bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary zinc intake and migraine in adults: a cross‐sectional analysis of the National Health and Nutrition Examination Survey 1999–2004
Authors: Liu Huanxian , Wang Qi , Dong Zhao , Yu Shengyuan
Published: January 2023

Objective

The study examined the relationship between dietary zinc intake and migraine.

Background

Neuroinflammatory and oxidative stress are involved in the pathogenesis of migraine. Little is known about the effects of zinc, an anti‐inflammatory and antioxidant trace element, on migraine.

Methods

The US National Health and Nutrition Examination Survey data from 1999 to 2004 were analyzed for this cross‐sectional study. Participants who had severe headache or migraine were classified as having migraine. Dietary zinc intake was evaluated using the 24 h dietary recall system.

Results

A total of 11,088 participants were included, of whom, 20.2% (2236/11,088) reported having migraine disease. Compared to the lowest dietary zinc intake quintile (Q1, ≤5.9 mg/day), the adjusted odds ratios for migraine in Q2 (6.0–8.4 mg/day), Q3 (8.5–11.2 mg/day), Q4 (11.3–15.7 mg/day), and Q5 (≥15.8 mg/day) were 0.73 (95% confidence interval [CI]: 0.61–0.88, p = 0.004), 0.71 (95% CI: 0.56–0.91, p = 0.013), 0.71 (95% CI: 0.57–0.90, p = 0.008), and 0.70 (95% CI: 0.52–0.94, p = 0.029), respectively. Sensitivity analysis of zinc supplementation survey participants also showed an association between dietary zinc intake and migraine. Compared to the lowest total zinc intake quintile (Q1: 0.5–9.6 mg/day), the adjusted odds ratios for migraine in Q3 (19.3–24.3 mg/day) and Q4 (24.4–32.5 mg/day) were 0.62 (95% CI: 0.46–0.83, p = 0.019) and 0.67 (95% CI: 0.49–0.91, p = 0.045), respectively.

Conclusions

Our findings indicate an inverse association between dietary zinc intake and migraine in adult Americans.
Promotion of glyoxylic acid penetration into human hair by glycolic acid
Authors: Uyama Makoto , Okabe Shinya , Kurashima Takumi , Kurinobu Rie , Takechi Miwa , Yoshiba Ryo , Miyoshi Rina , Noda Seigi , Kaneko Mio , Ikemoto Yuka , Takahara Atsushi , Higaki Yuji , Hama Tetsuya
Published: January 2023

Objective

Glyoxylic acid (GA) is widely used as a straight perming agent for hair care products, however, advanced GA penetration‐enhancing agents are desired due to the peculiar odour and hair colour fading caused by the continuous use of GA products. Hence, it is important to develop a penetration‐enhancing agent that helps minimize the GA concentration. We have found that the combined use of GA and glycolic acid (GCA) has a strong hair straightening effect.

Methods

Straightening hair test was carried out to the evaluation of the effect of additives. Liquid chromatography‐mass spectrometry (LC/MS) was performed to quantify the GA penetration amount into human hair. Attenuated total reflection (ATR) Fourier transform‐infrared spectroscopy (FT‐IR) and FT‐IR microscope were implemented to estimate the localization of GA in the hair.

Results

Straightening hair tests indicated that the hair straightening effect by GA was enhanced by the presence of GCA. LC/MS results showed that the addition of GCA enhanced the amount of GA that penetrated human hair by about four times. ATR FT‐IR and FT‐IR microscope measurements indicated that GA was localized more in the innermost region of hair (medulla) than the cortex and cuticle. The GA accumulated in the medulla disappeared after a hair straightener treatment at 180°C due to the chemical reaction.

Conclusions

The GA penetration‐enhancing effect of GCA is worth investigating to reduce the GA concentration in products for more comfortable use.
Effect of Na2SiO3 concentration on corrosion resistance and wear resistance of MAO ceramic film on the Al‐Mg‐Sc alloy
Authors: Wu Mingjin , Jiang Feng
Published: January 2023

Although Al‐Mg‐Sc alloy was widely applied to aviation aerospace field, they were vulnerable to local corrosion and wear in the process of long‐term service in severe environmental conditions. In this paper, micro‐arc oxidation (MAO) ceramic films on Al‐Mg‐Sc alloy substrate were prepared in electrolyte solutions with different Na2SiO3 concentrations, and the corrosion resistance and wear resistance of the MAO samples were studied. The experimental results of potentiodynamic polarization (PDS) and long‐term immersion tests indicated that the MAO ceramic film prepared in 10 g/L Na2SiO3 electrolyte solution had the best corrosion resistance, as manifested by no obvious cracks, serious collapse and corrosion products on the sample surface and no deep cracks and corrosion paths in the cross‐sectional area. The increase of Na2SiO3 concentration in electrolyte solution also improved the wear resistance of MAO ceramic film, as manifested by low wear depth (10 μm)and width (1 mm) of the MAO ceramic film prepared in 10 g/L Na2SiO3 electrolyte solution against GCr15 steel ball. Studies in mechanisms suggested that as the Na2SiO3 concentration in the electrolyte increased, the MAO ceramic film became denser, which could prevent the penetration of corrosive medium, promote the generation of the anti‐wear layer with SiO2 as the main component to enhance the wear resistance. MAO ceramic film formed in Na2SiO3 electrolyte solution provided good protective performance for Al‐Mg‐Sc alloy in the corrosion and wear conditions, which had a broader application prospect.
Layered immunity and layered leukemogenicity: Developmentally restricted mechanisms of pediatric leukemia initiation
Authors: Mendoza‐Castrejon Jonny , Magee Jeffrey A.
Published: January 2023

Hematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs) arise in successive waves during ontogeny, and their properties change significantly throughout life. Ontological changes in HSCs/MPPs underlie corresponding changes in mechanisms of pediatric leukemia initiation. As HSCs and MPPs progress from fetal to neonatal, juvenile and adult stages of life, they undergo transcriptional and epigenetic reprogramming that modifies immune output to meet age‐specific pathogenic challenges. Some immune cells arise exclusively from fetal HSCs/MPPs. We propose that this layered immunity instructs cell fates that underlie a parallel layered leukemogenicity. Indeed, some pediatric leukemias, such as juvenile myelomonocytic leukemia, myeloid leukemia of Down syndrome, and infant pre‐B‐cell acute lymphoblastic leukemia, are age‐restricted. They only present during infancy or early childhood. These leukemias likely arise from fetal progenitors that lose competence for transformation as they age. Other childhood leukemias, such as non‐infant pre‐B‐cell acute lymphoblastic leukemia and acute myeloid leukemia, have mutation profiles that are common in childhood but rare in morphologically similar adult leukemias. These differences could reflect temporal changes in mechanisms of mutagenesis or changes in how progenitors respond to a given mutation at different ages. Interactions between leukemogenic mutations and normal developmental switches offer potential targets for therapy.
Model and efficient algorithm for the portfolio selection problem with real‐world constraints under value‐at‐risk measure
Authors: Hooshmand F. , Anoushirvani Z. , MirHassani S.A.
Published: January 2023

Value‐at‐risk (VaR) is a widely acceptable risk measure in finance and particularly, in the portfolio selection problem (PSP). However, due to the non‐convexity, its incorporation into an optimization model makes it challenging and difficult to solve. Hence, the development of iterative‐based heuristic algorithms (IBHAs) utilizing the problem structure would be valuable. The existing IBHAs are either inefficient in terms of solution quality and running time or are just applicable to solve simple PSPs without any real‐world constraint (i.e., cardinality, position size, and transaction cost constraints). To overcome these shortcomings, in this paper, we present a novel IBHA to efficiently solve the PSP with real‐world constraints under VaR measure. Our method is based on iterative resolution of two restricted versions of the original model in which some of the binary variables utilized in the formulation of VaR measure are fixed at specific values. Computational experiments over real‐world instances indicate that not only the running time of our algorithm is short, but also its solution quality is much better than the existing IBHAs in 97% of instances with an average improvement of about 10%.
Elastosis in lung carcinoma: Immunohistochemical, ultrastructural and clinical studies
Authors: Fukushima Mitsuhiro , Fukuda Yuh , Kawamoto Masashi , Yamanaka Nobuaki
Published: January 2023

Elastosis is the pathological finding of focal deposits of elastic fibers in abnormal amounts within tissue. It is well described in the case of infiltrating carcinoma of the breast, but elastosis in lung carcinoma has not been previously documented in detail. We investigated the characteristics of elastosis in lung carcinoma with light and electron microscopies, and immunohistochemistry for α‐1‐antitrypsin. A total of 184 surgically resected primary lung carcinomas were studied. Elastosis was detected in adenocarcinomas (85/106), squamous cell carcinomas (11/60) and adenosquamous carcinomas (5/7), but not in small‐cell carcinomas (n = 4) or large‐cell carcinomas (n = 5). The degree of elastosis in each case was divided into one of five grades, graded as 3+ to 1–. The score of elastosis was significantly higher in adenocarcinoma than that in squamous‐cell carcinoma (P< 0.01). In the cases of adenocarcinoma, the mean score of elastosis in the well‐differentiated type (WD n = 43) was higher than that in the moderately differentiated (MD) (n = 39; P = 0.012) and poorly differentiated (PD) types (n = 24; P < 0.01). The mean score of elastosis in MD adenocarcinoma was also higher than that in the PD type (P < 0.01). Light‐ and electron‐microscopic analyses revealed that these elastic fibers in elastosis were composed of aggregates of thick mature and fine immature elastic fibers, and were positive for α‐1‐antitrypsin. It is suggested that both degraded elastic fibers and newly synthesized fibers are contained in the elastosis of lung carcinoma. Although no significant evidence was detected to suggest any correlation between elastosis and the degree of tumor invasion, the survival curves of adenocarcinomas with elastosis showed a significantly improved prognosis than of those without elastosis in the cases of stages IA and IB (n = 52; P = 0.026).
Electrostatic energy storage performances of La(Ni2/3Ta1/3)O3‐modified Na0.5Bi0.5TiO3 lead‐free ceramics
Authors: Weng Nan , Zhang Ji , Wang Jiajia , Pan Tianze , Wang Jing , Wang Yaojin
Published: January 2023

