bluuebunny/crossref_metadata_2025 huggingface dataset:
High affinity of β-amyloid proteins to cerebral capillaries: implications in chronic lead exposure-induced neurotoxicity in rats
Authors: Liu Luke L. , Shen Xiaoli , Gu Huiying , Zhao Gang , Du Yansheng , Zheng Wei
Published: April 2023

Lead (Pb) is a known environmental risk factor in the etiology of Alzheimer’s disease (AD). The existing reports suggest that Pb exposure increases beta-amyloid (Aβ) levels in brain tissues and cerebrospinal fluid (CSF) and facilitates the formation of amyloid plaques, which is a pathological hallmark for AD. Pb exposure has long been associated with cerebral vasculature injury. Yet it remained unclear if Pb exposure caused excessive Ab buildup in cerebral vasculature, which may damage the blood–brain barrier and cause abnormal Ab accumulation. This study was designed to investigate the impact of chronic Pb exposure on Aβ accumulation in cerebral capillary and the expression of low-density lipoprotein receptor protein-1 (LRP1), a critical Aβ transporter, in brain capillary and parenchyma. Sprague–Dawley rats received daily oral gavage at doses of 0, 14 (low-dose), and 27 (high-dose) mg Pb/kg as Pb acetate, 5 d/wk, for 4 or 8 wks. At the end of Pb exposure, a solution containing Aβ40 was infused into the brain via the cannulated internal carotid artery. Data by ELISA showed a strikingly high affinity of Ab to cerebral vasculature, which was approximately 7–14 times higher than that to the parenchymal fractions collected from control brains. Pb exposure further aggravated the Aβ accumulation in cerebral vasculature in a dose-dependent manner. Western blot analyses revealed that Pb exposure decreased LRP1 expression in cortical capillaries and hippocampal parenchyma. Immunohistochemistry (IHC) studies further revealed a disrupted distribution of LRP1 alongside hippocampal vasculature accompanied with a decreased expression in hippocampal neurons by Pb exposure. Taken together, the current study demonstrated that the cerebral vasculature naturally possessed a high affinity to Aβ present in circulating blood. Pb exposure significantly increased Aβ accumulation in cerebral vasculature; such an increased Aβ accumulation was due partly to the diminished expression of LRP1 in response to Pb in tested brain regions. Perceivably, Pb-facilitated Ab aggravation in cerebral vasculature may contribute to Pb-associated amyloid alterations.
Multifaceted implementation and sustainability of a protocol for prehospital anaesthesia: a retrospective analysis of 2115 patients from helicopter emergency medical services
Authors: Ångerman Susanne , Kirves Hetti , Nurmi Jouni
Published: April 2023

Background

Prehospital emergency anaesthesia (PHEA) is a high-risk procedure. We developed a prehospital anaesthesia protocol for helicopter emergency medical services (HEMS) that standardises the process and involves ambulance crews as active team members to increase efficiency and patient safety. The aim of the current study was to evaluate this change and its sustainability in (i) on-scene time, (ii) intubation first-pass success rate, and (iii) protocol compliance after a multifaceted implementation process.

Methods

The protocol was implemented in 2015 in a HEMS unit and collaborating emergency medical service systems. The implementation comprised dissemination of information, lectures, simulations, skill stations, academic detailing, and cognitive aids. The methods were tailored based on implementation science frameworks. Data from missions were gathered from mission databases and patient records.

Results

During the study period (2012–2020), 2381 adults underwent PHEA. The implementation year was excluded; 656 patients were analysed before and 1459 patients after implementation of the protocol. Baseline characteristics and patient categories were similar. On-scene time was significantly redused after the implementation (median 32 [IQR 25–42] vs. 29 [IQR 21–39] minutes,p < 0.001). First pass success rate increased constantly during the follow-up period from 74.4% (95% CI 70.7–77.8%) to 97.6% (95% CI 96.7–98.3%),p = 0.0001. Use of mechanical ventilation increased from 70.6% (95% CI 67.0–73.9%) to 93.4% (95% CI 92.3–94.8%),p = 0.0001, and use of rocuronium increased from 86.4% (95% CI 83.6–88.9%) to 98.5% (95% CI 97.7–99.0%), respectively. Deterioration in compliance indicators was not observed.

Conclusions

We concluded that clinical performance in PHEA can be significantly improved through multifaceted implementation strategies.
Skin biopsy in adult patients with meningococcal purpura fulminans: a multicenter retrospective cohort study
Authors: Contou Damien , Béduneau Gaëtan , Rabault Charlotte , Sonneville Romain , Marchalot Antoine , Coudroy Rémi , Roux Damien , Cour Martin , Massol Julien , Préau Sébastien , de Prost Nicolas ,   The HOPEFUL Study Group, Pène Frédéric , Colin Gwenhaël , Barbier François , Toufik Kamel , Quelven Quentin , Schnell Guillaume , Ehrmann Stephan , Messet Hélène , Kimmoun Antoine , Beuret Pascal , Bruel Cédric , Colling Delphine , Conia Alexandre , Martin Luis Ensenyat , Reuter Danielle , Das Vincent , Challier Marion , Jozwiak Mathieu , Galbois Arnaud , Fraisse Mégan , Jaber Samir , Jochmans Sébastien , Kalfon Pierre , Conrad Marie , Lautrette Alexandre , Darreau Cédric , Lerolle Nicolas , Georges Hugues , Mégarbane Bruno , Pichereau Claire , Urbina Tomas , Maury Eric , de Prost Nicolas , Quenot Jean-Pierre , Sauneuf Bertrand , Schmidt Matthieu , Valette Xavier , Zafrani Lara , Da Silva Daniel , Rigault Guillaume , Woerther Paul-Louis
Published: April 2023

Background

Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF.

