bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipose-derived stem cells alleviate liver injury induced by type 1 diabetes mellitus by inhibiting mitochondrial stress and attenuating inflammation
Authors: Hou Yanli , Ding Wenyu , Wu Peishan , Liu Changqing , Ding Lina , Liu Junjun , Wang Xiaolei
Published: April 2022

Background

Type 1 diabetes mellitus (T1D) is a worldwide health priority due to autoimmune destruction and is associated with an increased risk of multiorgan complications. Among these complications, effective interventions for liver injury, which can progress to liver fibrosis and hepatocellular carcinoma, are lacking. Although stem cell injection has a therapeutic effect on T1D, whether it can cure liver injury and the underlying mechanisms need further investigation.

Methods

Sprague–Dawley rats with streptozotocin (STZ)-induced T1D were treated with adipose-derived stem cell (ADSC) or PBS via the tail vein formed the ADSC group or STZ group. Body weights and blood glucose levels were examined weekly for 6 weeks. RNA-seq and PCR array were used to detect the difference in gene expression of the livers between groups.

Results

In this study, we found that ADSCs injection alleviated hepatic oxidative stress and injury and improved liver function in rats with T1D; potential mechanisms included cytokine activity, energy metabolism and immune regulation were potentially involved, as determined by RNA-seq. Moreover, ADSC treatment altered the fibroblast growth factor 21 (FGF21) and transforming growth factor β (TGF-β) levels in T1D rat livers, implying its repair capacity. Disordered intracellular energy metabolism, which is closely related to mitochondrial stress and dysfunction, was inhibited by ADSC treatment. PCR array and ingenuity pathway analyses suggested that the ADSC-induced suppression of mitochondrial stress is related to decreased necroptosis and apoptosis. Moreover, mitochondria-related alterations caused liver inflammation, resulting in liver injury involving the T lymphocyte-mediated immune response.

Conclusions

Overall, these results improve our understanding of the curative effect of ADSCs on T1D complications: ADSCs attenuate liver injury by inhibiting mitochondrial stress (apoptosis and dysfunctional energy metabolism) and alleviating inflammation (inflammasome expression and immune disorder). These results are important for early intervention in liver injury and for delaying the development of liver lesions in patients with T1D.
Return to work after cell transplantation in patients with angiitis-induced critical limb ischaemia and factors related: a single-centre retrospective cohort study
Authors: Liu Hao , Liu Yifan , Pan Tianyue , Fang Yuan , Fang Gang , Jiang Xiaolang , Chen Bin , Wei Zheng , Gu Shiyang , Liu Peng , Fu Weiguo , Dong Zhihui
Published: April 2022

Background

Angiitis-induced critical limb ischaemia (AICLI) patients, who are usually young and have a high amputation rate, always lose their ability to return to the labour force. Return to work (RTW) not only indicates patients’ physical health, showing that they could undertake the work, but also demonstrates their psychological well-being. While cell transplantation showed satisfactory efficacy in limb salvage, few studies of AICLI patients’ RTW after transplantation have been reported.

Methods

From May 2009 to May 2021, AICLI patients who underwent cell transplantation and completed no less than 12 months of follow-up were retrospectively enrolled. The primary endpoint was RTW. Patient demographics and characteristics of the ischaemic limbs were reviewed to analyse independent risk factors for RTW.

Results

A total of 171 AICLI patients (170 males) were enrolled with a mean age of 41.9 ± 9.6 years (range: 20–57 years). The 12-month and 24-month RTW cumulative rates were 69.4% (95% confidence interval [CI] 61.6–75.6%) and 70.1% (95% CI 62.3–76.2%), respectively. Age < 40 years (odds ratio [OR] 2.659, 95% CI 1.138–6.719) and preoperative occupation as a mental worker (OR 8.930, 95% CI 2.665–42.847) were identified as independent protective factors for RTW. Perioperative limb infection with ulcer or gangrene (OR 0.250, 95% CI 0.075–0.779) was identified as an independent risk factor.

Conclusion

AICLI patients who underwent cell transplantation usually had a satisfactory midterm RTW cumulative rate. AICLI patients < 40 years old with preoperative occupation as mental workers were more likely to return to work. Prevention of limb infection during the perioperative period is of great significance to RTW.
Chaperone-mediated autophagy plays an important role in regulating retinal progenitor cell homeostasis
Authors: Jin Caixia , Ou Qingjian , Chen Jie , Wang Tao , Zhang Jieping , Wang Zhe , Wang Yuanyuan , Tian Haibin , Xu Jing-Ying , Gao Furong , Wang Juan , Li Jiao , Lu Lixia , Xu Guo-Tong
Published: April 2022

Purpose

To explore the function and regulatory mechanism of IFITM3 in mouse neural retinal progenitor cells (mNRPCs), which was found to be very important not only in the development of the retina in embryos but also in NRPCs after birth.

