bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploratory evaluation of an eye-tracking system in patients with advanced spinal muscular atrophy type I receiving nusinersen
Authors: Yae Yukako , Yuge Kotaro , Maeda Toshiyuki , Ichinose Fumio , Matsuo Muneaki , Kobayashi Osamu , Okanari Kazuo , Baba Yusei , Yonee Chihiro , Maruyama Shinsuke , Shibata Minoru , Fujii Tatsuya , Chinen Madoka , Yamashita Yushiro 
Published: September 2022

ObjectiveThis study evaluated the feasibility of a matching-pair test using eye-tracking technology to assess nusinersen effectiveness in patients with advanced spinal muscular atrophy (SMA) type I.MethodsThis prospective, observational study enrolled patients with 5q-SMA type I who had lost gross motor function. Three different levels of matching-pair tests were conducted using the eye-gaze system (My Tobii; TobiiDynavox Inc.) at baseline, and after 9 and 24 weeks of nusinersen treatment. The primary endpoint was the change from baseline in matching-pair test scores and response times (i.e., the time to answer matching-pair test) at 24 weeks from baseline. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Pediatric Quality of Life inventory for patients with Neuromuscular Disease (PedsQL-NM) and Numerical Rating Scale (NRS) scores were also assessed as secondary endpoints. Analysis of ocular fixation was performed as an additional analysis. This study was registered at https://www.umin.ac.jp/ctr/ (UMIN000033935).ResultsSeven patients (one male, six female) aged 5–21 years (median 11 years) were enrolled; all patients were bedridden and six patients were ventilated. All seven patients were able to conduct level 1 matching-pair tests at each assessment; five patients were also able to conduct levels 2 and 3. Two patients (those with the highest CHOP-INTEND scores) were able to complete all tests correctly within 60 s. There was a non-significant trend toward improvement in CHOP-INTEND, PedsQL-NM, and NRS scores over the 6-month period. There were no significant differences in the number of actions, errors, correct answers, or response times between baseline and Week 9 or 24 at any level. However, the result of an additional analysis suggests that detection of eye movement would be useful to evaluate for advanced SMA.ConclusionsEye-tracking systems are possibly feasible for the assessment of treatment efficacy in patients with advanced SMA type I.
Effects of cannabinoid exposure on short-term memory and medial orbitofrontal cortex function and chemistry in adolescent female rhesus macaques
Authors: Kohut Stephen J. , Cao Lei , Mintzopolous Dionyssios , Jiang Shan , Nikas Spyros P. , Makriyannis Alexandros , Zou Chun S. , Jensen J. Eric , Frederick Blaise B. , Bergman Jack , Kangas Brian D. 
Published: September 2022

AimThere is increasing concern that cannabinoid exposure during adolescence may disturb brain maturation and produce long-term cognitive deficits. However, studies in human subjects have provided limited evidence for such causality. The present study utilized behavioral and neuroimaging endpoints in female non-human primates to examine the effects of acute and chronic exposure during adolescence to the cannabinoid receptor full agonist, AM2389, on cognitive processing and brain function and chemistry.Materials and methodsAdolescent female rhesus macaques were trained on a titrating-delay matching-to-sample (TDMTS) touchscreen task that assays working memory. TDMTS performance was assessed before and during chronic exposure to AM2389, following antagonist (rimonabant) administration, and after discontinuation of the chronic regimen. Resting-state fMRI connectivity and magnetic resonance spectroscopy data were acquired prior to drug treatment, during chronic exposure, and following its discontinuation. Voxels were placed in the medial orbitofrontal cortex (mOFC), a region involved in memory processing that undergoes maturation during adolescence.ResultsTDMTS performance was dose-dependently disrupted by acute AM2389; however, chronic treatment resulted in tolerance to these effects. TDMTS performance also was disrupted by discontinuation of the chronic regimen but surprisingly, not by rimonabant administration during chronic AM2389 treatment. mOFC N-acetylaspartate/creatine ratio decreased after acute and chronic administration but returned to baseline values following discontinuation of chronic treatment. Finally, intra-network functional connectivity (mOFC) increased during the chronic regimen and returned to baseline values following its discontinuation.ConclusionNeural effects of a cannabinergic drug may persist during chronic exposure, notwithstanding the development of tolerance to behavioral effects. However, such effects dissipate upon discontinuation, reflecting the restorative capacity of affected brain processes.
Dietary diversity and determinants of young adults in central China: A cross-sectional study from 2015 to 2020
Authors: Zhou Yi , Wang Jiangang , Duan Yinglong , Luo Xiaofei , Wan Ziyu , Luo Yating , Li Ying , Wang Yaqin , Xie Jianfei 
Published: September 2022

