bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the performance of surfactant and charcoal-based cleaning products to effectively remove PAHs from firefighter gear
Authors: Hossain MD Tanjim , Girase Arjunsing G. , Ormond R. Bryan
Published: May 2023

Firefighters regularly respond to fire scenes where a mixture of chemicals including volatile, semi-volatile, and nonvolatile compounds are present in smoke and soot. Polycyclic aromatic hydrocarbons (PAHs) are common contaminants at fire scenes that may be deposited on the gear and the individual firefighter. Laundering is a common approach for the decontamination of contaminated gear. Surfactants are widely used by firefighters during laundering to remove PAHs as they are generally non-toxic and biodegradable. The removal of PAHs depends on the surfactant types, chemistries, and concentrations. This study evaluated the effect of surfactant concentrations to remove persistent contaminants like PAHs from turnout gear. The cleaning performance of different types of surfactants was also evaluated. Outer shell fabrics were contaminated with a standard mixture of 16 PAH compounds, and two commercial detergents were used at different concentrations. Additionally, the cleaning efficacy of eight commercially available regular and charcoal-based cleaning products was also determined against PAHs at a single surfactant concentration. For the decontamination method, a bench-scale washing procedure simulating the National Fire Protection Assocation 1851 laundering process was used. The removal efficacy of high molecular weight (HMW) PAHs were found to be lower compared to the low molecular weight PAHs for any type or any concentration of detergent. Our research also showed that the recommended surfactant concentrations provided by detergent manufacturers can be ineffective at removing the HMW PAHs from heavily contaminated fabric. With 1 mL of detergent in a 100-mL bath, which is multiple times higher than recommended amount, only 40% of HMW PAHs were removed. The cleaning efficacy can be increased to above 90% by using higher concentrations of detergents. This research shows that firefighters may need to use a higher concentration of detergent than the recommended amount to effectively remove PAHs from the gear. All the regular and charcoal-based detergents were able to remove PAHs effectively from contaminated fabrics when a higher concentration of detergent was used.
Micro milling of fused silica using picosecond laser shaped single crystal diamond tools
Authors: Song Jiacheng , Tong Zhen , Yao Zhenqiang , Jiang Xiangqian
Published: May 2023

Fused silica is widely used as a material for optical lenses owing to its excellent optical properties and low thermal expansion coefficient. However, as a hard and brittle material, there is very limited option of processing technologies to machining fused silica with surface structures. In this paper, a picosecond laser based single crystal diamond tool fabrication technology is proposed to generate micro milling tools with different geometrical designs, and the tool cutting performance is experimentally tested through micro-milling of fused silica under different cutting conditions. An optimal picosecond laser processing path is proposed to inhibit the graphitization of diamond tool and improve the concentricity of tool blades, and a multi-edge milling tool with a minimum rotary diameter of 0.4 mm can be obtained. The effects of rake angle on cutting force and the degree of brittle damage on the subsurface of fused silica are studied by micro milling tests of fused silica using the laser-shaped tools. The results show that the fused silica machined by diamond milling tool with a rake angle of −30° has the best surface finish (Ra = 41.2 nm). Using this laser-machined milling tool, a plurality of micro Fresnel lenses with aperture of 1.6 mm were successfully machined on a fused silica sheet.
Prevalence and pattern of multimorbidity among chronic kidney disease patients: a community study in chronic kidney disease hotspot area of Eastern India
Authors: Palo Subrata Kumar , Nayak Soumya Ranjan , Sahoo Debadutta , Nayak Swetalina , Mohapatra Ashis Kumar , Sahoo Aviram , Dash Pujarini , Pati Sanghamitra
Published: May 2023

Introduction

Chronic kidney disease (CKD) is mostly asymptomatic until reaching an advanced stage. Although conditions such as hypertension and diabetes can cause it, CKD can itself lead to secondary hypertension and cardiovascular disease (CVD). Understanding the types and prevalence of associated chronic conditions among CKD patient could help improve screening for early detection and case management.

Methods

A cross sectional study of 252 CKD patients in Cuttack, Odisha (from the last 4 years CKD data base) was telephonically carried out using a validated Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC) tool with the help of an android Open Data Kit (ODK). Univariate descriptive analysis was done to determine the socio-demographic distribution of CKD patients. A Cramer’s heat map was generated for showing Cramer’s coefficient value of association of each diseases.

Results

The mean age of participants was 54.11 (±11.5) years and 83.7% were male. Among the participants, 92.9% had chronic conditions (24.2% with one, 26.2% with two and 42.5% with three or more chronic conditions). Most prevalent chronic conditions were hypertension (48.4%), peptic ulcer disease (29.4%), osteoarthritis (27.8%) and diabetes (13.1%). Hypertension and osteoarthritis were found to be most commonly associated (Cramer’s V coefficient = 0.3).

Conclusion

Increased vulnerability to chronic conditions among CKD patients make them at higher risk for mortality and compromised quality of life. Regular screening of CKD patient for other chronic conditions (hypertension, diabetes, peptic ulcer disease, osteoarthritis and heart diseases) would help in detecting them early and undertake prompt management. The existing national program could be leveraged to achieve this.
Sex differences in the genetics of sarcoidosis across European and African ancestry populations
Authors: Xiong Ying , Kullberg Susanna , Garman Lori , Pezant Nathan , Ellinghaus David , Vasila Vasiliki , Eklund Anders , Rybicki Benjamin A. , Iannuzzi Michael C. , Schreiber Stefan , Müller-Quernheim Joachim , Montgomery Courtney G. , Grunewald Johan , Padyukov Leonid , Rivera Natalia V.
Published: May 2023

Background

Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren’s syndrome (LS) and non-Löfgren’s syndrome (non-LS).

