bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of life cycle and venation pattern on the coordination between stomatal and vein densities of herbs
Authors: Liu Guolan , Fu Peili , Mao Qinggong , Xia Jiangbao , Zhao Wanli
Published: February 2024

Life cycle (annual vs perennial) and leaf venation pattern (parallel and reticular) are known to be related to water use strategies in herb species and critical adaptation to certain climatic conditions. However, the effect of these two traits and how they influence the coordination between vein density (vein length per area, VLA) and stomatal density (SD) remains unclear. In this study, we examined the leaves of 53 herb species from a subtropical botanical garden in Guangdong Province, China, including herbs with different life cycles and leaf venation patterns. We assessed 21 leaf water-related functional traits for all species, including leaf area (LA), major and minor VLA, major and minor vein diameter (VD), SD and stomatal length (SL). The results showed no significant differences in mean SD and SL between either functional group (parallel venation vs reticular venation and annual vs perennial). However, parallel vein herbs and perennial herbs displayed a significantly higher mean LA and minor VD, and lower minor VLA compared to reticular vein herbs and annual herbs, respectively. There was a linear correlation between total VLA and SD in perennial and reticular vein herbs, but this kind of correlation was not found in annual and parallel vein herbs. The major VLA and minor VD were significantly affected by the interaction between life cycle and leaf venation pattern. Our findings suggested that VLA, rather than SD, may serve as a more adaptable structure regulated by herbaceous plants to support the coordination between leaf water supply and demand in the context of different life cycles and leaf venation patterns. The results of the present study provide mechanistic understandings of functional advantages of different leaf types, which may involve in species fitness in community assembly and divergent responses to climate changes.
A Prospective, Multicenter, Evaluator-Blind, Randomized, Controlled Study of Belotero Balance (+), a Hyaluronic Acid Filler With Lidocaine, for Correction of Infraorbital Hollowing in Adults
Authors: Biesman Brian S , Montes Jose R , Radusky Ross C , Mersmann Sabine , Graul Virginia W
Published: February 2024

Background

The infraorbital hollow (IOH) is a concavity that interrupts the smooth transition between the lower eyelid and the cheek, resulting in a fatigued and aged appearance. Injectable fillers may be utilized to correct volume deficit in the under-eye area, restoring a more youthful appearance.

Objectives

The objective was to demonstrate the effectiveness and safety of a cohesive polydensified matrix (CPM) hyaluronic acid (HA) filler with lidocaine (Belotero Balance (+)) for correcting volume deficit in the IOH.

Methods

Eligible patients with a moderate or severe rating on the Merz Infraorbital Hollow Assessment Scale (MIHAS) were randomized 2:1 to treatment or control. Controls remained untreated until Week 8 and were then treated. Touch-up injections were allowed; retreatment was offered only in the treatment group. Effectiveness was evaluated with the MIHAS. Adverse events were recorded over a 76-week period.

Results

The estimated average response rate (≥1 point MIHAS improvement) was 80.6% (95% CI, 71.4-87.4) in treated patients and 1.9% (95% CI, 0.3-10.2) in controls at Week 8. The difference in estimated response rates was 78.7% (95% CI, 66.3-85.6), demonstrating a statistically significant, superior response rate in treated patients compared to untreated controls. A total of 88 of 97 (90.7%) patients who responded to treatment at Week 8 retained improvement 48 weeks after treatment. Use of Belotero Balance (+) in the IOH had a favorable safety profile, with no unexpected adverse events reported.

Conclusions

Belotero Balance (+) is a safe and effective treatment for correcting volume deficit in the IOH.
Revisiting Level of Evidence Ratings in Plastic Surgery: A Call to Action
Authors: Covone Jason , ElHawary Hassan , Abdulkarim Shafic , Janis Jeffrey E
Published: February 2024

Background

Evidence-based medicine underpins medical and surgical practice, with level of evidence (LOE) being a key aspect that allows clinicians and researchers to better discriminate the methodological context by which studies are conducted and appropriately interpret their conclusions, and more specifically the strength of their recommendations.

Objectives

The aim of this study was to reassess the LOE of articles published in plastic surgery journals.

Methods

To assess the overall LOE of publications from January 1 to December 31, 2021, a review of the following plastic surgery journals was performed: Aesthetic Surgery Journal (ASJ), Annals of Plastic Surgery (Annals), Journal of Plastic Reconstructive and Aesthetic Surgery (JRPAS), Plastic and Reconstructive Surgery (PRS), and Plastic and Reconstructive Surgery Global Open (PRS GO).

Results

Of 3698 PUBMED articles, 1649 original articles and systematic reviews were analyzed. The average LOE for each journal was: ASJ 3.02 ± 0.94, Annals 3.49 ± 0.62, JPRAS 3.33 ± 0.77, PRS 2.91 ± 0.77, and PRS GO 3.45 ± 0.70. The collective average LOE was 3.28 ± 0.78. Only 4.4% were LOE 1 and 7.3% were LOE 2. Compared to past studies, PRS showed a significant LOE improvement (P = .0254), while ASJ and JPRAS saw nonsignificant changes; Annals experienced a significant decrease (P = .0092).

