bluuebunny/crossref_metadata_2025 huggingface dataset:
Sandwich Structures With Bio-Inspired Viscoelastic Optimized Suture Face Sheets for Blast Mitigation
Authors: Raut Manish Suresh , Patel Mital Limjibhai , Verma Harshit , Gopalakrishnan S , Jagadeesh Gopalan
Published: April 2023

In this paper, the performance of a novel bio-inspired face sheet in mitigating the effects of blast loading is investigated. The new design of the face sheet consists of an optimized bio-inspired suture structure sandwiched between two aluminium plates. The suture profile is obtained by performing structural optimization using Genetic Algorithm, wherein the dynamic responses obtained using a novel viscoelastic finite element formulation are used. The performance of this optimized suture-based face sheet is experimentally tested in a vertical shock tube which validates the results obtained using commercial finite element software Abaqus. The hybrid sandwich structure composed of an aluminium honeycomb core sandwiched between the developed face sheets is evaluated numerically for its blast resistance performance. The study shows that the proposed face sheet design, not only reduces the stresses in the face sheets significantly, but also reduces the core stresses compared to conventional aluminium face sheet–based sandwich structures. Several parametric studies are presented for axial and transverse shock loading on this hybrid sandwich structures that give more insight into their wave propagation characteristics.
The international dynamics of counter-peace
Authors: Richmond Oliver P. , Pogodda Sandra , Visoka Gëzim
Published: April 2023

Peace processes and international order are interdependent: while the latter provides the normative framework for the former, peacemaking tools and their underlying ideology also maintain international order. They indicate its viability and legitimacy partly by meeting local claims as well as though the maintenance of geopolitical balances. In the emerging multipolar order, the international peace architecture (IPA), dominated by the liberal international order (LIO), is contested through counter-peace processes. These processes contest the nature of the state, state-society relations and increasingly international order itself. This paper investigates the tactics and strategies of regional actors and great powers, where they engage in peace and order related activities or interventions. Given the weakness and inconsistency of the IPA and the LIO, such contestation leads to challenges to international order itself, often at the expense of the claims of social movements and civil society networks.
Local political space: Localism, the left-right dimension and anti-elitism
Authors: Otjes Simon
Published: April 2023

This paper presents a three-dimensional approach to party political conflict at the local level, drawing from an anti-elitism dimension, the left-right dimension and a localism dimension. More than 4500 parties participating in the 2014 and 2018 Dutch municipal elections are placed on these dimensions on the basis of their manifestos using quantitative textual analysis. A three-pronged approach is used to justify this three-dimensional model. The three dimensions are shown to be empirically distinctive. They are revealed to reflect meaningful differences between parties that are also visible in their names; and finally, these dimensions are shown to predict participation in local executive coalitions.
‘Provision of safety netting information during child health consultations; a systematic narrative review of caregivers’ perspectives’
Authors: Owen Dave , Latter Sue
Published: April 2023

Safety netting (SN) provides specific information to caregivers identifying need to re-consult. SN is often used to bridge diagnostic uncertainty for first-contact healthcare professionals. This systematic narrative review investigated experiences of caregivers’ regarding SN information received during acute child health consultations. Searches between April and December 2021 of six bibliographic databases (CINAHL, PsycINFO, BNI, EMCARE, MEDLINE and Web of Science) identified 3258 records. No studies were excluded based on quality and nine papers were included; the Mixed Methods Appraisal Tool was used to critically analyse papers and findings were summarised narratively. Four themes emerged: Importance of receiving Red-Flag-Symptom information, influences of specific mediums for information transfer to caregivers, key principles of SN as desired by caregivers and contextual influences of information transfer to caregivers. Quality of evidence was fair; review findings could provide underpinning principles to enable first-contact clinicians to enhance their person-centred approach to SN practice. There was a paucity of evidence generally, with a relatively small number of studies that captured specific SN activity during consultations. More research is also needed to capture the full-breadth of first-contact clinicians, particularly in non-clinical settings such as the home or school.
A feminist embodied ethics of social media use: Corporeal vulnerability and relational care practices
Authors: Toffoletti Kim , Thorpe Holly , Olive Rebecca , Pavlidis Adele , Moran Claire
Published: April 2023

This article adopts a feminist relational orientation to investigate the care practices that women develop when producing and engaging with body-focussed content online. We propose and argue for an embodied ethics of social media use to understand women’s enactments and exchanges as they relate to shared corporeal concerns. Drawing on qualitative interview data, and using Judith Butler’s understanding of corporeal vulnerability as the basis for mutual recognition, this article investigates social actors’ ethical orientations towards, and attempts at, improving the collective experiences of women in the context of Instagram use for physical activity. We identify several ways in which exercising women practice an embodied ethics of care on Instagram, including sharing unedited images of themselves, not judging others’ bodies, awareness-raising and supporting others. By conceptualising women’s everyday social media encounters as an embodied ethical practice, this study develops new theoretical insights to understand women’s sharing of body-focussed content online.
Patterns of Party Positioning in Referendums in Switzerland
Authors: Hornig Eike-Christian
Published: April 2023