BackgroundEarly adulthood is a vulnerable period for improved nutrition at all phases of the life cycle. However, there is limited research on diversity information in young adults from middle-income countries undergoing an apparent nutritional transition. The purpose of this study was to explore dietary diversity and determinants among young adults aged 18–35 years in central China.MethodsFrom January 2015 to December 2020, a cross-sectional survey of 49,021 young adults in a health management center of central China was conducted through report and phone-assisted self-report for information. The outcome variable was the Dietary Diversity Score. Independent variables included age, sex, race, material status, education, BMI, taste preference, regular meals, midnight snacks, sugared beverage/coffee consumption, and smoking/drinking status. Multivariate logistic regression was performed.ResultsOf 49,021 young adults, 38,374 (78.3%) reported insufficient dietary diversity, and 422 (0.9%) reported sufficient dietary diversity. Light taste preference [adjusted odds ratio (aOR) = 2.325; 95% CI: 1.779, 3.039] and those who had meals regularly (aOR = 1.241; 95% CI: 1.018, 1.513) and consumed coffee (aOR = 2.765; 95% CI: 2.257, 3.387) were more likely to be associated with sufficient dietary diversity. Midnight snacks (aOR = 0.728; 95% CI: 0.588, 0.901) and sugary beverages (aOR = 0.666; 95% CI: 0.535, 0.829) were less likely to be associated with sufficient dietary diversity. Higher BMI (aOR = 1.092; 95% CI: 1.061, 1.125) was associated with higher odds of sufficient dietary diversity. Additionally, participants who were 18–30 years old, with master or above degree and away from cigarette/alcohol were more likely to report better dietary diversity.ConclusionOur results painted a less than ideal nutritional condition affecting young adults. High-fat/sugar/salt dietary practices can lead to low dietary diversity, while high dietary diversity might have adverse BMI outcomes in youth. This study highlighted the importance of increasing the diversity of healthy and selective food items before wide recommendation for dietary diversity.
The impact of changes in taste, smell, and eating behavior in children with cancer undergoing chemotherapy: A qualitative study
Authors: van den Brink Mirjam , ter Hedde Minke M. , van den Heuvel Emmy , Tissing Wim J. E. , Havermans Remco C. 
Published: September 2022

Background and aimsTaste changes are the third most common bothersome symptom during treatment in children with cancer. However, it is still unclear what the essence of these taste changes are, to what degree concomitant changes in sense of smell qualify this bothersome treatment symptom and how much of an impact these changes have on the life of children with cancer. The aim of this study was to explore characteristics of both taste and smell changes and to gain insight into the impact of these changes in children with cancer receiving chemotherapy.MethodsSemi-structured interviews were performed until data saturation was achieved in each age group (6–12, 13–17 years). This resulted in an in-depth description of taste and smell changes, including its impact on the life of 27 children with various cancer types receiving chemotherapy. Thematic analysis of interview data was performed.ResultsInterview data could be grouped into three main themes, namely changes in (1) taste, (2) smell, and (3) eating behavior. As expected, most children reported experiencing taste and smell changes just after start of treatment, but changes varied greatly between children; that is, some reported changes in intensity (increased or decreased), whereas others reported different perceptions or preferences (from sweet to savory). Taste and smell changes (regardless of direction) negatively impacted quality of life, with these changes commonly described as “disappointing” or “frustrating.” Interestingly, particular chemotherapeutic agents were frequently mentioned regarding taste and smell changes, prompting sensory-specific coping strategies. Children's eating behavior changed in terms of alterations in food liking and appetite, sometimes due to chemosensory changes, but children also mentioned specific medication or hospital food being responsible for their altered eating behavior.ConclusionsBoth taste and smell changes are common in children with cancer. The essence of these changes varies widely, but taste and smell changes are generally considered bothersome treatment symptoms. Ways to cope with taste or smell changes specifically were described by the children warranting further research and offering the opportunity for enhancing patient-centered care.
A novel signature of combing cuproptosis- with ferroptosis-related genes for prediction of prognosis, immunologic therapy responses and drug sensitivity in hepatocellular carcinoma
Authors: Zhao Chuanbing , Zhang Zhengle , Jing Tao 
Published: September 2022

