Early and rapid development of bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation.

Bronchiolitis obliterans (BO) is a form of graft-versus-host disease (GVHD) in the lung and manifests as moderate to severe airflow obstruction after hematopoietic stem cell transplantation (HCT). New-onset airflow obstruction on spirometry is considered diagnostic of bronchiolitis obliterans syndrome (BOS). BOS affects about 5% of all HCT recipients. In general, BO is thought of as a late complication of HCT, usually occurring after day 100 post-transplantation. However, the onset of airflow obstruction can be rapid and is most often irreversible even with treatment. We describe a patient who rapidly developed severe airflow obstruction less than one month after transplantation following the development of upper airway symptoms. Despite aggressive immunosuppression, the patient had no improvement in airflow obstruction. We hypothesize that early screening and treatment may help prevent BOS after HCT.

Case report of substantial reconstruction of second ray segment by osteo-tendo-cutaneous pedicled radial forearm flap.

Introduction and importance: The hand is one of the most vital organ that the surgeon aims to preserve its function and natural appearance. Gunshot injuries are common, especially in a war zone, and unfortunately, they create complex wounds that are hard to reconstruct and infection is very common. In this article, we report rebuilding segment of index finger with a pedicled osteo-tendo-cutaneous radial forearm flap. Case presentation: A 50-year-old man-African with no past medical comorbidities, sustained trauma to his left index finger by high-velocity injury that led to composite tissue loss including metacarpal and proximal phalanx. After applying the initial irrigation and dressing to the wound, his hand was supported by a volar cast then he was referred to the hospital. The hand was examined at the operation room and the index finger was found to be hanged with a medial skin pedicle with necrotic and exposed bone and tendon. He underwent a session of debridement followed by reconstruction using a pedicled osteo-cutaneous radial forearm flap accompanied with metacarpophalangeal joint arthrodesis. Clinical discussion: A significant number of war-related hand injuries resulted in amputations because there were not enough facilities or doctors. While they are alternatives to free flap, abdominal and regional flaps won't yield the same outcomes. The second ray of the hand is reshaped using a radial flap, producing an acceptable result. Conclusion: The Radial forearm flap was used to reconstruct segment of index finger and fulfill our requirements, which include bone, tendon, and skin cover. Additionally, this is a simple and single stage procedure and micro-surgical equipment is not necessary.

Vegetation-edaphic correlation and importance value index in himalayan 'ecotone' temperate conifer forest using the multivariate technique.

Himalayan 'Ecotone' temperate conifer forest is the cradle of life for human survival and wildlife existence. In spite of the importance of these areas, they have not been studied in depth. This study aimed to quantify the floristic structure, important value index (IVI), topographic and edaphic variables between 2019 and 2020 utilizing circular quadrant method (10 m x 10 m). The upper-storey layer consisted of 17 tree species belongs to 12 families and 9 orders. Middle-storey shrubs comprised of 23 species representing 14 families and 12 orders. A total of 43 species of herbs, grasses, and ferns were identified from the ground-storey layer, representing 25 families and 21 orders. Upper-storey vegetation structure was dominated by Pinus roxburghii (22.45 %) and middle-storey by Dodonaea viscosa (7.69 %). However, the ground layer vegetation was diverse in species composition (43 species) and distribution. The floral vegetation structure was encompassing of three floral communities which were diverse in IVI, such as, in Piro-Aial (Group 2), Pinus roxburghii (54.46 x 15.94) had the highest IVI value, followed by Pinus wallichiana (45.21 x 14.85) in Piwa-Quin (Group 3) and Ailanthus altissima (22.84 x 19.25) in Aial-Qugal (Group 1). However, the IVI values for Aesculus indica, Celtis australis, and Quercus incana in Aial-Qugal (Group 1) were not determined due to low detection rate. Nevertheless, eleven of these species showed 0 IVI values in Piro-Aial (Group 2) and Piwa-Quin (Group 3). CCA ordination biplot illustrated the significant differences among floral communities and its distribution, which impacted by temperature, rainfall, soil pH, altitude, and topographic features. Ward's agglomerative clustering finding reflected 'Ecotone' temperate conifer forest is rich and diverse floristic structure.

