bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Blood‐Brain Barrier and Beyond: Challenges and Opportunities for Novel CNS Therapeutics
Authors: de Lange Elizabeth C. M. , Hammarlund Udenaes Margareta
Published: February 2022

This review addresses questions on how to accomplish successful central nervous system (CNS) drug delivery (i.e., having the right concentration at the right CNS site, at the right time), by understanding the rate and extent of blood‐brain barrier (BBB) transport and intra‐CNS distribution in relation to CNS target site(s) exposure. To this end, we need to obtain and integrate quantitative and connected data on BBB using the Combinatory Mapping Approach that includes in vivo and ex vivo animal measurements, and the physiologically based comprehensive LEICNSPK3.0 mathematical model that can translate from animals to humans. For small molecules, slow diffusional BBB transport and active influx and efflux BBB transport determine the differences between plasma and CNS pharmacokinetics. Obviously, active efflux is important for limiting CNS drug delivery. Furthermore, liposomal formulations of small molecules may to a certain extent circumvent active influx and efflux at the BBB. Interestingly, for CNS pathologies, despite all reported disease associated BBB and CNS functional changes in animals and humans, integrative studies typically show a lack of changes on CNS drug delivery for the small molecules. In contrast, the understanding of the complex vesicle‐based BBB transport modes that are important for CNS delivery of large molecules is in progress, and their BBB transport seems to be significantly affected by CNS diseases. In conclusion, today, CNS drug delivery of small drugs can be well assessed and understood by integrative approaches, although there is still quite a long way to go to understand CNS drug delivery of large molecules.
Push‐out bond strength of the calcium silicate‐based endodontic cements in the presence of blood: A systematic review and meta‐analysis of in vitro studies
Authors: Alipour Mahdieh , Faraji Gavgani Leili , Ghasemi Negin
Published: February 2022

Objectives

The push‐out bond strength (POBS) of calcium silicate‐based cements (CSCs) to the dentinal wall is considered one of the essential physical properties for clinical success. The presence of blood in the treatment area affects the POBS of these types of cement. This study aimed to evaluate the impact of blood contamination on the bond strength of CSCs and dentinal walls.

Material and Methods

This systematic review was performed by searching electronic databases (MEDLINE‐PubMed, Scopus, and EMBASE) to include relevant in vitro studies published between 1992 and April 2020. Two reviewers independently evaluated the selected studies and extracted data on the type of studied CSCs, evaluated area of the teeth, sample size, the dimension of a prepared area, slice thickness, storage duration, the setting of the universal testing machine (UTM), effects of blood contamination on POBS of CSCs and their failure modes. The bond strength of evaluated CSCs in studies was used for network meta‐analysis.

Results

Initial searches identified 292 articles, while only 13 articles met the inclusion criteria. Full texts of these articles were evaluated, and data extraction was performed. The effect of blood contamination on bond strength to the dentinal wall was assessed in various CSCs such as PMTA, Biodentine, and AMTA. The network meta‐analysis results showed that the bond strength of Biodentine was significantly higher than other types of cement in blood presence (p < .05).

Conclusions

Based on the current systematic review, despite controversies among the result of the different articles and the lack of data for some CSCs like bioaggregate, it could be concluded that the bond strength of Biodentine to the dentinal wall is better than other evaluated CSCs in the presence of blood.
Impaired tongue motor control after temporomandibular disorder: A proof‐of‐concept case‐control study of tongue print
Authors: Alvarado Caroline , Arminjon Audrey , Damieux‐Verdeaux Clovis , Lhotte Claire , Condemine Chloé , Cousin Anne‐Sabine , Sigaux Nicolas , Bouletreau Pierre , Mateo Sébastien
Published: February 2022

Background

Temporomandibular disorder (TMD) perturbs the tongue motor control and consequently impairs oral function, but strength training reduces this impairment. However, tongue motor control is widely reduced to a matter of strength.

Objectives

To investigate the accuracy of the tongue placement as a measure of tongue motor control in patients with TMD compared with age‐ and sex‐matched healthy participants.

Material and Methods

This proof‐of‐concept case‐control study was prospective, observational, and part of the TMIQ study (NCT04102306). After pointing against a wood stick while maintaining the tongue as sharp as possible, the examinator drew the contour of the tongue print on the wood stick, which was then scanned for image analyses to compute the area for each participant using ImageJ.

Results

A total of 94 participants were included, all patients with TMD (n = 47) diagnosed with myalgia, 61% with intra‐articular joint disorder accordingly to the DC/TMD. The median (IQR) tongue print area was 117 (111) mm2 for the TMD group and 93.5 (76.2) mm2 for the control group (V = 352, p = .04) and the median [95% confidence interval] difference was 25.4 [1.3; 51.0] mm². Overlapping of the 95% confidence intervals of the area evidenced no significant difference between the categories of the DC/TMD. The corrected each area–total correlation (r = .24) suggests a reasonably homogenous thus valid measure.