Ceramic capacitors with high electrostatic energy storage performances have captured much research interest in latest years. Sodium bismuth titanate (Na0.5Bi0.5TiO3)‐based ferroelectric ceramics show great potential due to their environment‐friendly composition, high polarization, and excellent relaxor properties. However, the nonergodic relaxor state of Na0.5Bi0.5TiO3‐based ceramics hampers the decrement of remanent polarization, leading to poor energy storage performance. Herein, the (1 − x)Na0.5Bi0.5TiO3–xLa(Ni2/3Ta1/3)O3 ceramics were designed to generate the transformation between nonergodic and ergodic relaxor state. As a result, the ceramics exhibit improved dielectric relaxation, slim polarization–electric field loops, and flattened current–electric field curves due to highly dynamic polar nanoregions. Particularly, the 0.85Na0.5Bi0.5TiO3–0.15La(Ni2/3Ta1/3)O3 ceramics show large breakdown electric field Eb (345 kV/cm), high recoverable energy density Wrec (3.6 J/cm3), and efficiency η (80.6%), revealing potential applications in electrostatic energy storage.
Sintering temperature–induced structural transition in LaCrO3‐based conducting oxides synthesized from nano‐powders
Authors: Liu Zenghui , Xu Jun , Zhai Junni , Guo Zhixuan , Wan Hongyan , Xue Tao , Li Jingrui , Niu Gang , Shi Peng , Wang Lingyan , Ren Wei , Tian Bian , Liu Hongzhong , Jiang Zhuangde , Ye Zuo‐Guang
Published: January 2023

Preparation condition plays a critical role in the structure and properties of ceramics. However, exactly how it affects lanthanum chromate (LaCrO3)‐based conducting oxides remains poorly understood. In this work, the effects of sintering temperature on the crystal structure, microstructure, and electrical conductivity of pure and Sr2+‐/Ca2+‐substituted LaCrO3 ceramics have been investigated. It is found that the calcining temperature can be reduced by 200–300 K to obtain a single‐perovskite structure by using nano‐powders as raw materials. A sintering temperature–induced structural transition from orthorhombic Pbnm phase to rhombohedral phase is found in La0.8Sr0.2CrO3, and the possible mechanism is attributed to a thermally induced transformation of the thermodynamic metastable orthorhombic to stable rhombohedral phase after thermal treatment at higher temperatures. The electrical conductivity in a broad temperature range (from room temperature up to 1923 K) is measured. The conductivity increases with the elevated sintering temperature and soaking time, and it shows a remarkable enhancement by introducing the Sr and Ca ions. These results suggest that the sintering temperature should be well controlled and optimized to obtain desired crystal structure and electrical conductivity in LaCrO3‐based materials for various applications.
Building feature‐based machine learning regression to quantify urban material stocks: A Hong Kong study
Authors: Yuan Liang , Lu Weisheng , Xue Fan , Li Maosu
Published: January 2023

Urban material stock (UMS) represents elegant thinking by perceiving cities as a repository of construction materials that can be reused in the future, rather than a burdensome generator of construction and demolition waste. Many studies have attempted to quantify UMS but they often fall short in accuracy, primarily owing to the lack of proper quantification methods or good data available at a micro level. This research aims to develop a simple but satisfactory model for UMS quantification by focusing on individual buildings. Generally, it is a “bottom‐up” approach that uses building features to proximate the material stocks of individual buildings. The research benefits from a set of valuable, “post‐mortem” ground truth data related to 71 buildings that have been demolished in Hong Kong. By comparing a series of machine learning‐based models, a multiple linear regression model with six building features, namely building type, building year, height, perimeter, total floor area, and total floor number, is found to yield a satisfactory estimate of building material stocks with a mean absolute percentage error of 9.1%, root‐mean‐square error of 474.13, and R‐square of 0.93. The major contribution of this research is to predict a building's material stock based on several easy‐to‐obtain building features. The methodology of machine learning regression is novel. The model provides a useful reference for quantifying UMS in other regions. Future explorations are recommended to calibrate the model when data in these regions is available.
New developments and concepts in the diagnosis and management of diabetes insipidus (AVP‐deficiency and resistance)
Authors: Angelousi Anna , Alexandraki Krystallenia I. , Mytareli Chrysoula , Grossman Ashley B. , Kaltsas Gregory
Published: January 2023