Parties play an important role in the study of direct democracy, but mainly as independent variables. To start investigating the way in which parties position themselves in referendums, a new framework is presented and tested for plausibility. As case study the complex but well observed case of Swiss Direct Democracy was chosen. First, a differentiated understanding of what a party position in a referendum process is leads to the identification of four different stages of positioning for Swiss parties. The main message of the theoretical framework is that positioning logics of different parties in one vote can be similar when there are underlying mechanisms applying to all parties. Four ideal type models of party positioning show how. To explore their plausibility, an original data set of 162 single positions of five Swiss political parties in 37 national referendums between 2015 and 2019 is compiled. Using qualitative methods, first results show that Swiss parties’ positioning in referendums is not as strongly dominated by policy as one could expect,given the strong polarization of the party system. In consequence, this demands for an update of our understanding of the interplay of direct democracy and political parties as a two-way channel.
Implementation of Quitline Financial Incentives to Increase Counseling Sessions Among Adults Who Use Menthol Tobacco Products
Authors: Bourne Dana E. , Williams Rhonda , Osbahr Lisa , Roemhildt Maria , Villanti Andrea C.
Published: April 2023

Since 2017, the Vermont Tobacco Control Program (VTCP) has worked to reduce the impact of flavored tobacco products on Vermonters. With the proposed U.S. Food and Drug Administration (FDA) rules banning menthol cigarettes and flavored cigars and proposed legislation banning sales of all menthol and flavored tobacco products in Vermont, VTCP prioritized resources to support cessation among Vermonters who use menthol tobacco products. In March 2021, VTCP began offering a tailored quitline protocol for adults who use menthol tobacco, including financial incentives, for completed coaching sessions. From March 2021 to May 2022, 66 quitline callers enrolled in the menthol incentive protocol, representing 8% of all quitline callers and 25% of participants in the state’s quitline incentive programs. A greater proportion of callers in the menthol incentive program completed three or more quitline calls (58% vs. 38%) and enrolled in phone and text support (61% vs. 32%). Quitline callers enrolled in any incentive protocols (menthol, Medicaid/uninsured, or pregnant) were more likely to request one or two forms of nicotine replacement therapy (NRT). Quitlines remain an effective, evidence-based method of tobacco cessation, especially in reaching vulnerable populations. Given the targeted marketing of menthol brands to Black and African American populations, LGBTQ+ populations, youth, and neighborhoods with lower incomes, addressing menthol cigarette use is key to improving health equity and health of Vermonters. Early data indicates that the use of financial incentives can increase engagement with a state quitline among menthol tobacco users through greater completion of cessation coaching calls, enrollment in text message support, and NRT usage.
The new era of prostate-specific membrane antigen-directed immunotherapies and beyond in advanced prostate cancer: a review
Authors: Martin Felicity C. , Dorff Tanya B. , Tran Ben
Published: April 2023

The lack of success in prostate cancer from immune checkpoint inhibitors, which is likely multifactorial, has led to the development and investigation of a number of other novel immunotherapeutic techniques, including antibody–drug conjugates, T-cell redirected bispecific therapies, cancer vaccines and chimeric antigen receptor T-cell therapies. Prostate-specific membrane antigen (PSMA) is a tumour-associated antigen (TAA) that is highly expressed in metastatic prostate cancer and has been validated as an effective target for radionuclide treatment. But while PSMA has thus far been the ‘front runner’ target for these novel immunotherapeutic techniques, it may not be the ideal target for immunotherapy and there are other potential targetable TAAs that will require further exploration. This review will focus on these various PSMA-directed therapies, as well as other potential targets for immunotherapy beyond PSMA.
Circulating tumor DNA: Response Evaluation Criteria in Solid Tumors – can we RECIST? Focus on colorectal cancer
Authors: Spindler Karen-Lise Garm , Jakobsen Anders
Published: April 2023

Interest in the measurement of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) has increased during the past decade. The analysis of quantitative ctDNA changes as a general response evaluation criterion during systemic treatment is a scientific approach with high clinical potential, and results can be transferred to a pan-cancer concept if relevantly investigated. The purpose of this overview is to discuss the current evidence for ctDNA as a marker of response in metastatic CRC (mCRC) and to propose criteria for definitions of response to systemic therapies applicable in prospective clinical trials. We discuss the literature, which supports a new definition of ctDNA Response Evaluation Criteria in Solid Tumors. Finally, we discuss the challenges in preparations of the optimal trial design to establish the true clinical utility of ctDNA.
Functional MRI during tongue strength tasks before and after partial glossectomy: Insights into the cortical activation of tongue motor function
Authors: Peck Kyung K , Cho Nicholas S , Pasquini Luca , Jenabi Mehrnaz , Branski Ryan C , Lazarus Cathy L , Kraus Dennis H , Holodny Andrei I
Published: April 2023

Aim

Because the tongue is a midline structure, studies on the neural correlates of lateralized tongue function are challenging and remain limited. Patients with tongue cancer who undergo unilateral partial glossectomy may be a unique cohort to study tongue-associated cortical activation, particularly regarding brain hemispheric lateralization. This longitudinal functional magnetic resonance imaging (fMRI) study investigated cortical activation changes for three tongue tasks before and after left-sided partial glossectomy in patients with squamous cell carcinoma of the tongue.

