bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystatin C for estimation of glomerular filtration rate in patients with spinal cord injury
Authors: Jenkins Margaret A. , Brown Douglas J. , Ierino Francesco L. , Ratnaike Sujiva I.
Published: July 2003

Background: Serum creatinine is not a satisfactory marker of glomerular filtration rate (GFR) in patients with spinal cord injury (SCI) who have varying degrees of muscle atrophy. In contrast to serum creatinine, serum cystatin C, a 13-kDa protein, is not affected by muscle mass and is therefore potentially a useful marker of GFR in patients with SCI. In addition, cystatin C is not dependent on sex or age and is not secreted by the renal tubule.

Aim: We assessed serum cystatin C as a surrogate marker of GFR in SCI patients.

Methods: Cystatin C was analysed using a particle-enhanced immunonephelometric assay (Dade Behring) in serum samples sent for routine measurement of creatinine (64 patients) and creatinine clearance (27 patients) from patients in the Spinal Unit of the Austin Health. We compared these results with serum cystatin C of 57 non-SCI patients who had had a creatinine clearance measurement during the study period.

Results: In patients with SCI, the reciprocal of cystatin C had a stronger correlation (r = 0·48, P<0·01) with creatinine clearance than the reciprocal of serum creatinine (r = 0·25, P<0·19). Further, the value of serum creatinine was much lower for a given creatinine clearance in SCI patients than in non-SCI patients; the serum cystatin C concentrations were equivalent.

Conclusion: The serum cystatin C is a convenient and more reliable surrogate marker of GFR than serum creatinine and will enable early detection of renal impairment. We need to confirm this finding with a larger study, including comparison with an accepted gold standard for GFR.
Glutathione peroxidase activity in blood cells from aspirin-induced asthma patients
Authors: Hassan A. M.
Published: July 2003

Aspirin and other inhibitors of cyclo-oxygenase precipitate acute bronchospasm in about 10% of adult asthmatics. It has been assumed that cyclo-oxygenase is involved in the pathogenesis of bronchospasm, but the precise mechanism remains poorly understood. The oxygenation products of arachidonic acid include hydroperoxyeicosatetraenoic acid and cyclic endoperoxides. Glutathione peroxidase (GPX) reduces semi-stable hydroperoxides to less reactive alcohols and removes H2O2 involved in inflammation. GPX could, therefore, modulate oxidation of arachidonic acid in the cyclo-oxygenase and lipoxygenase pathways, but the involvement of GPX in the pathogenesis of asthma has received little attention. We measured GPX activity in platelets, peripheral blood lymphocytes (PBL), red blood cells (RBC) and plasma from 13 patients with aspirin-induced asthma (AIA). Age- and sex-matched healthy individuals served as the comparison group. The patients had significantly higher GPX activity in platelets (P = 0·05) and tended to have high GPX activity (P = 0·08) in plasma but not in RBC or PBL. The results suggest that the increased GPX activity may be an adaptive advantage in AIA to protect against increased free radical production by inflammatory cells. That the higher GPX activity was not evident in all cell types studied may indicate a differential role played by them as effector cells in the pathogenesis of AIA.
Diagnostic value of adenosine deaminase in tuberculous pleural effusion: a meta-analysis
Authors: Goto Masashi , Noguchi Yoshinori , Koyama Hiroshi , Hira Kenji , Shimbo Takuro , Fukui Tsuguya
Published: July 2003

Background: Many studies have investigated the usefulness of adenosine deaminase activity (ADA) in pleural fluid for the early diagnosis of tuberculous pleurisy. To summarize the diagnostic characteristics of ADA we undertook a meta-analysis using a summary receiver operating characteristic (SROC) curve method.

Methods: Data sources were MEDLINE (1966-1999), the Cochrane Library and bibliographies of review and original articles. Studies were included if the absolute numbers of true positive, false negative, true negative and false positive observations were available or could be derived from the data presented; gold standards were described explicitly; and the criteria for a positive ADA result were reported. We constructed an SROC curve based on these extracted data to estimate the test characteristics.

Results: Forty articles were available for analysis. The gold standards used were pleural biopsy histology, microbiological examination of pleural fluid, pleural biopsy and sputum and the patient's clinical course or combinations of these. The sensitivity of ADA reported in the articles ranged from 47·1% to 100% and the specificity from 50·0% to 100%. The summary measure of test characteristics derived from the SROC curve was 92·2% for both sensitivity and specificity.

Conclusions: The test performance of ADA in tuberculous pleural effusion is reasonably good. Measurement of pleural ADA is thus likely to be a useful diagnostic tool for tuberculous pleurisy.
Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India
Authors: Kumar Prabhat , Luthra Kalpana , Dwivedi Manjari , Behl Vinay K , Pandey Ravinder M. , Misra Anoop
Published: July 2003

Objectives: Several factors, including abdominal obesity, insulin resistance, diabetes mellitus and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of apolipoprotein E (apo E) gene polymorphisms in premature myocardial infarction (MI) in this population. This study aimed to study the role of apo E gene polymorphisms in premature MI patients and their relation to serum lipid levels.

Design and methods: Apo E gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors.

