bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel heterozygous variants in the EP300 gene cause Rubinstein–Taybi syndrome 2: Reports from two Chinese children
Authors: Du Caiqi , Li Zhuoguang , Zou Biao , Li Xuesong , Chen Fan , Liang Yan , Luo Xiaoping , Shu Sainan
Published: May 2023

Background

Rubinstein–Taybi syndrome (RSTS) is a rare autosomal‐dominant genetic disease caused by variants of CREBBP (RSTS1) or EP300 (RSTS2) gene. RSTS2 is much less common, with less than 200 reported cases worldwide to date. More reports are still needed to increase the understanding of its clinical manifestations and genetic characteristics.

Methods

The clinical data of two children with RSTS2 were analyzed retrospectively, and their clinical manifestations, auxiliary examinations, and mutational spectrum were summarized. Liquid chromatography–tandem mass spectrometer (LC–MS/MS) technology was used to detect the levels of steroid hormones if possible.

Results

After analyzing the clinical and genetic characteristics of two boys with RSTS2 (0.7 and 10.4 years old, respectively) admitted in our hospital, we identified two novel heterozygous variants in the EP300 exon 22 (c.3750C > A, p. Cys1250*, pathogenic; c.1889A > G, p. Tyr630Cys, likely pathogenic), which could account for their phenotype. In addition to common clinical manifestations such as special facial features, microcephaly, growth retardation, intellectual disability, speech delay, congenital heart defect, recurrent respiratory infections, and immunodeficiency, we found one of them had a rare feature of adrenal insufficiency, and LC–MS/MS detection showed an overall decrease in steroid hormones.

Conclusion

In our study, we identified two novel variants in the EP300 exon 22, and for the first time, we reported a case of RSTS2 associated with adrenal insufficiency, which will enrich the clinical and mutational spectrum of this syndrome.
Global well‐posedness of the 3D primitive equations with only horizontal eddy diffusivity and delays in both convective and heat source terms
Authors: Liu Wenjun , Fan Zhenduo , Tan Shenyang
Published: May 2023

In ocean and atmospheric dynamics, the strong horizontal turbulent mixing tends to produce horizontal eddy viscosity, so the horizontal scale is much larger than the vertical scale. At the same time, as a fluid, the motion of the atmosphere or the ocean has a delayed property to some extent. In this paper, we consider 3D viscous primitive equations with only horizontal eddy diffusivity and delays in both convective and heat source terms. With some suitable assumptions on delay term, we prove the existence and uniqueness of strong solution with
initial data and obtain the existence and uniqueness of the stationary solution. Moreover, we prove that the strong solution converges exponentially to the stationary solution under some suitable assumptions.
Adoption and Utilization of Heat and Moisture Exchangers (HMEs) in the Tracheostomy Patient
Authors: Kearney Ann , Norris Kristi , Bertelsen Carol , Samad Idris , Cambridge Maribeth , Croft Glenn , Peavler Staci , Groen Christa , Doyle Philip C. , Damrose Edward J.
Published: May 2023

Objective

Management of tracheostomized patients typically involves a conventional external humidification system (CEHS). CEHS are noisy, negatively impact patient mobility, and increases costs. Additionally, they prevent phonation and the ability to cough. Alternatively, heat and moisture exchange (HME) devices have been used in laryngectomized patients. We present an institutional quality improvement project exploring the use and efficacy of an HME device following tracheostomy.

Methods

Health care professionals and stakeholders from multiple disciplines were identified: otolaryngology, nursing, administration, case management, and speech‐language pathology. The focus was on an otolaryngology acute care nursing unit. Protocols for product acquisition, nursing education, care flowcharts, and discharge planning were established. Efficacy was assessed by tracking patient pulmonary status, nursing notes, and questionnaires.

Results

Seventy‐one tracheostomized patients were enrolled. Two patients (2.8%) were unable to tolerate the HME. There were no complications from mucous plugging or respiratory distress. Eighty‐nine percent of nursing staff surveyed preferred the use of an HME device over CEHS, particularly for ease of patient mobility. Additional favorable findings were patient satisfaction, cost savings, reduced noise, communication, and ease of discharge education and planning.

Discussion

Replacing CEHS with HMEs provides distinct advantages, with a positive impact on patients, family members, and health care personnel. Resistance to changing from the traditional standard of care was alleviated with education, focused training, and positive outcomes.

Implications for Practice

These data indicate that an HME device is safe and offers advantages to both patients and nurses over traditional CEHS.
Unique Measurements of Intranasal Trigeminal Function: A Pilot Study
Authors: Durrant Frederick G. , Chen Tiffany , Poupore Nicolas S. , Nguyen Shaun A. , Chapurin Nikita , Schlosser Rodney J.
Published: May 2023

Objective

To investigate novel methods of measuring intranasal trigeminal function and correlate to validated measures of trigeminal function.

Study Design

Prospective cohort study.

Setting

Tertiary medical center.

