bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of ICOSL/ICOS pathway-regulated long non-coding RNAs on liver fibrosis in mice infected with Schistosoma japonicum
Authors: Huang Ping , Xu Jing , Jiang Suqin , Zhang Yanan , Wang Xinyi , Xiong Chunrong , Xia Chaoming 
Published: July 2024

Abstract
Background
The primary pathogenic mechanism of schistosomiasis-associated liver fibrosis involves the deposition of schistosome eggs, leading to the formation of liver egg granulomas and subsequent liver fibrosis. Hepatic stellate cells are abnormally activated, resulting in excessive collagen deposition and fibrosis development. While specific long non-coding RNAs (lncRNAs) have been associated with fibrotic processes, their roles in schistosomiasis-associated liver fibrosis remain unclear.

Methods
Our previous research indicated that downregulating the ICOSL/ICOS could partially alleviate liver fibrosis. In this study, we established a schistosomiasis infection model in C57BL/6 and ICOSL knockout (KO) mice, and the liver pathology changes were observed at various weeks postinfection (wpi) using hematoxylin and eosin and Masson’s trichrome staining. Within the first 4 wpi, no significant liver abnormalities were observed. However, mice exhibited evident egg granulomas and fibrosis in their livers at 7 wpi. Notably, ICOSL-KO mice had significantly smaller pathological variations compared with simultaneously infected C57BL/6 mice. To investigate the impact of lncRNAs on schistosomiasis-associated liver fibrosis, quantitative real-time polymerase chain reaction (RT-qPCR) was used to monitor the dynamic changes of lncRNAs in hepatic stellate cells of infected mice.

Results
The results demonstrated that lncRNA-H19, -MALAT1, -PVT1, -P21 and -GAS5 all participated in liver fibrosis formation after schistosome infection. In addition, ICOSL-KO mice exhibited significantly inhibited expression of lncRNA-H19, -MALAT1 and -PVT1 after 7 wpi. In contrast, they showed enhanced expression of lncRNA-P21 and -GAS5 compared with C57BL/6 mice, influencing liver fibrosis development. Furthermore, small interfering RNA transfection (siRNA) in JS-1 cells in vitro confirmed that lncRNA-H19, -MALAT1, and -PVT1 promoted liver fibrosis, whereas lncRNA-P21 and -GAS5 had the opposite effect on key fibrotic molecules, including α- smooth muscle actin and collagen I expression.

Conclusions
This study uncovers that ICOSL/ICOS may play a role in activating hepatic stellate cells and promoting liver fibrosis in mice infected with Schistosoma japonicum by dynamically regulating the expression of specific lncRNAs. These findings offer potential therapeutic targets for schistosomiasis-associated liver fibrosis.

Graphical Abstract
DNA methylation-mediated suppression of TUSC1 expression regulates the malignant progression of esophagogastric junction cancer
Authors: Liu Zhiqiang , Xia Ganshu , Liang Xiaolong , Li Baozhong , Deng Jingyu 
Published: July 2024

Abstract
Background
Esophagogastric junction cancer (EJC) refers to malignant tumors that develop at the junction between the stomach and the esophagus. TUSC1 is a recently identified tumor suppressor gene known for its involvement in various types of cancer. The objective of this investigation was to elucidate the regulatory influence of DNA methylation on TUSC1 expression and its role in the progression of EJC.

Methods
Bioinformatics software was utilized to analyze the expression of TUSC1, enriched pathways, and highly methylated sites in the promoter region. TUSC1 expression in EJC was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB), and immunohistochemistry. Methylation-specific PCR was employed to detect the methylation level of TUSC1. To analyze the effects of TUSC1 and 5-AZA-2 on tumor cell proliferation, migration, invasion, cell cycle, and apoptosis, several assays including CCK-8, colony formation, transwell, and flow cytometry were conducted. The expression of MDM2 was assessed using qRT-PCR and WB. WB detected the expression of p53, and p-p53, markers for EJC cell proliferation, epithelial-mesenchymal transition, and apoptosis. The role of TUSC1 in tumor occurrence in vivo was examined using a xenograft mouse model.

