bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice
Authors: Ma Pingchuan , Mo Rufan , Liao Huabao , Qiu Chengjie , Wu Genhao , Yang Caixia , Zhang Yunxiao , Zhao Yiran , Song Xue-Jun
Published: June 2022

Background

Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive.

Methods

Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice. Continuous feeding of antibiotics (ABX) cocktail was used to cause major depletion of the gut microbiota. Fecal microbiota, biochemical changes in the spinal cord and dorsal root ganglion (DRG), and the behaviorally expressed painful syndromes were assessed.

Results

Under condition of gut microbiota depletion, CCI, OXA, or STZ treatment-induced thermal hyperalgesia or mechanical allodynia were prevented or completely suppressed. Gut microbiota depletion also prevented CCI or STZ treatment-induced glial cell activation in the spinal cord and inhibited cytokine production in DRG in OXA model. Interestingly, STZ treatment failed to induce the diabetic high blood glucose and painful hypersensitivity in animals with the gut microbiota depletion. ABX feeding starting simultaneously with CCI, OXA, or STZ treatment resulted in instant analgesia in all the animals. ABX feeding starting after establishment of the neuropathic pain in CCI- and STZ-, but not OXA-treated animals produced significant alleviation of the thermal hyeralgesia or mechanical allodynia. Transplantation of fecal bacteria from SPF mice to ABX-treated mice partially restored the gut microbiota and fully rescued the behaviorally expressed neuropathic pain, of which, Akkermansia, Bacteroides, and Desulfovibrionaceae phylus may play a key role.

Conclusion

This study demonstrates distinct roles of gut microbiota in the pathogenesis of chronic painful conditions with nerve injury, chemotherapy and diabetic neuropathy and supports the clinical significance of fecal bacteria transplantation.
Are verbatim transcripts necessary in applied qualitative research: experiences from two community-based intervention trials in Ghana
Authors: Hill Zelee , Tawiah-Agyemang Charlotte , Kirkwood Betty , Kendall Carl
Published: June 2022

Conducting qualitative research within public health trials requires balancing timely data collection with the need to maintain data quality. Verbatim transcription of interviews is the conventional way of recording qualitative data, but is time consuming and can severely delay the availability of research findings. Expanding field notes into fair notes is a quicker alternative method, but is not usually recommended as interviewers select and interpret what they record. We used the fair note methodology in Ghana, and found that where research questions are relatively simple, and interviewers undergo sufficient training and supervision, fair notes can decrease data collection and analysis time, while still providing detailed and relevant information to the study team. Interviewers liked the method and felt it made them more reflective and analytical and improved their interview technique. The exception was focus group discussions, where the fair note approach failed to capture the interaction and richness of discussions, capturing group consensus rather than the discussions leading to this consensus.
Pooled prevalence and genetic diversity of norovirus in Africa: a systematic review and meta-analysis
Authors: Afework Dessie Tegegne , Shumie Mulu Kebede , Endalew Getachew Ferede , Adugna Aschalew Gelaw , Tarekegn Baye Gelaw
Published: June 2022

Background

Noroviruses are the leading cause of acute gastroenteritis in all age groups globally. The problem is magnified in developing countries including Africa. These viruses are highly prevalent with high genetic diversity and fast evolution rates. With this dynamicity, there are no recent review in the past five years in Africa. Therefore, this review and meta-analysis aimed to assess the prevalence and genetic diversity of noroviruses in Africa and tried to address the change in the prevalence and genetic diverisity the virus has been observed in Africa and in the world.

Methods

Twenty-one studies for the pooled prevalence, and 11 out of the 21 studies for genetic characterization of norovirus were included. Studies conducted since 2006, among symptomatic cases of all age groups in Africa, conducted with any study design, used molecular diagnostic methods and reported since 2015, were included and considered for the main meta-analysis. PubMed, Cochrane Library, and Google Scholar were searched to obtain the studies. The quality the studies was assessed using the JBI assessment tool. Data from studies reporting both asymptomatic and symptomatic cases, that did not meet the inclusion criteria were reviewed and included as discussion points. Data was entered to excel and imported to STATA 2011 to compute the prevalence and genetic diversity. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis.

Result

The pooled prevalence of norovirus was 20.2% (95% CI: 15.91, 24.4). The highest (36.3%) prevalence was reported in Ghana. Genogroup II noroviruses were dominant and reported as 89.5% (95% CI: 87.8, 96). The highest and lowest prevalence of this genogroup were reported in Ethiopia (98.3%), and in Burkina Faso (72.4%), respectively. Diversified genotypes had been identified with an overall prevalence of GII. 4 NoV (50.8%) which was followed by GII.6, GII.17, GI.3 and GII.2 with a pooled prevalence of 7.7, 5.1, 4.6, and 4.2%, respectively.

