bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing Kinship Caregivers’ Ambivalence and Internalized Stigma to Improve Acceptance of Financial Assistance for Children in Foster Care
Authors: Ansong David , Appiah-Kubi Jamal , Amoako Emmanuel O , Brevard Kanisha , Denby Ramona W
Published: January 2025

Financial assistance programs, such as the Kinship Guardianship Assistance Program, provide essential ongoing support for the care of children when reunification with their biological parents or adoption by other families is not feasible. However, these programs are underutilized by relatives who step in to provide stable, permanent homes for these children, partly due to unresolved internal conflicts about accepting financial support for caring for family members. Formative data (N = 178) and Bayesian inferential methods were used to examine whether a tailored training and support program for kinship caregivers could influence the internal conflict and attitudes of these caregivers concerning their acceptance of financial assistance. The study also assessed whether reductions in internal conflicts differed by program delivery mode: in-person versus virtual. Findings indicate that internal conflicts and stigma (a) reduced after participation in the program, (b) reduced with both delivery modes, with greater reductions among the virtual participants, but (c) did not reduce for participants of the standard foster parent training program. Results trending in the desired direction indicate that kin-specific training and programs may have crossover effects on internalized financial stigma, thus highlighting the need for future evaluations to affirm these results and inform intervention planning.
Emotional job demands diminish employees’ sympathy over 9 years, but only for those with a low learning goal orientation
Authors: Reh Susan , Scheibe Susanne
Published: January 2025

Many professions require emotional effort from employees to perform their jobs effectively. Research on the consequences of such emotional job demands (EJDs) for employees has yielded mixed findings with only a few longitudinal studies. This study’s aim is to improve the understanding of how EJDs affect the development of employees’ emotional functioning over time, specifically the degree of sympathy they experience toward others, and which factors enhance or buffer this relationship. Drawing on the theoretical model of strengths and vulnerabilities integration, we predict that occupation-level EJDs reduce employees’ sympathy over a 9-year time period. At the same time, we predict that a learning goal orientation (LGO), the motivation for task mastery and self-improvement, buffers the potentially negative effects of EJDs on sympathy changes. We test our model using data from N = 831 working adults from the second and third waves of the Midlife in the United States survey in combination with data from the Occupational Information Network. In line with predictions, results from latent change score models show that although sympathy on average increases over the 9-year span, EJDs have a negative effect on these changes and a LGO moderates this effect so that EJDs have a negative effect on sympathy changes only for employees low in LGO. We discuss implications for theory and practice.
Screening blueberry genotypes for susceptibility to mummy berry in Mount Vernon, WA, 2024
Authors: Puri Purnima , Elcan Adam , DeVetter Lisa , Mattupalli Chakradhar
Published: January 2025

Mummy berry, caused by the fungal pathogen Monilinia vaccinii-corymbosi, negatively impacts profitable production of blueberry (Vaccinium corymbosum L.) in the Pacific Northwest. This report describes a screenhouse trial conducted at Washington State University Mount Vernon Northwestern Washington Research and Extension Center in 2024 to evaluate twenty blueberry genotypes for susceptibility to mummy berry. Differential responses among the tested genotypes were observed for the number of blighted shoots and flower clusters as well as the percent of infected fruits.
Social, Emotional, and Behavioral Functioning in Adolescents with Klinefelter Syndrome
Authors: Jünger Anja L. , Lasecke Meagan , Foland-Ross Lara C. , Jordan Tracy L. , Sundstrom Jamie L. , Wun Vanessa Lozano , Witkin Gregory A. , Ikomi Chijioke , Ross Judith , Reiss Allan L.
Published: January 2025

Objective:

Klinefelter syndrome (KS) is a common genetic condition in males associated with an extra X chromosome (i.e., 47,XXY). Individuals with KS often experience androgen insufficiency and tall stature and are at increased risk for depression, anxiety, and social challenges. This cross-sectional study investigates social and emotional functions in 52 boys with KS and 62 typically developing (TD) boys, aged 8 to 13 years.

Methods:

Self-report measures of anxiety, depression, and behavior and parent-report measures of social functioning and behavior were completed. In primary analyses, linear regression was used to test the effect of group (KS, TD) on standardized scores derived from widely used rating scales. In secondary analyses, we explored the influence of pubertal status on these scores and concordance between self- and parent ratings.

Results:

Our results indicate that boys with KS exhibit significantly increased anxiety, depression, and social difficulties relative to TD peers. Among participants with KS, peripubertal boys generally experienced more difficulties in aspects of social and emotional functioning as compared to prepubertal boys. Concordance analyses revealed differences between parent- and child-reports.

Conclusion:

These findings indicate that alterations in social, emotional, and behavioral functions are present in boys and adolescents with KS and may be influenced by puberty.
Neurodevelopmental and Mental Health Outcomes in a National Clinical Sample of Youth With Sex Chromosome Trisomies Compared With Matched Controls
Authors: Hall Adriana , Furniss Anna , Tartaglia Nicole N. , Janusz Jennifer , Wilson Rebecca , Middleton Caitlin , Martin Sydney , Frazier Jacqueline , Martinez-Chadrom Michele , Hansen-Moore Jennifer , Ikomi Chijioke , Ross Judith , Vogiaski Maria G. , Morrow Leela , Christakis Dimitri A. , Lean Rachel E. , Nokoff Natalie , Pyle Laura , Davis Shanlee M.
Published: January 2025

Objective:

To compare the prevalence of neurodevelopmental and mental health diagnoses in a national sample of youth with sex chromosome trisomies (SCTs) with matched controls.