Results: Higher frequencies of the apo E4 allele (P<0·0001) and of genotypes E3/E4 (P<0·005) and E4/E4 (P<0·005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45·7 (4·9-421·3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8·7 (0·9-86·6)] and those with a high waist : hip ratio [OR (95% CI): 5·6 (1·4-21·2)].

Conclusion: Based on the robust association, the apo E4 allele should be considered as an independent risk factor for premature MI in Asian Indians.
Genetic polymorphism of thiopurine S-methyltransferase in Argentina
Authors: Laróvere L. E. , de Kremer R. Dodelson , Lambooy L. H. J. , De Abreu R. A.
Published: July 2003

Background: Thiopurine methyltransferase (TPMT) catalyses the S-methylation of 6-thiopurine drugs, which are commonly used in the treatment of autoimmune diseases, leukaemia and organ transplantation. TPMT activity is polymorphic as a result of gene mutations. Ethnic variations in phenotype and genotype have been identified in previous population studies, but no information was available within Latin-American populations.

Aim: To establish the genetic polymorphism of TPMT in an Argentine population.

Methods: TPMT enzymatic activity of 147 healthy Argentine subjects was measured using a high-performance liquid chromatography method. The genotyping assay for nine defective alleles (TPMT*2 - *8) was based on restriction fragment length polymorphism polymerase chain reaction and allele-specific polymerase chain reaction methods.

Results: All subjects had detectable TPMT activity. Twelve individuals with low to intermediate activity were heterozygous for one of the mutant alleles: nine were TPMT*1/*3A, two TPMT*1/*2 and one TPMT*1/*4. All examined subjects with normal activity had wild-type genotype (TPMT*1/*1).

Conclusion: Variant TPMT alleles were present in 8·2% of the examined subjects, which is in accordance with other studies. The frequency of TPMT*3A, TPMT*2 and TPMT*4 was 3·1%, 0·7% and 0·3%, respectively. TPMT*3A was the most prevalent allele, which is in accordance with results from Caucasian populations. This study provides the first analysis of TPMT activity and allele frequency distribution in Argentina, South America.
Urinary free deoxypyridinoline excretion in lactating and non-lactating Arabic women of the United Arab Emirates
Authors: Miller C. J. , Dunn E. V. , Thomas E. J. , Sankarankutty M.
Published: July 2003

Background: This study aimed to measure urinary free deoxypyridinoline (Dpd) excretion in non-lactating and lactating Arabic women of the United Arab Emirates.

Methods: Morning urine specimens were obtained from 679 non-pregnant, non-lactating women and 268 lactating women. Commercial enzyme-linked immunoassay kits were used for urinary free Dpd determinations.

Results: For the non-lactating women, the mean urinary free Dpd excretion was 9·20 nmol/mmol creatinine (95% confidence interval: 8·82-9·59). This result was significantly higher than those reported elsewhere. There was a trend towards lower Dpd excretion with increasing age (ANOVA test of linearity P<0·05). Urinary free Dpd in lactating women was 9·92 (9·33-10·5); this was not significantly different from that of non-lactating women (P=0·052). Dpd excretion was higher in the first month post-partum, with a significant trend towards diminishing levels thereafter, returning to non-lactating levels by 9 months post-partum (ANOVA test for linearity P<0·005).

Conclusion: Dpd excretion in UAE Arabic women aged 20-44 years was higher than in other groups. This could be due to ethnicity or vitamin D status.
Evaluation of two new high-sensitivity methods for C-reactive protein
Authors: Rothkrantz-Kos Snjezana , Bekers Otto , Gubbels Armand , Drent Marjolein , Schmitz Maria P. J. , van Dieijen-Visser Marja P.
Published: July 2003

Background: The implementation of a high-sensitivity C-reactive protein (hs-CRP) assay as a routine laboratory parameter may be necessary. It would be most practical to use one CRP method giving reliable results for the whole concentration range. We report here the evaluation of two new hs-CRP methods, which cover both the low and the high concentration ranges.

Methods: The BN ProSpec hs-CRP (Dade Behring) and Synchron LX 201 PRO hs-CRP methods were compared with the existing hs-CRP IMMAGE1 method (taken as a reference) and, for the high concentration range, also with the routine Synchron LX1 20 CRP method (all from Beckman). Agreement among methods was examined for 521 samples. Reference values were estimated in 291 blood donors. Additionally, the influence of sample turbidity, a major problem of the present Synchron LX20 CRP method, was evaluated.

Results: Measurement of CPR by the BN ProSpec was linear down to 0·2 mg/L, whereas the linearity of Synchron LX20 PRO showed some systematic discrepancies. Over the whole measured range (0·2-250 mg/L), precision (coefficient of variation, CV) was ≤3·7% for the BN ProSpec and ≤6·1% for the LX20 PRO. The Synchron LX20 PRO hs-CRP method was found to be superior to the current routine Synchron LX20 CRP method with regard to precision in the low concentration range and the influence of sample turbidity. Both in the low concentration range and especially in the high concentration range, large discrepancies between methods were observed.

