bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unmet medical needs definition and incentives: stakeholders perspectives on the reform of the EU pharmaceutical legislation
Authors: Wens Io , Claessens Zilke , Vanneste Alice , Barbier Liese , Janssens Rosanne , Huys Isabelle 
Published: January 2025

IntroductionThe 2020 pharmaceutical strategy for Europe stressed that rethinking regulatory policies to foster innovation in disease areas with unmet medical needs (UMN) is one of the European Commission’s (EC) priority areas. To understand stakeholders’ views regarding appropriate UMN criteria and incentives, the EC developed a survey and launched it for public consultation between September and December 2021. This study aims to assess stakeholders’ views on the policy revisions proposed by the EC, particularly those regarding the definition of UMN, its criteria and incentives and evaluate how stakeholders’ views are reflected in the proposed reform of the EU pharmaceutical legislation of 2023.MethodsThe public consultation survey comprised 14 questions including multiple-choice and open answer questions about the reform of the pharmaceutical legislation. A mixed-method analysis was conducted on publicly available data of stakeholders’ responses, including descriptive and quantitative statistics for multiple-choice questions and a qualitative thematic framework analysis for open answer questions. A subgroup analysis was performed to assess differences and similarities in stakeholders’ views, and results were compared with the proposed reform of the EU pharmaceutical legislation.ResultsA total of 478 participants completed the survey consisting of 36% industry, 19% end-users, 17% healthcare providers, 7.5% researchers and 7.5% public bodies. All stakeholder groups favored including “absence of satisfactory authorized treatment” and “disease seriousness” as defining criteria for UMN. However, stakeholders disagreed on including the criterion “lack of access for patients,” with public bodies and industry being less in favour. Industry favored maintaining or having additional incentives like transferable exclusivity vouchers on top of current intellectual property rights to foster innovation. In contrast, other stakeholders supported alternative proposals, namely enhancing the use of scientific advice and implementing expediting measures for regulatory evaluation of medicines targeting UMN.ConclusionStakeholders agreed on including availability of alternatives and disease seriousness in the UMN definition but highlighted its ambiguity. Industry participants supported additional incentives like transferable exclusivity vouchers, whereas others preferred scientific and regulatory support. These findings underscore the need for further discussion on UMN criteria and incentives to stimulate innovation while ensuring patient-centric outcomes and equitable access to medicines across Europe.
Long-term effects of combining anaerobic digestate with other organic waste products on soil microbial communities
Authors: Mora-Salguero Daniela , Montenach Denis , Gilles Manon , Jean-Baptiste Vincent , Sadet-Bourgeteau Sophie 
Published: January 2025

IntroductionAgriculture is undergoing an agroecological transition characterized by adopting new practices to reduce chemical fertilizer inputs. In this context, digestates are emerging as sustainable substitutes for mineral fertilizers. However, large-scale application of digestates in agricultural fields requires rigorous studies to evaluate their long-term effects on soil microbial communities, which are crucial for ecosystem functioning and resilience.Material and methodsThis study presents provides a comparative analysis in long-term field conditions of fertilization strategies combining annual applications of raw digestate with biennial applications of different organic waste products (OWPs)—biowaste compost (BIO), farmyard manure (FYM), and urban sewage sludge (SLU)—and compares them to combinations of the same OWPs with mineral fertilizers. The cumulative effects of repeated OWP applications, paired with two nitrogen sources—organic (digestate) and chemical (mineral fertilizer)—were assessed through soil physicochemical and microbial analyses. We hypothesized that the combined effect varied according to the N-supply sources and that this effect also depended on the type of OWP applied. Soil microbial communities were characterized using high-throughput sequencing targeting 16S and 18S ribosomal RNA genes, following DNA extraction from soil samples collected in 2022, six years after the initial digestate application.ResultsThe results indicated that combining OWPs rich in stable and recalcitrant organic matter, such as BIO and FYM, with raw digestate, offers an improved fertilization practice. This approach maintains soil organic carbon (SOC) levels, increases soil phosphorus and potassium content, and stimulates microbial communities differently than nitrogen supplied via mineral fertilizers. While microbial biomass showed no significant variation across treatments, microbial diversity indices exhibited differences based on the type of OWP and nitrogen source. The fertilization strategies moderately influenced prokaryotic and fungal community structures, with distinct patterns depending on the OWP and nitrogen source. Notably, fungal communities responded more strongly to treatment variations than prokaryotic communities.DiscussionThis study provides new insights into the cumulative effects of substituting mineral fertilizers with digestates on soil microbial communities and soil physicochemical parameters. The sustainable development of agroecosystems significantly depends on a better understanding of the complex responses of soil microbial communities to different fertilization regimes. Future research should continue to assess the long-term impact of digestate application on soil microbiota in real agronomic field conditions, considering associated agricultural practices.
Epidemiology and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in patients with hematological malignancies from 2014 to 2022
Authors: Li Meng , Ye Liyan , Yu Zhenghao , Yao Hongwu , Liu Yunxi , Wang Guanglei , Du Mingmei 
Published: January 2025

