bluuebunny/crossref_metadata_2025_split huggingface dataset:
The threat of an indigenous medicinal plant encroacher: Artemisia afra in Klipriviersberg Nature Reserve, Johannesburg, South Africa
Authors: Setshedi Kgalalelo T. A. , Newete Solomon W. , Witkowski Ed T. F. 
Published: August 2022

AbstractArtemisia afra was identified as an encroaching shrub in the Klipriviersberg Nature Reserve (KNR). Ecological factors that influence the encroachment of A. afra and its population structure were unknown, making it difficult to monitor and control the spread of the plant. This study assessed the density and size‐class distributions (SCD) of A. afra across the main habitats in the KNR (streamside, plains and ridges, with ridges divided into crest, mid‐slope and bottom slope), as well as the relationship between A. afra density and certain ecological factors. Results showed that there was a significant difference (p < 0.05) between plant density on the different habitats with the ridge and bottom slope having by far the highest density (>900 plants/ha). Canopy volume was considered the best measure for the SCD of A. afra. Overall, the population structure of A. afra displayed an inverse J‐shaped curve, indicating that despite clearing efforts and the drought of 2015–2016, it is effectively a recruiting population. Over 71% of the A. afra population were flowering, suggesting relatively rapid attainment of reproductive maturity, and high seed production. Hence, the high levels of encroachment are likely to continue. Further research on controlling A. afra with the integrated use of more intense winter fires, herbicides and the feasibility of sustainable harvesting of this medicinal plant should be undertaken. We also need a much better understanding of the regeneration ecology of A. afra in order to better control it.
Efficacy of intravenous immunoglobulin in the treatment of recurrent spontaneous abortion: A systematic review and meta‐analysis
Authors: Shi Yimin , Tan Dongmei , Hao Baozhen , Zhang Xiurong , Geng Wei , Wang Yayu , Sun Jianyi , Zhao Yue 
Published: August 2022

AbstractObjectiveWe aimed to evaluate the efficacy of IVIG in the treatment with patients with recurrent spontaneous abortion (RSA).MethodsPubMed, Embase, Web of science, Cochrane library were searched for randomized controlled (RCTs) about effect of IVIG on RSA from inception to August 20, 2021. Values of standardized mean differences (SMD) were determined for continuous outcomes.ResultsA total of 15 articles involving 902 patients were included in meta‐analysis. Compared with the control group, IVIG can increase the live birth rate of recurrent spontaneous abortion patients [OR = 3.06, 95%CI (1.23, 7.64, P = .02]. However, recurrent abortion was divided into primary and secondary abortion for subgroup analysis, and there was no statistical difference. Besides, IVIG can also increase the expression in peripheral blood CD3+[OR = .4, 95%CI(‐2.47, 3.15, P = .81],CD4+[OR = 1.16, 95%CI(‐4.60, 6.93, P = .69], and a decrease in the expression of CD8+[OR = ‐1.78, 95%CI(‐5.30, 1.75, P = .32], but there is no statistical significance.ConclusionsIVIG can significantly increase the live birth rate of recurrent spontaneous abortion. However, the evidence needs further verification and the curative effect is uncertain. It is necessary to further explore the pathogenesis of recurrent abortion and the mechanism of IVIG in the treatment of recurrent spontaneous abortion. Besides, more high‐quality randomized controlled trials suitable for population, race, dosage and timing of IVIG in the treatment of recurrent abortion are needed to confirm its effectiveness, and effective systematic evaluation is also needed to evaluate its use benefit.
Coculture of adipose‐derived mesenchymal stem cells/macrophages on decellularized placental sponge promotes differentiation into the osteogenic lineage
Authors: Khosrowpour Zahra , Hashemi Seyed Mahmoud , Mohammadi‐Yeganeh Samira , Moghtadaei Mehdi , Brouki Milan Peiman , Moroni Lorenzo , Kundu Subhas C. , Gholipourmalekabadi Mazaher 
Published: August 2022

