bluuebunny/crossref_metadata_2025 huggingface dataset:
IBPGNET: lung adenocarcinoma recurrence prediction based on neural network interpretability
Authors: Xu Zhanyu , Liao Haibo , Huang Liuliu , Chen Qingfeng , Lan Wei , Li Shikang
Published: April 2024

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Early-stage patients have a 30–50% probability of metastatic recurrence after surgical treatment. Here, we propose a new computational framework, Interpretable Biological Pathway Graph Neural Networks (IBPGNET), based on pathway hierarchy relationships to predict LUAD recurrence and explore the internal regulatory mechanisms of LUAD. IBPGNET can integrate different omics data efficiently and provide global interpretability. In addition, our experimental results show that IBPGNET outperforms other classification methods in 5-fold cross-validation. IBPGNET identified PSMC1 and PSMD11 as genes associated with LUAD recurrence, and their expression levels were significantly higher in LUAD cells than in normal cells. The knockdown of PSMC1 and PSMD11 in LUAD cells increased their sensitivity to afatinib and decreased cell migration, invasion and proliferation. In addition, the cells showed significantly lower EGFR expression, indicating that PSMC1 and PSMD11 may mediate therapeutic sensitivity through EGFR expression.
SEAOP: a statistical ensemble approach for outlier detection in quantitative proteomics data
Authors: Huang Jinze , Zhao Yang , Meng Bo , Lu Ao , Wei Yaoguang , Dong Lianhua , Fang Xiang , An Dong , Dai Xinhua
Published: April 2024

Quality control in quantitative proteomics is a persistent challenge, particularly in identifying and managing outliers. Unsupervised learning models, which rely on data structure rather than predefined labels, offer potential solutions. However, without clear labels, their effectiveness might be compromised. Single models are susceptible to the randomness of parameters and initialization, which can result in a high rate of false positives. Ensemble models, on the other hand, have shown capabilities in effectively mitigating the impacts of such randomness and assisting in accurately detecting true outliers. Therefore, we introduced SEAOP, a Python toolbox that utilizes an ensemble mechanism by integrating multi-round data management and a statistics-based decision pipeline with multiple models. Specifically, SEAOP uses multi-round resampling to create diverse sub-data spaces and employs outlier detection methods to identify candidate outliers in each space. Candidates are then aggregated as confirmed outliers via a chi-square test, adhering to a 95% confidence level, to ensure the precision of the unsupervised approaches. Additionally, SEAOP introduces a visualization strategy, specifically designed to intuitively and effectively display the distribution of both outlier and non-outlier samples. Optimal hyperparameter models of SEAOP for outlier detection were identified by using a gradient-simulated standard dataset and Mann–Kendall trend test. The performance of the SEAOP toolbox was evaluated using three experimental datasets, confirming its reliability and accuracy in handling quantitative proteomics.
Leveraging multi-omics data to empower quantitative systems pharmacology in immuno-oncology
Authors: Arulraj Theinmozhi , Wang Hanwen , Ippolito Alberto , Zhang Shuming , Fertig Elana J , Popel Aleksander S
Published: April 2024

Understanding the intricate interactions of cancer cells with the tumor microenvironment (TME) is a pre-requisite for the optimization of immunotherapy. Mechanistic models such as quantitative systems pharmacology (QSP) provide insights into the TME dynamics and predict the efficacy of immunotherapy in virtual patient populations/digital twins but require vast amounts of multimodal data for parameterization. Large-scale datasets characterizing the TME are available due to recent advances in bioinformatics for multi-omics data. Here, we discuss the perspectives of leveraging omics-derived bioinformatics estimates to inform QSP models and circumvent the challenges of model calibration and validation in immuno-oncology.
PCAO2: an ontology for integration of prostate cancer associated genotypic, phenotypic and lifestyle data
Authors: Yu Chunjiang , Zong Hui , Chen Yalan , Zhou Yibin , Liu Xingyun , Lin Yuxin , Li Jiakun , Zheng Xiaonan , Min Hua , Shen Bairong
Published: April 2024