BackgroundOur study aimed to construct a novel signature (CRFs) of combing cuproptosis-related genes with ferroptosis-related genes for the prediction of the prognosis, responses of immunological therapy, and drug sensitivity of hepatocellular carcinoma (HCC) patients.MethodsThe RNA sequencing and corresponding clinical data of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), GSE76427, GSE144269, GSE140580, Cancer Cell Line Encyclopedia (CCLE), and IMvigor210 cohorts. CRFs was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm. The analyses involved in the prognosis, response to immunologic therapy, efficacy of transcatheter arterial chemoembolization (TACE) therapy, and drug sensitivity were performed. Furthermore, the molecular function, somatic mutation, and stemness analyses were further performed between the low- and high-risk groups, respectively. In this study, the statistical analyses were performed by using the diverse packages of R 4.1.3 software and Cytoscape 3.8.0.ResultsCRFs included seven genes (G6PD, NRAS, RRM2, SQSTM1, SRXN1, TXNRD1, and ZFP69B). Multivariate Cox regression analyses demonstrated that CRFs were an independent risk factor for prognosis. In addition, these patients in the high-risk group presented with worse prognoses and a significant state of immunosuppression. Moreover, patients in the high-risk group might achieve greater outcomes after receiving immunologic therapy, while patients in the low-risk group are sensitive to TACE. Furthermore, we discovered that patients in the high-risk group may benefit from the administration of sunitinib. In addition, enhanced mRANsi and tumor mutation burden (TMB) yielded in the high-risk group. Additionally, the functions enriched in the low-risk group differed from those in the other group.ConclusionIn summary, CRFs may be regarded not only as a novel biomarker of worse prognosis, but also as an excellent predictor of immunotherapy response, efficacy of TACE and drug sensitivity in HCC, which is worthy of clinical promotion.
Case report: Long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: The emerging therapeutic role of casirivimab/imdevimab
Authors: Ballotta Laura , Simonetti Omar , D’Agaro Pierlanfranco , Segat Ludovica , Koncan Raffaella , Martinez-Orellana Pamela , Dattola Federica , Orsini Emanuele , Marcello Alessandro , Dal Monego Simeone , Licastro Danilo , Misin Andrea , Mohamed Sara , Sbisà Eugenio , Lucchini Elisa , De Sabbata Giovanni Maria , Zaja Francesco , Luzzati Roberto 
Published: September 2022

Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild–moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.
Transarterial chemoembolization combined with apatinib with or without PD-1 inhibitors in BCLC stage C hepatocellular carcinoma: A multicenter retrospective study
Authors: Xia Wei-Li , Zhao Xiao-Hui , Guo Yuan- , Cao Guang-Shao , Wu Gang , Fan Wei-Jun , Yao Quan-Jun , Xu Shi-Jun , Guo Chen-Yang , Hu Hong-Tao , Li Hai-Liang 
Published: September 2022