Conclusions

ASJ and PRS showed the highest LOE among the journals analyzed. Despite this, low LOE studies remain prevalent in plastic surgery. This paper serves as a call to action for both researchers and academic journals to elevate the standard, offering several strategies to help improve the LOE in plastic surgery.
Evaluation of landscaping and vegetation management to suppress host-seeking Ixodes scapularis (Ixodida: Ixodidae) nymphs on residential properties in Connecticut, USA
Authors: Linske Megan A , Williams Scott C
Published: February 2024

Ticks and tick-borne diseases are of increasing concern across the United States, particularly in the Northeast. Ixodes scapularis Say (Ixodida: Ixodidae) remains the primary vector for the Lyme disease spirochete, Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt, and Brenner). Prior studies established that I. scapularis can be found in greatest abundance in the 1-m forested ecotone surrounding the lawn edge in residential backyards. Our study was conducted on 42 properties in Guilford, CT, and sought to expand upon this premise by determining which key habitat features were associated with increased densities of host-seeking I. scapularis nymphs. We quantified nymphal abundances in 19 different habitat types that were posited to influence densities. We determined that nymphal I. scapularis densities were greatest in forested areas closest to lawn edges with leaf litter or understory vegetation present, as well as short lawns adjacent to woodland edges. Additionally, we determined that there were no significant declines in nymphal I. scapularis density where leaf litter was removed, lawns were left unmowed, or woodchip barriers were installed. Bird feeders and woodpiles were not associated with increased nymphal I. scapularis densities. However, areas adjacent to stone walls did have nearly 3 times the density of I. scapularis nymphs present compared with habitats without stone walls. The culmination of the results from this study can be utilized to create more targeted acaricide applications rather than broadcast spraying, as well as increase homeowner awareness for areas with heightened risk for exposure to nymphal I. scapularis, which are deemed the most epidemiologically important species and stage for pathogen transfer to humans.
How Polarised are Citizens? Measuring Ideology from the Ground up
Authors: Draca Mirko , Schwarz Carlo
Published: February 2024

We investigate whether the ideological polarisation of citizens has increased in Western democracies. We propose a novel methodology to identify individual ideologies by applying latent Dirichlet allocation to political survey data. This approach indicates that questions related to confidence in institutions play a leading role in defining citizen ideologies, in addition to the questions associated with the traditional left-right scale. We decompose the shift in ideological positions across the population over time and measure polarisation. This reveals evidence of a ‘disappearing centre’ in a sub-group of countries with citizens shifting away from centrist ideologies into anti-establishment ‘anarchist’ ideologies. This trend is especially pronounced for the United States.
Keratan sulfate, an electrosensory neurosentient bioresponsive cell instructive glycosaminoglycan
Authors: Melrose James
Published: February 2024

The roles of keratan sulfate (KS) as a proton detection glycosaminoglycan in neurosensory processes in the central and peripheral nervous systems is reviewed. The functional properties of the KS-proteoglycans aggrecan, phosphacan, podocalyxcin as components of perineuronal nets in neurosensory processes in neuronal plasticity, cognitive learning and memory are also discussed. KS-glycoconjugate neurosensory gels used in electrolocation in elasmobranch fish species and KS substituted mucin like conjugates in some tissue contexts in mammals need to be considered in sensory signalling. Parallels are drawn between KS’s roles in elasmobranch fish neurosensory processes and its roles in mammalian electro mechanical transduction of acoustic liquid displacement signals in the cochlea by the tectorial membrane and stereocilia of sensory inner and outer hair cells into neural signals for sound interpretation. The sophisticated structural and functional proteins which maintain the unique high precision physical properties of stereocilia in the detection, transmittance and interpretation of acoustic signals in the hearing process are important. The maintenance of the material properties of stereocilia are essential in sound transmission processes. Specific, emerging roles for low sulfation KS in sensory bioregulation are contrasted with the properties of high charge density KS isoforms. Some speculations are made on how the molecular and electrical properties of KS may be of potential application in futuristic nanoelectronic, memristor technology in advanced ultrafast computing devices with low energy requirements in nanomachines, nanobots or molecular switches which could be potentially useful in artificial synapse development. Application of KS in such innovative areas in bioregulation are eagerly awaited.
The Effects of Rearing Environment on Organization of the Olfactory System and Brain of Juvenile Sockeye Salmon, Oncorhynchus nerka
Authors: Ward Russell H , Quinn Thomas P , Dittman Andrew H , Yopak Kara E
Published: February 2024

