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Ammonia is a gas that produces zero carbon emissions when used in energy storage systems. Hence, there is increasing interest for the application of ammonia as fuel in various energy storage devices, specifically solid oxide fuel cells (SOFCs), as it has the potential to be efficient and environmentally friendly. In addition, compared to other fuel cells, SOFCs fed with ammonia offer various benefits such as such as sustainability and safety. This review compares and contrasts the opportunities and challenges of ammonia fuel cell technologies and helps to analyze their working principles. The main goal of this review is to investigate the viability of an "all-protonic" fuel cell using ammonia fuel while also highlighting the key challenges and limitations of implementing such technology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF) drive susceptibility to Mycobacterium tuberculosis (M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALF versus control-ALF (non-HIV-infected people). We further found a deficiency of surfactant protein D (SP-D) and reduced binding of SP-D to M.tb that had been exposed to HIV-ALF. Primary human macrophages infected with M.tb exposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, based on the limited number of participants in this study, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoring M.tb and potentially other pulmonary infections., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh., Methods: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables., Results: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development., Conclusions: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress., Competing Interests: Declaration of Competing Interest This work was supported by Global Development grants [OPPGD759 and OPP1165144] from the Bill & Melinda Gates Foundation to the University of California, Berkeley and by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health [grant number K01AI136885 to AL]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. In the interest of full disclosure and transparency, we would like to disclose the roles of co-authors. Douglas Granger is the founder and chief scientific and strategy advisor at Salimetrics LLC and SalivaBio LLC, and these relationships are managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and the University of California at Irvine. Liying Yan is the president of EpigenDx, Inc. Ann Meyer is the Associate Director of Operations at EpigenDx, Inc., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A number of studies have detected relationships between weather and diarrhea. Few have investigated associations with specific enteric pathogens. Understanding pathogen-specific relationships with weather is crucial to inform public health in low-resource settings that are especially vulnerable to climate change., Objectives: Our objectives were to identify weather and environmental risk factors associated with diarrhea and enteropathogen prevalence in young children in rural Bangladesh, a population with high diarrheal disease burden and vulnerability to weather shifts under climate change., Methods: We matched temperature, precipitation, surface water, and humidity data to observational longitudinal data from a cluster-randomized trial that measured diarrhea and enteropathogen prevalence in children 6 months-5.5 years from 2012-2016. We fit generalized additive mixed models with cubic regression splines and restricted maximum likelihood estimation for smoothing parameters., Results: Comparing weeks with 30°C versus 15°C average temperature, prevalence was 3.5% higher for diarrhea, 7.3% higher for Shiga toxin-producing Escherichia coli (STEC), 17.3% higher for enterotoxigenic E. coli (ETEC), and 8.0% higher for Cryptosporidium. Above-median weekly precipitation (median: 13mm; range: 0-396mm) was associated with 29% higher diarrhea (adjusted prevalence ratio 1.29, 95% CI 1.07, 1.55); higher Cryptosporidium, ETEC, STEC, Shigella, Campylobacter, Aeromonas, and adenovirus 40/41; and lower Giardia, sapovirus, and norovirus prevalence. Other associations were weak or null., Discussion: Higher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Our findings emphasize the heterogeneity of the relationships between hydrometeorological variables and specific enteropathogens, which can be masked when looking at composite measures like all-cause diarrhea. Our results suggest that preventive interventions targeted to reduce enteropathogens just before and during the rainy season may more effectively reduce child diarrhea and enteric pathogen carriage in rural Bangladesh and in settings with similar meteorological characteristics, infrastructure, and enteropathogen transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Grembi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood., (© 2024. The Author(s).)

Competing Interests: Declaration of Conflicting Interests : The author reports no conflicts of interest in this work.

Pentafluorophenyl (PFP) stationary phase is one of the most important phases after the C18 phase in terms of its applications. Three embedded polar groups (EPG)-containing stationary phases were newly synthesized to act the EPGs as additional interaction sites. The silica surface was initially modified with (3-aminopropyl)trimethoxysilane (APS). The APS-modified silicas were coupled with 2,3,4,5,6-pentafluorobenzoic acid, 2,3,4,5,6-pentafluorophenylacetic acid, and 2,3,4,5,6-pentafluoro-anilino(oxo)acetic acid to obtain Sil-PFP-BA, Sil-PFP-AA, and Sil-PFP-AN phases, respectively. The new phases were characterized by elemental analysis, ATR-FTIR, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The phases were evaluated with the Tanaka and Neue tests in reversed-phase liquid chromatography (RPLC). In addition, they were characterized as hydrophilic phases by the Tanaka test protocol used in hydrophilic interaction chromatography (HILIC) separation mode. The Sil-PFP-AA phase showed the highest molecular shape selectivity in RPLC, while Sil-PFP-AN achieved the highest separability in HILIC compared to the commercial PFP reference column. The Sil-PFP-AA phase was successfully applied for the analysis of capsaicinoids from real samples of fresh chili peppers (Capsicum spp.) in RPLC and the Sil-PFP-AN phase for vitamin C (ascorbic acid) in HILIC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Abul K. Mallik reports financial support was provided by Alexander von Humboldt Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Numerous bacteria naturally occur within spatially organised, multicellular communities called biofilms. Moreover, most bacterial infections proceed with biofilm formation, posing major challenges to human health. Within biofilms, bacterial cells are embedded in a primarily self-produced extracellular matrix, which is a defining feature of all biofilms. The biofilm matrix is a complex, viscous mixture primarily composed of polymeric substances such as polysaccharides, filamentous protein fibres, and extracellular DNA. The structured arrangement of the matrix bestows bacteria with beneficial emergent properties that are not displayed by planktonic cells, conferring protection against physical and chemical stresses, including antibiotic treatment. However, a lack of multi-scale information at the molecular level has prevented a better understanding of this matrix and its properties. Here, we review recent progress on the molecular characterisation of filamentous biofilm matrix components and their three-dimensional spatial organisation within biofilms., (© 2024 The Author(s).)

