bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Anlotinib and PD-1/L1 Inhibitors as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer Patients who Have Achieved Stable-Disease After First-Line Treatment with Chemotherapy and Immunotherapy: A Retrospective Study
Authors: Peng Yi , Wu De , Tang Jing , Li Xiaobing 
Published: February 2025

Objective To develop personalized treatment strategies for maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Materials and Methods We analyzed data from ES-SCLC patients who achieved stable disease (SD) following initial chemotherapy combined with immunotherapy. These patients subsequently received maintenance therapy (MT) with a combination of anlotinib and PD-1/L1 inhibitors. The primary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Results Preliminary findings suggest that this regimen is highly effective, with a median PFS of 6 months and OS of 13.5 months, alongside a DCR exceeding 60%. Subgroup analysis revealed enhanced efficacy in patients with fewer than three metastatic sites and those who experienced hypertension, proteinuria, or hand-foot syndrome during MT. Mechanistic studies showed a notable increase in the proportion of CD8+ T cells in the peripheral blood post-MT, correlating with improved outcomes. These findings imply that the therapeutic effect of MT may be partly due to the direct activation of CD8+ T cells, producing a synergistic anti-tumor response. Despite the prevalence of AEs, AEs were generally manageable, underscoring anlotinib’s potential in this context. Conclusion The combination of anlotinib and PD-1/L1 inhibitors offers promising efficacy and manageable AEs in MT, making it a viable option for ES-SCLC patients who achieve SD post-initial therapy. These results justify further prospective studies to validate this approach.
Derivation and Validation of Risk Score Including Nutritional Status Among Patients With Chronic Limb-threatening Ischemia: Insight From I-PAD NAGANO Registry
Authors: Okina Yoshiteru , Ueki Yasushi , Kato Tamon , Miura Takashi , Oyama Yushi , Hashizume Naoto , Yokota Daisuke , Taki Minami , Senda Keisuke , Wakabayashi Tadamasa , Fujimori Koki , Karube Kenichi , Sakai Takahiro , Sunohara Daisuke , Nomi Hidetomo , Kanzaki Yusuke , Machida Keisuke , Kashiwagi Daisuke , Saigusa Tatsuya , Ebisawa Soichiro , Okada Ayako , Motoki Hirohiko , Kuwahara Koichiro 
Published: February 2025

Purpose: Geriatric nutritional related index (GNRI) is a simple and well-established screening method of nutritional status. We aimed to develop and validate a scoring system including GNRI to predict long-term outcomes in patients with chronic limb-threatening ischemia (CLTI) undergoing endovascular treatment (EVT). Materials and methods: Patients undergoing EVT for symptomatic LEAD from August 2015 to August 2016 were enrolled into the I-PAD NAGANO registry, a prospective, multicenter, observational registry. We identified predictors of amputation-free survival (AFS) at 5 years using Cox proportional hazards regression and developed a risk scoring system. The predictive performance of the risk score was assessed. Results: A total of 126 patients with CLTI were analyzed. Cox multivariate analysis revealed GNRI score <92 points, ≥72 years of age, hemodialysis, heart failure, and anemia to be significant predictors. We developed a 5-item risk score (I-PAD CLTI score) assigning points to each factor based on the magnitude of association with AFS at 5 years. The I-PAD CLTI score showed a c-index of 0.80 for 5-year AFS. Patients with high score (≥7 points, n=50) had an increased risk of AFS at 5 years compared with those with low score (<7 points, n=68) (26.5% vs 72.1%, p<0.001). Conclusion: A simple 5-item risk score including nutritional status showed reasonable discriminative and prognostic ability for long-term AFS among patients with CLTI. Clinical Impact The I-PAD CLTI score, a simple five-item risk score including nutritional status determined by geriatric nutritional related index, showed reasonable discriminative and prognostic ability for long-term amputation free survival among patients with chronic limb-threatening ischemia. This risk score may be useful for clinicians to accurately predict patient’s prognosis and thus identify high-risk patients who may derive the greater clinical benefit from more intensive risk modification. Further research is required to test the clinical utility of risk-score-based treatment approach to improve the prognosis of patients with chronic limb-threatening ischemia.
Assessing the Role of Nasal Irrigation in Chronic Otorrhea in Children With Tympanostomy Tubes
Authors: Kulasek Michal , Mercier Erika , Bergeron Mathieu 
Published: February 2025