Diabetes insipidus (DI) is a disorder characterised by the excretion of large amounts of hypotonic urine, with a prevalence of 1 per 25,000 population. Central DI (CDI), better now referred to as arginine vasopressin (AVP)‐deficiency, is the most common form of DI resulting from deficiency of the hormone AVP from the pituitary. The less common nephrogenic DI (NDI) or AVP‐resistance develops secondary to AVP resistance in the kidneys. The majority of causes of DI are acquired, with CDI developing when more than 80% of AVP‐secreting neurons are damaged. Inherited/familial CDI causes account for approximately 1% of cases. Although the pathogenesis of NDI is unclear, more than 280 disease‐causing mutations affecting the AVP2 protein or AVP V2 receptor, as well as in aquaporin 2 (AQP2), have been described. Although the cAMP/protein kinase A pathway remains the major regulatory pathway of AVP/AQP2 action, in vitro data have also revealed additional cAMP independent pathways of NDI pathogenesis. Diagnosing partial forms of DI, and distinguishing them from primary polydipsia, can be challenging, previously necessitating the use of the water deprivation test. However, measurements of circulating copeptin levels, especially after stimulation, are increasingly replacing the classical tests in clinical practice because of their ease of use and high sensitivity and specificity. The treatment of CDI relies on desmopressin administration, whereas NDI requires the management of any underlying diseases, removal of offending drugs and, in some cases, administration of diuretics. A better understanding of the pathophysiology of DI has led to novel evolving therapeutic agents that are under clinical trial.
Effects of fermented broccoli stem and leaf residue on growth performance, serum characteristics and meat quality of growing pigs
Authors: Sun Hong , Qian Zhongcang , Wu Yifei , Tang Jiangwu , Shen Qi , Li Jiahui , Yao Xiaohong , Wang Xin
Published: January 2023

The aim of this study was to evaluate the effects of fermented broccoli stem and leaf residue (FBR) on the growth performance, serum biochemical characteristics, and meat quality of growing pigs. A total of 72 growing pigs (Durox × Landrace × Yorkshire) were subjected to three dietary treatments with different levels (0%, 5% and 10%) of FBR with three replicates for an experimental period of 70 day. The average daily feed intake of growing pigs was higher (p < 0.05) in the 5% FBR treatment compared with the control group (0% FBR). The serum urea nitrogen content in growing pigs was lower (p < 0.05) in the 5% and 10% FBR treatments. The lightness value was higher (p < 0.05) in the longissimus dorsi muscle of pigs fed 5% and 10% FBR diets compared with the control group, and the yellowness value was increased in pigs fed the 10% FBR diet compared with pigs fed the control diet. Overall, the beneficial effects of FBR supplementation on serum biochemical parameters, and meat colour without undermining the growth performance indicate that up to 10% FBR could be used in diets to enhance the production of growing pigs.
Ideological Positions and Committee Chair Appointments
Authors: Rehmert Jochen , Fujimura Naofumi
Published: January 2023

Committee chairs hold crucial positions in the legislative process and can push or quell legislative initiatives. While extant studies examine the formal powers and legislative consequences of committee chairs, we know less about their appointment. We examine who ruling parties (principal) appoint to committee chairs (agent) in order to minimize the risk of policy moving away from government positions. Using data from Japan (2003–2017) on the LDP, we test expectations derived from the principal‐agent framework, conditional on committee type. Japan makes an ideal case to study intraparty chair appointments due to its coalitions' office‐allocation patterns. We find that the party leadership appoints as chairs ideologically close MPs to committees with jurisdiction on high policy. However, we find no effect for chair appointments on particularistic committees. Using additional data on bill‐amendment rates, we emphasize the legislative consequences of political appointments in the legislative process.
The fusion crust of the Winchcombe meteorite: A preserved record of atmospheric entry processes
Authors: Genge Matthew J. , Alesbrook Luke , Almeida Natasha V. , Bates Helena C. , Bland Phil A. , Boyd Mark R. , Burchell Mark J. , Collins Gareth S. , Cornwell Luke T. , Daly Luke , Devillepoix Hadrien A. R. , van Ginneken Matthias , Greshake Ansgar , Hallatt Daniel , Hamann Christopher , Hecht Lutz , Jenkins Laura E. , Johnson Diane , Jones Rosie , King Ashley J. , Mansour Haithem , McMullan Sarah , Mitchell Jennifer T. , Rollinson Gavyn , Russell Sara S. , Schröder Christian , Stephen Natasha R. , Suttle Martin D. , Tandy Jon D. , Trimby Patrick , Sansom Eleanor K. , Spathis Vassilia , Willcocks Francesca M. , Wozniakiewicz Penelope J.
Published: January 2023