Methods

A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed.

Results

Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients.

Conclusions

Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment.
DREAMS: deep read-level error model for sequencing data applied to low-frequency variant calling and circulating tumor DNA detection
Authors: Christensen Mikkel H. , Drue Simon O. , Rasmussen Mads H. , Frydendahl Amanda , Lyskjær Iben , Demuth Christina , Nors Jesper , Gotschalck Kåre A. , Iversen Lene H. , Andersen Claus L. , Pedersen Jakob Skou
Published: April 2023

Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions. Using DREAMS, we develop statistical methods for variant calling (DREAMS-vc) and cancer detection (DREAMS-cc). For evaluation, we generate deep targeted NGS data of matching tumor and plasma DNA from 85 colorectal cancer patients. The DREAMS approach performs better than state-of-the-art methods for variant calling and cancer detection.
SNV-FEAST: microbial source tracking with single nucleotide variants
Authors: Briscoe Leah , Halperin Eran , Garud Nandita R.
Published: April 2023

Elucidating the sources of a microbiome can provide insight into the ecological dynamics responsible for the formation of these communities. Source tracking approaches to date leverage species abundance information; however, single nucleotide variants (SNVs) may be more informative because of their high specificity to certain sources. To overcome the computational burden of utilizing all SNVs for a given sample, we introduce a novel method to identify signature SNVs for source tracking. Signature SNVs used as input into a previously designed source tracking algorithm, FEAST, can more accurately estimate contributions than species and provide novel insights, demonstrated in three case studies.
Boosting genome editing efficiency in human cells and plants with novel LbCas12a variants
Authors: Zhang Liyang , Li Gen , Zhang Yingxiao , Cheng Yanhao , Roberts Nathaniel , Glenn Steve E. , DeZwaan-McCabe Diane , Rube H. Tomas , Manthey Jeff , Coleman Gary , Vakulskas Christopher A. , Qi Yiping
Published: April 2023

Background

Cas12a (formerly known as Cpf1), the class II type V CRISPR nuclease, has been widely used for genome editing in mammalian cells and plants due to its distinct characteristics from Cas9. Despite being one of the most robust Cas12a nucleases, LbCas12a in general is less efficient than SpCas9 for genome editing in human cells, animals, and plants.

Results

To improve the editing efficiency of LbCas12a, we conduct saturation mutagenesis inE. coliand identify 1977 positive point mutations of LbCas12a. We selectively assess the editing efficiency of 56 LbCas12a variants in human cells, identifying an optimal LbCas12a variant (RVQ: G146R/R182V/E795Q) with the most robust editing activity. We further test LbCas12a-RV, LbCas12a-RRV, and LbCas12a-RVQ in plants and find LbCas12a-RV has robust editing activity in rice and tomato protoplasts. Interestingly, LbCas12a-RRV, resulting from the stacking of RV and D156R, displays improved editing efficiency in stably transformed rice and poplar plants, leading to up to 100% editing efficiency inT0plants of both plant species. Moreover, this high-efficiency editing occurs even at the non-canonical TTV PAM sites.

Conclusions

Our results demonstrate that LbCas12a-RVQ is a powerful tool for genome editing in human cells while LbCas12a-RRV confers robust genome editing in plants. Our study reveals the tremendous potential of these LbCas12a variants for advancing precision genome editing applications across a wide range of organisms.
m6A readers ECT2/ECT3/ECT4 enhance mRNA stability through direct recruitment of the poly(A) binding proteins in Arabidopsis
Authors: Song Peizhe , Wei Lianhuan , Chen Zixin , Cai Zhihe , Lu Qiang , Wang Chunling , Tian Enlin , Jia Guifang
Published: April 2023

Background

RNAN6-methyladenosine (m6A) modification is critical for plant growth and crop yield. m6A reader proteins can recognize m6A modifications to facilitate the functions of m6A in gene regulation. ECT2, ECT3, and ECT4 are m6A readers that are known to redundantly regulate trichome branching and leaf growth, but their molecular functions remain unclear.

Results

Here, we show that ECT2, ECT3, and ECT4 directly interact with each other in the cytoplasm and perform genetically redundant functions in abscisic acid (ABA) response regulation during seed germination and post-germination growth. We reveal that ECT2/ECT3/ECT4 promote the stabilization of their targeted m6A-modified mRNAs, but have no function in alternative polyadenylation and translation. We find that ECT2 directly interacts with the poly(A) binding proteins, PAB2 and PAB4, and maintains the stabilization of m6A-modified mRNAs. Disruption ofECT2/ECT3/ECT4destabilizes mRNAs of ABA signaling-related genes, thereby promoting the accumulation of ABI5 and leading to ABA hypersensitivity.

