bluuebunny/crossref_metadata_2025 huggingface dataset:
S2k guideline: Diagnosis and therapy of localized scleroderma
Authors: Kreuter Alexander , Moinzadeh Pia , Kinberger Maria , Horneff Gerd , Worm Margitta , Werner Ricardo N. , Hammacher Andreas , Krieg Thomas , Wenzel Jörg , Oeschger Michael , Weibel Lisa , Müllegger Robert , Hunzelmann Nicolas
Published: March 2024

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second‐line systemic therapies. In the case of linear LoS, autologous adipose‐derived stem cell transplantation can also be performed for correcting soft tissue defects.
Perception, Reason, and Intuition in the Development Of Expertise: Reflections on Zhuangzi and Contemporary Western Theory
Authors: Waks Leonard
Published: March 2024

In this paper, Leonard Waks investigates connections between listening and expertise or mastery, contrasting approaches from Eastern and Western philosophy. The first section accounts for listening in the Daoist classic Zhuangzi, a work addressing themes in Chinese philosophy through metaphor and story narratives. In one story a character named “Confucius” advises a student to fast the mind and listen recklessly. The affinity between reckless and what has been called “apophatic” listening is demonstrated by the shared feature of mental emptiness — listening without the imposition of conceptual categories. The second section demonstrates close affinities between the account of listening and expertise or mastery in the Zhuangzi and in the account of expert perception in contemporary Western philosophy and psychology, as exemplified by phenomenologist Hubert Dreyfus.
Computer vision for automated seizure detection and classification: A systematic review
Authors: Brown Brandon M. , Boyne Aidan M. H. , Hassan Adel M. , Allam Anthony K. , Cotton R. James , Haneef Zulfi
Published: March 2024

Computer vision (CV) shows increasing promise as an efficient, low‐cost tool for video seizure detection and classification. Here, we provide an overview of the fundamental concepts needed to understand CV and summarize the structure and performance of various model architectures used in video seizure analysis. We conduct a systematic literature review of the PubMed, Embase, and Web of Science databases from January 1, 2000 to September 15, 2023, to identify the strengths and limitations of CV seizure analysis methods and discuss the utility of these models when applied to different clinical seizure phenotypes. Reviews, nonhuman studies, and those with insufficient or poor quality data are excluded from the review. Of the 1942 records identified, 45 meet inclusion criteria and are analyzed. We conclude that the field has shown tremendous growth over the past 2 decades, leading to several model architectures with impressive accuracy and efficiency. The rapid and scalable detection offered by CV models holds the potential to reduce sudden unexpected death in epilepsy and help alleviate resource limitations in epilepsy monitoring units. However, a lack of standardized, thorough validation measures and concerns about patient privacy remain important obstacles for widespread acceptance and adoption. Investigation into the performance of models across varied datasets from clinical and nonclinical environments is an essential area for further research.
The elusive nature of neutrality: The role of values in couple therapy
Authors: Feldman Tamara
Published: March 2024

This paper will explore the role of the therapist's values in couple therapy and the challenge these values pose to therapeutic neutrality. It will illuminate how the therapist's values shape what is considered healthy and unhealthy, functional and dysfunctional, and hence frame the problem the couple therapist seeks to treat. Values have particular relevance for couple treatment because the conversations the couple therapist facilitates may unwittingly privilege one partner's needs and wishes over the other's, creating the potential for therapeutic misalliances. This paper will explore common values and their impact on treatment, including the values of monogamy, gender equity, and talk intimacy (emotional expression as a path to intimacy). It will conclude by discussing how couple therapists can avoid partisanship with one partner and maintain a balanced approach in their couple work.
Detected and projected temperature changes in the area of Mediterranean Montenegro
Authors: Burić Dragan
Published: March 2024

