bluuebunny/crossref_metadata_2025_split huggingface dataset:
The validity of Arabic version of Vestibular Disorder Activities of Daily Living Scale in common episodic vestibular disorders during and in between the attacks: a cross-sectional study
Authors: Badawood Halla , Aldosari Manar , Alshugihi Sara , Mohamad Alfarghal , Al-Hakami Hadi , Al-Garni Mohammed 
Published: August 2022

Abstract
Background
Activities of daily living (ADLs) are activities oriented toward taking care of one’s own body independently. Vestibular Disorder Activities of Daily Living Scale (VADL) includes 28 questions designed to specifically assess the effects of different vestibular disorders on activities of daily living and assess the validity and reliability of the Arabic version of VADL and applying it to assess severity of the attacks related to most common episodic vestibular disorders. The Arabic version of VADL was distributed to 52 participants, recruiting two participants per question. The participants filled up the Arabic version of VADL scale, in-between and during the vertigo episodes.

Results
All participants have been diagnosed as having one of these vestibular disorders benign paroxysmal positional vertigo (BPPV), vestibular migraine, and Meniere’s disease. The reliability analysis was calculated with Cronbach’s alpha score, and it was 0.980, indicating high reliability. There was a positive correlation between the VADL scores during and in between the attacks of vertigo for the three diseases (p = 0.03). There was a statistical difference between the three disorders during and in between the attacks (p-value during the attack < 0.0001, p-value in between the attacks = 0.046). Meniere’s disease had the most negative impacts on daily activities performance, followed by BPPV, and vestibular migraine had the least effect. There was statistically significant correlation between VADL and visual analog scale (VAS) during and in between the attacks (Pearson correlation 0.74, p < 0.0001).

Conclusion
The Arabic version of VADL scale has high validity and an excellent reliability among our demographic population. Meniere’s disease has the worst impact on patients’ performance in activities of daily living compared to BPPV and vestibular migraine.
A time-efficient protocol for transthoracic echocardiography during transfemoral transcatheter aortic valve implantation: early identification and effective management of intraprocedural complications
Authors: Savvoulidis Panagiotis , Moody William E. , Steeds Rick , Ludman Peter F. , Bradley Joseph R. , Singh Aldrin , Lawton Ewa , Nadir M. Adnan , Doshi Sagar N. 
Published: August 2022

AbstractTransfemoral transcatheter aortic valve implantation (TAVI) under conscious sedation is the most widely used method of implantation. Echocardiography is used to detect complications and to assess the implantation result. The aim of this paper is to provide a time-efficient protocol when transthoracic echocardiography (TTE) is used to guide TAVI procedures.
Tumor Mutational Burden as a Predictor of First-Line Immune Checkpoint Inhibitor Versus Carboplatin Benefit in Cisplatin-Unfit Patients With Urothelial Carcinoma
Authors: Graf Ryon P. , Fisher Virginia , Huang Richard S.P. , Hamdani Omar , Gjoerup Ole V. , Stanke Jennifer , Creeden James , Levy Mia A. , Oxnard Geoffrey R. , Gupta Shilpa 
Published: August 2022