Methods

Forty‐one subjects without nasal congestion were assessed. The trigeminal temperature function of the cool/warmth detection threshold and cold/heat pain threshold was measured with the Thermal Sensory Analyzer (TSA) device, as previously validated at buccal mucosa and infraorbital skin. Identical temperature sensory function was assessed at the anterior septum and inferior turbinate. Lateralization of trigeminal odorants eucalyptol, isothiocyanate, and acetic acid was conducted. Visual analog scales (VAS) of trigeminal function were collected.

Results

Extraoral cheek site and oral site thermal measures were moderately correlated, suggesting consistent assessment of trigeminal function. Nearly all intranasal thermal measures correlated between the septum and turbinate (significant correlations [ρ] ranged from .3 to .8). Oral and extraoral cheek sites had modest correlations to intranasal cold and heat pain (ρ = .4‐.5). The oral site had modest correlations of cold and heat detection to intranasal sites, with turbinate appearing to have the most correlations. Isothiocyanate lateralization was the most closely correlated to intranasal thermal scores for cold and heat pain. Turbinate thermal measures had weak correlations with trigeminal VAS scores (ρ = .3‐.4).

Conclusion

Intranasal trigeminal measures of thermal function correlate to validated extraoral and intraoral thermal measures. The turbinate appears to have stronger correlations to the septum than found in the mouth and face. TSA testing might provide a rapid, novel method of intranasal trigeminal function assessment.
Managing the risk of MOC
Authors: Chosnek Jack
Published: May 2023

During the execution of a change using Management of Change (MOC), the risk to the facility is increased because things are in flux until the change is completed and documented and personnel trained. During this time P&IDs, SOPs, and other procedures are being developed or changed. Construction or tie‐ins in preparation, or as part of the change, are going on. Thus, during the change until it is complete, the potential for error, and therefore the risk, is increased. This potential for error emanates from the use of not‐yet implemented P&IDs, the use of unapproved or old procedures, and unintended connections and flows from or to piping that contains hazardous materials. Additional risk results from an incorrect workflow where the appropriate individuals were not included in the review or the necessary approvals are bypassed. Another possible risk is unknowingly impacting an existing safeguard by changing related equipment. Thus, the MOC process needs to be carefully managed, not only for an individual MOC but the aggregate of all the MOCs that are being worked on at the same time. The elements for minimizing the risk of a change are described, and a tool to monitor the MOC process, which includes automatic metrics, is illustrated.
Development of a sensitive and quantitative HPLC‐FLD method for the determination of obestatin in human plasma
Authors: Atila Karaca Sakine , Temel Tuncer , Yeniceli Uğur Duygu
Published: May 2023

Obestatin is a gastrointestinal system peptide. The quantification of this peptide is conventionally performed using immunological techniques. In this study, a selective and sensitive HPLC method coupled with fluorescence detection for the quantitation of obestatin in human plasma was developed and validated. The separation was obtained on a C18 (4.6 × 100 mm, 3.5‐μm particles) column using a mobile phase composed of acetonitrile and water, both including 0.1% trifluoroacetic acid. The developed method was found to be linear in the concentration range of 20 to 1000 ng/mL, with a coefficient of determination of 0.9982. The precision results were less than 10%, and the accuracy results were between 92% and 107%. The detection and quantification limit values were obtained as 2.8 and 9.4 ng/mL, respectively. Analyte solutions were found stable for 24 h at room temperature, three freeze–thaw cycles, and 2 weeks at −20°C. The developed method was successfully used for the quantification of obestatin in human plasma samples. In conclusion, the developed method is sensitive and specific for measuring the plasma concentrations of obestatin.
Physiologically‐based pharmacokinetic modeling of quinidine to establish a CYP3A4, P‐gp, and CYP2D6 drug–drug–gene interaction network
Authors: Feick Denise , Rüdesheim Simeon , Marok Fatima Zahra , Selzer Dominik , Loer Helena Leonie Hanae , Teutonico Donato , Frechen Sebastian , van der Lee Maaike , Moes Dirk Jan A. R. , Swen Jesse J. , Schwab Matthias , Lehr Thorsten
Published: May 2023