Conclusion

Our study reveals a unified functional model of m6A mediated by m6A readers in plants. In this model, ECT2/ECT3/ECT4 promote stabilization of their target mRNAs in the cytoplasm.
Focal breast edema and breast edema score on T2-weighted images provides valuable biological information for invasive breast cancer
Authors: Chen Yanhong , Wang Lijun , Luo Ran , Liu Huanhuan , Zhang Yuzhen , Wang Dengbin
Published: April 2023

Background

Various features extracted from breast MRI have the potential to serve as noninvasive biomarkers for the prediction of the biologic behavior of breast cancer. The purpose of this study was to investigate the value of focal breast edema and breast edema score (BES) on T2-weighted images in providing valuable biological information for breast cancer patients’ personalized treatment.

Method

Two hundred and five lesions in 201 patients with invasive breast cancer confirmed by surgery or biopsy in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from November 2018 to October 2019 were retrospectively recruited and analyzed in this study. Focal edema and BES were evaluated at fat-suppressed T2 weighted imaging. All the lesions were divided into two groups according to the presence of focal edema. The differences in clinicopathological characteristics between the two groups and between different BES were compared.

Results

Two hundred and five lesions in 201 patients with invasive breast cancer were retrospectively recruited and analyzed in this study. On the fat-suppressed T2WI, focal edema was detected in 102 of 205 lesions (49.8%). BES was positively correlated with tumor size (p < 0.001), histologic grade (p = 0.006), Ki-67 index (p < 0.001), and N stage (p = 0.007), and was negatively correlated with expression of ER and PR (p < 0.001). Higher BES was more likely to present in patients with non-luminal breast cancer (p < 0.001) and suggested the possibility of a higher N stage.

Conclusions

Focal edema on T2WI of breast MRI indicates stronger tumor invasiveness, in which non-luminal breast cancer is more inclined to present focal edema. Breast edema score, a novel and practical tool, helps guide the individualized treatment of patients with invasive breast cancer.

Graphical Abstract

Critical relevance statement

Focal edema on T2WI of breast MRI indicates stronger tumor invasiveness. Breast edema score helps guide the individualized treatment of patients with invasive breast cancer.
Glia maturation factor-γ is required for initiation and maintenance of hematopoietic stem and progenitor cells
Authors: Li Honghu , Luo Qian , Cai Shuyang , Tie Ruxiu , Meng Ye , Shan Wei , Xu Yulin , Zeng Xiangjun , Qian Pengxu , Huang He
Published: April 2023

Background

In vertebrates, hematopoietic stem and progenitor cells (HSPCs) emerge from hemogenic endothelium in the floor of the dorsal aorta and subsequently migrate to secondary niches where they expand and differentiate into committed lineages. Glia maturation factor γ (gmfg) is a key regulator of actin dynamics that was shown to be highly expressed in hematopoietic tissue. Our goal is to investigate the role and mechanism of gmfg in embryonic HSPC development.

Methods

In-depth bioinformatics analysis of our published RNA-seq data identified gmfg as a cogent candidate gene implicated in HSPC development. Loss and gain-of-function strategies were applied to study the biological function of gmfg. Whole-mount in situ hybridization, confocal microscopy, flow cytometry, and western blotting were used to evaluate changes in the number of various hematopoietic cells and expression levels of cell proliferation, cell apoptosis and hematopoietic-related markers. RNA-seq was performed to screen signaling pathways responsible for gmfg deficiency-induced defects in HSPC initiation. The effect of gmfg on YAP sublocalization was assessed in vitro by utilizing HUVEC cell line.

Results

We took advantage of zebrafish embryos to illustrate that loss of gmfg impaired HSPC initiation and maintenance. In gmfg-deficient embryos, the number of hemogenic endothelium and HSPCs was significantly reduced, with the accompanying decreased number of erythrocytes, myelocytes and lymphocytes. We found that blood flow modulates gmfg expression and gmfg overexpression could partially rescue the reduction of HSPCs in the absence of blood flow. Assays in zebrafish and HUVEC showed that gmfg deficiency suppressed the activity of YAP, a well-established blood flow mediator, by preventing its shuttling from cytoplasm to nucleus. During HSPC initiation, loss of gmfg resulted in Notch inactivation and the induction of Notch intracellular domain could partially restore the HSPC loss in gmfg-deficient embryos.

Conclusions

We conclude that gmfg mediates blood flow-induced HSPC maintenance via regulation of YAP, and contributes to HSPC initiation through the modulation of Notch signaling. Our findings reveal a brand-new aspect of gmfg function and highlight a novel mechanism for embryonic HSPC development.
Atmospheric pressure predicts probability of departure for migratory songbirds
Authors: Cooper Nathan W. , Dossman Bryant C. , Berrigan Lucas E. , Brown J. Morgan , Cormier Dominic A. , Bégin-Marchand Camille , Rodewald Amanda D. , Taylor Philip D. , Tremblay Junior A. , Marra Peter P.
Published: April 2023

Background

Weather can have both delayed and immediate impacts on animal populations, and species have evolved behavioral adaptions to respond to weather conditions. Weather has long been hypothesized to affect the timing and intensity of avian migration, and radar studies have demonstrated strong correlations between weather and broad-scale migration patterns. How weather affects individual decisions about the initiation of migratory flights, particularly at the beginning of migration, remains uncertain.

Methods

Here, we combine automated radio telemetry data from four species of songbirds collected at five breeding and wintering sites in North America with hourly weather data from a global weather model. We use these data to determine how wind profit, atmospheric pressure, precipitation, and cloud cover affect probability of departure from breeding and wintering sites.