The goal of this research is to present the results of a detailed analysis of detected and projected temperature changes in Montenegro. A total of 10 temperature parameters from 18 meteorological stations were used. Initially, an analysis of temperature changes during the instrumental period (1961–2020) was conducted, followed by the results of high‐resolution (12.5 km) bias‐corrected projections from the regional ALADIN, REMO and CCLM4 models for the period 2021–2100, according to the RCP4.5 and RCP8.5 scenarios (representative concentration pathways). The simple difference method and trend method were employed for research purposes. Compared with the period 1961–1990, the highest temperature increase during 1991–2020 is observed in summer (TSu), while the rates of increase were slower in spring, winter and autumn (TSp, TW and TA). The average annual maximum temperature (TYx) registered a higher increase compared with the average minimum (TYn). Frosty days (FD) decreased, while the number of summer and tropical days (SU and TD) increased. The projection results indicate that the period 2021–2050 is expected to be warmer, the period 2051–2080 even warmer, and the period 2081–2100 is expected to be the warmest. In the last analysed period (2081–2100), according to the RCP8.5 scenario, the average TSu is expected to be higher by 3.7–4.6°C (CCLM4), 4.1–4.7°C (ALADIN) and 4.7–5.8°C (REMO), with an anticipated increase in TW ranging between 3.3–4.5°C (ALADIN), 3.6–5.4°C (CCLM4) and 3.4–5.6°C (REMO). In the period 2021–2100, according to the RCP4.5 scenario, the expected average trend values for TYx (TYn) are expected to be (°C/decade) 0.24 (0.26), 0.16 (0.12) and 0.20 (0.23) for the ALADIN, REMO and CCLM4 models, respectively, and according to the RCP8.5 scenario, 0.47 (0.52), 0.63 (0.57) and 0.51 (0.53), respectively. These findings have implications for planning mitigation and adaptation measures to address climate change, particularly in strategic economic sectors such as tourism, agriculture and water management in Montenegro.
A data‐driven approach to improve online consumer subscriptions by combining data visualization and machine learning methods
Authors: Fernandes Elizabeth , Moro Sérgio , Cortez Paulo
Published: March 2024

Effective online consumer research helps companies on defining a successful strategy to increase user loyalty and shape brand engagement. Digital innovation introduced a dramatic change in businesses, particularly in the online news industry. Content consumers have a wide offer across different channels which increase the digital challenge for online news media companies to retain their readers and convert them into online subscribers. Furthermore, digital news publishers often strive to balance revenue sources in online business models. Thus, this study fills a gap in the literature on media consumer research by proposing a data‐driven approach that combines two machine learning (ML) models to allow managers dynamically improve their marketing and editorial strategies. Firstly, the authors present an online user profiling to identify consumer segments based on the interplay between several engagement’ variables substantiated in the literature research. Second, as few studies have explored the factors influencing users' intention to pay for such services, the eXtreme Gradient Boosting ML algorithm identifies the predictors of consumer's willingness to pay. Third, a dashboard presents the key performance indicators across the audience funnel. Thus, practical implications and business suggestions are presented in a two‐fold strategy to maximize revenue from digital subscriptions and advertising. Findings provide new insights into an engagement approach and the relation to acquire a digital subscription in online content platforms. We believe that the provided recommendations are potentially useful to help marketing and editorial teams to manage their customer engagement process across the funnel in a more efficient way.
Factors shaping the adoption of sustainable vegan diets
Authors: Shah Sweety , Thanki Joshi Heena
Published: March 2024

The quality and choices of food contribute significantly to human well‐being and support the development of healthy communities worldwide. Despite being the world's largest vegetarian nation, India predominantly follows lacto‐vegetarianism, allowing dairy consumption and creating a distinct dietary landscape shaped by influences from religious, social, and cultural beliefs. This complexity, where dairy and cultural‐religious factors play pivotal roles, makes India a compelling and unique case for understanding the intricacies of adopting vegan dietary preferences. In the present study, an integrated model derived from the health belief model (HBM), the value attitude behavior (VAB) model, and social stigma was adopted as the theoretical framework. The study analyses the interactive effect of perceived benefits, barriers, environmental beliefs, health beliefs, and anti‐speciesism values, with the novel inclusion of social stigma as an independent variable affecting attitudes and intentions toward adopting a vegan diet. To achieve its objective, the study employed a quantitative methodology, recording consumers' responses through a structured questionnaire. The analysis encompassed 504 valid responses from Indian consumers from diverse backgrounds and varied locations. The result unveiled several noteworthy and unique trends. It was found that perceived benefits had a positive impact, while perceived barriers had a negative impact on the health beliefs associated with a vegan diet. Environmental beliefs, health beliefs, and anti‐speciesism values exhibited a positive influence on individuals' attitudes toward adopting a vegan diet. Conversely, social stigma had a negative impact on attitudes toward a vegan diet. Attitude emerged as a pivotal mediator, connecting the social stigma to the vegan diet adoption behavior. The findings of the study offer valuable insights for policymakers, manufacturers, and marketers seeking to encourage the adoption of vegan diets in countries with predominantly vegetarian populations. Additionally, the study puts forth actionable strategies, outlined as implications to promote the widespread adoption of the vegan diet.
Validation study on the 2 mm diameter cutoff in lymph node‐positive cases following radical prostatectomy in accordance with the AJCC/UICC TNM 8th edition: Real‐world data analysis from a Japanese cohort
Authors: Kato Masashi , Shiota Masaki , Kimura Takahiro , Hanazawa Ryoichi , Hirakawa Akihiro , Takamatsu Dai , Tashiro Kojiro , Matsui Yoshiyuki , Hashine Katsuyoshi , Saito Ryoichi , Yokomizo Akira , Yamamoto Yoshiyuki , Narita Shintaro , Hashimoto Kohei , Matsumoto Hiroaki , Akamatsu Shusuke , Nishiyama Naotaka , Eto Masatoshi , Kitamura Hiroshi , Tsuzuki Toyonori ,   the Japanese Urological Oncology Group
Published: March 2024

