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In this study, the hydrogen reduction mechanism of MoO3 was analyzed in detail using Ti–Mo core–shell powder manufactured through a milling and reduction process. MoO3 and Ti powders were ball-milled to refine the MoO3 powder and coat it onto the Ti powder to fabricated core-shell structure. Subsequently, the milled powder was heat-treated at 600°C in a hydrogen atmosphere to reduce MoO3 to nano-sized Mo. In addition, the reduction behavior of MoO3 was analyzed by varing the reduction times to 1, 10, 30 min and 1, 3, 5 h. Phase analysis was conducted using X-ray diffraction, and oxidation state analysis was conducted using X-ray photoelectron spectroscopy. Morphology analysis was performed using scanning electron microscopy, and elemental analysis was conducted using electron probe micro-analysis. It was confirmed that Mo9O26 and Mo4O11 intermediate phases were formed sequentially as MoO3 was reduced to MoO2, and Mo9O26 had a plate shape with a thickness of sub-70 nm, and Mo4O11 exhibited a thickness of sub-300 nm. Especially, the Mo2O3 intermediate phase, previously studied only theoretically, was experimentally confirmed for the first time in the reduction process from MoO2 to Mo. Furthermore, the analysis of Mo-oxide intermediate phases was explained by the structural characteristics of the core–shell. The shell of Mo oxide was thick and dense, making it difficult for the vapor phase necessary for CVT reduction to penetrate and diffuse into the shell. As a result, the rapid CVT reduction occurred outside the shell, while relatively slower reduction occurred inside the shell where intermediate phases were observed.

BackgroundMast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored.ObjectivesTo elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity.MethodsKeloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids.ResultsThe scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples.ConclusionsscRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.

BackgroundHuman papillomavirus (HPV) can cause cancers in men and women. Despite the availability of an effective vaccine, HPV vaccination coverage remains suboptimal among college students. Literature showed that hesitancy for HPV vaccination is a leading barrier to the uptake in this group. However, prior interventions have shown limitations in reducing HPV vaccine hesitancy in college students. Thus, this study examined a conventional educational approach using a vaccine information statement (VIS), and subsequently explored college students’ HPV vaccine hesitancy and the potential of virtual reality (VR) technology to overcoming the limitations of interventional efforts.MethodsWe employed a mixed-methods design along with convenience sampling, constituting a one-way pre- and post-intervention (HPV VIS) survey (Study A) and individual interviews (Study B). All data collections occurred with 44 college students at an urban public university at the mid-south region of the U.S. between October 2022 and April 2023. Study A assessed changes in HPV vaccination outcomes including knowledge, beliefs/attitudes, vaccine hesitancy, and intentions. Study B measured college students’ primary reasons for HPV vaccine hesitancy and preferred strategies for the vaccination promotion including VR-based education. We conducted paired t-test and Wilcoxon signed ranks test for quantitative data and framework analysis for qualitative data.ResultsParticipants reported significant improvements in knowledge [t(43) = 6.68, p

This study aimed to assess the predictive ability of the shock index (SI) and the shock index, pediatric age-adjusted (SIPA) for mortality among pediatric patients with trauma (aged ≤ 18 years). A systematic search used PubMed, Embase, and Cochrane Library databases to identify pertinent articles published from their inception to 13 February 2023. For each SI and SIPA, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) with the corresponding 95% confidence intervals were calculated. We planned a priori meta-regression analyses to explore heterogeneity using the following covariates: country, clinical setting, type of center, data source, and cutoff value. Twelve studies were included based on the inclusion criteria. Among them, nine studies with 195,469 patients were included for the SIPA at the hospital, four studies with 4,970 patients were included for the pre-hospital SIPA, and seven studies with 606,445 patients were included to assess the ability of the SI in predicting mortality. The pooled sensitivity and specificity with 95% confidence interval for predicting mortality were as follows: 0.58 (0.44-0.70) and 0.72 (0.60-0.82), respectively, for the SIPA at the hospital; 0.61 (0.47-0.74) and 0.67 (0.61-0.73), respectively, for the pre-hospital SIPA; and 0.71 (0.59-0.81) and 0.45 (0.31-0.59), respectively for the SI. The DOR were 3.80, 3.28, and 2.06 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The AUC were 0.693, 0.689, and 0.618 for the SIPA at the hospital, pre-hospital SIPA, and SI, respectively. The SI and SIPA are simple predictive tools with sufficient accuracy that can be readily applied to pediatric patients with trauma, but SIPA and SI should be utilized cautiously due to their limited sensitivity and specificity, respectively.

ABSTRACTPatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases.

Background We compared preoperative residual gastric volume (GV) between the first and second stages of total knee arthroplasty (TKA) in older adults after drinking carbohydrate-containing fluid 2 h prior to surgery. Methods In this study, 36 patients, aged > 65 years, scheduled for staged bilateral TKA with one-week interval, were enrolled. The patients consumed 400 ml of carbohydrate-containing fluid 2 h prior to surgery. Before the induction of spinal anesthesia, the gastric antral cross-sectional area was measured at the first and second TKA using ultrasound, and the residual GV was calculated. The primary outcome was the residual GV. Qualitative GV (grades 0, 1, and 2) and analgesic consumption after the first TKA were assessed as secondary outcomes. Results The GV (median [Q1, Q3]) was greater in the second-stage TKA (41.1 [22.5, 62.8] ml) than in the first-stage TKA (10.3 [0.0, 27.1] ml) (P < 0.001). In the qualitative assessment, the distribution was not different between the two stages of TKA (P = 0.219) and only one patient showed grade 2 gastric content in the second TKA. When opioid consumption was converted to an equivalent dose of morphine, an average of 53.9 mg of morphine was required after the first TKA. Conclusions Residual GV after drinking carbohydrate-containing fluid differed according to the stage of TKA, showing a larger residual GV in the second TKA than in the first one. In older adults scheduled to undergo bilateral staged TKA, caution is required in preoperative fasting practice, especially in second-stage surgery.

Abstract The plant toxin ricin, especially its cytotoxic A chain (RTA), can be genetically engineered with targeting ligands to develop specific anti-cancer recombinant immunotoxins (RITs). Here, we used affibody molecules targeting two cancer biomarkers, the receptors HER2 and EGFR, along with the KDEL signal peptide to construct two cancer-specific ricin-based RITs, HER2Afb-RTA-KDEL and EGFRAfb-RTA-KDEL. The affibodies successfully provided target-specificity and subsequent receptor-mediated endocytosis and the KDEL signal peptide routed the RITs through the retrograde transport pathway, effectively delivering RTA to the cytosol as well as avoiding the alternate recycling pathway that typical cancer cells frequently have. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain (AlBD) to construct AlBD/HER2Afb/RTA-KDEL. Systemic administration of AlBD-containing RITs to tumor-bearing mice significantly suppressed tumor growth without any noticeable side-effects. Collectively, combining target-selective affibody molecules, a cytotoxic RTA, and an intracellularly designating peptide, we successfully developed cancer-specific and efficacious ricin-based RITs. This approach can be applied to develop novel protein-based “magic bullets” to effectively suppress tumors that are resistant to conventional anti-cancer drugs. Graphical Abstract

Background: The lysosome has emerged as a promising target for overcoming chemoresistance, owing to its role in facilitating the lysosomal sequestration of drugs. The lysosomal calcium channel TRPML1 not only influences lysosomal biogenesis but also coordinates both endocytosis and exocytosis. This study explored the modulation of cisplatin sensitivity by regulating TRPML1-mediated lysosomal exocytosis and identified the metabolomic profile altered by TRPML1 inhibition. Methods: We used four types of ovarian cancer cells: two cancer cell lines (OVCAR8 and TOV21G) and two patient-derived ovarian cancer cells. Metabolomic analyses were conducted to identify altered metabolites by TRPML1 inhibition. Results: Lysosomal exocytosis in response to cisplatin was observed in resistant cancer cells, whereas the phenomenon was absent in sensitive cancer cells. Through the pharmacological intervention of TRPML1, lysosomal exocytosis was interrupted, leading to the sensitization of resistant cancer cells to cisplatin treatment. To assess the impact of lysosomal exocytosis on chemoresistance, we conducted an untargeted metabolomic analysis on cisplatin-resistant ovarian cancer cells with TRPML1 inhibition. Among the 1446 differentially identified metabolites, we focused on 84 significant metabolites. Metabolite set analysis revealed their involvement in diverse pathways. Conclusions: These findings collectively have the potential to enhance our understanding of the interplay between lysosomal exocytosis and chemoresistance, providing valuable insights for the development of innovative therapeutic strategies.