Dysfunction of Thyroid Hormones Following Acute Coronary Syndrome in a Tertiary Care Hospital in Dhaka City.

In cardiovascular homeostasis thyroid hormone plays an important role. We planned to study the changes in thyroid hormone profile in acute coronary syndrome patients admitted in the coronary care unit and compare them between two groups: unstable angina/non-ST elevated Myocardial infarction (UA/NSTEMI) and ST elevated Myocardial infarction (STEMI). This study was a hospital based descriptive cross sectional study which was conducted from 01 March 2018 to 01 February 2019 in Coronary Care Unit of Bangladesh Medical College Hospital and laboratory tests were done in Microbiology Department of Bangladesh Medical College, Dhaka, Bangladesh. Eighty three cases of acute coronary syndromes were taken for the study. Troponin-I was measured as cardiac marker, Electrocardiogram, Complete blood count, blood glucose level, Blood urea, serum creatinine, serum electrolytes, Fasting lipid profile, Thyroid profile, Echocardiography 2D were done. Most of the respondents were distributed in age group 46-60 years where 34(64.15%) male and 19(35.85%) female. Out of 83 Acute Coronary Syndrome (ACS) patients, 27(32.53%) hypertensive, 22(26.50%) diabetic and 16(19.27%) were Chronic kidney disease (CKD). Abnormal lipid profile was present in 30(43.47%) patients. Among total 52 male and 31 female 9(17.30%) male and 6(19.35%) female had abnormal thyroid function. We further elaborated abnormal thyroid function tests in STEMI group and UA/Non STEMI group of ACS patients. We found 10 patients in STEMI group and 5 patients in UA/Non STEMI group with abnormal thyroid function 29.41% and 10.20% respectively which was not statistically significant (p=0.025). This study depicts abnormality in thyroid hormone profile in 18.07% patients of ACS. Abnormal thyroid function increases risk of coronary artery disease. TSH level of ACS patients on hospital admission could be helpful to evaluate further prognosis of the disease.

Evaluation of Antimicrobial Efficacy and Clinical Outcomes of Triphala and 2.5% Sodium Hypochlorite as Intraradicular Irrigants in Pulpectomy of Primary Teeth.

A natural irrigation solution with a broad spectrum of antimicrobial coverage, triphala was selected for the pulpectomy procedure. Because of its natural ingredients, it is well-known for promoting tissue healing. It also supposedly has certain additional qualities as compared to usual irrigation solutions that are made chemically. Although 2.5% NaOCl is thought to be perfect since it meets most of the requirements for an irrigation solution but it cannot be optimized for pulpectomy procedure. Primary teeth that were recommended for pulpectomy underwent this randomized controlled experiment. Two groups of eighty-four primary teeth were randomly assigned to receive irrigations: triphala in Group A; 2.5% Sodium hypochlorite in Group B. Sample were taken from infected primary root canals. A sterile test tube with bhi broth as the transport media was used to collect pre- and post-irrigation samples using sterile absorbent paper tips. On agar media, microorganisms were cultivated and their mean colony count was assessed. Following the procedure, the patient's follow-up visits at one, two and three months were used to evaluate the clinical result. The post-microbial colony count was dramatically reduced (p<0.001) by both irrigation treatments. Triphala in Group A is demonstrating desirable efficacy. Clinical success was found satisfactory in both the groups studied (p<0.001). But statistically significant difference was not found (p=0.175). Considering undesirable properties of sodium hypochlorite triphala can be a better alternative as a root canal irrigants in pulpectomy of primary teeth.

Pavement ant extract is a chemotaxis repellent for C. elegans.

