bluuebunny/crossref_metadata_2025_split huggingface dataset:
The burden of left ventricular assist device (LVAD) infections on costs, lengths of stay, antimicrobial consumption and resistance: a prospective case control approach
Authors: Ficinski Matthew , West Jennifer , Glassman Shannon , Wojciechowski Katrina , Gutowski Jennifer , Laguio-Vila Maryrose , Feitell Scott , Lesho Emil 
Published: December 2024

Abstract
Background
Congestive heart failure has reached pandemic levels, and left-ventricular assist devices (LVAD) are increasingly used to treat refractory heart failure. Infection is a leading complication of LVADs. Despite numerous reports (most being retrospective), several knowledge gaps pertaining to the epidemiology and burden of an LVAD-associated infection (LVADi) remain. We sought to address these gaps using a prospective, case-control design.

Methods
All patients who received an LVAD from November 1, 2018 to August 31, 2023 (n = 110) were included and prospectively monitored until death. Data were extracted from clinical encounters and medical records in real-time or near real-time and imported to Excel and REDcap electronic data capture tools. An LVADi was ascertained using definitions from the mechanical circulatory support academic research consortium in conjunction with and the U.S. National Health Safety Network. All meeting those definitions were included as ‘cases.’ Patients with no LVADi were controls. Excess lengths-of-stays (LOS) and direct costs were calculated from billing records using a commercial cost accounting software platform (Strata®, Chicago, IL).

Results
The amount of healthcare contact before implantation and discharge to a rehabilitation or skilled nursing facility instead of home were the primary risks for infection, resulting in mean excesses of 25 hospital and 60 antibiotic-days and $43,000 per event. One-third occurred > 1 year after implantation. 35% developed > 1 infection. Gram-negative, fungal, and antimicrobial-resistant organisms predominated deep or repeat infections. 7.2% developed ≥ 3 infections. Organisms became increasingly antimicrobial resistant with subsequent infections, leading to extensive or pan-drug resistance in 4.5% of patients. The burden of an LVADi was 1862 excess hospital days, 3960 excess antibiotic days, and $3.4 million.

Conclusions
Patients with LVADis had significant increases in costs, LOS, readmissions, and antibiotic usage. Antimicrobial resistance varied directly with the number of repeat infections and antibiotic exposure. Identification of factors associated with LVADi, and quantification of the burden of LVADi can inform prevention efforts and lead to reduced infection rates. As preventing infections in the first place is also important for limiting the emergence of antimicrobial resistance, we offer strategies to avoid LVADis.

Trial registry
Not applicable.
All that glitters is not gold: the impact of the Nutri-score label on food with geographical indication
Authors: Stiletto Alice , Cembalo Luigi , Trestini Samuele 
Published: December 2024

AbstractThe European Union is discussing the introduction of a mandatory front-of-pack label to address the rise in nutrition-related diseases. The Nutri-Score (NS) is the most supported candidate in the EU, despite some controversies exist. Specifically, the policy behind the NS system (i.e., the Farm to Fork Strategy—F2F) appears to conflict with the geographical indication (GI) policy, as the same products (GIs) are promoted for their superior quality by the GI policy and frequently classified as products to be avoided by the NS system. Moreover, the NS system, by encouraging the food industry to reformulate products to improve their nutritional quality, places the GIs in a disadvantageous position, due to their strict product specification. To explore the interactions between these two policies, this paper assesses the effect of the NS on retail prices of both GI and non-GI products in the French market, where this system is widely used. A hedonic price analysis was conducted on 254 raw hams (score D or E) through the estimation of a quantile regression model. Results highlight that the presence of the NS decreases the retail price of raw hams, limited to the high-priced segments. Interestingly, the negative effect is consistent for both GI and non-GI hams, suggesting that the GI label does not mitigate the impact of the NS.
Can people with longstanding bulimia nervosa suffer from severe and enduring eating disorder? A qualitative study
Authors: Robinson Paul H , Guidetti Giulia , Kasriel Jessica , Khawandanah Jomana , Hughes Maxine , Hachem Zeinab 
Published: December 2024

Abstract
Objectives
To interview a series of individuals with bulimia nervosa of longstanding to establish their symptoms and examine the suggestion, using qualitative analysis, that the term “Severe and Enduring Bulimia Nervosa (SEED-BN)” might be appropriate and helpful.

