bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual functionality of pyrimidine and flavone in targeting genomic variants of EGFR and ER receptors to influence the differential survival rates in breast cancer patients
Authors: Avti Pramod K , Singh Jitender , Dahiya Divya , Khanduja Krishan L
Published: December 2023

Breast cancer ranks as one of the most prevalent forms of cancer and stands as the primary global cause of mortality among women. Overexpression of EGFR and ER receptors or their genomic alterations leads to malignant transformation, disease aggression and is linked to poor patient survival outcomes. The clinical breast cancer patient’s genomic expression, survival analysis, and computational drug-targeting approaches were used to identify best-hit phytochemicals for therapeutic purposes. Breast cancer patients have genomic alterations in EGFR (4%, n = 5699) and ER (9%, n = 8461), with the highest proportion being missense mutations. No statistically significant difference was observed in the patient survival rates between the altered and unaltered ER groups, unlike EGFR, with the lowest survival rates in the altered group. Computational screening of natural compound libraries (7711) against each EGFR (3POZ) and ER (3ERT) receptor shortlists the best-hit 3 compounds with minimum docking score (ΔG = −7.9 to −10.8), MMGBSA (−40.16 to −51.91 kcal/mol), strong intermolecular H-bonding, drug-like properties with least kd, and ki. MD simulation studies display stable RMSD, RMSF, and good residual correlation of best-hit common compounds (PubChem ID: 5281672 and 5280863) targeting both EGFR and ER receptors. In vitro, studies revealed that these common drugs exhibited a high anti-proliferative effect on MCF-7 and MDA-MB-231 breast cancer cells, with effective IC50 values (15–40 μM) and lower free energy, kd, and ki (5281672 > 5280863 > 5330286) much affecting HEK-293 non-cancerous cells, indicating the safety profile. The experimental and computational correlation studies suggest that the highly expressed EGFR and ER receptors in breast cancer patients having poor survival rates can be effectively targeted with best-hit common potent drugs with a multi-target therapeutic approach.

Insight Box: The findings of this study provide valuable insights into the genomic/proteomic data, breast cancer patient’s survival analysis, and EGFR and ER receptor variants structural analysis. The genetic alterations analysis of EGFR and ER/ESR1 in breast cancer patients reveals the high frequency of mutation types, which affect patient’s survival rate and targeted therapies. The common best-hit compounds affect the cell survival patterns with effective IC50, drug-like properties having lower equilibrium and dissociation constants demonstrating the anti-proliferative effects. This work integrates altered receptor structural analysis, molecular interaction-based simulations, and ADMET properties to illuminate the identified best hits phytochemicals potential efficacy targeting both EGFR and ER receptors, demonstrating a multi-target therapeutic approach.
Confusion, unfair competition and legal action in OAPI countries
Authors: Lowe Gnintedem Patrick Juvet
Published: December 2023

This paper analyses the interpretation of confusion and the consequences it has on legal action, considering its compliance with the international framework and with regard to the case law of the African Intellectual Property Organization (OAPI) Member States. It argues that provisions of the Bangui Agreement (2015), in particular Annex VIII on unfair competition, are in compliance with international agreements, and the substantial interpretation of confusion made by the case law of the OAPI countries is appropriate. Although OAPI statutory bodies have the possibility to appreciate likelihood of confusion, only the judicial judges have the ultimate authority to give a binding interpretation. When confusion concerns a registered intellectual property right (IPR), a plaintiff can introduce both an action for infringement and an action for unfair competition, or only one of these actions. However, the action for unfair competition has a larger spectrum; it can be introduced even when there is no registered IPR, provided that a separate fault is demonstrated, in combination with the other constitutive elements of unfair competition. Reference made by judges either to national civil liability provisions, to Annex VIII, or to both provisions, as the legal basis of the action for unfair competition, should be harmonized in favour of Annex VIII, even if, in practice, it has not proved to be damaging for any litigant.
Leaf and root traits are partially coordinated but they show contrasting multi-trait-based community trait dispersion patterns in a subtropical forest
Authors: Luo Wenqi , Valverde-Barrantes Oscar J , Weemstra Monique , Cahill James F , Wang Zi , He Dong , Chen Yongfa , Chu Chengjin , Wang Youshi
Published: December 2023

The ecology of plant species relies on the synchronous functioning of leaves and roots, but few studies have simultaneously examined the community trait dispersion (CTD) patterns of both organs. We measured 16 analogous leaf and root traits on 44 co-occurring woody species in a subtropical forest in southern China, aiming to examine whether leaf and root traits were coordinated, organized into parallel trait axes, exhibited similar CTD, and displayed consistent responses in CTD and community-weighted means of (CWM) traits over environmental gradients. While the first axes of leaf and root trait variation similarly exhibited a fast–slow continuum, leaf traits covered a secondary “carbon economics” axis, contrasting to root traits depicting a collaboration axis reflecting species’ mycorrhizal dependency. Analogous leaf and root chemical traits were generally coordinated but less so for morphological traits. At the community level, changes in the CWM of the first axes were generally consistent among organs with more conservative traits found as increasing elevation but not for the second axis. While root traits became thinner and more conservative as soil phosphorus concentration decreased, leaf traits rarely varied. When different trait axes were combined, leaf traits were overdispersed but tended to converge with increased elevation and soil potassium and phosphorus levels, whereas root traits were clustered but tended to diverge along the same gradients. Our study highlights fine filtering of different suites of traits above- and belowground, which in turn might reduce overall niche overlap among species and promote coexistence with diverse functional designs.
Quality, diversity, and impact: (The first) 10 years of theJournal of Professions and Organization
Authors: Brock David M
Published: December 2023

