bluuebunny/crossref_metadata_2025 huggingface dataset:
Cosmc regulates O-glycan extension in murine hepatocytes
Authors: Aryal Rajindra P , Noel Maxence , Zeng Junwei , Matsumoto Yasuyuki , Sinard Rachael , Waki Hannah , Erger Florian , Reusch Björn , Beck Bodo B , Cummings Richard D
Published: August 2024

Hepatocytes synthesize a vast number of glycoproteins found in their membranes and secretions, many of which contain O-glycans linked to Ser/Thr residues. As the functions and distribution of O-glycans on hepatocyte-derived membrane glycoproteins and blood glycoproteins are not well understood, we generated mice with a targeted deletion of Cosmc (C1Galt1c1) in hepatocytes. Liver glycoproteins in WT mice express typical sialylated core 1 O-glycans (T antigen/CD176) (Galβ1-3GalNAcα1-O-Ser/Thr), whereas the Cosmc knockout hepatocytes (HEP-Cosmc-KO) lack extended O-glycans and express the Tn antigen (CD175) (GalNAcα1-O-Ser/Thr). Tn-containing glycoproteins occur in the sera of HEP-Cosmc-KO mice but not in WT mice. The LDL-receptor (LDLR), a well-studied O-glycosylated glycoprotein in hepatocytes, behaves as a ∼145kD glycoprotein in WT liver lysates, whereas it is reduced to ∼120 kDa in lysates from HEP-Cosmc-KO mice. Interestingly, the expression of the LDLR, as well as HMG-CoA reductase, which is typically altered in response to dysregulated cholesterol metabolism, are similar between WT and HEP-Cosmc-KO mice, indicating no significant effect by Cosmc deletion on either LDLR stability or cholesterol metabolism. Consistent with this, we observed no detectable phenotype in the HEP-Cosmc-KO mice regarding development, appearance or aging compared to WT. These results provide surprising, novel information about the pathway of O-glycosylation in the liver.
Qualitative system dynamics modelling to support the design and implementation of tuberculosis infection prevention and control measures in South African primary healthcare facilities
Authors: Diaconu Karin , Karat Aaron , Bozzani Fiammetta , McCreesh Nicky , Falconer Jennifer , Voce Anna , Vassall Anna , Grant Alison D , Kielmann Karina
Published: August 2024

Tuberculosis infection prevention and control (TB IPC) measures are a cornerstone of policy, but measures are diverse and variably implemented. Limited attention has been paid to the health system environment, which influences successful implementation of these measures. We used qualitative system dynamics and group-model-building methods to (1) develop a qualitative causal map of the interlinked drivers of Mycobacterium tuberculosis (Mtb) transmission in South African primary healthcare facilities, which in turn helped us to (2) identify plausible IPC interventions to reduce risk of transmission. Two 1-day participatory workshops were held in 2019 with policymakers and decision makers at national and provincial levels and patient advocates and health professionals at clinic and district levels. Causal loop diagrams were generated by participants and combined by investigators. The research team reviewed diagrams to identify the drivers of nosocomial transmission of Mtb in primary healthcare facilities. Interventions proposed by participants were mapped onto diagrams to identify anticipated mechanisms of action and effect. Three systemic drivers were identified: (1) Mtb nosocomial transmission is driven by bottlenecks in patient flow at given times; (2) IPC implementation and clinic processes are anchored within a staff ‘culture of nominal compliance’; and (3) limited systems learning at the policy level inhibits effective clinic management and IPC implementation. Interventions prioritized by workshop participants included infrastructural, organizational and behavioural strategies that target three areas: (1) improve air quality, (2) improve use of personal protective equipment and (3) reduce the number of individuals in the clinic. In addition to core mechanisms, participants elaborated specific additional enablers who would help sustain implementation. Qualitative system dynamics modelling methods allowed us to capture stakeholder views and potential solutions to address the problem of sub-optimal TB IPC implementation. The participatory elements of system dynamics modelling facilitated problem-solving and inclusion of multiple factors frequently neglected when considering implementation.
Malus sieversii: a historical, genetic, and conservational perspective of the primary progenitor species of domesticated apples
Authors: Tegtmeier Richard , Švara Anže , Gritsenko Dilyara , Khan Awais
Published: August 2024

Apples are one of the most valued tree fruit crops around the world. Currently, a few highly popular and economically successful apple cultivars dominate the commercial production and serve as main genetic contributors to the development of new apple cultivars. This limited level of genetic diversity grown as a clonally propagated monoculture renders the apple industry vulnerable to the wide range of weather events, pests, and pathogens. Wild apple species are an excellent source of beneficial alleles for the wide range of biotic and abiotic stressors challenging apple production. However, the biological barriers of breeding with small-fruited wild apples greatly limit their use. Using a closely related wild species of apple such as Malus sieversii can improve the efficiency of breeding efforts and broaden the base of available genetics. M. sieversii is the main progenitor of the domesticated apple, native to Central Asia. The similarity of fruit morphology to domesticated apples and resistances to abiotic and biotic stresses makes it appealing for apple breeding programs. However, this important species is under threat of extinction in its native range. Preserving the wild apple forests in Central Asia is vital for ensuring the sustainable protection of this important genetic resource. The insufficient awareness about the complete range of challenges and opportunities associated with M. sieversii hinders the maximization of its potential benefits. This review aims to provide comprehensive information on the cultural and historical context of M. sieversii, current genetic knowledge for breeding, and the conservation challenges of wild apple forests.
Less or More Labour Law for Social Change?
Authors: Breznik Maja
Published: August 2024

