bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors
Authors: Do Hung , Wang Jinan , Miao Yinglong
Published: February 2023

G-protein-coupled receptors (GPCRs) are the largest superfamily of human membrane proteins and represent primary targets of ~ 1/3 of currently marketed drugs. Allosteric modulators have emerged as more selective drug candidates compared with orthosteric agonists and antagonists. However, many X-ray and cryo-EM structures of GPCRs resolved so far exhibit negligible differences upon binding of positive and negative allosteric modulators (PAMs and NAMs). Mechanism of dynamic allosteric modulation in GPCRs remains unclear. In this work, we have systematically mapped dynamic changes in free energy landscapes of GPCRs upon binding of allosteric modulators using the Gaussian accelerated molecular dynamics (GaMD), Deep Learning (DL) and free energy prOfiling Workflow (GLOW). A total of 18 available high-resolution experimental structures of allosteric modulator-bound class A and B GPCRs were collected for simulations. A number of 8 computational models were generated to examine selectivity of the modulators by changing their target receptors to different subtypes. All-atom GaMD simulations were performed for a total of 66 µs on 44 GPCR systems in the presence/absence of the modulator. DL and free energy calculations revealed significantly reduced conformational space of GPCRs upon modulator binding. While the modulator-free GPCRs often sampled multiple low-energy conformational states, the NAMs and PAMs confined the inactive and active agonist-G protein-bound GPCRs, respectively, to mostly only one specific conformation for signaling. Such cooperative effects were significantly reduced for binding of the selective modulators to “non-cognate” receptor subtypes in the computational models. Therefore, comprehensive DL of extensive GaMD simulations has revealed a general dynamic mechanism of GPCR allostery, which will greatly facilitate rational design of selective allosteric drugs of GPCRs.
Sublaminar Decompression and Fusion Versus Sublaminar Trimming Laminoplasty: a Retrospective Cohort.
Authors: Ali Elsayed Mohamed Selem , Nafea Waleed Mohamed Nafea , Saleh Mohammed Khalid Saleh
Published: February 2023

Background: Many surgical options for treating lumbar degenerative disorders have been used to improve health related outcome of those patients. The aim of the study is to compare the functional and radiological outcome of the two techniques in management of Lumbar spinal stenosis (LSS).
Methods: Sixty patients with Lumbar spinal stenosis were included in a retrospective cohort study at zagazig university hospital. The inclusion criteria were patients with single level LSS with back and /or leg pain with instability on dynamic radiology not responding to medical treatment. We excluded patients with pathological fracture, high grade spondylolisthesis and infection. Patients were divided into two groups according to the method of treatment done. Group one included patients with sublaminar trimming Laminoplasty with instrumented fusion. The second group included patients with sublaminar decompression with instrumented fusion. Patients were assessed clinically using visual analogue scale (VAS) for back and leg pain and the Owestry Disability Index (ODI) for the disability. Plain x-ray, CT and MRI was done for all patients preoperative and we measured AP-thecal sac area, foraminal height and the thecal sac area for all patients (pre- and post-operative).
Results: comparing both groups there were no difference in relation to demographic data nor in the diagnosis of the spinal stenosis. Group-2 had longer hospital stay. Both groups improved clinically post-operatively with no statistical difference between them. However, the rate of improvement in group-2 in relation to leg pain was better. Both groups improved radiologically, but AP-thecal sac area, foraminal height and the thecal sac area were much improved in group-2 (p-value<0.001) in comparison to group-1.
Conclusion: Sublaminar decompression can particularly achieve better central, foraminal and lateral recess decompression together with a better fusion rate and hence, can be used as alternative to different laminotomy decompression techniques for treating different lumbar degenerative disorders.
Essential oil profile of yarrow (Achillea spp. and Tanacetum spp.) ecotypes and their allelopathic potential to suppress redroot pigweed (Amaranthus retroflexus L.)
Authors: Niazipoor Gholamreza , AghaAlikhani Majid , Mokhtassi-Bidgoli Ali , Vitalini Sara
Published: February 2023

As far as we know, there is no information on the effect of Achillea residuals on controlling weeds when considering the effective compounds of the aerial parts of this plant. Thus, in a pot experiment, the allelopathic effect of dry material from the flower, leaf and stem of Tanacetum polycephalum L. and 9 Achillea spp. (Achillea santolina L., A. millefolium L., A. nobilis L., A. conferta DC., A. vermicularis Trin., A. beibersteinii Afan., A. talagonica Boiss., A. tenuifolia Lam., A. aleppica DC.) applied to the soil on the growth of redroot pigweed (Amaranthus retroflexus L.) seedling was tested. Five different ratios of aerial dry material of different species as residues (at 0, 10, 20, 40, and 50 g kg− 1 dry weight) were used in the pots. Achillea residual had a significant effect on the growth of redroot pigweed. Achillea vermicolaris, A.conferta, A. aleppica, and A. nobilis were the most effective species at stopping the growth of redroot pigweed. Based on the results of GC/MS analyses, 152 different compounds were found in the essential oil of Achillea spp. Partial least squares regression between effective doses for controlling redroot pigweed and allelochemical compounds of Achillea species showed that cis-Menth-2-en-1-ol, α-Terpinyl, propionate and Bornyl acetate had the most effect on inhibiting the growth of redroot pigweed. Our research revealed that the Achillea genus has a lot of potential as a bioherbicide. This means that its leftovers or mulch could be used as a good cover crop to get rid of redroot pigweed.
Maternal origin of children-onset asthma: evidence from observational study and instrumental variable analysis
Authors: Jin Siyi , Wu Yuxuan , Zhang Shuo , Gao Tongyu , Liu Ying , Ping Zeng , Wang Ting
Published: February 2023