Methods

A meta-analysis of genome-wide association studies was conducted on Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden (n = 3,843), Germany (n = 3,342), and the United States (n = 2,918), followed by an SNP lookup in the UK Biobank (UKB, n = 387,945). A genome-wide association study based on Immunochip data consisting of 141,000 single nucleotide polymorphisms (SNPs) was conducted in the sex groups. The association test was based on logistic regression using the additive model in LS and non-LS sex groups independently. Additionally, gene-based analysis, gene expression, expression quantitative trait loci (eQTL) mapping, and pathway analysis were performed to discover functionally relevant mechanisms related to sarcoidosis and biological sex.

Results

We identified sex-dependent genetic variations in LS and non-LS sex groups. Genetic findings in LS sex groups were explicitly located in the extended Major Histocompatibility Complex (xMHC). In non-LS, genetic differences in the sex groups were primarily located in the MHC class II subregion and ANXA11. Gene-based analysis and eQTL enrichment revealed distinct sex-specific gene expression patterns in various tissues and immune cell types. In LS sex groups, a pathway map related to antigen presentation machinery by IFN-gamma. In non-LS, pathway maps related to immune response lectin-induced complement pathway in males and related to maturation and migration of dendritic cells in skin sensitization in females were identified.

Conclusion

Our findings provide new evidence for a sex bias underlying sarcoidosis genetic architecture, particularly in clinical phenotypes LS and non-LS. Biological sex likely plays a role in disease mechanisms in sarcoidosis.
Development and validation of an electronic database-based frailty index to predict mortality and hospitalization in a population-based study of adults with SARS-CoV-2
Authors: Rebora Paola , Scirè Carlo Alberto , Occhino Giuseppe , Bortolan Francesco , Leoni Olivia , Cideni Francesco , Zucchelli Alberto , Focà Emanuele , Marengoni Alessandra , Bellelli Giuseppe , Valsecchi Maria Grazia
Published: May 2023

Background

Electronic health databases are used to identify people at risk of poor outcomes. Using electronic regional health databases (e-RHD), we aimed to develop and validate a frailty index (FI), compare it with a clinically based FI, and assess its association with health outcomes in community-dwellers with SARS-CoV-2.

Methods

Data retrieved from the Lombardy e-RHD were used to develop a 40-item FI (e-RHD-FI) in adults (i.e., aged ≥18 years) with a positive nasopharyngeal swab polymerase chain reaction test for SARS-CoV-2 by May 20, 2021. The considered deficits referred to the health status before SARS-CoV-2. The e-RHD-FI was validated against a clinically based FI (c-FI) obtained from a cohort of people hospitalized with COVID-19 and in-hospital mortality was evaluated. e-RHD-FI performance was evaluated to predict 30-day mortality, hospitalization, and 60-day COVID-19 WHO clinical progression scale, in Regional Health System beneficiaries with SARS-CoV-2.

Results

We calculated the e-RHD-FI in 689,197 adults (51.9% females, median age 52 years). On the clinical cohort, e-RHD-FI correlated with c-FI and was significantly associated with in-hospital mortality. In a multivariable Cox model, adjusted for confounders, each 0.1-point increment of e-RHD-FI was associated with increased 30-day mortality (Hazard Ratio, HR 1.45, 99% Confidence Intervals, CI: 1.42–1.47), 30-day hospitalization (HR per 0.1-point increment = 1.47, 99%CI: 1.46–1.49), and WHO clinical progression scale (Odds Ratio = 1.84 of deteriorating by one category, 99%CI 1.80–1.87).

Conclusion

The e-RHD-FI can predict 30-day mortality, 30-day hospitalization, and WHO clinical progression scale in a large population of community-dwellers with SARS-CoV-2 test positivity. Our findings support the need to assess frailty with e-RHD.
Clinical Pharmacy Faculty Provision of Direct Patient Care, Challenges, and Opportunities
Authors: Korayem Ghazwa B. , Alqahtani Lama Ali , Alsulaiman Sultanah Hisham , Alhammad Abdullah M. , Badreldin Hisham A. , Alkhudair Nora , Al Sulaiman Khalid , Aljuhani Ohoud
Published: May 2023

Background

The quadripartite mission of clinical track faculty members involves research, teaching, services, and direct patient care. However, the extent of faculty involvement in direct patient care remains a challenge. Thus, the study’s objective is to evaluate the effort spent on direct patient care by clinical faculty of pharmacy schools in Saudi Arabia (S.A.) and identify factors that hinder or facilitate providing direct patient care services.

Methods

This multi-institutional, cross-sectional questionnaire study conducted between July 2021 and March 2022 involved several pharmacy schools’ clinical pharmacy faculty members in S.A. The primary outcome was the percentage of time/effort spent on patient care services and other academic responsibilities. The secondary outcomes were the factors affecting the effort spent on direct patient care and the barriers preventing the provision of clinical services.