Abstract The twisted index of 3d N $$ \mathcal{N} $$ = 2 gauge theories on S 1 × Σ has an algebro-geometric interpretation as the Witten index of an effective supersymmetric quantum mechanics. In this paper, we consider the contributions to the supersymmetric quantum mechanics from topological saddle points in supersymmetric localisation of abelian gauge theories. Topological saddles are configurations where the matter fields vanish and the gauge symmetry is unbroken, which exist for non-vanishing effective Chern-Simons levels. We compute the contributions to the twisted index from both topological and vortex-like saddles points and show that their combination recovers the Jeffrey-Kirwan residue prescription for the twisted index and its wall-crossing.

Abstract Given the high prevalence of child undernutrition in Bangladesh, multi‐sectoral approaches involving livelihood promotion have potential to mitigate the burden of undernutrition. This study examined the impact of an economic development (ED) program providing poultry assets, gardening skills and saving training added to the Positive Deviant (PD)/Hearth program (PDH/ED), compared to PD/Hearth only (PDH). A total of 1029 children who attended PD/Hearth sessions in September–November 2018 at 6–13 months of age were enrolled in the cohort study in July–August 2019. The cohort, comprised of 532 children in the PDH/ED group and 593 children in the PDH group, was reassessed in November 2020. The program impact on child nutrition, food security, crop production, dietary quality and household income was estimated using a difference‐in‐differences approach accounting for the sociodemographic differences between PDH/ED and PDH groups. Compared to the PDH group, the PDH/ED group showed increases in child dietary diversity score (DDS) (+0.32), child minimum dietary diversity (13.7 percentage points [pp]), and maternal DDS (+0.28) (all p

Abstract Endoplasmic reticulum (ER) stress has been linked to anesthesia-induced neurotoxicity, but melatonin seems to play a protective role against ER stress. Synchronized Caenorhabditis elegans were exposed to isoflurane during the developmental period; melatonin treatment was used to evaluate its role in preventing the defective unfolded protein response (UPR) and ER-associated protein degradation (ERAD). The induced expression of hsp-4::GFP by isoflurane was attenuated in the isoflurane-melatonin group. Isoflurane upregulated the expression of ire-1, whereas melatonin did not induce ire-1 expression in C. elegans even after isoflurane exposure. With luzindole treatment, the effect of melatonin on the level of ire-1 was significantly attenuated. The reduced expression of sel-1, sel-11, cdc-48.1, and cdc-48.2 due to isoflurane was restored by melatonin, although not up to the level of the control group. The amount of polyubiquitinated proteins was increased in the isoflurane group; however, melatonin suppressed its accumulation, which was significantly inhibited by a proteasome inhibitor, MG132. The chemotaxis index of the isoflurane-melatonin group was improved compared with the isoflurane group. Melatonin may be a potential preventive molecule against defective UPR and ERAD caused by repeated anesthesia exposure. The ire-1 branch of the UPR and ERAD pathways can be the target of melatonin to reduce anesthesia-induced ER stress.

Abstract Aims This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). Methods We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges’ g. To assess publication bias, Egger’s test and p-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators. Results Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges’ g 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges’ g −0.58; 95% CI −0.87 to −0.28), time in bed (Hedges’ g −0.64; 95% CI −1.02 to −0.26) and total sleep time (Hedges’ g −0.64; 95% CI −1.01 to −0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges’ g 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges’ g 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges’ g 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges’ g 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25–8.75). Conclusion We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.