AbstractBackgroundSeveral factors like three‐dimensional microstructure, growth factors, cytokines, cell–cell communication, and coculture with functional cells can affect the stem cells behavior and differentiation. The purpose of this study was to investigate the potential of decellularized placental sponge as adipose‐derived mesenchymal stem cells (AD‐MSCs) and macrophage coculture systems, and guiding the osteogenic differentiation of stem cells.MethodsThe decellularized placental sponge (DPS) was fabricated, and its mechanical characteristics were evaluated using degradation assay, swelling rate, and pore size determination. Its structure was also investigated using hematoxylin and eosin staining and scanning electron microscopy. Mouse peritoneal macrophages and AD‐MSCs were isolated and characterized. The differentiation potential of AD‐MSCs co‐cultured with macrophages was evaluated by RT‐qPCR of osteogenic genes on the surface of DPS. The in vivo biocompatibility of DPS was determined by subcutaneous implantation of scaffold and histological evaluations of the implanted site.ResultsThe DPS had 67% porosity with an average pore size of 238 μm. The in vitro degradation assay showed around 25% weight loss during 30 days in PBS. The swelling rate was around 50% during 72 h. The coculture of AD‐MSCs/macrophages on the DPS showed a significant upregulation of four differentiation osteogenic lineage genes in AD‐MSCs on days 14 and 21 and a significantly higher mineralization rate than the groups without DPS. Subcutaneous implantation of DPS showed in vivo biocompatibility of scaffold during 28 days follow‐up.ConclusionsOur findings suggest the decellularized placental sponge as an excellent bone substitute providing a naturally derived matrix substrate with biostructure close to the natural bone that guided differentiation of stem cells toward bone cells and a promising coculture substrate for crosstalk of macrophage and mesenchymal stem cells in vitro.
Nitrous oxide in labour predicted newborn screening total homocysteine and is a potential risk factor for infant vitamin B12 deficiency
Authors: Ljungblad Ulf Wike , Lindberg Morten , Eklund Erik A. , Saeves Ingjerd , Bjørke‐Monsen Anne‐Lise , Tangeraas Trine 
Published: August 2022

AbstractAimRisk factors for vitamin B12 deficiency in infants are not fully understood. The aim of the study was to assess predictors of total homocysteine and methylmalonic acid analysed in newborn screening dried blood spots.MethodsIn a Norwegian case control study, we analysed total homocysteine and methylmalonic acid in newborn screening dried blood spots of 86 infants clinically diagnosed with vitamin B12 deficiency during 2012–2018. Results were compared to 252 healthy infants and 400 dried blood spot controls. Medical records were reviewed, and mothers completed questionnaires.ResultsBoth total homocysteine and methylmalonic acid were significantly higher on newborn screening dried blood spots in infants later clinically diagnosed with vitamin B12 deficiency than controls. Multiple regression analysis showed that the dose of nitrous oxide during labour was the strongest predictor for total homocysteine level in newborn screening dried blood spots for all infants, with larger effect in infants later clinically diagnosed with vitamin B12 deficiency than controls.ConclusionNitrous oxide dose during labour was a predictor for total homocysteine and may impact the interpretation of total homocysteine analysis in newborn screening. Nitrous oxide is suggested as a contributing risk factor for infants prone to develop vitamin B12 deficiency.
The role of high‐conductance calcium‐activated potassium channel in headache and migraine pathophysiology
Authors: Al‐Karagholi Mohammad Al‐Mahdi , Hakbilen Cemile Ceren , Ashina Messoud 
Published: August 2022

AbstractMigraine is a common, neurovascular headache disorder with a complex molecular interplay. The involvement of ion channels in the pathogenesis of migraine gathered considerable attention with the findings that different ion channels subfamilies are expressed in trigeminovascular system, the physiological substrate of migraine pain, and several ion channel openers investigated in clinical trials with diverse primary endpoints caused headache as a frequent side effect. High‐conductance (big) calcium‐activated potassium (BKCa) channel is expressed in the cranial arteries and the trigeminal pain pathway. Recent clinical research revealed that infusion of BKCa channel opener MaxiPost caused vasodilation, headache and migraine attack. Thus, BKCa channel is involved in pathophysiological mechanisms underlying headache and migraine, and targeting BKCa channel presents a new potential strategy for migraine treatment.
The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling
Authors: Bagalagel Alaa , Diri Reem , Noor Ahmad , Almasri Deina , Bakhsh Hussain T. , Kutbi Hussam I. , Al‐Gayyar Mohammed M. H. 
Published: August 2022