Results

A total of 44 faculty members took the survey. The percentage of effort spent on clinical education was highest at a median (IQR) of 37.5 (30, 50), followed by that spent on patient care [19 (10, 28.75)]. The percentages of effort spent on education and the length of academic experience were negatively associated with efforts spent on direct patient care. The most commonly reported barrier affecting fulfilling patient care duties was the lack of a clear practice policy (68%).

Conclusion

Although most clinical pharmacy faculty members were involved in direct patient care, half of them devoted only 20% or less of their time to it. An effective effort allocation for clinical faculty duties will require the development of a clinical faculty workload model that sets realistic expectations about the time spent on clinical and non-clinical duties.
Long-term use of somatostatin analogs for chronic gastrointestinal bleeding in hereditary hemorrhagic telangiectasia
Authors: Torres-Iglesias Raquel , Mora-Luján José María , Iriarte Adriana , Cerdà Pau , Alba Esther , Sánchez-Corral Miguel Ángel , Berrozpe Ana , Cruellas Francesc , Gamundí Enric , Ribas Jesús , Castellote Jose , Riera-Mestre Antoni
Published: May 2023

Background

Chronic bleeding due to gastrointestinal (GI) involvement in patients with hemorrhagic hereditary telangiectasia (HHT) can provoke severe anemia with high red blood cells (RBC) transfusion requirements. However, the evidence about how to deal with these patients is scarce. We aimed to assess the long-term efficacy and safety of somatostatin analogs (SA) for anemia management in HHT patients with GI involvement.

Methods

This is a prospective observational study including patients with HHT and GI involvement attended at a referral center. SA were considered for those patients with chronic anemia. Anemia-related variables were compared in patients receiving SA before and during treatment. Patients receiving SA were divided into responders (patients with minimal hemoglobin levels improvement >10 g/L and maintaining hemoglobin levels ≥80 g/L during treatment), and non-responders. Adverse effects during follow-up were collected.

Results

Among 119 HHT patients with GI involvement, 67 (56.3%) received SA. These patients showed lower minimal hemoglobin levels (73 [60–87] vs. 99 [70.2–122.5], p < 0.001), and more RBC transfusion requirements (61.2% vs. 38.5%, p = 0.014) than patients without SA therapy. Median treatment period was 20.9 ± 15.2 months. During treatment, there was a statistically significant improvement in minimum hemoglobin levels (94.7 ± 29.8 g/L vs. 74.7 ± 19.7, p < 0.001) and a reduction of patients with minimal hemoglobin levels <80 g/L (39 vs. 61%, p = 0.007) and RBC transfusions requirement (33.9% vs. 59.3%, p < 0.001). Sixteen (23.9%) patients showed mild adverse effects, mostly diarrhea or abdominal pain, leading to treatment discontinuation in 12 (17.9%) patients. Fifty-nine patients were eligible for efficacy assessment and 32 (54.2%) of them were considered responders. Age was associated with non-responder patients, OR 95% CI; 1.070 (1.014–1.130), p = 0.015.

Conclusion

SA can be considered a long-term effective and safe option for anemia management in HHT patients with GI bleeding. Older age is associated with poorer response.
Indocyanine green fluorescence angiography decreases the risk of anastomotic leakage after rectal cancer surgery: a systematic review and meta-analysis
Authors: Xia Shijun , Wu Wenjiang , Luo Lidan , Ma Lijuan , Yu Linchong , Li Yue
Published: May 2023

Background

Anastomotic leakage is a serious complication after rectal cancer resection. Intraoperative use of indocyanine green fluorescence angiography (ICGFA) can help prevent anastomotic leakage, but its use is controversial. We conducted a systematic review and meta-analysis to determine the efficacy of ICGFA in reducing anastomotic leakage.

Methods

Relevant data and research published until September 30, 2022, was retrieved from the PubMed, Embase, and Cochrane Library databases, and the difference in the incidence of anastomotic leakage after rectal cancer resection between ICGFA and standard treatment was compared.

Results

This meta-analysis included 22 studies with a total of 4,738 patients. The results showed that ICGFA use during surgery decreased the incidence of anastomotic leakage after rectal cancer surgery [risk ratio (RR) = 0.46; 95% confidence interval (95% CI), 0.39–0.56; p < 0.001]. Simultaneously, in subgroup analyses for different regions, ICGFA was found to be used to reduce the incidence of anastomotic leakage after rectal cancer surgery in Asia (RR = 0.33; 95% CI, 0.23–0.48; p < 0.00001) and Europe (RR = 0.38; 95% CI, 0.27–0.53; p < 0.00001) but not in North America (RR = 0.72; 95% CI, 0.40–1.29; p = 0.27). Regarding different levels of anastomotic leakage, ICGFA reduced the incidence of postoperative type A anastomotic leakage (RR = 0.25; 95% CI, 0.14–0.44; p < 0.00001) but did not reduce the incidence of type B (RR = 0.70; 95% CI, 0.38–1.31; p = 0.27) and type C (RR = 0.97; 95% CI, 0.51–1.97; p = 0.93) anastomotic leakages.

Conclusion

ICGFA has been linked to a reduction in anastomotic leakage after rectal cancer resection. However, multicenter randomized controlled trials with larger sample sizes are required for further validation.
Prediction of postoperative visual acuity in patients with age-related cataracts using macular optical coherence tomography-based deep learning method
Authors: Wang Jingwen , Wang Jinhong , Chen Dan , Wu Xingdi , Xu Zhe , Yu Xuewen , Sheng Siting , Lin Xueqi , Chen Xiang , Wu Jian , Ying Haochao , Xu Wen
Published: May 2023

Background

To predict postoperative visual acuity (VA) in patients with age-related cataracts using macular optical coherence tomography-based deep learning method.

