Polymerase chain reaction (PCR) technique is one of the molecular methods in amplifying DNA for the detection of malaria. However, the limitations of PCR especially when used for routine clinical practice can hamper its sensitivity and specificity. With that, this study focuses on designing a microfluidic device that will mimic the function of a conventional genus-specific PCR based on 18S rRNA gene to detect malaria parasites (Plasmodium falciparum) at low grade parasitemia. The design was drawn and simulated using ANSYS 14.5 Computational Fluid Dynamics (CFD). The simulation shows that adding loops to the design increases its relative deviation but to a minimal extent as compared to having only a straight path design, which indicates that looping is acceptable in designing a microfluidic device to minimize chip length. Also, increasing the cross-sectional area of the fluid path decreases the efficiency of the design, thus, the design with a relatively smaller cross-sectional area is favored. And lastly, among the three materials utilized, the chip made of polypropylene is the most efficient with a relative deviation of 0.94 as compared to polycarbonate and polydimethylsiloxane which have relative deviations of 2.78 and 1.92, respectively.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

Recently, Gohar et al. introduced a novel, local, and well-behaved fractional calculus. It possesses all the classical properties, and Its locality imposes simplicity and accuracy in modeling fractional order systems. In this article, we further develop the definitions and extend the classical properties of Gohar fractional calculus to address some of the open problems in Calculus. The fractional Gronwall's integral inequality, Taylor power series expansion, and Laplace transform are defined and applied to overcome some of the limitations in the classical integer-order calculus. The fractional Laplace transform is applied to solve Bernoulli-type logistic and Bertalanffy nonlinear fractional differential equations, and the criteria under which it can be applied to solve linear differential equations are investigated.

The production of biodiesel through transesterification routes generates large amounts of glycerol, approximately 10 m3 for every 90 m3 of the biodiesel produced. Taking into account this scenario, the valorization of glycerol using chemical routes that could be operated in biodiesel industry constitutes a promising approach to achieve added-value products. An interesting option is the production of ethers, which can be used as fuel additives in diesel engines to improve the combustion efficiency, reducing soot emission and increasing cetane index. In this study, a purification route was applied to crude glycerol and its valorization by etherification was evaluated. The glycerol contents of purified samples were above 98% wt. The purified and commercial glycerol was used to obtain ethers. Etherification reactions were carried out with different alcohols (ethanol, isopropanol and 3-methyl-1-butanol) into a batch reactor, using small amount of Amberlyst 15 as a catalyst, at autogenous pressure and solvent-free conditions. The glycerol conversion, selectivity and yield to ethers were evaluated. A glycerol conversion of 97% wt. with selectivity of 80% to monoether was obtained when using ethanol. For isopropanol, the glycerol conversion was up to 95% (76% of monoether and 22% of diether). However, the selectivity to ethers for 3-methyl-1-butanol was negligible (<3% wt.). A process simulation for purification and etherification steps integrated with a biodiesel production was assessed in terms of productivity and energy consumption, considering different scenarios of glycerol/alcohol molar ratios.

The increasing detection of infections of Trypanosoma cruzi, the etiological agent of Chagas disease, in non-endemic regions beyond Latin America has risen to be a major public health issue. With an impact in the millions of people, current treatments rely on antiquated drugs that produce severe side effects and are considered nearly ineffective for the chronic phase. The minimal progress in the development of new drugs highlights the need for advances in basic research on crucial biochemical pathways in T. cruzi to identify new targets. Here, we report on the T. cruzi presenilin-like transmembrane aspartyl enzyme, a protease of the aspartic class in a unique phylogenetic subgroup with T. vivax separate from protozoans. Computational analyses suggests it contains 9 transmembrane domains and an active site with the characteristic PALP motif of the A22 family. Multiple linear B-cell epitopes were identified by SPOT synthesis analysis with Chagasic patient sera. Two were chosen to generate rabbit antisera, whose signal was primarily localized to the flagellar pocket, intracellular vesicles and endoplasmic reticulum in parasites by whole cell immunofluorescence. The results suggest that the parasitic presenilin-like enzyme could have a role in the secretory pathway and serve as a biomarker for infections.

Data on the KIT mutation rate in skin melanoma in the central European region is missing. Accordingly, in a cohort of 79 double wild type (BRAF/NRAS) skin melanoma KIT mutation was assessed by Sanger sequencing of exons 9,11,13,17 and 18. In this skin melanoma cohort KIT mutation frequency was found to be 34/79 (43%) with a significantly higher rate in acrolentiginous melanoma (ALM) as compared to UV-induced common variants (20/34, 58.8% versus 14/45, 31.1%, p=0.014). Exon 11 was the most frequent mutation site (44.7%) followed by exon 9 (21.1%) equally characterizing UV-induced common histotypes and ALM tumors. KIT mutation hotspots were identified in exon 9 (c491/492), in exon 11 (c559,c572, c570), in exon 13 (c642), in exon 17 (c822) and in exon 18 (c853). The relatively high KIT mutation rate in skin melanoma in this central-European cohort justifies regular testing of this molecular target.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients. The R/R ratio, assessed as a combination of the paraoxonase 1 (PON1) gene, PON1 enzymatic activity, and early life time trauma (ELT), predicted the high-density lipoprotein cholesterol – paraoxonase 1 complex (HDL-PON1), reactive oxygen and nitrogen species (RONS), nitro-oxidative stress toxicity (NOSTOX), staging (number of depression and hypomanic episodes and suicidal attempts), and phenome (the Hamilton Depression and Anxiety scores and the Clinical Global Impression; current suicidal ideation; quality of life and disability measurements) scores. Partial Least Squares pathway analysis showed that 44.2% of the variance in the phenome was explained by ELT, RONS/NOSTOX, and staging scores. Cluster analysis conducted on all those feature sets discovered two distinct patient clusters, namely 69.5% of the patients were allocated to a class with high R/R, RONS/NOSTOX, staging, and phenome scores, and 30.5% to a class with increased staging and phenome scores. This classification cut across the bipolar (BP1/BP2) and major depression disorder classification and was more distinctive than the latter classifications. We constructed a nomothetic network model which reunited all features of mood disorders into a mechanistically transdiagnostic model.