Objectives

The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD).

Methods

Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance‐free survival (CRFS), metastasis‐free survival (MFS), cancer‐specific survival (CSS), and overall survival (OS).

Results

In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS.

Conclusions

Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2‐mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer.
Clinical efficacy of crushed prednisolone and hydrocolloid powder in the primary treatment of peristomal pyoderma gangrenosum and correlation to in vitro drug release data
Authors: Pearson Wendy Ann , Prentice David Andrew , Lim Lee Yong , Gianoncelli Olivia , Hashiguchi Alice , Parisella Tahlia Kate , Ta Jade Thien
Published: March 2024

We evaluated the primary application of crushed prednisolone combined with hydrocolloid powder for clinically diagnosed peristomal pyoderma gangrenosum (PPG). We present our data on this cohort and follow‐up of our previous patients. Of the 23 patients who were commenced on this regime, 18 healed (78%). Twenty‐two patients commenced on this regime as the primary treatment for their PPG, and for one, it was a rescue remedy after failed conventional therapy. Four patients with significant medical comorbidities failed to heal and one had their stomal reversal surgery before being fully healed. The proposed treatment regime for PPG is demonstrated to be effective, inexpensive and able to be managed in the patient's usual home environment. In vitro drug release analysis was undertaken, and data are presented to provide further insights into the efficacy of this regime.
Rhizoma Paridis saponins attenuate Gram‐negative bacteria‐induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways
Authors: Yang Yang , Wang Chaofan , Wang Juan , Yang Lingli , Lv Zheng , An Quan , Wang Yiming , Shao Xue , Wang Fei , Huo Tong , Liu Jiali , Luo Haoshu , Quan Qianghua
Published: March 2024

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram‐negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti‐inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH‐enriched Rhizoma Paridis extract (RPE) in treating the Gram‐negative bacteria‐induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)‐1β and IL‐6 in lipopolysaccharide (LPS)‐induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa‐B (NF‐κB) P65 in LPS‐induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch‐like ECH‐associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2‐related factor 2 (NRF2) and upregulate haem oxygenase‐1 (HO‐1). Moreover, RPE suppressed the mitogen‐activated protein kinase (MAPK) pathway. Therefore, PPH‐enriched RPE showed anti‐inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.
Diabetes treatment by conversion of gut epithelial cells to insulin‐producing cells
Authors: Accili Domenico , Talchai Shivatra C , Bouchi Ryotaro , Lee April Yun‐Kyoung , Du Wen , Kitamoto Takumi , McKimpson Wendy M , Belvedere Sandro , Lin Hua V
Published: March 2024

Insulin‐deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi‐closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high‐risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin‐producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin‐deficient diabetes, these inhibitors have resulted in robust glucose‐lowering responses and generation of insulin‐producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.
Seeing beyond skin deep: High‐resolution ultrasound in dermatology—A comprehensive review and future prospects
Authors: Liu Zhao Feng , Chew Christopher Y. , Honavar Shreyas , Maxwell Andrew , Sylivris Amy , Sheridan Adam
Published: March 2024