BackgroundWe aimed to describe the epidemiology, cross-transmission, interventions, and outcomes of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the hematological malignancies (HM) department of a hospital in China.MethodsThis prospective study was divided into three stages from 2014 to 2022: Period 1 (from 1 January 2014 to 4 March 2021), Period 2 (from 5 March 2021 to 31 December 2021), and Period 3 (from 1 January 2022 to 31 December 2022), with different measures implemented at each stage to evaluate the rate of new infections. The risk factors, epidemiological characteristics, data from all patients with CRKP, NGS gene sequencing molecular epidemiology analysis, and cross-transmission were described.ResultsA total of 217 patients with K. pneumoniae isolates, including 38 (17.5%) patients with CRKP isolates, were confirmed in the HM department. The total rate of CRKP in KP isolates was 17.5%. The predominant clone in the HM department was ST11 CRKP producing the KPC-2 enzyme (21, 70.0%). A total of 23 cases of HM department-acquired CRKP infections were identified, and five hospital cross-transmission events were observed. Four instances of CRKP dissemination were primarily related to clone ST11. Only one outbreak occurred at the end of Period 1, involving four cases of CRKP healthcare-associated infections (HAIs). After the implementation of outbreak intervention bundles at the end of Period 2, no cross-transmission occurred. The rate of CRKP in KP isolates decreased to 12.9% (only four CRKP isolates) in Period 3, down from a peak of 46.7% in Period 2 (including 14 CRKP isolates). Only one new carrier (0.9%) was identified during the two cross-sectional active screenings of the rectal swab. The 28-day mortality rate was 38.7% (12/31) in CRKP-infected patients.ConclusionThe prevalence of CRKP in the HM department was relatively low in the studied hospital. We found that interventions, including single-room isolation, enhanced disinfection, and skin decolonization, played a pivotal role in controlling the spread of HM-acquired CRKP infections.
Effects of fertilizer application on the bacterial community and weathering characteristics of typical purple parent rocks
Authors: Wang Xuan , Zhao Jixia , Li Chunpei , Deng Limei , Cui Rongyang , Zhou Tao , Hussain Zakir , Liu Gangcai 
Published: January 2025

IntroductionRock weathering is a fundamental process that shapes Earth’s topography, soil formation, and other surface processes. However, the mechanisms underlying the influence of fertilizer application on weathering remain poorly understood, especially with respect to bacterial intervention.MethodsIn this study, purple parent rocks from Shaximiao Group (J2s) and Penglaizhen Group (J3p) were selected to investigate the effects of fertilizer application on the bacterial community and weathering characteristics of these rock by leaching experiment.ResultsThe results revealed that: fertilizer application, especially when at high levels, greatly altered the abundance, diversity and composition of the bacterial community in weathered products. Through redundancy analysis, a decrease in pH and increases in available nutrients (AN and AP) resulting from fertilizer application were identified as the key factors driving changes of bacterial community composition in weathered products. Moreover, fertilizer application promotes the physical and chemical weathering of the parent rocks to some extent. This is especially true for the chemical weathering of J2s. Structural equation model indicated that fertilizer application affects weathering through multiple pathways by affecting the chemical properties (pH, C:N and AP), specific bacterial genera (IMCC26256, Ramlibacter, and Nitrosospira), and bacterial community composition of weathered products.DiscussionOur study links weathering characteristics with chemical properties and bacterial community changes of weathered products after fertilizer application, which plays a key role in controlling and predicting dynamic changes of rock weathering in space and time. It is helpful to further understand the law of human activities affecting the surface processes.
Sex-specific ultrasound imaging biomarkers of neurodegeneration in a mouse model
Authors: Russell Mark B. , Locke Drew P. , Adams Haley M. , Pelley Alexander R. , Saghian Rojan , Maekawa Alexandre S. , Stapleton Darcie , Mercer Grace V. , Sled John G. , Cahill Lindsay S. 
Published: January 2025