Background
An inverse association was observed between birthweight and children-onset asthma (COA), the origin of the connection however remains elusive. Instrumental variable causal inference analysis can be used to reveal the origin of such associationbut requires resolving the mixed genetic effect of birthweight into fetal/maternal-specific components.
Methods
We first performed a meta-analysis to study the relation between birthweight and COA using updated literature published from 2014 to 2020. Using maternal-specific instruments of birthweight, we next performed a genetic risk score (GRS) based Mendelian randomization (MR) to estimate the causal effect of low birthweight on COA in mother-offspring pairs (n=3,634) and father-offspring pairs (n=1,334) of the UK Biobank. Two sensitivity analyses of MR were applied to assess the robustness of our causal inference and another method called iMAP was conducted to offer complementary result regarding the direction of referred causality.
Results
The updated meta-analysis indicated individuals born with lower birthweight would be more vulnerable to asthma in childhood. The GRS-based MR analysis demonstrated a significantly negative maternal impact of birthweight on COA (β=-0.162, P=0.037) after adjusting for offspring’s genetic effect in mother-offspring pairs, but failed to repeat this relation in father-offspring pairs. Our sensitivity analyses showed such inverse association was robust against horizontal pleiotropy of used instruments (β=-0.169, P=0.030) and was not likely affected by preterm birth (β=-0.165, P=0.035). The iMAPresult also provided additional evidence supporting the causal influence of low birthweight on COA.
Conclusions
This study provides supportive evidence for the maternal origin of COA and helps guide early prevention for COA via improving intrauterine environments during pregnancy.
Relationship between changes in real-world arm use behavior and structural remodeling of white matter after ischemic stroke
Authors: Anmoto Naoya , Morita Suguru , Inagaki Aki , Horimoto Yoshihiko , Tajima Toshihisa , Sato Chikako , Hibino Hiroaki , Hibino Shin , Okita Yuho , Takebayashi Takashi
Published: February 2023

Background: Although associations between changes in upper-extremity motor impairment and structural changes in white matter after a stroke have been reported, no studies have been conducted to investigate the relationship between changes in real-world arm use and structural changes in white matter after a stroke. Objective: To investigate the correlation between changes in real-world arm use and white matter structure after an ischemic stroke. Methods: In the subacute phase after an ischemic stroke, 18 patients with upper-extremity paralysis underwent the clinical assessments (Fugl-Meyer assessment-upper extremity [FMA-UE] and Motor Activity Log [MAL]) before and after rehabilitation. Neural pathway integrity was also assessed using fractional anisotropy (FA) in diffusion tensor imaging. We assessed the correlation between changes in FA and clinical assessments. A similar sub-analysis was performed on 11 patients with moderate to severe paralysis. Results: Changes in FMA-UE did not correlate with changes in FA in each region of interest. However, changes in the MAL were positively correlated with changes in FA in the column and body of the fornix (r=0.699, p=0.017) and the ipsilesional posterior limb internal capsule (r=0.640, p=0.034) in sub-analysis. Furthermore, there was a tendency towards a correlation in the ipsilesional cingula of the cingulate gyrus in all patients (r=0.441, p=0.067) and in patients with moderate to severe paralysis (r=0.544, p=0.083). Conclusions: Changes in real-world arm use after an ischemic stroke may be associated with changes in the corticospinal tract and white matter structures, such as the fornix and cingulate, related to the reward system and behavioral learning.
Diagnosed and subjectively perceived long-term effects of COVID-19 infection on olfactory function assessed by supervised machine learning
Authors: Lötsch Jörn , Brosig Oskar , Slobodova Jana , Kringel Dario , Haehner Antje , Hummel Thomas
Published: February 2023

Background
Loss of olfactory function appears to be a typical COVID-19 symptom, at least in early variants of SARS-CoV2. The time that has elapsed since the emergence of COVID-19 now allows us to assess the long-term prognosis of its olfactory impact.
Methods
Participants (n = 722 of whom n = 464 reported having had COVID-19 dating back with a mode of 174 days) were approached and tested in a museum as a relatively unbiased environment. Olfactory function was diagnosed by assessing odor threshold and odor identification performance. Subjects also rated their actual olfactory function on a 100-mm visual analog scale and provided analogous retrospective estimates of their smelling ability before the COVID-19 infection and immediately after it.
Results
Diagnosed olfactory function did not differ in former COVID-19 patients from controls. Olfactory diagnoses included 20% decreased olfactory function in former patients and 18.7% in controls, which was not significant. Of former patients, 145 (31.2%) retrospectively reported temporarily reduced olfactory function. Only nine 9 patients (2.2%) reported ongoing reduction of their olfactory function. Overall, former patients rated their current olfactory function significantly better than controls. Supervised machine learning was able to detect past COVID-19 infection from self-assessment of current olfactory function, but not from diagnosed current olfactory function, better than by guessing, although accuracy was intermediate, not suggesting utility as a clinical test.
Conclusions
While retrospectively about one-third of former CVID-19 patients recalled olfactory symptoms associated with prior infection, the present results suggest a positive long-term prognosis for COVID-19-associated olfactory loss.
On the Location of the Nontrivial Zeros of the Riemann Zeta Function on the Critical Line
Authors: Arwashan Naji
Published: February 2023