In the field of labour law, recent contributions to the theory of legal form have addressed the question of whether the purpose of labour law is merely to reproduce capitalist social relations. The resulting debate has acted as a trigger for profound self-reflection among both labour law scholars and the labour movement. While the theory of legal form refers to labour law as ‘capitalist law’, other branches of labour law theory and scholarship, including those of the French legal scholar Alain Supiot, have characterised it as ‘collective’, ‘class’ or ‘social’ law. Both positions claim that the purpose of labour law is to enable transformative social change. Taking account of arguments put forward in this debate, the current paper examines employment practices and collective organising in four Slovenian companies. The aim is to determine how the dynamics that emerge between individual and collective labour rights can create the conditions for social change. The paper thereby addresses the question of whether less or more labour law is needed, and what kind of labour law. In conclusion, the analysis raises the issue of the role of universal labour rights.
Human Papillomavirus Prevalence Among Australian Men Aged 18–35 Years in 2015–2018 According to Vaccination Status and Sexual Orientation
Authors: Balgovind Prisha , Aung Eithandee , Shilling Hannah , Murray Gerald L , Molano Monica , Garland Suzanne M , Fairley Christopher K , Chen Marcus Y , Hocking Jane S , Ooi Catriona , McNulty Anna , McCloskey Jenny , McNamee Kathleen , Bateson Deborah , Owen Louise , Tabrizi Sepehr N , Machalek Dorothy A
Published: August 2024

Background

Australia introduced a national human papillomavirus (HPV) vaccination program for girls in 2007 and boys in 2013, achieving high coverage. We assessed HPV prevalence among men who have sex with women (MSW) and men who have sex with men (MSM) aged 18–35 years and examined program effects.

Methods

Between 2015–2018, men self-collected a penile or intra-anal swab for HPV genotyping. Vaccination status was confirmed with the National Register. HPV prevalence was examined by age groups and vaccination status.

Results

Prevalence of quadrivalent vaccine–targeted HPV types (6, 11, 16, 18) was 10.6% (95% confidence interval [CI], 8.7%–12.8%) in unvaccinated MSW and 10.7% (95% CI, 5.7%–19.3%) in vaccinated MSW (P = .96). Prevalence was 40.3% (95% CI, 36.0%–44.8%) in unvaccinated MSM and 29.9% (95% CI, 23.1%–37.8%) in vaccinated MSM (P = .02). Among those with confirmed doses, quadrivalent types were detected in 0% (95% CI, 0%–7.7%; n = 46) of men who had their first dose at 13–19 years and 37.2% (95% CI, 27.5%–47.8%; n = 94) in those who received their first dose at 20 years or older.

Conclusions

Our data demonstrate the importance of universal adolescent HPV vaccination to ensure MSM receive the same benefits as MSW.
How can we measure psychological safety in mental healthcare staff? Developing questionnaire items using a nominal groups technique
Authors: Vogt Katharina Sophie , Baker John , Coleman Rebecca , Kendal Sarah , Griffin Bethany , Anjum Taha , Ashley Kirsty Louise , Archer Bethany Lauren , Berry Katherine , Feldman Robyn , Gray Stephanie , Giles Sally Jane , Helliwell Benjamin James , Hill Chelsea , Hogan Aimee Elisha , Iwanow Magdalena , Jansen Timon Anton Arie , Johnson Zach , Kelly James A , Law Joshua , Mizen Emily , Obasohan Owenvbiugie Omorefe , Panagioti Maria , Smith-Wilkes Ffion , Steeg Sarah , Taylor Christopher D J , Tyler Natasha , Wade Sophie , Johnson Judith
Published: August 2024

There have been growing concerns about the well-being of staff in inpatient mental health settings, with studies suggesting that they have higher burnout and greater work-related stress levels than staff in other healthcare sectors. When addressing staff well-being, psychological safety can be a useful concept. However, there is no measure of psychological safety that is suitable for use in inpatient mental health settings. Edmondson (1999) is the most commonly used measure of psychological safety, but it was designed for use in general physical healthcare settings. As inpatient mental health settings are unique environments, transferability of knowledge from physical to mental healthcare settings cannot be assumed. We sought to develop questionnaire items that capture psychological safety among healthcare staff working in acute inpatient mental healthcare settings. We used the nominal group technique, a consensus method involving rounds of discussion, idea generation, and item rating/ranking to identify priorities. Twenty-eight stakeholders participated, including 4 who had lived experience of mental health problems, 11 academics and 18 healthcare professionals (8 participants identified with more than 1 category). The study involved a workshop with three parts: (i) an overview of current research and limitations of the Edmondson (1999) measure as outlined above, (ii) discussion on what items should be retained from the Edmondson (1999) measure, and (iii) discussion on what items should be added to the Edmondson (1999) measure. Twenty-one items were generated and retained to capture psychological safety in inpatient mental health settings. These measure professionals’ sense of being valued by their team and organization, feeling supported at work, feeling physically safe and protected from physical harm, and knowing they can raise concerns about risk and safety. This is the first study to generate questionnaire items suitable for measuring staff psychological safety in mental health settings. These have been generated via a consensus method to ensure stakeholders’ views are reflected. Further research is needed to evaluate factor structure, internal reliability, and convergent validity.
Identification of risk factors for adverse drug events in a general hospital
Authors: Pisetta Leticia Mara , Tonin Fernanda Zanardo , Akiyoshi Fernando Kenji , Santos Fábio André , Fernandes Daniel
Published: August 2024