Conclusion

The results suggest that TMD impairs the motor control of the tongue. Therefore, the sharpest tongue pointing test may constitute a simple and accessible clinical tool to assess the accuracy of tongue placement in TMD patients. The study was registered on ClinicalTrial.gov with identification number NCT04102306.
Hydrogen Spillover‐Enhanced Heterogeneously Catalyzed Hydrodeoxygenation for Biomass Upgrading
Authors: Geng Yanyan , Li Hao
Published: March 2022

Hydrodeoxygenation (HDO) is regarded as a promising technology for biomass upgrading to obtain sustainable and competitive chemicals and fuels. In fact, biomass HDO over heterogeneous solid catalysts is often accompanied by the phenomenon of hydrogen spillover, which further affects the catalytic performance. Thus, it is necessary to gain in‐depth understand the promoting effect of hydrogen spillover in the biomass HDO process to obtain desired conversion and selectivity. This Review summarized the extensive research on hydrogen spillover in biomass refining and discussed in detail the regulation mechanism of hydrogen spillover in biomass HDO process, mainly by regulating different active center sites on catalyst supports, such as metal sites, acid sites, surface functional groups, and defective sites, which exhibit independent and synergistic characteristics promoting catalyst activity, selectivity, and stability. Finally, the prospective of hydrogen spillover in biomass HDO applications was critically evaluated, and the key technical challenges in developing “hydrogen‐free” HDO and upgrading biofuels were highlighted. The presentation of hydrogen spillover‐enhanced catalytic biomass HDO in this Review will hopefully provide insight and guidance for further development of efficient catalysts and preparation of high‐value chemicals in the future.
Melatonin enhances osteoblastogenesis of senescent bone marrow stromal cells through NSD2‐mediated chromatin remodelling
Authors: Xie Ying , Han Na , Li Feng , Wang Lijuan , Liu Gerui , Hu Meilin , Wang Sheng , Wei Xuelei , Guo Jing , Jiang Hongmei , Wang Jingjing , Li Xin , Wang Yixuan , Wang Jingya , Bian Xiyun , Zhu Zhongjiao , Zhang Hui , Liu Chunhua , Liu Xiaozhi , Liu Zhiqiang
Published: February 2022

Background

Aging‐associated osteoporosis is frequently seen in the elderly in clinic, but efficient managements are limited because of unclear nosogenesis. The current study aims to investigate the role of melatonin on senescent bone marrow stromal cells (BMSCs) and the underlying regulating mechanism.

Methods

Melatonin levels were tested by ELISA. Gene expression profiles were performed by RNA‐sequencing, enrichment of H3K36me2 on gene promoters was analyzed by Chromatin Immunoprecipitation Sequencing (ChIP‐seq), and chromatin accessibility was determined by Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing (ATAC‐seq). Osteogenesis of BMSCs in vitro was measured by Alizarin Red and Alkaline Phosphatase staining, and in vivo effects of melatonin was assessed by histological staining and micro computed tomography (micro‐CT) scan. Correlation of NSD2 expression and severity of senile osteoporosis patients were analyzed by Pearson correlation.

Results

Melatonin levels were decreased during aging in human bone marrow, accompanied by downregulation of the histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) expression in the senescent BMSCs. Melatonin stimulated the expression of NSD2 through MT1/2‐mediated signaling pathways, resulting in the rebalancing of H3K36me2 and H3K27me3 modifications to increase chromatin accessibility of the osteogenic genes, runt‐related transcription factor 2 (RUNX2) and bone gamma‐carboxyglutamate protein (BGLAP). Melatonin promoted osteogenesis of BMSCs in vitro, and alleviates osteoporosis progression in the aging mice. In clinic, severity of senile osteoporosis (SOP) was negatively correlated with melatonin level in bone marrow, as well as NSD2 expression in BMSCs. Similarly, melatonin remarkably enhanced osteogenic differentiation of BMSCs derived from SOP patients in vitro.

Conclusions

Collectively, our study dissects previously unreported mechanistic insights into the epigenetic regulating machinery of melatonin in meliorating osteogenic differentiation of senescent BMSC, and provides evidence for application of melatonin in preventing aging‐associated bone loss.
Tumour cells are sensitised to ferroptosis via RB1CC1‐mediated transcriptional reprogramming
Authors: Xue Xiangfei , Ma Lifang , Zhang Xiao , Xu Xin , Guo Susu , Wang Yikun , Qiu Shiyu , Cui Jiangtao , Guo Wanxin , Yu Yongchun , Sun Fenyong , Shi Yi , Wang Jiayi
Published: February 2022

Background

Ferroptosis, a form of regulated cell death, is an important topic in the field of cancer research. However, the signalling pathways and factors that sensitise tumour cells to ferroptosis remain elusive.

Methods

We determined the level of ferroptosis in cells by measuring cell death and lipid reactive oxygen species (ROS) production. The expression of RB1‐inducible coiled‐coil 1 (RB1CC1) and related proteins was analyzed by immunoblotting and immunohistochemistry. Immunofluorescence was used to determine the subcellular localization of RB1CC1. We investigated the mechanism of RB1CC1 nuclear translocation by constructing a series of RB1CC1 variants. To examine the ferroptosis‐ and RB1CC1‐dependent transcriptional program in tumour cells, chromatin immunoprecipitation sequencing was performed. To assess the effect of c‐Jun N‐terminal kinase (JNK) agonists on strenthening imidazole ketone erastin (IKE) therapy, we constructed cell‐derived xenograft mouse models. Mouse models of hepatocellular carcinoma to elucidate the importance of Rb1cc1 in IKE‐based therapy of liver tumourigenesis.