Methods

Seven patients with squamous cell carcinoma involving the left tongue who underwent fMRI before and 6 months after unilateral partial glossectomy were studied. Post-surgical changes in laterality index (LI) values for tongue-associated precentral and postcentral gyri fMRI activation were calculated for the dry swallow, tongue press, and saliva sucking tasks. Group analysis fMRI activation maps were generated for each of the three tasks.

Results

There were significant differences in changes in LI values post-surgery between the tongue press ( p < 0.005; median: +0.24), saliva sucking (−0.10), and dry swallow tasks (−0.16). Decreased contralateral activation (change in LI ≥+0.20) was observed post-surgery during tongue press in six of seven patients, but only in two patients during saliva sucking and one patient during dry swallow ( p < 0.05). There was also increased activation in the supplementary motor area following surgery.

Conclusion

Post-surgical fMRI changes following left-sided partial glossectomy may suggest task-specific sensitivities to cortical activation changes following unilateral tongue deficits that may reflect the impacts of surgery and adaptive responses to tongue impairment.
Association between age, sex and cervical and upper cervical rotation tests. Descriptive and correlational study in healthy volunteers
Authors: Zárate-Tejero Carlos , Hidalgo-García César , Lucha-López Orosia , Hernández-Secorún Mar , Krauss John , Rodríguez-Rubio Pere
Published: April 2023

Background:

Active cervical spine rotation (ACROM Rot) shows cervical rotation and flexion rotation test (FRT); side-bending rotation test (SBRT) and upper cervical axial rotation test (C0–C2ART) are described to measure upper cervical rotation. The objectives of this study are (1) to describe the normal range of motion (ROM) of ACROM Rot, and the ROM in FRT, SBRT and C0–C2ART tests; (2) to explore the correlation among the four tests and (3) to investigate the influence of age and sex in their ROM.

Methods:

A cross-sectional study was carried out with healthy volunteers from 18 to 75 years of age. Tests were measured using a CROM device and a bubble inclinometer. Descriptive analysis was performed to establish normative data for the ROM tests. Correlation analysis was conducted to understand the relation between upper and global cervical rotation ROM and among the three upper cervical rotation tests. Linear regression models were developed to understand the influence of age and sex in the ROM of all tests.

Results:

Normative values were obtained from 122 healthy volunteers (50% male), by sex and age strata. The degree of correlation ranged between 0.582 ( p < 0.01) for FRT and ACROM Rot left and 0.217 ( p < 0.05) for SBRT and C0–C2ART left. Linear regression models showed the influence of sex for ACROM Rot right (men −4.64° less than women), SBRT (men −4.1° less than women) left and C0–C2ART right and left (men −2.24° and −1.78° less than women). The age influenced rotation ROM with a decrease for every 10 years of −2.11° and −1.96° for ACROM Rot right and left, of −1.72° and −1.26° for FRT right and left and −0.58° and −0.41° for C0–C2ART right and left in the linear regression models. No association was found between age and SBRT ( p = 0.63 for right SBRT and p = 0.49 for left SBRT).

Conclusion:

Weak-to-moderate correlation was found between the upper cervical spine rotation tests and with the ACROM. Women had a larger ROM in ACROM Rot right, SBRT left and C0–C2ART. Decreases in ROM related with age were observed for ACROM Rot, FRT and C0–C2ART but not for SBRT.
Improving access to HIV testing for pregnant women in community birth centres in Nigeria: an evaluation of the Prevention of Mother-to-Child Transmission program
Authors: Nwanja Esther , Akpan Uduak , Toyo Otoyo , Nwaokoro Pius , Badru Titilope , Gana Bala , Nwanja Ifeyinwa , Ayabi Oruayefe , Ayeni Bishop , Xavier Emem , Idemudia Augustine , Sanwo Olusola , Khamofu Hadiza , Bateganya Moses
Published: April 2023

Background:

The elimination of mother-to-child HIV transmission requires access to HIV testing services (HTS) for pregnant women. In Akwa Ibom, Nigeria, 76% of pregnant women receive antenatal care from traditional birth attendants and may not have access to HIV testing.

Objectives:

This study examines the contribution of traditional birth attendants and other healthcare workers in community birth centres in improving access to HTS among pregnant women and their HIV-exposed infants.

Design:

A retrospective cross-sectional study of previously collected programme data at two points in time to evaluate the prevention of mother-to-child transmission (PMTCT) programme.

Methods:

We assessed programme records before and after introducing an intervention that engaged traditional birth attendants and other healthcare workers in community birth centres to expand access to HTS among pregnant women and their HIV-exposed infants in Akwa Ibom State, Nigeria. Data were abstracted from the programme database for the preintervention period (April 2019 to September 2020) and the intervention period (October 2020 to March 2022). Data abstracted include the number of pregnant women tested for HIV, those diagnosed with HIV, the number of HIV-exposed infants who had samples collected for early infant diagnosis and those diagnosed with HIV. The data were analysed descriptively and inferentially.

