bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting the impact of public spaces on the mental health of rural migrants in Wuhan: an integrated multi-source data analysis
Authors: Gao Feifan , Cheng Hanbei , Li Zhigang , Yu Le
Published: March 2024

Current research on public spaces and mental health often focuses on the independent relationship of one or more social mediators, neglecting the nuanced implications and serial mechanisms inherent in the progressive social process. Using Wuhan city, China, as a study case with multi-source data, this research applies Multilevel Generalized Structural Equation Modeling and deep learning techniques to explore the differential effects of public spaces with varying degrees of publicness (i.e., typical, semi-, and privately owned) on rural migrants’ mental health. Crucially, this study scrutinizes both explicit (social interaction) and implicit (perceived integration) social mechanisms to revisit the relationships. The findings reveal that not all public spaces equally influence mental health, with typical and privately owned public spaces conferring profound benefits. Notably, public spaces impact mental health chiefly through perceived integration instead of through direct social interaction. Social interaction improves mental health primarily by enhancing perceived integration, suggesting that meaningful connections beyond superficial encounters are critical. In particular, we observed significant social effects in typical and privately owned public spaces but limited social functionality in semi-public spaces. This evidence contributes to the knowledge required to create supportive social environments within public spaces, integral to nurturing inclusive urban development.
TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer
Authors: Dai Xiaofeng , Wu Zhipeng , Ruan Ruiwen , Chen Jingyi , Huang Chunye , Lei Wan , Yao Yangyang , Li Li , Tang Xiaomei , Xiong Jianping , Feng Miao , Deng Jun
Published: March 2024

Background

The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear.

Methods

Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC).

Results

In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression.

Conclusions

Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.
Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients
Authors: Castresana-Aguirre Miguel , Johansson Annelie , Matikas Alexios , Foukakis Theodoros , Lindström Linda S. , Tobin Nicholas P.
Published: March 2024

Background

The clinical utility of gene signatures in older breast cancer patients remains unclear. We aimed to determine signature prognostic capacity in this patient subgroup.

Methods

Research versions of the genomic grade index (GGI), 70-gene, recurrence score (RS), cell cycle score (CCS), PAM50 risk-of-recurrence proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets (N = 9583). After filtering on age ≥ 70 years, and the presence of estrogen receptor (ER) and survival data, 871 patients remained. Signature prognostic capacity was tested in all (n = 871), ER-positive/lymph node-positive (ER + /LN + , n = 335) and ER-positive/lymph node-negative (ER + /LN−, n = 374) patients using Kaplan–Meier and multivariable Cox-proportional hazard (PH) modelling.

Results

All signatures were statistically significant in Kaplan–Meier analysis of all patients (Log-rank P < 0.001). This significance remained in multivariable analysis (Cox-PH, P ≤ 0.05). In ER + /LN + patients all signatures except PAM50 were significant in Kaplan–Meier analysis (Log-rank P ≤ 0.05) and remained so in multivariable analysis (Cox-PH, P ≤ 0.05). In ER + /LN− patients all except RS were significant in Kaplan–Meier analysis (Log-rank P ≤ 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox-PH, P ≤ 0.05).

Conclusions

We found that gene signatures provide prognostic information in survival analyses of all, ER + /LN + and ER + /LN- older (≥ 70 years) breast cancer patients, suggesting a potential role in aiding treatment decisions in older patients.
How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis
Authors: Han Yunan , Otegbeye Ebunoluwa E. , Stoll Carrie , Hardi Angela , Colditz Graham A. , Toriola Adetunji T.
Published: March 2024

Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and all were of moderate to high quality with NOS scores ranging from 5 to 8. We included 17 studies (11 case-control, 6 cohort) in final analysis. In case-control studies, weight gain after age 18 was associated with an increased risk of breast cancer (odds ratio [OR] = 1.25; 95% CI = 1.07–1.48), when comparing the highest versus the lowest categories of weight gain. Menopausal status was a source of heterogeneity, with weight gain after age 18 associated with an increased risk of breast cancer in postmenopausal women (OR = 1.53; 95% CI = 1.40–1.68), but not in premenopausal women (OR = 1.01; 95% CI = 0.92–1.12). Additionally, a 5 kg increase in weight was positively associated with postmenopausal breast cancer risk (OR = 1.12; 95%CI = 1.05–1.21) in case-control studies. Findings from cohort studies were identical, with a positive association between weight gain after age 18 and breast cancer incidence in postmenopausal women (relative risk [RR] = 1.30; 95% CI = 1.09–1.36), but not in premenopausal women (RR = 1.06; 95% CI = 0.92–1.22). Weight gain after age 18 is a risk factor for postmenopausal breast cancer, highlighting the importance of weight control from early adulthood to reduce the incidence of postmenopausal breast cancer.
Behavioral responses and life history traits of Taiwanese and Indonesian populations of Aedes aegypti surviving deltamethrin–clothianidin treatment
Authors: Silalahi Christina Natalina , Yasin Aqsa , Chen Mei-Er , Ahmad Intan , Neoh Kok-Boon
Published: March 2024