PURPOSE In real-world settings, patients with metastatic urothelial carcinoma (mUC) are often more frail than clinical trials, underscoring an unmet need to identify patients who might be spared first-line chemotherapy. We sought to determine whether tumor mutational burden (TMB) identifies patients with comparable or superior clinical benefit of first-line single-agent immune checkpoint inhibitors (ICPI) in real-world patients deemed cisplatin-unfit. METHODS Patients with mUC treated in first-line advanced setting (N = 401) received ICPI (n = 245) or carboplatin regiment without ICPI (n = 156) at physician's discretion in standard-of-care settings across approximately 280 US academic or community-based cancer clinics between March 2014 and July 2021. Deidentified data were captured into a real-world clinicogenomic database. All patients underwent testing using Foundation Medicine assays. Progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) comparing ICPI versus chemotherapy were adjusted for known treatment assignment imbalances using propensity scores. RESULTS TMB ≥ 10 was detected in 122 of 401 (30.4%) patients. Among patients receiving ICPI, those with TMB ≥ 10 had more favorable PFS (HR, 0.59; 95% CI, 0.41 to 0.85), TTNT (HR, 0.59; 95% CI, 0.43 to 0.83), and OS (HR, 0.47; 95% CI, 0.32 to 0.68). Comparing ICPI versus carboplatin, adjusting for imbalances, patients with TMB ≥ 10 had more favorable PFS (HR, 0.51; 95% CI, 0.32 to 0.82), TTNT (HR, 0.56; 95% CI, 0.35 to 0.91), and OS (HR, 0.56; 95% CI, 0.29 to 1.08) on ICPI versus chemotherapy, but not TMB < 10. Comparisons unadjusted for imbalances had similar associations. CONCLUSIONS In real-world settings, mUC patients with TMB ≥ 10 have more favorable outcomes on first-line single-agent ICPI than carboplatin, adding clinical validity to TMB assessed by an existing US Food and Drug Administration–approved platform.
Targeted Therapies in Pheochromocytoma and Paraganglioma
Authors: Wang Katharina , Crona Joakim , Beuschlein Felix , Grossman Ashley B , Pacak Karel , Nölting Svenja 
Published: August 2022

Abstract
Molecular targeted therapy plays an increasingly important role in the treatment of metastatic pheochromocytomas and paragangliomas (PPGLs), which are rare tumors but remain difficult to treat. This mini-review provides an overview of established molecular targeted therapies in present use, and perspectives on those currently under development and evaluation in clinical trials. Recently published research articles, guidelines, and expert views on molecular targeted therapies in PPGLs are systematically reviewed and summarized. Some tyrosine kinase inhibitors (sunitinib, cabozantinib) are already in clinical use with some promising results, but without formal approval for the treatment of PPGLs. Sunitinib is the only therapeutic option which has been investigated in a randomized placebo-controlled clinical trial. It is clinically used as a first-, second-, or third-line therapeutic option for the treatment of progressive metastatic PPGLs. Some other promising molecular targeted therapies (hypoxia-inducible factor 2 alpha [HIF2α] inhibitors, tumor vaccination together with checkpoint inhibitors, antiangiogenic therapies, kinase signaling inhibitors) are under evaluation in clinical trials. The HIF2α inhibitor belzutifan may prove to be particularly interesting for cluster 1B-/VHL/EPAS1-related PPGLs, whereas antiangiogenic therapies seem to be primarily effective in cluster 1A-/SDHx-related PPGLs. Some combination therapies currently being evaluated in clinical trials, such as temozolomide/olaparib, temozolomide/talazoparib, or cabozantinib/atezolizumab, will provide data for novel therapy for metastatic PPGLs. It is likely that advances in such molecular targeted therapies will play an essential role in the future treatment of these tumors, with more personalized therapy options paving the way towards improved therapeutic outcomes.
Metabolic and Genetic Markers Improve Prediction of Incident Type 2 Diabetes: A Nested Case-Control Study in Chinese
Authors: Liu Jia , Wang Lu , Qian Yun , Shen Qian , Yang Man , Dong Yunqiu , Chen Hai , Yang Zhijie , Liu Yaqi , Cui Xuan , Ma Hongxia , Jin Guangfu 
Published: August 2022