Results

RB1CC1 is upregulated by lipid ROS and that nuclear translocation of phosphorylation of RB1CC1 at Ser537 was essential for sensitising ferroptosis in tumour cells. Upon ferroptosis induction, nuclear RB1CC1 sharing forkhead box (FOX)‐binding motifs recruits elongator acetyltransferase complex subunit 3 (ELP3) to strengthen H4K12Ac histone modifications within enhancers linked to ferroptosis. This also stimulated transcription of ferroptosis‐associated genes, such as coiled‐coil–helix–coiled‐coil–helix domain containing 3 (CHCHD3), which enhanced mitochondrial function to elevate mitochondrial ROS early following induction of ferroptosis. FDA‐approved JNK activators reinforced RB1CC1 nuclear translocation and sensitised cells to ferroptosis, which strongly suggested that JNK is upstream of RB1CC1. Nuclear localisation of RB1CC1 correlated with lipid peroxidation in clinical lung cancer specimens. Rb1cc1 was essential for ferroptosis agonists to suppress liver tumourigenesis in mice.

Conclusions

Our findings indicate that RB1CC1‐associated signalling sensitises tumour cells to ferroptosis and that targeting RB1CC1 may be beneficial for tumour treatment.
Maternal deprivation and milk replacement affect the integrity of gray and white matter in the developing lamb brain
Authors: Love Scott A. , Haslin Emmanuelle , Bellardie Manon , Andersson Frédéric , Barantin Laurent , Filipiak Isabelle , Adriaensen Hans , Fazekas Csilla L. , Leroy Laurène , Zelena Dóra , Morisse Mélody , Elleboudt Frédéric , Moussu Christian , Lévy Frédéric , Nowak Raymond , Chaillou Elodie
Published: February 2022

The psychoendocrine evaluation of lamb development has demonstrated that maternal deprivation and milk replacement alters health, behavior, and endocrine profiles. While lambs are able to discriminate familiar and non‐familiar conspecifics (mother or lamb), only lambs reared with their mother develop such clear social discrimination or preference. Lambs reared without mother display no preference for a specific lamb from its own group. Differences in exploratory and emotional behaviors between mother‐reared and mother‐deprived lambs have also been reported. As these behavioural abilities are supported by the brain, we hypothesize that rearing with maternal deprivation and milk replacement leads to altered brain development and maturation. To test this hypothesis, we examined brain morphometric and microstructural variables extracted from in vivo T1‐weighted and diffusion‐weighted magnetic resonance images acquired longitudinally (1 week, 1.5 months, and 4.5 months of age) in mother‐reared and mother‐deprived lambs. From the morphometric variables the caudate nuclei volume was found to be smaller for mother‐deprived than for mother‐reared lambs. T1‐weighted signal intensity and radial diffusivity were higher for mother‐deprived than for mother‐reared lambs in both the white and gray matters. The fractional anisotropy of the white matter was lower for mother‐deprived than for mother‐reared lambs. Based on these morphometric and microstructural characteristics we conclude that maternal deprivation delays and affects lamb brain growth and maturation.
Inhibition Effect of Oryzanol on the Degradation of Tocopherol and the Oxidation Kinetic of Rice Bran Oils with Different Content of Oryzanol and Tocopherol
Authors: Huang Jianhua , Chen Chuying , Zhao Zhengmei , Li Xu , Wang Xingguo , Jin Qingzhe , Tang Junjun
Published: February 2022

The purpose of this study is to investigate the inhibitory effect of oryzanol on the degradation of tocopherol during heating of rice bran oil at 110 and 170 °C and the oxidation kinetics of rice bran oil. Results demonstrate the degradation of oryzanol and tocopherol in rice bran oils follow the first‐order kinetic models. The higher concentration of oryzanol has no inhibitory effect on the degradation of tocopherol when the concentration of tocopherol in rice bran oil is 500 mg kg−1. However, when the concentrations of tocopherol reach 1500 and 2000 mg kg−1, higher oryzanol concentration make the inhibitory effects on the degradation of tocopherol more pronounced. Compared with rice bran oils containing lower levels of tocopherol and oryzanol, rice bran oils containing higher levels of tocopherol and oryzanol have higher activation energy (Ea), activation enthalpy (ΔH), and activation entropy (ΔS) and a larger temperature acceleration factor (Q10), which indicate that higher levels of oryzanol and tocopherol promote the thermal oxidation of rice bran oil. Therefore, in the compound application of tocopherol and oryzanol in rice bran oil, the influence of its content on the thermal oxidation of oil should be fully considered.

Practical Application: This study may be useful for the grain and oil industry because studies on the degradation kinetics of oryzanol and tocopherol during heating of rice bran oil and oxidation kinetics of rice bran oil are still lacking in the literature. The results of this study is valuable for predicting and evaluating the oxidation process and nutritional properties of rice bran oils under various thermal oxidation conditions.
Palladium‐Catalyzed C(sp2/sp3)−H Arylation of Aryl Glycinamide Derivatives Using Picolinamide as Directing Group
Authors: Martínez‐Flores Sebastián , Mujica‐Martinez Cesar A. , Polindara‐García Luis A.
Published: March 2022

A Pd(II)‐catalyzed C(sp2/sp3)−H bond arylation protocol has been developed to access ortho‐diaryl, ortho‐mono‐aryl, and biaryl‐diarylmethane‐glycinamide derivatives bearing picolinamide as directing group. Mechanistic details of the process have been obtained by computational modelling of the activation reaction through DFT calculations.
Observation of Mercury Underpotential Deposition on an Ir Surface using the Electrochemical Quartz Crystal Microbalance Technique
Authors: Nagai Tsukasa , Siroma Zyun , Akita Tomoki , Ioroi Tsutomu
Published: March 2022

