
Published: November 2023

Background

School-based universal social and emotional learning (SEL) interventions implemented during the transition to adolescence may be efficacious in preventing the development of mental health difficulties. This protocol describes a two-arm parallel cluster randomised controlled trial to investigate the impact of a universal SEL intervention (Passport, compared to usual provision) on internalising symptoms (primary outcome), emotion regulation, well-being, loneliness, social support, bullying, academic attainment, and health-related quality of life in English primary school pupils aged 9–11 years. A developer-led trial demonstrated the feasibility, acceptability, and utility of Passport; this will be the first independent trial.

Methods

Sixty primary schools will be recruited across the Greater Manchester city region and surrounding areas, involving 2400 pupils aged 8–9 at baseline. Schools will be allocated to the intervention arm to implement Passport over 18 weekly sessions or to the control arm to implement the usual school curriculum. Random allocation will be at school level following completion of baseline measures, with minimisation to ensure balance across trial arms in school size and free school meal eligibility. Measures will be collected at baseline, post-intervention (12 months post-baseline), and at 12 months follow-up (24 months post-baseline). The primary outcome analysis (intervention effects on internalising symptoms at post-intervention) will comprise a two-level (school, child) hierarchical linear model, following the intention-to-treat principle. Additional analyses will be undertaken to assess intervention effects on secondary outcomes, maintenance effects for all outcomes, intervention compliance moderator effects, subgroup moderator effects, and mechanisms underpinning intervention effects on the primary outcome. A mixed-methods implementation and process evaluation will examine factors that influence implementation, and a health economic evaluation will assess the cost-effectiveness of the intervention.

Discussion

Findings will provide educators with crucial knowledge of whether and how increasing emotion regulation through a universal intervention impacts internalising symptoms and a range of related outcomes. Findings will also inform policy related to the promotion of mental health among children and young people. If the intervention is found to be efficacious in reducing internalising symptoms and is also cost-effective, it may offer high potential as a preventative intervention for widespread implementation.

Trial registration

ISRCTN12875599; registered on 24 November 2022
Molecular detection of Babesia spp. in dogs in Germany (2007–2020) and identification of potential risk factors for infection
Authors: Schäfer Ingo , Helm Christina Sabine , von Samson-Himmelstjerna Georg , Krücken Jürgen , Kottmann Tanja , Holtdirk Annette , Kohn Barbara , Hendrickx Guy , Marsboom Cedric , Müller Elisabeth
Published: November 2023

Background

In Europe, canine babesiosis is most frequently caused by Babesia canis and Babesia vogeli, and occasionally by Babesia gibsoni.. In Germany, B. canis is recognized as endemic. The aims of this study were to assess how often Babesia spp. infections were diagnosed in a commercial laboratory in samples from dogs from Germany, and to evaluate potential risk factors for infection.

Methods

The database of the LABOKLIN laboratory was screened for Babesia spp.-positive polymerase chain reaction (PCR) tests for dogs for the period January 2007–December 2020. Sequencing was performed for positive tests from 2018 and 2019. Binary logistic regression analysis was performed to determine the effects of sex, season, and year of testing. Questionnaires were sent to the submitting veterinarians to obtain information on travel abroad, tick infestation, and ectoparasite prophylaxis of the respective dogs. Fisher’s exact test was used to calculate statistical significance and P < 0.05 was considered statistically significant.

Results

In total, 659 out of 20,914 dogs (3.2%) tested positive for Babesia spp. by PCR. Of 172 sequenced samples, B. canis was identified in 156, B. vogeli in nine, B. gibsoni in five, and B. vulpes in two. Season had a statistically significant impact on test results when summer/winter (1.6% tested positive) was compared to spring/autumn (4.7%), with peaks in April (5.2%) and October (7.4%) [P < 0.001, odds ratio (OR) = 3.16]. Sex (male 3.5%, female 2.8%; P = 0.012, OR = 1.49) and age (< 7 years old 4.0%, ≥ 7 years old 2.3%; P < 0.001, OR = 1.76) of the tested dogs also had a statistically significant effect. A statistically significant impact was demonstrated for observed tick attachment (P < 0.001, OR = 7.62) and lack of ectoparasite prophylaxis (P = 0.001, OR = 3.03). The frequency of positive Babesia spp. tests did not significantly differ between the 659 dogs that had never left Germany and the 1506 dogs with known stays abroad (P = 0.088).

