bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase 3 trial of total neoadjuvant therapy (induction chemotherapy, neoadjuvant chemoradiation, neoadjuvant chemotherapy, and surgery) vs. standard long-term chemoradiation therapy (neoadjuvant chemoradiation, surgery, and adjuvant chemotherapy) in locally advanced rectal cancer
Authors: Foroughi Freshte , Javadinia Seyed Alireza , Salek Roham 
Published: December 2024

PurposeThe management of rectal adenocarcinoma has evolved during the last decade, shifting from a conventional neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy in all cases to a total neoadjuvant approach, especially in locally advanced tumors when a sphincter-sparing surgery has been planned. However, the exact indications and the neoadjuvant regimen with the highest response remain unresolved. We aimed to assess whether administering neoadjuvant chemotherapy before and after preoperative chemoradiotherapy could increase the pathological complete response (pCR) rates.MethodsWe conducted a phase 3, multicenter, randomized trial at four hospitals in Iran. Adult patients with a newly diagnosed, biopsy-proven, locally advanced non-metastatic rectal adenocarcinoma with an ECOG performance status of 0–2 were randomly assigned (2:2) to either the total neoadjuvant treatment (TNT) or the standard-of-care groups using a block randomized design. Investigators and participants were not masked to treatment allocation and groups. The TNT group received neoadjuvant chemotherapy with FOLFOX6 (intravenous 85 mg/m2 oxaliplatin and 400 mg/m2 leucovorin, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2,400 mg/m2 over 46 h every 14 days for four cycles before and four cycles after chemoradiotherapy), chemoradiotherapy (50.4 Gy during 28 fractions and 800 mg/m2 concurrent oral capecitabine twice daily 5 days per week), and total mesorectal excision. The standard-of-care group received neoadjuvant chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (eight cycles). The primary endpoint was the pathological complete response. Safety analyses were conducted on treated patients.ResultsOverall, 25 and 27 patients were enrolled in the TNT and standard-of-care groups, respectively. Both groups were similar in terms of gender, age, and tumor differentiation. The tumors in the standard-of-care group were significantly located closer to the anal verge compared with those in the TNT group (9.4 ± 3.7 cm in TNT vs. 6.8 ± 4 cm in standard, p = 0.02). A pCR was reached in 48% (12/25) and 25.9% (7/27) of patients in the TNT and standard-of-care groups, respectively (p = 0.4). The R0 resection rates were identical between the two groups (92% vs. 88.9%, p = 0.3). Moreover, the toxicity rates were similar between the two groups.ConclusionOur results showed that TNT is a safe and feasible treatment approach in patients with rectal cancer and may improve the overall pCR rate compared with standard treatment.Clinical trial registrationhttps://irct.behdasht.gov.ir/trial/65666, identifier IRCT20220723055527N1.
Spontaneous adverse drug reactions reported in a thirteen-year pharmacovigilance program in a tertiary university hospital
Authors: Montané E. , Sanz Y. , Martin S. , Pérez-Mañá C. , Papaseit E. , Hladun O. , De la Rosa G. , Farré M. 
Published: December 2024