Results

We found that the probability of departure was related to changes in atmospheric pressure, almost completely regardless of species, season, or location. Individuals were more likely to depart on nights when atmospheric pressure had been rising over the past 24 h, which is predictive of fair weather over the next several days. By contrast, wind profit, precipitation, and cloud cover were each only informative predictors of departure probability in a single species.

Conclusions

Our results suggest that individual birds actively use weather information to inform decision-making regarding the initiation of departure from the breeding and wintering grounds. We propose that birds likely choose which date to depart on migration in a hierarchical fashion with weather not influencing decision-making until after the departure window has already been narrowed down by other ultimate and proximate factors.
Identification of an unusual pale green material on the surface of an ancient Chinese bronze vessel and application of laser cleaning to its removal
Authors: Shen Yijia , Zhang Guangmin , Zhou Xinguang
Published: April 2023

An ancient Chinese bronze vessel represented a typical difficult situation for conservation: a large quantity of an unwanted pale green material of unknown nature adhered to a surface fully decorated with delicate relief. The diagnostic itinerary, beginning with in-situ Raman spectroscopy analysis and followed by scanning electron microscopy-energy dispersive spectroscopy and X-ray diffraction, was found to be advantageous in revealing the presence of both inorganic and organic compounds in the pale green material. Irradiation with pulsed Nd:YAG 1064 nm laser in LQS regime (100 ns) followed by chemical cleaning using a low-toxicity solvent mixture proved to be respectful towards the original patina of the bronze as well as of high efficiency. Tentative analyses with the Raman spectroscopy and hyperspectral imaging were conducted to provide further indications on quality and visual effect during the cleaning result assessment. In parallel with the analyses and interventions on the bronze vessel, experiments were also carried out on mock-up samples in order to further explore the Raman scatter property and reactivity with laser ablation of mixed materials. The study provided reference for the optimization of diagnostic and conservation for the bronze artwork with similar situation.
Furosemide exacerbated the impairment of renal function, oxygenation and medullary damage in a rat model of renal ischemia/reperfusion induced AKI
Authors: Dilken Olcay , Ince Can , Kapucu Aysegul , Heeman Paul M. , Ergin Bülent
Published: April 2023

Background

Perioperative acute kidney injury (AKI) caused by ischemia–reperfusion (IR) is a significant contributor to mortality and morbidity after major surgery. Furosemide is commonly used in postoperative patients to promote diuresis and reduce tissue edema. However, the effects of furosemide on renal microcirculation, oxygenation and function are poorly understood during perioperative period following ischemic insult. Herein, we investigated the effects of furosemide in rats subjected IR insult.

Methods

24 Wistar albino rats were divided into 4 groups, with 6 in each; Sham-operated Control (C), Control + Furosemide (C + F), ischemia/reperfusion (IR), and IR + F. After induction of anesthesia (BL), supra-aortic occlusion was applied to IR and IR + F groups for 45 min followed by ongoing reperfusion for 15 min (T1) and 2 h (T2). Furosemide infusion was initiated simultaneously in the intervention groups after ischemia. Renal blood flow (RBF), vascular resistance (RVR), oxygen delivery (DO2ren) and consumption (VO2ren), sodium reabsorption (TNa+), oxygen utilization efficiency (VO2/TNa+), cortical (CμO2) and medullary (MμO2) microvascular oxygen pressures, urine output (UO) and creatinine clearance (Ccr) were measured. Biomarkers of inflammation, oxidative and nitrosative stress were measured and kidneys were harvested for histological analysis.

Results

IR significantly decreased RBF, mainly by increasing RVR, which was exacerbated in the IR + F group at T2 (2198 ± 879 vs 4233 ± 2636 dyne/s/cm5, p = 0.07). CμO2 (61.6 ± 6.8 vs 86 ± 6.6 mmHg) and MμO2 (51.1 ± 4.1 vs 68.7 ± 4.9 mmHg, p < 0.05) were both reduced after IR and did not improve by furosemide. Moreover, VO2/TNa+ increased in the IR + F group at T2 with respect to the IR group (IR: 3.3 ± 2 vs IR + F: 8.2 ± 10 p = 0.07) suggesting a possible deterioration of oxygen utilization. Ccr did not change, but plasma creatinine increased significantly in IR + F groups. Histopathology revealed widespread damage both in the cortex and medulla in IR, IR + F and C + F groups.

Conclusion

Renal microvascular oxygenation, renal function, renal vascular resistance, oxygen utilization and damage were not improved by furosemide administration after IR insult. Our study suggests that furosemide may cause additional structural and functional impairment to the kidney following ischemic injury and should be used with caution.
Case report: therapeutic monitoring of vancomycin in an acute liver failure patient with anuria under high-flow continuous hemodiafiltration
Authors: Ito Yuriko , Nakade Junya , Seki Akihiro , Gabata Ryosuke , Okazaki Mitsuyoshi , Nakanuma Shinichi , Fujita Arimi , Shimada Tsutomu , Yamashita Taro , Yagi Shintaro , Taniguchi Takumi , Sai Yoshimichi
Published: April 2023

Background

High-flow continuous hemodiafiltration (HF-CHDF) combines diffusive and convective solute removal and is employed for artificial liver adjuvant therapy. However, there is no report on dosage planning of vancomycin (VCM) in patients with acute liver failure under HF-CHDF.

