bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental Factors in Helicobacter pylori-Related Gastric Precancerous Lesions in Venezuela
Authors: Kato Ikuko , Vivas Jorge , Plummer Martyn , Lopez Gladys , Peraza Simon , Castro Dennis , Sanchez Victor , Cano Elsa , Andrade Olga , Garcia Rita , Franceschi Silvia , Oliver Walter , Muñoz Nubia
Published: June 2022

Although Helicobacter pylori (HP) infection has been acknowledged to play an etiological role in gastric carcinogenesis, its relatively weak association particularly in developing countries suggests critical roles of cofactors. Among a population with an extremely high prevalence of HP infection (≈95%) in Venezuela, we examined the relationship of household characteristics, smoking, alcohol drinking, dietary consumption, and plasma nutrient levels with the prevalence of three different stages of gastric precancerous lesions, chronic atrophic gastritis (AG; n = 337), intestinal metaplasia (IM; n = 551), and dysplasia (n = 157), in comparison with those without any of these lesions (n = 1154). Length of refrigerator use was marginally inversely associated with the prevalence of the precursor lesions studied. The association was most pronounced for AG followed by dysplasia. On the other hand, smoking status was a significant predictor for IM and dysplasia. Those smoking ≥10 cigarettes/day had 1.8-fold risk of IM and 3.6-fold risk of dysplasia compared with never smokers. There were no associations with alcohol consumption. When six food groups known to be associated with stomach cancer risk in Venezuela were tested, the prevalence of these lesions progressively increased with increasing starchy vegetable consumption and decreasing fresh fruit/fruit juice consumption. The association with fruits was more evident for dysplasia and AG and that with starchy vegetables for IM and AG. However, there were no inverse associations with plasma antioxidant vitamins. These findings offer important public health implications in preventing progression of HP-associated gastric precancerous lesions in high-risk populations.
Aspirin, NSAIDs, and Colorectal Cancer: Possible Involvement in an Insulin-Related Pathway
Authors: Slattery Martha L. , Samowitz Wade , Hoffman Michael , Ma Khi Ne , Levin Theodore R. , Neuhausen Susan
Published: June 2022

Introduction: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce risk of colorectal cancer. Although inhibition of cyclooxygenase (COX)-2 is generally thought to be the relevant mechanism, aspirin-like drugs apparently are involved in other pathways and mechanisms. We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer. Methods: Genetic polymorphisms of five genes identified as being involved in an insulin-related pathway were genotyped using data collected in a case-control study of 1346 incident colon cancer cases and 1544 population-based controls and 952 incident rectal cancer cases and 1205 controls. Genotypes assessed were the 3′ untranslated region poly(A) and the intron 8 BsmI polymorphisms of the VDR gene, a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide −202 of the IGFBP3, the Gly972Arg polymorphism of the IRS1 gene, and the Gly1057Asp polymorphism of the IRS2 gene. Results: Use of aspirin and NSAIDs was associated with a decreased risk of colorectal cancer, with slightly greater protection from NSAIDs than aspirin for rectal cancer. We observed a significant interaction between IRS1 genotype and aspirin/NSAIDs use and risk of colorectal cancer. Relative to the GR/RR IRS1 genotype, a protective effect from the GG IRS1 genotype was seen in those who did not use NSAIDs; use of NSAIDs was protective for all genotypes. These associations were especially strong for those diagnosed prior to age 65 (P interaction = 0.0006). We also observed a significant interaction between aspirin/NSAIDs use and the VDR gene. Having the SS or BB VDR genotypes reduced risk of colorectal cancer among non-aspirin/NSAID users; however, aspirin/NSAIDs reduced risk for all VDR genotypes. Conclusions: These data support the protective effect of aspirin and NSAIDs on colorectal cancer risk. In addition, the observed interactions for aspirin/NSAIDs and IRS1 and VDR genotypes suggest that mechanisms other than COX-2 inhibition may be contributing to the protective effect of aspirin and NSAIDs on colorectal cancer risk.
Pap Testing Adherence among Vietnamese American Women
Authors: Taylor Victoria M. , Yasui Yutaka , Burke Nancy , Nguyen Tung , Acorda Elizabeth , Thai Hue , Qu Pingping , Jackson J. Carey
Published: June 2022

Objectives: Vietnamese American women are five times more likely to be diagnosed with cervical cancer than their White counterparts. Previous research has demonstrated low levels of Papanicolaou (Pap) testing among Vietnamese. Our study objective was to examine factors associated with interval Pap testing adherence. Methods: A population-based, in-person survey of Vietnamese women aged 18–64 years was conducted. Questionnaire content was guided by the Health Behavior Framework (HBF). The study sample was randomly selected from 1639 south Seattle households. Statistical methods included χ2 tests and logistic regression. Results: The response rate among eligible households was 82%, and the study included 352 women. Sixty-eight percent of the participants had been screened during the preceding 3 years. The following HBF factors were associated (P < 0.05) with interval Pap testing in bivariate comparisons: believing Pap tests decrease the risk of cervical cancer and believing cervical cancer is curable if detected early (perceived effectiveness); knowing testing is necessary for women who are asymptomatic, sexually inactive, or postmenopausal (knowledge); reporting concern about pain/discomfort as a barrier to screening (barriers); family member(s) and friend(s) had suggested testing (social support); doctor(s) had recommended testing; and had asked doctor(s) for testing (communication with provider). In a multivariate analysis, being married, knowing Pap testing is necessary for asymptomatic women, doctor(s) had recommended testing, and had asked doctor(s) for testing were independently associated (P < 0.05) with screening participation. Conclusion: Our results confirm low levels of Pap testing among Vietnamese women and demonstrate the importance of physician-patient communication in increasing screening adherence. Health education efforts should target unmarried women and reinforce the importance of Pap testing for all Vietnamese women.
On-Schedule Mammography Rescreening in the National Breast and Cervical Cancer Early Detection Program
Authors: Bobo Janet Kay , Shapiro Jean A. , Schulman Jane , Wolters Charles L.
Published: June 2022