Synopsis

Pacific salmon (Oncorhynchus spp.) hatch and feed in freshwater habitats, migrate to sea to mature, and return to spawn at natal sites. The final, riverine stages of the return migrations are mediated by chemical properties of the natal stream that they learned as juveniles. Like some other fish, salmon growth is asymptotic; they grow continuously throughout life toward a maximum size. The continued growth of the nervous system may be plastic in response to environmental variables. Due to the ecological, cultural, and economic importance of Pacific salmon, individuals are often reared in hatcheries and released into the wild as juveniles to supplement natural populations. However, hatchery-reared individuals display lower survivorship and may also stray (i.e., spawn in a non-natal stream) at higher rates than their wild counterparts. Hatchery environments may lack stimuli needed to promote normal development of the nervous system, thus leading to behavioral deficits and a higher incidence of straying. This study compared the peripheral olfactory system and brain organization of hatchery-reared and wild-origin sockeye salmon fry (Oncorhynchus nerka). Surface area of the olfactory rosette, diameter of the olfactory nerve, total brain size, and size of major brain regions were measured from histological sections and compared between wild and hatchery-origin individuals. Hatchery-origin fish had significantly larger optic tecta, and marginally insignificant, yet noteworthy trends, existed in the valvula cerebelli (hatchery > wild) and olfactory bulbs (hatchery < wild). We also found a putative difference in olfactory nerve diameter (dmin) (hatchery > wild), but the validity of this finding needs further analyses with higher resolution methods. Overall, these results provide insight into the potential effects of hatchery rearing on nervous system development in salmonids, and may explain behavioral deficits displayed by hatchery-origin individuals post-release.
Active case-finding of tuberculosis compared with symptom-driven standard of care: a modelling analysis
Authors: Malhotra Akash , Ryckman Theresa S , Johnson Karl , Uhlig Elizabeth , Creswell Jacob , Kendall Emily A , Dowdy David W , Sohn Hojoon
Published: February 2024

Background

In settings with large case detection gaps, active case-finding (ACF) may play a critical role in the uberculosis (TB) response. However, ACF is resource intensive, and its effectiveness depends on whether people detected with TB through ACF might otherwise spontaneously resolve or be diagnosed through routine care. We analysed the potential effectiveness of ACF for TB relative to the counterfactual scenario of routine care alone.

Methods

We constructed a Markov simulation model of TB natural history, diagnosis, symptoms, ACF and treatment, using a hypothetical reference setting using data from South East Asian countries. We calibrated the model to empirical data using Bayesian methods, and simulated potential 5-year outcomes with an ‘aspirational’ ACF intervention (reflecting maximum possible effectiveness) compared with the standard-of-care outcomes.

Results

Under the standard of care, 51% (95% credible interval, CrI: 31%, 75%) of people with prevalent TB at baseline were estimated to be diagnosed and linked to care over 5 years. With aspirational ACF, this increased to 88% (95% CrI: 84%, 94%). Most of this difference represented people who were diagnosed and treated through ACF but experienced spontaneous resolution under standard-of-care. Aspirational ACF was projected to reduce the average duration of TB disease by 12 months (95% CrI: 6%, 18%) and TB-associated disability-adjusted life-years by 71% (95% CrI: 67%, 76%).

Conclusion

These data illustrate the importance of considering outcomes in a counterfactual standard of care scenario, as well as trade-offs between overdiagnosis and averted morbidity through earlier diagnosis—not just for TB, but for any disease in which population-based screening is recommended.
Spincare System Demonstrates Safety and Efficacy in Treating Partial-Thickness Burns
Authors: Haik Josef , Ullmann Yehuda , Gur Eyal , Biros Erik , Kornhaber Rachel , Cleary Michelle , Kruchevsky Dani , Zissman Sivan , Namir Yossi , Harats Moti
Published: February 2024

Partial-thickness burns are the most common form of burns, affecting the dermis and possibly resulting in scarring and infection. The Spincare System is a new device that uses electrospinning technology to create a temporary skin-like matrix that can be applied to wounds. This study evaluated the performance, safety, and efficacy of Spincare in treating superficial to partial-thickness burns not considered for surgery. A prospective single-arm, open-label, multicenter study was conducted in 3 adult burn units across Israel. Forty-four patients with superficial to intermediate burns of up to 10% of TBSA were enrolled. Spincare was applied to the wounds, and follow-up visits were performed on days 7, 14, and 21 and months 3 and 6 posttreatment. Thirty-one patients with 36 wounds completed the day 21 visit. The mean wound healing area on day 21 was 97.26 ± 9.41%, and the mean healing time was 12.8 ± 4.3 days. Only one moderate adverse event was observed concerning the treatment, and it is important to acknowledge the potential progression of this hypertrophic scar into a keloid. This study demonstrated that Spincare is a safe and effective device for treating superficial to intermediate partial-thickness burns. Spincare achieved rapid and complete wound healing with a low incidence of adverse events.
Development and validation of a nomogram for radiation-induced hepatic toxicity after intensity modulated radiotherapy for hepatocellular carcinoma: a retrospective study
Authors: Wu Qiaoyuan , Wang Yudan , Wei Yuxin , Yang Zhengqiang , Chen Kai , Li Jianxu , Li Liqing , Su Tingshi , Liang Shixiong
Published: February 2024

Objective

This study aimed to construct a nomogram to predict radiation-induced hepatic toxicity in patients with hepatocellular carcinoma treated with intensity-modulated radiotherapy.

Methods

This study reviewed the clinical characteristics and dose–volume parameters of 196 patients with hepatocellular carcinoma. Radiation-induced hepatic toxicity was defined as progression of the Child–Pugh score caused by intensity-modulated radiotherapy. Factors relevant to radiation-induced hepatic toxicity were selected using receiver operating characteristic and univariate logistic analysis. A risk assessment model was developed, and its discrimination was validated.