Results
TUSC1 expression was significantly downregulated in EJC. Overexpression of TUSC1 and treatment with 5-AZA-2 inhibited the malignant progression of EJC cells. In EJC, low methylation levels promoted the expression of TUSC1. Upregulation of TUSC1 suppressed the expression of MDM2 and activated the p53 signaling pathway. Inactivation of this pathway attenuated the inhibitory effect of TUSC1 overexpression on EJC cell proliferation, migration, invasion, and other behaviors. Animal experiments demonstrated that TUSC1 overexpression inhibited EJC tumor growth and metastasis in vivo.

Conclusion
TUSC1 was commonly downregulated in EJC and regulated by methylation. It repressed the malignant progression of EJC tumors by mediating the p53 pathway, suggesting its potential as a diagnostic and therapeutic target for EJC.
Adult sex change leads to extensive forebrain reorganization in clownfish
Authors: Parker Coltan G. , Gruenhagen George W. , Hegarty Brianna E. , Histed Abigail R. , Streelman Jeffrey T. , Rhodes Justin S. , Johnson Zachary V. 
Published: July 2024

Abstract
Background
Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation.

Methods
This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain.

Results
We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of sexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation.

Conclusions
This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish.
Estimating the synthetic accessibility of molecules with building block and reaction-aware SAScore
Authors: Chen Shuan , Jung Yousung 
Published: July 2024

AbstractSynthetic accessibility prediction is a task to estimate how easily a given molecule might be synthesizable in the laboratory, playing a crucial role in computer-aided molecular design. Although synthesis planning programs can determine synthesis routes, their slow processing times make them impractical for large-scale molecule screening. On the other hand, existing rapid synthesis accessibility estimation methods offer speed but typically lack integration with actual synthesis routes and building block information. In this work, we introduce BR-SAScore, an enhanced version of SAScore that integrates the available building block information (B) and reaction knowledge (R) from synthesis planning programs into the scoring process. In particular, we differentiate fragments inherent in building blocks and fragments to be derived from synthesis (reactions) when scoring synthetic accessibility. Compared to existing methods, our experimental findings demonstrate that BR-SAScore offers more accurate and precise identification of a molecule's synthetic accessibility by the synthesis planning program with a fast calculation time. Moreover, we illustrate how BR-SAScore provides chemically interpretable results, aligning with the capability of the synthesis planning program embedded with the same reaction knowledge and available building blocks.Scientific contributionWe introduce BR-SAScore, an extension of SAScore, to estimate the synthetic accessibility of molecules by leveraging known building-block and reactivity information. In our experiments, BR-SAScore shows superior prediction performance on predicting molecule synthetic accessibility compared to previous methods, including SAScore and deep-learning models, while requiring significantly less computation time. In addition, we show that BR-SAScore is able to precisely identify the chemical fragment contributing to the synthetic infeasibility, holding great potential for future molecule synthesizability optimization.
Silibinins and curcumin as promising ligands against mutant cystic fibrosis transmembrane regulator protein
Authors: Akram Areeba , Sakhawat Azra , Ghani Muhammad Usman , Khan Muhammad Umer , Rehman Raima , Ali Qurban , Jin-liang Peng , Ali Daoud 
Published: July 2024