Objective: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides free cancer screening to many low-income, underinsured women annually but does not routinely collect all data necessary for precise estimation of mammography rescreening rates among enrollees. Materials and Methods: To determine the percentages rescreened and to identify factors that encourage on-schedule rescreening, telephone interview and medical record data were collected from 1685 enrollees in Maryland, New York, Ohio, and Texas at least 30 months after their 1997 index mammogram. Results: Overall, 72.4% [95% confidence interval (95% CI) = 70.1–74.7] were rescreened within 18 months and 81.5% (95% CI = 79.6–83.5) within 30 months. At 30 months, the adjusted odds ratios (ORs) for rescreening were higher among Hispanics (OR = 1.95, 95% CI = 1.15–3.28), women with a history of breast cancer before the index mammogram (OR = 3.36, 95% CI = 1.07–10.53), and those who had used hormone replacement therapy before their index mammogram (OR =1.94, 95% CI = 1.30–2.91). The 30-month adjusted ORs were lower for women who reported poor health status (OR = 0.60, 95% CI = 0.42–0.85), did not have a usual source of care (OR = 0.61, 95% CI = 0.40–0.94), did not know if they could have another free mammogram (OR = 0.28, 95% CI = 0.14–0.51), described their index screen as their first mammogram ever (OR for no prior mammograms versus three or more = 0.40, 95% CI = 0.27–0.60), did not recall receiving a rescreening reminder (OR = 0.35, 95% CI = 0.25–0.48), or did not think they had been encouraged to rescreen by their provider (OR = 0.61, 95% CI = 0.44–0.86). Discussion: Rescreening behavior in this sample of NBCCEDP enrollees was comparable with that observed in other populations. To facilitate routine rescreening among low-income women, ongoing efforts are needed to ensure they receive annual reminders and encouragements from their medical providers and that they know how to obtain the services they need.
Soy Isoflavones Do Not Modulate Prostate-Specific Antigen Concentrations in Older Men in a Randomized Controlled Trial
Authors: Adams Kenneth F. , Chen Chu , Newton Katherine M. , Potter John D. , Lampe Johanna W.
Published: June 2022

Mortality rates for prostate cancer are low in Asia but high in the West. One explanation is the high level of soy consumption in Asia. Soy isoflavones reduce prostate tumor growth in many, but not all, animal models. Elevated levels of serum prostate-specific antigen (PSA) are a marker of prostate tumor growth. Our objective was to determine whether 12-month soy isoflavone supplementation would alter serum PSA concentrations in healthy, older men. The parent study was a double-blinded, parallel-arm, randomized trial in which participants were assigned to consume either a soy protein drink providing 83 mg/day isoflavones (+ISO) or a similar drink with isoflavones removed (−ISO). Participants in the parent study were 85% men. Of the 128 men enrolled in the trial, 112 completed. These men were later contacted for consent to allow their stored sera to be analyzed for PSA and 81 men consented. We measured PSA in serum collected at 0 and 12 months using a commercial radioimmunometric assay. Serum PSA concentrations increased in both groups over the 12-month intervention, but the changes were similar: Geometric mean PSA concentration increased 0.5% more in the +ISO group than in the −ISO group (P = 0.94; 95% confidence interval = −17.3 to 22.2). The proportion of participants having a serum PSA velocity greater than 1 ng/ml/year was similar in the +ISO and −ISO groups (17.6% versus 12.8%; P = 0.54). We found no evidence that a 12-month 83 mg/day isoflavone treatment alters serum PSA concentration or velocity in seemingly healthy men aged 50–80 years.
Effects of a Moderate Intensity Exercise Intervention on Estrogen Metabolism in Postmenopausal Women
Authors: Atkinson Charlotte , Lampe Johanna W. , Tworoger Shelley S. , Ulrich Cornelia M. , Bowen Deborah , Irwin Melinda L. , Schwartz Robert S. , Rajan Bharat K. , Yasui Yutaka , Potter John D. , McTiernan Anne
Published: June 2022

