bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-type feature fusion based on graph neural network for drug-drug interaction prediction
Authors: He Changxiang , Liu Yuru , Li Hao , Zhang Hui , Mao Yaping , Qin Xiaofei , Liu Lele , Zhang Xuedian 
Published: June 2022

Abstract
Background
Drug-Drug interactions (DDIs) are a challenging problem in drug research. Drug combination therapy is an effective solution to treat diseases, but it can also cause serious side effects. Therefore, DDIs prediction is critical in pharmacology. Recently, researchers have been using deep learning techniques to predict DDIs. However, these methods only consider single information of the drug and have shortcomings in robustness and scalability.

Results
In this paper, we propose a multi-type feature fusion based on graph neural network model (MFFGNN) for DDI prediction, which can effectively fuse the topological information in molecular graphs, the interaction information between drugs and the local chemical context in SMILES sequences. In MFFGNN, to fully learn the topological information of drugs, we propose a novel feature extraction module to capture the global features for the molecular graph and the local features for each atom of the molecular graph. In addition, in the multi-type feature fusion module, we use the gating mechanism in each graph convolution layer to solve the over-smoothing problem during information delivery. We perform extensive experiments on multiple real datasets. The results show that MFFGNN outperforms some state-of-the-art models for DDI prediction. Moreover, the cross-dataset experiment results further show that MFFGNN has good generalization performance.

Conclusions
Our proposed model can efficiently integrate the information from SMILES sequences, molecular graphs and drug-drug interaction networks. We find that a multi-type feature fusion model can accurately predict DDIs. It may contribute to discovering novel DDIs.
Low physical activity is the strongest factor associated with frailty phenotype and frailty index: data from baseline phase of Birjand Longitudinal Aging Study (BLAS)
Authors: Sobhani Ameneh , Sharifi Farshad , Fadayevatan Reza , Kamrani Ahmad Ali Akbari , Moodi Mitra , Khorashadizadeh Masoumeh , Kazemi Toba , Khodabakhshi Huriye , Fakhrzadeh Hossein , Arzaghi Masoud , Badrkhahan Seyedeh Zahra , Hosseini Raziye Sadat , Monji Hadi , Nikkhah Amirabbas 
Published: June 2022

Abstract
Background
Frailty is the most complicated expression of aging that is related to disability or multi-morbidity. The aim of the present study was to estimate the prevalence of frailty and its associated factors among community-dwelling aged population.

Methods
A total of 1529 eligible community- dwelling older adults (≥ 60 years) were enrolled in the baseline phase of Birjand Longitudinal Aging Study (BLAS) from 2019 to 2020. Their frailty status was assessed using the Fried’s frailty phenotype and frailty index. Sociodemographic factors, including sex, age, marital status, and education level, were collected. Health status assessment included the history of hypertension, diabetes mellitus, cardiovascular disease, Alzheimer’s diseases and dementia, and other health conditions. Furthermore, functional assessment (ADL, IADL) and anthropometric measurements including height, weight, waist, calf, and mid-arm circumference were made and the body mass index was calculated. The nutrition status and polypharmacy (use 3 or more medication) were also evaluated.

Results
The prevalence of frailty was 21.69% according to the frailty phenotype and 23.97% according to the frailty index. A multiple logistic regression model showed a strong association between low physical activity and frailty phenotype (OR = 36.31, CI = 16.99–77.56, P < 0.01), and frailty index (OR = 15.46, CI = 5.65–42.34, P < 0.01). Other factors like old age (≥80), female sex, malnutrition, polypharmacy, obesity, and arthritis were also associated with frailty. The Kappa coefficient of the agreement between these two instruments was 0.18.

Conclusion
It seems that low physical activity is the most important determinant of frailty. Low physical activity and some other factors may be preventable or modifiable and thus serve as clinically relevant targets for intervention.
Safety use of high frequency oscillatory ventilation in transport of newborn infants affected by severe respiratory failure: preliminary data in central Tuscany
Authors: Belli Gilda , Dovadola Ilaria , Berti Elettra , Padrini Letizia , Agostini Elisabetta , Serafini Lisa , Ingargiola Anna , Gabbrielli Gabriella , Sandini Elena , Azzarà Angelo , Catarzi Serena , Cioni Maria Luce , Petrucci Letizia , Paternoster Filomena , Moroni Marco 
Published: June 2022