Results:

Before the intervention, 39,305 pregnant women and 2248 HIV-exposed infants were tested for HIV. After the intervention, the number of pregnant women tested increased to 127,005 and the number of HIV-exposed infants tested increased to 2490. Among pregnant women, the postintervention testing increased by 3.2-fold, with community birth centres reporting 63% of all tests. The intervention also resulted in an 11% increase in HIV-exposed infants benefitting from early infant diagnosis with community birth centres reporting 5% of all tests. Of those diagnosed with HIV, 24% of pregnant women and 12% of infants were diagnosed at community birth centres.

Conclusion:

Community-based HIV testing for pregnant women can reduce mother-to-child transmission and improve early diagnosis and treatment of exposed infants. Collaboration with birth attendants is crucial to ensure testing opportunities are not missed. Prospective research is needed to understand the clinical outcomes of intervention programmes in the community.
In memory of Will Steffen, 1947–2023
Authors: Oldfield Frank
Published: April 2023

Will Steffen’s death has prompted the present article that attempts to summarise the many aspects of his contribution to our understanding of Earth System science, his role as an outstanding leader and communicator and the affection and respect he earned from his many colleagues, friends and associates. Personal recollections of Will from his time as Executive Director of the International Geosphere-Biosphere Programme (IGBP) and as contributor to and fellow editor of the Anthropocene Review are also included.
Dysautonomia in two littermate kittens
Authors: Černá Petra , Botts Michaela M , Watson Allison , Carr Susan V
Published: April 2023

Case summary

Two 6-month-old littermate Russian Blue cross kittens presented for megaesophagus, intermittent vomiting and regurgitation. The male kitten was diagnosed with aspiration pneumonia and was suspected to have a hiatal hernia on thoracic radiographs. It presented 1 month later in acute respiratory distress and was euthanized. Post-mortem examination revealed a severe gastroesophageal intussusception with approximately 90% of the stomach inverted into the distal esophagus. Histologic examination confirmed dysautonomia with marked neuronal dropout and degeneration with necrosis, satellitosis of the celiac ganglion and the myenteric and submucosal plexuses throughout the gastrointestinal tract. The less-affected littermate showed improvement on cisapride and was doing well at home at the time of writing.

Relevance and novel information

Dysautonomia is rare in cats, with only a few reports of affected littermates. Both kittens are significantly younger than the median age previously reported. Detailed descriptions of diagnostic and histopathology findings are included. Gastroesophageal intussusception is a novel complication to consider when managing feline dysautonomia.
The Role of Frailty and Sarcopenia in Predicting Major Adverse Events, Length of Stay and Reoperation Following En Bloc Resection of Primary Tumours of the Spine
Authors: Moskven Eryck , Lasry Oliver , Singh Supriya , Flexman Alana M. , Street John T. , Dea Nicolas , Fisher Charles G. , Ailon Tamir , Dvorak Marcel F. , Kwon Brian K. , Paquette Scott J. , Charest-Morin Raphaële
Published: April 2023

Study Design

Retrospective observational cohort study.

Objective

En bloc resection for primary tumours of the spine is associated with a high rate of adverse events (AEs). The objective was to explore the relationship between frailty/sarcopenia and major perioperative AEs, length of stay (LOS), and unplanned reoperation following en bloc resection of primary spinal tumours.

Methods

This is a unicentre study consisting of adult patients undergoing en bloc resection for a primary spine tumor. Frailty was calculated with the modified frailty index (mFI) and spine tumour frailty index (STFI). Sarcopenia was quantified with the total psoas area/vertebral body area ratio (TPA/VB) at L3 and L4. Univariable regression analysis was used to quantify the association between frailty/sarcopenia and major perioperative AEs, LOS and unplanned reoperation.

Results

95 patients met the inclusion criteria. The mFI and STFI identified a frailty prevalence of 3% and 18%. Mean CT TPA/VB ratios were 1.47 (SD ± .05) and 1.83 (SD ± .06) at L3 and L4. Inter-observer reliability was .93 and .99 for CT and MRI L3 and L4 TPA/VB ratios. Unadjusted analysis demonstrated sarcopenia and mFI did not predict perioperative AEs, LOS or unplanned reoperation. Frailty defined by an STFI score ≥2 predicted unplanned reoperation for surgical site infection (SSI) ( P < .05).

Conclusions

The STFI was only associated with unplanned reoperation for SSI on unadjusted analysis, while the mFI and sarcopenia were not predictive of any outcome. Further studies are needed to investigate the relationship between frailty, sarcopenia and perioperative outcomes following en bloc resection of primary spinal tumors.
Small Savings Scheme of the Post Office and Savings Habit of People: The Role of Financial Consultant
Authors: Mohanta Giridhari
Published: April 2023