Conclusion: Although acceptable performance was found for the Synchron LX20 PRO hs-CRP method, overall the performance of the BN ProSpec hs-CRP method was superior. However, standardization among assays needs further improvement in both the low and the high concentration ranges.
Reference ranges for muscle carnitine concentration in children
Authors: Angsten Gertrud , Cederblad Gitten , Meurling Staffan
Published: July 2003

Background: We investigated muscle and plasma carnitine concentrations in children to establish reference intervals for use following biopsy of skeletal muscle.

Methods: The study comprised 50 children from newborns up to 14 years of age, all undergoing elective surgery. They were divided into six age groups, the youngest 0-2 days and the oldest 11-14 years. The samples were taken at the beginning of surgery.

Results: Gestational age was a major determinant of the total muscle carnitine concentration in newborns (Spearman's rs = 0·692, P < 0·01). This concentration was low during the first year, but subsequently did not differ between age groups. In neonates the median value (range) for total carnitine concentration in skeletal muscle was 5·9 (2·2-15·9) µmol/g dry weight and the free to total carnitine ratio was 62 (31-81)%. In children 1-12 months old the corresponding figures were 6·0 (3·5-7·9) µmol/g dry weight and 51 (28-71)% and in those 1-14 years they were 12·1 (6·6-17·4) µmol/g dry weight and 76 (42-92)%.

Conclusion: This study shows that muscle carnitine concentrations in newborns are dependent on gestational age. The data suggest that there is an accretion of carnitine in skeletal muscle during the first year of life. Reference intervals are given.
A comparative study of tissue transglutaminase antibodies and endomysium antibody immunofluorescence in routine clinical laboratory practice
Authors: Sinclair David , Pearce Callum B , Saas Michael S. L. , Poller David
Published: July 2003

Background: The demand for screening for coeliac disease has grown rapidly over the last few years. Laboratories depending on immunofluorescence assays are faced with an increasing workload using a labour-intensive test, and an alternative to this test has been sought. This study compares tissue transglutaminase (TTG) and endomysium antibodies (EMA) in a routine clinical laboratory situation.

Methods: An immunofluorescence IgA EMA test was compared with a guinea pig TTG antibody ELISA for 816 unselected requests for gut antibody screening. Discrepant results were investigated more fully using a variety of human source TTG antigen kits.

Results: Guinea pig TTG ELISA and EMA assays showed agreement for 93·6% of samples. Four samples were misclassified and 48 samples gave false positive TTG results. Study of 46 EMA samples (this group included 39 of the 'discrepant' negative EMA/positive guinea pig TTG group) using three different human purified and/or recombinant TTG sources showed that 42 patients had no TTG antibodies using human sources, three were misclassified and one patient had negative EMA and positive TTG results that could not be readily explained. Further study of 32 EMA positive samples showed almost complete agreement between the human source TTG kits.

Conclusions: We can recommend the replacement of EMA with ELISA for TTG antibodies for the routine screening for coeliac disease, but all positive TTG antibodies should still be followed up with IgA EMA and samples should be screened for IgA deficiency.
Measurement of urinary porphyrins and porphyrin precursors in Dutch hospital laboratories: a review of quality control over 5 years
Authors: Zuijderhoudt Floris M. J. , Weykamp Cas W. , Willems Hans L.
Published: July 2003

Background: We evaluated a quality control scheme for the measurement of urinary uroporphyrin, coproporphyrin, total urinary porphyrins and precursors of urinary porphyrins, δ-aminolevulinic acid and porphobilinogen that was performed in The Netherlands during a period of 5 years.

Methods: Six quality control samples were distributed each year to the participating laboratories. Mean concentrations and the corresponding coefficients of variation were calculated.

Results: Coefficients of variation varied widely and were very high in the concentration ranges that can be found in patients with low-grade porphyria.

Conclusion: Commutable calibrators are needed to improve the laboratory diagnosis of porphyria.
Rapid genetic testing for Gaucher disease by reverse hybridization
Authors: Halsall David J. , Kriegshäuser Gernot , Moritz Anne , Elsey Terence S. , Oberkanins Christian
Published: July 2003

Background: We evaluated a reverse hybridization method for the simultaneous detection of nine mutations that are associated with Gaucher disease.

Results and conclusion: Results were in agreement with those obtained by a polymerase chain reaction-restriction digestion method. The hybridization method produced results more quickly and with less operator input.
Severe hypokalaemia and weakness due to Nurofen® misuse
Authors: Chetty R. , Baoku Y. , Mildner R. , Banerjee A. , Vallance D. , Haddon A. , Labib M.
Published: July 2003

Nephrotoxicity from non-steroidal anti-inflammatory drugs (NSAID) is well recognized. We report a case of severe hypokalaemia and weakness due to renal tubular acidosis in a young woman who was taking 40-60 tablets per day of Nurofen Plus® (ibuprofen 200 mg and codeine phosphate 12·8 mg). Proprietary brands of ibuprofen are freely available to the public and those containing codeine may be potentially subject to abuse. This case highlights the need to be aware of this potential and of the life-threatening electrolyte and acid-base disturbances that might be encountered with the widespread availability of these types of NSAID.
Major ketogenesis and the absence of an osmolar gap in an atypical case of alcoholic ketoacidosis
Authors: Renom G. , Maisonneuve N. , Kim I. , Dehon B. , Azar R.
Published: July 2003