This essay marks, reviews, and celebrates the first decade of the Journal of Professions and Organization. It begins with a brief review of the journal’s founding, initial scope, and objectives. This is followed by an analysis of all the articles published in the first decade (2014–23) of the journal’s existence. Finally, turning to the future, we consider at topics and initiatives that are becoming relevant as we approach JPO’s second decade.
The Forgotten Dreams of History-from-Below
Authors: Satia Priya
Published: December 2023

In his 2003 essay, “On Agency,” Walter Johnson faulted the way scholars’ focus on agency presumed a “unidirectional trade between past and present,” treating “history writing as a mode of redress.” It marginalized “human-ness lived outside the conventions” of a “liberal notion of selfhood.” Restoring agency to the enslaved made the scholar feel better about themselves without making the world any better: “therapy rather than politics.” Looking back on this pivotal assessment of social history from the vantage of twenty years, its criticisms seem relevant to the use of agency in its time (and ours) more than to the concept’s original invention in the era of decolonization after World War II. In that time, drawing on anticolonial thought, history-from-below emerged precisely to contest liberal notions of selfhood and reform the existing, whiggish two-way trade between past and present. Revisiting that turn reminds us that questions raised by the category of “agency” were present at its making and that it is unlikely that academic scholarship can fulfill more than a therapeutic function without affiliated struggles to remake the academy and popular politics. Reminding us of history-from-below's foundational commitment to building up “the present-life of the past” and challenging the individuated ideal of selfhood, this essay notes the continued urgency of recovering alternative subjectivities as we face the planetary crisis created by dominance of Enlightenment notions of history and selfhood. Though scholarship in the academy may not be capable of the political impact Johnson imagined, it nevertheless furthers history’s actual end of internal transformation.
On the Agency of Environmental History
Authors: Demuth Bathsheba
Published: December 2023

Twenty years ago, Walter Johnson warned historians not to rely on a concept that let both user and audience alike feel better without doing better. The concept in question was agency. Down the metaphorical hall and many a literal one, environmental historians were also talking about agency. The proximity is not surprising: the new social history Johnson addressed in 2003 came up alongside environmental history.
Liver transplantation due to fulminant hepatitis A in a traveller visiting friends and relatives in Comoros
Authors: Diallo Safiétou , Borentain Patrick , Motte Anne , Gautret Philippe , Colson Philippe
Published: December 2023

An unvaccinated adult migrant from Comoros to France presented with fulminant hepatitis A after a 5-month-stay in Comoros visiting friends and relatives. People who have lived in hepatitis A endemic areas should be tested for hepatitis A virus (HAV) IgG before travelling to an HAV hyperendemic country to assess the benefit of vaccination.
Introducing a randomized controlled trial into Family Proceedings: Describing the ‘how?’ and defending the ‘why?’
Authors: Atkinson Carol , Forde Matt , Crawford Karen , Henderson Marion , Wilson Philip , Ougrin Dennis , Minnis Helen
Published: December 2023

In 2011, a randomized controlled trial (RCT) of a mental health intervention for families with children under the age of 5 years coming into the Scottish care system was launched, called the Best Services Trial (BeST). When attempts were made to expand the study to English sites, the local leadership Judge objected, concerned that randomization in family proceedings was unfair, potentially discriminatory, and unlawful. Considerations about parental consent, fairness of randomization, and an understanding that the new intervention might be no better, or even harmful, compared to current best practices were crucial in addressing these concerns. In 2017, BeST was launched in England utilizing a randomized methodology. Significant input into the design of BeST came from the leadership Judge who had previously considered randomization unlawful. In July 2021, 383 families with 488 children had been recruited across both Scottish and English sites. Follow-up continues and 76 per cent of families continue to participate at 2.5 years after entering the study. Although there were undoubted challenges in designing and implementing BeST, with hindsight, the objections raised to the testing of interventions randomly were demonstrably resolvable and the process of randomization encountered no legal challenges. This is the first time an RCT has been accommodated within live proceedings in the family justice arena in England and Wales and one of a relatively few such RCTs conducted internationally.
DNA Conserved in Diverse Animals Since the Precambrian Controls Genes for Embryonic Development
Authors: Frith Martin C , Ni Shengliang
Published: December 2023

