bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring treatment impacts on symptoms in adults with hypoparathyroidism: findings from the PaTHway trial
Authors: Brod Meryl , Pfeiffer Kathryn M. , Beck Jane F. , Smith Alden 
Published: August 2024

Abstract
Background
Hypoparathyroidism is a rare endocrine disease frequently associated with serious physical and cognitive symptoms. This study’s purpose was to understand the impacts of the phase 3 PaTHway clinical trial treatment, TransCon PTH, on patients’ overall, physical, and cognitive hypoparathyroidism signs/symptoms and what patients consider meaningful improvement.

Methods
Individual telephone exit interviews were conducted with patients who recently completed the PaTHway trial blinded period. Using a semi-structured interview guide, interviews focused on trial treatment impact on hypoparathyroidism symptoms following the symptom list in the Hypoparathyroidism Patient Experience Scale-Symptom (HPES-Symptom). Meaningful changes in hypoparathyroidism symptoms were assessed with the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) measures. Interviewees were probed on the meaningfulness of reported changes in symptoms from prior to starting trial treatment to the past 2 weeks/current time. Interviews were audiotaped and transcribed. Transcripts were coded for emerging concepts and themes/subthemes covered in the interview guide based on an adapted grounded theory approach.

Results
Nineteen adults with hypoparathyroidism participated in interviews in the United States (n = 13, 68.4%) and Canada (n = 6, 31.6%). Marked improvements in physical and cognitive symptoms were described among trial treatment group respondents. The majority of participants who reported experiencing hypoparathyroidism physical symptoms pre-trial indicated symptom improvement with treatment, including muscle twitching (100%, n = 15), low energy (92.9%, n = 13), feeling tired (92.3%, n = 12), muscle weakness (92.9%, n = 13), tingling without numbness (84.6%, n = 11), trouble sleeping (92.3%, n = 12), muscle cramping (92.3%, n = 12), tingling with numbness (92.3%, n = 12), muscle spasms (100%, n = 12), and pain (90.9%, n = 10). Most participants who reported experiencing cognitive symptoms pre-trial reported symptom improvement with treatment, including difficulty finding the right words (86.7%, n = 13), difficulty concentrating (93.3%, n = 14), trouble remembering (92.9%, n = 13), trouble thinking clearly (85.7%, n = 12), and difficulty understanding information (83.3%, n = 10). Those in the placebo group reported limited or no improvement. The vast majority of participants affirmed that the improvements they experienced in symptom frequency on the PGIS/PGIC and HPES–Symptom were meaningful.

Conclusions
Findings indicate that TransCon PTH treatment improved participants’ physical and cognitive hypoparathyroidism symptoms in meaningful ways, while reducing the daily burden associated with conventional therapy.

Trial registration
NCT04701203 Registered: 06 January 2021. https://clinicaltrials.gov/study/NCT04701203?term=NCT04701203&rank=1.
Analysis of different bioactive compounds in the tissue of the epigeic earthworm, Eisenia fetida
Authors: Shetty Aishwarya , Biradar Pulikeshi M. 
Published: August 2024

Abstract
Background
Eisenia fetida is the epigeic earthworm renowned for organic waste management in vermitechnology. The medicinal properties of earthworm biomass is gaining much more importance in extracting various biomolecules. Therefore, the present study was carried out to analyze the bioactive compounds of Eisenia fetida by using gas chromatography and mass spectroscopy analysis of four different solvent extract and highlighting their biological activities.

Results
The analysis showed the presence of 17, 22, 21 and 18 bioactive compounds in chloroform, ethyl acetate, methanol and distilled water solvent extract, respectively. Each compound were analyzed based on their peak number, R-time and Base m/z values. The molecular formula, molecular weight, compound nature, their structure and biological activities were tabulated.