In this paper we focus our attention on the zeta series ζ (s) = Σ∞n=1 1/ns in the domain of 0 < σ < 1 Even though the series is divergent in that domain, but we will find that its divergence will satisfy an asymptotic equation that involves the values of the zeta function in that same domain. Applying that equation to the critical line will lead us to a function that calculates the value of a convergent series of cosine waves; and interestingly we will find that the finite sum of that series is a combined wave that reorganizes the location of the nontrivial zeros of the Riemann zeta function on the critical line.
MSC code 11E45
The role of nutrients, light and litter in causing species loss in an alpine meadow community
Authors: Ren Zhengwei , Zhao Wei , Zhou Xiaolong , Bang Shaohao , Yao Wanwan
Published: February 2023

The loss of species diversity in nutrient-enriched grasslands is often explained by several single hypotheses, but they do not consider the potential multiple roles of soil availability, light, and plant productivity. Using a 2-year field experiment of multiple nutrient additions (nitrogen, phosphorus and potassium, NPK) in an alpine meadow on the eastern Qinghai-Tibet Plateau, we test whether the three competition hypotheses (niche dimension-diversity hypothesis, litter hypothesis and light competition hypothesis) can simultaneously explain the decline in species richness following NPK addition. Our results found that increased soil nutrients (PC1 scores obtained by Principal Component Analysis) with NPK addition directly led to a decline in species richness. Light limitation with increasing ANPP following NPK addition indirectly accelerated competitive exclusion and caused species loss. Increased ANPP was mainly dependent on a larger proportion of the grass Elymus.nutansin NPK-fertilized plots compared to control plots, suggesting the important role of the dominant species limiting light availability following NPK addition. However, our result does not support the litter hypothesis, possibly because the seasonal grazing behavior of the herbivore (i.e yak) mitigates negative effect of litter on species richness. Overall, these results indicate that belowground soil nutrient and aboveground light availability are consistently important for structuring species diversity, suggesting that the decline in species diversity with nutrient enrichment is caused by multiple ecological mechanisms simultaneously.
Atsttrin Regulates Osteoblastogenesis and Osteoclastogenesis through TNFR Pathway
Authors: Wei Jianlu , Liu Kaiwen , Liu Jinbo , Zhao Wei , Wang Zihao , Qiao Fei , Shi Jie , He Qiting , Meng Qunbo , Cheng Lei
Published: February 2023

Osteoporosis is a systemic metabolic bone disease. Osteoporosis is believed to be a systemic inflammatory condition in which inflammatory cytokines play an important role. Among these molecules, tumor necrosis factor-α (TNF-α) plays an important role in the initiation and development of osteoporosis. Atsttrin is an engineered protein derived from the growth factor, progranulin (PGRN). It’s well accepted Atsttrin inhibits TNF-α’s function by binding tumor necrosis factor-α receptors (TNFRs). The aim of this study was to investigate the role of Atsttrin in osteoporosis. Present study use cell TRAP staining to determine the role of Atsttrin in osteoclastogenesis. Alkaline phosphatase staining of cells was examined for ostoblastogenesis. Western blotting and ELISA assay were taken for the measurement of protein level and phorsphorylation. Real time PCR was used to test the transcriptional level expression. Gene silence method was taken for the pathway investigation. By applying these methods, we found Atsttrin inhibited TNF-α-induced osteoclastogenesis and inflammatory destruction. Further mechanism studies indicated Atsttrin inhibited TNF-α- induced osteoclastogenesis though TNFR1 signaling pathway. Moreover, Atsttrin rescued TNF-α-mediated inhibition of osteoblastogenesis via TNFR1 pathway. Importantly, present study found Atsttrin could not induce osteoblast differentiation, however, Atsttrin could significantly enhance osteoblastogenesis through TNFR2-Akt-Erk1/2 signaling.
Group VIII Transition Metal (Fe, Ru &Os) embedded Graphitic Carbon Nitride as an Acetone Sensor: A First Principle Investigation
Authors: Nihal Nihal , Sharma Rahul , Kaur Navjot , Sharma Mamta , Choudhary B. C. , Goswamy J. K.
Published: February 2023

