bluuebunny/crossref_metadata_2025 huggingface dataset:
CRUSE®—An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria
Authors: Neisinger Sophia , Sousa Pinto Bernardo , Ramanauskaite Aiste , Bousquet Jean , Weller Karsten , Metz Martin , Magerl Markus , Kocatürk Emek , Cherrez‐Ojeda Ivan , Gimenez‐Arnau Ana M. , Parisi Claudio Alberto S. , Altrichter Sabine , Ensina Luis Felipe , Bouillet Laurence , Asero Riccardo , Gonçalo Margarida , Guillet Carole , Rutkowski Krzysztof , Bernstein Jonathan A. , Hardin Hannah , Godse Kiran , Brzoza Zenon , Sousa Jose Ignacio Larco , Thomsen Simon Francis , van Doorn Martijn , Hide Michihiro , Ye Young‐Min , Vandersee Staffan , Lapiņa Lāsma , Peter Jonny , Zhao Zuotao , Han Lianyi , Nasr Iman , Rockmann‐Helmbach Heike , Sørensen Jennifer Astrup , Kara Rabia Öztaş , Kurjāne Natalja , Kurchenko Andrii I. , Kaidashev Igor , Tsaryk Vladyslav , Stepanenko Roman , Maurer Marcus
Published: January 2024

Background

Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user‐friendly platform to complete patient‐reported outcome measures (PROMs) on their mobile devices. CRUSE®, the Chronic Urticaria Self Evaluation app, aims to address this unmet need.

Methods

CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real‐time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations.

Results

CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country‐specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second‐generation antihistamines were used in 74.0% of days.

Conclusions

The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.
Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors
Authors: Bhatt Rikesh , van den Hout Ardo , Antoniou Antonis C. , Shah Mitul , Ficorella Lorenzo , Steggall Emily , Easton Douglas F. , Pharoah Paul D. P. , Pashayan Nora
Published: January 2024

Background

Genetic, lifestyle, reproductive, and anthropometric factors are associated with the risk of developing breast cancer. However, it is not yet known whether polygenic risk score (PRS) and absolute risk based on a combination of risk factors are associated with the risk of progression of breast cancer. This study aims to estimate the distribution of sojourn time (pre‐clinical screen‐detectable period) and mammographic sensitivity by absolute breast cancer risk derived from polygenic proﬁle and the other risk factors.

Methods

The authors used data from a population‐based case‐control study. Six categories of 10‐year absolute risk based on different combinations of risk factors were derived using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm. Women were classiﬁed into low, medium, and high‐risk groups. The authors constructed a continuous‐time multistate model. To calculate the sojourn time, they simulated the trajectories of subjects through the disease states.

Results

There was little diﬀerence in sojourn time with a large overlap in the 95% conﬁdence interval (CI) between the risk groups across the six risk categories and PRS studied. However, the age of entry into the screen‐detectable state varied by risk category, with the mean age of entry of 53.4 years (95% CI, 52.2–54.1) and 57.0 years (95% CI, 55.1–57.7) in the high‐risk and low‐risk women, respectively.

Conclusion

In risk‐stratiﬁed breast screening, the age at the start of screening, but not necessarily the frequency of screening, should be tailored to a woman’s risk level. The optimal risk‐stratiﬁed screening strategy that would improve the beneﬁt‐to‐harm balance and the cost‐eﬀectiveness of the screening programs needs to be studied.
Efficacy of reinforcing sutures for prevention of anastomotic leakage after low anterior resection for rectal cancer: A systematic review and meta‐analysis
Authors: Wang Shuanhu , Zhang Yi , Tao Song , Liu Yakui , Shi Yi , Guan Jiajia , Liu Mulin
Published: January 2024

Background and Objectives

Anastomotic leakage is a serious complication following surgery for cancer of the rectum. It is not clear whether reinforcing sutures could prevent anastomotic leakage. Therefore, this study aims at evaluating the efficacy of reinforcing sutures on anastomotic leakage.

Methods

We searched PubMed, Embase, and the Cochrane Library databases from inception to January 31, 2023. We included studies comparing anastomosis with reinforcing sutures to anastomosis without reinforcing sutures after low anterior resection. Risk of bias was assessed by the Cochrane tool for RCTs and the Risk of Bias in Non‐Randomized Studies (ROBINS)‐I tool for observational studies. The overall quality of evidence for primary outcome was assessed using Grading of Recommendations Assessment, Development, and Evaluations methodology.

Results

Two RCTs (345 patients) and four observational studies (783 patients) were included. Anastomotic leakage occurred in 4.4% (24 of 548) of patients with reinforcing sutures and 11.9% (69 of 580) of patients without reinforcing sutures. Meta‐analysis showed a lower incidence of anastomotic leakage (RR, 0.41; 95% CI 0.25 to 0.66, low certainty) in patients with reinforcing sutures. Operative time (WMD, −3.66; 95% CI −18.58 to 11.25) and reoperation for anastomotic leakage (RR, 0.69; 95% CI 0.23 to 2.08) were similar between patients with reinforcing sutures and those without reinforcing sutures.