The small savings scheme plays a vital role in mobilizing savings for the economy, and the post office provides a variety of products to people to promote a savings habit. The current research attempts to analyze the moderation effect of financial consultants in relationship between the small savings scheme of the post office, financial literacy and behavior, and the savings habit of people. The study exhibits a significant positive impact of predictors and moderation variables on savings habits. In this regard, a two-phase structural equation modeling (SEM) has been employed to validate the hypothesized measurement model using confirmatory factor analysis (CFA), and in the next phase, the structural model verifies the hypothesized association between exogenous and endogenous variables to draw rational inferences. And a positive effect of predictors and interaction variables is observed. Finally, the study concluded with an important suggestion for the investment manager and other intermediaries: integrate the financial engineering process by giving due importance to investor needs.
On the holobiont ‘predictome’ of immunocompetence in pigs
Authors: Calle-García Joan , Ramayo-Caldas Yuliaxis , Zingaretti Laura M. , Quintanilla Raquel , Ballester María , Pérez-Enciso Miguel
Published: May 2023

Background

Gut microbial composition plays an important role in numerous traits, including immune response. Integration of host genomic information with microbiome data is a natural step in the prediction of complex traits, although methods to optimize this are still largely unexplored. In this paper, we assess the impact of different modelling strategies on the predictive capacity for six porcine immunocompetence traits when both genotype and microbiota data are available.

Methods

We used phenotypic data on six immunity traits and the relative abundance of gut bacterial communities on 400 Duroc pigs that were genotyped for 70 k SNPs. We compared the predictive accuracy, defined as the correlation between predicted and observed phenotypes, of a wide catalogue of models: reproducing kernel Hilbert space (RKHS), Bayes C, and an ensemble method, using a range of priors and microbial clustering strategies. Combined (holobiont) models that include both genotype and microbiome data were compared with partial models that use one source of variation only.

Results

Overall, holobiont models performed better than partial models. Host genotype was especially relevant for predicting adaptive immunity traits (i.e., concentration of immunoglobulins M and G), whereas microbial composition was important for predicting innate immunity traits (i.e., concentration of haptoglobin and C-reactive protein and lymphocyte phagocytic capacity). None of the models was uniformly best across all traits. We observed a greater variability in predictive accuracies across models when microbiability (the variance explained by the microbiome) was high. Clustering microbial abundances did not necessarily increase predictive accuracy.

Conclusions

Gut microbiota information is useful for predicting immunocompetence traits, especially those related to innate immunity. Modelling microbiome abundances deserves special attention when microbiability is high. Clustering microbial data for prediction is not recommended by default.
Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs
Authors: Wu Tong , Li Na , Luo Fengyuan , Chen Zhihong , Ma Liyuan , Hu Tao , Hong Guini , Li Hongdong
Published: April 2023

Background

Pyroptosis is closely related to cancer prognosis. In this study, we tried to construct an individualized prognostic risk model for hepatocellular carcinoma (HCC) based on within-sample relative expression orderings (REOs) of pyroptosis-related lncRNAs (PRlncRNAs).

Methods

RNA-seq data of 343 HCC samples derived from The Cancer Genome Atlas (TCGA) database were analyzed. PRlncRNAs were detected based on differentially expressed lncRNAs between sample groups clustered by 40 reported pyroptosis-related genes (PRGs). Univariate Cox regression was used to screen out prognosis-related PRlncRNA pairs. Then, based on REOs of prognosis-related PRlncRNA pairs, a risk model for HCC was constructed by combining LASSO and stepwise multivariate Cox regression analysis. Finally, a prognosis-related competing endogenous RNA (ceRNA) network was built based on information about lncRNA–miRNA–mRNA interactions derived from the miRNet and TargetScan databases.

Results

Hierarchical clustering of HCC patients according to the 40 PRGs identified two groups with a significant survival difference (Kaplan–Meier log-rank, p = 0.026). Between the two groups, 104 differentially expressed lncRNAs were identified (|log2(FC)|> 1 and FDR < 5%). Among them, 83 PRlncRNA pairs showed significant associations between their REOs within HCC samples and overall survival (Univariate Cox regression, p < 0.005). An optimal 11-PRlncRNA-pair prognostic risk model was constructed for HCC. The areas under the curves (AUCs) of time-dependent receiver operating characteristic (ROC) curves of the risk model for 1-, 3-, and 5-year survival were 0.737, 0.705, and 0.797 in the validation set, respectively. Gene Set Enrichment Analysis showed that inflammation-related interleukin signaling pathways were upregulated in the predicted high-risk group (p < 0.05). Tumor immune infiltration analysis revealed a higher abundance of regulatory T cells (Tregs) and M2 macrophages and a lower abundance of CD8 + T cells in the high-risk group, indicating that excessive pyroptosis might occur in high-risk patients. Finally, eleven lncRNA–miRNA–mRNA regulatory axes associated with pyroptosis were established.

Conclusion

Our risk model allowed us to determine the robustness of the REO-based PRlncRNA prognostic biomarkers in the stratification of HCC patients at high and low risk. The model is also helpful for understanding the molecular mechanisms between pyroptosis and HCC prognosis. High-risk patients may have excessive pyroptosis and thus be less sensitive to immune therapy.
Different clinical phenotypes of a pair of siblings with familial hypercholesterolemia: a case report and literature review
Authors: Wang Ze-Ping , Wu Ya-Jie , Gao Ying , Qian Jie , Liu Long-Tao , Guo Yuan-Lin , Li Jian-Jun , Chen Ke-Ji
Published: May 2023

Background

Familial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background.

