bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression-Mediating Pathways From Household Adversity to Antiretroviral Therapy Nonadherence Among Children and Adolescents Living With HIV in Zambia: A Structural Equation Modeling Approach
Authors: Rosen Joseph G. , Mbizvo Michael T. , Phiri Lyson , Chibuye Mwelwa , Namukonda Edith S. , Kayeyi Nkomba 
Published: March 2023

Background:
In Zambia, half of children and adolescents living with HIV (CALWH) on antiretroviral therapy (ART) are virologically unsuppressed. Depressive symptoms are associated with ART nonadherence but have received insufficient attention as mediating factors in the relationship between HIV self-management and household-level adversities. We aimed to quantify theorized pathways from indicators of household adversity to ART adherence, partially mediated by depressive symptoms, among CALWH in 2 Zambian provinces.

Setting:
In July–September 2017, we enrolled 544 CALWH aged 5–17 years and their adult caregivers into a year-long prospective cohort study.

Methods:
At baseline, CALWH–caregiver dyads completed an interviewer-administered questionnaire, which included validated measures of recent (past 6 months) depressive symptomatology and self-reported past-month ART adherence (never versus sometimes or often missing medication doses). We used structural equation modeling with theta parameterization to identify statistically significant (P < 0.05) pathways from household adversities (past-month food insecurity and caregiver self-reported health) to depression (modeled latently), ART adherence, and poor physical health in the past 2 weeks.

Results:
Most CALWH (mean age: 11 years, 59% female) exhibited depressive symptomatology (81%). In our structural equation model, food insecurity significantly predicted elevated depressive symptomatology (ß = 0.128), which was associated inversely with daily ART adherence (ß = −0.249) and positively with poor physical health (ß = 0.359). Neither food insecurity nor poor caregiver health was directly associated with ART nonadherence or poor physical health.

Conclusions:
Using structural equation modeling, we found that depressive symptomatology fully mediated the relationship between food insecurity, ART nonadherence, and poor health among CALWH.
Assessment of Microglial Activation in Alzheimer Disease Using 18F-PBR06 PET
Authors: Carter Kelsey , Cicero Steven , Rissanen Eero , Dubey Shipra , Weiner Howard L. , Singhal Tarun 
Published: March 2023

Abstract
A 69-year-old woman with progressive short-term memory deficits was diagnosed with Alzheimer disease (MMSE 26/30, CDR 0.5) and underwent PET using 18F-PBR06, a second-generation 18-kDa translocator protein ligand, targeting brain microglia and astrocytes. SUV and voxel-by-voxel binding potential maps (using simplified reference tissue method and a cerebellar pseudo-reference region) were generated. Images showed evidence of increased glial activation in biparietal cortices (including bilateral precuneus and posterior cingulate gyri) and bilateral frontal cortices. After 6 years of clinical follow-up, patient progressed to moderate cognitive impairment (CDR 2.0) and required assistance for activities of daily living.
Lymphoma Masquerading as Lung Cancer
Authors: Ng Hong Zhi Alvin , Cheng Lenith Tai Jit , Ngam Pei Ing , Sinha Arvind Kumar , Loi Hoi Yin 
Published: March 2023

Abstract
Lymphoma typically manifests as lymphadenopathy, with or without solid organ involvement. Lymphomatous masses tend to respect anatomical structures, encasing rather than invading them. Tumor thrombus formation is a rare presentation in lymphoma that has been previously described in the liver and kidneys. We report an unusual presentation of B-cell lymphoma with imaging findings suggestive of metastatic lung cancer with tumor thrombus in the pulmonary vein and left atrium.
Routine Pathology Examination of Breast Tissue in Adolescent Reduction Mammaplasty
Authors: Hajebian H. Harvak , Puyana Salomon , Mejia Natalia , Van Wert Mary K. , Babycos Christopher R. , Friel Michael T. 
Published: March 2023

Background
Routine pathology examination of breast tissue in reduction mammaplasty (RM) is performed with aims of detecting incidental malignancy or risk-increasing lesions. In adolescent patients, the reported incidence ranges between 0% to 0.01%, and costs of pathology claims range between $23 and $614 per analysis. We aim to investigate the rate of incidental findings and the cost-effectiveness of routine pathology examination in adolescent RM.

