bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Muscle MRI and Clinical Findings in Women With Pathogenic Dystrophin Gene Variants
Authors: Fornander Freja , Solheim Tuva Åsatun , Eisum Anne-Sofie Vibæk , Poulsen Nanna Scharff , Andersen Annarita Ghosh , Dahlqvist Julia Rebecka , Dunø Morten , Vissing John 
Published: September 2021

Objective: To explore fat replacement, muscle strength, and clinical features in women heterozygous for a pathogenic DMD variant, we prospectively examined 53 women, assuming that some of these women—despite of the recessive X-linked inheritance—manifested clinical symptoms.Methods: We performed a cross-sectional observational study using MRI and stationary dynamometry of lower extremities, extracted blood muscle biomarkers, and investigated subjective complaints. Results were compared with 19 healthy women.Results:DMD variant carriers were weaker and had higher fat fractions than controls in all investigated muscle groups (p &lt; 0.02). Fat fractions were 18% in carriers vs. 11% in controls in thighs (p = 0.008), and 15 vs. 11% in calf muscles (p = 0.032). Seventy-two percent had fat fractions deviating from controls by two standard deviations (SDs) in one or more of the 16 investigated muscle groups. On strength testing, 40% of the carriers had results deviating from control muscle strength by two SDs in one or more dynamometry assessments. Forty-three carriers (81%) had either reduced muscle strength (&lt;2 SDs from control mean) and/or elevated muscle fat fraction (&gt;2 SDs from control mean). Thirty of these had subjective symptoms. Blood creatine kinase and myoglobin were elevated in 57% of the carriers.Conclusion: Using quantitative methods, this study shows that both clinically symptomatic and asymptomatic women with pathogenic DMD variants show a high prevalence of muscle affection. Longitudinal studies in female carriers of pathogenic DMD variants are needed to follow the evolution of these changes.
Relationship Between Orthostatic Hypotension and Cognitive Functions in Multiple System Atrophy: A Longitudinal Study
Authors: Cuoco Sofia , Carotenuto Immacolata , Cappiello Arianna , Scannapieco Sara , Russillo Maria Claudia , Andreozzi Valentina , Forino Lorenzo , Amboni Marianna , Picillo Marina , Erro Roberto , Barone Paolo , Pellecchia Maria Teresa 
Published: September 2021

Introduction: The aim of this study is to investigate the impact of orthostatic hypotension (OH) on cognitive functions in patients with multiple system atrophy (MSA) followed over time.Methods: Thirty-two MSA patients were enrolled and underwent a comprehensive neuropsychological battery; at baseline (T0) 15 out of 32 patients presented OH, assessed by means of orthostatic standing test. All patients underwent a follow-up (T1) evaluation 12 months after baseline. Thirteen out of 32 patients also underwent a second follow-up (T2) evaluation at 24 months. Changes over time on different neuropsychological tasks were compared between patients with and without OH by means of Mann-Whitney's U-test. Moreover, clinical categories of normal cognition, mild cognitive impairment, and dementia were determined, and changes at T1 and T2 in global cognitive status were compared between patients with and without OH.Results: At T0, patients with OH had better performance on words/non-words repetition task (p = 0.02) compared to patients without OH. Compared to patients without OH, patients with OH performed worse on semantic association task (p &lt; 0.01) at T1 and on Stroop test-error effect (p = 0.04) at T2. The percentage of patients with worsened cognitive status at T1 was higher among patients with OH than among patients without OH (93 vs. 59%, p = 0.03). OH (β = −4.67, p = 0.01), education (β = 0.45, p = 0.02), age (β = 0.19, p = 0.03), and Montreal Cognitive Assessment battery (MOCA) score at T0 (β = −0.26, p = 0.04) were significant predictors of global cognitive status worsening at T1.Discussion: We found that global cognitive status worsened at 1-year follow-up in 93% of patients with OH, and OH, along with age, education, and MOCA score, predicted cognitive worsening over time. To clarify the relationship between OH and cognitive dysfunction in MSA, we suggest the use of clinical categories of normal cognition, mild cognitive impairment, and dementia in further longitudinal studies on MSA patients with and without OH.
A Prospective Multicenter Registry on Feasibility, Safety, and Outcome of Endovascular Recanalization in Childhood Stroke (Save ChildS Pro)
Authors: Sporns Peter B. , Kemmling André , Lee Sarah , Fullerton Heather , Kunz Wolfgang G. , Wilson Jenny L. , Mackay Mark T. , Steinlin Maja , Fiehler Jens , Psychogios Marios , Wildgruber Moritz 
Published: September 2021

