bluuebunny/crossref_metadata_2025 huggingface dataset:
The progression of non-culprit coronary lesion is related to higher SII, SIRI, and PIV in patients with ACS
Authors: Yilu Zhou , Zhanglong Wang , Fanke Huang , Jing Guan , Yue Wang , Yuwen Chen , Bingqing Li , Jianfeng Lv
Published: December 2024

Coronary heart disease pathogenesis is intricately linked to inflammation. Acute coronary syndrome (ACS) is a coronary heart disease that seriously affects the prognosis of patients. New immune-inflammatory indices such as systemic immune inflammation index (SII), system inflammation response index (SIRI), and pan-immune-inflammation value (PIV) have emerged as potential biomarkers, offering reflection into systemic inflammatory states and assisting in the prognosis of diverse diseases. This research explored the association between the new immune-inflammatory indices (SII, SIRI, and PIV) and the progression of non-culprit coronary lesions (NCL) in patients with ACS after percutaneous coronary intervention (PCI). Our study investigated the potential association between the immune-inflammatory index (SII, SIRI, and PIV) and NCL progression in patients with ACS following PCI. We conducted a retrospective analysis of patients with ACS who underwent PCI twice at a single-center from 2019 to 2023. Clinical and angiographic features were collected from electronic medical records. The primary outcome was NCL progression. All patients were divided into a progression group and a non-progression group based on angiographies. The clinical and angiographic features were analyzed. The study included 311 ACS patients (progression group: 97 males, 34 females; non-progression group: male 146 males, 34 females). The SII, SIRI, and PIV were significantly higher in the NCL progression group than in the non-progression group (P < .001). Logistic regression analysis showed that SII, SIRI, and PIV were independent risk factors for the NCL progression and positively correlated with it (OR: 1.002, P < .001; OR: 2.188, P < .001; OR: 1.003, P < .001). ROC showed that the SII value was the highest in terms of sensitivity with a value of 67.18% (AUC = 0.7288, P < .001), and the SIRI was the highest in terms of specificity with a value of 79.44% (AUC = 0.6974, P < .001). The SII, SIRI, and PIV are valuable predictors of NCL progression in patients with ACS. Higher SII, SIRI, and PIV are related to the progression of NCL.
Risk factors and predictive model for acute postoperative pain after hip and knee arthroplasty
Authors: Chen Wanling , Chen Wenjie , Wan Weiliang
Published: December 2024

Background:

This study aims to identify key factors influencing acute postoperative pain (APP) following hip and knee arthroplasty, and to develop a predictive model to optimize pain management.

Methods:

The study included 492 patients who underwent hip or knee replacement surgery at our institution from July 2021 to July 2024. Preoperative, intraoperative, and postoperative data were collected. Least Absolute Shrinkage and Selection Operator regression and multivariate logistic regression analyses were utilized to identify factors significantly associated with the occurrence of APP.

Results:

The findings indicated that factors such as body mass index, diabetes, history of long-term use of analgesics, preoperative Visual Analogue Scale scores, Pain Catastrophizing Scale scores, duration of surgery, and intraoperative blood loss were closely linked to the occurrence of APP. Additionally, the preoperative use of prophylactic analgesics, postoperative use of analgesic pumps, and implementation of nerve blocks significantly reduced the risk of APP.

Conclusion:

This study identified several factors closely related to APP after hip and knee arthroplasty and provided a basis for postoperative pain management through the developed predictive model. The research underscores the importance of comprehensive preoperative assessment and the implementation of targeted pain prevention measures. Future studies are recommended to expand the sample size and include multiple centers to enhance the generalizability and practicality of these findings.
Prescription regularity and pharmacodynamics mechanism of traditional Chinese medicine in autoimmune hepatitis: A data mining and network pharmacology study
Authors: Guo Di , Li Xin , Wei Shiya , Cai Fenqing , Liu Yang
Published: December 2024

This study aims to provide a basis and reference for traditional Chinese medicine (TCM) in treating autoimmune hepatitis (AIH) by exploring the prescription patterns of traditional Chinese medicine (TCM) in treating autoimmune hepatitis (AIH) and predicting the potential mechanisms of core TCM formula. Literature on AIH treated with TCM for was retrieved from WANFANG DATA, China national knowledge infrastructure, and CQVIP databases. The herbals listed in all the prescriptions were analyzed for frequency, correlation, association, and clustering, to filter out the core TCM formula for treating AIH. The core herbals included in the core TCM formula were selected to construct an intersection target network of core herbals-active ingredients-disease-related targets. Gene ontology enrichment and KEGG pathway enrichment analyses were then conducted to reveal the potential mechanism of the core TCM formula in treating AIH. A total of 122 Chinese herbal compound prescriptions involving 196 Chinese herbals were included in this study. These herbals were mostly sweet or bitter in taste, cold in property, and restoring the liver and spleen meridian. Based on the results of frequency, correlation rules, and clustering, the combination of “Atractylodes macrocephala Koidz.-Glycyrrhizae Radix et Rhizoma-Cynanchum otophyllum Schneid-Bupleuri Radix-Poria cocos (Schw.) Wolf.” was considered as the core TCM formula in treat AIH, which contains 113 active ingredients (including quercetin, kaempferol, naringenin, licochalcone A, and formononetin) and 138 AIH-related targets (involving TP53, AKT1, JUN, STAT3). Moreover, the targets regulated by the core TCM formula are mainly enriched in the biological processes, such as cellular response to lipids, response to inorganic substances, response to hormones, and IL-17 signaling pathway, TNF signaling pathway, and PI3K-Akt signaling pathway. The core TCM formula “Atractylodes macrocephala Koidz.-Glycyrrhizae Radix et Rhizoma-Cynanchum otophyllum Schneid-Bupleuri Radix-Poria cocos (Schw.) Wolf.” may have a good potential in treating AIH and is worthy of exploring further to develop innovative drugs for this disorder.
Developing a nomogram prediction model to enhance diagnostic accuracy of supplemental ultrasound post-negative mammography
Authors: Li Cheng , Luo Yong , Jiang Yan , Wu Xumiao , Li Qi
Published: December 2024

