bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores
Authors: Leonard Sean , Guertin Hailey , Odoardi Natalya , Miller Michael R. , Patel Maitray A. , Daley Mark , Cepinskas Gediminas , Fraser Douglas D.
Published: March 2024

Background

Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores.

Methods

Pediatric patients that met sepsis criteria were enrolled, and clinical data and blood samples were collected. Fifty-eight inflammatory plasma biomarker concentrations were determined using immunoassays. The data were analyzed with both conventional statistics and machine learning.

Results

Twenty sepsis patients were enrolled (median age 13 years), with infectious pathogens identified in 75%. Vasopressors were administered to 85% of patients, while 55% received invasive ventilation and 20% were ventilated non-invasively. A total of 24 inflammatory biomarkers were significantly different between sepsis patients and age/sex-matched healthy controls. Nine biomarkers (IL-6, IL-8, MCP-1, M-CSF, IL-1RA, hyaluronan, HSP70, MMP3, and MMP10) yielded AUC parameters > 0.9 (95% CIs: 0.837-1.000; p < 0.001). Boruta feature reduction yielded 6 critical biomarkers with their relative importance: IL-8 (12.2%), MCP-1 (11.6%), HSP70 (11.6%), hyaluronan (11.5%), M-CSF (11.5%), and IL-6 (11.5%); combinations of 2 biomarkers yielded AUC values of 1.00 (95% CI: 1.00–1.00; p < 0.001). Specific biomarkers strongly correlated with illness severity scoring, as well as other clinical variables. IL-3 specifically distinguished bacterial versus viral infection (p < 0.005).

Conclusions

Specific inflammatory biomarkers were identified as markers of pediatric sepsis and strongly correlated to both clinical variables and sepsis severity.
RNA-seq analysis of chlorogenic acid intervention in duck embryo fibroblasts infected with duck plague virus
Authors: Yang Yunyun , Zhang Qiandong , Cai Haiqing , Feng Yi , Wen Anlin , Yang Ying , Wen Ming
Published: March 2024

Introduction

Chlorogenic acid, the primary active component in Chinese medicines like honeysuckle, exhibits anti-inflammatory and antiviral effects. It has been demonstrated that chlorogenic acid effectively prevents and treats Duck enteritis virus (DEV) infection. This study aims to further elucidate the mechanism by which chlorogenic acid prevents DEV infection.

Methods

Duck embryo fibroblast (DEF) cells were pre-treated with chlorogenic acid before being infected with DEV. Cell samples were collected at different time points for transcriptomic sequencing, while qPCR was used to detect the proliferation of DEV. Additionally, 30-day-old ducks were treated with chlorogenic acid, and their lymphoid organs were harvested for histopathological sections to observe pathological damage. The proliferation of DEV in the lymphoid organs was also detected using qPCR Based on the transcriptomic sequencing results, NF-κB1 gene was silenced by RNAi technology to analyze the effect of NF-κB1 gene on DEV proliferation.

Results

Compared to the viral infection group, DEF cells in the chlorogenic acid intervention group exhibited significantly reduced DEV load (P < 0.05). Transcriptomic sequencing results suggested that chlorogenic acid inhibited DEV proliferation in DEF cells by regulating NF-κB signaling pathway. The results of RNAi silencing suggested that in the three treatment groups, compared with the DEV experimental group, there was no significant difference in the effect of pre-transfection after transfection on DEV proliferation, while both the pre-transfection after transfection and the simultaneous transfection group showed significant inhibition on DEV proliferation Furthermore, compared to the virus infection group, ducks in the chlorogenic acid intervention group showed significantly decreased DEV load in their lymphoid organs (P < 0.05), along with alleviated pathological damage such as nuclear pyretosis and nuclear fragmentation.

Conclusions

Chlorogenic acid effectively inhibits DEV proliferation in DEF and duck lymphatic organs, mitigates viral-induced pathological damage, and provides a theoretical basis for screening targeted drugs against DEV.
The Rothman Index predicts unplanned readmissions to intensive care associated with increased mortality and hospital length of stay: a propensity-matched cohort study
Authors: Stahel Philip F. , Belk Kathy W. , McInnis Samantha J. , Holland Kathryn , Nanz Roy , Beals Joseph , Gosnell Jaclyn , Ogundele Olufunmilayo , Mastriani Katherine S.
Published: March 2024

Background

Patients with unplanned readmissions to the intensive care unit (ICU) are at high risk of preventable adverse events. The Rothman Index represents an objective real-time grading system of a patient’s clinical condition and a predictive tool of clinical deterioration over time. This study was designed to test the hypothesis that the Rothman Index represents a sensitive predictor of unanticipated ICU readmissions.

Methods

A retrospective propensity-matched cohort study was performed at a tertiary referral academic medical center in the United States from January 1, 2022, to December 31, 2022. Inclusion criteria were adult patients admitted to an ICU and readmitted within seven days of transfer to a lower level of care. The control group consisted of patients who were downgraded from ICU without a subsequent readmission. The primary outcome measure was in-hospital mortality or discharge to hospice for end-of-life care. Secondary outcome measures were overall hospital length of stay, ICU length of stay, and 30-day readmission rates. Propensity matching was used to control for differences between the study cohorts. Regression analyses were performed to determine independent risk factors of an unplanned readmission to ICU.