Controlled charge flows are fundamental to many areas of science and technology, serving as carriers of energy and information, as probes of material properties and dynamics 1 and as a means of revealing 2,3 or even inducing 4,5 broken symmetries. Emerging methods for light-based current control 5-16 offer particularly promising routes beyond the speed and adaptability limitations of conventional voltage-driven systems. However, optical generation and manipulation of currents at nanometre spatial scales remains a basic challenge and a crucial step towards scalable optoelectronic systems for microelectronics and information science. Here we introduce vectorial optoelectronic metasurfaces in which ultrafast light pulses induce local directional charge flows around symmetry-broken plasmonic nanostructures, with tunable responses and arbitrary patterning down to subdiffractive nanometre scales. Local symmetries and vectorial currents are revealed by polarization-dependent and wavelength-sensitive electrical readout and terahertz (THz) emission, whereas spatially tailored global currents are demonstrated in the direct generation of elusive broadband THz vector beams 17 . We show that, in graphene, a detailed interplay between electrodynamic, thermodynamic and hydrodynamic degrees of freedom gives rise to rapidly evolving nanoscale driving forces and charge flows under the extremely spatially and temporally localized excitation. These results set the stage for versatile patterning and optical control over nanoscale currents in materials diagnostics, THz spectroscopies, nanomagnetism and ultrafast information processing., (© 2024. The Author(s).)

This article summarizes my personal life story, from early education in India to research, teaching, and other activities in Boston and San Francisco. I have tried to illustrate how unplanned events shape one's path, and why the willingness to go with the flow is among one's most valuable attributes.

Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5 ∘ , and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.

Inoviruses are filamentous phages infecting numerous prokaryotic phyla. Inoviruses can self-assemble into mesoscale structures with liquid-crystalline order, termed tactoids, which protect bacterial cells in Pseudomonas aeruginosa biofilms from antibiotics. Here, we investigate the structural, biophysical, and protective properties of tactoids formed by the P. aeruginosa phage Pf4 and Escherichia coli phage fd. A cryo-EM structure of the capsid from fd revealed distinct biochemical properties compared to Pf4. Fd and Pf4 formed tactoids with different morphologies that arise from differing phage geometries and packing densities, which in turn gave rise to different tactoid emergent properties. Finally, we showed that tactoids formed by either phage protect rod-shaped bacteria from antibiotic treatment, and that direct association with a tactoid is required for protection, demonstrating the formation of a diffusion barrier by the tactoid. This study provides insights into how filamentous molecules protect bacteria from extraneous substances in biofilms and in host-associated infections., (© 2023. The Author(s).)

Column purchasing cost is an important issue for an analyst to analyze complex sample matrices. Here, we report the development of an amino acid (β-alanine)-derived stationary phase (Sil-Ala-C12) with strategic and effective interaction sites (amide and urea as embedded polar groups with C12 alkyl chain) able to separate various kinds of analytes. Owing to the balanced hydrophobicity and hydrophilicity of the phase, it showed exceptional separation abilities in both reversed-phase high-performance liquid chromatography (RP-HPLC) as a hydrophobic phase and hydrophilic interaction chromatography (HILIC) as a hydrophilic phase. Remarkably, the baseline separation was achieved for the challenging β- and γ-isomers of tocopherol. Usually, three columns such as pentafluorophenyl or C30, C18, and sulfobetaine HILIC are required for the analysis of vitamin E, capsaicinoids, and vitamin C in chili peppers ( Capsicum spp.), respectively. However, only Sil-Ala-C12 was able to separate these analytes. A single column can serve 3-4 purposes, which suggests that Sil-Ala-C12 had the potential to reduce column purchasing costs.

Background: Poor immune function increases children's risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period., Objectives: We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth., Methods: We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution., Results: At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36])., Conclusion: Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child's immune status., (© 2023 The Authors.)

Growth-preservation techniques are utilized in early onset scoliosis (EOS) cases requiring surgical intervention. The Shilla technique corrects the deformity by reducing additional surgeries with its growth-guidance effect. As with other techniques, various problems can be encountered following the administration of the Shilla technique. The aim of this study was to examine the effect of complications encountered with the Shilla treatment on correction and growth. Sixteen patients with a follow-up period of at least one year after receiving Shilla growth guidance for EOS were included in this retrospective study. No complications occurred, and no unplanned surgery was required in 50% of the cases. Of the remaining eight patients with postoperative implant-related complications (50%), six (37.5%) required unplanned surgery; this consequently caused implant failure in the proximal region in five cases (31.25%) and deep tissue infection around the implant in one case (6.25%). Deformity correction, spine length, and quality-of-life scores significantly improved in EOS through Shilla growth guidance. In terms of spinal growth and deformity correction, there were no significant differences between patients with implant-related problems and individuals without occurrences. Although implant-related problems were detected in our dataset and corresponding unexpected surgeries were necessary, these complications had no significant unfavorable influence on correction and spine growth.

Chaperone-Usher Pathway (CUP) pili are major adhesins in Gram-negative bacteria, mediating bacterial adherence to biotic and abiotic surfaces. While classical CUP pili have been extensively characterized, little is known about so-called archaic CUP pili, which are phylogenetically widespread and promote biofilm formation by several human pathogens. In this study, we present the electron cryomicroscopy structure of the archaic CupE pilus from the opportunistic human pathogen Pseudomonas aeruginosa. We show that CupE1 subunits within the pilus are arranged in a zigzag architecture, containing an N-terminal donor β-strand extending from each subunit into the next, where it is anchored by hydrophobic interactions, with comparatively weaker interactions at the rest of the inter-subunit interface. Imaging CupE pili on the surface of P. aeruginosa cells using electron cryotomography shows that CupE pili adopt variable curvatures in response to their environment, which might facilitate their role in promoting cellular attachment. Finally, bioinformatic analysis shows the widespread abundance of cupE genes in isolates of P. aeruginosa and the co-occurrence of cupE with other cup clusters, suggesting interdependence of cup pili in regulating bacterial adherence within biofilms. Taken together, our study provides insights into the architecture of archaic CUP pili, providing a structural basis for understanding their role in promoting cellular adhesion and biofilm formation in P. aeruginosa., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Böhning et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Novel stationary phases have been emerging recently. A β-alanine-derived embedded urea and amide group-containing C18 phase (Sil-Ala-C18) was prepared for the first time. The media were packed into a 150 × 2.1 mm HPLC column, and the newly designed column was evaluated with the Tanaka and Neue test protocols in reversed-phase liquid chromatography (RPLC) separation mode. Moreover, it was characterized by the Tanaka test protocol in hydrophilic interaction chromatography (HILIC) separation mode. The new phase was characterized by elemental analysis, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and solid-state 13 C cross-polarization magic angle spinning (CP/MAS) NMR spectroscopy at variable temperatures. The chromatographic evaluation involved very good separation of nonpolar shape-constrained isomers, polar and basic compounds in RPLC, and highly polar compounds in HILIC compared to the commercial reference columns. The Sil-Ala-C18 phase was able to separate the challenging β- and γ-isomers of tocopherol. The phase was also successfully applied for the separation of the isomers of tocopherol (vitamin E) and capsaicinoids from real samples of chili peppers ( Capsicum spp. ) in RPLC and ascorbic acid (vitamin C) in HILIC.

Background: Reliable and valid measurement of early child development are necessary for the design of effective interventions, programs, and policies to improve early child outcomes. One widely used measure in low- and middle-income countries (LMICs) is the Bayley Scales of Infant and Toddler Development III (Bayley-III). Alternatively, the Bangladeshi-adapted Ages and Stages Questionnaire Inventory (ASQ:I) can be administered more quickly, inexpensively, and with less training than the Bayley-III. We aimed to assess the concurrent validity of the Bangladeshi-adapted ASQ:I with the Bayley-III in children 4-27 months old in rural Bangladesh., Methods: The sample was a sub-sample (n = 244) of endline participants from an evaluation of an early child development intervention (July-August 2018). We assessed concurrent validity between internally age-standardized domain-specific and total scores using Pearson correlations both overall and stratified by age and intervention status. We also assessed correlations between scores and variables theoretically related to child development including maternal education and stimulation in the home., Results: The overall correlation between ASQ:I and Bayley-III total scores was moderate (r = 0.42 95% CI: 0.30-0.53), with no systematic differences by intervention status. Overall, concurrent validity was highest for the gross motor domain (r = 0.51, 0.40-0.60), and lowest for the fine motor domain (r = 0.20, 0.04-0.33). Total ASQ:I and Bayley-III scores were positively correlated with child stimulation and maternal education., Conclusion: The Bangladeshi-adapted ASQ:I is a low-cost tool that can be feasibly administered in rural Bangladesh, is moderately correlated with the Bayley-III, and can be used to measure child development when human, time, or financial resources are constrained., (© 2023. The Author(s).)

The textile industries of Bangladesh contribute significantly to the country's economy, accounting for more than 40% of total annual export. The quest of new technologies for efficient water and energy use in cotton knit dyeing could result in significant water savings and improve environmental sustainability. Textile wet processing consumes a lot of utilities (water and energy), and the water generates a lot of waste, which enhances chemical consumption and effluent management costs. The cotton knit fabric used in this study was pretreated and dyed utilizing ultrasonication at a lower temperature than conventional pretreatment and dyeing techniques in an attempt to establish ecofriendly wet processing in the textile industry. The bath chemicals were reused up to two times before dyeing in conventional techniques, and fabric properties such as whiteness index, weight loss, bursting strength, color fastness to light, washing, perspiration, rubbing, color strength and durability, or dimensional stability were evaluated and compared with the values obtained by conventional techniques. The color matching of reactive dyed fabric for ultrasonic pretreated fabric with and without reusing bath chemicals was determined. The sonicated scoured and bleached fabric's whiteness index was found to be acceptable, with relatively low weight loss; however, the bursting strength was found to be increased. Color fastness to light, washing, perspiration, and rubbing were found to be comparable to the conventional technique for low temperature ultrasonicated pretreated and reuse-1 pretreated dyed knit fabric. The results also revealed that there was no color degradation during ultrasonication. FT-IR spectroscopy and scanning electron microscopy (SEM) revealed no significant changes in the chemical composition of cellulose or the fabric shape of pretreated and dyed cotton knit fabric after ultrasonication., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Context: There remains significant variability in the use of postoperative opioids. On one end, it is proven that appropriate pain control is a critical aspect of patient management; on the other end, past few decades have been associated with major increases in opioid-related overdoses and addiction treatment. We hypothesized that several pre- and postoperative risk factors affecting long-term opioid use could be identified., Purpose: Evaluation of factors associated with minimum 5-year postoperative opioid use following adult spinal deformity surgery., Study Design/setting: Prospectively followed study group database., Patient Sample: Adult spinal deformity patients who underwent elective spine surgery between 2009 and 2016 were included., Outcome Measures: Opioid usage or otherwise at minimum 5 years follow-up. Use of nonopioid analgesics, weak and strong opioids METHODS: Retrospective analysis of patients undergoing elective spinal deformity surgery. A total of 37 factors comprising patient characteristics, radiographic measurements, operative details, preoperative and early postoperative opioid use, and mechanical complications and revisions were analyzed. Details on identified factors were provided., Results: A total of 265 patients (215F, 50M) from five sites were included. The mean follow-up duration was 68.4±11.7 (60-102) months. On average, 10.6±3.5 levels were fused. Preoperatively, 64 (24.2%) patients were using opioids. The rate of opioid users increased to 33.6% at 6 weeks and decreased to 21.5% at 6 months. During follow-up, there were patients who discontinued opioids, while others have started and/or restarted using opioids. As a result, 59 (22.3%) patients were still on opioids at the latest follow-up. Multivariate analyses showed that factors independently affecting opioid use at an average of 68 months postoperatively, in order of significance, were opioid use at sixth weeks, preoperative opioid use and opioid use at sixth months with the odds ratios of 2.88, 2.51, and 2.38 respectively. At these time points, factors such as age, number of comorbidities, tobacco use, the time of the last prior spine surgery and postoperative sagittal plane alignment affected opioid usage rates., Conclusions: Opioid usage at 6 weeks was found to be more predictive of long-term opioid use compared to preoperative use. Patients should be well informed to have realistic expectations regarding opioid use when considering adult spinal deformity surgery., Competing Interests: Declarations of Competing Interests One or more of the authors declare financial or professional relationships on ICMJE-NASSJ disclosure forms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Anatomical variations in the spine can be seen in each transitional border, either toward the skull as 'cranial shifts' or away as caudal shifts. Cranial shifting (CS) occurs when there is presence of occipitalization, C7 cervical costae or prominent transverse processes, thoracolumbar transitional vertebrae (TLTV) at T12 level, L5 sacralization, and sacrococcygeal fusion. We termed the coexistence of sacralization of L5 and absence or remarkable reduction of T12 rib size in AIS as Abul cranial shift (ACS). In this descriptive clinical study, primary aim was to investigate the incidence of ACS in AIS., Methods: Retrospective analysis of 187 surgically treated AIS cases was performed. Demographic data were recorded. The incidence of the specific set of anatomic variations including lumbosacral transitional vertebrae, TLTV, transverse process changes in C7 vertebrae, and posterior lumbosacral neural arch cleft formations (NACf) were evaluated in the radiological images., Results: 36 (19%) of 187 cases had ACS. ACS was detected in only 1 of 19 male cases (5%), while in 35 of 168 female cases (21%). Forty-one cases had sacralization of L5 (22%). There were only eleven pair of ribs in 14 (7%) of 187 cases and 10 (28%) of 36 ACS cases. Forty cases had NACf (21%). ACS and NACf coexistence were observed in 8 (22%) of 36 ACS cases., Conclusion: Accurate spinal column assessment is critical in adolescent idiopathic scoliosis (AIS). ACS may be observed in up to one in five AIS cases and its presence should not be neglected to avoid wrong level surgery., (© 2022. The Author(s), under exclusive licence to Scoliosis Research Society.)

