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Optimization of environmental DNA-based methods: A case study for detecting brook tro...
Erika Myler
Yoamel Milián-García

Erika Myler

and 4 more

June 01, 2024
The utility of eDNA for fish species and community monitoring is well-established using targeted amplification (i.e., qPCR and ddPCR) and passive sequencing approaches (i.e., metabarcoding). However, the lack of optimized and standardized methods reduces the sensitivity of this approach and precludes the reliable comparison of findings across studies, respectively. DNA extraction is a prime target for optimization efforts because the extraction method is highly variable across eDNA studies despite being the most influential factor in detection efficiency across the entire post-collection workflow. Sequence analysis is arguably the least standardized step in the workflow, with new bioinformatics pipelines frequently emerging in the literature and being implemented with innumerable unique combinations of parameter values. The current study aimed to support the optimization and standardization of eDNA methods for fish detection by assessing two commercial DNA extraction kits manufactured by Qiagen and Macherey-Nagel on cost, time, and performance specifications and comparing the success of brook trout detection by metabarcoding across three bioinformatics pipelines, qPCR, and ddPCR. Our protocols were effective in detecting brook trout in all 20 samples analyzed. Brook trout eDNA was detected by ddPCR in nine (90%) Qiagen extracts but only seven (70%) Macherey-Nagel extracts. In comparison, detection success was equal across the two extraction kits using qPCR (70%) and metabarcoding (100%). The metabarcoding pipelines performed equally well in detecting brook trout with no significant differences in read numbers associated with the target species. Under our experimental conditions, the Qiagen kit was selected as the preferred kit due to its overall good performance and considerably lower cost despite a slightly longer extraction time.
The Future of Immunology: A Lofoten Perspective
Pawel Borowicz
Carolyn King

Pawel Borowicz

and 5 more

June 01, 2024
One major goal of immunological research is to understand fundamental mechanisms of immune system function and translate these discoveries into innovative approaches for diagnosing, treating, and ideally, preventing disease. Recent years have seen dramatic progress in our appreciation of basic immunologic principles and the pace of taking discoveries to patients is often breath-taking. This is an amazing time for immunologists and the future for the next generation of scientists is bright, indeed. An international meeting held in August 2023 on the Lofoten Islands in Norway provided a forum for discussing promising pathways for future research in our field. This 4th Lofoten workshop was also an opportunity to address another issue, just as important as the future of immunologic research. The recent COVID-19 pandemic highlighted the international phenomenon of a communication gulf between scientists and the public. This manifested itself with both misinformation and deliberate disinformation campaigns around the pandemic, potential treatments for COVID-19, and tragically, the importance of vaccination for individual and community health. The August workshop was an ideal opportunity for scientists from around the world to discuss their experiences in efforts at disseminating non-partisan, trustworthy information that would be useful for their communities. This report summarizes views on future directions in immunologic research presented at round-table discussions at the workshop and subsequent responses to surveys sent to meeting participants. It also summarizes some of the conversation around the responsibility of scientists to communicate with the non-science community and approaches we may use to meet this obligation.
Breaking down silos: The Gastroenterology Immunology Neuroscience (GIN) Discovery Pro...
Juliana Silva
Emma Halmos

Juliana Silva

and 3 more

June 01, 2024
The Gastroenterology Immunology Neuroscience (GIN) Discovery Program represents a new model for research that overcomes the limitations imposed by traditional ‘research silos’ in medical science. By adopting a cross-disciplinary, highly-integrated approach, the GIN Program unites the fields of gastroenterology, immunology, and neuroscience to comprehensively address chronic health challenges. This initiative not only bridges the gaps between basic science, clinical research, and patient care but also emphasises the importance of diversity in ideas, perspectives, and approaches when fostering innovation. The program’s organic, bottom-up growth strategy has facilitated the formation of a vibrant, interdisciplinary community, captivating attention from both national and international institutions. With a vision to create effective therapeutic solutions and pioneer advancements in gut-immune-brain axis research, the GIN Program exemplifies the power of interdisciplinary collaboration. This innovative commitment to change the landscape of medical research aims to inspire similar models that prioritise open communication, mutual respect, and a commitment to groundbreaking science.
Gastrodin alleviates angiotensin Ⅱ-induced hypertension and myocardial apoptosis and...
Nanhui Xu
Qiurong Xie