Rationale: Early evidence for the benefit of mechanical thrombectomy (MT) in pediatric patients with intracranial large vessel occlusion has been shown in previous retrospective cohorts. Higher-level evidence is needed to overcome the limitations of these studies such as the lack of a control group and the retrospective design. Randomized trials will very likely not be feasible, and several open questions remain, for example, the impact of arteriopathic etiologies or a possible lower age limit for MT. Save ChildS Pro therefore aims to demonstrate the safety and effectiveness of MT in pediatric patients compared to the best medical management and intravenous thrombolysis.Design: Save ChildS Pro is designed as a worldwide multicenter prospective registry comparing the safety and effectiveness of MT to the best medical care alone in the treatment of pediatric arterial ischemic stroke (AIS). It will include pediatric patients (&lt;18 years) with symptomatic acute intracranial arterial occlusion who underwent either MT or best medical treatment including intravenous thrombolysis.Outcomes: The primary endpoint of Save ChildS Pro is the modified Rankin Scale score at 90 days post-stroke. Secondary endpoints will comprise the decrease of the Pediatric National Institutes of Health Stroke Scale score from admission to discharge and rate of complications.Discussion: Save ChildS Pro aims to provide high-level evidence for MT for pediatric patients with AIS, thereby improving functional outcome and quality of life and reducing the individual, societal, and economic burden of death and disability resulting from pediatric stroke.Clinical Trial Registration: Save ChildS Pro is registered at the German Clinical Trials Registry (DRKS; identifier: DRKS00018960).
The Relationships Among Transverse Sinus Stenosis Measured by CT Venography, Venous Trans-stenotic Pressure Gradient and Intracranial Pressure in Patients With Unilateral Venous Pulsatile Tinnitus
Authors: Qiu Xiaoyu , Zhao Pengfei , Li Xiaoshuai , Ding Heyu , Lv Han , Zeng Rong , Wang Guopeng , Jin Long , Yang Zhenghan , Gong Shusheng , Wang Zhenchang 
Published: September 2021

ObjectivesTo assess a non-invasive means of predicting a venous trans-stenotic pressure gradient (TPG) and intracranial pressure (ICP) as opposed to invasive examinations in unilateral venous pulsatile tinnitus (PT) patients.MethodsThirty patients with unilateral venous PT who presented symptomatic-sided transverse sinus stenosis (TSS) on computed tomography venography (CTV), ipsilateral TPG measured by digital subtraction angiography (DSA) and cerebrospinal fluid (CSF) pressure measured by lumbar puncture were included. The ratio of TSS was calculated by dividing the cross-sectional areas of the maximal stenosed transverse sinus by that of the adjacent normal transverse sinus on CTV. The correlations among and predictive values of TSS, TPG, and ICP were analyzed.ResultsIn patients with unilateral venous PT, the symptomatic-sided and average bilateral TSS values were 78 ± 11 and 77 ± 9%; ICP, 230.50 ± 55.75 mmH2O; and the TPG, 9.51 ± 5.76 mmHg. The symptomatic-sided TSS was linearly and positively correlated with TPG (R2 = 0.400), and the symptomatic-sided and bilateral average TSS both showed weak correlations with ICP (R2 = 0.288, R′2 = 0.156). When the degree of TSS increased by 10%, the TPG and ICP increased by approximately 3.3 mmHg and 25.8 mmH2O, respectively. The receiver operating characteristic curve showed the optimal threshold of ipsilateral TSS for a positive TPG was 0.75, while TSS had no significant predictive value for ICP (p &gt; 0.05). TPG and ICP also exhibited a linear positive correlation (R2 = 0.552). When ICP increased by 10 mmH2O, the TPG increased by approximately 0.77 mmHg, and the optimal threshold of ICP for a positive TPG was 227.5.ConclusionTSS, TPG, and ICP are interrelated. TSS measured by CTV can predict TPG in patients with unilateral venous PT.
Glucagon-Like Peptide-2 Modulates Enteric Paneth Cells Immune Response and Alleviates Gut Inflammation During Intravenous Fluid Infusion in Mice With a Central Catheter
Authors: Deng Guifang , Lei Qiucheng , Gao Xuejin , Zhang Yupeng , Zheng Huazhen , Bi Jingcheng , Wang Xinying 
Published: September 2021