Background

Indoor residual spraying (IRS) capitalizes on the natural behavior of mosquitoes because Aedes aegypti commonly seeks indoor resting sites after a blood meal. This behavior allows mosquitoes to be exposed to insecticide-treated surfaces and subsequently killed. Combinations of deltamethrin and clothianidin with different modes of action have shown promise in IRS, effectively targeting both susceptible and pyrethroid-resistant malaria vectors. However, the effects of this approach on Aedes mosquitoes remain unclear. The present study tested the effects of deltamethrin–clothianidin mixture treatment on behavioral responses and life history traits of Taiwanese and Indonesian populations of Ae. aegypti.

Methods

We adopted an excito-repellent approach to explore the behavioral responses of pyrethroid-resistant Ae. aegypti populations from Indonesia and Taiwan to a deltamethrin–clothianidin mixture used in contact irritancy and non-contact repellency treatments. We further evaluated the life history traits of surviving mosquitoes (i.e., delayed mortality after 7-day post-treatment, longevity, fecundity, and egg hatching) and investigated the potential transgenerational hormetic effects of insecticide exposure (i.e., development rate and survival of immatures and adult mosquitos).

Results

All tested field populations of Ae. aegypti displayed strong contact irritancy responses; the percentage of escape upon insecticide exposure ranged from 38.8% to 84.7%. However, repellent effects were limited, with the escape percentage ranging from 4.3% to 48.9%. We did not observe immediate knockdown or mortality after 24 h, and less than 15% of the mosquitoes exhibited delayed mortality after a 7-day exposure period. However, the carryover effects of insecticide exposure on the survival of immature mosquitoes resulted in approximately 25% higher immature mortality than that in the control. By contrast, we further documented stimulated survivor reproduction and accelerated transgenerational immature development resulting from the sublethal effects of the insecticide mixture. In particular, the number of eggs laid by treated (both treatments) female mosquitoes increased by at least 60% compared with that of eggs laid by control female mosquitoes.

Conclusions

IRS with deltamethrin–clothianidin effectively deters Aedes mosquitoes from entering residential areas and thereby reduces mosquito bites. However, the application rate (deltamethrin: 25 mg/m2; clothianidin: 200 mg/m2) may be insufficient to effectively kill Aedes mosquitoes. Insecticide response appears to vary across mosquito species; their behavioral and physiological responses to sublethal doses have crucial implications for mosquito control programs.

Graphical Abstract
Gastrosplenic fistula due to splenic lymphoma: two case reports and review of the literature
Authors: Ksontini Feryel Letaief , Zaimi Yosra , Nefzi Isaad , Khrouf Salim , Ayari Myriam , Sghaier Sonia , Zidi Asma , Magherbi Houcine , Ayadi Mouna
Published: March 2024

Background

Gastrosplenic fistula is a rare and potentially fatal complication of various conditions. Lymphoma is the most common cause. It can occur spontaneously or after chemotherapy. Gastrosplenic fistula diagnosis can be confused with a splenic abscess because of the presence of air into the mass. The computed tomography identification of the fistulous tract is the key to a right diagnosis. Treatment modalities include surgical resection, chemotherapy, or a combination of both.

Case presentation

Here we report two patients with gastrosplenic fistula due to diffuse large B cell lymphoma. The first patient was a 54-year-old Caucasian woman with an enormous primary splenic diffuse large B cell lymphoma leading to the development of a spontaneous fistula in the stomach. The second patient was a 48-year-old Caucasian male patient with an enormous splenic diffuse large B cell lymphoma complicated by fistula after chemotherapy. Both patients died of septic shock several days after surgery.

Conclusion

Gastrosplenic fistula is a rare complication with a poor-prognosis, for which surgery is currently the preferred treatment.
Metabolic signatures and potential biomarkers of sarcopenia in suburb-dwelling older Chinese: based on untargeted GC–MS and LC–MS
Authors: Han Peipei , Yuan Chunhua , Chen Xiaoyu , Hu Yuanqing , Hu Xiaodan , Xu Zhangtao , Guo Qi
Published: March 2024

Background

Untargeted metabolomics can be used to expand our understanding of the pathogenesis of sarcopenia. However, the metabolic signatures of sarcopenia patients have not been thoroughly investigated. Herein, we explored metabolites associated with sarcopenia by untargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) and identified possible diagnostic markers.