Dislocation of the proximal interphalangeal joint of the fifth toe is an uncommon injury. When it is diagnosed in the acute phase, closed reduction is commonly an adequate treatment option. We describe a rare case of a 7-year-old patient who presented with late-diagnosed isolated dislocation of the proximal interphalangeal joint of the fifth toe. Although there are a few reported cases of late-diagnosis combined fracture-dislocation of the toes in both adult and pediatric age groups in the literature, belatedly diagnosed dislocation of the fifth toe without accompanying fracture in the pediatric population, to our knowledge, has not yet been reported. This patient achieved good clinical outcomes after treatment via open reduction and internal fixation.

We aimed to evaluate the intraobserver and inter- observer variations of the five primary classification systems for assessing tibial plateau fractures via standard X-Ray, biplanar and reconstructed 3D CT images. Using anteroposterior (AP) - lateral X-Ray, and CT images, one hundred tibial plateau fractures were evaluated and classified by four surgeons according to the AO, Moore, Schatzker, modified Duparc, and 3-column classification systems. Each observer evaluated the radiographs and CT images separately - listed each time randomly - on a total of 3 occasions: with an initial evaluation, and then subsequently in weeks 4 and 8. Intra- and interobserver variabilities were assessed using the Kappa statistics. Intra- and interobserver variabilities were 0.55 ± 0.03 and 0.50 ± 0.05 for AO, 0.58 ± 0.08 and 0.56 ± 0.02 for Schatzker, 0.52 ± 0.06 and 0.49 ± 0.04 for Moore, 0.58 ± 0.06 and 0.51± 0.06 for the modified Duparc, and 0.66 ± 0.03 and 0.68 ± 0.02 for the 3-column classification. Evaluation of tibial plateau fractures using 3-column classification in conjunction with radiographic classifications has higher levels of consistency compared to radiographic classifications alone.

Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M.tb), is responsible for >1.5 million deaths worldwide annually. Innate immune cells, especially macrophages, are the first to encounter M.tb, and their response dictates the course of infection. During infection, macrophages exert a variety of immune factors involved in either controlling or promoting the growth of M.tb. Research on this topic has been performed in both in vitro and in vivo animal models with discrepant results in some cases based on the model of study. Herein, we review macrophage resistance and susceptibility immune factors, focusing primarily on recent advances in the field. We include macrophage cellular pathways, bioeffector proteins and molecules, cytokines and chemokines, associated microbiological factors and bacterial strains, and host genetic factors in innate immune genes. Recent advances in mechanisms underlying macrophage resistance and susceptibility factors will aid in the successful development of host-directed therapeutics, a topic emphasized throughout this review.

Angiogenesis inhibitor drugs targeting vascular endothelial growth factor (VEGF) signaling to the endothelial cell (EC) are used to treat various cancer types. However, primary or secondary resistance to therapy is common. Clinical and pre-clinical studies suggest that alternative pro-angiogenic factors are upregulated after VEGF pathway inhibition. Therefore, identification of alternative pro-angiogenic pathway(s) is critical for the development of more effective anti-angiogenic therapy. Here we study the role of apelin as a pro-angiogenic G-protein-coupled receptor ligand in tumor growth and angiogenesis. We found that loss of apelin in mice delayed the primary tumor growth of Lewis lung carcinoma 1 and B16F10 melanoma when combined with the VEGF receptor tyrosine kinase inhibitor, sunitinib. Targeting apelin in combination with sunitinib markedly reduced the tumor vessel density, and decreased microvessel remodeling. Apelin loss reduced angiogenic sprouting and tip cell marker gene expression in comparison to the sunitinib-alone-treated mice. Single-cell RNA sequencing of tumor EC demonstrated that the loss of apelin prevented EC tip cell differentiation. Thus, apelin is a potent pro-angiogenic cue that supports initiation of tumor neovascularization. Together, our data suggest that targeting apelin may be useful as adjuvant therapy in combination with VEGF signaling inhibition to inhibit the growth of advanced tumors., (© 2022 Federation of American Societies for Experimental Biology.)

The pathogen Mycobacterium tuberculosis (M.tb) resides in human macrophages, wherein it exploits host lipids for survival. However, little is known about the interaction between M.tb and macrophage plasmalogens, a subclass of glycerophospholipids with a vinyl ether bond at the sn-1 position of the glycerol backbone. Lysoplasmalogens, produced from plasmalogens by hydrolysis at the sn-2 carbon by phospholipase A 2 , are potentially toxic but can be broken down by host lysoplasmalogenase, an integral membrane protein of the YhhN family that hydrolyzes the vinyl ether bond to release a fatty aldehyde and glycerophospho-ethanolamine or glycerophospho-choline. Curiously, M.tb encodes its own YhhN protein (MtbYhhN), despite having no endogenous plasmalogens. To understand the purpose of this protein, the gene for MtbYhhN (Rv1401) was cloned and expressed in Mycobacterium smegmatis (M.smeg). We found the partially purified protein exhibited abundant lysoplasmalogenase activity specific for lysoplasmenylethanolamine or lysoplasmenylcholine (pLPC) (V max ∼15.5 μmol/min/mg; K m ∼83 μM). Based on cell density, we determined that lysoplasmenylethanolamine, pLPC, lysophosphatidylcholine, and lysophosphatidylethanolamine were not toxic to M.smeg cells, but pLPC and LPC were highly toxic to M.smeg spheroplasts, which are cell wall-deficient mycobacterial forms. Importantly, spheroplasts prepared from M.smeg cells overexpressing MtbYhhN were protected from membrane disruption/lysis by pLPC, which was rapidly depleted from the media. Finally, we found that overexpression of full-length MtbYhhN in M.smeg increased its survival within human macrophages by 2.6-fold compared to vector controls. These data support the hypothesis that MtbYhhN protein confers a growth advantage for mycobacteria in macrophages by cleaving toxic host pLPC into potentially energy-producing products., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article, (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This retrospective study aimed to present the clinical and radiological features of functional scoliosis due to LLD and LLD concurrent with AIS; it also aimed to define their relationships for differentiating functional scoliosis due to LLD and LLD concurrent with AIS., Methods: This study was conducted as a single-center retrospective comparative study on 47 scoliosis patients with diagnosed LLD, aged 10-18 years. Cases with a diagnosis of structural LLD were divided into two groups according to the presence or absence of concurrent AIS. Data on demographics and the angle of trunk rotation on a sacral basis (ATR sacrum ) were recorded. Limb length was clinically measured with a tape measure and clinical LLD (C-LLD) scoliometer test. Cobb angle, axial rotation, pelvic obliquity, and radiological LLD (R-LLD) were obtained from standing spine radiographs and measured by two blinded orthopedic spine surgeons., Results: The prevalence of LLD was 6.7% in scoliosis patients in our study population. Cobb angle and apical rotation were higher in the LLD concurrent with AIS group than in the LLD group (p ≤ 0.05). The C-LLD scoliometer test results were strongly correlated with both C-LLD tape measure (r = 0.651; p = 0.000) and ATR sacrum (r = 0.688; p = 0.000)., Conclusion: LLD may develop as a result of adaptive changes due to scoliosis, or a concurrent condition to scoliosis. Cobb angle and apical rotation are the features that differentiate AIS from functional scoliosis in patients with LLD. The C-LLD scoliometer test can be an effective, practical, and useful method for measuring C-LLD, but its validity and reliability should be determined., Trial Registration: This study was retrospectively registered at ClinicalTrials.gov (number: NCT04713397, date of registration: 01/14/2021)., Level of Evidence: III., (© 2021. Scoliosis Research Society.)

Various toxic chemicals are discharging to the environment due to rapid industrialization and polluting soil, water, and air causing numerous diseases including life-threatening cancer. Among these pollutants, Cr(VI) or hexavalent chromium is one of the most carcinogenic and toxic contaminants hostile to human health and other living things. Therefore, along with other contaminants, the removal of Cr(VI) efficiently is very crucial to keep our environment neat and clean. On the other hand, silica has a lot of room to modify its surfaces as it is available with various sizes, shapes, pore sizes, surface areas etc. and the surface silanol groups are susceptible to design and prepare adsorbents for Cr(VI). This review emphases on the progress in the development of different types of silica-based adsorbents by modifying the surfaces of silica and their application for the removal of Cr(VI) from wastewater. Toxicity of Cr(VI), different silica surface modification processes, and removal techniques are also highlighted. The adsorption capacities of the surface-modified silica materials with other parameters are discussed extensively to understand how to select the best condition, silica and modifiers to achieve optimum removal performance. The adsorption mechanisms of various adsorbents are also discussed. Finally, future prospects are summarized and some suggestions are given to enhance the adsorption capacities of the surface-modified silica materials., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to determine the adequacy of spine surgery fellowship training (SSFT) in Turkey and what is needed for further development by interviewing current fellows., Methods: Forty male orthopaedics and traumatology or neurosurgery specialists who had completed SSFT in three different spine centers in Turkey between 2010 and 2018 were asked to complete a survey with 29 questions about SSFT in Turkey. Thirty specialists responded, and the collected data were analyzed., Results: Twenty-seven (90%) participants were orthopaedic and traumatology specialists and three (10%) were neurosurgery specialists, with a mean age of 39 (range = 35-53) years. Most participants received their residency training in the provinces where their fellowship training took place (11 (37%) in İstanbul and 7 (23%) in Ankara). The mean duration between residency training and the start of SSFT was 4 (range = 0-14) years, and the mean SSFT duration was 8 (range = 1-18) months. Seventy percent of participants had participated in spine surgery cases during their residency. Twenty-three (77%) participants reported that spine surgery training in their hospital during their residency was inadequate. Seventeen (57%) participants felt that they could not independently perform spine surgery cases before SSFT. All three centers (100%) participating in the study that offered SSFT were non-public institutions such as private hospitals and private university hospitals of medicine managed by a dedicated mentor with personal commitment, without any accreditation for SSFT. While 25 (83%) participants indicated that they felt competent enough to perform a standard spinal deformity surgery case independently at the end of SSFT, 5 (17%) indicated the opposite. This proportion, which was 43% at the end of residency, increased to 83% after SSFT., Conclusion: The results of this study have demonstrated the importance of SSFT in spine surgery as a specialty with a potentially high risk of complications that require prolonged case observation, challenging work-up, and adequate equipment. In this regard, there is a need for regulations on accreditation in government health facilities that provide ideal conditions. We propose to offer SSFT to all surgeons interested in spine surgery in Turkey by conducting further studies supported by an optimal health sector that ensures the appropriate requirements, in accordance with the declaration of TOTEK (The Turkish Orthopaedics and Traumatology Education Council), training workshops, and an accredited master's degree program in spine surgery or subspecialty.

