bluuebunny/crossref_metadata_2025_split huggingface dataset:
Izokibep for the treatment of moderate-to-severe plaque psoriasis: a phase II, randomized, placebo-controlled, double-blind, dose-finding multicentre study including long-term treatment
Authors: Gerdes Sascha , Staubach Petra , Dirschka Thomas , Wetzel Dieter , Weirich Oliver , Niesmann Johannes  , da Mota Rodrigo , Rothhaar Alex , Ardabili Michael , Vlasitz Gerda , Feldwisch Joachim , Osterling Koskinen Lisa , Ohlman Sven , Peloso Paul M , Brun Nikolai C , Frejd Fredrik Y 
Published: September 2023

Abstract

Background
Monoclonal antibodies to interleukin (IL)-17 have shown strong efficacy in patients with psoriasis. Izokibep is a unique IL-17A inhibitor with a small molecular size and favourable distribution to sites of inflammation.

Objectives
To evaluate the dose response, efficacy and safety of izokibep in patients with plaque psoriasis.

Methods
In this double-blind, randomized, phase II dose-finding study (AFFIRM-35) in adults with moderate-to-severe plaque psoriasis and inadequate response to two or more standard therapies, patients were randomized (1:1:1:1:1) to placebo or izokibep 2, 20, 80 or 160 mg every 2 weeks for 12 weeks. During the remainder of the 52-week core study, patients given placebo were switched to izokibep 80 mg, and dosing intervals were adapted based on Psoriasis Area and Severity Index (PASI) scores for all patients. The core study was followed by two optional consecutive 1-year extension periods for a total duration of 3 years. The primary endpoint was a 90% reduction in PASI score (PASI 90) at week 12. Additional efficacy outcomes and adverse event (AE) rates were evaluated.

Results
In total, 109 patients were randomized [safety set, n = 108 (one exclusion criteria failure); full analysis set, n = 106]. At week 12, PASI 90 response rates were 0%, 5%, 19%, 71% and 59% for the placebo, 2-, 20-, 80- and 160-mg izokibep groups, respectively. Rapid dose-dependent improvements were also observed across other efficacy outcomes. During the placebo-controlled period, AEs in the izokibep groups were similar to placebo except for mild injection site reactions. AEs were generally mild to moderate and the drug was well tolerated. Izokibep maintained efficacy at the higher dosage groups for up to 3 years, with no new safety signals.

Conclusions
Data from this phase II study indicate that izokibep is well tolerated and efficacious in the treatment of plaque psoriasis. Higher doses or more frequent dosing could be explored to further enhance response rates.
Sexual harassment, sexual assault and rape by colleagues in the surgical workforce, and how women and men are living different realities: observational study using NHS population-derived weights
Authors: Begeny Christopher T , Arshad Homa , Cuming Tamzin , Dhariwal Daljit K , Fisher Rebecca A , Franklin Marieta D , Jackson Philippa C , McLachlan Greta M , Searle Rosalind H , Newlands Carrie 
Published: September 2023

Abstract

Background
This observational study, paired with National Health Service (NHS) workforce population data, examined gender differences in surgical workforce members’ experiences with sexual misconduct (sexual harassment, sexual assault, rape) among colleagues in the past 5 years, and their views of the adequacy of accountable organizations in dealing with this issue.

Methods
This was a survey of UK surgical workforce members, recruited via surgical organizations.

Results
Some 1704 individuals participated, with 1434 (51.5 per cent women) eligible for primary unweighted analyses. Weighted analyses, grounded in NHS England surgical workforce population data, used 756 NHS England participants. Weighted and unweighted analyses showed that, compared with men, women were significantly more likely to report witnessing, and be a target of, sexual misconduct. Among women, 63.3 per cent reported being the target of sexual harassment versus 23.7 per cent of men (89.5 per cent witnessing versus 81.0 per cent of men). Additionally, 29.9 per cent of women had been sexually assaulted versus 6.9 per cent of men (35.9 per cent witnessing versus 17.1 per cent of men), with 10.9 per cent of women experiencing forced physical contact for career opportunities (a form of sexual assault) versus 0.7 per cent of men. Being raped by a colleague was reported by 0.8 per cent of women versus 0.1 per cent of men (1.9 per cent witnessing versus 0.6 per cent of men). Evaluations of organizations’ adequacy in handling sexual misconduct were significantly lower among women than men, ranging from a low of 15.1 per cent for the General Medical Council to a high of 31.1 per cent for the Royal Colleges (men’s evaluations: 48.6 and 60.2 per cent respectively).

