bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic neuronal activation leads to elevated lactate dehydrogenase A through the AMP-activated protein kinase/hypoxia-inducible factor-1α hypoxia pathway
Authors: Ksendzovsky Alexander , Bachani Muznabanu , Altshuler Marcelle , Walbridge Stuart , Mortazavi Armin , Moyer Mitchell , Chen Chixiang , Fayed Islam , Steiner Joseph , Edwards Nancy , Inati Sara K , Jahanipour Jahandar , Maric Dragan , Heiss John D , Kapur Jaideep , Zaghloul Kareem A 
Published: November 2022

Abstract
Recent studies suggest that changes in neuronal metabolism are associated with epilepsy. High rates of ATP depletion, lactate dehydrogenase A and lactate production have all been found in epilepsy patients, animal and tissue culture models. As such, it can be hypothesized that chronic seizures lead to continuing elevations in neuronal energy demand which may lead to an adapted metabolic response and elevations of lactate dehydrogenase A. In this study, we examine elevations in the lactate dehydrogenase A protein as a long-term cellular adaptation to elevated metabolic demand from chronic neuronal activation. We investigate this cellular adaptation in human tissue samples and explore the mechanisms of lactate dehydrogenase A upregulation using cultured neurones treated with low Mg2+, a manipulation that leads to NMDA-mediated neuronal activation. We demonstrate that human epileptic tissue preferentially upregulates neuronal lactate dehydrogenase A, and that in neuronal cultures chronic and repeated elevations in neural activity lead to upregulation of neuronal lactate dehydrogenase A. Similar to states of hypoxia, this metabolic change occurs through the AMP-activated protein kinase/hypoxia-inducible factor-1α pathway. Our data therefore reveal a novel long-term bioenergetic adaptation that occurs in chronically activated neurones and provide a basis for understanding the interplay between metabolism and neural activity during epilepsy.
Surgical removal of a bullet in the heart through a trans-mitral approach: a case report
Authors: Cammardella Antonio Giovanni , Lio Antonio , De Luca Leonardo , Bergonzini Marcello , Musumeci Francesco 
Published: November 2022

Abstract

Background
Retained cardiac missiles have been considered bullets, shrapnel, or pellets included in the heart or the pericardial sac. In asymptomatic patients with retained cardiac missiles, the role of surgery is still debated.

Case summary
We describe the case of successful surgical treatment of a retained missile localized within the left ventricle in close proximity of the posterior mitral leaflet. The operation was performed through a transatrial approach, detaching the posterior mitral leaflet. The post-operative course was uneventful. The patient was discharged on the seventh post-operative day. At 30-day follow-up visit, the patient was in good conditions, with normal mitral valve function.

Discussion
The management of retained cardiac missiles should be individualized. If a decision is made to operate, multiple imaging techniques including echocardiography and computed tomography scan are mandatory to precisely locate the bullet.
Clozapine therapeutic drug monitoring – experience from a large London NHS trust
Authors: Attard A , Miah M , Chopra P , Wakelam J , Stanniland C 
Published: November 2022

Abstract

Introduction
Clozapine is a high-risk drug that is used widely in Secondary and Tertiary Centres.1 Therapeutic Drug Monitoring (TDM) advice and recommendation is readily available from distinguished authors.2,3 The rate of clozapine TDM, appropriate sample collection for TDM, appropriate actions following a clozapine level varies between services and prescribers within our organisation.

Aim
To establish how many current West London NHS Trust (WLT) patients had a clozapine TDM, how many plasma samples collected for TDM were done appropriately, the proportion of patients with an appropriately collected plasma sample result within the largely accepted therapeutic range, and whether there was documentation that the plasma level was reviewed and if any prescription changes were made.

Methods
Approval to undertake the service evaluation was given by the Trust clinical governance and audit committee as ethical review as not required. No patient identifiable details were shared or collected. All patients who had been registered on the Trusts clozapine patient monitoring service for over 8 weeks were enrolled. Anonymised patient demographic data was collected including concomitant medication. Plasma levels were sought for every patient enrolled. The appropriateness of the samples taken were scrutinised. The plasma level result was collected. Electronic patient notes were also scrutinised to assess actions following the plasma level result. Data were collected in a binary yes/no format and results calculated as a percentage. Data was stored and collected in accordance to Trust General Data Protection Regulation (GDPR).