Importance Nasal irrigation (NI) is effective in the treatment of sinonasal disease; however, its efficacy in treating otologic conditions is undetermined. Chronic otorrhea (CO) is an important complication in children with tympanostomy tubes (TT), requiring additional treatment. Objective Determine potential factors of NI that put children with TT at risk of developing CO. Study design Case-control study. Setting Single tertiary level of care pediatric hospital. Participants Consecutive patients under the age of 18 with bilateral TT presenting between June and September 2023 were selected. Intervention All patients in this study used NI. Main outcome measures The main outcome was the development of CO, defined as 10 or more consecutive days of ear drainage despite proper treatment. Results Twenty consecutive patients with CO were recruited and compared to 100 consecutive controls without CO. The mean age was similar, with 22.9 ± 18.4 months for the CO group and 25.2 ± 16.4 months for the control group ( P = .59). An immediate discharge occurred more frequently in the CO group (80%) than in the control group (46%, P = .005; OR: 4.70; 95% CI: 1.5-13.5). A fast rate of administration of NI was more prevalent in the CO group (75%) compared to the control group (51%, P = .049; OR: 2.88; 95% CI: 1.0-7.6). TT insertion under local anesthesia occurred more frequently in the CO group (45%) than in the control group (22%, P = .03; OR: 2.9; 95% CI: 1.1-7.4). No statistical difference was found between groups in the frequency and volume of NI. No patients with CO used a small volume of NI (≤5 mL). Conclusion and relevance A fast rate of administration of NI was correlated with an increased risk of CO. Patients should be encouraged to apply gentle pressure as it could potentially prevent this complication.
A Performance-Based Adaptation Index for Automated Insulin Delivery Systems
Authors: Diaz C. Jenny L. , Colmegna Patricio , Pryor Elliot , Breton Marc D. 
Published: February 2025

Background: Automated insulin delivery (AID) algorithms can benefit from tuning of their aggressiveness to meet individual needs, as insulin requirements vary among and within users. We introduce the Performance-Based Adaptation Index (PAI), a tool designed to enable automatic adjustment of an AID system aggressiveness based on continuous glucose monitoring (CGM) metrics. Methods: PAI integrates two CGM-based metrics—one for hypoglycemia and another for hyperglycemia exposure—over a previous time window into a single index ([Formula: see text]). We propose two methods to compute [Formula: see text]: one based on time in range (TIR, 70-180 mg/dL), and the other on glycemic risk indices. Using [Formula: see text], we developed a multiplicative strategy to adjust the AID system’s aggressiveness, accounting for situations where [Formula: see text] cannot be reliably calculated. The feasibility of this method was assessed in-silico using the UVA/Padova Type 1 Diabetes Simulator and our full closed-loop algorithm (UVA-model predictive control (MPC)) across five scenarios: optimal tuning (baseline), conservative and aggressive tunings, and temporary and permanent changes in insulin needs. Glycemic outcomes were evaluated from the simulated glucose traces. Results: Negligible performance variations were observed in the baseline scenario. For the conservative scenario, adjusting [Formula: see text] improved TIR (35.1% vs 71.8%) and increased total daily insulin (32.1 U vs 41.2 U). Conversely, for the aggressive scenario, it reduced hypoglycemia exposure (TBR: 2.6% vs 1.4%) and overall insulin usage (45.6 U vs 43.0 U). Conclusion: In-silico results demonstrated the safety and efficacy of using PAI to automatically tune the UVA-MPC controller, achieving TIR values above 70% under fully closed-loop conditions and across various physiological states. Clinical validation of these results is warranted.
Ratio of non-protein calories to grams of amino acids and amino acid blood levels in preterm infants receiving parenteral nutrition
Authors: Huston Robert K , Clark Reese H , Chace Donald H 
Published: February 2025