Methods

Published single-cell sequencing data were used to analyze IFITM3 expression in mNRPCs. RNA interference was used to knock down the expression of IFITM3. CCK-8 assays were used to analyze cell viability. RNA-seq was used to assess mRNA expression, as confirmed by real-time quantitative PCR, and immunofluorescence assays and western blots were used to validate the levels of relative proteins, and autophagy flux assay. Lysosomal trackers were used to track the organelle changes.

Results

The results of single-cell sequencing data showed that IFITM3 is highly expressed in the embryo, and after birth, RNA-seq showed high IFITM3 expression in mNRPCs. Proliferation and cell viability were greatly reduced after IFITM3 was knocked down. The cell membrane system and lysosomes were dramatically changed, and lysosomes were activated and evidently agglomerated in RAMP-treated cells. The expression of LAMP1 was significantly increased with lysosome agglomeration after treatment with rapamycin (RAMP). Further detection showed that SQSTM1/P62, HSC70 and LAMP-2A were upregulated, while no significant difference in LC3A/B expression was observed; no autophagic flux was generated.

Conclusion

IFITM3 regulates mNRPC viability and proliferation mainly through chaperone-mediated autophagy (CMA) but not macroautophagy (MA). IFITM3 plays a significant role in maintaining the homeostasis of progenitor cell self-renewal by sustaining low-level activation of CMA to eliminate deleterious factors in cells.
Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial
Authors: Karyana Muhammad , Djaharuddin Irawaty , Rif’ati Lutfah , Arif Mansyur , Choi Mi Kyung , Angginy Nova , Yoon Aeri , Han Jumi , Josh Fonny , Arlinda Dona , Narulita Asvin , Muchtar Faisal , Bakri Rizki Auliah , Irmansyah s
Published: April 2022

Background

Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection.

Methods

This phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107cells and 1.0 × 108cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period.

Results

There were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups.

Conclusions

Our clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19.

Trial registration

ClinicalTrials.gov, NCT04535856. Registered 2 September 2020,https://clinicaltrials.gov/ct2/show/NCT04535856
Histone chaperone HIRA complex regulates retrotransposons in embryonic stem cells
Authors: Zhang Miao , Zhao Xin , Feng Xiao , Hu Xiao , Zhao Xuan , Lu Wange , Lu Xinyi
Published: April 2022

Background

Histone cell cycle regulator (HIRA) complex is an important histone chaperone that mediates the deposition of the H3.3 histone variant onto chromatin independently from DNA synthesis. However, it is still unknown whether it participates in the expression control of retrotransposons and cell fate determination.

Methods

We screened the role of HIRA complex members in repressing the expression of retrotransposons by shRNA depletion in embryonic stem cells (ESCs) followed by RT-qPCR. RNA-seq was used to study the expression profiles after depletion of individual HIRA member. RT-qPCR and western blot were used to determine overexpression of HIRA complex members. Chromatin immunoprecipitation (ChIP)-qPCR was used to find the binding of H3.3, HIRA members to chromatin. Co-immunoprecipitation was used to identify the interaction between Hira mutant and Ubn2. ChIP-qPCR was used to identify H3.3 deposition change and western blot of chromatin extract was used to validate the epigenetic change. Bioinformatics analysis was applied for the analysis of available ChIP-seq data.

Results

We revealed that Hira, Ubn2, and Ubn1 were the main repressors of 2-cell marker retrotransposon MERVL among HIRA complex members. Surprisingly, Ubn2 and Hira targeted different groups of retrotransposons and retrotransposon-derived long noncoding RNAs (lncRNAs), despite that they partially shared target genes. Furthermore, Ubn2 prevented ESCs to gain a 2-cell like state or activate trophectodermal genes upon differentiation. Mechanistically, Ubn2 and Hira suppressed retrotransposons by regulating the deposition of histone H3.3. Decreased H3.3 deposition, that was associated with the loss of Ubn2 or Hira, caused the reduction of H3K9me2 and H3K9me3, which are known repressive marks of retrotransposons.

Conclusions

Overall, our findings shed light on the distinct roles of HIRA complex members in controlling retrotransposons and cell fate conversion in ESCs.
Systemic evolutionary chemical space exploration for drug discovery
Authors: Lu Chong , Liu Shien , Shi Weihua , Yu Jun , Zhou Zhou , Zhang Xiaoxiao , Lu Xiaoli , Cai Faji , Xia Ning , Wang Yikai
Published: April 2022

Chemical space exploration is a major task of the hit-finding process during the pursuit of novel chemical entities. Compared with other screening technologies, computational de novo design has become a popular approach to overcome the limitation of current chemical libraries. Here, we reported a de novo design platform named systemic evolutionary chemical space explorer (SECSE). The platform was conceptually inspired by fragment-based drug design, that miniaturized a “lego-building” process within the pocket of a certain target. The key to virtual hits generation was then turned into a computational search problem. To enhance search and optimization, human intelligence and deep learning were integrated. Application of SECSE against phosphoglycerate dehydrogenase (PHGDH), proved its potential in finding novel and diverse small molecules that are attractive starting points for further validation. This platform is open-sourced and the code is available at http://github.com/KeenThera/SECSE.
In vivo vesicular acetylcholine transporter density in human peripheral organs: an [18F]FEOBV PET/CT study
Authors: Horsager Jacob , Okkels Niels , Van Den Berge Nathalie , Jacobsen Jan , Schact Anna , Munk Ole Lajord , Vang Kim , Bender Dirk , Brooks David J. , Borghammer Per
Published: April 2022

Background

The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [18F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53–86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands.

