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Abstract Optical pulse shaping stands as a formidable technique in ultrafast optics, radio-frequency photonics, and quantum communications. While existing systems rely on bulk optics or integrated platforms with planar waveguide sections for spatial dispersion, they face limitations in achieving finer (few- or sub-GHz) spectrum control. These methods either demand considerable space or suffer from pronounced phase errors and optical losses when assembled to achieve fine resolution. Addressing these challenges, we present a foundry-fabricated six-channel silicon photonic shaper using microresonator filter banks with inline phase control and high spectral resolution. Leveraging existing comb-based spectroscopic techniques, we devise a system to mitigate thermal crosstalk and enable the versatile use of our on-chip shaper. Our results demonstrate the shaper’s ability to phase-compensate six comb lines at tunable channel spacings of 3, 4, and 5 GHz. Specifically, at a 3 GHz channel spacing, we showcase the generation of arbitrary waveforms in the time domain. This scalable design and control scheme holds promise in meeting future demands for high-precision spectral shaping capabilities.

ABSTRACT3D-printed ABS samples are treated with acetone and coated with copper oxide (CuO) for varying durations to understand how these treatment processes affect their mechanical and tribological properties. Tensile strength, flexural strength, coefficient of friction, and wear of ABS were analyzed under various pre-treatment and coating conditions and it is proved that acetone treatment and CuO coating can be effectively used to tune such properties to meet desired specifications. For 3D-printed ABS structures, CuO coating significantly enhances their tensile strength without acetone treatment. Although acetone treatment reduces their tensile strength as demonstrated, CuO coating can increase it again which means their tensile strength can be tuned by using the two processes. Furthermore, both acetone treatment and CuO coating improve their flexural strength. Additionally, acetone treatment and CuO coating both decrease their coefficient of friction. FESEM and EDS analyses were conducted on the structures to analyze and verify their wear properties.

Abstract Background Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied. Methods Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal–Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC. Results There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response. Conclusions Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer. Trial registration NCT02022202 . Registered 20 December 2013.

Cu–Ni–Sn spinodal alloys (Spinodal bronze) are potential materials with robust applications in components associated with defence applications like bearings, propellers, bushes, and shafts of heavily loaded aircraft, off-road vehicles, and warships. This paper presents a comparative study using water, Brine solution, and SAE 40 oil as the quenching media in regular bronze (Cu–6Sn) and spinodal bronze (Cu–9Ni–6Sn) alloys. Morphological analysis was conducted by optical microscopy, transmission electron microscopy (TEM), and X-ray diffraction technique (XRD) on bronze and spinodal bronze samples immersed in the three different quenching media to understand the grain size and hardness values better. Tribological analysis was performed to analyze the effect of quenching media on the wear aspects of bronze and spinodal bronze samples. The hardness value of the brine-aged spinodal bronze samples was as high as 320 Hv, and the grain size was very low in the range of 60 μm. A quantitative comparison between brine-aged regular bronze and brine-aged spinodal bronze showed that the hardness (Hv) was almost 80% higher for brine-aged spinodal bronze. Further, the grain size was approximately 30% finer for spinodal bronze when compared with regular bronze. When the load was increased in spinodal bronze samples, there was an initial dip in wear rate followed by a marginal increase. There was a steady increase in friction coefficient with a rise in load for brine-aged regular bronze and spinodal bronze samples. These results indicate that brine solution is the most effective quenching medium for cast Cu–Ni–Sn spinodal alloys.

The current study exhibits the influence of aging temperatures on the metallurgical, hardness, and dry-sliding wear behaviour of LM25 (Al-6.6Si-0.2Mg) alloy reinforced with Al2O3 particles. The LM25 alloy reinforced with 10 wt% of alumina particles was fabricated using the liquid metallurgy route followed by solutionizing and aging. The baseline LM25 alloy and its composite were solutionized at 538 °C for 8 h and were aged at 155, 165, and 175 °C for 12 h. Optical, FESEM, EDS, and X-ray diffraction analysis were done on the fabricated alloy and its composite in all conditions. The microstructure revealed the formation of the Mg2Si phase in the baseline alloy and the MgAl2O4 spinel generated at the composite interface of the aluminium matrix. The heat-treated alloy and composites were tested for their hardness on the Vickers microhardness tester. It was concluded that the aging temperature of 155 °C displayed significant enhancement in hardness values for tested samples. The heat-treated alloy and composite samples displayed an increment of 96% and 55% in hardness values relative to LM25. The wear rate and friction coefficient for the fabricated samples were analyzed using the pin-on-disc tribometer under dry sliding conditions. The hardness value increased from the as-cast state to samples aged at 155 °C and then decreased at 165 and 175 °C. Based on the wear study, a 14% and 25% decrease in the wear rate values for heat-treated alloy and composites were noted when sliding velocity was increased from 1 m/s to 3 m/s. However, the coefficient of friction (COF) decreased by 23% and 13% for the specimens in the same conditions. Furthermore, a similar trend was displayed by age-hardened LM25 alloy and the composite when subjected to varying load (5, 10, 15 N) condition. Lastly, the worn-out surface mechanisms were examined using FESEM analysis. Amongst the investigated samples, LM25/10 wt% Al2O3 composite aged at 155 °C revealed the least wear rate when subjected to an external load of 5 N and sliding velocity of 2 m/s. Therefore, it can be suggested to manufacture components in the automotive industry.

Background and Objective The study aimed to explore the antioxidant and antifungal properties of the invasive and prolific weed species Lantana camara. The weed distributed globally belonging to the Verbenaceae family is not confined to a specific region making the studys findings relevant and applicable worldwide.Methods The methodology involved assessing the free radical scavenging activity of the methanolic extract from L. camara leaves through in vitro tests against specific fungi utilizing the well diffusion method. The crude extract was isolated characterized and evaluated for its antioxidantfree radical scavenging activity by the DPPH 11-diphenyl-2-picrylhydrazyl radical method and further assessed for antifungal properties. Phytochemical screening and detection of phenolic and flavonoid content were conducted.Results Phytochemical constituents present in the L. camara leaf demonstrated antimycotic and anti-oxidant properties. The crude extract demonstrated free radical scavenging activity RSA ranging from 26.11 ww to 47.5 ww at concentrations varying from 30 microgmL to 150 microgmL. It showed high antioxidant activity at 150 microgmL concentration with an IC50 value of 1.8 to 24.1. Additionally it exhibited antifungal activity against certain Candida albicans species with a zone of inhibition of 9 mm comparable to the standard ketoconazole. Conclusion The findings suggest that L. camara may serve as a potential source of antioxidant and antifungal agents. However further research is needed to explore their complete potential and to ensure safety for medicinal purposes.

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.

Reactivation of fetal hemoglobin (HbF) is a commonly adapted strategy to ameliorate β-hemoglobinopathies. However, the continued production of defective adult hemoglobin (HbA) limits HbF tetramer production affecting the therapeutic benefits. Here, we evaluated deletional hereditary persistence of fetal hemoglobin (HPFH) mutations and identified an 11-kb sequence, encompassing putative repressor region (PRR) to β-globin exon-1 (βE1), as the core deletion that ablates HbA and exhibits superior HbF production compared with HPFH or other well-established targets. PRR-βE1-edited hematopoietic stem and progenitor cells (HSPCs) retained their genome integrity and their engraftment potential to repopulate for long-term hematopoiesis in immunocompromised mice producing HbF positive cells in vivo. Furthermore, PRR-βE1 gene editing is feasible without ex vivo HSPC culture. Importantly, the editing induced therapeutically significant levels of HbF to reverse the phenotypes of both sickle cell disease and β-thalassemia major. These findings imply that PRR-βE1 gene editing of patient HSPCs could lead to improved therapeutic outcomes for β-hemoglobinopathy gene therapy.

Advancements in gene delivery and editing have expanded the applications of autologous hematopoietic stem and progenitor cells (HSPCs) for the treatment of monogenic and acquired diseases. The gene editing toolbox is growing, and the ability to achieve gene editing with mRNA or protein delivered intracellularly by vehicles, such as electroporation and nanoparticles, has highlighted the potential of gene editing in HSPCs. Ongoing phase I/II clinical trials with gene-edited HSPCs for β-hemoglobinopathies provide hope for treating monogenic diseases. The development of safe and efficient gene editing reagents and their delivery into hard-to-transfect HSPCs have been critical drivers in the rapid translation of HSPC gene editing into clinical studies. This review article summarizes the available payloads and delivery vehicles for gene editing HSPCs and their potential impact on therapeutic applications.

Full tomography of biphoton frequency comb states requires frequency mixing operations which are hard to scale. Here, the authors propose and demonstrate a protocol exploiting advanced Bayesian statistical methods and randomized measurements coming from complex mode mixing in electro-optic phase modulators.

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in irreversible visual loss usually in patients belonging to the age group of 15–35 years. Clinically, the patients present with sequential or bilateral, painless, progressive visual loss with central (or ceco-central) scotomas. Although the three mutations, namely, G11778A, T14484C, and G3460A contribute to >95% of LHON cases globally, the relative frequency of each mutation varies. Aims and Objectives: We aimed to assess the clinical and genetic profile of patients with mutation-positive LHON at a north Indian tertiary care center. Materials and Methodology: One hundred sixty-one patients (61 prospective and 100 retrospective) presenting with the clinical diagnosis of LHON were screened for the three known mitochondrial mutations (G1178A, G3460A, T14448C). Patients were assessed for detailed clinical, ophthalmological, and neurological examinations. Five milliliter of blood sample was taken to assess the three known mutations using DNA isolation and Sanger sequencing. Results and Discussion: Clinical profile of 83 patients with both positive and negative mutations was analyzed. Twenty-three out of 161 patients (14.3%) tested positive for either of the three mutations. The majority of the patients harbored G11778A mutation (56.52%) followed by T14484C (34.78%) and G3460A (8.69%). No statistical difference could be noted between the clinical profiles of mutation-negative and -positive patients.

Multisystem inflammatory syndrome in children (MIS-C) has emerged as one of the several challenges thrown by the ongoing severe acute respiratory syndrome-coronavirus 2 pandemic. Although diagnostic criteria of MIS-C have now been established to raise the clinical suspicion for the condition, the Kawasaki disease (KD)-like phenotype of MIS-C presents with additional therapeutic dilemmas. The treatment guidance till date remains empirical with consideration of intravenous immunoglobulin (IVIG) and glucocorticoids. However, treatment of cases refractory to the current conventional therapy with respect to biologics remains uncertain. We describe here, an 8-year-old boy with MIS-C (KD-like phenotype) with severe cardiac dysfunction refractory to IVIG and pulse methylprednisolone who responded to tumor necrosis factor-α inhibition using infliximab.

Abstract Background Allatotropin, a neuropeptide found in several invertebrates indirectly regulates vitellogenesis by stimulating juvenile hormone biosynthesis by the corpora allata. Here, we cloned and expressed the gene encoding allatotropin of Spodoptera litura (tobacco cutworm), a polyphagous pest in the Asian tropics. This study is aimed at studying the effect of recombinant protein on egg-laying in females of S. litura as it could be used as a method to control the pests from a reproductive perspective. Results The protein encodes a full-length open reading frame consisting of 173 amino acids and was rich in arginine (10%) and glutamic acid (9.3%). The theoretical pI of the protein was 5.47 and a hydrophobic signal peptide of 22 residues was predicted. The recombinant allatotropin was expressed in Escherichia coli BL21 (DE3) and purified by nickel exchange chromatography. The molecular weight of the recombinant protein was about 37 kDa and expression levels up to 5.3 mg/ml were achieved. Injection assay in vitro indicated that allatotropin induces egg-laying during the first scotophase after treatment in females of Spodoptera litura. Conclusion Allatotropin induces egg-laying in female moths and could be a potential molecule for the development of control strategies against Spodoptera litura. In this strategy, the protein if delivered to the females before mating may lead to accelerated egg deposition much before she encounters the male moths, thus the population being checked as the eggs deposited by the females are unfertilized. Thus, the present work could lead to the development of a protein based biopesticide resulting into a species-specific and an eco-friendly way of pest control.

Abstract I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY’s prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.