Conclusions

While observational data suggest that, there is a clear benefit in terms of reducing the risk of anastomotic leakage with the use of reinforcing sutures, RCT data are less clear. Further large, prospective studies are warranted to determine whether a true clinically important benefit exists with this technique.
Subcutaneous Marzeptacog Alfa (Activated) for On‐Demand Treatment of Bleeding Events in Subjects With Hemophilia A or B With Inhibitors
Authors: Faraj Alan , Nyberg Joakim , Blouse Grant E. , Knudsen Tom , Simonsson Ulrika S. H.
Published: January 2024

Marzeptacog alfa (MarzAA) is under development for subcutaneous treatment of episodic bleeds in patients with hemophilia A/B and was studied in a phase III trial evaluating MarzAA compared with standard‐of‐care (SoC) for on‐demand use. The work presented here aimed to evaluate MarzAA and SoC treatment of bleeding events on a standardized four‐point efficacy scale (poor, fair, good, and excellent). Two continuous‐time Markov modeling approaches were explored; a four‐state model analyzing all four categories of bleeding improvement and a two‐state model analyzing a binarized outcome (treatment failure (poor/fair), and treatment success (good/excellent)). Different covariates impacting improvement of bleeding episodes as well as a putative relationship between MarzAA exposure and improvement of bleeding episodes were evaluated. In the final four‐state model, higher baseline diastolic blood pressure and higher age (> 33 years of age) were found to negatively and positively impact improvement of bleeding condition, respectively. Bleeding events occurring in knees and ankles were found to improve faster than bleeding events at other locations. The covariate effects had most impact on early treatment success (≤ 3 hours) whereas at later timepoints (> 12 hours), treatment success was similar for all patients indicating that these covariates might be clinically relevant for early treatment response. A statistically significant relationship between MarzAA zero‐order absorption and improvement of bleedings (P < 0.05) were identified albeit with low precision. No statistically significant difference in treatment response between MarzAA and intravenous SoC was identified, indicating the potential of MarzAA for treatment of episodic bleeding events with a favorable subcutaneous administration route.
Manure, Environmental Impact, and Soil Health: Technologies, Application, and Benefits
Authors: Bock Bert
Published: January 2024

This is the fourth article in our series on soil health and greenhouse gas emissions on U.S. dairies associated with crop production. In this article, we’ll look at innovative manure products that might help dairy farmers better manage their manure resources and answer some key questions. Earn 1 CEU in Sustainability by reading this article and taking the quiz at https://web.sciencesocieties.org/Learning‐Center/Courses.
A Novel Optimization Method for TEG System Performance Based on Temperature and Heat Flux
Authors: Zhou Yifu , Hu Zhen , Jin Weiliang , Luo Jieqiong , Li Gongping , Gu Long , Zhang Shixu
Published: January 2024

The thermoelectric generator (TEG) can convert heat to electricity and is widely used. To overcome the limitation for low efficiency of thermoelectric materials, optimizing the performance of TEG in given system is necessary. This study proposes a method to match individual TEG components to the system environment based on two boundary conditions—temperature and heat flux. With this method, TEG geometrical parameters can be determined to optimize the system performance by varying temperature as an independent variable. Using this method, the TEG in an undersea Radioisotope thermoelectric generator (u‐RTG) is optimized. The TEG system exhibits an output power of 14.10 W when powered by a 200 W heat source. The simulate result in the comprehensive system model of u‐RTG is 14.04 W, which has 0.45% deviation from the TEG optimization result. It is proved that the TEG optimized by this method matches the system, the optimization results are accurate.
Enhancing performance of solar stills ‐ A review
Authors: Sinha Anjali , Venkatesh S. , Kumar Rajendran Senthil
Published: January 2024

Solar stills can be an easy and environmentally viable solution in today's world, where a lack of fresh water sources is a major challenge. Solar stills, on the other hand, aren't economically viable due to their poor efficiency. It has been the subject of several studies to improve its efficiency and output. The goal of this review article is to understand and summarize recent studies conducted to improve the efficiency and commercial viability of solar stills. It focuses on using experimental and numerical techniques to manipulate different parameters that affect freshwater production in stills in order to arrive at a suitable condition where the efficiency and productivity of the solar still are maximized. Effects of modifications such as addition of baffles, fans, fins, phase change material (PCM), etc., and its consequent influence on freshwater production rate are presented in this article. Fins, for example, improved the efficiency of solar still by about 40% and productivity by about 16%. PCMs too increased the productivity rate by around 50%–90% depending on the type of PCM used. Baffles were found to be more effective when they were mounted closer to the front wall of the solar still. The findings and conclusions of all the studies are summarized. This review article aims to provide an overview of solar stills and the various modifications that may be done to improve their overall efficiency.
Spray drying encapsulation of essential oils: Insights on various factors affecting the physicochemical properties of the microcapsules
Authors: Phanse Shirish K. , Chandra Sudeshna
Published: January 2024