Nanhui Xu

and 12 more

June 01, 2024
Gastrodin is one of the foremost effective components of traditional Chinese medicine Gastrodia elata Bl., which has been widely used for anti-hypertension in China. However, the protection from myocardial apoptosis in hypertension of gastrodin has not been systematic studied. Our current study investigated the therapeutic effects and underlying mechanisms of gastrodin on cardiac protection in hypertensive mice. Treatment of gastrodin in Ang II-infused C57BL/6 mice significantly alleviated the increase of blood pressure, cardiac dysfunction, heart tibial ratio, and cardiac pathological changes. Kyoto Encyclopedia of Genes and Genomes pathway analyses applied in the data of RNA-sequencing by gastrodin treatment identified 697 up-regulated transcripts and 714 down-regulated transcripts, as well as 1105 enriched signaling pathways, which also revealed that apoptosis and PRDX2/p53 pathway were involved in the cardiac protection role of gastrodin. Consistently, gastrodin treatment significantly reduced the cell apoptosis in cardiac tissues of Ang II-infused mice and Ang II-stimulated H9c2 cells. In addition, gastrodin treatment significantly also decreased the Bax/Bcl-2 ratio on protein level, and down-regulated the protein levels of cleaved-caspase3, cleaved-caspase9, PRDX2 and p53 in both cardiac tissues and H9c2 cells stimulated with Ang II. In conclusion, gastrodin treatment exhibits cardiac protection by reducing myocardial apoptosis and suppressing PRDX2/p53 pathway activation in vitro and in vivo.
Mesenchymal Stromal Cells Over-expression Mutant IL-2 Enhance Treg Function in CIA Mi...
Zhicheng Tang
Fan Yang

Zhicheng Tang

and 8 more

June 01, 2024
Objectives: Research indicates that low doses of interleukin-2 (IL-2) can effectively mitigate RA symptoms by promoting Treg cells, while high doses may enhance immune responses. Consequently, this study employed mutated IL-2 to minimize its impact on CD8 + T and NK cell activation while preserving its influence on Treg cells. Methods: We constructed IL-2 mutants by overlap PCR and assessed its impact on the proliferation and functionality of Treg cells by flow cytometry and PCR. Furthermore, the synergistic effects of mutated IL-2 and MSC on collagen-induced arthritis (CIA) in mice were evaluated through the infusion of lentiviral-transfected mesenchymal stromal cell (MSC) for CIA treatment and through pathological section staining to assess inflammatory joint injury, cartilage destruction, and osteoclast infiltration. Results: Mutant IL-2 demonstrated targeted enhancement of both the proportion and proliferative activity of Treg cells with a diminished capacity to stimulate the proliferation of CD8 + T cells and NK cells relative to wild-type IL-2. Moreover, MSC-mutant IL-2 significantly augmented the proportion of Treg cells compared to either MSC or mutant IL-2 in isolation. Treatment with MSC-mutant IL-2 infusion in CIA mice ameliorated arthritis symptoms and reduced inflammatory infiltration and cartilage damage in their joints. Conclusion: Mutant IL-2 enhances Treg function and proliferation while exerting reduced effects on CD8 + and NK cell activation. MSC expressing mutant IL-2 demonstrates therapeutic benefits in CIA by increasing the proportion of Treg cells and reducing the proportion of CD8 + T cells.
Biodegrable pure Zn stent decorated with lanthanide doped cerium oxide coating toward...
Yuemei Li
Yongmei Li

Yuemei Li

and 1 more

June 01, 2024
Zn alloy stent has become a promising implantable cardiac patch stent. However, traditional Zn alloy stents not only easily induce neointimal hyperplasia, but also cannot improve reperfusion ischemia after myocardial infarction. Here, the Yb/Er/CeO 2 coating grow on the surface of Zn substrate, which inhibits the release of Zn 2+ and enhances the proliferation of vascular endothelial cells. This layer improves re-endothelialization and avoiding restenosis. Yb/Er/CeO 2 coating generates the transition from the valence band to conduction band under 980 nm excitation, which forms transfer energy of photo-induced electron-hole pairs. This transfer energy can catalyze H 2O and O 2 to generate a chemical link group, which accelerate the deposition rate of drug-eluting coating PLGA and increase the corrosion resistance of Zn stents. Particularly, the Yb/Er/CeO 2 coating exhibits good catalytic ability for active oxygen species (ROS), which can effectively scavenge myocardial cells damage. Yb/Er/CeO 2 nanoparticles layer (Nps) improve mitochondrial function and increases oxidative phosphorylation, which achieves anti-damage effects. Zn@Yb/Er/CeO 2/PLGA can serve as an excellent myocardial patch scaffold for repairing damaged myocardial cells, which has promising applications in the treatment of cardiovascular diseases.
The SNARC effect involves both representation and response-selection processing stage...
Weibin Yang
Lizhu Yan

