bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Transoral Incisionless Fundoplication in Salvage Therapy for Recurrent Reflux
Authors: Lee Michelle E. , Ghosh Gaurav , Mahadev Srihari 
Published: April 2023

Background: Gastroesophageal reflux (GERD) occurs when anatomic barriers fail to prevent retrograde movement of stomach contents into the esophagus. When lifestyle and medications fail to relieve patients’ symptoms, anti-reflux procedures can be safe and effective options for addressing the mechanical deficits (such as reduced lower-esophageal sphincter pressure, hiatal hernia, and/or patulous diaphragmatic hiatus) contributing to GERD. When laparoscopic fundoplication treatment of GERD fails, repeat surgical treatment is an option—but comes with risk of increased morbidity when compared to the primary fundoplication. Transoral incisionless fundoplication (TIF) is an endoscopic anti-reflux procedure that may be an alternative option for salvage therapy in patients with recurrent GERD. Methods: This review will explore fundoplication failure, the theoretical role for TIF in this setting, and the literature to support TIF as endoscopic rescue at this time. Literature review of studies reporting TIF for salvage therapy outcomes was performed, revealing 2 published papers. Results: TIF as salvage therapy has been shown in patients with minimal recurrent hiatal hernia but a loose fundoplication to be feasible, safe, and effective with improvement of GERD symptom scores and acid exposure time. However, this has only been shown in small, retrospective studies at this time. Conclusion: TIF may be a reasonable alternative to repeat laparoscopic fundoplication in patients with a small hiatal hernia.
A new prediction model of hepatocellular carcinoma based on N7-methylguanosine modification
Authors: Yang Li , Wang Yi-ran , Mou Zhi-qiang , Xiong Ping-fu , Deng Kun , Wen Jian , Li Jing 
Published: April 2023

Abstract
Purpose
Hepatocellular carcinoma (HCC) is a kind of primary liver cancer. It is a common malignant tumor of digestive system that is difficult to predict the prognosis of patients. As an important epigenetic modification, N7 methyl guanosine (m7G) is indispensable in gene regulation. This regulation may affect the development and occurrence of cancer. However, the prognosis of long non coding RNAs (lncRNAs) in HCC is limited, especially how m7G-related lncRNAs regulate the development of HCC has not been reported.

Methods
The Cancer Genome Atlas (TCGA) provides us with the expression data and corresponding clinical information of HCC patients we need. We used a series of statistical methods to screen four kinds of m7G-related lncRNAs related to HCC prognosis and through a series of verifications, the results were in line with our expectations. Finally, we also explored the IC50 difference and correlation analysis of various common chemotherapy drugs.

Result
Our study identified four differentially expressed m7g-related lncRNAs associated with HCC prognosis. Survival curve analysis showed that high risk lncRNAs would lead to poor prognosis of HCC patients. M7G signature's AUC was 0.789, which shows that the prognosis model we studied has certain significance in predicting the prognosis of HCC patients. Moreover, our study found that different risk groups have different immune and tumor related pathways through gene set enrichment analysis. In addition, many immune cell functions are significantly different among different risk groups, such as T cell functions, including coordination of type I INF response and coordination of type II INF response. The expression of PDCD1, HHLA2, CTLA-4 and many other immune checkpoints in different risk groups is also different. Additionally, we analyzed the differences of IC50 and risk correlation of 15 chemotherapeutic drugs among different risk groups.

Conclusion
A novel lncRNAs associated with m7G predicts the prognosis of HCC.
Ultra-short echo time MR imaging in assessing cartilage endplate damage and relationship between its lesion and disc degeneration for chronic low back pain patients
Authors: Ji Zhilin , Li Yue , Dou Weiqiang , Zhu Yaru , Shi Yin , Zou Yuefen 
Published: April 2023

Abstract
Objective
To investigate the feasibility of ultra-short echo time (UTE) magnetic resonance imaging (MRI) in the assessment of cartilage endplate (CEP) damage and further evaluate the relationship between total endplate score (TEPS) and lumbar intervertebral disc (IVD) degeneration for chronic low back pain patients.

Materials and methods
IVD were measured in 35 patients using UTE imaging at 3T MR. Subtracted UTE images between short and long TEs were obtained to depict anatomy of CEP. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated to assess the image quality quantitatively. A new grading criterion for endplate damage evaluation was developed based on Rajasekaran.S grading system in this study. Two radiologists were employed to evaluate CEP and bony vertebral endplates (VEP) using this new grading criterion and assess TEPS, independently. Cohen’s kappa analysis was applied to evaluate the inter-observer agreement of endplate damage assessment between two radiologists, and the Kendall’s TAU-B analysis was employed to determine the relationship between TEPS and IVD degeneration evaluated with Pfirrmann grading.