A new case of alcoholic ketoacidosis (AKA) is presented because of unusual clinical and biochemical features. Although it shares some similarities with typical cases of AKA, it appears as unique because of predominantly neurological, rather than abdominal symptoms, major ketogenesis with normal ketone body ratio, the presence of large amounts of propanediol and the absence of an osmolar gap.
Measurement Properties of the Oxford Shoulder Score and Minimal Clinically Important Changes After Primary Total Shoulder Replacement Surgery
Authors: Fang Yi Ying , Ackerman Ilana N. , Page Richard , Harris Ian A. , Cashman Kara , Lorimer Michelle , Heath Emma , Soh Sze‐Ee
Published: January 2024

Objective

We evaluated the measurement properties of the Oxford Shoulder Score (OSS) and estimated the minimal clinically important change (MCIC) in patients undergoing primary total shoulder replacement in Australia.

Methods

Deidentified data from the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. Pre‐ and 6‐month postoperative OSS scores were used, with the 5‐level EuroQoL quality of life instrument and shoulder pain scores used as comparators. Floor and ceiling effects, internal consistency reliability, construct validity, and responsiveness to change were evaluated using standard psychometric methods. Mean change and predictive modeling approaches (with and without adjustment for the proportion of improved patients) were used to calculate MCIC thresholds, with patient‐perceived improvement after surgery as the anchor.

Results

Preoperative OSS data were available for 1,117 patients (59% female; 90% aged ≥60 years) undergoing primary total shoulder replacement. No floor or ceiling effects were observed pre‐ or postoperatively. The OSS showed high internal consistency reliability (Cronbach alpha >0.89), good construct validity, and high responsiveness to change (effect size 1.88). The MCIC derived from the mean change method was 6.50 points (95% confidence interval [95% CI] 4.41–8.61). The predictive modeling approach produced an MCIC estimate of 8.42 points (95% CI 5.68–12.23) after adjustment.

Conclusion

The OSS has good measurement properties to capture pain and function outcomes after shoulder replacement procedures and is highly responsive to change. Based on robust methods, an increase in OSS scores of at least eight points can be considered as meaningful improvement after surgery from the patient's perspective.

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H2S‐Mediated Gas Therapy and HSP90 Downregulation Synergically Enhance Tumor Microwave Thermal Therapy
Authors: Li Shimei , Chen Zengzhen , Guo Wenna , Tan Longfei , Wu Qiong , Ren Xiangling , Fu Changhui , Wang Qiaozheng , Huang Zhongbing , Meng Xianwei
Published: January 2024

Microwave thermal therapy (MWTT) is a novel clinical treatment of tumors via inducing thermal effect and anti‐tumor immune response, exhibiting advantages of deep penetration, minimal invasion, and high heat conversion efficiency. However, effective ablation is difficult to cover the entire tumor area, and heat‐shock protein 90 (HSP90) is often upregulated after ablation to generate heat tolerance of sublethal tumors and weaken the induced antitumor immune effect, resulting in a high rate of tumor recurrence and metastasis. Herein, a multifunctional nanoregulator of metal phenolic network‐coated ZnS (ZnS@Ga‐tannic acid, ZGT) is proposed to release H2S for synergically enhancing MWTT. Under the costimulation of MW radiation and acidic tumor microenvironment, ZGT can improve the MW thermal effects of tumors to promote thermal damage and release H2S to induce tumor apoptosis. The released H2S can also inhibit the production of ATP and then downregulate the expression of HSP90, strengthening the activated systemic antitumor immune response after ablation. This nanoregulator provides a new way for achieving compensation effect for MWTT. The strategy of H2S gas to downregulate HSP90 and positively regulate antitumor immune response introduces a novel direction for reducing the risk of tumor recurrence and metastasis after thermal therapy.
A Versatile Intestine‐on‐Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease
Authors: Nguyen Oanh T. P. , Misun Patrick M. , Hierlemann Andreas , Lohasz Christian
Published: January 2024

The multifactorial nature of inflammatory bowel disease (IBD) necessitates reliable and practical experimental models to elucidate its etiology and pathogenesis. To model the intestinal microenvironment at the onset of IBD in vitro, it is important to incorporate relevant cellular and noncellular components before inducing stepwise pathogenic developments. A novel intestine‐on‐chip system for investigating multiple aspects of IBD's immunopathogenesis is presented. The system includes an array of tight and polarized barrier models formed from intestinal epithelial cells on an in‐vivo‐like subepithelial matrix within one week. The dynamic remodeling of the subepithelial matrix by cells or their secretome demonstrates the physiological relevance of the on‐chip barrier models. The system design enables introduction of various immune cell types and inflammatory stimuli at specific locations in the same barrier model, which facilitates investigations of the distinct roles of each cell type in intestinal inflammation development. It is showed that inflammatory behavior manifests in an upregulated expression of inflammatory markers and cytokines (TNF‐α). The neutralizing effect of the anti‐inflammatory antibody Infliximab on levels of TNF‐α and its inducible cytokines could be explicitly shown. Overall, an innovative approach to systematically developing a microphysiological system to comprehend immune‐system‐mediated disorders of IBD and to identify new therapeutic strategies is presented.
Feature analysis of generic AI models for CO2 equilibrium solubility into amines systems
Authors: Lan Ting , Dong Shoulong , Luo Hui , Bai Liju , Liu Helei
Published: January 2024