DNA that controls gene expression (e.g. enhancers, promoters) has seemed almost never to be conserved between distantly related animals, like vertebrates and arthropods. This is mysterious, because development of such animals is partly organized by homologous genes with similar complex expression patterns, termed “deep homology.” Here, we report 25 regulatory DNA segments conserved across bilaterian animals, of which 7 are also conserved in cnidaria (coral and sea anemone). They control developmental genes (e.g. Nr2f, Ptch, Rfx1/3, Sall, Smad6, Sp5, Tbx2/3), including six homeobox genes: Gsx, Hmx, Meis, Msx, Six1/2, and Zfhx3/4. The segments contain perfectly or near-perfectly conserved CCAAT boxes, E-boxes, and other sequences recognized by regulatory proteins. More such DNA conservation will surely be found soon, as more genomes are published and sequence comparison is optimized. This reveals a control system for animal development conserved since the Precambrian.
A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR
Authors: Huber Andrew D , Poudel Shyaron , Wu Jing , Miller Darcie J , Lin Wenwei , Yang Lei , Bwayi Monicah N , Rimmer Mary Ashley , Gee Rebecca R Florke , Seetharaman Jayaraman , Chai Sergio C , Chen Taosheng
Published: December 2023

Bromodomain and extraterminal (BET) proteins are extensively studied in multiple pathologies, including cancer. BET proteins modulate transcription of various genes, including those synonymous with cancer, such as MYC. Thus, BET inhibitors are a major area of drug development efforts. (+)-JQ1 (JQ1) is the prototype inhibitor and is a common tool to probe BET functions. While showing therapeutic promise, JQ1 is not clinically usable, partly due to metabolic instability. Here, we show that JQ1 and the BET-inactive (−)-JQ1 are agonists of pregnane X receptor (PXR), a nuclear receptor that transcriptionally regulates genes encoding drug-metabolizing enzymes such as CYP3A4, which was previously shown to oxidize JQ1. A PXR-JQ1 co-crystal structure identified JQ1′s tert-butyl moiety as a PXR anchor and explains binding by (−)-JQ1. Analogs differing at the tert-butyl lost PXR binding, validating our structural findings. Evaluation in liver cell models revealed both PXR-dependent and PXR-independent modulation of CYP3A4 expression by BET inhibitors. We have characterized a non-BET JQ1 target, a mechanism of physiological JQ1 instability, a biological function of (−)-JQ1, and BET-dependent transcriptional regulation of drug metabolism genes.
Visualizing cancer-originating acetate uptake through monocarboxylate transporter 1 in reactive astrocytes in the glioblastoma tumor microenvironment
Authors: Kim Dongwoo , Ko Hae Young , Chung Jee-In , Park Yongmin Mason , Lee Sangwon , Kim Seon Yoo , Kim Jisu , Chun Joong-Hyun , Han Kyung-Seok , Lee Misu , Ju Yeon Ha , Park Sun Jun , Park Ki Duk , Nam Min-Ho , Kim Se Hoon , Shim Jin-Kyoung , Park Youngjoo , Lim Hyunkeong , Park Jaekyung , Lee Gwan-Ho , Kim Hyunjin , Kim Suhyun , Park Uiyeol , Ryu Hoon , Lee So Yun , Park Sunghyouk , Kang Seok-Gu , Chang Jong Hee , Lee C Justin , Yun Mijin
Published: December 2023

Background

Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explore 11C-acetate PET as an imaging technique for detecting reactive astrogliosis.

Methods

Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated 11C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and monocarboxylate transporter 1 (MCT1) expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of 11C-acetate uptake beyond MRI and prognosis.

Results

Elevated 11C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of 11C-acetate uptake beyond contrast-enhanced MRI was associated with a worse prognosis.

Conclusions

Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of 11C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.
Impact of unhealthy food and beverage consumption on children’s risk of dental caries: a systematic review
Authors: Large Jessica F , Madigan Claire , Pradeilles Rebecca , Markey Oonagh , Boxer Benjamin , Rousham Emily K
Published: December 2023

Context

The impact of unhealthy foods and beverages, namely those high in sugar, salt, and saturated or trans fats, has been studied extensively in relation to weight, body composition, and noncommunicable diseases, but less so in relation to the risk of dental caries. Few previous reviews have examined the evidence from all countries globally.

Objective

A systematic review was conducted to assess the impact of unhealthy food and beverage consumption on the risk of dental caries in children aged ≤10 years, commissioned by the World Health Organization to inform updated complementary feeding recommendations.

Data Sources

Systematic searches were conducted in the PubMed, Cochrane, and Embase databases for articles meeting the inclusion criteria dating from January 1971 to March 2022; supplementary searches were undertaken for articles from that period to June 2022.

Data Extraction

Unhealthy foods and beverages were identified using nutrient- and food-based approaches. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I).

Data Analysis

A total of 30 023 unique citations were screened, yielding 37 studies for inclusion. Studies were conducted in high-income (n = 23 [62.2%]) or middle-income countries (n = 14 [37.8%]). Evidence synthesis was performed narratively, stratified by age (0 years to <2 years, 2 years to <5 years, and 5 years to ≤10 years) and exposure (unhealthy foods and unhealthy beverages). The heterogeneity of the exposures and comparators across studies was high. Almost all studies (n = 34) reported positive associations between the consumption of sugar-sweetened beverages or foods high in free sugars and dental caries. However, 67.6% of studies were assessed as having serious risk of bias.