Conclusion
The presence of a wide range of bioactive compounds in the epigeic earthworm, Eisenia fetida, justifies the pharmacological use in curing various diseases.
Abundance and diversity of macro-invertebrates in the selected mangrove species along the coast of Mbegani in Bagamoyo District, Tanzania
Authors: Olotu Moses I. , Mganga Nyatwere D. , Simbili Abeli A. 
Published: August 2024

Abstract
Background
Mangrove forests are highly productive ecosystems that serve as biodiversity points, containing many organisations, contributing to carbon storage, improving water quality and providing ecosystem goods and services to improve local means of subsistence. These resilient ecosystems are characterised by their morphological modification and their particular respiratory structures (pneumatophores), which allow them to proliferate in salt-rich environments. Mangroves play a crucial role in maintaining invertebrate and fishery resources, providing shelter and nutrients to a diverse range of species. However, mangrove ecosystems are threatened by anthropogenic activities such as the extraction of building materials, firewood, crushing plants and salt manufacturing, resulting in the disintegration of ecosystems and the loss of inhabitants. This study aimed to determine the abundance and diversity of macro-benthic invertebrates on the different parts (roots, stems and leaves) of common mangrove species of the Mbegani coast, along the Indian Ocean using a completely randomised design.

Results
The sampling was done using a 1 m2 quadrat focussed on the three mangrove parts, viz. roots, stems and leaves. The results showed that the highest percentage of macro-invertebrates were recorded on Bruguera gymnorhiza (66.8%), followed by Avicennia marina (20.8%) and the least were Ceriops tagal (12.4%), such variation differed significantly between the three mangrove species across the selected plots (F(2,524) = 5.71, p = 0.035). The stems (54.4%) inhabited a large number of macro-invertebrates, followed by roots (32.8%) and the least were leaves (12.8%), which varied significantly between the three mangrove parts sampled across the selected mangrove species (F(2,524) = 7.25; p = 0.008). The majority of macro-invertebrates were planktonic feeders stuck on stems or herbivores shuttling between the roots and leaves of the plants. Macro-invertebrates recorded on Bruguiera gymnorhiza were more diverse than those found in C. tagal. The findings emphasise the importance of macro-invertebrates in the ecological balance of mangrove ecosystems.

Conclusion
The study concludes that mangroves in the Mbegani ecosystem have a high potential for biodiversity and are important for the coastal community and the ecosystem of the Bagamoyo District. The results contribute to coastal resources management programmes and future surveillance activities.
Accurate, automated classification of radiographic knee osteoarthritis severity using a novel method of deep learning: Plug-in modules
Authors: Lee Do Weon , Song Dae Seok , Han Hyuk-Soo , Ro Du Hyun 
Published: August 2024

AbstractBackgroundFine-grained classification deals with data with a large degree of similarity, such as cat or bird species, and similarly, knee osteoarthritis severity classification [Kellgren–Lawrence (KL) grading] is one such fine-grained classification task. Recently, a plug-in module (PIM) that can be integrated into convolutional neural-network-based or transformer-based networks has been shown to provide strong discriminative regions for fine-grained classification, with results that outperformed the previous deep learning models. PIM utilizes each pixel of an image as an independent feature and can subsequently better classify images with minor differences. It was hypothesized that, as a fine-grained classification task, knee osteoarthritis severity may be classified well using PIMs. The aim of the study was to develop this automated knee osteoarthritis classification model.MethodsA deep learning model that classifies knee osteoarthritis severity of a radiograph was developed utilizing PIMs. A retrospective analysis on prospectively collected data was performed. The model was trained and developed using the Osteoarthritis Initiative dataset and was subsequently tested on an independent dataset, the Multicenter Osteoarthritis Study (test set size: 17,040). The final deep learning model was designed through an ensemble of four different PIMs.ResultsThe accuracy of the model was 84%, 43%, 70%, 81%, and 96% for KL grade 0, 1, 2, 3, and 4, respectively, with an overall accuracy of 75.7%.ConclusionsThe ensemble of PIMs could classify knee osteoarthritis severity using simple radiographs with a fine accuracy. Although improvements will be needed in the future, the model has been proven to have the potential to be clinically useful.
The predictors of coronary slow flow in patients undergoing coronary angiography
Authors: Ermawan Romi , Pintaningrum Yusra , Indrayana Yanna 
Published: August 2024

Abstract
Background
A new challenge in coronary artery disease treatment has emerged, where specific populations exhibit ischemic symptoms without any obstruction in the epicardial coronary artery. Instead, they exhibit slow coronary contrast flow, referred to as coronary slow flow (CSF). This study aims to identify several predictors of CSF.