AbstractCystic Fibrosis Transmembrane Regulator (CFTR) is a significant protein that is responsible for the movement of ions across cell membranes. The cystic fibrosis (CF) occur due to the mutations in the CFTR gene as it produces the dysfunctional CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands selection was performed through virtual screening and top 3 ligands choose out of 65 ligands silibinins, curcumin, demethoxycurcumin were selected with a reference drug Trikafta (R*). According to docking, ADMET analyses, the natural ligands (Silibinins and Curcumin) displayed best binding energy, pharmacokinetic and free toxicity than other natural compounds and reference drug (R*). An MD simulation for 200 ns was also established to ensure that natural ligands (Silibinins and Curcumin) attached to the target protein favorably and dynamically, and that protein–ligand complex stability was maintained. It is concluded that silibinins and curcumins have a better capacity to decrease the effect of mutant CFTR protein through improved trafficking and the restoration of original function. In conclusion, in silico studies demonstrate the potential of silibinins and curcumin as therapeutic agents for cystic fibrosis, particularly for the D614G mutated protein. Their ability to increase CFTR function while reducing cellular stress and inflammation, together with their favorable safety profile and accessibility could make them valuable additions to cystic fibrosis treatment options. Further experimental and clinical validation will be required to fully realize their potential and include them into effective therapy regimens.
Effectiveness of a culturally tailored HIV intervention in promoting PrEP among black women who use drugs in community supervision programs in New York City: a randomized clinical trial
Authors: Goddard-Eckrich Dawn , McCrimmon Tara , Bond Keosha , Chang Mingway , Hunt Timothy , Hall Jennifer , Russo Mary , Ramesh Vineha , Johnson Karen A. , Downey Dget L. , Wu Elwin , El-Bassel Nabila , Gilbert Louisa 
Published: July 2024

Abstract
Background
In the U.S. there are significant racial and gender disparities in the uptake of pre-exposure prophylaxis (PrEP). Black Americans represented 14% of PrEP users in 2022, but accounted for 42% of new HIV diagnoses in 2021 and in the South, Black people represented 48% of new HIV diagnoses in 2021 but only 21% of PrEP users in 2022. Women who use drugs may be even less likely than women who do not use drugs have initiated PrEP. Moreover, women involved in community supervision programs (CSP) are less likely to initiate or use PrEP, More PrEP interventions that focus on Black women with recent history of drug use in CSPs are needed to reduce inequities in PrEP uptake.

Methods
We conducted a secondary analysis from a randomized clinical trial with a sub-sample (n = 336) of the total (N = 352) participants from the parent study (E-WORTH), who tested HIV negative at baseline were considered PrEP-eligible. Black women were recruited from CSPs in New York City (NYC), with recent substance use. Participants were randomized to either E-WORTH (n = 172) an HIV testing plus, receive a 5-session, culturally-tailored, group-based HIV prevention intervention, versus an HIV testing control group (n = 180). The 5 sessions included an introduction to PrEP and access. This paper reports outcomes on improved awareness of PrEP, willingness to use PrEP, and PrEP uptake over the 12-month follow-up period. HIV outcomes are reported in a previous paper.

Results
Compared to control participants, participants in this study assigned to E-WORTH had significantly greater odds of being aware of PrEP as a biomedical HIV prevention strategy (OR = 3.25, 95% CI = 1.64–6.46, p = 0.001), and indicated a greater willingness to use PrEP as an HIV prevention method (b = 0.19, 95% CI = 0.06–0.32, p = 0.004) over the entire 12-month follow-up period.

Conclusions
These findings underscore the effectiveness of a culturally-tailored intervention for Black women in CSP settings in increasing awareness, and intention to initiate PrEP. Low uptake of PrEP in both arms highlight the need for providing more robust PrEP-on-demand strategies that are integrated into other services such as substance abuse treatment.