Newborn piglets are susceptible to a highly contagious enteritis caused by the porcine epidemic diarrhea virus (PEDV), associated with high levels of mortality worldwide. There is pressing need for a rapid, safe, and cost-effective vaccine to safeguard pigs from getting infected by PEDV. PEDV belongs to the coronavirus family and is characterized by high levels of mutability. The primary goal of a PEDV vaccine is to provide immunity to newborn piglets through vaccination of sows. Plant-based vaccines are becoming more popular because they have low manufacturing costs, are easily scalable, have high thermostability, and a long shelf life. This is in contrast to conventional vaccines which include inactivated, live, and/or recombinant types that can be expensive and have limited ability to respond to rapidly mutating viruses. The binding of the virus to host cell receptors is primarily facilitated by the N-terminal subunit of the viral spike protein (S1), which also contains several epitopes that are recognized by virus-neutralizing antibodies. As a result, we generated a recombinant S1 protein using a plant-based vaccine platform. We found that the recombinant protein was highly glycosylated, comparable to the native viral antigen. Vaccination of pregnant sows at four and two weeks before farrowing led to the development of humoral immunity specific to S1 in the suckling piglets. In addition, we noted significant viral neutralization titers in both vaccinated sows and piglets. When challenged with PEDV, piglets born from vaccinated sows displayed less severe clinical symptoms and significantly lower mortality rates compared to piglets born from non-vaccinated sows.

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/β-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/β-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/β-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of β-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/β-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

Abstract By incorporating higher-form symmetries, we propose a refined definition of the theories obtained by compactification of the 6d (2, 0) theory on a three-manifold M 3. This generalization is applicable to both the 3d N $$ \mathcal{N} $$ = 2 and N $$ \mathcal{N} $$ = 1 supersymmetric reductions. An observable that is sensitive to the higher-form symmetries is the Witten index, which can be computed by counting solutions to a set of Bethe equations that are determined by M 3. This is carried out in detail for M 3 a Seifert manifold, where we compute a refined version of the Witten index. In the context of the 3d-3d correspondence, we complement this analysis in the dual topological theory, and determine the refined counting of flat connections on M 3, which matches the Witten index computation that takes the higher-form symmetries into account.

In South Korea, domestic cattle, pigs, and goats were subjected to mandatory foot-and-mouth disease (FMD) vaccination and year-round serosurveillance since 2011. In 2020, approximately USD 95 million was spent solely for FMD vaccine purchase for 59 million livestock, and 1.25 million samples were tested to estimate the population immunity and demonstrate the absence of virus circulation. As the FMD vaccination program was revised in 2018, the post-vaccination monitoring (PVM) was designed to evaluate the effectiveness of the vaccine program of three vaccines approved for routine use. To this end, monitoring post-vaccination immunity has been conducted by collecting 35,626 serum samples at 28 days post-vaccination following regular national vaccinations, which were carried out in April and in October in 2020. The design of the serological test for PVM was specially targeted at particular livestock groups, including dairy cattle, goats, and beef cattle aged 6–12 months, which were generally estimated to have a low expected seroprevalence. The risk factors had also been identified, considering the increased likelihood of infection in a particular location, herd size, and husbandry system applied in a targeted sample collection. Serum sample collection and SP-O and NSP antibody tests were performed by local veterinary laboratories using commercially available ELISAs. The current FMD vaccination program, which was performed twice a year following the regimen of primary vaccination and boost, resulted in over 80% population immunity. The seroprevalence monitored after the vaccination in fall was higher than the one studied in spring except in pigs. It was demonstrated that the seroprevalence of risk-based targeted samples ranged from 93.8 to 100% in cattle, 63.2 to 100% in pigs, and 20.0 to 100% in goats. Of note is the area near the North Korean borders which showed a relatively low seroprevalence among the targeted regions, and no NSP sero-positive reactor was detected in this region. When subpopulation immunity at the individual level was assessed, the seroprevalence in young cattle stock was slightly lower (95.8%) than that of adults (98.4%). In conclusion, the FMD vaccination campaign has been successfully implemented in Korea, and the PVM can be a supplementary program for massive routine surveillance in terms of providing timely information needed both to estimate population immunity and to properly target “risk-based surveillance.”