As a consequence of intense industrialization in the last few decades, the amount of agro-industrial wastes has increasing, where new forms of valorization are crucial. In this work, 5 residual biomasses from Maranhão (Brazil) were investigted as supports for immobilization of lipase from Thermomyces lanuginosus (TLL). The new biocatalysts BM-TLL (babaçu mesocarp) and RH-TLL (rice husk) showed immobilization efficiencies >98% and hydrolytic activities of 5,331 U.g-1 and 4.608 U. g-1 respectively against 142 U. g-1 by Lipozyme® TL IM. High esterification activities were also found, with 141.4 U.g-1 and 396.4 U.g-1 from BM-TLL and RH-TLL against 113.5 U.g-1 by TL IM. Results of porosimetry, SEM and BET demonstrated BM and RH supports are mesoporous materials with large hydrophobic area, allowing a mixture of hydrophobic adsorption and confinement, resulting in hyperactivation of TLL. These biocatalysts were applied in the production of hexyl laurate, where RH-TLL was able to generate 94% conversion in 4 h. Desorption with Triton X-100 and NaCl confirmed that new biocatalysts were more efficient with 5 times less protein than commercial TL IM. All results demonstrated that residual biomass was able to produce robust and stable biocatalysts containing immobilized TLL with better results than commercial preparations.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

The electronic transport stability in nanodevices composed by metal/trans-polyacetylene /metal with different long length has contributed greatly for performance, homogeneity, stability, organization of the chains, reproducibility and higher conductivity. In this paper, we present an analytical study of the electronic transport characteristics from dimerized trans-polyacetylene (trans-PA) molecules containing an odd-even number of sites coupled to metal leads (left and right) in T-shaped geometry using the extended Su-Schrieffer-Heeger (SSH) model based on tight-binding Hamiltonian with the Non-Equilibrium Green´s Function (NEGF) via Heisenberg´s equation of motion and the Keldysh´s formalism. Due to the complexity of the T-shaped odd-even chain, our proposal was to test the effects on the finite-length network for three, four, five sites and furthermore foresee for 17-sites. We show how to tune dimerization strength () coupling to the parameters and T-shaped geometry of the device to which it affects the overlap integral localized at the three endpoints of the T-shaped system, making both the odd and even chains to undergo a metal-insulator transition in their electronic behavior. The results reached through control parity of the chain plane of the parameters governing () the electronic and experimental tunneling allow a better understanding of the subject.

This note applies the Logistic model approximation to determine the suitable start and end dates for the observed epidemic curves in the total number of cases for different countries. The Logistic model is presented and explicit relations for the beginning and end dates are obtained together with the total epidemic duration. Using data from Brazil, Germany, Italy, and South Korea, the extreme dates are calculated. Since the epidemic onset time is found, a fair comparison of the epidemic curve for these countries is obtained. The result does not depend on the poor statistics available in the early phase of the epidemic when the initial number of infectives is unknown. In fact, the total duration depends only on the characteristic time parameter of the LM model.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

This work presents significant results obtained by the application of global optimization techniques to the design of finite, normal form games with mixed strategies. To that end, the Fuzzy ASA global optimization method is applied to several design examples of strategic games, demonstrating its effectiveness in obtaining payoff functions whose corresponding games present a previously established Nash equilibrium. In other words, the game designer becomes able to choose a convenient Nash equilibrium for a generic finite state strategic game and the proposed method computes payoff functions that will realize the desired equilibrium, making it possible for the players to reach the favorable conditions represented by the chosen equilibrium. Considering that game theory is a very significant approach for modeling interactions between competing agents, and Nash equilibrium represents a powerful solution concept, portraying situations in which joint strategies are optimal in the sense that players cannot benefit from individually modifying their current strategies provided that other players do not change their strategies as well, it is natural to infer that the proposed method may be very useful for strategists in general. In summary, it is a genuine instance of artificial inference of payoff functions after a process of global machine learning, applied to their numerical components.

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

The topical therapy with rifampicin (RF)-based formulations is beneficial to treat infections and to healing the wounds. Despite recent research highlighting the antibiotic's significant an-ti-inflammatory properties, limited topical wound healing products are currently available. Present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contributes to the healing process of a wound. The methods used were at first the synthesis of the copolymer of al-ginate and pNVCL via grafting from technique and radical polymerization followed by wa-ter-in-oil-in water (W/O/W) emulsification by using as oil phase PLGA dissolved in dichloromethane (DCM). The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192 µg/mL for the nanoparticle, 208 µg/mL for pure rifampicin, and 718 µg/mL for the rifampicin-loaded nanopar-ticles. Considering the double role Rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used more with the wound irrigation post-surgery to avoid infections and to contribute to the healing.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

Castor oil may be differentiated from other non-edible vegetable oils because of its main composition of hydroxylated fatty acids. Ricinoleic acid comprises 80–90% wt. of fatty acids in castor oil (Ricinus communis). In this study, the thermo-oxidative stability and tribological behavior of bio-based lubricant samples synthesized from castor oil using isoamyl alcohol were evaluated. Initially, the compositional and physicochemical properties of the obtained samples were assessed using 1H NMR, FTIR, and ASTM methods. Oxidative stability of the samples was evaluated using Rancimat method at 110 °C under air flow. The final biolubricant sample (BL2), obtained after esterification, epoxidation, and oxirane rings opening reactions, presented an oxidation stability time (OST) of 14.3 h. The thermal stability was also evaluated by thermogravimetry (TG) from the mass variations under inert and oxidative atmosphere. BL2 showed higher thermal stability compared to the other samples, demonstrating higher decomposition temperatures in both inert (339.04 °C) and oxidative (338.47 °C) atmospheres, for a mass loss of 50%. The tribological properties of the samples were evaluated using a four-ball tribometer configuration. The BL1 and BL2 samples exhibited lower friction coefficients than the mineral oil sample (MOS) by 21.5% and 43.1%, respectively. Regarding wear, the observed wear scar diameter (WSD) was also lower in BL1 and BL2 compared to MOS by 5.2% and 40.4%, respectively. The results of the tribological evaluation suggest that both samples obtained in this study have promising potential for applications in lubricating machines and mechanical systems.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