Trial Registration
ClinicalTrials.gov Identifier: NCT02391233.
Process validation and preclinical development of a new PET cerebral blood flow tracer [11C]MMP for initial clinical trials
Authors: Toyohara Jun , Tago Tetsuro , Sakata Muneyuki 
Published: July 2024

Abstract
Background
2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is commonly used for diagnosis of dementia because brain glucose metabolism reflects neuronal activity. However, as [18F]FDG is an analogue of glucose, accumulation of tracer in the brain is affected by plasma glucose levels. In contrast, cerebral blood flow (CBF) tracers are theoretically unaffected by plasma glucose levels and are therefore expected to be useful alternatives for the diagnosis of dementia in patients with diabetes. The techniques currently used for CBF imaging using single photon emission computed tomography (SPECT) and [15O]H2O positron emission tomography (PET), but these are limited by their insufficient resolution and sensitivity for regional brain imaging, especially in patients with brain atrophy. N-isopropyl-4-[11C]methylamphetamine ([11C]MMP) is a possible CBF tracer with high resolution and sensitivity that exhibits comparable performance to that of [15O]H2O in conscious monkey brains. We performed process validation of the radiosynthesis and preclinical development of [11C]MMP prior to clinical translation.

Results
The decay-corrected yields of [11C]MMP at the end of synthesis were 41.4 ± 6.5%, with 99.7 ± 0.3% radiochemical purity, and 192.3 ± 22.5 MBq/nmol molar activity. All process validation batches complied with the product specifications. The acute toxicity of MMP was evaluated at a dose of 3.55 mg/kg body weight, which is 10,000 times the potential maximum clinical dose of [11C]MMP. The acute toxicity of [11C]MMP injection at 150 or 200 times, to administer a postulated dose of 740 MBq of [11C]MMP, was also evaluated after the decay-out of 11C. No acute toxicity of MMP and [11C]MMP injection was found. No mutagenic activity was observed for MMP. The effective dose calculated according to the Medical Internal Radiation Dose (MIRD) method was 5.4 µSv/MBq, and the maximum absorbed dose to the bladder wall was 57.6 µGy/MBq. MMP, a derivative of phenylalkylamine, showed binding to the sigma receptor, but had approximately 1/100 of the affinity of existing sigma receptor imaging agents. The affinity for other brain neuroreceptors was low.

Conclusions
[11C]MMP shows acceptable pharmacological safety at the dose required for adequate PET imaging. The potential risk associated with [11C]MMP PET imaging is well within the acceptable dose limit.
Evaluating diagnostic accuracy of an RT-PCR test for the detection of SARS-CoV-2 in saliva
Authors: Samsunder Natasha , Sivro Aida , Hassan-Moosa Razia , Lewis Lara , Kara Zahra , Baxter Cheryl , Karim Quarraisha Abdool , Karim Salim Abdool , Kharsany Ayesha B. M. , Naidoo Kogieleum , Ngcapu Sinaye 
Published: July 2024

Abstract
Background and objective
Saliva has been proposed as a potential more convenient, cost-effective, and easier sample for diagnosing SARS-CoV-2 infections, but there is limited knowledge of the impact of saliva volumes and stages of infection on its sensitivity and specificity.

Methods
In this study, we assessed the performance of SARS-CoV-2 testing in 171 saliva samples from 52 mostly mildly symptomatic patients (aged 18 to 70 years) with a positive reference standard result at screening. The samples were collected at different volumes (50, 100, 300, and 500 µl of saliva) and at different stages of the disease (at enrollment, day 7, 14, and 28 post SARS-CoV-2 diagnosis). Imperfect nasopharyngeal (NP) swab nucleic acid amplification testing was used as a reference. We used a logistic regression with generalized estimating equations to estimate sensitivity, specificity, PPV, and NPV, accounting for the correlation between repeated observations.

Results
The sensitivity and specificity values were consistent across saliva volumes. The sensitivity of saliva samples ranged from 70.2% (95% CI, 49.3–85.0%) for 100 μl to 81.0% (95% CI, 51.9–94.4%) for 300 μl of saliva collected. The specificity values ranged between 75.8% (95% CI, 55.0–88.9%) for 50 μl and 78.8% (95% CI, 63.2–88.9%) for 100 μl saliva compared to NP swab samples. The overall percentage of positive results in NP swabs and saliva specimens remained comparable throughout the study visits. We observed no significant difference in cycle number values between saliva and NP swab specimens, irrespective of saliva volume tested.