Exposure to acetone, widely used volatile organic compound (VOC) in various industries: chemicals, pharmaceuticals, and teaching/research laboratories, causes throat, nose, and eye irritation. Further, it is an explosive and flammable VOC. Hence it becomes crucial to detect acetone efficiently. Graphitic carbon nitride (gCN) can be a promising material for sensing, provided its low adsorption and poor electrical conductivity are improved upon by adding some transition metal. In the present work, we have investigated the sensing behavior of pristine graphitic carbon nitride (gCN) and group VIII transition metal (Fe, Ru & Os) embedded gCN monolayer (Y/gCN) for acetone sensing using DFT calculations. Structural and electronic properties such as adsorption energy, band structure, and density of states (DOS) have been studied. The calculated adsorption energy of pristine gCN is -1.32 eV which improves to –10.52, -8.75, and − 7.23eV for Fe, Ru, and Os embedded gCN, respectively. Band structure also reflects that the addition of Fe, Ru, and Os in gCN results in the shrinking of band gap gCN after acetone adsorption. Further, after the adsorption of acetone, the DOS values also exhibit a drastic increase from a value of 13.48 eV− 1 for pristine gCN to 439,423 and 332 eV− 1 for Fe, Ru and Os embedded gCN. The charge transfer between acetone and substrate materials suggests improved sensing properties after group VIII-TM addition in pristine gCN. The I-V plot has been employed to investigate the change in the sensing response of gCN after adding Fe, Ru, and Os in it. The present study reveals that the sensing performance of the group VIII-TM (Fe, Ru & Os) embedded gCN is significantly enhanced with the best response for Fe/gCN compared to pristine gCN, and it can be a promising material for acetone sensing.
Clinical outcomes of teeth adjacent to the site of mandibulotomy or mandibulectomy in patients with head and neck cancer: results from a multidisciplinary mono-institutional head and neck tumor board
Authors: Castagnola Raffaella , Rupe Cosimo , Gioco Gioele , Almadori Giovanni , Galli Jacopo , Tagliaferri Luca , Cassano Alessandra , Gallenzi Patrizia , Lajolo Carlo
Published: February 2023

Introduction:The aim of this case series wasto evaluatethe necrosis of teeth adjacent to the site of mandibulotomy or mandibulectomy in a cohort of patients suffering from head and neck cancers.Methods:Fourteen patients who underwent segmental mandibulectomy or paramedian mandibulotomy for oral, oropharynx or major salivary gland cancer and a total of 23 teeth were included in this case series. Twelve patients underwent adjuvant head and neck radiotherapy. Cold sensitivity pulp testing and/or electric pulp testing were performed on teeth at the margin of mandibulectomy and on teeth adjacent to mandibulotomy after surgery. A “positive” response was considered the healthy state, and “negative” was considered the diseased state of the tooth.Results:The 10 patients who underwent mandibulotomy had 12 teeth with a negative response. The 4 patients treated by mandibulectomy had two positive and three negative responses to cold and electric pulp tests. Fifteen out of 23 teeth (65.2%) showed a negative response to sensitivity testing.Conclusions:Tooth necrosis seems to be a common event after mandibulectomy and mandibulotomy.Clinical Relevance:To avoid post-surgery complications, performing root canal therapy before surgery on the teeth adjacent to the surgical site could be an appropriate strategy.
Silver nitrate (AgNO3) and Pyrazinamide (PZA) as ethylene inhibitors ameliorate in vitro salt tolerance of tomato (Lycopersicon esculentum L) plant.
Authors: Zarei Somayeh , Ehsanpour Ali Akbar
Published: February 2023

The purpose of this research was to find out how in vitro culture of tomato explants respond to salt stress by silver nitrate (AgNO3) and pyrazinamide (PZA) as ethylene inhibitors. Tomato seedlings were grown on MS medium containing NaCl (0, 100, 150 mM) and supplemented with AgNO3 (0, 2, 4, mg. L-1) and pyrazinamide (PZA) (0, 2, 4,mg. L-1) to study growth parameters and antioxidant enzymes responses. Salt-stressed plants showed limited growth and a significant decrease in fresh and dry weight. Salinity accelerated oxidative damage by increasing hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in tomato leaves. In the present of AgNO3 and PZA, in vitro grown tomato plants increased fresh and dry weight total chlorophyll, carotenoid in particular at 4 mg. L-1 AgNO3 and 4 mg. L-1 PZA. Moreover, silver nitrate and PZA reduced H2O2 and MDA contents and oxidative damage by enhancing antioxidant enzyme activity, including catalase, superoxide dismutase, and ascorbate peroxidase under salt stress. According to our findings, AgNO3 and PZA improved in vitro salinity tolerance of tomato plant by interfering ethylene action or ethylene generation and increasing biochemical responses.
Stochastic-based vulnerability curves for the out-of-plane seismic safety assessment of URM walls
Authors: Bernardo Vasco , Costa Alfredo Campos , Lourenço Paulo B.
Published: February 2023

