Background and Purpose: Colorectal cancer (CRC) is a major health problem worldwide. Dicarbonyl electrophiles, such as iso-levuglandins (isoLGs), are generated from lipid peroxidation and form covalent adducts with amine-containing macromolecules. We have shown high levels of adducts of isoLGs in colonic epithelial cells from patients with CRC. We thus investigated the role of these reactive aldehydes on colon cancer development. Experimental Approach: We investigated the effect of oral treatment with 2-hydroxybenzylamine (2-HOBA), a natural compound derived from buckwheat seeds that acts as a potent scavenger of electrophiles, on colon carcinogenesis using the azoxymethane-dextran sulfate sodium model of colitis-associated carcinogenesis and mice with epithelial-specific deletion of the adenomatous polyposis coli gene, as a model of sporadic cancer. We also tested 2-HOBA in a murine xenograft of human HCT116 CRC cells implanted into the flank of nude mice. Key Results: 2-HOBA is bioavailable in the colon of mice after supplementation in the drinking water and does affect the colonic microbiome. However, it reduced the level of isoLG adducts to lysine as well as tumorigenesis in both models of CRC. In parallel, we found that NRF2 activation and signaling was decreased in the colon of 2-HOBA-treated mice. Last, the growth of human tumors is significantly attenuated by 2-HOBA supplementation. Conclusion and Implications: 2-HOBA, which has been shown to be safe in humans, reduces colon tumorigenesis and growth of tumor cells in three distinct models of CRC. Thus, 2-HOBA represents a promising natural compound for the prevention and treatment of CRC.

A document by Muhammad Musaddique Ali Rafique. Click on the document to view its contents.

Background: Outcomes for children with high-risk renal (HRR) and INI-1-deficient (INI-) tumors are unacceptably poor. Concerns about excessive toxicity – as many are infants and/or undergo nephrectomy – have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies. As cause of death for children with these cancers remains overwhelmingly more from progressive disease rather than treatment toxicity, we examined the tolerability of an intensive ifosfamide-containing-regimen. Procedure: Retrospective review of children with HRR/INI- tumors treated at a single institution with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, carboplatin, etoposide (VDC-ICE) from 2006-2016. The primary outcome was regimen tolerability including kidney injury and grade 3-5 non-hematologic toxicities. Results: Fourteen patients with a median age of 1.7 years (range 0.1-10.5) treated with VDC-ICE were identified. Diagnosis included malignant rhabdoid tumor (n=9) [primary renal (n=2)]; diffuse anaplastic Wilms tumor (n=3); clear cell sarcoma of the kidney (n=1); and anaplastic chordoma (n=1). All children with primary renal tumors (43%) underwent complete (n=5) or partial nephrectomy (n=1) before chemotherapy. Nine (64%) completed all intended cycles of chemotherapy; n=5 (36%) did not due to disease progression. Unplanned hospitalizations occurred in 13 (93%) patients, most commonly for febrile neutropenia. No patient experienced severe organ toxicity, diminished renal function, treatment discontinuation due to toxicities, or treatment-related death. Conclusions: In children with HRR/INI- tumors, VDC-ICE chemotherapy was well-tolerated without excessive toxicities, even amongst young patients with solitary kidneys. Concerns about toxicity should not preclude an intensive ifosfamide-containing regimen from use in future trials in this population.