Abstract
Background
Neonatal Emergency Transport Services play a fundamental role in neonatal care. Stabilization before transport of newborns suffering from severe respiratory failure is often a challenging problem and some critically ill infants may benefit from High Frequency Oscillatory Ventilation (HFOV) as rescue treatment. In these cases, transition to conventional ventilation for transport may cause a deterioration in clinical conditions. HFOV during neonatal transport has been only exceptionally used, due to technical difficulties. Since May 2018, a new neonatal transport unit is available at the Neonatal Protected Transport Service of the Meyer University Hospital in Florence, equipped with a pulmonary ventilator capable of delivering HFOV. Therefore, we conducted an analysis on patients transferred in HFOV to Neonatal Intensive Care Unit (NICU), in order to evaluate the safety and feasibility of its use during neonatal transport.

Methods
A retrospective analysis was performed reviewing medical records of the neonates transported by Meyer Children Hospital’s Neonatal Transport Service between May 2018 and December 2020, and newborns treated with HFOV during ground neonatal transport were identified. Safety was assessed by the comparison of vital signs, hemogas-analysis values and pulmonary ventilator parameters, at the time of departure and upon arrival in NICU. The dose of inotropes, the main respiratory complications (air leak, dislocation or obstruction of the endotracheal tube, loss of chest vibrations) and the number of deaths and transfer failures were recorded.

Results
Out of the approximate 400 newborns transported during the analysis period, 9 were transported in HFOV. We did not find any statistically significant difference in vital parameters, hemogas-analytical values and pulmonary ventilator settings recorded before and after neonatal transport of the nine patients’ parameters (p > 0,05). No patient required additional inotropes during transport. No transport-related deaths or significant complications occurred during transport.

Conclusions
The interest of our report is in the possibility of using HFOV during inter-hospital neonatal transfer. As far as our experience has shown, HFOV appears to be safe for the transportation of newborns with severe respiratory failure. Nevertheless, further larger, prospective and multicentre studies are needed to better evaluate the safety and efficacy of HFOV during neonatal transport.
Spirometry as a motivator for smoking cessation among patients attending the smoking cessation clinic of Monastir
Authors: Ben Fredj Manel , Garrach Behaeddin , Bennasrallah Cyrine , Migaou Asma , Abroug Hela , Dhouib Wafa , Zemni Imen , Kacem Meriem , Bouanene Ines , Belguith Sriha Asma 
Published: June 2022

Abstract
Background
The choice of spirometry, a biomarker of lung health, as a motivator for smoking cessation is based on its fidelity in emphasizing tobacco adverse effects. Yet, there is a paucity of evidence on its efficacy, and the findings are currently inconclusive. The aim of this study was to determine whether a spirometry and lung age communication has an effect on smoking cessation rates.

Methodology
We conducted a randomized controlled trial among patients who attended the smoking cessation clinic (SCC) at Fattouma Bourguiba University Hospital in Monastir, from June 2017 to February 2020. Participants were assigned into two groups, a control arm receiving standard program and intervention arm receiving a spirometry and lung age announcement along with usual care. The primary outcomes were the smoking cessation rates after one year of follow-up between the intervention arm and the control arm.

Results
At one-year endpoint, a total of 456 were reachable for assessment, 236 in control group and 220 in spirometry group, which leads to a loss rate equal to 8.8%. One-year smoking cessation rate was higher among the intervention group than among control group (25.5% versus 16.5%), with a considerable statistical significance (p = 0.019). Lung age was significantly higher at paired comparison with chronological age.

Conclusion
Smoking cessation is still a challenging procedure with a high risk of relapse, making very valuable any approach that may increase motivation in both unmotivated and motivated smokers. This study is an additional evidence for spirometry and lung age announcement as motivators for smoking cessation.

Trial registration
Pan African Clinical Trial Registry database (PACTR202110595729653), 06/10/ 2021.
Quercetin treatment protects the Achilles tendons of rats from oxidative stress induced by hyperglycemia
Authors: Yoshikawa Tomoya , Mifune Yutaka , Inui Atsuyuki , Nishimoto Hanako , Yamaura Kohei , Mukohara Shintaro , Shinohara Issei , Kuroda Ryosuke 
Published: June 2022

Abstract
Background
Quercetin, a flavonoid abundantly in vegetables and fruits, exerts antioxidant and anti-inflammatory effects. We investigated the protective effects of quercetin against oxidative stress in the Achilles tendons of diabetic rats.

