bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota profile of COVID-19 patients: Prognosis and risk stratification (MicroCOVID-19 study)
Authors: Nobre José Guilherme , Delgadinho Mariana , Silva Carina , Mendes Joana , Mateus Vanessa , Ribeiro Edna , Costa Diogo Alpuim , Lopes Miguel , Pedroso Ana Isabel , Trigueiros Frederico , Rodrigues Maria Inês , de Sousa Cristina Lino , Brito Miguel 
Published: November 2022

BackgroundGut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the microbiota profile of infected patients with SARS-CoV-2 (milder or severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case–control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS.ResultsFirmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore, Escherichia coli, Actinomyces naeslundii, and Dorea longicatena were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups.ConclusionWe can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.
The European Prevention of Alzheimer's Dementia Programme: An Innovative Medicines Initiative-funded partnership to facilitate secondary prevention of Alzheimer's disease dementia
Authors: Saunders Stina , Gregory Sarah , Clement Matthew H. S. , Birck Cindy , Geyten Serge van der , Ritchie Craig W. 
Published: November 2022

IntroductionTens of millions of people worldwide will develop Alzheimer's disease (AD), and only by intervening early in the preclinical disease can we make a fundamental difference to the rates of late-stage disease where clinical symptoms and societal burden manifest. However, collectively utilizing data, samples, and knowledge amassed by large-scale projects such as the Innovative Medicines Initiative (IMI)-funded European Prevention of Alzheimer's Dementia (EPAD) program will enable the research community to learn, adapt, and implement change.MethodIn the current article, we define and discuss the substantial assets of the EPAD project for the scientific community, patient population, and industry, describe the EPAD structure with a focus on how the public and private sector interacted and collaborated within the project, reflect how IMI specifically supported the achievements of the above, and conclude with a view for future.ResultsThe EPAD project was a €64-million investment to facilitate secondary prevention of AD dementia research. The project recruited over 2,000 research participants into the EPAD longitudinal cohort study (LCS) and included over 400 researchers from 39 partners. The EPAD LCS data and biobank are freely available and easily accessible via the Alzheimer's Disease Data Initiative's (ADDI) AD Workbench platform and the University of Edinburgh's Sample Access Committee. The trial delivery network established within the EPAD program is being incorporated into the truly global offering from the Global Alzheimer's Platform (GAP) for trial delivery, and the almost 100 early-career researchers who were part of the EPAD Academy will take forward their experience and learning from EPAD to the next stage of their careers.DiscussionThrough GAP, IMI-Neuronet, and follow-on funding from the Alzheimer's Association for the data and sample access systems, the EPAD assets will be maintained and, as and when sponsors seek a new platform trial to be established, the learnings from EPAD will ensure that this can be developed to be even more successful than this first pan-European attempt.
Preliminary evidence of safety and effectiveness of Loxoprofen Sodium Cataplasm combined with physiotherapy for myofascial pain syndrome treatment: A randomized controlled pilot clinical trial
Authors: Zhou Xuewen , Li Xuelian , Wang Ziyang , Huang Dong 
Published: November 2022

