bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating the assessment of quality of life in care and research in pulmonary fibrosis
Authors: Aronson Kerri I. , Swigris Jeffrey J. , Wijsenbeek Marlies 
Published: July 2024

Purpose of review
Pulmonary fibrosis (PF) negatively influences health-related quality of life (HRQOL). Patients living with PF have voiced the desire for a focus on symptoms and HRQOL in both disease monitoring and treatment decisions.

Recent findings
Currently available disease modifying treatments do little to impact HRQOL. Newer studies evaluating pharmacologic and nonpharmacologic therapies targeting symptoms and HRQOL in PF have been conducted with some promising results. There is increasing recognition of the importance of incorporating HRQOL as a higher tier endpoint in clinical trials. Disease-specific measure of HRQOL have been developed for those living with PF, and there is ongoing work to better understand the validity and reliability characteristics of these tools. In addition to research, there is recognition of the potential benefits of measuring HRQOL and symptoms in clinical practice in facilitate integrating patient perspective into care and allow for more personalized treatment approaches.

Summary
There is increased momentum to discover treatments that impact HRQOL in PF. More work is desperately needed to identify better treatment targets, and to incorporate HRQOL and symptoms as higher tier endpoints in clinical trials. Further work is also needed to address the practicalities of integrating HRQOL measurement into clinical care.
Sexual health in transgender and gender diverse people
Authors: Zhang Xinyuan , Neuville Paul , Skokan Alexander J. 
Published: July 2024

Purpose of review
Sexual health and sexual function are critical to the wellbeing of cisgender, transgender, and gender diverse populations. To date, there has been only limited patient-focused evaluation of sexual function in transgender and gender diverse patients at several stages in their gender-affirming medical care. There remains a need to better understand the impact of gender affirming medical and surgical therapy on sexual health, and to develop evidence-based treatments to address sexual dysfunction when present.

Recent findings
The impact of gender-affirming hormone therapy on sexual health is complex and evolves over time on treatment. Despite high incidences of complications, major genital gender-affirming surgeries such as vulvovaginoplasty and penile implant placement after phalloplasty yield high patient satisfaction. While treatments to preserve or restore erections and to improve vaginal lubrication have been trialed based upon literature in cisgender populations, there remains minimal evidence to guide medical treatment of sexual dysfunction ranging from erectile dysfunction to dyspareunia.

Summary
There is a continued need for ongoing efforts to develop patient-reported outcome measures and rigorous investigation of sexual health preservation and restoration treatments in transgender and gender diverse populations.
Expanding the Spectrum of NUTM1-Rearranged Sarcoma
Authors: Zhu Peipei , Sun Ke , Lao I. Weng , Yu Lin , Bai Qianming , Zhou Xiaoyan , Wang Jian 
Published: July 2024

Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1-rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5 cm (mean: 6 cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24 mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24 mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12 mo after diagnosis). Our study further demonstrated that NUTM1-rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.
Methods of diagnostic meta-analysis: comparing the generalized linear mixed model and the split component synthesis model
Authors: Zar Lubna A. , Alsharif Fatima R. , Zar Amna , Alwisi Nouran , Tluli Omar , Syed Asma , Doi Suhail A. 
Published: July 2024

Purpose of reviewDiagnostic meta-analyses combine data from several diagnostic test accuracy (DTA) studies to provide an in-depth assessment of a specific diagnostic test's performance across diverse populations and settings. Additionally, knowledge on common methods of diagnostic meta-analyses is crucial for researchers to make informed decisions on best practice for reporting analyses and results. This article provides an overview of commonly used methods of diagnostic meta-analyses using real-life and simulation data.Recent findingsAdvances in methods of diagnostic meta-analyses in recent years have increased uncertainty among researchers in relation to the most suitable method to be used. Currently, the most popular approaches for diagnostic evidence synthesis include hierarchical summary operating characteristic (HSROC) and bivariate random effects models though other methods such as the split component synthesis method have been proposed. In addition, different software modules exist for DTA meta-analyses.SummaryThis article presents a thorough evaluation of current frequentist DTA meta-analysis methods implementing both simulated and real-world data. By understanding the recent methods of diagnostic meta-analyses and their limitations, clinicians may better be equipped in selecting the optimum approach to improve clinical judgement and consequently better patient outcomes.
Describing and assessing behavioural symptoms in amyotrophic lateral sclerosis with and without frontotemporal dementia: a scoping review
Authors: Trucco Ana Paula , Backhouse Tamara , Mioshi Eneida 
Published: July 2024

Purpose of review
Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by the disease. A scoping review of studies published between 2011 and 2024 was conducted to present the breadth of behavioural symptoms in ALS and ALSFTD, explore how they are described and assessed, and identify patterns in the literature.