Conclusion

The overall pooled prevalence of norovirus was high in Africa with the dominance of genogroup II and GII.4 genotype. This prevalence is comparable with some reviews done in the same time frame around the world. However, in Africa, an in increasing trained of pooled prevalence had been reported through time. Likewise, a variable distribution of non-GII.4 norovirus genotypes were reported as compared to those studies done in the world of the same time frame, and those previous reviews done in Africa. Therefore, continuous surveillance is required in Africa to support future interventions and vaccine programs.
Generation of the salicylic acid deficient Arabidopsis via a synthetic salicylic acid hydroxylase expression cassette
Authors: Cai Zilin , Guo Hao , Shen Shijing , Yu Qilu , Wang Jinbin , Zhu Engao , Zhang Pinghua , Song Lili , Zhang Yanjun , Zhang Kewei
Published: June 2022

Background

Salicylic acid (SA) is one of the plant hormones, which plays crucial roles in signaling transduction in plant growth, disease resistance, and leaf senescence. Arabidopsis (Arabidopsis thaliana) SA 3-hydroxylase (S3H) and 5-hydroxylase (S5H) are key enzymes which maintain SA homeostasis by catalyzing SA to 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA, respectively.

Results

SA deficient transgenic Arabidopsis lines were generated by introducing two binary vectors S5Hpro::EGFP-S3H and 35Spro::EGFP-S3H respectively, in which the expression of S3H is under the control of the S5H promoter or CaMV 35S promoter. Compared with the constitutive expression of S3H gene under the control of 35S promoter, the S3H gene under the native S5H promoter is activated by endogenous SA and results in a dynamic control of SA catabolism in a feedback mode. The SA accumulation, growth, leaf senescence, and pathogen resistance of the S5Hpro::GFP-S3H transgenic plants were investigated in parallel with NahG transgenic plants. The SA levels in the S5Hpro::EGFP-S3H transgenic plants were similar to or slightly lower than those of NahG transgenic Arabidopsis and resulted in SA deficient phenotypes. The low-SA trait of the S5Hpro::EGFP-S3H transgenic lines was inherited stably in the later generations.

Conclusions

Compared with NahG transgenic lines producing by-product catechol, S5Hpro::EGFP-S3H transgenic lines reduce SA levels by converting SA to a native product 2,3-DHBA for catabolism. Together, we provide new SA-deficient germplasms for the investigations of SA signaling in plant development, leaf senescence, and disease resistance.
Effect of medium with moderate temperature on patient's body temperature during percutaneous endoscopic lumbar discectomy
Authors: Sun Maji , Chu Fuchao , Zhang Lidong , Zhao Rui , Liu Xiaona , Yu Huilin , Pan Bin , Wu Jibin , Yuan Feng
Published: June 2022

Purpose

To explore the influence of irrigating fluid at different temperatures on patients' body temperature and local inflammatory mediators during spinal endoscopy.

Methods

110 cases of intervertebral foramen surgery in our hospital from January 2019 to October 2021 were randomly divided into control group and observation group. Operations of both groups were performed by the same experienced chief physician. The observation group was irrigated with 37 °C constant temperature saline, while the control group was irrigated at room temperature. The effect was evaluated by monitoring the intraoperative temperature, postoperative VAS score and the levels of inflammatory factors, such as TNF-α, IL-1, IL-6 and IL-10 in drainage fluid.

Results

After 30 min of operation, overall temperature of the control group dropped significantly, and 50 cases (90.9%) had hypothermia, P < 0.05. There was no significant difference in preoperative VAS score between the two groups P > 0.05. The VAS score of observation group was significantly lower than that of control group at 6 h and 1 month after operation, P < 0.05. At 0, 3 and 6 h after operation, the values of TNF-α, IL-1, IL-6 and IL-10 in the observation group were significantly lower than those in the control group (P < 0.05).

Conclusions

Isothermal flushing solution can reduce the incidence of hypothermia and effectively alleviate local inflammatory reaction.
Artificial intelligence-directed acupuncture: a review
Authors: Wang Yulin , Shi Xiuming , Efferth Thomas , Shang Dong
Published: June 2022