Reported models have disadvantages such as poor prediction accuracy and time‐consuming. And they can not reflect the impact of chemical reactions on CO2 solubility. To compensate for these deficiencies, parameters representing operational parameters, physical properties, chemical properties, and molecular properties are introduced as input variables. A series of models are constructed by three algorithms: back propagation neural network, radial basis function neural network, and random forest. The model with the best prediction performance is level OPCM (RBFNN), with the AARE of only 1.52%. By ranking the importance of the features using the RF algorithm, PCO2, was found to be the key parameter affecting the CO2 loadings, with M being the least important. Using the screened key parameters to model the model, as well as optimizing the structure, can further improve the predictive performance of the model. The full process development and optimization model framework constructed in this article can provide practical guidance for the development of machine learning models.
Whole genome sequencing as a first‐tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil
Authors: Migliavacca Michele P. , Sobreira Joselito , Bermeo Diana , Gomes Mireille , Alencar Dayse , Sussuchi Luciane , Souza Camila Alves , Silva Juliana Santos , Kroll José Eduardo , Burger Matheus , Guarischi‐Sousa Rodrigo , Villela Darine , Yamamoto Guilherme L. , Milanezi Fernanda , Horigoshi Nelson , Cesar Regina Grigolli , de Carvalho Werther Brunow , Honjo Rachel Sayuri , Bertola Debora Romeo , Kim Chong Ae , de Souza Lucian , Procianoy Renato S. , Silveria Rita C. , Rosenberg Carla , Giugliani Roberto , Campana Gustavo Aguiar , Scapulatempo‐Neto Cristovam , Sobreira Nara
Published: January 2024

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first‐tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X‐linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.
Health‐Poverty Inequality in Australia from 2001 to 2018
Authors: Jun Dajung , Sutton Matt
Published: January 2024

While established measures gauge poverty across diverse aspects of life, a definitive metric for health poverty in Australia remains absent. This study examines health poverty trends, identifying priorities for interventions to improve overall population health. We define health poverty as the state of falling below a specified minimum threshold in any critical health aspect, encompassing physical function, role function, social function, pain, mental health and vitality. Additionally, mortality (i.e., dying within 1 year) is integrated into the health poverty measure. The percentage of the overall adult population grappling with health poverty was 42 per cent in 2001, falling to 37 per cent in 2009 before ascending to 43 per cent in 2018. The level of health poverty was more prevalent among women, older age groups and Indigenous individuals than in men, younger age groups or non‐Indigenous people, respectively. By meticulously monitoring health poverty trends across various dimensions, this study unveils the sociodemographic group susceptible to health poverty and quantifies its impact on overall population well‐being. The investigation highlights poor role functioning and vitality deficiency as pivotal components contributing to health poverty.
CuI/DMAP‐Catalyzed Oxidative Alkynylation of 7‐Azaindoles: Synthetic Scope and Mechanistic Studies
Authors: Talukdar Vishal , Mondal Krishanu , Kumar Dhaked Devendra , Das Parthasarathi
Published: January 2024

An efficient and practical method for the N‐alkynylation of 7‐azaindoles has been established by using CuI/DMAP catalytic system at room temperature and in open air. This simple protocol has been successfully employed in the synthesis of a wide range of N‐alkynylated 7‐azaindoles with good yields. Also, this approach is well‐suited for large‐scale N‐alkynylation reactions. The designed N‐alkynylated 7‐azaindoles were further subjected to Cu‐/Ir‐catalyzed alkyne–azide cycloaddition (CuAAC/IrAAC) or “click” reaction for the rapid synthesis of 1,4‐/1,5 disubstituted 1,2,3‐triazole decorated 7‐azaindoles. A mechanistic study based on density functional theory (DFT) calculations and ultraviolet–visible (UV) spectroscopic studies revealed that the CuI and DMAP combination formed a [CuII(DMAP)2I2] species, which acts as an active catalyst. The DFT method was used to assess the energetic viability of an organometallic in the C−N bond formation pathway originating from the [CuII(DMAP)2I2] complex. We expect that the newly designed Cu/DMAP/alkyne system will offer valuable insights into the field of Cu‐catalyzed transformations.
Spontaneous nanoemulsification of cinnamon essential oil: Formulation, characterization, and antibacterial and antibiofilm activity against fish spoilage caused by Serratia rubidaea BFMO8
Authors: Arul Raj Jasmin Suriya , Aliyas Sheena , Poomany Arul Soundara Rajan Yolin Angel , Murugan Kasi , Karuppiah Ponmurugan , Arumugam Natarajan , Almansour Abdulrahman I. , Karthikeyan Perumal
Published: January 2024