Results
Well structural CEP was depicted on subtracted UTE images and confirmed by high SNR (33.06±2.92) and CNR values (9.4±2.08). Qualified subtracted UTE images were used by two radiologists to evaluate the degree of CEP and VEP damage. Excellent inter-observer agreement was confirmed by high value in Cohen’s kappa test (0.839, P < 0.001). Ensured by this, 138 endplates from 69 IVDs of 35 patients were classified into six grades based on the new grading criterion and TEPS of each endplate was calculated. In addition, the degeneration degree of IVDs were classified into five grades. Finally, using Kendall’s TAU-B analysis, significant relationship was obtained between endplate damage related TEPS and IVD degeneration (r = 0.864, P < 0.001).

Conclusion
Ensured by high image quality, UTE imaging might be considered an effective tool to assess CEP damage. Additionally, further calculated TEPS has shown strong positive association with IVD degeneration, suggesting that the severity of endplate damage is highly linked with the degree of IVD degeneration.
The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).
Authors: Mendez Lucas C. , Dhar Aneesh , Laidley David , Moussa Madeleine , Gomez Jose A. , Chin Joseph , Lee T-Y , Thiessen Jonathan D. , Hoover Douglas , Surrey Kathleen , Helou Joelle , Velker Vikram , Correa Rohann J. , D’Souza David , Bayani Jane , Bauman Glenn 
Published: April 2023

Abstract
Background
Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues.

Methods
ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment.

Discussion
ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy.

Trial registration
NCT05230251 (ClinicalTrials.gov).
Bifrontal electroconvulsive therapy leads to improvement of cerebral glucose hypometabolism in frontotemporal dementia with comorbid psychotic depression – a case report
Authors: Schröder Sebastian , Bönig Lena , Proskynitopoulos Phileas Johannes , Janke Eva , Heck Johannes , Mahmoudi Nima , Groh Adrian , Berding Georg , Wedegärtner Felix , Deest-Gaubatz Stephanie , Maier Hannah Benedictine , Bleich Stefan , Frieling Helge , Schulze Westhoff Martin 
Published: April 2023

Abstract
Background
Differentiating depression and dementia in elderly patients represents a major clinical challenge for psychiatrists. Pharmacological and non-pharmacological treatment options for both conditions are often used cautiously due to fear of adverse effects. If a clinically indicated therapy is not initiated due to fear of adverse effects, the quality of life of affected patients may significantly be reduced.

Case presentation
Here, we describe the case of a 65-year-old woman who presented to the department of psychiatry of a university hospital with depressed mood, pronounced anxiety, and nihilistic thoughts. While several pharmacological treatments remained without clinical response, further behavioral observation in conjunction with 18F-fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed the diagnosis of frontotemporal dementia (FTD). To counter the pharmacological treatment resistance of psychotic depression, we decided to perform electroconvulsive therapy (ECT). Remarkably, ten sessions of ECT yielded an almost complete remission of depressive symptoms. In addition, the patient’s delusional ideas disappeared. A follow-up 18F-FDG PET/CT after the ECT series still showed a frontally and parieto-temporally accentuated hypometabolism, albeit with a clear regression compared to the previous image. The follow-up 18F-FDG PET/CT thus corroborated the diagnosis of FTD, while on the other hand it demonstrated the success of ECT.

Conclusions
In this case, ECT was a beneficial treatment option for depressive symptoms in FTD. Also, 18F-FDG PET/CT should be discussed as a valuable tool in differentiating depression and dementia and as an indicator of treatment response.
Suubi + Adherence4Youth: a study protocol to optimize the Suubi Intervention for Adherence to HIV treatment for youth living with HIV in Uganda
Authors: Ssewamala Fred M. , Sauceda John A. , Brathwaite Rachel , Neilands Torsten B. , Nabunya Proscovia , Brown Derek , Sensoy Bahar Ozge , Namuwonge Flavia , Nakasujja Noeline , Mugarura Allan , Mwebembezi Abel , Nartey Portia , Mukasa Barbara , Gwadz Marya 
Published: April 2023