Methods
A single-center retrospective review of the pathology results for 132 breast specimens from 66 consecutive RM patients was performed. Data collected for analysis included breast cancer risk factors, demographic information, and operative variables.

Results
Zero cases of incidental malignant or risk-increasing lesions were found among the 132 breast specimens from 66 patients aged between 10 and 24 years. Of the 132 specimens, 34 (26%) contained benign fibrocystic disease, which was significantly associated a body mass index greater than 30 kg/m2 and tissue resection weight greater than 1000 g per breast (P = 0.003, P = 0.007) respectively.

Conclusions
Based on the available data, the use of routine specimen analysis costs more than US $150 million for one breast cancer diagnosis during RM in this age group. In our study, zero atypical, precancerous, or cancerous lesions were detected in a 7-year analysis. The results of this study support the current literature, which reports no occurrence of incidental findings in young women and may promote a greater understanding of evidence-based healthcare spending while concomitantly decreasing the strain placed on histopathology services.
Predicting phenotype to mechanotype relationships in cells based on intracellular signaling network
Authors: Karabay Esra T. , Turnlund Amy , Grear Jessica , Fraley Stephanie I. , Katira Parag 
Published: March 2023

ABSTRACTCells originating from the same tissue can respond differently to external signals depending on the genotypic and phenotypic state of the cell and its local environment. We have developed a semi-quantitative-computational model to analyze the intracellular signaling network and its outcome in the presence of multiple external signals including growth factors, hormones, and extracellular matrix. We use this model to analyze the cell’s mechanical response to external stimuli and identify the key internal elements of the network that drive specific outcomes within the response space. The model is built upon the Boolean approach to network modeling, where the state of any given node is determined using the state of the connecting nodes and Boolean logic. This allows us to analyze the network behavior without the need to estimate all the various interaction rates between different cellular components. However, such an approach is limited in its ability to predict network dynamics and temporal evolution of the cell state. So, we introduce modularity in the model and incorporate dynamical aspects, mass-action kinetics, and chemo-mechanical effects on only certain transition rates within specific modules as required, creating a Boolean-Hybrid-Modular (BoHyM) signal transduction model. We present this model as a comprehensive, cell-type agnostic, user-modifiable tool to investigate how extra-and intra-cellular signaling can regulate cellular cytoskeletal components and consequently influence cell-substrate interactions, force generation, and migration. Using this tool, we show how slight changes in signaling network architectures due to phenotypic changes can alter cellular response to stress hormone signaling in an environment-dependent manner. The tool also allows isolating effector proteins driving specific cellular mechanical responses. Ultimately, we show the utility of the tool in analyzing transient chemo-mechanical dynamics of cells in response to time-varying chemical stimuli.
Distinct Myeloid Derived Suppressor Cell Populations Promote Tumor Aggression in Glioblastoma
Authors: Jackson Christina , Cherry Christopher , Bom Sadhana , Dykema Arbor G. , Thompson Elizabeth , Zheng Ming , Ji Zhicheng , Hou Wenpin , Li Runzhe , Zhang Hao , Choi John , Rodriguez Fausto , Weingart Jon , Yegnasubramanian Srinivasan , Lim Michael , Bettegowda Chetan , Powell Jonathan , Eliesseff Jennifer , Ji Hongkai , Pardoll Drew 
Published: March 2023