Conclusion
Sexual misconduct in the past 5 years has been experienced widely, with women affected disproportionately. Accountable organizations are not regarded as dealing adequately with this issue.
Why focusing on our strengths matters: reflections on leaving a volunteer role I actually liked
Authors: Lyons Kristen 
Published: September 2023

Abstract
In this article I describe the recent process of leaving a volunteer role that had, over a number of years, brought me much joy and satisfaction. This process of leaving gave me the opportunity to reflect on the kinds of organisational cultures that may work best in supporting volunteers and paid staff, as well as organisations themselves, to flourish. Through my journey of leaving, I describe the value of asset based approaches, and caring for people for who they are, not de-valuing them for who they are not, as part of creating constructive and positive outcome oriented organisations.
Hypoxia inducible factor prolyl hydroxylase inhibitors: what a meta-analysis could tell us
Authors: Locatelli Francesco , Zoccali Carmine 
Published: September 2023

ABSTRACT
Meta-analyses offer an estimate of the overall effect size and help address the inconsistency in findings across studies. The risk is the overemphasis on statistical significance while underrepresenting or misinterpreting clinical significance. There's also a lack of standardized methods for quantifying and reporting clinical significance and these measures are often missing or inconsistently reported in many meta-analyses, making it difficult for readers to determine the clinical relevance of the findings. A major merit of Minutolo's meta-analysis is to formally evaluate efficacy and safety of Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHI) as class and as single agents in comparison with ESA, by selecting from only phase-3 randomised clinical trials (RCTs) that compared HIF-PHIs with erythropoiesis-stimulating agents (ESAs) in dialysis and non-dialysis patients. From a clinical perspective, the primary evaluation in this meta-analysis should have been the percentage of patients able to reach and maintain the target haemoglobin (Hb) levels throughout the trials but only a few RCTs selected this primary end point. Any claimed superiority of one drug over another should consider the selected doses. The amount of iron administered to patients, their iron stores and level of inflammation are important confounding factors that affect the reliability of any comparison.
Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors
Authors: Wu Lei-Lei , Lin Wei-Kang , Qian Jia-Yi , Ma Shang-Shang , Li Ming-Jun , Li Kun , Li Zhi-Xin , Lan Gang , Xie Dong 
Published: September 2023

Abstract

OBJECTIVES
Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I–IIA ADC.

METHODS
We included 1585 patients with pathologically diagnosed stage I–IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan–Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS.

RESULTS
Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717–0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P &lt; 0.001) after effective cut-off values of risk points were found based on the nomogram.

CONCLUSIONS
We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I–IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I–IIA ADC patients.
The gut microbiome of the healthy population in Kolkata, India, is a reservoir of antimicrobial resistance genes emphasizing the need of enforcing antimicrobial stewardship
Authors: De Rituparna , Kanungo Suman , Mukhopadhyay Asish Kumar , Dutta Shanta 
Published: September 2023

Abstract
Antimicrobial resistance (AMR) alleviation warrants antimicrobial stewardship (AS) entailing the indispensability of epidemiological surveillance. We undertook a small-scale surveillance in Kolkata to detect the presence of antimicrobial resistance genes (ARGs) in the healthy gut microbiome. We found that it was a reservoir of ARGs against common antibiotics. A targeted Polymerase Chain Reaction (PCR) and sequencing-based ARGs detection against tetracyclines, macrolides, trimethoprim, sulfamethoxazole, aminoglycosides, amphenicol, and mobile genetic element (MGE) markers were deployed in 25 fecal samples. Relative abundance and frequency of ARGs were calculated. We detected markers against all these classes of antibiotics. 100% samples carried aminoglycoside resistance marker and int1U. A comparison with our previously published diarrheal resistome from the same spatial and temporal frame revealed that a higher diversity of ARGs were detected in the community and a higher rate of isolation of tetC, msrA, tmp, and sul-2 was found. The presence of common markers in the two cohorts proves that the gut microbiome has been contaminated with ARGs and which are being disseminated among different ecosystems. This is an issue of discerning concern for public health. The study raises an alarming picture of the AMR crisis in low-middle and emergent economies. It emphasizes the strict enforcement of AS in the community.
Reproducibility of human landmark identification in morphological mandible prototypes: major parameters for a 3D CBCT approach
Authors: Fontes Rebeca Menezes Vaz Queiroz , de Carvalho Nunes Tiago Alves , dos Santos Machado Ricardo Filipe , Ribeiro Patricia Miranda Leite , Marques Jeidson Antônio Morais , Corte-Real Ana 
Published: September 2023