Results
In total 316 patients were included. 97% of these patients had evidence of TDM levels done during the time of the audit. 88% of these patients’ samples were done correctly. Only 45% of patients had levels within the widely acceptable therapeutic range. Of those patients whose levels fell outside the therapeutic range less than half (42%) had documentation that the level was reviewed.

Discussion/Conclusion
It is widely accepted that clozapine TDM when done accurately can be a vital source of information to inform prescribers on the appropriate dose, concordance and toxicity of clozapine therapy. Our Trust showed evidence of routine clozapine TDM. There was some variation in the appropriate sample collection but what was most alarming is the lack of documentation that action was taken when the TDM level was outside the general acceptable range. Standardising the actions following clozapine TDM needs to be a priority for the Trust if clozapine TDM is to continue to be carried out in almost 100% of the patient population.

References
1. Taylor DM, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry 14th Edition. Wiley Blackwell.
2. Taylor DM et al. The use of clozapine plasma levels in optimising therapy. Psych Bull 1995:19:753-755
3. Perry PJ. Therapeutic drug monitoring of antipsychotics. Psychopharmacology 200; 148:83-89
Antimicrobial resistance patterns of bacterial pathogens recovered from the urine of patients at Canadian hospitals from 2009 to 2020
Authors: Walkty Andrew , Karlowsky James A , Lagace-Wiens Philippe , Baxter Melanie R , Adam Heather J , Zhanel George G 
Published: November 2022

Abstract

Objectives
To investigate in vitro susceptibility patterns of bacterial pathogens recovered from the urine of outpatients (isolates from outpatient clinics or emergency departments) and hospital inpatients across Canada from 2009 to 2020 as part of the CANWARD study

Methods
Canadian hospital microbiology laboratories submitted bacterial pathogens cultured from urine to the CANWARD study coordinating laboratory on an annual basis (January 2009 to December 2020). Antimicrobial susceptibility testing was performed by CLSI broth microdilution, with MICs interpreted by current CLSI breakpoints.

Results
In total, 4644 urinary pathogens were included in this study. Escherichia coli was recovered most frequently (53.3% of all isolates), followed by Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus. Together, these six species accounted for 84.2% of study isolates. Nitrofurantoin demonstrated excellent in vitro activity versus E. coli, with 97.6% of outpatient and 96.1% of inpatient isolates remaining susceptible. In contrast, E. coli susceptibility rates were lower for ciprofloxacin (outpatient 79.5%, inpatient 65.9%) and trimethoprim/sulfamethoxazole (outpatient 75.2%, inpatient 73.5%). The percentage of E. coli isolates that were phenotypically positive for ESBL production significantly increased from 4.2% (2009–11) to 11.3% (2018–20). A similar although less pronounced temporal trend was observed with ESBL-producing K. pneumoniae.

Conclusions
E. coli was the pathogen most frequently recovered from the urine of Canadian patients, and the proportion of isolates that were ESBL producers increased over time. Susceptibility data presented here suggest that ciprofloxacin and trimethoprim/sulfamethoxazole may be suboptimal for the empirical treatment of complicated urinary infections.
The Art of Visualising Reality: Jīva Gosvāmī’s Aesthetics and the Role of Ritual Imagination
Authors: Herbert Alan 
Published: November 2022