Results

A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs.

Conclusion

High [18F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [18F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration.

Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1.
Measuring disability-adjusted life years (DALYs) due to COVID-19 in Scotland, 2020
Authors: Wyper Grant M. A. , Fletcher Eilidh , Grant Ian , McCartney Gerry , Fischbacher Colin , Harding Oliver , Jones Hannah , de Haro Moro Maria Teresa , Speybroeck Niko , Devleesschauwer Brecht , Stockton Diane L.
Published: April 2022

Background

Disability-adjusted life years (DALYs) combine the impact of morbidity and mortality and can enable comprehensive, and comparable, assessments of direct and indirect health harms due to COVID-19. Our aim was to estimate DALYs directly due to COVID-19 in Scotland, during 2020; and contextualise its population impact relative to other causes of disease and injury.

Methods

National deaths and daily case data were used. Deaths were based on underlying and contributory causes recorded on death certificates. We calculated DALYs based on the COVID-19 consensus model and methods outlined by the European Burden of Disease Network. DALYs were presented as a range, using a sensitivity analysis based on Years of Life Lost estimates using: cause-specific; and COVID-19 related deaths. All COVID-19 estimates were for 2020.

Results

In 2020, estimates of COVID-19 DALYs in Scotland ranged from 96,500 to 108,200. Direct COVID-19 DALYs were substantial enough to be framed as the second leading cause of disease and injury, with only ischaemic heart disease having a larger impact on population health. Mortality contributed 98% of total DALYs.

Conclusions

The direct population health impact of COVID-19 has been very substantial. Despite unprecedented mitigation efforts, COVID-19 developed from a single identified case in early 2020 to a condition with an impact in Scotland second only to ischaemic heart disease. Periodic estimation of DALYs during 2021, and beyond, will provide indications of the impact of DALYs averted due to the national rollout of the vaccination programme and other continued mitigation efforts, although new variants may pose significant challenges.
Does food security exist among farm households? Evidence from Ghana
Authors: Acheampong Patricia Pinamang , Obeng Elvis Agyei , Opoku Monica , Brobbey Lydia , Sakyiamah Bernard
Published: April 2022

Background

Food security exists when households have physical, social and economic access to sufficient, safe and nutritious food at all times that meets their dietary needs and food preferences for an active and healthy life. Food security remains a serious challenge for many households in Ghana and the situation is even more prevalent among smallholder farmers. Therefore, this study had its objectives to assess food security status and also estimate their determinants for policy recommendations.

Methodology

Using data collected from 2,603 farm households across Ghana and employing an ordered probit model the determinants of food security among farm households were assessed. The food security indicator, Food Consumption Score (FCS) which combines diet diversity, frequency of consumption and relative nutritional importance of different food groups was used to determine food security status of farm households.

Results

Results showed that farm households (76%) across Ghana were within the acceptable household food consumption groups. Nonetheless, 19% and 6% of farm households, respectively, were within the borderline and poor food consumption groups, respectively. Determinants of food security included experience, gender, improved variety adoption, access to credit and location.

Conclusion

Food security risk is prevalent among farm households in Ghana. Based on the results on determinants of food security, the suggestions are that government and private institutions should create an enabling environment to enhancing credit access and encouraging adoptions of improved crops varieties for increased production.
Personality metatraits predict resilience among family caregivers responsible for a dependent youth’s chronic respiratory management
Authors: Dong Sidai , Elliott Timothy R. , Luo Wen , Warren Ann Marie , Warren Robert
Published: April 2022

Background

Family caregivers of children and youth with severe neurodisabilities that require chronic respiratory management often report a compromised quality of life. In this cross-sectional study, we used DeYoung’s (Psychol Inq 21(1): 26–33, 2010. 10.1080/10478401003648674) conceptualization of two personality metatraits, Alpha and Beta, to test their theorized role in facilitating resilience among these family caregivers. We expected higher Alpha and Beta would exhibit direct, beneficial effects on caregiver mental and physical health quality of life (QoL), and they would operate through self-reported resilience and coping to exert positive, indirect effects on caregiver QoL.

Methods

Family caregivers of children and youth at an outpatient chronic respiratory management clinic were informed of the study. Of the 68 who consented, 61 provided complete data on measures of personality traits, coping styles, and physical and mental health-related QoL. Factor analytic techniques verified the two personality metatraits, consistent with the DeYoung model. The metatraits were then used as predictor variables in a path model to predict physical and mental health-related QoL. Self-reported resilience and a coping variable were examined as possible mediators of the personality-QoL relationship.