Conclusions
The saliva collection offers a promising approach for population-based testing.
Novel use of hot biopsy forceps for removal of tracheobronchial stent-related granulation tissue
Authors: Pahuja Sourabh , Bajad Pradeep , Khanna Arjun , Agarwal Satyam 
Published: July 2024

AbstractPatients with malignant central airway obstruction often present with dyspnea and sometimes with frank respiratory failure. Airway stenting has become a routine modality in the management of these patients. A correctly placed airway stent will give good relief in dyspnea and respiratory failure and will even improve the patient's ECOG (Eastern Cooperative Oncology Group) performance score. The common complications associated with stents are migration, fracture, infection, and obstruction by tumors, granulation tissue, and secretions. These complications are more pronounced with metallic stents. Surveillance bronchoscopy should ideally be done in these patients at least 4–6 weeks post-stent insertion. Removal of granulation tissue has been attempted with modalities like lasers, Argon plasma coagulation, cryotherapy, and snare electrocautery. Here, we present a novel case of post-stent granulation tissue, which was removed and debulked with the help of electrocoagulation bronchoscopy biopsy forceps (hot biopsy forceps).Conclusion Hot biopsy forceps can be safely and easily used for the removal of granulation tissue in patients post-tracheobronchial stent insertion.
Assessing Patient Perspectives and the Health Equity of a Digital Cancer Symptom Remote Monitoring and Management System
Authors: Mooney Kathi , Beck Susan L. , Wilson Christina , Coombs Lorinda , Whisenant Meagan , Moraitis Ann Marie , Sloss Elizabeth A. , Alekhina Natalya , Lloyd Jennifer , Steinbach Mary , Nicholson Bridget , Iacob Eli , Donaldson Gary 
Published: July 2024

PURPOSE People with cancer experience poorly controlled symptoms that persist between treatment visits. Automated digital technology can remotely monitor and facilitate symptom management at home. Essential to digital interventions is patient engagement, user satisfaction, and intervention benefits that are distributed across patient populations so as not to perpetuate inequities. We evaluated Symptom Care at Home (SCH), an automated digital platform, to determine patient engagement, satisfaction, and whether intervention subgroups gained similar symptom reduction benefits. METHODS 358 patients with cancer receiving a course of chemotherapy were randomly assigned to SCH or usual care (UC). Both groups reported daily on 11 symptoms and completed the SF36 (Short Form Health Survey) monthly. SCH participants received immediate automated self-care coaching on reported symptoms. As needed, nurse practitioners followed up for poorly controlled symptoms. RESULTS The average participant was White (83%), female (75%), and urban-dwelling (78.6%). Daily call adherence was 90% of expected days. Participants reported high user satisfaction. SCH participants had lower symptom burden than UC in all subgroups: age, sex, race, income, residence type, diagnosis, and stage (all P < .001 effect size 0.33-0.65), except for stages I and II cancers. Non-White and lower-income SCH participants gained a higher magnitude of symptom reduction than White participants and higher-income participants. Additionally, SCH men gained higher SF36 mental health (MH) benefit. There were no differences on other SF36 indices. CONCLUSION Participants were highly satisfied and consistently engaged the SCH platform. SCH men gained large MH improvements, perhaps from increased comfort in sharing concerns through automated interactions. Although all intervention subgroups benefited, non-White participants and those with lower income gained higher symptom reduction benefit, suggesting that systematic care through digital tools can overcome existing disparities in symptom care outcomes.
Exploring the Gut Microbiota: Key Insights Into Its Role in Obesity, Metabolic Syndrome, and Type 2 Diabetes
Authors: Sasidharan Pillai Sabitha , Gagnon Charles A , Foster Christy , Ashraf Ambika P 
Published: July 2024

Abstract
The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols.