bluuebunny/crossref_metadata_2025 huggingface dataset:
Virgin flaxseed oil supplemented or not with tocopherols and phytosterols prevents liver steatosis induced by high‐fat diets in male Wistar rats
Authors: Scanarotti Ignacio Gabriel , Sain Juliana , Fabro Ana , Bernal Claudio Adrián
Published: March 2024

This study aimed to investigate the effect of a virgin flaxseed oil (FO) rich in n − 3 polyunsaturated fatty acid, supplemented or not with a bioactive supplement (BS) containing tocopherols and phytosterols on the prevention of nonalcoholic fatty liver disease in a high‐fat (HF) animal model. Male Wistar rats were fed 60 days with a recommended (SO7, soybean oil 7%) or an HF diet (fat, 30%) containing soybean (SO30), corn (CO30), or FO (FO30) or the same oils supplemented with 1% of BS (SO30BS, CO30BS, or FO30BS, respectively). Hepatic and dietary FA composition, triacylglycerides (TAGs) content in serum and liver, nutritional parameters, in vivo TAG‐secretion rate, liver histology, mRNA levels of β‐oxidation‐related genes, and carnitine palmitoyl transferase‐1a (CPT‐1a) enzyme activity were determined. At HF levels, FO30 and FO30BS groups showed the highest total n − 3 PUFA levels in diets and were associated with lower weight gain, liver TAG content, and microsteatosis degree. The CPT‐1a activity was enhanced in FO30 and FO30BS, showing differences only by the type of dietary oil. The BS supplementation induced an increase in the β‐oxidation‐related gene expression. Virgin FO prevented liver steatosis and hepatomegaly induced by HF diets. The BS supplementation reduced body fat accumulation and enhanced expression of β‐oxidation related genes, without affecting hepatic TAG content.

Practical Applications: Scientific knowledge of functional lipids with high oxidative stability and biological activity has great practical application in reducing non‐communicable chronic diseases. This study provides evidence on the potential synergic and complementary effects of virgin FO, TP, and PS to be used for the prevention of the metabolic hepatic disorders involved during the evolution of the different steps of NAFLD. Specifically, based on different biological mechanisms, this stable combination of bioactive lipids could prevent not only the development of exacerbated hepatic TAG accumulation but also the hepatocellular injury seen at different stages from hepatic steatosis to steatohepatitis.
Synthesis of Artemisinin G from Artemisinin via Photocatalysis
Authors: Wang Menghan , Liu Xiaoling , Zheng Xiaoshan , Luo Yining , Gao Yu , Chen Haijun
Published: March 2024

Photoredox catalysis has become a mainstay in synthetic methodology over the past decade. However, its application in the functionalization of natural products remains to be further explored. Herein, we report an efficient approach to synthesize artemisinin G from artemisinin via photocatalysis in high yield.
Practical and Divergent Synthesis of Carbocyclic Pyrazolo[3,4‐d]pyrimidine Nucleoside Analogues
Authors: Van de Velde Ewout , Van Hauwermeiren Anouk , Van Pelt Natascha , Matheeussen An , Caljon Guy , Van Calenbergh Serge
Published: March 2024

A concise set of 4‐substituted pyrazolo[3,4‐d]pyrimidine carboriboside analogues was synthesized in a divergent fashion via a central intermediate. An oxaziridine reagent allowed the synthesis of a crucial hydrazine glycon intermediate, which was transformed through a base‐build‐up strategy into the desired intermediate using a commercially available pyrimidine building block. Reaction with a variety of nucleophiles allowed late‐stage diversification. All analogues were evaluated for activity against a representative panel of Trypanosomatida. A methoxy‐substituted analogue displayed single‐digit micromolar activity against two subspecies of Trypanosoma brucei in cellular assays.
Implementation frameworks guiding digital self‐management intervention in chronic pain: A scoping review
Authors: de la Vega R. , Bartels S. L. , Wicksell R. W.
Published: March 2024

Background and Objective

The development, evaluation and implementation of digital self‐management interventions for chronic pain have increased exponentially. While intervention outcomes appear promising to improve well‐being and functioning in target populations, it is unclear how the development and evaluation processes were structured and how implementation was planned and executed. The aim of this systematic review is to provide a comprehensive overview of implementation frameworks used to guide and evaluate scientific innovation in chronic pain.

Databases and Data Treatment

Four bibliography databases (Medline, Web of Science, PsycInfo, CINAHL) and two registries (PubMed Central, MedaRxiv) were systematically searched. Hits (n = 6830) and full texts (n = 351) were screened and read by two independent reviewers. Peer‐reviewed articles that met the inclusion criteria were included in the narrative synthesis.