Acupuncture is widely used around the whole world nowadays and exhibits significant efficacy against many chronic diseases, especially in pain-related diseases. With the rapid development of artificial intelligence (AI), its implementation into acupuncture has achieved a series of significant breakthroughs in many areas of acupuncture practice, such as acupoints selection and prescription, acupuncture manipulation identification, acupuncture efficacy prediction, and so on. The paper will discuss the significant theoretical and technical achievements in AI-directed acupuncture. AI-based data mining methods uncovered crucial acupoint combinations for treating various diseases, which provide a scientific basis for acupoints prescription in clinical practice. Furthermore, the rapid development of modern TCM instruments facilitates the integration of modern medical instruments, AI techniques, and acupuncture. This integration significantly improves the quantification, objectification, and standardization of acupuncture as well as the delivery of clinical personalized acupuncture therapy. Machine learning-based clinical efficacy prediction of acupuncture can help doctors screen patients who may benefit from acupuncture treatment. However, the existing challenges require additional work for developing AI-directed acupuncture. Some include a better understanding of ancient Chinese philosophy for AI researchers, TCM acupuncture theory-based explanation of the knowledge discoveries, construction of acupuncture databases, and clinical trials for novel knowledge validation. This review aims to summarize the major contribution of AI techniques to the discovery of novel acupuncture knowledge, the improvement for acupuncture safety and efficacy, the development and inheritance of acupuncture, and the major challenges for the further development of AI-directed acupuncture. The development of acupuncture can progress with the help of AI.
Distribution of five clinically important neuroglial proteins in the human brain
Authors: Sjölin Karl , Kultima Kim , Larsson Anders , Freyhult Eva , Zjukovskaja Christina , Alkass Kanar , Burman Joachim
Published: June 2022

Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.
Cleavage of tropomodulin-3 by asparagine endopeptidase promotes cancer malignancy by actin remodeling and SND1/RhoA signaling
Authors: Chen Binghong , Wang Mengying , Qiu Junjun , Liao Keman , Zhang Wenrui , Lv Qi , Ma Chunhui , Qian Zhongrun , Shi Zhonggang , Liang Rong , Lin Yan , Ye Jiazhou , Qiu Yongming , Lin Yingying
Published: June 2022

Background

Abnormal proliferation and migration of cells are hallmarks of cancer initiation and malignancy. Asparagine endopeptidase (AEP) has specific substrate cleavage ability and plays a pro-cancer role in a variety of cancers. However, the underlying mechanism of AEP in cancer proliferation and migration still remains unclear.

Methods

Co-immunoprecipitation and following mass spectrometry were used to identify the substrate of AEP. Western blotting was applied to measure the expression of proteins. Single cell/nuclear-sequences were done to detect the heterogeneous expression of Tmod3 in tumor tissues. CCK-8 assay, flow cytometry assays, colony formation assay, Transwell assay and scratch wound-healing assay were performed as cellular functional experiments. Mouse intracranial xenograft tumors were studied in in vivo experiments.

Results

Here we showed that AEP cleaved a ubiquitous cytoskeleton regulatory protein, tropomodulin-3 (Tmod3) at asparagine 157 (N157) and produced two functional truncations (tTmod3-N and tTmod3-C). Truncated Tmod3 was detected in diverse tumors and was found to be associated with poor prognosis of high-grade glioma. Functional studies showed that tTmod3-N and tTmod3-C enhanced cancer cell migration and proliferation, respectively. Animal models further revealed the tumor-promoting effects of AEP truncated Tmod3 in vivo. Mechanistically, tTmod3-N was enriched in the cell cortex and competitively inhibited the pointed-end capping effect of wild-type Tmod3 on filamentous actin (F-actin), leading to actin remodeling. tTmod3-C translocated to the nucleus, where it interacted with Staphylococcal Nuclease And Tudor Domain Containing 1 (SND1), facilitating the transcription of Ras Homolog Family Member A/Cyclin Dependent Kinases (RhoA/CDKs).

Conclusion

The newly identified AEP-Tmod3 protease signaling axis is a novel “dual-regulation” mechanism of tumor cell proliferation and migration. Our work provides new clues to the underlying mechanisms of cancer proliferation and invasive progression and evidence for targeting AEP or Tmod3 for therapy.
PITX2C increases the stemness features of hepatocellular carcinoma cells by up-regulating key developmental factors in liver progenitor
Authors: Jiang Lingxi , Wang Xia , Ma Fangfang , Wang Xuelong , Shi Minmin , Yan Qian , Liu Ming , Chen Juan , Shi Chaoran , Guan Xin-yuan
Published: June 2022

Background

Tumor cells exhibited phenotypic and molecular characteristics similar to their lineage progenitor cells. Liver developmental signaling pathways are showed to be associated with HCC development and oncogenesis. The similarities of expression profiling between liver progenitors (LPs) and HCC suggest that understanding the molecular mechanism during liver development could provide insights into HCC.

Methods

To profile the dynamic gene expression during liver development, cells from an in vitro liver differentiation model and two paired hepatocellular carcinoma (HCC) samples were analyzed using deep RNA sequencing. The expression levels of selected genes were analyzed by qRT-PCR. Moreover, the role of a key transcription factor, pituitary homeobox 2 (PITX2), was characterized via in vitro and vivo functional assays. Furthermore, molecular mechanism studies were performed to unveil how PITX2C regulate the key developmental factors in LPs, thereby increasing the stemness of HCC.

