bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT1 is transcriptionally repressed by YY1 and suppresses ferroptosis in rheumatoid arthritis
Authors: Zhan Yuwei , Yang Zhou , Zhan Feng , Huang Yanyan , Lin Shudian
Published: March 2023

Background

Sirtuin 1 (SIRT1) is reported downregulated in rheumatoid arthritis (RA), and the protective effects of SIRT1 on tissue damage and organ failure may be related to cellular ferroptosis. However, the exact mechanism by which SIRT1 regulates RA remains unclear.

Methods

Quantitative real-time PCR (qPCR) and western blot assays were performed to explore the expressions of SIRT1 and Yin Yang 1 (YY1). CCK-8 assay was used for cytoactive detection. The interaction between SIRT1 and YY1 was validated by dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). DCFH-DA assay and iron assay were applied to detect the reactive oxygen species (ROS) and iron ion levels.

Results

In the serum of RA patients, SIRT1 was downregulated, but YY1 was upregulated. In LPS-induced synoviocytes, SIRT1 could increase cell viability and decrease ROS and iron levels. Mechanistically, YY1 downregulated the expression of SIRT1 by inhibiting its transcription. YY1 overexpression partly revised the effects of SIRT1 on ferroptosis in synoviocytes.

Conclusion

SIRT1 is transcriptionally repressed by YY1 and inhibits the ferroptosis of synoviocytes induced by LPS, so as to relieve the pathological process of RA. Therefore, SIRT1 might be a new diagnosis and therapeutic target of RA.
The role of different innate and environmental factors in Tm-22-mediated resistance to tomato mottle mosaic virus
Authors: Tettey Carlos Kwesi , Mu Xiu-Qi , Ma Hua-Yu , Chen Xin-Yang , Geng Chao , Tian Yan-Ping , Yan Zhi-Yong , Li Xiang-Dong
Published: March 2023

Tomato mottle mosaic virus (ToMMV) poses a threat to production and quality of tomato fruits. The Tm-22 gene confers resistance to some tobamoviruses by recognizing viral movement proteins. However, Tm-22-mediated resistance against ToMMV is not well known. Here, we found that ToMMV could infect wild-type but not Tm-22 transgenic Nicotiana benthamiana plants and could also infect tomato cultivar Moneymaker but not resistant cultivar Jili with homozygous Tm-22. Chimeric viral ToMMVToBRFV−MP with swapped ToMMV MP to MP of tomato brown rugose fruit virus could systemically infect Tm-22 transgenic N. benthamiana and tomato cultivars Jili plants. Further, transient expression of ToMMV MP in the leaves of Tm-22 transgenic N. benthamiana plants induced hypersensitive response-associated cell death, suggesting that the MP of ToMMV was the avirulent factor for the Tm-22 resistance gene. ToMMV could infect Tm-22-containing cultivar Jinpeng 1 but not Chaobei. Sequence analysis revealed that cultivars Chaobei and Jinpeng 1 were heterozygous, where Chaobei consists of Tm-22 and Tm-2 genes, while Jinpeng 1 consists of Tm-22 and tm-2 genes. Transient co-expression assays showed that both Tm-22 and Tm-2 but not tm-2 could recognize ToMMV MP and induce hypersensitivity response-associated cell death in N. benthamiana leaves, suggesting that homozygous tomato harboring Tm-22 and heterozygous tomato containing Tm-22 and Tm-2 may exhibit more durable resistance to ToMMV than heterozygous tomato carrying Tm-22 and tm-2. Further, Tm-22 transgenic N. benthamiana and tomato cultivar Jili plants with silenced Tm-22 gene were susceptible to ToMMV. Also, silencing type-I J-domain MIP1 gene compromised Tm-22-mediated resistance to ToMMV in Tm-22 transgenic N. benthamiana and tomato cultivar Jili. Moreover, we found that viral RNA could accumulate in the systemic leaves of Tm-22 transgenic N. benthamiana plants and tomato cultivar Jili at 35°C, but not at 20, 25, or 30°C. Altogether, our findings reveal that the Tm-22 confers resistance to ToMMV by recognizing MP, and the resistance is regulated by the allele combinations, accumulation levels of Tm-22, MIP1, and the temperature.
Association of CYP1A2 and GST gene variants with asthma in cases presenting with allergic chronic rhinosinusitis
Authors: Jangala Madhavi , Manche Santoshi Kumari , Katika Madhu Mohan , Koralla Raja Meghanadh , Akka Jyothy
Published: March 2023

Background

Inter-individual differences in regulation and activity of xenobiotic metabolizing enzymes (XMEs) CYP1A and GST might cause distinct susceptibility to chronic rhinosinusitis (CRS) phenotypes that need to be explored. Therefore, the present study aimed to evaluate the role and risk of CYP1A and GST gene variants in allergic CRS subjects with and without asthma. A total of 224 allergic CRS cases with asthma, 252 allergic CRS cases without asthma, and 350 healthy control subjects were subjected to genetic analysis. Gene variants of cytochrome P450 (CYP1A1 T3801 rs4646903, A2455G rs1048943, C2453A rs1799814 and CYP1A2 G3858A rs2069514, T739G rs2069526, C163A rs762551) and glutathione S-transferase P (GSTP1 A313G rs1605 & C341T rs1799811) were investigated by polymerase chain reaction-restriction fragment length polymorphism and GSTM1null, and GSTT1null by multiplex PCR methods.