Weibin Yang

and 3 more

May 31, 2024
The processing stage (i.e., the early semantic representation stage, the late response-selection stage, or both) at which the spatial-numerical association of response codes (SNARC) effect occurs is still controversial. The two-stage processing model hypothesizes that the SNARC effect involves both stages and that different interference factors acting at the two stages might be the core reason for the observed stage flexibility of the SNARC effect. To test this hypothesis, the present study was designed to elicit the SNARC, Stroop (semantic-representation stage related), and Simon (response-selection stage related) effects together in one magnitude comparison task and used the event-related potentials (ERPs) to observe the temporal dynamics of these effects. The behavioral results showed no interaction between the Stroop and Simon effects, while these two effects both interacted with the SNARC effect. Furthermore, the ERP results showed an interaction of the Stroop effect with the SNARC effect for the early sensory P1 component, while the interaction of the Simon effect with the SNARC effect was evident for the late N2 and P300 components. The current study repeatedly verified the independence of Stroop and Simon effects. Most importantly, the temporal-specific interactions among the SNARC effect and the other two stage-related factors provided further evidence to support the two-stage processing model that the SNARC effect involves both the representation and response-selection stages.
Familial Hypercholesterolemia presenting with Acute Coronary Syndrome (NSTEMI)
Gaurav Chaudhary
Akshyaya Pradhan

Gaurav Chaudhary

and 5 more

May 31, 2024
Familial hypercholesterolemia (FH) is the most common metabolic disorder and is inherited in an autosomal dominant fashion. FH presents with xanthomas and early coronary artery disease, owing to relatively high levels of low-density lipid-cholesterol (LDL-C) compared to hypercholesterolemia without a genetic predisposition. The first clinical manifestation of this condition could be an acute coronary syndrome in undiagnosed and unsuspecting patient. Various clinical criteria are available to make a diagnosis of FH and a clinician should use the one which he is familiar with. Owing to very high LDL-C levels patients often need multiple oral lipid lowering agents to achieve the desired LDL-C goal. There are multiple novel parenteral lipid lowering agents in offing and some are in pipeline with advantage of high potency and weekly or monthly dosing. This case report emphasizes the importance of FH screening and aggressive treatment to decrease morbidity and mortality in the general population.
YELLOW NAIL SYNDROME: a case report
Franco Alfano
Gian Luca Casoni