Results

A total of 5,261 ICU patients met the inclusion criteria, of which 212 patients (4%) had an unanticipated readmission to the ICU within 7 days. The study cohort and control group were stratified by propensity matching into equal group sizes of n = 181. Lower Rothman Index scores (reflecting higher physiologic acuity) at the time of downgrade from the ICU were significantly associated with an unplanned readmission to the ICU (p < 0.0001). Patients readmitted to ICU had a lower mean Rothman Index score (p < 0.0001) and significantly increased rates of mortality (19.3% vs. 2.2%, p < 0.0001) and discharge to hospice (14.4% vs. 6.1%, p = 0.0073) compared to the control group of patients without ICU readmission. The overall length of ICU stay (mean 8.0 vs. 2.2 days, p < 0.0001) and total length of hospital stay (mean 15.8 vs. 7.3 days, p < 0.0001) were significantly increased in patients readmitted to ICU, compared to the control group.

Conclusion

The Rothman Index represents a sensitive predictor of unanticipated readmissions to ICU, associated with a significantly increased mortality and overall ICU and hospital length of stay. The Rothman Index should be considered as a real-time objective measure for prediction of a safe downgrade from ICU to a lower level of care.
Preparation and property analysis of antioxidant of carbazole derivatives
Authors: Zhang Zhi-quan , Zhu Bao-wei , Zhang Jing-yu , Chen Hong
Published: March 2024

Carbazole derivatives can be used as antioxidants in the lubricating oil industry. The alkylation of carbazole with 2-chloro-2-methylpropane and 2-bromopropane catalyzed by anhydrous aluminum chloride was studied. Initially, 3,6-di-iso-propylcarbazole and 3,6-di-tert-butylcarbazole were using dichloromethane and dibromomethane as solvents at room temperature, respectively. The synthesis conditions were optimized. Subsequently, the effects of reaction time, catalyst dosage, and molar ratio of carbazole to alkylating agent were investigated, and orthogonal experiments were performed. The structures of the carbazole derivatives were characterized by Fourier infrared spectroscopy (FT-IR), mass spectrum (MS) and nuclear magnetic resonance spectroscopy (NMR). The thermal stability of the synthesized carbazole derivatives was investigated by differential scanning calorimetry (DSC). The carbazole derivatives were added into the lubricating oil with a mass fraction of 0.8% and the miscibility, stability and oxidation resistance of the mixed system were evaluated by mechanical stirring and a rotary pressure vessel oxidation test (RPVOT). The DSC results showed that there was good thermal stability for the carbazole derivatives. The mechanical stirring method revealed good solubility and stability for the mixture of oil and carbazole derivatives. The RPVOT results showed that isopropyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.39 times, and tert-butyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.91 times. The antioxidant effect of tert-butyl carbazole derivatives was better than that of isopropyl carbazole derivatives.
EnZolv delignification of cotton spinning mill waste and optimization of process parameters using response surface methodology (RSM)
Authors: Subramaniam Santhoshkumar , Karunanandham Kumutha , Raja A. S. M. , Shukla S. K. , Uthandi Sivakumar
Published: March 2024

Background

EnZolv is a novel enzyme-based, eco-friendly biomass pretreatment process that has shown great potential in the field of textile engineering and biotechnology. It employs laccase from Hexagonia hirta MSF2 and 2% ethanol in the process of delignification. The process is designed to evaluate optimal conditions to remove lignin and other impurities from cotton spinning mill waste (CSMW), without compromising the quality and strength of the fibers. CSMW is a low-cost and readily available source of cellulose, making it an ideal candidate for delignification using EnZolv. By optimizing the pretreatment conditions and harnessing the potential of enzymatic delignification, this research aims to contribute to more sustainable and efficient ways of utilizing lignocellulosic biomass in various industries for the production of biochemical and bioproducts.

Results

The present study emphasizes the EnZolv pretreatment in the delignification of cotton spinning mill wastes irrespective of the cellulose content. EnZolv process parameters such as, moisture content, enzyme load, incubation time, incubation temperature, and shaking speed were optimized. Under pre-optimized conditions, the percent lignin reduction was 61.34%, 61.64%, 41.85%, 35.34%, and 35.83% in blowroom droppings (BD), flat strips (FS), lickerin fly (LF), microdust (MD) and comber noils (CN), respectively. Using response surface methodology (RSM), the statistically optimized EnZolv pretreatment conditions showed lignin reduction of 59.16%, 62.88%, 48.26%, 34.64%, and 45.99% in BD, FS, LF, MD, and CN, respectively.

Conclusion

Traditional chemical-based pretreatment methods often involve harsh chemicals and high energy consumption, which can have detrimental effects on the environment. In contrast, EnZolv offers a greener approach by utilizing enzymes that are biodegradable and more environmentally friendly. The resulting fibers from EnZolv treatment exhibit improved properties that make them suitable for various applications. Some of the key properties include enhanced cellulose recovery, reduced lignin content, and improved biophysical and structural characteristics. These improvements can contribute to the fiber's performance and processability in different industries and future thrust for the production of cellulose-derived and lignin-derived bioproducts.

Graphical Abstract
Conjoined lumbosacral nerve root: a case report
Authors: Takagi Yasutaka , Yamada Hiroshi , Ebara Hidehumi , Hayashi Hiroyuki , Inatani Hiroyuki , Toyooka Kazu , Mori Akari , Kitano Yoshiyuki , Ryu Yasuji , Nakanami Aki , Yahata Tetsutaro , Tsuchiya Hiroyuki
Published: March 2024

Background

In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery.