Background: Glucagon-like peptide-2 (GLP-2) has protective effects on gastrointestinal functions. Our previous study found that GLP-2 could significantly reduce intestinal permeability and bacterial translocation in total parenteral nutrition (TPN) animal model. However, the effects of GLP-2 on the impairment of the intestinal Paneth cells immune function and gut inflammation during intravenous fluid infusion mainly consisted of nutritional materials is currently scattered.Objective: The current study was aimed to investigate the efficacy of the GLP-2 in alleviating gut inflammation and modulating enteric Paneth cells immune response in parenterally fed mice and its underlying mechanisms.Methods: Thirty-six male ICR mice underwent venous catheterization were divided into 3 groups: Chow, TPN, and TPN+GLP-2 groups. GLP-2 was administered intravenously at 60 μg/day for 5 days. The small intestine tissue and serum samples were collected on the 7th day.Results: Compared with the TPN group, the expression of tight junction proteins occludin and claudin-1 were significantly increased in the TPN+GLP-2 group. In addition, the expression of lysozyme, sPLA2, insulin-like growth factor-1, and epithelial protection and repair genes were improved in the TPN+GLP-2 group. The levels of IL-6 and TNF-α proteins and mRNAs in the ileum tissues were remarkably reduced in the TPN+GLP-2 group, while IL-10 protein and mRNA level were elevated in the TPN+GLP-2 group (all p &lt; 0.05). Moreover, the TPN+GLP-2 group has higher levels of serum endotoxin, D-lactic acid, and MPO than those of the TPN group.Conclusions: GLP-2 alleviated gut inflammation and improved enteric Paneth cells immune responses through intravenous fluid infusion, possibly by improving the functioning of epithelial protection and repair, and reducing mucosal inflammatory responses.
Exploring Innovations in Human Milk Analysis in the Neonatal Intensive Care Unit: A Survey of the United States
Authors: Ramey Stacey R. , Merlino Barr Stephanie , Moore Katie A. , Groh-Wargo Sharon 
Published: September 2021

Introduction: Human milk (HM) is the ideal enteral feeding for nearly all infants and offers unique benefits to the very low birthweight (VLBW) infant population. It is a challenge to meet the high nutrient requirements of VLBW infants due to the known variability of HM composition. Human milk analysis (HMA) assesses the composition of HM and allows for individualized fortification. Due to recent U.S. Food and Drug Administration (FDA) approval, it has relatively recent availability for clinical use in the US.Aim: To identify current practices of HMA and individualized fortification in neonatal intensive care units (NICUs) across the United States (US) and to inform future translational research efforts implementing this nutrition management method.Methods: An institutional review board (IRB) approved survey was created and collected data on the following subjects such as NICU demographics, feeding practices, HM usage, HM fortification practices, and HMA practices. It was distributed from 10/30–12/21/2020 via online pediatric nutrition groups and listservs selected to reach the intended audience of NICU dietitians and other clinical staff. Each response was assessed prior to inclusion, and descriptive analysis was performed.Results: About 225 survey responses were recorded during the survey period with 119 entries included in the analysis. This represented 36 states and Washington D.C., primarily from level III and IV NICUs. HMA was reported in 11.8% of responding NICUs. The most commonly owned technology for HMA is the Creamatocrit Plus TM (EKF Diagnostics), followed by the HM Analyzer by Miris (Uppsala, Sweden). In NICUs practicing HMA, 84.6% are doing so clinically.Discussion: Feeding guidelines and fortification of HM remain standard of care, and interest in HMA was common in this survey. Despite the interest, very few NICUs are performing HMA and individualized fortification. Barriers identified include determining who should receive individualized fortification and how often, collecting a representative sample, and the cost and personnel required.Conclusions: Human milk analysis and individualized fortification are emerging practices within NICUs in the US. Few are using it in the clinical setting with large variation in execution among respondents and many logistical concerns regarding implementation. Future research may be beneficial to evaluate how practices change as HMA and individualized fortification gain popularity and become more commonly used in the clinical setting.
Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment
Authors: Nero Camilla , Ciccarone Francesca , Pietragalla Antonella , Duranti Simona , Daniele Gennaro , Scambia Giovanni , Lorusso Domenica 
Published: September 2021

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient’s risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).
Rictor Activates Cav 1 Through the Akt Signaling Pathway to Inhibit the Apoptosis of Gastric Cancer Cells
Authors: Cao Rui-zhen , Min Li , Liu Si , Tian Ru-yue , Jiang Hai-yan , Liu Juan , Shao Lin-lin , Cheng Rui , Zhu Sheng-tao , Guo Shui-long , Li Peng 
Published: September 2021