Foot-and-mouth disease (FMD) is one of the most contagious diseases in cloven hoof animals. Vaccination can prevent or control FMD, and vaccine antigens should be matched against circulating viruses. According to phylogenetic analyses, field isolates in this region belonged to genotype V and showed low genetic similarity with the Asia1 Shamir vaccine, the OIE-recommended vaccine strain. In this study, we investigated whether pigs vaccinated with the Asia1 Shamir vaccine could be protected from challenges with the Asia1/MOG/05 virus, one of the genotype V field isolates. Eight pigs were divided into either vaccinated or nonvaccinated control groups. After two vaccinations with Asia1 Shamir, both groups of pigs were challenged with the Asia1/MOG/05 field isolate at 2 weeks after the second vaccination. In the control group, symptoms appeared at 2 days post-infection (dpi). The clinical sign score peaked at 4 dpi, and this coincided with virus shedding through nasal discharge. Neutralizing antibody titers peaked at 17 dpi. In the vaccinated group, clinical signs were delayed compared with the control group, and the highest score was shown at 10 dpi accompanied with virus nasal shedding, which peaked at 11 dpi. Neutralizing antibodies were induced 2 weeks after the second vaccination and peaked at 17 dpi. In conclusion, Asia1 Shamir vaccination in pigs provided partial protection from Asia1/MOG/05 virus infection.

Abstract We study the dependence of supersymmetric partition functions on continuous parameters for the flavor symmetry group, G F , for 2d N $$ \mathcal{N} $$ = (0, 2) and 4d N $$ \mathcal{N} $$ = 1 supersymmetric quantum field theories. In any diffeomorphism-invariant scheme and in the presence of G F ’t Hooft anomalies, the supersymmetric Ward identities imply that the partition function has a non-holomorphic dependence on the flavor parameters. We show this explicitly for the 2d torus partition function, Z T 2 $$ {Z}_{T^2} $$ , and for a large class of 4d partition functions on half-BPS four-manifolds, Z M 4 $$ {Z}_{{\mathcal{M}}^4} $$ — in particular, for M $$ \mathcal{M} $$ 4 = S 3 × S 1 and M $$ \mathcal{M} $$ 4 = Σ g × T 2. We propose a new expression for Z M d − 1 × S 1 $$ {Z}_{{\mathcal{M}}_{d-1}\times {S}^1} $$ , which differs from earlier holomorphic results by the introduction of a non-holomorphic “Casimir” pre-factor. The latter is fixed by studying the “high temperature” limit of the partition function. Our proposal agrees with the supersymmetric Ward identities, and with explicit calculations of the absolute value of the partition function using a gauge-invariant zeta-function regularization.

Abstract We explore the geometric interpretation of the twisted index of 3d N $$ \mathcal{N} $$ = 4 gauge theories on S 1 × Σ where Σ is a closed Riemann surface. We focus on a rich class of supersymmetric quiver gauge theories that have isolated vacua under generic mass and FI parameter deformations. We show that the path integral localises to a moduli space of solutions to generalised vortex equations on Σ, which can be understood algebraically as quasi-maps to the Higgs branch. We show that the twisted index reproduces the virtual Euler characteristic of the moduli spaces of twisted quasi-maps and demonstrate that this agrees with the contour integral representation introduced in previous work. Finally, we investigate 3d N $$ \mathcal{N} $$ = 4 mirror symmetry in this context, which implies an equality of enumerative invariants associated to mirror pairs of Higgs branches under the exchange of equivariant and degree counting parameters.

Introduction: Advent of new technologies leads the construction industry in utilizing the modern techniques, especially in the earthwork process. The machine guidance system is one of such examples which allows the operator to work more efficiently by using the design on the display screen. Methods: This paper outlines a new Building Information Modeling (BIM) approach to earthwork design with the development of module system which calculates the actual earth volume and generates a TIN surface for machine guidance. This method has importance in generating Triangular Irregular Network (TIN) surface which can be used for visualization of the 3D model as well as for the machine guidance. Results and discussion: The integration of IT based system with the earthwork site results in higher efficiency and productivity. In earthwork process, the proper flow of information is essential as it can increase the transparency and lead to process improvement. This module provides an easy approach for the model generation with its user-friendly interface.