Soccer is the leading cause of all sports-related ocular injuries in Europe and Israel and leads to blindness at a disproportionately high rate, especially among children (Thompson et al., 2019). With soccer being the most popular sport in the world, it is surprising the only solution to ocular injuries are sports glasses which can cause direct damage to the eye and impair peripheral vision by 15%, calling for an alternative (Smith & Jones, 2020). This work, based on an imported facial model, focuses on both the qualitative and quantitative aspects of building a personalized, low-cost (through optimizing material needed), superior apparatus to conventional sports glasses. The quantitative side examines a modified and model-validated (through a SRS of thirty unique extrapolated points) multivariate linear regression equation, based on horizontal and vertical rotation angles (n=60) trained with residual and computer simulation data, that can accurately extrapolate and quantify ocular impact from all horizontal and vertical rotation angles and a modified Hertzian Contact Stress Equation to determine the thickness of the apparatus using the elasticity modulus, impact force, and geometrical facial and soccer-ball features. The qualitative side examines where firstly, ocular impact is most prevalent, and secondly, where most impact is seen from rotating the ball horizontally and vertically through analysis of Pearson’s Correlation Coefficient at the supraorbital, medial canthus, infraorbital, and lateral canthus regions from both regression equations as well as a cost-benefit analysis for comparison with conventional sports glasses. The findings discovered in this work lay the groundwork for future research to build a customized low-cost ocular injury prevention device which can simultaneously ensure complete ocular safety while enhancing athletic performance for over 250,000,000 players (Johnson & Garcia, 2022).

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

The growing concerns about floods have highlighted the need for accurate and detailed precipitation data as extreme precipitation occurrences can lead to catastrophic floods, resulting in significant economic losses and casualties. Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement (GPM-IMERG) is a commonly used high-resolution gridded precipitation dataset and is recognized as trustworthy alternative sources of precipitation data. The aim of this study is to comprehensively evaluate the performance of GPM IMERG Early (IMERG-E), Late (IMERG-L), and Run Final (IMERG-F) in precipitation estimation and their capability in detecting extreme rainfall indices over southwestern Iran during 2001-2020. The Asfezari gridded precipitation data which are developed using a dense of ground-based observation were utilized as the reference dataset. The findings indicate that the IMERG-F performs reasonably well in capturing many extreme precipitation events (defined by various indices). All the three products showed a better performance in capturing fixed and non-threshold precipitation indices across the study region. The findings also revealed that both IMERG-E and IMERG-L have problems in rainfall estimation over elevated areas showing values of overestimations. Examining the effect of land cover type on the accuracy of the precipitation products suggest that both IMERG-E and IMERG-L show large and highly unrealistic overestimations over inland water bodies and permanent wetlands. The results of the current study highlight the potential of IMERG-F as a valuable source of data for precipitation monitoring in the region.

This article aims to analyze the relationship between non-obstructive coronary artery disease (NOCAD) and atrial fibrillation (AF), exploring the underlying pathophysiological mechanisms and implications for clinical management. NOCAD and AF are prevalent cardiovascular conditions that often coexist, yet their interrelation is not well understood. NOCAD, characterized by the presence of atherosclerotic plaques without significant luminal stenosis, can lead to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. Atrial fibrillation, on the other hand, is the most common sustained cardiac arrhythmia, associated with an increased risk of stroke and heart failure, which may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Therefore, NOCAD and AF seems to be a complex Interplay with one begets another.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

In a continuation and extension of an earlier publication, the calculation of the refractivity and polarizability of organic molecules at standard conditions is presented, applying a commonly applicable computer algorithm based on an atom-group additivity method, where the molecules are broken down into their constituting atoms, these again being further characterized by their immediate neighbor atoms. The calculation of their group contributions, carried out by means of a fast Gauss–Seidel fitting calculus, used the experimental data of 5988 molecules from literature. An immediate subsequent ten-fold cross-validation test confirmed the extraordinary accuracy of the prediction of the molar refractivity, indicated by a correlation coefficient R^2 and a cross-validated analog Q^2 of 0.9997, a standard deviation σ of 0.38, a cross-validated analog S of 0.41, and a mean absolute deviation of 0.76%. The high reliability of the predictions has been exemplified with three classes of molecules: ionic liquids, silicon- and boron-containing compounds. The corresponding molecular polarizabilities have been calculated indirectly from the refractivity using the inverse Lorentz-Lorenz relation. In addition, it could be shown that there is a close relationship between the "true" volume and the refractivity of a molecule, revealing an excellent correlation coefficient R^2 of 0.9645 and a mean absolute deviation of 7.53%.

Background: The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System was developed as an intuitive and research-based scoring system that could be validated through beta testing and easily introduced to healthcare providers of several subspecialties who treat nasal obstruction and breathing disorders (MDs, PAs, PTs, APRNs, DDSs, and DCs). This scoring system was shown to increase the knowledge of airway function, nasal measurement parameters, and identification of proper treatment options for sleep and breathing disorders. The basis for the DAFNE score was developed from a systematic review of nasal measurement data. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were used to identify studies validating nasal function measurement parameters to create the algorithm for the DAFNE Score™. The systematic review was accomplished using the 2020 ‘Preferred Reporting Items for Systematic Reviews’ (PRISMA) guidelines. Results: Twenty studies met the inclusion criteria for systematic review. Primary outcomes measurements demonstrated reliability, repeatability and validity of the DAFNE measurement technologies, data and output. Conclusions: The data analysis and systematic review uncovered a need and framework to develop and validate a web-based software algorithm for global access to improve the understanding of data interpretation of nasal measurements from three nasal measurement technologies. DAFNE Scoring should be used as an adjunct tool in routine clinical practice and research to further understand the technology data output and how to collaborate with other healthcare providers to improve patient outcomes.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N=3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N=1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N=373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N=2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N=2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules, for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R² of 0.6066.