Earthquakes are a major cause of damage and human losses to the built environment, including cultural heritages, monumental buildings and historical centers. In the last decades the seismic performance of buildings has received special attention due to the interest in the built heritage conservation and protection of human life, particularly with respect to masonry structures which have shown evidence of poor behavior once subjected to seismic loads. The present work contributes to the seismic safety assessment of the out-of-plane behavior of unreinforced masonry walls through a displacement-based approach, providing the capacity for different out-of-plane geometric indexes and its seismic response in different earthquake-prone regions. The analyses are conducted using a seismic probabilistic framework, considering the most common out-of-plane mechanisms, different material properties, various slenderness ratios, and a wide range of seismicity levels to cover the seismic hazard in Europe. The results presented can be useful for seismic safety assessment and to incorporate vulnerability models for seismic risk analysis.
KK-LC-1, a biomarker for prognosis of immunotherapy for primary liver cancer
Authors: Zhu Sihui , Jin Yuncheng , Zhou Mingzhen , Li Lin , Song Xueru , Su Xinyu , Liu Baorui , Shen Jie
Published: February 2023

Purpose
There is mounting evidence that patients with liver cancer can benefit from Immune checkpoint inhibitors. However, due to the high cost and low efficacy, we aimed to explore new biomarkers for predicting the efficacy of immunotherapy.
Methods
Specimens and medical records of liver cancer patients treated at Drum Tower Hospital of Nanjing University were collected, and the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in tissues as well as the corresponding antibodies in serum were examined to find biomarkers related to the prognosis of immunotherapy and to explore its mechanism in the development of liver cancer.
Results
KK-LC-1 expression was found to be 34.4% in histopathological specimens from 131 patients and was significantly correlated with Foxp3 expression (P = 0.0356). The expression of Foxp3 in the tissues of 24 patients who received immunotherapy was significantly correlated with overall survival (OS) (P = 0.0247), and there was also a tendency for prolonged OS in patients with high expression of KK-LC-1. In addition, the expression of KK-LC-1 antibody in the serum of patients who received immunotherapy with a first efficacy evaluation of stable disease (SD) was significantly higher than those with PR (P = 0.0413).
Conclusions
Expression of KK-LC-1 in both tissues and serum has been shown to correlate with the prognosis of patients treated with immunotherapy, and KK-LC-1 is a potential therapeutic target for oncological immunotherapy.
Comprehensive Analysis of KNSTRN Immunoassays and KNSTRN-related ceRNA Network in Hepatocellular Carcinoma
Authors: Jin Liang , Zhang Xiaojing , Fan Ming , Li Weimin , Lai Quanyou , Peng Wei , Zhang Xuan
Published: February 2023

Background: The role of Kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) in Hepatocellular Carcinoma (HCC) remains not fully determined.
Methods: Based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, we first investigated the potential oncogenic functions of KNSTRN Using R and various computational tools in HCC.
Results: Detailed results revealed that elevated expression of KNSTRN was considerably associated with bad overall survival (HR=1.48, 95%CI 1.05-2.09, P= 0.027) and progress free interval (HR=1.41, 95%CI 1.05-1.89, P= 0.021) in HCC. GO/KEGG functional enrichment analysis showed that KNSTRN is closely related to chromosome segregation, spindle, ATPase activity, tubulin binding, and cell cycle signaling pathway. TIMER databases analysis showed the correlationsbetween KNSTRN expression and tumor-infiltrating immune cells, biomarkers of immune cells and immune checkpoint expression. Moreover, KNSTRN level was significantly positively associated with immunosuppressive cell in tumor microenvironment (TME), including regulatory T cells (Tregs), myeloid derived suppressor cells (MDSCs), and cancer-associated fibrocytes (CAFs). Finally, the two possible ceRNA networks in LIHC were constructed by correlation analysis, and all these ceRNA networks contained KNSTRN.
Conclusion: KNSTRN can be used as a novel biomarker for the diagnosis and prognosis of HCC, and is related to tumor immune infiltration and ceRNA network.
Bufotalin-loaded biomimetic prussian blue nanoparticles for colorectal cancer chemo-photothermal therapy via induce ferroptosis
Authors: Wu Yi , Tian Jiahui , Luo Mengjie , Wu Zhengchun , Cao Ruiyun , Fu Chunyan , Yang Jialu , Peng Qian , Liu Rushi , Liu Bin
Published: February 2023

Background: As a ferroptosis-inducing platform, based on its release of iron and ferrous ions to induce production of reactive oxygen species (ROS), it has attracted extensive attention in cancer treatment. Since iron-based nanomaterials such as prussian blue (PB), can only produce limited ROS. Bufotalin (CS-5), a promising ferroptosis inducer, was introduced to improve the efficiency of ferroptosis. However, the clinical application of CS-5 was limited by cardiotoxicity and high renal clearance rate. Therefore, we constructed a biomimetic nanosystem (PB@CS-5@M) with satisfactory tumor enrichment ability and long blood circulation time for the treatment of colorectal cancer induced by ferroptosis.
Results: In this work, the PB@CS-5@M has efficient loading of CS-5, which significantly reduces the cardiotoxicity of CS-5. After photothermal therapy, the high temperature caused by laser stimulation triggers the release of CS-5, iron and ferrous ions to kill colorectal cancer cells. Furthermore, the ability of CS-5 to significantly down-regulate the expression of GPX4 and HIF-1a, induce ROS production and damage mitochondria to induce ferroptosis in colorectal cancer was amplified. In addition, the down-regulation of HSP70 expression under laser stimulation effectively improved the chemosensitivity of HCT116 cells to CS-5.
Conclusions: The chemotherapeutic effect of CS-5 combined with the photothermal effect of PB can effectively treat colon cancer by inducing ferroptosis.
Paradoxical behaviour of rainfall and temperature over ecologically sensitive areas along the Western Ghats
Authors: Mann Rohit , Saini Deepak , Sharma Swati , Dhorde Amit , Gupta Anju
Published: February 2023

