bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effect of hydroxytyrosol and tyrosol metabolites in LPS-induced vascular barrier derangement in vitro
Authors: Zodio Sonia , Serreli Gabriele , Melis Maria Paola , Franchi Benedetta , Boronat Anna , de la Torre Rafael , Deiana Monica
Published: April 2024

Introduction

The maintenance of endothelial barrier function is essential for vasal homeostasis and prevention of cardiovascular diseases. Among the toxic stimuli involved in the initiation of atherosclerotic lesions, Gram negative lipopolysaccharide (LPS) has been reported to be able to trigger endothelial dysfunction, through the alteration of barrier permeability and inflammatory response. Hydroxytyrosol (HT) and tyrosol (Tyr), the major phenolic compounds of extra virgin olive oil (EVOO), as wells as their circulating sulphated and glucuronidated metabolites have been shown to exert anti-inflammatory effects at endothelial level.

Methods

In this study we investigated the protective effects of HT and Tyr metabolites on LPS-induced alteration of permeability in Human Umbilical Vein Endothelial Cells (HUVEC) monolayers and examined underlying signaling pathways, focusing on tight junction (TJ) proteins, mitogen-activated protein kinase (MAPK) and NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation.

Results

It was shown that LPS-increased permeability in HUVEC cells was due to the alteration of TJ protein level, following the activation of MAPK and NLRP3. HT and Tyr sulphated and glucuronidated metabolites were able to limit the effects exerted by LPS, acting as signaling molecules with an efficacy comparable to that of their precursors HT and Tyr.

Discussion

The obtained results add a further piece to the understanding of HT and Tyr metabolites mechanisms of action in vascular protection.
Untargeted metabolomics based on ultra-high performance liquid chromatography-mass spectrometry/MS reveals the lipid-lowering mechanism of taurine in hyperlipidemia mice
Authors: Guo Xinzhe , Ou Tong , Yang Xinyu , Song Qi , Zhu Lin , Mi Shengquan , Zhang Jing , Zhang Yanzhen , Chen Wen , Guo Junxia
Published: April 2024

Introduction

Taurine has a prominent lipid-lowering effect on hyperlipidemia. However, a comprehensive analysis of the effects of taurine on endogenous metabolites in hyperlipidemia has not been documented. This study aimed to explore the impact of taurine on multiple metabolites associated with hyperlipidemia.

Methods

The hyperlipidemic mouse model was induced by high-fat diet (HFD). Taurine was administered via oral gavage at doses of 700  mg/kg/day for 14  weeks. Evaluation of body weight, serum lipid levels, and histopathology of the liver and adipose tissue was performed to confirm the lipid-lowering effect of taurine. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabonomics analyses of serum, urine, feces, and liver, coupled with multivariate data analysis, were conducted to assess changes in the endogenous metabolites.

Results and discussion

Biochemical and histological examinations demonstrated that taurine administration prevented weight gain and dyslipidemia, and alleviated lipid deposition in the liver and adipose tissue in hyperlipidemic mice. A total of 76 differential metabolites were identified by UPLC-MS-based metabolomics approach, mainly involving BAs, GPs, SMs, DGs, TGs, PUFAs and amino acids. Taurine was found to partially prevent HFDinduced abnormalities in the aforementioned metabolites. Using KEGG database and MetaboAnalyst software, it was determined that taurine effectively alleviates metabolic abnormalities caused by HFD, including fatty acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, diacylglycerol metabolism, amino acid metabolism, bile acid and taurine metabolism, taurine and hypotaurine metabolism. Moreover, DGs, GPs and SMs, and taurine itself may serve as active metabolites in facilitating various anti-hyperlipidemia signal pathways associated with taurine. This study provides new evidence for taurine to prevent hyperlipidemia.
Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study
Authors: Dasgupta Archya , DiCenzo Daniel , Sannachi Lakshmanan , Gandhi Sonal , Pezo Rossana C. , Eisen Andrea , Warner Ellen , Wright Frances C. , Look-Hong Nicole , Sadeghi-Naini Ali , Curpen Belinda , Kolios Michael C. , Trudeau Maureen , Czarnota Gregory J.
Published: April 2024

Background

In patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy.

Methods

The phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination.

Results

Between June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation.

Conclusion

The study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study.

Clinical trial registration

clinicaltrials.gov, ID NCT04050228.
Investigation of the hypoglycemic mechanism of the ShenQi compound formula through metabonomics and 16S rRNA sequencing
Authors: Gao Juan , Zhou Xiujuan , Gao Hong , Xu Guiping , Xie Chunguang , Xie Hongyan
Published: April 2024

Introduction: Herbal formulations are renowned for their complex biological activities, acting on multiple targets and pathways, as evidenced by in vitro studies. However, the hypoglycemic effect and underlying mechanisms of Shenqi Compound (SQ), a traditional Chinese herbal formula, remain elusive. This study aimed to elucidate the hypoglycemic effects of SQ and explore its mechanisms of action, focusing on intestinal flora and metabolomics.