Case presentation

A 20-year-old woman (154 cm tall, weighing 50 kg) was transferred to the intensive care unit (ICU) with acute liver failure associated with autoimmune liver disease. On the following day, HF-CHDF was started due to elevated plasma ammonia concentration. On ICU day 8, VCM was started for suspected pneumonia and meningitis (30 mg/kg loading dose, then 20 mg/kg every 12 hrs). However, on ICU day 10, VCM blood concentration was under the limit of detection (< 3.0 μg/mL) and the patient developed anuria. The VCM dose was increased to 20 mg/kg every 6 hrs. Calculation with a one-compartment model using the HF-CHDF blood flow rate as a surrogate for VCM clearance, together with hematocrit and protein binding ratio, predicted a trough VCM blood concentration of 15 μg/mL. The observed concentration was about 12 μg/mL. The difference may represent non-HF-CHDF clearance. Finally, living donor liver transplantation was performed.

Conclusion

We report an acute liver failure patient with anuria under HF-CHDF in whom VCM administration failed to produce an effective blood concentration, likely due to HF-CHDF-enhanced clearance. VCM dosage adjustment proved successful, and was confirmed by calculation using a one-compartment model.
Polycyclic aromatic hydrocarbon (PAH) biodegradation capacity revealed by a genome-function relationship approach
Authors: Huang Yue , Li Liguan , Yin Xiaole , Zhang Tong
Published: April 2023

Background

Polycyclic aromatic hydrocarbon (PAH) contamination has been a worldwide environmental issue because of its impact on ecosystems and human health. Biodegradation plays an important role in PAH removal in natural environments. To date, many PAH-degrading strains and degradation genes have been reported. However, a comprehensive PAH-degrading gene database is still lacking, hindering a deep understanding of PAH degraders in the era of big data. Furthermore, the relationships between the PAH-catabolic genotype and phenotype remain unclear.

Results

Here, we established a bacterial PAH-degrading gene database and explored PAH biodegradation capability via a genome-function relationship approach. The investigation of functional genes in the experimentally verified PAH degraders indicated that genes encoding hydratase-aldolase could serve as a biomarker for preliminarily identifying potential degraders. Additionally, a genome-centric interpretation of PAH-degrading genes was performed in the public genome database, demonstrating that they were ubiquitous in Proteobacteria and Actinobacteria. Meanwhile, the global phylogenetic distribution was generally consistent with the culture-based evidence. Notably, a few strains affiliated with the genera without any previously known PAH degraders (Hyphomonas, Hoeflea, Henriciella, Saccharomonospora, Sciscionella, Tepidiphilus, and Xenophilus) also bore a complete PAH-catabolic gene cluster, implying their potential of PAH biodegradation. Moreover, a random forest analysis was applied to predict the PAH-degrading trait in the complete genome database, revealing 28 newly predicted PAH degraders, of which nine strains encoded a complete PAH-catabolic pathway.

Conclusions

Our results established a comprehensive PAH-degrading gene database and a genome-function relationship approach, which revealed several potential novel PAH-degrader lineages. Importantly, this genome-centric and function-oriented approach can overcome the bottleneck of conventional cultivation-based biodegradation research and substantially expand our current knowledge on the potential degraders of environmental pollutants.
Intergenerational trajectories of inherited vulnerabilities amongst young women refugees in South Africa
Authors: Crankshaw Tamaryn L. , Freedman Jane , Mutambara Victoria M.
Published: April 2023

There is a paucity of scholarship examining the situated vulnerabilities of young women refugees who are either born in (second generation) or young children/adolescents on arrival in their host country (“1.5 generation”) and how these may impact intergenerational vulnerability or resilience. Based on qualitative research carried out in eThekwini (formerly known as Durban), South Africa amongst young women refugees (18–24 years) we highlight the issue of “inherited vulnerability”, examining how vulnerabilities can be transmitted across the refugee generations due to legal, economic and social structures which produce and maintain situations of inequality, rendering young women vulnerable to violence, exploitation and negative sexual and reproductive health outcomes. Ending the legal limbo in which they live and ensuring access to education and employment opportunities would help break the cycle of intergenerational precarity and support resilience of these young women as they transition to adulthood in South Africa.
PET/CT imaging 2 h after injection of [18F]PSMA-1007 can lead to higher staging of prostate cancer than imaging after 1 h
Authors: Hvittfeldt Erland , Bitzén Ulrika , Minarik David , Oddstig Jenny , Olsson Berit , Trägårdh Elin
Published: April 2023

Background

[18F]PSMA-1007 is a prostate specific membrane antigen (PSMA) ligand for positron emission tomography (PET) imaging of prostate cancer. Current guidelines recommend imaging 90–120 min after injection but strong data about optimal timing is lacking. Our aim was to study whether imaging after 1 h and 2 h leads to a different number of detected lesions, with a specific focus on lesions that might lead to a change in treatment.

Methods

195 patients underwent PET with computed tomography imaging 1 and 2 h after injection of [18F]PSMA-1007. Three readers assessed the status of the prostate or prostate bed and suspected metastases. We analyzed the location and number of found metastases to determine N- and M-stage of patients. We also analyzed standardized uptake values (SUV) in lesions and in normal tissue.

Results

Significantly more pelvic lymph nodes and bone metastases were found and higher N- and M-stages were seen after 2 h. In twelve patients (6.1%) two or three readers agreed on a higher N- or M-stage after 2 h. Conversely, in two patients (1.0%), two readers agreed on a higher stage at 1 h. SUVs in suspected malignant lesions and in normal tissues were higher at 2 h, but lower in the blood pool and urinary bladder.