Disease ontologies facilitate the semantic organization and representation of domain-specific knowledge. In the case of prostate cancer (PCa), large volumes of research results and clinical data have been accumulated and needed to be standardized for sharing and translational researches. A formal representation of PCa-associated knowledge will be essential to the diverse data standardization, data sharing and the future knowledge graph extraction, deep phenotyping and explainable artificial intelligence developing. In this study, we constructed an updated PCa ontology (PCAO2) based on the ontology development life cycle. An online information retrieval system was designed to ensure the usability of the ontology. The PCAO2 with a subclass-based taxonomic hierarchy covers the major biomedical concepts for PCa-associated genotypic, phenotypic and lifestyle data. The current version of the PCAO2 contains 633 concepts organized under three biomedical viewpoints, namely, epidemiology, diagnosis and treatment. These concepts are enriched by the addition of definition, synonym, relationship and reference. For the precision diagnosis and treatment, the PCa-associated genes and lifestyles are integrated in the viewpoint of epidemiological aspects of PCa. PCAO2 provides a standardized and systematized semantic framework for studying large amounts of heterogeneous PCa data and knowledge, which can be further, edited and enriched by the scientific community. The PCAO2 is freely available at https://bioportal.bioontology.org/ontologies/PCAO, http://pcaontology.net/ and http://pcaontology.net/mobile/.
Multilevel superposition for deciphering the conformational variability of protein ensembles
Authors: Amisaki Takashi
Published: April 2024

The dynamics and variability of protein conformations are directly linked to their functions. Many comparative studies of X-ray protein structures have been conducted to elucidate the relevant conformational changes, dynamics and heterogeneity. The rapid increase in the number of experimentally determined structures has made comparison an effective tool for investigating protein structures. For example, it is now possible to compare structural ensembles formed by enzyme species, variants or the type of ligands bound to them. In this study, the author developed a multilevel model for estimating two covariance matrices that represent inter- and intra-ensemble variability in the Cartesian coordinate space. Principal component analysis using the two estimated covariance matrices identified the inter-/intra-enzyme variabilities, which seemed to be important for the enzyme functions, with the illustrative examples of cytochrome P450 family 2 enzymes and class A $\beta$-lactamases. In P450, in which each enzyme has its own active site of a distinct size, an active-site motion shared universally between the enzymes was captured as the first principal mode of the intra-enzyme covariance matrix. In this case, the method was useful for understanding the conformational variability after adjusting for the differences between enzyme sizes. The developed method is advantageous in small ensemble-size problems and hence promising for use in comparative studies on experimentally determined structures where ensemble sizes are smaller than those generated, for example, by molecular dynamics simulations.
Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects
Authors: Serrano del Pueblo Víctor M , Serrano-Heras Gemma , Romero Sánchez Carlos M , Landete Pepa Piqueras , Rojas-Bartolome Laura , Feria Inmaculada , Morris Richard G M , Strange Bryan , Mansilla Francisco , Zhang Linda , Castro-Robles Beatriz , Arias-Salazar Lourdes , López-López Susana , Payá María , Segura Tomás , Muñoz-López Mónica
Published: April 2024

Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in long COVID and the potential association between them.

To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy control subjects chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI.

The mean global cognitive function of patients with long COVID assessed by Addenbrooke’s Cognitive Examination-III screening test [overall cognitive level (OCLz) = −0.39 ± 0.12] was significantly below the infection recovered-controls (OCLz = +0.32 ± 0.16, P < 0.01). We observed that 48% of patients with long COVID had episodic memory deficit, with 27% also with impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients’ cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency.

This study shows that patients with neurological long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.
Flexibility of brain dynamics is increased and predicts clinical impairment in relapsing–remitting but not in secondary progressive multiple sclerosis
Authors: Cipriano Lorenzo , Minino Roberta , Liparoti Marianna , Polverino Arianna , Romano Antonella , Bonavita Simona , Pirozzi Maria Agnese , Quarantelli Mario , Jirsa Viktor , Sorrentino Giuseppe , Sorrentino Pierpaolo , Troisi Lopez Emahnuel
Published: April 2024

Large-scale brain activity has long been investigated under the erroneous assumption of stationarity. Nowadays, we know that resting-state functional connectivity is characterized by aperiodic, scale-free bursts of activity (i.e. neuronal avalanches) that intermittently recruit different brain regions. These different patterns of activity represent a measure of brain flexibility, whose reduction has been found to predict clinical impairment in multiple neurodegenerative diseases such as Parkinson’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease. Brain flexibility has been recently found increased in multiple sclerosis, but its relationship with clinical disability remains elusive. Also, potential differences in brain dynamics according to the multiple sclerosis clinical phenotypes remain unexplored so far. We performed a brain dynamics study quantifying brain flexibility utilizing the ‘functional repertoire’ (i.e. the number of configurations of active brain areas) through source reconstruction of magnetoencephalography signals in a cohort of 25 multiple sclerosis patients (10 relapsing–remitting multiple sclerosis and 15 secondary progressive multiple sclerosis) and 25 healthy controls. Multiple sclerosis patients showed a greater number of unique reconfigurations at fast time scales as compared with healthy controls. This difference was mainly driven by the relapsing–remitting multiple sclerosis phenotype, whereas no significant differences in brain dynamics were found between secondary progressive multiple sclerosis and healthy controls. Brain flexibility also showed a different predictive power on clinical disability according to the multiple sclerosis type. For the first time, we investigated brain dynamics in multiple sclerosis patients through high temporal resolution techniques, unveiling differences in brain flexibility according to the multiple sclerosis phenotype and its relationship with clinical disability.
Comment on ‘Does internal validity play a factor in ChatGPT’s success?’
Authors: Kleebayoon Amnuay , Wiwanitkit Viroj
Published: April 2024