Methods: A Type 2 diabetes mellitus (T2DM) rat model was established through a high-fat diet, followed by variable glucose and insulin injections to mimic the fluctuating glycemic conditions seen in diabetes.

Results: An eight-week regimen of SQ significantly mitigated hyperglycemia, inflammation, and insulin resistance in these rats. Notably, SQ beneficially modulated the gut microbiota by increasing populations of beneficial bacteria, such as Lachnospiraceae_NK4A136_group and Akkermansia, while reducing and inhibiting harmful strains such as Ruminococcus and Phascolarctobacterium. Metabolomics analyses revealed that SQ intervention corrected disturbances in Testosterone enanthate and Glycerophospholipid metabolism.

Discussion: Our findings highlight the hypoglycemic potential of SQ and its mechanisms via modulation of the gut microbiota and metabolic pathways, offering a theoretical foundation for the use of herbal medicine in diabetes management.
Efficacy and safety of total glucosides of paeony in the treatment of recurrent aphthous ulcers: a systematic review and meta-analysis
Authors: Liu Zijian , Liu Xingyun , Han Yangping , Wang Yutian , Guo Qianyun , Lu Mingxing , Li Shufang , Han Ying , Liu Hongwei
Published: April 2024

Background: Recurrent aphthous ulcer (RAU) had high prevalence and lacked widely recognized treatment. Total glucosides of paeony (TGP) was used in the treatment of RAU in recent years. This study was to summarize the efficacy and safety of TGP in the treatment of RAU.

Methods: We searched eight commonly used databases for relevant studies that published before 1 November 2023. Primary outcome was visual analogue scale (VAS). Secondary outcomes included overall response rate, significant response rate, ulcer healing time, interval, number of ulcers, and serum inflammatory factors. We conducted the meta-analysis, assessed risk of bias and the confidence of the evidence, by using Stata 15.0, Review Manager 5.4, and Gradepro.

Results: Nine randomized controlled trials (RCTs) encompassing 883 patients with RAU were included in the final analysis. The VAS in the TGP group was lower than that in the control group (MD = −1.18, 95% CI = −1.58 to −0.78, p < 0.001, moderate-certainty evidence), subgroup analysis suggested longer (>8 weeks) medication and observation led to a more significant reduction in pain (p = 0.02). Moreover, TGP had higher overall response rate (RR = 1.18, 95% CI = 1.04 to 1.33, p = 0.008, very low-certainty evidence) and significant response rate (RR = 1.72, 95% CI = 1.38 to 2.14, p < 0.001, very low-certainty evidence), accelerated ulcer healing (MD = −1.79, 95% CI = −2.67 to −0.91, p < 0.001, low-certainty evidence), and extended intervals (MD = 23.60, 95% CI = 14.17 to 33.03, p < 0.001, very low-certainty evidence). The efficacy of TGP in reducing the number of ulcers showed no significant difference compared to the control group (MD = −1.66, 95% CI = −3.60 to 0.28, p = 0.09, low-certainty evidence). Moreover, TGP treatment was associated with a higher incidence of abdominal symptoms (RR = 3.27, 95% CI = 1.62 to 6.60, p < 0.001).

Conclusion: TGP appears to hold promise as a widely-used clinical therapeutic option for treating RAU. Nevertheless, further rigorous studies of high quality are required to validate its effectiveness.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=471154, Identifier CRD42023471154
A lidar for detecting atmospheric turbulence based on modified Von Karman turbulence power spectrum
Authors: Zhou Longxia , Mao Jiandong
Published: April 2024

Introduction: Atmospheric turbulence is a kind of random vortex motion. A series of turbulent effects, such as fluctuation of light intensity, occur when laser is transmitted in atmospheric turbulence.

Methods: In order to verify the possibility of detecting atmospheric turbulence by the Mie-scattering lidar, firstly, based on the power spectrum method, the Zernike polynomial method is used to simulate generation of the modified Von Karman turbulent phase screen by low-frequency compensation. By comparing the obtained phase structure function with the theoretical value, the accuracy of the method is verified. Moreover, the transmission process of the Gaussian beam from Mie-scattering lidar through the phase screen is simulated, and the transmission characteristics of the beam under modified Von Karman turbulence are obtained by analyzing the fluctuation of light intensity. Secondly, based on the guidance for simulation analysis, a Miescattering lidar system for detecting the intensity of atmospheric turbulence was developed in Yinchuan area, and the atmospheric turbulence profile was inverted by detected scintillation index.

Results: The results show it is feasible to use the Zernike polynomial method perform the low-frequency compensation, and the compensation effect of low order is better than that of high order compensation. The scintillation index of simulation is consistent with the actual detection result, and has the very high accuracy, indicating that the atmospheric turbulence detection using Mie-scattering lidar is effective.

