bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should We Be Testing for Mycoplasma genitalium on Initial Presentation? Trends in Persistent/Recurrent Urethritis Among Men Presenting for Care in STD Clinics, 2015–2019, STD Surveillance Network
Authors: Llata Eloisa , Tromble Erin , Schumacher Christina , Huspeni Dawn , Asbel Lenore , Pathela Preeti , Kohn Robert , Kerani Roxanne P. , Barbee Lindley , Bachmann Laura 
Published: April 2024

Background

Mycoplasma genitalium is a major contributor to persistent/recurrent urethritis cases. However, there are limited published studies on recent trends of persistent/recurrent urethritis.

Methods
A retrospective analysis was conducted of men presenting with symptomatic urethritis in 16 sexually transmitted disease (STD) clinics from 2015 to 2019. Poisson regression was used to assess trends in the annual proportions of urethritis episodes with follow-up (FU) characterized with persistent/recurrent urethritis symptoms. Results were also stratified by results of chlamydia (CT) and gonorrhea (NG) testing and treatment prescribed.

Results
There were 99,897 urethritis episodes, from 67,546 unique men. The proportion of episodes with persistent/recurrent symptomatic FU visits increased 50.8% over a 4-year period (annual percentage change [APC], 11.3%; 95% confidence interval [CI], 6.5–16.3). Similar trends were observed in nonchlamydial nongonococcal urethritis episodes (APC, 12.7%; 95% CI, 6.8–18.9) but increases among those positive for NG (APC, 12.1%; 95% CI, −2.3 to -28.5) or for CT (APC, 7.3%; 95% CI, −6.7 to 23.5) were not statistically significant. Among episodes who received azithromycin as first-line treatment, increases in the proportion of persistent/recurrent FU visits were observed (APC, 12.6%; 95% CI, 8.6–16.7). For episodes where first-line treatment was doxycycline, no significant increases were detected (APC, 4.3%; 95% CI, −0.3 to 9.2).

Conclusions
We found an increase in the proportion of urethritis episodes with persistent or recurrent symptoms over time. Given these observed trends in episodes negative for NG or CT, an etiology not detectable by routine diagnostics was a likely factor in increased persistence, suggesting patients with urethritis may benefit from diagnostic testing for M. genitalium during an initial symptomatic presentation.
Addressing Cervical Cancer Screening Through Self-Sampling and HPV Testing Among Under-Screened Women: A Case Study in the Decentralized Portuguese Setting
Authors: Pereira Sara da Graça , Nobre Luís , Ribeiro Marina , Carvalho Patrícia , Morais Ana , Sousa Rita , Moniz Ana Paula , Matos Francisco , Fernandes Graça , Pimentel João Pedro , Marinho José Carlos , Sá José Luís e , Ilhéu Olga , Rebelo Teresa , Fonseca-Moutinho José , Prazeres Hugo , Nobre Rui Jorge , Loureiro Fernanda 
Published: April 2024

AbstractBackgroundCervical cancer (CC) screening is crucial for reducing its incidence. However, encouraging participation among under-screened women remains challenging. Portugal’s decentralized health regions provide an ideal case study due to a significant proportion of eligible women avoiding regular screening. Globally, self-sampling has emerged as a promising solution to enhance screening attendance. This study aims to assess self-sampling acceptance among under-screened women in central Portugal, contributing to the existing knowledge of self-sampling in CC screening.Methods801 women aged 30-59, not participating in the Central Region’s CC Screening for 4 or more years, were randomly recruited. Women who accepted to participate in the study received cervicovaginal self-sampling kits at home. Women with a positive high-risk human papillomavirus (hr-HPV) test result were invited for gynaecological follow-up.ResultsAmong the 687 eligible women, 307 (44.7%) accepted, and 198 (28.8%) provided specimens for hr-HPV testing. Out of twelve positive cases, eleven underwent gynaecological follow-up, identifying six cervical lesions.ConclusionsThe study highlights the potential of self-sampling and HPV testing to enhance CC screening in Portugal, with encouraging acceptance and effective detection of cervical lesions. These findings offer a promising solution for addressing under-screening among eligible women in the decentralized health regions of Portugal.
Predictive posture stabilization before contact with moving objects: equivalence of smooth pursuit tracking and peripheral vision
Authors: Sinha Oindrila , Rosenquist Taylor , Fedorshak Alyssa , Kpankpa John , Albenze Eliza , Bonnet Cedrick , Bertucco Matteo , Kurtzer Isaac , Singh Tarkeshwar 
Published: April 2024