Aquatic environments are generally heterogeneous in space and time, and the marine organisms have their ways response to those environmental heterogeneities. Cutlassfish (Trichiurus spp.) once is one of the “Chinese Four Major Marine Fish Species” along the coast of northwest Pacific Ocean. There are some comments on the cutlassfish (T. spp.) name identification. In this study, three cutlassfish species, namely, the largehead hairtail (T. japonicas) in East China Sea (ECS), Chinese short-tailed hairtail (T. brevis), and South China Sea (SCS) cutlassfish (T. nanhaiensis), have been identified in the northwest Pacific Ocean. This work integrated 115 studies in cutlassfish population dynamics from 24 sites across 8 countries in the world. The biomass distribution of T. japonicas in the ECS and T. nanhaiensis in SCS, was found to be highly correlated with water temperature and salinity. Spatiotemporal heterogeneity of cutlassfish is found to correlate with both genetic and environmental characteristics in the northwest Pacific Ocean (e.g., density dependency, primary productivity and climate ocean oscillation). Closely related species coexisting in the same shelf region (e.g., T. japonicus and T. nanhaiensis in ESC) often differ in diet and microhabitat. The difference of skull phenology between T. nanhaiens and T. brevis is found to correlate with species separation and environmental heterogeneity. With the implications for the design of ecological research programs on cutlassfish, our study found that the effect of temporal changes outweighs (to some extent) the effect of spatial changes on cutlassfish in those shelf regions.

The calculation of the vapour pressure of organic molecules at 298.15K is presented using a commonly applicable computer algorithm based on the group-additivity method. The basic principle of this method rests on the complete breakdown of the molecules into their constituting atoms, further characterized by their immediate neighbour atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting algorithm using the experimental data of 2036 molecules from literature. A ten-fold cross-validation procedure has been carried out to test the applicability of this method, which confirmed excellent quality for the prediction of the vapour pressure, expressed in log(pa), with a cross-validated correlation coefficient Q2 of 0.9938 and a standard deviation  of 0.26. Based on these data, the molecules' standard Gibbs free energy G°vap has been calculated. Furthermore, using their enthalpies of vaporization, predicted by an analogous group-additivity approach published earlier, the standard entropy of vaporization S°vap has been determined and compared with experimental data of 1129 molecules, exhibiting excellent conformance with a correlation coefficient R2 of 0.9598, a standard error  of 8.14 J/mol/K and a medium absolute deviation of 4.68%.

Abstract: Background: The diagnosis of nasal airway disorders relies on questionnaires, subjective data, and objective data. Interpretation of objective data obtained from measurement technology is not well understood by providers and researchers who use the equipment to test nasal airway function, justifying the need to cre-ate a new clinical tool. The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System is a web-based scoring system that allows healthcare providers (MDs, PAs, PTs, APRNs, DMDs, DDSs, SLPs, and DCs) and researchers who treat nasal obstruction and breathing disorders to make more accurate diagnostic decisions, select the appropriate treatment for individualized patient care, monitor treatment progression and outcomes, and show how to approach a collaborative care model with other healthcare professionals. The current technologies, such as 4-phase rhinomanometry, use a simple approach that relies on a measurement tracing intersecting a color-coded y-axis on a four-quadrant graph with diagnostic numeric data output de-scribing nasal airflow and resistance. This is a good source of biofeedback demonstrating abnormal nasal breathing patterns but lacks interpretation guidelines to describe the severity of disease. The more sophisti-cated proprietary DAFNE approach uses multiple parameters which include airflow restriction, speed, vol-ume, and patient characteristics to identify patients’ disease progression much more accurately. Additionally, it explains how to segregate patients into appropriate treatment options which minimizes risks and compli-cations associated with sleep and breathing disorders while improving patient outcomes. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were necessary to identify studies which determined the ranges of nasal function measurement parameters among three airway measurement technologies used in writing the DAFNE Score algorithm. The performance of DAFNE was evaluated compared to the research data and patient demographics used in previous studies. Results: By using primary outcome measurements from the literature, we were able to create a reliable, re-peatable, and validated tool to facilitate patient identification, treatment stratification, and collaboration for sleep and nasal breathing dysfunction. Subsequently, we found DAFNE could be used to identify the appro-priateness of a sleep study. Conclusions: DAFNE Scoring System has demonstrated the ability to detect high risk patients in the pediatric and adult populations susceptible of sleep apnea and breathing dysfunction needing a sleep study and treatment to improve nasal airway function and sleep. DAFNE Scoring System should be used as an adjunct tool in routine clinical practice and research to further understand the technol-ogy data output, identify patients at risk, stratify treatment options, progress, and stabilization after treatment, and how to collaborate with other healthcare providers to improve patient outcomes.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. It has been shown that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on way to an endemic form, however the threat of the virus is more for susceptible (older people and immunocompromised) people. The human body has more bacterial cells than its own, thus making us more bacterial than humans. As a consequence, the bacteriomes in the human body heavily influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. in major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. that have a positive effect on the functionality of the immune system and human health. These select bacterial spp. could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. that could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacy.

Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

The primary objective of this study is to determine the existence of a significant correlation between inflammation levels, as measured by inflammatory markers IL-6, IL-1β, and TNF-α, and the severity of depressive symptoms assessed using HAM-D assessment scale. This could provide additional evidence supporting the hypothesis that inflammation plays a notable role in the pathogenesis of depression. The data analysis supports the hypothesis that the biological mechanisms of inflammation contributes to the clinical manifestations of depression. Elevated levels of inflammatory markers, especially interleukins (IL6, IL1β), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) have been identified in patients with major depressive disorder compared to the findings in healthy controls. Materials and Methods: Inflammatory markers (IL-6, IL-1β, and TNF-α) were measured in a sample of 31 patients hospitalized at the Socola Institute of Psychiatry in Iasi, Romania, and compared to a control group with no psychiatric or inflammatory conditions. One of the main objectives is to determine if there is a significant correlation between inflammation levels, measured by inflammatory markers (IL-6, IL-1β, and TNF-α), and the severity of depressive symptoms assessed using HAM-D scores. Conclusions: The study results suggest a significant correlation between inflammation levels measured by inflammatory markers IL-1β and IL-6 and the severity of depressive symptoms evaluated by HAM-D scores in the study group. These findings support the hypothesis that inflammation may play an important role in the development or exacerbation of depressive symptoms. The relationship between inflammation and depression is also influenced by risk and protective factors that require further research.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. The biomechanics of the cornea plays a significant role in managing patients with glaucoma. While evidence suggests a higher risk of glaucoma in patients with thin and stiffer corneas, it also affects the measurement of intraocular pressure (IOP). We reviewed the pertinent literature to help the understanding of corneal biomechanics and how it can help optimize clinical and surgical treatments and a better approach to diagnosing and managing patients with glaucoma.

This study investigates the comparative performance of autoencoders and traditional machine learning (ML) algorithms in predicting tumor dynamics following Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). The research retrospectively analyzed clinical data from 77 patients (median age: 64 years; 45 males, 32 females) treated at the “Prof. Dr. NicolaeOblu” Emergency Clinic Hospital-Iasi. The dataset comprised 12 variables, including socio-demographic, clinical, treatment, and radiosurgery-related factors. The primary outcome was tumor progression or regression within three months post-GKRS, with 71 cases of regression and 6 cases of progression observed. Traditional ML models—Logistic Regression, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Extra Trees, Random Forest, and XGBoost—were evaluated, achieving accuracy rates ranging from 0.91 (KNN) to 1.00 (Extra Trees). When incorporating features extracted by autoencoders, the performance of these models generally improved, especially with compression in the bottleneck layer. For instance, Logistic Regression's accuracy increased from 0.91 to 0.94, while SVM's accuracy improved significantly from 0.85 to 0.96. XGBoost consistently performed well across both traditional and hybrid setups, maintaining an accuracy of 0.94 with an AUC of 0.98. The findings suggest that hybrid approaches combining deep learning with traditional ML techniques can significantly enhance predictive accuracy and robustness, particularly in the context of GKRS for BMs. This improved performance has potential implications for more informed clinical decision-making in personalized medicine.

The work proposes a new approach for evolutionary global optimization which, in simple terms, may be described as a fusion of quantum and simulated annealing. This becomes possible by using basic concepts from Homotopy Theory, conjugated to the already existing Fuzzy Adaptive Simulated Annealing paradigm and other components. In this fashion, it occurs a temporal and nonlinear superposition of the two types of annealing, provoking interesting effects in runtime, including the so-called quantum tunneling, when there is a sudden transition between attraction basins of different minima without "climbing" potential barriers. In addition, the proposal includes a generalization of the "deformation" of Hamiltonians used in quantum annealing by suggesting the use of general homotopies between the surface corresponding to the cost function under processing and another specific landscape, being this possible because of the ability of Fuzzy ASA of handling time-varying objective functions. The proposed paradigm shows that it is possible and beneficial to superpose the two types of annealing, displaying amazing numerical results and suggesting a kind of interlacing or synergic behavior - perhaps we could call it an "annealing entanglement". Finally, given the fast advances in commercial quantum annealing processors, it seems sensible to expect that an implementation of the proposed approach using such devices may occur very soon. In order to demonstrate the efficacy of the proposed algorithm, some significant and detailed examples are included in the text, so as to illustrate and clarify the presented ideas.

In this paper the problem of sampling from uniform probability distributions is approached by means of space-filling curves (SFCs), a topological concept that has found a number of important applications in recent years. Departing from the theoretical fact that they are surjective but not necessarilly injective, the investigation focused upon the structure of the distributions obtained when their domain is swept in a uniform and discrete manner, and the corresponding values used to build histograms, that are approximations of their true PDFs. This work concentrates on the real interval [0,1], and the Sierpinski space-filling curve was chosen because of its favorable computational properties. In order to validate the results, the Kullback-Leibler distance is used when comparing the obtained distributions in several levels of granularity with other already established sampling methods. In truth, the generation of uniform random numbers is a deterministic simulation of randomness using numerical operations. In this fashion, sequences resulting from this sort of process are not truly random.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

Assessment of the environmental impact of organic chemicals has become an important subject in chemical science. Efficient quantitative descriptors of their impact are their partition coefficients logPow, logKoa and logKaw. We present a group-additivity method that has proven its versatility for the reliable prediction of many other molecular descriptors for the calculation of the first two partition coefficients and indirectly of the third with high dependability. Based on the experimental logPow data of 3332 molecules and the experimental logKoa data of 1900 molecules at 298.15K the respective partition coefficients have been calculated with cross-validated standard deviations of only 0.42 and 0.48 log units and a goodness of fit Q^2 of 0.9599 and 0.9717, respectively, in a range of ca. 17 log units for both descriptors. The third partition coefficient logKaw has been derived from the calculated values of the former two descriptors and compared with the experimentally determined logKaw values of 1937 molecules, yielding a standard deviation of 0.67 log units and a correlation coefficient R^2 of 0.9467. This approach enabled the quick calculation of 29462 logPow, 27069 logKoa and 26220 logKaw values for the more than 37100 molecules of ChemBrain's database available to the public.