Methods
12 participants with Bulimia Nervosa, one male, were interviewed with the help of an interview guide. Interviews were recorded and transcribed. Transcripts were analysed using Thematic Analysis.

Results
Participants with Bulimia Nervosa described serious problems in many realms, especially social, psychological, family and relationships.

Conclusions
Bulimia nervosa of long duration is associated with many serious symptoms. It seems likely that recognition of long-standing bulimia nervosa as a severe and enduring eating disorder could encourage clinicians and families to pay attention to the wide variety of problems suffered by this group. Further research is required to examine this proposal.
Enhancing social-emotional skills in early childhood: intervention study on the effectiveness of social and emotional learning
Authors: Hosokawa Rikuya , Matsumoto Yuki , Nishida Chizuko , Funato Keiko , Mitani Aki 
Published: December 2024

Abstract
Background
Social and emotional learning (SEL) is crucial for developing skills such as emotional regulation, cooperation, and goal achievement. Deficits in these skills are linked to later academic and behavioral problems. While SEL interventions have been widely implemented internationally, few have been tested in early childhood settings in Japan, and their effectiveness remains unclear. In 2022, the Fun FRIENDS social and emotional learning program was introduced in class units for 4–5-year-olds attending kindergartens and children’s schools in Wakayama Prefecture, Japan. Thus, this study examined the effectiveness of the Fun FRIENDS program in children aged 4–5 years in Japan.

Methods
Fun FRIENDS is based on a cognitive-behavioral approach designed to teach participants how to cope with anxiety and stress, and to develop resilience and confidence. The program consists of 10 weekly sessions of approximately 1 h each. The intervention group comprised 115 children from two facilities, while the control group comprised 93 children from three facilities. Intervention effectiveness was evaluated through changes in externalizing (e.g., aggression, oppositional behavior) and internalizing behaviors (e.g., anxiety, depression), measured using the Strengths and Difficulties Questionnaire. Finally, data from 94 participants in the intervention group and 66 participants in the control group were analyzed.

Results
In the intervention group, externalizing behaviors showed a significant reduction both before and after the intervention and internalizing behaviors also decreased significantly. Conversely, the control group did not exhibit any significant changes in either externalizing or internalizing behaviors before or after the intervention. The effect size for externalizing behaviors in the target group was 0.744, while the effect size for internalizing behaviors was 0.653.

Conclusions
Social and emotional learning programs in classrooms may effectively control problem behaviors in early childhood and prevent school maladjustment. A whole-class approach can reach more children, maximizing the preventive effects. The program can improve academic performance and social adaptation, contributing to the long-term development of psychological health and social skills. Nevertheless, further longitudinal research is required to assess the program’s long-term effects. In summary, strengthening the focus on social-emotional learning in early childhood education policy is key to realizing long-term benefits for child development.
State of the art CRISPR-based strategies for cancer diagnostics and treatment
Authors: Di Carlo Emma , Sorrentino Carlo 
Published: December 2024

AbstractClustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a groundbreaking and dynamic molecular tool for DNA and RNA “surgery”. CRISPR/Cas9 is the most widely applied system in oncology research. It is a major advancement in genome manipulation due to its precision, efficiency, scalability and versatility compared to previous gene editing methods. It has shown great potential not only in the targeting of oncogenes or genes coding for immune checkpoint molecules, and in engineering T cells, but also in targeting epigenomic disturbances, which contribute to cancer development and progression. It has proven useful for detecting genetic mutations, enabling the large-scale screening of genes involved in tumor onset, progression and drug resistance, and in speeding up the development of highly targeted therapies tailored to the genetic and immunological profiles of the patient’s tumor. Furthermore, the recently discovered Cas12 and Cas13 systems have expanded Cas9-based editing applications, providing new opportunities in the diagnosis and treatment of cancer. In addition to traditional cis-cleavage, they exhibit trans-cleavage activity, which enables their use as sensitive and specific diagnostic tools. Diagnostic platforms like DETECTR, which employs the Cas12 enzyme, that cuts single-stranded DNA reporters, and SHERLOCK, which uses Cas12, or Cas13, that specifically target and cleave single-stranded RNA, can be exploited to speed up and advance oncological diagnostics. Overall, CRISPR platform has the great potential to improve molecular diagnostics and the functionality and safety of engineered cellular medicines. Here, we will emphasize the potentially transformative impact of CRISPR technology in the field of oncology compared to traditional treatments, diagnostic and prognostic approaches, and highlight the opportunities and challenges raised by using the newly introduced CRISPR-based systems for cancer diagnosis and therapy.
Unlocking higher methane yields and digestate nitrogen availability in soil through thermal treatment of feedstocks in a two-step anaerobic digestion
Authors: Nyang’au Jared Onyango , El Mahdi Jihane , Møller Henrik Bjarne , Sørensen Peter 
Published: December 2024

Abstract
Background
There is an increasing interest in using lignocellulosic feedstocks for biogas production. Treatment of these feedstocks prior to anaerobic digestion (AD) can enhance their accessibility to microorganisms involved in the process. To improve the digestion of recalcitrant feedstocks and boost biogas yields, many biogas plants now employ two-step AD systems, extending substrate residence times. However, the combined effect of feedstock treatment and two-step AD on methane yield and fertiliser value of digestates are underexplored. This study, therefore, evaluated the effectiveness of thermal treatment (TT) of pre-digested agricultural feedstocks before a secondary AD step on the carbon (C) and nitrogen (N) dynamics of digestates following application to soil. It also investigated the effects of TT on methane yields. Pre-digested feedstock (PDF) was treated at three different temperatures (70 °C, 120 °C and 180 °C) for 60 min, followed by parallel secondary AD steps using lab-scale continuous stirred-tank reactors (CSTR) and a batch test. Thermally treated feedstocks with and without a secondary AD step were applied to soil to study C and N dynamics and turnover for 2 months.

Results
TT at 180 °C increased ultimate CH4 yields by 7.2%; however, it decreased the net mineral N release in soil from 42 to 34% (of N input). Adding a secondary AD step increased the net mineral N release in soil from an average of 39% to 47% (of N input), with the effect of TT levelling off. Moreover, the secondary AD step significantly reduced C mineralisation rates from an average of 37% to 26% (of C applied).

Conclusions
Overall, TT at 120–180 °C can improve biogas yields of recalcitrant feedstocks, but it may lead to the formation of refractory nitrogen compounds resistant to further degradation during AD, potentially resulting in a lower N fertiliser value of digestates.

Graphical Abstract
Relation between magnetopause position and reconnection rate under quasi-steady solar wind dynamic pressure
Authors: Kim Hyangpyo , Connor Hyunju Kim , Zou Ying , Park Jaeheung , Nakamura Rumi , McWilliams Kathryn 
Published: December 2024

AbstractThe lunar environment heliospheric X-ray imager (LEXI) and solar wind–magnetosphere–ionosphere link explorer (SMILE) will observe the magnetopause motion in soft X-rays to understand dayside reconnection modes as a function of solar wind conditions after their respective launches in the near future. To support their successful science mission, we investigate the relationship between the magnetopause position and the dayside reconnection rate by utilizing super dual auroral radar network (SuperDARN) observations and widely used empirical models of magnetopause position (Shue et al. in J Geophys Res 103:17691–17700. https://doi.org/10.1029/98JA01103, 1998 and Lin et al. in J Geophys Res 115:A04207. https://doi.org/10.1029/2009JA014235, 2010). We select three cases when the interplanetary magnetic field rotates during periods of quasi-steady solar wind dynamic pressure. We first estimate the dayside reconnection rate by calculating the electric field along the open–closed magnetic field boundary (OCB) in the OCB moving reference frame. Then, we estimate the magnetopause position near the local noon by inputting NASA OMNI solar wind data into the empirical magnetopause models. The reconnection rate shows anti-correlation with the magnetopause position that it generally increases as the magnetopause located closer to Earth and vice versa. Our result also confirms that the reconnection rate increases as the empirical coupling efficiency between solar wind and the magnetosphere increases.
Graphical abstract
Non-affinity platform for processing knob-into-hole bispecific antibody
Authors: Wang Xiaoyang , Li Min , Li Mengting , Hong Huoyan , Gao Kai , Zhao Puya 
Published: December 2024