AbstractPostural stabilization is essential to effectively interact with our environment. Humans preemptively adjust their posture to counteract impending disturbances, such as those encountered during interactions with moving objects, a phenomenon known as anticipatory postural adjustments (APAs). APAs are thought to be influenced by predictive models that incorporate object motion via retinal motion and extra-retinal signals. Building on our previous work that examined APAs in relation to the perceived momentum of moving objects, here we explored the impact of object motion within different visual field sectors on the human capacity to anticipate motion and prepare APAs for contact between virtual moving objects and the limb. Participants interacted with objects moving towards them under different gaze conditions. In one condition, participants fixated on either a central point (central fixation) or left-right of the moving object (peripheral fixation), while in another, they followed the moving object with smooth pursuit eye movements (SPEM). We found that APAs had the smallest magnitude in the central fixation condition and that no notable differences in APAs were apparent between the SPEM and peripheral fixation conditions. This suggests that the visual system can accurately perceive motion of objects in peripheral vision for posture stabilization. Using Bayesian Model Averaging, we also evaluated the contribution of different gaze variables, such as eye velocity and gain (ratio of eye and object velocity) and showed that both eye velocity and gain signals were significant predictors of APAs. Taken together, our study underscores the roles of oculomotor signals in modulation of APAs.New and NoteworthyWe show that the human visuomotor system can detect motion in peripheral vision and make anticipatory adjustments to posture before contact with moving objects, just as effectively as when the eye movement system tracks those objects through smooth pursuit eye movements. These findings pave the way for research into how age-induced changes in spatial vision, eye movements, and motion perception could affect the control of limb movements and postural stability during motion-mediated interactions with objects.
Inactivation of a non-canonical gp130 signaling arm attenuates chronic systemic inflammation and multimorbidity induced by a high-fat diet
Authors: Lee Youngjoo , Sarkar Arijita , Tassey Jade , Levi Jonathan N. , Lee Siyoung , Liu Nancy Q. , Drake Andrew C. , Magallanes Jenny , Stevic Una , Lu Jinxiu , Ge Dawei , Tang Hanhan , Mkaratigwa Tadiwanashe , Bian Fangzhou , Shkhyan Ruzanna , Bonaguidi Michael , Evseenko Denis 
Published: April 2024

AbstractInterleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Recently, we discovered that a non-canonical signaling pathway downstream of tyrosine (Y) 814 within the intracellular domain of gp130, the IL-6 co-receptor, is responsible for the recruitment and activation of SRC family of kinases (SFK). Mice with constitutive genetic inactivation of gp130 Y814 (F814 mice) show accelerated resolution of inflammatory response and superior regenerative outcomes in skin wound healing and posttraumatic models of osteoarthritis. The current study was designed to explore if selective genetic or pharmacological inhibition of the non-canonical gp130-Y814/SFK signaling reduces systemic chronic inflammation and multimorbidity in a high-fat diet (HFD)-induced model of accelerated aging. F814 mice showed significantly reduced inflammatory response to HFD in adipose and liver tissue, with significantly reduced levels of systemic inflammation compared to wild type mice. F814 mice were also protected from HFD-induced bone loss and cartilage degeneration. Pharmacological inhibition of gp130-Y814/SFK in mice on HFD mirrored the effects observed in F814 mice on HFD; furthermore, this pharmacological treatment also demonstrated a marked increase in physical activity levels and protective effects against inflammation-associated suppression of neurogenesis in the brain tissue compared to the control group. These findings suggest that selective inhibition of SFK signaling downstream of gp130 receptor represents a promising strategy to alleviate systemic chronic inflammation. Increased degenerative changes and tissue senescence are inevitable in obese and aged organisms, but we demonstrated that the systemic response and inflammation-associated multi-morbidity can be therapeutically mitigated.
Genetic Analysis and Functional Assessment of aTGFBR2Variant in Micrognathia and Cleft Palate
Authors: Michaels JES-Rite , Husami Ammar , Vontell Andrew M. , Brugmann Samantha A. , Stottmann Rolf W. 
Published: April 2024