Conclusion: These simulations and experiments play a significant guiding role for the similar lidar to detect atmospheric turbulence.
Resveratrol facilitates bone formation in high-glucose conditions
Authors: Hwang Sung-Min , Kim Tae-Young , Kim Anna , Kim Yong-Gun , Park Jin-Woo , Lee Jae-Mok , Kim Jae-Young , Suh Jo-Young
Published: April 2024

Periodontitis is known to be affected by high-glucose conditions, which poses a challenge to periodontal tissue regeneration, particularly in bone formation. In this study, the potential effects of resveratrol (3,5,4′-trihydroxystilbene, RSV) in facilitating bone formation under high-glucose conditions after periodontitis has been investigated. We focused on the analysis of osteoblasts and periodontal ligament cells, which are essential for bone formation including cell proliferation and differentiation. And we aimed to investigate the impact of RSV on bone healing, employed diabetic mouse model induced by streptozotocin and confirmed through histological observation. High-glucose conditions adversely affected cell proliferation and ALP activity in both MC3T3-E1 and hPDLF in vitro, with more significant impact on MC3T3-E1 cells. RSV under high-glucose conditions had positive effects on both, showing early-stage effects for MC3T3-E1 cells and later-stage effects for hPDLF cells. RSV seemed to have a more pronounced rescuing role in MC3T3-E1 cells. Increased ALP activity was observed and the expression levels of significant genes, such as Col 1, TGF-β1, ALP, and OC, in osteogenic differentiation were exhibited stage-specific expression patterns. Upregulated Col 1 and TGF-β1 were detected in the early stage, and then ALP and OC expressions became more pronounced in the later stages. Similarly, stronger positive reactions against RUNX2 were detected in the RSV-treated group compared to the control. Furthermore, in in vivo experiment, RSV stimulates the growth and differentiation of osteoblasts, thereby promoting bone formation. High-glucose levels have the potential to impair cellular functions and the regenerative capacity to facilitate bone formation with MC3T3-E1 rather than hPDLF cells. Resveratrol appears to facilitate the inherent abilities of MC3T3-E1 cells compared with hPDLF cells, indicating its potential capacity to restore functionality during periodontal regeneration.
Correlation between epicardial adipose tissue and myocardial injury in patients with COVID-19
Authors: Su Tianhong , Zhong Bincheng , Tang Chao , Qiao Shunsong , Feng Yu , Peng Hao , Gu Xiaosong
Published: April 2024

Background: Many people infected with COVID-19 develop myocardial injury. Epicardial adipose tissue (EAT) is among the various risk factors contributing to coronary artery disease. However, its correlation with myocardial injury in patients diagnosed with COVID-19 remains uncertain.

Methods: We examined myocardial biomarkers in population affected by COVID-19 during the period from December 2022 to January 2023. The patients without myocardial injury were referred to as group A (n = 152) and those with myocardial injury were referred to as group B (n = 212).

Results: 1) The A group and the B group exhibitedstatistically significant differences in terms of age, TC, CRP, Cr, BUN, LDL-C, IL-6, BNP, LVEF and EAT (p < 0.05). 2) EAT volumehad a close relationship with IL-6, LDL-C, cTnI, and CRP (p < 0.05); the corresponding correlation coefficient values were 0.24, 0.21, 0.24, and 0.16. In contrast to those with lower EAT volume, more subjects with a higher volume of EAT had myocardial injury (p < 0.05). Regression analysis showed that EAT, LDL-C, Age and Cr were established as independent risk variables for myocardial injury in subjects affected by COVID-19. 3) In COVID-19 patients, the likelihood of myocardial injury rised notably as EAT levels increase (p < 0.001). Addition of EAT to the basic risk model for myocardial injury resulted in improved reclassification. (Net reclassification index: 58.17%, 95% CI: 38.35%, 77.99%, p < 0.001).

Conclusion: Patients suffering from COVID-19 with higher volume EAT was prone to follow myocardial injury and EAT was an independent predictor of heart damage in these individuals.
A porcine large animal model of radiofrequency ablation-induced left bundle branch block
Authors: Wiedmann Felix , Jamros Max , Herlt Valerie , Paasche Amelie , Kraft Manuel , Beck Moritz , Prüser Merten , Erkal Atilla , Harder Maren , Zaradzki Marcin , Soethoff Jasmin , Karck Matthias , Frey Norbert , Schmidt Constanze
Published: April 2024

Background

Electrocardiographic (ECG) features of left bundle branch (LBB) block (LBBB) can be observed in up to 20%–30% of patients suffering from heart failure with reduced ejection fraction. However, predicting which LBBB patients will benefit from cardiac resynchronization therapy (CRT) or conduction system pacing remains challenging. This study aimed to establish a translational model of LBBB to enhance our understanding of its pathophysiology and improve therapeutic approaches.