Ant behavior relies on a collection of natural products, from following trail pheromones during foraging to warding off potential predators. How nervous systems sense these compounds to initiate a behavioral response remains unclear. Here, we used Caenorhabditis elegans chemotaxis assays to investigate how ant compounds are detected by heterospecific nervous systems. We found that C. elegans avoid extracts of the pavement ant ( Tetramorium immigrans ) and either osm-9 or tax-4 ion channels are required for this response. These experiments were conducted in an undergraduate laboratory course, demonstrating that new insights into interspecies interactions can be generated through genuine research experiences in a classroom setting.

Formulation and evaluation of azithromycin-loaded silver nanoparticles for the treatment of infected wounds.

Infected wounds pose a significant challenge in healthcare, requiring innovative therapeutic strategies. Therefore, there is a critical need for innovative pharmaceutical materials to improve wound healing and combat bacterial growth. This study examined the efficacy of azithromycin-loaded silver nanoparticles (AZM-AgNPs) in treating infected wounds. AgNPs synthesized using a green method with Quinoa seed extract were loaded with AZM. Characterization techniques, including X-ray Powder Diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and Uv-Vis analysis were utilized. The agar diffusion assay and determination of the MIC were used to assess the initial antibacterial impact of the formulations on both MRSA and E. coli. In addition, the antimicrobial, wound-healing effects and histological changes following treatment with the AZM-AgNPs were assessed using an infected rat model. The nanoparticles had size of 24.9 ± 15.2 nm for AgNPs and 34.7 ± 9.7 nm for AZM-AgNPs. The Langmuir model accurately characterized the adsorption of AZM onto the AgNP surface, indicating a maximum loading capacity of 162.73 mg/g. AZM-AgNPs exhibited superior antibacterial properties in vivo and in vitro compared to controls. Using the agar diffusion technique, AZM-AgNPs showed enhanced zones of inhibition against E. coli and MRSA, which was coupled with decreased MIC levels. In addition, in vivo studies showed that AZM-AgNP treated rats had the best outcome characterized by improved healing process, lower bacterial counts and superior epithelialization, compared to the control group. In conclusion, AZM-AgNPs can be synthesized using a green method with Quinoa seed with successful loading of azithromycin onto silver nanoparticles. In vitro and in vivo studies suggest the promising use of AZM-AgNPs as an effective therapeutic agent for infected wounds.

Principal component analysis of phenotypic and breeding value data for semen traits in Egyptian buffalo bulls.

Buffalo bull semen traits are economically important traits that influence farm fertility and profitability. Genetic improvement of semen characteristics is an important detail of the genetic improvement. This study was conducted to assess the relationship between the breeding values as well as the phenotypic values for semen traits (VOL, MM, LS, AS and CONC) of the Egyptian buffalo bulls. A total of 7761 normal semen ejaculates were collected and characterized at ILMTC laboratory from 26 bulls from 2009 to 2019. For VOL, MM, LS, AS, and CONC, the actual means were 3.89 mL, 62.37%, 60.64%, 3.94%, and 0.67 × 109 sperm/mL, respectively. The prediction of breeding values for semen traits was estimated using a Bayesian procedure. The estimated standardized EBVs and phenotypic values were used in the principal component analysis (PCA). Of five PCs, one PC (PC1) had > 1 eigenvalues that was responsible for 87.19% of the total variation of SEBV, and two PCs had > 1 eigenvalues that were responsible for 59.61% and 21.35% of the total variation of the phenotypic values. Together, PC1 and PC2 accounted for 97.97% of the total variance of SEBV and 80.96% of the total variance of phenotypic values. A graphs of the first two components showed the traits separated into two different directions by group. This indicates each group was under similar genetic influence. Therefore, selection can be done separately for each group without influencing the other. Principal component analysis reduced variables to describe the key information in buffalo semen data.

Novel RP-HPLC method for estimation of a newly developed combination of tizanidine and etoricoxib in rat plasma: Eight criteria for greens evaluation.