Fusion crusts form during the atmospheric entry heating of meteorites and preserve a record of the conditions that occurred during deceleration in the atmosphere. The fusion crust of the Winchcombe meteorite closely resembles that of other stony meteorites, and in particular CM2 chondrites, since it is dominated by olivine phenocrysts set in a glassy mesostasis with magnetite, and is highly vesicular. Dehydration cracks are unusually abundant in Winchcombe. Failure of this weak layer is an additional ablation mechanism to produce large numbers of particles during deceleration, consistent with the observation of pulses of plasma in videos of the Winchcombe fireball. Calving events might provide an observable phenomenon related to meteorites that are particularly susceptible to dehydration. Oscillatory zoning is observed within olivine phenocrysts in the fusion crust, in contrast to other meteorites, perhaps owing to temperature fluctuations resulting from calving events. Magnetite monolayers are found in the crust, and have also not been previously reported, and form discontinuous strata. These features grade into magnetite rims formed on the external surface of the crust and suggest the trapping of surface magnetite by collapse of melt. Magnetite monolayers may be a feature of meteorites that undergo significant degassing. Silicate warts with dendritic textures were observed and are suggested to be droplets ablated from another stone in the shower. They, therefore, represent the first evidence for intershower transfer of ablation materials and are consistent with the other evidence in the Winchcombe meteorite for unusually intense gas loss and ablation, despite its low entry velocity.
Donor‐specific antibodies after heart transplantation for Fontan‐associated protein‐losing enteropathy
Authors: Magnetta Defne A. , Hoch Virginia L. , Pinelli David , Monge Michael , Pahl Elfriede , Thrush Philip T.
Published: January 2023

Background

Despite ubiquitous exposure to sensitizing events, most Fontan PLE patients have low panel reactive antibodies (PRA). To assess whether they are at risk for donor‐specific antibody (DSA) memory response following heart transplantation (HT) when their PLE resolves, DSA profiles, incidence of rejection, and graft outcomes in Fontan recipients with and without PLE were compared.

Methods

Patient characteristics, appearance of newly detected DSA (nDSA), and graft outcomes were compared between patients with and without PLE using Wilcoxon rank‐sum and Chi‐squared tests. DSA burden was quantified using titers and time to nDSA, incidence of rejection, and graft outcomes were compared using Kaplan–Meier curves and the log‐rank test.

Results

Characteristics of patients with and without PLE were similar. Lymphocyte and albumin levels were lower in the PLE group, and flow PRA were comparable. Graft failure, CAV, and ACR were similar between the two groups, but AMR occurred more frequently in the PLE group (p = .03). Nearly 50% of PLE patients experienced class II nDSA by 1‐year post‐HT, compared to 30% of non‐PLE patients, but this difference was statistically not significant. Antibody burden did not differ between groups.

Conclusions

In this cohort, PLE was associated with AMR within the first‐year post‐HT, despite no significant difference in nDSA. Small patient numbers limited statistical comparison of nDSA in this cohort. PLE may be a risk factor for AMR post‐HT, and the possibility of a clinically important DSA memory response remains. Larger studies are necessary to better understand these preliminary findings.
A positive correlation between daily spiritual practice and reduced depressive symptoms among older adults: evidence from a nationally representative survey among the Indian population
Authors: Muhammad T. , Sulaiman KM. , Ansari Salmaan
Published: January 2023

Background

This study explored the factors associated with daily spiritual experiences of older adults and the association of daily spiritual experiences with major depressive disorder among older Indian adults.

Methods

Data for this study were derived from the Longitudinal Ageing Study in India (LASI) wave‐1. The sample size was 31 464 older adults age 60 years and above. Daily spiritual experience was assessed from four items (Cronbach's alpha: 0.89) adapted from the daily spiritual experience scale (DSES). Major depressive disorder was calculated using the Short Form Composite International Diagnostic Interview (CIDI‐SF). Descriptive, bivariate and multivariable forward stepwise logistic regression analyses were conducted to fulfil the objectives of the study.

Results

A proportion of 87.46% of older adults reported daily spiritual experiences in the study. Women had higher odds of spiritual experiences than men (adjusted odds ratio (aOR): 1.243; confidence interval (CI): 1.041–1.484). Older adults with higher education, those who were retired, those who reported community involvement or were physically active or belonged to the richest wealth quintile had higher odds of having daily spiritual experiences in comparison to older adults from the poorest wealth quintile. Further, older adults with daily spiritual experiences had significantly lower odds of major depressive disorder (aOR: 0.810; CI: 0.681–0.964) than older adults who did not report daily spiritual experiences.