Results

In total, 10 studies were identified that report on seven distinct interventions. Five implementation frameworks were utilized across these studies: Behavioural Interventions using Technology (BIT); Consolidated Framework for Implementation Research (CFIR); mHealth Agile and User‐Centered Research and Development Lifecycle; Medical Research Council (MRC); Reach, Effectiveness, Adoption Implementation, and Maintenance (RE‐AIM). Frameworks were operationalized using qualitative and quantitative methods, evaluating the innovation on various levels (e.g., individual vs. organizational) and applying a variety of study designs (e.g., single‐arm or large trials).

Conclusions

By utilizing implementation frameworks, access to evidence‐based chronic pain care may be increased. Although the evidence on the utility of implementation frameworks to guide and evaluate digital self‐management interventions is still limited, the body of literature is increasing. Future studies are urged to operationalize, communicate and discuss the innovation process, to promote transparency and replicability.

Significance

The use of implementation frameworks to guide and evaluate digital self‐management interventions for chronic pain is a recent development in the field. Several promising examples exist and are presented in this review. Currently, the evidence is still limited, and prospective studies need to transparently operationalize, communicate and discuss their efforts. By utilizing an implementation framework, promising interventions can be made available to end‐users, closing the research‐to‐clinical practice gap and increasing access to evidence‐based care to people with chronic pain.
Selective harmonic elimination in PUC‐5 multilevel inverter using hybrid IGWO‐DE algorithm
Authors: Sifat Zaid , Hussain Md Tahmid , Khan Mohd Anas , Hussain Md Shahbaz , Sarwar Adil , Tariq Mohd , Hasan Mehedi
Published: March 2024

The use of a multilevel inverter has received significant attention in recent years due to its numerous advantages. Because of the widespread use of multilevel inverters in industries and applications that require a wide range of voltages, achieving high‐quality voltage has presented a number of challenges. Many studies have been carried out to address the problem of unwanted harmonics in multilevel inverters. The inverter switching can be done at a low frequency using the Selective Harmonic Elimination (SHE) technique, and the unwanted harmonics can be significantly reduced; however, the issue with SHE is solving the transcendental equations and determining the optimum switching angle. To address this problem, a new and improved hybrid algorithm is proposed that combines two evolutionary algorithms, gray wolf optimization (GWO) with an improved and new convergence factor and Differential evolution (DE) with a dynamic scaling factor using a crossover operator. In this paper, the optimum switching angles for a packed U cell 5‐level inverter are estimated using the proposed algorithm for distinct modulation index values, and simulation results are compared with different algorithms. The simulation result of the proposed algorithm, IGWO‐DE is confirmed through experiment.
Recent Developments in Graphitic Carbon Nitride and Its Interfaces for Effective Water Splitting
Authors: Padasalagi Anita B. , Doddamani Jyothi S. , Hodlur Rajashree M. , Rabinal Mohammad Hussain Kasim
Published: March 2024

Electrocatalytic and photocatalytic water splitting are effective pathways for energy conversion to overcome from the reliance on the depletion fossil fuels and preclude the severe degradation of global climate. The review begins with the basic principle and mechanisms involved in both electro/photocatalysis of water splitting. Graphitic carbon nitride (g‐C3N4) is an interesting catalyst for water splitting due to its layered conjugated metal free semiconductor, owing to its unique physicochemical characteristics. However to improve some of the features of g‐C3N4 including long term stability, large active sites, electronic band structure, low recombination rate of photogenerated charges, and many more, interface engineering with different materials have been introduced to improve the catalytic activity. The review emphasizes the basics of g‐C3N4 with its interesting properties such as chemical and thermal stability, large surface area, unique optoelectronic properties, exfoliated layered structure, and tunable surface functional groups. The various strategies that have been used to modulate catalytic activity of this material are discussed, including morphology modulation, elemental doping, interface engineering with metals, and semiconductors. Towards end of the review, a summary and future perspective is presented.
Rotatory seizures: Three video case reports
Authors: Güniken Mete Aykut , Zanapalıoğlu Ümit , Ertürk Cetin Ozdem
Published: March 2024

Content available: Video
Motorizing the buckled blister for rotary actuation
Authors: Yang Pengfei , Huang Ruixing , Dang Fei , Shan Baoxiang , Wang Dewen , Liu Hong , Li Yi , Liao Xiangbiao
Published: March 2024

Snap‐through bistability was widely exploited for rapid hopping in micro‐electro‐mechanical systems and soft robots. However, considerable energy input was required to trigger the transition between discrete buckling states blocked by potential wells. Here a dynamic buckling mechanism of a buckled blister constrained inside an outer ring is explored for eliciting rotary actuation via a localized change of curvature in the blister. Due to rotational invariance of the buckled blister, lower energy supply is required to initiate the snap‐through of buckling compared to conventional bistable mechanism. The controllability in rotational speed and output torque of the bimetallic blister‐based rotator inside a rigid stator is exhibited, and the locomotion is demonstrated with two elastic rings via localized pneumatic actuators. With broad choices of stimulus and material for rings, the findings illustrate the promising potential of two nested rings to create active motions for diverse applications including gearless motors, peristaltic pumps, and locomotive robots.
Detection of biological loads in sewage using the automated robot‐driven photoelectrochemical biosensing platform
Authors: Zhang Yiming , Chen Zhi , Wei Songrui , Zhang Yujun , Fu Hai , Zhang Han , Li Defa , Xie Zhongjian
Published: March 2024