High‐resolution ultrasound (HRUS), operating at frequencies of 20–25 MHz, is a non‐invasive imaging tool that offers dermatologists the ability to visualize structures beneath the skin surface. The objective of this review is to present a comprehensive overview of HRUS applications, emphasising its utility in diagnosing, characterising and managing various dermatological conditions. We undertook a comprehensive literature review on the dermatological application of HRUS across Medline, Embase and Cochrane Library databases, while also incorporating our own clinical experience of over 16 years with the tool. In normal skin, the epidermis and dermis are hyperechoic, and the subcutaneous layer is hypoechoic. Basal cell carcinomas appear hypoechoic with irregular margins, while the presence of hyperechoic inclusion bodies suggests aggressive pathology. Squamous cell carcinomas pose challenges due to acoustic shadow artefacts from the thickened stratum corneum. Melanomas are homogenous hypoechoic lesions, with HRUS used to accurately predict Breslow thickness. HRUS provides dermatologists with a valuable adjunct to traditional clinical examination. Future advancement in image resolution and the standardisation of diagnostic parameters may further expand its utility.
Long‐term effects of management intensity and bioclimatic variables on leatherjacket (Tipula paludosa Meigen) populations at farm scale
Authors: Moffat Aisling , Cole Lorna , Lacey Seán , Harrison Billy , Konkolewska Agnieszka , McCracken Davy , Evans Andy K. , Gaffney Michael T. , Brennan Fiona , Jackson Gail E. , McNamara Louise
Published: March 2024

Leatherjackets (Tipula spp.) are soil‐dwelling pests associated with agriculture. Land management decisions made at farm scale can have subsequent effects on their populations. Between 1980 and 2020, surveys were conducted across Scotland to collect field histories and larval population data from grassland farms. To assess the impact of management and bioclimatic factors on leatherjacket occurrence over time, this study investigated data from fields continuously sampled between 2009 and 2018. We utilized a Generalized Linear Mixed‐Effect Model on a dataset of 61 fields on 19 farms. Results indicated three significant factors affecting larval populations; field size, grazing type and application of insecticides or herbicides (referred to collectively as pesticides). Larval populations were significantly lower in fields that were larger in size and under sheep grazing, compared to no grazing. Pesticide application also caused a significant reduction in larval populations. Management variables were amalgamated to create a Management Intensity Index, revealing significantly increased larval populations under low‐management systems. These results, coupled with significant effects of bioclimatic variables, pinpoint predictive signals for high infestations and potential routes for control strategies.
Dissecting the Long‐Term Performance of the Chinese Stock Market
Authors: ALLEN FRANKLIN , QIAN JUN (QJ) , SHAN CHENYU , ZHU JULIE LEI
Published: March 2024

Domestically listed Chinese (A‐share) firms have lower stock returns than externally listed Chinese, developed, and emerging country firms during 2000 to 2018. They also have lower net cash flows than matched unlisted Chinese firms. The underperformance of both stock and accounting returns is more pronounced for large A‐share firms, while small firms show no underperformance along either dimension. Investor sentiment explains low stock returns in the cross‐country and within‐A‐share samples. Institutional deficiencies in listing and delisting processes and weak corporate governance in terms of shareholder value creation are consistent with the underperformance in stock returns and net cash flows.
Parent‐child conflict in Mexican‐origin families: Charting development from adolescence to young adulthood
Authors: Son Daye , Updegraff Kimberly A. , Umaña‐Taylor Adriana J.
Published: March 2024

Grounded in developmental and cultural‐ecological perspectives, the current study examined trajectories of parent‐youth conflict regarding everyday issues across adolescence and into young adulthood. Data came from 246 Mexican‐origin families in the southwestern United States with younger siblings (51% female, Mage = 12.8, SD = 0.58), older siblings (Mage = 15.5, SD = 1.57), mothers (Mage = 39.0; SD = 4.6), and fathers (Mage = 41.7; SD = 5.8) and were collected at four time points over an 8‐year period. Multilevel modeling analyses revealed linear declines in mother‐youth and father‐youth conflict across ages 12–22. Youth, but not parent, familism values were associated with variation in parent‐youth conflict. This study extends understanding of culturally and developmentally salient processes of mother‐youth and father‐youth relationships in Mexican‐origin families.
Untreated Allergy Among Middle School Students: Associations with Socioeconomic Adversities and Academic, Behavior, and Health Difficulties
Authors: Chau Kénora , Chau Nearkasen
Published: March 2024

BACKGROUND

Many adolescents with allergy do not receive physician treatment (allergyuntreated). We explored its association with socioeconomic adversities and academic‐behavior‐health difficulties, which remain unaddressed.

