bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Dupilumab as Effective in Intrinsic Atopic Dermatitis as It Is in Extrinsic Atopic Dermatitis?
Authors: Gelato Federica , Mastorino Luca , Stepkina Ekaterina , Cavaliere Giovanni , Ribero Simone , Quaglino Pietro , Ortoncelli Michela
Published: March 2023

Atopic dermatitis (AD) can be subclassified into the more frequent extrinsic type (EAD), with elevated serum IgE levels and frequent association with other atopic conditions, and the less frequent intrinsic type (IAD), with normal IgE levels and no history of atopy. This retrospective study has the objective to compare the efficacy of dupilumab therapy in patients with IAD versus EAD in a real-life setting. We studied a group of 360 patients treated with dupilumab for moderate-to-severe AD of whom 49 had IAD (IgE < 200 kU/L and no history of other atopic conditions) and 311 had EAD (IgE ≥ 200 kU/L and/or history of atopy). There were no statistically significant differences in the achievement of EASI75 between IAD and EAD patients either at 16, 32, or 48 weeks (61% vs. 50%; 66% vs. 60%; and 53% vs. 65%, respectively). Similarly, there were no statistically significant differences in the achievement of EASI90 or the reduction in NRSpp, NRSsd, and DLQI at each timepoint. Additionally, mean absolute eosinophils and IgE values were significantly higher in the EAD group at all timepoints. This study confirms that dupilumab, targeting the Th2 pathway, which is known to be overexpressed in all AD phenotypes, appears to be equally effective in the two populations regardless of IgE levels.
Influence of Joint Flexibility, Hand Grip Strength and Pain on Oral Hygiene in Musculoskeletal Disorders—A Non-Interventional Clinical Study
Authors: Ahmad Irshad , Togoo Rafi Ahmad , M. Alharthi Demah Saleh , M. Alhassan Atheer Ali , O. Alqahtani Deena Ali , Mukherjee Debjani , Alharthi Mohammed Saleh , Ahmad Fuzail , Ahmed Hashim , Hasan Shahnaz , Alshehri Mohammed M. , Uddin Shadab
Published: March 2023

Diseases of the oral cavity and musculoskeletal disorders (MSDs) are common occurrences. They are commonly linked with partial mobility, resulting in limited visits to dentists for routine oral care, causing poor periodontal condition, bleeding, gingival inflammation, and increased depth of periodontal pockets. The present study was conducted to measure joint movements, hand grip strength, and pain in joints and their association with oral health. Materials and methods: The study included 200 subjects, half suffering from back, neck, shoulder, elbow, and wrist problems, belonging to different age groups and professions; 100 had joint pain, and 100 were without joint pain. The study assessed individuals exposed to oral health issues by measuring the strength of hand grip, flexibility, and pain score of the back, neck, shoulder, elbow, and wrist. The strength of the hand grip and the angle of the elbow and shoulder were measured in addition to a questionnaire to assess the relationship between back pain and oral health. To evaluate dental health status and oral hygiene, the total number of decayed, missing, and filled teeth (DMF/T) and Oral Hygiene Index—Simplified (OHI-S) indices were used. Results: The difference between all demographic parameters was statistically significant (p < 0.05). It was observed that there was a significant difference in calculus, debris, and dental caries scores in both groups, with significantly lower scores and better oral hygiene in patients without joint pain. Concerning pain score and joint movements, the group without joint pain showed a significantly better range of movements and less pain than patients suffering from joint pain, and statistically a significant difference (p < 0.05) was observed between both groups. Conclusion: The present study revealed that musculoskeletal disorders, pain in the neck and hand, and restricted movements were common among professionals. We observed that pain in joints, neck, and hands, with restricted movements, caused a serious impact on the maintenance of oral hygiene practices among subjects of different professions.
Implementing Carotid Ultrasonography in Optimizing Primary Cardiovascular Prevention Strategy: Has the Time Come?
Authors: Kollias Anastasios , Kyriakoulis Konstantinos G. , Stathopoulou Panagiota , Stergiou George
Published: March 2023

The cardiovascular (CV) disease continuum begins from a cluster of CV risk factors, proceeds with the development of asymptomatic atherosclerotic lesions and ends with the occurrence of CV events [...]
Outcomes and Follow-Up after Hepatitis C Eradication with Direct-Acting Antivirals
Authors: Lynch Erica Nicola , Russo Francesco Paolo
Published: March 2023