The effectiveness of mammography in women with dense breasts is compromised by a high rate of false-negative results. While supplemental ultrasound increases sensitivity, its low positive predictive value (PPV) leads to more unnecessary biopsies. This study aims to develop a nomogram model to predict the malignancy of breast masses that are additionally identified as suspicious by supplemental ultrasound after an initial negative screening mammography. The goal is to improve the PPV of supplemental ultrasound and potentially reduce unnecessary biopsies. In this study, eligible data were collected retrospectively and then randomized into training and validation sets. The Least Absolute Shrinkage and Selection Operator was used to identify the most important predictive variables in the training set. The maximum Youden index determined the optimal model threshold, and model performance was evaluated using receiver operating characteristic curves, calibration curves, decision curve analyses, and metrics such as sensitivity, specificity, PPV, and negative predictive value. The study included 425 breast masses, 345 benign and 80 malignant. These were divided into 298 for the training set and 127 for the validation set. Least Absolute Shrinkage and Selection Operator identified the 5 most important predictive variables for the construction of the model. The model showed strong discrimination with area under the curve values of 0.91 (0.87–0.95) for the training set and 0.88 (0.81–0.96) for the validation set. Hosmer–Lemeshow tests indicated a good model fit, with P-values of 0.78 and 0.12 for the training and validation sets, respectively. In addition, decision curve analyses highlighted the clinical utility of the model. The model also showed commendable diagnostic performance in terms of sensitivity, specificity, PPV, and negative predictive value. The nomogram model significantly increased the PPV of supplemental ultrasound from 0.18 to 0.56 in the training set and from 0.21 to 0.56 in the validation set. This study successfully developed a nomogram model to predict the malignancy of suspicious breast masses additionally identified by supplemental ultrasound. The model shows robust performance and significantly improves the PPV of supplemental ultrasound, suggesting a promising way to reduce unnecessary biopsies in such cases.
Pulmonary mucinous adenocarcinoma: A case report and literature review
Authors: Qian Minghui , Lyu Ruibing , Xiao Long , Shi Benqi , Liu Nian , Yuan Yaqian , Wang Wenju , Li Xin
Published: December 2024

Rationale:

Pulmonary mucinous adenocarcinoma (PMA) is a rare subtype of lung adenocarcinoma. Computed tomography images of PMA show pneumonia-like findings, solitary pulmonary nodules or ground-glass opacity with consolidation. Misdiagnosis can delay genetic diagnosis. This article reported a case of PMA presenting with unique imaging findings.

Patient concerns:

An 85-year-old female patient was admitted to our hospital with persistent-cough and expectoration. Anti-infection treatment was largely ineffective.

Diagnoses:

Bronchoscopy with bronchoalveolar lavage and liquid-based cytology revealed the presence of tumor cells. Lung biopsy confirmed the diagnosis of PMA.

Interventions:

Symptomatic treatment was administrated, including anti-infection, relief of cough and expectoration. Bronchoscopy and lung puncture were performed to help clarify the cause of the disease.

Outcomes:

The patient’s course was uneventful, and she was discharged in good condition. After admission, the patient continued to receive anti-tumor immunotherapy in the oncology department.

Lessons:

PMA is a subtype of lung adenocarcinoma and has a low incidence. PMA usually presents with atypical clinical symptoms and signs, and it is difficult to be diagnosed based on imaging findings. It is often undiagnosed and misdiagnosed. Clinicians must increase awareness about the need for timely diagnosis, so as to develop more targeted treatment and achieve a better prognosis.
Revision after knee arthroplasty due to Mycoplasma hominis infection: A case report and literature review
Authors: Liu Kang , Yang Zhi , Xie Weipeng , Wang Sicheng , Hu Shouye
Published: December 2024

Rationale:

Mycoplasma hominis is an opportunistic pathogen commonly found in the human genitourinary system. However, infections caused by Mycoplasma hominis following knee arthroplasty are relatively rare.

Patient concerns:

A 68-year-old male patient underwent bilateral total knee arthroplasty 2 years ago due to osteoarthritis. Over the past 3 months, he developed persistent swelling and pain in both knees, along with the formation of a mass in the left knee. The patient also has a history of type 2 diabetes and hypoalbuminemia.