Results

Correlational analyses isolated a coping variable that met criteria as a possible mediator. The path model exhibited good fit to the data. The Alpha metatrait—characterized by emotional stability, self-regulation, perseverance, and intrinsic motivation—was directly predictive of caregiver mental health. The Beta metatrait, reflecting a disposition for adaptive flexibility, responsiveness, and interpersonal initiative, demonstrated significant indirect effects to physical and mental health through its positive association with coping efforts to maintain social support and a sense of self.

Conclusions

Consistent with DeYoung’s conceptualization, higher Alpha and Beta predicted caregiver resilience, albeit through different pathways. The emotional stability, perseverance and emotional regulation associated with Alpha likely accounted for its positive association with caregiver mental health. Beta, in contrast, may operate through their adaptive flexibility, personal resourcefulness and social engagement to augment coping efforts that involve others and support family activities, which, in turn, promote their own physical and mental health. Limitations of the cross-sectional design, and potential theoretical and clinical implications of the personality metatraits and their relation to resilience are discussed.
Sperm DNA damage compromises embryo development, but not oocyte fertilisation in pigs
Authors: Mateo-Otero Yentel , Llavanera Marc , Recuero Sandra , Delgado-Bermúdez Ariadna , Barranco Isabel , Ribas-Maynou Jordi , Yeste Marc
Published: April 2022

Background

The assessment of sperm DNA integrity has been proposed as a complementary test to conventional mammalian semen analysis. In this sense, single-strand (SSB) and double-strand (DSB) DNA breaks, the two types of sperm DNA fragmentation (SDF), have been reported to have different aetiologies and to be associated to different fertility outcomes in bovine and humans. Considering that no studies in porcine have addressed how SDF may affect sperm quality and fertility outcomes, the present work aimed to determine the impact of global DNA damage, SSB and DSB on sperm quality and in vitro fertilising ability. To this end, 24 ejaculates (one per boar) were split into three aliquots: the first was used to assess sperm quality parameters through a computer-assisted sperm analysis (CASA) system and flow cytometry; the second was used to perform in vitro fertilisation, and the third, to evaluate sperm DNA integrity using alkaline and neutral Comet assays.

Results

The results showed that global DNA damage negatively correlates (P < 0.05) with normal sperm morphology (R = − 0.460) and progressive motility (R = − 0.419), and positively with the percentage of non-viable sperm (R = 0.507). Multiple regression analyses showed that non-viable sperm were related to SSB (β = − 0.754). In addition, while fertilisation did not seem to be affected by sperm DNA integrity, global DNA damage, DSB and SSB were found to be correlated to embryo development outcomes. Specifically, whereas global DNA damage and DSB negatively affected (P < 0.05) the later preimplantation embryo stages (percentage of early blastocyst/blastocyst D6: for global DNA damage, R = − 0.458, and for DSB, R = − 0.551; and percentage of hatching/hatched blastocyst D6: for global DNA damage, R = − 0.505, and for DSB, R = − 0.447), global DNA damage and SSB had a negative impact (P < 0.05) on the developmental competency of fertilised embryos (R = − 0.532 and R = − 0.515, respectively). Remarkably, multiple regression analyses supported the associations found in correlation analyses. Finally, the present work also found that the inclusion of Comet assays to the conventional sperm quality tests improves the prediction of blastocyst formation (AUC = 0.9021,P < 0.05), but not fertilisation rates (P > 0.05).

Conclusion

Considering all these findings, this work sets a useful model to study how SDF negatively influences fertility.
Transfer of brotizolam, periciazine, and sulpiride in cord blood and breast milk, and alprazolam in breast milk: a case report
Authors: Saito Jumpei , Tachibana Yoshiyuki , Wada Yuka Sano , Yakuwa Naho , Kawasaki Hiroyo , Suzuki Tomo , Sago Haruhiko , Yamatani Akimasa , Murashima Atsuko
Published: April 2022

Background

A high prevalence of mental disorders including depression, anxiety, somatoform, and dissociative disorder is reported during pregnancy, however, information on the transfer of antipsychotics across the placenta and into breast milk is limited. We evaluated brotizolam, periciazine and sulpiride in cord blood, maternal serum, and breast milk, and alprazolam in breast milk.

Case presentation

A 38-year-old woman with dissociative disorder was treated with brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and alprazolam during lactation. The drug concentration ratios for both cord blood and maternal serum were 33.3 and 61.5% for brotizolam and sulpiride, respectively, and periciazine (metabolite of propericiazine) was not detected in the cord blood. In breast milk, alprazolam (0.9 ng/mL), sulpiride (445.8 ng/mL), and periciazine (0.3 ng/mL) concentrations were noted at 7.5 h after the last dose on postpartum, whereas brotizolam was not detected. The relative infant doses via breast milk were 1.4, 2.7 and 0.02% of the maternal daily dose, respectively. The neonate had no congenital anomalies and did not experience any severe withdrawal symptoms after birth.