Angiogenesis is required in embryonic development and tissue repair in the adult. Vascular endothelial growth factor (VEGF) initiates angiogenesis, and VEGF or its receptor is targeted therapeutically to block pathological angiogenesis. Additional pro-angiogenic cues, such as CXCL12 acting via the CXCR4 receptor, co-operate with VEGF/VEGFR2 to cue vascular patterning. We studied the role of FGD5, an endothelial Rho GTP/GDP exchange factor (RhoGEF), to regulate CXCR4-dependent signals in the endothelial cell (EC). Patient-derived renal cell carcinomas produce a complex milieu of growth factors that stimulated sprouting angiogenesis and endothelial tip cell differentiation ex vivo that was blocked by EC FGD5 loss. In a simplified model, CXCL12 augmented sprouting and tip gene expression under conditions where VEGF was limiting. CXCL12-stimulated tip cell differentiation was dependent on PI3 kinase (PI3K)-β activity. Knockdown of EC FGD5 abolished CXCR4 signaling to PI3K-β and Akt. Further, inhibition of Rac1, a Rho GTPase required for PI3K-β activity, recapitulated the signaling defects of FGD5 deficiency, suggesting that FGD5 may regulate PI3K-β activity through Rac1. Overexpression of a RhoGEF deficient, Dbl domain-deleted FGD5 mutant reduced CXCL12-stimulated Akt phosphorylation and failed to rescue PI3K signaling in native FGD5-deficient EC, indicating that FGD5 RhoGEF activity is required for FDG5 function. Endothelial expression of mutant PI3K-β with an inactivated Rho binding domain confirmed that CXCL12-stimulated PI3K activity in EC requires Rac1-GTP co-regulation. Together, this data identify the role of FGD5 to generate Rac1-GTP to regulate pro-angiogenic CXCR4-dependent PI3K-β signaling in EC. Inhibition of FGD5 activity may complement current angiogenesis inhibitor drugs., (© 2021 Federation of American Societies for Experimental Biology.)

Targeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential. Benzothiazole-based derivatives have emerged as potent inhibitors of enzymes such as EGFR, VEGFR, PI3K, topoisomerases, and thymidylate kinases. Several researchers have designed, synthesized, and evaluated benzothiazole scaffold-based enzyme inhibitors. Of these, several inhibitors have entered various phases of clinical trials. This review describes the recent advances and developments of benzothiazole architecture-based derivatives as potent anticancer agents., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Protonic ceramic fuel cells (PCFCs) have become the most efficient, clean and cost-effective electrochemical energy conversion devices in recent years. While significant progress has been made in developing proton conducting electrolyte materials, mechanical strength and durability still need to be improved for efficient applications. We report that adding 5 mol% Zn to the Y-doped barium cerate-zirconate perovskite electrolyte material can significantly improve the sintering properties, mechanical strength, durability and performance. Using same proton conducting material in anodes, electrolytes and cathodes to make a strong structural backbone shows clear advantages in mechanical strength over other arrangements with different materials. Rietveld analysis of the X-ray and neutron diffraction data of BaCe 0.7 Zr 0.1 Y 0.15 Zn 0.05 O 3-δ (BCZYZn05) revealed a pure orthorhombic structure belonging to the Pbnm space group. Structural and electrochemical analyses indicate highly dense and high proton conductivity at intermediate temperature (400-700 °C). The anode-supported single cell, NiO-BCZYZn05|BCZYZn05|BSCF-BCZYZn05, demonstrates a peak power density of 872 mW cm -2 at 700 °C which is one of the highest power density in an all-protonic solid oxide fuel cell. This observation represents an important step towards commercially viable SOFC technology., (© 2021. The Author(s).)

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth., Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders., Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes., Conclusions: Consistent with the metabolic telomere attrition hypothesis , our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories., Funding: Funded by the Bill and Melinda Gates Foundation., Clinical Trial Number: NCT01590095., Competing Interests: AL, CS, AH, SA, JB, AS, MR, SF, PM, SA, MR, LU, RN, KP, FD, PK, SL J.L. is a co-founder of Telomere Diagnostics Inc, a telomere measurement company. Assays and all other activity for the current report are, however, unrelated to this company. All other co-authors have no competing interests to declare. AM, BA, ST, JL, MH, MM, LF, JC No competing interests declared, (© 2021, Lin et al.)

Background: Minimally invasive percutaneous plate osteosynthesis (MIPO) and intramedullary nailing (IMN) are the two most commonly used methods for distal tibial extra-articular fractures; however, the ideal treatment is still on debate. The aim of this study was to compare MIPO and IMN in the treatment of distal tibial extra-articular fractures in terms of cost analysis according to health insurance records in Turkey., Methods: The data of patients who underwent either MIPO or IMN for the treatment of distal tibial extra-articular fractures between 2013 and 2018 were analyzed in this retrospective study. Patients' clinical data, as well as the overall expenses from the first admission until return to work including hospitalization, and all outpatient controls had been reviewed from the hospital's billing department. The total amount of money paid per month by Turkish National Social Security Institution to the patient until the patient's returns to work were also recorded., Results: 118 consecutive patients (35 female-83 male) with the mean age of 37.2±13.4 were participated to the study. IMN group consisted of 57 patients with a mean age of 36.7±12.8 years, and MIPO group consisted of 61 patients with a mean age of 37.8±13.6 years. No significant differences were observed between study groups in terms patients' age, gender, fracture classification (AO/OTA: Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association), soft-tissue injury (Tscherne classification), presence of type 1 open fracture, and presence of accompanying fibula fracture. There was no statistical difference between two groups in terms of pre-operative hospital stay (p=0.713). However, the mean length of hospital stay was significantly higher in the MIPO group (p=<0.001). The means of number of total outpatient controls, time to union, and return to work were also significantly higher in the MIPO group (p=0.005, p<0.001 and p<0.001, respectively). The mean hospital cost until discharge and the mean total cost until return to work were significantly higher in the MIPO group (p=0.001 and 0.001, respectively). The mean total costs of hospital stay and outpatient controls were also significantly higher in the MIPO group (p=0.001 and 0.004, respectively). The mean implant costs did not significantly differ between groups (p=0.179)., Conclusion: According to the results acquired from the present study, IMN is a better option compared to MIPO for the treatment of extra-articular distal tibial fractures in terms of costs paid by the national health insurance in Turkey.