The contemporary food industry's uses of nanoemulsions (NEs) include food processing, effective nutraceutical delivery, the development of functional chemicals, and the synthesis of natural preservatives, such as phytocompounds. Although cinnamon essential oil (CEO) is widely used in the cosmetic, pharmaceutical, and food industries, it is difficult to add to aqueous‐based food formulations due to its weak stability and poor water solubility. This study describes the formulation of a CEO nanoemulsion (CEONE) by spontaneous emulsification and evaluates its antibacterial and antibiofilm properties against biofilm‐forming Serratia rubidaea BFMO8 isolated from spoiled emperor fish (Lethrinus miniatus). Bacteria causing spoilage in emperor fish were isolated and identified as S. rubidaea using common morphological, cultural, and 16S RNA sequencing methods, and their ability to form biofilms and their susceptibility to CEONE were assessed using biofilm‐specific methods. The spontaneous emulsification formulation of CEONE was accomplished using water and Tween 20 surfactant by manipulating organic and aqueous phase interface properties and controlling particle growth by capping surfactant increases. The best emulsification, with highly stable nano‐size droplets, was accomplished at 750 rpm and a 1:3 ratio concentration. The stable CEONE droplet size, polydispersity index, and zeta potential values were 204.8 nm, 0.115, and −6.05 mV, respectively. FTIR and high‐resolution liquid chromatography‐mass spectrometry (HR‐LCMS) analyses have revealed carboxyl, carbonyl, and phenol‐like primary phytochemical functional groups in CEO and CEONE, which contribute to their antibacterial and antibiofilm properties.
Der Mühlensteg in Besigheim
Authors: Keil Andreas , Linden Sebastian , Sander Christiane
Published: January 2024

In dem kleinen Ort Besigheim, nördlich von Stuttgart, wurde vor dem historischen, denkmalgeschützten Stadtbild eine Fußgängerbrücke über die Enz gebaut. Mit einer gekrümmten Spannweite von ca. 70 m und schräg verlaufenden Hängeseilen, die nur mit der Außenkante des Überbaus verbunden sind, bietet die einhüftige, selbstverankerte Hängebrücke Fußgängern eine direkte Verbindung vom Enzpark in das mittelalterliche Stadtzentrum. Darüber hinaus können Radfahrer den Fluss über die neue Querung von einem Ufer zum anderen überqueren. Obwohl es sich bei der Fußgängerbrücke um eine hochtechnische Leichtbaukonstruktion handelt, nimmt sie Rücksicht auf den örtlichen Kontext und bezieht die angrenzende denkmalgeschützte Wassermühle behutsam mit ein. So trägt die Brücke in Form und Funktion zum Park mit dem dazugehörigen Uferspielplatz bei und ermöglicht es den Besuchern, den Fluss und das historische Stadtbild auf neue Weise zu erleben.
Ippia Alba Essential Oil: A Promising Complementary Therapy for Breast Cancer
Authors: Hedhili Lassaad
Published: January 2024

Breast cancer remains a pressing global health issue, spurring exploration into innovative therapies. This review focuses on Lippia alba (Mill.) essential oil‘s potential as a complementary breast cancer treatment. With growing interest in natural approaches, Lippia alba shows promise in breast cancer management. The review will explore Lippia alba‘s multifaceted role in treatment, highlighting its anticancer effects on breast cancer cells, potential synergy with conventional treatments, safety profiles, and existing clinical evidence. It will also address knowledge gaps, stressing the need for further research to unlock Lippia alba‘s full therapeutic potential in breast cancer therapy. In a field craving novel therapies, this review offers a timely analysis. Despite the lack of existing reviews on this topic, Lippia alba‘s significance cannot be understated. As research progresses, this article will be a valuable resource for researchers and healthcare practitioners seeking to augment breast cancer management through complementary therapies.
Computational Evaluation of Bioactive Compounds from Dysphania ambrosioides Leaves
Authors: Kadi Mounime , Berraouaan Ali , Driouech Mounia , Ziyyat Abderrahim , Mekhfi Hassan , Bnouham Mohamed , Legssyer Abdelkhaleq
Published: January 2024

Dysphania ambrosioides has been reported to have many medicinal properties, due to its possession of a multitude of biologically active molecules contained in its leaves. However, very few studies have been reported to evaluate their pharmacological properties. Consequently, in the present study, many computational tools have been performed to predict drug similarity and ADMET properties. Besides, the inhibitory potential of D.ambrosioides major compounds against Bacterial, Fungal and cardiovascular main receptor targets has been investigated. This study suggests that Carvone oxide, 5‐Isopropenyl‐2‐Methylenecyclohexanol, and Caryophyllene oxide were the most active molecules belonging to D. ambrosioides Leaves, possessing drug‐likeness with satisfactory bioactivity scores, having good pharmacokinetic values. Metabolism and toxicities were further studied using FAME3, GLORY, and pred‐hERG. Slight cardiotoxicity and cytotoxicity were predicted, respectively, for Caryophyllene oxide and Carvone oxide, 5‐Isopropenyl‐2‐Methylenecyclohexanol. Good inhibitory activities of the three compounds against Bacterial, Fungal, and Cardiovascular receptor targets. Hence, this is a comprehensive in silico approach to evaluate D.ambrosioides Leaves main phytocompounds in the background of its potential in future drug development
Alkaloids and Lignans from the Aerial Parts of Rauvolfia tetraphylla Inhibit NO Production in LPS‐activated RAW 264.7 Cells
Authors: Tung Ninh Khac Thanh , Dung Duong Thi , Kiem Phan Van , Hang Dan Thi Thuy , Nhiem Nguyen Xuan , The Nguyen Van , Seo Yohan , Kang Jong Seong , Tai Bui Huu
Published: January 2024