Background Studies evaluating the optimal intake of amino acids for preterm infants have often not considered the effect of the non-protein calorie to grams of amino acids ratio (NPKcal:g AA) in parenteral nutrition solutions. The objectives of this study were to document the ratio in a group of preterm infants and explore any associations of the ratio to AA and acylcarnitine levels. Methods This was descriptive cohort study of data collected from a previously published prospective study evaluating the influence that gestational age had on amino acid and acylcarnitine profiles in preterm infants ≤31 weeks postmenstrual age. Acylcarnitine and AA levels on day of life 7 of three study groups, based upon terciles of the NPKcal:g AA, who were receiving minimal enteral feedings and an enterally fed comparison group were measured. Growth velocities and changes in z-scores were also evaluated. Results NPKcal:g AA terciles were: 6.3–17.6:1 (low, N = 153), 17.7–21.2:1 (mid, N = 150), and 21.3–36.2:1 (high, N = 159). Higher levels of ornithine, citrulline, blood urea nitrogen, isovalerylcarnitine + methylbutyrylcarnitine, and octenoylcarnitine were found in the low versus the high group. From day 1–42 of life, the low group had a lower head circumference (HC) growth velocity and the low and mid groups had more negative HC changes in z-scores versus the enteral group. Conclusions This study suggests that preterm infants may receive parenteral nutrition solutions containing inadequate energy to prevent oxidation of administered AA. The impact of inadequate non-protein caloric intake needs to be considered when evaluating growth and outcomes in nutritional studies of VLBW infants.
Care partner experience with telepresence robots in long-term care during COVID-19 pandemic
Authors: Hu Grace , Wong Joey , Ren Lily Haopu , Kleiss Sarah , Berndt Annette , Wong Lily , Hussein Ali , Ahmed Nazia , Mann Jim , Hung Lillian 
Published: February 2025

Objective As people living with dementia move into long-term care (LTC), their care partners face a difficult role change from primary caregiver to visitor, losing a significant degree of control and direct care involvement. The COVID-19 pandemic exacerbated these challenges with health risks, changing care home protocols, and government policies. To help address these challenges, this study aimed to investigate the experiences of care partners who used telepresence robots to maintain contact with and care for their loved ones during the pandemic. Methods This study was guided by the Collaborative Action Research (CAR) approach. Along with interdisciplinary researchers and trainees, our team included patient and family partners as co-researchers throughout the project. We conducted semi-structured interviews with 20 care partners who used the robots in five urban Canadian LTC homes between May 2021 and August 2023. Results Thematic analysis identified four key themes characterizing their experiences using the robot: (a) decreases care partner burden, (b) facilitates care partner–staff relationship, (c) creates relational autonomy, and (d) expands the scope of what is possible. Conclusion The results of the study suggest that telepresence robots can play a useful role in enhancing the caregiving experience for informal care partners in multifaceted ways. Care partners reported positive benefits of having the robot assist their virtual visits. However, further research is needed to determine the sustainability of robot implementation among diverse geographic regions and care home compositions.
China's National Education Conference Matters: Major Education Discursive Blueprinting in 2024
Authors: Hou (侯滟斯) Yansi 
Published: February 2025

Purpose This study aims to analyze the blueprint for China's future education development outlined in China's National Education Conference of September 2024, and to examine the role of conference speeches in shaping China's education policymaking. Design/Approach/Methods This study thematically analyzed both the conference speech and the related press releases. Findings Regarding the speech content, five key tasks outlined in the conference speeches for building a strong education system by 2035 were identified. These tasks address the public's demand for high-quality education and the needs of national development. Regarding the speech structure, the conference speeches were structured into four main parts, each serving a distinct function in shaping education policy. Originality/Value This study contributes to a deeper understanding of China's recent policy directions for education development. It also sheds light on the discursive blueprinting function of conference speeches in China's education policymaking process.
Inhaled nitric oxide for the treatment of COVID–19: an open-label, parallel, randomised controlled trial
Authors: Friedrich Frederico , Cypel Marcelo , Michaelsen Vinicius Schenk , Brum Marcos Otávio Antunes , Ramos Fabiano , Marco Roberta , Chatkin Gustavo , Grun Lucas Kich , dos Santos Letícya Simone Melo , Santos Amanda Paz , Fernandes Morgana Thaís Carollo , Paungartner Luciana Medeiros , Maranghello Marcelo Scheffer , Lantmann Caroline , Eggers Gustavo , Sanches Gustavo Duenhas , Marinovich Daniel , Rosa Regis Goulart , Barbé-Tuana Florencia María , Jones Marcus Herbert 
Published: February 2025