Methods

Forty-eight elderly subjects with sarcopenia were age and sex matched with 48 elderly subjects without sarcopenia. We first used untargeted GC/LC–MS to analyze the plasma of these participants and then combined it with a large number of multivariate statistical analyses to analyze the data. Finally, based on a multidimensional analysis of the metabolites, the most critical metabolites were considered to be biomarkers of sarcopenia.

Results

According to variable importance in the project (VIP > 1) and the p-value of t-test (p < 0.05), a total of 55 metabolites by GC–MS and 85 metabolites by LC–MS were identified between sarcopenia subjects and normal controls, and these were mostly lipids and lipid-like molecules. Among the top 20 metabolites, seven phosphatidylcholines, seven lysophosphatidylcholines (LysoPCs), phosphatidylinositol, sphingomyelin, palmitamide, L-2-amino-3-oxobutanoic acid, and palmitic acid were downregulated in the sarcopenia group; only ethylamine was upregulated. Among that, three metabolites of LysoPC(17:0), L-2-amino-3-oxobutanoic acid, and palmitic acid showed very good prediction capacity with AUCs of 0.887 (95% CI = 0.817–0.957), 0.836 (95% CI = 0.751–0.921), and 0.805 (95% CI = 0.717–0.893), respectively.

Conclusions

These findings show that metabonomic analysis has great potential to be applied to sarcopenia. The identified metabolites could be potential biomarkers and could be used to study sarcopenia pathomechanisms.
RNA-RBP interactions recognition using multi-label learning and feature attention allocation
Authors: Han Huirui , Talpur Bandeh Ali , Liu Wei , Wang Limei , Ahmed Bilal , Sarhan Nadia , Awwad Emad Mahrous
Published: March 2024

In this study, we present a sophisticated multi-label deep learning framework for the prediction of RNA-RBP (RNA-binding protein) interactions, a critical aspect in understanding RNA functionality modulation and its implications in disease pathogenesis. Our approach leverages machine learning to develop a rapid and cost-efficient predictive model for these interactions. The proposed model captures the complex characteristics of RNA and recognizes corresponding RBPs through its dual-module architecture. The first module employs convolutional neural networks (CNNs) for intricate feature extraction from RNA sequences, enabling the model to discern nuanced patterns and attributes. The second module is a multi-view multi-label classification system incorporating a feature attention mechanism. The second module is a multi-view multi-label classification system that utilizes a feature attention mechanism. This mechanism is designed to intricately analyze and distinguish between common and unique deep features derived from the diverse RNA characteristics. To evaluate the model's efficacy, extensive experiments were conducted on a comprehensive RNA-RBP interaction dataset. The results emphasize substantial improvements in the model's ability to predict RNA-RBP interactions compared to existing methodologies. This advancement emphasizes the model's potential in contributing to the understanding of RNA-mediated biological processes and disease etiology.
Macroalgal microbiomes unveil a valuable genetic resource for halogen metabolism
Authors: Lavecchia Anna , Fosso Bruno , Engelen Aschwin H. , Borin Sara , Manzari Caterina , Picardi Ernesto , Pesole Graziano , Placido Antonio
Published: March 2024

Background

Macroalgae, especially reds (Rhodophyta Division) and browns (Phaeophyta Division), are known for producing various halogenated compounds. Yet, the reasons underlying their production and the fate of these metabolites remain largely unknown. Some theories suggest their potential antimicrobial activity and involvement in interactions between macroalgae and prokaryotes. However, detailed investigations are currently missing on how the genetic information of prokaryotic communities associated with macroalgae may influence the fate of organohalogenated molecules.

Results

To address this challenge, we created a specialized dataset containing 161 enzymes, each with a complete enzyme commission number, known to be involved in halogen metabolism. This dataset served as a reference to annotate the corresponding genes encoded in both the metagenomic contigs and 98 metagenome-assembled genomes (MAGs) obtained from the microbiome of 2 red (Sphaerococcus coronopifolius and Asparagopsis taxiformis) and 1 brown (Halopteris scoparia) macroalgae. We detected many dehalogenation-related genes, particularly those with hydrolytic functions, suggesting their potential involvement in the degradation of a wide spectrum of halocarbons and haloaromatic molecules, including anthropogenic compounds. We uncovered an array of degradative gene functions within MAGs, spanning various bacterial orders such as Rhodobacterales, Rhizobiales, Caulobacterales, Geminicoccales, Sphingomonadales, Granulosicoccales, Microtrichales, and Pseudomonadales. Less abundant than degradative functions, we also uncovered genes associated with the biosynthesis of halogenated antimicrobial compounds and metabolites.