Abstract
This paper reconstructs an otherwise problematic role of ritual imagination in the sixteenth-century Gauḍīya Vaiṣṇava thinker Jīva Gosvāmī’s seminal treatise, Ṣaṭ-sandarbha. As part of his explanation of worship under the broader theme of bhakti as practice, the author recasts a set of Pāñcarātric visualisation rituals to suit Gauḍīya theology and praxis centred on devotional visualisations of divine forms. However, while explaining the rituals, he paradoxically claims that the visualised forms, despite being imagined, are not to be considered imaginative. I argue that this paradox dissolves if we view Jīva’s rationale on this issue through the lens of a similarly re-orientated version of ancient dramatic and poetic rasa theory that he employs to map the higher experiences of devotion at the culmination of his treatise. Although he does not mention using this strategy for the visualisation rituals, it can be inferred through the correlations I make between his descriptions of their visualised content and certain categories of rasa theory. Through this reconstructive analysis, the reality of the ritual imaginals can be explained and the paradox dissolved.
Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice
Authors: Yu Jun-Ma , Hu Rui , Mao Yu , Tai Yingju , Qun Sen , Zhang Zhi , Chen Danyang , Jin Yan 
Published: November 2022

ABSTRACTChronic pain is a significant problem that afflicts individuals and society, and for which the current clinical treatment is inadequate. In addition, the neural circuit and molecular mechanisms subserving chronic pain remain largely uncharacterized. Herein we identified enhanced activity of a glutamatergic neuronal circuit that encompasses projections from the ventral posterolateral nucleus (VPLGlu) to the glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu), driving allodynia in mouse models of chronic pain. Optogenetic inhibition of this VPLGlu→S1HLGlu circuit reversed allodynia, whereas the enhancement of its activity provoked hyperalgesia in control mice. In addition, we found that the expression and function of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) were increased in VPLGlu neurons under conditions of chronic pain. Using in vivo calcium imaging, we demonstrated that downregulation of HCN2 channels in the VPLGlu neurons abrogated the rise in S1HLGlu neuronal activity while alleviating allodynia in mice with chronic pain. With these data, we propose that dysfunction in HCN2 channels in the VPLGlu→S1HLGlu thalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.
Transgenic PDGF-BB sericin hydrogel potentiates bone regeneration of BMP9-stimulated mesenchymal stem cells through a crosstalk of the Smad-STAT pathways
Authors: Zhang Hui-Jie , Li Fu-Shu , Wang Feng , Wang Han , He Tong-Chuan , Reid Russell R , He Bai-Cheng , Xia Qingyou 
Published: November 2022

Abstract
Silk as a natural biomaterial is considered as a promising bone substitute in tissue regeneration. Sericin and fibroin are the main components of silk and display unique features for their programmable mechanical properties, biocompatibility, biodegradability and morphological plasticity. It has been reported that sericin recombinant growth factors (GFs) can support cell proliferation and induce stem cell differentiation through cross-talk of signaling pathways during tissue regeneration. The transgenic technology allows the productions of bioactive heterologous GFs as fusion proteins with sericin, which are then fabricated into solid matrix or hydrogel format. Herein, using an injectable hydrogel derived from transgenic platelet-derived GF (PDGF)-BB silk sericin, we demonstrated that the PDGF-BB sericin hydrogel effectively augmented osteogenesis induced by bone morphogenetic protein (BMP9)-stimulated mesenchymal stem cells (MSCs) in vivo and in vitro, while inhibiting adipogenic differentiation. Further gene expression and protein–protein interactions studies demonstrated that BMP9 and PDGF-BB synergistically induced osteogenic differentiation through the cross-talk between Smad and Stat3 pathways in MSCs. Thus, our results provide a novel strategy to encapsulate osteogenic factors and osteoblastic progenitors in transgenic sericin-based hydrogel for robust bone tissue engineering.
Religion as a Resource in an Increasingly Polarized Society
Authors: Cavendish James 
Published: November 2022

Abstract
Recent research in the social scientific study of religion has drawn attention to how distinct religious identities and cultures have supported nationalist impulses and fueled political polarization across a variety of national contexts. This growing body of literature makes it clear that religious ideals and identities can be used to frame issues, draw boundaries, and drive a wedge down the middle of the political landscape. What is less frequently analyzed are the various ways that religion can provide resources to depolarize society. This article identifies the various resources that religion can offer for depolarization, and calls for future research aimed not only at better understanding the extent and nature of religion’s deployment of these resources, but also their effectiveness in countering the polarizing dynamics in contemporary society.
Incorporation of rapid association/dissociation processes in tissues into the monkey and human physiologically based pharmacokinetic models for manganese
Authors: Campbell Jerry L , Clewell Harvey J , Van Landingham Cynthia , Gentry P Robinan , Keene Athena M , Taylor Michael D , Andersen Melvin E 
Published: November 2022