The concept of ecosystem services (ESs) provides a valuable approach to communicate societies' dependence on natural ecosystems, assisting in the evaluation of measures to protect vegetation in watersheds that promote water-related ESs. Vegetation cover and land use are important factors related to the capacity of ecosystems to provide soil loss regulation and sediment retention services, which are highly relevant for sediment management in watersheds draining into reservoirs with multiple water uses. This study aims to assess the relationship between potential changes in land use and land cover and the sediment retention service provided by riparian vegetation in a watershed draining into a hydroelectric reservoir in the Brazilian Cerrado. Sediment load was selected as a physical variable that affects different water uses in reservoirs, with these uses being dependent on the quality or quantity of stored water. Scenarios were analyzed to represent landscape reconfigurations from a baseline condition in order to account for the recovery of riparian vegetation by the agricultural sector, as foreseen in the Brazilian Forest Code. To map and quantify variations in annual sediment retention, the InVEST model was used, which allows estimating an integrated response of the drainage basin to large-scale land use changes over time and space. The results show that for the drainage basin of the Corumbá IV Hydroelectric Power Plant (HPP), the recovery of riparian areas occupied by annual crops has the potential to generate greater benefits to water use in the reservoir. In the studied catchment area, 14% of the total vegetation deficit in riparian areas is occupied by crops, while 86% is occupied by pastures. This highlights the buffering role of riparian vegetation as an effective practice for managing sediment flows originating from sheet erosion in agricultural landscapes. The methodology employed in this study allows for the quantification and mapping of the effects of soil and water conservation measures in river basins. This enables the prioritization of sectoral efforts for the restoration of native vegetation, considering the highest returns in benefits perceived by water users affected by sediment input in reservoirs. The study's results reinforce the importance of conserving vegetation in riparian areas and their surroundings for sediment retention, highlighting the role of these areas as assets in providing water-related ecosystem services.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

Adjunctive treatment of periodontitis lacks solutions allowing enough time for wound healing in the periodontal pockets by avoiding a fast re-colonization. Such a solution might be an antibiotic containing formulation with a controlled release over weeks. Here, a recently described minocycline containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development and degradation studies. Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning- and scanning electron microscopy. Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased dosage dependent and reduced bone loss compared to non-treated group was observed. Thereby, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over weeks. The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.

Satellite communication (Satcom) is an artificial geostationary satellite that facilitates a wide range of telecommunications. Considering its quality of service (QoS) and security is crucial in government/military applications. The most challenging situation for efficient Satcom is radio frequency interference (RFI) environment. Thus, it is necessary to ensure that transmissions are incorruptible or at least sense the quality of its spectrum. This paper presents a new method to recognize received signal characteristics using a hierarchical classification in a multi-layer perceptron neural network. We consider signal modulation and the type of RFI as the characteristics of a real-time video stream transmitted in the direct broadcast satellite. Four different modulation types are investigated in this study. Moreover, the combination of the communication signal with various kinds of interference and their effects on the classification method widely have been analyzed. Besides, two robust feature selection techniques have been developed to reduce the data-set dimensional, which leads to optimizing the classification process. The results show that the Genetic Algorithm (GA) slightly outperforms Principal Component Analysis (PCA) for feature selection. Furthermore, the robustness of the proposed techniques is assessed to detect unknown signals at different signal to noise ratios.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

In this paper, we report a comprehensive and consistent annotation of the locus encoding the horse T cell receptor b-chain (TRB), as inferred from the most recent genome assembly. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species stud-ied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV, belonging to 29 subgroups, 2 TRBD, 13 TRBJ and 2 TRBC genes, were iden-tified. The general genomic organization resembles that of other mammals, with a V-cluster of 135 TRBV genes, located upstream of two in-tandem aligned TRBD-J-C clusters, and an inverted TRBV gene at the 3’ end of the last TRBC gene. However, the horse b-chain repertoire would be affected by a high number of non-functional TRBV genes. Thus, we queried a transcriptomic da-taset derived from splenic tissue of a healthy adult horse, using each TRBJ gene as a probe to ana-lyse clonotypes encompassing the V(D)J junction. This analysis provided insights into the usage of the TRBV, TRBD and TRBJ genes and the variability of the juxtaposition region. Our results clearly demonstrated that the horse β-chain constitutes a complex level of variability broadly like that described in other mammalian species.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Background: Existing human cell immortalization methods made the cells obtain oncogenesis phenotype and/or caused the cells gain and/or lose chromosomes. Immortalized normal human T cells lines provide critical in vitro models for basic research and therapeutic products development.Methods: We utilized a CRISPR/Cas9 system to replace a single copy of the exon 2 of the cell cycle inhibitor gene CDKN2A (encoding p16 and p14 proteins) with a single copy of human telomerase reverse transcriptase (hTERT) to immortalize human primary CD8⁺ T cells (hCD8⁺T-TERT). By using Cas9 protein and low donor DNA copies/cell, we successfully immortalized hCD8⁺T cells with a single copy of hTERT transgene, which also avoided uncontrolled insertion of Cas9 gene and guide RNA vector.Results: Human primary CD8+ cells were immortalized and expanded more than 2.6 × 10⁷ times. Characterization of the cells revealed that the immortalized CD8⁺ T-TERT cells retained most of the cell surface markers and normal karyotype. The CD8⁺ T-TERT cells also retained the dependence of IL-2 and CD3/CD28 activator for survival and expansion.Conclusion: we established a stable immortalized CD8⁺ T cell line that had a phenotype consistent with T cells and will be a useful research model.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

This article discusses an international scientific expedition to Greenland that researched geography, geodesy, botany, and glaciology of the area. The results here focus on the geodetic and glaciological results obtained with the eBee drone in the eastern part of Greenland at the front of the Knud Rasmussen glacier. From two overflights nearby the glacier front, it was possible to obtain the speed of the glacier flow and the distribution of velocities in the glacier stream. The results correlate with other measurement methods and this technology has been shown as feasible. Of course, there are more accurate and long-term options or devices for monitoring the flow of glaciers. In this case of short-term visits to the site, the possibility of using a drone is interesting and the results show not only the flow speed of the glacier, but also the shape and structure from a height of up to 200m. The second part of the paper focuses on the analysis of modern satellite images of the Knud Rasmussen glacier from Google Earth (Landsat series 1984-2016) and a comparison with historical aerial images from 1932-1933. Experimentally, historical images were processed photogrammetrically into a 3D model.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

This manuscript explores significant advancements and emerging challenges in CAR T cell therapies, focusing on the production methodologies and regulatory complexities. The discussion highlights ongoing challenges like the lack of in vivo persistence, lengthy production times, and elevated costs associated with current CAR T cell therapies. It analyzes innovative solutions such as genetic engineering techniques aimed at enhancing cellular efficacy and endurance, alongside cutting-edge manufacturing processes, including closed systems and development of allogeneic products. These advancements hold promise for reducing costs and improving production efficiency, potentially increasing patient access to these transformative therapies globally. Furthermore, the manuscript underscores the necessity for expanding ongoing research and enhancing regulatory frameworks to fully realize and implement these innovations in CAR T cell manufacturing and bring these innovations to fruition.