Abstract
The establishment of anthropometric measurements is of fundamental importance for the correct identification of human bodies. The objective of this study was to evaluate the accuracy and reliability of two-dimensional craniometric landmarks obtained from three-dimensional cone beam computed tomography reconstructions for forensic identification of humans. Computed tomography images with voxel sizes of 0.25, 0.3, and 0.4 mm were obtained using i-CAT® three-dimensional equipment. Ten landmarks were randomly selected, and 10 measurements were demarcated in the three-dimensional reconstruction to evaluate the mandibular condyle, ramus, and body. This study demonstrated that protocols with voxels of 0.3 mm should be preferentially indicated for the evaluation of linear and angular measurements. Implementing our methodology using prototypes for clinical and forensic simulations allows comparisons with human databases in identification issues.
A comparative analysis of stably expressed genes across diverse angiosperms exposes flexibility in underlying promoter architecture
Authors: Yang Eric J Y , Maranas Cassandra J , Nemhauser Jennifer L 
Published: September 2023

Abstract
Promoters regulate both the amplitude and pattern of gene expression—key factors needed for optimization of many synthetic biology applications. Previous work in Arabidopsis found that promoters that contain a TATA-box element tend to be expressed only under specific conditions or in particular tissues, while promoters that lack any known promoter elements, thus designated as Coreless, tend to be expressed more uniformly. To test whether this trend represents a conserved promoter design rule, we identified stably expressed genes across multiple angiosperm species using publicly available RNA-seq data. Comparisons between core promoter architectures and gene expression stability revealed differences in core promoter usage in monocots and eudicots. Furthermore, when tracing the evolution of a given promoter across species, we found that core promoter type was not a strong predictor of expression pattern. Our analysis suggests that core promoter types are correlative rather than causative in promoter expression patterns and highlights the challenges in finding or building constitutive promoters that will work across diverse plant species.
Association of food intake with a risk of metabolic dysfunction-associated fatty liver disease: a cross-sectional study
Authors: Huang Xian-Hua , Peng He-Wei , Huang Jing-Ru , Yu Rong , Hu Zhi-Jian , Peng Xian-E 
Published: September 2023

AbstractBackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease, the risk of which can be increased by poor diet. The objective of this study was to evaluate the associations between food items and MAFLD, and to propose reasonable dietary recommendations for the prevention of MAFLD.MethodsPhysical examination data were collected from April 2015 through August 2017 at Nanping First Hospital (n = 3,563). Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score.ResultsBeverages (soft drinks and sugar-sweetened beverages) and instant noodles were positively associated with MAFLD risk, adjusting for smoking, drinking, tea intake, and weekly hours of physical activity [adjusted odds ratio (ORadjusted): 1.568; P = 0.044; ORadjusted: 4.363; P = 0.001]. Milk, tubers, and vegetables were negatively associated with MAFLD risk (ORadjusted: 0.912; P = 0.002; ORadjusted: 0.633; P = 0.007; ORadjusted: 0.962; P = 0.028). In subgroup analysis, the results showed that women [odds ratio (OR): 0.341, 95% confidence interval (CI): 0.172–0.676] had a significantly lower risk of MAFLD through consuming more tubers than men (OR: 0.732, 95% CI: 0.564–0.951).ConclusionsThese findings suggest that reducing consumption of beverages (soft drinks and sugar-sweetened beverages) and instant noodles, and consuming more milk, vegetables, and tubers may reduce the risk of MAFLD.
Kodaira Dimension of Fibrations Over Abelian Varieties
Authors: Meng Fanjun , Popa Mihnea 
Published: September 2023

Abstract
We prove an additivity result for the log Kodaira dimension of algebraic fiber spaces over abelian varieties, a superadditivity result for fiber spaces over varieties of maximal Albanese dimension, as well as a subadditivity result for log pairs.
Green HPLC Method for Simultaneous Analysis of Three Natural Antioxidants by Analytical Quality by Design
Authors: Jonnalagadda Ramya , Rathinam Seetharaman , Nagappan Krishnaveni , Chandrasekar Vinodhini 
Published: September 2023

Abstract

Background
Glutathione, silybin, and curcumin are well-known potential antioxidants that are recommended as adjuvant therapy in cancer treatment.