AbstractThe diversity of genetic programs and cellular plasticity of glioma-associated myeloid cells, and thus their contribution to tumor growth and immune evasion, is poorly understood. We performed single cell RNA-sequencing of immune and tumor cells from 33 glioma patients of varying tumor grades. We identified two populations characteristic of myeloid derived suppressor cells (MDSC), unique to glioblastoma (GBM) and absent in grades II and III tumors: i) an early progenitor population (E-MDSC) characterized by strong upregulation of multiple catabolic, anabolic, oxidative stress, and hypoxia pathways typically observed within tumor cells themselves, and ii) a monocytic MDSC (M-MDSC) population. The E-MDSCs geographically co-localize with a subset of highly metabolic glioma stem-like tumor cells with a mesenchymal program in the pseudopalisading region, a pathognomonic feature of GBMs associated with poor prognosis. Ligand-receptor interaction analysis revealed symbiotic cross-talk between the stemlike tumor cells and E-MDSCs in GBM, whereby glioma stem cells produce chemokines attracting E-MDSCs, which in turn produce growth and survival factors for the tumor cells. Our large-scale single-cell analysis elucidated unique MDSC populations as key facilitators of GBM progression and mediators of tumor immunosuppression, suggesting that targeting these specific myeloid compartments, including their metabolic programs, may be a promising therapeutic intervention in this deadly cancer.One-Sentence SummaryAggressive glioblastoma harbors two unique myeloid populations capable of promoting stem-like properties of tumor cells and suppressing T cell function in the tumor microenvironment.
The Influence of Variable-Heavy (VH) Chain Families on IgG2,3,4on FcγRs and Antibody Superantigens Protein G and L Binding using Biolayer Interferometry
Authors: Deacy Anthony M. , Gan Samuel Ken-En 
Published: March 2023

ABSTRACTBackgroundAs the most abundant immunoglobulin in blood and the most common human isotype used for therapeutic monoclonal antibodies, the engagement and subsequent activation of its Fc receptors by IgGs are crucial for antibody function. While generally assumed to be relatively constant within subtypes, recent studies have shown the antibody variable regions to exert distal effects of modulating antibody–receptor interactions on many antibody isotypes. Such effects are also expected for IgG and its subtypes with the in-depth understanding of these V-region effects highly relevant for engineering antibodies, antibody purifications, and understanding to how robust the microbial immune evasion proteins are.MethodsIn this study, we created a panel of IgG2/IgG3/IgG4antibodies by changing the VHfamily (VH1-7) frameworks while retaining the complementarity determining regions of Pertuzumab and measured the interaction of the IgGs with FcγRIa, FcγRIIaH167, FcγRIIaR167, FcγRIIb/c, FcγRIIIaF176, FcγRIIIaV176, FcγRIIIbNA1, and FcγRIIIbNA2receptors alongside antibody superantigens proteins L and G using biolayer interferometry.ResultsThe library of 21 IgGs demonstrated that the VHframeworks influenced receptor binding sites on the constant region of the subtypes significantly, providing non-canonical interactions and non-interactions. However, there was minimal influence on the binding of bacterial B-cell superantigens Proteins L and G on the IgGs, showing their robustness against V-region effects.ConclusionsThese results demonstrate the importance of the V-regions during humanization of therapeutic antibodies that can confer or diminish FcR-dependent immune responses, while remaining both suitable and susceptible to the binding by bacterial antibody superantigens in antibody purification and be present with normal flora.STATEMENT OF SIGNIFICANCEIgGs are the predominant isotype for clinical and research applications. Despite the vast amount of research to study it, particularly on IgG1, there remains a gap in understanding how the variable regions and the receptor binding sites can influence one another in the other IgG subtypes, across the IgG subtypes with different hinges and makeup. This study investigates the effect of these variable regions on the engagement of receptors and also how bacterial antibody superantigens present in microflora and used in antibody purification can exert distal effects.
Ultrastructural comparison of human kidney organoids and human fetal kidneys reveals features of hyperglycemic culture
Authors: Schumacher Anika , Joris Virginie , van Griensven Martijn , LaPointe Vanessa 
Published: March 2023