Spray drying is a process that involves instantaneous conversion of a liquid or slurry into a free‐flowing powder in the presence of hot air or nitrogen gas current in a drying chamber. The technique is usually used to encapsulate active molecules like essential oils, plant extracts, fragrances, flavours and enzymes within a wall material. The encapsulation provides chemical and physical stability to the actives by converting them into free‐flowing powders which prevents their susceptibility to external atmospheric conditions like temperature, humidity, UV exposure and chemical oxidation. Spray drying encapsulation has an edge over other encapsulation techniques because it is fast, simple, efficient and economically feasible. The article focuses on encapsulating various essential oils within natural polymers and emulsifiers by spray drying methods to form stable microcapsules. The review also provides information on different types of spray drying equipment and process parameters like the type of atomiszer and nozzles, inlet–outlet temperature and type of cyclones. All the process parameters and materials are found to influence the physicochemical properties of the microencapsulates of essential oils. The review also discusses the effects of process parameters and materials on the encapsulation efficiency, moisture content, bulk and tapped density, agglomeration properties and thermal stability of the microencapsulates. Thus, the consolidated review will provide an overview of various optimization parameters and governing factors for obtaining microencapsulates of essential oils.
Bilayer coatings for extension of the shelf life of fish fillets: Incorporating seaweed sulfated polysaccharides in chitosan‐alginate LbL structures
Authors: Khorami Fatemeh , Babaei Sedigheh , Valizadeh Shahriyar , Naseri Mahmood , Golmakani Mohammad‐Taghi
Published: January 2024

The aim of this study was to develop a new active coating of layer‐by‐layer (LbL) structure composed of alginate (as polyanions) and chitosan (as a polycation) containing sulfated polysaccharide (fucoidan) from Sargassum angustifolium, to protect rainbow trout fillets during refrigerated storage. Chitosan and alginate do not combine with each other as a homogeneous solution, so they are suitable for multilayer coatings. The results demonstrated that coating samples with chitosan and fucoidan significantly improved the quality of fish fillets and extended their shelf life from 6 to 16 days. The chemical values (TBARS and TVB‐N) and bacterial growth (total viable count (TVC), total psychrophilic count (PTC), and lactic acid bacteria (LAB)) indicated lower levels in the LbL coating samples containing fucoidan compared to the alginate and control samples. Among the different coating samples, the LbL coating with fucoidan (AChF1) exhibited lower weight loss, improved chromaticity (L*, a*, and b*), and minimal changes in mechanical and sensory evaluations. Based on the findings, AChF1 was the most effective treatment for increasing the shelf life of rainbow trout fillets during refrigerated storage. Therefore, it has potential applications in the food packaging industry.
Allicin inhibits the biological activities of cervical cancer cells by suppressing circEIF4G2
Authors: Yifan Mao , Rui Xu , Yuan Li , Feiyun Jiang
Published: January 2024

Allicin is a safe herbal extract believed to have antitumor effects, which, however, remain unclear. The aim of the present work was to discuss Allicin antitumor effects on cervical cancer using cell experiments. Using Hela and Siha to our research objectives in our study, first step, difference concentration of Allicin (20, 40, and 80 μM) treated Hela and Siha cell lines, and next step, discuss circEIF4G2 effects in Allicin antitumor effects in Hela and Siha cell lines; the cell proliferation and EdU‐positive cell number by CCK‐8 and EdU staining; cell apoptosis rate by flow cytometry; invasion cell number by transwell assay; wound healing rate by wound healing assay; and relative mRNA and protein levels using qRT‐PCR and WB assay. With Allicin supplement, the cell proliferation and EdU‐positive cell number were significantly depressed with cell apoptosis rate significantly increasing; invasion cell number and wound healing rate significantly suppressed with circEIF4G2 mRNA expression significantly down‐regulation (p < .05, respectively). However, there was no significant difference among Allicin, si‐circEIF4G2, and Allicin+si‐circEIF4G2 in cell biological activities including cell proliferation, apoptosis, invasion and migration, and relative gene and protein expression. Allicin depresses biological activities of cervical cancer cells through down‐regulating circEIF4G2/HOXA1/AKT/mTOR.
Indigenous knowledge and nutritional and morphological characterization of okra (Abelmoschus esculentus (L.) Moecnh) varieties in Western Ethiopia
Authors: Mohammed Hasebu Yassin , Teferra Tadesse Fikre , Sime Getachew
Published: January 2024