Conclusion

The functional data provided here contribute to understanding the still largely unexplored role of unknown prokaryotes. These findings support the hypothesis that macroalgae function as holobionts, where the metabolism of halogenated compounds might play a role in symbiogenesis and act as a possible defense mechanism against environmental chemical stressors. Furthermore, bacterial groups, previously never connected with organohalogen metabolism, e.g., Caulobacterales, Geminicoccales, Granulosicoccales, and Microtrichales, functionally characterized through MAGs reconstruction, revealed a biotechnologically relevant gene content, useful in synthetic biology, and bioprospecting applications.
New material connections in a mother-of-pearl Enconchado from the Viceroyalty of New Spain
Authors: Dismukes Avalon H. , Lazarte José L. , Centeno Silvia A.
Published: March 2024

Adoration of the Magi (ca. 1695–1700), an enconchado painting attributed to Miguel González, active in Mexico in the late seventeenth century, exemplifies the refinement of the arts produced in Spanish America as a response to the taste for Asian goods during the seventeenth and eighteenth centuries. The painting and its original mother-of-pearl inlaid frame were examined and analyzed using non-invasive and micro-sampling methods, an approach that permitted answering outstanding questions about the stratigraphy, pigments, and the use of shells throughout the painting and frame. The identification of the mother-of-pearl, determined to be from a Pinctada species, was a central focus of this study. In addition to the inlaid shells in the painting and frame, shell fragments were observed mixed with gypsum in the ground preparation of the painting by SEM–EDS. To our knowledge, this is a novel identification of marine shells in the ground of an easel painting. Traces of workmanship in the inlaid shells observed by SEM and optical microscopy are possibly connected to pre-Hispanic methodologies of mother-of-pearl refinement.

Graphical Abstract
Sustainable threads: analyzing the impact of corporate social performance, CSR message authenticity and information transparency on purchase intentions
Authors: Jung Hye Jung , Tian Xinyu , Oh Kyung Wha
Published: March 2024

With the deepening exploration of the study on corporate social responsibility (CSR), CSR has progressively gained significance for enterprises. This study aims to analyze the impact of fashion companies’ information disclosure on the intention of Chinese consumers who purchase clothing by providing information related to the environment, suppliers, manufacturing processes, and pricing. An experimental study was conducted using stimuli on 412 consumers in Shandong Province, China. The research results are as follows. First, it was found that consumers’ perception of Corporate Social Performance (CSP) has a positive effect on the authenticity of Corporate Social Responsibility (CSR) message and consumers’ subjective norms. Second, CSR message authenticity and consumer subjective norms mediate the perception of CSP in the process of leading to purchasing activities. Third, consumers perceive the authenticity of a company’s CSR activities according to the degree of transparent information disclosure of the cost and manufacturing process of its products. This study shows that the CSR information provided by the company is authentic depending on the degree of CSR information transparency of the company, and that it leads to a purchase intention when consumers judge that the company’s CSR activities are authentic. Accordingly, it is suggested that many fashion companies’ CSR activities lead to product purchases when they are continuously conducted on environmental, social problems, and transparency in the production process.
Characterization of two SGNH family cell death-inducing proteins from the horticulturally important fungal pathogen Botrytis cinerea based on the optimized prokaryotic expression system
Authors: Zhang Xiaokang , Zhang Zhanquan , Chen Tong , Chen Yong , Li Boqiang , Tian Shiping
Published: March 2024

Botrytis cinerea is one of the most destructive phytopathogenic fungi, causing significant losses to horticultural crops. As a necrotrophic fungus, B. cinerea obtains nutrients by killing host cells. Secreted cell death-inducing proteins (CDIPs) play a crucial role in necrotrophic infection; however, only a limited number have been reported. For high-throughput CDIP screening, we optimized the prokaryotic expression system and compared its efficiency with other commonly used protein expression systems. The optimized prokaryotic expression system showed superior effectiveness and efficiency and was selected for subsequent CDIP screening. The screening system verified fifty-five candidate proteins and identified two novel SGNH family CDIPs: BcRAE and BcFAT. BcRAE and BcFAT exhibited high expression levels throughout the infection process. Site-directed mutagenesis targeting conserved Ser residues abolished the cell death-inducing activity of both BcRAE and BcFAT. Moreover, the transient expression of BcRAE and BcFAT in plants enhanced plant resistance against B. cinerea without inducing cell death, independent of their enzymatic activities. Our results suggest a high-efficiency screening system for high-throughput CDIP screening and provide new targets for further study of B. cinerea-plant interactions.
Clinical outcomes with paliperidone palmitate 3-monthly injection as monotherapy: observational 3-year follow-up of patients with schizophrenia
Authors: Clark Ivana , Wallman Phoebe , Gee Siobhan , Taylor David
Published: March 2024

Background

Paliperidone palmitate 3-monthly (PP3M) has been tested in 1-year controlled studies. The aim of this study was to examine the relapse outcomes with PP3M monotherapy at 3 years in patients with schizophrenia.