ObjectivesWe aimed to assess the characteristics of adverse drug reactions (ADRs) collected in a university hospital.MethodsA retrospective analysis of ADRs spontaneously reported in the Hospital Pharmacovigilance Program database (RutiRAM) over a 13-year period was conducted. The analysis included a description of ADRs [System Organ Class (SOC)] and their seriousness, the drugs involved [level 1 of the Anatomical Therapeutic Chemical (ATC) Classification System], drug-drug interactions, medication errors, drugs ‘under additional monitoring’, positive rechallenge, and the ‘pharmacovigilance interest’ of ADRs. An ADR was considered of ‘pharmacovigilance interest’ when it was serious, and/or produced sequelae, and/or affected the paediatric population, and/or when the suspected drug was ‘under additional monitoring’. Additionally, an exploratory analysis for bivariate associations through an automated method was performed.ResultsA total of 2,148 spontaneous ADRs were registered in the RutiRAM database, with 92.5% recorded by medical doctors. The mean age of cases was 59.2 years (SD 20.9), range 1 day–99 years; 5.7% were paediatric, 46.2% adults, and 48.1% elderly. The drugs most often involved were anti-infectives (ATC group J), mainly amoxicillin-clavulanic acid. ‘Blood system disorders’ were the most frequent SOC ADRs, and skin rashes were the most frequent ADRs. The 63.2% of ADRs were considered of ‘pharmacovigilance interest’. Almost half of ADRs were hospital-acquired, and these were related to medication error; serious ADRs were related to drug-drug interactions and elderly patients, and involved drugs ‘under additional monitoring’ were related to younger ones.ConclusionThis is the first study to overview of ADRs reported in an HPVP over more than a decade. Almost two-thirds of the ADRs collected in the RutiRAM database are of sufficient quality to be classified as ‘pharmacovigilance interest’, and thus can contribute to signal detection and the issuing of drug alerts by pharmacovigilance systems. Analysing ADRs in hospitals contributes to patient safety by implementing relevant actions to prevent medication errors or ADRs, some of which can be applied to other centres.
Association between moderate-to-vigorous physical activity and chronic disease risk in adults and elderly: insights from the UK Biobank study
Authors: Ng Kei Shing , Lian Jie , Huang Fan , Yu Yan , Vardhanabhuti Varut 
Published: December 2024

BackgroundThis study aimed to determine the associations between different intensities of moderate to vigorous physical activity (MVPA) and the incidence of chronic diseases, and to assess the risk levels associated with these activities over time.MethodsA prospective cohort study (UK Biobank Activity Project) with data collected between June 2013 and December 2015 included 59,896 adults (mean age = 59.68; male = 38.03%) free from chronic diseases. Participants were categorized into tertiles based on their weekly MVPA: lowest (&lt;224 min for males, &lt;143 min for females), medium (224–444 min for males, 143–308 min for females), and highest (≥444 min for males, ≥308 min for females), stratified by gender. The mean onset of chronic disease symptoms occurred at 3.57 years, with participants followed up during this period. Wearable accelerometry data were used to quantify MVPA levels.FindingsLowest tertile of MVPA were significantly correlated with increased risks of chronic disease (24%–110% increased risk) based on odds ratios (ORs), with dose-response relationship observed. In males with the lowest tertile of MVPA, significant associations were identified with type 2 diabetes mellitus (T2DM) (OR = 1.90; CI: 1.44–2.51), neurodegenerative disease (OR = 1.80; CI: 1.19–2.71), metabolic syndrome (OR = 1.34; CI: 1.18–1.53), hypertension (OR = 1.27; CI: 1.12–1.44), and atherosclerotic cardiovascular disease (ASCVD) (OR = 1.24; CI: 1.03–1.49). In females, the lowest tertile of MVPA levels were associated with increased risks of neurodegenerative disease (OR = 2.10; CI: 1.36–3.24), T2DM (OR = 1.88; CI: 1.37–2.58), cerebrovascular disease (OR = 1.61; CI: 1.12–2.29), ASCVD (OR = 1.58; CI: 1.23–2.03), metabolic syndrome (OR = 1.49; CI: 1.32–1.69), and hypertension (OR = 1.44; CI: 1.29–1.61). Longitudinally, the lowest tertile of MVPA in males showed elevated risks for neurodegenerative disease (HR = 2.13; CI: 1.24–3.66), T2DM (HR = 1.83; CI: 1.30–2.57), hypertension (HR = 1.33; CI: 1.15–1.53), metabolic syndrome (HR = 1.32; CI: 1.14–1.54), and ASCVD (HR = 1.29; CI: 1.03–1.61). In females, the lowest tertile of MVPA was associated with similar risks for ASCVD (HR = 1.59; CI: 1.16–2.20), T2DM (HR = 1.57; CI: 1.08–2.29), hypertension (HR = 1.53; CI: 1.34–1.74), and metabolic syndrome (HR = 1.50; CI: 1.29–1.73).ConclusionUsing wearable accelerometry data, this study demonstrated the quantifiable risks of chronic diseases and their development, highlighting the importance of MVPA.
Animal-Assisted Therapy in palliative care: a scoping review
Authors: Palomino-Lázaro Laura , Rueda-Extremera María , Cantero-García María 
Published: December 2024