Development of a technique to measure electrochemical surface area (ECSA) is essential to evaluate the activity and durability of Ir‐based catalysts for polymer electrolyte membrane (PEM) water electrolysis. Mercury underpotential deposition (Hg‐UPD) on Ir and IrOx in perchloric acid has been reported to be useful for ECSA evaluation. However, previous methods need to be carefully evaluated for reproducibility due to the presence of Hg(II)/Hg(I) redox reactions, and differences in UPD potentials between studies. Here, the electrochemical behavior of an Ir electrode in a mercury nitrate containing solution was investigated using the electrochemical quartz crystal microbalance method. We confirmed that a Hg adatom is reversibly adsorbed and desorbed on an Ir surface at potentials over 0.7 V vs the reversible hydrogen electrode in both perchloric acid and sulfuric acid. These results contribute to the establishment of a reproducible method for ECSA calculations for Ir‐based catalysts.
How Does Location Determine the Economic Competitiveness of Grid‐Scale Emerging Photovoltaics?
Authors: Nieto-Díaz Balder A. , Crossland Andrew F. , Groves Christopher
Published: March 2022

Emerging photovoltaic (PV) devices with perovskite or organic absorber layers may play a substantial role in our energy future due to their potential low‐cost manufacture and differing properties compared to established silicon equivalents. However, it is not clear to what extent physical and human geography influences the cost competitiveness of emerging PV, and consequently, how emerging PV should be optimized for differing locations. Herein, a levelized cost of energy (LCOE) model is used to examine the influence of insolation and economic factors by predicting the price of energy from emerging PV in eight different countries. Herein, it is demonstrated that capital costs play an important role in competitiveness, with low capital cost locations (e.g., India) benefitting more from low module costs and improved degradation, whereas high‐cost locations (e.g., Japan) benefitted more from improved efficiency. The importance of considering location is demonstrated in the results as part of selecting which emerging PV is used, which is emphasized by predictions of LCOE for emerging PV devices reported in the literature over an 8 year period.
Palaeoproterozoic S‐type granites from Garhwal Himalaya, NW India: Geochemistry, Sm–Nd isotope systematics and tectonic implications
Authors: Mishra Sumit , Slabunov Alexander I. , Nainwal Harish C. , Singh Vinod K. , Singh Pradip K. , Nesterova Natalia S. , Svetov Sergei A.
Published: March 2022

A combined geochemical and Sm–Nd isotopic study on the Palaeoproterozoic (1,845 Ma) granites of the Lesser Himalayan Crystalline Sequence (LHCS) in the Garhwal region of NW India has been done in the present study. These granite samples are characterized by high silica, alumina, and potash and belong to a peraluminous to strongly peraluminous series, having molar A/CNK values of 1.01 to 2.4. The low P2O5 contents and its negative correlation with SiO2 presiding out that the granites have S‐type affinity, also supported by various classification diagrams (ACF; SiO2 vs. P2O5, Na2O + K2O‐CaO, and Th). The concentration of trace elements Ba, Sr, Nb, and Ti are low, and Rb, Th, U, and Pb are found to be high. The granites have low total rare earth elements contents of 56.19–229.16 ppm with enrichment in Light rare earth elements (LREE) ([La/Yb]N = 1.61–15.08) and negative europium anomaly (Eu/Eu* = 0.12–0.31). Sm–Nd isotope studies were also performed for three granite samples. Estimated model ages as 2.5–2.7 Ga, indicates the contribution of the Archean crustal substrate as their protolith source. Therefore, we assume that the melting of metasedimentary rocks with Archean protolith can form these peraluminous granites in an accretional–collisional event, during the Palaeoproterozoic on the western flank of the Columbia supercontinent.
Ethnicity, disease severity, and survival in Canadian patients with primary biliary cholangitis
Authors: Roberts Surain B. , Hirschfield Gideon M. , Worobetz Lawrence J. , Vincent Catherine , Flemming Jennifer A. , Cheung Angela , Qumosani Karim , Swain Mark , Grbic Dusanka , Ko Hin Hin , Peltekian Kevork , Selzner Nazia , Abrahamyan Lusine , Aziz Bishoi , Lytvyak Ellina , Tirona Kattleya , Gulamhusein Aliya F. , Janssen Harry L. A. , Montano‐Loza Aldo J. , Mason Andrew L. , Hansen Bettina E. ,   the Canadian Network for Autoimmune Liver Disease (CaNAL)
Published: February 2022

Background and Aims

We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC).

Approach and Results

Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event–free and liver transplantation–free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed‐effects regression. Health‐related quality of life was assessed using the Short Form 36, the PBC‐40 questionnaire, and the 5‐D Itch scale and analyzed using mixed‐effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant–free and event‐free survival compared to White patients (HR, 3.66; 95% CI, 2.23–6.01; HR, 3.09; 95% CI, 1.94–4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow‐up.