Real‐time polymerase chain reaction (RT‐PCR) remains the most prevalent molecular detection technology for sewage analysis but is plagued with numerous disadvantages, such as time consumption, high manpower requirements, and susceptibility to false negatives. In this study, an automated robot‐driven photoelectrochemical (PEC) biosensing platform is constructed, that utilizes the CRISPR/Cas12a system to achieve fast, ultrasensitive, high specificity detection of biological loads in sewage. The Shennong‐1 robot integrates several functional modules, involving sewage sampling and pretreatment to streamline the sewage monitoring. A screen‐printed electrode is employed with a vertical graphene‐based working electrode and enhanced with surface‐deposited Au nanoparticles (NPs). CdTe/ZnS quantum dots (QDs) are further fabricated through the double‐stranded DNA (dsDNA) anchored on Au NPs. Using the cDNA template of Omicron BA.5 spike gene as a model, the PEC biosensor demonstrates excellent analytical performance, with a lower detection limit of 2.93 × 102 zm and an outstanding selectivity at the level of single‐base mutation recognition. Furthermore, the rapid, accurate detection of BA.5 in sewage demonstrates the feasibility of the PEC platform for sewage monitoring. In conclusion, this platform allows early detection and tracking of infectious disease outbreaks, providing timely data support for public health institutions to take appropriate prevention and control measures.
Sudan's healthcare crisis: The struggle of kidney patients amidst conflict
Authors: Konozy Emadeldin Hassan E.
Published: March 2024

Background and Aim

Conflicts, akin to other crises, disrupt lives and healthcare infrastructure, disproportionately affecting vulnerable individuals. The ongoing Sudanese conflict, initiated on April 15, 2023, between the Sudanese Armed Forces (SAF) and the Rapid Support Force (RSF), triggers significant population displacement, healthcare facility closures, and a scarcity of medical resources. Amid the intense conflict in Khartoum, reports of deceased individuals in the streets heighten concerns about public health, emphasizing the gravity of the situation. This crisis compounds the challenges faced by Sudan's already fragile healthcare system, impacting over 5 million displaced individuals, including those reliant on life‐saving hemodialysis sessions. This commentary aims to illuminate the challenges confronting kidney dialysis patients in war‐torn Sudan, emphasizing the impact on the Al‐Goled hemodialysis center.

Methodology

This commentary relies on reports from the American Society of Nephrology (ASN), European Renal Association (ERA), and The International Society of Nephrology (ISN), along with recent journal articles discussing the consequences of ongoing conflicts. Personal observations in Al‐Goled contribute to the insights, and data from the Al‐Goled hemodialysis center in Sudan illuminate the struggles faced by kidney dialysis patients during the conflict, presented as a case study.

Results

Kidney dialysis patients, crucial for regular hemodialysis sessions, confront severe challenges due to the overwhelming conflict. With an estimated 8000 kidney failure patients in Sudan, disruptions in healthcare services, targeted attacks on medical staff, and a shortage of resources exacerbate their plight. The Al‐Goled hemodialysis center, initially designed for 30 daily sessions, experiences a surge in demand, accommodating 85 patients daily—an alarming 183% increase. Limited resources, machine malfunctions, and a shortage of medications contribute to the loss of 13 patients' lives.

Conclusions

The conflict in Sudan disproportionately impacts kidney dialysis patients, causing disruptions in essential healthcare services. The surge in demand at the Al‐Goled center underscores the broader impact on healthcare institutions nationwide. Local efforts to source medical supplies face bureaucratic hurdles and complex exportation procedures, impeding support for kidney patients. Patients, once receiving 3 weekly sessions, now struggle to secure even one, jeopardizing their well‐being. Urgent international intervention is needed to cease the conflict and ensure the safety of healthcare facilities, especially for vulnerable populations like kidney dialysis patients.
“You have to start with what they know:” Cultivating genius and joy with multilingual adolescents
Authors: Zoeller Emily
Published: March 2024

A historically responsive literacy (HRL) approach (Muhammad, 2020a, 2020b) fosters literary pursuits in learners, preparing them to transcend skill development and use literacy to shape a more just and compassionate world. Despite its transformative potential, not enough is known about HRL application with multilinguals, especially in secondary literacy settings. This study uses the HRL framework to explore the cases of six teachers and how they cultivate genius with their multilingual students. I analyze participant narratives and teaching examples from their bilingual settings, focusing on pedagogies of translanguaging and Transliteracy. Findings show how teachers centered students' strengths in language and literacy and this supported the development of skills and identity. Cultivating genius in students amplified joy for students and teachers. For equitable literacy instruction of multilinguals, teacher development must support pedagogy that builds on multilinguals' assets and engages multiple literary pursuits.
Excess iron accumulation mediated senescence in diabetic kidney injury
Authors: Cheng Xueer , Li Yanyan , Chen Li , Jiang Chunjie , Peng Shufen , Yao Ping , Tang Yuhan
Published: March 2024