The antiarrhythmic agent quinidine is a potent inhibitor of cytochrome P450 (CYP) 2D6 and P‐glycoprotein (P‐gp) and is therefore recommended for use in clinical drug–drug interaction (DDI) studies. However, as quinidine is also a substrate of CYP3A4 and P‐gp, it is susceptible to DDIs involving these proteins. Physiologically‐based pharmacokinetic (PBPK) modeling can help to mechanistically assess the absorption, distribution, metabolism, and excretion processes of a drug and has proven its usefulness in predicting even complex interaction scenarios. The objectives of the presented work were to develop a PBPK model of quinidine and to integrate the model into a comprehensive drug–drug(–gene) interaction (DD(G)I) network with a diverse set of CYP3A4 and P‐gp perpetrators as well as CYP2D6 and P‐gp victims. The quinidine parent‐metabolite model including 3‐hydroxyquinidine was developed using pharmacokinetic profiles from clinical studies after intravenous and oral administration covering a broad dosing range (0.1–600 mg). The model covers efflux transport via P‐gp and metabolic transformation to either 3‐hydroxyquinidine or unspecified metabolites via CYP3A4. The 3‐hydroxyquinidine model includes further metabolism by CYP3A4 as well as an unspecific hepatic clearance. Model performance was assessed graphically and quantitatively with greater than 90% of predicted pharmacokinetic parameters within two‐fold of corresponding observed values. The model was successfully used to simulate various DD(G)I scenarios with greater than 90% of predicted DD(G)I pharmacokinetic parameter ratios within two‐fold prediction success limits. The presented network will be provided to the research community and can be extended to include further perpetrators, victims, and targets, to support investigations of DD(G)Is.
Metal–Organic Framework–Derived Mesoporous B‐Doped CoO/Co@N‐Doped Carbon Hybrid 3D Heterostructured Interfaces with Modulated Cobalt Oxidation States for Alkaline Water Splitting
Authors: Cha Dun Chan , Singh Thangjam Ibomcha , Maibam Ashakiran , Kim Tae Hyeong , Nam Dong Hwan , Babarao Ravichandar , Lee Seunghyun
Published: May 2023

Heteroatom‐doped transition metal‐oxides of high oxygen evolution reaction (OER) activities interfaced with metals of low hydrogen adsorption energy barrier for efficient hydrogen evolution reaction (HER) when uniformly embedded in a conductive nitrogen‐doped carbon (NC) matrix, can mitigate the low‐conductivity and high‐agglomeration of metal‐nanoparticles in carbon matrix and enhances their bifunctional activities. Thus, a 3D mesoporous heterostructure of boron (B)‐doped cobalt‐oxide/cobalt‐metal nanohybrids embedded in NC and grown on a Ni foam substrate (B‐CoO/Co@NC/NF) is developed as a binder‐free bifunctional electrocatalyst for alkaline water‐splitting via a post‐synthetic modification of the metal–organic framework and subsequent annealing in different Ar/H2 gas ratios. B‐CoO/Co@NC/NF prepared using 10% H2 gas (B‐CoO/Co@NC/NF [10% H2]) shows the lowest HER overpotential (196 mV) and B‐CoO/Co@NC/NF (Ar), developed in Ar, shows an OER overpotential of 307 mV at 10 mA cm−2 with excellent long‐term durability for 100 h. The best anode and cathode electrocatalyst‐based electrolyzer (B‐CoO/Co@NC/NF (Ar)(+)//B‐CoO/Co@NC/NF (10% H2)(−)) generates a current density of 10 mA cm−2 with only 1.62 V with long‐term stability. Further, density functional theory investigations demonstrate the effect of B‐doping on electronic structure and reaction mechanism of the electrocatalysts for optimal interaction with reaction intermediates for efficient alkaline water‐splitting which corroborates the experimental results.
Adaptive solving strategy synthesis for symbolic execution
Authors: Chen Zhenbang , Zhang Guofeng , Chen Zehua , Shuai Ziqi , Pan Weiyu , Zhang Yufeng , Wang Ji
Published: May 2023

Constraint solving is the enabling technique for symbolic execution. The advancement of constraint solving boosts the development and application of symbolic execution. Modern Satisfiability Modulo Theories (SMT) solvers provide the mechanism of solving strategy, allowing users to control the solving procedure. This mechanism significantly improves the solver's generalization ability. We observe that the symbolic executions of different programs are different constraint solving problems. Therefore, we propose synthesizing solving strategies for a program to fit the program's symbolic execution best. To achieve this, we propose an adaptive framework for synthesizing solving strategies, in which the constraints are classified into different categories, and the solving strategies are synthesized for different categories on demand. We propose novel synthesis algorithms that combine the offline trained deep learning models and online tuning to synthesize the solving strategy. The algorithms balance the synthesis overhead and the improvement achieved by the synthesized solving strategy. We have implemented our method on the state‐of‐the‐art symbolic execution engine KLEE for C programs and Symbolic Pathfinder (SPF) for Java programs. The results of the extensive experiments indicate that our method effectively improves the efficiency of symbolic execution. For the Coreutils benchmark, our method, on average, increases the numbers of paths and queries by 74.37% and 73.94% under Breadth First Search (BFS), respectively. Besides, we applied our method to a different benchmark of C programs and a benchmark of Java programs to validate the generalization ability. The results demonstrate that for the C benchmark, our method increases the numbers of paths and queries by 71.09% and 70.60% under BFS, respectively; For the Java benchmark, our method increases the numbers of paths and queries by 50.31% and 49.93% under BFS, respectively. These results show that our method has a good generalization ability.
Spatial dynamic panel models with missing data
Authors: Liu Jin , Zhou Jing , Lan Wei , Wang Hansheng
Published: May 2023