A novel environmentally friendly reversed-phase high-performance liquid chromatography (RP-HPLC) method has been effectively validated for simultaneously measuring a prospective conjunction of tizanidine (TIZ) and etoricoxib (ETC), the combined medicine, in rat plasma. The technique employs diclofenac potassium as the internal standard, guaranteeing dependable and precise outcomes. This study aimed to assess the impact of the suggested combination therapy on treating inflammation resulting from rheumatoid arthritis (RA) in a rat model. The procedure was performed using an Agilent series 1200 model HPLC apparatus. The chromatographic conditions consist of isocratic elution mode, C18 column with dimensions of 150 mm × 4.6 mm × 5 µm, flow rate of 1.5 mL/min, wavelength of 230 nm, temperature of 50°C, and injection volume of 10 µL. The elution was performed using a mobile phase consisting of a phosphate buffer with a pH of 3.5 and acetonitrile in a ratio of 80:20 v/v. Calibration curves were conducted for TIZ and ETC within the 1-50 µg/mL range, demonstrating linear trends with R2 values over 0.999. The effectiveness and eco-friendliness of the proposed method were evaluated using eight separate environmentally conscious metrics. The addition of TIZ and ETC to arthritic rodents amplified these effects significantly. Furthermore, TIZ and ETC significantly reduced serum levels in arthritic rodents, and safety investigations revealed normal complete blood count, liver, and renal functions. TIZ and ETC appear to have antiarthritic, anti-inflammatory, and safe combinations, making them viable future treatment options for RA that are also safe and efficacious. Following validation by United States Food and Drug Administration (US-FDA) rules, all goods met the criteria.

Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS.

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and increased membrane permeability, which represents the leading cause of mortality in ICUs. Mechanical ventilation strategies are at the forefront of supportive approaches for ARDS. Recently, an increasing understanding of RNA biology, function, and regulation, as well as the success of RNA vaccines, has spurred enthusiasm for the emergence of novel RNA-based therapeutics. The most common types of RNA seen in development are silencing (si)RNAs, antisense oligonucleotide therapy (ASO), and messenger (m)RNAs that collectively account for 80% of the RNA therapeutics pipeline. These three RNA platforms are the most mature, with approved products and demonstrated commercial success. Most recently, miRNAs have emerged as pivotal regulators of gene expression. Their dysregulation in various clinical conditions offers insights into ARDS pathogenesis and offers the innovative possibility of using microRNAs as targeted therapy. This review synthesizes the current state of the literature to contextualize the therapeutic potential of miRNA modulation. It considers the potential for miR-based therapeutics as a nuanced approach that incorporates the complexity of ARDS pathophysiology and the multifaceted nature of miRNA interactions.

Learning to stand with sensorimotor delays generalizes across directions and from hand to leg effectors.

Humans receive sensory information from the past, requiring the brain to overcome delays to perform daily motor skills such as standing upright. Because delays vary throughout the body and change over a lifetime, it would be advantageous to generalize learned control policies of balancing with delays across contexts. However, not all forms of learning generalize. Here, we use a robotic simulator to impose delays into human balance. When delays are imposed in one direction of standing, participants are initially unstable but relearn to balance by reducing the variability of their motor actions and transfer balance improvements to untrained directions. Upon returning to normal standing, aftereffects from learning are observed as small oscillations in control, yet they do not destabilize balance. Remarkably, when participants train to balance with delays using their hand, learning transfers to standing with the legs. Our findings establish that humans use experience to broadly update their neural control to balance with delays.

Eltrombopag improves platelet engraftment after haploidentical bone marrow transplantation: Results of a Phase II study.