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high‐fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, β‐galactosidase staining, 5‐ethynyl‐2‐deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16/p21 knockdown, and the supernatant of HG‐treated cells caused increased LDH release from normal cells. Iron metabolism‐related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50 μM) upregulated gamma‐H2A.X variant histone and increased the senescence markers in HG‐treated cells. The treatment of deferoxamine (0.5 μM) had the opposite effect. Compared to the non‐DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co‐localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.
Budding and regeneration potential of a calyx of a freshwater Kamptozoan, Urnatella gracilis
Authors: Ishii Teruhisa , Ooga Keiko , Kato Manami , Sakai Ayako
Published: March 2024

There are only two freshwater Kamptozoans worldwide: Urnatella gracilis Leidy, 1851 and Loxosomatoides sirindhornae Wood, 2005. U. gracilis is present in Japan and is expanding its distribution, especially in Lake Hachiro. We investigated the budding and regeneration potential of a calyx of U. gracilis to clarify the mechanisms underlying its ability of regeneration. Our experiments revealed that the formation of a new calyx at the most apical position and strong adaptation to freshwater in pH 7.0. Budding successfully occurred in water with 0% salinity, however, in water with 0.15%–0.3% salinity budding was occurred in low level. These features may be very useful for propagation at Lake Hachiro in which it has to be expected that no sexual reproduction is observed because of low temperatures below 28°C. Now as Lake Hachiro has water with no salinity and almost pH 7.0, Lake Hachiro is a good place to live for U. gracilis.
Overexpression of multidrug resistance‐associated protein 1 protects against cardiotoxicity by augmenting the doxorubicin efflux from cardiomyocytes
Authors: Kok Cindy Y. , Igoor Sindhu , Rao Renuka , Tsurusaki Shinya , Titus Tracy , MacLean Lauren M. , Kadian Megha , Skelton Rhys , Chong James J. H. , Kizana Eddy
Published: March 2024

Doxorubicin is a commonly used anti‐cancer drug used in treating a variety of malignancies. However, a major adverse effect is cardiotoxicity, which is dose dependent and can be either acute or chronic. Doxorubicin causes injury by DNA damage, the formation of free reactive oxygen radicals and induction of apoptosis. Our aim is to induce expression of the multidrug resistance‐associated protein 1 (MRP1) in cardiomyocytes derived from human iPS cells (hiPSC‐CM), to determine whether this will allow cells to effectively remove doxorubicin and confer cardioprotection. We generated a lentivirus vector encoding MRP1 (LV.MRP1) and validated its function in HEK293T cells and stem cell‐derived cardiomyocytes (hiPSC‐CM) by quantitative PCR and western blot analysis. The activity of the overexpressed MRP1 was also tested, by quantifying the amount of fluorescent dye exported from the cell by the transporter. We demonstrated reduced dye sequestration in cells overexpressing MRP1. Finally, we demonstrated that hiPSC‐CM transduced with LV.MRP1 were protected against doxorubicin injury. In conclusion, we have shown that we can successfully overexpress MRP1 protein in hiPSC‐CM, with functional transporter activity leading to protection against doxorubicin‐induced toxicity.
Quantifying exposure biases in early instrumental land surface air temperature observations
Authors: Wallis Emily J. , Osborn Timothy J. , Taylor Michael , Jones Philip D. , Joshi Manoj , Hawkins Ed
Published: March 2024

Exposure biases are a pervasive non‐climatic change in land air temperature records which have been introduced as a result of changes in the way thermometers were sheltered from solar radiation and the elements over time. Exposure biases have not been widely accounted for in observational records, due to difficulties detecting/correcting the bias using traditional homogenisation techniques; therefore, exposure biases still contribute significant uncertainty to the early period in global temperature compilations. Here, an empirical approach to address the bias arising from the introduction of Stevenson‐type screens from the late‐19th century is presented. The approach consists of: (1) an empirical analysis of 54 parallel measurement series to identify the characteristics of the exposure bias in four exposure classes; (2) the development of bias‐estimation models based on an analysis of which variables influence the bias; and (3) the application of the models to an extended version of CRUTEM5 (CRUTEM5_ext), based on exposure metadata, to quantify and reduce the bias. Step one identified differences between the temperatures recorded in Stevenson screens and early exposures, which vary seasonally, diurnally, and with location and exposure class. The largest biases (in mean temperatures) were found in freestanding exposures (up to −0.78°C annually) and in summer, while the smallest biases were generally found in wall‐mounted exposures (near‐0°C annually) and in winter. Significant relationships between the bias and temperature, downward top of atmosphere and/or received shortwave downward solar radiation were found in each exposure class and led to the development of three regression‐based bias‐estimation models. Application of these models to 1,960 mid‐latitude stations in CRUTEM5_ext, resulted in small (≤0.016°C) positive adjustments to the Northern Hemisphere mid‐latitude mean before 1880, and larger (≤−0.1°C) negative adjustments to the Northern and Southern Hemisphere mid‐latitude means between 1882–1934 and 1856–1900, respectively. Larger adjustments were estimated regionally: up to −0.57°C annually and −0.79°C seasonally in individual grid cells.
Can large language models replace humans in systematic reviews? Evaluating GPT‐4's efficacy in screening and extracting data from peer‐reviewed and grey literature in multiple languages
Authors: Khraisha Qusai , Put Sophie , Kappenberg Johanna , Warraitch Azza , Hadfield Kristin
Published: March 2024