Missing data are a common problem that researchers face in practice. In this article, we focus on the missing response problem for a spatial dynamic panel data (SDPD) model, which allows for both spatial and temporal dependencies. A logistic regression with a set of prespecified covariates is used to model the missingness mechanism, which is assumed to be missing at random (MAR). A weighted maximum likelihood estimator (WMLE) is proposed for parameter estimation in the presence of incomplete data. The associated asymptotic properties are investigated. Thereafter, we develop a novel imputation method, which makes use of the information from spatial dependence, temporal dependence and exogenous regression covariates. Lastly, the performance of WMLE and the proposed imputation method are demonstrated by both simulation studies and a real data example.
Developing RRI and Research Ethics in Universities
Authors: Bernal-Sánchez Laura , Feenstra Ramón A.
Published: May 2023

This work examines the process of developing responsible research and innovation (RRI) at Universitat Jaume I, a public university in Castelló Spain. In this context, the chapter presents some basic characteristics of RRI implementation by exploring thestepsin the process, and some barriers and drivers. In particular, the authors examine the development of a code of good research practice and the university’s ethics committees. Both tools are developed in line with the European ETHNA System project, which provides practical guides for RRI institutionalisation processes.
Does the peer-led Honest, Open, Proud program reduce stigma’s impact for everyone? An individual participant data meta-regression analysis
Authors: Klein Thomas , Kösters Markus , Corrigan Patrick W. , Mak Winnie W. S. , Sheehan Lindsay , Conley Colleen S. , Oexle Nathalie , Rüsch Nicolas
Published: May 2023

Purpose

Many people with mental illness experience self-stigma and stigma-related stress and struggle with decisions whether to disclose their condition to others. The peer-led Honest, Open, Proud (HOP) group program supports them in their disclosure decisions. In randomized controlled trials, HOP has shown positive effects on self-stigma and stigma stress on average. This study examined individual predictors of HOP outcomes and tested the hypothesis that stigma stress reduction at the end of HOP mediates positive HOP effects at follow-up.

Methods

Six RCTs were included with data at baseline, post (after the HOP program) and at 3- or 4-week follow-up. Baseline variables were entered in meta-regression models to predict change in self-stigma, stigma stress, depressive symptoms and quality of life among HOP participants. Mediation models examined change in stigma stress (post) as a mediator of HOP effects on self-stigma, depressive symptoms, and quality of life at follow-up.

Results

More shame at baseline, and for some outcomes reduced empowerment, predicted reduced HOP effects on stigma stress, self-stigma, depressive symptoms, and quality of life. Younger age was related to greater improvements in stigma stress after the HOP program. Stigma stress reductions at the end of HOP mediated positive effects on self-stigma, depressive symptoms and quality of life at follow-up.

Conclusion

Participants who are initially less burdened by shame may benefit more from HOP. Stigma stress reduction could be a key mechanism of change that mediates effects on more distal outcomes. Implications for the further development of HOP are discussed.
Prevalence of pelvic floor dysfunction in recreational athletes: a cross-sectional survey
Authors: Campbell K. Gillian , Batt Mark E. , Drummond Avril
Published: May 2023

Introduction and hypothesis

Pelvic floor dysfunction (PFD) affects many women and participation in elite sport and high-impact exercise has been reported as a potential risk. However, few studies have investigated the effects of exercising at recreational levels on PFD. Our aim was to investigate levels of PFD in women exercising at, or above, UK guidelines for health and compare them with levels in non-exercisers.

Method

Data on levels of PFD and potential risk factors (age, hormonal status, body mass index, constipation, parity, forceps delivery, and recreational exercise) were collected using a cross-sectional survey distributed via social media. The International Consultation Incontinence Questionnaire (ICIQ) Urinary Incontinence Short Form was used to estimate prevalence of urinary incontinence (UI). Selected questions from the ICIQ vaginal symptom and bowel symptom questionnaires were used to estimate prevalence of anal incontinence (AI) and pelvic organ prolapse (POP). Logistic regression analysis was used to compare exercisers and non-exercisers after adjusting for potential confounders.

Results

We recruited 1,598 adult women (1,141 exercisers and 457 non-exercisers). The majority were parous. High prevalence of UI (70%), AI (52%) and POP (18%) was reported. No significant association was found between recreational exercise and PFD despite adjustment for confounders, or further investigation regarding exercise involving impact, although some increased reporting of AI was seen in those exercising for over 10 hours per week.

Conclusion

High levels of all PFD were reported but no significant association was found between recreational exercise and symptoms. However, data suggest that women modify their exercise regimes as required. Few symptomatic women sought professional help.
Expanding the boundaries of atomic spectroscopy at the single-cell level: critical review of SP-ICP-MS, LIBS and LA-ICP-MS advances for the elemental analysis of tissues and single cells
Authors: Davison Claire , Beste Dany , Bailey Melanie , Felipe-Sotelo Mónica
Published: May 2023