Results
This case–control study was conducted at the Regional General Hospital of West Nusa Tenggara Province in Indonesia from December 2016 to February 2024. The study involved sixty subjects, with 30 in each group of CSF and normal epicardial coronary artery angiogram (NECA). CSF is enforced by the TIMI frame count (TFC) greater than 27 frames. Among all the predictors studied, coronary artery diameter (p < 0.001) and random blood sugar (p = 0.049) were found to affect the CSF significantly. In the multivariate analysis, coronary artery diameter remained a significant predictor (adjusted OR 10.08, 95% CI 2.64–38.50, p < 0.001), with an optimal cut-off point of more than 3.56 mm, a sensitivity of 76.7%, and a specificity of 70.7% (AUC = 0.787, p < 0.001).

Conclusion
The coronary artery diameter strongly predicts CSF in patients undergoing coronary angiography.
Analysis of the association between the Slit2 biomarker and systemic lupus erythematosus
Authors: Farrag Sara , Mostafa Naema Mohamed , Mohamed Eman Safwat , Kamal Dalia Tarik , Abdelaziz Marwa Mahmoud 
Published: August 2024

Abstract
Background
To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients.

Results
The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients’ demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%.

Conclusion
While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index.

Trial registration
NCT05105217. Registered 3 November 2021
Effects of HOX family regulator-mediated modification patterns and immunity characteristics on tumor-associated cell type in endometrial cancer
Authors: Yang JiaoLin , Li JinPeng , Li SuFen , Yang YuTong , Su HuanCheng , Guo HongRui , Lei Jing , Wang YaLin , Wen KaiTing , Li Xia , Zhang SanYuan , Wang Zhe 
Published: August 2024

AbstractEndometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.
Cardiac calcified amorphous tumor in a patient with lung cancer
Authors: Hatori Kyohei , Mohara Jun , Shibata Satoru , Murata Miyuki , Fukuda Nobuaki , Hiroi Shitoshi , Koyano Tetsuya 
Published: August 2024

Abstract
Background
Calcified amorphous tumor of the heart is a rare non-neoplastic cardiac mass composed of calcified nodules over amorphous fibrous tissue with degeneration and some chronic inflammation. Calcified amorphous tumor is often associated with mitral annular calcification in patients with end-stage renal disease on dialysis. However, the exact etiology of calcified amorphous tumors remains uncertain.

Case presentation
A 77-year-old female with lung cancer showed a tumor with large mobility in the left ventricular outflow tract on transthoracic echocardiography. She had mitral annular calcification, although her renal function was normal. The tumor was excised surgically. Pathologically, the extracted specimen consisted of a calcified lesion without tumor tissue and was diagnosed as a calcified amorphous tumor.

Conclusions
As the patient had no other risk factors for calcified amorphous tumor except mitral annular calcification, we considered the association of blood coagulation abnormalities due to cancer-related thrombosis. This case suggests that calcified amorphous tumors may be associated with malignant tumors.
First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data
Authors: Long Georgina V. , Lipson Evan J. , Hodi F. Stephen , Ascierto Paolo A. , Larkin James , Lao Christopher , Grob Jean-Jacques , Ejzykowicz Flavia , Moshyk Andriy , Garcia-Horton Viviana , Zhou Zheng-Yi , Xin Yiqiao , Palaia Jennell , McDonald Laura , Keidel Sarah , Salvatore Anthony , Patel Divya , Sakkal Leon A. , Tawbi Hussein , Schadendorf Dirk 
Published: August 2024

PURPOSE
Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial.

METHODS
Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory.

RESULTS

After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma,
BRAF
-mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23%
v
61%) and any-grade TRAEs leading to discontinuation (17%
v
41%).