A new surgical approach for nephroblastoma with a tumor thrombus in the lower vena cava reaching the right atriumDear editor:Malignant renal tumors account for 6% of all pediatric tumors, with Wilms’ tumor (WT) being the most prevalent1. Tumor emboli (TE) invade the inferior vena cava (IVC) and reach the right atrium in 5–10% of patients2. IVC thrombectomyis is a complex procedure with a surgical complication rate of 16.2–20.3%3 . Preoperative chemotherapy can reduce tumor and thrombi volumes and improve patient survival. Preoperative chemotherapy and delayed surgery are usually recommended to reduce the size/extent of the TE and minimize surgical complications4; nevertheless, TE adhesion to the vascular wall (VW) is common and can result in fracturing of thrombi and difficulty in removing emboli. The right atrium and IVC are opened and TE are removed during cardiopulmonary bypass (CPB) and deep hypothermic circulation arrest (DHCA) 5, 6. Invasion of the VW by tumor thrombi may necessitate partial resection and repair. However, this can increase intraoperative blood loss and transfusion rate and carries a risk of disseminating intravascular coagulation and tumor spread7. Small movable thrombi can be removed through a buttonhole in the vessel, while larger thrombi may require more extensive cavotomies, and adherent thrombi require partial resection/reconstruction. However, the use of bioartificial blood vessels or vascular patch materials carries a risk of thrombosis and infection, and autologous vascular transplantation can cause damage8 . As children grow, they require patch materials with growth potential. Falciform ligament (FL) is useful for repairing the IVC during liver surgery. FL is easy to obtain and adjust in size/shape. Compared to polyester/polytetrafluoroethylene, vascular repair with FL is associated with a lower risk of thrombosis and graft infection, and no risk of rejection or need for therapeutic anticoagulation9, 10.There are currently no reports on tumor thrombus (TT) removal from the IVC and right atrium without CPB and CHCA. Here, we report a novel pediatric surgical technique wherein the right atrium was incised before thrombectomy was performed without CPB and DHCA, and FL was used to repair the IVC.A 5-year-old girl was diagnosed with WT with an IVC TT. Tumor size was reduced after four cycles of the CCCG-WT-2016 chemotherapy regimen (from 11.3×8.5×12.2 cm to 3.8×5.0×6.2 cm). The patient then underwent right radical nephrectomy and thrombectomy without CPB and DHAC. An intraoperative ultrasound showed that the TT had invaded the IVC and entered the pericardium over the second hepatic hilum, moving 1.5 cm into the right atrium. (Fig. 1). The left renal vein and IVC were cut longitudinally, and the thrombi in the left renal vein, IVC, and right atrium were removed. The TT adhered to the blood vessel wall and into the surrounding branches showing drill-like growth, which was fully removed. The longest vascular occlusion time was 33 min. Continuous sutures with 4-0 silk were used to repair the blood vessels. Complete resection of the right renal tumor, perirenal fat sac, and ureter was achieved. Stenosis of the IVC blocked blood flow, and the liver was enlarged. Therefore, blood flow could not be returned to the abdominal cavity, and the patient’s blood pressure decreased to 40/30 mmHg. The diaphragm was reopened and the suture was removed from the right anterior stenosis of the IVC. The right vessel wall of the IVC was found to have been eroded by the tumor and was not amenable to suturing. A 3-cm long and 1-cm wide section of the FL of the liver was resected and used to suture the forearm of the IVC continuously with 5-0 silk to repair the VW. Upon release of the clamp the IVC filled, the blood supply was restored, and the swelling/congestion of the liver was relieved. The patient made a full recovery and was discharged 10 days later without complications. Over the next 3 years of follow-up, the patient developed normally into a healthy school-age child.Blocking the right atrium below the level of the coronary artery, below the sinoatrial node, can thus be used to open the right atrium and remove TTs without CPB or DHCA, which offers a viable new surgical protocol. Fibrosis of blood vessels and TTs caused by multiple courses of chemotherapy in the IVC, and adhesion of these TTs, can lead to thickening and brittleness of the blood vessel walls and stenosis of the lumen. This can necessitate TT removal and suturing of the VW after a longitudinal split, which can in turn lead to further stenosis of the lumen, resulting in reflux disturbance of the hepatic venous system and systemic circulatory system below the second porta hepatis. The body adapts slowly and establishes systemic collateral circulation in the process of tumor growth; therefore, the enlargement and reconstruction of the vascular segment of the IVC at the diaphragm level can solve the problem of blood return obstruction. In contrast to more rigid materials, the FL is a strong double-sided peritoneum with excellent tension resistance and smooth surfaces suitable for facing blood vessels. It is easy to obtain, its removal has no deleterious effects, and it is, therefore, an ideal material for repairing the IVC. This case demonstrates that this surgical technique is safe and effective.