Findings
This scoping review identified 3939 articles, with 111/3939 meeting eligibility criteria. Most studies were from Australia (23.22%), Italy (16.94%) and the UK (14.29%); 75.67% were cross-sectional. Sample size ranged from 1 to 1013, as case studies were included. Overall mean age (100/111 studies) was 61.32 (SD = 4.15). Proportion of male patients (reported 102/111 studies) was 61.49%; mean disease duration (reported in 86/111 records) was 32.63 months (SD = 24.72). Papers described a broad range of behavioural symptoms (465 examples), which were thematically collated into seven categories: disinhibition (27.74%), apathy (25.16%), perseverative/compulsive behaviours (17.42%), hyperorality (10.53%), loss of sympathy or empathy (8.6%), psychotic symptoms (7.74%), and loss of insight about disease and changes (2.8%). Most studies (78.37%) used validated behavioural assessments that elicited carer's perspectives.

Summary
Despite extensive evidence of behavioural symptoms in ALS, implementation of assessments and management of behavioural symptoms in clinical care remain limited. Clinicians must assess behavioural symptoms, as these can negatively affect disease prognosis, patient treatment engagement and increase family distress. Measures capturing carers’ perspectives through interviews are ideal as they can reveal anosognosia, lack of sympathy and lack of empathy.
Unlocking a New Path: An Autophagometer that Measures Flux Using a Non-Fluorescent Immunohistochemistry Method
Authors: Shojaei Shahla , Barzegar Behrooz Amir , Cordani Marco , Aghaei Mahmood , Azarpira Negar , Klionsky Daniel J. , Ghavami Saeid 
Published: July 2024

AbstractMacroautophagy/autophagy, a crucial cellular process, is typically measured using fluorescence-based techniques, which can be costly, complex, and impractical for clinical settings. In this paper, we introduce a novel, cost-effective, non-fluorescent immunohistochemistry (IHC) method for evaluating autophagy flux. This technique, based on antigen-antibody reactions and chromogenic detection, provides clear, quantifiable results under standard light microscopy, eliminating the need for expensive equipment and specialized reagents. Our method simplifies technical requirements, making it accessible to routine clinical laboratories and research settings with limited resources. By comparing our approach with traditional fluorescence methods, we demonstrate its superior effectiveness, cost-efficiency, and applicability to patient samples. This innovative technique has the potential to significantly advance autophagy research and improve clinical diagnostics, offering a practical and robust tool for studying autophagy mechanisms in diseases such as cancer and neurodegenerative disorders. Our non-fluorescent IHC method represents a significant step forward in evaluating autophagy flux, making it more accessible and reliable, with the promise of enhancing our understanding and treatment of autophagy-related diseases.
Dopamine transmission at D1 and D2 receptors in the nucleus accumbens contributes to the expression of incubation of cocaine craving
Authors: Weber Sophia J. , Kawa Alex B. , Moutier Alana L. , Beutler Madelyn M. , Koyshman Lara M. , Moreno Cloe D. , Westlake Jonathan G. , Wunsch Amanda M. , Wolf Marina E. 
Published: July 2024

ABSTRACTRelapse represents a consistent clinical problem for individuals with substance use disorder. In the incubation of craving model of persistent craving and relapse, cue-induced drug seeking progressively intensifies or ‘incubates’ during the first weeks of abstinence from drug self-administration and then remains high for months. Previously, we and others have demonstrated that expression of incubated cocaine craving requires strengthening of excitatory synaptic transmission in the nucleus accumbens core (NAcc). However, despite the importance of dopaminergic signaling in the NAcc for motivated behavior, little is known about the role that dopamine (DA) plays in the incubation of cocaine craving. Here we used fiber photometry to measure DA transients in the NAcc of male and female rats during cue-induced seeking tests conducted in early abstinence from cocaine self-administration, prior to incubation, and late abstinence, after incubation of craving has plateaued. We observed DA transients time-locked to cue-induced responding but their magnitude did not differ significantly when measured during early versus late abstinence seeking tests. Next, we tested for a functional role of these DA transients by injecting DA receptor antagonists into the NAcc just before the cue-induced seeking test. Blockade of either D1 or D2 DA receptors reduced cue-induced cocaine seeking after but not before incubation. We found no main effect of sex in our experiments. These results suggest that DA contributes to incubated cocaine seeking but the emergence of this role reflects changes in postsynaptic responsiveness to DA rather than presynaptic alterations.
Epigenetic memory of temperature sensed during somatic embryo maturation in 2-year-old maritime pine trees
Authors: Trontin J.-F. , Sow M.D. , Delaunay A. , Modesto I. , Teyssier C. , Reymond I. , Canlet F. , Boizot N. , Le Metté C. , Gibert A. , Chaparro C. , Daviaud C. , Tost J. , Miguel C. , Lelu-Walter M.-A. , Maury S. 
Published: July 2024