Results

TG genotype of CYP1A2 rs2069526 (OR 1.73, 95% CI 1.20–2.50, p < 0.002), TC genotype of CYP1A1 rs4646903 (OR 1.43, 95% CI 1.03–1.98, p < 0.031) and GSTM1del (OR 1.87, 95% CI 1.24–2.81, p < 0.003) and were found to be significantly associated with only allergic CRS cases. CYP1A2 rs2069526 (OR 2.33, 95% CI 1.61–3.37, p < 0.001), GG genotype of GSTP1 rs1605 (OR 4.75, 95% CI 2.62–8.63, p < 0.001), GSTM1del (OR 1.82, 95% CI 1.19–2.78, p < 0.006), GSTM1/GSTT1 double null (OR 2.58, 95% CI 1.36–4.87, p < 0.004) and were found to be significantly associated with asthma in allergic CRS cases. Further, G-G-C haplotype of CYP1A2 rs2069514, rs2069526 and rs762551 gene variants was found to increase the risk for asthma by 5 folds in allergic CRS subjects (OR 5.53, 95% CI 1.76–17.31, p < 0.003) while T-G-C haplotype of CYP1A1 rs4646903, rs1048943, rs1799814 (OR 0.11, 95% CI (0.01–0.95, p < 0.045) and A-T haplotype of GSTP1 rs1605, rs1799811 (OR 0.27, 95% CI (0.08–0.89, p < 0.032) showed protective effect in allergic CRS group.

Conclusion

The present study reports the significantly increased association of CYP1A2, GSTM, and GSTP gene variants with asthma in allergic CRS.
A continuous quality improvement strategy to strengthen screening practices and facilitate the routine use of intravenous iron for treating anaemia in pregnant and postpartum women in Nigeria: a study protocol
Authors: Eboreime Ejemai , Banke-Thomas Aduragbemi , Obi-Jeff Chisom , Adelabu Yusuf , Balogun Mobolanle , Aiyenigba Adejoke A. , Oluwole Esther O. , Akinajo Opeyemi R. , Afolabi Bosede B.
Published: March 2023

Background

Pregnancy-related anaemia is a public health challenge across Africa. Over 50% of pregnant women in Africa get diagnosed with this condition, and up to 75% of these are caused by iron deficiency. The condition is a significant contributor to the high maternal deaths across the continent and, in particular, Nigeria, which accounts for about 34% of global maternal deaths. Whereas oral iron is the mainstay treatment for pregnancy-related anaemia in Nigeria, this treatment is not very effective given the slow absorption of the medication, and its gastrointestinal adverse effects which lead to poor compliance by women. Intravenous iron is an alternative therapy which can rapidly replenish iron stores, but fears of anaphylactic reactions, as well as several misconceptions, have inhibited its routine use. Newer and safer intravenous iron formulations, such as ferric carboxymaltose, present an opportunity to overcome some concerns relating to adherence. Routine use of this formulation will, however, require addressing misconceptions and systemic barriers to adoption in the continuum of care of obstetric women from screening to treatment. This study aims to test the options to strengthen routine screening for anaemia during and immediately after pregnancy, as well as evaluate and improve conditions necessary to deliver ferric carboxymaltose to pregnant and postpartum women with moderate to severe anaemia.

Methods

This study will be conducted in a cluster of six health facilities in Lagos State, Nigeria. The study will employ continuous quality improvement through the Diagnose-Intervene-Verify-Adjust framework and Tanahashi’s model for health system evaluation to identify and improve systemic bottlenecks to the adoption and implementation of the intervention. Participatory Action Research will be employed to engage health system actors, health services users, and other stakeholders to facilitate change. Evaluation will be guided by the consolidated framework for implementation research and the normalisation process theory.

Discussion

We expect the study to evolve transferable knowledge on barriers and facilitators to the routine use of intravenous iron that will inform scale-up across Nigeria, as well as the adoption of the intervention and strategies in other countries across Africa.
The Implementation Playbook: study protocol for the development and feasibility evaluation of a digital tool for effective implementation of evidence-based innovations
Authors: Barwick Melanie , Brown Jacquie , Petricca Kadia , Stevens Bonnie , Powell Byron J. , Jaouich Alexia , Shakespeare Jill , Seto Emily
Published: March 2023

Background

Evidence-based innovations can improve health outcomes, but only if successfully implemented. Implementation can be complex, highly susceptible to failure, costly and resource intensive. Internationally, there is an urgent need to improve the implementation of effective innovations. Successful implementation is best guided by implementation science, but organizations lack implementation know-how and have difficulty applying it. Implementation support is typically shared in static, non-interactive, overly academic guides and is rarely evaluated. In-person implementation facilitation is often soft-funded, costly, and scarce. This study seeks to improve effective implementation by (1) developing a first-in-kind digital tool to guide pragmatic, empirically based and self-directed implementation planning in real-time; and (2) exploring the tool’s feasibility in six health organizations implementing different innovations.