Conclusions

Imaging at 2 h after injection of [18F]PSMA-1007 leads to more suspected metastases found than after 1 h, with higher staging in some patients and possible effect on patient treatment.
Bacillus spp. isolated from pepper leaves and their function and inhibition of the fungal plant pathogen Colletotrichum scovillei
Authors: Wei Lijuan , Yang Chengde , Cui Lingxiao , Jin Mengjun , Osei Richard
Published: April 2023

Background

Pepper is a popular ingredient in many Chinese households; however, anthracnose caused by Colletotrichum spp. has greatly decreased pepper production. The genus Bacillus is widely known for its important role in the development and protection of plants from phytopathogenic fungi.

Results

Fifty-eight endophytic strains were isolated from pepper leaves and tested for antifungal activity in this study. Specifically, L1-7 and L3-5 displayed growth inhibition rates of 79 and 80% against C. scovillei mycelium, respectively, while 25 of these strains all had growth inhibition rates of greater than 60%. Bacillus amyloliquefaciens and B. velezensis, based on culture and morphological identification with 16S rDNA and gyrB gene sequence analyses, were determined to be the respective species L1-7 and L3-5. Additionally, it was discovered that these two antagonistic endophytic bacteria could fix nitrogen, produce indoleacetic acid (IAA) and have a high salt tolerance. Pot experiments again showed excellent control of the pathogen C. scovillei by L1-7 and L3-5, with 80.64 and 73.39% control, respectively. Therefore, B. amyloliquefaciens (L1-7) and B. velezensis (L3-5) can be applied as biological control agents to protect peppers against C. scovillei-caused anthracnose.

Conclusion

Bacillus amyloliquefaciens (L1-7) and B. velezensis (L3-5) can be applied as biological control agents to protect peppers against C. scovillei-caused anthracnose. Thus, they can serve as promising biocontrol agents and plant growth promoters, and future research on the pertinent bacteria will serve as a useful guide for the creation of microbial resources.
Prevalence and determinants of antimicrobial resistance of pathogens isolated from cancer patients in an intensive care unit in Alexandria, Egypt
Authors: Mohamed Nancy , Ghazal Abeer , Ahmed Asmaa Abdel Hameed , Zaki Adel
Published: April 2023

Background

Infections caused by multidrug-resistant organisms (MDROs) are a globally increasing threat among critically ill patients, especially those with underlying malignancies. We aimed to assess the prevalence and susceptibility patterns of MDROs among cancer patients in intensive care units (ICU), and their predictors.

Methods

Over 4 years, we retrospectively reviewed medical records of 497 malignancy patients in the ICU of a tertiary hospital in Alexandria, Egypt. The data for various factors, such as demographic characteristics, comorbidities, causative pathogen, and antimicrobial resistance (AMR), were collected and analyzed using univariate analysis. Logistic multivariate regression analysis was used to estimate the probability of developing MDROs among this population.

Results

A total of 748 isolates were obtained from 1249 specimens. Gram-negative bacteria detected (459) comprised 61.4% of all isolates, while only 75 (10%) were gram-positive, and 214 (28.6%) were fungal pathogens. The most frequently encountered isolate was Klebsiella pneumoniae (n = 183), of which 107 were carbapenem-resistant (CR) and 62 were extended-spectrum beta-lactamase (ESBL)-producing. This was followed by Escherichia coli (n = 136), of which 17 were CR and 100 were ESBL-producing strains, while 3 were resistant to quinolones. Acinetobacter baumannii came in third (n = 67), with 63 being CR. The overall susceptibility of gram-negative bacteria was recorded as highest to colistin (97.3%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcal species among gram-positive bacteria were 54.6% and 33.3%, respectively, with no resistance reported to vancomycin or linezolid. Among the MDRO infection predictors were neutropenia, recent antibiotics use, and receiving chemotherapy. Neutropenia had the highest odds ratio (OR: 2.3, CI: 1.28–4.09), followed by recent antibiotics use (OR: 1.8, CI: 1.22–2.59).

Conclusion

Gram-negative bacilli were the most frequently reported MDROs, with resistance to higher generation cephalosporins and even carbapenems limiting antibiotic treatment options to older class antibiotics, such as colistin, with potential side effects, including nephrotoxicity. Estimating AMR probability using the prediction model of risk factors, such as neutropenia and previous antibiotics use, may be functional in the rapid identification of higher-risk patients.
A journey to explore the health properties of traditional Korean diet: a commentary
Authors: Choi Sang-Woon
Published: April 2023

Modern food consumption in Korea has been modified to the Western style in parallel with the rapid globalization and economic growth, which might be a cause of skyrocketing increase of cardiometabolic disorders such as obesity, type 2 diabetes mellitus, insulin resistance, dyslipidemia, hypertension, coronary artery disease, metabolic syndrome, and non-alcoholic fatty liver disease. This is not a Korea-specific phenomenon but also a worldwide common public health problem. A plausible mechanism underlying the unhealthy changes could be genetics, especially metabolic genes that cannot adequately respond to the fast dietary changes and are unable to deal with the high intake of animal fat and calorie. If this is true, then the following questions are raised: (1) do we need to go back to the traditional K-diet (K-diet) to reduce the development of these unhealthy cardiometabolic disorders?, (2) if so, what could be the underlying mechanism by which K-diet may convey those health effects?, and (3) if the K-diet is not sufficient enough to solve the current problem, how can we modify the K-diet to fit our purposes?
Electroconvulsive therapy in Oman: a national audit of demographics and standards
Authors: Al-Mahrouqi Tamadhir , Al-Balushi Naser , Al-Hamrashdi Saif , Al-Harrasi Ahmed
Published: April 2023