Results

Eighty-eight (44.90%) and 28 (14.29%) patients had radiation-induced hepatic toxicity ≥ 1 (Child–Pugh ≥ 1) and radiation-induced hepatic toxicity ≥ 2 (Child–Pugh ≥ 2). Pre-treatment Child–Pugh, body mass index and dose–volume parameters were correlated with radiation-induced hepatic toxicity ≥ 1 using univariate logistic analysis. V15 had the best predictive effectiveness among the dose–volume parameters in both the training (area under the curve: 0.763, 95% confidence interval: 0.683–0.842, P < 0.001) and validation cohorts (area under the curve: 0.759, 95% confidence interval: 0.635–0.883, P < 0.001). The area under the curve values of the model that was constructed by pre-treatment Child–Pugh, body mass index and V15 for radiation-induced hepatic toxicity ≥1 were 0.799 (95% confidence interval: 0.719–0.878, P < 0.001) and 0.775 (95% confidence interval: 0.657–0.894, P < 0.001) in the training and validation cohorts, respectively. Patients with a body mass index ≤ 20.425, Barcelona clinic liver cancer = C, Hepatitis B Virus-positive, Eastern Cooperative Oncology Group = 1–2 and hepatic fibrosis require lower V15 dose limits.

Conclusions

Risk assessment model constructed from Pre-treatment Child–Pugh, V15 and body mass index can guide individualized patient selection of toxicity minimization strategies.
Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line
Authors: Momtazkari Sarah , Choudhury Anahita Dev , Yong Zachary Wei Ern , Thanh Le Dong , Canh Hiep Nguyen , Harada Kenichi , Hori Toshiyuki , Osato Motomi , Takahashi Chiaki , Koh Cai Ping , Voon Dominic Chih-Cheng
Published: February 2024

A well-documented Achilles heel of current cancer immunotherapy approaches is T cell exhaustion within solid tumor tissues. The proinflammatory cytokine interleukin (IL)-23 has been utilized to augment chimeric antigen receptor (CAR) T cell survival and tumor immunity. However, in-depth interrogation of molecular events downstream of IL-23/IL-23 receptor signaling is hampered by a paucity of suitable cell models. The current study investigates the differential contribution of IL-2 and IL-23 to the maintenance and differentiation of the IL-23 responsive Kit225 T-cell line. We observed that IL-23 enhanced cellular fitness and survival but was insufficient to drive proliferation. IL-23 rapidly induced phosphorylation of STAT1, STAT3, and STAT4, and messenger RNA expression of IL17A, the archetypal effector cytokine of T helper 17 (Th17) cells, but not their lineage markers RORC and NCR1. These observations suggest that IL-23 endowed Th17/ILC3-like effector function but did not promote their differentiation. In contrast, spontaneous differentiation of Kit225 cells toward a Th17/ILC3-like phenotype was induced by prolonged IL-2 withdrawal. This was marked by strongly elevated basal IL17A and IL17F expression and the secretion of IL-17. Together, our data present Kit225 cells as a valuable model for studying the interplay between cytokines and their contribution to T cell survival, proliferation, and differentiation.
Influence of non-gravitational forces on the co-orbital motion
Authors: Qi Yi , Ding Ying , Qiao Dong
Published: February 2024

In the Solar system, there exist many non-gravitational perturbations for co-orbital objects, such as the solar radiation pressure, Yarkovsky effect, and so forth. Their effects play important roles in the dynamics of co-orbital objects as they lead to long-term perturbations accumulating. The motivation of this paper is to investigate the general mechanism of the non-gravitational force on the co-orbital motion in the circular restricted three-body problem. We propose an effective method for perturbed co-orbital motions by analysing the locus of the co-orbital objects in a two-dimensional map. Several expressions derived uncover how the non-gravitational force acts on orbital parameters. Taking the Sun–Jupiter system as an example, we implement numerical computations to demonstrate the validity of our results. Numerical computation shows that most of loci of co-orbital motions are in agreement with our conclusions. Some interesting phenomena of perturbed co-orbital motion, such as the co-orbital transition and escape, are found and explained. The results obtained from this paper provide an efficient approach to analyse the evolution of perturbed co-orbital motions.
Investigating the hard state of MAXI J1820 + 070: a comprehensive Bayesian approach to black hole spin and accretion properties
Authors: Dias Sachin D , Vaughan Simon , Lefkir Mehdy , Wynn Graham
Published: February 2024

We analyse the X-ray spectrum of the black hole (BH) X-ray binary MAXI J1820 + 070 using observations from XMM-Newton and NuSTAR during ‘hard’ states of its 2018–2019 outburst. We take a fully Bayesian approach, and this is one of the first papers to present a fully Bayesian workflow for the analysis of an X-ray binary X-ray spectrum. This allows us to leverage the relatively well-understood distance and binary system properties (like inclination and BH mass), as well as information from the XMM-Newton RGS data to assess the foreground X-ray absorption. We employ a spectral model for a ‘vanilla’ disc-corona system: the disc is flat and in the plane perpendicular to the axis of the jet and the BH spin, the disc extends inwards to the innermost stable circular orbit around the BH, and the (non-thermal) hard X-ray photons are up-scattered soft X-ray photons originating from the disc thermal emission. Together, these provide tight constraints on the spectral model and, in combination with the strong prior information about the system, mean we can then constrain other parameters that are poorly understood such as the disc colour correction factor. By marginalizing over all the parameters, we calculate a posterior density for the BH spin parameter, a. Our modelling suggests a preference for low or negative spin values, although this could plausibly be reproduced by higher spins and a modest degree of disc truncation. This approach demonstrates the efficacy and some of the complexities of Bayesian methods for X-ray spectral analysis.
Landscape of RNA pseudouridylation in archaeon Sulfolobus islandicus
Authors: Li Yuqian , Wu Songlin , Ye Keqiong
Published: February 2024