AbstractPatients with ulcerative colitis (UC) experience diarrhoea, hematochezia and abdominal pain. UC is a well‐known health challenge affecting 200–250 per 100 000 individuals worldwide, with a similar prevalence in both sexes and elevated upon activation of gut immune responses. We evaluated the potential therapeutic effects of cycloastragenol in experimentally induced UC rats and examined the modulation of sphingosine kinase (SphK), macrophage inflammatory protein (MIP)‐1α and miR‐143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP‐1α, B‐cell lymphoma 2 (BCL2), BCL2‐associated X (BAX), miR‐143, NF‐κB, tumour necrosis factor (TNF)‐α and active caspase‐3. Colon sections were examined using electron microscopy; additional sections were stained with haematoxylin–eosin or immunostained with anti‐TNF‐α and anti‐caspase‐3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a nondistinct brush border with atypical microvilli. Haematoxylin–eosin staining showed damaged intestinal glands, severe haemorrhage and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP‐1α, BAX, NF‐κB, TNF‐α and active caspase‐3, associated with BCL2 and miR‐143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP‐1α/miR‐143, subsequently deactivating inflammatory and apoptotic pathways.
Rare germline ATM variants of uncertain significance in chronic lymphocytic leukaemia and other cancers
Authors: Petrackova Anna , Savara Jakub , Turcsanyi Peter , Gajdos Petr , Papajik Tomas , Kriegova Eva 
Published: August 2022

SummaryGermline pathogenic ATM (ataxia‐telangiectasia mutated) variants are associated with the risk of multiple cancers; however, genetic testing reveals a large number of ATM variants of uncertain significance (VUS). Here, we studied germline ATM variants occurring in a real‐world cohort of 336 patients with chronic lymphocytic leukaemia (CLL) and public cancer whole‐exome/genome‐sequencing datasets (445 CLL, 75 mantle cell lymphoma, 216 metastatic breast cancer, 140 lung cancer patients). We found that two‐thirds of rare germline ATM variants are pathogenic (18%–50%) or VUS‐predicted pathogenic (50%–82%), depending on cancer type and reaching a prevalence of up to 8%, and one‐third are VUS‐predicted benign. Patients with both pathogenic and VUS‐predicted pathogenic variants, all heterozygous, mostly missense, are more predisposed to biallelic ATM inactivation by acquiring deletion (del)11q than patients without these variants, similar to patients with somatic ATM variants. A functional assay of ATM activity in primary CLL cells proved that VUS‐predicted pathogenic ATM variants partially reduce ATM activity and concurrent del(11q) leads to complete loss of ATM activity. The rare germline variants were associated with reduced progression‐free survival in CLL on novel agents, comparable to somatic ATM or TP53 disruptions. Our results highlight the need to determine the pathogenicity of VUS in clinically relevant genes such as ATM.
Donepezil inhibits neuromuscular junctional acetylcholinesterase and enhances synaptic transmission and function in isolated skeletal muscle
Authors: Redman Robert R. , Mackenzie Harry , Dissanayake Kosala N. , Eddleston Michael , Ribchester Richard R. 
Published: August 2022

Background and PurposeDonepezil, a piperidine inhibitor of acetylcholinesterase (AChE) prescribed for treatment of Alzheimer's disease, has adverse neuromuscular effects in humans, including requirement for higher concentrations of non‐depolarising neuromuscular blockers during surgery. Here, we examined the effects of donepezil on synaptic transmission at neuromuscular junctions (NMJs) in isolated nerve‐muscle preparations from mice.Experimental ApproachWe measured effects of therapeutic concentrations of donepezil (10 nM to 1 μM) on AChE enzymic activity, muscle force responses to repetitive stimulation, and spontaneous and evoked endplate potentials (EPPs) recorded intracellularly from flexor digitorum brevis muscles from CD01 or C57BlWldS mice.Key ResultsDonepezil inhibited muscle AChE with an approximate IC50 of 30 nM. Tetanic stimulation in sub‐micromolar concentrations of donepezil prolonged post‐tetanic muscle contractions. Preliminary Fluo4‐imaging indicated an association of these contractions with an increase and slow decay of intracellular Ca2+ transients at motor endplates. Donepezil prolonged spontaneous miniature EPP (MEPP) decay time constants by about 65% and extended evoked EPP duration almost threefold. The mean frequency of spontaneous MEPPs was unaffected but the incidence of ‘giant’ MEPPs (gMEPPs), some exceeding 10 mV in amplitude, was increased. Neither mean MEPP amplitude (excluding gMEPPs), mean EPP amplitude, quantal content or synaptic depression during repetitive stimulation were significantly altered by concentrations of donepezil up to 1 μM.Conclusion and ImplicationsAdverse neuromuscular signs associated with donepezil therapy, including relative insensitivity to neuromuscular blockers, are probably due to inhibition of AChE at NMJs, prolonging the action of ACh on postsynaptic nicotinic acetylcholine receptors but without substantively impairing evoked ACh release.
Dysferlinopathies: Clinical and genetic variability
Authors: Ivanova Alisa , Smirnikhina Svetlana , Lavrov Alexander 
Published: August 2022