AbstractBackgroundSuubi is an evidenced based multi-component intervention that targets psychosocial and economic hardships to improve ART adherence, viral suppression, mental health, family financial stability, and family cohesion for adolescents living with HIV (ALHIV) in Uganda. Suubi was originally tested as a combined package of four components: 1) Financial Literacy Training; 2) incentivized matched Youth Savings Accounts with income-generating activities; 3) a manualized and visual-based intervention for ART adherence and stigma reduction; and 4) engagement with HIV treatment-experienced role models. However, it is unknown if each component in Suubi had a positive effect, how the components interacted, or if fewer components could have produced equivalent effects. Hence, the overall goal of this new study is to identify the most impactful and sustainable economic and psychosocial components across 48 health clinics in Uganda.MethodsA total of 576 ALHIV (aged 11–17 years at enrollment) will be recruited from 48 clinics and each clinic will be randomized to one of 16 study conditions. Each condition represents every possible combination of the 4 components noted above. Assessments will be conducted at baseline, 12, 24, 36 and 48- months post-intervention initiation. Using the multi-phase optimization strategy (MOST), we will identify the optimal combination of components and associated costs for viral suppression, as well as test key mediators and moderators of the component-viral suppression relationship.DiscussionThe study is a shift in the paradigm of research to use new thinking to build/un-pack highly efficacious interventions that lead to new scientific knowledge in terms of understanding what drives an intervention’s success and how to iterate on them in ways that are more efficient, affordable and scalable. The study advances intervention science for HIV care outcomes globally.Trial RegistrationThis project was registered at clinicaltrials.gov (NCT05600621) on October, 31, 2022.https://clinicaltrials.gov/ct2/show/NCT05600621
Utility of vaginal vault cytology in the local recurrence of cervical cancer
Authors: Nakamura Kazuto , Yamashita Soichi , Kigure Keiko , Nishimura Toshio , Ito Ikuro , Azuma Anri , Nakao Kohshiro , Ando Ken , Kanuma Tatsuya 
Published: April 2023

Abstract
Background
In Japan, 8000 women were newly diagnosed with cervical cancer in 2018. The healthcare insurance policy in Japan allows physicians to utilize vaginal volt cytology tests and serum biomarker measurement at every visit and imaging analysis at an adequate interval with screening for recurrence after initial treatment. However, the major surveillance guidelines published in the United States and European countries recommend focusing on pelvic examinations and symptom reviews to avoid unnecessary tests. This study aimed to reassess the benefits of standard surveillance methods adopted in this study by retrospective analysis.

Methods
From January 2009 to December 2015, the medical records of patients with recurrence who were initially diagnosed with International Federation of Gynecology and Obstetrics stage I–III cervical cancer were collected for this study. Clinicopathological data were statistically analyzed to identify significant factors. In the first 2 years, the patients underwent regular surveillance, including pelvic examination, serum tumor marker tests, vaginal vault cytology every 1–3 months, and imaging analysis at 6- to 12-month intervals. In the following 2 years, the patients received a regular check with the same methods every 4 months and an annual imaging analysis. Afterward, the patients had regular screening every 6 to 12 months.

Results
In the study period, 84 of the 981 patients experienced recurrence, and 88.1% had an asymptomatic recurrence. The disease-free interval was not related to the recurrence site. In univariate analysis, primary treatment, recurrence site, and diagnostic method were significant factors for survival outcomes. In contrast, multivariate analysis indicated that only primary treatment was a significant factor. In patients with local recurrence, multivariate analysis demonstrated that radiation as salvage therapy was an independent predictive factor for overall survival after recurrence.

Conclusions
In this retrospective study, routine imaging analysis and serum biomarker measurement did not contribute to patient prognosis after recurrence. In contrast, vaginal vault cytology can improve survival after recurrence in some patients. Tailored surveillance methods based on individual disease conditions and treatment modalities can improve post-recurrent survival outcomes.
Optimizing yeast for high-level production of kaempferol and quercetin
Authors: Tartik Musa , Liu Juan , Mohedano Marta Tous , Mao Jiwei , Chen Yun 
Published: April 2023

Abstract
Background
Two important flavonoids, kaempferol and quercetin possess remarkably potent biological impacts on human health. However, their structural complexity and low abundance in nature make both bulk chemical synthesis and extraction from native plants difficult. Therefore microbial production via heterologous expression of plant enzymes can be a safe and sustainable route for their production. Despite several attempts reported in microbial hosts, the production levels of kaempferol and quercetin still stay far behind compared to many other microbial-produced flavonoids.