Physical activity has been associated with reduced breast cancer risk, potentially via hormonal pathways, and high urinary excretion of 2-hydroxyestrone (2-OH E1) relative to 16α-hydroxyestrone (16α-OH E1) also has been associated with reduced breast cancer risk. Studies suggest that body composition and exercise can influence estrogen metabolism. We determined the effects of a 12-month moderate intensity aerobic exercise intervention on urinary 2-OH E1, 16α-OH E1, and their ratio in overweight and obese, previously sedentary, postmenopausal women, ages 50–75 years. Women were randomized to a 12-month exercise intervention (n = 87) or stretching control group (n = 86); 170 completed the study. Urinary 2- and 16α-OH E1 were measured in spot urines collected at baseline, 3, and 12 months. Body composition was measured at baseline and 12 months. Differences between exercisers and controls for excretion of estrogen metabolites were determined using general estimating equations. Further analyses assessed change in estrogen metabolites and their ratio by subgroups of change in body composition. Overall, there were no significant effects of the exercise intervention on 2-OH E1, 16α-OH E1, or their ratio (P > 0.05). There appeared to be an effect of change in intra-abdominal fat and adherence to the exercise intervention on change in the estrogen metabolites or their ratio. However, this did not reflect a potentially desirable change in estrogen metabolites associated with the exercise intervention. Thus, this 12-month moderate intensity exercise intervention did not significantly alter urinary excretion of 2-OH E1, 16α-OH E1, or their ratio in this population of women.
Using Nuclear Morphometry to Discriminate the Tumorigenic Potential of Cells: A Comparison of Statistical Methods
Authors: Wolfe Pamela , Murphy James , McGinley John , Zhu Zongjian , Jiang Weiqin , Gottschall E. Brigitte , Thompson Henry J.
Published: June 2022

Despite interest in the use of nuclear morphometry for cancer diagnosis and prognosis as well as to monitor changes in cancer risk, no generally accepted statistical method has emerged for the analysis of these data. To evaluate different statistical approaches, Feulgen-stained nuclei from a human lung epithelial cell line, BEAS-2B, and a human lung adenocarcinoma (non-small cell) cancer cell line, NCI-H522, were subjected to morphometric analysis using a CAS-200 imaging system. The morphometric characteristics of these two cell lines differed significantly. Therefore, we proceeded to address the question of which statistical approach was most effective in classifying individual cells into the cell lines from which they were derived. The statistical techniques evaluated ranged from simple, traditional, parametric approaches to newer machine learning techniques. The multivariate techniques were compared based on a systematic cross-validation approach using 10 fixed partitions of the data to compute the misclassification rate for each method. For comparisons across cell lines at the level of each morphometric feature, we found little to distinguish nonparametric from parametric approaches. Among the linear models applied, logistic regression had the highest percentage of correct classifications; among the nonlinear and nonparametric methods applied, the Classification and Regression Trees model provided the highest percentage of correct classifications. Classification and Regression Trees has appealing characteristics: there are no assumptions about the distribution of the variables to be used, there is no need to specify which interactions to test, and there is no difficulty in handling complex, high-dimensional data sets containing mixed data types.
Challenges Predicting the Cardiovascular Future for Survivors of Childhood Cancer
Authors: Mulrooney Daniel A.
Published: June 2022

Cardiovascular disease (CVD) risk stratification relies on assessment of nonmodifiable (age, sex, family history) and modifiable (weight, tobacco, physical activity, blood pressure, glucose/lipid levels) risk factors. Cancer therapy, itself a potential risk factor, may alter metabolism in long-term survivors of childhood cancer resulting in premature acquisition of age-related modifiable CVD risk factors. For survivors exposed to cardiotoxic therapies, the risk for CVD is significantly augmented by obesity, diabetes, dyslipidemia, and hypertension. An understanding of these risks may not be well communicated as survivors return to primary care and general population screening practices may be insufficient. Lipshultz and colleagues recruited childhood cancer survivors to return to their treating institution for a comprehensive clinical assessment. Interestingly, compared with a noncancer age-, sex-, and race/ethnicity-matched National Health and Nutrition Examination Survey population, cardiometabolic profiles were largely similar. However, cancer survivors had a higher prevalence of prehypertension/hypertension (38.4% vs. 30.1%, P = 0.04) and a lower prevalence of the metabolic syndrome (11.9% vs. 18.7%, P = 0.05). Applying general population CVD risk calculators and a cancer-specific model from the Childhood Cancer Survivor Study, risk estimates were notably higher when cardiotoxic cancer treatment exposures were included.

See related article by Lipshultz et al., p. 536
The Right to Privacy in the Digital Age as Expressed in a Muslim Country: A Case Study of Kuwait
Authors: al-Mutairi Noura H.
Published: June 2022

This article is primarily concerned with setting a definition for the right to privacy in the digital age, which reflects its meaning and social value in Kuwait as an Arab — Muslim country. While ‘ḥurmah’ is considered as equivalent to ‘privacy’, under the primary sources of Islamic law, its meanings do not provide a sufficient explanation of what is meant by privacy. Also, most Arabic academics, instead of focusing on the illustration of privacy from the perspective of Islamic law, have tended to demonstrate the term ‘privacy’ according to Western theories, without considering the differences between Western and Islamic cultures and the value of that right in each. As such, this article has illustrated and explained the prevalent Western theories, but with reflection from the perspective of Islamic law, in order to set a definition for that right which reflects its meaning and social value in Kuwait as a Muslim country.
Outcry over The Second Sex
Authors: Chaperon Sylvie , Millman Sophia
Published: June 2022

This article explores the critical reception of The Second Sex in France in 1949. Situating debates about the book in the context of the Cold War and the intellectual hegemony of existentialism, the author analyzes the main points of disagreement among different political factions—traditional Catholics, communists, members of the noncommunist left, and progressive Christians. She argues that the sexual questions Simone de Beauvoir raised in the public sphere fueled the primary points of contention.
Dyckia pseudodelicata, a new species of the D. selloa complex (Bromeliaceae, Pitcairnioideae) from Rio Grande do Sul, Brazil
Authors: BÜNEKER HENRIQUE MALLMANN , MARIATH JORGE ERNESTO DE ARAUJO
Published: June 2022