Methods
Cells were collected from the Achilles tendons of Sprague–Dawley rats and cultured under four conditions: regular glucose (RG) without quercetin (Quer-), RG with quercetin (Quer +), high-glucose (HG) Quer-, and HG Quer + . The expression of genes related to NADPH oxidase (NOX) and inflammation, reactive oxygen species accumulation, and apoptosis rates was analyzed. Additionally, diabetic rats were divided into two groups and subjected to quercetin (group Q) or no quercetin (group C) treatment. Histological evaluation and expression analysis of relevant genes in the Achilles tendon were performed.

Results
In rat tendon-derived cells, the expression of Nox1, Nox4, and Il6; reactive oxygen species accumulation; and apoptosis rates were significantly decreased by quercetin treatment in the HG group. The collagen fiber arrangement was significantly disorganized in the diabetic rat Achilles tendons in group C compared with that in group Q. The mRNA and protein expression levels of NOX1 and NOX4 were significantly decreased upon quercetin treatment. Furthermore, the expression of Il6, type III collagen, Mmp2, and Timp2 was significantly decreased, whereas that of type I collagen was significantly increased in group Q compared with that in group C.

Conclusions
Quercetin treatment decreases NOX expression and thus exerts antioxidant and anti-inflammatory effects in the Achilles tendons of diabetic rats. Quercetin treatment may be effective against diabetic tendinopathy.
Intake of whole grain foods and risk of coronary heart disease in US men and women
Authors: Hu Yang , Willett Walter C. , Manson Jo Ann E. , Rosner Bernard , Hu Frank B. , Sun Qi 
Published: June 2022

Abstract
Background
Epidemiological studies have demonstrated a favorable association of whole grain intake with coronary heart disease (CHD) risk, although whether such an inverse association holds true for individual whole grain foods that have various nutritional profiles has not been examined.

Methods
We followed 74,244 women from Nurses’ Health Study since 1986, 91,430 women from Nurses’ Health Study II since 1991, and 39,455 men from the Health Professionals Follow-Up Study since 1984, who did not have a history of cardiovascular disease or cancer at baseline. Intake of seven individual whole grain foods was repeatedly assessed using a validated semi-quantitative food frequency questionnaire every 2–4 years since baseline. CHD diagnoses were ascertained through review of medical records or death certificates.

Results
We documented 9461 CHD cases during an average of 25.8 years’ follow-up. In the multivariable-adjusted model, the pooled hazard ratio (HR) (95% CI) of CHD risk corresponding to each one serving/day consumption of total whole grains was 0.93 (0.90–0.95; p trend <0.0001). Higher consumption of most individual whole grain foods was associated with significantly lower risk of CHD. Comparing participants consuming ≥1 serving/day with those consuming < 1 serving/month, the multivariable-adjusted pooled HRs (95% CIs) of CHD were 0.83 (0.78–0.89) for whole grain cold breakfast cereal, 0.92 (0.86–0.99) for dark bread, and 1.08 (0.96–1.22) for popcorn. For other whole grain foods with lower overall intake levels, comparing intake level of ≥2 servings/week with < 1 serving/month, the pooled hazard ratios (95% CIs) were 0.79 (0.74–0.84) for oatmeal, 0.79 (0.71–0.87) for brown rice, 0.84 (0.78–0.90) for added bran, and 0.87 (0.77–0.99) for wheat germ. Cubic spline regression suggested non-linear associations for certain whole grain foods: the risk reduction plateaued approximately over 2 servings/day for total whole grains, 0.5 serving/day for both cold breakfast cereal and dark bread, 0.5 serving/week for oatmeal, 1 serving/week for brown rice, and 2 serving/week for added bran (p for non-linearity <0.01 for all associations).

Conclusions
These data suggest that higher consumption of total whole grains, as well as individual whole grain foods except popcorn, were significantly associated with lower CHD risk. The inverse associations may plateau at various intake levels for total whole grain and individual whole grain foods. This study provides further evidence in support of increasing whole grain intake for the prevention of CHD in US populations.
Single medium-sized hepatocellular carcinoma treated with sequential conventional transarterial chemoembolization (cTACE) and microwave ablation at 4 weeks versus cTACE alone: a propensity score
Authors: Zhu Zi-yi , Yuan Mu , Yang Pei-Pei , Xie Bo , Wei Jian-zhu , Qin Zhong-qiang , Qian Zhen , Wang Zhao-Ying , Fan Long-Fei , Qian Jing-yu , Tan Yu-lin 
Published: June 2022