Franco Alfano

and 2 more

May 31, 2024
Title PageYELLOW NAIL SYNDROME: a case reportIntroductionYellow Nail Syndrome (YNS) is a rare disorder characterised by the triad of yellow and thickened nails, respiratory manifestations and lower limbs lymphedema. Two out of three clinical characteristics are required to diagnosis [1]. Less than 400 cases are described in literature with a prevalence of < 1/1.000.000. The diagnosis is clinical, particularly based on nail abnormalities, pulmonary manifestations, lymphedema and sinusitis. YNS is a condition of unknown aetiology, usually sporadic or presenting as a paraneoplastic syndrome, associated with cancer. To date there is not a specific treatment for YNS [1]. Resolution has been observed in up to 30% of patients, either spontaneously, or after cancer treatments in case of a paraneoplastic condition [1]. Herein we present a paraneoplastic case of YNS in a 67-years old never-smoker female, complaining chronic productive purulent cough for the last two years, after diagnosis of breast cancer.Key Clinical MessageYellow nail syndrome is a rare disorder affecting multiple districts. The diagnosis is clinical, based on nail abnormalities, pulmonary manifestations and lymphedema.The aetiology is unknown, usually presenting spontaneously or as a paraneoplastic syndrome.There is not an established treatment, while resolution is scarce.Case ReportCase History . A 67-years old never-smoker female was referred to a Respiratory outpatient clinic complaining productive purulent cough for the last two years despite treatments with mucolytic and antitussive. Two years before, following a diagnosis of left ductal mucinous breast cancer (G2 pT1No), she underwent quadrant surgery and local radiotherapy. Since then in remission and currently receiving hormonal therapy with anastrozole. She has a history of atrial fibrillation treated with warfarin and she refers otitis and sinusitis of recent onset (3 months). The high resolution thoracic CT scan highlighted bronchiectasis in the lower right inferior bronchus with mucus plugs. Spirometry was performed in stable conditions showing mild obstruction. A short course of oral clarithromycin was not effective in reducing respiratory symptoms. The thoracic CT scan performed after 6 months showed a parenchymal consolidation (organising pneumonia) in the lower right lobe (Fig 1A). She was then referred to our Outpatient clinic.Methods . She reported that during the last year her nails turned yellow, thicker and frail with slowed growth of both finger and toenails (Fig. 1B). Onychomycosis was excluded by a Dermatologic evaluation and Wood’s lamp test. No history of lower limb lymphedema was reported. Due to persistent respiratory symptoms resistant to antibiotic therapy a bronchoscopy was performed showing purulent material dripping from the nasal districts and mucous-purulent secretions in the lower right bronchus, in the absence of sign of malignancy. Based on xantonychia, bronchiectasis and sinusitis a diagnosis of yellow nail syndrome was performed.Conclusion and Results . A short course of azithromycin was started although the bronchoscopy culture resulted negative, with partial remission of the productive cough. The patient was subsequently chronically treated with low dose azithromycin (500 mg twice/week), a cycling combination of N-Acetyl-L-Cysteine + Lactoferrin + Resveratrol; cycling oral Vitamin E and inhaled umeclidinium. After six-months the patients referred remission of the chronic productive cough, otitis and sinusitis; the yellow nails condition remained unchanged. She is continuing the regular oncologist follow up, still in remission.DiscussionYellow Nail Syndrome (YNS) - OMIM 153300; ORPHA662 - is a rare disorder characterised by the triad of yellow and thickened nails, respiratory manifestations and primary lymphedema [1]. Two out of three clinical characteristics are required to diagnose YNS [1]. First described in 1927, the current definition dates back to 1966 [2]. There are less than 400 cases described in literature with a prevalence < 1/1.000.000. YNS is a condition of unknown aetiology, usually sporadic and affecting adults over 50 years worldwide, with no gender predominance [1] The completed triad is present only in 27-60% of cases, with nail chromonychia being the main clinical manifestation, as shown in Table 1. The diagnosis is clinical, particularly based on nail abnormalities, pulmonary manifestations, lymphedema and sinusitis. Chromonychia (nail discoloration), together with xantonychia (yellow nail coloration), progressive thickening and hardening of the nail plate and a slow growth (reduced by half), are the main characteristics of the YNS [1]. Respiratory manifestations occur in 60-70% of patients, with chronic cough as the most frequent symptom [3, 4]. Pleural effusion presents in up to 46% of cases, usually bilateral with a lattescent appearance (chylothorax); bronchiectasis in 44% [1, 4]. Both chronic and acute rhinosinusitis are common, presenting in 14-83% of cases with daily mucopurulent rhinorrhea and nasal obstruction [1]. Lower limbs lymphedema is present in 29-80% of cases, usually bilateral [1]. A lymphatic disorder with defective lymphatic drainage has been hypothesised as a possible cause of lymphedema, pleural effusion and subungual tissue sclerosis with nail alterations [1]. Another hypothesis considers microvasculopathy and protein leakage [3, 5]. YNS may present as a paraneoplastic syndrome, associated with malignant diseases, such as lung and breast cancer or non-Hodgkin lymphoma [1]. The paraneoplastic presentation could be due to lymphatic micro-obstruction, possibly correlated with circulating tumour microemboli [6], or due to cancer histopathology. Other diseases described associated with YNS are autoimmune and immunodeficiency [1]. Differential diagnosis is broad and involves: asbestos-related disease, heart failure, connective tissue diseases, malignancies and onychomycosis are the main ones [4]. To date there is not a specific treatment for YNS. Resolution has been observed in up to 30% of patients, either spontaneously, or after cancer treatments in case of a paraneoplastic condition [1]. Oral α-tocopherol (vitamin E) at 1000-1200 IU/day, is considered the only partially effective agent nail alterations [1]. Regular antifungal treatment (itraconazole or fluconazole) and oral zinc sulphate were also tried, with scarce evidence [1]. A randomised study using topic vitamin E preparation showed no difference versus placebo [7]. Acute exacerbations of bronchiectasis and sinusitis can be treated with antibiotics and symptomatic drugs, whereas for recurrent flares up or poor symptom control, low dose oral azithromycin (250 mg 3 times/week), and a physiotherapy program should be prescribed. Flu and pneumococcal vaccinations are recommended [1]. Surgical intervention for recurrent or large pleural effusions can be useful, while somatostatin analogues as octreotide for chylothorax can be tried [1]. Complete decongestive therapy is an option for lymphedema volume reduction [1].
Respiratory infection induced episode of alveolar hemorrhage in the pediatric diffuse...
Qing Wei
Xun Chen