Conclusions

Indigenous Canadians with PBC present with advanced disease and have worse long‐term outcomes compared to White patients.
Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
Authors: Martínez‐Arranz Ibon , Bruzzone Chiara , Noureddin Mazen , Gil‐Redondo Ruben , Mincholé Itziar , Bizkarguenaga Maider , Arretxe Enara , Iruarrizaga‐Lejarreta Marta , Fernández‐Ramos David , Lopitz‐Otsoa Fernando , Mayo Rebeca , Embade Nieves , Newberry Elizabeth , Mittendorf Bettina , Izquierdo‐Sánchez Laura , Smid Vaclav , Arnold Jorge , Iruzubieta Paula , Pérez Castaño Ylenia , Krawczyk Marcin , Marigorta Urko M. , Morrison Martine C. , Kleemann Robert , Martín‐Duce Antonio , Hayardeny Liat , Vitek Libor , Bruha Radan , Aller de la Fuente Rocío , Crespo Javier , Romero‐Gomez Manuel , Banales Jesus M , Arrese Marco , Cusi Kenneth , Bugianesi Elisabetta , Klein Samuel , Lu Shelly C. , Anstee Quentin M. , Millet Oscar , Davidson Nicholas O. , Alonso Cristina , Mato José M.
Published: February 2022

Background and Aims

We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors.

Approach and Results

We analyzed serum metabolome from 1154 individuals with biopsy‐proven NAFLD, and from four mouse models of NAFLD with impaired VLDL‐triglyceride (TG) secretion, and one with normal VLDL‐TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL‐TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL‐TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL‐TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL‐TG and VLDL–apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10‐year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin‐like phospholipase domain‐containing protein 3 NAFLD risk allele were lower in subtype A.

Conclusions

Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.
Retracted: Clinical Characteristics and Risk Factors Associated with Severe Disease Progression among COVID‐19 Patients In Wad Medani Isolation Centers: A Multicenter Retrospective Cross‐Sectional Study
Authors: Yousif Mohammed Yousif Elnaeem , Eljack Mohammed Mahmmoud Fadel Allah , Haroun Mazin S. , Abbasher Hussien Mohamed Ahmed Khabab , Amir Osman , Alfatih Mohammed , Al Shiekh Akram Khalid Al Tigany , Ahmed Mazin Abdelraham Osman , Nour Alshareef , Alhusseini Radi Tofaha , Osman Waddah Aljaely Mohammed , Abdulkarim Mohamed , Omer Mohammed Eltahier Abdalla , Mahgoub Ibrahim M.
Published: March 2022

Background

Since December 2019, (COVID‐19) has had a significant impact on global health systems. Because little is known about the clinical characteristics and risk factors connected with COVID‐19 severity in Sudanese patients, it is vital to summarize the clinical characteristics of COVID‐19 patients and to investigate the risk factors linked to COVID‐19 severity.

Objectives

We aimed to assess the clinical characteristics of COVID‐19 patients and look into risk factors associated with COVID‐19 severity.

Methods

This is a retrospective cross‐sectional study that took place in two Isolation Centers in Wad Medani, Gezira State, Sudan. Four hundred and eighteen patients were included between May 2020 and May 2021. All COVID‐19 patients over the age of 18 who were proven COVID‐19 positive by nucleic acid testing or had characteristics suggestive of COVID‐19 on a chest CT scan and had a complete medical record in the study period were included.

Results

The participants in this study were 418 confirmed COVID‐19 cases with a median age of 66.313 years. There were 279 men (66.7%) among the patients. The most prevalent comorbidities were hypertension (n = 195; 46.7%) and diabetes (n = 187; 44.7%). Fever (n = 303; 72.5%), cough (n = 278; 66.5%), and dyspnea (n = 256; 61.2%) were the most prevalent symptoms at the onset of COVID‐19. The overall mortality rate (n = 148) was 35.4%. Patients with severe illness had a mortality rate of 42.3% (n = 118). Older age, anemia, neutrophilia, and lymphocytopenia, as well as higher glucose, HbA1c, and creatinine levels, were all linked to severe COVID‐19, according to the chi‐square test and analysis of variance analysis.

Conclusion

Sixteen variables were found to be associated with COVID‐19 severity. These patients are more prone to go through a serious infection and as a result have a greater death rate than those who do not have these characteristics.
Peatland drainage alters soil structure and water retention properties: Implications for ecosystem function and management
Authors: Word Clayton S. , McLaughlin Daniel L. , Strahm Brian D. , Stewart Ryan D. , Varner J. Morgan , Wurster Frederic C. , Amestoy Trevor J. , Link Nicholas T.
Published: February 2022

Peatland functions (e.g., carbon sequestration and flora diversity) are largely driven by soil moisture dynamics and thus dependent on interactions between hydrologic regimes and organic soil properties. Understanding these interactions is particularly important in drained peatlands, where drier conditions may alter soil properties with feedbacks to soil water retention and associated ecosystem functions. In this work, we focused on the Great Dismal Swamp (GDS) in Virginia, USA, a historically drained, temperate peatland with ongoing hydrologic restoration efforts. Two distinct soil layers varying in thickness exist at GDS: an upper layer with subangular blocky structure thought to be a result of past drainage, and a sapric lower layer with a massive structure more representative of an undisturbed state. To understand the occurrence and consequences of these distinct layers, we used continuous water table data and analysed soil physical and hydraulic properties to characterize soil profiles at 16 locations. We found significant differences between layer properties, where upper layers had lower fibre and organic matter contents and higher bulk densities. Further, moisture release curves demonstrated lower water retention in upper layers compared with lower layers and key differences in pore structure, with upper layers having higher macroporosity. Upper layers varied in thickness across sampling locations (~0.30 to 1.0 m) with a transition to lower soil layers typically occurring at depths below contemporary water level observations, suggesting that the upper layer may be a result of historical drainage and deeper water table conditions. Yet, upper layers with more frequent saturation exhibited higher water retention and lower macroporosity compared with drier upper layers, thus indicating potential recovery following re‐wetting efforts. These findings highlight how past drainage influences soil properties and water retention, with important implications for current management objectives at GDS and other drained peatland systems.
TAR DNA‐binding protein 43 oligomers in physiology and pathology
Authors: Lye Yuh Shen , Chen Yun‐Ru
Published: March 2022