Adverse events (AEs), and particularly adverse drug events (ADEs), represent a health problem as they can cause permanent damage or death. Understanding the frequency, location, and causes of ADEs can prevent harm to patients. The Global Trigger Tool, produced by the Institute for Healthcare Improvement (GTT/IHI), is widely used to identify AEs. Recognizing the profile of patients who suffer ADEs can reveal clinical or individual characteristics that predispose to the occurrence of AEs. A cross-sectional study was carried out through a retrospective analysis of 120 medical charts of patients discharged from hospital between October 2020 and April 2021. Patients over 18 years old, with a length of stay of more than 24 h, were included. The list of triggers used was from the medication module of the GTT/IHI, which was adapted for use in the institution. Two primary reviewers and a medical reviewer applied this tool. The primary reviewers independently assessed the randomized charts. A meeting to achieve consensus among the reviewers was held every 2 weeks to validate the identified ADEs; classifications were based on harm severity. Multivariate logistic regression was utilized to assess the variables that predicted the occurrence of ADEs, using the backward stepwise method. A total of 43 ADEs were identified, with a frequency of 36 per 100 admissions (43/120). Of these, five ADEs (12%) were responsible for patients being admitted to hospital. In the case of in-hospital ADEs, there were 42.2 per 1000 patients/day. The clinical manifestation of altered kidney function (16%) and the anatomical drug group of the nervous system (33%) were the most frequent ADEs. The multivariate logistic regression model was significant (×2 = 44.960, P < .001), indicating that factors such as: known drug allergy [odds ratio 5.728; 95% confidence interval (CI): 1.249, 26.274, P = .025]; being clinically hospitalized (odds ratio 7.504; 95% CI: 1.654, 34.037; P = .009); number of medicines used (odds ratio 1.100; 95% CI: 1.054, 1.148; P < .001); and being under the care of internal medicine (odds ratio 3.633; 95% CI: 1.257, 10.511; P = .017) were predictor variables associated with the occurrence of ADEs. A significant percentage of hospitalized patients experienced at least one ADE, with rates surpassing those found in similar studies. The GTT/IHI effectively assessed medication-related harm, emphasizing the need for tailored triggers based on population characteristics. Predictor variables can inform preventive strategies. Overall, the tool facilitated a localized risk assessment of medication use.
Single and Unhoused Population at Risk for Self-Inflicted Burn Injury: A Retrospective Analysis of an Urban American Burn Center’s Experience
Authors: Manasyan Artur , Malkoff Nicolas , Cannata Brigette , Stanton Eloise W , Yenikomshian Haig A , Gillenwater T Justin , Stoycos Sarah A
Published: August 2024

Despite the growing recognition of self-harm as a pressing public health issue, demographic risk factors of self-inflicted burn (SIB) injuries in the United States have not been extensively described. In this retrospective study, we seek to identify demographic risk factors and patterns associated with SIB injuries at an urban burn center. Charts were reviewed of patients admitted to a single American Burn Association-verified burn unit between 2015 and 2023 with a history of SIB injury, identified with ICD10 code X76.XXXA. Descriptive statistics, Welch’s t-test of unequal variances, and chi-squared analysis were performed. A total of 3212 patients were admitted to our institution for the management of acute burn injury, with 94 (2.9%) patients presenting with SIB injury. SIB patients were more likely than the control cohort to be male (P = .035), single (P = .008), unhoused (P < .001), live alone (P < 0.001), and have documented psychiatric diagnoses (72.3% vs 2.1%, P < .001). They had larger %TBSA affected (P < .001) and higher rates of inhalation injury (P < .001). The SIB cohort also showed significantly higher rates of positive urine toxicology results, primarily for stimulants and opiates (P < .001). Patients with SIBs had longer hospital stays (21.7 ± 2.6 days vs 12.0 ± 22.1 days, P = .006), higher rates of ICU admission (P < .001), and mechanical ventilation requirement (P < .001). Mental health support services, substance abuse rehabilitation programs, and community outreach need to be prioritized, especially targeting vulnerable populations such as the unhoused.
Specificity in the Inter-American Court of Human Rights
Authors: Buitrago-Rey Nicolás , Núñez-Fernández Paloma , Pérez-Liñán Aníbal , Suárez-Torres Angélica
Published: August 2024