BackgroundMyofascial pain syndrome (MPS) is one of the most common causes of chronic skeletal muscle pain, which is closely related to skeletal muscle myofascial trigger point (MTRP). Since there is no first-line treatment for MPS, we investigated Loxoprofen Sodium Cataplasm combined with physiotherapy as a non-invasive therapy in patients at different levels to a protocol with superior efficacy that is safe and easy to promote. Moreover, this treatment could represent an alternative therapeutic strategy for low-income patients to a safer, more convenient, and more economical treatment scheme.MethodsA randomized clinical study was aimed at evaluating the safety and efficacy of Loxoprofen Sodium Cataplasm combined with physiotherapy in patients diagnosed with MPS in the pain clinic. We screened 100 patients with MPS, and using a computer-generated random allocation sequence, we stratified patients in a ratio of 2:1:1:1 (A: B: C: D) to one of the four treatment groups. Group A received Loxoprofen Sodium Cataplasm combined with extracorporeal shock wave therapy (ESWT) and transcutaneous electrical nerve stimulation (TENS). Group B received Loxoprofen Sodium Cataplasm alone. Group C received physiotherapy alone. Group D received Flurbiprofen Cataplasm combined with physiotherapy. After 2 weeks of treatment, the overall efficiency and secondary assessment indicators, including visual analog scale (VAS) scores, chronic soft tissue injury (CSTI) scores, Oswestry Disability Index (ODI) scores, or Northwick Park Neck Pain Questionnaire (NPQ) scores, were evaluated before and after treatment to analyze the difference in efficacy of each group.ResultsAll groups were well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in overall efficiency (primary efficacy endpoint) (P = 0.0078) were observed in subjects of groups A and C.ConclusionShowing valuable data of efficacy in primary and secondary endpoints, Loxoprofen Sodium Cataplasm combined with physiotherapy is superior in the treatment of MPS.Trial registration numberhttps://www.chictr.org.cn/ (ChiCTR2100054756).
Lenvatinib as second-line treatment in patients with unresectable hepatocellular carcinoma: A retrospective analysis
Authors: Qin He-nan , Ning Zhen , Sun Rui , Jin Chen-xing , Guo Xin , Wang A-man , Liu Ji-wei 
Published: November 2022

ObjectiveThe purpose of this study is to determine the efficacy and safety of lenvatinib as second-line therapy in Chinese patients with unresectable hepatocellular carcinoma (HCC).MethodsWe performed a retrospective analysis of Chinese patients with unresectable HCC who received second-line treatment of lenvatinib at three institutions from November 2018 to February 2022. Demographic and clinicopathologic characteristics, data on the treatment regimens were obtained from medical records. Tumor response was evaluated every 4-6 weeks by modified Response Evaluation Criteria in Solid Tumors (mRECIST).ResultsIn total, 50 patients with unresectable HCC who received second-line treatment of lenvatinib were enrolled in this study. The objective response rate (ORR) was 18.0% and the disease control rate (DCR) was 74.0%, respectively. The duration of response (DoR) was 6.0 months. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 8.5 months, respectively. Patients who received ICIs combined with anti-angiogenic inhibitors as first-line therapy, achieving CR/PR at first-line therapy, with PFS≥6months at first-line therapy had a higher DCR. Univariate and multivariate analysis showed that AFP (ng/ml)&lt;400, absence of extrahepatic metastasis, Child-Pugh A, tumor number&lt;3, ICIs combined with anti-angiogenic inhibitors as first-line therapy, CR/PR to first-line therapy, and PFS≥6months at first-line therapy were independent factors of favorable PFS. Univariate analysis showed that absence of extrahepatic metastasis, tumor number&lt;3, ICIs combined with anti-angiogenic inhibitors as first-line therapy, and PFS≥6months at first-line therapy were significantly associated with longer OS. Multivariate analysis showed that absence of extrahepatic metastasis, Child-Pugh A, tumor number&lt;3, CR/PR to first-line therapy and PFS≥6months at first-line therapy were independent prognostic factors of OS. The majority of AEs were grade 1-2, and were reversible. Grade 3/4 AEs occurred in 12 patients (24.0%) and were mostly connected with hand-foot skin reactions (10.0%), and 10 patients had lenvatinib dose reductions. Two toxicity-related treatment interruptions were attributed to grade 3 hand-foot skin reaction, and grade 4 proteinuria, respectively.ConclusionThis study confirms the efficacy and safety of lenvatinib as second-line therapy after progression on sorafenib or ICIs combined with anti-angiogenic inhibitors.
Integrated systemic analysis of FAM72A to identify its clinical relevance, biological function, and relationship to drug sensitivity in hepatocellular carcinoma
Authors: Zhou Qi , Chen Lingjun , Yang Luo , Zhou Haoxiong , Chen Yan , Guo Yunwei 
Published: November 2022