Three previously undescribed compounds named rauvolphyllas A−C (1‐3), along with thirteen known compounds, 18β‐hydroxy‐3‐epi‐α‐yohimbine (4), yohimbine (5), α‐yohimbine (6), 17‐epi‐α‐yohimbine (7), (E)‐vallesiachotamine (8), (Z)‐vallesiachotamine (9), 16S‐E‐isositsirikine (10), Nb–methylisoajimaline (11), Nb–methylajimaline (12), ajimaline (13), (+)‐lyoniresinol 3α‐O‐β‐D‐glucopyranoside (14), (+)‐isolarisiresinol 3α‐O‐β‐D‐glucopyranoside (15), and (−)‐lyoniresinol 3α‐O‐β‐D‐glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR‐ESI‐MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11–13 exhibited nitric oxide production inhibition activity in LPS‐activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56 μM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66 μM. The other isolates were inactive with IC50 values over 100 μM.
Kinetic, Thermodynamic, and Parametric Studies on Batch Synthesis of 1,1‐Diethoxybutane Catalyzed by Amberlyst‐15 Wet
Authors: Tikekar Ketaki , Singh Kailash , Upadhyaya Sushant
Published: January 2024

1,1‐Diethoxybutane is a high‐potential biofuel additive that enhances various fuel properties, which include cetane number, lubricity, biodegradability, and flash point. This work presents a kinetic and thermodynamic study on the acetalization reaction between butanal and ethanol in the presence of Amberlyst‐15 wet in a batch reactor. The experiments were conducted in the temperature range 313–333 K at atmospheric pressure with three different initial molar ratios of reactants and catalyst loadings. An optimal parameter setting to achieve maximum equilibrium conversion of butanal was derived from a parametric study with these three factors. The equilibrium constant for the reaction was determined. Standard thermodynamic properties of the reaction, such as enthalpy, entropy, and Gibbs free energy, were experimentally evaluated. The activity‐based two‐parameter Langmuir‐Hinshelwood‐Hougen‐Watson rate expression was used for reaction kinetics. The activity coefficients were calculated by the UNIFAC method. The kinetic parameters and the activation energy were evaluated from the experimental data. The experimental data and data predicted by the model were found to be in good agreement.
Hormones Concentration in an Aqueous Two‐Phase System: Experimental and Computational Analysis
Authors: Buarque Filipe S. , Lima Thailan S. P. , Carniel Adriano , Ribeiro Bernardo D. , Coelho Maria A. Z. , Souza Ranyere L. , Soares Cleide M. F. , Pereira Matheus M. , Lima Álvaro S.
Published: January 2024

Estrogens are emergent pollutants found in low levels in water bodies, and for this reason they require concentration for quantification. In this study, aqueous two‐phase systems (ATPSs) were used as an alternative strategy to improve hormone detection and quantification from real water samples. In addition, a predictive computational method (COSMO‐RS) was used to understand better the migration of hormones between the two phases at the molecular level. Water samples previously analyzed as hormone‐free were added to the 250‐fold concentrated ATPS, where it was possible to detect and quantify concentrations of these micropollutants in the range of 9.3–29.19 ng L−1.
Convergent Synthesis of the Nonreducing Hexasaccharide Fragment and the Dodecasaccharide Scaffold of Marine Lipopolysaccharide Axinelloside A
Authors: Zeng Changgen , Zhang Haoliang , Zhu Dapeng , Yu Biao
Published: January 2024

A convergent synthesis of the dodecasaccharide scaffold of axinelloside A was achieved through Au(I)‐catalyzed [6+6] glycosylation. The initially devised [3+1+2] assembly of the nonreducing hexasaccharide fragment was low‐yielding, whereas a convergent [3+3] glycosylation under Au(I) catalysis was proven feasible, allowing for a semi‐gram scale preparation of the wanted hexasaccharide. The requisite 1,2‐cis glycosidic bonds were forged in a highly stereoselective fashion by virtue of remote acetyl group participation, and judicious manipulation of protecting groups. The synthetic dodecasaccharide has been properly protected for the downstream elaboration toward its natural form.
Investigating the influence of surface shear stress on the stability of gravity‐driven multilayer liquid flow
Authors: Tomar Dharmendra S.
Published: January 2024

We conducted a linear stability analysis on the behaviour of two gravity‐driven Newtonian liquid layers flowing down an inclined rigid plane, subjected to external shear stress at the free surface, in both the direction of and opposite to gravity. A long wave asymptotic analysis was conducted to examine the influence of several parameters, including liquid film thickness (β), viscosity ratio (μr), and external shear stress (τ), on the interfacial modes of both gas–liquid (GL) and liquid–liquid (LL). For viscosity ratios (μr) < 1 and Reynolds number (Re) = 0, the observations indicate that the LL mode exhibits instability attributed to O(k) instability. This phenomenon is manifest when an external shear stress is applied at the GL interface, specifically within a defined range of negative shear stress values. When and , the investigation reveals the presence of two complex conjugate roots when external shear stress opposes the direction of gravity. One of these roots, referred to as the positive root, is associated with the leading (or zero) order instability that renders the GL mode unstable. The other root corresponds to the leading (or zero) order stability, contributing to the stability of the LL mode. In contrast, when external shear stress acts along the gravity direction, we observe that the GL mode is stable while the LL mode becomes unstable due to O(k) instability for various values of β. This finding highlights the importance of the direction of external shear stress in determining the interfacial mode's stability behaviour.
Association between treatment‐emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study
Authors: Piscaglia Fabio , Ikeda Kenji , Cheng Ann‐Lii , Kudo Masatoshi , Ikeda Masafumi , Breder Valery , Ryoo Baek‐Yeol , Mody Kalgi , Ren Min , Ramji Zahra , Sung Max W.
Published: January 2024