Methods

Ideation emerged from a paper-based resource, The Implementation Game©, and a revision called The Implementation Roadmap©; both integrate core implementation components from evidence, models and frameworks to guide structured, explicit, and pragmatic planning. Prior funding also generated user personas and high-level product requirements. This study will design, develop, and evaluate the feasibility of a digital tool called The Implementation Playbook©. In Phase 1, user-centred design and usability testing will inform tool content, visual interface, and functions to produce a minimum viable product. Phase 2 will explore the Playbook’s feasibility in six purposefully selected health organizations sampled for maximum variation. Organizations will use the Playbook for up to 24 months to implement an innovation of their choosing. Mixed methods will gather: (i) field notes from implementation team check-in meetings; (ii) interviews with implementation teams about their experience using the tool; (iii) user free-form content entered into the tool as teams work through implementation planning; (iv) Organizational Readiness for Implementing Change questionnaire; (v) System Usability Scale; and (vi) tool metrics on how users progressed through activities and the time required to do so.

Discussion

Effective implementation of evidence-based innovations is essential for optimal health. We seek to develop a prototype digital tool and demonstrate its feasibility and usefulness across organizations implementing different innovations. This technology could fill a significant need globally, be highly scalable, and potentially valid for diverse organizations implementing various innovations.
MANIFEST: Pelabresib in Combination With Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Myelofibrosis
Authors: Mascarenhas John , Kremyanskaya Marina , Patriarca Andrea , Palandri Francesca , Devos Timothy , Passamonti Francesco , Rampal Raajit K. , Mead Adam J. , Hobbs Gabriella , Scandura Joseph M. , Talpaz Moshe , Granacher Nikki , Somervaille Tim C. P. , Hoffman Ronald , Wondergem Marielle J. , Salama Mohamed E. , Colak Gozde , Cui Jike , Kiladjian Jean-Jacques , Vannucchi Alessandro M. , Verstovsek Srdan , Curto-García Natalia , Harrison Claire , Gupta Vikas
Published: March 2023

PURPOSE

Standard therapy for myelofibrosis comprises Janus kinase inhibitors (JAKis), yet spleen response rates of 30%-40%, high discontinuation rates, and a lack of disease modification highlight an unmet need. Pelabresib (CPI-0610) is an investigational, selective oral bromodomain and extraterminal domain inhibitor (BETi).

METHODS

MANIFEST (ClinicalTrails.gov identifier: NCT02158858 ), a global, open-label, nonrandomized, multicohort, phase II study, includes a cohort of JAKi-naïve patients with myelofibrosis treated with pelabresib and ruxolitinib. The primary end point is a spleen volume reduction of ≥ 35% (SVR35) at 24 weeks.

RESULTS

Eighty-four patients received ≥ 1 dose of pelabresib and ruxolitinib. The median age was 68 (range, 37-85) years; 24% of patients were intermediate-1 risk, 61% were intermediate-2 risk, and 16% were high risk as per the Dynamic International Prognostic Scoring System; 66% (55 of 84) of patients had a hemoglobin level of < 10 g/dL at baseline. At 24 weeks, 68% (57 of 84) achieved SVR35, and 56% (46 of 82) achieved a total symptom score reduction of ≥ 50% (TSS50). Additional benefits at week 24 included 36% (29 of 84) of patients with improved hemoglobin levels (mean, 1.3 g/dL; median, 0.8 g/dL), 28% (16 of 57) with ≥ 1 grade improvement in fibrosis, and 29.5% (13 of 44) with > 25% reduction in JAK2V617F-mutant allele fraction, which was associated with SVR35 response ( P = .018, Fisher's exact test). At 48 weeks, 60% (47 of 79) of patients had SVR35 response. Grade 3 or 4 toxicities seen in ≥ 10% patients were thrombocytopenia (12%) and anemia (35%), leading to treatment discontinuation in three patients. 95% (80 of 84) of the study participants continued combination therapy beyond 24 weeks.

CONCLUSION

The rational combination of the BETi pelabresib and ruxolitinib in JAKi-naïve patients with myelofibrosis was well tolerated and showed durable improvements in spleen and symptom burden, with associated biomarker findings of potential disease-modifying activity.
Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Authors: Cobleigh Melody A. , Vogel Charles L. , Tripathy Debu , Robert Nicholas J. , Scholl Susy , Fehrenbacher Louis , Wolter Janet M. , Paton Virginia , Shak Steven , Lieberman Gracie , Slamon Dennis J.
Published: March 2023

PURPOSE

Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease.

PATIENTS AND METHODS

Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals.

RESULTS

Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events.