Conclusion

Use of brotizolam, propericiazine, and sulpiride during pregnancy and lactation, and use of alprazolam during lactation were acceptable in this case.
Endurance rivalry and female choice jointly influence male mating success in the emerald treefrog (Zhangixalus prasinatus), a lek-chorusing anuran
Authors: Cheng Yuan-Cheng , Chen Yi-Huey , Chang Chunwen , Chuang Ming-Feng , Hsu Yuying
Published: April 2022

Background

Endurance rivalry and female choice are two important mechanisms of sexual selection in lek-breeding species. Endurance rivalry is when males compete for opportunities to mate by spending more time in leks than others (interaction-independent male-male competition). Because high-quality males can afford to have high lek attendance, females have a higher chance of mating with good-quality males even when they mate randomly. The good gene hypothesis proposes that females can pass good genes on to their offspring by choosing males that display elaborate morphological and/or behavioral traits that reflect the males’ genetic quality. The relative importance of lek attendance and female choice to males’ mating success in anurans is rarely evaluated. In this study, we investigated how these two mechanisms might jointly shape males’ morphological traits in the lek-chorusing emerald treefrog Zhangixalus prasinatus.

Results

Our results show that (1) male lek attendance is positively correlated with body size and condition, and males with higher lek attendance have higher mating success, (2) the dominant frequency of males’ advertisement calls are negatively correlated with body size and males producing lower frequency calls have higher mating success, (3) male body size, but not body condition, has a non-significant positive relationship with mating success and (4) females show preference for calls with lower dominant frequencies in two-choice playback.

Conclusions

Overall, both endurance rivalry and female choice play an important role in the mating success of male emerald treefrogs in the field and both are influenced by male body size/condition. By mating with males that have higher lek attendance and produce lower frequency calls, selection may indirectly favor larger males.
Dietary factors associated with gastric cancer - a review
Authors: Richa  , Sharma Neha , Sageena Geetanjali
Published: April 2022

Background

Cancer is considered one of the primary illnesses that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. As most of the target-specific anticancer drugs failed to achieve the expected result so far, new multi-targeted therapies using natural products have become significant. Natural products are readily applicable, inexpensive, accessible and acceptable therapeutic approaches with minimum cytotoxicity. This review explores the relationship between dietary factors and the probability of development of gastric cancer. Over the years, it has been proven that there are many natural products that have chemo-preventative effects such as vitamins, probiotics and prebiotics, green tea, and resveratrol on gastric cancer. Many investigations have looked into the links between dietary components and the risk of stomach cancer and a variety of protective and deleterious factors have been identified in our diet that is associated with gastric cancer. In this study, we have summarized the preventive and injurious components that affect the incidence of gastric cancer.

Conclusion

Based on the potential of natural products for the discovery of new compounds for the treatment of diseases, the purpose of the present review was to investigate the importance of dietary products mitigating the impacts due to the development of gastric cancer. The current analysis proves the protective as well as harmful roles of many elements which are found in our diet in the development of gastric cancer. Our findings can have significant public health implications in terms of gastric cancer prevention. There is an inherent need to offer an insight into benefits and risks, clinical trial designs future translational and cohort studies before effectively clinically translated.
A case of refractory systemic lupus erythematosus with monocytosis exhibiting somatic KRAS mutation
Authors: Law Sze-Ming , Akizuki Shuji , Morinobu Akio , Ohmura Koichiro
Published: April 2022

Background

Systemic lupus erythematosus (SLE), an autoimmune disorder that damages various organ systems, is caused by a combination of genetic and environmental factors. Although germline mutations of several genes are known to cause juvenile SLE, most of the susceptibility genetic variants of adult SLE are common variants of the population, somatic mutations that cause or exacerbate SLE have not been reported. We hereby report a refractory SLE case with monocytosis accompanying somatic KRAS mutation that have been shown to cause lupus-like symptoms.

Case presentation

A 60-year-old female patient who had been diagnosed with SLE was admitted to our hospital. Although prednisolone and tacrolimus treatments had kept her thrombocytopenia and anti-DNA Ab level at bay for more than 4 years, a diagnosis of transverse myelitis was made when she became acutely ill with pleocytosis. Elevated cells (predominately monocytes), protein, IgG, and IL-6 levels were also found in the cerebrospinal fluid (CSF) of the patient. Standard pulse treatments of methylprednisolone, high-dose of prednisolone, and intravenous cyclophosphamide in combination with plasma exchange could not alleviate the refractory neural and autoimmune manifestation. Monocytosis of peripheral blood was also noted. Flow cytometric analysis revealed elevated ratio of CD14+CD16+ atypical monocytes, which excluded the possibility of chronic myelomonocytic leukemia. Lupus-like symptoms with monocytosis reminded us of Ras-associated autoimmune leukoproliferative disorder, and Sanger sequencing of KRAS and NRAS genes from the patients’ peripheral blood mononuclear cells (PBMC), sorted CD3+ lymphocytes and CD14+ monocytes, and cerebrospinal fluid were performed. An activating KRAS somatic mutation was found in the patients’ DNA at the time of encephalomyelitis diagnosis.

Conclusion

Somatic mutations of some genes including KRAS may cause the refractoriness of SLE.
A three-factor benefits framework for understanding consumer preference for scented household products: psychological interactions and implications for future development
Authors: Herz Rachel S. , Larsson Maria , Trujillo Rafael , Casola Marisa C. , Ahmed Farah K. , Lipe Stacy , Brashear Morgan E.
Published: April 2022

Humans have deliberately scented their environment for purpose or pleasure for millennia. In the contemporary marketplace most consumers prefer and purchase scented versions of common household products. However, the drivers of this consumer preference have not been elucidated. To explain the attraction to scent in household products we propose a novel three-factor framework, comprising functional benefits (malodor mitigation, base odor coverage, freshening), in-use experience benefits (cleanliness, efficacy, pleasure), and emotional benefits (increasing in confidence, mood and nostalgia). To support this framework, we present new data from a market research survey on US consumer purchasing habits and attitudes towards home cleaning, laundry, and air freshening products. Further substantiating our framework, a focused review of olfactory psychological science illustrating the central role of scent in cognition, wellbeing, motivated behavior, and social behavior, as well as sensory marketing research highlights the benefits and implications of scent in consumer household products. Based on our three-factor framework we go on to discuss the potential for scent to influence health and raise issues to consider (such as potential negative responding to fragranced products). We conclude by showcasing new opportunities for future research in olfactory science and on scented household products that can advance the positive impacts of scent.
Micro-credentials in leveraging emergency remote teaching: the relationship between novice users’ insights and identity in Malaysia
Authors: Kumar Jeya Amantha , Richard Rachel Jasmine , Osman Sharifah , Lowrence Kevin
Published: April 2022

Micro-credentials have gained much popularity in recent years, and their popularity has skyrocketed due to emergency remote teaching instigated by the pandemic. It has been defined as a platform that provides credentials based on validated competencies. Nevertheless, in Malaysian HEI, such a concept is still novel and identifying insights on the benefits, challenges, and application are still scarce. Similarly, it was observed that there is a lack of observation on how students’ digital learning identity and their perception of professional relevance are influenced by such platform. Henceforth, based on the adapted enriched virtual model approach, a micro-credentials course was implemented to complement the new “normal” classes for a pre-service teacher’s instructional design course. A mixed-method triangulation design was used to explore the qualitative findings operationalized by open-ended questions (N = 74) with data obtained from the Digital Learning Identity Survey (DLIS) and Constructivist On-Line Learning Environment Survey (COLLES) (N = 72). The findings indicated that respondents had an overall positive perception of the use of micro-credentials to complement and overcome online learning challenges mainly due to substandard internet connectivity; nevertheless, they are unaware of the value of such credentials in their future profession. Conversely, their new identity as digital learners and experiences with a blended approach of online learning, especially with micro-credentials, was successful in shaping their identity as aspiring educators that embrace technology for teaching and learning.
A systematic review and recommendations for prom instruments for older people with frailty in emergency care
Authors: van Oppen James David , Alshibani Abdullah , Coats Timothy John , Graham Blair , Holch Patricia , Lalseta Jagruti , Mackintosh Nicola , Richardson Vivien , Riley Peter , Valderas Jose M. , Conroy Simon Paul
Published: April 2022

Introduction

The current service metrics used to evaluate quality in emergency care do not account for specific healthcare outcome goals for older people living with frailty. These have previously been classified under themes of ‘Autonomy’ and ‘Functioning’. There is no person-reported outcome measure (PROM) for older people with frailty and emergency care needs. This study aimed to identify and co-produce recommendations for instruments potentially suitable for use in this population.

Methods

In this systematic review, we searched six databases for PROMs used between 2010 and 2021 by older people living with frailty receiving acute hospital care. Studies were reviewed against predefined eligibility criteria and appraised for quality using the COSMIN Risk of Bias checklist. Data were extracted to map instrument constructs against an existing framework of acute healthcare outcome goals. Instrument face and content validity were assessed by lay collaborators. Recommendations for instruments with potential emergency care suitability were formed through co-production.

Results

Of 9392 unique citations screened, we appraised the full texts of 158 studies. Nine studies were identified, evaluating nine PROMs. Quality of included studies ranged from ‘doubtful’ to ‘very good’. Most instruments had strong evidence for measurement properties. PROMs mainly assessed ‘Functioning’ constructs, with limited coverage of ‘Autonomy’. Five instruments were considered too burdensome for the emergency care setting or too specific for older people living with frailty.