AbstractBispecific antibodies hold significant potential as next-generation biotherapeutics owing to their ability to simultaneously bind to two targets. However, the development of bispecific antibodies as biotherapeutics has been hindered by the high levels of byproducts produced, including both high molecular weight and low molecular weight variants. In addition, the inevitable expression of homodimers in host cells presents further obstacles to the commercial development of bispecific antibodies as therapeutics. These byproducts, which share similar physicochemical properties with the target, pose several challenges for downstream purification processes. In this study, we present a non-protein A purification platform that employ a one-step polishing chromatography to purify bispecific antibodies. Mixed-mode Capto adhere resin was used to capture the target protein at pH 7.90 ± 0.10, followed by anion exchange chromatography as a polishing step. Overall, the results of this two-step chromatography purification method demonstrated at final product purity of 98% as assessed by size-exclusion high-performance liquid chromatography (SEC-HPLC) and 98% by reversed-phase-high-performance liquid chromatography (RP-HPLC), with residual host cell proteins controlled at 10 ppm and an excellent recovery rate of approximately 60%. This study presents a non-protein A capture platform, offering a simplified, streamlined, and competitive alternative to conventional affinity chromatography.
Graphical Abstract
Comparative analysis of metabolic characteristics and prognostic stratification of HER2-low and HER2-zero breast cancer using 18F-FDG PET/CT imaging
Authors: Gao Yuan , Yin Lei , Ma Linlin , Wu Caixia , Zhu Xiaojuan , Liu Hongjin , Liang Li , Chen Jinzhi , Chen Yulong , Ye Jingming , Xu Ling , Liu Meng 
Published: December 2024

Abstract
Background
Recent advancements in novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have highlighted the emerging HER2-low breast cancer subtype with promising therapeutic efficacy. This study aimed to comparatively analyze the metabolic characteristics and prognostic stratification of HER2-low and HER2-zero breast cancer using baseline fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging.

Methods
Consecutive patients with newly diagnosed breast cancer who underwent 18F-FDG PET/CT prior to therapy in our hospital were retrospectively reviewed. The relationship between metabolic parameters (maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), total lesion glycolysis (TLG), and metabolic tumor volume (MTV)) in primary lesions and HER2 expression was analyzed. The survival analyses were performed to identify the prognostic factors for disease-free survival (DFS) in patients with HER2-negative (HER2-low versus -zero).

Results
In total, 258 patients (mean age: 54 ± 12 years) were included. In hormone receptor (HR)-positive subgroup, SUVmax and TLR were significantly higher in HER2-low than in HER2-zero (P = 0.045 and 0.03, respectively). But in HR-negative subgroup, there was no significant metabolic difference between HER2-low and HER2-zero (All P > 0.05). The four metabolic parameters were significant predictors of DFS in HER2-negative patients (All P < 0.01), but there was no significant difference in DFS between HER2-low and -zero, regardless of tumor metabolism. Moreover, in HER2-zero patients, the DFS of patients with high metabolism was significantly shorter than that of patients with low metabolism (PSUVmax = 0.002, PMTV = 0.03, PTLG= 0.005, PTLR < 0.001, respectively), but without a similar finding in HER2-low patients.