Methods:

Patients in PEDSnet and a diagnosis code mapping to 47,XXY/Klinefelter syndrome (n = 1171), 47,XYY/Double Y syndrome (n = 243), or 47,XXX/Trisomy X syndrome (n = 262) were matched with controls using propensity scores. Generalized estimating equations computed odds ratios (OR) with 95% confidence intervals (CI) for the prevalence of diagnoses within the neurodevelopmental and mental health composites, psychotropic medication prescriptions, and encounters with behavioral health and therapy providers. Alpha was set at 0.0025 to account for multiple comparisons.

Results:

Patients with SCTs had higher odds of diagnoses within the neurodevelopmental (OR 6.3, 95% CI, 5.7–7.2) and mental health composites (OR 2.7, 95% CI, 2.3–3.2) compared with matched controls. All neurodevelopmental diagnoses were more prevalent among all SCT groups compared with controls. Within the mental health composite, only the prevalence of anxiety and mood disorder was higher in all SCT groups. A higher proportion of patients with SCTs had psychotropic prescriptions compared with controls (stimulants 13.1% vs 5.2%, selective serotonin reuptake inhibitors 8.7% vs 2.8%, antipsychotics 6.5% vs 2.4%, p < 0.0001 for all). Overall, 48% of patients with SCTs had a clinical encounter with a behavioral health provider vs 16.6% of controls (OR 5.6, 95% CI, 4.1–5.1).

Conclusion:

Compared with matched controls, youth with SCTs receiving care at US tertiary care pediatric centers have disproportionately high rates of neurodevelopmental and mental health conditions, emphasizing the need for appropriate screening and intervention in these populations.
Effect of Childhood Adversity on the Relationship Between Family Resilience and Behavioral or Conduct Problems in Children With Special Healthcare Needs
Authors: Chowdhury Suman Kanti , Aydin Rihana Aaliyah , Puri Harsha , Sundaramurugan Suruthi , Rao Nagashree Ravi , Skinner Haille , Sauls Rachel , Brice Dowensly Jean , Tsang Steven , Bakour Chighaf , Kirby Russell S.
Published: January 2025

Objective:

Behavioral or conduct problems (BCPs) are common co-occurring conditions in children with special health care needs (CSHCNs), affecting their developmental and functional milestones. The role of family resilience in mitigating BCPs among these children and how adverse childhood experiences (ACEs) affect this dynamic remain largely unclear. The aim of the study was to disentangle the complex interplay between family resilience, ACEs, and BCPs by examining how ACEs moderate the relationship between family resilience and BCPs.

Methods:

The study included 19,922 CSHCNs aged 3 to 17 years from the 2020-2021 National Survey of Children's Health. Weighted analysis was conducted using the Rao-Scott χ2 test and multivariable logistic regression to account for the complex survey design.

Results:

Children from families with no and low resilience as compared with high-resilient families had 1.78 times (odds ratio [OR]: 1.78, 95% confidence interval [CI], 1.31–2.43) and 1.44 times (OR: 1.44, 95% CI, 1.18–1.76) higher odds of BCPs, respectively. While the odds of BCPs decreased in nonresilient families as ACEs increased from none to 1 ACE, 2 or more ACEs versus no ACE increased the odds of BCPs in low-resilient families from 1.42 times (OR: 1.42, 95% CI, 1.03–1.94) to 1.51 times (OR: 1.51, 95% CI, 1.13–2.02).

Conclusion:

The findings suggest that family resilience is associated with a lower likelihood of BCPs in CSHCNs. ACEs have varying effects on the relationship between family resilience and BCPs across different levels of family resilience. These results highlight the importance of strengthening family resilience and addressing ACEs in interventions to reduce behavioral issues in CSHCNs.
A Narrative Review of the Vulvar Disease Literature With Images of Women of Color
Authors: Ashenafi Gabriela , Dehaeck Ulrike C. , Madnani Nina A. , Parker-Featherstone Ebony C. , Saunders Natalie A. , Welch Kathryn C. , Mallhi Arshpreet Kaur , Haefner Hope K.
Published: January 2025

Objective

To assess the existing literature on vulvar disease in women of color (WOC).

Methods

A narrative review was conducted to assess the literature on vulvar disease in WOC and evaluate the presence of images in this population. The search encompassed PubMed and OVID using relevant terms related to vulvar conditions and various groups of WOC. Case reports, as well as posters were excluded. Books on this topic were searched using these two search engines and Google, as well as the Taubman Health Sciences Library at the University of Michigan. This library contains numerous books on vulvar diseases commonly used by health care providers.

Results

This query identified 24 journal publications on vulvar diseases in WOC. Twenty-six books, commonly used by health care providers, were found to have been published with vulvar images of WOC. However, only 1 focused specifically on vulvar diseases in WOC.