AbstractInduced pluripotent stem cell (iPSC)–derived kidney organoids have the potential for a large variety of applications. However, they do not persist long in culture, for which reasons are still unclear. Furthermore, their morphological maturation, an essential feature for kidney function, has not been sufficiently assessed. Kidney organoids are transcriptionally much alike end-of-first-trimester fetal kidneys and present many of the same cell types. From large transmission electron microscopy tilescans of specific regions of interest, we compared the ultrastructures of iPSC-derived kidney organoids at various timepoints to human fetal kidneys of the first trimester. Unlike healthy fetal kidneys, large glycogen deposits developed over time in all organoid cell types, but particularly in podocytes and in chondrocytes, one of the off-target populations that contaminate the culture. Deeper investigation showed that glycogen synthase kinase 3b (GSK3β) levels and activation were diminished over time, correlated with the accumulation of glycogen. Activated YAP was strongly expressed and large lipid droplets accumulated over time in proximal tubules. Accordingly, EGFR signaling increased significantly over time. Mitochondria in glomeruli and tubules contained few or no cristae, indicating mitochondrial damage. Together these features are known for hyperglycemic cultures and diabetic nephropathy. Measuring the glucose concentration in the kidney organoid culture medium showed a concentration of 2.94 g/mL, which is considered an elevated, pre-diabetic–like concentrationin vitro. In summary, our ultrastructural assessment of iPSC-derived kidney organoids using an age-matched fetal human reference allowed the evaluation of cellular morphology, and we identified intracellular features that can inform the cellular state, which is particularly important while physiological testing of organoids is limited.Translational StatementKidney organoids hold promise as a future treatment for patients with end-stage kidney disease. The engineering of kidney organoids with correct and healthy morphologyin vitrois therefore essential, to guarantee functionality after transplantation. The present study provided deeper insights into the structural organization and ultrastructure of cells in kidney organoids compared to age-matched human fetal kidneys. Accordingly, we found several features in the regular kidney organoid culture, which are known to occur in hyperglycemic cultures and diabetic nephropathy, indicating that the current medium composition may be inducing pathological cellular phenotypes. This study therefore creates a better understanding of current limitations in the kidney organoid culture, increases knowledge of their function and cellular organization, and sets the foundation for further research to create advanced organoids.
Incidences of Helicobacter infection in pigs and tracing occupational hazard in pig farmers
Authors: Pegu Seema Rani , Rajkhowa Swaraj , Das Pranab Jyoti , Sonowal Joyshikh , Sengar Gyanendra Singh , Deb Rajib , Choudhury Manjisa , Deka Nabajyoti , Paul Souvik , Doley Juwar , Sarma Dilip Kumar , Das Samir , Mohan N. H. , Thomas Rajendran , Gupta V.K. 
Published: March 2023

AbstractHelicobacter species(H. sp.) is a gram-negative spiral-shaped motile bacteria that causes gastritis in pigs and also colonizes the human stomach. The current study seeks to assess the prevalence of variousH. sp. in the gastric mucosa of slaughtered and dead pigs, as well as the prevalence ofHelicobacterinfection among pig farmers. A total of 403 stomach samples from various pig slaughter points, 74 necropsy samples from various pig farms and 97 stool samples from pig farmers were collected from Assam, India. Among 477 pig stomach samples tested, 214 samples with gastritis (20.09%) showed Gram negative, spiral-shaped organisms in brush cytology from the mucosal surface, and the rest of the 263 stomach samples without any gastric lesion showed only 3.04% Gram negative, spiral-shaped organisms. In ultrastructure investigation, Scanning Electron Microscopy (SEM) of the four urease positive stomach samples revealed a tightly coiledHelicobacter bacterium(spiral-shaped) found in the mucous lining of the stomach. In histopathological examination of pars esophagia, cardiac and fundic mucosa showed chronic gastritis associated with hemorrhagic necrosis, leucocytic infiltration with neutrophils and macrophages, and lymphoid aggregates (lymphoid follicles) etc. PCR confirmed 16S rRNA genes ofHelicobacter suis(H. suis) where a total of 42 (19.63%) out of 214 pig stomach samples and 2 (2.08%) out of 96 stool samples of pig farmers were found positive forH. suis. of these 96 stool samples of pig farmers 3 (3.12%) were confirmed positive forHelicobacter pylori(H. pylori) Phosphoglucosamine mutase gene in PCR. Phylogenic analysis of the 16S rRNA gene ofH. suisshowed distinct clusters with otherH. sp. In conclusion, this study provides evidence for the prevalence ofHelicobacterboth in pig gastric mucosa and human stool. The findings highlight the need for improved sanitation and hygiene practices among pig farmers to minimize the risk ofHelicobacterinfection in humans.
De novoGenome Assembly, Functional Annotation and SSR Mining ofCitrus reticulata“Kinnow” from Pakistan
Authors: Jabeen Sadia , Saif Rashid , Distefano Gaetano , Haq Rukhama , Haider Waseem , Hayat Akber , Naz Shagufta 
Published: March 2023