Comment on ‘Does internal validity play a factor in ChatGPT’s success?’ by Ahuja and Lio
Diphenylanthracene-based amorphous molecular fluorophores for triplet–triplet annihilation upconversion system
Authors: Naemura Shungo , Matsui Ryoma , Matsumoto Ikumi , Iimori Toshifumi , Nakano Hideyuki
Published: April 2024

Novel diphenylanthracene-based amorphous molecular fluorophores have been designed and synthesized. They were found to exhibit fluorescence emission with fairly high quantum efficiencies both in solution, crystalline state, and amorphous state. Triplet–triplet annihilation upconversion emissions have been achieved not only in toluene solutions but also as amorphous solids using present novel fluorophores as acceptors combined with platinum(II) octaethylporphyrin as a donor.
Moderate salt restriction in primary aldosteronism improves bone metabolism through attenuation of urinary calcium and phosphate losses
Authors: Schneider Holger , Brüdgam Denise , Nowotny Hanna F , Schmidmaier Ralf , Reincke Martin , Adolf Christian
Published: April 2024

Accumulating evidence links osteoporosis and dietary salt consumption. Primary aldosteronism (PA) is a model disease with increased dietary salt intake and constitutes an independent risk factor for osteoporosis. We, thus, assessed whether a short-term moderate reduction in salt intake in PA results in detectable osteoanabolic effects. Forty-one patients with PA on stable mineralocorticoid receptor antagonist therapy were subjected to a 12-week salt restriction. Serum and urinary electrolytes, markers of bone turnover, and a 15 steroids plasma profile were registered. After 12 weeks, urinary calcium and phosphate decreased, while plasma testosterone, serum phosphate, and bone alkaline phosphatase (BAP) all increased significantly. Longitudinal changes in BAP were independently correlated with changes in serum phosphate, parathyroid hormone, and urinary calcium in multivariate analysis. Salt restriction in PA limits urinary calcium and phosphate losses and may confer favorable osteoanabolic effects. Our findings suggest that salt restriction should be considered in patients with PA to improve bone health.
Long-term reliability of the phospholamban (PLN) p.(Arg14del) risk model in predicting major ventricular arrhythmia: a landmark study
Authors: van der Heide Myrthe Y C , Verstraelen Tom E , van Lint Freyja H M , Bosman Laurens P , de Brouwer Remco , Proost Virginnio M , van Drie Esmée , Taha Karim , Zwinderman Aeilko H , Dickhoff Cathelijne , Schoonderwoerd Bas A , Germans Tjeerd , Houweling Arjan C , Gimeno-Blanes Juan R , van der Zwaag Paul A , de Boer Rudolf A , Cox Moniek G P J , van Tintelen J Peter , Wilde Arthur A M
Published: April 2024

Aims

Recently, a genetic variant-specific prediction model for phospholamban (PLN) p.(Arg14del)-positive individuals was developed to predict individual major ventricular arrhythmia (VA) risk to support decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. This model predicts major VA risk from baseline data, but iterative evaluation of major VA risk may be warranted considering that the risk factors for major VA are progressive. Our aim is to evaluate the diagnostic performance of the PLN p.(Arg14del) risk model at 3-year follow-up.

Methods and results

We performed a landmark analysis 3 years after presentation and selected only patients with no prior major VA. Data were collected of 268 PLN p.(Arg14del)-positive subjects, aged 43.5 ± 16.3 years, 38.9% male. After the 3 years landmark, subjects had a mean follow-up of 4.0 years (± 3.5 years) and 28 (10%) subjects experienced major VA with an annual event rate of 2.6% [95% confidence interval (CI) 1.6–3.6], defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. The PLN p.(Arg14del) risk score yielded good discrimination in the 3 years landmark cohort with a C-statistic of 0.83 (95% CI 0.79–0.87) and calibration slope of 0.97.

