bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiarmed DNA jumper and metal-organic frameworks–functionalized paper-based bioplatform for small extracellular vesicle–derived miRNAs assay
Authors: Qiu Xiaopei , Yang Huisi , Shen Man , Xu Hanqing , Wang Yingran , Liu Shuai , Liu Qian , Sun Minghui , Ding Zishan , Zhang Ligai , Wang Jun , Liang Taotao , Luo Dan , Gao Mingxuan , Chen Ming , Bao Jing
Published: May 2024

Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.
Development and validation of a model for predicting upstage in minimally invasive lung adenocarcinoma in Chinese people
Authors: Liao Yida , Li Zhixin , Song Linhong , Xue Yang , Chen Xiangru , Feng Gang
Published: May 2024

Background

Sublobar resection for ground-glass opacity became a recommend surgery choice supported by the JCOG0804/JCOG0802/JCOG1211 results. Sublobar resection includes segmentectomy and wedge resection, wedge resection is suitable for non-invasive lesions, but in clinical practice, when pathologists are uncertain about the intraoperative frozen diagnosis of invasive lesions, difficulty in choosing the appropriate operation occurs. The purpose of this study was to analyze how to select invasive lesions with clinic-pathological characters.

Methods

A retrospective study was conducted on 134 cases of pulmonary nodules diagnosed with minimally invasive adenocarcinoma by intraoperative freezing examination. The patients were divided into two groups according to intraoperative frozen results: the minimally invasive adenocarcinoma group and the at least minimally invasive adenocarcinoma group. A variety of clinical features were collected. Chi-square tests and multiple regression logistic analysis were used to screen out independent risk factors related to pathological upstage, and then ROC curves were established. In addition, an independent validation set included 1164 cases was collected.

Results

Independent risk factors related to pathological upstage were CT value, maximum tumor diameter, and frozen result of AL-MIA. The AUC of diagnostic mode was 71.1% [95%CI: 60.8-81.3%]. The independent validation included 1164 patients, 417 (35.8%) patients had paraffin-based pathology of invasive adenocarcinoma. The AUC of diagnostic mode was 75.7% [95%CI: 72.9-78.4%].

Conclusions

The intraoperative frozen diagnosis was AL-MIA, maximum tumor diameter larger than 15 mm and CT value is more than − 450Hu, highly suggesting that the lung GGO was invasive adenocarcinoma which represent a higher risk to recurrence. For these patients, sublobectomy would be insufficient, lobectomy or complementary treatment is encouraged.
Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances
Authors: Guan Yuxuan , Li Fuzhen , Li Na , Yang Peizeng
Published: May 2024

Behcet’s disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet’s uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.
White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis
Authors: Wei Yi-Chia , Kung Yi-Chia , Lin Ching-Po , Chen Chih-Ken , Lin Chemin , Tseng Rung-Yu , Chen Yao-Liang , Huang Wen-Yi , Chen Pin-Yuan , Chong Shin-Tai , Shyu Yu-Chiau , Chang Wei-Chou , Yeh Chun-Hung
Published: May 2024

Background

Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD.

Methods

Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018–2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments.

Results

The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aβ42 level (r = −0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019).

The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05).

Conclusion

Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aβ42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.
An-Gong-Niu-Huang-Wan (AGNHW) regulates cerebral blood flow by improving hypoperfusion, cerebrovascular reactivity and microcirculation disturbances after stroke
Authors: Zhang Xiao , Pei Jiamin , Xue Luping , Zhao Zhe , Xu Renhao , Zhang Cong , Zhang Cong , Fu Lijie , Zhang Xiangjian , Cui Lili
Published: May 2024

Background

The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved.

Methods

Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels.

Results

AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP.

Conclusions

AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.
Comparing the effects of contact duration on cow and calf performance beyond separation - a prospective cohort study
Authors: Sørby Johanne , Holmøy Ingrid Hunter , Nødtvedt Ane , Ferneborg Sabine , Johnsen Julie Føske
Published: May 2024