AbstractCleft lip and cleft palate are among the most common congenital anomalies and are the result of incomplete fusion of embryonic craniofacial processes or palatal shelves, respectively. We know that genetics play a large role in these anomalies but the list of known causal genes is far from complete. As part of a larger sequencing effort of patients with micrognathia and cleft palate we identified a candidate variant intransforming growth factor beta receptor 2(TGFBR2) which is rare, changing a highly conserved amino acid, and predicted to be pathogenic by a number of metrics. The family history and population genetics would suggest this specific variant would be incompletely penetrant, but this gene has been convincingly implicated in craniofacial development. In order to test the hypothesis this might be a causal variant, we used genome editing to create the orthologous variant in a new mouse model. Surprisingly,Tgfbr2V387Mmice did not exhibit craniofacial anomalies or have reduced survival suggesting this is, in fact, not a causal variant for cleft palate/ micrognathia. The discrepancy between in silico predictions and mouse phenotypes highlights the complexity of translating human genetic findings to mouse models. We expect these findings will aid in interpretation of future variants seen inTGFBR2from ongoing sequencing of patients with congenital craniofacial anomalies.
Plasma membrane and cytoplasmic compartmentalization: a dynamic structural framework required for pollen tube tip growth
Authors: Fritz Carolin , Reimann Theresa Maria , Adler Jeremy , Knab Johanna , Schulmeister Sylwia , Kriechbaum Choy , Müller Sabine , Parmryd Ingela , Kost Benedikt 
Published: April 2024

AbstractRapid, unidirectional pollen tube tip growth is essential for fertilization and is widely employed as a model of polar cell expansion, a process crucial for plant morphogenesis. Different proteins and lipids with key functions in the control of polar cell expansion are associated with distinct domains of the plasma membrane (PM) at the pollen tube tip. These domains need to be dynamically maintained during tip growth, which depends on massive secretory and endocytic membrane traffic. Very little is currently known about the regulatory and cellular mechanisms responsible for the compartmentalization of the pollen tube PM. To provide a reliable structural framework for the further characterization of these mechanisms, an integrated quantitative map was compiled of the relative positions in normally growing tobacco pollen tubes of PM domains 1) enriched in key signaling proteins or lipids, 2) displaying high membrane order, or 3) in contact with cytoplasmic structures playing important roles in apical membrane traffic. Previously identified secretory and endocytic PM domains were also included into this map. Internalization of regulatory proteins or lipids associated with PM regions overlapping with the endocytic domain was assessed based on brefeldin A (BFA) treatment. These analyses revealed remarkable aspects of the structural organization of tobacco pollen tube tips, which enhance our understanding of tip growth by providing important insights into 1) RAC/ROP signaling, 2) phosphatidylinositol 4,5-bisphosphate (PI4,5P2) metabolism and functions, 3) trafficking of signaling lipids, 4) functions of domains displaying high membrane order, and 5) Ca2+regulation of secretion.SummaryQuantitative mapping of plasma membrane and cytoplasmic domains at the tip of elongating tobacco pollen provides important insights into regulatory and cellular mechanisms essential for tip growth.
Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression
Authors: Lee Sang-Hoon , Kim Hyun-Jun , Kim Seon-Wook , Lee Hyunju , Jung Da-Woon , Williams Darren Reece 
Published: April 2024

AbstractSkeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule that plays important roles in immunity and cancer. However, the role of DUSP22 in skeletal muscle wasting is unknown. In this study, DUSP22 was found to be upregulated in sarcopenia patients and models of skeletal muscle wasting. DUSP22 knockdown or pharmacological inhibition prevented multiple forms of muscle wasting. Mechanistically, targeting DUSP22 suppressed FOXO3a, a master regulator of skeletal muscle wasting, via downregulation of the stress-activated kinase JNK, which occurred independently of aberrant Akt activation. DUSP22 targeting was also effective in human skeletal muscle cells undergoing atrophy. In conclusion, phosphatase DUSP22 is a novel target for preventing skeletal muscle wasting. The DUSP22-JNK-FOXO3a axis could be exploited to treat sarcopenia or related aging disorders.
Metaproteomics and DNA metabarcoding as tools to assess dietary intake in humans
Authors: Petrone Brianna L. , Bartlett Alexandria , Jiang Sharon , Korenek Abigail , Vintila Simina , Tenekjian Christine , Yancy William S. , David Lawrence A. , Kleiner Manuel 
Published: April 2024

AbstractObjective biomarkers of food intake are a sought-after goal in nutrition research. Most biomarker development to date has focused on metabolites detected in blood, urine, skin or hair, but detection of consumed foods in stool has also been shown to be possible via DNA sequencing. An additional food macromolecule in stool that harbors sequence information is protein. However, the use of protein as an intake biomarker has only been explored to a very limited extent. Here, we evaluate and compare measurement of residual food-derived DNA and protein in stool as potential biomarkers of intake. We performed a pilot study of DNA sequencing-based metabarcoding (FoodSeq) and mass spectrometry-based metaproteomics in five individuals’ stool sampled in short, longitudinal bursts accompanied by detailed diet records (n=27 total samples). Dietary data provided by stool DNA, stool protein, and written diet record independently identified a strong within-person dietary signature, identified similar food taxa, and had significantly similar global structure in two of the three pairwise comparisons between measurement techniques (DNA-to-protein and DNA-to-diet record). Metaproteomics identified proteins including myosin, ovalbumin, and beta-lactoglobulin that differentiated food tissue types like beef from dairy and chicken from egg, distinctions that were not possible by DNA alone. Overall, our results lay the groundwork for development of targeted metaproteomic assays for dietary assessment and demonstrate that diverse molecular components of food can be leveraged to study food intake using stool samples.
The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1
Authors: Romero Rodrigo , Chu Tinyi , González-Robles Tania J. , Smith Perianne , Xie Yubin , Kaur Harmanpreet , Yoder Sara , Zhao Huiyong , Mao Chenyi , Kang Wenfei , Pulina Maria V. , Lawrence Kayla E. , Gopalan Anuradha , Zaidi Samir , Yoo Kwangmin , Choi Jungmin , Fan Ning , Gerstner Olivia , Karthaus Wouter R. , DeStanchina Elisa , Ruggles Kelly V. , Westcott Peter M.K. , Chaligné Ronan , Pe’er Dana , Sawyers Charles L. 
Published: April 2024

ABSTRACTLineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatilein vivoplatform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e.g.,Rb1-/-;Trp53-/-;cMyc+orPten-/-;Trp53-/-;cMyc+), but only those withRb1deletion progress to ASCL1+ neuroendocrine prostate cancer (NEPC), a highly aggressive, androgen receptor signaling inhibitor (ARSI)-resistant tumor. Importantly, we show this lineage transition requires a nativein vivomicroenvironment not replicated by conventional organoid culture. By integrating multiplexed immunofluorescence, spatial transcriptomics and PrismSpot to identify cell type-specific spatial gene modules, we reveal that ASCL1+ cells arise from KRT8+ luminal epithelial cells that progressively acquire transcriptional heterogeneity, producing large ASCL1+;KRT8-NEPC clusters.Ascl1loss in established NEPC results in transient tumor regression followed by recurrence; however,Ascl1deletion prior to transplantation completely abrogates lineage plasticity, yielding adenocarcinomas with elevated AR expression and marked sensitivity to castration. The dynamic feature of this model reveals the importance of timing of therapies focused on lineage plasticity and offers a platform for identification of additional lineage plasticity drivers.
A promiscuous mechanism to phase separate eukaryotic carbon fixation in the green lineage
Authors: Barrett James , Naduthodi Mihris I.S. , Mao Yuwei , Dégut Clément , Musiał Sabina , Salter Aidan , Leake Mark C. , Plevin Michael J. , McCormick Alistair J. , Blaza James N. , Mackinder Luke C.M. 
Published: April 2024