Objective
Based on the principles of Analytical Quality by Design (AQbD) and green analytical chemistry, a simple, robust, and environmentally benign HPLC method for the simultaneous estimation of glutathione, silybin, and curcumin in bulk and formulation was performed.

Method
Elution was achieved by an Agilent Eclipse XDB C18 (150 mm × 4.6 mm id, 3.5 μm) column using a gradient mobile phase composed of ethanol–water pH 6.7 (with 0.1%, v/v orthophosphoric acid) and 1.07 mL/min flow rate with PDA detection at 215 nm. Critical method variables were identified by risk assessment using an Ishikawa diagram, and multivariate optimization of the experimental conditions for the HPLC technique was accomplished by central composite design using design of experiments (DoE) software.

Results
The separation was achieved within 15 min, where the retention time of glutathione, silybin, and curcumin were 3.3, 4.9, and 7.3 min, respectively. The standard curve was linear in the range of 3.75–26.25 µg/mL for glutathione, 62.50–437.50 µg/mL for silybin, and 12.5–87.50 µg/mL for curcumin. The developed method was validated as per ICH guidelines Q2 (R1), and all the parameters are within specified limits.

Conclusions
The proposed method is simple, precise, and robust, which can be employed for routine analysis and also concluded to be a greener approach according to AGREE, Green Analytical Procedure Index, and analytical eco-scale tools.

Highlights
The chosen antioxidants were evaluated for the very first time simultaneously using the chromatographic technique in bulk and dosage forms employing green solvents. The peak purity of all three compounds was studied using a PDA detector. Wastage was reduced in terms of time, cost, and solvents by employing AQbD elements and tools. Complete application of environmentally sustainable safe solvents were employed.
Prevalence of ∆8-tetrahydrocannabinol carboxylic acid in workplace drug testing
Authors: Vikingsson Svante , Hart E. Dale , Winecker Ruth E , Cone Edward J , Kuntz David J , Clark Michael , Jacques Martin , Hayes Eugene D , Flegel Ronald R 
Published: September 2023

Abstract
∆8-Tetrahydrocannabinol (∆8-THC) recently became widely available as an alternative to cannabis. ∆8-THC is likely impairing and poses a threat to workplace and traffic safety. In the present study, the prevalence of ∆8-THC in workplace drug testing was investigated by analyzing 1,504 urine specimens with a positive immunoassay cannabinoid initial test using a liquid chromatography–tandem mass spectrometry (LC–MS-MS) method quantifying 15 cannabinoid analytes after hydrolysis. ∆8-tetrahydrocannabinol-9-carboxylic acid (∆8-THC-COOH) was detected in 378 urine specimens (15 ng/mL cutoff), compared to 1,144 specimens containing ∆9-THC-COOH. The data could be divided into three general groups. There were 964 (76%) ∆9-THC-COOH-dominant (&lt;10% ∆8-THC-COOH) and 139 (11%) ∆8-THC-COOH-dominant (&gt;90% ∆8-THC-COOH) specimens, with the remaining 164 (13%) specimens showing a mixture of both analytes (&gt;90% ∆8-THC-COOH). Similar concentrations of ∆9-THC-COOH (median 187 ng/mL) and ∆8-THC-COOH (150 ng/mL) as the dominant species support the use of similar cutoffs and decision rules for both analytes. Apart from the carboxylic acid metabolites, 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-∆9-THC, n = 1,282), ∆9-tetrahydrocannabivarin-9-carboxylic acid (∆9-THCV-COOH, n = 1,058), ∆9-THC (n = 746) and 7-hydroxy-cannabidiol (7-OH-CBD, n = 506) were the most prevalent analytes. Two specimens (0.13%) contained ≥140 ng/mL ∆9-THC without ∆9-THC-COOH, which could be due to genetic variability in the drug-metabolizing enzyme CYP2C9 or an adulterant targeting ∆9-THC-COOH. The cannabinoid immunoassay was repeated, and five specimens (0.33%) generated negative initial tests despite ∆9-THC-COOH concentrations of 54–1,000 ng/mL, potentially indicative of adulteration. The use of ∆8-THC is widespread in the US population, and all forensic laboratories should consider adding ∆8-THC and/or ∆8-THC-COOH to their scope of testing. Similar urinary concentrations were observed for both analytes, indicating that the decision rules used for ∆9-THC-COOH are also appropriate for ∆8-THC-COOH.
Interpretative problems due to the presence of chloromethcathinone isomers in the biological material from postmortem cases
Authors: Romańczuk Agnieszka , Rojek Sebastian , Synowiec Kamil , Maciów-Głąb Martyna , Kula Karol 
Published: September 2023