TAR DNA‐binding protein 43 (TDP‐43) is an RNA/DNA‐binding protein involved in RNA regulation and diseases. In 2006, TDP‐43 inclusions were found in the disease lesions of several neurodegenerative diseases. It is the pathological hallmark in both amyotrophic lateral sclerosis and frontotemporal lobar dementia. It also presents in a large portion of patients with Alzheimer's disease. TDP‐43 is prone to aggregate; however, the role of TDP‐43 oligomers remains poorly understood in both physiological and pathological conditions. In this review, we emphasize the role of oligomeric TDP‐43 in both physiological and pathological conditions and discuss the potential mechanisms of oligomer formation. Finally, we suggest therapeutic strategies against the TDP‐43 oligomers in neurodegenerative diseases.
Impact of a cardiology pharmacist‐led intervention on high‐intensity statin prescribing upon discharge after acute myocardial infarction
Authors: Montepara Courtney A , Oberst Cassidy E , Fyock Jordan O , Martin Hailey M , Noll Micaleigh D , Nemecek Branden D , Covvey Jordan R , Talreja Om N , Elston Colleen A
Published: March 2022

Introduction

Standard of care after an acute myocardial infarction (AMI) includes high‐intensity statin therapy to lower the risk of future cardiovascular events. However, the use of high‐intensity statins post‐AMI remains suboptimal, presenting an opportunity for clinical pharmacist services to improve clinical care.

Objective

To evaluate the impact of a cardiology clinical pharmacist intervention upon the rate of high‐intensity statins issued at hospital discharge after AMI.

Methods

This was a single‐center, pre‐post study that included patients 18 to 75 years of age who were discharged from one investigative site with a primary diagnosis of AMI (as determined by ICD‐10 codes) between July 2019 to December 2020. The primary outcome was the proportion of patients prescribed high‐intensity statins, defined as atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg daily, at discharge pre and postimplementation of a cardiology clinical pharmacist intervention. Patients were stratified into two groups for comparison: pre‐ (07/01/2019‐3/31/2020) and post‐ (04/01/2020‐12/31/2020) intervention, for which the latter included cardiology pharmacist‐driven communication and documentation via the electronic health record.

Results

A total of 418 patients were included: 223 (53.3%) preintervention and 195 (46.7%) postintervention. The overall cohort was approximately two‐thirds men and 90% Caucasian, with a mean ± SD age of 61.4 ± 9.7 years; the pre and postintervention groups were similar in terms of demographics. The rate of high‐intensity statin prescribing at discharge improved from 83.0% preintervention to 95.4% postintervention (P <.0001). A total of 9.9%, 1.8%, and 5.4% of patients in the preintervention group received moderate‐intensity, low‐intensity, or no statin at discharge, respectively, lowering to 3.1%, 1.0%, and 0.5% postintervention.

Conclusion

There was a statistically significant increase in the rate of high‐intensity statin prescribing post‐AMI after the implementation of targeted cardiology clinical pharmacist services.
Tracking Strain-Specific Morphogenesis and Angiogenesis of Murine Calvaria with Large-Scale Optoacoustic and Ultrasound Microscopy
Authors: Li Weiye , Liu Yu-Hang , Estrada Héctor , Rebling Johannes , Reiss Michael , Galli Serena , Nombela-Arrieta César , Razansky Daniel
Published: February 2022

Skull bone development is a dynamic and well-coordinated process playing a key role in maturation and maintenance of the bone marrow (BM), fracture healing, and progression of diseases such as osteoarthritis or osteoporosis. At present, dynamic transformation of the growing bone (osteogenesis) as well as its vascularization (angiogenesis) remain largely unexplored due to the lack of suitable in vivo imaging techniques capable of noninvasive visualization of the whole developing calvaria at capillary-level resolution. We present a longitudinal study on skull bone development using ultrasound-aided large-scale optoacoustic microscopy (U-LSOM). Skull bone morphogenesis and microvascular growth patterns were monitored in three common mouse strains (C57BL/6J, CD-1, and Athymic Nude-Foxn1nu) at the whole-calvaria scale over a 3-month period. Strain-specific differences in skull development were revealed by quantitative analysis of bone and vessel parameters, indicating the coupling between angiogenesis and osteogenesis during skull bone growth in a minimally invasive and label-free manner. The method further enabled identifying BM-specific sinusoidal vessels, and superficial skull vessels penetrating into BM compartments. Our approach furnishes a new high-throughput longitudinal in vivo imaging platform to study morphological and vascular skull alterations in health and disease, shedding light on the critical links between blood vessel formation, skull growth, and regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Single‐cell RNA sequencing reveals the cell types heterogenicity of human discoid lateral meniscus cells
Authors: Sun Hao , Zhang Wenhui , Liu Fangzhou , Li Deng , Cai Zhiqing , Huang Zhencheng , Chen Meiyi , Lin Zhencan , Xu Jie , Ma Ruofan
Published: February 2022