We propose the new species Dyckia pseudodelicata which is described and illustrated here, and provide data on its distribution and habitat. We compare the new species to the related Dyckia delicata and highlight their morphological differences. Morphological features that have been little explored in Dyckia taxonomy proved to be diagnostic in our analysis, such as the presence and morphology of trichomes on the petal margins and the position of ovules in relation to the longitudinal axis of the ovary and their disposition in the placenta.
Thermally Induced Optical Reflection of Sound (THORS) in Ambient Air: Characterization and Temporal Dynamics
Authors: Kazal Daniel S. , Reardon Alex J. , Cullum Brian M.
Published: June 2022

Thermally induced optical reflection of sound (THORS) provides a means to manipulate sound waves without the need for traditional acoustically engineered structures. By photothermally exciting a medium, with infrared light, a barrier can be formed due to abrupt changes in compressibility of the excited medium. Discovery and initial characterization of the THORS phenomenon utilized air saturated with ethanol vapor as the absorbing medium and a CO2 laser, operating at 9.6 µm, as the excitation source to achieve acoustic reflection efficiencies of 25–30% of the incident wave. In this work, we demonstrate for the first time, the ability to generate THORS barriers in ambient air (i.e., without the need for ethanol vapor). Employing atmospheric water vapor as the absorbing medium and a modulated, multiline carbon monoxide laser, operating at 5.5 ± 0.25 µm, THORS barriers capable of acoustic and ultrasonic reflection–suppression efficiencies greater than 70% are readily generated. To achieve these significant reflection–suppression efficiencies, the temporal dynamics of THORS barriers in ambient air were characterized using 300 kHz ultrasonic pulses incident on the barriers, revealing three different operational regimes. In the first regime, a single laser pulse generates a transient THORS barrier that lasts tens of milliseconds and exhibits minimal acoustic reflectivity. In the second regime, multiple laser pulses interact with the water vapor prior to complete relaxation of the THORS barrier from the previous excitation pulse, resulting in an additive response and reflectivity/suppression efficiencies as great as 72%. Finally, in the third regime, non-modulated continuous wave (CW) excitation of the water vapor occurs resulting in no measurable acoustic reflectivity/suppression from the THORS barrier. This work characterizes these different regimes and the optimal modulation timing to generate efficient continuous acoustic barriers using THORS.
Designs of human–robot interaction using depth sensor-based hand gesture communication for smart material-handling robot operations
Authors: Ding Ing-Jr , Su Jun-Lin
Published: June 2022

With rapid developments in biometric recognition, a great deal of attention is being paid to robots which interact smartly with humans and communicate certain types of biometrical information. Such human–machine interaction (HMI), also well-known as human–robot interaction (HRI), will, in the future, prove an important development when it comes to automotive manufacturing applications. Currently, hand gesture recognition-based HRI designs are being practically used in various areas of automotive manufacturing, assembly lines, supply chains, and collaborative inspection. However, very few studies are focused on material-handling robot interactions combined with hand gesture communication of the operator. The current work develops a depth sensor-based dynamic hand gesture recognition scheme for continuous-time operations with material-handling robots. The proposed approach properly employs the Kinect depth sensor to extract features of Hu moment invariants from depth data, through which feature-based template match hand gesture recognition is developed. In order to construct continuous-time robot operations using dynamic hand gestures with concatenations of a series of hand gesture actions, the wake-up reminder scheme using fingertip detection calculations is established to accurately denote the starting, ending, and switching timestamps of a series of gesture actions. To be able to perform typical template match on continuous-time dynamic hand gesture recognition with the ability of real-time recognition, representative frame estimates using centroid, middle, and middle-region voting approaches are also presented and combined with template match computations. Experimental results show that, in certain continuous-time periods, the proposed complete hand gesture recognition framework can provide a smooth operation for the material-handling robot when compared with robots controlled using only extractions of full frames; presented representative frames estimated by middle-region voting will maintain fast computations and still reach the competitive recognition accuracy of 90.8%. The method proposed in this study can facilitate the smart assembly line and human–robot collaborations in automotive manufacturing.
Revisiting party system structuration in Latin America and Europe: Economic and socio-cultural dimensions
Authors: Martínez-Gallardo Cecilia , Cerda Nicolás de la , Hartlyn Jonathan , Hooghe Liesbet , Marks Gary , Bakker Ryan
Published: June 2022

The degree to which party systems are ideologically and programmatically structured is central to democracy. This article analyzes differences in the extent and nature of programmatic structuration in Latin America and Europe, using a new original data source, the Chapel Hill Expert Survey-Latin America (CHES-LA), in combination with the long-standing CHES-Europe. First, we demonstrate the reliability of CHES-LA in relation to CHES-Europe, and substantiate its validity by comparing it to other expert, elite and party manifesto surveys in Latin America. Using confirmatory factor analysis, we then show that while party system structuration in Latin America is somewhat lower than in Europe, it is also of a decisively different nature. In Latin America economic and socio-cultural policy positions are largely captured in a single overlapping dimension; in Europe, by contrast, competition occurs overwhelmingly along two dimensions, each with distinct clusters of policy positions.
Hypoglycemic agents and glycemic variability in individuals with type 2 diabetes: A systematic review and network meta-analysis
Authors: Oh SuA , Purja Sujata , Shin Hocheol , Kim Minji , Kim Eunyoung
Published: June 2022

While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing glycemic control. Our goal was to learn more about the impact of hypoglycemic agents on HbA1c levels and GV in patients with T2D. A systematic review and network meta-analysis (NMA) of randomized controlled trials were performed to assess the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter (SGLT)-2 inhibitors, dipeptidyl peptidase (DPP)-4 inhibitors, sulfonylurea and thiazolidinediones on Mean Amplitude of Glycemic Excursions (MAGE) and HbA1c. Searches were performed using PubMed and EMBASE. A random-effect model was used in the NMA, and the surface under the cumulative ranking was used to rank comparisons. All studies were checked for quality according to their design and also for heterogeneity before inclusion in this NMA. The highest reduction in MAGE was achieved by GLP-1 RAs (SUCRA 0.83), followed by DPP-4 inhibitors (SUCRA: 0.72), and thiazolidinediones (SUCRA: 0.69). In terms of HbA1c reduction, GLP-1 RAs were the most effective (SUCRA 0.81), followed by DPP-4 inhibitors (SUCRA 0.72) and sulfonylurea (SUCRA 0.65). Our findings indicated that GLP-1 RAs have relatively high efficacy in terms of HbA1c and MAGE reduction when compared with other hypoglycemic agents and can thus have clinical application. Future studies with a larger sample size and appropriate subgroup analyses are warranted to completely understand the glycemic effects of these agents in various patients with T2D. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42021256363).
spatialLIBD: an R/Bioconductor package to visualize spatially-resolved transcriptomics data
Authors: Pardo Brenda , Spangler Abby , Weber Lukas M. , Page Stephanie C. , Hicks Stephanie C. , Jaffe Andrew E. , Martinowich Keri , Maynard Kristen R. , Collado-Torres Leonardo
Published: June 2022

Background

Spatially-resolved transcriptomics has now enabled the quantification of high-throughput and transcriptome-wide gene expression in intact tissue while also retaining the spatial coordinates. Incorporating the precise spatial mapping of gene activity advances our understanding of intact tissue-specific biological processes. In order to interpret these novel spatial data types, interactive visualization tools are necessary.

Results

We describe spatialLIBD, an R/Bioconductor package to interactively explore spatially-resolved transcriptomics data generated with the 10x Genomics Visium platform. The package contains functions to interactively access, visualize, and inspect the observed spatial gene expression data and data-driven clusters identified with supervised or unsupervised analyses, either on the user’s computer or through a web application.

Conclusions

spatialLIBD is available at https://bioconductor.org/packages/spatialLIBD. It is fully compatible with SpatialExperiment and the Bioconductor ecosystem. Its functionality facilitates analyzing and interactively exploring spatially-resolved data from the Visium platform.
In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation
Authors: Najafabadi Maryam Mohammadi , Soleimani Masoud , Ahmadvand Mohammad , Zomorrod Mina Soufi , Mousavi Seied Asadollah
Published: June 2022

Introduction

BKPyV associated hemorrhagic cystitis (BKPyV-HC) is a major and prevalent outcome of hematopoietic stem cell transplantation (HSCT) with no standard treatment option. Adoptive T cell therapy (ACT) against transplant-associated viruses has shown promising potential. We sought to produce virus-specific T cells (VSTs) against BKPyV with the aim of treating refractory HSCT-associated HC.

Methods

Peripheral blood mononuclear cells (PBMC) from healthy donors were isolated by Ficoll-Hypaque density gradient centrifugation. BKPyV-pulsed, monocyte-derived dendritic cells (mo-DCs) and T cells were co-cultured and expanded over 2–3 weeks with the addition of IL-2. The T cells were examined for various functional assays.

Results

Comparison analysis of Carboxyfluorescein diacetate succinimidyl ester (CFSE) indicated that the percentage of proliferated cells were significantly higher in donors (49.62 ± 7.09%) than controls (7.96 ± 4.55%). Furthermore, expanded T cells exhibited specificity to BKPyV antigens by IFN-γ ELISPOT assay. The expanded cells showed cytotoxic function versus human lymphoblastoid cell line (LCL). Final VST products mainly comprised of CD8/CD69 double-positive T cells, which were significantly higher in donors (46.8 ± 7.1%) than controls (16.91 ± 3.40%).

Conclusion

In this study we demonstrated the feasibility of producing functional BKPyV-specific T cells in healthy donors using BKPyV PepMixes. These functional cells were able to proliferate and produce IFN-γ cytokine in response to BKPyV PepMixes. In addition, these T cells had cytotoxic ability against BKPyV antigen-expressing target cells.
Novel γδ T cell-based prognostic signature to estimate risk and aid therapy in hepatocellular carcinoma
Authors: Wang Jingrui , Ling Sunbin , Ni Jie , Wan Yafeng
Published: June 2022

Background

Numerous studies have revealed that gamma delta (γδ) T cell infiltration plays a crucial regulatory role in hepatocellular carcinoma (HCC) development. Nonetheless, a comprehensive analysis of γδ T cell infiltration in prognosis evaluation and therapeutic prediction remains unclear.