Treatment of hepatitis C (HCV) has been revolutionized with the introduction of direct-acting antivirals (DAAs). Patients can be treated at more advanced stages of liver disease, with a growing number of cirrhotic patients achieving sustained virological response (SVR). Long-term outcomes for cured patients and the optimal follow-up care of patients after SVR are yet to be defined, because most studies on cirrhotic patients cured with DAAs have a short follow-up period. There are many open questions related to patient management after viral eradication with DAAs, such as which could be the most reliable non-invasive tool to predict liver-related complications, or to what extent viral eradication reduces the risk of liver disease progression in the long term. Growing evidence supports the personalization of follow-up care based on individual risk. The aim of this narrative review is to analyze the impact of viral eradication with DAAs on clinically significant portal hypertension, hepatocellular carcinoma, and extrahepatic manifestations, as well as to summarize indications for optimal follow-up care of HCV patients treated with DAAs.
Periodontal Disease in Young Adults as a Risk Factor for Subclinical Atherosclerosis: A Clinical, Biochemical and Immunological Study
Authors: Cicmil Smiljka , Cicmil Ana , Pavlic Verica , Krunić Jelena , Sladoje Puhalo Dragana , Bokonjić Dejan , Čolić Miodrag
Published: March 2023

Although a strong relationship between periodontal disease (PD) and atherosclerosis was shown in adults, little data are published in younger PD patients. Therefore, this study aimed to investigate and correlate clinical parameters of PD, pro- and immunoregulatory cytokines in gingival crevicular fluid (GCF) and serum, biochemical and hematological parameters associated with atherosclerosis risk, and carotid intima-media thickness (IMT) in our younger study participants (n = 78) (mean age 35.92 ± 3.36 years) who were divided into two equal groups: subjects with and without PD. PD patients had higher values of IMT, hs-CRP, triglycerides, total cholesterol, and LDL; most proinflammatory and Th1/Th17-associated cytokines in GCF; and IL-8, IL-12, IL-18, and IL-17A in serum compared to subjects without PD. These cytokines in GCF positively correlated with most clinical periodontal parameters. Clinical periodontal parameters, TNF-α and IL-8 in GCF and IL-17A, hs-CRP, and LDL in serum, had more significant predictive roles in developing subclinical atherosclerosis (IMT ≥ 0.75 mm) in comparison with other cytokines, fibrinogen, and other lipid status parameters. Hs-CRP correlated better with the proinflammatory cytokines than the parameters of lipid status. Except for serum IL-17A, there was no significant association of clinical and immunological PD parameters with lipid status. Overall, these results suggest that dyslipidemia and PD status seem to be independent risk factors for subclinical atherosclerosis in our younger PD population.
Adult Body Height Is Associated with the Risk of Type 2 but Not Type 1 Diabetes Mellitus: A Retrospective Cohort Study of 783,029 Individuals in Germany
Authors: Loosen Sven H. , Krieg Sarah , Krieg Andreas , Luedde Tom , Kostev Karel , Roderburg Christoph
Published: March 2023