Background: PI3Kα (Phosphoinositide 3-kinase α) regulates multiple downstream signaling pathways controlling cell survival, growth, and proliferation and is an attractive therapeutic target in cancer and obesity. The clinically-approved PI3Kα inhibitor, BYL719, is in further clinical trials for cancer and overgrowth syndrome. However, the potential impact of PI3Kα inhibition on the heart and following myocardial infarction (MI) is unclear. We aim to determine whether PI3Kα inhibition affects cardiac physiology and post-MI remodeling and to elucidate the underlying molecular mechanisms., Methods and Results: Wildtype (WT) 12-wk old male mice receiving BYL719 (daily, p.o.) for 10 days showed reduction in left ventricular longitudinal strain with normal ejection fraction, weight loss, mild cardiac atrophy, body composition alteration, and prolonged QT C interval. RNASeq analysis showed gene expression changes in multiple pathways including extracellular matrix remodeling and signaling complexes. After MI, both p110α and phospho-Akt protein levels were increased in human and mouse hearts. Pharmacological PI3Kα inhibition aggravated cardiac dysfunction and resulted in adverse post-MI remodeling, with increased apoptosis, elevated inflammation, suppressed hypertrophy, decreased coronary blood vessel density, and inhibited Akt/GSK3β/eNOS signaling. Selective genetic ablation of PI3Kα in endothelial cells was associated with worsened post-MI cardiac function and reduced coronary blood vessel density. In vitro, BYL719 suppressed Akt/eNOS activation, cell viability, proliferation, and angiogenic sprouting in coronary and human umbilical vein endothelial cells. Cardiomyocyte-specific genetic PI3Kα ablation resulted in mild cardiac systolic dysfunction at baseline. After MI, cardiac function markedly deteriorated with increased mortality concordant with greater apoptosis and reduced hypertrophy. In isolated adult mouse cardiomyocytes, BYL719 decreased hypoxia-associated activation of Akt/GSK3β signaling and cell survival., Conclusions: PI3Kα is required for cell survival (endothelial cells and cardiomyocytes) hypertrophic response, and angiogenesis to maintain cardiac function after MI. Therefore, PI3Kα inhibition that is used as anti-cancer treatment, can be cardiotoxic, especially after MI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Metasurfaces have recently entered the realm of quantum photonics, enabling manipulation of quantum light using a compact nanophotonic platform. Realizing the full potential of metasurfaces at the deepest quantum level requires the ability to tune coherent light-matter interactions continuously in space and time. Here, we introduce the concept of space-time quantum metasurfaces for arbitrary control of the spectral, spatial, and spin properties of nonclassical light using a compact photonic platform. We show that space-time quantum metasurfaces allow on-demand tailoring of entanglement among all degrees of freedom of a single photon. We also show that spatiotemporal modulation induces asymmetry at the fundamental level of quantum fluctuations, resulting in the generation of steered and vortex photon pairs out of vacuum. Space-time quantum metasurfaces have the potential to enable novel photonic functionalities, such as encoding quantum information into high-dimensional color qudits using designer modulation protocols, sculpting multispectral and multispatial modes in spontaneous emission, and generating reconfigurable hyperentanglement for high-capacity quantum communications.

Purpose: Magnetically controlled growing rods (MCGR) allow more frequent outpatient lengthenings to better mimic the physiological growth. The assessment of distractions with radiographs raised concerns regarding ionizing radiation exposure in growing children. The aim was to assess the necessity of radiographs after every lengthening of MCGR., Methods: A retrospective analysis of 30 consecutive patients (19F, 11 M) treated in a single institution between 2011 and 2017. Planned radiographs were taken based on a protocol, updated over the years to involve less frequent acquisitions. Unplanned radiographs were obtained after a patient complaint or a significant clinical examination finding. Outcome measures were preoperative and postoperative radiographic measurements, and complications such as proximal and distal junctional kyphosis and failure, rod or actuator breakage, collapse of previously achieved height or failure to lengthen and worsening of deformity., Results: Mean age at surgery was 7.5 (4-11) years. Mean follow-up was 45 (24-84) months. Mean number of lengthenings and radiographs per patient were 14.4 (8-23), and 13.2 (5-46), respectively. Nine patients (30%) experienced a total of 13 mechanical complications. Almost all complications were detected in unplanned radiographs. The probability of detecting a mechanical complication was significantly lower (p < 0.00001) in planned radiographs., Conclusions: Radiographs taken after routine lengthenings of MCGR are not likely to reveal any significant finding, since only 0.9% of planned radiographs displayed a mechanical complication. Exposing growing children to radiation with an intention of checking the MCGR device after every lengthening could not be justified. Obtaining post-lengthening radiographs with a decreased frequency and after a significant complaint or clinical finding may be considered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Aim: To evaluate antimicrobial activity of extracellular metabolites (EMs) of endophytic fungal isolates (EFIs) from Azadirachta indica . Materials & methods: EFIs were identified by internal transcribed spacer (ITS) sequencing. Antimicrobial activity, and minimum inhibitor concentration (MIC) and minimum bactericidal concentration (MBC) were determined using agar diffusion and microdilution method, respectively. Results: Seventeen EFIs were isolated from different organs of A. indica . Eight of them were identified based on ITS sequencing. The EMs of EFIs inhibited the growth of six multidrug-resistant (MDR) bacterial superbugs and three phytopathogenic fungi. The MDR bacterial superbugs are resistant to six commercial antibiotics of different generations but susceptible to EMs of EFIs. The MIC (0.125-1.0 μg/μl), MBC (0.5-4.0 μg/μl) and minimum fungicidal concentration (1.0-4.0 μg/μl) of the EMs from EFIs are lower enough. Conclusion: The EMs of the EFIs have promising antimicrobial activity against MDR bacteria and phytopathogenic fungi.