Okra (Abelmoschus esculentus (L.) Moecnh) is a versatile crop that is widely grown in western Ethiopia, despite that it is less researched. This study, therefore, investigates the traditional knowledge, nutritional, and morphological characteristics of two commonly grown okra varieties (Kenketse and Sharma) in west Ethiopia. A semi‐structured questionnaire, checklist, and observations were used to collect primary data from households, key informants, and farms. In addition, proximate composition parameters like moisture content, total ash, crude fat, crude protein, crude fiber, utilizable carbohydrates, and gross energy fruits were measured through laboratory analysis. Fruit morphological traits, including fruit dimensions such as length and width, were determined using a digital Vernier caliper. For data analysis, SPSS software was used. The results revealed that the entire plant is used for both food and ethnomedicinal purposes. Curing ailments such as stomach pain, constipation, wound/cut, heart discomfort, back pain, malaria, diarrhea, and amoebae were among the medical benefits of okra. The proximate composition (%) on a dry matter basis of okra fruits differed significantly (p < .05) by cultivar type and drying method. Moisture (3.69%–5.24%), total ash (6.60%–8.01%), crude fat (4.87%–8.58%), crude protein (4.06%–5.23%), crude fiber (12.85%–15.26%), utilizable carbohydrate (56.42%–67.63%), and gross energy contents (326–341 kcal) were the ranges of the various proximate and energy levels. Morphological characteristics of fruit and leaf length, width, and length‐to‐width ratio varied with cultivar type, where Sharma had more than double the length of Kenketse (70.1 vs. 187.1 mm). Despite being an undervalued native vegetable crop in Ethiopia, the study's findings show that okra is a multipurpose vegetable for promoting human health and ensuring food and nutritional security. Therefore, stepping up its production, marketing, and consumption could help alleviate the food shortage and improve human nutrition and health in the study areas.
The microfoundations of international commitment decisions: Creating joint opportunity meanings
Authors: Eriksson Mikael , Tippmann Esther
Published: January 2024

Research Summary

Despite a vast body of theory on internationalization processes, little is known about the microfoundations of how firms deal with internal groups' diverse views when trying to make international commitment decisions. Drawing on the concept of opportunity formation and a detailed case study, we develop a model that shows how, under the condition of diverse internal meanings, firms can make an international commitment decision by creating “joint opportunity meanings.” We show how imagination plays an essential role in achieving this decision. Our study contributes to global strategy in multiple ways, including detailing some microfoundations of internationalization process theory, assessing group‐level dynamics in global strategy decision‐making, and advancing insights into the relationship between opportunity formation and imagination.

Managerial Summary

This paper explains how global organizations can reach a decision to commit to an opportunity in a foreign market in a situation characterized by disagreement among internal groups. We found how it was critical to move from diverse views on an opportunity to joint opportunity meanings, whereby the groups mutually accomplish a description of the opportunity with an agreed and common terminology that is ambiguous enough to accommodate remaining diversity in views. In this process, managers' forward‐looking imaginations, in combination with socialization and symbolic actions, were crucial. Our paper highlights how local ideas in complex multinationals can be spread with the intent to reach key decision‐makers and how firms can reach sufficiently overlapping meanings that enable them to strategically move forward while allowing for the plurality of views that multinationals often exhibit.
Japanese physicians' perceptions of conflicts of interest with pharmaceutical companies: Estimating two different questioning approaches
Authors: Saito Hiroaki , Ozaki Akihiko , Murakami Michio , Takebayashi Yoshitake
Published: January 2024

Despite being one of the world's largest pharmaceutical markets, interactions between Japanese physicians and pharmaceutical companies often remain opaque. Importantly, potential conflicts of interest associated with these interactions can compromise patient care and increase costs. We conducted an online survey of Japanese physicians to elucidate perspectives on pharmaceutical company promotional activities and how these influence physician prescribing patterns. Anticipating that physicians might downplay their reliance on, or the value of, pharmaceutical company‐provided information, the survey incorporated a direct questioning method and an unmatched count technique (UCT) to identify hidden perceptions on factors likely to influence prescribing. Overall, 1080 eligible physicians participated. Of these, 105 (9.7%) self‐identified as hospital directors or managers. Surprisingly, nearly twice as many participants responding to direct questioning (18.9%) versus those responding to the UCT (10.1%) asserted that information provided by pharmaceutical companies was important when prescribing medicine. Hospital directors or managers (adjusted odds ratio [adjOR] 2.56, 95% confidence interval [95% CI]: 1.00–6.54, reference = physician without title) and frequent interactions with pharmaceutical sales representatives (adjOR 5.96, 95% CI: 1.88–18.9, reference = rare interaction) significantly valued the information from sales representatives and sponsored lectures when considering prescribing decisions. Additionally, 77.1% of respondents believed that sales representatives provide fair, neutral, or relatively honest and unbiased information about their products. Few Japanese physicians acknowledged the influence of industry‐provided information on prescribing patterns. Our study uniquely applies two distinct question formats, providing a novel approach to understanding the depth of physician‐industry relationships and the effectiveness of various survey methodologies.
Context is key: A 34‐country analysis investigating how similar HRM systems emerge from similar contexts
Authors: Mayrhofer Wolfgang , Biemann Torsten , Koch‐Bayram Irmela , Rapp Marco L.
Published: January 2024

Using an institutional lens, we investigate the isomorphic effects of both external and internal contexts on human resource management (HRM) systems. Our analysis uses data from 4768 organizations across 34 countries to focus on the similarities in HRM systems. By employing distance matrices, a commonly adopted method in geographic science, we find that both external and internal contexts affect (dis)similarities in HRM systems. Organizations in similar environments exhibit more similar HRM systems. Furthermore, we find that the devolvement of HRM activities from HRM to line management reduces the similarity of HRM systems across organizations. By contrast, a strong strategic position of HRM does not yield a comparable effect. Our study's main contributions include elucidating the multifaceted relationship between context and HRM, highlighting the HRM department's role in this relationship, clarifying the context–HRM connection via the concept of isomorphic pressures, and illustrating the use of distance matrices as tool with great explanatory power for the analysis of similarities among HRM phenomena.
Machine learning‐assisted search for novel coagulants: When machine learning can be efficient even if data availability is low
Authors: Rovenchak Andrij , Druchok Maksym
Published: January 2024