Methods

Fourteen male pigs underwent radiofrequency catheter ablation of the proximal LBB under fluoroscopy and ECG guidance. Comprehensive clinical assessments (12-lead ECG, bloodsampling, echocardiography, electroanatomical mapping) were conducted before LBBB induction, after 7, and 21 days. Three pigs received CRT pacemakers 7 days after LBB ablation to assess resynchronization feasibility.

Results

Following proximal LBB ablation, ECGs displayed characteristic LBBB features, including QRS widening, slurring in left lateral leads, and QRS axis changes. QRS duration increased from 64.2 ± 4.2 ms to 86.6 ± 12.1 ms, and R wave peak time in V6 extended from 21.3 ± 3.6 ms to 45.7 ± 12.6 ms. Echocardiography confirmed cardiac electromechanical dyssynchrony, with septal flash appearance, prolonged septal-to-posterior-wall motion delay, and extended ventricular electromechanical delays. Electroanatomical mapping revealed a left ventricular breakthrough site shift and significantly prolonged left ventricular activation times. RF-induced LBBB persisted for 3 weeks. CRT reduced QRS duration to 75.9 ± 8.6 ms, demonstrating successful resynchronization.

Conclusion

This porcine model accurately replicates the electrical and electromechanical characteristics of LBBB observed in patients. It provides a practical, cost-effective, and reproducible platform to investigate molecular and translational aspects of cardiac electromechanical dyssynchrony in a controlled and clinically relevant setting.
Characterization of Bacillus amyloliquefaciens BA-4 and its biocontrol potential against Fusarium-related apple replant disease
Authors: Li Bo , He Xiaoxing , Guo Saiya , Li Dongxu , Wang Yanan , Meng Xianglong , Dai Pengbo , Hu Tongle , Cao Keqiang , Wang Shutong
Published: April 2024

Apple replant disease (ARD), caused by Fusarium pathogens, is a formidable threat to the renewal of apple varieties in China, necessitating the development of effective and sustainable control strategies. In this study, the bacterial strain BA-4 was isolated from the rhizosphere soil of healthy apple trees in a replanted orchard, demonstrating a broad-spectrum antifungal activity against five crucial apple fungal pathogens. Based on its morphology, physiological and biochemical traits, utilization of carbon sources, and Gram stain, strain BA-4 was tentatively identified as Bacillus amyloliquefaciens. Phylogenetic analysis using 16S rDNA and gyrB genes conclusively identified BA-4 as B. amyloliquefaciens. In-depth investigations into B. amyloliquefaciens BA-4 revealed that the strain possesses the capacity to could secrete cell wall degrading enzymes (protease and cellulase), produce molecules analogous to indole-3-acetic acid (IAA) and siderophores, and solubilize phosphorus and potassium. The diverse attributes observed in B. amyloliquefaciens BA-4 underscore its potential as a versatile microorganism with multifaceted benefits for both plant well-being and soil fertility. The extracellular metabolites produced by BA-4 displayed a robust inhibitory effect on Fusarium hyphal growth and spore germination, inducing irregular swelling, atrophy, and abnormal branching of fungal hyphae. In greenhouse experiments, BA-4 markedly reduced the disease index of Fusarium-related ARD, exhibiting protective and therapeutic efficiencies exceeding 80% and 50%, respectively. Moreover, BA-4 demonstrated plant-promoting abilities on both bean and Malus robusta Rehd. (MR) seedlings, leading to increased plant height and primary root length. Field experiments further validated the biocontrol effectiveness of BA-4, demonstrating its ability to mitigate ARD symptoms in MR seedlings with a notable 33.34% reduction in mortality rate and improved biomass. Additionally, BA-4 demonstrates robust and stable colonization capabilities in apple rhizosphere soil, particularly within the 10-20 cm soil layer, which indicates that it has long-term effectiveness potential in field conditions. Overall, B. amyloliquefaciens BA-4 emerges as a promising biocontrol agent with broad-spectrum antagonistic capabilities, positive effects on plant growth, and strong colonization abilities for the sustainable management of ARD in apple cultivation.
Comparative functional analyses of PHR1, PHL1, and PHL4 transcription factors in regulating Arabidopsis responses to phosphate starvation
Authors: Wang Zhen , Zheng Zai , Liu Dong
Published: April 2024