Qing Wei

and 6 more

May 31, 2024
Background Respiratory infection is a common trigger for the episode of alveolar hemorrhage in the pediatric diffuse alveolar hemorrahge (DAH). Whereas, a futher detailed study hasn’t been conducted. The aim of this study was to explore the etiological spectrum, clinical features, treatment strategies and outcomes of the respiratory infection induced episode of alveolar hemorrhage (RIIEAH) in the pediatric DAH. Methods The cases of pediatric DAH who had RIIEAH and a definite etiological diagnosis were included. A retrospective study was conducted. Results 1. A total of 16 cases with 21 RIIEAHs were included. Twelve RIIEAHs occurred at the unstable stage, 6 RIIEAHs occurred at the stable stage and 3 RIIEAHs occurred at the end stage. All the RIIEAHs with respiratory failure (n=5) and requirment of invasive mechanical ventilation (n=3) occurred at the unstable or end stage. 2. In the majority of the RIIEAHs (n=19), etiological diagnosis was identified by detecting the nucleic acid of the pathogens. Of these, bronchoalveolar lavage fluid was the most commonly used specimen in 12 RIIEAHs. The majority of the RIIEAHs (n=19) were caused by a single pathogen including mycoplasma pneumoniae (Mp) in 7 RIIEAHs, coronavirus (CoV) in 3 RIIEAHs, haemophilus influenzae (Hi) in 3 RIIEAHs, chlamydia pneumoniae in 2 RIIEAHs, human metapneumovirus in 2 RIIEAHs, acinetobacter baumannii in 1 RIIEAH and pueumocystis carinii in 1 RIIEAH. The rest 2 RIIEAHs were caused by the mixed pathogens including klebsiella pneumoniae and streptococcus pneumoniae in 1 RIIEAH, rhinovirus and CoV in 1 RIIEAH. 3. The majority of the RIIEAHs (n=19) presented with prodromal symptoms and most of them (n=15) occurred within 3 days from the prodromal symptoms. Either worsening anemia or hemoptysis was found in 13 RIIEAHs and dyspnea was found in 9 RIIEAHs. All the 12 RIIEAHs in which bronchosopy had been performed presented with bleeding on bronchoscopy. 4. An intensive glucocorticoid therapy was administrated in the 19 RIIEAHs and a targeted anti-infection treatment was administrated in the 11 RIIEAHs. The majority of the RIIEAHs (n=19) resolved, whereas there was 1 case death. Conclusions 1. RIIEAH could be caused by a varity of pathogens and could occur at any disease stage of pediatric DAH. 2. It usually occurred at the early stage of respiratory infection and presented with worsening anemia or hemoptysis. 3. Bronchoscopy had a good diagnostic value for RIIEAH and idenifying the etiology. 4. An intensive glucocorticoid therapy seemed to be effective and necessary.
Potential of Raman-reflectance combination to quantify liver steatosis and fat drople...
Hao Guo
Vanessa S. Zions

Hao Guo

and 3 more

May 31, 2024
This study explores a combined strategy of Raman and reflectance spectroscopy for quantifying liver fat content and fat droplet size, crucial in assessing donor livers. By using Monte Carlo simulations and experimental setups with oil-in-water phantoms, our findings indicate that Raman scattering can solely differentiate between varying fat contents, while reflectance intensity is influenced by both fat content and oil droplet size, with a more pronounced sensitivity to fat droplet size. This study demonstrates the efficacy of combined Raman and reflectance spectroscopy in assessing liver steatosis and fat droplet size, potentially aiding in assessing donor livers for transplantation.
Augmented reality-based interactive scheme for robot-assisted percutaneous renal punc...
Yiwei Zhuang
Shuyi Wang

Yiwei Zhuang

and 6 more

May 31, 2024
In this paper, we present an Augmented Reality (AR)-based application combined with a robotic system for percutaneous renal puncture navigation interaction and demonstrate its technical feasibility. Our system provides an intuitive interaction scheme between the surgeon and the robot without the need for traditional external input devices, and applies an image-target-based 3D registration scheme to transform the coordinate system between Hololens2 and the robot without using additional tracking devices. Users can visualise the abdominal puncture phantom and obtain 3D depth information of the lesion site by wearing Hololens2 and control the robot directly using buttons or gestures. To investigate the accuracy and feasibility of the proposed interaction scheme, six subjects were recruited to complete 3D registration alignment accuracy experiments, and puncture positioning accuracy experiments using ultrasound unaided navigation, AR unaided navigation and AR robotic navigation. The results showed that the average alignment error of 3D registration was 3.61±1.05 mm. The average positioning errors of ultrasound freehand navigation, AR freehand navigation and AR robotic navigation were 7.67±2.00 mm, 6.13±1.07 mm and 5.52±0.37 mm, respectively; the average puncture times were 34.86±1.67 s, 22.40±2.07 s, and 29.41±1.37 s.
A semi-automated workflow for DIA-based global discovery to pathway-driven PRM analys...
Jennifer Guergues
Jessica Wohlfahrt