Background: Human papilloma virus (HPV) vaccination prevents the development of HPV-associated malignancies. Adolescent and young adult (AYA) survivors of childhood cancers and patients with sickle cell disease (SCD) are two vulnerable patient populations who would significantly benefit from HPV vaccination. Objective: In this mixed method study we determine the HPV vaccination rate amongst the AYA SCD and childhood cancer survivor populations. We then sought to describe patient and caregiver beliefs regarding HPV vaccination. Design/Method: We performed a retrospective chart review looking at vaccination status for patients seen in our clinics in 2019. Qualitative data was then collected via audio recorded interviews. Interviews were analyzed with a thematic content approach to understand attitudes regarding the HPV vaccination. Results: We found a notable difference between the rate of HPV vaccinations and other age-appropriate vaccinations in our childhood cancers survivors and patients with SCD. Qualitative interviews found that caregivers and AYA’s relied heavily on physician, recommendations for HPV vaccination, with a preference for subspecialist recommendation. A strong recommendation from a trusted subspecialty provider would create reassurance about vaccination and reduce misconceptions and concerns for side effects in the context of a chronic illness. Conclusion: Counseling from subspecialists could have a strong impact on understanding of the HPV vaccine in the context of chronic illness. This would likely help overcome many of the barriers to vaccination that are encountered by patients with SCD or oncology survivors.

Functional microbes have important application potential in the remediation of contaminated sites. The research on the application of chlorobenzenes (CBs) degrader in situ remediation is still limited. This study focused on the degradation performance of CBs degrader Serratia marcescens strain TF-1 in laboratory culture and contaminated soil. TF-1 assimilated chlorobenzene (CB) with degradation rate of 0.22-0.66 mg·g cell -1·h -1 in concentration of 20-200 mg·L -1. In addition, TF-1 also used sodium succinate and sodium citrate as substrates to co-metabolize CB, with degradation rates of 0.26-2.00 and 0.31-1.72 mol·g cell -1·h -1, respectively. The addition of TF-1 and sodium succinate in contaminated soil can remarkably promote the removal of CBs. Finally, combination of biostimulation and bioaugmentation using sodium succinate and TF-1 were carried out in a test field and CBs were almost completely removed by TF-1 within 10 d. Sequence analysis suggested that TF-1 colonized successfully in field soil, and the indigenous microorganism Azoarcus could be enriched. The novel strain was used for in-situ CBs biodegradation for the first time, and the results provide guidance for remediation of organic contaminated soil.

Although environmental DNA (eDNA) of aquatic species has been widely explored, the quantitative assessments of fish remain a challenge. eDNA approach proposed by Fukaya et al. (2021) gave a reliable abundance (the total fish population in the study area) estimates of coastal fish but was not as useful for assessing spatial distribution because of fewer eDNA samples relative to the study area. Hence, we evaluated the ability of the eDNA approach to estimate the abundance and distribution of fish in a semi-enclosed bay based on a numerical study. The evaluation was conducted as a case study on the ability of the eDNA approach according to the number of eDNA samples. Our study revealed that the eDNA approach can reliably estimate fish abundance regardless of the number of eDNA samples, if outliers of the fish density estimates are eliminated. However, when estimating spatial distribution, significant estimates were obtained only under those conditions wherein the eDNA concentration was identified in more than 70% of the study area. Therefore, it is necessary to explore other methodologies for broadly estimating eDNA concentrations with fewer samples. We have confirmed that the eDNA approach can reflect fish abundance but has limitations in estimating fish distribution. From above results, we expect our results to provide researchers with more insights into estimating the abundance and spatial distribution of fish using eDNA.