To cope with phosphate (Pi) starvation, plants trigger an array of adaptive responses to sustain their growth and development. These responses are largely controlled at transcriptional levels. In Arabidopsis (Arabidopsis thaliana), PHOSPHATE RESPONSE 1 (PHR1) is a key regulator of plant physiological and transcriptional responses to Pi starvation. PHR1 belongs to a MYB-CC-type transcription factor family which contains 15 members. In this PHR1 family, PHR1/PHR1-like 1(PHL1) and PHL2/PHL3 form two distinct modules in regulating plant development and transcriptional responses to Pi starvation. PHL4 is the most closely related member to PHR1. Previously, using the phr1phl4 mutant, we showed that PHL4 is also involved in regulating plant Pi responses. However, the precise roles of PHL1 and PHL4 in regulating plant Pi responses and their functional relationships with PHR1 have not been clearly defined. In this work, we further used the phl1phl4 and phr1phl1phl4 mutants to perform comparative phenotypic and transcriptomic analyses with phr1, phr1phl1, and phr1phl4. The results showed that both PHL1 and PHL4 act redundantly and equally with PHR1 to regulate leaf senescence, Pi starvation induced-inhibition of primary root growth, and accumulation of anthocyanins in shoots. Unlike PHR1 and PHL1, however, the role of PHL4 in maintaining Pi homeostasis is negligible. In regulating transcriptional responses to Pi starvation at genomic levels, both PHL1 and PHL4 play minor roles when acts alone, however, they act synergistically with PHR1. In regulating Pi starvation-responsive genes, PHL4 also function less than PHL1 in terms of the number of the genes it regulates and the magnitude of gene transcription it affects. Furthermore, no synergistic interaction was found between PHL1 and PHL4 in regulating plant response to Pi starvation. Therefore, our results clarified the roles of PHL1 and PHL4 in regulating plant responses to Pi starvation. In addition, this work revealed a new function of these three transcription factors in regulating flowering time.
Reducing suicides in mental healthcare: results from a 4-year follow-up implementation study in the Netherlands (SUPRANET)
Authors: Setkowski Kim , van Balkom Anton J. L. M. , Hoogendoorn Adriaan W. , Franx Gerdien , Veerbeek Marjolein , de Winter Remco F. P. , Gilissen Renske
Published: April 2024

Objective

In 2016, the SUicide PRevention Action NETwork (SUPRANET) was launched. The SUPRANET intervention aims at better implementing the suicide prevention guideline. An implementation study was developed to evaluate the impact of SUPRANET over time on three outcomes: 1) suicides, 2) registration of suicide attempts, and 3) professionals’ knowledge and adherence to the guideline.

Methods

This study included 13 institutions, and used an uncontrolled longitudinal prospective design, collecting biannual data on a 2-level structure (institutional and team level). Suicides and suicide attempts were extracted from data systems. Professionals’ knowledge and adherence were measured using a self-report questionnaire. A three-step interrupted time series analysis (ITSA) was performed for the first two outcomes. Step 1 assessed whether institutions executed the SUPRANET intervention as intended. Step 2 examined if institutions complied with the four guideline recommendations. Based on steps 1 and 2, institutions were classified as below or above average and after that, included as moderators in step 3 to examine the effect of SUPRANET over time compared to the baseline. The third outcome was analyzed with a longitudinal multilevel regression analysis, and tested for moderation.

Results

After institutions were labeled based on their efforts and investments made (below average vs above average), we found no statistically significant difference in suicides (standardized mortality ratio) between the two groups relative to the baseline. Institutions labeled as above average did register significantly more suicide attempts directly after the start of the intervention (78.8 per 100,000 patients, p<0.001, 95%CI=(51.3 per 100,000, 106.4 per 100,000)), and as the study progressed, they continued to report a significantly greater improvement in the number of registered attempts compared with institutions assigned as below average (8.7 per 100,000 patients per half year, p=0.004, 95%CI=(3.3 per 100,000, 14.1 per 100,000)). Professionals working at institutions that invested more in the SUPRANET activities adhered significantly better to the guideline over time (b=1.39, 95%CI=(0.12,2.65), p=0.032).

Conclusion

Institutions labeled as above average registered significantly more suicide attempts and also better adhered to the guideline compared with institutions that had performed less well. Although no convincing intervention effect on suicides was found within the study period, we do think that this network is potentially able to reduce suicides. Continuous investments and fully implementing as many guideline recommendations as possible are essential to achieve the biggest drop in suicides.
Regression discontinuity design for the study of health effects of exposures acting early in life
Authors: Popovic Maja , Zugna Daniela , Tilling Kate , Richiardi Lorenzo
Published: April 2024