Background: Diabetes mellitus is a major global health burden associated with high morbidity and mortality. Although a short adult body height has been associated with increased risk of type 2 diabetes (T2D), there are large inconsistencies between the studies. Therefore, we aimed to investigate the association between body height and T2D in a large cohort of adult outpatients in Germany. Methods: A total of 783,029 adult outpatients with available body height data from the Disease Analyzer (IQVIA) database were included in Germany between 2010 and 2020. The incidence of diabetes mellitus (type 1 and type 2) was evaluated as a function of the patients’ body height stratified by age, sex, and body-mass-index (BMI). Results: In both women and men in all age groups, incidence of T2D decreased with the increasing body height (<50, 51–60, 61–70, and >70 years). There was no association between the body height and the individual HbA1c value. In multivariable Cox regression analyses adjusted for patient age and BMI, hazard ratios for the development of T2D were 1.15 (95% CI: 1.13–1.17) for each 10 cm decrease in body height in women and 1.10 (95% CI: 1.09–1.12) in men. No significant association was found between body height and the development of T1D. Conclusions: We present the first data from a large cohort of outpatients in Germany, providing strong evidence for an association between adult body height and T2D. These data add to the current literature and might help in implementing body height into existing diabetes risk stratification tools to further reduce morbidity and mortality worldwide.
The Eosinophil-to-Lymphocyte Ratio Acts as an Indicator for Improvement of Clinical Signs and Itch by Upadacitinib Treatment in Atopic Dermatitis
Authors: Hagino Teppei , Saeki Hidehisa , Fujimoto Eita , Kanda Naoko
Published: March 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease with severe itch. The eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are reported to reflect itch or the severity of AD. We examined if these parameters may act as indicators for therapeutic effects of the Janus kinase 1 inhibitor upadacitinib for patients with AD in real-world clinical practice. Between August 2021 and September 2023, 65 Japanese patients (aged ≥ 12 years) with moderate to severe AD were treated with 15 mg/day of oral upadacitinib, plus twice daily topical corticosteroids. Before treatment, the baseline ELR, NLR, MLR, and PLR levels positively correlated with the eczema area and severity index (EASI), while the baseline NLR and PLR levels positively correlated with the peak pruritus-numerical rating scale (PP-NRS). After upadacitinib treatment, ELR and NLR remarkably decreased at week 4 and the reduced levels were maintained until week 24, in parallel with EASI and PP-NRS, while MLR and PLR transiently reduced at week 4, but returned to baseline levels after week 12. The percent reduction of ELR significantly correlated with the percent reductions of EASI and PP-NRS at weeks 4, 12, and 24 of upadacitinib treatment. ELR may act as an indicator for the improvement of clinical signs and itch by upadacitinib treatment in AD.
Nail Apparatus Melanoma: Current Management and Future Perspectives
Authors: Ito Takamichi , Hashimoto Hiroki , Kaku-Ito Yumiko , Tanaka Yuka , Nakahara Takeshi
Published: March 2023

Nail apparatus melanoma (NAM) is a rare type of cutaneous melanoma that belongs to the acral melanoma subtype. NAM is managed principally in accordance with the general treatment for cutaneous melanoma, but there is scarce evidence in support of this in the literature. Acral melanoma is genetically different from non-acral cutaneous melanoma, while recently accumulated data suggest that NAM also has a different genetic background from acral melanoma. In this review, we focus on recent advances in the management of NAM. Localized NAM should be surgically removed; amputation of the digit and digit-preserving surgery have been reported. Sentinel lymph node biopsy can be considered for invasive NAM for the purpose of accurate staging. However, it is yet to be clarified whether patients with metastatic sentinel lymph nodes can be safely spared completion lymph node dissection. Similar to cutaneous melanoma, immune checkpoint inhibitors and BRAF/MEK inhibitors are used as the first-line treatment for metastatic NAM, but data on the efficacy of these therapies remain scarce. The therapeutic effects of immune checkpoint inhibitors could be lower for NAM than for cutaneous melanoma. This review highlights the urgent need to accumulate data to better define the optimal management of this rare melanoma.
Neurologic Consultations and Headache during Pregnancy and in Puerperium: A Retrospective Chart Review
Authors: Zimmermann Julia S. M. , Fousse Mathias , Juhasz-Böss Ingolf , Radosa Julia C. , Solomayer Erich-Franz , Mühl-Benninghaus Ruben
Published: March 2023

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients—indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging.
Non-Invasive Intracranial Pressure Monitoring
Authors: Müller Sebastian Johannes , Henkes Elina , Gounis Matthew J. , Felber Stephan , Ganslandt Oliver , Henkes Hans
Published: March 2023