Conclusion

The PLN p.(Arg14del) risk model has sustained good model performance up to 3 years follow-up in PLN p.(Arg14del)-positive subjects with no history of major VA. It may therefore be used to support decision-making for primary prevention ICD implantation not merely at presentation but also up to at least 3 years of follow-up.
Light conditions and the evolution of the visual system in birds
Authors: Fröhlich Arkadiusz , Ducatez Simon , Neˇmec Pavel , Sol Daniel
Published: April 2024

Despite vision being an essential sense for many animals, the intuitively appealing notion that the visual system has been shaped by environmental light conditions is backed by insufficient evidence. Based on a comprehensive phylogenetic comparative analysis of birds, we investigate if exposure to different light conditions might have triggered evolutionary divergence in the visual system through pressures on light sensitivity, visual acuity, and neural processing capacity. Our analyses suggest that birds that have adopted nocturnal habits evolved eyes with larger corneal diameters and, to a lesser extent, longer axial length than diurnal species. However, we found no evidence that sensing and processing organs were selected together, as observed in diurnal birds. Rather than enlarging the processing centers, we found a tendency among nocturnal species to either reduce or maintain the size of the two main brain centers involved in vision—the optic tectum and the wulst. These results suggest a mosaic pattern of evolution, wherein optimization of the eye optics for efficient light capture in nocturnal species may have compromised visual acuity and central processing capacity.
Sacred Space, Mourning and the War Dead in Protestant Germany, 1945–
Authors: Brodie Thomas
Published: April 2024

Using the Flensburg Memorial Dispute of 1967 as a microstudy, this article explores how Germany’s twentieth-century war dead have been represented within Protestant sacred space since 1945. It highlights the central role played by church spaces in the mourning and commemoration of Germany’s war dead and the tremendous difficulties accompanying attempts to redesign these iconographies in the later twentieth century in the face of popular sentiment.
Associations of Social Support With Physical and Mental Health Symptom Burden After COVID-19 Hospitalization Among Older Adults
Authors: Lee Seohyuk , McAvay Gail J , Geda Mary , Chattopadhyay Sumon , Acampora Denise , Araujo Katy , Charpentier Peter , Gill Thomas M , Hajduk Alexandra M , Cohen Andrew B , Ferrante Lauren E
Published: April 2024

Background

Despite significant support system disruptions during the coronavirus 2019 (COVID-19) pandemic, little is known about the relationship between social support and symptom burden among older adults following COVID-19 hospitalization.

Methods

From a prospective cohort of 341 community-living persons aged ≥60 years hospitalized with COVID-19 between June 2020 and June 2021 who underwent follow-up at 1, 3, and 6 months after discharge, we identified 311 participants with ≥1 follow-up assessment. Social support prehospitalization was ascertained using a 5-item version of the Medical Outcomes Study Social Support Survey (range, 5–25), with low social support defined as a score ≤15. At hospitalization and each follow-up assessment, 14 physical symptoms were assessed using a modified Edmonton Symptom Assessment System inclusive of COVID-19-relevant symptoms. Mental health symptoms were assessed using Patient Health Questionnaire-4. Longitudinal associations between social support and physical and mental health symptoms, respectively, were evaluated through multivariable regression.

Results

Participants’ mean age was 71.3 years (standard deviation, 8.5), 52.4% were female, and 34.2% were of Black race or Hispanic ethnicity. 11.8% reported low social support. Over the 6-month follow-up period, low social support was independently associated with higher burden of physical symptoms (adjusted rate ratio [aRR], 1.26; 95% confidence interval [CI], 1.05–1.52), but not mental health symptoms (aRR, 1.14; 95% CI, 0.85–1.53).

Conclusions

Low social support is associated with greater physical, but not mental health, symptom burden among older survivors of COVID-19 hospitalization. Our findings suggest a potential need for social support screening and interventions to improve post-COVID-19 symptom management in this vulnerable group.
Claims-Based Frailty Index and Its Relationship With Commonly Used Clinical Frailty Measures
Authors: Sison Stephanie Denise M , Shi Sandra M , Oh Gahee , Jeong Sohyun , McCarthy Ellen P , Kim Dae Hyun
Published: April 2024

Background

The relationship of claims-based frailty index (CFI), a validated measure to identify frail individuals using Medicare data, and frailty measures used in clinical practice has not yet been fully explored.

Methods

We identified community-dwelling participants of the 2015 National Health and Aging Trends Study (NHATS) whose CFI scores could be calculated using linked Medicare claims. We calculated 9 commonly used clinical frailty measures from their NHATS in-person examination: Study of Osteoporotic Fracture Index (SOF), FRAIL Scale, Frailty Phenotype, Clinical Frailty Scale (CFS), Vulnerable Elder Survey-13 (VES-13), Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI), Edmonton Frail Scale (EFS), and 40-item Frailty Index (FI). Using equipercentile method, CFI scores were linked to clinical frailty measures. C-statistics and test characteristics of CFI to identify frailty as defined by each clinical frailty measure were calculated.