Conclusion

The study suggests that daily spiritual practices can be a strategy to reduce major depressive symptoms and improve mental health and wellbeing of older adults, and future studies are warranted on this direction.
Do Citizens Judge Health Experts Through a Partisan Lens? Evidence from a Factorial Survey Experiment
Authors: Hanimann Anina
Published: January 2023

Scholars have claimed that right‐wing citizens are more skeptical about experts than left‐wing citizens. This article, however, argues that depending on their party affiliation, citizens prefer certain kinds of expertise over others. I confronted Swiss adults (N = 2,465) with individual risk advice on either flu vaccination or colorectal cancer screening. The quote varied regarding the expert providing the advice (e.g., academic, administration, or corporation) and the degree of policy advocacy. The citizens then assessed the experts' credibility and their own behavioral intention (e.g., get a flu shot). Citizens across the political spectrum are more likely to positively evaluate experts who represent institutions aligned with their beliefs. Moreover, right‐wing citizens are more skeptical about experts who advocate for specific policies than their left‐wing counterparts. This study underscores the need for a better understanding of how partisanship affects expert perceptions to manage health policy problems and other science‐based issues.
Interaction Between Surface and Underground Waters of the Itapemirim and Itabapoana River Basins in the Southern part of the State of Espírito Santo, Southeastern Brazil
Authors: Gonçalves José Augusto Costa , Almeida Milena Stefany Lage , Vieira Eliane Maria , Paiva Brenda Luiza Ferreira , Ferreira Mariana Araújo Mendes , Marcellino Lázaro Correa
Published: January 2023

Itapemirim River basin and part of the Itabapoana River basin are located in the southern area of the State of Espírito Santo, covering 26 municipalities. Knowledge of these basins’ hydrogeological characteristics provides information on the groundwater potential and the behavior of the river base flow during dry seasons. The objective of this study is to assess the relationship between surface and underground waters from the analysis of hydrograph units and information from tubular well logs. The Itabapoana River basin had the highest flow rates with mean specific capacity of 1415.1 m3 /h/m, while Itapemirim River basin wells yielded 0.6941 m3 /h/m. The percentage of underground discharge in relation to the total discharge exceeded 60% during all seasons in both basins.
Aproximaciones teórico - metodológicas en estudios territoriales: el caso del semillero de investigación: territorialidades periféricas urbano-rurales en la ciudad contemporánea
Authors: Pérez Martínez Manuel Enrique , Aranda Palacios Saida , Ramírez Ramos Yoame , Ortiz Ibarra Anabell , Alvarado Arias Natalia , Pulido Alejandra , Builes Gaitán Jenny Liliana , Reyes Guarnizo Andrea Bibiana , Pérez Alves Isabel , Navarro Alvarado Lina Estefanía , Tobar Eraso Deicy Alejandra , Zambrano López Kelly Yuliana , Quintero Gutiérrez María Camila , Marsiglia Escudero Viviana , Bernal Mora Martha Isabel , González Vivian Julieth
Published: January 2023

Los capítulos que integran este libro surgen de las contribuciones exploratorias realizadas por un equipo de jóvenes investigadoras quienes participaron en el proceso de formación teórica y metodológica virtual ofrecido durante 2021 por el semillero de investigación Territorialidades Urbano-Rurales en la Ciudad Contemporánea, promovido por el profesor e investigador Manuel Enrique Pérez Martínez de la Facultad de Estudios Ambientales y Rurales de la Pontificia Universidad Javeriana.
Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial
Authors: Kremer Lisa Jean , Medlicott Natalie , Sime Mary Jane , Broadbent Roland , Edmonds Liza , Berry Mary Judith , Austin Nicola C , Alsweiler Jane M , Reith David M
Published: January 2023

Objective

To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 μL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE).

Design

Multicentre, prospective, randomised controlled, non-inferiority clinical trial.

Setting

Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021.

Patients

Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE.

Interventions

The intervention: microdrop (approximately 7 μL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered.

Main outcome measures

The primary outcome measure was an ophthalmologist-determined successful ROPEE.

Results

One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction −0.05 to 0.05) and for Māori (95% CI no continuity correction −0.02 to 0.19).

Conclusion

VLD microdrops enable safe and effective screening for ROPEE in both Māori and non-Māori preterm infants.

Trial registration number

ACTRN12619000795190.
Hydroxychloroquine retinopathy screening guidelines: a false positive
Authors: Guven Tolga Kamil , Alexander Adam , Smith Guy T
Published: January 2023

Hydroxychloroquine sulphate (HCQ) is widely used for the treatment of a variety of rheumatological and dermatological conditions. Despite the advantages of HCQ as a treatment option, it is important to be aware of its potential retinal toxicity, which may be irreversible and progressive. In December 2020, The Royal College of Ophthalmologists published revised recommendations on monitoring HCQ retinopathy. Our case report highlights some of the shortcomings of blindly following their monitoring algorithm by presenting a case where apparent HCQ retinopathy resolved after Yttrium Aluminium Garnet (YAG) laser capsulotomy. The case reiterates the importance of thorough clinical examination. We suggest that while the acquisition of the spectral domain optical coherence tomography and fundus autofluorescence may be objective, their interpretation is subjective. Even with the use of artificial intelligence algorithms, false positives may be generated if the tests are confounded by copathology. There is no gold-standard test for detecting HCQ toxicity.
Biotissue stent for supraciliary outflow in open-angle glaucoma patients: surgical procedure and first clinical results of an aqueous drainage biostent
Authors: Ianchulev Tsontcho , Weinreb Robert N , Kamthan Gautam , Calvo Ernesto , Pamnani Ravinder , Ahmed Iqbal K
Published: January 2023

Background/aims

To report a first-in-human trial in open-angle glaucoma (OAG) subjects treated with a new microinterventional biostent-reinforced cyclodialysis technique to enhance supraciliary aqueous drainage.