Human rights bodies formulate highly specific orders to minimize the risk of State non-compliance. However, specificity comes at a cost, reducing State autonomy when local agents implement measures on the ground. This article develops the concept of specificity in human rights reparations and analyses the specificity formulas deployed by the Inter-American Court of Human Rights in structural measures as a form of positive subsidiarity. We employ qualitative data analysis software to process 322 measures of non-repetition ordered by the Inter-American Court through to the end of 2020. This analysis identifies two modes of specificity: process-based, which defines procedures for compliance, and outcome-based, which sets the goals for the State. After coding over 800 segments of text from Court decisions, we outline an exhaustive legal framework with 26 process-based categories and 2 outcome-based forms of specificity. We conclude that outcome-based specificity can help courts balance positive subsidiarity and State autonomy in the design of reparations.
The deubiquitinase USP44 enhances cisplatin chemosensitivity through stabilizing STUB1 to promote LRPPRC degradation in neuroblastoma
Authors: Zeng Liang , Li Ying-Qing , He Shi-Wei , Xu Hui , Zhang Ruizhong , Chen Kai , Qin Liang-Jun , Zhu Xun-Hua , Li Yi-Lin , Li Le , Liu Na , Wang Hai-Yun
Published: August 2024

Background

Dysregulated deubiquitinating enzymes (DUBs) execute as intrinsic oncogenes or tumor suppressors and are involved in chemoresistance in cancers. However, the functions and exact molecular mechanisms remain largely unclear in neuroblastoma.

Methods

Here, an R2 screening strategy based on the standard deviation values was used to identify the most important DUB, USP44, in neuroblastoma with stage 4. We validated the role of USP44 regulation upon cisplatin treatment in vitro and in vivo experiments, revealing the molecular mechanisms associated with USP44 regulation and cisplatin sensitivity in neuroblastoma.

Results

We found that low USP44 expression was associated with an inferior prognosis in neuroblastoma patients. Overexpression of USP44 enhanced neuroblastoma cell sensitivity to cisplatin in vitro and in vivo. Mechanistically, USP44 recruited and stabilized the E3 ubiquitin ligase STUB1 by removing its K48-linked polyubiquitin chains at Lys30, and STUB1 further reinforced the K48-linked polyubiquitination of LRPPRC at Lys453 and promoted its protein degradation, thus enhancing the accumulation of mitochondrial reactive oxygen species (mROS), in turn facilitating neuroblastoma cell apoptosis and cisplatin sensitivity. Additionally, overexpression of LRPPRC reversed the promoting effect of USP44 on cell apoptosis in cisplatin-treated neuroblastoma cells.

Conclusions

Our findings demonstrate that the USP44–STUB1–LRPPRC axis plays a pivotal role in neuroblastoma chemoresistance and provides potential targets for neuroblastoma therapy and prognostication.
Clinical, molecular, and genetic features of spinal meningiomas
Authors: Deska-Gauthier Dylan , Hachem Laureen D , Wang Justin Z , Landry Alex P , Yefet Leeor , Gui Chloe , Ellengbogen Yosef , Badhiwala Jetan , Zadeh Gelareh , Nassiri Farshad
Published: August 2024

Spinal meningiomas comprise 25%–46% of all primary spinal tumors. While the majority are benign and slow-growing, when left untreated, they can result in significant neurological decline. Emerging clinical, imaging, and molecular data have begun to reveal spinal meningiomas as distinct tumor subtypes compared to their intracranial counterparts. Moreover, recent studies indicate molecular and genetic subtype heterogeneity of spinal meningiomas both within and across the classically defined WHO grades. In the current review, we focus on recent advances highlighting the epidemiological, pathological, molecular/genetic, and clinical characteristics of spinal meningiomas. Furthermore, we explore patient and tumor-specific factors that predict prognosis and postoperative outcomes. We highlight areas that require further investigation, specifically efforts aimed at linking unique molecular, genetic, and imaging characteristics to distinct clinical presentations to better predict and manage patient outcomes.
Tumor volume features predict survival outcomes for patients diagnosed with diffuse intrinsic pontine glioma
Authors: Spencer D’Andre , Bonner Erin R , Tor-Díez Carlos , Liu Xinyang , Bougher Kristen , Prasad Rachna , Gordish-Dressman Heather , Eze Augustine , Packer Roger J , Nazarian Javad , Linguraru Marius George , Bornhorst Miriam
Published: August 2024

Background

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood central nervous system tumor. Diagnosis and monitoring of tumor response to therapy is based on magnetic resonance imaging (MRI). MRI-based analyses of tumor volume and appearance may aid in the prediction of patient overall survival (OS).

Methods

Contrast-enhanced T1- and FLAIR/T2-weighted MR images were retrospectively collected from children with classical DIPG diagnosed by imaging (n = 43 patients). MRI features were evaluated at diagnosis (n = 43 patients) and post-radiation (n = 40 patients) to determine OS outcome predictors. Features included 3D tumor volume (Twv), contrast-enhancing tumor core volume (Tc), Tc relative to Twv (TC/Twv), and Twv relative to whole brain volume. Support vector machine (SVM) learning was used to identify feature combinations that predicted OS outcome (defined as OS shorter or longer than 12 months from diagnosis).