Diagnoses:

Joint fluid samples from both knees were collected for metagenomic sequencing (mNGS), which detected Mycoplasma hominis infection. Histopathological examination confirmed chronic infection.

Interventions:

The patient underwent 1-stage revision surgery for the left knee, followed by intravenous doxycycline (100 mg, q12h) and intra-articular injections of vancomycin (0.5 g/d) and meropenem (0.5 g/d) for 2 weeks. Afterward, the patient was switched to oral rifampin (450 mg daily) and moxifloxacin (400 mg daily) for six weeks. Following improvement in the left knee symptoms, 1-stage revision surgery was performed on the right knee. The same antibiotic regimen was used postoperatively.

Outcomes:

The patient experienced significant postoperative improvement, with marked pain relief and no signs of recurrent infection. The knee remained stable, and functional recovery was observed. To date, there have been no signs of infection recurrence during follow-up.

Lessons:

After joint arthroplasty, if a patient has persistent infection symptoms, does not respond to beta-lactam antibiotics, and has negative blood cultures, Mycoplasma infection should be considered. In this instance, the use of mNGS proved highly effective in diagnosing this atypical pathogen. The patient improved significantly after 1-stage revision surgery and targeted antibiotic therapy, though longer follow-up is needed to confirm long-term outcomes. Additionally, limited access to mNGS in some regions may delay diagnosis and treatment.
The American Rescue Plan Act and Access to Health Care for Latinos According to Citizenship Status
Authors: Lopez Mercado Damaris , Mortensen Karoline , Rivera-González Alexandra C. , Stimpson Jim P. , Vargas Bustamante Arturo , Roby Dylan H. , Chen Jie , Barajas Clara B. , Ortega Alexander N.
Published: December 2024

Objective:

We studied patterns in health care access between Latino and non-Latino White adults according to citizenship status before and after the American Rescue Plan Act (ARPA) of 2021 was enacted to determine whether inequities changed.

Methods:

This study used 2019–2022 National Health Survey Interview data. Differences in predicted probabilities from logistic regression models were used to estimate changes in health care access outcomes (any insurance coverage, private insurance coverage, delaying care due to cost, and having a usual source of care) among Latino citizens, Latino noncitizens, and non-Latino White citizens in periods before and after ARPA’s enactment (2019–2020 vs 2021–2022).

Results:

Adjusted models observed that inequities in health care access did not change between Latino and non-Latino White citizens from the 2019–2020 period to the 2021–2022 period. Moreover, the health insurance gap widened by 5.8 percentage points between Latino noncitizens and non-Latino White citizens (P < 0.01) and by 5.2 percentage points between Latino noncitizens and Latino citizens (P < 0.05) from the 2019–2020 period to the 2021–2022 period. The private insurance coverage gap widened by 6.8 percentage points between Latino noncitizens and non-Latino White citizens (P < 0.01) and by 6.9 percentage points between Latino noncitizens and Latino citizens (P < 0.01) from the 2019–2020 period to the 2021–2022 period.

Conclusion:

ARPA may have helped increase White citizens’ insurance coverage, but this benefit did not extend to Latinos, regardless of citizenship status. Developing more inclusive health policies that do not have restrictions based on citizenship and legal authorization status is an important step toward reducing health care inequities.
Knowledge of Medical Interpretation Rights Among Individuals With Non-English Language Preference
Authors: Linares Miguel , Lipsitz Stuart , Shaykevich Shimon , Samal Lipika , Rodriguez Jorge A.
Published: December 2024

Objectives:

We aimed to identify demographic, acculturation, and health care factors associated with self-reported knowledge of the right to medical interpretation among individuals with non-English language preference (NELP) in California.

Background:

NELP is a significant social determinant of health contributing to adverse health outcomes through barriers in communication, limited health literacy, and biases in care delivery. The ability of patients with NELP to self-advocate for interpreter services is crucial yet hindered by various factors, including a lack of knowledge about their rights.

Methods:

This cross-sectional study used pooled data from the California Health Interview Survey from 2012 to 2021. Subjects were 12,219 adults with NELP, representing 2,516,157 individuals in California. The primary outcome was self-reported knowledge of the right to medical interpretation. Covariates included demographic, acculturation, and health care factors.

Results:

Of the participants, 28.6% were unaware of their rights to interpretation. Married females had higher odds of knowledge, while recent immigrants (≤5 y in the United States), those with mixed language households, no doctor visits in the past year, no insurance, and self-reported poorer health had lower odds. Sociodemographic factors like age, race, ethnicity, education, and geography﻿ showed no significant association.

Conclusions:

Nearly one-third of individuals with NELP lack awareness of their right to medical interpretation. Factors such as recent immigration, poor health, and limited health care contact are significant barriers. In addition to system and policy level changes, interventions targeting these vulnerable groups are needed to improve health equity and empower patients to use interpreter services.
Push-Pull Motivators and Perceived Health Care Quality on Remote Health Management Intentions—Evidence From the Indian Internet Population
Authors: Bright Helen Pradheep , Lysander Manohar Hansa
Published: December 2024

Background and Objectives:

Hospitals offered remote health care services to enable seamless and safe execution of health care operations during the pandemic while ensuring all stakeholders’ quality of life and well-being. We explore various push and pull motivational factors that can influence customers’ intentions to adopt remote health care services. We also examine the mediating role of perceived health care quality in light of their hedonic experience during the pandemic.