METHODS

This cross‐sectional school‐based‐population study compared the above factors of middle‐school adolescents with allergyuntreated and those with treated allergy (allergytreated) (mean age = 13.5 ± 1.2) from north‐eastern France. Participants completed a questionnaire collecting socioeconomic adversities (nonintact family, low parents' education, insufficient family income, poor social support, suffered verbal/physical violence, and sexual abuse), low academic performance, excessive screen time, substance use, sleep difficulty, poor physical health, depressive symptoms, suicide attempt, poor quality of life, and allergytreated/allergyuntreated.

RESULTS

Logistic regression models showed that allergyuntreated was associated with all the factors considered (sex‐age‐class‐level‐adjusted odds ratio (saclOR) reaching 3.94, p < .001) and the risk score (number of main criteria: suffered sexual abuse, excessive screen time, poor quality of life, cannabis use, low parents' education, and poor social support): saclOR 4.75, 9.23, 15.64, and 31.73 (p < .001) for risk scores 1, 2, 3, and ≥4, versus risk score = 0 (pseudo‐R2 = 11.1%).

CONCLUSIONS

Socioeconomic adversities and academic‐behavior‐health difficulties may be used to detect adolescents with allergyuntreated for care.
Social network analysis, habitus and the field of literary activity
Authors: Li Li , Corbett John
Published: March 2024

Social network analysis that draws upon the correspondence of writers has the potential to indicate aspects of the writers' habitus, that is, the economic, social and cultural capital represented by the relations between authors, poets and dramatists, and their correspondents. Social network analysis can visualise and reveal otherwise covert aspects of the field of literary activity. In particular, it can show the flow of cultural, symbolic, social and economic capital through the literary ecosystem. The article presents an introduction to social network analysis, describes a modest case study, and identifies possible future research directions.
Characteristics and outcome of anti‐hepatitis D virus positive patients with hepatocellular carcinoma
Authors: Giannini Edoardo G. , Pasta Andrea , Pieri Giulia , Plaz Torres Maria Corina , Marseglia Mariarosaria , Pelizzaro Filippo , Sangiovanni Angelo , Cabibbo Giuseppe , Ghittoni Giorgia , Di Marco Mariella , Foschi Francesco Giuseppe , Guarino Maria , Biasini Elisabetta , Saitta Carlo , Campani Claudia , Svegliati‐Baroni Gianluca , Gasbarrini Antonio , Brunetto Maurizia Rossana , Magalotti Donatella , Azzaroli Francesco , Mega Andrea , Sacco Rodolfo , Nardone Gerardo , Sacerdoti David , Masotto Alberto , Vidili Gianpaolo , Bucci Laura , Vitale Alessandro , Trevisani Franco ,   for the Italian Liver Cancer (ITA.LI.CA) group
Published: March 2024

Background & Aims

Chronic hepatitis D virus (HDV) often leads to end‐stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection.

Methods

We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti‐HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups.

Results

Patients with HBV/HDV had worse liver function [Model for End‐stage Liver Disease score: 11 vs. 9, p < .0001; Child‐Turcotte‐Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan‐in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106).

Conclusions

In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.
Contribution of combined stressors on density and gene expression dynamics of the copepod Temora longicornis in the North Sea
Authors: Semmouri Ilias , De Schamphelaere Karel A. C. , Van Nieuwerburgh Filip , Deforce Dieter , Janssen Colin R. , Asselman Jana
Published: March 2024