BackgroundThe family with sequence similarity 72 member A (FAM72A) protein has been identified as an effector of multiple pathological processes in many cancers. The value of FAM72A in HCC remains largely unknown.MethodsData from TCGA-LIHC, ICGC-LIRI-JP, IMvigor210, cBioPortal, GeneMANIA, and TIMER were processed and visualized to explore the association between FAM72A and the prognosis, stemness phenotype, mutational burden, immune cell infiltration, and drug sensitivity in HCC patients. Potential pathways were also revealed. Furthermore, we experimentally verified the results in vivo and in vitro using immunohistochemistry, western blotting, and CCK-8 assays.ResultsFirst, FAM72A mRNA expression was significantly upregulated in HCC. High FAM72A expression was independently associated with a poor prognosis. Experimental validation confirmed that FAM72A was remarkably overexpressed in HCC patients and mice. Moreover, FAM72A knockdown suppressed HCC cell proliferation. In addition, the frequency of TP53 mutations was significantly higher in the high FAM72A expression group. Subsequently, the enrichment analysis revealed that FAM72A was closely related to immune processes and mTOR pathways. Silencing FAM72A increased the expression levels of mTOR in HCC cell lines. The FAM72A-mTOR pathway was strongly associated with a poor prognosis for patients with HCC. Patients with high FAM72A expression levels might be more resistant to sorafenib. Furthermore, the expression of FAM72A and mTOR was significantly associated with the abundance of some tumor-infiltrating immune cells, especially CD4+ T cells. Finally, patients with high levels of FAM72A and mTOR were more sensitive to immunotherapy.ConclusionsFAM72A, a member of the FAM72 family, might be a prognostic and immunotherapeutic target for HCC patients.
Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study
Authors: Zhao Jingzhu , Chi Yihebali , Hu Chuanxiang , Chen Xiaohong , Ge Minghua , Zhang Yuan , Guo Zhuming , Wang Jun , Chen Jie , Zhang Jiewu , Cheng Ying , Li Zhendong , Liu Hui , Qin Jianwu , Zhu Jingqiang , Cheng Ruochuan , Xu Zhengang , Li Dapeng , Tang Pingzhang , Gao Ming , Zheng Xiangqian 
Published: November 2022

BackgroundMedullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031.MethodsIn ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed.ResultsPatients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15–0.68) and 0.44 (95% CI, 0.20–0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22–0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population.ConclusionThis sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.
Importance of quadratus lumborum muscle trigger point injection and prolotherapy technique for lower back and buttock pain
Authors: Sirh Soo-Ji , Sirh So-Woon , Mun Hah-Yong , Sirh Heon-Man 
Published: November 2022

BackgroundLow back pain is a heterogeneous disease. Myofascial pain and enthesopathy of the quadratus lumborum muscle are important causes of lower back and/or buttock pain. However, a concrete, safe, and effective injection technique for the treatment of trigger points and enthesopathy in the quadratus lumborum muscle has not yet been developed.ObjectivesWe aimed to evaluate the importance of the quadratus lumborum muscle and introduce an effective landmark-based blind injection technique for treating quadratus lumborum trigger points and enthesopathy.MethodsAdult patients (n = 17) with lower back and/or buttock pain were placed in the lateral decubitus position. Next, we delicately palpated the quadratus lumborum muscle to accurately locate its lesions, including trigger points, taut bands, and tendon lesions, after five key landmarks had been identified. A newly designed 60–90-mm, 28G thin hypodermic needle was inserted at the tender points. The needle was typically advanced until its tip touched the transverse process to treat myofascial trigger points and tendon lesions in the iliolumbar and lumbocostal fibers, excluding superficial trigger points of the iliocostal fibers. Subsequently, lidocaine (0.5%) or a mixture of lidocaine (0.5%) and dextrose (12.5–15%) was injected.ResultsThe pretreatment visual analog scale score for all 17 patients decreased from ≥4–8/10 (mean 5.588) to 0–1/10 (mean 0.294) after completion of all treatments. The total number of treatments was one to four in acute and subacute cases and two to eight in chronic cases. The mean follow-up period was 73.5 days (treatment period: range, 4 to 43 days + at least 60 days of follow-up).ConclusionsHerein, we describe for the first time a landmark-based integrated injection technique for the treatment of trigger points and myofascial pain in the quadratus lumborum; this technique is safe, effective, and can be used with or without steroids, fluoroscopy, or ultrasound guidance.
Different profiles of lipoprotein particles associate various degrees of cardiac involvement in adolescents with morbid obesity
Authors: Siurana José M. , Sabaté-Rotés Anna , Amigó Núria , Martínez-Micaelo Neus , Arciniegas Larry , Riaza Lucia , Mogas Eduard , Rosés-Noguer Ferran , Ventura Paula S. , Yeste Diego 
Published: November 2022