(1) Background: Intracranial pressure (ICP) monitoring plays a key role in the treatment of patients in intensive care units, as well as during long-term surgeries and interventions. The gold standard is invasive measurement and monitoring via ventricular drainage or a parenchymal probe. In recent decades, numerous methods for non-invasive measurement have been evaluated but none have become established in routine clinical practice. The aim of this study was to reflect on the current state of research and shed light on relevant techniques for future clinical application. (2) Methods: We performed a PubMed search for “non-invasive AND ICP AND (measurement OR monitoring)” and identified 306 results. On the basis of these search results, we conducted an in-depth source analysis to identify additional methods. Studies were analyzed for design, patient type (e.g., infants, adults, and shunt patients), statistical evaluation (correlation, accuracy, and reliability), number of included measurements, and statistical assessment of accuracy and reliability. (3) Results: MRI-ICP and two-depth Doppler showed the most potential (and were the most complex methods). Tympanic membrane temperature, diffuse correlation spectroscopy, natural resonance frequency, and retinal vein approaches were also promising. (4) Conclusions: To date, no convincing evidence supports the use of a particular method for non-invasive intracranial pressure measurement. However, many new approaches are under development.
Anterior and Apical Prolapse: Comparison of Vaginal Mesh Surgery to Vaginal Surgery with No Mesh
Authors: Cassagne Charlotte , Perriard Francoise , Cornille Arnaud , Salerno Jennifer , Panel Laure
Published: March 2023

Aim of the study: The aim of this study was to evaluate the anatomical results after an anterior sacrospinous ligament fixation (ASSLF) with native tissue repair (anterior colporraphy and apical suspension with prolene) compared to mesh repair for the correction of anterior prolapse at 12 months after surgery. Materials and methods: A monocentric prospective study comparing two similar cohorts who underwent ASSLF was conducted. The primary endpoint was the gain in the position of the Ba point relative to its position before surgery and twelve months after surgery. The secondary endpoints consisted of objective results, which were assessed using validated questionnaires. Results: Fifty-three women were included in the native tissue repair group between June 2019 and March 2020. They were compared to 53 women operated on with anterior and apical mesh. There was no difference with respect to the Ba point after 1 year between the two groups (−2 [−3; 1.5]; −2 [−3; 1], p = 0.9789). The apex was significantly better corrected in the native tissue repair group (−7 vs. −6, p = 0.0007). There was also a better correction on the rectocele in the native tissue repair group (−3 vs. −2, p = 0.0178). The rate of Stage 2 anterior vaginal prolapse at one year was approximately 30% in both groups (no statistical difference). Conclusions: ASSFL without mesh does not increase the risk of cystocele recurrence at 1 year after surgery. A future prospective comparison of this native tissue repair technique with mesh suspension is necessary to explore these preliminary findings.
Corneal Neurotization—Indications, Surgical Techniques and Outcomes
Authors: Dragnea Diana Carmen , Krolo Iva , Koppen Carina , Faris Callum , Van den Bogerd Bert , Ní Dhubhghaill Sorcha
Published: March 2023

Corneal neurotization is a promising surgical approach for the treatment of moderate to severe neurotrophic keratopathy. This technique aims to restore corneal sensation by transferring healthy nerves, either directly or via a conduit, to the anesthetic cornea. This review provides a report on the current state of development, evidence, and experience in the field. We summarize the data available from clinical reports and case series, placing an emphasis on the diversity of the surgical techniques reported. While these data are encouraging, they also highlight the need for a consensus in reporting outcomes and highlight how the next step will involve validating putative outcome parameters when researching and reporting corneal neurotization surgery.
Statistical Analysis and Optimization of the Experimental Results on Performance of Green Aluminum-7075 Hybrid Composites
Authors: Adesina Olanrewaju Seun , Akinwande Abayomi Adewale , Balogun Oluwatosin Abiodun , Adediran Adeolu Adesoji , Sanyaolu Olufemi Oluseun , Romanovski Valentin
Published: March 2023

The present study assessed the potential of engaging response surface analysis in the experimental design, modeling, and optimization of the strength performance of aluminum-7075 green composite. The design of the experiment was carried out via the Box–Behnken method and the independent variables are rice husk ash (RHA) at 3–12 wt.%, glass powder (GP) at 2–10 wt.%, and stirring temperature (ST) at 600–800 °C. Responses examined are yield, ultimate tensile, flexural, and impact strengths, as well as microhardness and compressive strength. ANOVA analysis revealed that the input factors had consequential contributions to each response, eventually presenting regression models statistically fit to represent the experimental data, further affirmed by the diagnostic plots. The result of the optimization envisaged an optimal combination at 7.2% RHA, 6.2 GP, and 695 °C with a desirability of 0.910. A comparison between the predicted values for the responses and the values of the validation experiment revealed an error of <5% for each response. Consequently, the models are certified adequate for response predictions at 95% confidence, and the optimum combination is adequate for the design of the composite.
Heme Oxygenase-1 Is Upregulated during Differentiation of Keratinocytes but Its Expression Is Dispensable for Cornification of Murine Epidermis
Authors: Surbek Marta , Sukseree Supawadee , Sachslehner Attila Placido , Copic Dragan , Golabi Bahar , Nagelreiter Ionela Mariana , Tschachler Erwin , Eckhart Leopold
Published: March 2023