Methods

A total of 2,051 eyes from 2,051 patients with age-related cataracts were included. Preoperative optical coherence tomography (OCT) images and best-corrected visual acuity (BCVA) were collected. Five novel models (I, II, III, IV, and V) were proposed to predict postoperative BCVA. The dataset was randomly divided into a training (n = 1,231), validation (n = 410), and test set (n = 410). The performance of the models in predicting exact postoperative BCVA was evaluated using mean absolute error (MAE) and root mean square error (RMSE). The performance of the models in predicting whether postoperative BCVA was improved by at least two lines in the visual chart (0.2LogMAR) was evaluated using precision, sensitivity, accuracy, F1 and area under curve (AUC).

Results

Model V containing preoperative OCT images with horizontal and vertical B-scans, macular morphological feature indices, and preoperative BCVA had a better performance in predicting postoperative VA, with the lowest MAE (0.1250 and 0.1194LogMAR) and RMSE (0.2284 and 0.2362LogMAR), and the highest precision (90.7% and 91.7%), sensitivity (93.4% and 93.8%), accuracy (88% and 89%), F1 (92% and 92.7%) and AUCs (0.856 and 0.854) in the validation and test datasets, respectively.

Conclusion

The model had a good performance in predicting postoperative VA, when the input information contained preoperative OCT scans, macular morphological feature indices, and preoperative BCVA. The preoperative BCVA and macular OCT indices were of great significance in predicting postoperative VA in patients with age-related cataracts.
The prognostic effects of the geriatric nutritional risk index on elderly acute kidney injury patients in intensive care units
Authors: Liao Dan , Deng Yonghua , Li Xinchun , Huang Ju , Li Jiayue , Pu Ming , Zhang Fenglian , Wang Lijun
Published: May 2023

Introduction

The geriatric nutritional risk index (GNRI), a nutritional screening tool specifically for the aging population, has been proven to be associated with worse outcomes in chronic kidney disease patients, especially in the hemodialysis population. However, the predictive validity of GNRI in critically ill elderly patients with acute kidney injury (AKI) is yet to be determined. This analysis sought to examine the prognostic effects of GNRI on elderly AKI patients in intensive care units (ICUs).

Methods

We collected elderly AKI patient-relevant data from the Medical Information Mart for Intensive Care III database. AKI was diagnosed and staged according to the “Kidney Disease Improving Global Outcomes” criteria. In the study, 1-year mortality was considered the primary outcome, whereas in-hospital, ICU, 28-day and 90-day mortality, and prolonged length of stay in ICU and hospital were selected as the secondary outcomes.

Results

In all, 3,501 elderly patients with AKI were selected for this study, with a 1-year mortality rate of 36.4%. We classified the study population into low (≤98) and high (>98) GNRI groups based on the best cutoff value. The incidence of endpoints was remarkably lower in patients with elevated GNRI (p < 0.001). When stratified by the AKI stage, patients with high GNRI at AKI stages 1, 2, and 3 had markedly lower 1-year mortality than those with low GNRI (all p < 0.05). The multivariable regression analysis identified the independent prognostic ability of GNRI on the research outcomes (all p < 0.05). Restricted cubic spline exhibited a linear correlation between GNRI and 1-year death (p for non-linearity = 0.434). The prognostic implication of GNRI on 1-year mortality was still significant in patients with the most subgroups.

Conclusion

In critically ill elderly patients with AKI, elevated GNRI upon admission was strongly correlated with a lower risk of unfavorable outcomes.
Assessment of causal associations among gut microbiota, metabolites, and celiac disease: a bidirectional Mendelian randomization study
Authors: Li Ting , Feng Yan , Wang Chun , Shi Tian , Abudurexiti Adilai , Zhang Mengxia , Gao Feng
Published: May 2023

Background

A growing number of studies have implicated that gut microbial abundance and metabolite concentration alterations are associated with celiac disease (CD). However, the causal relationship underlying these associations is unclear. Here, we used Mendelian randomization (MR) to reveal the causal effect of gut microbiota and metabolites on CD.

Methods

Genome-wide association study (GWAS) summary-level data for gut microbiota, metabolites, and CD were extracted from published GWASs. Causal bacterial taxa and metabolites for CD were determined by two-sample MR analyses. The robustness of the results was assessed with sensitivity analyses. Finally, reverse causality was investigated with a reverse MR analysis.

Results

Genetically, increased genus Bifidobacterium was potentially associated with higher CD risk (odds ratio [OR] = 1.447, 95% confidence interval [CI]: 1.054–1.988, p = 0.022) while phylum Lentisphaerae (OR = 0.798, 95% CI: 0.648–0.983, p = 0.034) and genus Coprobacter (OR = 0.683, 95% CI: 0.531–0.880, p = 0.003) were related to lower CD risk. Moreover, there were suggestive associations between CD and the following seven metabolites: 1-oleoylglycerophosphoethanolamine, 1-palmitoylglycerophosphoethanolamine, 1,6-anhydroglucose, phenylacetylglutamine, tryptophan betaine, 10-undecenoate, and tyrosine. Sensitivity analyses deemed the results reliable without pleiotropy.