Results

Features associated with poor OS outcome included the presence of contrast-enhancing tumor at diagnosis, >15% Tc/Twv post-radiation therapy (RT), and >20% ∆Tc/Twv post-RT. Consistently, SVM learning identified Tc/Twv at diagnosis (prediction accuracy of 74%) and ∆Tc/Twv at <2 months post-RT (accuracy = 75%) as primary features of poor survival.

Conclusions

This study demonstrates that tumor imaging features at diagnosis and within 4 months of RT can predict differential OS outcomes in DIPG. These findings provide a framework for incorporating tumor volume-based predictive analyses into the clinical setting, with the potential for treatment customization based on tumor risk characteristics and future applications of machine-learning-based analysis.
Capacity to Consent to Sex: A Historical Perspective
Authors: Lammasniemi Laura
Published: August 2024

This article provides a historical perspective on capacity to consent to sex. It examines who could make decisions about sex, whose consent mattered and why. The article draws from legal history and from transcripts and testimonies in unreported sexual offence cases in England, heard in the Central Criminal Court in London and the regional assizes between the years of 1918 and 1950. These cases, often involving vulnerable complainants below the age of consent and those with mental disabilities, show that the concept of capacity was neither fixed nor clearly articulated. The article argues that, historically, capacity was not a biological or medical construct, but rather a social one, influenced by notions of class, gender and even eugenic ideals. The article demonstrates that, during this period, sexual offence law enabled social and population control, and that, despite significant legislative advances, capacity remains a fraught concept.
Prioritizing social vulnerability in urban heat mitigation
Authors: Fung Kwun Yip , Yang Zong-Liang , Martilli Alberto , Krayenhoff E Scott , Niyogi Dev
Published: August 2024

We utilized city-scale simulations to quantitatively compare the diverse urban overheating mitigation strategies, specifically tied to social vulnerability and their cooling efficacies during heatwaves. We enhanced the Weather Research and Forecasting model to encompass the urban tree effect and calculate the Universal Thermal Climate Index for assessing thermal comfort. Taking Houston, Texas, and United States as an example, the study reveals that equitably mitigating urban overheat is achievable by considering the city's demographic composition and physical structure. The study results show that while urban trees may yield less cooling impact (0.27 K of Universal Thermal Climate Index in daytime) relative to cool roofs (0.30 K), the urban trees strategy can emerge as an effective approach for enhancing community resilience in heat stress-related outcomes. Social vulnerability-based heat mitigation was reviewed as vulnerability-weighted daily cumulative heat stress change. The results underscore: (i) importance of considering the community resilience when evaluating heat mitigation impact and (ii) the need to assess planting spaces for urban trees, rooftop areas, and neighborhood vulnerability when designing community-oriented urban overheating mitigation strategies.
A hybrid approach to generating diatomic line lists for high resolution studies of exoplanets and other hot astronomical objects: updates to ExoMol MgO, TiO, and VO line lists
Authors: McKemmish Laura K , Bowesman Charles A , Kefala Kyriaki , Perri Armando N , Syme Anna-Maree , Yurchenko Sergei N , Tennyson Jonathan
Published: August 2024

The best molecular line lists for astrophysical applications today require both high accuracy of line positions for strong lines as well as high overall completeness. The former is required to enable, for example, molecular detection in high-resolution cross-correlation observations of exoplanets, while completeness is required for accurate spectroscopic and radiative properties over broad temperature and spectral ranges. The use of empirical energies generated with the marvel procedure is a standard way to improve accuracy; here we explore methods of extending the use of these levels using predicted shifts and isotopologue extrapolation, as well as augmenting the levels from other sources such as effective Hamiltonian studies. These methods are used to update ExoMol line lists for the main $^{24}$Mg$^{16}$O and $^{48}$Ti$^{16}$O isotopologues, as well as for $^{24}$Mg$^{17}$O, $^{24}$Mg$^{18}$O, $^{25}$Mg$^{16}$O, $^{26}$Mg$^{16}$O, $^{46}$Ti$^{16}$O, $^{47}$Ti$^{16}$O, $^{49}$Ti$^{16}$O, and $^{50}$Ti$^{16}$O; new marvel results for $^{51}$V$^{16}$O are also presented.
Extending weeknight sleep duration in late-sleeping adolescents using morning bright light on weekends: a 3-week maintenance study
Authors: Crowley Stephanie J , Poole Elaine , Adams John , Eastman Charmane I
Published: August 2024

Study Objectives

Our sleep extension intervention in adolescents showed that gradually shifting weekday bedtime earlier plus one weekend of morning bright light advanced circadian phase and increased weeknight sleep duration. Here, we examine at-home maintenance of these changes.