Results

PITX2 was found to exhibit a similar expression pattern to specific markers of LPs. PITX2 consists of three isoforms (PITX2A/B/C). The expression of PITX2 is associated with tumor size and overall survival rate, whereas only PITX2C expression is associated with AFP and differentiation in clinical patients. PITX2A/B/C has distinct functions in HCC tumorigenicity. PITX2C promotes HCC metastasis, self-renewal and chemoresistance. Molecular mechanism studies showed that PITX2C could up-regulate RALYL which could enhance HCC stemness via the TGF-β pathway. Furthermore, ChIP assays confirmed the role of PITX2C in regulating key developmental factors in LP.

Conclusion

PITX2C is a newly discovered transcription factor involved in hepatic differentiation and could increase HCC stemness by upregulating key transcriptional factors related to liver development.
Storing and analyzing a genome on a blockchain
Authors: Gürsoy Gamze , Brannon Charlotte M. , Ni Eric , Wagner Sarah , Khanna Amol , Gerstein Mark
Published: June 2022

There are major efforts underway to make genome sequencing a routine part of clinical practice. A critical barrier to these is achieving practical solutions for data ownership and integrity. Blockchain provides solutions to these challenges in other realms, such as finance. However, its use in genomics is stymied due to the difficulty in storing large-scale data on-chain, slow transaction speeds, and limitations on querying. To overcome these roadblocks, we developed a private blockchain network to store genomic variants and reference-aligned reads on-chain. It uses nested database indexing with an accompanying tool suite to rapidly access and analyze the data.
Conversion sweet sorghum biomass to produce value-added products
Authors: Hu Wei , Zhou Libin , Chen Ji-hong
Published: June 2022

Currently, most biotechnological products are produced from sugar- or starch-containing crops via microbial conversion, but accelerating the conflict with food supply. Thus, it has become increasingly interesting for industrial biotechnology to seek alternative non-food feedstock, such as sweet sorghum. Value-added chemical production from sweet sorghum not only alleviates dependency and conflict for traditional starch feedstocks (especially corn), but also improves efficient utilization of semi‐arid agricultural land resources, especially for China. Sweet sorghum is rich in components, such as fermentable carbohydrates, insoluble lignocellulosic parts and bioactive compounds, making it more likely to produce value-added chemicals. Thus, this review highlights detailed bioconversion methods and its applications for the production of value-added products from sweet sorghum biomass. Moreover, strategies and new perspectives on improving the production economics of sweet sorghum biomass utilization are also discussed, aiming to develop a competitive sweet sorghum-based economy.
Climate change diminishes the potential habitat of the bont tick (Amblyomma hebraeum): evidence from Mashonaland Central Province, Zimbabwe
Authors: Tagwireyi Paradzayi , Ndebele Manuel , Chikurunhe Wilmot
Published: June 2022

Background

Understanding the response of vector habitats to climate change is essential for vector management. Increasingly, there is fear that climate change may cause vectors to be more important for animal husbandry in the future. Therefore, knowledge about the current and future spatial distribution of vectors, including ticks (Ixodida), is progressively becoming more critical to animal disease control.

Methods

Our study produced present (2018) and future (2050) bont tick (Amblyomma hebraeum) niche models for Mashonaland Central Province, Zimbabwe. Specifically, our approach used the Ensemble algorithm in Biomod2 package in R 3.4.4 with a suite of physical and anthropogenic covariates against the tick’s presence-only location data obtained from cattle dipping facilities.

Results

Our models showed that currently (the year 2018) the bont tick potentially occurs in 17,008 km2, which is 60% of Mashonaland Central Province. However, the models showed that in the future (the year 2050), the bont tick will occur in 13,323 km2, which is 47% of Mashonaland Central Province. Thus, the models predicted an ~ 13% reduction in the potential habitat, about 3685 km2of the study area. Temperature, elevation and rainfall were the most important variables explaining the present and future potential habitat of the bont tick.

Conclusion

Results of our study are essential in informing programmes that seek to control the bont tick in Mashonaland Central Province, Zimbabwe and similar environments.

Graphical Abstract
Dark-light cycle disrupts bone metabolism and suppresses joint deterioration in osteoarthritic rats
Authors: Song Xiaopeng , Zhao Mingchao , Tang Jilang , Ma Tianwen , Bai Hui , Wang Xinyu , Liu Lin , Li Ting , Xu Xinyu , Sheng Xuanbo , Zhao Binger , Wang Yingying , Wang Tiantian , Guo Yingchao , Zhang Xinmin , Gao Li
Published: June 2022

Background

Light alteration affects the internal environment and metabolic homeostasis of the body through circadian rhythm disorders (CRD). CRD is one of the factors that induce and accelerate osteoarthritis (OA). Therefore, the aim of this study was to evaluate the effects of continuous dark-light (DL) cycle on joint inflammation, bone structure, and metabolism in normal and OA Sprague-Dawley (SD) rats.