Pseudouridine, one of the most abundant RNA modifications, is synthesized by stand-alone or RNA-guided pseudouridine synthases. Here, we comprehensively mapped pseudouridines in rRNAs, tRNAs and small RNAs in the archaeon Sulfolobus islandicus and identified Cbf5-associated H/ACA RNAs. Through genetic deletion and in vitro modification assays, we determined the responsible enzymes for these modifications. The pseudouridylation machinery in S. islandicus consists of the stand-alone enzymes aPus7 and aPus10, and six H/ACA RNA-guided enzymes that account for all identified pseudouridines. These H/ACA RNAs guide the modification of all eleven sites in rRNAs, two sites in tRNAs, and two sites in CRISPR RNAs. One H/ACA RNA shows exceptional versatility by targeting eight different sites. aPus7 and aPus10 are responsible for modifying positions 13, 54 and 55 in tRNAs. We identified four atypical H/ACA RNAs that lack the lower stem and the ACA motif and confirmed their function both in vivo and in vitro. Intriguingly, atypical H/ACA RNAs can be modified by Cbf5 in a guide-independent manner. Our data provide the first global view of pseudouridylation in archaea and reveal unexpected structures, substrates, and activities of archaeal H/ACA RNPs.
A sensitive and scalable fluorescence anisotropy single stranded RNA targeting approach for monitoring riboswitch conformational states
Authors: Rivera Maira , Ayon Omma S , Diaconescu-Grabari Suzana , Pottel Joshua , Moitessier Nicolas , Mittermaier Anthony , McKeague Maureen
Published: February 2024

The capacity of riboswitches to undergo conformational changes in response to binding their native ligands is closely tied to their functional roles and is an attractive target for antimicrobial drug design. Here, we established a probe-based fluorescence anisotropy assay to monitor riboswitch conformational switching with high sensitivity and throughput. Using the Bacillus subtillis yitJ S-Box (SAM-I), Fusobacterium nucleatum impX RFN element of (FMN) and class-I cyclic-di-GMP from Vibrio cholerae riboswitches as model systems, we developed short fluorescent DNA probes that specifically recognize either ligand-free or -bound riboswitch conformational states. We showed that increasing concentrations of native ligands cause measurable and reproducible changes in fluorescence anisotropy that correlate with riboswitch conformational changes observed by native gel analysis. Furthermore, we applied our assay to several ligand analogues and confirmed that it can discriminate between ligands that bind, triggering the native conformational change, from those that bind without causing the conformational change. This new platform opens the possibility of high-throughput screening compound libraries to identify potential new antibiotics that specifically target functional conformational changes in riboswitches.
Urinary C4d and progression of kidney disease in IgA vasculitis
Authors: Yu Guizhen , Zhao Jie , Wang Meifang , Chen Yang , Feng Shi , Li Bingjue , Wang Cuili , Wang Yucheng , Jiang Hong , Chen Jianghua
Published: February 2024

Background

Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) is the most common secondary IgA nephropathy (IgAN). Urinary C4d have been identified associated with the development and progression in primary IgAN; however, its role in kidney disease progression of IgAVN is still unclear.

Methods

This study enrolled 139 patients with IgAVN, 18 healthy subjects, 23 focal segmental glomerulosclerosis patients and 38 IgAN patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% estimated glomerular filtration rate decline or end-stage kidney disease, was assessed using Cox proportional hazards models and restricted cubic splines.

Results

The levels of urinary C4d/creatinine (Cr) in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/Cr were associated with higher proteinuria and severe Oxford C lesions, and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of Ln(urinary C4d/Cr). After adjustment for clinical data, higher levels of urinary C4d/Cr were associated with kidney disease progression in IgAVN [per Ln-transformed urinary C4d/Cr, hazard ratio 1.573, 95% confidence interval (CI) 1.101–2.245; P = .013]. Compared with the lower C4d/Cr group, the hazard ratio was 5.539 (95% CI 1.135–27.035; P = .034) for the higher levels group.

Conclusions

Higher levels of urinary C4d/Cr were associated with kidney disease progression event in patients with IgAVN.
Atezolizumab Plus Carboplatin and Etoposide in Patients with Untreated Extensive-Stage Small-Cell Lung Cancer: Interim Results of the MAURIS Phase IIIb Trial
Authors: Bria Emilio , Morgillo Floriana , Garassino Marina Chiara , Ciardiello Fortunato , Ardizzoni Andrea , Stefani Alessio , Verderame Francesco , Morabito Alessandro , Chella Antonio , Tonini Giuseppe , Gilli Marina , Del Signore Ester , Berardi Rossana , Mencoboni Manlio , Bearz Alessandra , Delmonte Angelo , Migliorino Marta Rita , Gridelli Cesare , Pazzola Antonio , Iero Manuela , De Marinis Filippo
Published: February 2024

Background

MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab + carboplatin/etoposide in patients with newly diagnosed, extensive-stage small-cell lung cancer (ES-SCLC). The primary objective is the safety evaluation.