Background

Consumers, the industry, and many farmers have shown increased interest in alternative management systems that allow for cow-calf contact (CCC) and this topic has become an important focus of research for a sustainable dairy industry. Among the many knowledge gaps still existing in this novel research field, there is a need for further research to investigate effects of CCC beyond the nursing period (i.e., after cow-calf separation). Moreover, multi-herd observational studies are scarce. Therefore, the aim of this study was to investigate the within-herd effect of CCC on machine milk yield and calf growth beyond separation. In this prospective cohort study, we studied all cows and their calves (Norwegian Red breed) born between September 1st 2021 and January 31th 2022 at three Norwegian dairy farms, investigating the impact of CCC on machine milk yield and calf average daily gain (ADG) after separation of the cow-calf pair. The follow-up period was 305 d for cows and six months for calves. Machine milk yield was automatically registered at each milking and calf heart girth was measured once a month. As various contact durations emerged, they were categorized into three groups: no contact (NC 0–3 d), short duration (4–30 d) and long duration (> 30 d). Data were analyzed with linear mixed models with the individual animal as the unit of interest. For cows, days in milk (DIM) from date of separation up to 305 DIM were included in the analysis as a continuous variable. For calves, age up to 195 d was used in the statistical analysis.

Results

We found no differences in machine milk yield after separation across the different contact groups: cows with no contact (n = 28), short duration (n = 51) and long duration (n = 27) of contact, all exhibited comparable milk yields from the time of separation until the end of lactation. Furthermore, in the case of calves, no disparities in average daily gain (ADG) were identified for any of the contact groups: calves with no contact (n = 39), short duration (n = 61) and long duration (n = 38) of contact, displayed comparable growth during the first six months of life.

Conclusions

Our findings indicate no negative effects of CCC on machine milk yield after separation, nor any sustained effects on calf growth under the conditions of this study. More multi-herd observational studies conducted on-farm is needed to expand the understanding of effects of CCC on cow and calf performance after separation.
The clinical relevance of fixation failure after pubic symphysis plating for anterior pelvic ring injuries: an observational cohort study with long-term follow-up
Authors: Notov Dmitry , Knorr Eva , Spiegl Ulrich J.A. , Osterhoff Georg , Höch Andreas , Kleber Christian , Pieroh Philipp
Published: May 2024

Background

Open reduction and plate fixation is a standard procedure for treating traumatic symphyseal disruptions, but has a high incidence of implant failure. Several studies have attempted to identify predictors for implant failure and discussed its impact on functional outcome presenting conflicting results. Therefore, this study aimed to identify predictors of implant failure and to investigate the impact of implant failure on pain and functional outcome.

Methods

In a single-center, retrospective, observational non-controlled cohort study in a level-1 trauma center from January 1, 2006, to December 31, 2017, 42 patients with a plate fixation of a traumatic symphyseal disruption aged ≥ 18 years with a minimum follow-up of 12 months were included. The following parameters were examined in terms of effect on occurrence of implant failure: age, body mass index (BMI), injury severity score (ISS), polytrauma, time to definitive treatment, postoperative weight-bearing, the occurrence of a surgical site infection, fracture severity, type of posterior injury, anterior and posterior fixation. A total of 25/42 patients consented to attend the follow- up examination, where pain was assessed using the Numerical Rating Scale and functional outcome using the Majeed Pelvic Score.

Results

Sixteen patients had an anterior implant failure (16/42; 37%). None of the parameters studied were predictive for implant failure. The median follow-up time was six years and 8/25 patients had implant failure. There was no difference in the Numerical Rating Scale, but the work-adjusted Majeed Pelvic Score showed a better outcome for patients with implant failure.

Conclusion

implant failure after symphyseal disruptions is not predictable, but appears to be clinically irrelevant. Therefore, an additional sacroiliac screw to prevent implant failure should be critically discussed and plate removal should be avoided in asymptomatic patients.
Broad proteomics analysis of seeding-induced aggregation of α-synuclein in M83 neurons reveals remodeling of proteostasis mechanisms that might contribute to Parkinson’s disease pathogenesis
Authors: Lumpkin Casey J. , Patel Hiral , Potts Gregory K. , Chaurasia Shilpi , Gibilisco Lauren , Srivastava Gyan P. , Lee Janice Y. , Brown Nathan J. , Amarante Patricia , Williams Jon D. , Karran Eric , Townsend Matthew , Woods Dori , Ravikumar Brinda
Published: May 2024

Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson’s disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD. We identified gross changes in the proteome that coincided with the formation of large Lewy body-like α-syn aggregates in these neurons. We used protein-protein interaction (PPI)-based network analysis to identify key protein clusters modulating specific biological pathways that may be dysregulated and identified several mechanisms that regulate protein homeostasis (proteostasis). The observed changes in the proteome may include both homeostatic compensation and dysregulation due to α-syn aggregation and a greater understanding of both processes and their role in α-syn-related proteostasis may lead to improved therapeutic options for patients with PD and related disorders.
Examining the oleoylethanolamide supplement effects on glycemic status, oxidative stress, inflammation, and anti-mullerian hormone in polycystic ovary syndrome
Authors: Shivyari Fatemeh Taghizadeh , Pakniat Hamideh , Nooshabadi Mohamadreza Rashidi , Rostami Shaghayegh , Haghighian Hossein Khadem , Shiri-Shahsavari Mohammad Reza
Published: May 2024

Objective

This clinical trial was designed and conducted due to the anti-inflammatory potential of Oleoylethanolamide (OEA) to examine the effect of OEA supplement on glycemic status, oxidative stress, inflammatory factors, and anti-Mullerian hormone (AMH) in women with polycystic ovary syndrome (PCOS).

Method

This study was a randomized clinical trial, double-blinded, placebo-controlled that was carried out on 90 women with PCOS. Patients were divided into two groups: receiving an OEA supplement (n = 45) or a placebo (n = 45). The intervention group received 125 mg/day OEA and the placebo group received the wheat flour for 8 weeks. Demographic data were collected through questionnaires. Fasting blood sugar (FBS), insulin resistance (IR), total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and AMH were measured before and after the study.

Results

Data analysis of food recall and physical activity questionnaires, showed no significant differences between the two groups (p > 0.05). Biochemical factors including glycemic status, MDA, inflammatory factors, and AMH decreased significantly (p < 0.05). TAC increased remarkably (p < 0.05) in comparison between the two groups, after the intervention.

Conclusion

OEA supplement with anti-inflammatory characteristics could be efficient independent of diet changes and physical activity in improving disrupted biochemical factors, so both supplementation or food resources of this fatty acid could be considered as a compensatory remedy in patients with PCOS.

Trial Registration

This study was retrospectively (09-01-2022) registered in the Iranian website (www.irct.ir) for registration of clinical trials (IRCT20141025019669N20).
The impact of elder abuse training on subacute health providers and older adults: study protocol for a randomized control trial
Authors: Cavuoto Marina G. , Markusevska Simona , Stevens Catriona , Reyes Patricia , Renshaw Gianna , Peters Micah D. J. , Dow Briony , Feldman Peter , Gilbert Andrew , Manias Elizabeth , Mortimer Duncan , Enticott Joanne , Cooper Claudia , Antoniades Josefine , Appleton Brenda , Nakrem Sigrid , O’Brien Meghan , Ostaszkiewicz Joan , Eckert Marion , Durston Cheryl , Brijnath Bianca
Published: May 2024

Background

Elder abuse often goes unreported and undetected. Older people may be ashamed, fearful, or otherwise reticent to disclose abuse, and many health providers are not confident in asking about it. In the No More Shame study, we will evaluate a co-designed, multi-component intervention that aims to improve health providers’ recognition, response, and referral of elder abuse.

Methods

This is a single-blinded, pragmatic, cluster randomised controlled trial. Ten subacute hospital sites (i.e. clusters) across Australia will be allocated 1:1, stratified by state to a multi-component intervention comprising a training programme for health providers, implementation of a screening tool and use of site champions, or no additional training or support. Outcomes will be collected at baseline, 4 and 9 months. Our co-primary outcomes are change in health providers’ knowledge of responding to elder abuse and older people’s sense of safety and quality of life. We will include all inpatients at participating sites, aged 65 + (or aged 50 + if Aboriginal or Torres Strait Islander), who are able to provide informed consent and all unit staff who provide direct care to older people; a sample size of at least 92 health providers and 612 older people will provide sufficient power for primary analyses.

Discussion

This will be one of the first trials in the world to evaluate a multi-component elder abuse intervention. If successful, it will provide the most robust evidence base to date for health providers to draw on to create a safe environment for reporting, response, and referral.

Trial registration

ANZCTR, ACTRN12623000676617p. Registered 22 June 2023.
Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans
Authors: Lin Long , Andersen Mette K. , Stæger Frederik Filip , Li Zilong , Hanghøj Kristian , Linneberg Allan , Grarup Niels , Jørgensen Marit Eika , Hansen Torben , Moltke Ida , Albrechtsen Anders
Published: May 2024

Background

Disease prevalence and mean phenotype values differ between many populations, including Inuit and Europeans. Whether these differences are partly explained by genetic differences or solely due to differences in environmental exposures is still unknown, because estimates of the genetic contribution to these means, which we will here refer to as mean genotypic values, are easily confounded, and because studies across genetically diverse populations are lacking.