Background: Accumulated clinical studies utilize intracardiac echocardiography (ICE) to guide percutaneous left atrial appendage closure (LAAO), but its procedural success and safety compared to traditional transesophageal echocardiography (TEE) remain elusive. We performed a meta-analysis to compare efficacy and safety between ICE and TEE for LAAO. Methods: Studies were screened with four online databases (including the Cochrane Library, Embase, PubMed, and Web of Science) from their inception to 1 December 2022. We utilized random or fixed-effect model to synthesize the clinical outcomes. Subgroup analysis was performed to screen the potential confounding factors. Results: A total of twenty eligible studies with 3,610 atrial fibrillation patients (1,564 patients for ICE and 2,046 patients for TEE) were enrolled. Compared with TEE group, there was no significant difference in procedural success rate (RR=1.01; 95% CI: 1.00,1.02; P=0.171; I²=0.00%), total procedural time [weighted mean difference (WMD) = -5.58; 95%CI: -15.97, 4.81; P=0.292; I²=96.40%], contrast volume (WMD=-2.61; 95%CI: -12.25, 7.02; P=0.595; I²=84.80%), and fluoroscopic time (WMD=-0.34; 95%CI: −2.09, 1.41; P=0.705; I²=82.80%) in the ICE group. Subgroup analysis revealed ICE showed less contrast use than TEE in the lower proportion paroxysmal atrial fibrillation group and lower proportion hypertension. Conclusion: Our study suggests that ICE may have comparable efficacy and safety compared to TEE for LAAO.

there are several advantages to the use of transbronchial lung cryobiopsy (TBLC), including less trauma, fewer complications, large and high-quality specimens, and lower cost. This procedure is mainly used for the etiological diagnosis of diffuse parenchymal lung diseases (DPLD) [2] and its most common complications, including bleeding and pneumothorax. Virtual bronchoscopy navigation (VBN) can assist bronchoscopists in pinpointing the target area in the lung and designing an appropriate navigation pathway to accurately reach the target lesion [3]. Thus, VBN improves the rate of diagnosis and reduces the risk of bleeding and pneumothorax. In this report, which we believe to be the first of its kind, we performed TBLC guided by VBN.

A 34-year-old woman presented with acute abdomen, and her paraclinical data showed evidence concerning renal failure and its consequences in addition to ascites upon ultrasonography. Her symptoms did not abate after dialysis, and she underwent laparotomy, which revealed bladder perforation. Consequently, cystorrhaphy and cystoplasty were done without postoperative complications.

Background: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with poor minimal residual disease (MRD) response. However, there is no consensus on the optimal conditioning regimen for allo-HSCT. Procedure: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen for children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort. The conditioning regimen for allo-HSCT comprised total body irradiation (TBI), etoposide (ETP) and cyclophosphamide (CY) (UMIN000002025). Results: Twenty patients with post-induction MRD ≥ 10 −3 and two with MRD that could not be evaluated underwent allo-HSCT. Engraftment was confirmed in all patients. No transplantation-related mortality was observed. The 3-year event-free survival and overall survival after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. Conclusion: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was highly effective and feasible for Japanese children with intermediate-risk relapsed ALL.

A massive upsurge in the number of measles cases has been recently reported from South Africa, with 382 confirmed cases spread across five regions: Gauteng, Limpopo, Mpumalanga, Free State, and North West. The number of daily cases has been growing, resulting in more throat swabs and blood samples being sent to the National Institute for Communicable Diseases (NICD) for polymerase chain reaction (PCR) and measles serology testing. A rapid response to control the outbreak has emerged. All parents and caregivers residing in South Africa have been urged to check their children’s and the populations’ measles vaccination status respectively. Plans for case management, and prevention of further spread, not only in the province but also to neighboring countries, will need external support and funding.

Germinal centers (GC) are the sites of B cell clonal expansion, somatic hypermutation and clonal selection, a process that leads to the production of antibodies of higher affinity [1](#ref-0001). Efforts have been made to understand the kinetic of events controlling the GC and the production of specific antibodies in protective as well in pathogenic responses, such as autoimmunity and allergy. The ability of newly mutated GC clones to capture and present antigen to T follicular helper cells (Tfh) in the light zone of the GC is crucial for clonal survival and selection. Tfh cells produce IL-21, a key cytokine for the GC reaction and antibody responses [2](#ref-0002). However, it was not understood how IL-21 acts independently on T and B cells to mediate the GC reaction. In this study Quast and colleagues [3](#ref-0003) contribute to elucidate the specific role of IL-21 on the GC reaction and how IL-21 bioavailability affects the outcome of the GC response. They demonstrate that IL-21 influences Tfh cell differentiation and expansion early, before the GC establishment, as well later during GC development, through both autocrine and paracrine mechanisms, regardless of cognate T-B cell interactions.