AbstractCitrus reticulata(Blanco) fruit is native to South East Asia which owns many of the nutritional, medicinal and economic advantages, locally known as “Kinnow” and one of the priced mandarin varieties (Dancy, Fuetrell’s Early and Honey) ofCitrusgenera renowned for its exclusive taste, vitamin richness, thin peel, long shelf-life and seedless characteristics in Pakistan. However, genetic improvement and breeding strategies of this valued variety are lacking due to the in-housed insufficient genomic and technical resources. Therefore, the current research was initiated to provide the base-linede-novogenome assembly ofC. reticulata(seedless kinnow) at a depth of 151x with Illumina paired-end short-read sequencing technology using HiSeq 2500. Whole-genome sequencing resulted in 139,436,350 raw reads (∼20.09 GB) of data, however, after removing the low-quality reads (1.08%), duplicated sequences (10.5%) and Illumina adaptors, 137,901,462 clean reads were obtained with (∼18.87 GB) of clean data which was further used for downstream variant calling analysis. In total, 348,861 scaffolds were generated with N50 value of 4827 which constitute 263,018,9 contigs ranging from 71-36,213 with total of 179,984,763 nucleotides. The GC content of the final draft assembly at 71-mer was 34.1%. Moreover, annotation was performed with “Hayai-Annotation Plants” tool which marked the whole-genome mapping with three main functional databases of interpro, Pfam and gene ontology. Additionally, in-silico identification of 111,032 Simple Sequence Repeats (SSR) was also accomplished with the help of GMATA tool, which may be used for further screening and genetic improvement of the citrus varieties by means of this current assembly as a resource of local reference genome.
A dual, catalytic role for the fission yeast Ccr4-Not complex in gene silencing and heterochromatin spreading
Authors: Challal Drice , Menant Alexandra , Goksal Can , Leroy Estelle , Al-Sady Bassem , Rougemaille Mathieu 
Published: March 2023

AbstractHeterochromatic gene silencing relies on combinatorial control by specific histone modifications, the occurrence of transcription, and/or RNA degradation. Once nucleated, heterochromatin propagates within defined chromosomal regions and is maintained throughout cell divisions to warrant proper genome expression and integrity. The fission yeast Ccr4-Not complex has been involved in gene silencing, but its relative contribution to distinct heterochromatin domains and its role in nucleation versus spreading have remained elusive. Here, we unveil major functions for Ccr4-Not in silencing and heterochromatin spreading at the mating type locus and subtelomeres. Mutations of the catalytic subunits Caf1 or Mot2, involved in RNA deadenylation and protein ubiquitinylation respectively, result in impaired propagation of H3K9me3 and massive accumulation of nucleation-distal heterochromatic transcripts. Both silencing and spreading defects are suppressed upon disruption of the heterochromatin antagonizing factor Epe1. Overall, our results position the Ccr4-Not complex as a critical, dual regulator of heterochromatic gene silencing and spreading.Author SummaryEukaryotic genomes are partitioned into relaxed, gene-rich regions, and condensed, gene-poor domains called heterochromatin. The maintenance of heterochromatin is crucial for proper genome expression and integrity, and requires multiple factors regulating histone modifications and/or the levels of RNA molecules produced from these regions. Such effectors not only promote heterochromatin assembly but also ensure its propagation from specific nucleation sites to defined domain boundaries. However, while the mechanisms involved in initiation of heterochromatin formation have been well documented, the molecular and biochemical properties underlying its spreading remain largely elusive. By combining genetic and single-cell approaches, we report here that the fission yeast Ccr4-Not complex, a multisubunit complex conserved throughout eukaryotes, is essential for efficient heterochromatin spreading to repress expression of nucleation-distal RNAs. The two catalytic activities of the complex, RNA deadenylation and protein ubiquitinylation, are each critical, thereby defining a dual enzymatic requirement in the process.