Methods:

We develop our conceptual framework based on push-pull motivational theory and investigate remote health management intentions. We carried out a case study in a multispecialty hospital in India. We collected data from 482 internet users who accessed their remote services during the pandemic, and we performed statistical analysis.

Results:

Our findings show the push and pull motivators significantly influencing internet populations’ remote health management intentions. The results also highlight the mediation of perceived health care quality between push factors and remote health management intentions.

Conclusions:

The push-pull motivators significantly regulate remote health care intentions among the internet population. Technologists and researchers must address these factors while introducing future remote services to widen adoption. This is one of the pioneering studies investigating people’s remote health care intentions post-pandemic.
123I-MIBG SPECT/CT in Evaluating Symptomatic Urinary Bladder Pheochromocytoma
Authors: Algodayan Sarah , Almehaidib Abdullah , Priftakis Dimitrios
Published: December 2024

Pheochromocytoma of the urinary bladder is a rare tumor that occurs in <1% of the extra-adrenal pheochromocytomas. Patients usually present with occult complaints, which can be misdiagnosed. We present a case of a patient with longstanding nonspecific debilitating symptoms. Functional imaging is crucial in diagnosing, localizing, staging, and guiding surgical planning of neuroendocrine tumors.
A Pilot Report on Extracting Symptom Onset Date and Time from Clinical Notes in Patients Presenting with Chest Pain
Authors: George Anjaly , Maisa Aashrith , Dreisbach Caitlin , Suba Sukardi
Published: December 2024

Acute coronary syndrome (ACS) is an acute heart disease that often evolves rapidly. In ACS patients presenting with no-ST-segment elevation (NSTE-ACS), the timing of symptom onset pre-hospital may inform the disease stage and prognosis. We pilot-tested two off-the-shelf natural language processing (NLP) pipelines, namelyparsedatetimeandregular expression(regex), to extract date and time (DateTime) information of patient-reported chest pain symptoms from electronic health records (EHR) clinical notes. We included three types of clinical notes (N=71): History and Physical (n=49), Emergency Department Screening (n=3), and Triage Notes (n=19). All notes were manually annotated for the true DateTime of symptom onset.Parsedatetimereturned matching DateTime outputs in 36 notes (50.7%), whileregexreturned zero matched outputs.Parsedatetimeperformed better thanregex, although it was still suboptimal. Both pipelines require constant refinement and custom improvements. Methods for a large-scale, automated DateTime extraction from EHR clinical notes further investigation.
Association between long-term stimulant treatment and the functional brain response to methylphenidate in adolescents and adults with attention-deficit/hyperactivity disorder
Authors: van der Pal Zarah , Reneman Liesbeth , Mutsaerts Henk JMM , Kaiser Antonia , Bottelier Marco A , Geurts Hilde M , Schrantee Anouk
Published: December 2024

Background

Stimulant medication is commonly used by children and adolescents with attention-deficit/hyperactivity disorder (ADHD), however its long-lasting effects on the developing brain remain unclear. In a previous randomized controlled trial (RCT) we found that short-term stimulant treatment influences the functional brain response to an acute methylphenidate-challenge in an age-dependent manner, in line with animal studies suggesting persisting effects on brain development.

Methods

In this 4-year naturalistic follow-up of the initial RCT, we investigated the long-term age-dependent effects of stimulant treatment on the functional brain response to methylphenidate in male children and adults with ADHD (n=56; adolescents aged 10-17 years, adults aged 23-43 years). At baseline and 4-year follow-up, we used pharmacological MRI to estimate relative cerebral blood flow (rCBF) before a single-dose methylphenidate-challenge (resting rCBF) and the rCBF-response to a single-dose methylphenidate-challenge. Linear mixed models were constructed to evaluate the effect of stimulant medication use, age and visit on resting rCBF and rCBF-response.

Results

We found no evidence for long-term age-dependent effects of stimulant treatment, suggesting that our previously identified short-term effects may be transient. We did identify age-dependent associations between rCBF-response in the medial prefrontal cortex and stimulant treatment, which were already present before treatment initiation but were unrelated to ADHD symptom severity. Moreover, rCBF-response was associated with dopamine D1 receptor distributions in adolescents only.

Conclusions

The identified age-dependent associations may potentially be mediated by changes in dopamine- and noradrenaline-related functioning, and may hold predictive value for (extent of) stimulant medication use after ADHD diagnosis in children and adolescents.
Cost-utility of aripiprazole once-monthly versus paliperidone palmitate once-monthly injectable for schizophrenia in China
Authors: An Yiping , Ding Jinxi , Li Wei , Fang Gang , Pi Zhipeng , Zhang Yumeng
Published: December 2024

Objectives

From the perspective of Chinese healthcare system, this study compared the cost-utility of aripiprazole once-monthly (AOM) and paliperidone palmitate once-monthly injectable for the treatment of adult Chinese patients with schizophrenia.