Case presentation

We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5–S disc degeneration. L5–S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved.

Conclusions

This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root.
PLOD2, a key factor for MRL MSC metabolism and chondroprotective properties
Authors: Bahraoui Sarah , Tejedor Gautier , Mausset-Bonnefont Anne-Laure , Autelitano François , Barthelaix Audrey , Terraza-Aguirre Claudia , Gisbert Vincent , Arribat Yoan , Jorgensen Christian , Wei Mingxing , Djouad Farida
Published: March 2024

Background

Initially discovered for its ability to regenerate ear holes, the Murphy Roth Large (MRL) mouse has been the subject of multiple research studies aimed at evaluating its ability to regenerate other body tissues and at deciphering the mechanisms underlying it. These enhanced abilities to regenerate, retained during adulthood, protect the MRL mouse from degenerative diseases such as osteoarthritis (OA). Here, we hypothesized that mesenchymal stromal/stem cells (MSC) derived from the regenerative MRL mouse could be involved in their regenerative potential through the release of pro-regenerative mediators.

Method

To address this hypothesis, we compared the secretome of MRL and BL6 MSC and identified several candidate molecules expressed at significantly higher levels by MRL MSC than by BL6 MSC. We selected one candidate, Plod2, and performed functional in vitro assays to evaluate its role on MRL MSC properties including metabolic profile, migration, and chondroprotective effects. To assess its contribution to MRL protection against OA, we used an experimental model for osteoarthritis induced by collagenase (CiOA).

Results

Among the candidate molecules highly expressed by MRL MSC, we focused our attention on procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). Plod2 silencing induced a decrease in the glycolytic function of MRL MSC, resulting in the alteration of their migratory and chondroprotective abilities in vitro. In vivo, we showed that Plod2 silencing in MRL MSC significantly impaired their capacity to protect mouse from developing OA.

Conclusion

Our results demonstrate that the chondroprotective and therapeutic properties of MRL MSC in the CiOA experimental model are in part mediated by PLOD2.
Human umbilical cord/placenta mesenchymal stem cell conditioned medium attenuates intestinal fibrosis in vivo and in vitro
Authors: Choi Yoon Jeong , Kim Woo Ram , Kim Duk Hwan , Kim Jee Hyun , Yoo Jun Hwan
Published: March 2024

Background

A significant unmet need in inflammatory bowel disease is the lack of anti-fibrotic agents targeting intestinal fibrosis. This study aimed to investigate the anti-fibrogenic properties and mechanisms of the conditioned medium (CM) from human umbilical cord/placenta-derived mesenchymal stem cells (UC/PL-MSC-CM) in a murine intestinal fibrosis model and human primary intestinal myofibroblasts (HIMFs).

Methods

UC/PL-MSC-CM was concentrated 15-fold using a 3 kDa cut-off filter. C57BL/6 mice aged 7 weeks old were randomly assigned to one of four groups: (1) control, (2) dextran sulfate sodium (DSS), (3) DSS + CM (late-phase treatment), and (4) DSS + CM (early-phase treatment). Chronic DSS colitis and intestinal fibrosis was induced by three cycles of DSS administration. One DSS cycle consisted of 7 days of oral DSS administration (1.75%, 2%, and 2.5% DSS), followed by 14 days of drinking water. UC/PL-MSC-CM was intraperitoneally administered in the late phase (from day 50, 10 times) or early phase (from day 29, 10 times) of DSS cycles. HIMFs were treated with TGF-β1 and co-treated with UC/PL-MSC-CM (10% of culture media) in the cellular model.

Results

In the animal study, UC/PL-MSC-CM reduced submucosa/muscularis propria thickness and collagen deposition, which improved intestinal fibrosis in chronic DSS colitis. The UC/PL-MSC-CM significantly reduced the expressions of procollagen1A1 and α-smooth muscle actin, which DSS significantly elevated. The anti-fibrogenic effect was more apparent in the UC-MSC-CM or early-phase treatment model. The UC/PL-MSC-CM reduced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs in the cellular model. The UC/PL-MSC-CM downregulated fibrogenesis by suppressing RhoA, MRTF-A, and SRF expression.

Conclusions

Human UC/PL-MSC-CM inhibits TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and chronic DSS colitis-induced intestinal fibrosis. Thus, it may be regarded as a novel candidate for stem cell-based therapy of intestinal fibrosis.
Motor neurons and endothelial cells additively promote development and fusion of human iPSC-derived skeletal myocytes
Authors: Das Suradip , Hilman Melanie C. , Yang Feikun , Mourkioti Foteini , Yang Wenli , Cullen D. Kacy
Published: March 2024

Background

Neurovascular cells have wide-ranging implications on skeletal muscle biology regulating myogenesis, maturation, and regeneration. Although several in vitro studies have investigated how motor neurons and endothelial cells interact with skeletal myocytes independently, there is limited knowledge about the combined effect of neural and vascular cells on muscle maturation and development.