IntroductionEarly detection of neurodegeneration is essential for optimizing interventions. The highly reproducible progression of neurodegeneration in the decrepit (dcr) mouse allows investigation of early biomarkers and mechanisms of brain injury.MethodsUsing high-frequency ultrasound, the common carotid arteries of female and male dcr and control mice were imaged longitudinally at time points bracketing the disease progression (50, 75, and 125 days of age) (n = 6 mice/group/sex).ResultsOver the disease time course, the female dcr mice demonstrated increased carotid artery blood flow and pulse wave velocity while the male dcr mice had a decrease in heart rate and no change in carotid artery ultrasound parameters. Early imaging biomarkers were sex-specific, with decreased carotid artery blood flow in female dcr mice and increased carotid artery diameter and decreased pulse wave velocity in males.DiscussionCarotid artery and wave reflection ultrasound is a promising screening tool for early detection of neurodegeneration.
Decremental response in patients with amyotrophic lateral sclerosis during repetitive nerve stimulation and its relationships with impaired homeostasis
Authors: Zhang Jinghong , Li Yang , Shi Qiang 
Published: January 2025

BackgroundPrevious studies have suggested that neuromuscular junction (NMJ) denervation plays a critical role in amyotrophic lateral sclerosis (ALS). Repetitive nerve stimulation (RNS) has been used as a technique to test neuromuscular transmission, but the sensitivity and stability of its parameters have not been investigated in patients with ALS. In addition, the impact of impaired homeostasis on NMJ stability in patients with ALS remains unclear.MethodsA total of 421 patients with ALS were enrolled. Data on their clinical, biochemical and electrophysiological indicators were divided into a training set (collected from June 2019 to June 2022) and a test set (collected from July 2022 to June 2023). The coefficient of variation (CV) was used to assess the extent of variability. Stepwise regression was used in independent variable selection and model building.ResultsIn patients with ALS, area decrement had a higher rate of abnormal result and a lower CV than amplitude decrement. No significant difference in the rate of abnormal decrement was found when the first compound muscle action potential (CMAP) was compared with either the fourth or fifth one. Moreover, multivariate regression analysis suggests high-density lipoprotein cholesterol (HDL-C) had the greatest impact on decremental response, followed by serum uric acid (UA) and forced vital capacity (FVC). Females had a larger range of area decrement than males.ConclusionDuring RNS test, assessing area decrement significantly enhances our ability to detect the impairment of neuromuscular transmission in patients with ALS. Independent factors contributing to decremental response need to be considered in drug development and clinical trials targeting NMJ in patients with ALS.
Aspirin modulates inflammatory biomarkers in patients with subcortical silent brain infarcts
Authors: Sung Wonjae , Kim Young Seo , Lee Kyu-Yong , Jung Jae-A , Choi Hojin , Lee Young Joo , Koh Seong-Ho 
Published: January 2025