Methods

Leveraging the unique genetic properties of the small, admixed and historically isolated Greenlandic population, we estimated the differences in mean genotypic value between Inuit and European genetic ancestry using an admixed sibling design. Analyses were performed across 26 metabolic phenotypes, in 1474 admixed sibling pairs present in a cohort of 5996 Greenlanders.

Results

After FDR correction for multiple testing, we found significantly lower mean genotypic values in Inuit genetic ancestry compared to European genetic ancestry for body weight (effect size per percentage of Inuit genetic ancestry (se), −0.51 (0.16) kg/%), body mass index (−0.20 (0.06) kg/m2/%), fat percentage (−0.38 (0.13) %/%), waist circumference (−0.42 (0.16) cm/%), hip circumference (−0.38 (0.11) cm/%) and fasting serum insulin levels (−1.07 (0.51) pmol/l/%). The direction of the effects was consistent with the observed mean phenotype differences between Inuit and European genetic ancestry. No difference in mean genotypic value was observed for height, markers of glucose homeostasis, or circulating lipid levels.

Conclusions

We show that mean genotypic values for some metabolic phenotypes differ between two human populations using a method not easily confounded by possible differences in environmental exposures. Our study illustrates the importance of performing genetic studies in diverse populations.
Dystrophic calcinosis: structural and morphological composition, and evaluation of ethylenediaminetetraacetic acid (‘EDTA’) for potential local treatment
Authors: Lee Phillip , Green Lorraine , Marzec Bartosz , Meldrum Fiona , Del Galdo Francesco , Alcacer-Pitarch Begonya
Published: May 2024

Background

To perform a detailed morphological analysis of the inorganic portion of two different clinical presentations of calcium-based deposits retrieved from subjects with SSc and identify a chemical dissolution of these deposits suitable for clinical use.

Methods

Chemical analysis using Fourier Transform IR spectroscopy (‘FTIR’), Raman microscopy, Powder X-Ray Diffraction (‘PXRD’), and Transmission Electron Microscopy (‘TEM’) was undertaken of two distinct types of calcinosis deposits: paste and stone. Calcinosis sample titration with ethylenediaminetetraacetic acid (‘EDTA’) assessed the concentration at which the EDTA dissolved the calcinosis deposits in vitro.

Results

FTIR spectra of the samples displayed peaks characteristic of hydroxyapatite, where signals attributable to the phosphate and carbonate ions were all identified. Polymorph characterization using Raman spectra were identical to a hydroxyapatite reference while the PXRD and electron diffraction patterns conclusively identified the mineral present as hydroxyapatite. TEM analysis showed differences of morphology between the samples. Rounded particles from stone samples were up to a few micron in size, while needle-like crystals from paste samples reached up to 0.5 µm in length.

Calcium phosphate deposits were effectively dissolved with 3% aqueous solutions of EDTA, in vitro. Complete dissolution of both types of deposit was achieved in approximately 30 min using a molar ratio of EDTA/HAp of ≈ 300.

Conclusions

Stone and paste calcium-based deposits both comprise hydroxyapatite, but the constituent crystals vary in size and morphology. Hydroxyapatite is the only crystalline polymorph present in the SSc-related calcinosis deposits. Hydroxyapatite can be dissolved in vitro using a dosage of EDTA considered safe for clinical application. Further research is required to establish the optimal medium to develop the medical product, determine the protocol for clinical application, and to assess the effectiveness of EDTA for local treatment of dystrophic calcinosis.
Social epidemiology of online dating in U.S. early adolescents
Authors: Nagata Jason M. , Balasubramanian Priyadharshini , Shim Joan E. , Talebloo Jonanne , Yen Felicia , Al-shoaibi Abubakr A.A. , Shao Iris Yuefan , Ganson Kyle T. , Testa Alexander , Kiss Orsolya , Baker Fiona C.
Published: May 2024

Objective

To investigate the prevalence and sociodemographic associations of online dating in a demographically diverse U.S. national cohort of early adolescents.

Methods

We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018–2020, ages 11–12;N = 10,157). Multivariable logistic regression analyses were employed to estimate associations between sociodemographic factors (e.g., age, sex, race/ethnicity, sexual orientation, household income, parental education) and early adolescent-reported online dating behaviors.