Results

Of the 3 963 older adults, 44.5% were ≥75 years, 59.4% were female, and 82.3% were non-Hispanic White. A CFI of 0.25 was equipercentile to the following clinical frailty measure scores: SOF 1.4, FRAIL 1.8, Phenotype 1.8, CFS 5.4, VES-13 5.7, TFI 4.6, GFI 5.0, EFS 6.0, and FI 0.26. The C-statistics of using CFI to identify frailty as defined by each clinical measure were ≥0.70, except for CFS and VES-13. The optimal CFI cutpoints to identify frailty per clinical frailty measure ranged from 0.212 to 0.242, with sensitivity and specificity of 0.37–0.83 and 0.66–0.84, respectively.

Conclusions

Understanding the relationship of CFI and commonly used clinical frailty measures can enhance the interpretability and potential utility of CFI.
Gladstone and Ireland: a financial approach
Authors: Kanter Douglas
Published: April 2024

This article examines William Gladstone’s Irish policy through the prism of his commitment to ‘sound’ finance, a fiscal programme involving low taxation, minimal government expenditure, balanced budgets and free trade. These prescriptions, it argues, served as an unintentional stimulus to Irish nationalism while also encouraging Gladstone’s receptivity to Home Rule, because by the 1880s he had become convinced that the cost of governing Ireland within the framework of the Union was imperilling ‘sound’ finance throughout the United Kingdom. Viewed from the vantage of fiscal policy, it concludes, Gladstone’s approach to Ireland was characterized by ideological rigidity rather than political adaptability.
Diagnostic survey of analytical methods used to determine bone mineralization in pigs
Authors: Williams Hadley R , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Goodband Robert D , Bergstrom Jon R , Rahe Michael C , Siepker Christopher L , Sitthicharoenchai Panchan , Ensley Steve M , Radke Scott L , Gebhardt Jordan T
Published: April 2024

Pigs from 64 commercial sites across 14 production systems in the Midwest United States were evaluated for baseline biological measurements used to determine bone mineralization. There were three pigs selected from each commercial site representing: 1) a clinically normal pig (healthy), 2) a pig with evidence of clinical lameness (lame), and 3) a pig from a hospital pen that was assumed to have recent low feed intake (unhealthy). Pigs ranged in age from nursery to market weight, with the three pigs sampled from each site representing the same age or phase of production. Blood, urine, metacarpal, fibula, 2nd rib, and 10th rib were collected and analyzed. Each bone was measured for density and ash (defatted and non-defatted technique). A bone × pig type interaction (P < 0.001) was observed for defatted and non-defatted bone ash and density. For defatted bone ash, there were no differences among pig types for the fibulas, 2nd rib, and 10th rib (P > 0.10), but metacarpals from healthy pigs had greater (P < 0.05) percentage bone ash compared to unhealthy pigs, with the lame pigs intermediate. For non-defatted bone ash, there were no differences among pig types for metacarpals and fibulas (P > 0.10), but unhealthy pigs had greater (P < 0.05) non-defatted percentage bone ash for 2nd and 10th ribs compared to healthy pigs, with lame pigs intermediate. Healthy and lame pigs had greater (P < 0.05) bone density than unhealthy pigs for metacarpals and fibulas, with no difference observed for ribs (P > 0.10). Healthy pigs had greater (P < 0.05) serum Ca and 25(OH)D3 compared to unhealthy pigs, with lame pigs intermediate. Healthy pigs had greater (P < 0.05) serum P compared to unhealthy and lame pigs, with no differences between the unhealthy and lame pigs. Unhealthy pigs excreted significantly more (P < 0.05) P and creatinine in the urine compared to healthy pigs with lame pigs intermediate. In summary, there are differences in serum Ca, P, and vitamin D among healthy, lame, and unhealthy pigs. Differences in bone mineralization among pig types varied depending on the analytical procedure and bone, with a considerable range in values within pig type across the 14 production systems sampled.
Do perfectionism, body image concerns, and intimacy predict genitopelvic pain in the postpartum? A prospective study of new mothers
Authors: Dubé Sandrine , Beaulieu Noémie , Bergeron Sophie , Lafontaine Marie-France , Péloquin Katherine , Brault-Labbé Anne , Gosselin Patrick , Brassard Audrey
Published: April 2024

Background

Genitopelvic pain following childbirth is common and likely to challenge the psychological, relational, and sexual well-being of new mothers. While genitopelvic pain generally decreases during the postpartum period, personal and interpersonal characteristics may explain why genitopelvic pain persists beyond the period of physical recovery in some mothers. Body image concerns, increased stress, and relationship challenges would be particularly salient during pregnancy and the postpartum period, which could put new mothers at greater risk of sexual difficulties. Also, mothers may display a negative appraisal regarding genitopelvic pain and doubt their ability to cope with it, which may contribute to the pain.