The impact of multiple environmental and anthropogenic stressors on the marine environment remains poorly understood. Therefore, we studied the contribution of environmental variables to the densities and gene expression of the dominant zooplankton species in the Belgian part of the North Sea, the calanoid copepod Temora longicornis. We observed a reduced density of copepods, which were also smaller in size, in samples taken from nearshore locations when compared to those obtained from offshore stations. To assess the factors influencing the population dynamics of this species, we applied generalised additive models. These models allowed us to quantify the relative contribution of temperature, nutrient levels, salinity, turbidity, concentrations of photosynthetic pigments, as well as chemical pollutants such as polychlorinated biphenyls and polycyclic aromatic hydrocarbons (PAHs), on copepod density. Temperature and Secchi depth, a proxy for turbidity, were the most important environmental variables predicting the densities of T. longicornis, followed by summed PAH and chlorophyll concentrations. Analysing gene expression in field‐collected adults, we observed significant variation in metabolic and stress‐response genes. Temperature correlated significantly with genes involved in proteolytic activities, and encoding heat shock proteins. Yet, concentrations of anthropogenic chemicals did not induce significant differences in the gene expression of genes involved in the copepod's fatty acid metabolism or well‐known stress‐related genes, such as glutathione transferases or cytochrome P450. Our study highlights the potential of gene expression biomonitoring and underscores the significance of a changing environment in future studies.
A case of autoimmune glial fibrillary acidic protein astrocytopathy with excessive startle response and cortical hyperexcitability
Authors: Tanimura Jun , Kaneko Kikuko , Hashimoto Takao
Published: March 2024

We herein report a 60‐year‐old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP‐A) with excessive startle response (ESR), or hyperekplexia. Short‐latency somatosensory evoked potentials (SSEPs) revealed high‐amplitude potentials of the early cortical component. Anti‐GFAPα antibodies in the spinal fluid were positive. The hyperekplexia, other clinical symptoms, and SSEP abnormalities were resolved by corticosteroid therapy. The present case demonstrates that ESR can be associated with GFAP‐A, and its pathophysiology may be cortical hyperexcitability.
Proximal esophageal impedance baseline increases the yield of impedance‐pH and is associated with response to PPIs in chronic cough patients
Authors: Ribolsi Mentore , De Bortoli Nicola , Frazzoni Marzio , Marchetti Lorenzo , Savarino Edoardo , Cicala Michele
Published: March 2024

Background

Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements.

Aim

To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response.

Methods

Demographic, clinical, endoscopy findings, impedance‐pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus.

Results

One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance‐pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non‐responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance‐pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm.

Conclusions

The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance‐pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux‐related cough.
Dystocia frequency and causes in horses with pregnancy disorders or a history of dystocia: A prospective study
Authors: Ellerbrock Markus , Krohn Judith , Büttner Kathrin , Wehrend Axel
Published: March 2024

Dystocia typically presents a life‐threatening condition for both the mare and the foal. This prospective long‐term study aimed to ascertain whether mares with prior pregnancy disorders or a history of dystocia were at a higher risk of experiencing subsequent dystocia in comparison to those without such medical antecedents. To achieve this goal, the authors analysed 207 parturitions and 164 mares over a 10‐year period. Of these, 57 were associated with pregnancy disorders or prior dystocia (Group 1), while 150 parturitions followed uneventful pregnancies in mares that had not yet experienced dystocia (Group 2). Mares in Group 1 were significantly more likely to develop dystocia than those in Group 2 (p = .0180; odds ratio = 2.98). Foetal causes of dystocia were more prevalent than maternal causes (p < .0389). Maternal mortality stood at 0.5%, and neonatal mortality reached 1.9%. The results demonstrate that mares are at significantly higher risk of developing dystocia after experiencing pregnancy disorders or parturition complications during previous pregnancies, emphasizing the need for systematic birth monitoring.
Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study
Authors: Lei Hao , Xing Zixuan , Chen Xin , Dai Yilin , Cheng Baochen , Wang Shengbang , Kang Tong , Wang Qian , Zhang Jing , Jia Jinjing , Zheng Yan
Published: March 2024

Background

Frailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear.

Methods

First, we conducted a two‐sample Mendelian randomization based on genome‐wide association studies (GWAS) to investigate genetic causality between frailty index and common diseases in dermatology. Inverse variance weighted was used to estimate causality. Second, expression quantitative trait locus (eQTLs) analysis was conducted to identify the genes affected by Single nucleotide polymorphisms (SNPs). Third, we performed function and pathway enrichment, transcriptome‐wide association studies (TWAS) analysis based on eQTLs.

Results

It was shown that the rise of frailty index could increase the risk of psoriasis (IVW, beta = 0.916, OR = 2.500, 95%CI:1.418‐4.408, p = 0.002) through Mendelian randomization (MR), and there was no heterogeneity and pleiotropy. There was no causality between the frailty index and other common diseases in dermatology. We found 31 eQTLs based on strongly correlated SNPs in the causality. TWAS analysis found that the expressions of four genes were closely related to psoriasis, including HLA‐DQA1, HLA‐DQA2, HLA‐DRB1 and HLA‐DQB1.