CONCLUSION
Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most—but not all—subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.
GFR Decline Predicts Total Mortality and Mediates the Effect of Tryptophan Metabolism on Death Risk in Type 2 Diabetes
Authors: Lamacchia Olga , Menzaghi Claudia , Copetti Massimiliano , Mastroianno Mario , Corsano Chiara , Prehn Cornelia , Adamski Jerzy , Fontana Andrea , Trischitta Vincenzo , De Cosmo Salvatore 
Published: August 2024

Abstract

Context
The independent role of glomerular filtration rate (GFR) decline in shaping the risk of mortality in people with type 2 diabetes has only been partially addressed.

Objective
The objective of the study was 2-fold: (1) to investigate the association between all-cause mortality and eGFR changes over time; (2) to understand whether renal dysfunction mediates the effect of tryptophan metabolism on death risk.

Methods
Prospective study with an average follow-up of 14.8 years at a research hospital. The aggregate Gargano Mortality Study included 962 patients with type 2 diabetes who had at least 3 eGFR recordings and at least 1.5 years of follow-up. This was an observational study, with no interventions. Rate of all-cause mortality was measured.

Results
Age- and sex-adjusted annual incident rate of mortality was 2.75 events per 100 person-years. The median annual rate of decline of eGFR was 1.3 mL/min per 1.73 m2 per year (range −3.7; 7.8). The decline of kidney function was strongly and independently associated with the risk of death. Serum kynurenine to tryptophan ratio (KTR) was associated with both eGFR decline and all-cause mortality. Causal mediation analysis showed that 24.3% of the association between KTR and mortality was mediated by eGFR decline.

Conclusion
In patients with type 2 diabetes, eGFR decline is independently associated with the risk of all-cause mortality and mediates a significant proportion of the association between tryptophan metabolism and death.
Prevalence of Metabolic Dysfunction-associated Steatotic Liver Disease and Cardiometabolic Risk Factor in US Adolescents
Authors: Zheng Xiaoyan , Zhao Dongying , Wang Liwei , Wang Yiwen , Chen Yan , Zhang Yongjun 
Published: August 2024

Abstract

Context
Metabolic dysfunction-associated steatotic liver disease (MASLD) is widespread worldwide, and a strong link between MASLD and cardiometabolic risk factors (CMRFs) was highlighted in this study.

Objective
This study characterized the prevalence of MASLD in adolescent population and overlapping CMRFs conditions in MASLD.

Methods
This is a cross-sectional study of US adolescents aged 12 to 19 years in the 2017 through 2020 cycles of the National Health and Nutrition Examination Survey. The relationship between CMRFs and liver steatosis, evaluated by the median controlled attenuation parameter (CAP), was assessed.

Results
The prevalence of MASLD in adolescents was 23.77%. Isolated overweight/obesity (35%) was the top CMRF. Non-Hispanic Black patients had the highest proportion of overweight/obesity plus elevated glucose (24%), whereas non-Hispanic Asians had the highest burden of dyslipidemia (2%, 14%, and 19%). Except for hypertension, overweight/obesity (β = 48.7; 95% CI, 43.4-54.0), hypertriglyceridemia (β = 15.5; 95% CI, 7.2-28.3), low HDL-C (β = 10.0; 95% CI, 3.1-16.9), elevated glucose (β = 6.9; 95% CI, 0.6-13.2) were all significantly associated with increased CAP values. Increased CAP was linked to the synergistic interactions between overweight/obesity and dyslipidemia or elevated glucose (overweight/obesity and elevated glucose: relative excess risk due to interaction [RERI] = 8.21, attributable proportion due to interaction [AP] = 0.45, synergy index [SI] = 1.91; overweight/obesity and hypertriglyceridemia: RERI = 19.00, AP = 0.69, SI = 3.53; overweight/obesity and low high-density lipoprotein cholesterol: RERI = 10.83, AP = 0.58, SI = 2.61). Adolescents with combination of overweight/obesity, dyslipidemia (β = 15.1; 95% CI, 0.1-30.2) and combination of overweight/obesity, dyslipidemia and elevated glucose (β = 48.0; 95% CI, 23.3-72.6) had a significantly higher CAP values.

Conclusion
The prevalence of MASLD was alarmingly high in adolescents, and overweight/obesity was the most important CMRF. Overweight/obesity and dyslipidemia or elevated glucose had positive additive interaction effects on liver steatosis.