Regression discontinuity design (RDD) is a quasi-experimental approach to study the causal effect of an exposure on later outcomes by exploiting the discontinuity in the exposure probability at an assignment variable cut-off. With the intent of facilitating the use of RDD in the Developmental Origins of Health and Disease (DOHaD) research, we describe the main aspects of the study design and review the studies, assignment variables and exposures that have been investigated to identify short- and long-term health effects of early life exposures. We also provide a brief overview of some of the methodological considerations for the RDD identification using an example of a DOHaD study. An increasing number of studies investigating the effects of early life environmental stressors on health outcomes use RDD, mostly in the context of education, social and welfare policies, healthcare organization and insurance, and clinical management. Age and calendar time are the mostly used assignment variables to study the effects of various early life policies and programs, shock events and guidelines. Maternal and newborn characteristics, such as age, birth weight and gestational age are frequently used assignment variables to study the effects of the type of neonatal care, health insurance, and newborn benefits, while socioeconomic measures have been used to study the effects of social and welfare programs. RDD has advantages, including intuitive interpretation, and transparent and simple graphical representation. It provides valid causal estimates if the assumptions, relatively weak compared to other non-experimental study designs, are met. Its use to study health effects of exposures acting early in life has been limited to studies based on registries and administrative databases, while birth cohort data has not been exploited so far using this design. Local causal effect around the cut-off, difficulty in reaching high statistical power compared to other study designs, and the rarity of settings outside of policy and program evaluations hamper the widespread use of RDD in the DOHaD research. Still, the assignment variables’ cut-offs for exposures applied in previous studies can be used, if appropriate, in other settings and with additional outcomes to address different research questions.
A review of spiral wound membrane modules and processes for groundwater treatment
Authors: Tabi Rita Namoe , Boakye Patrick , Agyemang Frank Ofori , Nxumalo Edward Ndumiso , Oduro-Kwarteng Sampson
Published: April 2024

The demand for freshwater keeps increasing on a global scale, and on the other hand, the availability of freshwater keeps diminishing. Groundwater has been identified as the largest source of freshwater that is readily accessible. Although the water is available for abstraction, it must be treated to meet application standards. Membrane processes are the options that industry and researchers are turning to for the purification of groundwater. This review provides an insight into the use of pressure-driven membrane processes for groundwater treatment, with focus on the spiral wound membrane module. A brief description of what a spiral wound module is and the plant set-up in which it is used is given. The various applications of the spiral wound module with regards to groundwater treatment have been reviewed. The shortcomings and challenges limiting the application of spiral wound modules and by extension, the treatment plant itself have been highlighted. To cap it all, the opportunities that can be exploited to overcome these challenges and position pressure-driven membrane processes for groundwater treatment as the go-to purification method have been discussed.
A novel deep learning method to segment parathyroid glands on intraoperative videos of thyroid surgery
Authors: Sang Tian , Yu Fan , Zhao Junjuan , Wu Bo , Ding Xuehai , Shen Chentian
Published: April 2024

Introduction

The utilization of artificial intelligence (AI) augments intraoperative safety and surgical training. The recognition of parathyroid glands (PGs) is difficult for inexperienced surgeons. The aim of this study was to find out whether deep learning could be used to auxiliary identification of PGs on intraoperative videos in patients undergoing thyroid surgery.

Methods

In this retrospective study, 50 patients undergoing thyroid surgery between 2021 and 2023 were randomly assigned (7:3 ratio) to a training cohort (n = 35) and a validation cohort (n = 15). The combined datasets included 98 videos with 9,944 annotated frames. An independent test cohort included 15 videos (1,500 frames) from an additional 15 patients. We developed a deep-learning model Video-Trans-U-HRNet to segment parathyroid glands in surgical videos, comparing it with three advanced medical AI methods on the internal validation cohort. Additionally, we assessed its performance against four surgeons (2 senior surgeons and 2 junior surgeons) on the independent test cohort, calculating precision and recall metrics for the model.

Results

Our model demonstrated superior performance compared to other AI models on the internal validation cohort. The DICE and accuracy achieved by our model were 0.760 and 74.7% respectively, surpassing Video-TransUnet (0.710, 70.1%), Video-SwinUnet (0.754, 73.6%), and TransUnet (0.705, 69.4%). For the external test, our method got 89.5% precision 77.3% recall and 70.8% accuracy. In the statistical analysis, our model demonstrated results comparable to those of senior surgeons (senior surgeon 1: χ2 = 0.989, p = 0.320; senior surgeon 2: χ2 = 1.373, p = 0.241) and outperformed 2 junior surgeons (junior surgeon 1: χ2 = 3.889, p = 0.048; junior surgeon 2: χ2 = 4.763, p = 0.029).

Discussion

We introduce an innovative intraoperative video method for identifying PGs, highlighting the potential advancements of AI in the surgical domain. The segmentation method employed for parathyroid glands in intraoperative videos offer surgeons supplementary guidance in locating real PGs. The method developed may have utility in facilitating training and decreasing the learning curve associated with the use of this technology.
Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy
Authors: Nakamura Michinari
Published: April 2024