The epidermal barrier of mammals is initially formed during embryonic development and continuously regenerated by the differentiation and cornification of keratinocytes in postnatal life. Cornification is associated with the breakdown of organelles and other cell components by mechanisms which are only incompletely understood. Here, we investigated whether heme oxygenase 1 (HO-1), which converts heme into biliverdin, ferrous iron and carbon monoxide, is required for normal cornification of epidermal keratinocytes. We show that HO-1 is transcriptionally upregulated during the terminal differentiation of human keratinocytes in vitro and in vivo. Immunohistochemistry demonstrated expression of HO-1 in the granular layer of the epidermis where keratinocytes undergo cornification. Next, we deleted the Hmox1 gene, which encodes HO-1, by crossing Hmox1-floxed and K14-Cre mice. The epidermis and isolated keratinocytes of the resulting Hmox1f/f K14-Cre mice lacked HO-1 expression. The genetic inactivation of HO-1 did not impair the expression of keratinocyte differentiation markers, loricrin and filaggrin. Likewise, the transglutaminase activity and formation of the stratum corneum were not altered in Hmox1f/f K14-Cre mice, suggesting that HO-1 is dispensable for epidermal cornification. The genetically modified mice generated in this study may be useful for future investigations of the potential roles of epidermal HO-1 in iron metabolism and responses to oxidative stress.
Reference Model-Based Deterministic Policy for Pitch and Depth Control of Autonomous Underwater Vehicle
Authors: Du Jiqing , Zhou Dan , Wang Wei , Arai Sachiyo
Published: March 2023

The Deep Reinforcement Learning (DRL) algorithm is an optimal control method with generalization capacity for complex nonlinear coupled systems. However, the DRL agent maintains control command saturation and response overshoot to achieve the fastest response. In this study, a reference model-based DRL control strategy termed Model-Reference Twin Delayed Deep Deterministic (MR-TD3) was proposed for controlling the pitch attitude and depth of an autonomous underwater vehicle (AUV) system. First, a reference model based on an actual AUV system was introduced to an actor–critic structure, where the input of the model was the reference target, the outputs were the smoothed reference targets, and the reference model parameters can adjust the response time and the smoothness. The input commands were limited to the saturation range. Then, the model state, the real state and the reference target were mapped to the control command through the Twin Delayed Deep Deterministic (TD3) agent for training. Finally, the trained neural network was applied to the AUV system environment for pitch and depth experiments. The results demonstrated that the controller can eliminate the response overshoot and control command saturation while improving the robustness, and the method also can extend to other control platforms such as autonomous guided vehicle or unmanned aerial vehicle.
Analysis of Performance of Passive Pre-Chamber on a Lean-Burn Natural Gas Engine under Low Load
Authors: Lu Changhao , Song Enzhe , Xu Congcong , Ni Zuo , Yang Xiyu , Dong Quan
Published: March 2023

Stable ultra-lean combustion is an effective way for natural gas engines to reduce NOx emissions, but it also has higher requirements for ignition stability. The passive pre-chamber can effectively increase the ignition energy and extend the lean-burn limit of natural gas engines. However, the scavenging capacity of the pre-chamber limits its performance under low engine load. In this paper, several passive pre-chambers are designed, and the CFD simulation is carried out to investigate the influence of direction, number and diameter of the nozzle on the scavenging process. The discharge of residual gas in the pre-chamber is mainly affected by the nozzle diameter, which varies from 5.9% to 1% when the nozzle diameter increases from 0.8 mm to 1.6 mm. At the same time, claw-shaped electrodes are applied in the pre-chamber to increase the combustion rate, which is validated in a cylinder combustion simulation. Finally, the passive pre-chamber is tested on a 6-cylinder natural gas engine under 25% load. The results show that, under the proper ignition timing, the excess air ratio (λ) can reach 1.9 under 25% load of propulsion characteristic with a low level of cyclic variation. At this time, the NOx emission can be as low as 0.34 g/kWh without aftertreatment equipment.
Study on Bearing Capacity of Reinforced Composite Pipe Pile Group in Reclaimed Stratum under Vertical Load
Authors: Bao Xiaohua , Cheng Zilong , Shen Jun , Zhang Xiaodong , Chen Xiangsheng , Cui Hongzhi
Published: March 2023