Slow platelet recovery frequently occurs after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with bone marrow graft and post-transplant cyclophosphamide (PCy)-based graft-versus-host disease (GVHD) prophylaxis. Improved platelet recovery may reduce the need for transfusions and improve outcomes. We investigated the safety and efficacy of eltrombopag, a thrombopoietin receptor agonist, at enhancing platelet recovery post-haplo-HSCT. The prospective study included patients ≥18 years of age who received haplo-HSCT with bone marrow graft and PCy. Patients received eltrombopag 300 mg/day starting on Day +5. The primary objective was to estimate platelet engraftment (>50 000/µL by Day 60). In a post hoc analysis, they were compared to a contemporary matched control group who did not receive eltrombopag. One hundred ten patients were included in the analysis (30 eltrombopag and 80 control). Seventy-three percent and 50% of patients in the eltrombopag group and control group, respectively, attained >50 000/µL platelet count by Day 60 (p = .043). No eltrombopag-related grade ≥4 adverse events were observed. Median time to platelet recovery (>20 000/µL) was 29 days with eltrombopag and 31 days for controls (p = .022), while its cumulative incidence was 90% (95% confidence interval [CI]: 78%-100%) with eltrombopag versus 67.5% (95% CI: 57%-78%) for controls (p = .014). Number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and non-relapse mortality were similar between groups. Overall, eltrombopag is safe and improves platelet recovery in patients undergoing haplo-HSCT with bone marrow graft and PCy.

Consensus-Based Overarching Principles and Recommendations on the Use of Biosimilars in the Treatment of Inflammatory Arthritis in the Gulf Region.

BACKGROUND: Though biologic agents have significantly improved the treatment of inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis), high costs, stringent regulations, strict reimbursement criteria, and existing patents have limited patient access to treatments. While being highly similar in quality, safety, and efficacy to biologic reference products, biosimilars can reduce the financial burden and prevent underutilization of medication. OBJECTIVE: The objective of this initiative was to develop an evidence-based consensus of overarching principles and recommendations aimed at standardizing the use of biosimilars in treating inflammatory arthritis in the Gulf region. METHODS: A task force of practicing rheumatologists, a clinical pharmacist, a health economist, patients, regulators, and payors from across the Gulf region developed recommendations and overarching principles based on the outputs of a systematic literature review conducted to address Patient-Intervention-Comparison-Outcome (PICO) questions specific to key challenges regarding the use of biosimilars for the treatment of inflammatory arthritis in the region. As the data before 2017 have been previously reviewed in another publication, the current review focused on data published between January 2017 and August 2022 (PROSPERO ID CRD42022364002). Consensus on each statement required a level of agreement of 70% or greater. RESULTS: Consensus was reached for five overarching principles and nine recommendations by the task force. The principles emphasize the importance of improving the awareness, understanding, and perception of biosimilars, as well as the need for regulated regional real-world data generation and protocols to make biosimilars a viable and affordable treatment option for all patients. The consensus recommendations advocate the need for shared treatment decisions between rheumatologists and patients when considering biosimilars. They further recommend that confirmation of a biosimilar's efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the reference product has been approved. Finally, there is a need for pharmacovigilance and national health policies governing the adoption and prescription of biosimilars in clinical practice across the region. CONCLUSIONS: These are the first consensus recommendations for the Gulf region based on a systematic literature review and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines, integrating clinical evidence with clinical expertise to optimize decision making for the use of biosimilars in patients with inflammatory arthritis. They were formulated based on predominantly international data because of the limited regional data and therefore can be generalized to serve as recommendations for healthcare professionals in other parts of the world.

Modified intermittent low negative pressure wound therapy for complex injuries: A case series.

INTRODUCTION AND IMPORTANCE: Combat wounds can be difficult to manage and can lead to disfigurement and infection. The closure of these wounds is crucial, as delayed closure also increases the risk of further complications. Military medicine has introduced negative pressure wound therapy, which modulates wounds perfectly through the microscopic and macroscopic configurations of the wound environment. It is expensive and not available worldwide, and several modifications using low cast materials were mentioned in literature. METHODS: We present a case series of four patients using the previously mentioned modified technique in combat wound management, and discuss the results, outcome, and justification for choosing this modality of treatment. All patients underwent a thorough debridement, followed by a modified negative pressure wound treatment for three weeks, employing readily available medical devices. RESULTS: All wounds healed successfully without complication and a simple closure was used to cover the resultant wound. CONCLUSION: Modified NPWT with limited resources is capable of promoting healing in conflict-related wounds through multifactorial properties and transforming reconstructive methods from complex to simple procedures in areas with a shortage of medical supplies and surgeons in addition to busy operating rooms.