BackgroundInhaled nitric oxide (iNO) in high concentration inhibits SARS-CoV-2 replication in epithelial cells and may prevent severe disease in hospitalized patients. To evaluate safety and efficacy of inhaled nitric oxide 160 ppm on supplemental oxygen in patients hospitalized with COVID-19.MethodsWe conducted an open-label, randomized clinical trial in hospitalized patients with COVID-19 receiving supplemental oxygen. Patients were randomly assigned to receive iNO for 6 h in addition to standard of care. The primary safety endpoint was assessed by incidence of adverse events (AEs). The secondary efficacy endpoint was the number of days free of supplemental oxygen within 15 days after randomization.ResultsFifty-five patients were enrolled, 27 in the iNO group and 27 in the control group, and one patient was excluded. No adverse events occurred with the inhalation of NO. Number of days free of supplemental oxygen (median, IQR) was 11 (8.0 to 13.0) in the iNO group and 8 (2.5 to 10.5) in the control group; p=0.044. The iNO group had a shorter length of hospital stay, 4.5 days (3.0 to 6.3) compared to 7.0 days (6.0–10.0) in the control group; p= 0.004. Clinical score was lower in the iNO group on days 3 and 5 (p=0.010 and p=0.033). The number of patients weaned from ventilatory support on day 3 was higher in the iNO group (n=9[33%]) when compared to controls (n=1[4%]); p= 0.005. Respiratory failure and mortality did not differ between the groups.ConclusionThe iNO treatment was well-tolerated and safe. Among adults hospitalized for COVID-19, iNO 160 ppm for 6 h increased the number of days free from supplemental oxygen, shortened the days of ventilatory support, the length of hospital stay and improved the clinical score.Clinical trial registration:ensaiosclinicos.gov.br, Identifier: RBR-8nfx26
Deupirfenidone (LYT-100) in post-acute sequelae of SARS-CoV-2 with respiratory complications
Authors: Kulkarni Tejaswini , Santiaguel Joel , Aul Raminder , Harnett Mark , Krop Julie , Chen Michael C. , Graham Camilla S. , Maher Toby M. 
Published: February 2025

IntroductionThe pathophysiology of respiratory complications in post-acute sequelae of SARS CoV-2 infection (PASC) is poorly understood but a high incidence of progressive pulmonary fibrosis was anticipated. Deupirfenidone (LYT-100) is a selectively deuterated form of pirfenidone which retains antifibrotic and anti-inflammatory activity but with improved tolerability. This study evaluated the safety and efficacy of deupirfenidone in PASC patients with respiratory complications.MethodsGlobal, double-blind, randomized placebo-controlled study evaluating deupirfenidone 750 mg BIDversusplacebo for 3 months in PASC patients with respiratory complications following hospitalization for acute COVID-19 infection severe enough to necessitate supplemental oxygen (NCT04652518).Results185 patients were randomized and treated (95 deupirfenidone, 90 placebo), with 177 included in the modified intention-to-treat population. Mean age was 54.5 years, 62.7% male, and 10.7% had prior mechanical ventilation. Six-minute walk distance improved across both arms between baseline and Day 91 (deupirfenidone 44.3m (95% CI 24.8, 63.8)versusplacebo 48.8m (95% CI 29.2, 68.4); p=0.70). Most common treatment-emergent adverse events (TEAEs) for deupirfenidoneversusplacebo included nausea (9.5%versus1.1%), upper abdominal discomfort (5.3%versus2.2%) and dyspepsia (6.3%versus1.1%). TEAEs leading to study drug discontinuation were 11.6% for deupirfenidoneversus4.4% for placebo. Discontinuations considered at least possibly related to deupirfenidone were 8.6%versus2.4% for placebo.DiscussionMajority of the patients with PASC and respiratory complications showed significant improvement over 91 days irrespective of treatment assignment. Deupirfenidone was well-tolerated, with low rates of TEAEs, that support further investigation in patients with IPF.
Endosperm culture-based allotriploid hybrid production from an interspecific cross of Haemanthus spp.: new insights into polyploidization and hybridization
Authors: Nakano Arisa , Mii Masahiro , Hoshino Yoichiro 
Published: February 2025

Abstract

Background
Allopolyploid plants are valuable for plant breeding because they have the advantage of polyploidization and hybridization, such as increased vigor and adaptability. Although biparental triploid endosperms have the potential to be used to produce allotriploid plants, the approach remains largely unexplored. Therefore, this study aimed to produce allotriploid plants from the endosperms of interspecific crosses between Haemanthus pauculifolius and H. albiflos.