Methods

Subjects (N=10; 74.1±7.9 years old) with OAG and cataracts underwent combined phacoemulsification cataract surgery with implantation of a permanent endoscleral supraciliary biostent to reinforce a controlled cyclodialysis cleft. The biostent comprised decellularised scleral allograft tissue microtrephined into a polymer tubular implant intraoperative/postoperative safety, intraocular pressure (IOP) and glaucoma medications were tracked through 12 months postimplantation.

Results

Baseline medicated IOP averaged 24.2±6.9 mm Hg with subjects using 1.3±0.8 IOP-lowering medications. Successful biostent implantation was achieved in all individuals without significant complications. Immediate IOP lowering was sustained through 1 year. Twelve-month mean IOP was reduced 40% from baseline to 14.6±3.2 mm Hg (p=0.004; paired two-tailed t-test), and 80% of patients achieved >20% IOP reduction. Biostenting reduced glaucoma medication use 62%, from a baseline mean of 1.3 required medications to 0.5 medications (p=0.037) at postoperative 12 months. The biotissue implant was well tolerated and demonstrated good endothelial safety with only 11% endothelial cell loss at 12 months after combined phaco-biostenting surgery, similar to that expected after phacoemulsification alone. Mean BCVA increased from baseline 20/130 Snellen to 20/36 at postoperative 12 months (p=0.001).

Conclusion

Supraciliary biostenting in OAG patients is well tolerated, has a good safety profile and produces long-term IOP-lowering while reducing glaucoma medication requirements.
Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials
Authors: Weng Qianlin , Goh Siew-Li , Wu Jing , Persson Monica S M , Wei Jie , Sarmanova Aliya , Li Xiaoxiao , Hall Michelle , Doherty Michael , Jiang Ting , Zeng Chao , Lei Guanghua , Zhang Weiya
Published: January 2023

Objective

Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol—the most commonly used analgesics for OA, remains unknown.

Design

Network meta-analysis.

Data sources

PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.

Eligibility criteria for selecting studies

Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.

Results

A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=−0.12, 95% credibility interval (CrI) −1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI −0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI −0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI −1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI −0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI −1.15 to 1.24; n=9 RCTs).

Conclusions

Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.

CRD42019135166
Modulation of myeloid and T cells in vivo by Bruton’s tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma
Authors: Sinha Meenal , Betts Courtney , Zhang Li , Griffith Madeline J , Solman Isabelle , Chen Brandon , Liu Eric , Tamaki Whitney , Stultz Jacob , Marquez Jaqueline , Sivagnanam Shamilene , Cheung Alexander , Pener Denise , Fahlman Anne , Taber Erin , Lerner Kimberly , Crocker Matthew , Todd Kendra , Rajagopalan Brindha , Ware Clarisha , Bridge Mark , Vo Johnson , Dragomanovich Hannah , Sudduth-Klinger Julie , Vaccaro Gina , Lopez Charles D , Tempero Margaret , Coussens Lisa M , Fong Lawrence
Published: January 2023

Background

In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC.

Methods

Previously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality.

Results

In the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator+(ICOS+) CD4+T cells and monocytes. Within the TME, ibrutinib monotherapy led to a trend in decreased B-cell abundance but increased interleukin-10+B-cell frequency. Monotherapy also led to a trend in increased mature CD208+dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1–) eomesodermin (EOMES+)) CD8+T-cell frequency, with a concomitantly decreased dysfunctional (PD-1+EOMES+) CD8+T-cell frequency. When ibrutinib was combined with chemotherapy, most of these immune changes were not observed. Patients with partial clinical responses had more diverse T and B cell receptor repertoires prior to therapy initiation.

Conclusion

Ibrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors.

Trial registration number

NCT02562898.
Association of immune-related adverse events with the outcomes of immune checkpoint inhibitors in patients with dMMR/MSI-H metastatic colorectal cancer
Authors: Nasca Vincenzo , Barretta Francesco , Corti Francesca , Lonardi Sara , Niger Monica , Elez Maria Elena , Fakih Marwan , Jayachandran Priya , Shah Aakash Tushar , Salati Massimiliano , Fenocchio Elisabetta , Salvatore Lisa , Cremolini Chiara , Ros Javier , Ambrosini Margherita , Mazzoli Giacomo , Intini Rossana , Overman Michael J , Miceli Rosalba , Pietrantonio Filippo
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

Methods

We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a ‘burden score’ constructed in a way that the same score value could be obtained by cumulating many low-grade irAEs or few high-grade irAEs; as a result, the lower the burden the better. Clearly, the irAE burden is not a baseline information, thus it was modeled as a time-dependent variable in univariable and multivariable Cox models.