Conclusion

The evidence indicates that the consumption of unhealthy food and beverages in children ≤10 years appears to increase the risk of dental caries. Further longitudinal studies with high-quality dietary assessments, including studies in low-income countries and children aged >5 years at baseline, are recommended in order to build a more robust evidence base for use in the development of policy recommendations.

Systematic Review Registration

PROSPERO registration no. CRD42020218109.
How to Design Consent for Health Data Research? An Analysis of Arguments of Solidarity
Authors: Wiertz Svenja
Published: December 2023

The article discusses the impact different concepts of solidarity can have on debates on models of consent for non-interventional research. It introduces three concepts of solidarity that have been referenced in bioethical debates: a purely descriptive concept, a concept that claims some derivative value for most but not all practices of solidarity, as well as a clearly normative concept where solidarity is tied to justice and taken to ground moral duties. It shows that regarding the rivalling models of study-specific consent, tiered consent and broad consent, the first two concepts can be taken to favour tiered consent while only normative solidarity supports a model of broad consent—or an argument to allow non-interventional research without requiring consent at all. As normative solidarity is tied to considerations of justice, however, the argument appears less straightforward than one might expect: It presupposes that the research contributes to overcoming existing social injustices.
The microtubule-nucleating factor MACERATOR tethers AUGMIN7 to microtubules and governs phragmoplast architecture
Authors: Schmidt-Marcec Sharol , Parish Alyssa , Smertenko Tetyana , Hickey Matthew , Piette Bernard M A G , Smertenko Andrei
Published: December 2023

The plant cytokinetic microtubule array, called the phragmoplast, exhibits higher microtubule dynamics in its center (midzone) than at the periphery (distal zone). This behavior is known as the axial asymmetry. Despite being a major characteristic of the phragmoplast, little is known about regulators of this phenomenon. Here we address the role of microtubule nucleation in axial asymmetry by characterizing MACERATOR (MACET) proteins in Arabidopsis thaliana and Nicotiana benthamiana with a combination of genetic, biochemical, and live-cell imaging assays, using photo-convertible microtubule probes, and modeling. MACET paralogs accumulate at the shrinking microtubule ends and decrease the tubulin OFF rate. Loss of MACET4 and MACET5 function abrogates axial asymmetry by suppressing microtubule dynamicity in the midzone. MACET4 also narrows the microtubule nucleation angle at the phragmoplast leading edge and functions as a microtubule tethering factor for AUGMIN COMPLEX SUBUNIT 7 (AUG7). The macet4 macet5 double mutant shows diminished clustering of AUG7 in the phragmoplast distal zone. Knockout of AUG7 does not affect MACET4 localization, axial asymmetry, or microtubule nucleation angle, but increases phragmoplast length and slows down phragmoplast expansion. The mce4-1 mce5 aug7-1 triple knockout is not viable. Experimental data and modeling demonstrate that microtubule nucleation factors regulate phragmoplast architecture and axial asymmetry directly by generating new microtubules and indirectly by modulating the abundance of free tubulin.
The E3 ligase TaGW2 mediates transcription factor TaARR12 degradation to promote drought resistance in wheat
Authors: Li Shumin , Zhang Yifang , Liu Yuling , Zhang Peiyin , Wang Xuemin , Chen Bin , Ding Li , Nie Yingxiong , Li Fangfang , Ma Zhenbing , Kang Zhensheng , Mao Hude
Published: December 2023

Drought stress limits crop yield, but the molecular modulators and their mechanisms underlying the trade-off between drought resistance and crop growth and development remain elusive. Here, a grain width and weight2 (GW2)-like really interesting new gene finger E3 ligase, TaGW2, was identified as a pivotal regulator of both kernel development and drought responses in wheat (Triticum aestivum). TaGW2 overexpression enhances drought resistance but leads to yield drag under full irrigation conditions. In contrast, TaGW2 knockdown or knockout attenuates drought resistance but remarkably increases kernel size and weight. Furthermore, TaGW2 directly interacts with and ubiquitinates the type-B Arabidopsis response regulator TaARR12, promoting its degradation via the 26S proteasome. Analysis of TaARR12 overexpression and knockdown lines indicated that TaARR12 represses the drought response but does not influence grain yield in wheat. Further DNA affinity purification sequencing combined with transcriptome analysis revealed that TaARR12 downregulates stress-responsive genes, especially group-A basic leucine zipper (bZIP) genes, resulting in impaired drought resistance. Notably, TaARR12 knockdown in the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated tagw2 knockout mutant leads to significantly higher drought resistance and grain yield compared to wild-type plants. Collectively, these findings show that the TaGW2–TaARR12 regulatory module is essential for drought responses, providing a strategy for improving stress resistance in high-yield wheat varieties.
m6A RNA methylation counteracts dark-induced leaf senescence in Arabidopsis
Authors: Sheikh Arsheed H , Tabassum Naheed , Rawat Anamika , Almeida Trapp Marilia , Nawaz Kashif , Hirt Heribert
Published: December 2023