Conclusion

It suggested that the frailty index had a significant positive causality on the risk of psoriasis, which was well documented by combined genomic, transcriptome, and proteome analyses.
Laser‐assisted dacryocystorhinostomy of acquired dacryops in a dog
Authors: Sesana Alberto , Smith David J. , Das Smita
Published: March 2024

Objective

To describe a novel minimally invasive surgical approach to treatment of a nasolacrimal duct cyst in a dog and outcome.

Animal Studied

A 10‐year‐old, male entire, Springer Spaniel with a chronic right‐sided maxillary swelling and associated right eye epiphora and sneezing.

Procedure

Computed tomography with dacryocystography confirmed a cystic structure and destruction of the right maxilla and zygomatic bone with invasion of the nasal cavity. Obstruction of the nasolacrimal duct was confirmed. Rhinoscopy was performed allowing visualization of the ventromedial wall of the cyst. Under direct visualization, dacryocystorhinostomy was performed and the wall of the cyst was ablated with the aid of a thulium laser fiber.

Results

No intraoperative complications occurred during the procedure. Full resolution of clinical signs was noted within 2 weeks of treatment. No recurrence had occurred on long‐term follow‐up at 32 months.

Conclusions

Laser‐assisted dacrocystorhinostomy under direct visualization was successful in the treatment and resolution of a nasolacrimal duct cyst (dacryops) in this case.
RhD mismatch does not affect haematopoietic recovery, graft‐versus‐host disease and survival in allogeneic haematopoietic cell transplantation: A Japanese registry‐based study
Authors: Konuma Takaaki , Uchida Naoyuki , Takeda Wataru , Doki Noriko , Yoshihara Satoshi , Nishida Tetsuya , Kuriyama Takuro , Tanaka Masatsugu , Ohigashi Hiroyuki , Nakamae Hirohisa , Katayama Yuta , Ota Shuichi , Hashii Yoshiko , Ishimaru Fumihiko , Fukuda Takahiro , Ohbiki Marie , Atsuta Yoshiko
Published: March 2024

Background and Objectives

ABO blood group mismatch between the donor and the recipient can affect the success of the transplant as well as problems with the red blood cells during allogeneic haematopoietic cell transplantation (HCT). However, the impact of the Rhesus (Rh) D mismatch on transplant outcomes in allogeneic HCT has been poorly elucidated.

Materials and Methods

We retrospectively evaluated the impact of the RhD mismatch on post‐transplant outcomes in 64,923 patients who underwent allogeneic HCT between 2000 and 2021 using a Japanese registry database.

Results

Out of the whole group, 64,293, 322, 270 and 38 HCTs were done when the recipient or donor was RhD‐mismatched with (+/+), (−/+), (+/−) or (−/−) combinations. The difference in RhD between recipient/donor (−/+), (+/−) and (−/−) did not affect haematopoietic recovery, acute and chronic graft‐versus‐host disease (GVHD), overall survival (OS), non‐relapse mortality (NRM) or relapse when RhD (+/+) was used as the reference group in multivariate analysis.

Conclusion

Our registry‐based study demonstrated that RhD mismatch between recipient and donor did not significantly impact haematopoietic recovery, GVHD, OS, NRM or relapse after allogeneic HCT. These data suggest that RhD mismatches may not need to be avoided for recipient and donor combinations in allogeneic HCT.
The effect of protein or amino acid provision on immobilization‐induced muscle atrophy in healthy adults: A systematic review and meta‐analysis
Authors: Hughes Alix K. , Francis Thomas , Rooney Jessica , Pollock Ross , Witard Oliver C.
Published: March 2024

Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta‐analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: −0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse‐induced muscle atrophy. Although the meta‐analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse‐induced decline in either outcome measurement. Additional high‐quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.
Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment
Authors: Fadahunsi Nicole , Petersen Jonas , Metz Sophia , Jakobsen Alexander , Vad Mathiesen Cecilie , Silke Buch-Rasmussen Alberte , Kurgan Nigel , Kjærgaard Larsen Jeppe , Andersen Rita C. , Topilko Thomas , Svendsen Charlotte , Apuschkin Mia , Skovbjerg Grethe , Hendrik Schmidt Jan , Houser Grace , Elgaard Jager Sara , Bach Anders , Deshmukh Atul S. , Kilpeläinen Tuomas O. , Strømgaard Kristian , Madsen Kenneth L. , Clemmensen Christoffer
Published: March 2024