Jennifer Guergues

and 5 more

May 31, 2024
Targeted proteomics, which includes parallel reaction monitoring (PRM), is typically utilized for more precise detection and quantitation of key proteins and/or pathways derived from complex discovery proteomics datasets. Initial discovery-based analysis using data independent acquisition (DIA) can obtain deep proteome coverage with low data missingness while targeted PRM assays can provide additional benefits in further eliminating missing data and optimizing measurement precision. However, PRM method development from bioinformatic predictions can be tedious and time-consuming because of the DIA output complexity. We address this limitation with a Python script that rapidly generates a PRM method for the TIMS-TOF platform using DIA data and a user-defined target list. To evaluate the script, DIA data generated from HeLa cell lysate (200 ng, 45-minute gradient method) as well as canonical pathway information from Ingenuity Pathway Analysis was utilized to generated a pathway-driven PRM method. Subsequent PRM analysis of targets within the example pathway, regulation of apoptosis, resulted in improved chromatographic data and enhanced quantitation precision (100% peptides below 10% CV with a median CV of 2.9%, n=3 technical replicates). The script is freely available at https://github.com/StevensOmicsLab/PRM-script and provides a framework that can be adapted to multiple DDA/DIA data outputs and instrument-specific PRM method types.
Effective and Life-Saving Retrograde Femoral and Jugular Vein Double Lumen Catheter I...
Ahmad Hosseinzadeh
Farzad Dalfardi

Ahmad Hosseinzadeh

and 4 more

May 31, 2024
Effective and Life-Saving Retrograde Femoral and Jugular Vein Double Lumen Catheter Insertion in Patients with Poor Hemodialysis Venous Access Who Needed Emergency Hemodialysis: A Case Series Running title: Retrograde double lumen catheter insertionAhmad Hosseinzadeh1, Farzad Dalfardi1, Reza Shahriarirad1, 2, Fatemehsadat Pezeshkian1, 2, *, Farhad Keikha31 Thoracic and Vascular Surgery Research Center, Shiraz University of Medical Sciences, Shiraz, 7134814336, Iran2 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, 7134814336, Iran3 School of Medicine, Shiraz University of Medical Sciences, Shiraz, 7134814336, IranCorresponding author: Fatemehsadat Pezeshkian; Shiraz University of Medical Sciences, Shiraz, 7134814336, Iran; ORCID:
Comparisons of Whole Saliva and Cell Free Saliva by DIA-Based Proteome Profiling
Lingling Jiao
huilin Dong

Lingling Jiao

and 11 more

May 31, 2024
Saliva has emerged as a promising diagnostic resource due to its accessibility, non-invasiveness, and repeatability, enabling early disease detection and timely intervention. However, current studies often overlook the distinction between whole saliva (WS) and cell-free saliva (CFS). This study aims to compare the proteomic profiles of WS and CFS, both with and without low-abundance proteins enrichment using nanoparticles, employing DIA-MS technology. Our findings reveal a substantial enhancement in the detectability of low-abundance proteins in saliva with utilization of nanoparticles, enabling identification of 12%-15% low-abundance proteins previously undetectable in WS or CFS. In total, 3817 saliva proteins were identified, with 3413 found in WS and 2340 in CFS. More interestingly, we found that it wasn’t the similarity of the samples that did the clustering, but rather it depended more on the different detection methods and sample types. And the predominant functions of the identified proteins in WS were related to oxidative phosphorylation and neurodegenerations, whereas those in CFS were primarily associated with nitrogen and glycosaminoglycan metabolism. And both exhibited functions in immune response and proteasome. This study represents the first comparison of WS and CFS, providing valuable experimental evidence for guiding the selection of research subjects in future salivomics studies.
Population Pharmacokinetics and Exposure-Response Relationship for Temsavir Following...
Ridhi Parasrampuria
Nilay Thakkar