Abstract: Seismic performance and loss assessments can have widely varying degrees of uncertainty. An essential issue is whether a particular assessed seismic loss or performance result has sufficient reliability to serve as the basis for risk management decisions and actions, including whether or not a code prescribed performance level is met, or if an assessed loss level is acceptable. A method is developed measuring the reliability of performance and loss assessments for individual buildings and for portfolios. Consideration is given to how well the building investigation and corresponding evaluation process have been performed, the qualifications of the person(s) doing the assessment, the thoroughness of the evaluation, and the technical validity of the assessment procedure or model. The approach characterizes the uncertainty of each component of the assessment procedure for each building in qualitative terms. The resulting reliability measure is likely to be most useful for the cases where an entity is determining whether/or not a building has acceptable life safety performance, or if a portfolio has an acceptably low risk of seismic damage loss over a given period of time. In both cases, the reliability must either be sufficient to warrant action, or serve to indicate need for improved assessment.

We estimate the effect of household social expenditure on vulnerability to poverty using the four latest cross-sectional waves of Ghana Living Standard Survey (GLSS) from 1999 to 2017. Using a 3-Stage Least Square and Quantile Regression, our results show a widening consumption ex-post welfare gap between the poorest households and the non-poor households in a per-cedi social expenditure. Also, we estimate the probability of an ex-ante poverty using vulnerability to expected poverty. The results, however, indicate that regardless of poverty status, household vulnerability to poverty increased consistently between 1999 and 2017, and the very poor households showing the severest vulnerability. Hence, it is concluded that social expenditure increases the chances of a poor household falling into chronic poverty a non-poor household into transient poverty in the future.

This study examines the bias in weighted least absolute deviation (WL1) estimation within the context of stationary first-order bifurcating autoregressive (BAR(1)) models, which are frequently employed to analyze binary tree-like data, including applications in cell lineage studies. Initial findings indicate that WL1 estimators can demonstrate substantial and problematic biases, especially when small to moderate sample sizes. The autoregressive parameter and the correlation between model errors influence the volume and direction of the bias. To address this issue, we propose two bootstrap-based bias-corrected estimators for the WL1 estimator. We conduct extensive simulations to assess the performance of these bias-corrected estimators. Our empirical findings demonstrate that these estimators effectively reduce the bias inherent in WL1 estimators, with their performance being particularly pronounced at the extremes of the autoregressive parameter range.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 93.0 µM-4·s-1 and 102 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

A co-curing resin system consisting of 9368 epoxy resin for prepreg and 6808 epoxy resin for resin transfer molding (RTM) was developed. A corresponding preparation method of novel polymer composite bolted T-joint with internal skeleton and external skin was proposed based on prepreg-RTM co-curing process, and novel T-joints were fabricated. A series of conventional configuration T-joints based on RTM process and T-joints made of 2A12 aluminum alloy were prepared simultaneously. Bending performances were studied on these T-joints experimentally. The results indicate that 9368 epoxy resin and 6808 epoxy resin exhibit good compatibility in rheological and thermophysical properties. The novel T-joints prepared with prepreg-RTM co-curing process show no obvious fiber local winding or resin-rich regions inside, and the interface quality between internal skeleton and external skin is excellent. The main failure modes of the novel T-joint under bending load include separation of skin and skeleton and fracture along the thickness on the base panel; the skeleton carries the main bending load, but there is still load transfer between external skin and internal skeleton through their interface. The internal damages of the novel T-joint are highly consistent with surface damages observed visually, facilitating the detection and timely discovery of damages. The initial stiffness, damage initiation load, and ultimate load of the novel T-joint are 1.65 times, 5.89 times, and 3.45 times that of conventional T-joint, respectively. When considering the influence of density, the relative initial stiffness and relative ultimate load of the novel T-joint are 1.44 times and 2.07 times that of aluminum alloy T-joint, respectively.

The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.

The purpose of this study is to investigate the perceived benefits of community gardening. A garden colony is a collection of adjacent plots of land primarily for the purpose of gardening. The methodology of this research consists of observations, interviews, questionnaires, and focus group. As a result of this research we found that gardening is a natural and safe way to meet the lifelong demands for a healthy life. We found specific mental and physical benefits as a result of this community gardening. We encourage communities to allow people to buy plots of land away from their homes to promote this healthy activity. The garden colony provides a place for individual renewal and restoration; this urban oasis offers a way to maintain and promote lifelong healthy living, and they are an important contribution to one’s life by adding a sense of meaning and purpose.

The novel coronavirus has presented specimen-access challenges to geoscientific researchers, including paleobiologists interested in fossil ammonoids. Ammonoid sutures are geometric patterns formed by the intersection of the septa and the shell wall, and have long been a diagnostic tool for ammonite researchers for such applications as species identification, taxonomic relationships, ontogenetic change, functional and evolutionary morphology, and other aspects of ammonoid paleobiology. Without access to specimens in museum and institutional collections, researchers must rely on previously published illustrations and photographs of ammonoid sutures. However, many of these illustrations were published decades ago without an index of scale. Suture tracings lacking a scale bar are not usable by researchers interested in applying the quantitativeness of fractal geometry to the interpretation of septal complexity. Additonally, distortion of the marginal elements of suture geometry occurs due to shell curvature near the venter and umbilicus. The revised approach described here eliminates the problem of missing scale information in fractal analysis of ammonite sutures, making use of just the lateral lobe and adjacent saddle. Our revised method’s non-requirement of a full hemisuture also facilitates comparisons among sutures within an ontogenetic sequence, or sutures from multiple ammonite taxa.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlighting the clinical importance, underlying mechanisms, and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