Methods

A 5-state Markov model was constructed to assess the cost-utility of 10 years of treatment with long-acting injections (LAI) for schizophrenia. The long-term costs and quality-adjusted life years (QALYs) were estimated. The outcome was the incremental cost-effectiveness ratio (ICER). The annual discount rate was set at 5 %. Willingness-to-pay (WTP) threshold of 1x GDP was used to judge the economics of intervention.

Results

In the base-case, the incremental costs of AOM relative to PP1M after 10 years of treatment were US$1,926.373 with an incremental QALYs of 0.306. The ICER for AOM was US$6,285.303/QALY, which was lower than the WTP threshold of US$12,538.306/QALY. The one-way sensitivity analysis and probability sensitivity analysis verified the robustness of the base-case. Scenario analysis showed that from 10 to 30 years, as the horizon increased, the ICER became smaller, and all were below the WTP.

Conclusions

This analysis showed that compared with PP1M, AOM represents a long-term cost-utility advantages for schizophrenia treatment in China.
Impact of bacterial translocation in stroke outcome. Soluble CD14 as early clinical marker and effect of TLR4
Authors: Granados-Martinez Cristina , Alfageme-Lopez Nuria , Diaz-Benito Blanca , Moraga Ana , Sevillano-Fernandez David , Alou-Cervera Luis , Encarnación Fernandez-Valle M. , Castejon-Ferrer David , Calleja-Castaño Patricia , Angeles Moro M. , Hernandez-Jimenez Macarena , Lizasoain Ignacio , Pradillo Jesus M.
Published: December 2024

Bacterial infections are among the most common complications in stroke patients. While some factors triggering these infections are well established, bacterial translocation (BT) from the intestine to other organs represents another significant factor to consider. In our study, we observed a high percentage of animals with intestinal barrier dysfunction (GBD) and BT following stroke, with typical intestinal bacteria even detected in the lungs. Moreover, this process not only exacerbates peripheral/central inflammation but also increases lesion size. In this context, our data in stroke patients demonstrate the presence of GBD, associated with elevated levels of soluble CD14 as a marker, and its strong correlation with neurological status, infarct volume, and the development of infections. Finally, our findings highlight the neuroprotective effects of the absence or pharmacological inhibition of TLR4 using ApTOLL, which not only reduces infarct volume and inflammation but also mitigates GBD/BT processes following experimental stroke.
Astrocyte-derived extracellular matrix proteins regulate synapse remodeling in stress-induced depression
Authors: Zhang Ran , Rodriguez-Rodriguez Patricia , Medrihan Lucian , Chang Jerry C. , Ferraro Tatiana , Del Cioppo Vasques Pedro , Wang Wei , Menard Caroline , Cathomas Flurin , Chan Kenny L. , Parise Lyonna , Shaham Shai , Roussarie Jean-Pierre , Troyanskaya Olga , Russo Scott J. , Milosevic Ana
Published: December 2024

Major depressive disorder (MDD) is a common mood condition affecting multiple brain regions and cell types. Changes in astrocyte function contribute to depressive-like behaviors. However, while neuronal mechanisms driving MDD have been studied in some detail, molecular mechanisms by which astrocytes promote depression have not been extensively explored. To uncover astrocyte contributions to MDD, we subjected male mice to chronic social defeat stress precipitated by encounters with a dominant male. Animals exposed to this treatment exhibit symptoms indicative of MDD, including reduced social interactions, anxiety, despair, and anhedonia. We then measured astrocyte translating mRNA expression changes in mice that underwent chronic social defeat and control animals using ribosome affinity purification. Bioinformatic analyses reveal significant alterations in the prefrontal cortex (PFC), consistent with previous studies implicating this brain region in MDD. Expression of genes encoding extracellular matrix (ECM) proteins, cell-cell interaction proteins, and proteins controlling glutamatergic synaptic function are significantly altered. These changes correlate with perturbation of glutamatergic transmission, measured by electrophysiology, and increased synaptic cleft size. Among ECM genes, increased expression of mRNA encoding the synaptic remodeling proteinsecretedproteinacidic andrich incysteine (Sparc) correlates the most with the depressive phenotype. Furthermore, presence of SPARC and other ECM proteins in synaptosomes is also increased and overexpressingSparcin PFC partially alleviates stress symptoms. Our results raise the possibility that increased expression ofSparcmay be a natural protective mechanism against stress-induced synaptic dysfunction in depression.
Nucleophosmin mutations lead to abnormal, but reversible, nucleoli architecture and aggregate formation – Implications for NPM1-targeting therapies in AML
Authors: Grundy Martin , Lucken Kellie , Xing Xiaomeng , Simpson Eva L. , Bayyoomi Ahmed , Beckett Alison J. , Prior Ian A. , Booth Daniel G. , Seedhouse Claire H.
Published: December 2024