ObjectiveWe evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib plus PD-1 inhibitors (TACE-AP) compared with TACE combined with apatinib (TACE-A) in patients with advanced hepatocellular carcinoma (HCC) and to explore the prognostic factors affecting patient survival.MethodsData from patients with unresectable HCC who received TACE-AP or TACE-A from December 2018 to June 2021 were collected retrospectively. The main outcome of the study was overall survival (OS) and prognostic factors affecting survival, while the secondary outcomes were progression-free survival (PFS), the objective response rate (ORR), and treatment-related adverse events (TRAEs). Propensity score matching (PSM) analysis was used to reduce patient selection bias, and the random survival forest (RF) model was employed to explore prognostic factors affecting patient survival.ResultsWe enrolled 216 patients, including 148 and 68 patients in the TACE-A and TACE-AP groups, respectively. A total of 59 pairs of patients were matched using PSM analysis. Before and after PSM, the OS, PFS, and ORR in the TACE-AP group were significantly higher than in the TACE-A group (before, OS: 22.5 months vs. 12.8 months, P &lt; 0.001; PFS: 6.7 months vs. 4.3 months, P &lt; 0.001; ORR: 63.2% vs. 34.5%, P &lt; 0.001; after, OS: 22.5 months vs. 12.0 months, P &lt; 0.001; PFS: 6.7 months vs. 4.3 months, P &lt; 0.001; ORR: 62.7% vs. 30.5%, P = 0.003). Multivariate Cox regression and RF models before and after PSM analysis revealed that the main prognostic factors affecting survival were tumor number, portal vein tumor thrombus (PVTT) invasion, alpha-fetoprotein (AFP) levels, total bilirubin (TBIL) level, and treatment. There was no significant difference in TRAEs between the two groups (P &gt; 0.05).ConclusionCompared with TACE-A, TACE-AP significantly improved OS, PFS, and ORR in patients with advanced HCC. The number of tumors, PVTT invasion, AFP levels, TBIL level, and treatment were significant prognostic factors associated with patient survival. All observed TRAEs were mild and controllable.
Impact of adjuvant radiation therapy after definitive surgery in senior adults >80 years old with advanced head and neck squamous cell carcinoma on overall survival
Authors: Butkus Joann M. , Crippen Meghan , Bar-Ad Voichita , Luginbuhl Adam 
Published: September 2022

BackgroundAdjuvant radiotherapy (RT) following surgical resection confers a survival benefit for adult patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We aim to investigate if adjuvant RT provides a similar survival advantage to patients ages 80+ through a national curated database.MethodsThis retrospective cohort study queried the National Cancer Database (NCDB) for all cases of HNSCC between 2004-2016. Patients treated with surgical resection alone were compared to those treated with surgery plus adjuvant RT. Overall survival (OS) was compared within adult (age &lt;80 years) and senior adult (age ≥80 years) cohorts using Kaplan-Meier analysis. Hazard ratios (HR) were assessed using Cox proportional hazards to account for differences in patient characteristics, primary site, and HNSCC stage.ResultsNCDB identified 16,504 locally advanced HNSCC treated with definitive surgery with 9,129 (55.3%) also receiving adjuvant RT. The mean age was 63.8 years (SD = 12.0) with 88.7% of patients ages &lt;80 years and 11.3% ages ≥80 years. In the adult cohort, adjuvant RT was associated with a significant increase in OS compared to surgery alone at 1 year (88.4% vs. 83.8%, p=&lt;0.001), 3 years (64.0% vs. 59.2%, p=&lt;0.001) and 5 years (52.8% vs. 47.2%, p=&lt;0.001). Treatment with surgery alone remained a significant predictor of mortality risk at 1 year (HR 1.48, 95% CI 1.35-1.64, p&lt;0.001), 3 years (HR 1.25, 95% CI 1.18-1.33, p&lt;0.001), and 5 years (HR of 1.23, 95% CI 1.17-1.30, p=&lt;0.001). In the senior adult cohort, there were no significant differences in OS between treatment groups at 1 year (73.4% vs. 74.8%, 0.296), 3 years (45.8% vs. 41.8%, p=0.465), or 5 years (28.2% vs. 27.7% p=0.759). Treatment with surgery alone was not a significant predictor of mortality risk at 1 year (HR 1.11, 95% CI 0.90-1.36, p=0.316), 3 years (HR 0.94, 95% CI 0.81-1.08, p=0.423), or 5 years (HR 0.95, 95% CI 0.83-1.08, p=0.476).ConclusionThe addition of adjuvant RT in senior patients (age ≥80 years) may not provide a similar OS benefit to that observed in younger patients. Further research is needed to best guide shared-decision making in this population.
Fruits of Hippophaë rhamnoides in human leukocytes and Caco-2 cell monolayer models—A question about their preventive role in lipopolysaccharide leakage and cytokine secretion in endotoxemia
Authors: Laskowska Anna K. , Wilczak Aleksandra , Skowrońska Weronika , Michel Piotr , Melzig Matthias F. , Czerwińska Monika E. 
Published: September 2022