Methods

Here, we report a triculture system comprising human-induced pluripotent stem cell (iPSC)-derived skeletal myocytes, human iPSC-derived motor neurons, and primary human endothelial cells maintained under controlled media conditions. Briefly, iPSCs were differentiated to generate skeletal muscle progenitor cells (SMPCs). These SMPCs were seeded at a density of 5 × 104 cells/well in 12-well plates and allowed to differentiate for 7 days before adding iPSC-derived motor neurons at a concentration of 0.5 × 104 cells/well. The neuromuscular coculture was maintained for another 7 days in coculture media before addition of primary human umbilical vein endothelial cells (HUVEC) also at 0.5 × 104 cells/well. The triculture was maintained for another 7 days in triculture media comprising equal portions of muscle differentiation media, coculture media, and vascular media. Extensive morphological, genetic, and molecular characterization was performed to understand the combined and individual effects of neural and vascular cells on skeletal muscle maturation.

Results

We observed that motor neurons independently promoted myofiber fusion, upregulated neuromuscular junction genes, and maintained a molecular niche supportive of muscle maturation. Endothelial cells independently did not support myofiber fusion and downregulated expression of LRP4 but did promote expression of type II specific myosin isoforms. However, neurovascular cells in combination exhibited additive increases in myofiber fusion and length, enhanced production of Agrin, along with upregulation of several key genes like MUSK, RAPSYN, DOK-7, and SLC2A4. Interestingly, more divergent effects were observed in expression of genes like MYH8, MYH1, MYH2, MYH4, and LRP4 and secretion of key molecular factors like amphiregulin and IGFBP-4.

Conclusions

Neurovascular cells when cultured in combination with skeletal myocytes promoted myocyte fusion with concomitant increase in expression of various neuromuscular genes. This triculture system may be used to gain a deeper understanding of the effects of the neurovascular niche on skeletal muscle biology and pathophysiology.
Does dynamic balance affect cube mental rotation task in badminton vs. volleyball female players?
Authors: Amara Samiha , Al-Hadabi Badriya , El-Ashkar Heba , Gmada Nabil , Habacha Hamdi , Mkaouer Bessem
Published: March 2024

Background

Changing from a static to a dynamic balance condition could affect the performance of a cognitive task such as mental rotation. Thus, the main goal of this study is to investigate aspects of visual-spatial cognition between two non-contact sports (i.e., badminton and volleyball) in different upright conditions (i.e., standing position, frontal balance, and sagittal balance).

Methods

Thirty-five volunteer female sports and physical education students, fourteen specialists in badminton and twenty-one specialists in volleyball agreed to participate in this study. Each of the assessments was a 3D cube mental rotation task with and/or without balance exercises (i.e., frontal and/or sagittal balance) on a wobble board. Five stimuli were used in the mental rotation task (i.e., 45°, 135°, 180°, 225° and 315° for objected-based cube condition with egocentric transformation) which included pairs of standard and comparison images.

Results

The findings indicate that there was a notable decrease (p < 0.001; d = 1.745) in response time in both dynamic balance conditions (i.e., frontal and sagittal balance) compared to standing position condition. In addition, results revealed significant interaction between balance conditions (i.e., frontal and/or sagittal balance) and groups (i.e., badminton and volleyball) in the response time at 225° angle and in the error percentage.

Conclusions

In sum, dynamic balance is also an activity that involves mental manipulation of objects in 3D space, which can enhance badminton and volleyball female players’ ability to rotate 3D cube stimuli.
Improving the performance of a spectral model to estimate total nitrogen content with small soil samples sizes
Authors: Tang Weihao , Hu Wenfeng , Li Chuang , Wu Jinjing , Liu Hong , Wang Chao , Luo Xiaochuan , Tang Rongnian
Published: March 2024

The application of near-infrared spectroscopy (NIRS) for rapid quantitative analysis of soil total nitrogen (STN) is of great significance to recycling nitrogen in the ecosystem and crops growth. However, collecting thousands of soil samples and chemical analysis are impracticable, more importantly a deviation from NIRS advantages of rapid, inexpensive and nondestructive. To more efficiently improve the estimation performance and reduce uncertainty of the model when working with small sample sizes (less than 100), solutions from soil particle size decomposition and model fusion were investigated. Elaborately, 123 Latosols samples were collected and decomposed them according to particle sizes to extend limited data at multiple scales. Based on all soil groups decomposed, a hyperspectral data recapture and model decision fusion method were implemented. The results demonstrated that the proposed method increased the scale of spectral data, extracted more STN-related spectral information, improved estimation accuracy, and reduced uncertainty. The fused model based on data from all decomposed groups yielded the best estimated results (root mean square error $$(RMSE) = 0.075g.kg^{-1}$$

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0.075
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.
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, $$R^2 = 0.784$$

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0.784

, and a ratio of performance to inter-quartile distance $$(RPIQ) = 3.787$$

(
R
P
I
Q
)
=
3.787

) on the validation set. Through a tenfold cross-validation, the weighted fusion model with six groups of particle sizes data showed an improvement of 0.307 in $$R^2_cv$$

R
c
2

v

and an improved RPIQ of 1.015 compared to models constructed using conventional machine learning (ML) techniques and limited pristine data ($$R^2_cv = 0.442, RMSE = 0.119$$

R
c
2

v
=
0.442
,
R
M
S
E
=
0.119

). Therefore, when utilizing NIRS to build rapid and accurate STN predictive models, the proposed method demonstrates great potential in improving the reliability of soil spectral models under small sample sizes.