AbstractIn earlier physiologically based pharmacokinetic (PBPK) models for manganese (Mn), the kinetics of transport of Mn into and out of tissues were primarily driven by slow rates of association and dissociation of Mn with tissue binding sites. However, Mn is known to show rapidly reversible binding in tissues. An updated Mn model for primates, following similar work with rats, was developed that included rapid association/dissociation processes with tissue Mn-binding sites, accumulation of free Mn in tissues after saturation of these Mn-binding sites and rapid rates of entry into tissues. This alternative structure successfully described Mn kinetics in tissues in monkeys exposed to Mn via various routes including oral, inhalation, and intraperitoneal, subcutaneous, or intravenous injection and whole-body kinetics and tissue levels in humans. An important contribution of this effort is showing that the extension of the rate constants for binding and cellular uptake established in the monkey were also able to describe kinetic data from humans. With a consistent model structure for monkeys and humans, there is less need to rely on cadaver data and whole-body tracer studies alone to calibrate a human model. The increased biological relevance of the Mn model structure and parameters provides greater confidence in applying the Mn PBPK models to risk assessment. This model is also well-suited to explicitly incorporate emerging information on the role of transporters in tissue disposition, intestinal uptake, and hepatobiliary excretion of Mn.
Feasibility and Utility of Wearable Bluetooth and RFID Sensors to Measure Care Interactions
Authors: Wei Sijia , Wright-Freeman Kayla , McConnell Eleanor S , Caves Kevin , Corazzini Kirsten N 
Published: November 2022

Abstract
Clinical care interactions influence important health outcomes in older adults such as nosocomial infections, falls, and care satisfaction. However, traditional measurements of interactions are often time-consuming, costly, biased, or they interfere with normal clinical care. Wearable sensors measure interpersonal contact with a high degree of spatial and temporal detail and accuracy when applied to examining the spread of infection. This study aims to test the feasibility of implementing two types of commercially available wearable sensors to collect spatial and temporal data for measuring care interactions in health care settings. EMBC02 (Bluetooth) and OpenBeacon (RFID) sensors were tested in a simulation laboratory. Five nursing students wore the sensors along with name tags and enacted a scenario of a fallen nursing home resident. Sensor data were plotted in Python and compared with video recordings of the simulated care interaction to determine sensor usability, accuracy, and precision. EMBC02 and OpenBeacon detected multiple wearers and provided spatial and temporal data. OpenBeacon showed better usability and validity than EMBC02 for using proximity data collected by sensors to infer care interactions. Both OpenBeacon and EMCB02 showed some limitations in accuracy and precision, such as increased data missingness due to idling function and high data noise. Bluetooth and RFID sensors measure different aspects of proximity. OpenBeacon outperformed EMBC02 for measuring care interactions. Combining Bluetooth with RFID may provide richer information for measuring and understanding care interactions. Simulation laboratories can be leveraged to test health technology before use in clinical research.
Crossing the Cervicothoracic Junction
Authors: Vickery Justin W. , Varas Emil E. , Abtahi Amir M. 
Published: November 2022