Unhealthy sources of fats, ultra-processed foods with added sugars, and a sedentary lifestyle make humans more susceptible to developing overweight and obesity. While lipids constitute an integral component of the organism, excessive and abnormal lipid accumulation that exceeds the storage capacity of lipid droplets disrupts the intracellular composition of fatty acids and results in the release of deleterious lipid species, thereby giving rise to a pathological state termed lipotoxicity. This condition induces endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory responses, and cell death. Recent advances in omics technologies and analytical methodologies and clinical research have provided novel insights into the mechanisms of lipotoxicity, including gut dysbiosis, epigenetic and epitranscriptomic modifications, dysfunction of lipid droplets, post-translational modifications, and altered membrane lipid composition. In this review, we discuss the recent knowledge on the mechanisms underlying the development of lipotoxicity and lipotoxic cardiometabolic disease in obesity, with a particular focus on lipotoxic and diabetic cardiomyopathy.
RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma
Authors: Krencz Ildikó , Sztankovics Dániel , Sebestyén Anna , Pápay Judit , Dankó Titanilla , Moldvai Dorottya , Lutz Elmar , Khoor Andras
Published: April 2024

RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.
A Strategic Roadmap for the Wine Sector in the Setúbal Peninsula
Authors: Costa Teresa , Teixeira Nuno , Cravidão Mário , Galvão Rosa , Nunes Sandra , Mares Pedro
Published: April 2024

The wine sector contributes significantly to economic, environmental and social development. In Portugal, the Setúbal Peninsula is one of the fourteen wine regions. Operated by numerous local businesses in a rural area, the wine industry generates enhanced value and provides jobs in the region. The main purpose of this research is to study the wine sector in the Setúbal Peninsula, Portugal, in the context of the COVID-19 pandemic and propose a roadmap, which includes strategic mitigation options regarding the impacts of the crisis. This study is based on qualitative data collected through in-depth interviews and focus group interviews. The results show that the wine sector presents a tendency toward concentration with the emergence of producers with scale and notoriety at a national level who, due to the greater dynamism of their activity, have sought international markets of great dimension and with a purchasing power, which values quality products. Finally, a business model is proposed, where companies are advised to offer competitive value propositions, which capitalize on the uniqueness of national grape varieties and traditional production processes in order to offer high-quality products at competitive prices on the global market.
Wing Efficiency Enhancement at Low Reynolds Number
Authors: Traub Lance W.
Published: April 2024

The aerodynamic performance of wings degrades severely at low Reynolds number; lift often becomes non-linear, while drag increases significantly, caused by large extents of separation. Consequently, a non-conventional wing design approach is implemented to assess its ability to enhance performance. The design methodology is that of wing segmentation, where the wing is divided into spanwise panels that can be separated, thereby yielding small gaps between the panels. A moderate aspect ratio wing comprised of four separate wing panels was manufactured and wind tunnel tested through a Re range from 40,000 to 80,000. Force balance data and surface flow visualization were used to characterize performance. The results indicate that segmentation is effective in significantly augmenting efficiency at Reynolds numbers at which the fused wing (i.e., no gaps) shows large extents of open separation. Drag is greatly reduced, while lift is increased, and stall is delayed. The benefit of segmentation was noted to diminish at higher Re where the fused wing’s performance improves markedly. Wing segmentation could find application in micro-unmanned-aerial-vehicle and drone design. Further study would entail the effects of AR and the number of spanwise panels on performance.
Seasonal Variations in Lunar-Assisted GEO Transfer Capability for Southward Launch
Authors: Choi Su-Jin , Lee Hoonhee
Published: April 2024

The launch azimuth of the Naro Space Center is limited toward the south of the Korean peninsula, at 170 ± 10 degrees, suitable for the polar orbit, sun-synchronous orbit, and safety range issues. In this circumstance, one option to send a satellite into GEO is to perform a dog-leg maneuver during ascent, thus forming a medium-inclination orbit under such a restrictive condition. However, this option requires an immense amount of energy for the dog-leg maneuver, as well as a plane change maneuver. The only remaining option is to raise the apogee to the Moon, utilizing lunar gravity to lower the inclination to near zero and then returning to the vicinity of the Earth at an altitude of 35,786 km without maneuver. In order to design lunar-assisted GEO transfer, all feasible paths are defined, but questions remain about how seasonal variations affect all these potential paths. Therefore, this study aims to design and analyze all available trajectories for the year 2031 using a high-fidelity dynamic model, root-finding algorithm, and well-arranged initial conditions, focusing on the impact of seasonal trends. The simulation results indicate that cislunar free-return trajectories generally require less ΔV compared to circumlunar free-return trajectories, and circumlunar trajectories are minimally affected by lunisolar effects due to their relatively short return time of flight. Conversely, cislunar trajectories show seasonal variations, so spring and fall seasons require up to 20 m/s less ΔV than summer and winter seasons due to the relatively long time of return duration.
In-Depth Characterization of Crown Gall Disease of Tobacco in Serbia
Authors: Iličić Renata , Jelušić Aleksandra , Barać Goran , Nikolić Dušan , Stošić Nemanja , Scortichini Marco , Milovanović Tatjana Popović
Published: April 2024