CONCLUSION

Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.
Higher-order shock wave structures and phase plane analysis in multicomponent dusty plasma
Authors: Kaur Rajneet , Slathia Geetika , Saini N. S.
Published: March 2023

In this investigation, dust acoustic (DA) shocks and dressed shocks formed due to the contribution of higher-order effects in a non-Maxwellian plasma have been examined. The reductive perturbation method is employed to derive the nonlinear Burgers and Burgers-type inhomogeneous equations with the contribution of higher-order effects of nonlinearity and dissipation. The properties of dust acoustic shocks and higher order (dressed shocks) are examined from the solutions of these nonlinear equations under the effect of various plasma parameters. Furthermore, the travelling wave analysis is used to obtain the dynamical system for the Burgers equation using bifurcation theory. The characteristic properties of DA periodic waves have also been analysed under the influence of various plasma parameters.
Evaluation of Stress Response in Middle-Aged Male Diabetic Hypertensive Patients
Authors: Alloqi Tahirbegolli Iliriana , Tahirbegolli Bernard , Şen Selçuk , Sayın Betül , Kaşkal Mert , Üresin Ali Yağız
Published: March 2023

Context

Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities.

Objective

We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them.

Methods

The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital.

Results

There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P < .0001], SBP [F (2.185, 60) = 12.080, P < .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P < .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively).

Conclusion

The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.
Ribosome biogenesis and function in development and disease
Authors: Ni Chunyang , Buszczak Michael
Published: March 2023

Although differential transcription drives the development of multicellular organisms, the ultimate readout of a protein-coding gene is ribosome-dependent mRNA translation. Ribosomes were once thought of as uniform molecular machines, but emerging evidence indicates that the complexity and diversity of ribosome biogenesis and function should be given a fresh look in the context of development. This Review begins with a discussion of different developmental disorders that have been linked with perturbations in ribosome production and function. We then highlight recent studies that reveal how different cells and tissues exhibit variable levels of ribosome production and protein synthesis, and how changes in protein synthesis capacity can influence specific cell fate decisions. We finish by touching upon ribosome heterogeneity in stress responses and development. These discussions highlight the importance of considering both ribosome levels and functional specialization in the context of development and disease.
Low-Level Laser Therapy Facilitates Postcontraction Recovery with Ischemic Preconditioning
Authors: CHEN YI-CHING , LIN YEN-TING , HU CHIA-LING , HWANG ING-SHIOU
Published: March 2023

Purpose

Despite early development of muscle fatigue, ischemic preconditioning is gaining popularity for strength training combined with low-load resistance exercise. This study investigated the effect of low-level laser (LLL) on postcontraction recovery with ischemic preconditioning.

Methods

Forty healthy adults (22.9 ± 3.5 yr) were allocated into sham (11 men, 9 women) and LLL (11 men, 9 women) groups. With ischemic preconditioning, they were trained with three bouts of intermittent wrist extension of 40% maximal voluntary contraction (MVC). During the recovery period, the LLL group received LLL (wavelength of 808 nm, 60 J) on the working muscle, whereas the sham group received no sham therapy. MVC, force fluctuations, and discharge variables of motor units (MU) for a trapezoidal contraction were compared between groups at baseline (T0), postcontraction (T1), and after-recovery (T2).

Results

At T2, the LLL group exhibited a higher normalized MVC (T2/T0; 86.22% ± 12.59%) than that of the sham group (71.70% ± 13.56%; P = 0.001). The LLL group had smaller normalized force fluctuations (LLL, 94.76% ± 21.95%; sham, 121.37% ± 29.02%; P = 0.002) with greater normalized electromyography amplitude (LLL, 94.33% ± 14.69%; sham, 73.57% ± 14.94%; P < 0.001) during trapezoidal contraction. In the LLL group, the smaller force fluctuations were associated with lower coefficients of variation of interspike intervals of MUs (LLL, 0.202 ± 0.053; sham, 0.208 ± 0.048; P = 0.004) with higher recruitment thresholds (LLL, 11.61 ± 12.68 %MVC; sham, 10.27 ± 12.73 %MVC; P = 0.003).

Conclusions

LLL expedites postcontraction recovery with ischemic preconditioning, manifesting as superior force generation capacity and force precision control for activation of MU with a higher recruitment threshold and lower discharge variability.
Reliability and Usefulness of the SKILLCOURT as a Computerized Agility and Motor–Cognitive Testing Tool
Authors: FRIEBE DAVID , HÜLSDÜNKER THORBEN , GIESCHE FLORIAN , BANZER WINFRIED , PFAB FLORIAN , HASER CHRISTIAN , VOGT LUTZ
Published: March 2023

Introduction

Agility and cognitive skills are essential in sports. However, standardized agility assessment tools often lack a reactive component, and cognitive assessments are performed using computer-based or paper-pencil tests. The SKILLCOURT is a newly developed testing and training device allowing agility and cognitive assessments in a more ecologically valid setting. This study evaluated the reliability and sensitivity to changes in performance (usefulness) of the SKILLCOURT technology.

Methods

In a test–retest (7 d, 3 months) design, 27 healthy adults (♀ = 12; age, 24.9 ± 3.3 yr) performed three trials of agility (Star Run, Random Star Run) and motor–cognitive tests (1-back, 2-back, executive function). Absolute and relative intersession and intrasession reliability was determined using the intraclass coefficient (ICC) and coefficient of variation (CV). A repeated-measures ANOVA was applied to identify potential learning effects between trials and test sessions. The smallest worthwhile change and typical error (TE) were calculated to investigate the intrasession and intersession usefulness of the tests.

Results

Agility tests revealed good relative and absolute intersession (ICC, 83–0.89; CV, 2.7%–4.1%) and intrasession (ICC, 7–0.84; CV, 2.4%–5.5%) reliability accompanied by adequate usefulness from test day 3 onward. Motor–cognitive tests showed good relative intersession reliability (ICC, 0.7–0.77) with marginal CV values (4.8%–8.6%). Adequate intrasession reliability and usefulness can be assumed from test day 2 (1-back test, executive function test) and day 3 (2-back test) onward. For all tests, learning effects were observed within and compared with test day 1.

Conclusions

The SKILLCOURT is a reliable diagnostic tool for assessing reactive agility and motor–cognitive performance. Because of learning effects, sufficient familiarization with the tests is required when used for diagnostic purposes.
Exploring the targeting spectrum of rocaglates among eIF4A homologs
Authors: Naineni Sai Kiran , Cencic Regina , Robert Francis , Brown Lauren E. , Haque Minza , Scott-Talib Jordan , Sénéchal Patrick , Schmeing T. Martin , Porco John A. , Pelletier Jerry
Published: March 2023

Inhibition of eukaryotic translation initiation through unscheduled RNA clamping of the DEAD-box (DDX) RNA helicases eIF4A1 and eIF4A2 has been documented for pateamine A (PatA) and rocaglates—two structurally different classes of compounds that share overlapping binding sites on eIF4A. Clamping of eIF4A to RNA causes steric blocks that interfere with ribosome binding and scanning, rationalizing the potency of these molecules since not all eIF4A molecules need to be engaged to elicit a biological effect. In addition to targeting translation, PatA and analogs have also been shown to target the eIF4A homolog, eIF4A3—a helicase necessary for exon junction complex (EJC) formation. EJCs are deposited on mRNAs upstream of exon-exon junctions and, when present downstream from premature termination codons (PTCs), participate in nonsense-mediated decay (NMD), a quality control mechanism aimed at preventing the production of dominant-negative or gain-of-function polypeptides from faulty mRNA transcripts. We find that rocaglates can also interact with eIF4A3 to induce RNA clamping. Rocaglates also inhibit EJC-dependent NMD in mammalian cells, but this does not appear to be due to induced eIF4A3-RNA clamping, but rather a secondary consequence of translation inhibition incurred by clamping eIF4A1 and eIF4A2 to mRNA.
Evaluation of patient profiles, treatment paradigms and clinical efficacy, and safety outcomes in adult patients with vitamin D deficiency or insufficiency in India: A multicenter, prospective, non-interventional study
Authors: Tiwaskar Mangesh , Soratia Zubair , Karmakar Arnab , Patil Neelkanth , Bhardwaj Vikas , Sharma Rakesh , Majid Sarfaraz , Rao Akhila , Ranjit SDI
Published: March 2023

Background: Nationwide studies assessing sociodemographic factors associated with poor vitamin D status and efficacy-safety of vitamin D supplementation in Indian clinical practice are limited.

Methods: In this multicenter, prospective, non-interventional study, patients with vitamin D deficiency (25[OH]D <20 ng/mL)/insufficiency (25[OH]D 21-29 ng/mL) were enrolled at 9 sites across India and prescribed vitamin D supplements per routine practice. Primary endpoints were patient profiles associated with vitamin D deficiency/insufficiency and change in visual analog scale (VAS) scores for clinical signs/symptoms from baseline to weeks 4 and 8. Key secondary endpoints were prescription pattern of vitamin D supplements and incidence of adverse drug reactions (ADRs)/serious ADRs. Change in systolic/diastolic blood pressure (SBP/DBP [hypertensive patients]) and glycated hemoglobin (HbA1c [diabetic patients]) were assessed from baseline to weeks 8 and 12, respectively. Paired t test was used to assess statistical significance, except for patient profile association, where analysis of variance model was used.

Results: Of 201 enrolled patients (mean [standard deviation] age: 43.4 [14.52] years), 61.7% were women. Most demographic and anthropometric factors, except for current sunscreen use (p=0.0297) and socioeconomic status (p=0.0222), were not significantly associated with vitamin D deficiency/insufficiency. Upper-lower class had significantly higher odds (p=0.033) for vitamin D deficiency versus insufficiency versus lower class. Most of the patients were prescribed 60000 IU/week orally. VAS scores for bone and lower back pain, bone loss, low bone mineral density, and muscle pain were significantly reduced at weeks 4 and 8 (p<0.001). SBP/DBP of hypertensive patients and HbA1c of diabetic patients were also significantly decreased (p<0.05). No ADRs/serious ADRs were observed.

Conclusion: Sunscreen use and socioeconomic status were significantly associated with vitamin D deficiency/insufficiency. Vitamin D supplementation improved clinical symptoms, HbA1c levels (diabetic patients), and SBP/DBP (hypertensive patients), without any adverse safety outcomes. Nevertheless, studies with long-term follow-up and larger sample sizes are warranted.
Case Report: A Rare Case of Eosinophilic Ureteritis in a Woman with Reccuring Bilateral Ureteric Strictures causing Hydroureteronephrosis
Authors: Matondang Sahat Basana Romanti Ezer , Imam Adistra , Darmawan Guntur , Achmadsyah Armand , Hilmy Ibrahim Abubakar , Harsanto Andrian , Sumardi Rochani
Published: March 2023

Introduction: Eosinophilic ureteritis is a very rare etiology of ureteric obstruction that leads to hydroureteronephrosis. We have only so far discovered a few case reports discussing eosinophilic ureteritis and the exact cause of this condition is poorly understood.

Clinical findings: we report a very interesting case of a 71-year-old patient presenting with general weakness and oliguria, computed tomography (CT) scan found bilateral hydroureteronephrosis caused by recurring ureteric strictures.

Diagnosis, interventions, and outcomes: ureterorenoscopy (URS) to extract a specimen for biopsy and laser fulguration to relieve ureteral strictures was performed. Double-J (DJ) stents were inserted both in the left and right ureters to overcome the ureteric strictures. Microscopy of the excised specimen revealed dominant eosinophilic infiltration. Therefore, diagnosis of eosinophilic ureteritis was made. In addition to stenting, Meropenem and Mirabegron was given to the patient. After a week of observation, the patient made a full recovery with no signs of initial symptoms.

Conclusion: It is important to consider eosinophilic ureteritis in the differential diagnosis of any ureteric stricture because it is a highly uncommon entity with variable clinical characteristics. The gold standard procedure, which should be utilized to make the diagnosis, is a histological examination.
Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in Plasmodium berghei ANKA
Authors: Chepngetich Jean , Muriithi Brenda , Gachie Beatrice , Thiong'o Kevin , Jepkorir Mercy , Gathirwa Jeremiah , Kimani Francis , Mwitari Peter , Kiboi Daniel
Published: March 2023

Background: Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable Plasmodium kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant Plasmodium berghei parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kβ), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in Plasmodium berghei ANKA.

Methods: We used in silico bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1. Using qPCR analysis, we finally measured the mRNA amount of PANK1, DAGK, and PI4Kβ at trophozoites and schizonts stages.

Results: We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kβ, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kβ possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His, while DAGK contained K270R and K292R mutations. PI4Kβ had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kβ in the trophozoites but upregulation at the schizonts stages in the AQr parasites.

Conclusions: The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and the impact on drug responses require further investigations in malaria parasites.
Energy skills as a driver to sustainable construction: current status, needs and proposed actions
Authors: Stojanovska-Georgievska Lihnida , Cerovsek Tomo , Funtik Tomas , Sandeva Ivana , Krleski Aleksandar , Spasevska Hristina , Ginovska Margarita
Published: March 2023

During the last two decades, intensified actions toward energy efficiency in construction have provoked the implementation of a significant number of EU-funded and national projects that have developed knowledge in the field of energy-efficient (EE) design and construction of new and refurbished buildings. The current study contributes to state-of-the-art research of the best practices in the field of energy skills at the EU level. The methodology used comprised of desk research on the status of the development of energy skills in construction and business, the status of demand, the level of awareness, and the current training schemes and certifications which are offered. The research is based on published reports, publications, and surveys, resulting in the identification of over 500 sources of information relevant to EE skills. Key findings address the challenges related to the transition of EE skills from the national to the inter-regional level, due to methodological differences, language barriers, and organizational issues. Special attention is given to identifying existing practices for the recognition of previous learning (RPL), and to mitigate barriers to further implementation of this method for upskilling and certification of professionals and workers.

In addition, we provide a base that shall allow us to evaluate the impact of existing initiatives on EE and digital skills management in the construction sectors through the survey conducted on an inter-regional level, including five different European countries. The survey results show regional divergence in the adoption of energy skills, but also concentrate on more general conclusions that will pave the way for the creation of upcoming training schemes for upskilling of the construction workforce involving both blue collars and white collars, and noting digital skills, cross-craft competences, and skills in renewable sources as the most in-demand to ensure sustainable construction
The SquAd derivation: A Square Additive approach to the turbulent Prandtl number
Authors: Moreau Vincent
Published: March 2023

Liquid metals have been chosen as primary coolant of innovative nuclear systems under current development. They present a very high thermal conductivity and hence a very low molecular Prandtl number. This feature challenges the modeling of turbulent thermal flows applying the Reynolds analogy. This paper addresses this challenge. A new formula for the turbulent Prandtl number is derived in terms of local variables available from two-equations turbulence models. The derivation is a direct consequence of the expected square additivity of the molecular and turbulent parameters defining the effective viscosity and the effective conductivity. The formula does not degenerate and leads to a Kays like formulation if approximated. While constrained by the quality of the turbulent viscosity modeling, it has the potential to improve the numerical simulation of turbulent thermal flows.
Interleukin-6-producing paraganglioma as a rare cause of systemic inflammatory response syndrome: a case report
Authors: Lee Yin Young , Chung Seung Min
Published: March 2023

Pheochromocytomas and paragangliomas (PPGLs) may secrete hormones or bioactive neuropeptides such as interleukin-6 (IL-6), which can mask the clinical manifestations of catecholamine hypersecretion. We report the case of a patient with delayed diagnosis of paraganglioma due to the development of IL-6-mediated systemic inflammatory response syndrome (SIRS). A 58-year-old woman presented with dyspnea and flank pain accompanied by SIRS and acute cardiac, kidney, and liver injuries. A left paravertebral mass was incidentally observed on abdominal computed tomography (CT). Biochemical tests revealed increased 24-hour urinary metanephrine (2.12 mg/day), plasma norepinephrine (1,588 pg/mL), plasma normetanephrine (2.27 nmol/L), and IL-6 (16.5 pg/mL) levels. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT showed increased uptake of FDG in the left paravertebral mass without metastases. The patient was finally diagnosed with functional paraganglioma crisis. The precipitating factor was unclear, but phendimetrazine tartrate, a norepinephrine-dopamine release drug that the patient regularly took, might have stimulated the paraganglioma. The patient’s body temperature and blood pressure were well controlled after alpha-blocker administration, and the retroperitoneal mass was surgically resected successfully. After surgery, the patient’s inflammatory, cardiac, renal, and hepatic biomarkers and catecholamine levels improved. In conclusion, our report emphasizes the importance of IL-6-producing PPGLs in the differential diagnosis of SIRS.
Diabetes in the context of dental treatment in an interdisciplinary approach
Authors: Cabon Julia , Pejas Julia , Zawilska Anna , Trzcionka Agata
Published: March 2023

Instroduction:  Diabetes, including its numerous complications, is one of fundamental challenges of modern medicine. Over the years, many types of this disease have been appointed, differing in both etiological background and method of treatment.
Dentists, when providing dental care to a patient burdened with diabetes, should pay special attention to the first symptoms reported by the patient as well as manifested in the oral cavity and surrounding tissues, e.g. in the form of xerostomia, hypertrophy of the salivary glands, changes on mucous membranes, impeded healing, or difficulties in combating local inflammation and infections, as well as in the form of physiological microflora disorders.
Aim of the study: The aim of the study is to emphasize the need for controlling diabetes for the sake of general and oral health.
Materials and methods: Our work is mainly based on the articles published in PubMed, websites or medical books. We were looking for keywords such as ‘diabetes’, ‘dental treatment’, ‘symptoms of diabetes’ or ‘oral cavity diseases’.
Results: Diabetes is often manifested by changes in the oral cavity, as evidenced by numerous scientific studies presented in the bibliography. Controlling the disease helps to eliminate lowering quality-of-life general symptoms and oral lesions.
Conclusions: Faced with the challenges of modern medicine, the dentist is obliged to inform the patient about the diagnostic and therapeutic possibilities of both diabetes itself and its symptoms occurring in the oral cavity and then take all steps to ensure that the patient's condition is stabilised.
Francuskie pokolenie lat 30.: École normale supérieure 1920-1940: Aron, Nizan, Sartre i Merleau-Ponty
Authors: Mróz Piotr
Published: March 2023

This will be a story – récit or text (in the sense of the early structuralists) that deliberately allows the participation of banished concepts, intuitions or simply words chased away (chassé) from the posthumanist narratives of the last decades of the 20th and first decades of the 21st century playing, however, a not insignificant role here. The story presented here – a continuation of the long-standing interests and publications of the writer of these words – though only seemingly looser in form, by no means departs from the requirements expected of academic dissertations. But the preoccupation with French esprit (it is one of those exiles from the 20th century humanities) – the spirit of freedom, contrariness, spontaneity, attachment to freedom of expression, that expression (the term of Maurice Merleau-Ponty belonging to our circle), ideas in constant motion, confrontation in a kind of agon – goes hand in hand with a correlated theme: the domain of the descriptions, analyses and reconstructions undertaken here. For we are writing about a particular stage of an individual’s formulation, his youth, a time of struggle, hope, but also sometimes inevitable defeats and failures; we are writing about a time that is so accurately reflected in the formula of rites of passage.
ASLAN SEMBOLİZMİNİN TARİHSEL YOLCULUĞU VE GÜNCEL LOGO TASARIMLARINDA KULLANIMI
Authors: TUTAYSALGIR Orhan , ARI Sevgi
Published: March 2023