IntroductionDyslipidemia secondary to obesity is a risk factor related to cardiovascular disease events, however a pathological conventional lipid profile (CLP) is infrequently found in obese children. The objective is to evaluate the advanced lipoprotein testing (ALT) and its relationship with cardiac changes, metabolic syndrome (MS) and inflammatory markers in a population of morbidly obese adolescents with normal CLP and without type 2 diabetes mellitus, the most common scenario in obese adolescents.MethodsProspective case-control research of 42 morbidly obese adolescents and 25 normal-weight adolescents, whose left ventricle (LV) morphology and function had been assessed. The ALT was obtained by proton nuclear magnetic resonance spectroscopy, and the results were compared according to the degree of cardiac involvement – normal heart, mild LV changes, and severe LV changes (specifically LV remodeling and systolic dysfunction) – and related to inflammation markers [highly-sensitive C-reactive protein and glycoprotein A (GlycA)] and insulin-resistance [homeostatic model assessment for insulin-resistance (HOMA-IR)]. A second analysis was performed to compare our results with the predominant ALT when only body mass index and metabolic syndrome criteria were considered.ResultsThe three cardiac involvement groups showed significant increases in HOMA-IR, inflammatory markers and ALT ratio LDL-P/HDL-P (40.0 vs. 43.9 vs. 47.1, p 0.012). When only cardiac change groups were considered, differences in small LDL-P (565.0 vs. 625.1 nmol/L, p 0.070), VLDL size and GlycA demonstrated better utility than just traditional risk factors to predict which subjects could present severe LV changes [AUC: 0.79 (95% CI: 0.54–1)]. In the second analysis, an atherosclerotic ALT was detected in morbidly obese subjects, characterized by a significant increase in large VLDL-P, small LDL-P, ratio LDL-P/HDL-P and ratio HDL-TG/HDL-C. Subjects with criteria for MS presented overall worse ALT (specially in triglyceride-enriched particles) and remnant cholesterol values.ConclusionsALT parameters and GlycA appear to be more reliable indicators of cardiac change severity than traditional CV risk factors. Particularly, the overage of LDL-P compared to HDL-P and the increase in small LDL-P with cholesterol-depleted LDL particles appear to be the key ALT's parameters involved in LV changes. Morbidly obese adolescents show an atherosclerotic ALT and those with MS present worse ALT values.
Influence of growth temperature and miscut angle of m-plane sapphire substrate on the semi-polar (11–22) AlN film grown by HVPE
Authors: Maosong Sun , Ting Liu , Yong Lu , Shuxin Tan , Xu Li , Jicai Zhang , Wenhong Sun 
Published: November 2022

The high-quality semi-polar (11-22) AlN thin films were grown on m-plane sapphire substrates by hydride vapor phase epitaxy (HVPE). The surface morphology and crystalline quality of the AlN film were greatly influenced by the growth temperature and the substrate miscut angle. As the temperature increased, the grain size on the surface increased and the grain density decreased. In addition, the higher growth temperature also resulted in smaller values of the full width at half maximum (FWHM) of X-ray rocking curves (XRC) when temperature was more than 1,460 °C. At high temperature of 1,530 °C, the introduction of 1° -off miscut angle to the substrate resulted in smooth surface, low density of stacking faults and low FWHM of XRC. The misfit dislocation density was calculated from the tilt angle of epilayer measured by X-ray reciprocal space mappings along [−1−123] AlN. The misfit dislocation density of the sample grown on 1° -off substrates was 6.7 × 105 cm−2. The improvement of crystal quality is believed to be due to the enhancement of adatom mobility at higher temperatures and also the appropriate miscut variation.
Recovery of the physiological status in professional basketball players using NESA neuromodulation treatment during different types of microcycles in season: A preliminary randomized clinical trial
Authors: García F. , Fernández D. , Vázquez-Guerrero J. , Font R. , Moreno-Planas B. , Álamo-Arce D. , Medina-Ramírez R. , Mallol-Soler M. 
Published: November 2022