Discoid lateral meniscus (DLM) is more prone to injury than a normally shaped meniscus. No study has compared the gene expression and cell heterogeneity between discoid and normal menisci. We aimed to identify specific cell clusters and their marker genes in discoid meniscus, thereby providing a theoretical basis for the treatment and etiology of DLM. ScRNA‐seq was used in DLM and osteoarthritis lateral meniscus (OAM) cells to identify cell subsets and their gene signatures. Pseudo‐time analysis and immunohistochemical staining were used to investigate the temporal and spatial distribution of DLM‐specific clusters. ScRNA‐seq identified nine clusters originating from DLM and OAM, composed of seven empirically defined populations and two novel populations specific to DLM, namely, the prehypertrophic chondrocyte 2 (PreHTC‐2) and regulatory chondrocyte (RegC‐2) populations. Single‐cell trajectory showed that RegC‐2 and PreHTC‐2 were mainly distributed in a specific cell fate, with the PreHTC‐2 marker gene HAPLN1 highly expressed at the end of this fate. Immunohistochemical staining showed that HAPLN1 + cells were mainly distributed in the white zone of DLM. Matrix metalloproteinase (MMP) variants were expressed in DLM and OAM, with MMP2 highly expressed in OAM‐dominant cell clusters, while MMP3 was highly expressed in DLM‐dominant cell clusters. We concluded that two novel cell clusters including PreHTC‐2 were identified using single‐cell sequencing, which were mainly distributed in the white areas of DLM. Differentiated MMP expression in the trajectory may be a possible mechanism of DLM formation.
Evaluation of the Efficacy of Dexmedetomidine as a Local Anesthetic Adjuvant in Children: A Meta‐Analysis of Randomized Controlled Trials
Authors: Sun Yan , Wu Zhilin , Sun ShuJun , Chen Rui , Dai Maosha , Dou Xiaoke , Lin Yun
Published: February 2022

Dexmedetomidine has been identified as a useful adjunct to improve the effect of nerve blocks in adults; however, its effect for children has not yet been fully investigated. This meta‐analysis aimed to evaluate the reliability and efficacy of dexmedetomidine as a local anesthetic adjunct for pediatric surgeries. Eligible studies were searched in Cochrane, Embase, PubMed, and CBM. RevMan 5.4 was used to assess the risk of bias of each study and perform statistical analysis. Stata 15.0 was used to evaluate the publication bias of primary outcomes. Thirteen randomized controlled trial (RCTs) involving 722 patients aged 6 months to 12 years were harvested. Statistical analysis showed that dexmedetomidine resulted in: a significantly longer duration of analgesia (standardized mean difference [SMD], 7.16; 95% confidence interval [95%CI], 4.88 to 9.43; P < .001; I2 = 98%); a reduction in the 1‐hour pain score (mean difference [MD], –0.27; 95%CI, –0.47 to –0.06; P = .01; I2 = 28%); cumulative doses of rescue analgesic required of 2 doses (risk ratio [RR], 0.26; 95%CI, 0.14 to 0.49; P < .001; I2 = 0) or 3 doses (RR, 0.04; 95%CI, 0.01 to 0.16; P < .001; I2 = 4%); the frequency of emergence agitation (RR, 0.44; 95%CI, 0.22 to 0.91; P = .03; I2 = 0); and a reduction in the onset time of blocks (mean difference –3.56; 95%CI, –6.39 to –0.74; P = .01; I2 = 90%). However, the incidence of some side effects, including hypotension, bradycardia, nausea and vomiting, pruritis, urinary retention, and respiratory depression, did not significantly differ between the dexmedetomidine group and the placebo group. Therefore, dexmedetomidine is a reliable and efficient adjunct to local anesthetics in children.
The necessary leadership skillsets for the high‐reliability organization framework adoption within acute healthcare organizations
Authors: Logan‐Athmer Amanda L.
Published: March 2022

This research explores the necessary leadership skills for the successful adoption of the High‐Reliability Organization (HRO) framework within acute healthcare organizations. Using a qualitative research design, organization leaders and experts at the executive, mid‐level, and front‐line levels were interviewed. The results were analyzed to correlate specific leadership skillsets and components to the most successful adoption strategies. In total, 20 skillsets were identified with seven representing data saturation. The seven vital skillsets include non‐hierarchical leadership, transparent and continuous communication, deference to expertise, ability to innovate, motivation through recognition, reflective of self, and commitment to visibility.
SARS‐COV‐2 genomic monitoring in the state of São Paulo unveils two emerging AY.43 sublineages
Authors: Lima Alex Ranieri Jerônimo , Ribeiro Gabriela , Viala Vincent Louis , de Lima Loyze Paola Oliveira , Martins Antonio Jorge , Barros Claudia Renata dos Santos , Marqueze Elaine Cristina , Bernardino Jardelina de Souza Todao , Moretti Debora Botequio , Rodrigues Evandra Strazza , Santos Elaine Vieira , Brassaloti Ricardo Augusto , Cassano Raquel de Lello Rocha Campos , Mariani Pilar Drummond Sampaio Corrêa , Clemente Luan Gaspar , Assato Patricia Akemi , Costa Felipe Allan da Silva da , Poleti Mirele Daiana , Lesbon Jessika Cristina Chagas , Mattos Elisangela Chicaroni , Banho Cecilia Artico , Sacchetto Lívia , Moraes Marília Mazzi , Palmieri Melissa , Martininghi Maiara , Caldeira Luiz Artur Vieira ,  Silva Fabiana Erica Vilanova da , Grotto Rejane Maria Tommasini , Souza‐Neto Jayme A. , Giovanetti Marta , Junior Alcantara Luiz Carlos , Nogueira Maurício Lacerda , Fukumasu Heidge , Coutinho Luiz Lehmann , Kashima Simone , Neto Raul Machado , Covas Dimas Tadeu , Slavov Svetoslav Nanev , Sampaio Sandra Coccuzzo , Elias Maria Carolina
Published: March 2022