Abstract:
The cervicothoracic junction (CTJ) is the site of transition in biomechanical, osseous, and alignment properties of the spine. The interface between the highly mobile, lordotic cervical spine and the rigid, kyphotic thoracic spine results increased the biomechanical stress experienced at this junction. The concentration of stress at this level has led to high rates of failure when instrumenting near or across the CTJ. The changes in osseous anatomy from the cervical spine to the thoracic spine present additional challenges in construct planning. For these reasons, a thorough understanding of the complexity of the cervicothoracic junction is necessary when operating near or across the CTJ. There are multiple options for cervical fixation, including lateral mass screws, pedicle screws, and laminar screws, each with its own advantages and risks. Instrumentation at C7 is controversial, and there is data supporting both its inclusion in constructs and no risk when this level is skipped. Thoracic pedicle screws are the preferred method of fixation in this region of the spine; however, the connection between cervical and thoracic screws can be challenging due to differences in alignment. Transitional rods and rod connectors mitigate some of the difficulties with this transition and have shown to be effective options. Recently, more investigation has looked into the failure of posterior cervical constructs which end at or near the CTJ. The trend in data has favored fixation to T1 or T2 rather than ending a construct at C7 due to the decreased rates of distal junction kyphosis. Although data on patient-reported outcomes with a length of constructs and the lowest instrumented vertebra is scarce, preliminary reports show no difference at this time. As posterior cervical instrumentation continues to increase in frequency, the CTJ will continue to be an area of difficulty in navigation and instrumentation. A thorough understanding of this region is necessary and continued research is needed to improve outcomes.

Level of Evidence:
Level V.
Aggressive angiomyxoma of pelvis: A case report and literature review
Authors: Lin Xue-Mei , Wang Li , Wang Qiong 
Published: November 2022

Rationale:
Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor primarily involving the lower genital tract of reproductive females. It often shares pathologic morphology with other mesenchymal lesions, which result in diagnostic difficulties for pathologists.

Patient concerns and diagnoses:
We described the case of a 32-year-old female presenting with a pelvic mass. Imaging examination showed a “swirling sign” within the mass. The mass was 10.2 × 10 × 7.7 cm, located in the right front of the uterus, with unclear demarcation from the surrounding organs and tissues. The gross appearance was grayish brown with a solid section and a myxedematous cut surface. Microscopically, it was a mesenchymal tumor with a presence of perivascular smooth muscle fibers radiating from the blood vessel and an infiltrative growth pattern. The pelvic AAM was diagnosed based on clinicopathologic and imaging features.

Interventions and outcomes:
A surgery with local excision of the mass was performed. The patient experienced 1 relapse during 2-year follow-up and underwent the radiation therapy.

Lessons:
When the pathological morphology of AAM overlaps with other mesenchymal lesions, the comprehensive understanding of tumor clinicopathological characteristics combined with imaging features is important for the accurate diagnosis of AAM.
Effect of dexmedetomidine on intrapulmonary shunt in patients with sevoflurane maintained during one-lung ventilation: A case–control study
Authors: Wang Yewen , Gong Chunzhi , Yu Fei , Zhang Quanyi 
Published: November 2022

Background:
The effects of dexmedetomidine on the circulatory system are complex. It is difficult to predict its effects on intrapulmonary shunts and hypoxic pulmonary vasoconstriction in patients with one-lung ventilation. This study aimed to investigate the effect of dexmedetomidine on intrapulmonary shunt in patients with sevoflurane during one-lung ventilation.

Methods:
Forty patients requiring thoracoscopic lobectomy were randomly divided into the dexmedetomidine group (Group D, n = 20) and the normal saline group (Group N, n = 20). The arterial partial pressure of oxygen (PaO2), pulmonary shunt fraction (Qs/Qt), mean end-tidal sevoflurane concentration, mean arterial pressure, and heart rate were compared between the 2 groups at 3 time points: (i) after 5 minutes of two-lung ventilation (T0), (ii) after 30 minutes of one-lung ventilation (OLV) (T1), and (iii) after 45 minutes of OLV (T2). The dosage of sevoflurane from the beginning of OLV to T2 was calculated.

Results:
There were no significant differences in age, body mass index, and FEV1/FVC between Groups D and N (P > .05). At T0, T1, and T2, the PaO2 levels of Group D and Group N were similar (P > .05), and the PaO2 levels of Group D and Group N decreased after OLV. The Qs/Qt level of Groups D and N were similar at T0 (P > .05), and the level of Groups D and N at T1 and T2 was higher than that at T0. The Qs/Qt of Group D was statistically significantly lower than that of Group N at T1 and T2 (P < .05).

Conclusion:
Compared with the control group, we found that dexmedetomidine can reduce the intrapulmonary shunt fraction and improve the body’s status during OLV.