Abstract
While many new psychoactive substances often disappear from the drug market rather quickly, some, such as synthetic cathinones (SCs), still remain due to their popularity among users. The current knowledge of SC concentrations in blood samples is based mainly on the published case reports of intoxications or fatalities caused by SC intake. The aim of the present study was to present and interpret the obtained toxicological analysis results of these cases, in which it was possible to determine or detect the presence of one of the isomers of chloromethcathinone (CMC) along with its intake biomarker—dihydro-CMC. These cases include 27 deaths reported at the Department of Forensic Medicine in Kraków in 2016–2022. CMC constitutes a major toxicological opinion challenge, in terms of toxicological evaluation of poisonings. As presented in this paper, a significant problem is its stability in the biological material and practices in the reporting of the obtained data. It is therefore important to monitor potential intake biomarkers that may show greater stability in the biological material than the parent drug. In the case of CMC isomers, the good biomarker of intake is the dihydro-CMC metabolite, which was detected in the blood sample in every case presented, even with the absence of the parent substance. Interpretation of the results obtained for CMC in terms of assessing their toxicity and possible cause of death is difficult. However, it should be taken into account that in cases of new psychoactive substance poisoning, an in-depth risk assessment is mandatory and the opinion of the unpredictability of the effects is taken as a principle.
Evaluation of the long-term stability of select phenylacetylindole, cycloalkylindole, quinolinyl, and carboxamide synthetic cannabinoids using LC–MS-MS
Authors: Phung Erika , Lee Daniel , Swart Cassandra , Ke Yiling , Moore-Bollinger Katherine , Bynum Nichole , Grabenauer Megan , Botch-Jones Sabra 
Published: September 2023

Abstract
Forensic toxicology laboratories often encounter casework backlogs, which raise concerns for drug stability that can be affected by long storage times, temperature and preservatives, or the lack thereof. The focus of this research was to evaluate the impact of these factors on the stability of 17 synthetic cannabinoids (SCs) in human whole blood and 10 associated metabolites in human urine. The fortified biological specimens were stored under room temperature (20°C), refrigerator (4°C) and freezer (–20°C) conditions for a period of 52 weeks. Preservatives included potassium oxalate, sodium ethylenediaminetetraacetic acid and sodium fluoride. Extraction of analytes was conducted using supported liquid extraction and analyzed using a liquid chromatograph-tandem mass spectrometer. Under all three storage conditions, the majority of urine metabolites were stable up to 9 weeks. All analytes in frozen sodium fluoride–preserved blood were stable at 21–52 weeks with the exception of APP-PICA. Analytes in the blood that were stable up to 52 weeks in the freezer generally had a core structure of a carbonyl substituent on a pyrazole or pyrrole with surrounding nonpolar groups. In contrast, compounds with two adjacent polar carbonyl functional groups experienced degradation at ≤1 week under ambient temperature and refrigeration. 5-Fluoropentyl analogs, XLR11 and 5-fluoro ADB-PINACA, in comparison to their counterpart analytes, UR144 and ADB-PINACA, were unstable at earlier time points under all temperatures. Based on these data, forensic blood evidence suggesting the presence of SC compounds is recommended to be frozen with sodium fluoride and potassium oxalate preservatives for optimal quantitative results.