Methods

Fourteen adolescents (15.3–17.9 years; 7 female) completed a 7-week study. After usual sleep at home (2-week baseline), intervention participants (n = 8) gradually advanced weekday bedtime (1 hour earlier than baseline during week 3; 2 hours earlier in week 4) and received bright light (~6000 lux; 2.5 hours) on both mornings of the intervening weekend. During three maintenance weeks, intervention participants were instructed to maintain their school-day wake-up time on all days, keep their early week four bedtimes, except on weekends when they could go to bed up to 1 hour later, and get a 2.5-hour light box exposure within 5 minutes of waking on one morning (Saturday or Sunday) of both weekends at home. Control participants (n = 6) slept as usual at home and did not receive weekend bright light. Dim light melatonin onset (DLMO) was measured after the 2-week baseline, 2-week intervention, and 3-week maintenance in all participants. Actigraphic sleep–wake was collected throughout.

Results

After the 2-week intervention, DLMOs advanced more compared to control (37.0 ± 40.0 minutes vs. −14.7 ± 16.6 minutes), weekday sleep duration increased by 69.7 ± 27.8 minutes and sleep onset was 103.7 ± 14.2 minutes earlier compared to baseline. After three maintenance weeks, intervention participants showed negligible DLMO delays (−4.9 ± 22.9 minutes); weekday fall-asleep times and sleep durations also remained stable.

Conclusions

Early circadian phase and extended sleep can be maintained with at-home weekend bright light.
Seasonality in embolism resistance and hydraulic capacitance jointly mediate hydraulic safety in branches and leaves of oriental cork oak (Quercus variabilis Bl.)
Authors: Huang Xin , Hou Zhuo-Liang , Ma Bo-Long , Zhao Han , Jiang Zai-Min , Cai Jing
Published: August 2024

Seasonality in temperate regions is prominent during the era of increased climatic variability. A hydraulic trait that can adjust to seasonally changing climatic conditions is crucial for tree safety. However, little attention has been paid to the intraspecific seasonality of drought-related traits and hydraulic safety of keystone forest trees. We examined seasonal variations in the key morphological and physiological traits as well as multiple hydraulic safety margins (SMs) at the branch and leaf levels in oriental cork oak (Quercus variabilis Bl.), which is predominant in Chinese temperate forests. Pneumatic measurements indicated that, as seasons progressed, the water potential at which 50% of branch embolisms occur (P50_branch) decreased from −3.34 to −4.23 MPa, with a coefficient of variation (CV) of 9.08%. Sapwood capacitance ranged from 48.19 to 248.08 kg m−3 MPa−1, peaking in autumn and reaching minimum in winter (CV 60.58%). Rehydration kinetics confirmed higher leaf embolism vulnerability (P50_leaf) in spring and autumn than those in summer, with values ranging from −1.06 to −3.02 MPa (CV 39.85%). All leaf pressure–volume (PV) traits shifted with growth, with CVs ranging from 6.95% to 46.69%. Sapwood density had significant negative correlations with P50_branch and hydraulic capacitance for elastic water storage, whereas leaf mass per area was linearly associated with PV traits but not with P50_leaf. Furthermore, the branch typical SMs (difference between branch midday water potential and P50_branch) were consistently >1.84 MPa, and vulnerability segmentation was prevalent throughout, implying a plausible hydraulic foundation for the dominance of Q. variabilis. Diverse hydraulic response patterns existed across seasons, leading to positive SMs mediated by the aforementioned physiological traits. Although Q. variabilis exhibits a high level of hydraulic safety, its susceptibility to sudden summer droughts may increase due to global climate change.
YAP activation in liver macrophages via depletion of MST1/MST2 enhances liver inflammation and fibrosis in MASLD
Authors: Zhang Jinqiang , Chen Weina , Song Kyoungsub , Song Kejing , Kolls Jay , Wu Tong
Published: August 2024

Macrophages have been recognized as pivotal players in the progression of MASLD/MASH. However, the molecular mechanisms underlying their multifaceted functions in the disease remain to be further clarified. In the current study, we developed a new mouse model with YAP activation in macrophages to delineate the effect and mechanism of YAP signaling in the pathogenesis of MASLD/MASH. Genetically modified mice, featuring specific depletion of both Mst1 and Mst2 in macrophages/monocytes, were generated and exposed to a high‐fat diet for 12 weeks to induce MASLD. Following this period, livers were collected for histopathological examination, and liver non‐parenchymal cells were isolated and subjected to various analyses, including single‐cell RNA‐sequencing, immunofluorescence and immunoblotting and qRT‐PCR to investigate the impact of YAP signaling on the progression of MASLD. Our data revealed that Mst1/2 depletion in liver macrophages enhanced liver inflammation and fibrosis in MASLD. Using single‐cell RNA‐sequencing, we showed that YAP activation via Mst1/2 depletion upregulated the expressions of both pro‐inflammatory genes and genes associated with resolution/tissue repair. We observed that YAP activation increases Kupffer cell populations (i.e., Kupffer‐2 and Kupffer‐3) which are importantly implicated in the pathogenesis of MASLD/MASH. Our data indicate that YAP activation via Mst1/2 deletion enhances both the pro‐inflammatory and tissue repairing functions of Kupffer‐1 and ‐2 cells at least in part through C1q. These YAP‐regulatory mechanisms control the plasticity of liver macrophages in the context of MASLD/MASH. Our findings provide important evidence supporting the critical regulatory role of YAP signaling in liver macrophage plasticity and the progression of MASLD. Therefore, targeting the Hippo‐YAP pathway may present a promising therapeutic strategy for the treatment of MASH.
Liver cancer in ovo models for preclinical testing
Authors: Garcia Paul , Wang Yan , Viallet Jean , Mehdi Nour El Houda , Montaut Emilie , Decaens Thomas , Emadali Anouk , Macek Jílková Zuzana
Published: August 2024