Abstract
Background
Microwave ablation (MWA) is a potentially curative treatment for unresectable patients with hepatocellular carcinoma (HCC) ≤ 3 cm, while its therapeutic efficacy decreases significantly for HCC > 3cm. Previous studies have demonstrated that conventional transarterial chemoembolization (cTACE) combined with MWA (cTACE-MWA) may improve local tumor control rate and reduce the recurrence rate for HCC > 3cm. However, there have been few study designs to analyze the clinical efficacy of cTACE-MWA for medium-sized HCC (3–5cm). Therefore, this study aims to compare the clinical efficacy and safety of cTACE-MWA with cTACE alone for a single medium-sized HCC of 3–5 cm in diameter.

Methods
We retrospectively investigate the data of 90 patients with a single medium-sized HCC who were referred to our hospital and underwent cTACE-MWA or cTACE alone from December 2017 to March 2020. Then, patients were identified with propensity score-matched (1:1). The local tumor response to treatment and time to progression (TTP) were compared using mRECIST criteria between the cTACE-MWA group and the cTACE group.

Results
A total of 42 patients were included after matching (cTACE-MWA: 21; cTACE: 21). Comparing with cTACE, cTACE-MWA demonstrate significantly better local tumor control (ORR: 95.2% vs 61.9%, p = 0.02; DCR: 95.2% vs 66.7%, p = 0.045) and TTP (median 19.8 months vs 6.8 months, p < 0.001). The 1- and 2-year cumulative probabilities of OS were 100% and 95% in the cTACE-MWA group, which were significantly higher than those in the cTACE group (95% and 76%) (p = 0.032). Multivariate Cox regression analysis illustrates that cTACE-MWA was associated with better TTP (hazard ratio, 0.28; 95% CI: 0.1, 0.76; p = 0.012), but tumor size was associated with worse TTP (hazard ratio, 1.71; 95% CI: 1.01, 2.89; p = 0.045).

Conclusions
cTACE followed by MWA improved TTP and OS in patients with a single medium-sized HCC, and no major complication was observed in this study.
Conversion surgery for microsatellite instability-high gastric cancer with a complete pathological response to pembrolizumab: a case report
Authors: Hidaka Yoshifumi , Arigami Takaaki , Osako Yusaku , Desaki Ryosuke , Hamanoue Masahiro , Takao Sonshin , Kirishima Mari , Ohtsuka Takao 
Published: June 2022

Abstract
Background
Immune checkpoint inhibitors are reportedly effective in treating microsatellite instability (MSI)-high gastric cancer. There are a few case reports of conversion surgery (CS) with nivolumab but none with pembrolizumab. Herein, we describe a patient with MSI-high gastric cancer who was successfully treated with pembrolizumab and underwent CS with a pathological complete response.

Case presentation
A 69-year-old man was diagnosed with stage III gastric cancer (T3N2M0) based on contrast-enhanced computed tomography, which revealed a neoplastic lesion and enlarged perigastric lymph nodes in the gastric lesser curvature. The anterior superior lymph node of the common hepatic artery (CHA) was determined to be unresectable due to invasion of the pancreatic head and CHA. Histopathologically, the biopsied tissue showed moderately differentiated adenocarcinoma, then determined to be MSI-high. After three courses of mFOLFOX6 therapy, the patient was diagnosed with progressive disease. Since one course of paclitaxel plus ramucirumab therapy caused grade 3 fatigue, his second-line therapy was switched to pembrolizumab monotherapy. After three courses, the primary tumor and perigastric lymph nodes had shrunk, and it was determined as a partial response. The anterior superior lymph node of the CHA became resectable based on the improvement of infiltration of the pancreatic head and CHA due to shrinkage of the lymph node. Tumor markers remained low; hence, distal gastrectomy plus D2 lymphadenectomy was performed at the end of six courses. Anterior superior lymph node of the CHA was confirmed by intraoperative ultrasonography, and the resection was completed safely. The gross examination of the resected specimen revealed an ulcer scar at the primary tumor site. The histopathological examination showed no viable tumor cell remnants in the primary tumor, which had a grade 3 histological response, and resection margins were negative. The lymph nodes showed mucus retention only in the anterior superior lymph node of the CHA, indicating the presence of metastasis, but no viable tumor cells remained. The patient commenced 6 months of adjuvant pembrolizumab monotherapy 3 months after surgery. Twenty months after surgery, there was no evidence of recurrence.