Background

Lenvatinib is approved as a first‐line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment‐emergent hypertension (CSTE‐HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE‐HTN on the efficacy and safety of lenvatinib in HCC.

Methods

Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE‐HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression‐free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks.

Results

A total of 212 patients in the lenvatinib arm developed CSTE‐HTN, and 264 did not. CSTE‐HTN first occurred at 3.7 weeks (median); the worst grade CSTE‐HTN occurred at 4.1 weeks (median). No patients had life‐threatening CSTE‐HTN and/or died due to CSTE‐HTN. Median OS was numerically longer in patients with versus without CSTE‐HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621–1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696–1.089). Median PFS was similar between patients with and without CSTE‐HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680–1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84–1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE‐HTN (34.5%).

Conclusions

In this retrospective analysis, CSTE‐HTN was associated with improved OS but not PFS. CSTE‐HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately.
A phase 1 study of triple‐targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF‐mutated cancers
Authors: Algazi Alain P. , Moon James , Lao Christopher D. , Chmielowski Bartosz , Kendra Kari L. , Lewis Karl D. , Gonzalez Rene , Kim Kevin , Godwin John E. , Curti Brendan D. , Latkovic‐Taber Michaella , Lomeli Shirley H. , Gufford Brandon T. , Scumpia Philip O. , Lo Roger S. , Othus Megan , Ribas Antoni
Published: January 2024

Background

Aberrant PI3K/AKT signaling in BRAF‐mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF‐mutated solid tumors (ClinicalTrials.gov identifier NCT01902173).

Methods

Patients with BRAF V600E/V600K–mutant solid tumors received oral dabrafenib at 150 mg twice daily with dose escalation of oral uprosertib starting at 50 mg daily, or, in the triplet cohorts, with dose escalation of both oral trametinib starting at 1.5 mg daily and oral uprosertib starting at 25 mg daily. Dose‐limiting toxicities (DLTs) were assessed within the first 56 days of treatment. Radiographic responses were assessed at 8‐week intervals.

Results

Twenty‐seven patients (22 evaluable) were enrolled in parallel doublet and triplet cohorts. No DLTs were observed in the doublet cohorts (N = 7). One patient had a DLT at the maximum administered dose of triplet therapy (dabrafenib 150 mg twice daily and trametinib 2 mg daily plus uprosertib 75 mg daily). Three patients in the doublet cohorts had partial responses (including one who had BRAF inhibitor‐resistant melanoma). Two patients in the triplet cohorts had a partial response, and one patient had an unconfirmed partial response. Pharmacokinetic data suggested reduced dabrafenib and dabrafenib metabolite exposure in patients who were also exposed to both trametinib and uprosertib, but not in whose who were exposed to uprosertib without trametinib.

Conclusions

Concomitant inhibition of both the MAPK and PI3K‐AKT pathways for the treatment of BRAF‐mutated cancers was well tolerated, leading to objective responses, but higher level drug‐drug interactions affected exposure to dabrafenib and its metabolites.
Interfacial Phenomena in Nanostructured Systems with Various Materials
Authors: Gun'ko Volodymyr M. , Turov Volodymyr V.
Published: January 2024

Interfacial phenomena linked to the behavior of bound water, organic solvents (co‐sorbates, dispersion media), hydrogen, methane, acids/bases, and salts bound to various silicas, polymers, and carbon materials were analyzed vs. temperature and concentrations using 1H NMR spectroscopy, differential scanning calorimetry (DSC) and other methods. The material characteristics were studied using microscopy, infrared spectroscopy (IR), small angle X‐ray scattering (SAXS), and nitrogen adsorption. Confined space effects (CSE) result in enhanced freezing point depression (FPD) and stronger diminution of solvent activity and colligative properties of liquid mixtures in narrower pores. Short hydrophobic functionalities (≡Si‐CH3, =Si(CH3)2) at a silica surface and the presence of nanopores result in differentiation of bound water into weakly (WAW, δH=0.2–2.0 ppm) and strongly (SAW, δH=4–6 ppm) associated waters of smaller solvent activity in smaller clusters located in narrower pores and unfrozen below a bulk freezing point. These effects are enhanced in hydrophobic dispersion media. Hydrophobic liquids could displace bound water into narrower pores inaccessible for their molecules larger than water and/or into broader pores to reduce contact area between immiscible liquids. The observed phenomena depend on sorbent/sorbate kinds and play an important role on practical applications of various sorbents.