Mental Health Assessment of Health Care Providers of Bangladesh during Covid-19 Pandemic: A Cross-Sectional Web-Based Study.

SARS COV 2 raised immense agony to everyone. As health care workers remains direct contact with patients, they are vulnerable to mental health disorder. The study was done to identify mental health status of health care providers of Bangladesh. It was a cross sectional web based survey among health care providers of bangladesh. A structured web based questionnaire was prepared both in Bangla and English version for better understanding. Total 2594 health care workers responded to online survey. Male were 1303(50.2%) and female were 1291(49.8%). Occupational demography shows 98.5% were physicians. Mean value of patient health questionnaire 9 (PHQ9) and generalized anxiety disorder (GAD) were 8.43±6.082 and 8.27±5.234 respectively among healthcare providers. To overcome anxiety and depression, 93.4% of HCW didn't receive any psychological material and 85.6% HCW didn't find physiological resources even through media. Despite many lacking, healthcare workers were resilient in our study.

Activation of cytotoxic lymphocytes through CD6 enhances killing of cancer cells.

Immune checkpoint inhibitors (ICIs) have demonstrated efficacy and improved survival in a growing number of cancers. Despite their success, ICIs are associated with immune-related adverse events that can interfere with their use. Therefore, safer approaches are needed. CD6, expressed by T-lymphocytes and human NK cells, engages in cell-cell interactions by binding to its ligands CD166 (ALCAM) and CD318 (CDCP1). CD6 is a target protein for regulating immune responses and is required for the development of several mouse models of autoimmunity. Interestingly, CD6 is exclusively expressed on immune cells while CD318 is strongly expressed on most cancers. Here we demonstrate that disrupting the CD6-CD318 axis with UMCD6, an anti-CD6 monoclonal antibody, prolongs survival of mice in xenograft mouse models of human breast and prostate cancer, treated with infusions of human lymphocytes. Analysis of tumor-infiltrating immune cells showed that augmentation of lymphocyte cytotoxicity by UMCD6 is due to effects of this antibody on NK, NKT and CD8 + T cells. In particular, tumor-infiltrating cytotoxic lymphocytes from UMCD6-treated mice expressed higher levels of perforin and were found in higher proportions than those from IgG-treated mice. Moreover, RNA-seq analysis of human NK-92 cells treated with UMCD6 revealed that UMCD6 up-regulates the NKG2D-DAP10 receptor complex, important in NK cell activation, as well as its downstream target PI3K. Our results now describe the phenotypic changes that occur on immune cells upon treatment with UMCD6 and further confirm that the CD6-CD318 axis can regulate the activation state of cytotoxic lymphocytes and their positioning within the tumor microenvironment.

Patient-reported treatment response in chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) treatment response is assessed using National Institutes of Health (NIH) Consensus Criteria in clinical trials, and by clinician assessment in routine practice. Patient-reported treatment response is central to the experience of chronic GvHD manifestations as well as treatment benefit and toxicity, but how they correlate with clinician- or NIH-responses has not been well-studied. We aimed to characterize 6-month patientreported response, determine associated chronic GvHD baseline organ features and changes, and evaluate which patientreported quality of life and chronic GvHD symptom burden measures correlated with patient-reported response. From two nationally representative Chronic GVHD Consortium prospective observational studies, 382 subjects were included in this analysis. Patient and clinician responses were categorized as improved (completely gone, very much better, moderately better, a little better) versus not improved (about the same, a little worse, moderately worse, very much worse). At six months, 270 (71%) patients perceived chronic GvHD improvement, while 112 (29%) perceived no improvement. Patient-reported response had limited correlation with either clinician-reported (kappa 0.37) or NIH chronic GvHD response criteria (kappa 0.18). Notably, patient-reported response at six months was significantly associated with subsequent failure-free survival. In multivariate analysis, NIH responses in eye, mouth, and lung had significant association with 6-month patient-reported response, as well as a change in Short Form 36 general health and role physical domains and Lee Symptom Score skin and eye changes. Based on these findings, patient-reported responses should be considered as an important complementary endpoint in chronic GvHD clinical trials and drug development.