Conclusion

We investigated the causal relationships between gut microbiota, metabolites, and CD with two-sample MR. Our findings suggest several novel potential therapeutic targets for CD treatment. Further understanding of the underlying mechanism may provide insights into CD pathogenesis.
Improvement effect of biochar on soil microbial community structure and metabolites of decline disease bayberry
Authors: Ren Haiying , Guo Hao , Shafiqul Islam Mohammad , Zaki Haitham E. M. , Wang Zhenshuo , Wang Hongyan , Qi Xingjiang , Guo Junning , Sun Li , Wang Qi , Li Bin , Li Gang , Radwan Khlode S. A.
Published: May 2023

Decline disease is a new disease that has recently caused severe damage in bayberry industry. The effect of biochar on decline disease was determined by investigating the changes in the vegetative growth and fruit quality of bayberry trees as well as soil physical and chemical properties, microbial community structure, and metabolites. Results indicated that the application of biochar could improve the vigor and fruit quality of diseased trees, and rhizosphere soil microbial diversity at the levels of phyla, orders, and genera. The relative abundance of Mycobacterium, Crossiella, Geminibasidium, and Fusarium were significantly increased, while Acidothermus, Bryobacter, Acidibacter, Cladophialophora, Mycena, and Rickenella were significantly decreased by biochar in rhizosphere soil of decline diseased bayberry. Analysis of redundancies (RDA) of microbial communities and soil characteristics revealed that the composition of bacterial and fungal communities was significantly affected by the pH, organic matter, alkali hydrolyzable nitrogen, available phosphorus, available potassium, exchangeable calcium and exchangeable magnesium in bayberry rhizosphere soil, and the contribution rates to fungi were larger than those to bacteria at the genus level. Biochar greatly influenced the metabolomics distribution of rhizosphere soils of decline disease bayberry. One hundred and nine different metabolites from both the presence and absence of biochar, mainly include acid, alcohol, ester, amine, amino acid, sterol, sugar, and other secondary metabolites, of which the contents of 52 metabolites were increased significantly such as aconitic acid, threonic acid, pimelic acid, epicatechin, and lyxose. The contents of 57 metabolites decreased significantly, such as conduritol β-expoxide, zymosterol, palatinitol, quinic acid, and isohexoic acid. There was a great difference between the absence and presence of biochar in 10 metabolic pathways, including thiamine metabolism, arginine and proline metabolism, glutathione metabolism, ATP-binding cassette (ABC) transporters, butanoate metabolism, cyanoamino acid metabolism, tyrosine metabolism, phenylalanine metabolism, phosphotransferase system (pts), and lysine degradation. There was a significant correlation between the relative content of microbial species and the content of secondary metabolites in rhizosphere soil at the levels of bacterial and fungal phyla, order, and genus. Overall, this study highlighted the significant influence of biochar in decline disease by regulating soil microbial community, physical and chemical properties, and secondary metabolites in rhizosphere soil, which provided a novel strategy for managing bayberry decline disease.
Spatiotemporal dissemination of ESBL-producing Enterobacterales in municipal sewer systems: a prospective, longitudinal study in the city of Basel, Switzerland
Authors: Gómez-Sanz Elena , Bagutti Claudia , Roth Jan A. , Alt Hug Monica , García-Martín Ana B. , Maurer Pekerman Laura , Schindler Ruth , Furger Reto , Eichenberger Lucas , Steffen Ingrid , Egli Adrian , Hübner Philipp , Stadler Tanja , Aguilar-Bultet Lisandra , Tschudin-Sutter Sarah
Published: May 2023

Background

The contribution of community and hospital sources to the transmission of extended-spectrum β-lactamase producing Enterobacterales (ESBL-PE) remains elusive.

Aim

To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel.

Methods

Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites, n = 17) or community and hospital wastewater (mixed sites, n = 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification.

Results

Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates, Escherichia coli (85%, 1,140/1,334) and Klebsiella pneumoniae (11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with E. coli consistently predominating. The proportion of K. pneumoniae isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of E. coli was higher in samples from urban sites (p = 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 102 vs. 1.6 × 102 CFU/mL). E. coli-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21).

Conclusion

ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent.
Acute stressors do not impair short-term memory or attention in an aged mouse model of amyloidosis
Authors: DiMarco Giuliana M. , Harris Breanna N. , Savonenko Alena V. , Soto Paul L.
Published: May 2023

Memory impairment in Alzheimer’s disease patients is thought to be associated with the accumulation of amyloid-beta peptides and tau proteins. However, inconsistent reports of cognitive deficits in pre-clinical studies have raised questions about the link between amyloid-beta and cognitive decline. One possible explanation may be that studies reporting memory deficits often involve behavioral assessments that entail a high stress component. In contrast, in tasks without a high stress component transgenic mice do not consistently show declines in memory. The glucocorticoid cascade hypothesis of aging and the vicious cycle of stress framework suggest that stress exacerbates dementia progression by initiating a cycle of hypothalamic-pituitary-adrenal axis activation and subsequent brain deterioration. Using the APPswe/PS1dE9 mouse model of amyloidosis, we assessed whether stressor exposure prior to testing differentially impaired cognitive performance of aged male and female mice. As part of a larger study, mice performed a delayed match-to-position (DMTP) or a 3-choice serial-reaction time (3CSRT) task. Unexpectedly, these mice did not exhibit cognitive declines during aging. Therefore, at 73 and 74 weeks of age, we exposed mice to a predator odor or forced swim stressor prior to testing to determine if stress revealed cognitive deficits. We predicted stressor exposure would decrease performance accuracy more robustly in transgenic vs. non-transgenic mice. Acute stressor exposure increased accuracy in the DMTP task, but not in the 3CSRT task. Our data suggest that acute stressor exposure prior to testing does not impair cognitive performance in APPswe/PS1dE9 mice.
Free fatty acids support oligodendrocyte survival in a mouse model of amyotrophic lateral sclerosis
Authors: Maruyama Takashi , Tanabe Shogo , Uyeda Akiko , Suzuki Tatsunori , Muramatsu Rieko
Published: May 2023