AbstractCO2fixation is commonly limited by inefficiency of the CO2-fixing enzyme Rubisco. Eukaryotic algae concentrate and fix CO2in phase-separated condensates called pyrenoids, which complete up to one-third of global CO2fixation. Condensation of Rubisco in pyrenoids is dependent on interaction with disordered linker proteins that show little conservation between species. We developed a sequence-independent bioinformatic pipeline to identify linker proteins in green algae. We report the linker fromChlorellaand demonstrate that it binds a conserved site on the Rubisco large subunit. We show theChlorellalinker phase separatesChlamydomonasRubisco and that despite their separation by ∼800 million years of evolution, theChlorellalinker can support the formation of a functional pyrenoid inChlamydomonas. This cross-species reactivity extends to plants, with theChlorellalinker able to drive condensation of some native plant Rubiscosin vitroandin planta. Our results represent an exciting frontier for pyrenoid engineering in plants, which is modelled to increase crop yields.
Characterization of liver-pancreas crosstalk following β-cell loss reveals a role for the molybdenum cofactor in β-cell regeneration
Authors: Karampelias Christos , Băloiu Bianca , Rathkolb Birgit , Silva-Buttkus Patricia da , Bachar-Wikström Etty , Marschall Susan , Fuchs Helmut , Durner Valerie Gailus- , Chu Lianhe , de Angelis Martin Hrabě , Andersson Olov 
Published: April 2024

AbstractRegeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration in a zebrafish model of β-cell ablation. Using lineage-tracing, we show that hepatocytes do not directly convert into β-cells even under extreme β-cell ablation conditions. A transcriptomics analysis of isolated hepatocytes following β-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role for the molybdenum cofactor (Moco) biosynthetic pathway in β-cell regeneration and glucose metabolism in zebrafish. Consistently,Mocs2haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.
HeterozygousEif4nif1Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women
Authors: Moriwaki Mika , Liu Lihua , James Emma R , Tolley Neal , O’Connora Ashley M , Emery Benjamin , Aston Kenneth Ivan , Campbell Robert A. , Welt Corrine K. 
Published: April 2024

AbstractWe created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. TheEif4enif1C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.1286C>G stop-gain mutation in exon 10. The hybrid offspring of CMV-Cremice withEif4enif1WT/flxmice were designatedEif4enif1WT/Δfor simplicity. A subset of female heterozygotes (Eif4enif1WT/Δ)had no litters. In those with litters, the final litter was earlier (5.4±2.6 vs. 10.5±0.7 months; p=0.02). Heterozygous breeding pair (Eif4enif1WT/Δx Eif4enif1WT/Δ)litter size was 60% of WT litter size (3.9±2.0 vs. 6.5±3.0 pups/litter;p<0.001). The genotypes were 35%Eif4enif1WT/flxand 65%Eif4enif1WT/Δ, with no homozygotes. Homozygote embryos did not develop beyond the 4-8 cell stage. The number of follicles in ovaries fromEif4enif1WT/Δmice was lower starting at the primordial (499±290 vs. 1445±381) and primary follicle stage (1069±346 vs. 1450±193) on day 10 (p<0.05). The preantral follicle number was lower starting on day 21 (213±86 vs. 522±227; p<0.01). Examination of ribosome protected mRNAs (RPR) demonstrated altered mRNA expression. TheEif4enif1stop-gain mice replicate the POI phenotype in women. The unique mouse model provides a platform to study regulation of protein translation across oocyte and embryo development in mammals.