Systematic reviews are vital for guiding practice, research and policy, although they are often slow and labour‐intensive. Large language models (LLMs) could speed up and automate systematic reviews, but their performance in such tasks has yet to be comprehensively evaluated against humans, and no study has tested Generative Pre‐Trained Transformer (GPT)‐4, the biggest LLM so far. This pre‐registered study uses a “human‐out‐of‐the‐loop” approach to evaluate GPT‐4's capability in title/abstract screening, full‐text review and data extraction across various literature types and languages. Although GPT‐4 had accuracy on par with human performance in some tasks, results were skewed by chance agreement and dataset imbalance. Adjusting for these caused performance scores to drop across all stages: for data extraction, performance was moderate, and for screening, it ranged from none in highly balanced literature datasets (~1:1) to moderate in those datasets where the ratio of inclusion to exclusion in studies was imbalanced (~1:3). When screening full‐text literature using highly reliable prompts, GPT‐4's performance was more robust, reaching “human‐like” levels. Although our findings indicate that, currently, substantial caution should be exercised if LLMs are being used to conduct systematic reviews, they also offer preliminary evidence that, for certain review tasks delivered under specific conditions, LLMs can rival human performance.
Use of natural‐based commercial products as an alternative for providing bioprotection against verticillium wilt of olive
Authors: Antón‐Domínguez Begoña I. , Díaz‐Díaz Miriam , Acedo‐Antequera Francisca A. , Trapero Carlos , Agustí‐Brisach Carlos
Published: March 2024

BACKGROUND

As a result of the ineffectiveness of existing control methods against Verticillium dahliae, the causal agent of verticillium wilt of olive (Olea europaea; VWO), it is necessary to search for sustainable and environmentally friendly alternatives, such as bioprotection by products based on plant extracts and other naturally synthesized compounds. Therefore, present study aimed to evaluate the effects of seven natural‐based commercial products on the inhibition of mycelial growth, the germination of V. dahliae conidia and microsclerotia, and disease progression in olive plants (cv. Picual). Aluminium lignosulfonate and a copper phosphonate salt (copper phosphite) were included for comparative purposes.

RESULTS

The seaweed and willow extracts and copper phosphite inhibited V. dahliae mycelial growth by more than 50% at the high doses tested. Most of the products inhibited conidial germination by up to 90% compared to the control at the high doses tested. However, none of the products showed efficacy above 50% in inhibiting microsclerotia germination. The willow extract was the most effective at reducing disease severity and progression in olive plants, with no significant differences compared to the non‐inoculated negative control.

CONCLUSION

The results of the present study suggest that the use of natural‐based products (i.e. seaweed and willow extracts) is a potential sustainable alternative in an integrated VWO control strategy. © 2024 Society of Chemical Industry.
The utility of layering systemic therapies in connective tissue diseases
Authors: Surjanto Kezia , Ji Lixin , Boh Erin , Bitar Carole
Published: March 2024

Background

Cutaneous manifestations in connective tissue diseases (CTDs) are often chronic and difficult to control.

Objectives

This study aims to review the use of combination systemic medications in CTDs and assess disease response.

Methods

An IRB‐approved, retrospective chart review was conducted at a single large academic institution in New Orleans, Louisiana. Inclusion criteria were adult patients with CTDs on two or more systemic therapies.

Results

Out of 101 patients, 37.62% were taking combination systemic agents. Of these patients, 44% were diagnosed with lupus, 18% with dermatomyositis (DM), 8% with systemic scleroderma (SSc), 10% with morphea/limited scleroderma (M), 12% with mixed connective tissue disease (MCTD), and 8% with rheumatoid arthritis (RA). The most common regimen for lupus, MCTD, and SSc patients was hydroxychloroquine (HCQ) + prednisone (PRED) + mycophenolate mofetil (MMF). DM patients were most commonly taking combinations of the above regimen with intravenous immunoglobulin (IVIG). Morphea and RA patients were on multiple combinations of steroid and nonsteroidal agents including MMF, IVIG, azathioprine, methotrexate, HCQ, sulfasalazine, upadacitinib, apremilast, and tofacitinib.