Methods

Multi-omic data on HCC patients were obtained from public databases. The CIBERSORT algorithm was applied to decipher the tumor immune microenvironment (TIME) of HCC. Weighted gene co-expression network analysis (WGCNA) was performed to determine significant modules with γδ T cell-specific genes. Kaplan-Meier survival curves and receiver operating characteristic analyses were used to validate prognostic capability. Additionally, the potential role of RFESD inhibition by si-RFESD in vitro was investigated using EdU and CCK-8 assays.

Results

A total of 16,421 genes from 746 HCC samples (616 cancer and 130 normal) were identified based on three distinct cohorts. Using WGCNA, candidate modules (brown) with 1755 significant corresponding genes were extracted as γδ T cell-specific genes. Next, a novel risk signature consisting of 11 hub genes was constructed using multiple bioinformatic analyses, which presented great prognosis prediction reliability. The risk score exhibited a significant correlation with ICI and chemotherapeutic targets. HCC samples with different risks experienced diverse signalling pathway activities. The possible interaction of risk score with tumor mutation burden (TMB) was further analyzed. Subsequently, the potential functions of the RFESD gene were explored in HCC, and knockdown of RFESD inhibited cell proliferation in HCC cells. Finally, a robust prognostic risk-clinical nomogram was developed and validated to quantify clinical outcomes.

Conclusions

Collectively, comprehensive analyses focusing on γδ T cell patterns will provide insights into prognosis prediction, the mechanisms of immune infiltration, and advanced therapy strategies in HCC.
Impulsive Lifestyle Counselling versus treatment as usual to reduce offending in people with co-occurring antisocial personality disorder and substance use disorder: a post hoc analysis
Authors: Hesse Morten , del Palacio-Gonzalez Adriana , Thylstrup Birgitte
Published: June 2022

Objectives

To assess the impact of a short psychoeducation intervention for antisocial personality disorder on offending after randomization to treatment.

Design

Multicentre, superiority, non-blinded randomized controlled trial. Random assignment was conducted in blocks of varying sizes at a central randomization centre. Participants were followed using national register data until 365 days after randomization, migration, or death, whichever occurred first.

Setting

Thirteen outpatient uptake areas in Denmark.

Participants

Patients with antisocial personality disorder in treatment for substance use disorders were randomized to treatment as usual (TAU,n = 80) or Impulsive Lifestyle Counselling (ILC,n = 96). A total of 165 patients could be linked to criminal records (TAU,n = 74; ILC,n = 91).

Intervention

ILC is a brief psychoeducational program targeting antisocial behavior. The trial was conducted between January 2012 and June 2014.

Outcomes

Number of criminal offences leading to convictions based on national registers.

Results

The mean number of offences was 2.76 in the TAU group (95% Poisson confidence interval [CI] = 2.39, 3.16) and 1.87 in the ILC group (95% CI = 0.97, 1.43). Negative binomial regression was used to assess total number of convictions, as well as convictions for violent, property, driving under the influence, and drug-related crimes. In both adjusted and unadjusted analyses, random assignment to ILC was associated with a lower number of total offences (incidence rate risk ratio [IRR] = 0.43,p = .013; adjusted IRR = 0.45,p < .001) and convictions related to violence (IRR = 0.19,p = .001 adjusted IRR = 0.19,p = .007) and property offences (unadjusted IRR = 0.30,p = 0.003, adjusted IRR = 0.42,p = 0.010). Differences between conditions were not significant for driving under the influence (unadjusted IRR = 0.49,p = .370; adjusted IRR = 0.53,p = .417) or drug offences (unadjusted IRR = 1.06,p = .907; adjusted IRR = 0.55,p = .223).

Conclusions

The ILC program shows promise in reducing offending behavior in people with comorbid substance use and antisocial personality disorder.

Trial registration

ISRCTN registry,ISRCTN67266318, 15/10/2012.
Impact of the ‘Healthy Youngsters, Healthy Dads’ program on physical activity and other health behaviours: a randomised controlled trial involving fathers and their preschool-aged children
Authors: Morgan Philip J. , Grounds Jacqueline A. , Ashton Lee M. , Collins Clare E. , Barnes Alyce T. , Pollock Emma R. , Kennedy Stevie-Lee , Rayward Anna T. , Saunders Kristen L. , Drew Ryan J. , Young Myles D.
Published: June 2022

Background

Targeting fathers may be a key strategy to increase physical activity among their preschool-aged children, but limited research exists in this area. The primary study aim was to examine the impact of a lifestyle program for fathers and their preschool-aged children on child physical activity levels.

Methods

A total of 125 fathers (aged: 38 ± 5.4 years, BMI: 28.1 ± 4.9 kg/m2) and 125 preschool-aged children (aged: 3.9 ± 0.8 years, BMI z-score: 0.3 ± 0.9, 39.2% girls) recruited from Newcastle, Australia, NSW were randomised to (i) the Healthy Youngsters, Healthy Dads (HYHD) program, or (ii) wait-list control group. The program included two fathers-only workshops (2 h each) and eight father-child weekly educational and practical sessions (75 min each), plus home-based activities targeting family physical activity and nutrition. Assessments took place at baseline, 10-weeks (post-intervention) and 9-months follow-up. The primary outcome was the children’s mean steps/day at 10-weeks. Secondary outcomes included: co-physical activity, fathers’ physical activity levels and parenting practices for physical activity and screen time behaviours, children’s fundamental movement skill (FMS) proficiency, plus accelerometer based light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA), screen time and adiposity for fathers and children. Process measures included; attendance, satisfaction, fidelity and retention. Linear mixed models estimated the treatment effect at all time-points for all outcomes.