Design of new drugs is a challenging process: a candidate molecule should satisfy multiple conditions to act properly and make the least side‐effect—perfect candidates selectively attach to and influence only targets, leaving off‐targets intact. The amount of experimental data about various properties of molecules constantly grows, promoting data‐driven approaches. However, the applicability of typical predictive machine learning techniques can be substantially limited by a lack of experimental data about a particular target. For example, there are many known Thrombin inhibitors (acting as anticoagulants), but a very limited number of known Protein C inhibitors (coagulants). In this study, we present our approach to suggest new inhibitor candidates by building an effective representation of chemical space. For this aim, we developed a deep learning model—autoencoder, trained on a large set of molecules in the SMILES format to map the chemical space. Further, we applied different sampling strategies to generate novel coagulant candidates. Symmetrically, we tested our approach on anticoagulant candidates, where we were able to predict their inhibition towards Thrombin. We also compare our approach with MegaMolBART—another deep learning generative model, but exploiting similar principles of navigation in a chemical space.
Machine learning‐guided design of potent darunavir analogs targeting HIV‐1 proteases: A computational approach for antiretroviral drug discovery
Authors: Chuntakaruk Hathaichanok , Boonpalit Kajjana , Kinchagawat Jiramet , Nakarin Fahsai , Khotavivattana Tanatorn , Aonbangkhen Chanat , Shigeta Yasuteru , Hengphasatporn Kowit , Nutanong Sarana , Rungrotmongkol Thanyada , Hannongbua Supot
Published: January 2024

In the pursuit of novel antiretroviral therapies for human immunodeficiency virus type‐1 (HIV‐1) proteases (PRs), recent improvements in drug discovery have embraced machine learning (ML) techniques to guide the design process. This study employs ensemble learning models to identify crucial substructures as significant features for drug development. Using molecular docking techniques, a collection of 160 darunavir (DRV) analogs was designed based on these key substructures and subsequently screened using molecular docking techniques. Chemical structures with high fitness scores were selected, combined, and one‐dimensional (1D) screening based on beyond Lipinski's rule of five (bRo5) and ADME (absorption, distribution, metabolism, and excretion) prediction implemented in the Combined Analog generator Tool (CAT) program. A total of 473 screened analogs were subjected to docking analysis through convolutional neural networks scoring function against both the wild‐type (WT) and 12 major mutated PRs. DRV analogs with negative changes in binding free energy () compared to DRV could be categorized into four attractive groups based on their interactions with the majority of vital PRs. The analysis of interaction profiles revealed that potent designed analogs, targeting both WT and mutant PRs, exhibited interactions with common key amino acid residues. This observation further confirms that the ML model‐guided approach effectively identified the substructures that play a crucial role in potent analogs. It is expected to function as a powerful computational tool, offering valuable guidance in the identification of chemical substructures for synthesis and subsequent experimental testing.
Novel 8‐wire basket catheter is useful for endoscopic removal of common bile duct stones up to 10 mm: A multicenter prospective study
Authors: Kaneko Takashi , Ishii Tomohiro , Hamanaka Jun , Goda Yoshihiro , Irie Kuniyasu , Doba Nobutaka , Kunishi Yosuke , Miwa Haruo , Sugimori Kazuya , Maeda Shin
Published: January 2024

Background/Purpose

Endoscopic treatment of common bile duct (CBD) stones involves the use of basket or balloon catheters; however, what is the appropriate device remains controversial. In this study we aimed to prospectively evaluate the usefulness of a novel 8‐wire helical basket (8WB) catheter made of Nitinol for the removal of CBD stones ≤10 mm.

Methods

We conducted a multicenter prospective trial. Patients with CBD stones ≤10 mm were enrolled. The primary endpoint was the rate of complete stone removal within 10 min using the 8WB. The number of cases was determined using a previous study of stone removal by a conventional basket catheter as a historical control.

Results

A total of 155 patients were enrolled and 139 were ultimately included in the analysis. Patients with a single stone were the most common (84 cases, 60.4%), with a median maximum stone diameter of 5 mm. The median stone removal time using the 8WB was 6 min. The complete stone removal rate was 95.0% (132/139). Adverse events were observed in 14 patients (10.1%).

Conclusions

The novel 8WB catheter is useful in the treatment of CBD stones ≤10 mm, presenting a high complete stone removal rate in this study.