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the white matter degeneration. Although changes in blood lipids are involved in the pathogenesis of neurological diseases, the pathological role of blood lipids in ALS remains unclear.

Methods and results

We performed lipidome analysis on the plasma of ALS model mice, mutant superoxide dismutase 1 (SOD1G93A) mice, and found that the concentration of free fatty acids (FFAs), including oleic acid (OA) and linoleic acid (LA), decreased prior to disease onset. An in vitro study revealed that OA and LA directly inhibited glutamate-induced oligodendrocytes cell death via free fatty acid receptor 1 (FFAR1). A cocktail containing OA/LA suppressed oligodendrocyte cell death in the spinal cord of SOD1G93A mice.

Discussion

These results suggested that the reduction of FFAs in the plasma is a pathogenic biomarker for ALS in the early stages, and supplying a deficiency in FFAs is a potential therapeutic approach for ALS by preventing oligodendrocyte cell death.
The influence of non-stationarity of spike signals on decoding performance in intracortical brain-computer interface: a simulation study
Authors: Wan Zijun , Liu Tengjun , Ran Xingchen , Liu Pengfu , Chen Weidong , Zhang Shaomin
Published: May 2023

Introduction

Intracortical Brain-Computer Interfaces (iBCI) establish a new pathway to restore motor functions in individuals with paralysis by interfacing directly with the brain to translate movement intention into action. However, the development of iBCI applications is hindered by the non-stationarity of neural signals induced by the recording degradation and neuronal property variance. Many iBCI decoders were developed to overcome this non-stationarity, but its effect on decoding performance remains largely unknown, posing a critical challenge for the practical application of iBCI.

Methods

To improve our understanding on the effect of non-stationarity, we conducted a 2D-cursor simulation study to examine the influence of various types of non-stationarities. Concentrating on spike signal changes in chronic intracortical recording, we used the following three metrics to simulate the non-stationarity: mean firing rate (MFR), number of isolated units (NIU), and neural preferred directions (PDs). MFR and NIU were decreased to simulate the recording degradation while PDs were changed to simulate the neuronal property variance. Performance evaluation based on simulation data was then conducted on three decoders and two different training schemes. Optimal Linear Estimation (OLE), Kalman Filter (KF), and Recurrent Neural Network (RNN) were implemented as decoders and trained using static and retrained schemes.

Results

In our evaluation, RNN decoder and retrained scheme showed consistent better performance under small recording degradation. However, the serious signal degradation would cause significant performance to drop eventually. On the other hand, RNN performs significantly better than the other two decoders in decoding simulated non-stationary spike signals, and the retrained scheme maintains the decoders’ high performance when changes are limited to PDs.

Discussion

Our simulation work demonstrates the effects of neural signal non-stationarity on decoding performance and serves as a reference for selecting decoders and training schemes in chronic iBCI. Our result suggests that comparing to KF and OLE, RNN has better or equivalent performance using both training schemes. Performance of decoders under static scheme is influenced by recording degradation and neuronal property variation while decoders under retrained scheme are only influenced by the former one.
Magnetic resonance spectroscopy investigation in the right human hippocampus following spinal cord injury
Authors: Pfyffer Dario , Zimmermann Sandra , Şimşek Kadir , Kreis Roland , Freund Patrick , Seif Maryam
Published: May 2023

Objective

Preclinical studies have shown that cognitive impairments following spinal cord injury (SCI), such as impaired spatial memory, are linked to inflammation, neurodegeneration, and reduced neurogenesis in the right hippocampus. This cross-sectional study aims to characterize metabolic and macrostructural changes in the right hippocampus and their association to cognitive function in traumatic SCI patients.

Methods

Within this cross-sectional study, cognitive function was assessed in 28 chronic traumatic SCI patients and 18 age-, sex-, and education-matched healthy controls by a visuospatial and verbal memory test. A magnetic resonance spectroscopy (MRS) and structural MRI protocol was performed in the right hippocampus of both groups to quantify metabolic concentrations and hippocampal volume, respectively. Group comparisons investigated changes between SCI patients and healthy controls and correlation analyses investigated their relationship to memory performance.

Results

Memory performance was similar in SCI patients and healthy controls. The quality of the recorded MR spectra was excellent in comparison to the best-practice reports for the hippocampus. Metabolite concentrations and volume of the hippocampus measured based on MRS and MRI were not different between two groups. Memory performance in SCI patients and healthy controls was not correlated with metabolic or structural measures.