Results

Among 331 patients, irAEs were reported in 144 (43.5%) patients. After a median follow-up time of 29.7 months, patients with higher burden of skin, endocrine and musculoskeletal irAEs (the latter two’s effect was confirmed at multivariable analysis) had longer overall survival (OS), as opposed to gastrointestinal, pneumonitis, neurological, liver, renal and other irAEs, which showed an harmful effect. Similar results were observed for progression-free survival (PFS). Based on the results retrieved from organ-specific irAEs, ‘aggregated’ burden scores were developed to distinguish ‘protective’ (endocrine and musculoskeletal) and ‘harmful’ (gastrointestinal, pneumonitis, neurological, hepatic) irAEs showing prognostic effects on OS and PFS.

Conclusions

Our results demonstrate that not all irAEs could exert a protective effect on oncologic outcome. An easy-to-use model for ICIs toxicity (burden score of protective and harmful irAEs) may be used as surrogate marker of response.
Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy
Authors: Dai Jie , Bai Xue , Gao Xuan , Tang Lirui , Chen Yu , Sun Linzi , Wei Xiaoting , Li Caili , Qi Zhonghui , Kong Yan , Cui Chuanliang , Chi Zhihong , Sheng Xinan , Xu Zelong , Lian Bin , Li Siming , Yan Xieqiao , Tang Bixia , Zhou Li , Wang Xuan , Xia Xuefeng , Guo Jun , Mao Lili , Si Lu
Published: January 2023

Background

Accumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and clinical characteristics between different anatomic locations of the primary lesions. Primary malignant melanoma of the esophagus (PMME) is a rare, highly aggressive disease with a poorer prognosis compared with that of non-esophageal mucosal melanoma (NEMM). In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis.

Methods

The response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. To explore the molecular mechanisms of the difference in therapeutic efficacy between PMME and NEMM, we performed genomic analysis, bulk RNA sequencing, and multiplex immunohistochemistry staining.

Results

We found that PMME (n=28) responded better to anti-PD-1 treatment than NEMM (n=64), with a significantly higher objective response rate (33.3% (95% CI 14.3% to 52.3%) vs 6.6% (95% CI 0.2% to 12.9%)) and disease control rate (74.1% (95% CI 56.4% to 91.7%) vs 37.7% (95% CI 25.2% to 50.2%)). Genomic sequencing analysis revealed that the genomic aberration landscape of PMME predominated in classical cancer driver genes, with approximately half of PMME cases harboring mutations inBRAF,N/KRAS, andNF1. In contrast, most NEMM cases were triple wild-type. Transcriptome analysis revealed that, compared with NEMM, PMME displayed more significant proliferation and inflammatory features with higher expression of genes related to antigen presentation and differentiation, and a less immunosuppressive signature with lower expression of inhibitory immune checkpoints and dedifferentiation-related genes. The multiplex immunohistochemical analysis also demonstrated higher CD8+T-cell infiltration in PMME than in NEMM.

Conclusions

PMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. Patient stratification based on anatomic origin can facilitate clinical decision-making in patients with mucosal melanoma following the verification of our results in future prospective studies.
Transcript capture and ultradeep long-read RNA sequencing (CAPLRseq) to diagnose HNPCC/Lynch syndrome
Authors: Schwenk Vincent , Leal Silva Rafaela Magalhaes , Scharf Florentine , Knaust Katharina , Wendlandt Martin , Häusser Tanja , Pickl Julia M A , Steinke-Lange Verena , Laner Andreas , Morak Monika , Holinski-Feder Elke , Wolf Dieter A
Published: January 2023

Purpose

Whereas most human genes encode multiple mRNA isoforms with distinct function, clinical workflows for assessing this heterogeneity are not readily available. This is a substantial shortcoming, considering that up to 25% of disease-causing gene variants are suspected of disrupting mRNA splicing or mRNA abundance. Long-read sequencing can readily portray mRNA isoform diversity, but its sensitivity is relatively low due to insufficient transcriptome penetration.

Methods

We developed and applied capture-based target enrichment from patient RNA samples combined with Oxford Nanopore long-read sequencing for the analysis of 123 hereditary cancer transcripts (capture and ultradeep long-read RNA sequencing (CAPLRseq)).

Results

Validating CAPLRseq, we confirmed 17 cases of hereditary non-polyposis colorectal cancer/Lynch syndrome based on the demonstration of splicing defects and loss of allele expression of mismatch repair genesMLH1,PMS2,MSH2andMSH6. Using CAPLRseq, we reclassified two variants of uncertain significance inMSH6andPMS2as either likely pathogenic or benign.

Conclusion

Our data show that CAPLRseq is an automatable and adaptable workflow for effective transcriptome-based identification of disease variants in a clinical diagnostic setting.