Conclusions

This study aims to assess the efficacy of combination systemic medications and disease response in CTDs. Lupus was the most common CTD in our study, with patients taking 2–4 combination medications. HCQ, MMF, and PRED were the most common medications used within a combination regimen with minimal adverse effects. Though our study has several limitations including its retrospective nature and small sample size, it shows that CTDs can be resistant to monotherapy and that combination therapy might be required. More research in layering systemic agents is needed since this topic is currently limited to minimal case series and clinical trials.
Crafting emotional engagement and immersive experiences: Comprehensive scale development for and validation of hospitality marketing storytelling involvement
Authors: Ahmed Sohel , Sharif Taimur , Ting Ding Hooi , Sharif Sharmin Jamal
Published: March 2024

This study develops and validates a scale for gauging consumer involvement in storytelling (to create memorable and emotionally resonant experiences) in hospitality marketing through four phases: qualitative inquiry, construct definition, item refinement, and nomological validation. Validation involves 24 in‐depth video interviews and consecutive online surveys. The hospitality marketing storytelling involvement scale, with four dimensions—contextual cues, emotional engagement, mental cognition, and immersive experience—comprising 14 items, precisely measures consumer involvement. The scale integrates narrative transportation theory and the elaboration likelihood model to enhance understanding of consumer engagement with fundamental human cognitive and emotional processes. The validated scale offers a valuable tool for marketers to precisely assess consumer involvement and strategically leverage storytelling to evoke emotions, foster brand loyalty, and judge campaign effectiveness. In diverse marketing contexts that elicit emotions, resonate with individuals, and foster immersive experiences, the scale demonstrates remarkable adaptability. Ultimately, it can help marketers craft compelling narratives, enhance brand perception, and strengthen consumer relationships, thereby contributing to emotional connections, optimizing strategies, and enhancing consumer engagement effectiveness.
Viscosity of Suspensions of Strongly Bonded Spherical Particles of Nickel‐Manganese‐Cobalt Mixed Oxides (NMC) in Molten Poly(Ethylene Carbonate) for Batteries
Authors: Flament Augustin , Desse Melinda , Bernard Pierre , Carrot Christian
Published: March 2024

Ionically conductive polymers highly filled with active materials, such as metal oxides are increasingly studied for their potential use in all solid‐state batteries. They offer the desirable processing ease of polymers for mass production despite interfacial issues that remain to be solved. In this study, it is shown that spherical particles of transition metal oxides can be introduced in co‐polymers of alkene carbonate and ethylene oxide at loading close to the maximum packing fraction, without imparting the processability in the melt of the material. In particular, the viscosity does not show any yield stress and the increase of viscosity shows that the intrinsic viscosity of the filler does not match with the usual 2.5 value in the limit of the Einstein's equation. Conversely, rheological data show that the value is rather close to unity consistently with theoretical arguments that predicted that this scaling factor should be unity when particle rotation is precluded. In the present case, this behavior is attributed to strong bonding between polymer and filler that is proved by electronic microscopy and by dynamical mechanical spectroscopy showing a relaxation due to bound polymer.
Obesity is Associated with Increased Risk of New‐Onset Chronic Rhinosinusitis: A United States Population‐Based Cohort Study
Authors: Hoying David , Kaelber David C. , Chaaban Mohamad R.
Published: March 2024

Objective

The aim of this study was to determine the risk of a new‐encounter diagnosis of unspecified chronic rhinosinusitis (CRS), CRS with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 and 2 years following body mass index (BMI) classification of obesity utilizing a large‐population‐based analytics platform.

Study Design

Retrospective cohort analysis

Setting

The U.S. Collaborative Network within the TriNetX Analytics platform contains deidentified electronic health record (EHR) data of more than 100 million patients and was used to determine the association between obesity and a new encounter diagnosis of 3 CRS phenotypes in this study.

Results

After 1:1 propensity score matching, patients with an overweight BMI and obesity were at a higher risk for a new‐encounter diagnosis of unspecified CRS and CRSwNP compared to healthy‐weight individuals. The obesity cohort had the greatest increased risk of new‐onset unspecified CRS with a relative risk of 1.23 (95% CI: 1.20‐1.25) and 1.26 (95% CI: 1.24‐1.28) 1 and 2 years following BMI classification, respectively.