Graphical Abstract
A balancing act: navigating the nuances of co-production in mental health research
Authors: Soklaridis Sophie , Harris Holly , Shier Rowen , Rovet Jordana , Black Georgia , Bellissimo Gail , Gruszecki Sam , Lin Elizabeth , Di Giandomenico Anna
Published: March 2024

Background

In the context of mental health research, co-production involves people with lived expertise, those with professional or academic expertise, and people with both of these perspectives collaborating to design and actualize research initiatives. In the literature, two dominant perspectives on co-production emerge. The first is in support of co-production, pointing to the transformative value of co-production for those involved, the quality of services developed through this process, as well as to broader system-level impacts (e.g. influencing changes in health system decision making, care practices, government policies, etc.). The second stance expresses scepticism about the capacity of co-production to engender genuine collaboration given the deeply ingrained power imbalances in the systems in which we operate. While some scholars have explored the intersections of these two perspectives, this body of literature remains limited.

Main text

This paper contributes to the literature base by exploring the nuances of co-production in health research. Using our mental health participatory action research project as a case example, we explore the nuances of co-production through four key values that we embraced:

Navigating power relations together

Multi-directional learning

Slow and steady wins the race

Connecting through vulnerability

Conclusions

By sharing these values and associated principles and practices, we invite readers to consider the complexities of co-production and explore how our experiences may inform their practice of co-production. Despite the inherent complexity of co-production, we contend that pursuing authentic and equitable collaborations is integral to shaping a more just and inclusive future in mental health research and the mental health system at large.
The histone deacetylase UvHOS2 regulates vegetative growth, conidiation, ustilaginoidin synthesis, and pathogenicity in Ustilaginoidea virens
Authors: Long Zhaoyi , Wang Peiying , Yu Qianheng , Wang Bo , Li Dayong , Yang Cui , Liu Ling , Duan Guohua , Sun Wenxian
Published: March 2024

Ustilaginoidea virens causes rice false smut, one of the most devastating rice diseases. The pathogen produces various types of mycotoxins, such as ustilaginoidins and ustiloxins, which are harmful to both human and animal health. Histone deacetylases in fungi play an important role in regulating chromatin structure and gene expression. However, there is limited knowledge about how histone deacetylases control pathogenicity and mycotoxin biosynthesis in U. virens. Here, we characterize a putative class I histone deacetylase UvHOS2 in U. virens. The UvHos2-deletion mutants exhibit retarded vegetative growth, reduced conidial production and germination, and attenuated virulence. UvHOS2 positively regulates tolerance to various environmental stresses, including cell wall, cell membrane integrity, osmotic and oxidative stresses. UvHOS2 reduces the acetylation levels of histones at multiple Lys sites, including H3K9, H3K14, H3K27, and H3K56. ChIP-PCR assays revealed that UvHOS2-mediated H3K9 deacetylation regulates the expression of ustilaginoidin biosynthesis genes. Consistently, transcriptome analysis indicates that UvHOS2 regulates the expression of the genes involved in secondary metabolism, mycelial growth, conidiogenesis, and pathogenicity, thereby controlling U. virens virulence and mycotoxin (ustilaginoidins and sorbicillinoids) biosynthesis. This study provides a theoretical reference for revealing the epigenetic regulation of pathogenicity and mycotoxin biosynthesis in plant pathogenic fungi.
Pattern of body fat distribution in patients of PCOS using DEXA-based indices
Authors: Birjees Sanna , Jehangir Majid , Rasool Mirza Vamiq , Amin Fiza , Qayoom Seema
Published: March 2024

Background

Considering the close link between polycystic ovary syndrome (PCOS) and metabolic syndrome considerable research has been devoted to studying the pattern of fat distribution in PCOS.

Objectives

The study aims to assess the usefulness of dual-energy X-ray absorptiometry (DEXA) based regional fat distribution indices as a predictor of the development of PCOS.

Methods

This case–control study recruited diagnosed cases of PCOS using Rotterdam Criteria (cases n = 86) and healthy age-matched controls (n = 90). DEXA was performed in both groups for assessment of total and regional body fat distribution after undergoing ultrasonography (USG) and baseline/biochemical evaluation.

Results

The study revealed a significant difference between cases and controls in trunk fat percentage (40.2% ± 9.1% vs 26.5% ± 9.1%; p < 0.001), android fat percentage (42.4% ± 41%vs 27.8% ± 1.51%; p < 0.001), total fat percentage (43.8% ± 8% vs28.5% ± 1.6%; p < 0.001), fat mass/ht2 (fat mass index) (8.82 ± 3% vs 4.8 ± 1.7%; p < 0.001), android/gynoid ratio (1.05 ± 0.1 vs 0.7 ± 0.2; p < 0.001), and trunk/limb fat mass ratio (1.06 ± 0.3 vs 0.69 ± 0.3; p 0.001). Multivariate analysis revealed a significant relation of trunk fat mass with android % fat, gynoid fat mass, and android-gynoid ratio.

Conclusions

The study demonstrates that there is a central pattern of fat distribution in patients with PCOS while the overall fat might not be increased which is well analyzed by DEXA. Hence, we suggest its use in the initial diagnostic workup and follow-up of PCOS patients for their body fat distribution and content.
Evaluation of molecular subtypes of breast cancer using MRI BI-RADS Lexicon
Authors: Shokeir Farah A. , Soliman Nermin , Khater Ashraf , Bayoumi Dalia
Published: March 2024

Background

Molecular subtyping of breast cancer is one of the prognostic factors which play a very important role in managing patient’s treatment plan. The MRI BI-RADS Lexicon is initially used to categorize breast lesions but recent attempts were employed to differentiate breast lesions based on their molecular subtypes using this lexicon. The study aimed to evaluate of the role of the MRI BI-RADS Lexicon in classifying different molecular subtypes of breast cancer especially after coupling with Kaiser scoring system.