Materials and Methods

Patients received atezolizumab + carboplatin/etoposide Q3W for 4-6 cycles in the induction phase, followed by atezolizumab maintenance Q3W. We presented the interim analysis on safety (referring to the induction phase) and clinical effectiveness, in all patients (N = 154) and in subgroups that received ≤3 (N = 23), 4 (N = 43), and 5-6 cycles (N = 89) of induction.

Results

At a median follow-up of 10.5 months, 139 patients (90.3%) discontinued treatment. Serious adverse events occurred in 29.9% of patients overall, and the rate was lower in patients with 5-6 cycles (19.1%) than in those with 4 (34.9%) or ≤3 (63.6%) cycles. Immune-mediated adverse events were reported in 14.9%, 15.7%, 11.6%, and 18.2% of patients, overall and by subgroup, respectively. The median overall survival and progression-free survival were 10.7 and 5.5 months, respectively. Overall, 111 patients (71.6%) had a tumor response.

Conclusions

Interim results provide further evidences about safety and efficacy profile of atezolizumab + carboplatin/etoposide treatment in a ES-SCLC patient population closer to that observed in clinical practice.

Clinical Trial Registration

Eudract No. 2019-001146-17, NCT04028050.
Increased α-ketoglutarate links the C3–C4 intermediate state to C4 photosynthesis in the genus Flaveria
Authors: Tang Qiming , Huang Yuhui , Ni Xiaoxiang , Lyu Ming-Ju Amy , Chen Genyun , Sage Rowan , Zhu Xin-Guang
Published: February 2024

As a complex trait, C4 photosynthesis has multiple independent origins in evolution. Phylogenetic evidence and theoretical analysis suggest that C2 photosynthesis, which is driven by glycine decarboxylation in the bundle sheath cell, may function as a bridge from C3 to C4 photosynthesis. However, the exact molecular mechanism underlying the transition between C2 photosynthesis to C4 photosynthesis remains elusive. Here, we provide evidence suggesting a role of higher α-ketoglutarate (AKG) concentration during this transition. Metabolomic data of 12 Flaveria species, including multiple photosynthetic types, show that AKG concentration initially increased in the C3–C4 intermediate with a further increase in C4 species. Petiole feeding of AKG increases the concentrations of C4-related metabolites in C3–C4 and C4 species but not the activity of C4-related enzymes. Sequence analysis shows that glutamate synthase (Fd-GOGAT), which catalyzes the generation of glutamate using AKG, was under strong positive selection during the evolution of C4 photosynthesis. Simulations with a constraint-based model for C3–C4 intermediate further show that decreasing the activity of Fd-GOGAT facilitated the transition from a C2-dominant to a C4-dominant CO2 concentrating mechanism. All these results provide insight into the mechanistic switch from C3–C4 intermediate to C4 photosynthesis.
Double blocking of carbon metabolism causes a large increase of Calvin–Benson cycle compounds in cyanobacteria
Authors: Domínguez-Lobo María Teresa , Roldán Miguel , Gutiérrez-Diánez Alba María , Florencio Francisco Javier , Muro-Pastor María Isabel
Published: February 2024

Carbon-flow-regulator A (CfrA) adapts carbon flux to nitrogen conditions in nondiazotrophic cyanobacteria. Under nitrogen deficiency, CfrA leads to the storage of excess carbon, which cannot combine with nitrogen, mainly as glycogen. cfrA overexpression from the arsenite-inducible, nitrogen-independent ParsB promoter allows analysis of the metabolic effects of CfrA accumulation. Considering that the main consequence of cfrA overexpression is glycogen accumulation, we examined carbon distribution in response to cfrA expression in Synechocystis sp. PCC 6803 strains impaired in synthesizing this polymer. We carried out a comparative phenotypic analysis to evaluate cfrA overexpression in the wild-type strain and in a mutant of ADP-glucose pyrophosphorylase (ΔglgC), which is unable to synthesize glycogen. The accumulation of CfrA in the wild-type background caused a photosynthetic readjustment although growth was not affected. However, in a ΔglgC strain, growth decreased depending on CfrA accumulation and photosynthesis was severely affected. An elemental analysis of the H, C, and N content of cells revealed that cfrA expression in the wild-type caused an increase in the C/N ratio, due to decreased nitrogen assimilation. Metabolomic study indicated that these cells store sucrose and glycosylglycerol, in addition to the previously described glycogen accumulation. However, cells deficient in glycogen synthesis accumulated large amounts of Calvin–Benson cycle intermediates as cfrA was expressed. These cells also showed increased levels of some amino acids, mainly alanine, serine, valine, isoleucine, and leucine. The findings suggest that by controlling cfrA expression, in different conditions and strains, we could change the distribution of fixed carbon, with potential biotechnological benefits.
The emergence of MedTok: a qualitative analysis of popular medical TikTok videos
Authors: Rosen Ross , Vasiloudes Vasilis , Mhaskar Rahul
Published: February 2024