Initial reports signify some specific isolated locations in different latitudes, revealing a paradoxical increase in both heavy and very heavy rainfall events and also an increment in total, i.e., in both rainfall and temperature, over ecologically sensitive areas along the Western Ghats (WG). This paper presents a coherent study of the full-scale of daily rainfall and temperature over 27 well-spaced stations in the study area to determine its extent and investigate whether or not this contradictory behaviour is real. Also, an attempt has been made to assess the differential behaviour of rainfall, temperature, and heavy rainfall events in association with land use and land cover change (LULC). The analysis revealed that rainfall and temperature over the study area are increasing, whereas heavy rainfall events have increased during 1981–2020 with strong peaks after 2000 around 18o-19oN (Mumbai metropolitan region), 14o-16oN (mining and quarrying regions in Goa), and 9o-12oN (a narrow strip of land spanning across the coastal towns of Karnataka and Kerala) latitudes. The majority of the rainfall excess years coincided with El-Nino years, indicating that El-Nino does not affect rainfall negatively. However, rainfall over the WG is influenced by local relief and cascading topography. The spatial pattern of average annual rainfall shows a decreasing trend from south to north because the elevation and span of rainfall occurrence are higher in the southern part of WG. The findings of the current research will help in building a strategy to address trends and patterns of climatic variables in association with LULC.
Production and quality evaluation of corn crackers fortified with freeze dried of banana peel and pulp
Authors: Mahmoud Khaled , Shedeed Naglaa , Hussein Ahmed
Published: February 2023

Crackers made from corn flour fortified with FDB-peel or FDB-pulp or FDB-peel and FDB-pulp. Results showed the moisture and total carbohydrate, were highest in FDB-Pulp while the FDB-Peel presented the highest ash, protein and dietary fiber. Higher content vitamin C in FDB-peel which is rich in potassium, phosphorus and calcium. Ferulic acid and Sinapic dominated phenolic profile of the FDB pulp and peel. Crackers sample (F5) showed a significant increase in dietary fiber and low calories. The sensory evaluation of (F3) had high score of overall acceptability; while (F2) got the lowest score on color and appearance. Present of Choline and vitamin C were increased as a result of adding the FDB peel and pulp powder to crackers. The total phenolic and antioxidants were increased with addition of FDB peel and pulp powder in crackers sample. The control samples were the most clearly oxidized, which was evidenced by the lowest IP values obtained. The lipid IP values of (F2) samples were found to be significantly higher. The peroxide and acid value in crackers samples were low compere with control. The FDB-pulp and FDB-peel products contain great deal of nutritional properties, and hence have potential utility for use as functional ingredient in food product development.
“No matter what, we just work with the trauma…”: Mental Health Therapists’ Care of Diverse Sexual and Gender Identity Citizens in Cambodia
Authors: Bertram Julie E. , Kryah Rachel , Vandermause Roxanne , Ean Nil , Paul Robert , Carrico Adam , Sophal Chhit , Bruce Steven , Gregory Kelly , Stein Ellen , Mannarino Julie
Published: February 2023

The convergence of trauma symptomatology, mental health symptoms, family and social difficulties, and intersectionality of diverse sexual and gender minority (SGM) individual issues is complex, multi-faceted, and challenging for the individuals in Cambodia who suffer them and for the therapists in Cambodia who meet individuals in treatment. We documented and analyzed the perspectives of mental health therapists in the context of a randomized control trial (RCT) intervention within the Mekong Project in Cambodia. The research questions explored perceptions of therapists’ care of mental health clients, therapist well-being, and experiences of navigating within a research environment in which SGM citizens with mental health concerns receive treatment. The larger study enrolled 150 Cambodian adults, among which 69 identified as SGM. Three key patterns emerged across our interpretations. Clients seek help when symptoms
interfere with daily life, therapists care for clients and themselves, and integrated research and practice is integral yet sometimes paradoxical. Therapists did not identify differences in terms of how they work with SGM clients compared with non-SGM clients. Future studies are warranted to examine a reciprocal academic-research partnership in which we examine therapists’ work alongside rural community members, evaluate the process of embedding and fortifying peer supports within educational systems, and study the wisdom of traditional and Buddhist healers to address the discrimination and violence that citizens who identify as SGM disproportionately suffer. National Library of Medicine (U.S.). (2020). Trauma Informed Treatment Algorithms for Novel Outcomes (TITAN). Identifier NCT04304378.
Voice reacquisition after total laryngectomy via tracheoesophageal speech in patients with head and neck cancer: A qualitative study
Authors: Iwai Miyoko , Ando Shoko , Sato Kazuki
Published: February 2023