Methods

This retrospective study was conducted on 147 patients with 170 malignant breast lesions. They underwent Pre-contrast and a Dynamic contrast MRI study. Retrospective interpretation of the morphological and dynamic criteria of the breast lesions based on the MRI BI-RADS criteria was carried out followed by reassessment of the same lesions by Kaiser scoring. Resulting data were correlated with histopathological and immunological characterization.

Results

Luminal subtypes were more frequently encountered as mass lesions, contrary to the Non-Luminal lesions which showed a more frequent non-mass presentation value (P 0.002). The shape, margin, internal enhancement pattern of the mass lesions showed significant variability between different molecular subtypes (P < 0.001, < 0.001, < 0.001) respectively. On Dynamic study, Plateau curve was a more evident pattern with Luminal lesions contrasting with their Non-Luminal counterparts which showed a washout pattern more frequently (P 0.0004). Most of luminal A cancers were presented as mass lesions with rim enhancement and categorized as BIRADS 4 while most of Her2neu positive cancers (including luminal B entity) were presented as non-mass lesions with irregular shape and dark internal septations and categorized as BIRADS 5 with statistically significant values (P < 0.001). Coupling with Kaiser scoring system improved the categorization of non-luminal tumors as BIRADS 5 lesions especially the aggressive TN cancers.

Conclusions

MRI-BIRADS lexicon can be of great value in the non-invasive molecular characterization of breast cancer. Kaiser score improved the categorization of TN cancers which were upgraded to BIRADS 5 category.
An Era of Advances in Systemic Therapies for Advanced Thyroid Cancer
Authors: Yun Karen M. , Cohen Ezra E.W.
Published: March 2024

Thyroid carcinomas comprise distinct pathologic subtypes. However, advancements in characterizing the molecular tumorigenesis of thyroid cancers have changed the treatment paradigm in the past decade. Genetic profiling has become an integral component of personalizing cancer care. Oral kinase inhibitors are currently standard-of-care therapies for progressive, radioactive iodine (RAI)–refractory differentiated thyroid carcinomas (DTCs) and medullary thyroid carcinomas (MTCs). Sorafenib, lenvatinib, and cabozantinib are multikinase inhibitors approved for patients with metastatic RAI-refractory DTC, whereas vandetanib and cabozantinib are approved for patients with MTC. Management of thyroid carcinomas has evolved such that targeted therapies have become therapeutic options for patients with
BRAF
,
RET
,
NTRK
,
ALK
, and
ROS1
alterations and even have reported efficacy in anaplastic thyroid carcinomas. In this article, we review the advances made over the years in the treatment of metastatic thyroid carcinoma and focus on the systemic therapies that have recently transformed the treatment landscape of advanced disease.
Implications of Immunogenicity Testing for Therapeutic Monoclonal Antibodies: A Quantitative Pharmacology Framework
Authors: Williams Jason H. , Liao Kai H. , Yin Donghua , Meng Xu
Published: March 2024

The interpretation of immunogenicity results for a mAb product and prediction of its clinical consequences remain difficult, despite enormous advances in methodologies and efforts toward the best practice for consistent data generation and reporting. To this end, the contribution from the clinical pharmacology discipline has been largely limited to comparing descriptively the pharmacokinetic (PK) profiles by antidrug antibodies (ADA) status or testing the significance of ADA as a covariate in a population PK setting, similar to the practice for small-molecule drugs in investigating the effect of an intrinsic/extrinsic factor on the drug disposition. There is a need for a mAb disposition framework that captures the dynamics of ADA formation and drug’s interactions with the ADA and target as parts of the drug distribution and elimination. Here we describe such a framework and examine it against the PK, ADA, and clinical response data from a phase 3 trial in patients treated with adalimumab. The proposed framework offered a generalized understanding of how the dose, target affinity, and drug/ADA analyte forms affects the manifestation of ADA response with regard to its detections and alterations of drug disposition and effectiveness. Furthermore, as an example, its utility for dose considerations was demonstrated through predicting for late-stage trials of a PCSK9 inhibitor in terms of development in ADA incidence and titers, and consequences on the drug disposition, interaction with target, and downstream lowering effect on LDL-C.

Graphical Abstract
Wey Dey Move
Authors: Adeyemo Dele
Published: March 2024

Four contemporary thinkers from different disciplines and geographies come together around the theme of Borders, Human Itineraries, and All Our Relation. Architect, artist, and urban theorist Dele Adeyemo (UK/Nigeria) calls attention to the complexity of Black infrastructures, questioning how “the environments that surround us condition the possibility of our being.” Poet Natalie Diaz (US/Mojave/Akimel O’otham) writes, “Like story, migration is the sensual movement of knowledge,” and asks, “What is the language we need to live right now?” Philosopher Nadia Yala Kisukidi (France) suggests there is no diasporic life “without the dynamics of fabulation, where we pass down, from generation to generation, the stories of our ancestors who walked barefoot for many months.” And cultural theorist Rinaldo Walcott (Canada) asks us to consider inheritances beyond white supremacist logics, “What might it mean to live a life, if we can’t risk desiring and working towards utopia?” Braided together in this book, the essays speak to each other in multiple ways, creating a revealing vision of the world as it is, and as it could be.
Fusings
Authors: Diaz Natalie
Published: March 2024