Conclusions

There is a notable scarcity of articles and books addressing vulvar conditions specifically in WOC. This gap in literature limits our understanding of how these conditions may uniquely affect this demographic population. Additional research and resources are essential to effectively represent and meet the health needs of WOC.
Engineering Programmable Nanobiomateris (PNBMs) for Cancer Nanotherapy
Authors: Wang Jinghui , Hou Jiaxin , Lu Kangjie , Bai Sule , Chen Yu , Yang Wanting , Wang Shuo , Li Guofeng , Wei Yen , Wang Xing , Xie Wensheng
Published: January 2025

With the rapid progress of nanotechnology, the development of multifunctional nanobiomaterials (NBMs) has brought about innovative strategies and improvements in tumor nanotherapy, particularly in achieving precise control over the therapeutic process for higher therapeutic efficacy while minimizing side effects. Considering the heterogeneous nature of the tumor microenvironment, NBMs need to be carefully regulated treatment in terms of timing, location, and dosage. This gives rise to the concept of "Programming Nanobiomaterials (PNBMs)" to deliver the appropriate dose of drugs at the optimal time and site in response to endogenous or exogenous stimuli, thereby facilitating accurate tumor clearance. The objective of this paper is to summarize current advances and applications of PNBMs in tumor nanotherapy. Additionally, It aims to discuss the utilization of PNBMs in tumor precision therapy in terms of component programming, size programming, hydrophilicity programming, cascade response programming, logic gate control programming, and multifactor response programming. Furthermore, we prospect the PNBMs fusion design, matching complicated microenvironments, degradability and safety, and clinical application potential, all of which will serve as a reference for the design and development of novel and efficient PNBMs in cancer nanotherapy.
Unusual association of primary parotid and conjunctival tuberculosis in a young immunocompetent patient: A case report
Authors: Hachimi Idrissi Mariam , Zaza Qamar , Benbachir Adam , Skalante Oumaima , Benaazza Soufiane , Allaoui Mohamed , Ben Lahlou Yassine , Benaissa Elmostafa , Chadli Mariama
Published: January 2025

2. Abstract

Extrapulmonary tuberculosis often presents as lymphadenitis. In the head and neck area, tuberculous involvement of the parotid gland is rare and challenging to diagnose due to non specific symptoms, which can be confused with a tumor. Tuberculous conjunctivitis, although uncommon, should be considered in cases of chronic, treatment-resistant conjunctivitis.
The association of primary parotid and conjunctival tuberculosis is exceptional. They are difficult to diagnose due to the non-specificity of their clinical, biological and radiological signs.  We report the case of a 24-year-old immunocompetent patient with no history of tuberculosis, who presented with intermittent swelling of the left parotid gland, accompanied by unilateral redness of the eye, which appeared two months later, in a context of fever and night sweats. The patient also reported a foreign body sensation in his eye, mild tearing, and photophobia . Clinical examination revealed painful, warm swelling of the left parotid gland, as well as localized granulomatous conjunctivitis.
Cervico-parotid CT and MRI revealed two well-limited, oval, left parotid formations with a slightly thickened and enhanced wall after injection of Gadolinium, suggestive a priori of abscessed collections.
The diagnosis of primary parotid and conjunctival tuberculosis was made on the basis of histological examination of the biopsies, as well as direct examination, culture and GeneXpert. The patient progressed well on anti-bacillary treatment.
Our work underlines the great importance of GeneXpert, which is a rapid and highly sensitive technique, effective in the diagnosis of extra pulmonary tuberculosis.
Spatial Profiling Reveals Equivalence-Derived Molecular Signatures of Brain Mimicry and Adaptation in Breast Cancer Brain Metastases
Authors: Garcia Maxine Umeh , Yeh Christine Yiwen , Godfrey Bryanna , Perez Pablo Nunez , Barisano Giuseppe , Varma Sushama , Ahmadian Saman , Toland Angus , Granucci Monica , Trinh Thy , Vogel Hannes , West Robert , Angelo Michael , Tian Lu , Plevritis Sylvia K. , Gephart Melanie Hayden
Published: January 2025

Brain metastases (BrMets), common for advanced-stage breast cancer patients, are associated with poor median survival and accompanied by severe neurologic decline. Halting the progression of breast cancer brain metastases (BCBMs) may require modulation of the tumor microenvironment (TME), yet little is known about the impact of the primary breast TME on brain tropism, or how, once there, metastatic breast cancer cells coexist with brain-resident cells (e.g., neurons and glia). Traditionally, studies in this space have focused on differential expression analysis, overlooking potential insights gained from investigating genes with equivalent expression between groups. This is particularly crucial in distant metastasis, where tumor cells may co-opt the transcriptional programs of the host organ (e.g., brain) to facilitate successful seeding and outgrowth. Prior to our work, no computational framework existed to determine biologically-relevant equivalent gene expression. To resolve molecular mechanisms of BCBM enabled by metastatic cancer cells and/or resident brain cells, we leveraged Nanostring GeoMx to perform spatially-resolved transcriptomic profiling on 235 patient-derived tissue cores from BCBM (including adjacent normal brain), primary invasive breast cancers, and normal (non-cancer) brain; analyzing 18,677 RNAs in 450 areas of interest (AOIs). We introduce the “Equivalent Expression Index” a highly specific and accurate algorithm that identifies statistically significant “Equivalently-Expressed Genes”. This method facilitated the identification of molecular remodeling and mimicry genes within tissue-specific TMEs. By integrating differential expression analysis with the Equivalent Expression Index, we discovered multiple novel gene signatures associated with BCBM and primary tumor brain-metastatic potential. We demonstrate that the Equivalent Expression Index is a powerful tool to uncover shared gene expression programs representing the adaptation of metastatic cells and brain-resident cells to the BCBM microenvironment.
Long-Term Effects of Radiation Therapy on Cerebral Microvessel Proteome: A Six-Month Post-Exposure Analysis
Authors: Subramanian Vikram , Juhr Denise , Giansanti Piero , Grumbach Isabella M.
Published: January 2025

Background

Radiation therapy (RT) treats primary and metastatic brain tumors, with about one million Americans surviving beyond six months post-treatment. However, up to 90% of survivors experience RT-induced cognitive impairment. Emerging evidence links cognitive decline to RT-induced endothelial dysfunction in brain microvessels, yetin vivostudies of endothelial injury remain limited. Investigating the molecular and cellular pathways connecting RT, endothelial dysfunction, and cognitive impairment is vital for developing targeted interventions. This study examines proteomic changes in cerebral microvessels following RT.