A new stiffened composite pipe pile was developed for improving the foundation of reclaimed ground in ocean engineering. To study the bearing capacity of the stiffened composite pipe pile group, a combination of field test and finite element method was used. Firstly, field tests were performed on the proposed single stiffened composite pipe pile. The single stiffened composite pipe pile model was verified by comparing the numerical simulation results with the field test results. The load transfer mechanism from the stiffened core to the cemented soil and the surrounding soil was clarified. Further, a 3D finite element model of the stiffened composite pipe pile group was established based on the single stiffened composite pipe pile model. Finally, the bearing capacity of the pile group and the stress distribution of each pile were analysed and the influence of the pile spacing on the pile bearing capacity was discussed. The results showed that the axial stress of both the side and corner piles decreased rapidly with an increase in the pile spacing, and the stress-bearing ratio decreased. The stress-bearing ratio of the central pile increases with an increase in pile spacing. The smaller the pile spacing, the larger the load proportion of the composite pile group and the larger the foundation settlement. The optimal design scheme was a composite pile with a 500 mm stiffened core diameter, 700 mm outer cemented soil diameter, and a spacing between piles of four times the cemented soil diameter (2.8 m) considering the group pile bearing capacity and the economic benefits of the project. These results provide a reference for the design and construction of stiffened composite piles for ground improvement projects.
Green Composites for Maritime Engineering: A Review
Authors: Crupi Vincenzo , Epasto Gabriella , Napolitano Francesco , Palomba Giulia , Papa Ilaria , Russo Pietro
Published: March 2023

Green composites have gained increasing attention in recent years as a sustainable alternative to traditional materials used in marine structures. These composites are made from biodegradable and renewable materials, making them environmentally friendly and reducing the subsequent carbon footprint. This review aims to provide a comprehensive overview of green composites materials and their applications in marine structures. This review includes a classification of the potential fibres and matrixes for green composites which are suitable for marine applications. The properties of green composites, such as their strength and Young’s modulus, are analysed and compared with those of traditional composites. An overview concerning current rules and regulations is presented. The applications of green composites in marine structures are reviewed, focusing on both shipbuilding and offshore applications. The main challenges in a wider application of green composites are also highlighted, as well as the benefits and future challenges.
Effects of Selenium Yeast Addition on the Growth, Intestinal Health, Immune Status and Body Composition of Juvenile Sea Cucumber Apostichopus japonicus before and after Aestivation
Authors: Zuo Rantao , Wu Xiangying , Wang Ziyao , Zhou Xiaohui , Chang Yaqing , Yang Zhilong , Huang Zuqiang , Ding Jun
Published: March 2023

This study was performed to investigate the effects of selenium yeast (Se-yeast) on the growth, intestinal health, immune status and body composition of juvenile Apostichopus japonicus before and after aestivation. Five experimental diets were formulated with increasing addition of Se-yeast (0, 0.5, 1.0, 1.5 and 2.0 mg/kg), with the diet without Se-yeast as the control. Each diet was randomly assigned to three tanks of juvenile A. japonicus (initial body weight: 2.96 ± 0.04 g). The whole experiment lasted for 135 days, which included a 45-day feeding experiment before aestivation, a 60-day aestivation phage and a 30-day feeding experiment after aestivation. The results showed that weight gain rate (WGR) was significantly increased by the increasing addition of Se-yeast before aestivation. After aestivation, WGR was markedly elevated by 1.0 mg/kg Se-yeast but was inhibited by 1.5–2.0 mg/kg Se-yeast. The evisceration rate (ER) of A. japonicus was obviously inhibited by the relatively higher addition level of Se-yeast (1.5–2.0 mg/kg) before aestivation. After aestivation, the ER was significantly inhibited by Se-yeast at an addition of 1.5 mg/kg. Before aestivation, the highest activities of all digestive enzymes were obtained by Se-yeast addition at a level equal to or above 1.0 mg/kg Se-yeast. After aestivation, the activities of most digestive enzymes were maximized by Se-yeast at the addition level of no more than 1.0 mg/kg. Before aestivation, the activities of nitric oxide synthase and alkaline phosphatase significantly increased by the increasing addition of Se-yeast. After aestivation, immune related parameters exhibited the highest or comparable values when the addition level of Se-yeast was equal to or less than 1.0 mg/kg. Notably, the selenium content in the body wall of A. japonicus increased significantly as Se-yeast addition increased in the diets. These results showed that Se-yeast at the addition level of 1.5–2.0 mg/kg before aestivation and 1.0–1.5 mg/kg after aestivation was beneficial for the promotion of growth, intestinal health and immune status of juvenile A. japonicus.
Regionally Varying Habitat Relationships in Lichens: The Concept and Evidence with an Emphasis on North-Temperate Ecosystems
Authors: Lõhmus Asko , Motiejūnaitė Jurga , Lõhmus Piret
Published: March 2023