Methods

This was an observational, non-interventional study of patients started on PP3M according to their clinical need. All patients had a diagnosis of schizophrenia (ICD-10 F20) and were between 18 and 65 years of age. The study took place in a mental health facility in South East London, UK.

Results

Among the 166 patients who started PP3M, 97 (58%) met inclusion criteria and were observed for 36 months. In total, five patients (5%) experienced a relapse (defined as step-up in clinical care) while on PP3M. There were no relapses between months 18 and 36. Of the original 97 patients, 56 (58%) remained on PP3M monotherapy at 3 years, and 71 (73%) remained on either PP3M or paliperidone palmitate one-monthly. Reasons for discontinuation of PP3M included patient refusal (n = 11, 33% of discontinuations) and adverse effects in (n = 8, 24%).

Conclusion

PP3M is a highly effective monotherapy treatment for reducing relapse in people with schizophrenia.
Cost-Effectiveness Analysis of Denosumab in the Prevention of Skeletal-Related Events Among Patients With Breast Cancer With Bone Metastasis in India
Authors: Wadhwa Raina , Gupta Nidhi , Dixit Jyoti , Malhotra Pankaj , Lakshmi PVM , Prinja Shankar
Published: March 2024

PURPOSE

Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India.

MATERIALS AND METHODS

A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks). The health outcomes were measured in terms of SREs averted and quality-adjusted life-years (QALYs) gained. The cost of each intervention scenario was measured using both the health system and the patient's perspectives. Indirect costs because of lost productivity were not included. The future costs and outcomes were discounted at the standard rate of 3%.

RESULTS

Over a lifetime, the incremental number of SREs averted with use of denosumab once every 4 weeks (compared with ZA once every 4 weeks and once every 12 weeks) among patients with luminal A, luminal B, human epidermal growth factor receptor 2–enriched, and triple negative breast cancer were estimated as 0.39, 0.26, 0.25, and 0.19, respectively. The number of QALYs lived were slightly higher in the denosumab arm (1.45-2.80) compared with ZA once every 4 weeks and once every 12 weeks arms (1.44-2.78). However, denosumab once every 4 weeks was not found to be a cost-effective alternative for either of the four molecular subtypes of breast cancer. ZA once every 12 weeks was found to be a cost-effective option with an average cost-effectiveness ratio ranging between ₹68,254 and ₹73,636.

CONCLUSION

ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India’s government-funded health insurance program.
TARGET: A Randomized, Noninferiority Trial of a Pretest, Patient-Driven Genetic Education Webtool Versus Genetic Counseling for Prostate Cancer Germline Testing
Authors: Loeb Stacy , Keith Scott W. , Cheng Heather H. , Leader Amy E. , Gross Laura , Sanchez Nolasco Tatiana , Byrne Nataliya , Hartman Rebecca , Brown Lauren H. , Pieczonka Christopher Michael , Gomella Leonard G. , Kelly William Kevin , Lallas Costas D. , Handley Nathan , Mille Patrick Johnston , Mark James Ryan , Brown Gordon Andrew , Chopra Sameer , McClellan Alexandra , Wise David R. , Hollifield Lucas , Giri Veda N.
Published: March 2024

PURPOSE

Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services.

METHODS

Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703 ) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers.

RESULTS

The analytic data set includes primary outcome data from 315 participants (GC [n = 162] and webtool [n = 153]). Mean difference in decisional conflict score changes between groups was –0.04 (one-sided 95% CI, –∞ to 2.54; P = .01), suggesting the patient-driven webtool was noninferior to GC. Overall, 145 (89.5%) GC and 120 (78.4%) in the webtool arm underwent GT, with pathogenic variants in 15.8% (8.7% in PCA genes). Satisfaction did not differ significantly between arms; knowledge of cancer genetics was higher but attitudes toward GT were less favorable in the webtool arm.