Methods

We conducted a comprehensive quantitative analysis comparing the proteome in cerebral microvessels from five control mice and five irradiated mice (12 Gy) 6 months after RT. Bioinformatics analyses included gene ontology (GO) enrichment, Mitocarta analysis, Ingenuity Pathway Analysis (IPA), and iPathwayGuide. Predictions from the analyses were validated by western blotting.

Results

Our data identified significant dysregulation of 414 proteins following RT, with 157 upregulated and 257 downregulated. Gene ontology analysis indicated that the majority of the dysregulated proteins were part of various metabolic pathways. Cross referencing with Mitocarta revealed a significant presence of mitochondrial proteins among the dysregulated proteins, indicating potential mitochondrial metabolic dysfunction. Further investigation with IPA analysis uncovered 76 enriched canonical pathways, 34 transcription regulators, 6 nuclear receptors, and 5 growth factors involved in RT-induced damage responses in cerebral microvessels. IPA canonical pathway analysis predicted mitochondrial dysfunction due to inhibition of various metabolic pathways in the irradiated group. Validation with western blotting confirmed the bioinformatics predictions from the proteomic dataset.

Conclusions

Our data show significant proteomic changes in cerebral microvessels 6 months post-radiation, including oxidative phosphorylation, the TCA cycle, and glycolysis, suggesting metabolic mechanisms of RT-induced microvascular dysfunction.
Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor within VivoAnti-alphaviral Activity
Authors: Hossain Mohammad Anwar , Mayo Abigail K. , Ghoshal Anirban , Taft-Benz Sharon A. , Anderson Elizabeth J. , Morales Noah L. , Pressey Katia D. , Vargason Ava M. , Brouwer Kim L. R. , Moorman Nathaniel J. , Heise Mark T. , Willson Timothy M.
Published: January 2025

RA-0002034 (1) is a potent covalent inhibitor targeting the alphavirus nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of1were investigated to evaluate its therapeutic potential. Pharmacokinetic profiling revealed rapid clearance in mice, predominantly mediated by glutathioneS-transferase (GST)-catalyzed conjugation. This metabolic liability contrasted with slower clearance observed in human hepatocytes and preclinical species such as rats, dogs, and monkeys. Cross-species studies confirmed the dominance of GST-driven metabolism in mice, whereas oxidative pathways were more pronounced in dogs. Despite rapid systemic clearance,1achieved antiviral efficacy in mice, reducing CHIKV viral loads in multiple tissues. Initial estimations of human hepatic clearance and half-life extrapolated from animal data indicate that b.i.d. dosing of1will be possible to maintain concentrations sufficient for antiviral activity in humans. These cross-species pharmacokinetic and metabolism studies support the continued evaluation of1as a promising anti-alphaviral therapeutic.

Graphical Abstract
Ants oscillate and scan more in navigation when the visual scene changes
Authors: Deeti Sudhakar , Cheng Ken
Published: January 2025

Solitarily foraging ants learn to navigate between important locations by comparing their current view with memorized scenes along a familiar route. As desert ants, in particular, travel between their nest and a food source, they establish stable and visually guided routes that guide them without relying on trail pheromones. We investigated how changes in familiar visual scenes affect the navigation of the red honey ant (Melophorus bagoti). In Experiment 1, ants were trained to follow a one-way diamond-shaped path to forage and return home. We manipulated scene familiarity by adding a board on their homebound route just before the nest. In Experiment 2, ants were trained to travel a straight path from their nest to a feeder, and we removed the prominent landmarks on the route after they had established a stable route. We predicted that these scene changes would cause the ants to deviate from their usual straight paths, slow down, scan more, and increase their lateral oscillations to gather additional information. Our findings showed that when the familiar scene was changed, ants oscillated more, slowed their speed, and increased scanning bouts, indicating a shift from exploiting known information to more actively exploring and learning new visual cues. These results suggest that scene familiarity plays a crucial role in ant navigation, and changes in their visual environment lead to distinct behavioral adaptations aimed at learning about the new cues.
Backward alpha oscillations shape perceptual bias under probabilistic cues
Authors: Tarasi Luca , Alamia Andrea , Romei Vincenzo
Published: January 2025