Habitat ecology of lichens (lichen-forming fungi) involves diverse adaptations to stressful environments where lichens use specific habitat conditions. Field observations confirm that such habitat ‘preferences’ can vary significantly across species’ distribution ranges, sometimes revealing abrupt changes over short distances. We critically review and generalize such empirical evidence as broad ecological patterns, link these with the likely physiological mechanisms and evolutionary processes involved, and outline the implications for lichen conservation. Non-replicated correlative studies remain only suggestive because the data are frequently compromised by sampling bias and pervasive random errors; further noise is related to unrecognized cryptic species. Replicated evidence exists for three macroecological patterns: (a) regional limiting factors excluding a species from a part of its microhabitat range in suboptimal areas; (b) microhabitat shifts to buffer regionally adverse macroclimates; (c) substrate suitability changed by the chemical environment, notably air pollution. All these appear to be primarily buffering physiological challenges of the adverse conditions at the macrohabitat scale or, in favorable environments, coping with competition or predation. The roles of plasticity, adaptation, dispersal, and population-level stochasticity remain to be studied. Although lichens can inhabit various novel microhabitats, there is no evidence for a related adaptive change. A precautionary approach to lichen conservation is to maintain long-term structural heterogeneity in lichen habitats, and consider lichen ecotypes as potential evolutionarily significant units and a bet-hedging strategy for addressing the climate change-related challenges to biodiversity.
Fungal–Lactobacteria Consortia and Enzymatic Catalysis for Polylactic Acid Production
Authors: de Eugenio Laura I. , Murguiondo Carlos , Galea-Outon Sandra , Prieto Alicia , Barriuso Jorge
Published: March 2023

Polylactic acid (PLA) is the main biobased plastic manufactured on an industrial scale. This polymer is synthetized by chemical methods, and there is a strong demand for the implementation of clean technologies. This work focuses on the microbial fermentation of agro-industrial waste rich in starch for the production of lactic acid (LA) in a consolidated bioprocess, followed by the enzymatic synthesis of PLA. Lactic acid bacteria (LAB) and the fungus Rhizopus oryzae were evaluated as natural LA producers in pure cultures or in fungal–lactobacteria co-cultures formed by an LAB and a fungus selected for its metabolic capacity to degrade starch and to form consortia with LAB. Microbial interaction was analyzed by scanning electron microscopy and biofilm production was quantified. The results show that the fungus Talaromyces amestolkiae and Lactiplantibacillus plantarum M9MG6-B2 establish a cooperative relationship to exploit the sugars from polysaccharides provided as carbon sources. Addition of the quorum sensing molecule dodecanol induced LA metabolism of the consortium and resulted in improved cooperation, producing 99% of the maximum theoretical yield of LA production from glucose and 65% from starch. Finally, l-PLA oligomers (up to 19-LA units) and polymers (greater than 5 kDa) were synthetized by LA polycondensation and enzymatic ring-opening polymerization catalyzed by the non-commercial lipase OPEr, naturally produced by the fungus Ophiostoma piceae.
Population Dynamics of Phytophthora infestans in Egypt Reveals Clonal Dominance of 23_A1 and Displacement of 13_A2 Clonal Lineage
Authors: El-Ganainy Sherif Mohamed , Ismail Ahmed Mahmoud , Soliman Maali Shaker , Ahmed Yosra , Sattar Muhammad Naeem , Chellappan Biju Vadakkemukadiyil , Cooke David E. L.
Published: March 2023