AbstractDysferlinopathies are a clinically heterogeneous group of diseases caused by mutations in the DYSF gene encoding the dysferlin protein. Dysferlin is mostly expressed in muscle tissues and is localized in the sarcolemma, where it performs its main function of resealing and maintaining of the integrity of the cell membrane. At least four forms of dysferlinopathies have been described: Miyoshi myopathy, limb‐girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset, and isolated hyperCKemia. Here we review the clinical features of different forms of dysferlinopathies and attempt to identify genotype–phenotype correlations. Because of the great clinical variability and rarety of the disease and mutations little is known, how different phenotypes develop as a result of different mutations. However, missense mutations seem to induce more severe disease than LoF, which is typical for many muscle dystrophies. The role of several specific mutations and possible gene modifiers is also discussed in the paper.
Diamond‐Blackfan anaemia caused by a de novo initiation codon mutation resulting in a shorter isoform of GATA1
Authors: Chen Tongtong , Zhang Qianqian , Shang Xuan , Zou Shaomin , Qin Jiaofeng , Li Kui , Lin Bin , Tao Zhenzhong , Long Xingjiang , Xu Xiangmin 
Published: August 2022

AbstractDiamond‐Blackfan anaemia (DBA) is an inherited marrow failure disorder characterised by selective erythroid aplasia. Herein, we reported a case of DBA caused by a novel GATA1 gene mutation. The proband manifested normocytic normochromic anaemia, while the parents were asymptomatic. Next‐generation sequencing identified a novel de novo mutation at GATA1 initiation codon (GATA1:c.3G>A) in the proband. The mutation led to a shortened GATA1 protein (GATA1s), which caused a reduction in full‐length functional GATA1 protein (GATA1fl). This is the first report of GATA1‐related DBA patient in the East Asian population, which expanded the mutational spectrum of DBA furthering understanding of its pathogenesis.
The analgesic and anti‐haemorrhagic efficacy of platelet‐rich plasma in tonsillectomy: A systematic review and meta‐analysis of randomised controlled trials
Authors: Albazee Ebraheem , Diab Sherein , Awad Ahmed K. , Aboeldahab Heba , Abdella Walid Shaban , Abu‐Zaid Ahmed 
Published: August 2022

AbstractObjectivesTo evaluate the analgesic and anti‐haemorrhagic efficacy of platelet‐rich plasma (PRP) among patients undergoing tonsillectomy.DesignA systematic review and meta‐analysis of randomised controlled trials (RCTs).SettingPubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases were screened from inception until July 2021, and updated in December 2021.ParticipantsPatients undergoing tonsillectomy.Main outcome measuresThe efficacy endpoints of postoperative pain and haemorrhage were summarised as standardised mean difference (SMD) and risk ratio (RR), respectively, with 95% confidence interval (CI).ResultsSeven RCTs Seven RCTs were analysed, comprising a total of 392 patients. Risk of bias evaluation showed an overall high risk in one RCT, low risk in four RCTs and some concerns in two RCTs. The pooled results revealed that the mean postoperative pain score was significantly reduced in favour of the PRP group compared with the control group (SMD = −1.38, 95% CI [−1.91, −0.85], p < 0.001). Subgroup analysis showed the effect estimate was statistically significant for early postoperative pain (Day 0 to Day 3), without substantial difference between both groups on late postoperative pain (Days 5 and 7). Moreover, the rate of postoperative haemorrhage was significantly reduced in favour of the PRP group compared with the control group (RR = 0.16, 95% CI [0.05, 0.50], p = 0.001). Subgroup analysis showed the effect estimate was statistically significant for the rate of primary and secondary haemorrhage.ConclusionPRP was associated with significant reduction in postoperative pain and haemorrhage among patients undergoing tonsillectomy.
Incidence of skin diseases in healthcare workers before and during the COVID‐19 pandemic at Trieste hospitals (northeastern Italy)
Authors: Piapan Linda , Bramuzzo Davide , Rui Francesca , Filon Francesca Larese 
Published: August 2022