Conclusions

The possibility of canine infection with B. canis needs to be especially taken into consideration in spring and autumn in Germany as the activity of the tick Dermacentor reticulatus, a potential vector for canine babesiosis, is highest in these seasons. Travel and importation of dogs are considered major factors associated with canine babesiosis in Germany. However, autochthonous Babesia spp. infections also occur in a considerable number of dogs in Germany.

Graphical Abstract
Multi-scale characterisation of homologous recombination deficiency in breast cancer
Authors: Jacobson Daniel H. , Pan Shi , Fisher Jasmin , Secrier Maria
Published: November 2023

Background

Homologous recombination is a robust, broadly error-free mechanism of double-strand break repair, and deficiencies lead to PARP inhibitor sensitivity. Patients displaying homologous recombination deficiency can be identified using ‘mutational signatures’. However, these patterns are difficult to reliably infer from exome sequencing. Additionally, as mutational signatures are a historical record of mutagenic processes, this limits their utility in describing the current status of a tumour.

Methods

We apply two methods for characterising homologous recombination deficiency in breast cancer to explore the features and heterogeneity associated with this phenotype. We develop a likelihood-based method which leverages small insertions and deletions for high-confidence classification of homologous recombination deficiency for exome-sequenced breast cancers. We then use multinomial elastic net regression modelling to develop a transcriptional signature of heterogeneous homologous recombination deficiency. This signature is then applied to single-cell RNA-sequenced breast cancer cohorts enabling analysis of homologous recombination deficiency heterogeneity and differential patterns of tumour microenvironment interactivity.

Results

We demonstrate that the inclusion of indel events, even at low levels, improves homologous recombination deficiency classification. Whilst BRCA-positive homologous recombination deficient samples display strong similarities to those harbouring BRCA1/2 defects, they appear to deviate in microenvironmental features such as hypoxic signalling. We then present a 228-gene transcriptional signature which simultaneously characterises homologous recombination deficiency and BRCA1/2-defect status, and is associated with PARP inhibitor response. Finally, we show that this signature is applicable to single-cell transcriptomics data and predict that these cells present a distinct milieu of interactions with their microenvironment compared to their homologous recombination proficient counterparts, typified by a decreased cancer cell response to TNFα signalling.

Conclusions

We apply multi-scale approaches to characterise homologous recombination deficiency in breast cancer through the development of mutational and transcriptional signatures. We demonstrate how indels can improve homologous recombination deficiency classification in exome-sequenced breast cancers. Additionally, we demonstrate the heterogeneity of homologous recombination deficiency, especially in relation to BRCA1/2-defect status, and show that indications of this feature can be captured at a single-cell level, enabling further investigations into interactions between DNA repair deficient cells and their tumour microenvironment.
Outer approximated projection and contraction method for solving variational inequalities
Authors: Uzor V. A. , Mewomo O. T. , Alakoya T. O. , Gibali A.
Published: November 2023

In this paper we focus on solving the classical variational inequality (VI) problem. Most common methods for solving VIs use some kind of projection onto the associated feasible set. Thus, when the involved set is not simple to project onto, then the applicability and computational effort of the proposed method could be arguable. One such scenario is when the given set is represented as a finite intersection of sublevel sets of convex functions. In this work we develop an outer approximation method that replaces the projection onto the VI’s feasible set by a simple, closed formula projection onto some “superset”. The proposed method also combines several known ideas such as the inertial technique and self-adaptive step size.

Under standard assumptions, a strong minimum-norm convergence is proved and several numerical experiments validate and exhibit the performance of our scheme.
Strategies to support substance use disorder care transitions from acute-care to community-based settings: a scoping review and typology
Authors: Krawczyk Noa , Rivera Bianca D. , Chang Ji E. , Grivel Margaux , Chen Yu-Heng , Nagappala Suhas , Englander Honora , McNeely Jennifer
Published: November 2023

Background

Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies.