AbstractEmbryogenesis is a brief but potentially critical phase in the tree life cycle for adaptive phenotypic plasticity. Using somatic embryogenesis in maritime pine, we found that temperature during the maturation phase affects embryo development and post-embryonic tree growth for up to three years. We examined whether this somatic stress memory could stem from temperature- and/or development-induced changes in DNA methylation. To do this, we developed a 200 Mb custom sequence capture bisulfite analysis of genes and promoters to identify differentially methylated cytosines (DMCs) between temperature treatments (18, 23, and 28°C) and developmental stages (immature and cotyledonary embryos, shoot apical meristem of 2-year-old plants) and investigate if these differences can be mitotically transmitted from embryonic to post-embryonic development (epigenetic memory). We revealed a high prevalence of temperature-induced DMCs in genes (8-14%) compared to promoters (less than 1%) in all 3 cytosine contexts. Developmental DMCs showed a comparable pattern but only in the CG context, and with a high trend towards hypo-methylation, particularly in the promoters. A high percentage of DMCs induced by developmental transitions were found memorized in genes (up to 45-50%) and promoters (up to 90%). In contrast, temperature-induced memory was lower and confined to genes after both embryonic (up to 14%) and post-embryonic development (up to 8%). Using stringent criteria, we identified ten genes involved in defense responses and adaptation, embryo development and chromatin regulation that are candidates for the establishment of a persistent epigenetic memory of temperature sensed during embryo maturation in maritime pine.Graphical abstract
Reversible control of kinase signaling through chemical-induced dephosphorylation
Authors: Sun Ying , Zhou Rihong , Hu Jin , Feng Shan , Hu Qi 
Published: July 2024

AbstractThe coordination between kinases and phosphatases is crucial for regulating the phosphorylation levels of essential signaling molecules. Methods enabling precise control of kinase activities are valuable for understanding the kinase functions and for developing targeted therapies. Here, we use the abscisic acid (ABA)-induced proximity system to reversibly control kinase signaling by recruiting phosphatases. Using this method, we found that the oncogenic tyrosine kinase BCR::ABL1 can be inhibited by recruiting various cytoplasmic phosphatases. We also discovered that the oncogenic serine/threonine kinase BRAF(V600E), which has been reported to bypass phosphorylation regulation, can be positively regulated by protein phosphatase 1 (PP1) and negatively regulated by PP5. Additionally, we observed that the dual-specificity kinase MEK1 can be inhibited by recruiting PP5. This suggests that bifunctional molecules capable of recruiting PP5 to MEK or RAF kinases could be promising anticancer drug candidates. Thus, the ABA-induced dephosphorylation method enables rapid screening of phosphatases to precisely control kinase signaling.
Colony context and size-dependent compensation mechanisms give rise to variations in nuclear growth trajectories
Authors: Dixon Julie C. , Frick Christopher L. , Leveille Chantelle L. , Garrison Philip , Lee Peyton A. , Mogre Saurabh S. , Morris Benjamin , Nivedita Nivedita , Vasan Ritvik , Chen Jianxu , Fraser Cameron L. , Gamlin Clare R. , Harris Leigh K. , Hendershott Melissa C. , Johnson Graham T. , Klein Kyle N. , Oluoch Sandra A. , Thirstrup Derek J. , Sluzewski M. Filip , Wilhelm Lyndsay , Yang Ruian , Toloudis Daniel M. , Viana Matheus P. , Theriot Julie A. , Rafelski Susanne M. 
Published: July 2024

SummaryTo investigate the fundamental question of how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we focused on nuclear growth in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days, and developed open-source tools for image and data analysis and an interactive timelapse viewer for exploring quantitative features of nuclear size and shape. We performed a data-driven analysis of nuclear growth variations across timescales. We found that individual nuclear volume growth trajectories arise from short timescale variations attributable to their spatiotemporal context within the colony. We identified a strikingly time-invariant volume compensation relationship between nuclear growth duration and starting volume across the population. Notably, we discovered that inheritance plays a crucial role in determining these two key nuclear growth features while other growth features are determined by their spatiotemporal context and are not inherited.
A distinct isoform of Msp300 (nesprin) organizes the perinuclear microtubule organizing center in adipocytes
Authors: Morton Garret M. , Toledo Maria Pilar , Zheng Chunfeng , Zheng Yiming , Megraw Timothy L. 
Published: July 2024