BackgroundRapamycin-insensitive companion of mammalian target of rapamycin (Rictor) protein is a core subunit of mammalian target of rapamycin complex 2, and is associated with cancer progression. However, the biological function of Rictor in cancer, particularly its clinical relevance in gastric cancer (GC) remains largely unknown.MethodsRictor expression and its association with clinicopathologic characteristics in GC were analyzed by immunohistochemistry. Effect of Rictor and Caveolin-1 (Cav 1) on GC cells apoptosis was evaluated via overexpression experiment in vitro. Mechanisms of Rictor and Cav 1 in GC were explored through overexpression and knockdown, by immunofluorescence and western blot analyses.ResultsRictor was upregulated in GC, and mainly located in the cytoplasm of cancer cells. Moreover, higher Rictor levels were associated with worse prognosis. Rictor could inhibit GC cell apoptosis and promote cell growth in vitro. The results of immunofluorescence revealed that Cav 1 localized in GC cell membrane but did not co-localize with Rictor. Further, Rictor regulated apoptosis-related proteins, long non-coding RNAs and also activated cellular signaling, thereby positively regulating Cav 1 expression. This effect was attenuated by the Akt inhibitor ly294002. Cav 1 did not significantly affect the ability of Rictor to inhibit tumor cell apoptosis.ConclusionsRictor is upregulated in GC and associated with worse prognosis. It inhibits tumor apoptosis and activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells. Rictor is, therefore, a promising prognostic biomarker and possible therapeutic target in GC patients.
The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis
Authors: Gan Kai , Gao Yue , Liu Kuangzheng , Xu Bin , Qin Weijun 
Published: September 2021

ObjectiveHuman Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in multiple malignancies and associated with patients’ prognosis, but its role in bladder cancer (BCa) remains elusive. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in BCa.MethodsPubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and BCa pathological features. TCGA was mined for the information regarding as well.ResultsOur study included 14 articles enrolling 1398 people. Expression of HER2 is higher in bladder cancer than in normal tissues. HER2 over-expression is associated with CIS, multifocal tumor, large tumor size, high tumor stage and grade, lymph node metastasis, progression, recurrence and papillary tumor. We could not find a significant association between HER2 expression and survival time in BCa patients.ConclusionsOur meta and bioinformatic analysis indicated that HER2 expression was related to pathological malignancy and poor prognosis in BCa.
Impact of Precision Medicine on Clinical Outcomes: A Single-Institution Retrospective Study
Authors: Quinn Ryann , Patel Rajvi , Sison Cristina , Singh Amandeep , Zhu Xin-Hua 
Published: September 2021

PurposeThe strategy of precision medicine has been widely adopted in the practice of oncology, although the efficacy remains unclear. This study assesses clinical outcomes in patients with an actionable alteration found during FoundationOne CDx™ (F1CDx) testing and who received a targeted therapy based on the results.Materials and MethodsThis is a retrospective cohort study of patients with tumors that underwent F1CDx from September 2012 to July 2018. F1CDx provided actionable alterations for patients to select appropriate therapies. The primary objective was to estimate the objective response rate (ORR) at 3 months from the start of study treatment. The secondary objectives were to estimate progression-free survival (PFS) and overall survival (OS).ResultsOne thousand patients underwent F1CDx testing. Six hundred fifty-two patients were identified as having actionable mutations. Thirty-eight patients (18 males and 20 females) received targeted therapy and were included in the study. The most common alterations were PD-1/PDL-1, high-TMB, P13K, and HER2/ERBB2. Patients received various treatments including nivolumab, pembrolizumab, trastuzumab, and everolimus. Eight (23.5%) and six (17.7%) patients achieved partial response (PR) and stable disease (SD), respectively; 20 (58.8%) had progression of disease (PD). The disease control rate was 41.2% (95% CI: 24.7% to 59.3%). The median PFS was 2.7 months (95% CI: 2.3 to 5.4 months), and median OS was 9.9 months (95% CI: 4.5 to 33.7 months).ConclusionOur results demonstrate promising data in precision medicine in real community oncology practice. It warrants further large and prospective studies in patients with actionable alterations.
Immune-Related Multiple-Organs Injuries Following ICI Treatment With Tislelizumab in an Advanced Non-Small Cell Lung Cancer Patient: A Case Report
Authors: Deng Chao , Yang Meng , Jiang Hong , Wang Renbin , Yang Zhaojun , Sun Hongliang , Cui Huijuan 
Published: September 2021

Immune-related adverse events (irAEs) following treatment with immune checkpoint inhibitors (ICIs) can affect almost any organ systems. Multiple-organs irAEs are a rare occurrence which makes its management and treatment very challenging. This is a case report of a 71-year-old man with advanced non-small cell lung cancer (NSCLC) who developed multiple-organs irAEs (lung, muscle, myocardium, liver, and pituitary) after a single cycle (21 days) of the BGB-A317 (Tislelizumab). After more than two months of immunosuppression treatment with glucocorticoids, the tumor and inflammatory lesions in the lung were reduced. The levels of serum creatase, cardiac troponin T (TNT), and hepatic transaminase were also reduced. Four months after the termination of ICI therapy, the lung tumor reappeared in the previous site. This rare case report supplies several experiences in the management of multiple-organs irAEs, including full-scale monitoring of immunological indicators, early differential diagnosis, and prompt glucocorticoid therapy. This patient was not a candidate for the ICI re-challenge therapy due to the number and seriousness of irAEs. Multiple-organs irAEs add complexity to the management, and additional research is needed to develop optimal therapeutic guidelines.