Methods

We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000 and 2021 that studied interventions linking patients with SUD from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research.

Results

Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) or alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care.

Conclusions

Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.
Signatures of adaptation in myopia-related genes on the sunlight exposure hypothesis
Authors: Xia Tian , Nakayama Kazuhiro
Published: November 2023

Background

Myopia is a common eye disorder that results from gene-environment interactions. The prevalence of myopia varies across populations, and exposure to bright sunlight may prevent its development. We hypothesize that local adaptation to light environments during human migration played a role in shaping the genetic basis of myopia, and we aim to investigate how the environment influences the genetic basis of myopia.

Method

We utilized the whole-genome variant data of the 1000 Genomes Project for analysis. We searched myopia-associated loci that were under selection in Europeans using population branch statistics and the number of segregating sites by length statistics. The outliers of these statistics were enriched in the Kyoto Encyclopedia of Genes and Genomes pathways and the gene ontology biological process terms in searching for pathways that were under selection. We applied Bayesian inference to estimate the correlation between environmental factors and allele frequencies of the selected loci and performed causal inference of myopia using two-sample Mendelian randomization analysis.

Results

We detected signatures of adaptation in vision and light perception pathways, supporting our hypothesis of sunlight adaptation. We discovered a strong correlation between latitude and allele frequencies in genes that are under significant selection, and we found pleiotropic effects of pigmentation or circadian rhythm genes on myopia, indicating that sunlight exposure influences the genetic diversity of myopia.

Conclusions

Myopia genes involved in light perception showed signs of selection. Local adaptation during human migration shaped the genetic basis of myopia and may have influenced its global prevalence distribution.
Cryptic behavior and activity cycles of a small mammal keystone species revealed through accelerometry: a case study of Merriam’s kangaroo rats (Dipodomys merriami)
Authors: Hanscom Ryan J. , Hill Jessica L. , Patterson Charlotte , Marbach Tyler , Sukumaran Jeet , Higham Timothy E. , Clark Rulon W.
Published: November 2023

Background

Kangaroo rats are small mammals that are among the most abundant vertebrates in many terrestrial ecosystems in Western North America and are considered both keystone species and ecosystem engineers, providing numerous linkages between other species as both consumers and resources. However, there are challenges to studying the behavior and activity of these species due to the difficulty of observing large numbers of individuals that are small, secretive, and nocturnal. Our goal was to develop an integrated approach of miniaturized animal-borne accelerometry and radiotelemetry to classify the cryptic behavior and activity cycles of kangaroo rats and test hypotheses of how their behavior is influenced by light cycles, moonlight, and weather.

Methods

We provide a proof-of-concept approach to effectively quantify behavioral patterns of small bodied (< 50 g), nocturnal, and terrestrial free-ranging mammals using large acceleration datasets by combining low-mass, miniaturized animal-borne accelerometers with radiotelemetry and advanced machine learning techniques. We developed a method of attachment and retrieval for deploying accelerometers, a non-disruptive method of gathering observational validation datasets for acceleration data on free-ranging nocturnal small mammals, and used these techniques on Merriam’s kangaroo rats to analyze how behavioral patterns relate to abiotic factors.

Results

We found that Merriam’s kangaroo rats are only active during the nighttime phases of the diel cycle and are particularly active during later light phases of the night (i.e., late night, morning twilight, and dawn). We found no reduction in activity or foraging associated with moonlight, indicating that kangaroo rats are actually more lunarphilic than lunarphobic. We also found that kangaroo rats increased foraging effort on more humid nights, most likely as a mechanism to avoid cutaneous water loss.