Senescence is an important physiological process which directly affects many agronomic traits in plants. Senescence induces chlorophyll degradation, phytohormone changes, cellular structure damage, and altered gene regulation. Although these physiological outputs are well defined, the molecular mechanisms employed are not known. Using dark-induced leaf senescence (DILS) as the experimental system, we investigated the role of N6-methyladenosine (m6A) mRNA methylation during senescence in Arabidopsis (Arabidopsis thaliana). Plants compromised in m6A machinery components like METHYLTRANSFERASE A (mta mutant) and VIRILIZER1 (vir-1 mutant) showed an enhanced DILS phenotype. This was accompanied by compromised chloroplast and photosynthesis performance in mta as well as accumulation of senescence-promoting camalexin and phytohormone jasmonic acid after dark treatment. m6A levels increased during DILS and destabilized senescence-related transcripts thereby preventing premature aging. Due to inefficient decay, senescence-related transcripts like ORESARA1 (ORE1), SENESCENCE-ASSOCIATED GENE 21 (SAG21), NAC-like, activated by AP3/PI (NAP), and NONYELLOWING 1 (NYE1) over-accumulated in mta thereby causing accelerated senescence during DILS. Overall, our data propose that m6A modification is involved in regulating the biological response to senescence in plants, providing targets for engineering stress tolerance of crops.
Cardiac computed tomography angiography with and without bolus tracking methods in infants with congenital heart disease
Authors: Yoshiura Takayuki , Masuda Takanori , Tahara Masahiro , Kobayashi Yukie , Kikuhara Yukari , Ishibashi Toru , Nonaka Haruki , Oku Takayuki , Sato Tomoyasu , Funama Yoshinori
Published: December 2023

The study investigated radiation dose, vascular computed tomography (CT) enhancement and image quality of cardiac computed tomography angiography (CCTA) with and without bolus tracking (BT) methods in infants with congenital heart disease (CHD). The volume CT dose index (CTDIvol) and dose length product (DLP) were recorded for all CT scans, and the effective dose was obtained using a conversion factors. The CT number for the ascending aorta (AO) and pulmonary artery (PA), image noise of muscle tissue and contrast-to-noise ratio (CNR) were measured and calculated. The median values in the groups with and without BT were 2.20 mGy versus 0.44 mGy for CTDIvol, 8.10 mGy·cm versus 6.20 mGy·cm for DLP, and 0.66 mSv versus 0.51 mSv for effective dose (p < 0.001). There were no statistical differences in vascular CT enhancement, image noise, and CNR. CCTA without BT methods can reduce the radiation dose while maintaining vascular CT enhancement and image quality compared to CCTA with BT methods.
Unlocking the Therapeutic Potential of Exosomes Derived From Nasal Olfactory Mucosal Mesenchymal Stem Cells: Restoring Synaptic Plasticity, Neurogenesis, and Neuroinflammation in Schizophrenia
Authors: Zhong Xiao-Lin , Huang Yan , Du Yang , He Li-Zheng , Chen Yue-wen , Cheng Yong , Liu Hua
Published: December 2023

Background and Hypothesis

Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM).

Study Design

We conducted a comprehensive investigation to assess the impact of intranasally delivered OM-MSC-exos on SCZ-like behaviors in MAM-induced mice. This study encompassed behavioral assessments, neuroinflammatory markers, glial activation, synaptic protein expression, and neurogenesis within the hippocampus.

Study Results

Our findings demonstrated that intranasal administration of OM-MSC-exos effectively ameliorated SCZ-like behaviors, specifically addressing social withdrawal and sensory gating deficits in the MAM-induced murine model. Furthermore, OM-MSC-exos intervention yielded a reduction in neuroinflammatory markers and a suppression of microglial activation within the hippocampus. Simultaneously, we observed an upregulation of key synaptic protein expression, including PSD95 and TH, the rate-limiting enzyme for dopamine biosynthesis.

Conclusions

Our study underscores the therapeutic potential of OM-MSC-exos in mitigating SCZ-like behavior. The OM-MSC-exos have the capacity to modulate glial cell activation, diminish neuroinflammation, and promote BDNF-associated synaptic plasticity and neurogenesis, thus ameliorating SCZ-like behaviors. In summary, intranasal administration of OM-MSC-exos offers a multifaceted approach to address SCZ mechanisms, promising innovative treatments for this intricate disorder.
Boundary work to what end? Analysing the acid mine drainage case in Gauteng, South Africa
Authors: Funke Nikki , Huitema Dave , Petersen Arthur
Published: December 2023

This article contributes a boundary work analysis of the case of acid mine drainage (AMD) in South Africa to the existing boundary work literature. We conduct our analysis by applying a synthesized multi-level boundary work framework to examine whether the knowledge that was produced during the boundary work conducted was usable and influential in decision-making and resulted in successful policy implementation. We conclude that contrary to expectations, a closed, technocratic boundary work process resulted in the relatively successful implementation of a short-term intervention in the AMD problem, whereas a subsequent open and deliberative process did not result in the successful implementation of the long-term policy solution. We ascribe this finding to the influence of critical enabling and constraining factors characterizing the South African socio-political context within which the AMD issue is situated, and therefore, we recommend adding a meta-analytical layer to boundary work analyses, especially in developing country contexts.
A new booid snake from the Eocene (Lutetian) Konservat-Lagerstätte of Geiseltal, Germany, and a new phylogenetic analysis of Booidea
Authors: Palci Alessandro , Onary Silvio , Lee Michael S Y , Smith Krister T , Wings Oliver , Rabi Márton , Georgalis Georgios L
Published: December 2023