Conclusion

Our study indicates an association between obesity and new‐onset unspecified CRS and CRSwNP. With the increasing prevalence of obesity in the United States population, it will be important to understand how obesity‐associated CRS may affect treatment response. Future prospective studies are needed to assess causality and define a mechanistic link.
Clonal analysis of metachronous double biliary tract cancers
Authors: Omori Yuko , Aoki Shuichi , Ono Yusuke , Kokumai Takashi , Yoshimachi Shingo , Sato Hideaki , Kusaka Akiko , Iseki Masahiro , Douchi Daisuke , Miura Takayuki , Maeda Shimpei , Ishida Masaharu , Mizuma Masamichi , Nakagawa Kei , Mizukami Yusuke , Furukawa Toru , Unno Michiaki
Published: March 2024

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC‐related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β‐catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence‐free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5‐year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Patterns of structural variants within TP53 introns and relocation of the TP53 promoter: a commentary†
Authors: Beird Hannah C , Lin Dimitri , Lazar Alexander J , Futreal P Andrew
Published: March 2024

Gene disruption from double‐strand DNA breaks within introns is a mechanism of inactivating the tumor suppressor TP53. This occurs more frequently in osteosarcoma and biliary adenocarcinoma compared with other cancer types. The patterns of intron breakpoints within TP53 do not correlate with prevalence, intron length, or overall genome‐wide levels of rearrangements. Therefore, these breakpoints appear to be selected for reasons other than to disrupt TP53. A recent article published by Saba et al in The Journal of Pathology illustrates a benefit to having breakpoints within intron 1 using high‐quality matched genomic and transcriptomic osteosarcoma sequencing data as well as in vitro validation. The authors describe how the rearrangement results in relocation of the TP53 promoter region to regions upstream of genes that encode members of cartilage, growth plate development, osteoclast formation, and other TP53‐related pathways. The upregulation of these genes by the TP53 promoter are gain‐of‐function events that are likely to promote tumor development and growth. Therefore, this article presents a potential new paradigm in which a single mutation would result in both the loss of a tumor suppressor and the gain of an oncogenic program. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Exploring variations in recommended first‐choice therapy for complicated urinary tract infections in males: Insights from outpatient settings across age, race, and ethnicity
Authors: Sine Kathryn , Lavoie Thomas , Caffrey Aisling R. , Lopes Vrishali V. , Dosa David , LaPlante Kerry L. , Appaneal Haley J.
Published: March 2024

Introduction

There are known disparities in the treatment of infectious diseases. However, disparities in treatment of complicated urinary tract infections (UTIs) are largely uninvestigated.

Objectives

We characterized UTI treatment among males in Veterans Affairs (VA) outpatient settings by age, race, and ethnicity and identified demographic characteristics predictive of recommended first‐choice antibiotic therapy.

Methods

We conducted a national, retrospective cohort study of male VA patients diagnosed with a UTI and dispensed an outpatient antibiotic from January 2010 through December 2020. Recommended first‐choice therapy for complicated UTI was defined as use of a recommended first‐line antibiotic drug choice regardless of area of involvement (ciprofloxacin, levofloxacin, or sulfamethoxazole/trimethoprim) and a recommended duration of 7 to 10 days of therapy. Multivariable models were used to identify demographic predictors of recommended first‐choice therapy (adjusted odds ratio [aOR] > 1).

Results

We identified a total of 157,898 males diagnosed and treated for a UTI in the outpatient setting. The average antibiotic duration was 9.4 days (±standard deviation [SD] 4.6), and 47.6% of patients were treated with ciprofloxacin, 25.1% with sulfamethoxazole/trimethoprim, 7.6% with nitrofurantoin, and 6.6% with levofloxacin. Only half of the male patients (50.6%, n = 79,928) were treated with recommended first‐choice therapy (first‐line drug choice and appropriate duration); 77.6% (n = 122,590) were treated with a recommended antibiotic choice and 65.9% (n = 104,070) with a recommended duration. Age 18–49 years (aOR 1.07, 95% confidence interval [CI] 1.03–1.11) versus age ≥65 years was the only demographic factor predictive of recommended first‐choice therapy.

Conclusions

Nearly half of the patients included in this study did not receive recommended first‐choice therapies; however, racial and ethnic disparities were not identified. Underutilization of recommended first‐choice antibiotic therapy in complicated UTIs continues to be an area of focus for antimicrobial stewardship programs.
Emotional distress and future healthcare utilization in oncology populations: A systematic review
Authors: Kirsch Janae L. , Roche Anne I. , Bronars Carrie , Donovan Kristine A. , Hassett Leslie C. , Ehlers Shawna L.
Published: March 2024

Objective

Emotional distress has been correlated with greater healthcare utilization and economic costs in cancer; however, the prospective relationship between positive distress screens and future healthcare utilization is less clear. Taken together, there is a critical need to synthesize studies examining the prospective relationship between emotional distress and future healthcare use to inform distress management protocols and motivate institutional resource allocation to distress management. The aim of the systematic review is to explore the relationship between emotional distress, measured via validated emotional distress questionnaires, and subsequent healthcare utilization in patients diagnosed with cancer.