Ridhi Parasrampuria

and 4 more

May 31, 2024
Aim: Fostemsavir (FTR), an extended-release prodrug of temsavir (TMR), is a human immunodeficiency virus type 1 (HIV-1) attachment inhibitor approved for the treatment of multidrug-resistant HIV-1 infection in heavily treatment-experienced (HTE) patients failing current antiretroviral treatment. A population PK and exposure-response analysis was performed to assess the influence of intrinsic/extrinsic factors and support regulatory approval of 600 mg BID fostemsavir regimen. Methods: Analysis was conducted using TMR data from seven clinical studies (Phases 1-3). Models were assessed using standard goodness of fit and parameter precision (root mean square error (%RSE)). Model-estimated exposure metrics were used to assess TMR PK- efficacy and safety exposure response relationships. Results: TMR PK was adequately described using a two-compartment model with zero and first-order absorption and first-order elimination. Clearance, volume and absorption parameters were precisely estimated (CL/F 51.0 L/hr (2.1% RSE), V2/F 257 1/hr (3.18 %RSE), Ka 2.33 1/hr (13.3 %RSE)). Concomitant CYP3A inducers and inhibitors were covariates on CL/F, and body weight was a covariate on CL/F, V2/F, Q/F, and V3/F. An Emax model described the trough TMR concentration (Ctau) - day 8 plasma HIV-1 RNA relationship (Emax 1.00 log10 c/mL (17.1 %RSE), EC50 64.3 ng/mL (98% RSE)). No exposure-safety relationships were evident. Simulation showed virologic response was achieved irrespective of coadministration with moderate CYP3A inducers, strong CYP3A inhibitors, changes in prandial status, or body weight. Conclusion: Results support administration of FTR 600 mg BID to decrease virologic load in HIV-1 HTE patients, with no dose adjustments necessary for intrinsic or extrinsic factors.
Doege-Potter syndrome in benign relapse of solitary fibrous tumor of the pleura: a ca...
Julián Rondón-Carvajal
Luis Rodríguez-Month

Julián Rondón-Carvajal

and 4 more

May 31, 2024
A document by Julián Rondón-Carvajal. Click on the document to view its contents.
Feedbacks: A new synthesis of causal loops across ecology
Donald DeAngelis
Linhao Xu

Donald DeAngelis

and 1 more

May 31, 2024
Feedbacks are the basic linkages of living systems. In living organisms, feedbacks regulate the processes of growth and homeostasis, as well as their interactions with their world. Feedbacks are equally important in ecological systems, which is why ‘feedback in ecology’ gets more than 2 million hits on Google. The ecological literature is rich in papers dealing with the role of feedback in various phenomena. However, attempts to embrace the subject of feedbacks as a whole in ecology are rare. Pichon et al. (in press) has done that, with skill and comprehensiveness. The paper succeeds in bringing the array of different types of feedbacks into a manageable order that makes this a valuable synthesis of the subject.
Arthropod traits as proxies for abundance trends in the Azorean Islands
Guilherme Oyarzabal
Pedro Cardoso

Guilherme Oyarzabal

and 11 more

May 31, 2024
Human activities drive ecological transformation, impacting island ecosystems from species diversity to ecological traits, mainly through habitat degradation and invasive species. Using two unique long-term datasets we aim to evaluate whether species traits (body size, trophic level, dispersal capacity and habitat occupancy) can predict temporal variations in the abundance of endemic, native non-endemic and exotic arthropods in the Azores Islands. We found that body size is crucial to predict arthropods abundance trends. Small-bodied herbivorous arthropods showed a decrease in abundance, while large-bodied indigenous arthropods increased in abundance, mainly in well-preserved areas. Also, large-bodied exotic arthropods increased in abundance across the entire archipelago. Moreover, endemic canopy dwellers increased in abundance, while endemic ground-dwellers decreased in abundance. Simultaneously, exotic arthropods showed the opposite result, increasing abundance in the ground while decreasing abundance in the canopy. Finally, habitat influenced both endemic and exotic spider abundance trends. Endemic spiders that occupy solely natural habitats experienced a decline in abundance, while exotic spiders in the same habitats increased in abundance. Our study underscores the significance of arthropod species traits in predicting abundance changes in island ecosystems over time, as well as the importance of monitoring species communities. Conservation efforts must extend beyond endangered species to protect non-threatened ones, given the increased extinction risk faced by even common species on islands. Monitoring and restoration programs are essential for preserving island ecosystems and safeguarding endemic arthropod populations.
Functional traits and habitat types rather than elevation predispose an African cycad...
Kantakwa  Sadiki
Kowiyou Yessoufou