Aim

The current study aimed to examine the role of perfectionism, body image concerns, and perceived intimacy in the occurrence and change in genitopelvic pain in new mothers in postpartum.

Methods

A total of 211 new mothers and their partners were recruited for a larger prospective dyadic study on the transition to parenthood.

Outcomes

Mothers completed a single item assessing genitopelvic pain, in addition to brief validated questionnaires measuring perfectionism, body image concerns, and perceived couple intimacy during pregnancy and at 4, 8, and 12 months postpartum.

Results

Five multilevel modeling analyses revealed that adaptive perfectionism, maladaptive perfectionism, and body image concerns were associated with a higher occurrence of genitopelvic pain from 4 to 12 months postpartum. Mothers’ and partners’ perceived intimacy was not significantly related to new mothers’ genitopelvic pain. None of the predictors modified the trajectory of genitopelvic pain over time.

Clinical Implications

Raising awareness among health care professionals regarding the role of perfectionism and body image concerns in genitopelvic pain may help them identify new mothers at risk of chronic genitopelvic pain, while offering a new avenue of intervention.

Strengths and Limitations

There has been little research examining the role of perfectionism, body image concerns, and intimacy in postpartum genitopelvic pain. Based on a longitudinal prospective approach, this study identified perfectionism and body image concerns as significant predictors of postpartum genitopelvic pain. However, prepregnancy genitopelvic pain, genitopelvic pain intensity, and sexual distress were not measured.

Conclusion

Adaptive and maladaptive perfectionism and body image concerns are associated with new mothers’ genitopelvic pain up to 12 months postpartum.
Nitric oxide, energy, and redox-dependent responses to hypoxia
Authors: Samant Sanjib Bal , Yadav Nidhi , Swain Jagannath , Joseph Josepheena , Kumari Aprajita , Praveen Afsana , Sahoo Ranjan Kumar , Manjunatha Girigowda , Seth Chandra Shekhar , Singla-Pareek Sneh Lata , Foyer Christine H , Pareek Ashwani , Gupta Kapuganti Jagadis
Published: April 2024

Hypoxia occurs when oxygen levels fall below the levels required for mitochondria to support respiration. Regulated hypoxia is associated with quiescence, particularly in storage organs (seeds) and stem cell niches. In contrast, environmentally induced hypoxia poses significant challenges for metabolically active cells that are adapted to aerobic respiration. The perception of oxygen availability through cysteine oxidases, which function as oxygen-sensing enzymes in plants that control the N-degron pathway, and the regulation of hypoxia-responsive genes and processes is essential to survival. Functioning together with reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2) and reactive nitrogen species (RNS), such as nitric oxide (·NO), nitrogen dioxide (·NO2), S-nitrosothiols (SNOs), and peroxynitrite (ONOO–), hypoxia signaling pathways trigger anatomical adaptations such as formation of aerenchyma, mobilization of sugar reserves for anaerobic germination, formation of aerial adventitious roots, and the hyponastic response. NO and H2O2 participate in local and systemic signaling pathways that facilitate acclimation to changing energetic requirements, controlling glycolytic fermentation, the γ-aminobutyric acid (GABA) shunt, and amino acid synthesis. NO enhances antioxidant capacity and contributes to the recycling of redox equivalents in energy metabolism through the phytoglobin (Pgb)–NO cycle. Here, we summarize current knowledge of the central role of NO and redox regulation in adaptive responses that prevent hypoxia-induced death in challenging conditions such as flooding.
Immune Responses in Discharged COVID-19 Patients With and Without Long COVID Symptoms
Authors: Wang Yeming , Guo Li , Cui Dan , Zhang Hui , Zhang Qiao , Ren Lili , Wang Geng , Zhang Xueyang , Huang Tingxuan , Chen Lan , Huang Lixue , Wang Xinming , Zhong Jinchuan , Wang Ying , Li Hui , Wang Jianwei , Cao Bin
Published: April 2024

The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)–immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a “one-size-fits-all” approach to future treatment modalities.
Prevalence of sexual dysfunction in Chinese patients with schizophrenia: a systematic review and meta-analysis
Authors: Zhang Linghui , Chen Yubin , Sun Yujing , Zhou Yuqiu , Li Qi , Jia Yannan
Published: April 2024

Background

There may be a higher risk of sexual dysfunction in the schizophrenia population. China has made significant contributions to the global community of patients with schizophrenia. Currently, there is no estimation of the prevalence of sexual dysfunction in Chinese patients with schizophrenia.

Aim

We conducted a meta-analysis to pool the evaluated prevalence of sexual dysfunction in Chinese patients with schizophrenia.

