bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of innovation efficiency in logistic enterprises: Evidence from China based on the three‐stage DEA‐Malmquist index model approach
Authors: Zhou Guanglan , Xu Yiru , Zhang Fangping 
Published: November 2023

AbstractContinuous improvement of technological innovation ability, adjustment of the development strategy, and enhancement of operational performance are of great theoretical and practical significance for logistics enterprises. This paper aims to analyze and evaluate the innovation efficiency of the logistics industry. The study utilizes the static three‐stage DEA model and the dynamic Malmquist index model, considering a total of 12 indicators related to innovation input, output, and environmental variables. A dataset of 2940 entries from 49 listed logistics enterprises from 2017 to 2021 was calculated. The analysis provides insights into the innovation efficiency of logistics enterprises from a static perspective and the innovation total factor productivity from a dynamic perspective and decomposition terms. Based on the analysis of environmental variables by the SFA model, it was found that DEA inefficiency is the combined result of environmental factors and management inefficiency. Environmental variables have both positive and negative effects on innovation. The improvement of the economic development level will lead to excess R&D investment. Increased government simple fund subsidies are not conducive to the efficient allocation of innovation resources within enterprises. The expansion of enterprise scale will increase R&D personnel and investment in fixed assets. A thriving technology market can encourage enterprises to improve their own conversion rate of scientific and technological output and give full play to their innovation ability. The dynamic Malmquist model analysis reveals a recution in the overall innovation efficiency of listed logistics enterprises over 5 years. The changes in total factor productivity and technological progress efficiency of all listed logistics enterprises are synchronized, with most enterprises exhibiting higher technological progress efficiency compared to comprehensive technical efficiency. The total factor productivity of logistics enterprise innovation is mainly affected by comprehensive technical efficiency.
Programmatic approach to patients with advanced ischemic cardiomyopathy: Integrating microaxial support into strategies for the modern era
Authors: Maigrot Jean‐Luc A. , Weiss Aaron J. , Tong Michael Z. Y. , Bakaeen Faisal , Soltesz Edward G. 
Published: November 2023

AbstractPatients with advanced ischemic cardiomyopathy manifesting as left ventricular dysfunction exist along a spectrum of severity and risk, and thus decision‐making surrounding optimal management is challenging. Treatment pathways can include medical therapy as well as revascularization through percutaneous coronary intervention or coronary artery bypass grafting. Additionally, temporary and durable mechanical circulatory support, as well as heart transplantation, may be optimal for select patients. Given this spectrum of risk and the complexity of treatment pathways, patients may not receive appropriate therapy given their perceived risk, which can lead to sub‐satisfactory outcomes. In this review, we discuss the identification of high‐risk ischemic cardiomyopathy patients, along with our programmatic approach to patient evaluation and perioperative optimization. We also discuss our strategies for therapeutic decision‐making designed to optimize both short‐ and long‐term patient outcomes.
Reduced neurogenesis in human hippocampus with Alzheimer's disease
Authors: Cao Yan , Liu Pan , Bian Hongfei , Jin Sixuan , Liu Jiaqi , Yu Ning , Cui Huan , Sun Fengrun , Qian Xiaojing , Qiu Wenying , Ma Chao 
Published: November 2023

AbstractAdult hippocampal neurogenesis (AHN), essential for the plasticity of hippocampal structure and function, may be disrupted in Alzheimer‘s disease (AD). However, the relationship between the changes in AHN and AD‐related pathology in humans remains uncertain. By utilizing advanced immunostaining techniques, we could identify multiple biomarkers representing different stages of AHN in postmortem human hippocampal tissue that exhibited various AD‐related neuropathological changes. In this study, we observed a significant presence of neurogenic cells in the hippocampus's dentate gyrus (DG) region in 30 individuals, including 14 individuals diagnosed with AD‐related neuropathological changes and the remaining 16 individuals without any neurological diseases. Further investigation revealed that patients with AD exhibited pronounced astrogliosis and reduced neurogenesis. Specifically, the number of neuroblasts, immature and early mature granule cells decreased significantly as AD advanced. Although the number of neural stem cells (NSCs) remained unchanged in AD patients compared with mentally healthy individuals, they tended to be more quiescent state regulated by Notch and bone morphogenetic protein (BMP) signaling pathways. These abnormalities were strongly associated with the neuropathological alterations in AD patients. These research findings provide potential insights into the underlying mechanisms that underpin the pathogenesis of AD.
Holmes tremor in progressive multifocal leukoencephalopathy: A video case report
Authors: Matsushima Takako , Ikeguchi Ryotaro , Iijima Mutsumi , Shimomura Ayato , Takahashi Shuntaro , Nakamichi Kazuo , Shimizu Yuko , Kitagawa Kazuo 
Published: November 2023

AbstractBackgroundProgressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the John Cunningham virus. Various brain regions are affected by PML. Therefore, patients with PML show various neurological symptoms. However, tremors are rare neurological symptoms of PML.Case PresentationA 49‐year‐old man developed intermittent slow tremor in the left hand, bilateral dysesthesia and gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the right parietofrontal lobe, right thalamus, left middle cerebellar peduncle, left dentate nucleus, pons and medulla oblongata on fluid‐attenuated inversion recovery images. The patient was positive for HIV antibodies. In addition, HIV‐1 RNA was increased. Quantitative real‐time polymerase chain reaction identified John Cunningham virus DNA in the cerebrospinal fluid; HIV‐associated PML was diagnosed. Surface electromyography showed 3‐Hz grouped discharges in the left flexor carpi ulnaris and extensor carpi radialis, which were consistent with Holmes tremor (HT). Although we administered antiretroviral therapy and mirtazapine, the neurological and radiological findings progressively worsened, and the patient died on day 90. Including the present case, there have been 10 reported cases of PML with HT.ConclusionsAlthough tremors are rarely observed in PML, HT might be a common tremor phenotype in patients with PML. If the neurologist observes HT in patients with multiple brain lesions, PML should be considered.
Functional analysis of the CTNS gene exonic variants predicted to affect splicing
Authors: Li Changying , Zhang Ruixiao , Pan Fengjiao , Xin Qing , Shi Xiaomeng , Guo Wencong , Qiao Dan , Wang Zhi , Zhang Yiyin , Liu Xuyan , Zhang Yan , Shao Leping 
Published: November 2023

AbstractCystinosis is a severe, monogenic systemic disease caused by variants in CTNS gene. Currently, there is growing evidence that exonic variants in many diseases can affect pre‐mRNA splicing. The impact of CTNS gene exonic variants on splicing regulation may be underestimated due to the lack of routine studies at the RNA level. Here, we analyzed 59 exonic variants in the CTNS gene using bioinformatics tools and identified candidate variants that may induce splicing alterations by minigene assays. We identified six exonic variants that induce splicing alterations by disrupting the ratio of exonic splicing enhancers/exonic splicing silencers (ESEs/ESSs) or by interfering with the recognition of classical splice sites, or both. Our results help in the correct molecular characterization of variants in cystinosis and inform emerging therapies. Furthermore, our work suggests that the combination of in silico and in vitro assays facilitates to assess the effects of DNA variants driving rare genetic diseases on splicing regulation and will enhance the clinical utility of variant functional annotation.
Outcomes of initially nonoperative management of diverticulitis with abscess formation in immunosuppressed patients. DIPLICAB study COLLABORATIVE group
Authors: Ocaña Juan , García‐Pérez Juan Carlos , Fernández‐Martínez Daniel , Aguirre Ignacio , Pascual Isabel , Lora Paola , Espin‐Basany Eloy , Labalde‐Martínez María , León Carmen , Pastor‐Peinado Paula , López‐Domínguez Carlota , Muñoz‐Plaza Nerea , Valle Ainhoa , Dujovne Paula , Alías David , Pérez‐Santiago Leticia , Correa Alba , Carmona María , Fernández‐Cebrián José María , Die Javier ,   collaborators from The DIPLICAB Study Collaborative Group
Published: November 2023