Results

Intention-to-treat analyses revealed a significant group-by-time effect for steps per day at 10-weeks (+ 1417, 95%CI: 449, 2384) and 9-months follow-up (+ 1480, 95%CI: 493, 2467) in intervention children compared to control. There were also favourable group-by-time effects for numerous secondary outcomes including fathers’ physical activity levels, children’s FMS proficiency, and several parenting constructs. No effects were observed for both fathers’ and children’s accelerometer based LPA or MVPA, co-physical activity, screen-time and adiposity measures. Process evaluation data revealed very high levels of satisfaction, attendance, retention, and intervention fidelity.

Conclusion

Engaging fathers in a lifestyle program is a promising strategy to increase physical activity among preschool-aged children. Additional benefits to fathers’ physical activity levels, children’s FMS proficiency and parenting practices further support the importance of engaging fathers to improve family health outcomes.

Trial Registration

Australian New Zealand Clinical Trials Registry: ACTRN12619000105145. Registered 24/01/2019.
A community edutainment intervention for gender-based violence, sexual and reproductive health, and maternal and child health in rural Senegal: a process evaluation
Authors: Le Port Agnes , Seye Moustapha , Heckert Jessica , Peterman Amber , Nganya Tchamwa Annick , Dione Malick , Fall Abdou Salam , Hidrobo Melissa
Published: June 2022

Background

Edutainment aims to spread educational messages in an entertaining way, and often reaches large audiences. While studies increasingly report the impacts of edutainment interventions, there is limited context-specific evidence on the underlying processes and barriers to effective delivery, especially in rural areas. This article presents results from a process evaluation of a community-based edutainment intervention designed to improve knowledge, attitudes, and practices on gender-based violence (GBV), sexual and reproductive health (SRH), and maternal and child health. The intervention focused on the television series,C’est la Vie!,screened through biweekly film clubs in rural Senegal and included post-screening discussions and thematic workshops, meant to reinforce messages, increase knowledge, and change social norms. The objectives of this study were to assess intervention adaptation, implementation fidelity, participants’ responsiveness or engagement, and series appropriateness.

Methods

The intervention was implemented from December 2019 to March 2020 in 120 villages in Kaolack and Kolda regions of Senegal, and targeted adolescent girls and young women aged 14 to 34. The process evaluation was carried out in March 2020 in 14 villages using: i) individual semi-structured interviews with implementers (n = 3), village chiefs (n = 8), married women (n = 9), adolescent girls (n = 8), and men (n = 8); ii) focus groups with men (n = 7, 29 participants) and women (n = 10, 100 participants); and iii) observations of screening sessions (n = 4) and post-screening discussions (n = 2). Data were analyzed using thematic and content analysis.

Results

The results highlight that adaptation of the intervention helped reach the target population and improved participant attendance, but might have compromised fidelity to original design, as intervention components were shortened and modified for rural delivery and some facilitators made ad hoc modifications. The screenings coverage and frequency were adequate; however, their duration was shortened due to COVID-19 restrictions in Senegal. Participant responsiveness was excellent, as was the series appropriateness for most topics, including GBV. SRH remains a sensitive topic for youth, especially when the film clubs included non-peers, such as slightly older women.

Conclusions

This study showed that using film clubs to deliver sensitive edutainment content in rural areas is feasible and has potential for scale-up.
One academic year under COVID-19 conditions: two multicenter cross-sectional evaluation studies among medical students in Bavarian medical schools, Germany students’ needs, difficulties, and concerns about digital teaching and learning
Authors: Holzmann-Littig Christopher , Zerban Nina L. , Storm Clara , Ulhaas Lilian , Pfeiffer Mona , Kotz Alexander , Wijnen-Meijer Marjo , Keil Stephanie , Huber Johanna
Published: June 2022

Background

Since March 2020, COVID-19 has created a need for adaptation in many areas of life. This study explores medical students’ perspectives on digital teaching under conditions of the COVID-19 pandemic. It focuses on expectations and concerns about digital teaching, the evaluation of specific aspects of teaching, and requests for future teaching.

Methods

Six German faculties have joined forces within the Bavarian network for medical education to develop and deploy a common core questionnaire. Cross-sectional surveys were conducted at the end of the summer semester 2020 and winter semester 2020/21. Medical students from different semesters participated in the online survey. Data was analyzed descriptively and/or inferentially. Item differences across semesters were examined using contingency tables and Chi2tests. Mean values were compared using the independent samples t-test; answer frequencies in retrospective and prospective concerns were compared using contingency tables and Chi2tests with Yates’ correction.

Results

In the summer semester 2020, 1565 students and in winter semester 2020/21, 1727 students took part in the survey. Students’ main prospective concern was lack of social exchange between fellow students (70%), but also with teachers. Second and third most often concerns were a lack of practical training (68%) and lack of integration of on-site digital teaching (50%). Approximately 7% of the students lacked sufficient access to technical equipment.. Approximately 39% of the students lacked a sufficient internet connection for synchronous digital teaching, 17% for asynchronous digital teaching. On-site teaching was the preferred form of teaching (60%), and there was a preference for asynchronous (24%) over synchronous (15%) digital teaching. Teaching recordings (79%) were particularly popular to complement future on-site teaching.