RNA-binding proteins (RBPs) govern the lifespan of nearly all transcripts and play key roles in adaptive responses in microbes. A robust approach to examine protein-RNA interactions involves irradiating cells with UV light to form covalent adducts between RBPs and their cognate RNAs. Combined with RNA or protein purification, these procedures can provide global RBP censuses or transcriptomic maps for all target sequences of a single protein in living cells. Recent development of novel methods has quickly populated the RBP landscape in microorganisms. Here, we provide an overview of prominent UV cross-linking techniques which have been applied to investigate RNA interactomes in microbes. By assessing their advantages and caveats, this technical evaluation intends to guide the selection of appropriate methods and experimental design as well as to encourage the use of complementary UV-dependent techniques to inspect RNA-binding activity.

Economical uranium adsorption from seawater remains a crucial task for energy and environmental safety. Aiming for improving the mass transfer rate of uranium adsorption. Herein, a novel 2D porous aromatic framework(PAF) based on nucleophilic substitution of 2,5-dichloro benzonitrile was synthesized, with an ordered prous structure, excellent stability and selectivity of uranium extraction from seawater. PAF shows excellent uranium adsorption capacity of 637 mg/g and 3.22 mg/g in simulated and real seawater because of highly accessible pores on the walls of open channels. In addition, benefiting from the super-hydrophilicity due to the presence of amidoxime groups attributes high selectivity and ultrafast kinetics with an uptake rate of 0.43±0.03 mg/g.day and allowing half-saturation within 1.35±0.09 day. This strategy demonstrates a potential of PAF not only in uranium trap but also possess a power to monitor water quality. This technique can be extended in other applications by sensible planning target ligands

In order to build UHV AC transmission lines at high altitudes, it is necessary to analyze the audible noise characteristics of the existing EHV transmission lines at high altitude areas to guide the design. The typical test data of audible noise for 750 kV single circuit transmission lines measured at the Guanting long-term observation station, located at an altitude of 1854 m, were collected. Two methods of sorting the test data of audible noise and extracting valid data were given. Then the levels of audible noise under different weather conditions were analyzed, which showed that audible noise was raised with the increase of instantaneous rainfall and snowfall. Typical frequency spectrums of audible noise under different weather were also obtained, the pure tone at 100 Hz was more prominent under rainy and snowy weather, and the pure tone oscillation attenuated at different positions. Audible noise at different locations presented the better attenuation characteristics with the increase of distance during rainy days. The statistical results and calculated difference of audible noise over 5.5 hours with continuous rainfall were obtained. For the quiet plateau areas, the calculated difference between audible noise during rainy days and fair weather can be taken as 25 dB.

In future modern power systems, reliability and resilience could be an extreme challenge caused by the stability issues of the bidirectional power converters (BPCs). The non-linear dynamics of DC link voltage (DCLV) of BPCs in interaction with the existing linear control schemes may decrease the stability margin and cause operating-point-dependent instability issues. Existing approaches may solve this issue by reducing the DCLV control loop bandwidth, which considerably degrades the system performance. To tackle this issue, first, the root cause of the instability challenge is analytically investigated, and then, a non-linear stabilizer control scheme based on Lyapunov theorem is proposed. Considering the non-linear dynamic of the BPCs and the interaction between dynamics of DC link voltage and AC currents in the proposed stabilizer, it guarantees the stability of the converter in both directions of power flow and the full range of loading conditions. The performance of the proposed scheme is verified through simulation of the system under various operating conditions, considering uncertainties, disturbances, and short-circuit events, and comparing it with that of prevalent controllers.

A document by Annarita Marrano. Click on the document to view its contents.