BackgroundAnimal-assisted therapy (AAT) is increasingly recognized as beneficial in palliative care, aiming to enhance the well-being of terminally ill patients. Palliative care focuses on holistic support for physical, emotional, social, and spiritual needs. AAT uses animal interactions to alleviate symptoms such as pain, anxiety, and depression, promoting social engagement and emotional comfort. This review assesses AAT’s effectiveness in enhancing the quality of life for palliative care recipients.AimSynthesizing literature on AAT in palliative care, the review examines its impact on physical symptoms, emotional well-being, social interactions, and overall comfort. By analyzing diverse studies, it aims to elucidate AAT’s therapeutic potential and identify research gaps.DesignScoping review.Data sourcesSearches in PubMed, ProQuest, Psychology Database, and Scopus identified relevant studies evaluating AAT interventions in palliative care. Data extraction focused on study characteristics, participant demographics, AAT interventions, and reported outcomes.ResultsStudies consistently report positive outcomes of AAT in palliative care, including reduced pain, anxiety, depression, and improved mood and well-being. AAT also enhances social interactions and emotional support, albeit with variations in study designs.ConclusionAAT holds promise for improving quality of life in palliative care by addressing physical, emotional, and social needs. Future research should standardize methodologies, explore mechanisms of action, and optimize AAT integration into comprehensive palliative care strategies.
The relationship between physical exercise and depressive symptoms in college students: the mediating role of rumination
Authors: Zhu Bei , Liu Qing , Jia Shuqi , Wang Xing , Man Qin 
Published: December 2024

ObjectiveThis study aims to explore the correlation between physical exercise, rumination, and depressive symptoms in college students, as well as to investigate the potential pathways through which physical exercise may impact depressive symptoms. This exploration offers valuable insights for the development of clinical exercise interventions.MethodsA cross-sectional study design was employed, with 2,902 participants recruited via convenience sampling. Structural equation modeling was utilized to explore the relationship between physical exercise and depressive symptoms in college students.Results1) Statistically significant differences were observed between depressed and non-depressed college students in terms of rumination, symptom rumination, reflective pondering, and compulsive meditation (all P &lt; 0.05); 2) Physical exercise was found to negatively predict symptom rumination (B=-0.083, P&lt;0.001), compulsive thinking (B=0.034, P&gt;0.05), reflective pondering (B=-0.038, P&lt;0.01), and BDI-II scores (B=-0.103, P&lt;0.001). Symptom rumination positively predicted BDI-II scores (B=0.648, P&lt;0.001), while compulsive thinking and reflective pondering were found to predict BDI-II scores positively (B=0.028, P&gt;0.05) and negatively (B=-0.041, P&gt;0.05), respectively. 3) Physical exercise exerted a direct effect of 59.09% on BDI-II scores (B: -0.065, 95% CI -0.104, -0.028), indicating that higher levels of physical exercise were associated with lower BDI-II scores. The coefficients for duration, intensity, and frequency were statistically significant (all P &lt; 0.05), with intensity and frequency exhibiting higher path coefficients. Rumination, as a latent variable, mediated 40.91% of the indirect effect (B: -0.045, 95% CI -0.077, -0.015), with symptom rumination emerging as a statistically significant pathway (P &lt; 0.05).ConclusionRumination may mediate the relationship between physical exercise and depressive symptoms, with varying mediating effects across different dimensions of rumination. The intensity and duration of physical exercise exert a stronger influence.
Interventions aiming to improve menstrual, sexual, reproductive, and mental health among out-of-school girls: a systematic review
Authors: Farquharson Karinn , Quinn-Savory Alexandra , Zulaika Garazi , Mason Linda , Nungo Susan , Nyothach Elizabeth , Unger Holger , Sivakami Muthusamy , Spinhoven Philip , Phillips-Howard Penelope A. , van Eijk Anna Maria 
Published: December 2024