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) andN-methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P< 5 × 10−8) for BF% and/or BMI. To further evaluate the functional role of postsynaptic density protein-95 (PSD-95; gene name:DLG4) and PICK1 in energy homeostasis, we used dimeric PSD-95/disc large/ZO-1 (PDZ) domain–targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising therapeutic avenue for sustained weight loss.
Nutrient scavenging-fueled growth in pancreatic cancer depends on caveolae-mediated endocytosis under nutrient-deprived conditions
Authors: Wolfe Adam R. , Cui Tiantian , Baie Sooin , Corrales-Guerrero Sergio , Webb Amy , Castro-Aceituno Veronica , Shyu Duan-Liang , Karasinska Joanna M. , Topham James T. , Renouf Daniel J. , Schaeffer David F. , Halloran Megan , Packard Rebecca , Robb Ryan , Chen Wei , Denko Nicholas , Lisanti Michael , Thompson Timothy C. , Frank Philippe , Williams Terence M.
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its nutrient-scavenging ability, crucial for tumor progression. Here, we investigated the roles of caveolae-mediated endocytosis (CME) in PDAC progression. Analysis of patient data across diverse datasets revealed a strong association of high caveolin-1 (Cav-1) expression with higher histologic grade, the most aggressive PDAC molecular subtypes, and worse clinical outcomes. Cav-1 loss markedly promoted longer overall and tumor-free survival in a genetically engineered mouse model. Cav-1–deficient tumor cell lines exhibited significantly reduced proliferation, particularly under low nutrient conditions. Supplementing cells with albumin rescued the growth of Cav-1–proficient PDAC cells, but not in Cav-1–deficient PDAC cells under low glutamine conditions. In addition, Cav-1 depletion led to significant metabolic defects, including decreased glycolytic and mitochondrial metabolism, and downstream protein translation signaling pathways. These findings highlight the crucial role of Cav-1 and CME in fueling pancreatic tumorigenesis, sustaining tumor growth, and promoting survival through nutrient scavenging.
Structure of the PCNA unloader Elg1-RFC
Authors: Zheng Fengwei , Yao Nina Y. , Georgescu Roxana E. , Li Huilin , O’Donnell Michael E.
Published: March 2024

During DNA replication, the proliferating cell nuclear antigen (PCNA) clamps are loaded onto primed sites for each Okazaki fragment synthesis by the AAA
+
heteropentamer replication factor C (RFC). PCNA encircling duplex DNA is quite stable and is removed from DNA by the dedicated clamp unloader Elg1-RFC. Here, we show the cryo-EM structure of Elg1-RFC in various states with PCNA. The structures reveal essential features of Elg1-RFC that explain how it is dedicated to PCNA unloading. Specifically, Elg1 contains two external loops that block opening of the Elg1-RFC complex for DNA binding, and an “Elg1 plug” domain that fills the central DNA binding chamber, thereby reinforcing the exclusive PCNA unloading activity of Elg1-RFC. Elg1-RFC was capable of unloading PCNA using non-hydrolyzable AMP-PNP. Both RFC and Elg1-RFC could remove PCNA from covalently closed circular DNA, indicating that PCNA unloading occurs by a mechanism that is distinct from PCNA loading. Implications for the PCNA unloading mechanism are discussed.
An e-Xist-ential two-edged sword for women
Authors: Zhang Zhenrui , Pillai Shiv
Published: March 2024

Xist-containing ribonucleoproteins drive autoimmunity in women.
In vitro
activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing
Klebsiella pneumoniae
Authors: Cienfuegos-Gallet Astrid V. , Shashkina Elena , Chu Tingyu , Zhu Zhichen , Wang Bingjie , Kreiswirth Barry N. , Chen Liang
Published: March 2024

We evaluated the
in vitro
activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing
Klebsiella pneumoniae
isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene (
bla
NDM-1
and
bla
OXA-48-like
) copy numbers are the main factors responsible for MEV-ATM non-susceptibility. Notably, MEV-ATM is actively against aztreonam-avibactam-resistant mutants due to CMY-16 mutations.