Methods

Interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α were used to evaluate the systemic inflammation in rats. The pathological changes and inflammatory reactions of the cartilage and synovium of the knee joint in rats were evaluated by Safranin O-fast green and immunological staining. Bone turnover was assessed by histomorphometry and μCT scanning, as well as bone metabolism markers and proteins. The expression changes of clock proteins BMAL1, NR1D1, PER3, and CRY1 in representative tissues were detected by western blotting.

Results

DL cycle significantly inhibited body weight gain in normal and OA rats. The levels of proinflammatory factors in the peripheral blood circulation and degradation enzymes in the cartilage were significantly decreased in OA+DL rats. DL cycle significantly destroyed the structure of subchondral bone in hindlimbs of OA rats and reduced trabecular bone numbers. The decrease of bone mineral density (BMD), percent bone volume with respect to total bone volume (BV/TV), trabecular number (TB.N), osteoclast number, and mineralization could also be found. The ratio of the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) in the bone marrow of OA rats was markedly increased under DL, along with the activation of the mononuclear/phagocyte system. The expression of representative clock proteins and genes BMAL1, PER3, and CRY1 were markedly changed in the tissues of OA+DL rats.

Conclusions

These results suggested that DL cycle dampened the arthritis and promoted bone resorption and bone mass loss.

Graphical abstract

DL cycle affects bone turnover by regulating osteoclast production in osteoarthritic rats.
Low reliability of DNA methylation across Illumina Infinium platforms in cord blood: implications for replication studies and meta-analyses of prenatal exposures
Authors: Olstad Emilie Willoch , Nordeng Hedvig Marie Egeland , Sandve Geir Kjetil , Lyle Robert , Gervin Kristina
Published: June 2022

Background

There is an increasing interest in the role of epigenetics in epidemiology, but the emerging research field faces several critical biological and technical challenges. In particular, recent studies have shown poor correlation of measured DNA methylation (DNAm) levels within and across Illumina Infinium platforms in various tissues. In this study, we have investigated concordance between 450 k and EPIC Infinium platforms in cord blood. We could not replicate our previous findings on the association of prenatal paracetamol exposure with cord blood DNAm, which prompted an investigation of cross-platform DNAm differences.

Results

This study is based on two DNAm data sets from cord blood samples selected from the Norwegian Mother, Father and Child Cohort Study (MoBa). DNAm of one data set was measured using the 450 k platform and the other data set was measured using the EPIC platform. Initial analyses of the EPIC data could not replicate any of our previous significant findings in the 450 k data on associations between prenatal paracetamol exposure and cord blood DNAm. A subset of the samples (n = 17) was included in both data sets, which enabled analyses of technical sources potentially contributing to the negative replication. Analyses of these 17 samples with repeated measurements revealed high per-sample correlations ($$\stackrel{\mathrm{-}}{\text{R}}\hspace{0.17em}\approx$$

R
-

≈

 0.99), but low per-CpG correlations ($$\stackrel{\mathrm{-}}{\text{R}}$$

R
-

 ≈ 0.24) between the platforms. 1.7% of the CpGs exhibited a mean DNAm difference across platforms > 0.1. Furthermore, only 26.7% of the CpGs exhibited a moderate or better cross-platform reliability (intra-class correlation coefficient ≥ 0.5).

Conclusion

The observations of low cross-platform probe correlation and reliability corroborate previous reports in other tissues. Our study cannot determine the origin of the differences between platforms. Nevertheless, it emulates the setting in studies using data from multiple Infinium platforms, often analysed several years apart. Therefore, the findings may have important implications for future epigenome-wide association studies (EWASs), in replication, meta-analyses and longitudinal studies. Cognisance and transparency of the challenges related to cross-platform studies may enhance the interpretation, replicability and validity of EWAS results both in cord blood and other tissues, ultimately improving the clinical relevance of epigenetic epidemiology.
Suspected cholinergic toxicity due to cevimeline hydrochloride and Bacopa monnieri interaction: a case report
Authors: Acquarulo Blake , Tandon Priya , Macica Carolyn M.
Published: June 2022

Background

Muscarinic agonists are indicated for the treatment of many conditions including ileus, urinary retention, glaucoma, and Sjögren’s syndrome. Due to their lack of tissue specificity, these drugs can lead to undesirable side effects at off-target sites and may be potentiated by supplements that impact the half-life of these drugs.

Case presentation

A 58-year-old Caucasian female with history of Sjögren’s syndrome, who was being managed with cevimeline, presented to the primary care office with reported hyperhidrosis, malaise, nausea, and tachycardia. She reported taking an herbal supplement containing B. monnieri and phosphatidylserine the previous night. It has been previously demonstrated that B. monnieri alters cytochrome P450 enzymes. Electrocardiogram showed no acute ST–T changes. Clinical improvement occurred with hydration and discontinuation of the supplement.