Conclusions

Small mammals are often integral to ecosystem functionality, as many of these species are highly abundant ecosystem engineers driving linkages in energy flow and nutrient transfer across trophic levels. Our work represents the first continuous detailed quantitative description of fine-scale behavioral activity budgets in kangaroo rats, and lays out a general framework for how to use miniaturized biologging devices on small and nocturnal mammals to examine behavioral responses to environmental factors.
Evaluation of the resistance of three maize varieties to Spodoptera frugiperda (J.E. Smith) and Ostrinia nubilalis Hübner in the Tonkpi region (Man, Côte d’Ivoire)
Authors: Diabate Dohouonan , Tah Gueu Tatiana Thérèse , Ble Yatanan Casimir , Tano Yao
Published: November 2023

Background

The corn borer Ostrinia nubilalis and the fall armyworm Spodoptera frugiperda larvae feed on the aerial parts of maize. It is responsible for significant yield losses and are therefore a cause of food insecurity. This study carried out to evaluate the resistance of three maize varieties (EV8766 SR-MRP, PR9131-SR, CEW-SR), in Tonkpi region’s, to S. frugiperda and O. nubilalis damages. Each maize variety seeds were sown on a one hectare plot subdivided into 6 elementary plots with 75 cm between rows and 40 cm between bunches. Sampling of S. frugiperda and O. nubilalis larvae on maize plants was carried out according to the FAO method, from the third to the fifth week after planting. Maize plants damaged, the intensity of infestation and the number of larvae on maize plants were recorded. Maize plants damaged by the insect pests were marked to avoid recounting. At maturity, 100 maize cobs were harvested per elementary plot, then the larvae number and the attacked cobs by S. frugiperda and O. nubilalis larvae were recorded.

Results

The lowest damage rate by S. frugiperda were recorded in maize variety EV8766-SR-MRP (23.33%); while, the highest damage rate were in the varieties PR9131-SR (43.33%) and CEW-SR (55%). There are no significant difference values of the density of S. frugiperda larvae per maize plant attacked between the three varieties. The index of intensification of maize plant damaged by S. frugiperda larvae was lower for the variety EV8766-SR-MRP (7.50%) and was moderate for the varieties PR9131-SR (15.42%) and CEW-SR (21.67%). The damage rates of O. nubilalis larvae on maize cobs varied between 9.6 and 22.0%. These damage rates were higher for the varieties PR9131-SR (21.83%) and CEW-SR (17.50%) and were lower for EV8766-SR-MRP (9.66%). There was not significantly different from the density of O. nubilalis larvae per maize cob attacked between the three varieties. It was between 1 to 1.2 larvae. Crop losses were lower for EV8766 SR-MRP (10.228%) than those of PR9131-SR and CEW-SR (19.338%).

Conclusions

The maize variety EV8766-SR-MRP is found to be the best variety in the control of, O. nubilalis and S. frugiperda.
Robotic arm-assisted unicondylar knee arthroplasty resulted in superior radiological accuracy: a propensity score-matched analysis
Authors: Yeung Matthew H. Y. , Fu Henry , Cheung Amy , Kwan Vincent Chan Wai , Cheung Man Hong , Chan Ping Keung , Chiu Kwong Yuen , Yan Chun Hoi
Published: November 2023

Introduction

Unicompartmental knee arthroplasty (UKA) is an effective surgical treatment for medial compartment arthritis of the knee, yet surgical outcomes are directly related to surgical execution. Robotic arm-assisted surgery aims to address these difficulties by allowing for detailed preoperative planning, real-time intraoperative assessment and haptic-controlled bone removal. This study aimed to compare the clinical and radiological outcomes between conventional manual mobile bearing and robot arm-assisted fixed bearing medial UKA in our local population.

Materials and methods

This is a retrospective case–control study of 148 UKAs performed at an academic institution with a minimum of 1-year follow-up. 74 robotic arm-assisted UKAs were matched to 74 conventional UKAs via propensity score matching. Radiological outcomes included postoperative mechanical axis and individual component alignment. Clinical parameters included a range of motion, Knee Society knee score and functional assessment taken before, 6 and 12 months after the operation.

Results

Robot arm-assisted UKA produced a more neutral component coronal alignment in both femoral component (robotic -0.2 ± 2.8, manual 2.6 ± 2.3; P = 0.043) and tibial component (robotic -0.3 ± 4.0, manual 1.7 ± 5.3; P < 0.001). While the postoperative mechanical axis was comparable, robot arm-assisted UKA demonstrated a smaller posterior tibial slope (robotic 5.7 ± 2.7, manual 8.2 ± 3.3; P = 0.02). Clinical outcomes did not show any statistically significant differences.