AbstractBackgroundOccupational skin diseases (OSDs) are common in healthcare workers (HCWs).ObjectivesTo investigate and compare the incidence and clinical features of OSDs among HCWs before and during the COVID‐19 pandemic.Materials and MethodsIncident cases of OSDs were investigated in the cohort of HCWs at Trieste Hospitals from 1 July 2018 (3340 workers) to 31 October 2021 (137 532 person‐months).ResultsThe monthly incidence was ranging from 0 to 11.90 cases per 10 000 person‐months in pre‐COVID‐19 period (cumulative incidence 4.22; 95% confidence interval [CI]: 2.9–6.0) and from 0 to 13.61 cases per 10 000 person‐months in COVID‐19 period (cumulative incidence 5.06; 95% CI: 3.6–6.9). The incidence rate ratio (IRR) between COVID‐19 and pre‐COVID‐19 period was 1.22 (95% CI: 0.73–1.98). The incidence of OSDs in the COVID‐19 period was 6.1 (4.2–8.6) and 2.7 (95% CI: 1.1–5.6) cases × 10 000 person‐months for women and men, respectively, with an IRR of 2.25 (95% CI: 0.98–5.9). Incidence in nurses in the COVID‐19 period was 6.7 (95% CI: 4.2–10.2) cases × 10 000 person‐months.ConclusionsIncidence of OSDs was a little bit higher during the COVID‐19 pandemic compared to the previous period but fluctuation of numbers were mainly related to calendar period, with higher incidence in winter and spring. Incidence data were higher than that observed in 2004–2013 in the same cohort. Face dermatitis cases doubled after the start of COVID‐19 pandemic. Overall data demonstrated a non‐significant increase of OSDs in HCWs during the pandemic, probably due to the preventive strategies set up in our cohort over the years.
Exosome‐shuttled mitochondrial transcription factor A mRNA promotes the osteogenesis of dental pulp stem cells through mitochondrial oxidative phosphorylation activation
Authors: Guo Jia , Zhou Feng , Liu Zhi , Cao Yuan , Zhao Wanming , Zhang Zheru , Zhai Qiming , Jin Yan , Li Bei , Jin Fang 
Published: August 2022

AbstractObjectivesThe treatment of bone defects by stem cells (MSCs) has achieved limited success over the recent few decades. The emergence of exosomes provides a new strategy for bone regeneration. Here, we aimed to investigate the effect and mechanisms of exosomes combined with dental pulp stem cells (DPSCs) on bone regeneration.Materials and MethodsWe isolated exosomes from stem cells from human exfoliated deciduous teeth (SHED) aggregates and evaluated the efficacy of exosomes combined with DPSCs in a cranial bone defect model. The potential mechanisms were further investigated.ResultsThe effect of exosomes combined with DPSCs was remarkable on bone regeneration in vivo and exosomes promoted osteogenic differentiation of DPSCs in vitro. Mechanistically, exosomes increased the expression of mitochondrial transcription factor A (TFAM) in DPSCs by transferring TFAM mRNA. Moreover, highly expressed TFAM in DPSCs enhanced glutamate metabolism and oxidative phosphorylation (OXPHOS) activity.ConclusionsConsequently, exosomes strengthened bone regeneration of DPSCs through the activation of mitochondrial aerobic metabolism. Our study provides a new potential strategy to improve DPSC‐based bone regenerative treatment.
Genetic evidence to inform management of rare genetic variants and gene flow: Balancing the conservation of the rare “Spirit bear” allele and population genetic diversity across a complex landscape
Authors: Henson Lauren H. , Service Christina , Stronen Astrid Vik , Moody Jason , Housty William , Reece Donald , vonHoldt Bridgett , Darimont Chris T. 
Published: August 2022

AbstractIncorporating genetic considerations into wildlife management can require balancing the conservation of rare genetic variants with the maintenance of gene flow. One system illustrating such trade‐offs is coastal British Columbia, Canada, where black bears (Ursus americanus) can carry a genetic variant responsible for white‐coated “Spirit bears.” We examined population genetic structure, diversity, and gene flow using 22 microsatellite loci for 357 individuals collected over a 23,500 km2 area from a long‐term noninvasive bear monitoring collaboration among the Gitga'at, Kitasoo/Xai'xais, Nuxalk, Haíɫzaqv, and Wuikinuxv First Nations and partnering scientists. We found broad‐ (two groups) and fine‐scale (eight groups) population structures. At the finer scale, three islands formed unique genetic groups and four genetic groups showed heterozygote deficiency, including two populations containing Spirit bear alleles. We additionally created effective estimation of migration surfaces and found that breaks among genetic groups and areas of lower than average migration aligned with wide waterways (>2 km). Given the apparent isolation of island groups, heterozygote deficiencies, and the distribution of the rare Spirit bear allele, we provide recommendations to prevent the loss of Spirit bear allele carriers and individuals contributing genetic diversity to isolated, genetically depauperate groups. More broadly, we highlight the value of locally led, fine‐scale genetic monitoring for wildlife management.