PurposeOut-of-school adolescent girls (OoSGs) can lack education on menstrual, sexual, reproductive, and mental health (SRMH) and be more vulnerable to SRMH harms. Targeted interventions could reduce these risks. We assessed interventions and their effectiveness among OoSGs globally.MethodsSix online databases were searched for interventional studies targeting SRMH problems in OoSGs. Two coders independently abstracted data from each eligible study, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We summarized results using forest plots.ResultsA total of 1,244 studies were screened; eight studies with sufficient information on SRMH outcomes were included (9,084 OoSGs, range 100–3,026 per study, overall study quality low-to-moderate). Six were educational programmes, and two were cash interventions; no study was directed at mental health. Participants were recruited through village census, outreach workers, and work locations. Some improvements were seen in indicators of SRMH knowledge (four studies), attitudes (one study), and risky sexual behaviors (four studies); however, no reduction was seen in human immunodeficiency virus or herpes simplex virus-2 incidence (two studies).DiscussionThis review suggests that programmes can improve OosG’s SRMH knowledge, attitudes, and practices and can be delivered in low resource contexts. Effective interventions are needed to support OoSGs, including interventions focusing on SRMH support incorporating elements of cash-transfer, and comprehensive sexual education, and to aid local policy and programming.
Silent signals: how N-acyl homoserine lactones drive oral microbial behaviour and health outcomes
Authors: Zhao Zelda Ziyi , Guo Lifeng , Shan Wenwen , Chu Chun Hung , Zhang Jing 
Published: December 2024

BackgroundN-acyl homoserine lactones (AHLs) are small signalling molecules predominantly secreted in Gram-negative bacteria.ObjectiveThe aim is to provide a comprehensive overview of AHLs in oral health.MethodsTwo independent researchers conducted a systematic search of English language publications up to 30 June 2024 in PubMed, Scopus and Web of Science. They screened the title and abstract to retrieve and map out relevant studies on AHLs in oral health, in order to identify key concepts, gaps in knowledge, and areas for further research.ResultsThis study identified 127 articles and included 42 articles. These studies identified AHLs in human oral samples like saliva, dental plaque, tongue swabs, and dentin caries. The studies also found that AHLs regulate cell-to-cell communication of bacteria (quorum sensing) in mature biofilm fostering the production of virulence factors that damage the immune system. AHLs also exert biological effects on human cells and influence oral diseases such as periodontitis and oral squamous carcinoma. Researchers developed AHL inhibitors to interfere with the quorum sensing process and interrupt the communication between bacteria. These inhibitors can be classified into three main categories based on their mechanisms of action to AHLs: AHL synthesis disruptors, AHL competitive inhibitors and AHL enzymatic degraders. These AHL inhibitors can be important tools in the fight against bacterial infections, particularly those caused by Gram-negative bacteria.ConclusionThe literatures indicate that AHLs, as quorum sensing molecules, influence bacterial communication. AHLs have a significant impact in bacterial pathogencity and play a potential role in the pathogenesis of oral diseases. Researchers have developed AHL inhibitors to disrupt bacterial quorum sensing, preventing bacteria from forming biofilms or expressing virulence factors. These studies on AHLs represent a new research direction to develop novel therapeutic strategies to manage oral diseases.
Evaluation of the Planet constellation’s daily coverage for estimating the number of vessels at Daikoku Pier automobile terminals, Port of Yokohama, Japan
Authors: Murata Hiroki , Imura Naoto , Nishinari Katsuhiro 
Published: December 2024

The automotive industry is a key industry in Japan; however, the worker shortage has affected transportation in the ports and harbors, including that of automobile shipping. Automobiles are shipped using roll-on/roll-off (Ro-Ro) ships. When many Ro-Ro ships dock at the same time, problems related to the shortage of workers and limited storage space for automobiles are exacerbated, decreasing transportation efficiency. The spatial resolution and temporal frequency of satellite imagery have improved with Planet Labs satellite constellations making daily observations of the Earth’s surface. Moreover, the field of remote sensing is seeing an increasing number of logistic applications. As such, this study aimed to evaluate the Planet constellation’s daily coverage for estimating the actual usage of seaport automobile terminals by counting the number of vessels in each image. Here, we focused on Daikoku Pier automobile terminals in the Port of Yokohama, Japan, from 2018 to 2023. Images were classified by visual interpretation into three categories: data available for analysis, data not available for analysis due to cloud, and lack of data. Over the 6-year period, 37.1% of the data were classified as data available for analysis; 21.2%, data not available for analysis due to cloud; and 41.8%, lack of data. The visual inspection survey was conducted twice, with an agreement rate of 90.5% between the two surveys. The number of vessels were then counted two times from “data available for analysis” class, and the discrepancies were corrected. This result was compared to the actual schedule information and the accuracy was 89.0%. The number of vessels docked at the same time tended to be lower in August than in other months. The days from the 25th to 31st tended to have a higher number of vessels than other days, regardless of the month. It seems difficult to use Planet constellation for daily site progress management because data was sometimes available 1 day per month. Planet constellation can be useful in estimating the actual usage through long-term monitoring. We expect that the results of this study will be helpful to those interested in using daily satellite imagery for improving work conditions and efficiencies.
Long-term stability of N-heterocyclic carbene (NHC) functionalized organic electrochemical transistor (OECT) for biosensing applications
Authors: Fan Jiaxin , Kang Seongdae , Gupta Manisha 
Published: December 2024