Conclusions

Four PROMs were recommended as potentially suitable for further validation with older people with frailty and emergency care needs: COOP/WONCA charts, EuroQol, McGill Quality of Life (Expanded), and Palliative care Outcome Scale.
Validation of the Shock Index, Modified Shock Index, and Shock Index-Paediatric age-Adjusted (SIPA) for predicting length of stay and outcome in children admitted to a paediatric intensive care unit
Authors: Nazar Monish , Kumar Hemanth , Krishnegowda Madhunandan , Unki Praveen , Veerappa Nandakumar , Srinivas Bharath Kumar
Published: April 2022

Background

Maintaining hemodynamic stability requires constant complex interaction between multiple vascular and extravascular factors. There are varieties of parameters that determine the same and few of them are used to predict the hemodynamic instability at earliest. Shock Index (SI), Modified Shock Index (MSI) and Shock Index-Pediatric age-Adjusted (SIPA) have been studied constantly in different clinical settings. They are best non-invasive measures for early prediction in resource poor setting or at community referral centers. We would like to compare the predictive value of each parameter in our tertiary care center.

Methods

It was a retrospective study carried out in PICU of a tertiary care centre and includes data collected from 15 August 2019 to 14 August 2021 over a period of 2 years. We recorded demographic data, age, gender, final diagnosis, outcome, and length of stay in PICU. We compared Outcome (Survived/Expired) and length of stay with SI ≥ 0.7 or < 0.7, MSI ≥ 1.3 or < 1.3 and SIPA > 1.22 or < 1.22 (age 4–6 years) > 1 or < 1 (7–12 years) and > 0.9 or < 0.9 (13–16 years).

Results

This study includes 235 children who were admitted to PICU during study period. The median age was 8 years the median length of stay was 5 days and mortality rate being 11.48% (27). Median SI, MSI were 0.78, 1.6 respectively. 61.70% (145) of patients had SI > 0.7. Median value of SI for septic shock patients was 0.92 on admission. The mortality of the patients with SI > 0.7 was 13.10% (19) and those with MSI > 1.3 was 14.89% (21). Mortality in accordance with SIPA for ages 4–6 years, 7–12 years, and 13–16 years were 15.25% (9), 23% (9) and 19.23% (5) respectively. Basically, SIPA was designed to monitor post trauma cases but in our study we got significant correlation with outcome and length of stay in conditions other than trauma.

Conclusions

The SI, MSI, and SIPA are simple bedside parameters may be used for prioritizing the patients who require strict monitoring on admission to PICU and intervention whenever required. These parameters were best in predicting the severity of sepsis and septic shock in comparison to other diagnosis. SIPA can be generalised for monitoring any high-risk case.
Recent trends in miRNA therapeutics and the application of plant miRNA for prevention and treatment of human diseases
Authors: Saiyed Atiyabanu N. , Vasavada Abhay R. , Johar S. R. Kaid
Published: April 2022

Background

Researchers now have a new avenue to investigate when it comes to miRNA-based therapeutics. miRNAs have the potential to be valuable biomarkers for disease detection. Variations in miRNA levels may be able to predict changes in normal physiological processes. At the epigenetic level, miRNA has been identified as a promising candidate for distinguishing and treating various diseases and defects.

Main body

In recent pharmacology, plants miRNA-based drugs have demonstrated a potential role in drug therapeutics. The purpose of this review paper is to discuss miRNA-based therapeutics, the role of miRNA in pharmacoepigenetics modulations, plant miRNA inter-kingdom regulation, and the therapeutic value and application of plant miRNA for cross-kingdom approaches. Target prediction and complementarity with host genes, as well as cross-kingdom gene interactions with plant miRNAs, are also revealed by bioinformatics research. We also show how plant miRNA can be transmitted from one species to another by crossing kingdom boundaries in this review. Despite several unidentified barriers to plant miRNA cross-transfer, plant miRNA-based gene regulation in trans-kingdom gene regulation may soon be valued as a possible approach in plant-based drug therapeutics.

Conclusion

This review summarised the biochemical synthesis of miRNAs, pharmacoepigenetics, drug therapeutics and miRNA transkingdom transfer.
Ethnobotany of stinging nettle (Urtica simensis Hochst. ex. A. Rich.) in the Oromia region of central and southeastern highlands of Ethiopia
Authors: Shonte Tigist Tadesse , Woldetsadik Kebede
Published: April 2022

Background

Stinging nettle, Urtica simensis, has a wide range of distribution in the highlands of Ethiopia with untapped potential for a sustainable supply of healthy and nutritious food. This study was conducted to document ethnobotanical uses of U. simensis and the associated traditional knowledge of the indigenous people and to identify the factors limiting harvesting and utilization of stinging nettle in North Shewa (R4), Bale and Arsi zones of the Oromia region, central and southeastern highlands of Ethiopia.