Conclusions

To our knowledge, there has only been one other documented cevimeline overdose, and it was not associated with an herbal supplementation interaction. Physicians should actively elicit herbal supplement information from patients to anticipate possible drug–herb interactions. An additional consideration of clinical relevance is the known genetic variability that may affect drug responsiveness due to differences in metabolism and half-life of drugs that arise from common genetic variants of cytochrome P450 genes.
Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: a successful phase 1, control-placebo group, clinical trial
Authors: Kaffash Farkhad Najmeh , Sedaghat Alireza , Reihani Hamidreza , Adhami Moghadam Amir , Bagheri Moghadam Ahmad , Khadem Ghaebi Nayereh , Khodadoust Mohammad Ali , Ganjali Rashin , Tafreshian Amir Reza , Tavakol-Afshari Jalil
Published: June 2022

Background

Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild–moderate COVID-19-induced ARDS patients.

Methods

Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × $${10}^{6}$$

10

6

cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period.

Results

During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P < 0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 were observed. Also, no significant changes were observed in CT scan images of patients during the study period.

Conclusion

Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results.

Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).
On a nonlinear second-order difference equation
Authors: Stević Stevo , Iričanin Bratislav , Kosmala Witold , Šmarda Zdeněk
Published: June 2022

We study a nonlinear second-order difference equation which considerably extends some equations in the literature. Our main result shows that the difference equation is solvable in closed form. Some applications of the main result are also given.
Numerical analysis of time-fractional Sobolev equation for fluid-driven processes in impermeable rocks
Authors: Avazzadeh Zakieh , Nikan Omid , Tenreiro Machado José , Rasoulizadeh Mohammad Navaz
Published: June 2022

This paper proposes a local meshless radial basis function (RBF) method to obtain the solution of the two-dimensional time-fractional Sobolev equation. The model is formulated with the Caputo fractional derivative. The method uses the RBF to approximate the spatial operator, and a finite-difference algorithm as the time-stepping approach for the solution in time. The stability of the technique is examined by using the matrix method. Finally, two numerical examples are given to verify the numerical performance and efficiency of the method.
Initial viral cycle threshold values in patients with COVID-19 and their clinical significance
Authors: AlBahrani Salma , Alghamdi Mohammed , Zakary Nawaf , Jebakumar Arulanantham Zechariah , AlZahrani Samirah Jamaan , ElGezery Mohamed Hany , Abdallah Khaled Omar , Al-Tawfiq Jaffar A.
Published: June 2022

Background

The connection between initial viral cycle threshold (Ct) values of the SARS-CoV-2 with symptoms and hospital course is not clearly studied.

Methods

This is a retrospective study of hospitalized COVID-19 patients from Jun 1st 2020 to March 30th, 2021 examining the relationship between initial viral cycle threshold (Ct) values of SARS-CoV-2 as obtained from nasopharyngeal samples. The clinical presentations and outcomes were analyzed in relation to the initial Ct values.

Results

The study included 202 hospitalized COVID-19 patients with a mean age (± SD) of 54.75 (± 15.93) and 123 (60.9%) males and 79 (39.1%) females. Of all the patients, the most frequent comorbidity was diabetes mellitus (95; 47%) and the most frequent symptoms were fever (148; 73.3%) and cough (141; 69.8%). There was no significant difference in relation to underlying conditions, clinical presentation, radiographic and laboratory data among those with low, medium and high Ct values. The mean Ct values showed no statistical change over the 10-month study period.

Conclusions

Initial SARS-CoV-2 Ct values did not show any association with clinical symptoms and did not predict the need for mechanical intubation or death.
Zinc oxide nanoparticles synthesized using Hyssopus Officinalis L. Extract Induced oxidative stress and changes the expression of key genes involved in inflammatory and antioxidant Systems
Authors: Rahimi Ghasem , Mohammad Kalateh Shah , Zarei Mahsa , Shokoohi Mohammad , Oskoueian Ehsan , Poorbagher Mahsa Rastegar Moghaddam , Karimi Ehsan
Published: June 2022

Background

Recent advances in the synthesis of bioactive nanoparticles resulted in the discovery and introduction of new bioactive nanoparticles to the pharmaceutical industry. In this regard, this research is aimed to synthesize the zinc oxide nanoparticles (ZnO-NPs) using Hyssopus officinalis L. extract and to evaluate the safety of nanoparticles using Balb/C mice.

Methods

Forty male mice were divided into four groups and received 0, 50, 100, and 200 mg/kg of ZnO-NPs for thirty days. At the end of the experiment, blood sugar, creatinine, aspartate aminotransferase (A.S.T.), and alanine aminotransferase (A.L.T.) were determined. Furthermore, histopathological and oxidative stress biomarker analyses in liver and kidney tissues were performed. The changes in the major inflammatory- and antioxidant-related genes were determined.