Four contemporary thinkers from different disciplines and geographies come together around the theme of Borders, Human Itineraries, and All Our Relation. Architect, artist, and urban theorist Dele Adeyemo (UK/Nigeria) calls attention to the complexity of Black infrastructures, questioning how “the environments that surround us condition the possibility of our being.” Poet Natalie Diaz (US/Mojave/Akimel O’otham) writes, “Like story, migration is the sensual movement of knowledge,” and asks, “What is the language we need to live right now?” Philosopher Nadia Yala Kisukidi (France) suggests there is no diasporic life “without the dynamics of fabulation, where we pass down, from generation to generation, the stories of our ancestors who walked barefoot for many months.” And cultural theorist Rinaldo Walcott (Canada) asks us to consider inheritances beyond white supremacist logics, “What might it mean to live a life, if we can’t risk desiring and working towards utopia?” Braided together in this book, the essays speak to each other in multiple ways, creating a revealing vision of the world as it is, and as it could be.
Endoscopic Supracerebellar Infratentorial Transpineal Approach for Posterior-Medial Thalamic Lesions: Surgical Technique and Clinical Experience
Authors: Xie Tao , Liu Shuang , Zhang Xiaobiao , Yang Liangliang , Liu Tengfei , Chen Ping , Li Zeyang
Published: March 2024

BACKGROUND AND OBJECTIVES:

Accessing lesions in the posterior-medial thalamus can be challenging because of their deep location and intricate neurovascular anatomy. This study aims to describe the techniques and feasibility of the endoscopic supracerebellar infratentorial transpineal approach for treating posterior-medial thalamus lesions.

METHODS:

We reviewed and analyzed the clinical outcomes and endoscopic surgical experience of 11 patients with posterior-medial thalamic lesions. The first 4 cases used the endoscopic midline supracerebellar infratentorial transpineal approach, whereas the subsequent 7 cases used the endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach. All cases involved the upward transposition of the pineal gland to access the posterior-medial thalamus. The extent of resection and the endoscopic techniques were the main focus of analysis. Neurological examinations and MRI/computed tomography follow-up were conducted for 3–12 months after surgery.

RESULTS:

The pathology of the group included 6 gliomas, 1 cavernous malformation, 1 inflammation, 1 melanoma, and 2 hematomas. All 11 patients achieved gross total resection (6 patients, 54.5%) or subtotal resection (5 patients, 45.5%) with no new neurological deficits. Most patients (9 patients, 81.8%) experienced improvement in Karnofsky Performance Status after surgery. Postoperative hydrocephalus occurred in 2 patients (18.2%) and was relieved by endoscopic third ventriculostomy.

CONCLUSION:

The endoscopic supracerebellar infratentorial transpineal approach is an effective approach for removing posterior-medial thalamic lesions that require access through the third ventricle surfaces of the thalamus. The endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach provides a more superior and lateral view of the posterior-medial thalamic lesions.
Completely Minimally Invasive Implant Removal and Transforaminal Lumbar Interbody Fusion for Adjacent Segment Disease: Case Series and Operative Video
Authors: Kondapavulur Sravani , Scheer Justin K. , Safaee Michael M. , Clark Aaron J.
Published: March 2024

BACKGROUND AND OBJECTIVES:

Adjacent segment disease is a relatively common late complication after lumbar fusion. If symptomatic, certain patients require fusion of the degenerated adjacent segment. Currently, there are no posterior completely minimally invasive techniques described for fusion of the adjacent segment above or below a previous fusion. We describe here a novel minimally invasive technique for both implant removal (MIS-IR) and adjacent level transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar stenosis.

METHODS:

Demographic, surgical, and radiographic outcome data were collected for patients with lumbar stenosis and previous lumbar fusion, who were treated with MIS-IR and MIS-TLIF through the same incision. Radiographic outcomes were assessed postoperatively and complications were assessed at the primary end point of 3 months.

RESULTS:

A total of 14 patients (7 female and 7 male), with average age 64.6 years (SD 13.4), were included in this case series. Nine patients had single-level MIS-IR with single-level MIS-TLIF. Three patients had 2-level MIS-IR with single-level MIS-TLIF. Two patients had single-level MIS-IR with 2-level MIS-TLIF. Only 1 patient had a postoperative complication—hematoma requiring same-day evacuation. There were no other complications at the primary end point and no fusion failure at the hardware removal levels to date (average follow-up, 11 months). Average increases in posterior disk height and foraminal height after MIS-TLIF were 4.44, and 2.18 mm, respectively.