Methods

Thirteen districts were purposively selected from the three zones and a total of 130 respondents were sampled, with consideration of gender, age, occupation, and wealth status. Data were collected using semistructured interviews, tour-guided field observations, and focus group discussions. IBM SPSS Statistical software package was used to analyze ethnobotanical data.

Results

Pearson’s chi-square analysis showed that there is a significant association (P < 0.05) between zones and districts in the ethnobotanical knowledge of use categories. Stinging nettle plants have an average use value index of 0.91 with a central role (FL = 44.8%) as a source of food and fodder. Cultural norms and values followed by lack of knowledge and stinginess were the main limiting factor for harvesting and consumption of U. simensis. Cultural norms and values showed significantly higher correlations with the various uses of U. simensis (r2 = 0.931, p < 0.001) indicating the stigma related to stinging nettle being associated as poor man food or famine food were probably a major limiting factor for the utilization of U. simensis.

Conclusions

Future strategic policies should consider U. simensis as a source of food and fodder to fight food insecurity and improve the wellbeing of society. There is a need for local level and countrywide awareness creation, domestication, and future research on value addition and processing for effective utilization of the plant.
Investment in North Sea seismic leading to new opportunities
Authors: Rowbotham Peter S. , Vermaas Marnix
Published: April 2022

Investment in seismic data leads to continued opportunities for redevelopment of existing oil and gas fields and for near-field exploration. This investment could range from acquisition and processing of new seismic where value is seen in applying modern acquisition techniques, purchasing existing processing of multiclient speculative data, or targeted reprocessing of spec or proprietary data. From our experience, seismic projects deliver the most value when they are undertaken with focus on the business objectives, when they are planned from end to end (preshot to seismic on the interpretation workstation and on to the drill bit), and when they are executed in an open and trusting contractual relationship. We demonstrate this for our North Sea region with evolutionary improvements in both seismic data quality and efficiency.
Hypothesis for the origin of anomalous VP/VS ratios in GOM subsalt mudrocks: Implications for pore pressure prediction
Authors: Bryndzia L. Taras
Published: April 2022

Acoustic properties of subsalt mudrocks from the Gulf of Mexico (GOM) often display unusual VP/VS ratio behavior that has been attributed to differences in the vertical and horizontal stress states below base salt. The observed VP/VS ratios are higher relative to established GOM mudrock calibrations, returning to trend with increasing depth below base salt. In the Mississippi Canyon area of the GOM, temperatures at base salt are lower by up to 40°F relative to the regional thermal gradient. The present study tested the hypothesis that the unusual mudrock acoustic properties were caused by precipitation of halite in mudrock pores due to cooling of a halite-saturated brine, caused by conductive loss of heat through overlying salt. A drop of approximately 40°F from 235°F for the normal thermal gradient, to the present-day subsalt temperature of 190°F, results in a reduction of soluble halite at saturation of up to about 30 volume percent (vol%). A Gassmann fluid substitution model in which solid halite replaces brine in mudrock pores was used to test this hypothesis. The results of the Gassmann fluid substitution model reproduce the observed acoustic log responses measured in subsalt mudrocks from prospect B, a deepwater GOM subsalt discovery. The results show that about 30 vol% solid halite could explain most of the observed deviations in VP/VS ratio, with model and observations returning to normal VP/VS behavior with 5%–10% solid halite substituted for brine at approximately 2500 ft below base salt. P-wave velocity-void ratio–vertical effective stress (VP-∊-σv) pore pressure models have traditionally fared poorly in subsalt mudrocks. Such models generally rely on VP-porosity relationships that are controlled by compaction in which the vertical effective stress, i.e., overburden stress, is the maximum historical stress. These conditions of stress and porosity are clearly not satisfied in subsalt mudrocks. Predicted velocities are too fast, inferred porosity and void ratios are too low, and subsequent estimates of pore pressure are too high. The model discussed in this paper explains the apparent disconnect between predicted and observed subsalt mudrock porosities and offers a relatively simple method for correcting them using the results of the Gassmann halite-brine fluid substitution model.
“Macandal. Makandal. Mackandal.” Man and Protean Pluralema
Authors: Rivera Prosdocimi Ines P.
Published: April 2022

This essay extends and contributes to existing scholarship by uncovering instances of cooperation and collaboration that suggest alternative views of Hispaniola and complicate contemporary political and social realities in the Dominican Republic. It focuses on Manuel Rueda’s 1998 Las metamorfosis de Makandal, in which François Makandal is imagined as a protean god. The author argues that Rueda’s Makandal is best understood as the embodiment of the vanguard poetic movement, Pluralismo. The Maroon becomes a central figure in the island’s story, as well as a figure of aesthetic possibilities and boundless exploration, like a pluralema. Rueda imagines a cosmic Makandal who is unhindered by racial or gender constructs, by space or time. Ultimately, he is a figure whose metamorphosis rewrites Hispaniola’s story and challenges rigid binaries that limit the way we view the Dominican Republic as a nation, Dominican national identity, Dominican-Haitian relations, and—more broadly—the island of Hispaniola.