AbstractContextIt is essential to improve the current predictive ability for type 2 diabetes (T2D) risk.ObjectiveWe aimed to identify novel metabolic markers for future T2D in Chinese individuals of Han ethnicity and to determine whether the combined effect of metabolic and genetic markers improves the accuracy of prediction models containing clinical factors.MethodsA nested case-control study containing 220 incident T2D patients and 220 age- and sex- matched controls from normoglycemic Chinese individuals of Han ethnicity was conducted within the Wuxi Non-Communicable Disease cohort with a 12-year follow-up. Metabolic profiling detection was performed by high-performance liquid chromatography‒mass spectrometry (HPLC-MS) by an untargeted strategy and 20 single nucleotide polymorphisms (SNPs) associated with T2D were genotyped using the Iplex Sequenom MassARRAY platform. Machine learning methods were used to identify metabolites associated with future T2D risk.ResultsWe found that abnormal levels of 5 metabolites were associated with increased risk of future T2D: riboflavin, cnidioside A, 2-methoxy-5-(1H-1, 2, 4-triazol-5-yl)- 4-(trifluoromethyl) pyridine, 7-methylxanthine, and mestranol. The genetic risk score (GRS) based on 20 SNPs was significantly associated with T2D risk (OR = 1.35; 95% CI, 1.08-1.70 per SD). The area under the receiver operating characteristic curve (AUC) was greater for the model containing metabolites, GRS, and clinical traits than for the model containing clinical traits only (0.960 vs 0.798, P = 7.91 × 10-16).ConclusionIn individuals with normal fasting glucose levels, abnormal levels of 5 metabolites were associated with future T2D. The combination of newly discovered metabolic markers and genetic markers could improve the prediction of incident T2D.
Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway
Authors: Jiang Xiao-yu , Guan Fei-fei , Ma Jia-xin , Dong Wei , Qi Xiao-long , Zhang Xu , Chen Wei , Gao Shan , Gao Xiang , Pan Shuo , Wang Ji-zheng , Ma Yuan-wu , Zhang Lian-feng , Lu Dan 
Published: August 2022

ABSTRACT
When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3β/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.
Proteasome granule formation is regulated through mitochondrial respiration and kinase signaling
Authors: Waite Kenrick A. , Roelofs Jeroen 
Published: August 2022

ABSTRACT
In the yeast Saccharomyces cerevisiae, proteasomes are enriched in cell nuclei, in which they execute important cellular functions. Nutrient stress can change this localization, indicating that proteasomes respond to the metabolic state of the cell. However, the signals that connect these processes remain poorly understood. Carbon starvation triggers a reversible translocation of proteasomes to cytosolic condensates known as proteasome storage granules. Surprisingly, we observed strongly reduced levels of proteasome granules when cells had active cellular respiration prior to starvation. This suggests that the mitochondrial activity of cells is a determining factor in the response of proteasomes to carbon starvation. Consistent with this, upon inhibition of mitochondrial function, we observed that proteasomes relocalize to granules. These links between proteasomes and metabolism involve specific signaling pathways, as we identified a mitogen-activated protein kinase (MAPK) cascade that is critical to the formation of proteasome granules after respiratory growth but not following glycolytic growth. Furthermore, the yeast homolog of AMP kinase, Snf1, is important for proteasome granule formation induced by mitochondrial inhibitors, but it is dispensable for granule formation following carbon starvation. We propose a model in which mitochondrial activity promotes nuclear localization of the proteasome.
This article has an associated First Person interview with the first author of the paper.
TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle
Authors: Guerra Paolo , Vuillemenot Luc-Alban P. E. , van Oppen Yulan B. , Been Marije , Milias-Argeitis Andreas 
Published: August 2022

ABSTRACT
Recent studies have revealed that the growth rate of budding yeast and mammalian cells varies during the cell cycle. By linking a multitude of signals to cell growth, the highly conserved target of rapamycin complex 1 (TORC1) and protein kinase A (PKA) pathways are prime candidates for mediating the dynamic coupling between growth and division. However, measurements of TORC1 and PKA activity during the cell cycle are still lacking. By following the localization dynamics of two TORC1 and PKA targets via time-lapse microscopy in hundreds of yeast (Saccharomyces cerevisiae) cells, we found that the activity of these pathways towards ribosome biogenesis fluctuates in synchrony with the cell cycle even under constant external conditions. Analysis of the effects of mutations of upstream TORC1 and PKA regulators suggests that internal metabolic signals partially mediate these activity changes. Our study reveals a new aspect of TORC1 and PKA signaling, which will be important for understanding growth regulation during the cell cycle.
Clinical and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Multicenter Retrospective Cohort Study of Tertiary Centers
Authors: Borella Fulvio , Cosma Stefano , Ferraioli Domenico , Ray-Coquard Isabelle , Chopin Nicolas , Meeus Pierre , Cockenpot Vincent , Valabrega Giorgio , Scotto Giulia , Turinetto Margherita , Biglia Nicoletta , Fuso Luca , Mariani Luca , Franchi Dorella , Vidal Urbinati Ailyn Mariela , Pino Ida , Bertschy Gianluca , Preti Mario , Benedetto Chiara , Castellano Isabella , Cassoni Paola , Bertero Luca 
Published: August 2022