Conclusions
Conversion surgery following pembrolizumab monotherapy has a potential utility for the treatment of MSI-high gastric cancer.
Prognostic value of p16, p53, and pcna in sarcoma and an evaluation of immune infiltration
Authors: Cai Dechao , Ma Xiao , Guo Huihui , Zhang Haotian , Bian Ashuai , Yu Haoran , Cheng Wendan 
Published: June 2022

Abstract
Background
p16, p53, and proliferating cell nuclear antigen (pcna) genes play significant roles in many chromatin modifications and have been found to be highly expressed in a variety of tumor tissues. Therefore, they have been used as target genes for some tumor therapies. However, the differential expressions of the p16, p53, and pcna genes in human sarcomas and their effects on prognosis have not been widely reported.

Methods
The Oncomine dataset was used to analyze the transcription levels of p16, p53, and pcna genes, and the gene expression profile interactive analysis (GEPIA) dataset was used to analyze the differential expressions of p16, p53, and pcna. The expression levels of p16, p53, and pcna were further analyzed by Western Blotting. GEPIA and Kaplan–Meier analyses were used to analyze the prognostic value of p16, p53, and pcna. Furthermore, p16, p53, and pcna gene mutations and their association with overall survival (OS) and disease-free survival (DFS) were analyzed using cBioPortal datasets. In addition, genes co-expressed with p16, p53, and pcna were analyzed using Oncomine. The DAVID dataset was used to analyze the functional enrichment of p16, p53, pcna, and their co-expressed genes by Gene Ontology (GO) and Metascape were used to construct a network map. Finally, the immune cell infiltration of p16, p53, and pcna in patients with sarcoma was reported by Tumor Immune Estimation Resource (TIMER).

Results
p16, p53, and pcna were up-regulated in human sarcoma tissues and almost all sarcoma cell lines. Western Blotting showed that the expression of p16, p53, and pcna was elevated in osteosarcoma cell lines. The expression of pcna was correlated with OS, the expression of p16, p53, and pcna was correlated with relapse-free survival, and the genetic mutation of p16 was negatively correlated with OS and DFS. We also found that p16, p53, and pcna genes were positively/negatively correlated with immune cell infiltration in sarcoma.

Conclusions
The results of this study showed that p16, p53, and pcna can significantly affect the survival and immune status of sarcoma patients. Therefore, p16, p53, and pcna could be used as potential biomarkers of prognosis and immune infiltration in human sarcoma and provide a possible therapeutic target for sarcoma.
Effects of COVID-19 lockdown on weight in a cohort of allergic children and adolescents
Authors: Brindisi Giulia , Di Marino Vincenza Patrizia , Olivero Francesca , De Canditiis Daniela , De Castro Giovanna , Zicari Anna Maria , Anania Caterina 
Published: June 2022

Abstract
Background
COVID-19 lockdown caused sudden changes in people’s lifestyle, as a consequence of the forced lockdown imposed by governments all over the world. We aimed to evaluate the impact of lockdown on body mass index (BMI) in a cohort of allergic children and adolescents.

Methods
From the first of June until the end of October 2020, we submitted a written questionnaire to all the patients who, after lockdown, carried out a visit at the Pediatric Allergy Unit of the Department of Mother-Child, Urological Science, Sapienza University of Rome. The questionnaire was composed by 10 questions, referring to the changes in their daily activities. Data were extrapolated from the questionnaire and then analyzed considering six variables: BMI before and BMI after lockdown, sugar intake, sport, screens, sleep, and anxiety.

Results
One hundred fifty-three patients agreed to answer our questionnaire. Results showed a statistically significant increase in the BMI after lockdown (20.97 kg/m2 ± 2.63) with respect to the BMI before lockdown (19.18 kg/m2 ± 2.70). A multivariate regression analysis showed that the two variables that mostly influenced the increase in BMI were sleep and anxiety.

Conclusions
For the analyzed cohort of allergic children and adolescents we obtained significant gain in BMI as consequences of lockdown, which can be explained by many factors: high consumption of consolatory food, less sport activities, more time spent in front of screens, sleep alteration associated with increased anxiety. All these factors acted together, although sleep alteration and increased anxiety were the most influential factors that led to the worsening or the onset of weight gain, creating the basis for future health problems.