Trial registration number: jRCT1032200324.
Liver‐directed gene therapy for inherited metabolic diseases
Authors: Baruteau Julien , Brunetti‐Pierri Nicola , Gissen Paul
Published: January 2024

Gene therapy clinical trials are rapidly expanding for inherited metabolic liver diseases whilst two gene therapy products have now been approved for liver based monogenic disorders. Liver‐directed gene therapy has recently become an option for treatment of haemophilias and is likely to become one of the favoured therapeutic strategies for inherited metabolic liver diseases in the near future. In this review, we present the different gene therapy vectors and strategies for liver‐targeting, including gene editing. We highlight the current development of viral and nonviral gene therapy for a number of inherited metabolic liver diseases including urea cycle defects, organic acidaemias, Crigler–Najjar disease, Wilson disease, glycogen storage disease Type Ia, phenylketonuria and maple syrup urine disease. We describe the main limitations and open questions for further gene therapy development: immunogenicity, inflammatory response, genotoxicity, gene therapy administration in a fibrotic liver. The follow‐up of a constantly growing number of gene therapy treated patients allows better understanding of its benefits and limitations and provides strategies to design safer and more efficacious treatments. Undoubtedly, liver‐targeting gene therapy offers a promising avenue for innovative therapies with an unprecedented potential to address the unmet needs of patients suffering from inherited metabolic diseases.
Chemical Shift‐Encoded MRI of the Lumbar Vertebral Bone Marrow for Detecting Osteoporosis With Low Trabecular Bone Quality in Patients With Breast Cancer Receiving Aromatase Inhibitors
Authors: Misaka Tomofumi , Hashimoto Yukihiko , Ashikaga Ryuichiro , Ishida Takayuki
Published: January 2024

Background

Osteoporosis with low trabecular bone quality (OLB) in patients with breast cancer receiving aromatase inhibitor (AI) therapy is associated with an increased risk of vertebral fractures. The capability of chemical shift‐encoded MRI (CSE‐MRI) in detecting OLB needs to be investigated.

Purpose

To assess the diagnostic performance of proton density fat fraction (PDFF) and R2* measurements from CSE‐MRI for detecting OLB in postmenopausal women with breast cancer undergoing AI therapy.

Study Type

Prospective.

Population

126 postmenopausal females (mean age: 69.5 ± 8.8 years) receiving AIs (average period: 41.6 ± 26.5 months) after breast cancer surgery.

Field Strength/Sequence

1.5‐T, three‐dimensional CSE‐MRI (six echoes), T1‐weighted Dixon, short tau inversion recovery, and diffusion‐weighted images.

Assessment

Both CSE‐MRI and dual‐energy x‐ray absorptiometry were performed on the same day. Measurements included averaged PDFF, R2*, bone mineral density (BMD), and trabecular bone score (TBS) from L1 to L4 vertebrae. A T‐score ≤ −2.5 from BMD measurements indicated osteoporosis, whereas T‐scores of ≤ − 2.5 plus TBS ≤‐3.7 indicated OLB. The diagnostic performance of PDFF, R2*, and the combination of PDFF and R2* for identifying osteoporosis or OLB was assessed.

Statistical Tests

Student's t‐test; Mann–Whitney U test; χ2 or Fisher exact tests; Pearson correlation; multivariate analysis; Receiver operating characteristic (ROC) analysis with the area under the curve (AUC); logistic regression model; intraclass correlation coefficient. A P‐value <0.05 was considered statistically significant.

Results

For detecting osteoporosis, AUC values were 0.59 (PDFF), 0.66 (R2*), and 0.65 (combined PDFF and R2*). Significant mean differences were noted between patients with and without OLB for PDFF (66.11 ± 5.36 vs. 57.49 ± 6.43) and R2* (46.62 ± 9.24 vs. 63.36 ± 12.44). AUC values for detecting OLB were 0.75 (PDFF), 0.82 (R2*), and 0.84 (combined PDFF and R2*).

Data Conclusion

R2* may perform better than PDFF for identifying OLB in patients with breast cancer receiving AIs.

Level of Evidence

2

Technical Efficacy

Stage 4
Ethically treated yet closely monitored: Ethical leadership, leaders' close monitoring, employees' uncertainty, and employees' organizational citizenship behavior
Authors: Sun Ui Young , Park Haeseen , Yun Seokhwa
Published: January 2024

Drawing on uncertainty management theory, we propose that employees' uncertainty is a distinct key mechanism explaining the relationship between ethical leadership and employees' organizational citizenship behavior (OCB). We contend that ethical leadership, by promoting a work environment governed by moral principles, reduces employees' sense of uncertainty and thereby fosters their OCB. However, we suggest that leaders' close monitoring, which ethical leaders may utilize to be informed about employees' adherence to their moral standards, nullifies these positive implications of ethical leadership. To test these contentions, we conducted an online vignette study (Study 1) and a field study (Study 2). In Study 1, we found a significant and negative main effect of ethical leadership on employees' uncertainty, but this effect was negated when leaders' close monitoring was high. In Study 2, we replicated the findings—ethical leadership was negatively related to employees' uncertainty and this relationship became nonsignificant when leaders' close monitoring was high. In addition, uncertainty was negatively related to employees' OCB toward the organization (OCBO) but not their OCB toward individuals (OCBI). Consequently, uncertainty mediated the relationship between ethical leadership and OCBO, and this mediation was moderated by close monitoring. However, such mediation and moderated mediation did not occur for OCBI. Taken together, our research reveals that close monitoring is not a viable strategy to be implemented alongside ethical leadership for managing employees' uncertainty and fostering their OCB.
Loose and Tight: Creative Formation but Rigid Use of Nominal Compounds in Conspiracist Texts
Authors: Miani Alessandro , van der Plas Lonneke , Bangerter Adrian
Published: January 2024