Delta VOC is highly diverse with more than 120 sublineages already described as of November 30, 2021. In this study, through active monitoring of circulating severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants in the state of São Paulo, southeast Brazil, we identified two emerging sublineages from the ancestral AY.43 strain which were classified as AY.43.1 and AY.43.2. These sublineages were defined by the following characteristic nonsynonymous mutations ORF1ab:A4133V and ORF3a:T14I for the AY.43.1 and ORF1ab:G1155C for the AY.43.2 and our analysis reveals that they might have a likely‐Brazilian origin. Much is still unknown regarding their dissemination in the state of São Paulo and Brazil as well as their potential impact on the ongoing vaccination process. However, the results obtained in this study reinforce the importance of genomic surveillance activity for timely identification of emerging SARS‐CoV‐2 variants which can impact the ongoing SARS‐CoV‐2 vaccination and public health policies.
Correlation between knee anatomy and joint laxity using principal component analysis
Authors: Shalhoub Sami , Cyr Adam , Maletsky Lorin P.
Published: February 2022

Knee articular geometry and surface morphology greatly affect knee joint mechanics. Intra‐subject variations in bone morphology and the passive range of motion have been well documented in the literature; however, the relationship between these two characteristics is not well understood. The objective of this study was to describe the correlation between knee joint anatomical features and passive range of motion using a statistical model. A principal component model was developed using femoral and tibial articular geometry, knee joint initial stance position, and the passive laxity envelope obtained from 27 cadaveric knees. The results from the principal component analysis showed high correlation between the anatomical features and the tibiofemoral passive envelope; an increase in the average femoral condyle radii, an increase in slope of the tibial spine, and a higher tibial plateau concavity correlated with a decrease in varus−valgus and internal−external range of motion. Understanding the correlation between anatomical features and tibiofemoral laxity could aid in the development of orthopedic implant designs by quantifying the effect of perturbing specific anatomical features on knee laxity and identifying specific implant femoral and tibial articular geometry necessary to obtain a targeted passive range of motion.
Riboflavin as a green sorbent in dispersive micro‐solid‐phase extraction of several pesticides from fruit juices combined with dispersive liquid–liquid microextraction
Authors: Abbasalizadeh Aysa , Sorouraddin Saeed Mohammad , Farajzadeh Mir Ali , Marzi Elnaz , Afshar Mogaddam Mohammad Reza
Published: February 2022

A vortex‐assisted dispersive micro‐solid‐phase extraction procedure using a new and green sorbent was developed as a simple, fast, and efficient sample preparation method for the extracting five pesticides in several fruit juice samples. In this study, for the first time, riboflavin was used as an efficient sorbent. A few milligrams of riboflavin was directly added into the aqueous solution containing the analytes to adsorb them. After adsorption the analytes, they were desorbed and more concentrated by a dispersive liquid–liquid microextraction procedure. The influence of several effective parameters such as amount of riboflavin, pH, vortex time, eluent nature and volume, and extraction solvent type and volume on the extraction efficiency was investigated. In optimal conditions, linear ranges of the calibration curves were broad. The limits of detection and quantification were attained in the ranges of 0.56–1.5  and 1.9–0.52 ng mL−1, respectively. The proposed method demonstrated to be suitable for concurrent extraction of the studied pesticides in various fruit juice samples with high enrichment factors (320–360) and precision (relative standard deviation ≤7.8% for intra‐ [n = 6] and interday [n = 4] precisions at a concentration of 25 ng mL−1 of each pesticide).
Kinetics study of CO2 absorption into methyldiethanolamine, potassium lysinate, and their blends in aqueous solution
Authors: Ramezani Rouzbeh , Di Felice Renzo
Published: February 2022

In this work, the kinetics for the reaction of CO2 with three chemical solvents were studied experimentally and theoretically. The CO2 absorption flux into the potassium lysinate (K‐Lys), methyldiethanolamine (MDEA), and their blends was measured over the CO2 partial pressure range of 50–500 kPa, and at temperatures 298.15, 303.15, and 313.15 K using a stirred cell reactor. The effect of the addition of K‐Lys on the absorption flux of CO2 into MDEA solution at low and high pressure was investigated. The reaction kinetics of CO2 absorption in CO2‐loaded MDEA, K‐Lys, and MDEA + K‐Lys solutions were also examined and absorption flux of CO2 as a function of CO2 loading was determined. The values of CO2 diffusivity, viscosity, the liquid mass transfer coefficient, the overall reaction rate constant, and the physical solubility of CO2 into MDEA + K‐Lys solution were reported. Furthermore, a standard kinetics model was developed to describe the CO2 absorption behavior in the solution at low and high pressures, for both unloaded and CO2‐loaded systems.