The development of haematopoietic stem cells into mature erythrocytes – erythropoiesis – is a controlled process characterized by cellular reorganization and drastic reshaping of the proteome landscape. Failure of ordered erythropoiesis is associated with anaemias and haematological malignancies. Although the ubiquitin system is a known crucial post-translational regulator in erythropoiesis, how the erythrocyte is reshaped by the ubiquitin system is poorly understood. By measuring the proteomic landscape of in vitro human erythropoiesis models, we found dynamic differential expression of subunits of the CTLH E3 ubiquitin ligase complex that formed maturation stage-dependent assemblies of topologically homologous RANBP9- and RANBP10-CTLH complexes. Moreover, protein abundance of CTLH’s cognate E2 ubiquitin conjugating enzyme UBE2H increased during terminal differentiation, and UBE2H expression depended on catalytically active CTLH E3 complexes. CRISPR-Cas9-mediated inactivation of CTLH E3 assemblies or UBE2H in erythroid progenitors revealed defects, including spontaneous and accelerated erythroid maturation as well as inefficient enucleation. Thus, we propose that dynamic maturation stage-specific changes of UBE2H-CTLH E2-E3 modules control the orderly progression of human erythropoiesis.

Abstract Objective The objective of this study was to establish the level of inter-examiner reliability for six common cervical manual and physical examination procedures used to assess the cervical spine. Materials: Reliability study that used a convenience sample of 51 patients between the ages of 16–70 years presenting with a chief complaint of neck pain. Two physical therapists independently performed the same series of cervical physical examination procedures on each of the participant. The clinicians were blinded to each other’s findings and the clinical status of the patient. Kappa coefficients (κ) were calculated for levels of agreement between the clinicians for each procedure. Results When assessing for asymmetrical motion, excellent levels of reliability (κ range: 0.88–0.96) were observed for the Bilateral Modified Lateral Shear (asymmetry criterion), Bilateral C2 Spinous Kick (asymmetry criterion) and Flexion-Rotation Tests. When pain provocation was used as the indicator of a positive test during palpation of the cervical facet joints, moderate to substantial levels of reliability (κ range: 0.53–0.76) were observed. When patients were instructed not to provide feedback to the clinicians about pain provocation during facet joint palpation and clinicians relied solely on their qualitative assessment of segmental mobility, the level of reliability was lower (κ range: 0.45–0.53). Due to 100 % prevalence of negative findings, Kappa values could not be calculated for the Sharp-Purser test or the Unilateral C2 Spinous Kick Test. Conclusions Most physical examination procedures examined in this study demonstrated moderate to excellent levels of inter-examiner reliability. Palpation for segmental mobility without pain provocation demonstrated a lower level of reliability compared to palpation for pain provocation. Correlation with clinical findings is necessary to establish validity and the applicability of these procedures in clinical practice.

Abstract Background Following head and neck trauma, the involvement of the cranio-cervical junction (CCJ) and its contribution to a patients transition to chronic pain, is poorly understood. The detection of hypermobility in this region is dependent on clinical examination and static imaging modalities such as x-ray, CT and MRI. Sagittal plane hypermobility of the CCJ is evaluated using saggital view, flexion-extension cervical radiographs. Frontal plane hypermobility is typically assessed using lateral bending and open mouth cervical radiographs. Unfortunately there is no established reliability surrounding the use of these measures. This study explores the reliability of radiographic measurements of lateral-bending open-mouth cervical radiographs. Methods Cervical open-mouth lateral-bending X-ray images were collected from 56 different patients between 18 and 60 years of age patients following cervical spine injury. These images were interpreted by two musculoskeletal radiologists and two clinicians (physiatrist and chiropractor), using a standard set of measurements. Measurements included qualitative and quantitative assessments of the amount of asymmetry noted between various osseous landmarks. Reliability statistics were calculated for levels of agreement using kappa coefficients (κ) and Intraclass Correlation Coefficients (ICC) for dichotomous and continuous variables, respectively. Results Reliability (κ) for qualitative assessments were moderate to substantial for asymmetry of neutral C2 spinous position, dens-lateral mass spacing, and “step off” between the lateral borders of the articular pillars of C2 and C1 lateral mass (κ range = .47–.78). ICC values for the quantitative measurements of dens-lateral mass spacing and “step off” between the lateral borders of the C2 articular pillars and C1 lateral mass were moderate to excellent (ICC range = .56–.97). Conclusions The qualitative and quantitative measurements used in this study demonstrated good to excellent inter-examiner reliability. Correlation with clinical findings is necessary to establish the utility of these measurements in clinical practice.

Transplantation of allogenic hematopoietic stem and progenitor cells (HSPCs) with C-C chemokine receptor type 5 (CCR5) Δ32 genotype generates HIV-1 resistant immune cells. CCR5 gene edited autologous HSPCs can be a potential alternative to hematopoietic stem cell transplantation (HSCT) from HLA-matched CCR5 null donor. However, the clinical application of gene edited autologous HSPCs is critically limited by the quality of the graft, as HIV also infects the HSPCs. In this study, by using mobilized HSPCs from healthy donors, we show that the CD34+CD90+ hematopoietic stem cells (HSCs) express 7-fold lower CD4/CCR5 HIV receptors, higher levels of SAMHD1 anti-viral restriction factor, and possess lower susceptibility to HIV infection than the CD34+CD90- hematopoietic progenitor cells. Further, the treatment with small molecule cocktail of Resveratrol, UM729 and SR1(RUS) improved the in vivo engraftment potential of CD34+CD90+ HSCs. To demonstrate that CD34+CD90+ HSC population as an ideal graft for HIV gene therapy, we sort purified CD34+CD90+ HSCs, treated with RUS and then gene edited the CCR5 with single sgRNA. On transplantation, 100,000 CD34+CD90+ HSCs were sufficient for long-term repopulation of the entire bone marrow of NBSGW mice. Importantly, the gene editing efficiency of ~90% in the infused product was maintained in vivo, facilitating the generation of CCR5 null immune cells, resistant to HIV infection. Altogether, CCR5 gene editing of CD34+CD90+ HSCs provide an ideal gene manipulation strategy for autologous HSCT based gene therapy for HIV infection.

A number of power electronics converter topologies are implemented as Wireless Power Transfer (WPT) systems applications expand. In these applications, the optimal converter design is essential for handling the high power and frequency operation. In this paper, Simulation & Hardware development of High frequency Inverter with 90KHz frequency with Pulse Width Modulation switching strategy is presented. The inverter topology is simulated in 2021a version MATLAB/Simulink with R and RL loads and its conversion ability is proven through relevant waveforms. Simultaneously designed and developed prototype model of power rating 100watt with Mosfet as switches at output voltage of 230V with R load and analyse the output behaviour of voltage waveforms at various loads. The outcomes show effective enhancements for the proposed design.

Background Chemotherapy-induced peripheral neuropathy is a common and often severe side effect from many chemotherapeutic agents, with limited treatment options. There is no literature on the use of topical cannabinoids for chemotherapy-induced neuropathy. Case Presentations The current manuscript presents a case series of patients presenting in oncology clinics at Sutter Health, CA and Mayo Clinic, Rochester, MN from April 2019 to December 2020 with chemotherapy-induced peripheral neuropathy who used topical creams containing the cannabinoids delta-nine-tetrahydrocannabinol (THC) and/or cannabidiol (CBD). Conclusions This case series suggests that topical cannabinoids may be helpful for patients with chemotherapy-induced peripheral neuropathy. This paper also discusses the potential mechanisms of action by which topical cannabinoids might alleviate established CIPN symptoms. A randomized placebo-controlled trial using a standardized product is planned to study the actual efficacy of such treatment.

Structural Maintenance of Chromosomes (SMC) complexes have ubiquitous roles in compacting DNA linearly, thereby promoting chromosome organization-segregation. Interaction between the Escherichia coli SMC complex, MukBEF, and matS-bound MatP in the chromosome replication termination region, ter, results in depletion of MukBEF from ter, a process essential for efficient daughter chromosome individualization and for preferential association of MukBEF with the replication origin region. Chromosome-associated MukBEF complexes also interact with topoisomerase IV (ParC2E2), so that their chromosome distribution mirrors that of MukBEF. We demonstrate that MatP and ParC have an overlapping binding interface on the MukB hinge, leading to their mutually exclusive binding, which occurs with the same dimer to dimer stoichiometry. Furthermore, we show that matS DNA competes with the MukB hinge for MatP binding. Cells expressing MukBEF complexes that are mutated at the ParC/MatP binding interface are impaired in ParC binding and have a mild defect in MukBEF function. These data highlight competitive binding as a means of globally regulating MukBEF-topoisomerase IV activity in space and time.