We describe two exceptionally preserved fossil snakes from the Eocene Konservat-Lagerstätte of Geiseltal, located in the state of Saxony-Anhalt, Germany. The two snake specimens, GMH LIX-3-1992 and GMH XXXVIII-20-1964, can be confidently identified as booids based on general morphology and were thus compared to other geographically and/or temporally close fossil booids. We found that GMH LIX-3-1992 is morphologically very similar to Eoconstrictor spinifer, also from Geiseltal, and to Eoconstrictor fischeri, from the middle Eocene of Messel, but differs from both in a number of cranial and vertebral features. Based on these differences we erect the new species Eoconstrictor barnesi sp. nov.; GMH XXXVIII-20-1964 is very similar to GMH LIX-3-1992 and the two differ only in features that are likely ontogenetic. Phylogenetic analyses of snakes using maximum parsimony and Bayesian inference on datasets inclusive of both morphological and molecular data consistently support a close affinity of E. barnesi to E. fischeri and E. spinifer. Our preferred phylogenetic hypothesis places the three species of Eoconstrictor in a clade that is sister to Neotropical Boidae, a result consistent with previous studies. The genus Eoconstrictor could provide an important calibration point for molecular clock studies of booids and snakes in general.
Fungal Trunk Diseases Causing Decline of Apricot and Plum Trees in the Czech Republic
Authors: Spetik Milan , Pecenka Jakub , Stuskova Katerina , Stepanova Bara , Eichmeier Ales , Kiss Tomas
Published: December 2023

Fungal trunk diseases (FTDs) have been a significant threat to the global stone fruit industry. FTDs are caused by a consortium of wood-decaying fungi. These fungi colonize woody tissues, causing cankers, dieback, and other decline-related symptoms in host plants. In this study, a detailed screening of the fungal microbiota associated with the decline of stone fruit trees in the Czech Republic was performed. The wood fragments of plum and apricot trees showing symptoms of FTDs were subjected to fungal isolation. The partial internal transcribed spacer region, partial beta-tubulin, and translation elongation factor 1-α genes were amplified from genomic DNA extracted from fungal cultures. All isolates were classified, and the taxonomic placement of pathogenic strains was illustrated in phylogenetic trees. The most abundant pathogenic genus was Dactylonectria (31%), followed by Biscogniauxia (13%), Thelonectria (10%), Eutypa (9%), Dothiorella (7%), Diplodia (6%), and Diaporthe (6%). The most frequent endophytic genus was Aposphaeria (17%). The pathogenicity of six fungal species (Cadophora daguensis, Collophorina africana, Cytospora sorbicola, Dothiorella sarmentorum, Eutypa lata, and E. petrakii var. petrakii) to four Prunus spp. was evaluated, and Koch’s postulates were fulfilled. All tested isolates caused lesions on at least one Prunus sp. The most aggressive species was E. lata, which caused the largest lesions on all four tested Prunus spp., followed by E. petrakii var. petrakii and D. sarmentorum. Japanese plum (Prunus salicina) and almond (P. amygdalus) were the most susceptible hosts, while apricot (P. armeniaca) was the least susceptible host in the pathogenicity trial.
Single cell RNA sequencing reveals emergent notochord‐derived cell subpopulations in the postnatal nucleus pulposus
Authors: Zhang Chenghao , Zhong Leilei , Lau Yian Khai , Wu Meilun , Yao Lutian , Schaer Thomas P. , Mauck Robert L. , Malhotra Neil R. , Qin Ling , Smith Lachlan J.
Published: December 2023

Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell‐based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord‐derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte‐like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor‐beta and phosphoinositide 3 kinase‐protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co‐localized with emerging glycosaminoglycan‐rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.
Get your 7-point golden medal for pain management in video-assisted thoracoscopic surgery
Authors: Hoogma Danny Feike , Brullot Liesbeth , Coppens Steve
Published: December 2023

Purpose of review

Thoracic surgery is evolving, necessitating an adaptation for perioperative anesthesia and analgesia. This review highlights the recent advancements in perioperative (multimodal) analgesia for minimally invasive thoracic surgery.

Recent findings

Continuous advancements in surgical techniques have led to a reduction in surgical trauma. However, managing perioperative pain remains a major challenge, impeding postoperative recovery. The traditional neuraxial technique is now deemed outdated for minimally invasive thoracic surgery. Instead, newer regional techniques have emerged, and traditional approaches have undergone (re-)evaluation by experts and professional societies to establish guidelines and practices. Assessing the quality of recovery, even

after discharge, has become a crucial factor in evaluating the effectiveness of these strategies, aiding clinicians in making informed decisions to improve perioperative care.