Results
In this study, Saccharomyces cerevisiae was engineered for high production of kaempferol and quercetin in minimal media from glucose. First, the kaempferol biosynthetic pathway was reconstructed via screening various F3H and FLS enzymes. In addition, we demonstrated that amplification of the rate-limiting enzyme AtFLS could reduce the dihydrokaempferol accumulation and improve kaempferol production. Increasing the availability of precursor malonyl-CoA further improved the production of kaempferol and quercetin. Furthermore, the highest amount of 956 mg L− 1 of kaempferol and 930 mg L− 1 of quercetin in yeast was reached in fed-batch fermentations.

Conclusions
De novo biosynthesis of kaempferol and quercetin in yeast was improved through increasing the upstream naringenin biosynthesis and debugging the flux-limiting enzymes together with fed-batch fermentations, up to gram per liter level. Our work provides a promising platform for sustainable and scalable production of kaempferol, quercetin and compounds derived thereof.
IL-33/ST2 antagonizes STING signal transduction via autophagy in response to acetaminophen-mediated toxicological immunity
Authors: Wang Zengbin , Sun Pei , Pan Banglun , Qiu Jiacheng , Zhang Xiaoxia , Shen Shuling , Ke Xiaoling , Tang Nanhong 
Published: April 2023

Abstract
Background
Interleukin-33 (IL-33), defined as "alarming", exert diverse functions through signaling via the suppression of tumorigenicity 2 (ST2). However, the physiological roles of IL-33/ST2 signaling during acetaminophen (APAP)-induced liver injury are still poorly understood by modern medicine (AILI). This research aims to explore the relationship between IL-33/ST2 and stimulator of interferon (IFN) response cGAMP interactor 1 (STING)-mediated signal transduction.

Methods
C57BL/6N mice (WT) and IL-33-deficient mice (KO) were intraperitoneally injected with APAP (250 mg/kg). Recombinant IL-33 (500 ng/mouse) and the cGAS/STING inhibitor RU.521 (200 g/kg) were combined to treat AILI. For mechanistic research in vitro, CRISPR-mediated KD technology, immunoprecipitation, mass spectrometry, and immunofluorescence were utilized.

Results
We discovered that IL-33 deficient mice had increased APAP-induced hepatotoxicity, DNA accumulation, and type 1 IFN production. Mechanistic analysis revealed that IL-33/ST2 enhanced the interaction between Beclin-1 and STING, disrupting STING dimerization, IRF3 phosphorylation, nuclear transport, and IFN-1 gene transcription in HepaRG and Huh7 cells. Beclin-1 interacted with the C-terminus of STING, causing Lys338 acetylation and autophagy degradation of STING. ST2 depletion increased STING signal transduction and IFN-1 promoter activity. Surprisingly, the cGAS/STING inhibitor RU.521 and recombinant IL-33 together improved AILI in vivo.

Conclusions
These results shed insight on the potential of inhibiting cGAS/STING as a therapy for AILI and emphasize the crucial role of IL-33/ST2 signaling in the regulation of APAP-induced STING signaling.

Graphical Abstract
MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8
Authors: Qin Tian , Shen Beilei , Li Entao , Jin Song , Luo Rongbo , Zhang Yiming , Qi Jing , Deng Xiuwen , Shi Zhuangzhuang , Wang Tiecheng , Zhou Yifa , Gao Yuwei 
Published: April 2023

Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes non-symptomatic infection, mild influenza-like symptoms to pneumonia, severe acute respiratory distress syndrome, and even death, reflecting different clinical symptoms of viral infection. However, the mechanism of its pathogenicity remains unclear. Host-specific traits have a breakthrough significance for studying the pathogenicity of SARS-CoV-2. We previously reported SARS-CoV-2/BMA8, a mouse-adapted strain, was lethal to aged BALB/c mice but not to aged C57BL/6N mice. Here, we further investigate the differences in pathogenicity of BMA8 strain against wild-type aged C57BL/6N and BALB/c mice.

Methods
Whole blood and tissues were collected from mice before and after BMA8 strain infection. Viral replication and infectivity were assessed by detection of viral RNA copies and viral titers; the degree of inflammation in mice was tested by whole blood cell count, ELISA and RT-qPCR assays; the pathogenicity of SARS-CoV-2/BMA8 in mice was measured by Histopathology and Immunohistochemistry; and the immune level of mice was evaluated by flow cytometry to detect the number of CD8+ T cells.

Results
Our results suggest that SARS-CoV-2/BMA8 strain caused lower pathogenicity and inflammation level in C57BL/6N mice than in BALB/c mice. Interestingly, BALB/c mice whose MHC class I haplotype is H-2Kd showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2Kb in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2Kb inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8+ T cells caused by SARS-CoV-2/BMA8 infection.

Conclusions
Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.