Predictive coding theory suggests that prior knowledge is crucial for optimizing human decision-making, with recent studies emphasizing the role of alpha-band oscillations in this process. Here, we employed a traveling waves approach to investigate how alpha oscillations integrate prior expectations during a perceptual decision-making task. Our findings demonstrated that expectation-based knowledge triggers the propagation of alpha traveling waves from frontal to occipital areas, with this increase associated with enhanced modulation of brain regions involved in stimulus processing and directly linked to prior-driven bias at the behavioral level. Moreover, participants who relied more on prior expectations exhibited stronger top-down signaling, whereas those who focused on sensory input showed a contrasting forward signaling pattern. These results highlight the role of alpha-band traveling waves in predictive mechanisms, suggesting that rhythmic interactions across brain regions facilitate this process and contribute to inter-individual differences in its implementation.
Resistance to BRAF inhibitors drives melanoma sensitivity to Chk1 inhibition
Authors: Carvalho Danielle G. , Kenski Juliana C. N. , Moreira Daniel A. , Rajão Matheus A. , Krijgsman Oscar , Furtado Carolina , Boroni Mariana , Viola João P. B. , Peeper Daniel S , Possik Patricia Abrao
Published: January 2025

BRAF inhibitor-resistant melanomas (BRAFiR) acquire (epi)genetic and functional alterations that enable them to evade alternative treatments. Identifying these alterations is critical to advancing treatment strategies. Here, we explored the effect of Chk1 inhibition (Chk1i) on BRAFiR cells, revealing higher sensitivity compared to treatment-naïve cells bothin vitroandin vivo. Using FUCCI-labeling and time-lapse microscopy, we show that S phase progression is required for Chk1i-induced cytotoxicity in BRAFiR cells, but not in treatment-naïve cells. Replication stress markers, including reduced BrdU incorporation and increased phospho-RPA and γH2AX, were exclusive to BRAFiR cells exposed to Chk1i. Untreated BRAFiR cells exhibited upregulated DNA replication genes, reduced progressing forks and increased origin firing, suggesting intrinsic replication changes. MAPK pathway reactivation in treatment-naïve cells mimicked BRAFiR traits, increasing sensitivity to Chk1i. These findings indicate that Chk1i exploits elevated replication stress specifically in BRAFiR, highlighting its therapeutic potential in overcoming MAPK inhibitor resistance in melanoma.
An artifact of recombinatorial cloning challenges established beliefs of plasmid co-transformation, selection, and maintenance
Authors: Geer Courtney L. , Charette J. Michael
Published: January 2025

Gateway cloning is an easy, efficient, accurate, and versatile cloning strategy. During Expression clone validation, we sometimes see an additional band co-migrating with the pDONR backbone. We show that this “mystery” band is not an artifact of aberrant recombination but instead originates from a co-transformation event. We find that the unselected pDONR plasmid is co-transformed intoE. coliwith the desired Expression vector in 9–29% of colonies and is maintained without antibiotic selection, despite plasmid incompatibility. We propose an easy strategy to screen for co-transformants. Our results challenge accepted beliefs of bacterial plasmid transformation, selection, and maintenance.
Community assembly modeling of microbial evolution within Barrett’s esophagus and esophageal adenocarcinoma
Authors: Guccione Caitlin , Sfiligoi Igor , Gonzalez Antonio , Shaffer Justin P. , Kazachkova Mariya , Weng Yuhan , McDonald Daniel , Shah Shailja C. , Minot Samuel S. , Paulson Thomas , Grady William M. , Alexandrov Ludmil B. , Knight Rob , Curtius Kit
Published: January 2025

Mathematical modeling of somatic evolution, a process impacting both host cells and microbial communities in the human body, can capture important dynamics driving carcinogenesis. Here we considered models for esophageal adenocarcinoma (EAC), a cancer that has dramatically increased in incidence over the past few decades in Western populations, with high case fatality rates due to late-stage diagnoses. Despite advancements in genomic analyses of the precursor Barrett’s esophagus (BE), prevention of late-stage EAC remains a significant clinical challenge. Previous microbiome studies in BE and EAC have focused on quantifying static microbial abundance differences rather than evolutionary dynamics. Using whole genome sequencing data from esophageal tissues, we first applied a robust bioinformatics pipeline to extract non-host DNA reads, mapped these putative reads to microbial taxa, and retained those taxa with high genomic coverage. When applying mathematical models of microbial evolution to sequential stages of progression to EAC, we observed evidence of neutral dynamics in community assembly within normal esophageal tissue and BE, but not EAC. In a case-control study of BE patients who progressed to EAC cancer outcomes (CO) versus those who had non-cancer outcomes (NCO) during follow-up (mean=10.5 years), we found thatHelicobacter pylorideviated significantly from the neutral expectation in BE NCO, suggesting that factors related toH. pyloriorH. pyloriinfection itself may influence EAC risk. Additionally, simulations incorporating selection recapitulated non-neutral behaviors observed in the datasets. Formally modeling dynamics during progression holds promise in clinical applications by offering a deeper understanding of microbial involvement in cancer development.
The Translational Landscape of Reactive Astrocytes Reveals the Impact of eIF2B-mediated Dysregulation in VWM Disease
Authors: Mandelboum Shir , Lev-Ari Liat , Atzmon Andrea , Herrero Melisa , Brezner Naama , Benhalevy Daniel , Elroy-Stein Orna
Published: January 2025