AbstractAimManagement of diverticulitis with abscess formation in immunosuppressed patients (IMS) remains unclear. The main objective of the study was to assess short‐ and long‐term outcomes between IMS and immunocompetent patients (IC). The secondary aim was to identify risk factors for emergency surgery.MethodsA nationwide retrospective cohort study was performed at 29 Spanish referral centres between 2015–2019 including consecutive patients with first episode of diverticulitis classified as modified Hinchey Ib or II. IMS included immunosuppressive therapy, biologic therapy, malignant neoplasm with active chemotherapy and chronic steroid therapy. A multivariate analysis was performed to identify independent risk factors to emergency surgery in IMS.ResultsA total of 1395 patients were included; 118 IMS and 1277 IC. There were no significant differences in emergency surgery between IMS and IC (19.5% and 13.5%, p = 0.075) but IMS was associated with higher mortality (15.1% vs. 0.6%, p < 0.001). Similar recurrent episodes were found between IMS and IC (28% vs. 28.2%, p = 0.963). Following multivariate analysis, immunosuppressive treatment, p = 0.002; OR: 3.35 (1.57–7.15), free gas bubbles, p < 0.001; OR: 2.91 (2.01–4.21), Hinchey II, p = 0.002; OR: 1.88 (1.26–2.83), use of morphine, p < 0.001; OR: 3.08 (1.98–4.80), abscess size ≥5 cm, p = 0.001; OR: 1.97 (1.33–2.93) and leucocytosis at third day, p < 0.001; OR: 1.001 (1.001–1.002) were independently associated with emergency surgery in IMS.ConclusionNonoperative management in IMS has been shown to be safe with similar treatment failure than IC. IMS presented higher mortality in emergency surgery and similar rate of recurrent diverticulitis than IC. Identifying risk factors to emergency surgery may anticipate emergency surgery.
Patient reported long‐term side effects on bowel function and anal pain in anal cancer survivors – 3‐ and 6‐year results from the Swedish national ANCA study
Authors: Axelsson Anna , Johansson Mia , Haglind Eva , Li Ying , Nilsson Per J. , Angenete Eva 
Published: November 2023

AbstractAimThe primary therapeutic option for anal cancer treatment is chemoradiotherapy resulting in 80% survival. The aim of this study was to assess long‐term bowel function impairment and anal pain at 3 and 6 years after anal cancer diagnosis, based on a hypothesis of an increase in impairment over time. A secondary aim was to investigate if chemoradiotherapy increased the risk for bowel impairment, compared to radiotherapy alone.MethodThe ANal CAncer study (ANCA) consists of a national Swedish cohort of patients diagnosed with anal cancer between 2011–2013. Patients within the study were invited to respond to a study‐specific questionnaire at 3‐ and 6‐years after diagnosis. Descriptive analyses for the primary endpoint and ordinal logistic regressions for secondary endpoint were performed.ResultsA total of 388 patients (84%) were included in the study. At 3 years of follow‐up, 264 patients were alive. A total of 195 of these patients (74%) answered a study specific questionnaire, and at 6 years 154 patients (67%). Fifty‐seven percent experienced bowel urgency at both 3 and 6 years. There was an increased risk for repeated bowel movement within 1 h (OR 2.44 [95% CI: 1.08–5.61, p = 0.03]) at 3 years in patients who had been treated by chemoradiation compared to radiotherapy alone.ConclusionsImpairment in bowel function and anal pain after anal cancer treatment should be expected and remains after 6 years. This suggests that long‐term follow‐up may be necessary in some form after customary follow‐up. The addition of chemotherapy increases long‐term side effects of bowel function.
TGF‐β3 mediates mitochondrial dynamics through the p‐Smad3/AMPK pathway
Authors: Du Xinmei , Duan Mengmeng , Kan Shiyi , Yang Yueyi , Xu Siqun , Wei Jieya , Li Jiazhou , Chen Hao , Zhou Xuedong , Xie Jing 
Published: November 2023