Immunotherapies have significantly improved the prognosis of patients with advanced hepatocellular carcinoma (HCC), although more than 70% of patients still do not respond to this first‐line treatment. Many new combination strategies are currently being explored, which drastically increases the need for preclinical models that would allow large‐scale testing of new immunotherapies and their combinations. We developed several in ovo (in the egg) human liver cancer models, based on human tumor xenografts of different liver cancer cell lines on the chicken embryo's chorioallantoic membrane. We characterized the angiogenesis, as well as the collagen accumulation and tumor immune microenvironment, and tested atezolizumab (anti‐PD‐L1) plus bevacizumab (anti‐VEGF) treatment. Our results show the involvement of chicken immune cells in tumor growth, reproducing a classical non‐inflamed “cold” as well as inflamed “hot” tumor status, depending on the in ovo liver cancer model. The treatment by atezolizumab and bevacizumab was highly efficient in the “hot” tumor model PLC/PRF/5 in ovo with the reduction of tumor size by 76% (p ≤ .0001) compared with the control, whereas the efficacy was limited in the “cold” Hep3B in ovo tumor. The contribution of the anti‐PD‐L1 blockade to the anti‐tumoral effect in the PLC/PRF/5 in ovo model was demonstrated by the efficacy of atezolizumab monotherapy (p = .0080, compared with the control). To conclude, our study provides a detailed characterization and rational arguments that could help to partially replace conventional laboratory animals with a more ethical model, suited to the current needs of preclinical research of new immunotherapies for liver cancer.
Posterior Cartilage Endplate Disruption on T1-weighted Magnetic Resonance Imaging as a Predictor for Postoperative Recurrence of Lumbar Disk Herniation
Authors: Inomata Kazuhiro , Takasawa Eiji , Mieda Tokue , Tsukui Toshiki , Takakura Kenta , Tomomatsu Yusuke , Honda Akira , Chikuda Hirotaka
Published: August 2024

Study design:

A retrospective cohort study.

Objective:

This study aimed to investigate the relationship between disruption of cartilage endplates and postoperative recurrence of lumber disk herniation (LDH) using preoperative T1-weighted magnetic resonance imaging (MRI-T1WI).

Summary of Background Data:

Recurrence of LDH is a relatively common complication after discectomy. Although several risk factors have been identified, their predictive capability remains limited. Previous histologic studies reported that cartilage endplates were present in 85% of patients with recurrent LDH.

Methods:

Patients with a single level of LDH who underwent open or microendoscopic discectomy were retrospectively reviewed. On the basis of preoperative sagittal MRI-T1WI, cartilage endplates were divided into anterior and posterior portions at the center of the disk and evaluated for discontinuity. Patient background characteristics, spinopelvic sagittal parameters, degrees of disk degeneration, and recurrence level were also evaluated.

Results:

A total of 100 patients were included in this study (mean age, 50.5 years old; 41% female). Symptomatic recurrence of LDH occurred in 15 patients (15%). There were no significant differences in patient background characteristics (age, 46.9 vs. 51.2 years old; %female, 60% vs. 38%; smoking, 33% vs. 41%; diabetes mellitus, 27% vs. 29%) or spinopelvic parameters (PI, 44.1 vs. 47.0 degrees; PT, 16.8 vs. 19.4 degrees; SS, 27.3 vs. 27.6 degrees; LL, 37.7 vs. 33.7 degrees). In the recurrence group, MRI-T1WI showed a higher rate of cartilage endplate disruption in the posterior portion than in the no-recurrence group (73% vs. 34%, P=0.01). A multivariate analysis demonstrated that the disruption of the posterior cartilage endplate remained an independent predictor of recurrence.

Conclusions:

Disruption in the posterior cartilage endplate on preoperative MRI-T1WI was closely associated with recurrence after LDH surgery. These results suggest that this MRI finding is a practical and useful predictor of LDH recurrence.

Level of Evidence:

Level III.
MACULAR THICKNESS FLUCTUATIONS AND VISUAL ACUITY OUTCOMES AFTER INTRAVITREAL DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA
Authors: Torres-Villaros Héloïse , Timoumi Rhyme , Fajnkuchen Franck , Klokner Arnaud , Giocanti-Aurégan Audrey
Published: August 2024

Purpose:

To assess macular thickness fluctuations and their association with visual acuity outcomes in eyes with diabetic macular edema treated with an intravitreal dexamethasone (DEX) implant.