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis.

A novel rheumatoid arthritis (RA) synovial fluid protein, Syntenin-1, and its receptor, Syndecan-1 (SDC-1), are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes (FLS). Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9, IL-1ß, IL-6, and CCL2 through SDC-1 ligation and HIF1α, or mTOR activation. Mechanistically, Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling. In Syntenin-1 reprogrammed endothelial cells, the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors, AMPK, PGC-1α, citrate, and inactive oxidative phosphorylation. Conversely, RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity. The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression. We found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS, which are also represented in RA explants. Similar to RA explants, morphological and transcriptome studies authenticated the importance of VEGFR1/2, Notch1, RAPTOR, and HIF1α pathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient animals. Consistently, dysregulation of SDC-1, mTOR, and HIF1α negated Syntenin-1 inflammatory phenotype in RA explants, while inhibition of HIF1α impaired synovial angiogenic imprint amplified by Syntenin-1. In conclusion, since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood, targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

Forest yield prediction under different climate change scenarios using data intelligent models in Pakistan / Previsão de produção florestal em diferentes cenários de mudanças climáticas usando modelos inteligentes de dados no Paquistão

Abstract This study aimed to develop and evaluate data driven models for prediction of forest yield under different climate change scenarios in the Gallies forest division of district Abbottabad, Pakistan. The Random Forest (RF) and Kernel Ridge Regression (KRR) models were developed and evaluated using yield data of two species (Blue pine and Silver fir) as an objective variable and climate data (temperature, humidity, rainfall and wind speed) as predictive variables. Prediction accuracy of both the models were assessed by means of root mean squared error (RMSE), mean absolute error (MAE), correlation coefficient (r), relative root mean squared error (RRMSE), Legates-McCabe's (LM), Willmott's index (WI) and Nash-Sutcliffe (NSE) metrics. Overall, the RF model outperformed the KRR model due to its higher accuracy in forecasting of forest yield. The study strongly recommends that RF model should be applied in other regions of the country for prediction of forest growth and yield, which may help in the management and future planning of forest productivity in Pakistan.

Resumo Este estudo teve como objetivo desenvolver e avaliar modelos baseados em dados para previsão da produção florestal em diferentes cenários de mudanças climáticas na divisão florestal Gallies do distrito de Abbottabad, Paquistão. Os modelos Random Forest (RF) e Kernel Ridge Regression (KRR) foram desenvolvidos e avaliados usando dados de produção de duas espécies (pinheiro-azul e abeto-prateado) como uma variável objetiva e dados climáticos (temperatura, umidade, precipitação e velocidade do vento) como preditivos variáveis. A precisão da previsão de ambos os modelos foi avaliada por meio de erro quadrático médio (RMSE), erro absoluto médio (MAE), coeficiente de correlação (r), erro quadrático médio relativo (RRMSE), Legates-McCabe's (LM), índice de Willmott (WI) e métricas Nash-Sutcliffe (NSE). No geral, o modelo RF superou o modelo KRR devido à sua maior precisão na previsão do rendimento florestal. O estudo recomenda fortemente que o modelo RF seja aplicado em outras regiões do país para previsão do crescimento e produtividade florestal, o que pode ajudar no manejo e planejamento futuro da produtividade florestal no Paquistão.