“Ormanların kralı” olarak anılan aslan, çağlar boyunca farklı kültürlerin görsel ve sözel anlatılarında kullanılmıştır. Aslan sembolünün köklü tarihi, her dönemde değişen inanç ve toplumsal yapıların, bu sembol üzerinden gözlemlenmesini mümkün kılar. Aslan sembolizmi şehirlerin, devletlerin ortaya çıkışı ve ardından gelen endüstrileşme süreci gibi insanlık tarihindeki önemli kırılmalarla etkileşim içindedir. Aslan sembolünün tarihsel süreç içerisindeki çeşitli kullanım alanlarının ve görsel niteliklerinin ele alındığı bu çalışmada, çağdaş örnekler üzerinden güncel bağlantılar incelenmiştir. Aslan sembolünün mitlerden topluluklara ve oradan da ticari kurumlara aktarılan yolculuğunda temsil ettiği değerlerin kökenleri ve bu değerler sisteminin ortaklık gösteren ve ayrılan yönleri çözümlenmiştir. Güncel markaların aslan figürünü seçmelerinin altındaki nedenler, söz konusu tarihsel incelemeye eşlik etmiştir. Görsel karakteri kültürler ve çağlar içerisinde değişiklik gösterse de aslan sembolü, güç, liderlik, üstünlük sahibi olma ve bu nitelikleri sürdürme isteğinin temsili olarak birçok toplum tarafından kabul görmüştür. Bu çalışma ile cesaretin, otoritenin ve gücün temsili olarak öne çıkan aslan sembolünün kimi kültürlerde savaşılan, kimi kültürlerde ise saygı duyulan bir figür olduğu ortaya çıkmıştır. Sembolün güncel logolardaki kullanımında, tarihten bugüne aslana atfedilen karakteristik özelliklerin değişmeden taşındığı gözlemlenmiştir. Ayrıca çağdaş logo tasarımlarında farklı görsel yapılar altında olsa da yapılan seçimlerin ortak kökenden beslendiği sonucuna varılmıştır.
Sivas Arkeoloji Müzesinde Bulunan El İşleme Peşkirler
Authors: KARAMAN Şirin , ÇAKMAKTEPE Mehmet Fatih
Published: March 2023

Türklerin Orta Asya’dan itibaren takip ettiğimiz süsleme meraklarını Anadolu topraklarında da arttırarak sürdürdüklerini görmekteyiz. Bu çalışmamamızda geleneksel el sanatları içinde zengin çeşitlemelerinden olan işleme örneklerinin yer aldığı peşkirler incelenmiştir. Önceleri ihtiyaçtan doğan fakat zamanla farklı anlamlar yüklenen çok değerli işleme örnekleri mevcuttur. Peşkir, günümüz peçetesinin geçmişteki görkemli temsilcisidir. Öyle ki sofraya oturanlarda hayranlık oluşturan ve ağzı silmekte tereddüt edilen işlemeli kumaşlardır. Bir kumaş üzerine birkaç renkli iplikle oluşturulan zarif bezlerdir. Sivas sahip olduğu köklü kültürel geçmişin izlerini halen taşımaya devam etmektedir. El sanatları varlığıyla onlarca müze oluşturabilecek eser kapasitesi bulunmaktadır. Buradaki peşkirlerde şu anda Sivas Arkeoloji müzesi depolarında sergilenecekleri günü beklemektedirler. Eskiden sergilenirken günümüzde henüz bir etnografya müzesi yapılmadığı için depolarda bekleyen peşkirleri günümüz insanlarına göstermek ve tanıtmak amaçlanmıştır. Bu nedenle peşkirler incelenmiş ve kumaş türleri, ebatları, işleme teknikleri, renk, motif ve desen kompozisyonları tespit edilmiştir. Motiflerin çizimleri yapılarak daha sonraki kullanımlar için hazır hale getirilmişlerdir.
Bistable RNA Pathways: (A Brief-Review)
Authors: G. Sankar G. Sankar
Published: March 2023

A Bistable RNA pairs have noteworthy importance in RNA ribo-switches, RNA thermometers and viroid replications, making this molecule particularly interesting to chemists and scientists working in field of biochemistry, virologists and computational chemistry. It adopts equilibrium between two distinct hairpin conformations. The two hairpin conformations adopt different functionality. In this review paper, we discuss the pathways used by bistable RNAs for switching confirmations and look into the future possibilities existing mechanisms can yield in RNA and retro-virus RNA studies.
Pharmacognostic Characterization and Antacid Activity of Aqueous Extract of Desmodium triflorum Linn and Pogostemon heyneanus Benth
Authors: Jayasuriya W.J.A. Banukie , Arawwawala L. D. A. Menuka , Gamage Shashani , Rathnasekara Himanshi , Dias Bhavantha , Suresh Sugandhika
Published: March 2023

Present study was aimed to investigate the antacid potential of Desmodium triflorum Linn whole plant and Pogostemon heyneanus Benth leaves and to establish their diagnostic characteristics. Powder microscopy, detailed anatomical characteristics, analysis of phytochemicals and Ultra-Performance Liquid Chromatography were done. In addition, neutralizing effects on artificial gastric acid (AGA) by aqueous extracts (AE) of the plants, their ethyl acetate fractions (EAF) and residual aqueous fractions (RAF) were determined. Fordtran’s model (a titration method) was used to evaluate the in vitro neutralization capacity. A modified model of Vatier's artificial stomach was used in the assessment of in vitro acid neutralization duration. Statistical analysis was performed using SPSS 25.0. Pharmacognostic study aids in establishing the standardization parameters. Treatments including AE, RAF of D. triflorum and P. heyneanus showed significant (P<0.01) acid neutralizing effects, duration for consistent neutralization and neutralization capacities. Findings of this study indicated that D. triflorum whole plant and P. heyneanus leaves possessed potent antacid effects.