Case presentation

We treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister.

Conclusions

Patients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.
A multiple case study of pre-diabetes care undertaken by general practice in Aotearoa/New Zealand: de-incentivised and de-prioritised work
Authors: Barthow Christine , Krebs Jeremy , McKinlay Eileen
Published: April 2023

Background

In Aotearoa/New Zealand (NZ) general practices diagnose and manage pre-diabetes. This work is important as it has the potential to delay or prevent the onset of Type 2 Diabetes (T2DM), reduce NZ’s health inequities, and the burden that T2DM places on health care services. However, no study has previously examined how this work routinely occurs in NZ.

Methods

Two case studies of practices serving ethnically and socio-economically diverse populations, followed by cross-case analysis.

Results

The NZ health care context including funding mechanisms, reporting targets, and the disease centred focus of care, acted together to dis-incentivise and de-prioritise pre-diabetes care in general practices. The social determinants of health differentially influenced patients’ ability to engage with and respond to pre-diabetes care, significantly impacting this work. Differing perspectives about the significance of pre-diabetes and gaps in systematic screening practices were identified. Interventions used were inconsistent and lacked comprehensive ongoing support.

Conclusions

Complex multi-layered factors impact on pre-diabetes care, and many of the barriers cannot be addressed at the general practice level. The practice serving the most disadvantaged population who concurrently have higher rates of pre-diabetes/T2DM were more adversely affected by the barriers identified.
Colorectal cancer screening completion by patients due or overdue for screening after reminders: a retrospective study
Authors: Ahmed Abdillahi M. , Bacchus Michael W. , Beal Stacy G. , Huber Katherine N. , Lee Ji-Hyun , Zhao Jing , George Thomas J. , Sattari Maryam
Published: May 2023

Background

Patient and clinician reminders were implemented as part of an adherence improvement project at University of Florida (UF) Internal Medicine Clinics. We sought to assess colorectal cancer (CRC) screening completion rates among patients not up-to-date with screening following distribution of reminders and to identify characteristics correlated with screening outcomes.

Methods

Retrospective chart review was performed for patients not up-to-date with CRC screening for whom at least one reminder (patient and/or clinician) was issued in June 2018. The primary endpoint, the completion of a CRC screening test, is characterized as the ratio of completed screening tests to the number of patients not up-to-date with screening. All analyses were performed using R 4.0 software.

Results

Of the 926 patients included, 403 (44%; 95% CI, 0.40–0.47) completed a CRC screening test within 24 months following a reminder. Family history of CRC (relative risk (RR) 1.33; P = 0.007), flu immunization within two years of the reminder (RR 1.23; P = 0.019), and receiving a patient reminder either alone (RR 1.62; P < 0.001) or in combination with a clinician reminder (RR 1.55; P = 0.006) were positively associated with CRC screening completion. Reporting being divorced, separated, or widowed was negatively associated with screening completion (RR 0.70; P = 0.004).

Conclusion

Reminders, in particular patient reminders, seem to be an effective method to enhance screening among patients not up-to-date with CRC screening. This study suggests that reminder efforts should be focused at the level of the patients and provides insight on target populations for practical interventions to further increase CRC screening adherence.
Development and validation of a questionnaire to measure the severity of pain, functional limitations, and reduction of sports ability for german-speaking patients with osteochondral lesions of the ankle (OCLA-G)
Authors: Lohrer Heinz , Wagner Stephanie , Wenning Markus , Kühle Jan , Schmal Hagen , Gollhofer Albert
Published: May 2023

Background

There is no patient-reported functional scale specific for osteochondral lesion of the ankle (OCLA). Therefore, the objectives of this study were to develop a questionnaire that measures symptom severity, function, and sports capacity in patients with osteochondral lesions of the ankle and to determine the psychometric properties of the tool in German language (OCLA-G).

Methods

The OCLA-G questionnaire was developed according to the COSMIN guidelines. Scalable items were generated from a literature search, based on an evaluation of 71 own OCLA patients, and from expert opinions. Following a twofold item reduction the questionnaire underwent explorative data analysis and principal component analysis. Validity and reliability were analysed in four groups of participants (40 patients with OCLA, 40 patients with other foot and ankle injuries, 40 asymptomatic athletes serving as a population at risk, and 40 asymptomatic persons playing sports not at risk). The minimum age for participation in the study was set at 18 years. The mean age was 39.3 ± 15.1 years.

Results

The final OCLA-G questionnaire consists of eight and five questions to mirror activities of daily life (ADL) and sports, respectively. Excellent internal consistency (Cronbach’s α = 0.950 for the ADL subscore and 0.965 for the sport subscale, respectively) was found. Spearman’s rank correlation coefficients for test-retest reliability were 0.992 for the ADL subscore and 0.999 for the sport subscale (p < 0.001). The results of the exploratory and confirmatory factor analyses indicated that item difficulty was between 23.4 and 62.8. The Pearson correlation for the OCLA subscales ADL and sport was 0.853 (p < 0.001). Construct validity as tested against the SF-12 questionnaire subscales (Physical and Mental component scale) were r = -0.164 to -0.663 (p < 0.05). Statistically, there was no ADL and sport OCLA mean score difference between OCLA patients and patients with other foot and ankle injuries (p = 0.993 and 0.179, respectively), but both groups differed from the uninjured control groups (p < 0.001). There were no ceiling or floor effects.