Mutations in theNPM1gene represent the most common (>30% of patients) genetic alteration in Acute Myeloid Leukaemia (AML) and results in the mis-localisation of the mutated NPM1 protein from a predominantly nucleolar localisation to a predominantly cytoplasmic distribution. Numerous studies of NPM1 mutated AML have focussed on the aberrant cytoplasmic localisation of the mutated protein but efforts to reverse this mis-localisation therapeutically have so far resulted in limited clinical benefit. More recently, attention has shifted towards the nucleus with studies showing that mutant NPM1 binds to specific chromatin regions, where it directly regulates oncogenic gene expression. Here, we use high resolution imaging to demonstrate that Nucleophosmin (NPM1) is critical for maintaining normal nucleoli architecture and specifically the integrity of the nucleoli rim. We report for the first time that NPM1 mutated cell lines and primary samples have aberrant nucleoli architecture and demonstrate that the abnormal nucleoli phenotype is reversible. We also report the novel finding that NPM1 mutated protein forms distinct aggregates in NPM1 mutated cells and characterise these for the first time. This work reveals how nucleolar organisation contributes to the molecular mechanisms underpinning NPM1 driven AML and reveals unexpected novel vulnerabilities to be exploited for therapeutic intervention.
Evaluation of subretinally delivered Cas9 ribonucleoproteins in murine and porcine animal models highlights key considerations for therapeutic translation of genetic medicines
Authors: Wei Spencer C. , Cantor Aaron J. , Walleshauser Jack , Mepani Rina , Melton Kory , Bans Ashil , Khekare Prachi , Gupta Suhani , Wang Jonathan , Soares Craig , Kiwan Radwan , Lee Jieun , McCawley Shannon , Jani Vihasi , Leong Weng In , Shahi Pawan K. , Chan Jean , Boivin Pierre , Otoupal Peter , Pattnaik Bikash R. , Gamm David M. , Saha Krishanu , Gowen Benjamin G. , Haak-Frendscho Mary , Janatpour Mary J. , Silverman Adam P.
Published: December 2024

Genetic medicines, including CRISPR/Cas technologies, extend tremendous promise for addressing unmet medical need in inherited retinal disorders and other indications; however, there remain challenges for the development of therapeutics. Herein, we evaluate genome editing by engineered Cas9 ribonucleoproteins (eRNP) in vivo via subretinal administration using mouse and pig animal models. Subretinal administration of adenine base editor and double strand break-inducing Cas9 nuclease eRNPs mediate genome editing in both species. Editing occurs in retinal pigmented epithelium (RPE) and photoreceptor cells, with favorable tolerability in both species. Using transgenic reporter strains, we determine that editing primarily occurs close to the site of administration, within the bleb region associated with subretinal injection. Our results show that subretinal administration of eRNPs in mice mediates base editing of up to 12% of the total neural retina, with an average rate of 7% observed at the highest dose tested. In contrast, a substantially lower editing efficiency was observed in minipigs; even with direct quantification of only the treated region, a maximum base editing rate of 1.5%, with an average rate of <1%, was observed. Our data highlight the importance of species consideration in translational studies for genetic medicines targeting the eye and provide an example of a lack of translation between small and larger animal models in the context of subretinal administration of Cas9 eRNPs.
Discovery of neuronal cell types by pairing whole cell reconstructions with RNA expression profiles
Authors: Ferreira Tiago A. , Eddison Mark , Copeland Monique , Lay Mary , Tenshaw Emily , Weldon Monet , Schauder David , Olbris Donald J. , Rokicki Konrad , Spruston Nelson , Tillberg Paul W. , Korff Wyatt , Dudman Joshua T. ,   The MouseLight Project Team
Published: December 2024

Effective classification of neuronal cell types requires both molecular and morphological descriptors to be collectedin situat single cell resolution. However, current spatial transcriptomics techniques are not compatible with imaging workflows that successfully reconstruct the morphology of complete axonal projections. Here, we introduce a new methodology that combines tissue clearing, submicron whole-brain two photon imaging, and Expansion-Assisted Iterative FluorescenceIn SituHybridization (EASI-FISH) to assign molecular identities to fully reconstructed neurons in the mouse brain, which we call morphoFISH. We used morphoFISH to molecularly identify a previously unknown population of cingulate neurons projecting ipsilaterally to the dorsal striatum and contralaterally to higher-order thalamus. By pairing whole-brain morphometry, improved techniques for nucleic acid preservation and spatial gene expression, morphoFISH offers a quantitative solution for discovery of multimodal cell types and complements existing techniques for characterization of increasingly fine-grained cellular heterogeneity in brain circuits.
The dentate gyrus provides flexibility for efficient spatial navigation
Authors: Soldi Natalia , Benas Sabrina , Kropff Emilio , Schinder Alejandro F. , Piatti Verónica C.
Published: December 2024

The hippocampus plays a critical role in spatial navigation and declarative memory. The dentate gyrus is the neurogenic region of the hippocampal formation and it has long been implicated in the fine separation of similar contexts or close object locations. However, it is unclear how an accurate discrimination could be beneficial to a goal-guided behavior in a changing environment. Therefore, we used chemogenetic inhibition to study the role of the dentate gyrus in a goal-guided spatial navigation paradigm over a familiar but dynamic crossword maze. Mice were challenged to localize a novel reward location from alternative pathways in two versions of the task with particular configurations in each experimental day. In the simple task, the two optimal paths to the goal shared some segments in their trajectory. In a more complex task, optimal trajectories demanded completely different directions to the reward location. Overall, mice with chemogenetic inhibition of the dentate gyrus were able to learn all the routes regardless the complexity of the task, similarly to control animals. However, after having solved a first route in the complex task, mice with dentate gyrus inhibition displayed an impairment to efficiently navigate over the alternate path. Our results demonstrate a role of the dentate gyrus in cognitive flexibility required to reach a goal in a changing familiar environment.
How the two-tier cross-domain control influence contractor’s design behavior: a configurational analysis
Authors: Yan Ling , Wen Shuangshuang , Li Qing
Published: December 2024