CONCLUSION

The results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.
Taxonomy of an Enslaved Heart
Authors: Goldberg Shari
Published: March 2024

“Taxonomy of an Enslaved Heart” opens up the figuration of heartache, so common to sentimental writings, to consider how it can signify anatomical pain as well. What does it mean to read figuratively—accepting that every instance of a heart broken or throbbing or heavy indexes emotional pain addressing the reader’s sympathy—and, at the same time, to literalize these instances, so that each one refers to a specific episode in the history of a circulatory system? This essay attempts to hold both in tension, even as they resist each other. Attending to texts by Harriet Jacobs, Mary Prince, Sojourner Truth, and James Baldwin, the essay argues for what it calls the story of the heart: a minoritized account of pain that deforms sentimental language to register at once somatically, mentally, and intersubjectively. Because of its insecure legibility, the story of the heart subverts the biopolitical logic of legitimacy that traps many patients who are Black, disabled, or both today. What emerges from holding figuration with literalization subtly shifts the illnesses we know and the conditions by which we know them.
Robotic Resection of a Sciatic Notch Lipoma Using the DaVinci Surgical System: 2-Dimensional Operative Video
Authors: Sadagopan Nishanth S. , Poylin Vitaliy Y. , Jun Changhan , El Tecle Najib E. , Wolinsky Jean-Paul
Published: March 2024

Sciatic notch lipomas are rare benign fatty tumors that can cause significant morbidity due to compression of the sciatic nerve. Surgical excision is the gold standard treatment, but traditional open techniques are associated with significant risks and prolonged recovery times. Robotic surgery provides opportunity to improve on traditional laparoscopic techniques by allowing better visualization of and access to regions of complex anatomy, including the pelvis. The potential benefits of robotic resection include reduced blood loss, minimized tissue trauma, and shorter hospital stays. Building on robotic techniques previously described by our group, we present a video of a robotic resection of a sciatic notch lipoma using the DaVinci Surgical System.
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The patient consented to the procedure. The procedure begins with the patient in lithotomy position, followed by the establishment of the robotic trocar sites in the peritoneum, including the endoscope, Da Vinci, and assistant ports. The advanced visualization and precise maneuverability allow for careful dissection and identification of vital structures, including the L5 and S1 nerve roots, with minimal tissue manipulation. Subtotal resection of the lipoma was achieved resulting in decompression of the sciatic nerve with preservation of the surrounding structures. This video highlights the technical aspects of the procedure, emphasizing the advantages of robotic assistance, such as enhanced dexterity, precision, and visualization. This new technique offers a promising alternative to open surgery for the management of sciatic notch lipomas, potentially improving patient outcomes and overall surgical experience.
Microsurgical Management of a Middle Cranial Fossa Dural Arteriovenous Fistula After Failed Embolization: 2-Dimensional Operative Video
Authors: Abramyan Arevik , Samaan Mena , Fried Arno , Roychowdhury Sudipta , Gupta Gaurav
Published: March 2024

Dural arteriovenous fistulas (DAVFs) are intracranial vascular lesions with abnormal communication between the dural arteries and dural and/or cortical venous systems. While benign DAVFs, like Cognard I and IIa/Borden I, can be observed, higher-grade DAVFs, such as Cognard IIb–V/Borden II and III, should be treated.
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This video article depicts the microsurgical management after embolization of a middle cranial fossa Cognard IV DAVF with venous varices causing mass effect in the right thalamus, basal ganglia, and posterior limb of the right internal capsule.

Initial attempts at embolization showed persistent arterial supply from the right ophthalmic artery and distal right internal maxillary artery, with sustaining cortical venous reflux. Microsurgical clipping was chosen because of venous congestion, associated risk of hemorrhage, and corresponding neurological symptoms. The patient consented to the procedure. Intraoperative angiography revealed successful obliteration of the fistula, and postoperative imaging displayed no residual DAVF and thrombosed venous varices without complications. The patient showed remarkable improvement, with a resolution of neurological deficits on discharge to rehabilitation.

This case highlights the potential efficacy of direct clipping after unsuccessful endovascular intervention for DAVFs. Understanding the angioarchitecture with identification of the fistulous point, using intraoperative imaging modalities, and ensuring comprehensive exposure are crucial steps in such microsurgical interventions.
A multistep computational approach reveals a neuro-mesenchymal cell population in the embryonic hematopoietic stem cell niche
Authors: Miladinovic Olivera , Canto Pierre-Yves , Pouget Claire , Piau Olivier , Radic Nevenka , Freschu Priscilla , Megherbi Alexandre , Brujas Prats Carla , Jacques Sebastien , Hirsinger Estelle , Geeverding Audrey , Dufour Sylvie , Petit Laurence , Souyri Michele , North Trista , Isambert Hervé , Traver David , Jaffredo Thierry , Charbord Pierre , Durand Charles
Published: March 2024