Results

The results showed that blood sugar and creatinine reduced significantly (P < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. The serum ALT and AST and lipid peroxidation in the liver and kidney tissues were increased significantly (p < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. Supplementation of ZnO-NPs suppressed the expression of antioxidant-related genes (SOD and CAT) and up-regulated the inflammatory biomarkers (iNOS and TNF- α). The concentration of 200 mg/Kg nanoparticles indicated cellular degeneration and necrosis in the liver and kidney tissues.

Conclusions

Overall, it can be concluded that supplementation of ZnO-NPs synthesized using Hyssopus Officinalis L. extract in this study at 50 mg/kg or higher concentrations might be toxic to the mice.
Avian diversity and bird-aircraft strike problems in Bahir Dar International Airport, Bahir Dar, Ethiopia
Authors: Tefera Tsegaye , Ejigu Dessalegn , Tassie Nega
Published: June 2022

Background

Bahir Dar International Airport and its surrounding habitats are known for their rich avifaunal diversity, which results in bird-aircraft collisions as a fundamental problem in the area. A study on bird diversity and bird-aircraft strikes at Bahir Dar International Airport was conducted between February 2020 and August 2020. Based on its vegetation structures, the study area was classified into four habitat types namely; bushland, grassland, wetland, and modified habitats. Transect and point count methods were used to collect data on avian diversity and abundance. Questionnaire surveys, interviews, and document analysis were used to gather information about incidents and protection measures against bird-aircraft strike problems. Shannon–Wiener diversity index, Simpson’s similarity index, ANOVA, and chi-square test were used for data analysis.

Results

A total of 80 avian species belonging to 15 orders and 40 families were identified in the study area. The highest species diversity (H’ = 3.59) and species evenness (E = 0.96) were recorded in modified habitats during the wet season. Relative abundance categories of birds in the study area showed that most were uncommon birds. Birds pose severe threats to aircraft in the airport and 92.3% of the respondents replied that most bird-aircraft strikes occurred early in the morning and late in the afternoon when birds remain more active. The majority (88.5%) of questionnaire participants confirmed that bird-aircraft strike incidents frequently occurred during the time of takeoff and landing of the aircraft. It is also known that on average forty bird-aircraft collisions per year happen at the airport.

Conclusion

Bahir Dar International Airport is rich in its bird diversity that recalls the aviation authority to work in collaboration with different organizations to avoid bird-aircraft strike problems using different control measures without compromising the conservation of birds.
Conscientiousness protects visual search performance from the impact of fatigue
Authors: Grady Justin N. , Cox Patrick H. , Nag Samoni , Mitroff Stephen R.
Published: June 2022

Visual search—looking for targets among distractors—underlies many critical professions (e.g., radiology, aviation security) that demand optimal performance. As such, it is important to identify, understand, and ameliorate negative factors such as fatigue—mental and/or physical tiredness that leads to diminished function. One way to reduce the detrimental effects is to minimize fatigue itself (e.g., scheduled breaks, adjusting pre-shift behaviors), but this is not always possible or sufficient. The current study explored whether some individuals are less susceptible to the impact of fatigue than others; specifically, if conscientiousness, the ability to control impulses and plan, moderates fatigue’s impact. Participants (N = 374) self-reported their energy (i.e., the inverse of fatigue) and conscientiousness levels and completed a search task. Self-report measures were gathered prior to completing the search task as part of a large set of surveys so that participants could not anticipate any particular research question. Preregistered linear mixed-effect analyses revealed main effects of energy level (lower state energy related to lower accuracy) and conscientiousness (more trait conscientiousness related to higher accuracy), and, critically, a significant interaction between energy level and conscientiousness. A follow-up analysis, that was designed to illustrate the nature of the primary result, divided participants into above- vs. below-median conscientiousness groups and revealed a significant negative relationship between energy level and accuracy for the below median, but not above-median, group. The results raise intriguing operational possibilities for visual search professions, with the most direct implication being the incorporation of conscientiousness measures to personnel selection processes.
Pre-Columbian red pine (Pinus resinosa Ait.) fire regimes of north-central Pennsylvania, USA
Authors: Marschall Joseph M. , Stambaugh Michael C. , Abadir Erin R. , Dey Daniel C. , Brose Patrick H. , Bearer Scott L. , Jones Benjamin C.
Published: June 2022

Background

Fire-dependent vegetation communities in the northeastern USA have undergone significant transitions since social and ecological disruptions associated with Euro-American colonization of North America. There is much interest, though little information available, about historical fire regimes of fire-adapted vegetation communities in the northeastern USA in pre-Columbian times (i.e., pre-1492 CE). We intensively investigated a red pine (Pinus resinosaAit.)—oak (Quercusspp.) forested landscape in north-central Pennsylvania, USA, for exceptionally old red pine remnants (stumps, snags) where previous research had suggested the potential to develop fire-scar and tree-ring chronologies which extend to time periods prior to 1492.