Conspiracy theories (CTs) are spectacular narratives, widely spread, that pose societal threats. We test whether CTs might be linguistically creative products, which would facilitate their transmission and thereby account for their widespread popularity. We analyzed nominal compounds (e.g., mind control, carbon dioxide; N = 1,713,568) from a large corpus of conspiracist and mainstream texts matched by topic. In conspiracist texts, compounds showed greater originality, divergence, and sophistication, but they were used with lower frequency and were more often repeated in different contexts. This pattern suggests a creative aspect in the generation of compounds, coupled with rigidity in their use. We interpret these findings as an effect of loosely defined conceptual boundaries among conspiracist writers, in conjunction with social functions like status or group signaling. Our findings not only contribute to the discourse on creativity in CTs but also provide insights into the communicative advantage of CTs.
Efficacy of all‐inside devices in reducing gap and step‐off in knee extension for ramp lesion repair: A cadaveric study
Authors: Kato Jiro , Fukushima Hiroaki , Hanaki Shunta , Kawanishi Yusuke , Kobayashi Makoto , Ota Kyohei , Yoshida Masato , Takenaga Tetsuya , Kawaguchi Yohei , Kuroyanagi Gen , Sakai Hiroaki , Murakami Hideki , Nozaki Masahiro
Published: January 2024

Purpose

The aim of this study is to assess the dynamics of the tear site of meniscal ramp lesions, particularly considering knee flexion angles, and validate anchor fixation using an all‐inside device.

Methods

Eight Thiel‐embalmed paired cadaveric knees with their whole bodies were used in this study. The ramp lesions were created arthroscopically, and ramp lesion dynamics were evaluated by gradually extending the knee from 90° of knee flexion. Changes in the gap and step‐off (0: no step‐off; 1: cross‐sectional overlap exists; and 2: tibial articular surface exposed) were evaluated at 90°, 60°, 30°, and 10° of knee flexion. After dynamic evaluation, all‐inside repairs of the ramp lesions using all‐inside devices were conducted. Dissection was performed to confirm the position of anchor fixation.

Results

As the knee was extended, the gap significantly decreased at all knee flexion angles. Similarly, the step‐off grade decreased as the knee was extended, and the step‐off completely disappeared in all cases when the knee was extended from 30° to 10°. The average knee flexion angle at which the gap and step‐off completely disappeared was 22.5°. After suturing the ramp lesion, arthroscopic evaluation showed that the gap had disappeared and the step‐off had been repaired in all cases. Anchor fixation locations were not found within the joint but were fixed to the semimembranosus tendon or its surrounding articular capsule. Overall, 31% (5/16) anchors were fixed to the attachment site of the semimembranosus tendon, whereas the remaining were fixed to the articular capsule, located peripherally to the semimembranosus tendon.

Conclusion

Suturing with an all‐inside device for ramp lesions is a good option, and the repair in knee extension was found to be reasonable, considering the dynamics of ramp lesions in this study.

Level of Evidence

Level IV.
Gastroesophageal Reflux and Chronic Rhinosinusitis: A Mendelian Randomization Study
Authors: Guo Tao , Xie Hui
Published: January 2024

Objective

Chronic rhinosinusitis (CRS) is associated with gastroesophageal reflux (GERD). However, the causal relationship is controversial. We conducted a two‐sample Mendelian Randomization (MR) analysis to explore this potential association.

Methods

Based on genome‐wide association studies (GWAS), a univariable MR was performed to explore the causal relationship of GERD with CRS. Instrumental variables (IVs) pertinent to anti‐GERD treatment were employed as a means of validation. The primary MR outcome was established using an inverse variance weighted (IVW) method, supplemented by multiple sensitivity analyses. Subsequently, a multivariable MR was conducted to account for potential confounding variables, thereby ascertaining a direct effect of GERD on CRS. Finally, a network MR analysis was carried out to elucidate the mediating role of asthma in the relationship between GERD and CRS.

Results

The univariable MR demonstrated an association between GERD and an elevated risk of CRS (IVW OR = 1.30, 95% CI = 1.18–1.45, p = 4.19 × 10−7). Omeprazole usage was associated with a reduction in CRS risk (IVW OR = 0.64, 95% CI = 0.42–0.98, p = 0.039). The causal relationship between GERD and CRS remained after adjusting for potential confounders, such as smoking characteristics, body mass index, asthma, allergic rhinitis, in the multivariable MR analysis. Besides, the proportion of the causal effect of GERD on CRS mediated by asthma was 19.65% (95% CI = 2.69%–36.62%).

Conclusion

GERD was independently associated with an increased risk of CRS. The mediating role of asthma between GERD and CRS also reveals that GERD is one of the mechanisms underlying unified airway disease.