A devastating genetic recessive neurodegenerative disorder, Vanishing White Matter Disease (VWMD), stems from mutations in eIF2B—a master regulator of mRNA translation initiation and mediator of cellular stress response. While astrocytes, the brain’s essential support cells, are known to be central to VWMD pathology, the molecular mechanisms underlying their dysfunction remain poorly understood. Our study reveals that even a mild mutation in eIF2B5 profoundly disrupts astrocyte mRNA translation regulation upon cytokine-mediated activation, affecting nearly one-third of all expressed genes. Through innovative integration of RNA-seq and Ribo-seq analyses using primary cell cultures of astrocytes isolated from eIF2B5R132H/R132Hmice, we discovered attempts to compensate for impaired protein production by increasing mRNA levels. However, this compensation proves insufficient to maintain critical cellular functions. Our comprehensive analysis uncovered significant disruptions in cellular energy production and protein synthesis machinery. We also predicted previously unknown defects in cholesterol biosynthesis within mutant astrocytes. Moreover, a meta-analysis of translation initiation scores pinpointed, for the first time, a short list of specific ’effector’ gene candidates that may drive disease progression. This powerful combination of transcriptome and translatome illuminates the complex pathophysiology of VWMD and identifies promising new biomarkers and therapeutic target opportunities.
Receipt of BNT162b2 KP.2 Vaccine and COVID-19 CVS MinuteClinic Visits in US Adults
Authors: Rudolph Abby E. , Khan Farid L. , Sun Xiaowu , Lupton Laura L. , Puzniak Laura A. , Jodar Luis , McLaughlin John M.
Published: January 2025

Using a test-negative design, we modeled the association between receipt of BNT162b2 KP.2 vaccine and symptomatic COVID-19 among adults testing for SARS-CoV-2 at walk-in clinics in a large US retail pharmacy chain (9/5/2024–12/8/2024). At a median of 37 days post-vaccination, those who received BNT162b2 KP.2 were 48% less likely to test positive.
Pan-Cancer Proteogenomic Network Analysis Uncovers Immune Microenvironment and Prognostic Biomarkers
Authors: Shi Wenhan , Guan Runing , Li Jiafeng , Chen Dongjing
Published: January 2025

Pan-cancer analysis provides valuable insights into common and distinct molecular mechanisms across various cancer types. Co-expression networks, which captured the cordinated expression of genes and proteins, offer potentials for identifying robust biomarkers and targeted therapies. However, current-existing co-expression construction method involves either RNA or Protein data in isolation, limiting our understanding on multi-perspective interactions in cancer. To address this gap, we integerated both the RNA and Protein data to constrcut a comprehensive pan-cancer co-expression network, combining both gene and proteomic layers of information across cancer types. This approach enables the identification of previously undetected co-expression relationships, highlighting key regulatory patterns in cancer analysis. Our study constructed a multi-perspective co-expression network, after that, we identified several conservation modules and compare the modules identified from RNA and Protein. We found out that the conservation modules identified differ significantly from RNA and Protein data. However, there are certain shared conservation modules, especially those related to IFN-gamma, IFN-alpha, and the activation of JAK_STAT. Then we identified several important immune-related pathways using RNA and Protein data and uncovered some modules with high prognostic value across cancers. As a novel pan-cancer analysis approach, it holds promise for advancing future cancer research, from the discovery of novel biomarkers to the design of personalized cancer therapies, thereby enabling more thorough and holistic cancer analysis.
Cytosolic transport of citrate protects nutrient-austere pancreatic cancer from ferroptosis
Authors: Kneebone Adam , Lindaur Kailey , Abbas Ata , Cassel Joel , Graff Sarah , Abood Gerard , Ding Xianzhong , Small William , Tatsuoka Curtis , Sidoli Simone , Salvino Joseph M. , Vaziri-Gohar Ali
Published: January 2025

Pancreatic cancer (PDAC) cells experience nutrient starvation in a poorly perfused tumor microenvironment. Metabolic dependencies that protect PDAC cells from detrimental oxidative stress in a nutrient-restricted niche represent as tumor-specific targets. While the role of mitochondria in supporting energy production and biosynthetic requirements of cells has been well investigated, their contribution to maintaining intracellular redox homeostasis when PDAC cells are exposed to nutrient deprivation is unknown. Our results demonstrate that cytosolic transport of citrate via SLC25A1 confers a survival advantage to PDAC cells by protecting them from ferroptosis, a well-established iron-dependent cell death mechanism, under nutrient-limited conditions. Employing selective SLC25A1 inhibitor or targeting mitochondrial OXPHOS dramatically reduced GPX4 expression and PDAC cell viability. Rescuing GPX4 expression with the products of both ACLY and ACO1-dependent pathways uncovered their critical role in conferring survival advantage under metabolic stress. Importantly, exogenous expression of GPX4 reversed redox imbalance and metabolic discordance resulting from the lack of SLC25A1 activity, indicating the requirement of citrate-induced GPX4 expression to support mitochondrial health and function. As observed with cultured cells under nutrient limitation, SLC25A1 function was revealed to be indispensable in pancreatic tumor microenvironment, and the reduced growth, due to the lack of SLC25A1 activity, was rescued with antioxidant NAC in preclinical models of PDAC. Lastly, SLC25A1 suppression was accompanied by elevated glutamine metabolism, and combination therapy with pharmacologic inhibitors of SLC25A1 and glutaminase inhibitor CB-839 dramatically suppressed tumor growth, highlighting this combinatorial approach as a potential therapeutic strategy in PDAC.
NimA promotes cell adhesion at the blood brain barrier ofDrosophilanervous system
Authors: Sakr Rosy , Monticelli Sara , Delaporte Claude , Zhang Gege , Tabiat Tarek , Giangrande Angela , Cattenoz Pierre B.
Published: January 2025

Glial cells are crucial for nervous system development and function, by clearing debris, protecting neurons, and ensuring neuronal survival. In Drosophila, glia also form the blood-brain barrier (BBB), which regulates neural stem cell proliferation and shields the nervous system while maintaining organism-wide communication. To uncover glial-specific roles, we compared their transcriptome with that of neurons and macrophages.