For the first time, we incorporated mesoporous micro-silica (5 μm, pore size = 50 nm) as a filler in epoxy resin aiming to enter polymer into the pore of the silica. As expected, the thermal stability of the composite increased remarkably, followed by noteworthy thermal degradation kinetics when compared to the controlled cured epoxy resin. Composites were prepared by the direct dispersion of modified nano-silica, modified mesoporous micro-silica, unmodified mesoporous micro-silica, non-porous micro-silica, and irregular micro-silica of various pore sizes as fillers in diglycidyl ether of bisphenol-A epoxy resin via ultra-sonication and shear mixing, followed by oven-curing with 4,4-diaminodiphenyl sulfone. DSC and TGA analyses demonstrated a higher glass transition temperature (increased by 3.65-5.75 °C) and very high activation energy for thermal degradation (average increase = 46.2%) was obtained for the same unmodified silica composite compared to pure epoxy, respectively., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Study Design: Retrospective analysis of prospectively collected data., Objective: To report the follow-up curve behaviors in different Sanders staging groups., Summary of Background Data: Vertebral body tethering (VBT) is a growth modulation technique that allows gradual spontaneous follow-up curve correction as the patient grows. There is a lack of scientific evidence regarding appropriate patient selection and timing of implantation., Methods: Patients were grouped into five as: Sanders 1, 2, 3, 4-5, and 6-7. Data were collected preoperatively, at the day before discharge, and at each follow-up. Outcome measures were pulmonary and mechanical complications, readmission, and reoperation rates. Demographic, perioperative, clinical, radiographic, and complication data were compared using Fisher-Freeman-Halton exact tests for categorical variables and Kruskal-Wallis tests for the continuous variables., Results: Thirty-one (29 F, 2 M) consecutive patients with a minimum of 12 months of follow-up were included. The mean age at surgery was 12.1 (10-14). The mean follow-up was 27.1 (12-62) months. The mean preoperative main thoracic curve magnitude was 47° ± 7.6°. For all curves, preoperative and first erect curve magnitudes, bending flexibility, and operative correction percentages were similar between groups (for all comparisons, P > 0.05). The median height gained during follow-up was different between groups (P < 0.001), which was reflected into median curve correction during follow-up. Total curve correction percentage was different between groups (P = 0.009). Four (12.9%) patients had pulmonary and six (19.4%) had mechanical complications. One (3.2%) patient required readmission and two (6.5%) required reoperation. Occurrence of pulmonary complications was similar in Sanders groups (P = 0.804), while mechanical complications and overcorrection was significantly higher in Sanders 2 patients (P = 0.002 and P = 0.018)., Conclusion: Follow-up curve behavior after VBT is different in patients having different Sanders stages. Sanders 2 patients experienced more overcorrection, thus timing and/or correction should be adjusted, since Sanders 3, 4, and 5 patients displayed a lesser risk of mechanical complications., Level of Evidence: 3.

Immune homeostasis in peripheral tissues is, to a large degree, maintained by the differentiation and action of regulatory T cells (Treg) specific for tissue Ags. Using a novel mouse model, we have studied the differentiation of naive CD4 + T cells into Foxp3 + Treg in response to a cutaneous Ag (OVA). We found that expression of OVA resulted in fatal autoimmunity and in prevention of peripheral Treg generation. Inhibiting mTOR activity with rapamycin rescued the generation of Foxp3 + T cells. When we varied the level of Ag expression to modulate TCR signaling, we found that low Ag concentrations promoted the generation of Foxp3 + T cells, whereas high levels expanded effector T cells and caused severe autoimmunity. Our findings indicate that the expression level of tissue Ag is a key determinant of the balance between tissue-reactive effector and peripheral Foxp3 + T cells, which determines the choice between tolerance and autoimmunity., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Angiogenesis inhibitors, such as the receptor tyrosine kinase (RTK) inhibitor sunitinib, target vascular endothelial growth factor (VEGF) signaling in cancers. However, only a fraction of patients respond, and most ultimately develop resistance to current angiogenesis inhibitor therapies. Activity of alternative pro-angiogenic growth factors, acting via RTK or G-protein coupled receptors (GPCR), may mediate VEGF inhibitor resistance. The phosphoinositide 3-kinase (PI3K)β isoform is uniquely coupled to both RTK and GPCRs. We investigated the role of endothelial cell (EC) PI3Kβ in tumor angiogenesis. Pro-angiogenic GPCR ligands were expressed by patient-derived renal cell carcinomas (PD-RCC), and selective inactivation of PI3Kβ reduced PD-RCC-stimulated EC spheroid sprouting. EC-specific PI3Kβ knockout (ΕC-βKO) in mice potentiated the sunitinib-induced reduction in subcutaneous growth of LLC1 and B16F10, and lung metastasis of B16F10 tumors. Compared to single-agent sunitinib treatment, tumors in sunitinib-treated ΕC-βKO mice showed a marked decrease in microvessel density, and reduced new vessel formation. The fraction of perfused mature tumor microvessels was increased in ΕC-βKO mice suggesting immature microvessels were most sensitive to combined sunitinib and PI3Kβ inactivation. Taken together, EC PI3Kβ inactivation with sunitinib inhibition reduces microvessel turnover and decreases heterogeneity of the tumor microenvironment, hence PI3Kβ inhibition may be a useful adjuvant antiangiogenesis therapy with sunitinib.

Equilibrium in the immune system is maintained by a balance between activation, which generates effector and memory cells, and suppression, which is mediated mainly by regulatory T cells. Understanding this balance and how to exploit it therapeutically is one of the dominant themes of modern immunology. The cytokine IL-2 was discovered as a growth factor for T cells and thus a key component of immune activation. It was initially used to boost immune responses in patients with cancer. Studies in experimental models and humans showed that the major function of IL-2 is to maintain functional regulatory T cells, and thus its essential function is in immune suppression. How the same cytokine can serve two opposing roles is a subject of current investigation. Because of these advances, IL-2 is now being tested as a cytokine for suppressing pathologic immune responses in autoimmune diseases and graft rejection. Fully understanding the biology of IL-2 may enable us to custom-design this cytokine for different applications in humans., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the impact of low-cost water, sanitation, handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural Bangladesh., Methods: We analyzed 1411 routine fecal samples from children 14±2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative PCR. Outcomes included the number of co-occurring pathogens; cumulative quantity of four stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat., Results: 326 (99.1%) control children had one or more enteropathogens detected (mean 3.8±1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: -11% [95% confidence interval [CI], -5 to -17%]; sapovirus: -9% [95%CI, -3 to -15%]; and adenovirus 40/41: -9% [95%CI, -2 to - 15%]). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm., Conclusions: WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, to identify factors that might play a role in conveying epigenetic memory through cell division, we report on the isolation of unfixed, native chromosomes from metaphase-arrested cells using flow cytometry and perform LC-MS/MS to identify chromosome-bound proteins. A quantitative proteomic comparison between metaphase-arrested cell lysates and chromosome-sorted samples reveals a cohort of proteins that were significantly enriched on mitotic ESC chromosomes. These include pluripotency-associated transcription factors, repressive chromatin-modifiers such as PRC2 and DNA methyl-transferases, and proteins governing chromosome architecture. Deletion of PRC2, Dnmt1/3a/3b or Mecp2 in ESCs leads to an increase in the size of individual mitotic chromosomes, consistent with de-condensation. Similar results were obtained by the experimental cleavage of cohesin. Thus, we identify chromosome-bound factors in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.