In the realm of minimally invasive thoracic surgery, perioperative analgesia is typically administered through systemic and regional techniques. Nevertheless, collaboration between anesthesiologists and surgeons, utilizing surgically placed nerve blocks and an active chest drain management, has the potential to significantly improve overall patient care.
Perioperative hemodynamic monitoring in cardiac surgery
Authors: Grant Michael C. , Salenger Rawn , Lobdell Kevin W.
Published: December 2023

Purpose of review

Cardiac surgery has traditionally relied upon invasive hemodynamic monitoring, including regular use of pulmonary artery catheters. More recently, there has been advancement in our understanding as well as broader adoption of less invasive alternatives. This review serves as an outline of the key perioperative hemodynamic monitoring options for cardiac surgery.

Recent findings

Recent study has revealed that the use of invasive monitoring such as pulmonary artery catheters or transesophageal echocardiography in low-risk patients undergoing low-risk cardiac surgery is of questionable benefit. Lesser invasive approaches such a pulse contour analysis or ultrasound may provide a useful alternative to assess patient hemodynamics and guide resuscitation therapy. A number of recent studies have been published to support broader indication for these evolving technologies.

More selective use of indwelling catheters for cardiac surgery has coincided with greater application of less invasive alternatives. Understanding the advantages and limitations of each tool allows the bedside clinician to identify which hemodynamic monitoring modality is most suitable for which patient.
Temporary mechanical circulatory support & enhancing recovery after cardiac surgery
Authors: Lobdell Kevin W. , Grant Michael C. , Salenger Rawn
Published: December 2023

Purpose of review

This review highlights the integration of enhanced recovery principles with temporary mechanical circulatory support associated with adult cardiac surgery.

Recent findings

Enhanced recovery elements and efforts have been associated with improvements in quality and value. Temporary mechanical circulatory support technologies have been successfully employed, improved, and the value of their proactive use to maintain hemodynamic goals and preserve long-term myocardial function is accruing.

Temporary mechanical circulatory support devices promise to enhance recovery by mitigating the risk of complications, such as postcardiotomy cardiogenic shock, organ dysfunction, and death, associated with adult cardiac surgery.
Mortality in Treatment-seeking Older Adults Receiving Medications for Opioid Use Disorder
Authors: Weber Andrea N. , Arndt Stephan , Miskle Benjamin , Bormann Nicholas L.
Published: December 2023

Objectives

Older adults (OAs; age 55+ years) are increasingly seeking specialty treatment of opioid use disorder. Previous analyses of the Treatment Episode Data Set—Discharges (TEDS-D) database have reported higher rates of in-treatment mortality for those receiving medications for opioid use disorder (MOUD). We evaluate current trends in mortality for treatment-seeking OAs.

Methods

Using the 2020 TEDS-D, logistic regression predicted in-treatment mortality for OAs from planned MOUD, service level, and interaction terms.

Results

Of the 26,993 OA treatment discharges, 679 people were discharged due to death (2.52%). OAs with MOUD (3.65%, 95% confidence interval [CI], 3.37%–3.95%) were significantly more likely to discharge due to death than those without MOUD (0.82%; 95% CI, 0.66%–1.01%). Most records were for nonintensive outpatient (83.7%; n = 22,588), which had the highest mortality (2.89%; 95% CI, 2.68%–3.11%); intensive services (n = 4405) had a mortality rate of 0.61% (95% CI, 0.42%–0.89%). Among OAs, planned MOUD with nonintensive outpatient services had a mortality rate of 4.17% (95% CI, 3.56%–4.9%).

Conclusions

This TEDS-D analysis extends previous literature highlighting a significant interaction between planned MOUD and service intensity on in-treatment mortality for OAs. Additional research is needed to address the causal mechanisms behind these interactions and inform the delivery of safe effective care in the growing OA population.
Themes of Liminality
Authors: Weiss Charlotte R. , Johnson-Koenke Rachel , Reed Sean M. , Willis Danny G. , Sousa Karen H.
Published: December 2023

Cancer family caregivers dwell in an evolving landscape of ambiguity and in-betweenness, as “betwixt and between,” in a space of unknowing. This space of unknowing exists within a transformational threshold of liminality, between what was known prior to the cancer and what will be known and embodied in the future. Theoretically grounded in Unitary Caring Science, this study used narrative inquiry alongside photo elicitation to cocreate cancer caregiver narratives and identify themes of liminality. Four thematic threads of liminality were identified as woven within and across the cancer caregiver narratives; stories of paradox, time warp, life disruption, and waiting in silence.
Hospital Volume and Quality of Care for Emergency Gynecologic Care
Authors: Kalinowska Vanessa , Huang Yongmei , Buckley Alexander , St Clair Caryn M. , Pua Tarah , Khoury-Collado Fady , Hou June Y. , Hershman Dawn L. , Wright Jason D.
Published: December 2023

OBJECTIVE:

To evaluate the association between hospital volume and the quality of gynecologic emergency care for tubal ectopic pregnancies, ovarian torsion, and pelvic inflammatory disease (PID).