AbstractIt is well recognized that mitochondrial dynamics plays a vital role in cartilage physiology. Any perturbation in mitochondrial dynamics could cause disorders in cartilage metabolism and even lead to the occurrence of cartilage diseases such as osteoarthritis (OA). TGF‐β3, as an important growth factor that appears in the joints of OA disease, shows its great potential in chondrocyte growth and metabolism. Nevertheless, the role of TGF‐β3 on mitochondrial dynamics is still not well understood. Here we aimed to investigate the effect of TGF‐β3 on mitochondrial dynamics of chondrocytes and reveal its underlying bio‐mechanism. By using transmission electron microscopy (TEM) for the number and morphology of mitochondria, western blotting for the protein expressions, immunofluorescence for the cytoplasmic distributions of proteins, and RNA sequencing for the transcriptome changes related to mitochondrial dynamics. We found that TGF‐β3 could increase the number of mitochondria in chondrocytes. TGF‐β3‐enhanced mitochondrial number was via promoting the mitochondrial fission. The mitochondrial fission induced by TGF‐β3 was mediated by AMPK signaling. TGF‐β3 activated canonical p‐Smad3 signaling and resultantly mediated AMPK‐induced mitochondrial fission. Taken together, these results elucidate an understanding of the role of TGF‐β3 on mitochondrial dynamics in chondrocytes and provide potential cues for therapeutic strategies in cartilage injury and OA disease in terms of energy metabolism.
Gene polymorphism and prediction of toxicity to platinum‐based chemotherapy in patients with gynecologic cancer
Authors: Huang Xuan , Li Junmin , Pang Xiaoying , Zhu Jialei , Pan Jiaqian , Li Yueyan , Tang Jing 
Published: November 2023

AbstractThe relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum‐based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first‐line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi‐square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi‐square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT‐treated patients with gynecologic cancer.
Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants
Authors: Hincelin‐Mery Agnes , Nicolas Xavier , Cantalloube Cathy , Pomponio Robert , Lewanczyk Pascale , Benamor Myriam , Ofengeim Dimitry , Krupka Emmanuel , Hsiao‐Nakamoto Jennifer , Eastenson Amy , Atassi Nazem 
Published: November 2023

AbstractSAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor‐interacting serine/threonine protein kinase 1 (RIPK1). This phase I first‐in‐human healthy participant study (NCT05795907) was comprised of three parts: randomized, double‐blind, placebo‐controlled single ascending dose (SAD; part 1a); 14‐day multiple ascending dose (MAD; part 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SAR443820; and a separate open‐label, single‐dose part 1b (PK‐cerebrospinal fluid [CSF]) to assess SAR443820 levels in CSF. SAR443820 was well‐tolerated in healthy participants, and no treatment discontinuation related to an adverse event (AE) occurred. Most common AEs were dizziness and headache. No clinically meaningful changes were noted in laboratory values, vital signs, or electrocardiogram parameters. SAR443820 had a favorable PK profile, with plasma half‐lives (geometric mean) ranged between 5.7–8.0 h and 7.2–8.9 h after single and repeated doses, respectively. There were no major deviations from dose proportionality for maximum concentration and area under the curve across SAR443820 doses. Mean CSF‐to‐unbound plasma concentration ratio ranged from 0.8 to 1.3 over time (assessed up to 10 h postdose), indicating high brain penetrance. High levels of inhibition of activated RIPK1, as measured by decrease in pS166‐RIPK1, were achieved in both SAD and MAD parts, with a maximum median inhibition from baseline close to 90% at predose (Ctrough) after multiple dosing in MAD, reflecting a marked RIPK1 target engagement at the peripheral level. These results support further development of SAR443820 in phase II trials in amyotrophic lateral sclerosis (NCT05237284) and multiple sclerosis (NCT05630547).
Trends in illicit drug use and their association with HIV transmission risks from behavioural surveillance of Australian gay and bisexual men
Authors: Takeuchi Jumpei , Chan Curtis , MacGibbon James , Broady Timothy R. , Lea Toby , Mao Limin , Bavinton Benjamin R. , Holt Martin 
Published: November 2023