AbstractBackgroundThe term uterine smooth muscle tumor of uncertain malignant potential (STUMP) indicates a rare, equivocal entity between benign leiomyomas and leiomyosarcomas. In the present study, we evaluated a comprehensive range of clinical, surgical, and pathological features in a large multicenter series of patients with STUMP to identify risk factors for recurrence.MethodsThis is a retrospective study performed by collecting consecutive cases diagnosed between January 2000 and December 2020 in five tertiary centers. Associations between STUMP recurrence and clinicopathological characteristics as well as surgical treatment modality were investigated.ResultsEighty-seven patients affected by STUMP were considered. Of them, 18 cases (20.7%) recurred: 11 as leiomyosarcoma (LMS) and 7 as STUMP. The mean time to recurrence was 79 months. We found that fragmentation/morcellation, epithelioid features, high mitotic count, Ki-67 value > 20%, progesterone receptor (PR) < 83%, and p16 diffuse expression were associated with higher risk of recurrence and shorter recurrence-free survival (RFS). Furthermore, morcellation/fragmentation and mitotic count remained independent risk factors for recurrence and shorter RFS after multivariate analysis, while the presence of epithelioid features was an independent risk factor for recurrence only.ConclusionsOur results suggest that morcellation is associated with risk of recurrence and shorter RFS, thus it should be avoided if a STUMP is suspected preoperatively. Epithelioid features, high proliferation activity, low PR expression, and diffuse p16 expression are also unfavorable prognostic factors, so patients presenting these features should be closely followed up.
Synthesis of Self-Doped Conductive Poly(3,4-ethylenedioxythiophene) (PEDOT) Bearing Phosphonic Acid Moieties
Authors: Kiriyama Kahori , Daijo Masato , Tsuchiya Keiho , Hatai Tomohiro , Hirao Toshikazu , Amaya Toru 
Published: August 2022

Abstract
The synthesis of self-doped conductive poly(3,4-ethylenedioxythiophene) (PEDOT) bearing phosphonic acid moieties is first reported. The UV-vis-NIR spectrum of the film clearly confirmed self-doping. The polymer exhibited good water solubility as a salt with NMe3, as demonstrated by filtration tests with a membrane filter (0.02 µm). This result is in contrast to a PEDOT/poly(4-styrene sulfonate) dispersion, which cannot pass through the filter. The conductivity of a drop-cast film reached 1.3 × 102 S cm−1. The thermogravimetric analysis and elementary analysis of the drop-cast film showed that the conductive polymer presents as a NMe3 salt, which might protect the materials from acid-induced corrosion. The developed conductive polymer has the potential for being applied in various organic electronic materials.
Association between Sleep, Sedentary Time, Physical Activity, and Adiposity in Adolescents: A Prospective Observational Study
Authors: KRACHT CHELSEA L. , KATZMARZYK PETER T. , CHAMPAGNE CATHERINE M. , BROYLES STEPHANIE T. , HSIA DANIEL S. , NEWTON ROBERT L. , STAIANO AMANDA E. 
Published: August 2022

ABSTRACT

Purpose
This study aimed to examine the effects of substituting sedentary time with sleep or physical activity on adiposity in a longitudinal sample of adolescents.

Methods
Adolescents (10–16 yr) were recruited for a prospective observational cohort. Parents and adolescents reported demographic characteristics and pubertal development. Accelerometry was used to measure sleep, physical activity, and sedentary time. Adiposity was quantified with imaging techniques. Isotemporal substitution modeling was conducted to examine the effect of substituting 10 min of sedentary time with sleep or differing intensities of physical activity. Results were stratified by sex and race and adjusted for covariates.