Metals have a fundamental role in microbiology, and accurate methods are needed for their identification and quantification. The inability to assess cellular heterogeneity is considered an impediment to the successful treatment of different diseases. Unlike bulk approaches, single-cell analysis allows elemental heterogeneity across genetically identical populations to be related to specific biological events and to the effectiveness of drugs. Single particle-inductively coupled plasma-mass spectrometry (SP-ICP-MS) can analyse single cells in suspension and measure this heterogeneity. Here we explore advances in instrumental design, compare mass analysers and discuss key parameters requiring optimisation. This review has identified that the effect of pre-treatment of cell suspensions and cell fixation approaches require further study and novel validation methods are needed as using bulk measurements is unsatisfactory. SP-ICP-MS has the advantage that a large number of cells can be analysed; however, it does not provide spatial information. Techniques based on laser ablation (LA) enable elemental mapping at the single-cell level, such as laser-induced breakdown spectroscopy (LIBS) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The sensitivity of commercial LIBS instruments restricts its use for sub-tissue applications; however, the capacity to analyse endogenous bulk components paired with developments in nano-LIBS technology shows great potential for cellular research. LA-ICP-MS offers high sensitivity for the direct analysis of single cells, but standardisation requires further development. The hyphenation of these trace elemental analysis techniques and their coupling with multi-omic technologies for single-cell analysis have enormous potential in answering fundamental biological questions.
Single-cell ICP-MS for studying the association of inorganic nanoparticles with cell lines derived from aquaculture species
Authors: Suárez-Oubiña Cristian , Herbello-Hermelo Paloma , Mallo Natalia , Vázquez María , Cabaleiro Santiago , Pinheiro Ivone , Rodríguez-Lorenzo Laura , Espiña Begoña , Bermejo-Barrera Pilar , Moreda-Piñeiro Antonio
Published: May 2023

The current research deals with the use of single-cell inductively coupled plasma-mass spectrometry (scICP-MS) for the assessment of titanium dioxide nanoparticle (TiO2 NP) and silver nanoparticle (Ag NP) associations in cell lines derived from aquaculture species (sea bass, sea bream, and clams). The optimization studies have considered the avoidance of high dissolved background, multi-cell peak coincidence, and possible spectral interferences. Optimum operating conditions were found when using a dwell time of 50 μs for silver and 100 μs for titanium. The assessment of associated TiO2 NPs by scICP-MS required the use of ammonia as a reaction gas (flow rate at 0.75 mL min−1) for interference-free titanium determinations (measurements at an m/z ratio of 131 from the 48Ti(NH)(NH3)4 adduct). The influence of other parameters such as the number of washing cycles and the cell concentration on accurate determinations by scICP-MS was also fully investigated. Cell exposure trials were performed using PVP-Ag NPs (15 and 100 nm, nominal diameter) and citrate-TiO2 NPs (5, 25, and 45 nm, nominal diameter) at nominal concentrations of 10 and 50 μg mL−1 for citrate-TiO2 NPs and 5.0 and 50 μg mL−1 for PVP-Ag NPs. Results have shown that citrate-TiO2 NPs interact with the outer cell membranes, being quite low in the number of citrate-TiO2 NPs that enters the cells (the high degree of aggregation is the main factor which leads to the aggregates being in the extracellular medium). In contrast, PVP-Ag NPs have been found to enter the cells.

Graphical abstract
A review of the importance of south-east Australian waters as a global hotspot for leatherback turtle foraging and entanglement threat in fisheries
Authors: Hays Graeme C. , Morrice Margie , Tromp Jared J.
Published: May 2023

Australia’s largest sea turtle is the leatherback (Dermochelys coriacea). Leatherbacks do not nest, or only rarely, in Australia, and hence receive relatively little research attention. Here we review the knowledge of leatherback turtle occurrence in south-east (SE) Australia, drawing on sightings information as well as satellite tracking data from turtles equipped at their nesting beaches in Indonesia, the Solomon Islands and Papua New Guinea that then travelled to Australia. These data reveal that SE Australia likely provides a globally important foraging area for this species. Sea turtle temperatures assigned to sightings of live leatherbacks, showed 95% were seen at SSTs ≥ 14 °C. Similar to other parts of the world, such as the North Atlantic, the 12–15 °C isotherms likely constrain the seasonal pole-wards migration of leatherbacks searching for their gelatinous prey. Climate warming is likely moving the foraging range of leatherbacks poleward. This study also highlights the vulnerability of this SE Australian population to anthropogenic threats. Of 605 sightings of leatherbacks, 11.6% were of dead individuals, generally washed ashore, in most cases likely after entanglement in fishing gear.
Artificial intelligence tools in clinical neuroradiology: essential medico-legal aspects
Authors: Hedderich Dennis M. , Weisstanner Christian , Van Cauter Sofie , Federau Christian , Edjlali Myriam , Radbruch Alexander , Gerke Sara , Haller Sven
Published: May 2023

Commercial software based on artificial intelligence (AI) is entering clinical practice in neuroradiology. Consequently, medico-legal aspects of using Software as a Medical Device (SaMD) become increasingly important. These medico-legal issues warrant an interdisciplinary approach and may affect the way we work in daily practice. In this article, we seek to address three major topics: medical malpractice liability, regulation of AI-based medical devices, and privacy protection in shared medical imaging data, thereby focusing on the legal frameworks of the European Union and the USA. As many of the presented concepts are very complex and, in part, remain yet unsolved, this article is not meant to be comprehensive but rather thought-provoking. The goal is to engage clinical neuroradiologists in the debate and equip them to actively shape these topics in the future.
Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing
Authors: Jang Sung Ill , Lee Hyung Keun , Chang Eun-Ju , Kim Somi , Kim So Young , Hong In Young , Kim Jong Kyoung , Lee Hye Sun , Yang Juyeon , Cho Jae Hee , Lee Dong Ki
Published: May 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance.