In August 2020, the unusual appearance of crown gall symptoms was observed on the tobacco plants (hybrid PVH2310) grown in fields in the Golubinci (Srem district, Serbia) locality. The causal agent isolated from galls located on tobacco roots formed circular, convex, and glistening light blue colonies, and then dark to olive-green-colored bacterial colonies on a semi-selective D1 medium. Molecular analysis based on multiplex PCR and multi-locus sequence analysis (MLSA) using concatenated sequences of the atpD, dnaK, glnA, and rpoB genes as well as 16S rRNA identified Serbian tobacco isolates such as Agrobacterium tumefaciens (biovar 1). Two duplex PCR methods confirmed the presence of the virD2 and virC genes in tobacco isolates. Pathogenicity tests performed on carrot discs and squash fruits resulted in tumor/gall formation after 12 to 16 days post inoculation, respectively. Pathogenicity was also confirmed on tobacco plants, where isolates caused tumor development 21−25 days after inoculation. API 50 CH generated results regarding the biochemical features of the Serbian tobacco isolates. As A. tumefaciens (biovar 1) as a cause of tobacco crown gall has previously been documented solely in Japan, there is presently no data on its wider occurrence. Therefore, this first detailed investigation of A. tumefaciens isolated from naturally infected tobacco in Serbia will contribute to a better understanding of it at the global level.
Evaluation of Quinoa Varieties for Adaptability and Yield Potential in Low Altitudes and Correlation with Agronomic Traits
Authors: Tang Peng , Ren Aixia , Jiang Zhijun , Wang Rongzhen , Cui Kaiyuan , Wu Xiangyun , Sun Min , Gao Zhiqiang , Anwar Sumera
Published: April 2024

The research conducted at the Shanxi Agricultural University’s Quinoa Experimental Model Base in Jinzhong, Shanxi Province, aimed to assess agronomic traits and their correlation with yield across 32 quinoa varieties. Three distinct yield categories emerged: low (≤1500 kg ha−1), middle (1500–2500 kg−1), and high (>2500 kg ha−1). High-yielding varieties demonstrated notable characteristics, including decreased plant height and increased leaf area per plant at maturity compared to low- and middle-yielding varieties. Moreover, the decline in leaf area per plant and root traits from flowering to maturity was less pronounced in the high-yielding varieties. The high-yielding varieties had a higher hardness of the stem base and middle stem by 12–13.7% and 6.3–11.5% compared to the medium- and low-yield varieties. Furthermore, high-yielding varieties indicated improvements in dry matter accumulation, decreased effective branch number, and increased main ear length and 1000-grain weight. Correlation analysis highlighted significant relationships between grain weight, yield, post-flowering senescence, and root and leaf characteristics. Structural equation model analysis revealed the negative impact of certain root and leaf traits on grain weight and yield, suggesting their importance in determining productivity. Notably, high-yielding varieties exhibited traits conducive to increased grain weight, including shorter plant height, slower root senescence, and enhanced post-flowering leaf resilience. These findings showed that understanding the relationship between agronomic traits and yield potential is crucial for optimizing quinoa production and promoting the sustainable development of this essential crop.
Artificial Intelligence in Healthcare: ChatGPT and Beyond
Authors: Hulsen Tim
Published: April 2024

Artificial intelligence (AI), the simulation of human intelligence processes by machines, is having a growing impact on healthcare [...]
Poly- and Perfluoroalkyl Substance (PFAS) Analysis in Environmental Matrices: An Overview of the Extraction and Chromatographic Detection Methods
Authors: Iannone Alessia , Carriera Fabiana , Di Fiore Cristina , Avino Pasquale
Published: April 2024

Per- and polyfluoroalkyl substances (PFASs) are carbon–fluorine compounds with widespread industrial and domestic use, posing potential toxicological risks to humans and ecosystems. Several analytical methods have been developed to assess the occurrence of PFASs in the environment, but a standardized method, applicable to all matrices, is still lacking. This paper reviews the extraction and chromatographic detection methods for PFAS assessment in environmental samples, considering parameters such as the LOD, LOQ, and recoveries. Solid phase extraction (SPE) is commonly used, showing high recovery rates for water, soil, and sediment samples using HBL and WAX polymeric sorbents (85–100% and 93–111.5%, respectively). LC-MS has demonstrated low LODs and LOQs in seawater (0.01–0.08 ng L−1; 0.03–0.24 ng L−1), marine sediment (0.002–0.018 ng g−1; 0.004–0.054 ng g−1), and dust (0.08–0.68 pg g−1; 0.26–2.25 pg g−1), indicating its sensitivity when detecting trace PFAS levels. Evaluating PFASs is crucial for the development of future removal strategies and risk assessments. Potential solutions including the use of PFAS substitutes and innovative adsorption techniques for their adsorption could present promise in reducing their environmental presence.