Results
Precisely identified embryo and endosperm pairs were used. Embryos were grown on half-strength Murashige and Skoog (MS) medium, and endosperms from interspecific crossing were cultured to induce callus formation and shoot regeneration, which then developed into plantlets. MS medium supplemented with 4-amino-3,5,6-trichloropicolinic acid (picloram) and 6-benzylaminopurine (BAP), or 2,4-dichloro phenoxy acetic acid (2,4-D) and BAP were used for callus induction, and callus formation rates were measured. Flow cytometry, karyotyping, and Sanger sequencing of the nuclear internal transcribed spacer (ITS) region, chloroplast (trnL-trnF region, matK gene), and mitochondrial (nad1 gene) DNA were performed on plantlets derived from embryos and endosperms, along with their parental plants. In this study, a total of 18 pairs of diploid and triploid plantlets were obtained from the embryo and endosperm, respectively. Callus formation rates were significantly higher on media with picloram and BAP compared to 2,4-D and BAP. ITS sequencing and karyotype analyses detected that all the 16 pairs of plantlets analyzed were hybrids, indicating that most endosperm-derived plantlets were allotriploid with a parental chromosome ratio of 2:1 (maternal: paternal). In addition, chloroplast DNA sequencing revealed maternal inheritance in the endosperm-derived plantlets, consistent with embryo-derived plantlets.

Conclusions
This study is the first to demonstrate the production of allotriploid hybrid plants through endosperm culture using seeds from interspecific crosses, as supported by cellular and genetic analyses. Additionally, the study established a novel system for simultaneously producing diploid and allotriploid hybrids from a single seed, providing valuable materials to study the effects of polyploidization and hybridization in allopolyploid plants. These findings contribute to plant breeding strategies and advance our understanding of hybridization, polyploidization, and allopolyploid plant development.
Physical activity and motivational readiness for physical activity behavior change in adults with non-communicable diseases in Germany: a trend analysis of two cross-sectional health surveys from the German GEDA study 2014/2015 and 2019/2020
Authors: Wenz Benjamin , Graf Jonathan , Sudeck Gorden , Geidl Wolfgang , Manz Kristin , Jordan Susanne , Teti Andrea , Gabrys Lars 
Published: February 2025

Abstract

Background
Physical activity (PA) is a cornerstone in maintaining a healthy lifestyle as well as in the prevention and rehabilitation of non-communicable diseases (NCD). First analysis of PA showed lower activity rates in adults with NCD compared to the general population. To improve health monitoring and to address World Health Organization (WHO) recommendations to systematically identify and track efforts to reduce inequalities in PA participation, trend analysis of PA in adults with NCD was performed for the period 2014/15 to 2019/20 for Germany. Furthermore, motivational readiness for PA behavior change was analysed based on the transtheoretical model (TTM).

Methods
Based on two population-based cross-sectional health surveys (GEDA 2014/15-EHIS and GEDA 2019/20-EHIS) for Germany (N = 46,724), the prevalence of meeting WHO PA guidelines was analysed for adults with certain NCD compared to the general population. PA was assessed by self-report via the European Health Interview Survey– Physical Activity Questionnaire (EHIS-PAQ). Trend analyses and logistic regression models were performed to calculate disease specific Odds Ratios (OR) for fulfilment of PA recommendations. Motivational readiness for PA was assessed with the stages of change according to the TTM with data of GEDA 2014/15-EHIS.

Results
Reporting any NCD is associated with lower fulfilment of health-enhancing aerobic PA in both surveys for almost all NCD, with lowest levels among adults reporting stroke, type 2 diabetes mellitus, chronic obstructive pulmonary disease, obesity and coronary heart disease. Sufficient muscle-strengthening was higher in adults with musculoskeletal diseases like osteoarthritis, lower back pain and neck pain compared to adults without these diseases. The prevalence of meeting WHO PA recommendations among adults with NCD remains at a low level. Sufficient health-enhancing aerobic PA tend to decrease in adults with NCD from 2014/15 to 2019/20, while sufficient muscle-strengthening increased in the same period. Motivational readiness for PA is lower for most adults with NCD, compared to the general adult population.

Conclusion
Lower rates of WHO PA recommendation fulfilment is recognized for most NCD groups compared to the population without NCD for both surveys, but the proportion of adults with NCD who meet the WHO PA recommendations differ widely between NCD groups. A positive trend from 2014/15 to 2019/20 can only be seen for adults with osteoarthritis. Based on our findings the implementation of PA promotion particular with regards to motivational readiness and disease specific PA measures is strongly recommended to improve prevention and ambulatory health care for adults with NCD.