Conclusion

Compared with conventional UKA, robotic arm-assisted UKA demonstrated improved component alignment and comparable clinical outcomes. Improved radiological accuracy with robotic-arm assistance demonstrated promising early results.
Analysing time-use composition as dependent variables in physical activity and sedentary behaviour research: different compositional data analysis approaches
Authors: von Rosen Philip
Published: November 2023

Recently, there has been a paradigm shift from considering physical activity and sedentary behaviour as “independent” risk factors of health to acknowledging their co-dependency and compositional nature. The focus is now on how these behaviours relate to each other rather than viewing them in isolation. Compositional data analysis (CoDA) is a methodology that has been developed specifically for compositional data and the number of publications using CoDA in physical activity and sedentary behaviour research has increased rapidly in the past years. Yet, only a small proportion of the published studies in physical activity and sedentary behaviour research have investigated the time-use composition as dependent variables. This could be related to challenges regarding the interpretation of the results and the lack of guidelines for deciding which statistical approach to use. Therefore, in this paper, four different approaches for analysing the time-use composition as dependent variables are presented and discussed. This paper advocates that the aim of research should guide how the dependent variable is defined and which data analysis approach is selected, and it encourages researchers to consider analysing time-use components as dependent variables in physical activity and sedentary behaviour research.
Breast Cancer Phenotypes in Africa: A Scoping Review and Meta-Analysis
Authors: Onyia Abimbola F. , Nana Toluwani A. , Adewale Elijah A. , Adebesin Ayomide O. , Adegboye Bose E. , Paimo Oluwatomiwa K. , De Campos Opeyemi C. , Bisi-Adeniyi Titilayo I. , Rotimi Oluwakemi A. , Oyelade Jelili O. , Rotimi Solomon O.
Published: November 2023

PURPOSE

Africans have been associated with more aggressive forms of breast cancer (BC). However, there is a lack of data regarding the incidence and distribution of different subtypes on the basis of phenotypic classification. This scoping review and meta-analysis was undertaken to determine the distribution pattern of BC phenotypes (luminal, human epidermal growth factor receptor 2 [HER2]+, and triple-negative breast cancer [TNBC]) across the African region.

METHODS

Four online databases (PubMed, Scopus, ProQuest, and EBSCOhost) were accessed to identify studies published between 2000 and 2022 reporting the representation of receptor status (estrogen receptor, progesterone receptor, and HER2) in African patients with BC. Furthermore, the meta-analysis was carried out using a random-effects model and pooled using the inverse variance method and logit transformation. 95% CI and I2 statistics were calculated using the Clopper-Pearson method to estimate between-study heterogeneity.

RESULTS

A total of 2,734 records were retrieved, of which 2,133 were retained for further screening. After the screening, 63 studies were finally selected for the scoping review and meta-analysis. The pooled frequency of luminal, HER2-positive (HER2+), and TNBC was estimated at 56.30%, 12.61%, and 28.10%, respectively. Northern Africa had the highest frequency of the luminal subtype, while West Africa showed higher frequencies of HER2+ and TNBC subtypes. The review also had a representation of only 24 countries in Africa.

CONCLUSION

Our results highlight the disparity in the representation of molecular subtypes among the people in different regions of Africa. There is a need to incorporate routine molecular subtyping into the management of African patients with BC.
Probing mean values and correlations of high-spin systems on a quantum computer
Authors: Kuzmak A. R. , Tkachuk V. M.
Published: November 2023

We consider simulation of the high spins on a quantum computer. The protocols which allow one to measure the mean value of spin and correlations between spins are proposed. As a result, we determine the time dependence of the mean values of spin-1 in the magnetic field prepared on the ibmq-santiago quantum computer. In addition, we study the evolution of two interacting spins on the ibmq-lima quantum computer. The time-dependencies of the mean value of spin-1 and correlations between these spins are detected. Finally, we generalize these protocols for the spins of arbitrary values.