The first hematopoietic stem and progenitor cells (HSPCs) emerge in the Aorta-Gonad-Mesonephros (AGM) region of the mid-gestation mouse embryo. However, the precise nature of their supportive mesenchymal microenvironment remains largely unexplored. Here, we profiled transcriptomes of laser micro-dissected aortic tissues at three developmental stages and individual AGM cells. Computational analyses allowed the identification of several cell subpopulations within the E11.5 AGM mesenchyme, with the presence of a yet unidentified subpopulation characterized by the dual expression of genes implicated in adhesive or neuronal functions. We confirmed the identity of this cell subset as a neuro-mesenchymal population, through morphological and lineage tracing assays. Loss of function in the zebrafish confirmed that Decorin, a characteristic extracellular matrix component of the neuro-mesenchyme, is essential for HSPC development. We further demonstrated that this cell population is not merely derived from the neural crest, and hence, is a bona fide novel subpopulation of the AGM mesenchyme.
Plasticity, symbionts and niche construction interact in shaping dung beetle development and evolution
Authors: Rohner Patrick T. , Jones Joshua A. , Moczek Armin P.
Published: March 2024

Developmental plasticity is an important product of evolutionary processes, allowing organisms to maintain high fitness in the face of environmental perturbations. Once evolved, plasticity also has the potential to influence subsequent evolutionary outcomes, for example, by shaping phenotypic variation visible to selection and facilitating the emergence of novel trait variants. Furthermore, organisms may not just respond to environmental conditions through plasticity but may also actively modify the abiotic and (sym)biotic environments to which they themselves respond, causing plasticity to interact in complex ways with niche construction. Here, we explore developmental mechanisms and evolutionary consequences of plasticity in horned dung beetles. First, we discuss how post-invasion evolution of plasticity in an introduced Onthophagus species facilitated rapid range expansion and concurrent local adaptation of life history and morphology to novel climatic conditions. Second, we discuss how, in addition to plastically responding to variation in nutritional conditions, dung beetles engage in behaviors that modify the environment that they themselves respond to during later development. We document that these environment-modifying behaviors mask heritable variation for life history traits within populations, thereby shielding genetic variants from selection. Such cryptic genetic variation may be released and become selectable when these behaviors are compromised. Together, this work documents the complex interactions between plasticity, symbionts and niche construction, and highlights the usefulness of an integrative Eco–Evo–Devo framework to study the varied mechanisms and consequences of plasticity in development and evolution.
Spatial covariation between genetic and epigenetic diversity in wild plant and animal populations: a meta-analysis
Authors: Langford Nadia , Fargeot Laura , Blanchet Simon
Published: March 2024

Epigenetic variation may be crucial in understanding the structure of wild populations, thereby aiding in their management and conservation. However, the relationship between epigenetic and genetic variation remains poorly understood, especially in wild populations. To address this, we conducted a meta-analysis of studies that examined the genetic and epigenetic structures of wild plant and animal populations. We aimed to determine whether epigenetic variation is spatially independent of genetic variation in the wild and to highlight the conditions under which epigenetic variation might be informative. We show a significant positive correlation between genetic and epigenetic pairwise differentiation, indicating that in wild populations, epigenetic diversity is closely linked to genetic differentiation. The correlation was weaker for population pairs that were weakly differentiated genetically, suggesting that in such cases, epigenetic marks might be independent of genetic marks. Additionally, we found that global levels of genetic and epigenetic differentiation were similar across plant and animal populations, except when populations were weakly differentiated genetically. In such cases, epigenetic differentiation was either higher or lower than genetic differentiation. Our results suggest that epigenetic information is particularly relevant in populations that have recently diverged genetically or are connected by gene flow. Future studies should consider the genetic structure of populations when inferring the role of epigenetic diversity in local adaptation in wild populations. Furthermore, there is a need to identify the factors that sustain the links between genetic and epigenetic diversity to improve our understanding of the interplay between these two forms of variation in wild populations.
Are parental condition transfer effects more widespread than is currently appreciated?
Authors: Walsh Matthew R. , Christian Anne , Feder Mikaela , Korte Meghan , Tran Kevin
Published: March 2024