Conclusion

This study suggests that the hippocampus may not be pathologically affected at a functional, metabolic, and macrostructural level in chronic SCI. This points toward the absence of significant and clinically relevant trauma-induced neurodegeneration in the hippocampus.
Brain fog in long COVID limits function and health status, independently of hospital severity and preexisting conditions
Authors: Nordvig Anna S. , Rajan Mangala , Lau Jennifer D. , Kingery Justin R. , Mahmud Meem , Chiang Gloria C. , De Leon Mony J. , Goyal Parag
Published: May 2023

Importance

The U.S. government has named post-acute sequelae of COVID-19 (longCOVID) as influential on disability rates. We previously showed that COVID-19 carries a medical/functional burden at 1  year, and that age and other risk factors of severe COVID-19 were not associated with increased longCOVID risk. Long-term longCOVID brain fog (BF) prevalence, risk factors and associated medical/functional factors are poorly understood, especially after mild SARS-CoV-2 infection.

Methods

A retrospective observational cohort study was conducted at an urban tertiary-care hospital. Of 1,032 acute COVID-19 survivors from March 3–May 15, 2020, 633 were called, 530 responded (59.2 ± 16.3  years, 44.5% female, 51.5% non-White) about BF prevalence, other longCOVID, post-acute ED/hospital utilization, perceived health/social network, effort tolerance, disability.

Results

At approximately 1-year, 31.9% (n = 169) experienced BF. Acute COVID-19 severity, age, and premorbid cardiopulmonary comorbidities did not differ between those with/without BF at 1  year. Patients with respiratory longCOVID had 54% higher risk of BF than those without respiratory longCOVID. BF associated with sleep disturbance (63% with BF vs.29% without BF, p < 0.0001), shortness of breath (46% vs.18%, p < 0.0001), weakness (49% vs.22%, p < 0.0001), dysosmia/dysgeusia (12% vs.5%, p < 0.004), activity limitations (p < 0.001), disability/leave (11% vs.3%, p < 0.0001), worsened perceived health since acute COVID-19 (66% vs.30%, p < 0.001) and social isolation (40% vs.29%, p < 0.02), despite no differences in premorbid comorbidities and age.

Conclusions and relevance

A year after COVID-19 infection, BF persists in a third of patients. COVID-19 severity is not a predictive risk factor. BF associates with other longCOVID and independently associates with persistent debility.
Deep brain stimulation for patients with refractory epilepsy: nuclei selection and surgical outcome
Authors: Yan Hao , Wang Xueyuan , Zhang Xiaohua , Qiao Liang , Gao Runshi , Ni Duanyu , Shu Wei , Xu Cuiping , Ren Liankun , Yu Tao
Published: May 2023

Objective

By studying the surgical outcome of deep brain stimulation (DBS) of different target nuclei for patients with refractory epilepsy, we aimed to explore a clinically feasible target nucleus selection strategy.

Methods

We selected patients with refractory epilepsy who were not eligible for resective surgery. For each patient, we performed DBS on a thalamic nucleus [anterior nucleus of the thalamus (ANT), subthalamic nucleus (STN), centromedian nucleus (CMN), or pulvinar nucleus (PN)] selected based on the location of the patient's epileptogenic zone (EZ) and the possible epileptic network involved. We monitored the clinical outcomes for at least 12 months and analyzed the clinical characteristics and seizure frequency changes to assess the postoperative efficacy of DBS on the different target nuclei.

Results

Out of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and four (8.9%) of them reported being seizure-free for at least 1 year. Among the patients with temporal lobe epilepsy (TLE, n = 36) and extratemporal lobe epilepsy (ETLE, n = 9), 22 (61.1%) and 7 (77.8%) responded to the treatment, respectively. Among the 45 patients who underwent ANT-DBS, 28 (62%) had focal to bilateral tonic-clonic seizures (FBTCS). Of these 28 patients, 18 (64%) responded to the treatment. Out of the 65 included patients, 16 had EZ related to the sensorimotor cortex and underwent STN-DBS. Among them, 13 (81.3%) responded to the treatment, and two (12.5%) were seizure-free for at least 6 months. Three patients had Lennox–Gastaut syndrome (LGS)-like epilepsy and underwent CMN-DBS; all of them responded to the treatment (seizure frequency reductions: 51.6%, 79.6%, and 79.5%). Finally, one patient with bilateral occipital lobe epilepsy underwent PN-DBS, reducing the seizure frequency by 69.7%.

Significance

ANT-DBS is effective for patients with TLE or ETLE. In addition, ANT-DBS is effective for patients with FBTCS. STN-DBS might be an optimal treatment for patients with motor seizures, especially when the EZ overlaps the sensorimotor cortex. CMN and PN may be considered modulating targets for patients with LGS-like epilepsy or occipital lobe epilepsy, respectively.
Neurorehabilitation robotics: how much control should therapists have?
Authors: Hasson Christopher J. , Manczurowsky Julia , Collins Emily C. , Yarossi Mathew
Published: May 2023