Preparations from Hippophaë rhamnoides L. (sea buckthorn) have been traditionally used in the treatment of skin and digestive disorders, such as gastritis, gastric and duodenal ulcers, uterine erosions, as well as oral, rectal, and vaginal mucositis, in particular in the Himalayan and Eurasian regions. An influence of an aqueous extract from the fruits of H. rhamnoides (HR) on leakage of lipopolysaccharide (LPS) from Escherichia coli through gut epithelium developed from the human colorectal adenocarcinoma (Caco-2) monolayer in vitro and glucose transporter 2 (GLUT2) translocation were the principal objectives of the study. Additionally, the effect of HR on the production of pro- and anti-inflammatory cytokines (interleukins: IL-8, IL-1β, IL-10, IL-6; tumor necrosis factor: TNF-α) by the Caco-2 cell line, human neutrophils (PMN), and peripheral blood mononuclear cells (PBMC) was evaluated. The concentration of LPS on the apical and basolateral sides of the Caco-2 monolayer was evaluated with a Limulus Amebocyte Lysate (LAL) assay. GLUT2 translocation was evaluated using an immunostaining assay, whereas secretion of cytokines by cell cultures was established with an enzyme-linked immunosorbent (ELISA) assay. HR (500 μg/ml) significantly inhibited LPS leakage through epithelial monolayer in vitro in comparison with non-treated control. The treatment of Caco-2 cells with HR (50–100 μg/ml) showed GLUT2 expression similar to the non-treated control. HR decreased the secretion of most pro-inflammatory cytokines in all tested models. HR might prevent low-grade chronic inflammation caused by metabolic endotoxemia through the prevention of the absorption of LPS and decrease of chemotactic factors released by immune and epithelial cells, which support its use in metabolic disorders in traditional medicine.
Long-term stimulation with alternating electric fields modulates the differentiation and mineralization of human pre-osteoblasts
Authors: Sahm Franziska , Freiin Grote Vivica , Zimmermann Julius , Haack Fiete , Uhrmacher Adelinde M. , van Rienen Ursula , Bader Rainer , Detsch Rainer , Jonitz-Heincke Anika 
Published: September 2022

Biophysical stimulation by electric fields can promote bone formation in bone defects of critical size. Even though, long-term effects of alternating electric fields on the differentiation of osteoblasts are not fully understood. Human pre-osteoblasts were stimulated over 31 days to gain more information about these cellular processes. An alternating electric field with 0.7 Vrms and 20 Hz at two distances was applied and viability, mineralization, gene expression, and protein release of differentiation factors were analyzed. The viability was enhanced during the first days of stimulation. A higher electric field resulted in upregulation of typical osteogenic markers like osteoprotegerin, osteopontin, and interleukin-6, but no significant changes in mineralization. Upregulation of the osteogenic markers could be detected with a lower electric field after the first days of stimulation. As a significant increase in the mineralized matrix was identified, an enhanced osteogenesis due to low alternating electric fields can be assumed.