Abstract We study 3d N = 2 $$ \mathcal{N}=2 $$ supersymmetric gauge theories on closed oriented Seifert manifolds — circle bundles over an orbifold Riemann surface —, with a gauge group G given by a product of simply-connected and/or unitary Lie groups. Our main result is an exact formula for the supersymmetric partition function on any Seifert manifold, generalizing previous results on lens spaces. We explain how the result for an arbitrary Seifert geometry can be obtained by combining simple building blocks, the “fibering operators.” These operators are half-BPS line defects, whose insertion along the S 1 fiber has the effect of changing the topology of the Seifert fibration. We also point out that most supersymmetric partition functions on Seifert manifolds admit a discrete refinement, corresponding to the freedom in choosing a three-dimensional spin structure. As a strong consistency check on our result, we show that the Seifert partition functions match exactly across infrared dualities. The duality relations are given by intricate (and seemingly new) mathematical identities, which we tested numerically. Finally, we discuss in detail the supersymmetric partition function on the lens space L(p, q) b with rational squashing parameter b 2 ∈ ℚ, comparing our formalism to previous results, and explaining the relationship between the fibering operators and the three-dimensional holomorphic blocks.

The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.

Early diagnosis and treatment of bacterial meningitis in children are essential, due to the high mortality and morbidity rates. However, lumbar puncture is often difficult, and cerebrospinal fluid (CSF) culture takes time. This meta-analysis aims to determine the diagnostic accuracy of blood procalcitonin for detecting bacterial meningitis in children. We conducted a systematic search on electronic databases to identify relevant studies. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated, and a hierarchical summary receiver operating characteristic curve and area under the curve (AUC) were determined. Eighteen studies with 1462 children were included in the analysis. The pooled sensitivity, specificity, and the DOR of blood procalcitonin for detecting bacterial meningitis were 0.87 (95% confidence interval (CI): 0.78–0.93); 0.85 (95% CI: 0.75–0.91), and 35.85 (95% CI: 10.68–120.28), respectively. The AUC for blood procalcitonin was 0.921. Blood procalcitonin also showed higher diagnostic accuracy for detecting bacterial meningitis than other conventional biomarkers, including serum C-reactive protein and leukocyte count, CSF leukocyte and neutrophil count, and CSF protein and glucose levels. Blood procalcitonin can be a good supplemental biomarker with high diagnostic accuracy in detecting bacterial meningitis in children.

Abstract We compute the supersymmetric partition function of N $$ \mathcal{N} $$ = 1 supersymmetric gauge theories with an R-symmetry on ℳ 4 ≅ ℳ g , p × S 1 $$ {\mathrm{\mathcal{M}}}_4\cong {\mathrm{\mathcal{M}}}_{g,p}\times {S}^1 $$ , a principal elliptic fiber bundle of degree p over a genus-g Riemann surface, Σ g . Equivalently, we compute the generalized supersymmetric index I ℳ g , p $$ {I_{\mathrm{\mathcal{M}}}}_{{}_{g,p}} $$ , with the supersymmetric three-manifold ℳ g , p $$ {\mathrm{\mathcal{M}}}_{g,p} $$ as the spatial slice. The ordinary N $$ \mathcal{N} $$ = 1 supersymmetric index on the round three-sphere is recovered as a special case. We approach this computation from the point of view of a topological A-model for the abelianized gauge fields on the base Σ g . This A-model — or A-twisted two-dimensional N $$ \mathcal{N} $$ = (2, 2) gauge theory — encodes all the information about the generalized indices, which are viewed as expectations values of some canonically-defined surface defects wrapped on T 2 inside Σ g × T 2. Being defined by compactification on the torus, the A-model also enjoys natural modular properties, governed by the four-dimensional ’t Hooft anomalies. As an application of our results, we provide new tests of Seiberg duality. We also present a new evaluation formula for the three-sphere index as a sum over two-dimensional vacua.