Conclusions

The following areas of education under COVID-19 conditions are highly important to medical students: adequacy of information sharing, integration of opportunities for exchange with fellow students and teachers, possibility to perform practical trainings. After the normalization of the pandemic situation, on-site teaching should be supplemented with blended learning concepts such as the inverted classroom model.

Graphical abstract

Percentages of results are rounded averages from summer and winter semesters.
Influence of fermented feed additive on gut morphology, immune status, and microbiota in broilers
Authors: Peng Wentong , Talpur Mir Zulqarnain , Zeng Yuxian , Xie Peipei , Li Jincheng , Wang Songbo , Wang Lina , Zhu Xiaotong , Gao Ping , Jiang Qingyan , Shu Gang , Zhang Haijun
Published: June 2022

Background

This study examined the effects of a solid-state fermented feed additive (FFA) on the small intestine histology/morphology, immunity and microbiota of broilers. Two hundred eighty-eight day-old Arbor Acre chicks, were randomly assigned to one of four groups (each group has 6 replicates, with each replicate containing 12 chickens). The negative control (NC; basal diet), the positive control (PC; basal diet +antibiotic 15 ppm), the fermented feed additive low dose (FFL; basal diet + 0.3 kg/t FFA), and the fermented feed additive high dose (FFH; 3 kg/t FFA) with Lactobacillus casei (L.casei).

Results

The study found that the FFH and FFL groups gained more weight (1-21d) and the FFL and PC diets had better feed conversion ratio (P < 0.05) than the NC from 0-42d. The FFH group had higher villus height (P < 0.05) in the duodenum than the PC and villus height to crypt depth ratio VH/CD compared to PC and FFL groups. The FFL chickens had greater (P < 0.05) jejunal and ileal villus height than PC and NC groups respectively. The FFL group had a higher ileal VH/CD ratio (P < 0.05). Jejunum VH/CD was higher in FFL and FFH (P < 0.05) than PC (P < 0.05). FFH had a smaller thymus than NC (P < 0.05). FFA diets also increased IL-10 expression (P < 0.05). While IL-1 and TLR4 mRNA expression decreased (P < 0.05) compared to NC. The microbiota analysis showed that the microorganisms that have pathogenic properties such as phylum Delsulfobacterota and class Desulfovibriona and Negativicutes was also significantly reduced in the group treated with FFH and PC while microorganisms having beneficial properties like Lactobacillaceae family, Lactobacillus aviarus genus and Lactobacillus spp were also tended to increase in the FFH and FFL fermented feed groups compared to the PC and NC groups.

Conclusion

These findings suggested that the FFA diet may modulate cecal microbiota by reducing pathogenic microorganisms such as phylum Delsulfobacterota and class Desulfovibriona and Negativicutes improve beneficial microorganisms like Lactobacillaceae family, Lactobacillus aviarus genus and Lactobacillus spp. While FFA diet also affect immunity, and gene expression related to immunity.
Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells
Authors: Berlak Mareike , Tucker Elizabeth , Dorel Mathurin , Winkler Annika , McGearey Aleixandria , Rodriguez-Fos Elias , da Costa Barbara Martins , Barker Karen , Fyle Elicia , Calton Elizabeth , Eising Selma , Ober Kim , Hughes Deborah , Koutroumanidou Eleni , Carter Paul , Stankunaite Reda , Proszek Paula , Jain Neha , Rosswog Carolina , Dorado-Garcia Heathcliff , Molenaar Jan Jasper , Hubank Mike , Barone Giuseppe , Anderson John , Lang Peter , Deubzer Hedwig Elisabeth , Künkele Annette , Fischer Matthias , Eggert Angelika , Kloft Charlotte , Henssen Anton George , Boettcher Michael , Hertwig Falk , Blüthgen Nils , Chesler Louis , Schulte Johannes Hubertus
Published: June 2022

Background

Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated anaplastic lymphoma kinase (ALK) inhibitor resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations.

Methods

Genome-wide forward genetic CRISPR-Cas9 based screens were performed to identify genes associated with ALK inhibitor resistance in neuroblastoma cell lines. Furthermore, the neuroblastoma cell line NBLW-R was rendered resistant by continuous exposure to ALK inhibitors. Genes identified to be associated with ALK inhibitor resistance were further investigated by generating suitable cell line models. In addition, tumor and liquid biopsy samples of four patients with ALK-mutated neuroblastomas before ALK inhibitor treatment and during tumor progression under treatment were genomically profiled.

Results

Both genome-wide CRISPR-Cas9-based screens and preclinical spontaneous ALKi resistance models identified NF1 loss and activating NRASQ61K mutations to confer resistance to chemically diverse ALKi. Moreover, human neuroblastomas recurrently developed de novo loss of NF1 and activating RAS mutations after ALKi treatment, leading to therapy resistance. Pathway-specific perturbations confirmed that NF1 loss and activating RAS mutations lead to RAS-MAPK signaling even in the presence of ALKi. Intriguingly, NF1 loss rendered neuroblastoma cells hypersensitive to MEK inhibition.

Conclusions

Our results provide a clinically relevant mechanistic model of ALKi resistance in neuroblastoma and highlight new clinically actionable collateral sensitivities in resistant cells.