AbstractIn many cell types, disparate non-centrosomal microtubule-organizing centers (ncMTOCs) replace functional centrosomes and serve the unique needs of the cell types in which they are formed. In Drosophila fat body cells (adipocytes), an ncMTOC is organized on the nuclear surface. This perinuclear ncMTOC is anchored by Msp300, encoded by one of two nesprin-encoding genes in Drosophila. Msp300 and the spectraplakin short stop (shot) are co-dependent for localization to the nuclear envelope to generate the ncMTOC where they recruit the microtubule minus-end stabilizer Patronin (CAMSAP). TheMsp300gene is complex, encoding at least eleven isoforms. Here we show that two Msp300 isoforms, Msp300-PE and -PG, are required and only one, Msp300-PE, appears sufficient for generation of the ncMTOC. Loss of Msp300-PE and -PG results in severe loss of localization of shot and Patronin, disruption of the MT array, nuclear mispositioning and loss of endosomal trafficking. Furthermore, upon loss of Msp300-PE and -PG, other isoforms are retained at the nuclear surface despite the loss of nuclear positioning and MT organization, indicating that they are not sufficient to generate the ncMTOC. Msp300-PE has an unusual domain structure including a lack of a KASH domain and very few spectrin repeats and appears therefore to have a highly derived function to generate an ncMTOC on the nuclear surface.
Social Vulnerability and Biological Aging in New York City: An Electronic Health Records-Based Study
Authors: Knobel Pablo , Colicino Elena , Klog Itai , Litke Rachel , Lane Kevin , Federman Alex , Mobbs Charles , Sade Maayan Yitshak 
Published: July 2024

AbstractChronological age is not an accurate predictor of morbidity and mortality risk, as individuals’ aging processes are diverse. Phenotypic age acceleration (PhenoAgeAccel) is a validated biological age measure incorporating chronological age and biomarkers from blood samples commonly used in clinical practice that can better reflect aging-related morbidity and mortality risk. The heterogeneity of age-related decline is not random, as environmental exposures can promote or impede healthy aging. Social Vulnerability Index (SVI) is a composite index accounting for different facets of the social, economic, and demographic environment grouped into four themes: socioeconomic status, household composition and disability, minority status and language, and housing and transportation. We aim to assess the concurrent and combined associations of the four SVI themes on PhenoAgeAccel and the differential effects on disadvantaged groups. We use electronic health records data from 31,913 patients from the Mount Sinai Health System (116,952 person-years) and calculate PhenoAge for years with available laboratory results (2011-2022). PhenoAge is calculated as a weighted linear combination of lab results and PhenoAgeAccel is the differential between PhenoAge and chronological age. A decile increase in the mixture of SVI dimensions was associated with an increase of 0.23 years (95% CI: 0.21, 0.25) in PhenoAgeAccel. The socioeconomic status dimension was the main driver of the association, accounting for 61% of the weight. Interaction models revealed a more substantial detrimental association for women and racial and ethnic minorities with differences in leading SVI themes. These findings suggest that neighborhood-level social vulnerability increases the biological age of its residents, increasing morbidity and mortality risks. Socioeconomic status has the larger detrimental role amongst the different facets of social environment.
Membrane Curvature Promotes ER-PM Contact Formation via Junctophilin-EHD Interactions
Authors: Yang Yang , Valencia Luis A. , Lu Chih-Hao , Nakamoto Melissa L. , Tsai Ching-Ting , Liu Chun , Yang Huaxiao , Zhang Wei , Jahed Zeinab , Lee Wan-Ru , Santoro Francesca , Liou Jen , Wu Joseph C. , Cui Bianxiao 
Published: July 2024

AbstractContact sites between the endoplasmic reticulum (ER) and the plasma membrane (PM) play a crucial role in governing calcium regulation and lipid homeostasis. Despite their significance, the factors regulating their spatial distribution on the PM remain elusive. Inspired by observations in cardiomyocytes, where ER-PM contact sites concentrate on tubular PM invaginations known as transverse tubules (T-tubules), we hypothesize that the PM curvature plays a role in ER-PM contact formation. Through precise control of PM invaginations, we show that PM curvatures locally induce the formation of ER-PM contacts in cardiomyocytes. Intriguingly, the junctophilin family of ER-PM tethering proteins, specifically expressed in excitable cells, is the key player in this process, while the ubiquitously expressed extended synaptotagmin 2 does not show a preference for PM curvature. At the mechanistic level, we find that the low complexity region (LCR) and the MORN motifs of junctophilins can independently bind to the PM, but both the LCR and MORN motifs are required for targeting PM curvatures. By examining the junctophilin interactome, we identify a family of curvature-sensing proteins, Eps15-homology domain containing proteins (EHDs), that interact with the MORN_LCR motifs and facilitate junctophilins’ preferential tethering to curved PM. These findings highlight the pivotal role of PM curvature in the formation of ER-PM contacts in cardiomyocytes and unveil a novel mechanism for the spatial regulation of ER-PM contacts through PM curvature modulation.