Results

Tree-ring and fire-scar chronologies recovered from red pine trees extend back to 1370 and 1402, respectively. Red pine trees were broadly distributed across this landscape (34.4 km2area) prior to 1492, and frequent fire (i.e., mean fire return intervals of 4.1 years at landscape scale, 9.7–11.7 years at smaller spatial scales (0.5–7.1 km2)) was observed in the time period prior to sustained contact between Indigenous peoples and Euro-American colonizers circa 1609.

Conclusions

This study resulted in the longest fire-scar record in eastern North America and offers unique foundational ecological information regarding pre-Columbian fire regimes of northeastern USA fire-adapted forest communities. Fire scars provide physical evidence that fire was an important ecological component of this landscape before and after 1492 and that the current period of reduced fire activity is unprecedented in the 500 years prior to fire exclusion practices that were widely adopted circa 1915. Beyond fire scars, the spatial and temporal extent of the red pine tree-ring record provides evidence that red pine, a fire-dependent species, was historically a more important component of this landscape than it is today. The conservation of red pine vegetation communities will require incorporating recurring fire into management plans, for the successful regeneration and perpetuation of red pine, and to sustain associated flora and fauna of conservation concern.
Laboratory information management system for COVID-19 non-clinical efficacy trial data
Authors: Yoon Suhyeon , Noh Hyuna , Jin Heejin , Lee Sungyoung , Han Soyul , Kim Sung-Hee , Kim Jiseon , Seo Jung Seon , Kim Jeong Jin , Park In Ho , Oh Jooyeon , Bae Joon-Yong , Lee Gee Eun , Woo Sun-Je , Seo Sun-Min , Kim Na-Won , Lee Youn Woo , Jang Hui Jeong , Hong Seung-Min , An Se-Hee , Lyoo Kwang-Soo , Yeom Minjoo , Lee Hanbyeul , Jung Bud , Yoon Sun-Woo , Kang Jung-Ah , Seok Sang-Hyuk , Lee Yu Jin , Kim Seo Yeon , Kim Young Been , Hwang Ji-Yeon , On Dain , Lim Soo-Yeon , Kim Sol Pin , Jang Ji Yun , Lee Ho , Kim Kyoungmi , Lee Hyo-Jung , Kim Hong Bin , Park Jun Won , Jeong Dae Gwin , Song Daesub , Choi Kang-Seuk , Lee Ho-Young , Choi Yang-Kyu , Choi Jung-ah , Song Manki , Park Man-Seong , Seo Jun-Young , Nam Ki Taek , Shin Jeon-Soo , Won Sungho , Yun Jun-Won , Seong Je Kyung
Published: June 2022

Background

As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research.

Results

In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research.

Conclusions

This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.
COVID-19 vaccination rates in hospitalized mentally ill patients compared to the general population in Germany: Results from the COVID Ψ Vac study
Authors: Wiegand Hauke F. , Maicher Birgit , Rueb Mike , Wessels Paula , Besteher Bianca , Hellwig Sabine , Pfennig Andrea , Rohner Henrik , Unterecker Stefan , Hölzel Lars P. , Philipsen Alexandra , Domschke Katharina , Falkai Peter , Lieb Klaus , Adorjan Kristina
Published: June 2022

Background

Mental illness is known to come along with a large mortality gap compared to thegeneral population and it is a risk for COVID-19 related morbidity andmortality. Achieving high vaccination rates in people with mental illness is therefore important. Reports are conflicting on whether vaccination rates comparable to those of the general population can be achieved and which variables represent risk factors for nonvaccination in people with mental illness.

Methods

The COVID Ψ Vac study collected routine data on vaccination status, diagnostic groups, sociodemographics, and setting characteristics from in- and day-clinic patients of 10 psychiatric hospitals in Germany in August 2021. Logistic regression modeling was used to determine risk factors for nonvaccination.

Results

Complete vaccination rates were 59% (n = 776) for the hospitalized patients with mental illness versus 64% for the regionally and age-matched general population. Partial vaccination rates were 68% (n = 893) for the hospitalised patients with mental illness versus 67% for the respective general population and six percentage (n = 74) of this hospitalized population were vaccinated during the hospital stay. Rates showed a large variation between hospital sites. An ICD-10 group F1, F2, or F4 main diagnosis, younger age, and coercive accommodation were further risk factors for nonvaccination in the model.

Conclusions

Vaccination rates were lower in hospitalized people with mental illness than in the general population. By targeting at-risk groups with low-threshold vaccination programs in all health institutions they get in contact with, vaccination rates comparable to those in the general population can be achieved.