Level of Evidence

3 Laryngoscope, 134:3086–3092, 2024
The sensitivity of laryngeal findings in predicting high‐grade dysplasia in patients with vocal fold leukoplakia undergoing office‐based biopsies: A retrospective analysis of 100 cases
Authors: Hosri Jad , Aoun Jessica , Yammine Yara , Ghadieh Justin , Hamdan Abdul‐Latif
Published: January 2024

Objective

To investigate the sensitivity of laryngeal findings in predicting high‐grade dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC) in patients with vocal fold leukoplakia.

Methods

A retrospective review of the medical records and video recordings of the laryngeal examination of patients with vocal fold leukoplakia who underwent un‐sedated office‐based laryngeal biopsy in a tertiary referral center between January 2022 and August 2023 was conducted. Laryngeal findings included the size, surface, projection, and edges of the lesion. Vocal fold leukoplakia was classified according to the WHO as benign, low‐grade dysplasia, high‐grade dysplasia/CIS, and squamous cell carcinoma.

Results

Seventy patients with 100 vocal fold leukoplakia were included. Size was found to have the highest sensitivity with an AUC of 0.730 (95% CI [0.618–0.842], p = 0.002) followed by surface and projection with AUCs of 0.672 (95% CI [0.548–0.795], p = 0.019) and 0.675 (95% CI [0.546–0.804], p = 0.017), respectively. Furthermore, the odds of diagnosing high‐risk lesions (high‐grade dysplasia/CIS and SCC) were the greatest when the lesion was large and rough (OR = 10.28; 95% CI [3.08–34.36]).

Conclusion

The morphological features of vocal fold leukoplakia may assist the physician in predicting the risk of malignancy. Large and rough lesions were more likely to harbor high‐grade dysplasia/CIS and SCC compared to small and smooth lesions.
Dietary Cannabidiol Activates PKA/AMPK Signaling and Attenuates Chronic Inflammation and Leaky Gut in DSS‐Induced Colitis Mice
Authors: Sun Qi , Bravo Iniguez Alejandro , Tian Qiyu , Du Min , Zhu Mei‐Jun
Published: January 2024

Scope

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk.

Methods and Results

Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)‐induced experimental colitis is evaluated. Eight‐week‐old mice were fed a standard diet supplemented with or without CBD (200 mg kg‐1) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP‐protein kinase A, extracellular signal‐regulated kinase ½, and AMP‐activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro‐inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS‐treated mice.

Conclusion

Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.
Role of Artificial Intelligence in Multinomial Decisions and Preventative Nutrition in Alzheimer's Disease
Authors: Soares Dias Portela Ariana , Saxena Vrinda , Rosenn Eric , Wang Shu‐Han , Masieri Sibilla , Palmieri Joshua , Pasinetti Giulio Maria
Published: January 2024

Alzheimer's disease (AD) affects 50 million people worldwide, an increase of 35 million since 2015, and it is known for memory loss and cognitive decline. Considering the morbidity associated with AD, it is important to explore lifestyle elements influencing the chances of developing AD, with special emphasis on nutritional aspects. This review will first discuss how dietary factors have an impact in AD development and the possible role of Artificial Intelligence (AI) and Machine Learning (ML) in preventative care of AD patients through nutrition. The Mediterranean‐DASH diets provide individuals with many nutrient benefits which assists the prevention of neurodegeneration by having neuroprotective roles. Lack of micronutrients, protein‐energy, and polyunsaturated fatty acids increase the chance of cognitive decline, loss of memory, and synaptic dysfunction among others.

ML software has the ability to design models of algorithms from data introduced to present practical solutions that are accessible and easy to use. It can give predictions for a precise medicine approach to evaluate individuals as a whole. There is no doubt the future of nutritional science lies on customizing diets for individuals to reduce dementia risk factors, maintain overall health and brain function.
Uplift behavior of nodular diaphragm wall: Experiment and theory
Authors: Wu Jiujiang , Zhang Yi , Li Yan , Wen Hua , Wang Lijuan
Published: January 2024

The nodular diaphragm wall (NDW) is a novel foundation that can provide significant uplift load resistance compared to a typical diaphragm wall foundation. With the advantages of low noise, cost‐effectiveness, high work efficiency, and construction abilities close to existing buildings, NDW has excellent engineering application prospects in urbanization construction. However, the scarce knowledge on the uplift resistance, failure mode, and calculation method of the NDW has hindered its application in practice. In this paper, indoor model tests based on particle image velocimetry (PIV) technology are carried out to investigate the uplift behavior of three NDW models with different amounts and locations of nodular parts. The load transfer mechanisms of the three NDW models are discussed in detail, and special attention is given to the failure mode analysis. In addition, a theoretical analysis is implemented based on the load transfer approach. The transfer function and associated critical parameters are discussed in detail. Accordingly, an iterative procedure is proposed to interpret the load transfer information of an uplift NDW in multilayered soils under different loading levels. The findings derived in this paper are helpful to the uplift deformation, capacity calculation, and design of NDW in practical engineering.