Methods

In this prospective, blinded, case–control study, a biomarker panel formula was generated using a development cohort—including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies—and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT).

Results

RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0–13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8–37.6).

Conclusions

The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT.

Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).
Exploiting docetaxel-induced tumor cell necrosis with tumor targeted delivery of IL-12
Authors: Franks S. Elizabeth , Santiago-Sanchez Ginette S. , Fabian Kellsye P. , Solocinski Kristen , Chariou Paul L. , Hamilton Duane H. , Kowalczyk Joshua T. , Padget Michelle R. , Gameiro Sofia R. , Schlom Jeffrey , Hodge James W.
Published: May 2023

There is strong evidence that chemotherapy can induce tumor necrosis which can be exploited for the targeted delivery of immuno-oncology agents into the tumor microenvironment (TME). We hypothesized that docetaxel, a chemotherapeutic agent that induces necrosis, in combination with the bifunctional molecule NHS-IL-12 (M9241), which delivers recombinant IL-12 through specific targeting of necrotic regions in the tumor, would provide a significant antitumor benefit in the poorly inflamed murine tumor model, EMT6 (breast), and in the moderately immune-infiltrated tumor model, MC38 (colorectal). Docetaxel, as monotherapy or in combination with NHS-IL-12, promoted tumor necrosis, leading to the improved accumulation and retention of NHS-IL-12 in the TME. Significant antitumor activity and prolonged survival were observed in cohorts receiving docetaxel and NHS-IL-12 combination therapy in both the MC38 and EMT6 murine models. The therapeutic effects were associated with increased tumor infiltrating lymphocytes and were dependent on CD8+ T cells. Transcriptomics of the TME of mice receiving the combination therapy revealed the upregulation of genes involving crosstalk between innate and adaptive immunity factors, as well as the downregulation of signatures of myeloid cells. In addition, docetaxel and NHS-IL-12 combination therapy effectively controlled tumor growth of PD-L1 wild-type and PD-L1 knockout MC38 in vivo, implying this combination could be applied in immune checkpoint refractory tumors, and/or tumors regardless of PD-L1 status. The data presented herein provide the rationale for the design of clinical studies employing this combination or similar combinations of agents.
A Scoping Review of Kidney Transplantation in Africa: How Far have We Come?
Authors: Davis Samuel Olawale , Zubair Abdulahi , Igbokwe Martin , Abu Moses , Chiedozie Chineme‐Anyaeze , Sanni Quadri , Jesuyajolu Damilola
Published: May 2023

Introduction

Kidney transplantation is a life‐saving treatment for end‐stage kidney disease (ESKD) patients. However, access to this treatment in Africa lags behind other regions, leading to significant disparities in care. We aimed to analyse the indications, demographics, and outcomes of kidney transplantation in Africa.

Method

We conducted a systematic review of studies from PubMed, Google Scholar, and African Journal Online using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. We pooled and analysed data on procedure type, graft outcomes, donor type, prophylaxis, post‐operative complications, and survival from 33 eligible studies.

Result

The most common causes of ESKD requiring transplantation were glomerulonephritis and nephroangiosclerosis. Open nephrectomy was the predominant surgical approach (95%). Living donors accounted for 56.3% (4221) of all donors, with 68.5% being related to the recipient. Cadaveric donors accounted for 43.7% (3280) of transplants. Graft rejection was the most common surgical complication (39.44%), and 60.49% of patients developed hypertension in the follow‐up period.

Conclusion

Our study highlights the potential of kidney transplantation to improve the lives of ESKD patients in Africa. However, further research and infrastructure development are necessary to make this treatment more widespread and successful.
One-stage product-line design heuristics: an empirical comparison
Authors: Baier Daniel , Voekler Sascha
Published: May 2023

Selecting or adjusting attribute-levels (e.g. components, equipments, flavors, ingredients, prices, tastes) for multiple new and/or status quo products is an important task for a focal firm in a dynamic market. Usually, the goal is to maximize expected overall buyers’ welfare based on consumers’ partworths or expected revenue, market share, and profit under given assumptions. However, in general, these so-called product-line design problems cannot be solved exactly in acceptable computing time. Therefore, heuristics have been proposed: Two-stage heuristics select promising candidates for single products and evaluate sets of them as product-lines. One-stage heuristics directly search for multiple attribute-level combinations. In this paper, Ant Colony Optimization, Genetic Algorithms, Particle Swarm Optimization, Simulated Annealing and, firstly, Cluster-based Genetic Algorithm and Max-Min Ant Systems are applied to 78 small- to large-size product-line design problem instances. In contrast to former comparisons, data is generated according to a large sample of commercial conjoint analysis applications (n = 2,089). The results are promising: The firstly applied heuristics outperform the established ones.
Biomineralisation and metal sequestration in a crustacean ectoparasite infecting the gills of a freshwater fish
Authors: Latief Lutfiyya , Gilbert Beric M. , Avenant-Oldewage Annemariè
Published: May 2023