Results

Overall, 0.4% (n = 38) of participants reported ever using a dating app. Males (AOR 2.72, 95% CI 1.11–6.78) had higher odds of online dating compared to females, and sexual minority identification (e.g., lesbian, gay, or bisexual; AOR 12.97, 95% CI 4.32–38.96) was associated with greater odds of online dating compared to heterosexual identification.

Conclusion

Given the occurrence of online dating among early adolescents despite age restrictions, interventions might address age misrepresentation. Adolescent sexual health education may consider incorporating anticipatory guidance on online dating, especially for males and sexual minorities. Future research could further investigate online dating patterns from early to late adolescence and associated health effects.
A comparison of oral bacteriome isolated from periodontal pockets of participants with or without diabetes mellitus in Uganda: a case control study
Authors: Kiryowa Haruna Muhmood , Buwembo William , Munabi Ian Guyton , Mwaka Erisa Sabakaki , Rwenyonyi Charles Mugisha , Kaddumukasa Mark , Kiguli Sarah
Published: May 2024

Objective

Diabetes mellitus predisposes patients to increased incidence and severe forms of periodontal disease. Currently, information on the bacterial diversity of patients with diabetes mellitus and periodontitis in Uganda is scanty. This study set out to describe the bacteria associated with periodontitis in patients with diabetes mellitus in Uganda, as part of a larger study describing the association between periodontal disease and diabetes mellitus.

Results

This was a case control involving 45 samples of gingival crevicular fluid collected from participants with periodontitis, the cases being 26 participants with diabetes mellitus and controls 19 participants without diabetes mellitus. Sequencing using the 16s Oxford nanopore long read protocol was followed by a bioinformatics analysis pipeline for alpha and beta diversity indices in the two groups. Multivariate tests were done to determine the differences in the bacterial composition in the two groups. Of the 739 Operational Taxonomic Units and 500 phyla identified, 37.9% (280/739) were from participants with diabetes mellitus. Analysis of beta diversity revealed a dissimilarity between the two study groups (CAP score = 0) with a significant association noted between periodontitis and the subgingival bacteria (P = 0.001). Diabetes mellitus reduced the quantity and altered the composition of the subgingival microbiome in the study participants.
Employment of diverse in vitro systems for analyzing multiple aspects of disease, hereditary hemorrhagic telangiectasia (HHT)
Authors: Koh Hyebin , Kang Woojoo , Mao Ying-Ying , Park Jisoo , Kim Sangjune , Hong Seok-Ho , Lee Jong-Hee
Published: May 2024

Background

In vitro disease modeling enables translational research by providing insight into disease pathophysiology and molecular mechanisms, leading to the development of novel therapeutics. Nevertheless, in vitro systems have limitations for recapitulating the complexity of tissues, and a single model system is insufficient to gain a comprehensive understanding of a disease.

Results

Here we explored the potential of using several models in combination to provide mechanistic insight into hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder. Genome editing was performed to establish hPSCs (H9) with ENG haploinsufficiency and several in vitro models were used to recapitulate the functional aspects of the cells that constitute blood vessels. In a 2D culture system, endothelial cells showed early senescence, reduced viability, and heightened susceptibility to apoptotic insults, and smooth muscle cells (SMCs) exhibited similar behavior to their wild-type counterparts. Features of HHT were evident in 3D blood-vessel organoid systems, including thickening of capillary structures, decreased interaction between ECs and surrounding SMCs, and reduced cell viability. Features of ENG haploinsufficiency were observed in arterial and venous EC subtypes, with arterial ECs showing significant impairments. Molecular biological approaches confirmed the significant downregulation of Notch signaling in HHT-ECs.

Conclusions

Overall, we demonstrated refined research strategies to enhance our comprehension of HHT, providing valuable insights for pathogenic analysis and the exploration of innovative therapeutic interventions. Additionally, these results underscore the importance of employing diverse in vitro systems to assess multiple aspects of disease, which is challenging using a single in vitro system.
Reverse triggering ? a novel or previously missed phenomenon?
Authors: Jackson Robert , Kim Audery , Moroz Nikolay , Damiani L. Felipe , Grieco Domenico Luca , Piraino Thomas , Friedrich Jan O. , Mercat Alain , Telias Irene , Brochard Laurent J.
Published: May 2024

Background

Reverse triggering (RT) was described in 2013 as a form of patient-ventilator asynchrony, where patient’s respiratory effort follows mechanical insufflation. Diagnosis requires esophageal pressure (Pes) or diaphragmatic electrical activity (EAdi), but RT can also be diagnosed using standard ventilator waveforms.