Background

We aim to address the dearth of knowledge regarding general electroconvulsive therapy practice in Oman, by examining and investigating the electroconvulsive therapy practices at all hospitals providing electroconvulsive therapy across the country, and to compare our local practice against the National Institute for Health and Care Excellence guidelines on the appropriate use of electroconvulsive therapy to inform the development of guidelines locally. Sultan Qaboos University Hospital and Al Masarra Hospital were included in a nationwide audit of all hospitals in Oman that administer electroconvulsive therapy. The demographics, diagnostic and electroconvulsive therapy indications, treatment characteristics, and side-effect profiles of all patients who had electroconvulsive therapy between January 2019 and December 2020 were collected from the hospital’s electronic data. A descriptive analysis of the results was performed.

Results

The total number of patients was 197 (92 males and 105 females). The most common diagnosis was schizophrenia 32.5%, followed by major depressive disorder 31.5%. The most common immediate side effect was headache 10.2%, followed by dizziness 7.1%, and amnesia 4.1%. Only 57.4% of patients who received electroconvulsive therapy met the NICE guidelines for appropriate electroconvulsive therapy use. Clinical status was assessed after each electroconvulsive therapy session for 66% of patients, and cognitive function monitoring was achieved for only 7.6% of patients.

Conclusions

The current audit has indicated that the assessment of the clinical status and cognitive functions of electroconvulsive therapy patients is inadequate. Because there is a significant rate of cognitive dysfunction following electroconvulsive therapy delivery, cognitive assessment before, during, and after therapy should be more rigorously implemented and documented.
Sphingosine 1-Phosphate Activates S1PR3 to Induce a Proinflammatory Phenotype in Human Myometrial Cells
Authors: Saurabh Kumar , Mbadhi Magdaleena Naemi , Prifti Kevin K , Martin Kaci T , Frolova Antonina I
Published: April 2023

One of the common mechanisms responsible for obstetric complications, affecting millions of women every year, is abnormal uterine contractility. Despite the critical importance of this process for women's health, the mechanisms of uterine contraction regulation remain poorly understood. The initiation of uterine smooth muscle (myometrial) contraction is an inflammatory process, accompanied by upregulation of proinflammatory genes and cytokine release. In this study, we show that sphingolipid metabolism is activated during human labor and that sphingosine 1-phosphate (S1P), the main bioactive sphingolipid, may modify the myometrial proinflammatory phenotype. Our data in both primary and immortalized human myometrial cells show that exogenous S1P induces a proinflammatory gene signature and upregulates the expression of known inflammatory markers of parturition, such as IL8 and COX2. Using expression of IL8 as a readout for S1P activity in myometrial cells, we established that these S1P effects are mediated through the activation of S1P receptor 3 (S1PR3) and downstream activation of ERK1/2 pathways. Inhibition of S1PR3 in human myometrial cells attenuates upregulation of IL8, COX2, and JUNB both at the mRNA and protein levels. Furthermore, activation of S1PR3 with a receptor-specific agonist recapitulated the effects seen after treatment with exogenous S1P. Collectively, these results suggest a signaling pathway activated by S1P in human myometrium during parturition and propose new targets for development of novel therapeutics to alter uterine contractility during management of preterm labor or labor dystocia.
Thyroid Stem Cell Speciation—a Major Role for PKC
Authors: Latif Rauf , Morshed Syed A , McCann Colin , Davies Terry F
Published: April 2023

Instructive signals that delineate the formation of thyroid follicles by thyrotropin (TSH) in stem cells are complex. Here, we have examined the role of protein kinase C (PKC) by using a unique Gαq/11 biased small molecule (MSq1) to develop thyroid progenitor cells. Mouse embryonic stem cells (mESCs) were differentiated into anterior endoderm cells and treated with either TSH or MSq1 in the presence or absence of PKC inhibitors. The transcriptional and translational response of key thyroid markers—sodium iodide symporter (NIS), thyroglobulin (TG), and thyrotropin receptor (TSHR) as well as potential signaling molecules—were then analyzed.

The data confirmed that MSq1 is a potent Gαq/11 activator with a major increase in Gαq/11 signaling when compared to TSH. MSq1 activation resulted in an increase in thyroid-specific genes, demonstrating that enhanced PKC signaling was able to induce their expression. The specificity of the PKC signals over the protein kinase A (PKA) pathway in regulating thyroid gene expression was shown by using a specific PKC enzyme inhibitor. The data revealed that TG and NIS expression were suppressed in the presence of the PKC inhibition but, in contrast, were not influenced by PKA inhibition. This indicated that PKC activation was the dominant pathway in the inductive process for thyroid hormone production. Furthermore, by examining PKC isoforms we found that PKCξ was the predominant form in the ES cells that mediated the effects. Since PKCξ can lead to activation of transforming growth factor-β–activated kinase (pTAK1), and its downstream effector nuclear factor κB (NFκB) complex, this demonstrated the involvement of the TAK1/NFκB pathway in thyroid speciation.
Revolutionizing radical prostatectomy - a comparative study of traditional and modern automated surgical techniques
Authors: Rojek Katarzyna , Szala-Czerwonka Karolina , Rejmer Adrian , Woś Natalia , Bednarz Lucjan , Wijas Karolina , Bialic Kinga , Bakalarczyk Rafał , Bialic Artur , Majewski Paweł
Published: April 2023