It has been suggested that parasites are effective bioindicators as they are sensitive to environmental changes and, in some cases, accumulate trace elements in higher concentrations than their hosts. Accumulated elements sequester in different organs. In monogenean and crustacean ectoparasites, sclerotised structures and egg yolk appear to be the preferred site for element sequestration. In this study, the sequestration of trace elements; Mg, Al, Ca, Fe, Cu, and Zn in Lamproglena clariae was studied from two rivers. Adult L. clariae were collected from the gills of Clarias gariepinus from Lake Heritage in the Crocodile River and in the Vaal River below the Vaal Dam, South Africa. Collected parasites were flash frozen in liquid nitrogen and sectioned with a cryomicrotome. Sections were treated with Phen-Green to observe fluorescent signals. Trace elements in the parasite were analysed using a scanning electron microscope with an energy-dispersive spectroscope (SEM–EDS). Results showed more intense fluorescence signals in the exoskeleton compared to tissues, and in the egg yolk. Analysis by SEM–EDS confirmed the presence of elements in the parasite from both sites. Levels of Al were higher in L. clariae from the Vaal River than those from Lake Heritage, and Fe was higher in L. clariae from Lake Heritage. Element distribution patterns in the parasite matched those in the water from the sites. Unlike other crustaceans, regulation of metals in adult females of L. clariae does not occur through moulting, but high levels occurred in the yolk.
Drivers of low-frequency Sahel precipitation variability: comparing CMIP5 and CMIP6 ensemble means with observations
Authors: Herman Rebecca Jean , Biasutti Michela , Kushnir Yochanan
Published: May 2023

Phases 5 and 6 of the Coupled Model Intercomparison Project (CMIP5 and CMIP6) both grossly underestimate the magnitude of low-frequency Sahel rainfall variability; but unlike CMIP5, CMIP6 mean historical precipitation does not even correlate with observed multi-decadal variability. We demarcate realms of simulated physical processes that may induce differences between these ensembles and prevent both from explaining observations. We partition all influences on simulated Sahelian precipitation variability into (1) teleconnections from sea surface temperature (SST); (2) atmospheric and (3) oceanic variability internal to the climate system; (4) the SST response to external radiative forcing; and (5) the “fast” (not mediated by SST) precipitation response to radiative forcing. In a vast improvement from previous ensembles, the mean spectral power of Sahel rainfall in CMIP6 atmosphere-only simulations is consistent with observed low-frequency variance. Low-frequency variability is dominated by teleconnections from observed global SST, and the fast response only hurts the performance of simulated precipitation. We estimate that the strength of simulated teleconnections is consistent with observations using the previously-established North Atlantic Relative Index (NARI) to approximate the role of global SST, and apply this relationship to the coupled ensembles to infer that both fail to explain low-frequency historical Sahel rainfall variability mostly because they cannot explain the observed combination of forced and internal variability in North Atlantic SST. Yet differences between CMIP5 and CMIP6 in mean Sahel precipitation and its correlation with observations do not derive from differences in NARI, but from the fast response or the role of other SST patterns.
Age and gender in gerontechnology development
Authors: Rießenberger Katja Antonia , Fischer Florian
Published: May 2023

Background

The challenges of the digital divide emerge with new technologies being created to address the needs of the increasing older population. This divide is influenced by the social dimensions of age and gender, often resulting in impaired participation of the affected demographic groups. Gerontechnological designs in which inadequate attention is paid to gender and old age easily run the risk of reproducing gender-specific and age-specific stereotypes. An approach to counteracting the digital exclusion of technology users is the introduction of co-creative methods of participatory design (PD). As there are diverse challenges when putting these methods into practice regarding their claim to be more socially inclusive and democratizing technology development, it is necessary to investigate the effect that age and gender could play when considering PD in gerontechnology.

Objective

This article aims to shed light on the intersection of age and gender as dimensions of horizontal inequalities in gerontechnology development to support the further development of co-creation practices.

Conclusion

The PD approaches can be regarded as suitable methodologies to descript age and gender in technology development as long as they are enhanced by a critical awareness of gendered and ageist patterns in society and technology development. The intersectional approach can contribute to further understanding of how current gerontechnology development practices promote the reinforcement and challenging of dominant discourses on old age and gender.
Characteristics of smell and taste disorders depending on etiology: a retrospective study
Authors: Trache Mihnea Cristian , Schipp Josef Maria Heinrich , Haack Mareike , Adderson-Kisser Christine , Högerle Catalina , Becker Sven , Betz Christian Stephan
Published: May 2023

Purpose

This study investigates the impact of etiology on the epidemiologic profile, disease severity, type of treatment and therapy outcome in smell and taste disorders.