Results
A total of 217 adolescents provided complete measures at both baseline and 2 yr later (58.1% White, 51.8% girls; 12.9 ± 1.9 yr at baseline). Sleep was negatively related to adiposity 2 yr later when considering other movement behaviors, but substituting baseline sedentary time with sleep was not related to future adiposity (P > 0.05). In boys and non-White adolescents, substituting sedentary time with vigorous-intensity physical activity was related to lower adiposity 2 yr later (P < 0.05). Substituting sedentary time for moderate- to vigorous-intensity physical activity was not associated with future adiposity.

Conclusions
Substituting sedentary time with vigorous-intensity physical activity was related to lower adiposity in later adolescence in certain groups. Opportunities to promote an adequate balance of sleep, sedentary time, and physical activity in all adolescents are encouraged for optimal development.
Case Report: A rare presentation of prostate cancer with peritoneal carcinomatosis and malignant ascites complicated by tumor lysis syndrome
Authors: Venkateswaran Aparajit Ram , Elzein Safa F. , Sulpizio Emilio D. , Chang Bernard , Kosty Michael P. 
Published: August 2022

Background: Only 32 cases of prostate cancer with peritoneal carcinomatosis and ascites have currently been reported in the literature. We present the first reported case of prostate cancer with peritoneal carcinomatosis and malignant ascites whose treatment was complicated by tumor lysis syndrome along with a literature review evaluating similar cases. Case: We present a rare case of a 78-year-old retired Caucasian male with recurrent metastatic prostate cancer and malignant ascites. He had previously received definitive radiotherapy for localized prostate cancer but presented with bilateral hydronephrosis and right-sided bladder wall thickening 10 years later. He had imaging evidence of locoregional recurrence with elevated prostate specific antigen (PSA) and was initiated on combined androgen blockade with intramuscular leuprolide and oral bicalutamide. After being transferred to Scripps Clinic, he was found to have a solitary right upper lobe pulmonary lesion for which he completed stereotactic body radiation therapy. Then, 10 months later, he developed new onset malignant ascites and was treated with two cycles of intravenous docetaxel. Treatment resulted in improvement in his ascites and reduction in PSA. Unfortunately, his course was complicated by tumor lysis syndrome, encephalopathy, Escherichia coli bacteremia, and a fatal saddle pulmonary embolism. Conclusions: (1) Occurrence of ascites in prostate cancer patients is associated with worse prognosis than non-ascitic variants. (2) More common etiologies of ascites must be evaluated for. (3) Ascitic fluid prostate specific antigen (PSA) measurement may aid in diagnosis of malignant ascites in cases with diagnostic uncertainty. (4) Patients with advanced disease may benefit from combined hormonal and cytotoxic therapies. (5) Awareness of the occurrence of tumor lysis syndrome (TLS) in patients treated for prostate cancer can help identify patients in whom prophylaxis would be beneficial.
A cross-sectional observational study to assess socio-demographic factors in newly diagnosed TB DM comorbidity
Authors: Hullalli Rashmi , Gudadinni M R , Motappa Rohith 
Published: August 2022

Background:Tuberculosis (TB) and diabetes mellitus (DM) co-morbidity is one of the rising public health problems. There is growing evidence that DM is an important risk factor for TB. This study was carried out to know the prevalence of DM among newly detected sputum positive pulmonary TB patients registered in District Tuberculosis Centre and to assess the risk factors of DM among TB patients.Methods:In a cross-sectional study, newly detected sputum positive pulmonary TB patients were screened for DM (those having symptoms of DM). Furthermore, they were diagnosed by detecting blood glucose levels (≥200 mg/dL). Mean, standard deviation (SD), Chi-squared and Fisher-Freeman-Halton exact tests were used to determine the significant associations. P-values less than 0.05 were considered to be statistically significant.Results:A total of 215 TB patients were included in this study. The prevalence of DM among TB patients was found to be 23.7% (2.8% known and 97.8% new cases). Significant associations were found between age (>46 years old), educational status, smoking habits, alcohol consumption, physical activity, presence of DM symptoms and family history of DM.Conclusions:Routine screening for DM is mandatory due to its increasing prevalence, which may help in early diagnosis and to reduce complications by proper management that in turn helps in the successful outcome of TB treatment.