Since its conception with the smallpox vaccination, worldwide-used vaccines have thwarted multiple pandemics including the recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks of CD4 T cells [T helper 1 (Th1); Th2, Th17] and CD8 T cells (T cytotoxic; Tc) as well as B cells (BIgM, BIgG, BIgA and BIgE) subsets during response to vaccination. Both T and B cell subsets forge central, peripheral and tissue-resident subsets during vaccination. It also became apparent that each vaccination formed the network of T regulatory subsets, namely CD4+CD25+Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+Foxp3− T regulatory 1 (Tr1) as well as many others, are shaping the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on presenting how pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work revealed that the Treg/Tr1 involvement evoked different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response by increasing a dose, changing the delivery route and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Ra chain) or anti-PD-1 (programmed cell death protein) monoclonal antibody (mAb) to decrease Tregs and boost the T/B cell immune response. All these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals as well as organ transplant patients.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

Graphene is a two-dimensional nanostructured material with intrinsic properties that show promising performance in various applications, including electronics, renewable energy, medicine, mechanical enforcement and others. This study reports a bottom-up approach for the conversion of cyclohexane into graphene nanoflakes, which were then deposited onto fiberglass using a non-thermal generator. The composite was characterized using transmission electron microscopy, which revealed the formation of stacked few-layer graphene with a partially disordered structure and a d-spacing of 0.358 nm between the layers. X-ray diffraction confirmed the observations from the TEM images. SEM images showed the agglomeration of carbonaceous material onto the fiberglass, which experienced some delamination due to the synthesis method. Raman spectroscopy indicated that the obtained graphene exhibited a predominance of defects in its structure. Additionally, Atomic Force Microscopy (AFM) analyses revealed the formation of graphene layers with varying levels of porosity.

Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. Results: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. Conclusions: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

COVID-19 has proven to be detrimental across the globe, most notably affecting the United States at an alarming rate compared to comparable countries. The pandemic has had multifactorial implications on the way communities in the United States prevent, prepare for, and address the virus; however, the impact of the pandemic on rural health is less well understood. Historically, rural communities have faced a unique set of challenges regarding accessing and receiving adequate healthcare, addressing chronic illness, and eliminating health disparities closely associated with the population’s socioeconomic status; the pandemic has exacerbated these challenges. The purpose of the current study was to conduct a systematic review of the literature to evaluate the effect of the COVID-19 pandemic on rural populations both at the individual and community level. Results indicated that rural health disparities increased both at the individual and system-wide levels as a direct result of the pandemic. Budget cuts significantly affected the infrastructure of rural hospitals resulting in them being unequipped to handle such high volumes of COVID-19 cases. The lack of infectious disease specialists, access to larger medical centers with substantial numbers of ICU beds and ventilators, and an overall lack of preparedness overwhelmed rural communities. Although comorbidities such as diabetes and heart disease were associated with poorer health outcomes for a multitude of reasons, the lack of clinic and physician availability for routine care during the pandemic further exacerbated the clinical link from COVID-19 positivity to comorbidities. Furthermore, mental health deteriorated as substance use increased to a greater extent in rural communities compared to urban, during the pandemic. This study shows that health comorbidities, mental health, substance use, health literacy, access to healthcare, among others can serve as key indicators for improving healthcare in rural communities. Future studies should seek to identify key issues that disproportionately affected rural communities in comparison to their urban counterparts considering the pandemic, as well as identify gaps in the availability of rural health resources that can improve the lives of millions of Americans now and during the next pandemic.

The proteomic profile of extracellular vesicles (EVs) has been of increasing interest, particularly in understanding cancer growth, drug resistance, and metastatic behavior. Emerging data suggests that cancer-derived EVs may carry an array of oncogenic cargo, including certain integrin proteins that may, in turn, promote cell detachment, migration, and selection of future metastatic sites. We previously reported a large comparison of secreted vesicle protein cargo across sixty diverse human cancer cell lines. Here, we analyze the distinct integrin profiles of these cancer EVs. We further demonstrate the enrichment of integrin receptors in breast cancer EVs compared to vesicles secreted from benign breast epithelial cells. Total EV integrin levels, including the quantity of integrins α2, αv, β4, and β5 correlate with breast tumor stage. In particular, integrin α2 also largely reflects progenitor cell expression, highlighting the utility of this integrin protein as a potential circulating biomarker of primary tumors. This study provides preliminary evidence of the value of vesicle-associated integrin proteins in cancer diagnosis and prediction of tumor stage. Differential expression of integrins across cancer cells, and selective packaging of integrins into EVs may contribute to further understanding the development and progression of tumor growth and metastasis across a variety of cancer types.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the key focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection in pre-clinical models and human trials. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses delivered by replication-deficient vector ChAdOx1. It focuses T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the beta-coronavirus family.

Qatar and other Gulf States have a diverse range of marine vegetation that is adapted to the stressful environmental conditions of seawater. The industrial wastewater produced by oil and gas activities adds further detrimental conditions for marine aquatic photosynthetic organ-isms on the Qatari coastlines. Thus, these organisms experience severe stress from both seawater and industrial wastewater. This review discusses the biodiversity in seawater around Qatar, as well as remediation methods and metabolic pathways to reduce the negative impacts of heavy metals and petroleum hydrocarbons produced during these activities. These methods include phyto-stabilization phyto-accumulation, phyto-volatilization, and phyto-degradation. Phy-to-degradation in particular is discussed in detail, including metabolic pathways such as alkane and aromatic-compound degradation pathways. The role of microorganisms that are adjacent to or associated with these aquatic marine organisms is discussed, including rhizosphere biodeg-radation. In this type of biodegradation, exudates are released by plant roots and supply nutrients to microorganisms in the rhizosphere, which enhances their ability to degrade organic pollutants. Special attention is paid to mangrove forests and their roles in remediating shores polluted by industrial wastewater. Seagrasses (Halodule uninervis, Halophila ovalis, and Thalassia hemprichii) and seaweeds (Chlorophyta, Phaeophyta, and Rhodophyta) around the peninsula of Qatar are also discussed.