CONCLUSION:

Minimally invasive spinal IR can be successfully completed along with adjacent level TLIF through the same incisions, via an all-posterior approach.
The Monetarists: The Making of the Chicago Monetary Tradition, 1927–1960
Authors: Binder Carola
Published: March 2024

Carola Binder of Haverford College reviews “The Monetarists: The Making of the Chicago Monetary Tradition, 1927–1960” by George S. Tavlas. The Econlit abstract of this book begins: “Considers the emergence and development of the Chicago monetary tradition into what became known as monetarism, describing it as it was reflected in the works of a small group of University of Chicago economists who preserved the importance of the quantity theory of money and defended the free-market system.”
The Problem of Twelve: When a Few Financial Institutions Control Everything
Authors: Posner Eric A.
Published: March 2024

Eric A. Posner of University of Chicago reviews “The Problem of Twelve: When a Few Financial Institutions Control Everything” by John Coates. The Econlit abstract of this book begins: “Explores issues that arise when a small number of actors acquire the means to exert outsized influence over the politics and economy of a nation, focusing in particular on the two late-twentieth-century institutions of index funds and private equity funds.”
What Universities Owe Democracy
Authors: Pelton M. Lee
Published: March 2024

M. Lee Pelton of The Boston Foundation reviews “What Universities Owe Democracy” by By Ronald J. Daniels. The Econlit abstract of this book begins: “Promotes the argument that colleges and universities are essential to the flourishing of liberal democracy, suggesting that these institutions have a responsibility to act in defense of the liberal democratic experiment.”
In vivo and in vitro color evaluation of clear thermoplastic retainers
Authors: Ζαφειριάδης Αναστάσιος
Published: March 2024

ΣΚΟΠΟΣ: Να εκτιμηθεί η in vitro επίδραση διαφορετικών διαλυμάτων χρώσης στο χρώμα των ναρθήκων Vivera® και η in vivo μεταβολή του χρώματος δύο διαφορετικών θερμοπλαστικών ναρθήκων συγκράτησης, Vivera® και Essix® C+. ΥΛΙΚΑ ΚΑΙ ΜΕΘΟΔΟΙ: Τριάντα ασθενείς μετά από ορθοδοντική θεραπεία τυχαιοποιήθηκαν σε δύο ομάδες και έλαβαν συγκρατητικούς νάρθηκες Vivera® και Essix® C+, αντίστοιχα. Τριάντα δείγματα υλικού Vivera® αποδόθηκαν σε πέντε ομάδες και βυθίστηκαν σε διαφορετικά χρωστικά διαλύματα. Για κάθε ένα από τα δείγματα μετρήθηκαν οι παράμετροι χρώματος CIE (L*, a*, b*) in vivo με φασματοφωτόμετρο SpectroShade™ Micro μετά από έως και 3 μήνες ενδοστοματικής χρήσης και in vitro με φασματοφωτόμετρο ορατού-υπεριώδους μετά από έως και μία εβδομάδα εμβάπτισης σε διάλυμα. Υπολογίστηκαν οι διαφορές χρώματος (ΔΕ) μεταξύ των ομάδων. Έγινε ανάλυση ANOVA του στατιστικού δείγματος και συγκρίσεις με τη μέθοδο Bonferroni με επίπεδο στατιστικής σημαντικότητας p < 0,05. ΑΠΟΤΕΛΕΣΜΑΤΑ: Δεν παρατηρήθηκαν in vivo σημαντικές διαφορές στη μεταβολή του χρώματος μεταξύ Vivera® και Essix® C+ στις μεταβολές ΔΕ. Βρέθηκαν σημαντικές διαφορές για τα δείγματα που εμβαπτίστηκαν in vitro σε καφέ, τσάι και κόκκινο κρασί. ΣΥΜΠΕΡΑΣΜΑΤΑ: Οι νάρθηκες Vivera® και Essix® C+ παρουσίασαν παρόμοιες μεταβολές χρώματος μετά από στοματική χρήση τριμήνου. Οι νάρθηκες Vivera® εμφάνισαν ορατές μεταβολές που προκλήθηκαν από καφέ, τσάι και κόκκινο κρασί. Όλες οι διαφορές που παρατηρήθηκαν θεωρήθηκαν κλινικά αποδεκτές (ΔΕ<3,7).
Understanding the determinants of the gender gap in physical activity and sports participation among young adults: a mixed-methods study
Authors: Cummins Hannah , Byrne Molly
Published: March 2024

Background An underexplored gender gap in physical activity (PA) and sport participation (SP) exists in those aged 18–24 in Ireland, with females less active than males. This research explored the determinants of PA and SP in both males and females through the lens of the Capability-Opportunity-Motivation-Behaviour (COM-B) model and the Theoretical Domains Framework (TDF), to enhance our understanding of the gender gap. A mixed methods design was employed involving (1) a quantitative secondary analysis of existing data from the Irish Sports Monitor (ISM) 2019, an evaluation of Irish SP and PA conducted biennially by Sport Ireland, the governing body for sport development in the country, and (2) qualitative semi-structured interviews to explore determinants of PA and SP, using a framework analysis approach. Methods A secondary analysis of existing ISM 2019 data from 158 individuals was conducted to explore gender differences in PA and SP behaviours in relation to capability, opportunity, and motivation. To further explore these differences, individuals (n = 16, 75% female) aged 18–24 were then invited to take part in semi-structured interviews to better understand determinants of their PA and SP behaviours and explore their experiences of the gender gap. Results Despite the gender gap identified through the ISM 2019, a secondary analysis found no significant difference between genders on predictors of PA and SP based on overall COM-B scores. However, semi-structured interviews suggested gender differences regarding self-reported determinants of PA and SP, particularly within the domain of social influence. Conclusions Social influence may be an important factor to target, particularly in relation to perceived support and encouragement, to increase female engagement in PA and SP. More research is required to explore this potentiality.