PurposeDeveloping large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets.Materials and methodsWe used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients). We trained a 3D U-Net convolutional neural network (CNN) segmentation model using our entire dataset, and used that model as a template to train models on the challenge datasets. We also trained versions of the template model using ablated proportions of our dataset, and evaluated the relative benefit of those templates for the final models. Finally, we trained a version of the template model using an out-of-domain brain cancer dataset, and evaluated the relevant benefit of that template for the final models. We used five-fold cross-validation (CV) for all training and evaluation across our entire dataset.ResultsOur model achieves state-of-the-art performance on our large dataset (mean overall Dice 0.916, average Hausdorff distance 0.135 across CV folds). Using this model as a pre-trained template for refining on two external datasets significantly enhanced performance (30% and 49% enhancement in Dice scores respectively). Mean overall Dice and mean average Hausdorff distance were 0.912 and 0.15 for the ProstateX-2 dataset, and 0.852 and 0.581 for the PROMISE12 dataset. Using even small quantities of data to train the template enhanced performance, with significant improvements using 5% or more of the data.ConclusionWe trained a state-of-the-art model using unrefined clinical prostate annotations and found that its use as a template model significantly improved performance in other prostate segmentation tasks, even when trained with only 5% of the original dataset.

NCC is responsible for around 30% of active epilepsy in endemic countries such as India. Knowing socioeconomic factors associated with NCC can help in decreasing the incidence of this disease. We intend to study socioeconomic risk factors in NCC patients and how these factors are different from patients without NCC. Consecutive 100 adult patients of NCC presenting to neurology services with probable NCC (symptomatic or asymptomatic) along with age- and sex-matched controls were interviewed with preset proforma and then data was compiled and analyzed statistically. The NCC group had significantly more people with lesser education level (53%) as compared to control group (42%) (P = 0.002), lower socioeconomic status, poor hand hygiene practices, and use of contaminated vegetables (40% NCC group, 1% control group, P < 0.0001). Open defecation practice was also more among NCC cases. Lower education and socioeconomic status, poor hand hygiene, and eating undercooked contaminated vegetables are modifiable factors that are more prevalent in patients of NCC compared to controls. Social interventions aiming at these will help to reduce NCC patients in our country. Keywords: Epilepsy, neurocysticercosis, seizure, Author(s): Aditya Choudhary (corresponding author) [1]; Neeraj Balaini [2]; Manoj Goyal [3]; Manish Modi [3]; Karthik V Mahesh [3]; Vivek Lal [3] Key Message: Social interventions aiming at improving educational [...]

Aim: This study was conducted with the objective of identifying and evaluating intrapartum fetal stress in connection with the type of delivery in bitches. Materials and Methods: A total of 26 bitches between 1 and 5 years, belonging to 10 different breeds were evaluated. Bitches were subjected to detailed clinico-gynecological examination based on history. Neonatal stress associated with spontaneous whelping (SW), assisted whelping (AW), and emergency cesarean section (EC) was evaluated using umbilical vein lactate (UL) estimation by collecting the blood from umbilical vein. Results: A high umbilical vein lactate value was associated with fetal distress. The mean umbilical lactate value was highest in EC (12.54±0.8 mmol/L) followed by AW (8.86±0.9 mmol/L) and the lowest value was found in SW (7.56±0.58 mmol/L). A significant increase (p

Counteracting oxidative stress is essential in all organisms. Here, the authors outline a mechanism used by actinomycete bacteria in which oxidation of zinc-binding RsrA blocks its interaction with σR by sequestering hydrophobic residues used to bind σRwithin its own core.

The Escherichia coli SMC complex, MukBEF, acts in chromosome segregation. MukBEF shares the distinctive architecture of other SMC complexes, with one prominent difference; unlike other kleisins, MukF forms dimers through its N-terminal domain. We show that a 4-helix bundle adjacent to the MukF dimerisation domain interacts functionally with the MukB coiled-coiled ‘neck’ adjacent to the ATPase head. We propose that this interaction leads to an asymmetric tripartite complex, as in other SMC complexes. Since MukF dimerisation is preserved during this interaction, MukF directs the formation of dimer of dimer MukBEF complexes, observed previously in vivo. The MukF N- and C-terminal domains stimulate MukB ATPase independently and additively. We demonstrate that impairment of the MukF interaction with MukB in vivo leads to ATP hydrolysis-dependent release of MukBEF complexes from chromosomes.

Endocarditis of percutaneously placed pulmonary valve is increasingly being recognized and reported as a potentially life-threatening complication. In this report, we discuss a 17-year-old male who presented with septic shock secondary to staphylococcal endocarditis of a percutaneously placed pulmonary valve.