Purpose: Speech rehabilitation contributes to improved quality of life for patients who have undergone laryngectomy for head and neck cancer. Tracheoesophageal speech (TES) provides better speech quality when rehabilitation is initiated early. However, patients must work on rebuilding their self-identity and develop the habit of cleaning and replacing their voice prostheses regularly. We aimed to attain a deeper theoretical understanding of the process involved in the transition from selection to adaptation to TES in patients with head and neck cancer.
Methods: Using grounded theory methodology, we interviewed 13 TES speakers (3 women) across peer support groups in Japan who had undergone laryngectomy for head and neck cancer. Semi-structured interviews were used to investigate what TES speakers thought of their voices, their preferred means of alternative communication, and how they have adapted.
Results: Participants emphasized the importance of communicating with their own voices, the adaptation process for which was influenced by anxiety related to losing one’s natural voice, confronting the reality of living without a voice, and coping with one’s new voice. Through this process, participants eventually learned to recognize the changed voice as one's own. However, despite voice restoration through TES, feelings of hopelessness persisted for many patients.
Conclusion: The value assigned “communicating with one’s own voice” is integral to the adaptation process for patients with head and neck cancer who undergo laryngectomies and use TES. However, some aspects of TES can easily lead to feelings of hopelessness, suggesting the importance of enhancing multifaceted support for speech rehabilitation.
An Intelligent and Hybrid PDOA+MO based MPPT Controlling Mechanism for Grid-PV Systems
Authors: Marlin S , Jebaseelan Sundarsingh
Published: February 2023

Due to its effectiveness and affordability, solar Photovoltaic (PV) systems are now being employed more and more in many application systems. The biggest challenge is still getting the most energy out from PV panels in a variety of climatic situations. In order to achieve the maximum energy production, several optimization-based MPPT controlling techniques have been developed in traditional works. However, it has significant issues with low convergence, computational complexity, a long time needed to find the best solution, and inefficiency. As a result, the goal of this research is to implement a novel and hybrid optimization technique, named as, Prairie Dog Optimization Algorithm (PDOA) + Mongoose Optimization (MO) for extracting the highest possible energy from PV panels. The original contribution of this work is to incorporate the functions of two different and recently developed optimization techniques for MPPT controlling. For this purpose, the PDOA and MO algorithms are taken into account, and the hybridized PDOA+MO provides the benefits of fast convergence, increased tracking efficiency, and reduced tracking time. The high gain Luo DC-DC converter is also used to increase PV's output power and voltage while minimising switching and conduction losses. Consequently, the voltage source inverter is used to suppress the level of harmonics for providing the quality improved AC output to the grid system. The suggested PDOA+MO algorithm's effectiveness and power tracking performance are validated through a thorough simulation analysis using a variety of parameters.
Llamas use social information from conspecifics and humans to solve a spatial detour task
Authors: Pahl Annkatrin , von Borstel Uta König , Brucks Désirée
Published: February 2023

Learning by observing others (i.e. social learning) is an important mechanism to reduce the costs of individual learning. Social learning can occur between conspecifics but also heterospecifics. Domestication processes might have changed the animals’ sensitivity to human social cues and recent research indicates that domesticated species are particularly good in learning socially from humans. Llamas (Lama glama) are an interesting model species for that purpose. Llamas were bred as pack animals, which requires close contact and cooperative behaviour towards humans. We investigated whether llamas learn socially from trained conspecifics and humans in a spatial detour task. Subjects were required to detour metal hurdles arranged in a V-shape to reach a food reward. Llamas were more successful in solving the task after both a human and a conspecific demonstrated the task compared to a control condition with no demonstrator. Individual differences in behaviour (i.e. food motivation and distraction) further affected the success rate. Animals did not necessarily use the same route as the demonstrators. This indicates that they did not copy the behaviour of the demonstrator but rather adopted the general detour behaviour. These results support the hypothesis that domestication affected the sensitivity to human social cues but also highlights the need to expand the range of domesticated species that are tested in this kind of paradigms.
Mental stress detection using multimodal characterization of PPG signal for personal healthcare applications
Authors: Paul Avishek , Chakraborty Abhishek , Sadhukhan Deboleena , Pal Saurabh , Mitra Madhuchhanda
Published: February 2023

With growing complexities in our society, mental stress has become inevitable in every human life. Long-term mental stress condition could instigate several chronic diseases and thus require its early evaluation. Existing mental stress estimation techniques mostly uses complicated, multi-channel and expert dependent electroencephalogram (EEG) based approaches. Moreover, the respiratory signal presents promising stress-related information, but its acquisition is also complicated and needs multimodal assistance. Hence, in this research a unique approach based on multimodal characterization of the easy-to-acquire Photoplethysmogram (PPG) signal is proposed to assess the stressed condition. Exclusively, the developed algorithm not only uses a primary PPG feature, but also derives the respiratory rate from the same PPG signal via simplified methodologies. The technique is evaluated on the PPG recordings collected from the publicly available DEAP dataset. Efficiency of these easy-to-compute features is then assessed via a simple threshold-based classification technique to categorize the stressed and the relaxed conditions with an average accuracy of 98.43%. Compared to the existing methods, the proposed algorithm not only shows improved performance but the associated simple methodology with minimum acquisition load also justifies its applicability in real-time standalone, personal healthcare applications.
Molecular structures, chemical descriptors and pancreatic lipase (1LPB) inhibition by natural products: A DFT investigation and molecular docking prediction
Authors: Allal Hamza , Nemdili Hacene , Zerizer Mohamed Amine , Zouchoune Bachir
Published: February 2023