Objective: To determine the effectiveness and gestational age-specific cut-off of Placental growth factor ( PlGF) in the second half of pregnancy for the prediction of adverse materno-fetal outcome among high-risk women. Methods: This secondary analysis explored associations between placental growth factor (PlGF) among women at high risk of PE at 20-22, 28-30, and 34-36 weeks of gestation. Women were divided into two groups based on PlGF levels cut-off derived after applying area under the receiver operating curve. Results: Of the 287 high risk women, 116(40.4%) had preeclampsia (PE). The cut off of PlGF was 224pg/ml, 211pg/ml and 176 pg/ml at 20-22, 28-30 and 34-36 weeks respectively, nearly 30% of the high risk women had PlGF below cut-off. The sensitivity and specificity of PE prediction using PlGF at 20-22 weeks was 81.0% and 72.2% respectively. For PlGF done at 28-30 weeks, the sensitivity and specificity of PE prediction till 32 weeks were 91.7% and 78.5% respectively. For PlGF done at 34-36 weeks, the sensitivity and specificity of PE prediction till 37 weeks was 95.8% and 73.3%, respectively. The negative predictive value of the PlGF at any gestation was nearly 90% or above for PE prediction till delivery. The accuracy of the test was highest at 28-30 weeks and for prediction before 37 weeks. Conclusion: The PlGF is a good marker to be done at 28-30 weeks for prediction of PE especially early onset and its adverse outcome; it can also be done at 34-36 weeks for preterm PE prediction.

This paper develops the stable adaptive time-dependent mesh scheme for a one-dimensional linear advection-diffusion equation with homogeneous Dirichlet boundary conditions and a sinusoidal initial condition. The aim is to present accurate stable moving nodes finite difference scheme with its stability and convergence. The boundary layer of the flow is exponential therefore difference scheme needs mesh refinement. The moving mesh method analyzes the problem physics and adjusts the mesh according to the problem as it moves nodes in the region of edges. We develop numerical results using four MMPDEs with varying numbers of nodes. A conservative semi-discretization finite difference scheme is used for the spatial derivative and backward Euler difference scheme is employed for the temporal derivative. We have presented five cases in detail to understand the physics of the problem. The proposed moving mesh finite difference method is considerably more efficient than the numerical methods offered in the literature.

Title page.Micro-emboli secondary to deep vein thrombosis as a cause of oxygen desaturation in covid 19 in pregnancy – a case report

Stress-related memory deficit is correlated with neurotransmitter system impairment. Exercise improves memory function and neurotransmitter. However, no studies have been performed to directly observe exercise-related effects on neurotransmitter in stress model, in association with memory function and hippocampal neuron. This study aimed to investigate the effect of exercise on hippocampal neuron and dopamine in stress model, followed by working memory in a passive avoid test. Our study found that stress rat had significantly neuron impairment and dopamine loss in hippocampus plus working memory deficit, which can be rescued by exercise. In summary, this study demonstrated that the neuroprotective effect of stress-associated working memory by treadmill exercise via ameliorated neuron impairment and dopamine loss.

Introduction With the rapid acceleration of the economic construction，the recent years have witnessed a huge development in the building industry． Based on the characteristics of the building industry，the technology of industrial robot has been introduced and the development of building robots has become an inevitable trend with pertinences． Methods In combination with the aspects of mechanical structure and control system and so on，the present situation of application and study of wall construction robots，decoration construction robots，maintenance construction robots，rescue construction robots and 3D printing construction robots at home and abroad are systematically reviewed in this paper．At the same time，from the aspects of structure design，sensor technology，navigation ＆ positioning technology and control system and so on. Conclusion out the future developmental direction of building robotics －－ integrating high－precision, lightweight design, intelligence and other features．

Some of the major future challenges in urban planning are related to population ageing. Although the improvement of longevity can certainly be regarded as a human development success, many issues emerge in parallel, including social, economic, and spatial aspects. The Covid-19 pandemic experience and social distancing measures implemented have highlighted the need for compact communities and neighborhoods and in this context, urban theories promoting locality and accessibility have gained significant momentum. This paper focuses especially on the 15-minute city concept and sets its core element, an isochrone of 15 minutes of walking under scrutiny, to highlight how ageing places urban planning theories under stress. It tests the assumption that time-oriented theories of accessibility which rely on population-wide conventions may overestimate the mobility capacity and walking speeds of older people, that may lead to fallacies in spatial analyses and urban planning practice, especially in ageing societies. The findings suggest that a 30% adjusted equivalent, such as a 20-minute convention for the 15-minute city, might be more appropriate for older age groups. This contributes to the broader discussion about proximity and the walkable city, regardless of whether it is based on a 5-, 10-, 15-, or 20-minute model.