Methods

We systematically searched PubMed, Web of Science, Embase, PsycINFO, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Medical Network, and Huayi Academic Literature Database from inception to September 2023. Meta-analysis was conducted with R version 4.3.1.

Outcomes

To examine the pooled prevalence of sexual dysfunctions among Chinese patients with schizophrenia.

Results

In our meta-analysis, we included 16 studies with 5417 participants, among whom 1727 experienced sexual dysfunction. The results of the meta-analysis reveal that the prevalence of sexual dysfunction in Chinese patients with schizophrenia is 50.43% (95% CI, 37.86%-62.95%). Subgroup analysis results indicate that various factors—including the specific type of dysfunction, duration of illness, assessment tools, mean ages, study region, gender, research setting, marital status, publication years, and type of antipsychotics—all have a particular impact on the occurrence rate of sexual dysfunction in Chinese patients with schizophrenia. Female patients had a slightly higher prevalence of sexual dysfunction than male patients (65.22% vs 54.84%).

Clinical Implications

The findings of this study can be used in high-quality nursing care for the schizophrenia population, particularly for the care of specific sexual dysfunction nursing.

Strengths and Limitations

This meta-analysis is the first to evaluate the prevalence of sexual dysfunction in China among patients with schizophrenia. The limited number of studies is the most important limitation.

Conclusions

The pooled prevalence of sexual dysfunction in Chinese patients with schizophrenia is relatively high, and the prevention and intervention of individual sexual dysfunctions in schizophrenia are advised.
Edward O. Bixler, PhD: from the Apollo project and chimpanzees to sleep epidemiology
Authors: Fernandez-Mendoza Julio , Calhoun Susan L , Bixler Edward O
Published: April 2024

What an honor to write about Dr. Edward O. Bixler’s contributions to the sleep field. In 1967, Dr. Bixler published a case report on a chimpanzee with implanted brain electrodes while working at an Air Force base in New Mexico. A few years later, in 1971, he published on the sleep effects of flurazepam in individuals with insomnia together with Dr. Anthony Kales, data that he had collected when the Sleep Research & Treatment Center (SRTC) was housed at the University of California Los Angeles. Dr. Bixler, a meticulous scientist, learned from Dr. Kales, a devoted clinician, to study “the whole patient, and all aspects of sleep,” a legacy that continued when the SRTC moved to Penn State in Hershey. Indeed, Dr. Bixler’s tenure at Penn State from 1971 until 2019 kept the science of the SRTC focused on that premise and helped translate scientific evidence into clinical care. He not only contributed early to the pharmacology of sleep and the effects of hypnotics, but he was also a pioneer in “sleep epidemiology.” His “Prevalence of sleep disorders in the Los Angeles metropolitan area” study of 1979 was the first rigorous epidemiological study on sleep disturbances. Starting in 1990, he established the Penn State Adult Cohort to estimate the prevalence and natural history of sleep-disordered breathing and other sleep disorders in adults. Inspired by life-course epidemiology, he established in 2001 the Penn State Child Cohort to estimate the same phenomena in children. This Living Legend paper captures and highlights Dr. Bixler’s enduring legacy to sleep science.
Rooting Race in Place: Whites’ Racial Learning in Southern Kinds of Places
Authors: Thomas James M , Burdine Madeline , Oakes Erin , Peairs Rhondalyn , Allgood-Crouse Angela M
Published: April 2024

We draw from 70 in-depth interviews with White southerners to examine their memories of and experiences with learning about race and whiteness. Our emphasis is on place and how it shapes Whites’ racial learning. To date, most research on racial learning centers ethno-racial minority children and their families and emphasizes when racial learning occurs. Less attention is paid to where it takes place. To remedy this, we center Southern kinds of places - those places and the social scenes within them that reflect, extend, and challenge dominant ideas about race and region. We examine three specific scenes - southern homes, southern schools, and southern college campuses - to illustrate how each shapes the racial lessons Whites receive. By bringing into focus the places White southerners draw upon when making sense of race, our research offers an important contribution to our understanding of whiteness and its transmission.
Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment
Authors: Minatoguchi Shinya , Fujita Yasuyuki , Niizuma Kuniyasu , Tominaga Teiji , Yamashita Toru , Abe Koji , Dezawa Mari
Published: April 2024

The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.
Comparing RT-PCR of Individual Samples with High-Throughput Sequencing of Pooled Plant Samples for Field-Level Surveillance of Viruses in Blackberry and Wild Rubus
Authors: Dantes Wanita , Boatwright Lucas , Cieniewicz Elizabeth J.
Published: April 2024