Conclusions

The OCLA-G was successfully developed as the first patient reported and injury specific outcome scale to measure the impact of OCLA induced symptoms on activities of daily living and sport. This study provides evidence for the reliability and validity of the OCLA-G assessing patients with OCLA.

Trial registration

The registration trial number is DRKS00009401 on DRKS. ‘Retrospectively registered’. Date of registration: 10/12/2015.
The genetic landscape of inherited retinal dystrophies in Arabs
Authors: Jaffal Lama , Joumaa Hawraa , Noureldine Jinane , Banjak Malak , Ibrahim Mariam , Mrad Zamzam , Salami Ali , Shamieh Said El
Published: May 2023

Inherited retinal dystrophies (IRDs) are a major cause of vision loss. Altogether are highly heterogeneous genotypically and phenotypically, exhibiting substantial differences worldwide. To shed more light on these conditions, we investigated the genetic and phenotypic landscape of IRDs in the Arabs globally and per country.

We analyzed 1,621 affected individuals from 16 Arabic countries reported in 198 articles. At the phenotypic level, rod-cone dystrophy (RCD) and Usher syndrome were the most prevalent conditions among non-syndromic and syndromic IRDs. At the gene level, TULP1, ABCA4, RP1, CRB1, MYO7A, RPE65, KCNV2, and IMPG2 were the most mutated genes. Interestingly, all except CRB1 were highly prevalent because they harbored founder mutations, implying that consanguinity is a major determinant in Arab countries. Of note, ~ 93% of the investigated individuals carried homozygous mutations. The country analysis for the IRDs conditions and their associated genotypes revealed that whereas Leber Congenital Amaurosis, RCD, and USHER syndrome were widely distributed, bestrophinopathies and non-syndromic hearing loss were restricted to specific countries (till now).

This study could be a starting point for initiating suitable health policies towards IRDs in the Arab world. The high degree of homozygosity urges the need for genetic counsellors to provide personalized information and support the affected individuals.
CDC light traps underestimate the protective efficacy of an indoor spatial repellent against bites from wild Anopheles arabiensis mosquitoes in Tanzania
Authors: Swai Johnson Kyeba , Kibondo Ummi Abdul , Ntabaliba Watson Samuel , Ngoyani Hassan Ahamad , Makungwa Noely Otto , Mseka Antony Pius , Chura Madeleine Rose , Mascari Thomas Michael , Moore Sarah Jane
Published: April 2023

Background

Methods for evaluating efficacy of core malaria interventions in experimental and operational settings are well established but gaps exist for spatial repellents (SR). The objective of this study was to compare three different techniques: (1) collection of blood-fed mosquitoes (feeding), (2) human landing catch (HLC), and (3) CDC light trap (CDC-LT) collections for measuring the indoor protective efficacy (PE) of the volatile pyrethroid SR product Mosquito Shield™

Methods

The PE of Mosquito Shield™ against a wild population of pyrethroid-resistant Anopheles arabiensis mosquitoes was determined via feeding, HLC, or CDC-LT using four simultaneous 3 by 3 Latin squares (LS) run using 12 experimental huts in Tanzania. On any given night each technique was assigned to two huts with control and two huts with treatment. The LS were run twice over 18 nights to give a sample size of 72 replicates for each technique. Data were analysed by negative binomial regression.

Results

The PE of Mosquito Shield™ measured as feeding inhibition was 84% (95% confidence interval (CI) 58–94% [Incidence Rate Ratio (IRR) 0.16 (0.06–0.42), p < 0.001]; landing inhibition 77% [64–86%, (IRR 0.23 (0.14–0.36) p < 0.001]; and reduction in numbers collected by CDC-LT 30% (0–56%) [IRR 0.70 (0.44–1.0) p = 0.160]. Analysis of the agreement of the PE measured by each technique relative to HLC indicated no statistical difference in PE measured by feeding inhibition and landing inhibition [IRR 0.73 (0.25–2.12) p = 0.568], but a significant difference in PE measured by CDC-LT and landing inhibition [IRR 3.13 (1.57–6.26) p = 0.001].

Conclusion

HLC gave a similar estimate of PE of Mosquito Shield™ against An. arabiensis mosquitoes when compared to measuring blood-feeding directly, while CDC-LT underestimated PE relative to the other techniques. The results of this study indicate that CDC-LT could not effectively estimate PE of the indoor spatial repellent in this setting. It is critical to first evaluate the use of CDC-LT (and other tools) in local settings prior to their use in entomological studies when evaluating the impact of indoor SR to ensure that they reflect the true PE of the intervention.
First trimester human umbilical cord perivascular cells (HUCPVC) modulate the kynurenine pathway and glutamate neurotransmission in an LPS-induced mouse model of neuroinflammation
Authors: Siddiqui Fyyaz , Gallagher Denis , Shuster-Hyman Hannah , Lopez Lianet , Gauthier-Fisher Andrée , Librach Clifford L
Published: May 2023

Background

The Kynurenine Pathway (KP) of tryptophan degradation and glutamate toxicity is implicated in several neurological disorders, including depression. The therapeutic potential of mesenchymal stromal cells (MSC), owing to their well documented phagocytosis-driven mechanism of immunomodulation and neuroprotection, has been tested in many neurological disorders. However, their potential to influence KP and the glutamatergic system has not yet been investigated. Hence, this study sought to investigate the effect of HUCPVC, a rich and potent source of MSC, on Lipopolysaccharide (LPS)-activated KP metabolites, KP enzymes, and key components of glutamate neurotransmission.