Robotic technologies for rehabilitating motor impairments from neurological injuries have been the focus of intensive research and capital investment for more than 30 years. However, these devices have failed to convincingly demonstrate greater restoration of patient function compared to conventional therapy. Nevertheless, robots have value in reducing the manual effort required for physical therapists to provide high-intensity, high-dose interventions. In most robotic systems, therapists remain outside the control loop to act as high-level supervisors, selecting and initiating robot control algorithms to achieve a therapeutic goal. The low-level physical interactions between the robot and the patient are handled by adaptive algorithms that can provide progressive therapy. In this perspective, we examine the physical therapist's role in the control of rehabilitation robotics and whether embedding therapists in lower-level robot control loops could enhance rehabilitation outcomes. We discuss how the features of many automated robotic systems, which can provide repeatable patterns of physical interaction, may work against the goal of driving neuroplastic changes that promote retention and generalization of sensorimotor learning in patients. We highlight the benefits and limitations of letting therapists physically interact with patients through online control of robotic rehabilitation systems, and explore the concept of trust in human-robot interaction as it applies to patient-robot-therapist relationships. We conclude by highlighting several open questions to guide the future of therapist-in-the-loop rehabilitation robotics, including how much control to give therapists and possible approaches for having the robotic system learn from therapist-patient interactions.
Engineering circuits of human iPSC-derived neurons and rat primary glia
Authors: Girardin Sophie , Ihle Stephan J. , Menghini Arianna , Krubner Magdalena , Tognola Leonardo , Duru Jens , Fruh Isabelle , Müller Matthias , Ruff Tobias , Vörös János
Published: May 2023

Novel in vitro platforms based on human neurons are needed to improve early drug testing and address the stalling drug discovery in neurological disorders. Topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons have the potential to become such a testing system. In this work, we build in vitro co-cultured circuits of human iPSC-derived neurons and rat primary glial cells using microfabricated polydimethylsiloxane (PDMS) structures on microelectrode arrays (MEAs). Our PDMS microstructures are designed in the shape of a stomach, which guides axons in one direction and thereby facilitates the unidirectional flow of information. Such circuits are created by seeding either dissociated cells or pre-aggregated spheroids at different neuron-to-glia ratios. Furthermore, an antifouling coating is developed to prevent axonal overgrowth in undesired locations of the microstructure. We assess the electrophysiological properties of different types of circuits over more than 50 days, including their stimulation-induced neural activity. Finally, we demonstrate the inhibitory effect of magnesium chloride on the electrical activity of our iPSC circuits as a proof-of-concept for screening of neuroactive compounds.
Lactate shuttling as an allostatic means of thermoregulation in the brain
Authors: Kane Daniel A. , Foo Alexander C. Y. , Noftall Erin B. , Brebner Karen , Marangoni D. Gerrard
Published: May 2023

Lactate, the redox-balanced end product of glycolysis, travels within and between cells to fulfill an array of physiologic functions. While evidence for the centrality of this lactate shuttling in mammalian metabolism continues to mount, its application to physical bioenergetics remains underexplored. Lactate represents a metabolic “cul-de-sac,” as it can only re-enter metabolism by first being converted back to pyruvate by lactate dehydrogenase (LDH). Given the differential distribution of lactate producing/consuming tissues during metabolic stresses (e.g., exercise), we hypothesize that lactate shuttling vis-à-vis the exchange of extracellular lactate between tissues serves a thermoregulatory function, i.e., an allostatic strategy to mitigate the consequences of elevated metabolic heat. To explore this idea, the rates of heat and respiratory oxygen consumption in saponin-permeabilized rat cortical brain samples fed lactate or pyruvate were measured. Heat and respiratory oxygen consumption rates, and calorespirometric ratios were lower during lactate vs. pyruvate-linked respiration. These results support the hypothesis of allostatic thermoregulation in the brain with lactate.
Functional-oriented, portable brain–computer interface training for hand motor recovery after stroke: a randomized controlled study
Authors: Fu Jianghong , Chen Shugeng , Shu Xiaokang , Lin Yifang , Jiang Zewu , Wei Dongshuai , Gao Jiajia , Jia Jie
Published: May 2023

Background

Brain–computer interfaces (BCIs) have been proven to be effective for hand motor recovery after stroke. Facing kinds of dysfunction of the paretic hand, the motor task of BCIs for hand rehabilitation is relatively single, and the operation of many BCI devices is complex for clinical use. Therefore, we proposed a functional-oriented, portable BCI equipment and explored the efficiency of hand motor recovery after a stroke.

Materials and methods

Stroke patients were randomly assigned to the BCI group and the control group. The BCI group received BCI-based grasp/open motor training, while the control group received task-oriented guidance training. Both groups received 20 sessions of motor training in 4 weeks, and each session lasted for 30 min. The Fugl–Meyer assessment of the upper limb (FMA-UE) was applied for the assessment of rehabilitation outcomes, and the EEG signals were obtained for processing.

Results

The progress of FMA-UE between the BCI group [10.50 (5.75, 16.50)] and the control group [5.00 (4.00, 8.00)] was significantly different (Z = −2.834, P = 0.005). Meanwhile, the FMA-UE of both groups improved significantly (P < 0.001). A total of 24 patients in the BCI group achieved the minimal clinically important difference (MCID) of FMA-UE with an effective rate of 80%, and 16 in the control group achieved the MCID, with an effective rate of 51.6%. The lateral index of the open task in the BCI group was significantly decreased (Z = −2.704, P = 0.007). The average BCI accuracy for 24 stroke patients in 20 sessions was 70.7%, which was improved by 5.0% in the final session compared with the first session.

Conclusion

Targeted hand movement and two motor task modes, namely grasp and open, to be applied in a BCI design may be suitable in stroke patients with hand dysfunction. The functional-oriented, portable BCI training can promote hand recovery after a stroke, and it is expected to be widely used in clinical practice. The lateral index change of inter-hemispheric balance may be the mechanism of motor recovery.

Trial registration number

ChiCTR2100044492.