Kantakwa Sadiki

and 2 more

May 31, 2024
The genus Encephalartos is entirely endemic to Africa. Like most cycad species, the genus is at risk of extinction. One of the threats jeopardizing the future of the genus is reproduction failure. Our objective is to investigate what predisposes Encephalartos species to reproduction failure. We collected functional traits of 430 individuals of Encephalartos villosus, including pre-dispersal seed predation and habitat types and elevation in Origi Gorge Nature Reserve in South Africa. Then, we analysed our data by fitting a structural equation model (SEM). Surprisingly, elevation does not predict pre-dispersal seed predations, adding to the inconsistent effects of elevation on seed predation. However, there was evidence of more predated seeds on plants with more leaves, fitting the patterns of resource concentration hypothesis which predicts more insect herbivores, particularly specialist herbivores, where food resources (e.g., leaves, flowers, fruits, and seeds) are abundant. We also found that more predated seeds are in open habitats, perhaps mirroring the specialist feeding behaviour of the weevil Antliarhinus zamiae feeding on the seeds of Encephalartos spp. Furthermore, taller plants tend to bear more predated seeds, potentially because taller plants are easy located by the weevil. Finally, large canopy correlates negatively with predated seeds, mirroring our finding of increased seed predation in open habitats. Our SEM explains 67% of the variations in pre-dispersal seed predations, suggesting that this metamodel provides insights into the predisposition of cycad seed to predations. Since open habitats correlate with more seed predation, we suggest that anthropogenic activities that contribute to open forest must be avoided if we are to limit seed predations.
Left Atrial Septal Pouch Thrombus: An Unusual Cause of An Embolic Stroke
Aditya Bhave
Aditya Patel

Aditya Bhave

and 7 more

May 31, 2024
A large proportion of ischemic strokes have an undetermined cause and are considered “cryptogenic.” A left atrial septal pouch (LASP) develops due to incomplete fusion of the septa primum and secundum, forming a pocket at the interatrial septum. It can be a potential site of blood stasis with resultant thrombus formation. LASP has a higher prevalence among patients who present with cryptogenic stroke, but it is rare to visualize a thrombus in the LASP. We present a case of stroke with visualization of a LASP with in-situ thrombus confirming a pathogenic role.
A FOURTH ORDER ITERATIVE SCHEME FOR THE COMPUTATION OF A MATRIX INVERSE SQUARE ROOT
Arif
Afia Shafique

Arif Rafiq

and 1 more

May 31, 2024
In this paper, we introduce a fourth-order iterative scheme tailored for a parametric matrix family to calculate the inverse square root of matrices. Initially, we will design a fourth-order algorithm for the matrix equation, followed by the development of a coupled scheme to address stability concerns. Moreover, we will conduct a comprehensive analysis of convergence and stability, substantiated by numerical examples.
Letter to Editor On “From Halley to Secant: Redefining root finding with memory-based...
Arif

Arif Rafiq

May 31, 2024
A document by Arif. Click on the document to view its contents.
The Genome of a “Living Fossil” shows a Correlation of Spider Diversification with Ho...
Yannis Schöneberg
Tracy Audisio

Yannis Schöneberg

and 11 more

May 31, 2024
Spiders are a hyper-diverse taxon and among the most abundant predators in nearly all terrestrial habitats. Their success is often attributed to key developments in their evolution such as silk and venom production and major apomorphies such as a whole-genome duplication. Resolving deep relationships within the spider tree of life has been historically challenging, making it difficult to measure the relative importance of these novelties. Whole-genome data offer an essential resource in these efforts, but also for functional genomic studies. Here, we present de novo assemblies for three spider species: Ryuthela nishihirai (Heptathelidae), a representative of the ancient Mesothelae, the suborder which is sister to all other extant spiders; Uloborus plumipes (Uloboridae), a cribellate orbweaver whose phylogenetic placement is especially challenging; and Cheiracanthium punctorium (Cheiracanthiidae), which represents only the second family to be sequenced in the hyper-diverse Dionycha clade. These genomes fill critical gaps in the spider tree of life. Using these novel genomes along with 25 previously published ones, we examine two proposed drivers of diversification: spidroin gene and structural hox cluster diversity. Our analyses show that spidroin diversification as well as hox cluster duplication and restructuring mirror spider diversification, hence suggesting a key role in the evolutionary success of the group. Our assemblies provide critical genomic resources to facilitate deeper investigations into spider evolution. The near chromosome-level genome of the “living fossil” R. nishihirai represents an especially important step forward, offering new insights into the origins of spider traits.
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