Social media is increasingly being used by the public as a medium for health information. Unfortunately, misinformation has become widely available on these sites, often being provided using content that is designed to be more popular and engaging, and it is difficult for the public to differentiate between what is true and what is false. TikTok is one of these platforms and has been rapidly growing over the last few years. As an increasing number of people look to TikTok for their health information, it is important that quality information is accessible and popular on the platform. We conducted a review of TikTok videos using the top 10 videos to show when searching for 13 common conditions. Characteristics of both the creator and video were recorded and analyzed. Videos on conditions commonly diagnosed younger were commonly produced by younger creators with the condition, often based on their own experiences. Conversely, videos on conditions commonly diagnosed older were commonly produced by healthcare professionals providing educational information. Though for conditions affecting older individuals healthcare professionals may be able to create didactic, educational videos, for those affecting younger individuals, it may be beneficial to partner with younger creators, or “influencers,” to produce more viral content. Further studies may expand on these ideas to encompass more facets of healthcare. As this study did not analyze the quality of the information in the videos, future research should also focus on determining the quality of popular content on TikTok and other social media platforms.
Evolution of fiscal systems: convergence or divergence?
Authors: Péligry Paloma , Ragot Xavier
Published: February 2024

We analyze the convergence or divergence of the diversity of fiscal systems after the financial crisis of 2007. Studying twenty-nine countries, we first document the evolution of the taxation of households, firms, labor, consumption, and capital. We identify three types of fiscal systems: liberal, intermediate, and high-redistribution, which can be ranked in ascending order of tax rates, confirming known typologies in the diversity of capitalism literature. Only the tax rate on corporate profits shows signs of downward convergence over the period. The other tax rates show rather signs of divergence. Second, a divergence is observed among the liberal and high-redistribution groups over the period. The European countries are converging toward the high-redistribution model, with the exception of Great Britain, which is moving toward the liberal model. Thus, the financial crisis seems to contribute not to the convergence, but to the divergence of fiscal systems.
MSC-Derived Small Extracellular Vesicles Exert Cardioprotective Effect Through Reducing VLCFAs and Apoptosis in Human Cardiac Organoid IRI Model
Authors: Poh Boon Min , Liew Lee Chuen , Soh Yan Ni Annie , Lai Ruenn Chai , Lim Sai Kiang , Ho Ying Swan , Soh Boon Seng
Published: February 2024

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for 31% of all deaths globally. Myocardial ischemia-reperfusion injury (IRI), a common complication of CVDs, is a major cause of mortality and morbidity. Studies have shown efficacious use of mesenchymal stem cells-derived small extracellular vesicles (MSCs-EVs) to mitigate IRI in animals, but few research has been done on human-related models. In this study, human embryonic stem cell-derived chambered cardiac organoid (CCO) was used as a model system to study the effects of MSC-EVs on myocardial IRI. The results revealed that MSC-EVs treatment reduced apoptosis and improved contraction resumption of the CCOs. Metabolomics analysis showed that this effect could be attributed to EVs’ ability to prevent the accumulation of unsaturated very long-chain fatty acids (VLCFAs). This was corroborated when inhibition of fatty acid synthase, which was reported to reduce VLCFAs, produced a similar protective effect to EVs. Overall, this study uncovered the mechanistic role of MSC-EVs in mitigating IRI that involves preventing the accumulation of unsaturated VLCFA, decreasing cell death, and improving contraction resumption in CCOs.
Comparative Performance Evaluation of Double-Stranded RNA High-Throughput Sequencing for the Detection of Viral Infection in Temperate Fruit Crops
Authors: Marais Armelle , Gentit Pascal , Brans Yoann , Renvoisé Jean Philippe , Faure Chantal , Saison Anne , Cousseau Pascaline , Castaing Julie , Chambon Fabien , Pion Angélique , Calado Grégory , Lefebvre Marie , Garnier Soraya , Latour François , Bresson Kévin , Grasseau Nathalie , Candresse Thierry
Published: February 2024

There is limited information on the compared performances of biological, serological. and molecular assays with high-throughput sequencing (HTS) for viral indexing in temperate fruit crops. Here, using a range of samples of predetermined virological status, we compared two performance criteria (inclusivity and analytical sensitivity) of enzyme-linked immunosorbent assay (ELISA), molecular hybridization, reverse transcription (RT)-PCR, and double-stranded RNA (dsRNA) HTS for the detection of a total of 14 viruses (10 genera) and four viroids (three genera). When undiluted samples from individual plants were used, ELISA had the lowest performance, with an overall detection rate of 68.7%, followed by RT-PCR (82.5%) and HTS (90.7%; 100% if considering only viruses). The lower performance of RT-PCR reflected the inability to amplify some isolates as a consequence of point mutations affecting primer-binding sites. In addition, HTS identified viruses that had not been identified by other assays in nearly two-thirds of the samples. Analysis of serial dilutions of fruit tree samples allowed comparison of analytical sensitivities for various viruses. ELISA showed the lowest analytical sensitivity, but RT-PCR showed higher analytical sensitivity than HTS for most of the samples. Overall, these results confirm the superiority of HTS over biological indexing in terms of speed and inclusivity and show that while the absolute analytical sensitivity of RT-PCR tends to be higher than that of HTS, PCR inclusivity is affected by viral genetic diversity. Taken together, these results make a strong case for the implementation of HTS-based approaches in fruit tree viral testing protocols supporting quarantine and certification programs.
Loss of chaperone‐mediated autophagy does not alter age‐related bone loss in male mice
Authors: Hendrixson James A. , James Alicen , Akel Nisreen S. , Laster Dominique J. , Crawford Julie A. , Berryhill Stuart B. , Onal Melda
Published: February 2024