Introduction and purpose:

Prostate cancer is a common malignancy seen worldwide and second most common cancer among Polish men as well as globally. The symptoms of prostate cancer depend on severity of the cancer. Prostate cancer diagnosis is typically established through physical examination- digital rectal examination (DRE), PSA (prostate specific antigen) testing and confirmed by histopathological examination. The choice of treatment method depends on many factors: disease severity, risk assessment (based on PSA, TNM and Gleason score), age of the patient and expected survival time. Treatment include surgery, hormone therapy, radiation therapy or chemotherapy. In some cases, the combination of methods can be used to achieve better outcomes.  

One of available treatment option is radical prostatectomy which includes open radical prostatectomy (ORP), laparoscopic and laparoscopic robot assisted radical prostatectomy (RARP). We aimed at presenting various outcomes comparing open radical prostatectomy and robot assisted radical prostatectomy.

State of knowledge:

In order to carry out the review of the topic we began to collect information and comprehensive research in PubMed database. The analysis focused on the treatment of prostate cancer especially radical prostatectomy methods, the course of surgical procedure, postoperative care, oncological results, intraoperative and postoperative complications.

Conclusion:

ORP and RARP ae two surgical procedures used in prostate cancer treatment. Both of them involve removal of the prostate gland but also have a multiplicity of differences. RARP is safe and less invasive alternative to ORP with shorter postoperative hospitalization. However, ORP is known for no necessity for expensive specialized equipment such as Da Vinci or Versius robot surgery system and shorter operative time.
Budd-Chiari Syndrome - classification, diagnostics, imaging and treatment
Authors: Rybkowska Agnieszka , Żuchnik Magda , Licak Gabriela , Bętkowska Paulina , Radulski Jakub , Paluch Michał , Tomkiewicz Michał , Tomkiewicz Julia , Sałata Piotr , Szczuraszek Paulina
Published: April 2023

Introduction: Budd-Chiari syndrome is a rare condition which can be defined as hepatic venous outflow obstruction occurring at any level between the small hepatic veins and junction of the inferior vena cava and the right atrium. Symptoms may vary from mild or even asymptomatic for many years to fulminant hepatic failure. Imaging is the mainstay of diagnosis of BCS. Laboratory and ematological tests are invaluable in recognizing hematological and coagulation disorders that may be identified in up to 75% of the patients. The recommended therapeutic approach to BCS is based on a stepwise algorithm beginning with medical treatment, endovascular treatment to restore vessel patency, placement of transjugular portosystemic shunt (TIPS), and orthotopic liver transplantation as a last resort rescue treatment.
The aim of the study: This study aims to gather current knowledge about clinical manifestations, diagnosis and treatment of Budd-Chiari syndrome.
Materials and methods: This review was based on available data collected in the PubMed database and Google Scholar web search engine, using the keywords: ’Budd-Chiari syndrome’ ,’hepatic venous outflow obstruction’.
Conclusions: The treatment of Budd-Chiari syndrome requires interdisciplinary cooperation, which has resulted in the increasing curability of this rare disease over the last years.
Is nicotine vaporization a better alternative to traditional cigarette smoking? E-cigarettes harmful effects summary and the management of EVALI based on the latest literature
Authors: Szawica Dominik , Kuźniar Aleksandra , Fularska Kamila , Oleszko Michał , Wąsiewicz Edward , Bernacki Radosław , Bernacki Piotr , Dutka Martyna , Zardzewiały Witold
Published: April 2023

Introduction: Electronic cigarettes are battery-powered devices that allow users to inhale vapor produced by heating a liquid (e-liquid) containing nicotine and other substances. The first such devices were introduced in China in 2003, and subsequently approved for use in the European Union in 2006 and the United States in 2007. The number of e-cigarette users is constantly growing, with the largest increases observed in the 18-24 age group. Various modifications led to the emergence of a new disease entity in 2019 called EVALI (e-cigarette or vaping product use-associated lung injury).

Aim of the study: To summarize the current state of knowledge about harmful substances contained in e-cigarettes and to systematize the latest methods of management in cases of suspected EVALI.

Methods and materials: A literature review was conducted using PubMed, Google Scholar, and ScienceDirect, including publications from the last 8 years, using the following keywords: "E-cigarette," "Electronic cigarette," "EVALI," "THC," "Vitamin E."

Results: Electronic cigarettes contain a number of substances harmful to health. E-cigarettes have not been approved as nicotine replacement therapy. The presence of vitamin E breakdown products in the respiratory tract of EVALI patients has been confirmed. Vitamin E was primarily used to increase the volume of e-liquids containing THC.

Conclusions: Electronic cigarettes should not be used due to the numerous harmful substances they contain. When using e-cigarettes, both the devices and the e-liquids should be purchased from reputable sellers approved in the respective country. EVALI is a potentially fatal disease, and prompt diagnosis facilitates treatment