IntroductionThis study aimed to identify differences in the levels of inflammation-related biomarkers between patients with subcortical silent brain infarcts (SBIs) and healthy controls. We also evaluated the effect of aspirin on the subcortical SBI inflammatory processes.MethodsConsecutive patients diagnosed with subcortical SBIs without a history of acute stroke were included. The demographic and clinical data of the 26 subjects with subcortical SBIs, such as the number and location of subcortical SBIs, were reviewed. Plasma levels of macrophage migration inhibitory factor (MIF), matrix metalloproteinase-9 (MMP-9), and visfatin were measured in patients with subcortical SBIs and ten healthy participants. These biomarkers were rechecked in patients with subcortical SBI 3 months after taking aspirin (100 mg/day).ResultsMIF and MMP-9 levels were significantly higher in patients with subcortical SBIs than in healthy control group (p = 0.031 and p = 0.026, respectively). Although MIF and MMP-9 did not show significant changes after taking aspirin for 3 months, the median plasma level of visfatin was significantly decreased from 1.00 ng/mL (range, 0.86–1.16 ng/mL) to 0.84 ng/mL (range, 0.77–0.91 ng/mL) (p = 0.002) after taking aspirin.DiscussionInflammation could be an essential factor in the pathogenesis of subcortical SBIs, and aspirin affects several inflammation-related biomarkers.
MoS2-based biosensor for SARS-CoV-2 detection: a numerical approach
Authors: Tene Talia , Tubon-Usca Gabriela , Gallegos Katherine Tixi , Mendoza Salazar María José , Vacacela Gomez Cristian 
Published: January 2025

Surface plasmon resonance (SPR) biosensors are powerful tools for highly sensitive and specific detection of biomolecules. This study introduces a MoS₂-based SPR biosensor optimized for SARS-CoV-2 detection. The sensor integrates a multilayer configuration, including a BK7 prism, Ag film (45 nm), S₃N₄ layer (13 nm), MoS₂ monolayer (0.65 nm), and functionalized ssDNA layer (5 nm). Systematic optimization of each layer improved plasmonic coupling, propagation, and specificity, achieving a balance between sensitivity, resolution, and efficiency. The optimized biosensor was evaluated across virus concentrations ranging from 0.01 to 150 mM. The proposed biosensor demonstrated excellent performance at moderate to high concentrations, with sensitivity up to 261.33°/RIU, a quality factor of 36.16 RIU−1, and a limit of detection of 1.91 × 10−5. An optimal figure of merit of 405.50 RIU−1 was achieved at 10 mM, highlighting the sensor’s diagnostic potential. However, challenges remain at very low concentrations (0.01–0.1 mM), where angular shifts, sensitivity, and signal-to-noise ratio were negligible.
Improved motor imagery skills after repetitive passive somatosensory stimulation: a parallel-group, pre-registered study
Authors: Kusano Kyoko , Hayashi Masaaki , Iwama Seitaro , Ushiba Junichi 
Published: January 2025

IntroductionMotor-imagery-based Brain-Machine Interface (MI-BMI) has been established as an effective treatment for post-stroke hemiplegia. However, the need for long-term intervention can represent a significant burden on patients. Here, we demonstrate that motor imagery (MI) instructions for BMI training, when supplemented with somatosensory stimulation in addition to conventional verbal instructions, can help enhance MI capabilities of healthy participants.MethodsSixteen participants performed MI during scalp EEG signal acquisition before and after somatosensory stimulation to assess MI-induced cortical excitability, as measured using the event-related desynchronization (ERD) of the sensorimotor rhythm (SMR). The non-dominant left hand was subjected to neuromuscular electrical stimulation above the sensory threshold but below the motor threshold (St-NMES), along with passive movement stimulation using an exoskeleton. Participants were randomly divided into an intervention group, which received somatosensory stimulation, and a control group, which remained at rest without stimulation.ResultsThe intervention group exhibited a significant increase in SMR-ERD compared to the control group, indicating that somatosensory stimulation contributed to improving MI ability.DiscussionThis study demonstrates that somatosensory stimulation, combining electrical and mechanical stimuli, can improve MI capability and enhance the excitability of the sensorimotor cortex in healthy individuals.
Evaluating the impact of donor eGFR and HLA-DR mismatch on graft survival in living donor kidney transplants
Authors: Budhiraja Pooja , Schold Jesse D. , Lopez Rocio , Arrigain Susana , Kaplan Bruce 
Published: January 2025