Purpose

The contractor’s design behavior in engineering procurement construction (EPC) mode plays a decisive role in controlling design risks, ensuring construction quality and improving project value in terms of project performance. Organizational control is an important way to intervene and strengthen organizational behavior. Reasonably arranging organizational control of the design projects in EPC mode will greatly affect the contractor’s design behavior choices and achieve project goals. There are few existing studies that focus on the contractor’s classification design behavior management from the perspective of two-tier cross-domain control of the design projects in EPC mode. To fill the knowledge gap, this study explores how the two-tier cross-domain control linkage effect affects the contractor’s design behavior choice of the design projects in EPC mode through a configuration analysis.

Design/methodology/approach

This study selects five antecedent variables from the perspective of two-tier cross-domain control (including inter-organizational and intra-organizational controls) through literature review. This study collected 290 valid responses from the design projects in EPC mode practitioners through a questionnaire survey and analyzed the data using fuzzy-set qualitative comparative analysis.

Findings

The results of the necessity and sufficiency analysis indicate that (1) single control is not a necessary condition for contractor’s design behavior, but outcome control and social control play a more universal role in generating a contractor’s design behavior. (2) The four paths that affect the contractor’s design proactive behavior can be divided into two groups: one emphasizes the combined effect of three inter-organizational control, while the other highlights the considerable impact of synergistic inter- and intra-organizational control. (3) There are four paths that affect the contractor’s design compliance behavior. Compared with the organizational configuration of the contractor’s proactive design behavior, process control should be combined with bureaucratic control and clan control to play a role in the absence of outcome control and social control.

Originality/value

This study provides a more detailed explanation for how the linkage effect of the two-tier cross-domain control affects the contractor’s design behavior of the design projects in EPC mode. It broadens the application of positive organizational behavior and organizational control theory. In practice, this study provides a suitable control path for mutual benefit and a win-win situation between owners and contractors to promote the success of the design projects in EPC mode.
How and when generative AI use affects employee incremental and radical creativity: an empirical study in China
Authors: Zhang Xin , Yu Peng , Ma Liang
Published: December 2024

Purpose

The potential of generative AI (GenAI) to stimulate employee creativity has received extensive attention from industry and academia. However, there is still limited research on strategically using GenAI to leverage its positive effects on employee creativity. This study aims to clarify the effects of different GenAI use purposes on employee creativity.

Design/methodology/approach

Based on self-determination theory, this study explores the effects of work-related and nonwork-related GenAI use on incremental and radical creativity through the mediator role of exploratory and exploitative learning and the boundary role of perceived ease of use. This study constructs a theoretical model and uses structural equation modeling to test the model by analyzing survey data from 330 employees.

Findings

(1) Work-related and nonwork-related GenAI use positively impacts incremental and radical creativity through exploratory and exploitative learning; (2) work-related GenAI use contributes more to exploitative learning than to exploratory learning, while nonwork-related GenAI use contributes more to exploratory learning than to exploitative learning; (3) exploitative learning has a stronger positive impact on incremental creativity, and exploratory learning has a stronger positive impact on radical creativity; (4) perceived ease of use weakens the positive effects of nonwork-related GenAI use on exploratory and exploitative learning.

Originality/value

First, this study enriches employee creativity research by revealing the relationship between different GenAI use purposes and incremental and radical creativity. Second, this study enriches employee creativity research by revealing the mediating role of exploratory and exploitative learning between GenAI use and incremental and radical creativity. Finally, this study enriches GenAI use research by revealing the moderating role of perceived ease of use between GenAI use and employee learning.
Sustainable finance, herding behavior and risk aversion during market volatility
Authors: Gavrilakis Nektarios , Floros Christos
Published: December 2024

Purpose

We investigate herding behavior and explore how risk aversion interacts with herding in a sample of selected sustainability indices. Furthermore, we evaluate volatility co-movements and dynamic and time-varying correlations of two notable indicators: the cross-sectional absolute deviation of returns (CSAD) and the risk aversion index (RAI). Moreover, we explore a spillover mechanism (in the short and long run) of risk aversion to sustainable investing.

Design/methodology/approach

Our study uses daily prices from 01/06/2012 to 15/07/2022 obtained from S&P Dow Jones Indices. We use autoregressive - Glosten, Jagannathan, and Runkle generalized autoregressive conditional heteroscedastic (AR(1)-GJR GARCH) methodologies to measure the impact of cross-sectional absolute deviation of returns (CSAD) and risk aversion (RAI) indicators on the conditional variance of selected sustainability indices. Furthermore, we employ dynamic conditional correlation with generalized autoregressive conditional heteroscedasticity, generalized autoregressive conditional heteroscedasticity generalized autoregressive conditional heteroscedasticity mixed data sampling and dynamic conditional correlation with mixed data sampling models to examine any dynamic correlation, spillover volatility effects and the predictability stance of the CSAD and the RAI factors on sustainable investing.