Our study identifies NimA, an uncharacterized member of the Nimrod scavenger receptor family, as a glial-specific protein consistently expressed during development. Unlike other family members, i.e. NimC1 (macrophage-specific), Draper (shared by glia and macrophages), and NimC4/Simu (restricted to embryonic stages), NimA is not involved in phagocytosis. Instead, it regulates cell-cell interactions and adhesion, crucial for maintaining the tight septate junctions of the larval BBB. Loss of NimA compromises BBB integrity, delays development, reduces brain size and impairs neural stem cell proliferation.

Altogether, the identification of a novel molecular player and more in general, of the glial-specific molecular landscape, are key to understand the contribution of glia to the construction and the function of the nervous system.
Redundant, weakly connected prefrontal hemispheres balance precision and capacity in spatial working memory
Authors: Tschiersch Melanie , Umakantha Akash , Williamson Ryan C. , Smith Matthew A. , Barbosa Joao , Compte Albert
Published: January 2025

How the prefrontal hemispheres coordinate to adapt to spatial working memory (WM) demands remains an open question. Recently, two models have been proposed: A specialized model, where each hemisphere governs contralateral behavior, and a redundant model, where both hemispheres equally guide behavior in the full visual space. To explore these alternatives, we analyzed simultaneous bilateral prefrontal cortex recordings from three macaque monkeys performing a visuo-spatial WM task. Each hemisphere represented targets across the full visual field and equally predicted behavioral imprecisions. Furthermore, memory errors were weakly correlated between hemispheres, suggesting that redundant, weakly coupled prefrontal hemispheres support spatial WM. Attractor model simulations showed that the hemispheric redundancy improved precision in simple tasks, whereas weak inter-hemispheric coupling allowed for specialized hemispheres in complex tasks. This interhemispheric architecture reconciles previous findings thought to support distinct models into a unified architecture, providing a versatile interhemispheric architecture that adapts to varying cognitive demands.
Immune-sensitization toMycobacterium tuberculosisAmong Young Children With and Without Tuberculosis
Authors: Gutierrez Jesús , Malone LaShaunda L. , Mohammadi Mitchka , Mukisa John , Atuhairwe Michael , Mwesigwa Simon Peter G. , Athieno Salome , Buwule Sharon , Ameda Faith , Kiyingi Sophie , Mupere Ezekiel , Stein Catherine M. , Lancioni Christina L.
Published: January 2025

Background

Identification of young children withMycobacterium tuberculosis(Mtb)-infection is critical to curb Tuberculosis (TB)-related pediatric morbidity and mortality. The optimal test to identify young children with evidence ofMtb-infection remains controversial.

Methods

Using a TB household contact (HHC) study design among 130 Ugandan children less than 5 years with establishedMtb-exposure, we compared the usefulness of the tuberculin skin test (TST) and QuantiFERON Gold Plus (QFT-Plus) to identify children with evidence forMtb-sensitization. We conducted univariate analysis to compare findings between children with and without TB disease, and performed a logistic regression model to estimate the odds of TB. We performed a sensitivity analysis by stratifying results by age (< 2 years vs. 2-5 years). Finally, we compared results of the QFT-Plus TB tube 1 and TB tube 2 to establish concordance.

Results

A 5 mm TST threshold identified the most children with evidence ofMtb-sensitization; this result was most pronounced in children with TB. Moreover, the odds of TB were 2 times higher [aOR: 2.09 (CI: 1.02 – 4.37)] among children with a positive TST. The QFT-Plus’ TB tube 1 and TB tube 2 results were highly correlated.

Conclusions

TST identified more TB-exposed young children with evidence ofMtb-immune-sensitization, when compared to QFT-Plus. These findings are highly relevant for children who are TB HHCs in endemic settings, and most at risk for TB following an exposure. We recommend that TST testing continue to be performed to assess forMtb-sensitization in young children.
Tissue Region Segmentation in H&E-Stained and IHC-Stained Pathology Slides of Specimens from Different Origins
Authors: Naghshineh Kani Sepideh , Soyak Burak Can , Gokce Melih , Duyar Zeynep , Alicikus Hasan , Yapıcıer Özlem , Oner Mustafa Umit
Published: January 2025

In the era of advancing digital pathology, integrating digital slides and deep learning-based decision support systems has become increasingly prevalent in clinical practice. The effectiveness of these systems heavily relies on tissue region segmentation, a process essential for slide scanning and success of deep learning (DL) models. While thresholding-based methods are fast, they usually do not accurately detect tissue regions, especially in diverse staining scenarios or debris-laden images. Hence, this study develops a fast, lightweight, accurate, and robust deep-learning framework for segmenting tissue regions in digital pathology slides of various tissue types with different staining. The model is trained and tested on datasets of seven tissue types collected from seven different institutes. Internal and external validation studies have shown promising results, with area under receiver operating characteristics curve values greater than 0.98. The model has a memory footprint of 19.8 MBs, and it takes approximately 22 seconds to segment out a digital pathology slide using the CPU. The model could be used in digital slide scanners to improve the scanning process and in the pre-processing stages of DL pipelines to prepare high-quality datasets.
Berry Supplement-Modified Human Microbiome Improves Immunotherapy Response in Mouse Models
Authors: Jahanbahkshi Shiva , Bibi Amna , Hoyd Rebecca , Dravillas Caroline , Williams Nyelia , Zhang Shiqi , Pallerla Aaditya , Suman Shankar , Amann Joseph , Goruganthu Mounika , Okimoto Tamio , Liu Yangyang , Bittoni Marisa A. , Shi Ni , Anand Alvin , Conrad Bailey , Nevers Lane , Heitman Kristen , Webb Maxine , Grainger Elizabeth M , Grogan Madison , Quiles Christian , Chen Tong , Presley Carolyn J. , Li Lang , Bradley Patrick , Vodovotz Yael , Carbone David P. , Clinton Steven K. , Zhu Jiangjiang , Spakowicz Daniel
Published: January 2025