Hypothesis

We wondered (1) how frequently RT would be present but undetected in the figures from literature, especially before 2013; (2) whether it would be more prevalent in the era of small tidal volumes after 2000.

Methods

We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from 1950 to 2017, with key words related to asynchrony to identify papers with figures including ventilator waveforms expected to display RT if present. Experts labelled waveforms. ‘Definite’ RT was identified when Pes or EAdi were in the tracing, and ‘possible’ RT when only flow and pressure waveforms were present. Expert assessment was compared to the author’s descriptions of waveforms.

Results

We found 65 appropriate papers published from 1977 to now, containing 181 ventilator waveforms. 21 cases of ‘possible’ RT and 25 cases of ‘definite’ RT were identified by the experts. 18.8% of waveforms prior to 2013 had evidence of RT. Most cases were published after 2000 (1 before vs. 45 after, p = 0.03). 54% of RT cases were attributed to different phenomena. A few cases of identified RT were already described prior to 2013 using different terminology (earliest in 1997). While RT cases attributed to different phenomena decreased after 2013, 60% of ‘possible’ RT remained missed.

Conclusion

RT has been present in the literature as early as 1997, but most cases were found after the introduction of low tidal volume ventilation in 2000. Following 2013, the number of undetected cases decreased, but RT are still commonly missed.

Prior Abstract

Reverse Triggering, A Missed Phenomenon in the Literature. Critical Care Canada Forum 2019 Abstracts. Can J Anesth/J Can Anesth 67 (Suppl 1), 1–162 (2020). https://doi-org.myaccess.library.utoronto.ca/https://doi.org/10.1007/s12630-019-01552-z.
Environmental drivers of tree species richness in the southernmost portion of the Paranaense forests
Authors: Toranza Carolina , Martínez-Lanfranco Juan Andrés , Haretche Federico , Brazeiro Alejandro
Published: May 2024

Background

The Rio de la Plata grassland region is dominated by temperate grasslands, with the scarce natural forests, influenced floristically by adjacent biogeographical provinces. Uruguay represents the southern limit for many tree species of the Paranaense Province, several of which inhabit the hillside forests. With many species shifting poleward due to climate change, we do not yet know how current environmental factors, particularly climatic ones, are linked to the tree diversity of this flora nowadays. The aim of this study is to understand the geographic pattern of tree richness in the hillside forests of Uruguay, evaluating the water–energy and the environmental heterogeneity hypotheses. The distribution of the hillside forest trees was obtained by compiling and updating the herbaria database and distribution maps of woody plants of Uruguay. The presence/absence of each species, and then the species richness, were georeferenced over a grid that covers Uruguay with 302 cells (660 km2). Over the same grid were compiled environmental variables associated with climate and environmental heterogeneity. The relationship between richness and environmental variables was studied by applying general linear models (GLM). As a strong autocorrelation was detected, a residuals auto-covariate term was incorporated into the GLM, to take into account the species richness spatial structure.

Results

The tree flora of the hillside forest was composed mainly by Paranaense species that show a latitudinal gradient, with two high richness cores, in the east and northeast of Uruguay. The final model including the environmental variables and the spatial term explained 84% of the variability of tree richness. Species richness showed a positive relationship with precipitation, forest cover, potential evapotranspiration and productivity, while a negative effect of temperature variation was found. The spatial component was the primary predictor, accounting for a 30% of spatial pattern of tree richness.

Conclusions

This study accounts for a large proportion of the environmental and spatial variations of the tree richness pattern of the Paranense flora in its southernmost portion. It brings support to both water–energy and environmental heterogeneity hypotheses, emphasizing the role of climate and its variation and the habitat availability on the hillside forest diversity.
Exploring the medicinal potential of Senna siamea roots: an integrated study of antibacterial and antioxidant activities, phytochemical analysis, ADMET profiling, and molecular docking insights
Authors: Gebrehiwot Hadush , Ensermu Urgessa , Dekebo Aman , Endale Milkyas , Hunsen Mo
Published: May 2024