The purpose of the study was to describe and compare recovery status after official basketball competition in players who underwent NESA neuromodulation treatment (NNT) in weeks with one or two matches. The recovery parameters of 12 professional male basketball players (mean ± SD, age: 20.6 ± 2.7 yr; height: 197.8 ± 11.7 cm; and body mass: 89.0 ± 21.2 kg) that competed in the LEB Plata (Spanish third division) were monitored 2 days after match-play over 6 weeks, and included: 1) the Hooper Test, which combines four subjective variables (sleep, stress, fatigue and soreness); 2) common biochemical markers (e.g., testosterone, cortisol and ratio T:C); and 3) lowest heart rate [HR], average HR, HR variability, sleep duration, awake time during night and onset latency before asleep). Players that completed NNT presented differences compared to the control group in sleep data. For instance, the lowest HR (p &lt; 0.001), average HR (p &lt; 0.001) and total awake time (p = 0.04) were significantly reduced in the NNT group. On the contrary, the control group presented greater values than the NNT group in the subjective Hooper Test, although only stress presented significant differences (Control 2.5 ± 1.2 vs. NNT cost or 3.2 ± 0.9; p = 0.01). Additionally, there were no significant differences in recovery parameters between weeks with one or two matches. In conclusion, the results suggest that players that underwent NNT tended to improve their sleep quality. Nevertheless, player’s values in the biochemical markers and wellness status remained similar in both groups. The fact that no significant differences were found between weeks with one or two matches could help basketball professionals to determine that a congested schedule does not seem to negatively alter recovery status.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04939181?term=NCT04939181, NCT04939181
Predicting acute termination and non-termination during ablation of human atrial fibrillation using quantitative indices
Authors: Kappel Cole , Reiss Michael , Rodrigo Miguel , Ganesan Prasanth , Narayan Sanjiv M. , Rappel Wouter-Jan 
Published: November 2022

Background: Termination of atrial fibrillation (AF), the most common arrhythmia in the United States, during catheter ablation is an attractive procedural endpoint, which has been associated with improved long-term outcome in some studies. It is not clear, however, whether it is possible to predict termination using clinical data. We developed and applied three quantitative indices in global multielectrode recordings of AF prior to ablation: average dominant frequency (ADF), spectral power index (SPI), and electrogram quality index (EQI).Methods: In N = 42 persistent AF patients (65 ± 9 years, 14% female) we collected unipolar electrograms from 64-pole baskets (Abbott, CA). We studied N = 17 patients in whom AF terminated during ablation (“Term”) and N = 25 in whom it did not (“Non-term”). For each index, we determined its ability to predict ablation by computing receiver operating characteristic (ROC) and calculated the area under the curve (AUC).Results: The ADF did not differ for Term and Non-term patients at 5.28 ± 0.82 Hz and 5.51 ± 0.81 Hz, respectively (p = 0.34). Conversely, the SPI for these two groups was. 0.85 (0.80–0.92) and 0.97 (0.93–0.98) and the EQI was 0.61 (0.58–0.64) and 0.56 (0.55–0.59) (p &lt; 0.0001). The AUC for predicting AF termination for the SPI was 0.85 ([0.68, 0.95] 95% CI), and for the EQI, 0.86 ([0.72, 0.95] 95% CI).Conclusion: Both the EQI and the SPI may provide a useful clinical tool to predict procedural ablation outcome in persistent AF patients. Future studies are required to identify which physiological features of AF are revealed by these indices and hence linked to AF termination or non-termination.