Blackberry production is increasing in the Southeastern United States with the availability of new cultivars. In addition to high production costs, growers are challenged by virus diseases. Blackberry yellow vein disease (BYVD) significantly limits blackberry production. BYVD is associated with the crinivirus blackberry yellow vein–associated virus in mixed infections with other viruses. The specific disease etiology and ecological factors underlying BYVD are not well understood and rely on the effective diagnosis of several viruses involved in the complex. In 2021, we collected samples from blackberry plants showing BYVD symptoms, asymptomatic blackberry plants, and wild Rosaceae spp. from nine farms across South Carolina, for a total of 372 individual plant samples. RNA from individual samples was isolated and pooled into sample groups (i.e., symptomatic, asymptomatic, and wild) from each farm for a total of 24 pooled samples. We sequenced the pooled RNA using Illumina and analyzed sequence profiles using the Virtool bioinformatics application. We also tested each plant for six viruses by reverse transcriptase PCR or reverse transcriptase quantitative PCR and compared plant (PCR)-level and field (high-throughput sequencing [HTS])-level data. Virtool detected 17 known viruses in the pooled samples, including 11 blackberry viruses. PCR testing was mostly consistent with HTS, with some notable disagreements for specific viruses. Our study demonstrates that HTS could be used as an efficient tool to detect viruses in bulked samples in blackberry fields, although limitations to using HTS for field-level surveillance are also discussed here.
Ten Challenges to Understanding and Managing the Insect-Transmitted, Xylem-Limited Bacterial Pathogen Xylella fastidiosa
Authors: De La Fuente Leonardo , Navas-Cortés Juan A. , Landa Blanca B.
Published: April 2024

An unprecedented plant health emergency in olives has been registered over the last decade in Italy, arguably more severe than what occurred repeatedly in grapes in the United States in the last 140 years. These emergencies are epidemics caused by a stealthy pathogen, the xylem-limited, insect-transmitted bacterium Xylella fastidiosa. Although these epidemics spurred research that answered many questions about the biology and management of this pathogen, many gaps in knowledge remain. For this review, we set out to represent both the U.S. and European perspectives on the most pressing challenges that need to be addressed. These are presented in 10 sections that we hope will stimulate discussion and interdisciplinary research. We reviewed intrinsic problems that arise from the fastidious growth of X. fastidiosa, the lack of specificity for insect transmission, and the economic and social importance of perennial mature woody plant hosts. Epidemiological models and predictions of pathogen establishment and disease expansion, vital for preparedness, are based on very limited data. Most of the current knowledge has been gathered from a few pathosystems, whereas several hundred remain to be studied, probably including those that will become the center of the next epidemic. Unfortunately, aspects of a particular pathosystem are not always transferable to others. We recommend diversification of research topics of both fundamental and applied nature addressing multiple pathosystems. Increasing preparedness through knowledge acquisition is the best strategy to anticipate and manage diseases caused by this pathogen, described as “the most dangerous plant bacterium known worldwide.”
Health Professionals Organizing for Climate Action: A Novel Community Organizing Fellowship
Authors: Basu Gaurab , Stojicic Pedja , Goldman Anna , Shaffer Jonathan , McCormick Danny
Published: April 2024

Problem

Climate change is a public health and health equity crisis. Health professionals are well positioned to advance solutions but may lack the training and self-efficacy needed to achieve them.

Approach

The Center for Health Equity Education and Advocacy at Cambridge Health Alliance, a Harvard Medical School Teaching Hospital, developed a novel, longitudinal fellowship that taught health professionals about health and health equity effects of climate change, as well as community organizing practices that may help them mitigate these effects. The fellowship cohort included 40 fellows organized into 12 teams and was conducted from January to June 2022. Each team developed a project to address climate change and received coaching from an experienced community organizer coach. Effects of the fellowship on participants’ knowledge, skills, and attitudes were evaluated using pre- and postfellowship surveys.

Outcomes

Surveys were analyzed for 38 of 40 (95%) participants who consented to the evaluation and completed both surveys. Surveys used a 7-point Likert scale for item responses. McNemar’s test for paired data was used to assess changes in the proportion of respondents who agreed (“somewhat agree”/“agree”/“strongly agree”) with statements in pre- vs postfellowship surveys. Statistically significant improvements were found for 11 of the 17 items assessing knowledge, skills, and attitudes. Participants’ views of the fellowship and its effects were assessed through additional items in the postfellowship survey. Most respondents agreed that the fellowship increased their knowledge of the connections between climate change and health equity (32/38, 84.2%) and prepared them to effectively participate in a community organizing campaign (37/38, 94.7%). Each of the 12 groups developed climate health projects by the fellowship’s end.

Next Steps

This novel fellowship was well received and effective in teaching community organizing to health professionals concerned about climate change. Future studies are needed to assess longer-term effects of the fellowship.