Methods

The immunomodulatory effect of peripherally administered HUCPVC on the expression profile of kynurenine pathway metabolites and enzymes was assessed in the plasma and brain of mice treated with LPS using LCMS and QPCR. An assessment of the glutamatergic system, including selected receptors, transporters and related proteins was also conducted by QPCR, immunohistochemistry and Western blot.

Results

HUCPVC were found to modulate LPS-induced activation of KP enzymes and metabolites in the brain associated with neurotoxicity. Moreover, the reduced expression of the glutamatergic components due to LPS was also found to be significantly improved by HUCPVC.

Conclusions

The immunomodulatory properties of HUCPVC appear to confer neuroprotection, at least in part, through their ability to modulate the KP in the brain. This KP modulation enhances neuroprotective regulators and downregulates neurotoxic consequences, including glutamate neurotoxicity, which is associated with neuroinflammation and depressive behavior.
Proteomics identifies differentially expressed proteins in glioblastoma U87 cells treated with hederagenin
Authors: Zhang Yesen , Han Yi , Shang Yuchun , Wang Xiangyu , Sun Jiwei
Published: April 2023

Objective

We investigated differentially expressed proteins (DEPs) in human glioblastoma U87 cells after treatment with hederagenin as a therapeutic screening mechanism and provided a theoretical basis for hederagenin in treating glioblastoma.

Methods

The Cell Counting Kit 8 assay was used to analyze the inhibitory effect of hederagenin on the proliferation of U87 cells. Protein was identified by tandem mass tags and LC-MS/MS analysis techniques. Annotation of DEPs, Gene Ontology enrichment and function, and Kyoto Encyclopedia of Genes and Genomes pathways and domains were all examined by bioinformatics. According to the TMT results, hub protein was selected from DEPs for WB verification.

Results

Protein quantitative analysis found 6522 proteins in total. Compared with the control group, 43 DEPs (P < 0.05) were involved in the highly enriched signaling pathway in the hederagenin group, among which 20 proteins were upregulated, and 23 proteins were downregulated. These different proteins are mainly involved in the longness regulating pathway–WORM, the hedgehog signaling pathway,Staphylococcus aureusinfection, complement, coagulation cascades, and mineral absorption. KIF7 and ATAD2B expression were significantly down-regulated and PHEX and TIMM9 expression were significantly upregulated, according to WB analysis, supporting the TMT findings.

Conclusion

Hederagenin inhibition of GBM U87 cells may be related to KIF7, which is mainly involved in the hedgehog signaling pathway. Our findings lay a foundation for additional study of the therapeutic mechanism of hederagenin.
Esophageal papillomatosis: an exceedingly rare disease
Authors: Li Dandan , Li Changfeng , Yan Yuxing , Liu Minya
Published: April 2023

If esophageal papilloma (EP) is a rare condition, esophageal papillomatosis (EPS) is a distinct rarity. To date, only 53 well documented cases have been described in English literature. However, the number of reports on EPS significantly increased to over 40 cases during the past 20 years. Perhaps, this is due to the broad use of endoscopy and related research achievements. Most of the cases are individual and it seems that there are no associations between them. And up to now no guidelines can be followed. To further understand this exceedingly rare disease, we had a comprehensive review of the epidemiology, etiology, clinical manifestations, pathogenesis, treatment, and clinical course of EPS.
Seizures provoked by over-the-counter cough and cold medications in an elderly patient: a case report
Authors: Alattiya Mohammed Kays , Joudeh Anwar I. , Hammamy Riyadh Ali
Published: April 2023

Background

Seizures are common neurological emergencies in the elderly that are frequently provoked. Geriatrics have higher rates of neurological disorders and other comorbidities that could affect seizure threshold.

Case presentation

An 83-year-old male Arabic patient presented to the emergency department with an acute confusional state and urinary incontinence followed by a witnessed tonic–clonic seizure in the hospital. Thorough investigations and imaging were positive only for nonspecific magnetic resonant imaging findings with a negative electroencephalogram. The patient was diagnosed with provoked seizure due to over-the-counter cold medications that included pseudoephedrine and caffeine. He was not prescribed antiepileptic medications at discharge and did not develop subsequent seizures up to this date.

Conclusion

Over-the-counter cough and cold medications with sympathomimetic ingredients can be associated with provoked seizures in the elderly. Physicians should be aware of the potentially serious adverse events associated with commonly used nonprescription sympathomimetics such as pseudoephedrine and caffeine in elderly patients.