It has long been recognized that the environment experienced by parents can influence the traits of offspring (i.e. ‘parental effects’). Much research has explored whether mothers respond to predictable shifts in environmental signals by modifying offspring phenotypes to best match future conditions. Many organisms experience conditions that theory predicts should favor the evolution of such ‘anticipatory parental effects’, but such predictions have received limited empirical support. ‘Condition transfer effects’ are an alternative to anticipatory effects that occur when the environment experienced by parents during development influences offspring fitness. Condition transfer effects occur when parents that experience high-quality conditions produce offspring that exhibit higher fitness irrespective of the environmental conditions in the offspring generation. Condition transfer effects are not driven by external signals but are instead a byproduct of past environmental quality. They are also likely adaptive but have received far less attention than anticipatory effects. Here, we review the generality of condition transfer effects and show that they are much more widespread than is currently appreciated. Condition transfer effects are observed across taxa and are commonly associated with experimental manipulations of resource conditions experienced by parents. Our Review calls for increased research into condition transfer effects when considering the role of parental effects in ecology and evolution.
Glucocorticoid effects on the brain: from adaptive developmental plasticity to allostatic overload
Authors: Eachus Helen , Ryu Soojin
Published: March 2024

Exposure to stress during early life may alter the developmental trajectory of an animal by a mechanism known as adaptive plasticity. For example, to enhance reproductive success in an adverse environment, it is known that animals accelerate their growth during development. However, these short-term fitness benefits are often associated with reduced longevity, a phenomenon known as the growth rate–lifespan trade-off. In humans, early life stress exposure compromises health later in life and increases disease susceptibility. Glucocorticoids (GCs) are major stress hormones implicated in these processes. This Review discusses the evidence for GC-mediated adaptive plasticity in development, leading to allostatic overload in later life. We focus on GC-induced effects on brain structure and function, including neurogenesis; highlight the need for longitudinal studies; and discuss approaches to identify molecular mechanisms mediating GC-induced alteration of the brain developmental trajectory leading to adult dysfunctions. Further understanding of how stress and GC exposure can alter developmental trajectories at the molecular and cellular level is of critical importance to reduce the burden of mental and physical ill health across the life course.
The plasticity of immune memory in invertebrates
Authors: Lanz-Mendoza Humberto , Gálvez Dumas , Contreras-Garduño Jorge
Published: March 2024

Whether specific immune protection after initial pathogen exposure (immune memory) occurs in invertebrates has long been uncertain. The absence of antibodies, B-cells and T-cells, and the short lifespans of invertebrates led to the hypothesis that immune memory does not occur in these organisms. However, research in the past two decades has supported the existence of immune memory in several invertebrate groups, including Ctenophora, Cnidaria, Nematoda, Mollusca and Arthropoda. Interestingly, some studies have demonstrated immune memory that is specific to the parasite strain. Nonetheless, other work does not provide support for immune memory in invertebrates or offers only partial support. Moreover, the expected biphasic immune response, a characteristic of adaptive immune memory in vertebrates, varies within and between invertebrate species. This variation may be attributed to the influence of biotic or abiotic factors, particularly parasites, on the outcome of immune memory. Despite its critical importance for survival, the role of phenotypic plasticity in immune memory has not been systematically examined in the past two decades. Additionally, the features of immune responses occurring in diverse environments have yet to be fully characterized.
Twenty years on from Developmental Plasticity and Evolution: middle-range theories and how to test them
Authors: Uller Tobias , Milocco Lisandro , Isanta-Navarro Jana , Cornwallis Charlie K. , Feiner Nathalie
Published: March 2024

In Developmental Plasticity and Evolution, Mary-Jane West-Eberhard argued that the developmental mechanisms that enable organisms to respond to their environment are fundamental causes of adaptation and diversification. Twenty years after publication of this book, this once so highly controversial claim appears to have been assimilated by a wealth of studies on ‘plasticity-led’ evolution. However, we suggest that the role of development in explanations for adaptive evolution remains underappreciated in this body of work. By combining concepts of evolvability from evolutionary developmental biology and quantitative genetics, we outline a framework that is more appropriate to identify developmental causes of adaptive evolution. This framework demonstrates how experimental and comparative developmental biology and physiology can be leveraged to put the role of plasticity in evolution to the test.
Developmental plasticity: a worm's eye view
Authors: Jarriault Sophie , Gally Christelle
Published: March 2024

Numerous examples of different phenotypic outcomes in response to varying environmental conditions have been described across phyla, from plants to mammals. Here, we examine the impact of the environment on different developmental traits, focusing in particular on one key environmental variable, nutrient availability. We present advances in our understanding of developmental plasticity in response to food variation using the nematode Caenorhabditis elegans, which provides a near-isogenic context while permitting lab-controlled environments and analysis of wild isolates. We discuss how this model has allowed investigators not only to describe developmental plasticity events at the organismal level but also to zoom in on the tissues involved in translating changes in the environment into a plastic response, as well as the underlying molecular pathways, and sometimes associated changes in behaviour. Lastly, we also discuss how early life starvation experiences can be logged to later impact adult physiological traits, and how such memory could be wired.