The increasing demand for the rapid identification of various pathogens and disease biomarkers makes it essential to develop selective and reliable biosensors. The three basic components of a biosensor are: (i) the bioreceptor that binds to the target analyte, (ii) the transducer that converts the signal, and (iii) a signal processing circuit. Integrating the biorecognition elements onto the transducer surface is a critical step that governs the selectivity and reliability of biosensors. Here, we present a novel approach for functionalizing aerosol jet-printed organic electrochemical transistors (OECTs) for biosensing applications. Our design utilizes a printed Au gate modified with N-heterocyclic carbene (NHC) linkers for biofunctionalization. NHC was selected due to its excellent stability and high binding affinity with transition metals, facilitating a robust biofunctionalization mechanism. Utilizing the NHC-Au surfaces, we developed OECT-based biosensors that successfully detected the biotin-streptavidin (biotin-SA) binding events as threshold voltage shift (ΔVT) of 193 ± 64 mV, which is approximately three-fold of that for bovine serum albumin (BSA) (62 ± 41 mV), indicating the NHC functionalized OECT-based biosensor is selective towards the target analyte. In addition, the NHC-Au electrode and the printed OECT both remained functional after 24 months of storage at room temperature, with comparable performances (ΔVT = 161 ± 30 mV for SA binding) as the freshly prepared ones, demonstrating outstanding long-term stability. To the best of our knowledge, this is the first study combining NHC and OECT for biosensing and showcasing 24-month long-term stability. Given the versatility of NHCs in forming highly stable covalent bonds with most transition metals, this study is an important demonstration of their application in bioelectronics. Thus, we have shown a prominent biosensor development technology based on carbenes and organic electronics, which can be adapted to various biomolecule detection and biomedical applications. The exceptional stability of the printed OECTs and NHC functionalized gate highlights their potential for long-term biosensing applications, paving the way for reliable bioelectronics.
The impact of mobile-assisted swimming applications on intrinsic motivation and fear reduction in aquatic environments among students in the swimming course
Authors: Alkasasbeh Walaa Jumah , Alawamleh Thekra , Aloran Hasan , Farash Tamara , Orhan Bekir Erhan 
Published: December 2024

IntroductionThis study investigates the impact of mobile-assisted swimming applications on intrinsic motivation and fear reduction in aquatic environments among students enrolled in a swimming course. While technological tools are increasingly integrated into physical education settings, their effects on motivation and psychological barriers such as fear of water remain underexplored.MethodsA total of 69 male and female students enrolled in the “Swimming Education and Training” course participated in the study. The Intrinsic Motivation Scale (IMS) and the Water Fear Assessment Questionnaire (WFAQ) were used to measure intrinsic motivation and water-related fear, respectively, before and after using a mobile-assisted swimming application. Data were analyzed to assess changes in motivation and fear, and potential relationships with demographic variables (gender, academic year, parental swimming experience, and university GPA) were explored.ResultsThe study found no statistically significant differences in intrinsic motivation levels before and after the use of the mobile-assisted swimming application. However, a statistically significant reduction in water fear was observed following the intervention. No significant relationships were found between demographic factors and either motivation or fear reduction.DiscussionThe results suggest that while the mobile-assisted swimming application did not significantly impact intrinsic motivation, it was effective in reducing fear of water among students. This highlights the potential of mobile applications in addressing psychological barriers in aquatic environments, supporting skill acquisition, and enhancing the overall learning experience in swimming courses. The absence of demographic influences suggests that the application's benefits may be broadly applicable across different student groups.