Nowadays, infectious diseases pose an alarming global threat to human health. The genus Senna is among the most well-known taxonomic categories commonly used in folk medicine to confront these challenges. Motivated by its traditional uses, a comprehensive study was conducted on the roots extract of Senna siamea, aiming to address the in vitro antibacterial and antioxidant efficacy of phytochemicals from the dichloromethane: methanol (1:1) roots extract of the plant, along with in silico computational studies. The separation of compounds was achieved using silica gel column chromatography. Whereas, the antibacterial and antioxidant activities were examined using paper disc diffusion and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays, respectively. Silica gel column chromatography of the dichloromethane: methanol (1:1) roots extract afforded lupeol (1), β-sitosterol (2a) and stigmasterol (2b), chrysophanol (3), betulinic acid (4), and glyceryl-1-hexacosanoate (5). Although these compounds have been previously reported from the plant, proof of their medicinal applications via in vitro and in silico studies is still lacking. Notably, our findings showed remarkable inhibition zones by the extract (18.00 ± 0.00 mm and 17.17 ± 0.24 mm) against E. coli and S. aureus, respectively, at 50 mg/mL compared to ciprofloxacin (23.33 ± 0.47 mm and 22.00 ± 0.00 mm, respectively), showcasing its potential antibacterial efficiency. Considerable inhibition zones were also recorded by chrysophanol (3) against E. coli (16.33 ± 0.24 mm) and S. pyogenes (16.00 ± 0.00 mm) at 2 mg/mL, compared to ciprofloxacin which showed 23.33 ± 0.47 mm and 21.67 ± 0.47 mm, respectively, signifying its potent antibacterial activities. In addition, the crude extract and chrysophanol (3) exhibited substantial IC50 values (1.24 and 1.71 µg/mL, respectively), suggesting their significant antioxidant potential compared to that of ascorbic acid (IC50: 0.53 µg/mL). Chrysophanol (3) fulfilled Lipinski’s rule with no violation and lupeol (1), β-sitosterol (2a), stigmasterol (2b), betulinic acid (4), and glyceryl-1-hexacosanoate (5) displayed one violation each which were in favor of the drug-likeness predictions. All the compounds exhibited no cytotoxicity and except betulinic acid (4), all the compounds also showed no carcinogenicity properties which were consistent with the prediction results of ciprofloxacin. The molecular docking computations revealed that all the compound isolates displayed strong and nearly strong binding affinities against all protein targets, ranging from − 6.6 kcal/mol to -9.2 kcal/mol (lupeol (1) against E. coli DNA gyrase B and topoisomerase II α, respectively). Thus, the present findings suggest the roots of Senna siamea for potential medicinal applications against multi-drug resistant pathogens hence validating its ethno-medicinal uses.
Transfemoral hepatic vein catheterization reduces procedure time in double vein embolization
Authors: Steffen Dominik A. , Najafi Arash , Binkert Christoph A.
Published: May 2024

Background

Double vein embolization with simultaneous embolization of the portal and hepatic vein aims to grow the future liver remnant in preparation for major hepatectomy. Transvenous hepatic vein embolization is usually done via a transjugular access. The purpose of this study is to describe the transfemoral approach as an alternative option and to discuss potential advantages.

Results

Twenty-three patients undergoing hepatic vein embolization via a transjugular (n = 10) or transfemoral access (n = 13) were evaluated retrospectively. In all cases the portal vein embolization was done first. All procedures were technically successful. There were no peri-interventional complications. Only two patients were not able to proceed to surgery. Standardized future liver remnant hypertrophy was non-inferior with the transfemoral approach compared to the transjugular route. Procedure time was significantly shorter in the transfemoral access group (40 ± 13 min) compared to the transjugular group (67 ± 13 min, p < 0.001).

Conclusion

Transfemoral hepatic vein embolization is feasible, safe, and faster due to easier catheterization, improved stability, and simpler patient preparation. These findings will need to be validated in larger studies.
Effects of environmental factors and storage periods on sesame seed quality and longevity
Authors: Gebregergis Zenawi , Baraki Fiseha , Fiseseha Dawit
Published: May 2024