AbstractIntroductionInvestigating drug trends among Australian gay and bisexual men (GBM) is crucial for understanding levels of use and the potential for harm, including HIV transmission risk.MethodUsing repeated, national, cross‐sectional survey data collected between 2012 and 2021 (69,567 surveys), trends of recent (previous 6 months) and frequent (weekly) drug use were analysed, using logistic regression models. The last round of data from each jurisdiction (6709 surveys) was used to compare GBM who reported no use, infrequent (less than weekly) use and frequent (at least weekly) use of party drugs to investigate the association between party drug use and HIV transmission risk, using multinomial logistic regression models.ResultsThere was a significant upward trend in any recent drug use (from 58.4% in 2012 to 64.1% in 2021; p < 0.001). Frequent party drug use remained a minority practice over the period (consistently less than 3%). In cross‐sectional analysis, frequent party drug users were more likely to report behaviours with HIV transmission risks, such as condomless anal intercourse without biomedical prevention strategies (30.0% vs. 13.1%; adjusted relative risk ratio [aRRR], 2.08; 95% CI, 1.24–3.47), weekly group sex (16.3% vs. 0.6%; aRRR, 12.36; 95% CI, 5.75–26.56) and more than 20 recent sexual partners (42.5% vs. 5.0%; aRRR, 21.44; 95% CI, 5.82–78.89), compared with GBM who did not use party drugs.Discussion and ConclusionOur findings suggest that the frequent use of party drugs remains a marker of HIV transmission risk among Australian GBM, despite the increased adoption of biomedical HIV prevention strategies over the past few years.
The effect of sleep disorders, school jet lag, and anxiety in students 8–10 years of age on traumatic dental injuries
Authors: Bernardino Veruska Medeiros Martins , de Lima Larissa Chaves Morais , Granja Gélica Lima , Neves Érick Tássio Barbosa , de Paiva Saul Martins , Granville‐Garcia Ana Flávia 
Published: November 2023

AbstractBackground/AimTraumatic dental injuries (TDI) constitute a public health problem. The aim of the present study was to investigate whether sleep disorders, school jet lag, and anxiety are associated with TDI in schoolchildren 8–10 years of age.MethodsAn analytical, cross‐sectional study was conducted with 739 pairs of parents/guardians and children enrolled in public and private schools. The parents/guardians answered a socioeconomic questionnaire, the Sleep Disturbance Scale for Children, Circadian Energy Scale, and Revised Children's Manifest Anxiety Scale. Four examiners underwent calibration exercises for the diagnosis of TDI (K > 0.80) using the criteria proposed by Andreasen (2007). A directed acyclic graph was used for the formulation of the theoretical model and statistical adjustments. Unadjusted and adjusted robust binary logistic regression analyses were performed (α = 5%).ResultsThe prevalence of TDI was 16.2%. The following variables remained associated with the outcome in the final model: family income less than or equal to the minimum monthly wage (OR = 1.77; 95% CI: 1.09–2.88; p = .02), child's height >137.6 cm (OR = 1.68; 95% CI: 1.06–2.64; p = .02), the occurrence of school jet lag (OR = 2.12; 95% CI: 1.27–3.53; p = .004), anxiety (OR = 1.77; 95% CI: 1.04–3.00; p = .04) and sleep disorders (OR = 1.63; 95% CI: 1.38–1.93; p = .05).ConclusionChildren from families with a lower income, taller children, those with school jet lag, those with anxiety and those with sleep disorders had a greater occurrence of TDI.
Existentialism and Exemplars
Authors: Kirkpatrick Kate 
Published: November 2023

AbstractIn this paper, Kate Kirkpatrick argues that the recent return to moral exemplars in exemplarist moral theory might benefit from engaging with existentialists' use of exemplars in two ways: first, by considering the role of negative exemplars and the power of emotions other than admiration in moral formation; and second, by considering objections to exemplarist education, in particular Simone de Beauvoir's objection that narrative exemplars often serve an ideological function and perpetuate oppressive ideals — especially (but not only) about women. After situating this discussion in ancient and recent debates about the role of literary narratives in moral formation, Kirkpatrick outlines a moral perfectionist reading of Beauvoir and an objection to exemplarist moral theory's reliance on exemplars that “we” admire on the basis that “the admirable” often serves to promote the interests of the powerful rather than the flourishing of all human beings. Finally, while agreeing with this symposium's editors that efforts to improve our understanding of how to use narrative exemplars in educational settings are valuable, she asks how, given the force of the Beauvoirian objection, their criterion of “appropriate critical reflection” might be met.