Methods:

The SD of all postbaseline central subfield thicknesses (CST) recorded over a 12-month period after the first injection of the DEX implant was used to quantify CST fluctuations. Linear regression models were used to identify factors associated with the visual acuity at 12 months (measured with the Early Treatment of Diabetic Retinopathy Study score) and predictors of CST SD.

Results:

A retrospective review of 80 eyes of 80 patients treated with the DEX implant for diabetic macular edema revealed a CST SD of 75.3 ± 50.3 µm. The CST SD was negatively associated with the visual acuity at 12 months (−7.7 Early Treatment of Diabetic Retinopathy Study letters for each 100-µm increase in CST SD, P = 0.01), while changes in CST from baseline did not show any significant association. Eyes were stratified into quartiles based on the CST SD, and a difference by −14.2 letters in visual acuity at 12 months was observed between the first and fourth quartiles (P <0.001). Significant predictors of CST SD included the baseline visual acuity (−12.0 µm for each 10-letter increase, P = 0.02) and the number of DEX injections received (n = 17.1, P = 0.03).

Conclusion:

Greater fluctuations in retinal thickness were found to be associated with poorer visual outcomes in eyes with diabetic macular edema treated with the DEX implant. Analyzing the CST SD could be a more predictive indicator of visual prognosis than individual measurements of the CST.
Efficacy and Safety of Interleukin-12/23 and Interleukin-23 Inhibitors for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jaber Fouad , Ayyad Mohammed , Alsakarneh Saqr , Alsharaeh Tala , Salahat Ahmed-Jordan , Jaber Mohammad , Gangwani Manesh Kumar , Abboud Yazan , Mohamed Islam , Ali Hassam , Kilani Yassine , Farraye Francis A. , Hashash Jana G.
Published: August 2024

Background:

Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC).

Study Question:

What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC?

Data Sources:

MEDLINE, Embase, Scopus, and Cochrane databases.

Study Design:

A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis.

Results:

In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66–2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39–2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34–2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53–2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60–2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11–2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86–1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86–0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36–0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)].

Conclusion:

Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.
18F FDG PET/CT versus 99m Tc MDP Bone scintigraphy in imaging of metastatic osseous disease in breast cancer patients; Solving the discrepancies in light of serum markers
Authors: Nasr Hatem , Alnajashi Nejoud , Farghaly Hussein , Alqarni Abdullah
Published: August 2024

Aim

To assess the performance of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99mTc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers.

Material and methods

We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan.

Results

In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans (P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS (r = 0.386; P = 0.018) but not to BMS (r = −0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS (r = 0.389; P = 0.017) and BMS (r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261).

Conclusion

FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions.
Valuing Nursing Practice
Authors: Porter-O'Grady Tim , Pappas Sharon
Published: August 2024

Nursing has always been a cost for the institutions within which nurses work. This fact has influenced almost everything that affects how nurses are utilized and valued. As a cost, nurses are closely managed on the margin, always constrained by the resource machinations of organizations and systems with little determination or enumeration of the contributions nurses make to the service and financial value represented by algorithms and metrics that enumerate and demonstrate nurse's impact and contribution to service and financial value. This article further pushes the boundaries of this circumstance, challenging nurse and health leaders to reconceptualize nursing contribution and recalibrate the determination and calculation of nursing value as a sustainable baseline for nursing leadership for the future.
Clinician Wellbeing and Mental Health Assessment Across Two Acute Care Hospitals During the COVID-19 Pandemic
Authors: Kaplow Roberta , Willis Polly , Steele Dinah , Swann Julie , Feistritzer Nancye R.
Published: August 2024

Objective

The purposes of this study were to determine whether positive work environments affect clinician wellbeing and mental health, and to identify participants’ priority interventions to improve clinician wellbeing. This study was designed to determine the potential benefit of modifying the aforementioned factors for clinicians and hospitals to impact positive patient outcomes.

Background

The SARS-CoV-2 virus pandemic has become one of the leading causes of death in the United States and worldwide, and has exacerbated widespread burnout among health care professionals. This has resulted in negative collateral implications for the stability of the clinician workforce. A Clinician Wellbeing study (CWS) was launched in two Magnet®-designated hospitals in the southeast. The CWS was part of a multi-site collaborative research project led by the Center for Health Outcomes and Policy Research (CHOPR) at the University of Pennsylvania School of Nursing.

Method

A cross-sectional observational study design was implemented. Data were collected through anonymous surveys of 708 registered nurses (RNs) and advanced practice providers (APPs) working in two Magnet hospitals in the southeastern United States. Each participant completed 8 surveys.

Results

Clinicians’ self-reported level of burnout was higher for both RNs and APPs at Emory University Hospital than Emory Saint Joseph’s Hospital including intent to leave and dissatisfaction with their jobs. RNs and APPs self-reported their overall health to be good or excellent and they reported sleep quality as fair. Both groups in both hospitals indicated that they experienced anxiety, depression, and stress. The APPs reported a higher percent that their work did not leave enough time for personal and family life. Data also indicated that the primary work environment concern was related to inadequate nurse staffing.

Conclusions

The data illuminated opportunities for the two hospitals to employ continuous improvement interventions to positively transform the work environment.