Density functional theory (DFT) calculations and molecular docking have been carried out on natural products containing eugenol, ginger, ascorbic acid, oleurpoein, piperine, hesperidin, quercetin, luteonil and curcumin in order to predict their biological activities and to analyse their pancreatic lipase inhibition. The biological activity predictions are based on the global and local chemical descriptors, namely, HOMO-LUMO gaps, chemical hardness, chemical potential, electrophilicity, dipole moment and Fukui functions. Our findings show that the studied compounds can be divided into two groups based on the chemical descriptors, one composed of those of low chemical descriptors, namely, eugenol, ginger, ascorbic acid and oleuropein and the second corresponds composed of piperine, hesperidin, quercetin, luteonil and curcumin in agreement with large HOMO-LUMO gaps and low electrophilicity for the former and conversely for the latter suggesting numerous and interesting biological activities. The frontier orbitals offer a deeper insight concerning the electron-donor and electron-acceptor capabilities, whereas, the local descriptors resulting from Fukui functions put emphasis on the active sites of different candidate ligands. The molecular docking was performed in order to compare and identify the inhibition activity of the natural candidate ligands against pancreatic lipase which were compared to that of synthesized ones. The molecular docking results revealed that the Luteonil compound has the best binding affinity of -8.56 kcal/mol due to their unique molecular structure and the position of -OH aromatic substituents.
An effective ER stress-related gene signature predicts overall survival and associates with tumor immunity of patients with endometrial cancer
Authors: Zhang Tangansu , Zhang Qian , Zhang Jun , Zhao Rong , Wei Sitian , Shi Rui , Liu Shuangge , Zhang Qi , Wang Hongbo
Published: February 2023

Background: Endometrial cancer (EC) is one of the worldwide gynecological malignancies with a very high incidence. Endoplasmic reticulum (ER) stress is a disturbance of cellular homeostasis that promotes cancer progression. In general， ER stress plays a critical role in tumor cell activities in various cancers. However, the mechanisms of ER stress on the progression of EC have not been fully elucidated.
Method: The ER Stress-related genes were obtained from GeneCards and GSEA, and both the RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The risk signature was constructed based on 4 prognosis-related genes with the Cox regression and the least absolute shrinkage and selection operator (LASSO) analyses. According to common method, the EC patients were randomly classified into the training and testing groups, and also categorized into a high-risk or a low-risk group based on the predetermined risk score. In addition, the factors such as functional enrichment, immune infiltration, and potential chemotherapies, were also analyzed.
Result: An ER Stress-related risk signature consisting of four genes (TRIB3, CREB3L3, XBP1, and PPP1R15A) was identified to predict the prognosis of EC patients. Based on the signature, all patients were classified into the high-risk and low-risk groups, respectively. Patients in the low-risk group demonstrate better prognoses than those in the high-risk group. A nomograph combined risk scores and clinical characteristics were employed to offer the survival of EC patients. As shown, the signature was closely related to the immune microenvironment corresponding to both the cell and pathway infiltration. In addition, several typical immune checkpoints including CTLA4 and CD28, already expressed a higher level in the low-risk group. Patients from both the high-risk and the low-risk responded differently to various chemotherapies.
Conclusion: In this paper, we established an effective ER Stress-related signature that could be utilized to prominently predict the overall prognosis of EC patients, as well as the association with immune infiltration and chemotherapy efficacy.
Diameter Growth of Eucalyptus Trees in Agroforestry Systems and Its Relation to Air Temperature and Precipitation
Authors: Flumignan Danilton Luiz , Silva Staël Caroline Rego Ribeiro da , Salton Júlio Cesar , Comunello Éder
Published: February 2023

In agroforestry systems, such as Integrated Crop-Livestock-Forest (iCLF), the agricultural, livestock and arboreal components are explored in the same field in rotation, succession or intercropping. Our objective was to investigate if the diameter growth of eucalyptus in agroforestry systems differs from those cultivated as a planted forest, as well as to assess whether there is a difference in its growth in face of the air temperature and precipitation. The study was held at Ponta Porã, Brazil, a region of humid subtropical climate with hot summers and soil classified as Oxisol, fertile, deep and clayey. Dendrometer bands measured the diameter growth of eucalyptus (Eucalyptus urograndis) cultivated as a forest and in iCLF, with eucalyptus rows distance of 12.5x12.5 m, 12.5 m one side x 25 m another side and 25x25 m. The study took place from four years and nine months after transplanting till six years and seven months (22 months). On iCLF, the inter-row was explored with grain crops (soybean or corn) and pasture. Climate data of air temperature and precipitation were used to investigate their influence or not on diameter growth. Eucalyptus diameter growth is higher when cultivated in agroforestry systems and this growth is as higher as larger is the distance between eucalyptus rows. Precipitation proved to strongly and positively influence the diameter growth, especially when cultivated in agroforestry systems. On the other hand, under the conditions of this study, air temperature showed little or no influence over the eucalyptus diameter growth.