Cancer outcomes have improved with immune checkpoint inhibitor (ICI) treatment; however, less than half of tumors respond. Emerging data show that some responses to ICI depend on the host’s microbiome. Here, we explore a dietary intervention to modify the microbiome and determine the response to ICIs. Following pre-clinical studies showing the benefit of black raspberries, we conducted a human intervention trial called the BEWELL Study (NCT04267874). The intervention increased the abundance of pro-ICI-response microbes (PIRMs). In mouse models, participants’ post-dietary intervention stool led to smaller tumor volumes following treatment with ICIs than pre-dietary intervention samples. One PIRM,Blautia obeum, was sufficient to improve ICI response. These results suggest that black raspberry nectar can modify the human gut microbiome to promote an improved response to ICIs.
Association between digital biomarkers, loneliness and social isolation: a systematic review and meta-analysis
Authors: Lau Yolanda , Chemas Natalia , Gokani Heema Ajeet , Morrell Rachel , Phannarus Harisd , Cooper Claudia , Walker Zuzana , Demnitz-King Harriet , Marchant Natalie L
Published: January 2025

Question

What is the current evidence base for the association between digital biomarkers from wrist-worn wearables, loneliness and social isolation in adults?

Study selection and analysis

We systematically searched six databases from inception to 24thSeptember, 2024. We narratively synthesised findings and pooled effect sizes using random-effects meta-analyses where possible.

Findings

We included 14 studies from 12 articles (12 assessing loneliness, two assessing social isolation). Eight studies used sleep metrics, four used physical activity metrics, and two studies used machine learning approaches. Three meta-analyses were conducted: worse sleep efficiency (SE), but not total sleep time or sleep onset latency, was associated with higher loneliness (Fisher’s z = −0.20, 95% CI −0.34 to −0.06, p = 0.006). Two studies examined wake after sleep onset (WASO), and found longer periods of WASO were associated with higher loneliness. These findings on loneliness were echoed in the study examining social isolation. One study found that lower total physical activity was associated with higher levels of loneliness and social isolation, while other activity intensities showed mixed evidence. Machine learning studies demonstrated high accuracy in predicting loneliness, though models using digital biomarkers from smartphones provided better accuracy.

Conclusions

Worse SE, more WASO, and lower total physical activity were associated with loneliness and social isolation, particularly in middle- and older-age. Digital biomarker-based machine learning studies are sparse but show potential in predicting loneliness. Leveraging digital biomarkers as proxy markers of loneliness and social isolation could facilitate early detection of these conditions.

Key messages of the articles

What is already known on this topic

Loneliness and social isolation are linked to negative health outcomes, including increased dementia risk. Digital biomarkers have shown potential in detecting mental health conditions and symptoms, but no systematic review has explored their association with loneliness and social isolation.

What this study adds

This review identified 14 studies examining the association between digital biomarkers and loneliness or social isolation. Worse sleep efficiency, more wake after sleep onset, and lower physical activity were associated with higher levels of loneliness and social isolation.

How this study might affect research, practice or policy

Digital biomarkers could support the early detection of loneliness and social isolation, enabling timely intervention.
Detection of alpha synuclein seeding activity in tear fluid in patients with Parkinson’s disease
Authors: Canaslan Sezgi , Schmitz Matthias , Maass Fabian , Hermann Peter , da Silva Correia Susana , Zhang Shuyu , van Riesen Christoph , Parchi Piero , Lingor Paul , Zerr Inga
Published: January 2025

Detection of alpha-synuclein seeding activity in tear fluid (TF) might provide a promising non-invasive biomarker for Parkinson’s disease (PD) diagnosis.

In this study, we applied the alpha-synuclein seeding amplification assay (aSynSAA) to detect misfolded alpha-synuclein (aSyn) aggregation in TF from PD patients. The discovery cohort included 11 PD patients and 13 controls, and the validation cohort consisted of 9 PD patients and 11 controls without synucleinopathies.

The aSynSAA yielded positive results in over 55% of PD patients. These findings were confirmed in a second cohort, including patients with prion diseases as a negative control for synuclein pathology. Our results demonstrate for the first time the ability of aSynSAA to distinguish between PD and control groups in TF, with PD showing the highest seeding activity compared to prion disease and control groups. Further comparisons between cerebrospinal fluid (CSF) and TF samples from the same individuals revealed consistent seeding results across both biofluids. These findings highlight the potential of tear fluid as a novel, accessible medium for detecting Lewy body-specific misfolded synuclein aggregation in PD, which could aid in early diagnosis and disease progression monitoring.