BackgroundThis study assesses the impact of human leukocyte antigen (HLA)-DR mismatch and donor-estimated glomerular filtration rate (eGFR) on outcomes of living donor kidney transplantation (LDKT), which are especially relevant to the availability of multiple donors and paired kidney exchanges.MethodsUsing data from the Scientific Registry of Transplant Recipients (SRTR), we retrospectively analyzed graft survival in adult LDKT recipients transplanted between January 2013 and September 2022. Recipients with 0 HLA-DR mismatches were compared to those with 1-2 HLA-DR mismatches. Cox models assessed the association between donor eGFR and graft and patient survival, stratifying by a) HLA-DR mismatches, and b) HLA-DR mismatches and recipient age.ResultsAmong 44,080 recipients, 7,195 had 0 HLA-DR mismatches and 36,885 had 1-2 HLA-DR mismatches. The recipients’ mean age was 49.1 for the 0 HLA-DR mismatch group and 50.4 for the 1-2 HLA-DR mismatch group. The donors’ mean age was 43.1 and 43.8, with an eGFR of 101.0 and 99.9 ml/min, respectively. A higher donor eGFR was associated with better graft survival. Stratified analyses showed higher donor eGFR levels reduced the risk of graft loss in cases with DR mismatch (p &lt; 0.001) but not in cases without HLA-DR mismatch (p = 0.81). This effect was significant for recipients aged 18-39 and over 60. Similar results were observed for patient survival.ConclusionsHigher donor eGFR was associated with lower risks of graft loss and patient death in the HLA-DR mismatch group but not the 0 HLA-DR mismatch group. These results emphasize the importance of considering both HLA-DR matching and donor kidney function, particularly for younger recipients to avoid sensitization for future transplants.
A cross-sectional study on the correlation between internal cerebral vein asymmetry and hemorrhagic transformation following endovascular thrombectomy
Authors: Lin Kunxin , Zhao Wenlong , Wu Quanhong , Zheng Yiru , Yang Bo , Fu Ying , Wang Ning , Fang Ling 
Published: January 2025

IntroductionHemorrhagic transformation (HT) is a severe complication in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) after endovascular treatment (EVT). We hypothesize that asymmetry of the internal cerebral veins (ICVs) on baseline CT angiogram (CTA) may serve as an adjunctive predictor of HT.MethodsWe conducted a study on consecutive AIS-LVO patients from November 2020 to April 2022. These patients had anterior circulation occlusions and were treated with EVT. Asymmetrical ICVs were assessed using CTA and defined as hypodensity (reduced opacification) on the ipsilateral side of occlusion compared to the contralateral side. The primary outcome was HT, defined as hemorrhage within the ischemic territory. This was evaluated using follow-up imaging (CT scan or magnetic resonance imaging) performed 48 h post-EVT. HT was classified into four subtypes based on the European Cooperative Acute Stroke Study-II criteria.ResultsA total of 126 patients were included, with an HT rate of 49.2% (62/126). ICV asymmetry was observed in 54.0% (68/126) of patients. The ICV asymmetry group exhibited a significantly higher risk of parenchymatous hematoma-type HT (33.8% vs. 15.5%, p = 0.019) and symptomatic intracerebral hemorrhage (sICH) (23.5% vs. 5.2%, p = 0.004). In multivariate logistic regression, ICV asymmetry (OR 3.809, 95% CI 1.582–9.171), baseline Alberta Stroke Program Early CT Score (OR 0.771, 95% CI 0.608–0.978), intravenous recombinant tissue plasminogen activator (OR 2.847, 95% CI 1.098–2.7.385), and poor collateral circulation (OR 3.998, 95% CI 1.572–10.169) were identified as independent risk factors of HT.ConclusionICV asymmetry, likely resulting from impaired autoregulation or tissue micro-perfusion hampering cerebral blood flow (CBF), is a novel radiological sign that independently predicts HT. It is associated with a higher risk of sICH in AIS-LVO patients after EVT. Further research is warranted to validate these findings.