Findings

Our empirical outcomes capture no-herding behavior but display herding on the risk aversion indicator. The cross-sectional dispersion of returns positively affects the conditional variance of all selected sustainable markets, besides emerging markets, while the risk aversion factor negatively influences the conditional variance for Europe and the USA. We have identified long-term contagion effects relating to the variability of returns in our sample, with the exception of emerging markets.

Practical implications

The dispersion of returns can predict the swings of long-term volatilities of Nordic and Europe markets, while the risk aversion factor can predict the long-run volatilities of sustainable markets except Nordic.

Originality/value

The current study presents, for the first time in the sustainable finance literature, an empirical analysis of herding and risk aversion in sustainable investment returns over time. Our findings offer valuable insights to fund managers, finance professionals and investors, providing them with an opportunity to proactively manage their portfolios and reduce financial risk by understanding the volatility behavior of sustainable investing. Furthermore, it is crucial to explore and understand how the dispersion of returns and risk aversion interact with sustainable markets for the construction of optimal portfolios.
Service failure type, response strategy and observers’ perceived helpfulness: evidence from TripAdvisor
Authors: Zhang Mingli , Cai Shensheng , Qiao Tong
Published: December 2024

Purpose

In social media context, service failures become public domain, making them visible to vast audiences of customers who are virtually present. Thus, this study aims to discuss the roles of service failure type and management response on observers’ perceived helpfulness.

Design/methodology/approach

The authors conducted econometric analyses on a dataset incorporating 107,984 reviews and 34,641 management responses to negative reviews.

Findings

The results reveal that, for process failures, specifying a form of action (initiatives for solving the problem) is associated with more perceived helpfulness of reviews than accounts (explanation) or acknowledgments (recognition and acceptance), while responding to an outcome failure by providing an account is associated with increased perceived helpfulness of reviews.

Practical implications

For process failures, managers should make every effort to convince observers through specific actions that similar failures are less likely to occur in the future. For outcome failures, managers should strive to provide clear and fast explanations of the failure causes to restore observers’ evaluation of the firm’s capabilities.

Originality/value

The authors’ work extends sparse insights on observers and sheds new light on the effect of service failure type and response strategy on observers’ actual behaviors. The interplay between service failure type and response strategy provides guidance on how to use management responses to influence potential customers.
4D printing with the assistance of electrical stimulation on polylactic acid coated with carbon nanotubes
Authors: Gholizadeh Ledari Reza , Zolfaghari Abbas
Published: December 2024

Purpose

This paper aims to present an innovative approach to fabricating an electrically responsive shape memory polymer (SMP).

Design/methodology/approach

Polymers that change shape over time when a stimulus is applied are known as SMPs. It uses polylactic acid (PLA) as the base material and carbon nanotubes (CNTs) as conductive additives. Instead of blending CNT with PLA, they were coated on the surface of the samples. The coating consisted of a mixture of CNT/ polycaprolactone. The samples were made using fused deposition modeling, an additive manufacturing method and the shape memory properties of the samples were analyzed under various parameters, including infill angle, coating layers and applied voltage. The voltage generates the Joule heating effect and results in the recovery of SMP to the original shape.

Findings

The highest conductivity of samples belongs to three coating layers, whose conductivity is equal to 0.51 S/cm. Under different parameter settings, the highest recorded shape recovery ratio reached 71.47% at voltage 60, infill angle 0 / 90 and two coating layers. This value emphasizes the remarkable ability of the developed material to return to its original shape. Furthermore, the maximum shape recovery speed observed was 0.3593 degree/s, providing valuable information about shape recovery speed under optimal conditions.

Originality/value

This paper presents the surface coating method and the effects of process parameters for activating shape memory using electric current. Compared to previous techniques, this method offers higher speed and requires less material, making it suitable for use in various industries.
A dialogue on trust in ethics processes for creative practice research education
Authors: Couzens Andrew James , Johnson Amy , Cattoni Jan
Published: December 2024

Purpose

Securing ethical approval can be a frustrating and opaque experience for some creative practice research students who may find the processes required of them not well suited to their specific inquiry. This can lead to an erosion of trust between students and their institutions. This paper aims to synthesize perspectives representing both creative practice research supervisors and Institutional Review Boards (IRBs) to develop recommendations for improving processes and supporting creative practice research training.

Design/methodology/approach

The authors used dialogical inquiry (Wells et al., 2021) to facilitate a dialogue between the authors, who represent different stakeholders in the ethical review process for creative arts research students. Focus topics for the dialogue were developed collaboratively based on existing literature.

Findings

Based on the dialogue, the authors make the following recommendations: frame ethics as part of project design alongside aims and methodology rather than as project logistics; structure ethics review processes to ensure ongoing engagement between research students and IRBs; and share exemplars and templates as part of research training. Additionally, the authors advocate for the need to create continuing opportunities for dialogue.

Originality/value

Previous work interrogating ethical review processes for creative practice research has adopted a clear position from either a creative practice researcher or an IRB member perspective. This dialogue facilitates a novel synthesis of these positions, ensuring the recommendations support the objectives of both IRBs and creative practice researchers.