Methods

This is a retrospective analysis of 270 patients that presented with a smell or taste disorder in a specialized, tertiary care center. An established questionnaire was used to collect data from patients and physicians. Olfactometry was performed with the Sniffin’ Sticks test kit, while gustometry was performed by taste strips.

Results

Post-traumatic etiology was associated with young age (median 46 years) and male sex, and showed the most severe degrees of smell loss compared to other etiologies (64.3% anosmia). Postinfectious causes occurred more frequently in females (77.3%) and correlated with a history of pharyngeal surgery, suggesting a vulnerability for virally mediated sensory dysfunction following adenoid/tonsil removal. Parosmia also correlated with both postinfectious etiology (62.5%) and female sex. In sinunasal etiology, the presence of nasal polyps worsened the overall olfactory test score by approximately 50%. In particular, smell threshold and discrimination were reduced, while smell identification was not significantly impacted by nasal polyp obstruction. Sinunasal dysfunction was the only etiology to show significant improvement after therapy (73.9% improved). Finally, we could establish good correlations between the subjective impairment and objective dysfunction for each sensory modality.

Conclusion

Each etiology of chemosensory dysfunction shows particular distributions of variables like sex, age, comorbidities and operations, disease severity, sensory threshold, discrimination and identification. This paper offers a detailed account of the correlations between the cause and the characteristics of smell and taste loss.
Alcohol and the vasculature: a love-hate relationship?
Authors: Li Huige , Xia Ning
Published: May 2023

Alcohol consumption is a leading risk factor and increases the risk of liver diseases, cancers, tuberculosis, and injuries. The relationship between alcohol use and cardiovascular risk is complex. While it is well established that heavy alcohol use and binge drinking harm cardiovascular health, the effect of light-to-moderate alcohol consumption remains controversial. Observational studies have repeatedly confirmed the U- or J-shaped relationship between alcohol consumption and cardiovascular disease risk, with the lowest risk observed in the light-to-moderate drinking group. However, the protective effect of low-level alcohol has been challenged by recent genetic epidemiological studies with Mendelian randomization. Such studies have their own limitations, and the application of this methodology in studying alcohol has been questioned. Results from the latest Global Burden of Diseases, Injuries, and Risk Factors Study suggest that the impact of alcohol consumption on health depends on the age structure and the distribution of disease burden and underlying causes in a given population. For young adults, even small amounts of alcohol cause heath loss. For older adults facing a high burden of cardiovascular diseases, light-to-moderate alcohol consumption may improve cardiovascular health outcomes. Mechanistically, all types of alcoholic beverages, including wine, spirits, and beer, have been shown to increase the levels of high-density lipoprotein cholesterol and adiponectin, and reduce the level of fibrinogen. Nonalcoholic components of wine, especially polyphenolic compounds like resveratrol, may additionally enhance endothelial nitric oxide production, and provide antioxidant and anti-inflammatory effects.
Macroalgal-derived alginate/wastepaper hydrogel to alleviate sunflower drought stress
Authors: Gomaa Mohamed , Aldaby Eman S. E.
Published: May 2023

Main conclusion

Alginate/wastepaper hydrogel mitigated sunflower drought stress by increasing the water holding capacity of the soil and decreasing phosphate leaching. The hydrogel promoted sunflower growth and decreased stress related biomarkers.

There is a growing interest in the development of biodegradable hydrogels for the alleviation of drought stress on plants. A novel hydrogel based on brown algal-derived alginate and wastepaper was developed and tested as a soil supplement for sunflower growth under moderate (75% field capacity (FC)) and extreme (50% FC) water-deficit stress. The hydrogel showed fast swelling in water, which obeyed the pseudo-first order kinetics. Besides, it increased the water holding capacity of the soil and exhibited a good phosphate adsorption (37 mg PO4− g−1 hydrogel after 6 days) in the soil, and more than 67% of the adsorbed phosphate was desorbed after 20 days. Thus, the phosphate leaching from the hydrogel-amended soil in a column experiment was only 2.77 mg after 4 times of over-irrigation, compared to 11.91 mg without the hydrogel. The hydrogel application promoted various root traits such as fresh and dry biomass, area, and length by > 2-, > 1.6-, > 1.35-, and > 1.3-folds under both water regimes in relation to the no-hydrogel treatments at the same conditions. Furthermore, the sunflower shoots exhibited similar proline contents to the well-watered control (100% FC), with > 50% reduction in relation to the drought-stressed plants under the same conditions. Similarly, the malondialdehyde contents were lowered by > 15%. The analysis of the antioxidant enzymes also indicated a marked reduction in the specific activities of catalase and ascorbate peroxidase under both 75 and 50% FC compared to the respective controls. Additionally, the hydrogel promoted the uptake of phosphate by sunflower roots. These results implied that the developed biodegradable hydrogel could be effectively applied as a soil additive to alleviate drought stress on crops.