Conclusion
Our study demonstrated the HR-positive HER2-low breast cancer exhibited a particularity in glucose metabolic profile. Additionally, HER2-zero patients with elevated metabolism were associated with inferior prognosis and warranted careful attention in clinical evaluations.
Revolutionizing treatment for disorders of consciousness: a multidisciplinary review of advancements in deep brain stimulation
Authors: Yang Yi , Cao Tian-Qing , He Sheng-Hong , Wang Lu-Chen , He Qi-Heng , Fan Ling-Zhong , Huang Yong-Zhi , Zhang Hao-Ran , Wang Yong , Dang Yuan-Yuan , Wang Nan , Chai Xiao-Ke , Wang Dong , Jiang Qiu-Hua , Li Xiao-Li , Liu Chen , Wang Shou-Yan 
Published: December 2024

AbstractAmong the existing research on the treatment of disorders of consciousness (DOC), deep brain stimulation (DBS) offers a highly promising therapeutic approach. This comprehensive review documents the historical development of DBS and its role in the treatment of DOC, tracing its progression from an experimental therapy to a detailed modulation approach based on the mesocircuit model hypothesis. The mesocircuit model hypothesis suggests that DOC arises from disruptions in a critical network of brain regions, providing a framework for refining DBS targets. We also discuss the multimodal approaches for assessing patients with DOC, encompassing clinical behavioral scales, electrophysiological assessment, and neuroimaging techniques methods. During the evolution of DOC therapy, the segmentation of central nuclei, the recording of single-neurons, and the analysis of local field potentials have emerged as favorable technical factors that enhance the efficacy of DBS treatment. Advances in computational models have also facilitated a deeper exploration of the neural dynamics associated with DOC, linking neuron-level dynamics with macroscopic behavioral changes. Despite showing promising outcomes, challenges remain in patient selection, precise target localization, and the determination of optimal stimulation parameters. Future research should focus on conducting large-scale controlled studies to delve into the pathophysiological mechanisms of DOC. It is imperative to further elucidate the precise modulatory effects of DBS on thalamo-cortical and cortico-cortical functional connectivity networks. Ultimately, by optimizing neuromodulation strategies, we aim to substantially enhance therapeutic outcomes and greatly expedite the process of consciousness recovery in patients.
Safety of talimogene laherparepvec: a real‐world retrospective pharmacovigilance study based on FDA Adverse Event Reporting System (FAERS)
Authors: Hong Yifan , Cheng Kebin , Qu Han , Wang Yuting , Wang Yuanyuan , Fan Guorong , Wu Zhenghua 
Published: December 2024

Abstract
Background
Oncolytic virus therapy is a rapidly evolving emerging approach for the medical management of cancer. Talimogene laherparepvec (T-VEC) is the first and only Food and Drug Administration (FDA)-approved oncolytic virus therapy. Considering that exactly how T-VEC works is not known, there is a strong need for a comprehensive pharmacovigilance study to identify safety signals of potential risks with T-VEC.

Objective
The objective of this study was to assess the risk of adverse events (AEs) related to T-VEC.

Methods
We implemented a pharmacovigilance study utilizing individual case safety reports (ICSRs) reported to the FDA Adverse Event Reporting System (FAERS) database dated from 2004 quarter 1 to 2023 quarter 3. In this study, we used two algorithms, reporting odds ratio (ROR) and information component (IC), to assess the risk of AEs related to T-VEC.

Results
A total of 1138 ICSRs of patients who received the T-VEC and reported to the FDA dated from 2004 quarter 1 to 2023 quarter 3 were available. A total of seven system organ classes (SOCs) demonstrated statistically significant signals, i.e. General disorders and administration site conditions, Injury, poisoning and procedural complication, Infections and infestations, Neoplasms benign, malignant and unspecified, Skin and subcutaneous tissue disorders, Hepatobiliary disorders, and Endocrine disorders. From the preferred term level perspective, the most reported AEs in T-VEC-treated patients were pyrexia, illness, influenza, influenza-like illness, and chills. Unexpected significant AEs were detected, such as sepsis, encephalitis, syncope, and lymphadenopathy.

Conclusions
Most AEs in T-VEC-treated patients have been previously mentioned in the prescriptive information or documented in other clinical trials. But safety signals were also be detected in 4 unexpected AEs (sepsis, encephalitis, syncope, and lymphadenopathy). Further clinical trials need to be undertaken to facilitate a more comprehensive comprehension of the safety profile of T-VEC.