METHODS:

In this cross-sectional analysis, we analyzed patients who presented for emergency care for tubal ectopic pregnancies, ovarian torsion, and PID using the Premier Healthcare Database from 2006 to 2020. We measured the following outcomes: methotrexate use for ectopic pregnancy, ovarian cystectomy for torsion, and guideline-based antibiotic use for PID. For each condition, we measured outlier hospitals that performed the above interventions at below the 10th percentile. Multivariable logistic regression models were used to analyze associations between outlier care and hospital factors such as annualized mean case volume, urban or rural location, teaching status, bed capacity, and geographic region, as well as hospital-level patient population factors, including age, insurance status, and race.

RESULTS:

A total of 602 hospitals treated patients with tubal ectopic pregnancies, of which 21.9% were outliers, with no cases managed with methotrexate. Of 512 hospitals treating patients with ovarian torsion, 17.4% were outliers, with no cases managed with cystectomy. Of 929 hospitals that treated patients with PID, 9.9% were deemed outliers with low rates of guideline-adherent antibiotic administration. Low-volume hospitals were more likely to be outliers with low rates of use of methotrexate for ectopic pregnancy (6.7% of high-volume hospitals vs 49.7% of low-volume hospitals were outliers; adjusted odds ratio [aOR] 0.13, 95% CI, 0.05–0.31 for high-volume hospitals) and cystectomy for torsion (34.9% of low-volume vs 2.4% of high-volume hospitals were outliers; aOR 0.05, 95% CI, 0.01–0.18 for high-volume hospitals). There was no association between hospital volume and lower rates of guideline-based antibiotic use for PID.

CONCLUSION:

Higher hospital volume is associated with use of conservative, fertility-preserving treatment of emergency gynecologic conditions, including ectopic pregnancy and ovarian torsion.
Prophylactic Intramedullary Rodding After Femoral Lengthening in Patients With Achondroplasia and Hypochondroplasia
Authors: Rovira Martí Pilar , Ginebreda Martí Ignacio , García Fontecha César
Published: December 2023

Background:

Femoral fracture after femoral lengthening in patients with achondroplasia and hypochondroplasia is a frequent complication, occurring in up to 30%. The purpose of this study is to demonstrate the effectiveness of prophylactic intramedullary rodding in preventing this complication.

Methods:

Multicenter retrospective study involving 86 femoral lengthening procedures in 43 patients with achondroplasia or hypochondroplasia. Forty-two femora (21 patients) were prophylactically managed with intramedullary Rush rodding after external fixation removal (11 females and 10 males, mean age 14.6 years) compared with 44 femora (22 patients) without prophylactic intramedullary rodding (13 females and 9 males, mean age 15.2 years). The mean amount of lengthening in the rodding group was 13.3 cm (52.6%) with an External Fixation Index of 25.8 days/cm; in patients without rodding was 14.3 cm (61.5%) and 24.5 days/cm, respectively.

Results:

Seven cases (15.9%) without rodding developed fractures. Four of them required surgical correction due to displacement or shortening. Only 1 patient (2.4%) had fracture of the femur after prophylactic rodding, and surgery was not required. The incidence of femur fracture was significantly lower in the prophylactic rodding group compared with the nonrodding group (2.4% vs. 15.9%, respectively; P=0.034). There were no cases of infection or avascular necrosis.

Conclusions:

Prophylactic intramedullary rodding is a safe and effective method for preventing femoral fractures after femoral lengthening in patients with achondroplasia or hypochondroplasia.

Level of Evidence:

Level III—a retrospective comparative study.
Long-Term Outcomes after Abdominal Radiation for Wilms Tumor
Authors: Conte Brianna , Shen Colette , Thompson Patrick , Davis Ian , Casey Dana L.
Published: December 2023

Background:

As radiation therapy (RT) for Wilms tumor (WT) evolves with more conformal techniques, it is necessary to evaluate patterns of failure and toxicity. We sought to determine the rate of local failure (LF) after abdominal RT in WT, specifically focusing on those with contained rupture treated with whole abdominal and pelvic RT (WAPRT) vs flank RT. Secondary objectives were to determine overall survival (OS), distant failure (DF), and late toxicities.

Methods:

A single institution retrospective study of 54 pediatric patients with WT treated with abdominal RT between May 2000 and October 2022. LF and DF were calculated through cumulative incidence function and OS by Kaplan-Meier method.

Results:

The median age was 4.5 years and the median follow-up was 6 years. Most patients (91%) had favorable histology. Only 1 patient experienced LF, 15 months from completion of RT (cumulative incidence 2% at 5 y). All patients who received unilateral flank radiation for contained rupture/spillage (n=13) experienced long-lasting intra-abdominal tumor control. A total of 5 patients experienced a DF at a median of 7 months, all in the lung. No patient relapsed in the lungs after upfront whole lung irradiation (n=16). OS was 96% at 5 years. Among 28 patients who followed through puberty, 4 female patients with prior WAPRT experienced hormonal irregularities/infertility.

Conclusion:

Unilateral flank radiation may be a viable alternative to WAPRT for contained rupture/spillage and should be further explored prospectively. Our results may also be utilized in the future for outcome and toxicity comparison as conformal radiation techniques evolve.