Chaperone‐mediated autophagy (CMA) is a lysosome‐dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age‐associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age‐associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS‐32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age‐related bone loss, we hypothesized that declining CMA contributes to the age‐associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA‐deficient mice and controls up to 24 months of age and examined age‐associated changes in bone mass and architecture. We showed that lack of CMA did not alter age‐associated decline in bone mineral density as measured by dual x‐ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA‐deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age‐related bone loss.
Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore
Authors: Griffiths Keren K. , Wang Aili , Jonas Elizabeth A. , Levy Richard J.
Published: February 2024

Pathological opening of the mitochondrial permeability transition pore (mPTP) is implicated in the pathogenesis of many disease processes such as myocardial ischemia, traumatic brain injury, Alzheimer's disease, and diabetes. While we have gained insight into mPTP biology over the last several decades, the lack of translation of this knowledge into successful clinical therapies underscores the need for continued investigation and use of different approaches to identify novel regulators of the mPTP with the hope of elucidating new therapeutic targets. Although the mPTP is known to be a voltage‐gated channel, the identity of its voltage sensor remains unknown. Here we found decreased gating potential of the mPTP and increased expression and activity of sulfide quinone oxidoreductase (SQOR) in newborn Fragile X syndrome (FXS) mouse heart mitochondria, a model system of coenzyme Q excess and relatively decreased mPTP open probability. We further found that pharmacological inhibition and genetic silencing of SQOR increased mPTP open probability in vitro in adult murine cardiac mitochondria and in the isolated‐perfused heart, likely by interfering with voltage sensing. Thus, SQOR is proposed to contribute to voltage sensing by the mPTP and may be a component of the voltage sensing apparatus that modulates the gating potential of the mPTP.
Does rickets carry an increased risk of osteomyelitis and septic arthritis? An aggregated electronic health record data study
Authors: Lavu Monish S. , Van Dorn Chloe , Bobak Lukas , Burkhart Robert J. , Kaelber David C. , Mistovich R. Justin
Published: February 2024

To investigate the prevalence of osteomyelitis and septic arthritis in pediatric patients with rickets, compared to the general population. A retrospective cohort study was conducted using the TriNetX analytics network, which aggregates deidentified electronic health record data from over 105 million US patients. We queried pediatric patients with rickets, based on ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) encounter diagnoses. Patients with any ICD-10-CM encounter diagnoses of osteomyelitis or septic arthritis were reported. We established a control cohort of pediatric patients without rickets. Of 7337 pediatric patients (≤18 years old) with a rickets diagnosis, 96 [1.31%, 95% confidence interval (CI): 1.05%–1.57%] had a diagnosis of osteomyelitis and 28 (0.38%, 95% CI: 0.24%–0.52%) had a diagnosis of septic arthritis. In comparison, of the 17 240 604 pediatric patients without a rickets diagnosis, 16 995 (0.10%, 95% CI: 0.10%–0.10%) had a diagnosis of osteomyelitis and 8521 (0.05%, 95% CI: 0.05%–0.05%) had a diagnosis of septic arthritis. The relative risk for an osteomyelitis diagnosis in pediatric patients with a rickets diagnosis was 13.27 (95% CI: 10.86–16.23), while the relative risk for a septic arthritis diagnosis was 7.72 (95% CI: 5.33–11.18). Pediatric patients with a diagnosis of rickets have over 10- and 5-times higher relative risks for having a diagnosis of osteomyelitis and septic arthritis, respectively, compared to those without a diagnosis of rickets. This is the first study to explore musculoskeletal infections in rickets patients, highlighting the importance of clinicians being vigilant about these conditions.
Improving Situation Awareness to Advance Patient Outcomes
Authors: Alqarrain Yaser , Roudsari Abdul , Courtney Karen L. , Tanaka Jim
Published: February 2024

Improving nurses' situation awareness skills would likely improve patient status recognition and prevent adverse events. Technologies such as electronic health record dashboards can be a promising approach to support nurses' situation awareness. However, the effect of these dashboards on this skill is unknown. This systematic literature review explores the evidence around interventions to improve nurses' situation awareness at the point of care. Current research on this subject is limited. Studies that examined the use of electronic health record dashboards as an intervention had weak evidence to support their effectiveness. Other interventions, including communication interventions and structured nursing assessments, may also improve situation awareness, but more research is needed to confirm this. It is important to carefully consider the design and content of situation awareness interventions, as well as the specific outcomes being measured, when designing situation awareness interventions. Overall, there is a need for higher-quality research in this area to determine the most effective interventions for improving nurse situation awareness. Future studies should focus on developing dashboards that follow a theoretical situation awareness model information and represent all situation awareness levels.