Sesame is one of the world’s oldest oil seed crops grown mainly for its seeds. Lengthened storage time, inappropriate staking, back warded threshing method and poor storage facilities are major causes for postharvest and quality losses of sesame seed. Therefore, the objective was to review the effect of storage time and storage conditions on sesame seed quality and longevity. Seed quality and longevity are mostly governed by moisture content, temperature, humidity, storage period, pre-storage conditions, and pest infestations. Moisture content is a pre-requisite for long-term seed storage, and is the most important factor affecting seed longevity. Sesame seeds remain consistent and viable up to 12 months under appropriate storage facilities and conditions, otherwise it get lessened its viability. The crop should be harvested at the appropriate time and seeds should be stored at 6% or lower moisture content. In the tropics where temperature is as high as 33 °C and relative humidity of about 80%, seeds deteriorate rapidly. Varietal mixtures and harvest conditions affect longevity of seeds in storage. Pests such as, Mites, Indian mealy moth, Weevils, Flour beetles, are serious problems in stored sesame seeds. Under low seed moisture content and temperature, insects may not be a problem. Oil seeds require high-quality constructions to prevent leakages and to allow easy access to the bin for sampling and monitoring. Therefore, sesame seeds should be stored in well-constructed room/ware house to maintain seed viability and longevity.
CsWRKY11 cooperates with CsNPR1 to regulate SA-triggered leaf de-greening and reactive oxygen species burst in cucumber
Authors: Zhang Dingyu , Zhu Ziwei , Yang Bing , Li Xiaofeng , Zhang Hongmei , Zhu Hongfang
Published: May 2024

Salicylic acid (SA) is a multi-functional phytohormone, regulating diverse processes of plant growth and development, especially triggering plant immune responses and initiating leaf senescence. However, the early SA signaling events remain elusive in most plant species apart from Arabidopsis, and even less is known about the multi-facet mechanism underlying SA-regulated processes. Here, we report the identification of a novel regulatory module in cucumber, CsNPR1-CsWRKY11, which mediates the regulation of SA-promoted leaf senescence and ROS burst. Our analyses demonstrate that under SA treatment, CsNPR1 recruits CsWRKY11 to bind to the promoter of CsWRKY11 to activate its expression, thus amplifying the primary SA signal. Then, CsWRKY11 cooperates with CsNPR1 to directly regulate the expression of both chlorophyll degradation and ROS biosynthesis related genes, thereby inducing leaf de-greening and ROS burst. Our study provides a solid line of evidence that CsNPR1 and CsWRKY11 constitute a key module in SA signaling pathway in cucumber, and gains an insight into the interconnected regulation of SA-triggered processes.
Renal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances
Authors: Salgia Nicholas J. , Zengin Zeynep B. , Pal Sumanta K. , Dizman Nazli
Published: May 2024

Renal cell carcinoma (RCC) is one of the 10 most commonly diagnosed solid tumors. Most RCCs are histologically defined as clear cell, comprising approximately 75% of diagnoses. However, the remaining RCC cases are composed of a heterogeneous combination of diverse histopathologic subtypes, each with unique pathogeneses and clinical features. Although the therapeutic approach to both localized and metastatic RCCs has dramatically changed, first with the advent of antiangiogenic targeted therapies and more recently with the approval of immune checkpoint inhibitor (ICI)–based combinations, these advances have primarily benefited the clear cell RCC patient population. As such, there remains critical gaps in the optimization of treatment regimens for patients with non–clear cell, or variant, RCC histologies. Herein, we detail recent advances in understanding the biology of RCC with variant histology and how such findings have guided novel clinical studies investigating precision oncology approaches for these rare subtypes. Among the most common variant histology RCCs are papillary RCC, comprising approximately 15%-20% of all diagnoses. Although a histopathologically diverse subset of tumors, papillary RCC is canonically associated with amplification of the MET protooncogene; recently completed and ongoing trials have investigated MET-directed therapies for this patient population. Finally, we discuss the unique biology of RCC with sarcomatoid dedifferentiation and the recent clinical findings detailing its paradoxical sensitivity to ICIs.
The Artless Devil in The Book of Margery Kempe
Authors: Fonzo Kimberly
Published: May 2024

This article argues that the devil's appearance in chapter 59 of The Book of Margery Kempe is a creative adaptation of Legenda aurea hagiographies in which a devil takes on the guise of a woman to seduce male saints. Like a male saint, Kempe is tempted with a sexual spectacle, but like a female saint, she is threatened with rape. This portrays the devil as an ineffectual tempter. In this way, the Book emulates episodes in the vitae of St. Bridget of Sweden and Marie d'Oignes in which the holy women outwit demonic trickery. By portraying the devil as an artless seducer, chapter 59 supplements methods of self-discernment outlined by Julian of Norwich in chapter 18 of the Book. This is because Julian's previous advice that Kempe will be able to tell God's visions from the devil's fails to reassure her as God shows her visions of damnation.