Methods

A systematic search of seven databases was conducted on 29 March 2022 and updated 3 August 2023. Eligibility criteria were: (1) peer‐reviewed, (2) quantitative or mixed methods, (3) adults (≥18 years) diagnosed with cancer, (4) cancer distress questionnaire(s) completed prior to healthcare utilization, and (5) written in English. Exclusion criteria included: (1) non‐emotional aspects of distress (i.e., spiritual or physical distress), (2) healthcare utilization characterized via economic or monetary variables, and (3) caregiver or non‐cancer populations.

Results

Nineteen peer‐reviewed articles were included in the review. There was significant heterogeneity in emotional distress instruments and type of healthcare utilization used. Most studies examining general distress or anxiety found that increased distress was predictive of greater future healthcare utilization.

Conclusion

The results suggest that individuals with higher levels of general distress and anxiety are at increased risk for future healthcare utilization.
Characterization of a Deglaciated Sediment Chronosequence in the High Arctic Using Near‐Surface Geoelectrical Monitoring Methods
Authors: Cimpoiasu Mihai O. , Kuras Oliver , Harrison Harry , Wilkinson Paul B. , Meldrum Philip , Chambers Jonathan E. , Liljestrand Dane , Oroza Carlos , Schmidt Steven K. , Sommers Pacifica , Irons Trevor P. , Bradley James A.
Published: March 2024

Accelerated climate warming is causing significant reductions in the volume of Arctic glaciers, such that previously ice‐capped bare ground is uncovered, harboring soil development. Monitoring the thermal and hydrologic characteristics of soils, which strongly affect microbial activity, is important to understand the evolution of emerging terrestrial landscapes. We instrumented two sites on the forefield of a retreating Svalbard glacier, representing sediment ages of approximately 5 and 60 years since exposure. Our instrumentation included an ERT array complemented by adjacent point sensor measurements of subsurface temperature and water content. Sediments were sampled at each location and at two more additional sites (120 and 2000 years old) along a chronosequence aligned with the direction of glacial retreat. Analysis suggests older sediments have a lower bulk density and contain fewer large minerals, which we interpret to be indicative of sediment reworking over time. Two months of monitoring data recorded during summer 2021 indicate that the 60‐year‐old sediments are stratified showing more spatially consistent changes in electrical resistivity, whereas the younger sediments show a more irregular structure, with consequences on heat and moisture conductibility. Furthermore, our sensors reveal that young sediments have a higher moisture content, but a lower moisture content variability.
Computational analyses of drug resistance mutations in katG and emb complexes in Mycobacterium tuberculosis
Authors: Basrai Aadam , Blundell Tom L. , Pandurangan Arun Prasad
Published: March 2024

The number of antibiotic resistant pathogens is increasing rapidly, and with this comes a substantial socioeconomic cost that threatens much of the world. To alleviate this problem, we must use antibiotics in a more responsible and informed way, further our understanding of the molecular basis of drug resistance, and design new antibiotics. Here, we focus on a key drug‐resistant pathogen, Mycobacterium tuberculosis, and computationally analyze trends in drug‐resistant mutations in genes of the proteins embA, embB, embC, and katG, which play essential roles in the action of the first‐line drugs ethambutol and isoniazid. We use docking to predict binding modes of isoniazid to katG that agree with suggested binding sites found in our laboratory using cryo‐EM. Using mutant stability predictions, we recapitulate the idea that resistance occurs when katG's heme cofactor is destabilized rather than due to a decrease in affinity to isoniazid. Conversely, we have identified resistance mutations that affect the affinity of ethambutol more drastically than the affinity of the natural substrate of embB. With this, we illustrate that we can distinguish between the two types of drug resistance—cofactor destabilization and drug affinity reduction—suggesting potential uses in the prediction of novel drug‐resistant mutations.
A case of severe Mycobacterium thermoresistibile pneumonia
Authors: Subramaniam Selvaraj , Kanhere Mrudula , Shephard Lisa , Burke Andrew , Saxon Sarah , Geake James
Published: March 2024

Mycobacterium thermoresistibile is a thermotolerant nontuberculous mycobacterium which can rarely result in human infection. Although immunosuppression has been identified as a risk factor for infection, it is possible that mycobacterial laboratories may have previously under‐recognized M. thermoresistibile as standard mycobacterial incubation temperatures are suboptimal for culture of this organism. Here, we present a case of severe M. thermoresistibile pneumonia associated with achalasia requiring life support in the intensive care unit. We speculated that the interplay between specific host and environmental risk factors contributed to acquisition of infection. Infection with this fastidious organism required prolonged treatment with multiple antimicrobials and adjunctive therapeutic drug monitoring which led to clinical cure despite residual lung injury. We also reviewed literature documenting cases of human infection with M. thermoresistibile. The diagnosis of M. thermoresistibile requires a high degree of clinical suspicion considering its association with immunosuppressive conditions, postulated environmental inoculation and eponymous culture growth characteristics.