Potato (Solanum tuberosum L.) and tomato (S. lycopersicum L.) are the most economically important vegetable crops in Egypt and worldwide. The winter crop in Egypt is particularly prone to late blight caused by Phytophthora infestans. A total of 152 P. infestans isolates were isolated from the 2013, 2014, 2016 and 2018 winter crops with 82 isolates from potato, 69 from tomato and one isolate from eggplant (S. melongena L.). All isolates belonged to the A1 mating type with no evidence of A2 or self-fertile strains. The majority of isolates (53%) were sensitive to metalaxyl, 32% were intermediate and 15% were resistant. Variation in aggressiveness between three P. infestans isolates EG-005 (13_A2) and EG-276 (23_A1) from potato, and EG-237 (23_A1) from eggplant was determined on tuber slices and leaflets of 10 potato cultivars. The eggplant isolate EG-237 showed higher sporulation capacity compared with the other tested isolates and was able to infect potato (Lady Rosetta cv) and tomato (Super Strain B cv). The simple sequence repeat (SSR) genotyping data showed that in contrast to our previous work (3-year period 2010–12) in which the proportion of 13_A2 lineage was 35%, all isolates belonged to the 23_A1 lineage. There was no evidence for the existence of the A2 mating type or 13_A2 lineage even in the destroyed field crops of some cultivars (Cara, Bellini and Valor) that had been reported as resistant to 23_A1. The data have been submitted into the Euroblight database to allow temporal and spatial genetic diversity to be examined in comparison with other regional P. infestans populations. The AVR2 and AVR2-like RXLR effector genes were amplified and sequenced. In the avirulent AVR2 gene, only one heterozygous SNP was detected at position 31 in the N terminus in six isolates out of eleven, whereas two heterozygous SNPs were detected at position 29 in the N-terminus and ninety-two in the C- terminus of the AVR2-like gene. This suggests that changes in the previously reported virulence profile of 23_A1 are not related to commercial cultivars carrying the R2 gene. In addition, this is the first report of P. infestans on eggplant in Egypt.
Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia
Authors: Bednarova Aneta , Habalova Viera , Iannaccone Silvia Farkasova , Tkac Ivan , Jarcuskova Dominika , Krivosova Michaela , Marcatili Matteo , Hlavacova Natasa
Published: March 2023

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.
High Homocysteine Levels Are Associated with Cognitive Impairment in Patients Who Recovered from COVID-19 in the Long Term
Authors: Oner Pinar , Yilmaz Seda , Doğan Serpil
Published: March 2023

In this study, we measured the levels of depression and cognition in people recovering from COVID-19. Moreover, we aimed to investigate the relationship between depression and cognition levels by measuring homocysteine concentrations. It included 62 people recovering from COVID-19 (at least 3 months after positive RT-PCR) and 64 people without COVID-19 (control group). At first, the homocysteine levels of participants were measured. Beck Depression Inventory (BDI) and Montreal Cognitive Assessment (MoCA) were performed to collect data. Homocysteine levels of the group recovering from COVID-19 (x− = 19.065 µmol/L) were higher than the control group (x− = 11.313 µmol/L). There was no significant difference between the groups for BDI scores. The MoCA scores of the group recovering from COVID-19 (x− = 20.774) were lower than the control group (x− = 24.297). There was a negative high (r = –0.705, p < 0.001) correlation between homocysteine levels and MoCA scores. Linear regression analysis is shown to be significant, and the MoCA explanatory value of the variables in the model is 58.6% (p < 0.0001). A 1 µmol/L observed increase in homocysteine level constituted a risk for a 0.765-point decrease in MOCA scores. In patients recovering from COVID-19, early interventions to high homocysteine levels may prevent cognitive impairments that may persist in the long term.
The Lübeck Medication Satisfaction Questionnaire—A Novel Measurement Tool for Therapy Satisfaction
Authors: Matrisch Ludwig , Rau Yannick , Karsten Hendrik , Graßhoff Hanna , Riemekasten Gabriela
Published: March 2023

Background: Therapy satisfaction is widely considered an important aspect of clinical care. Still, there are currently no freely available questionnaires for its measurement. We developed the Lübeck Medication Satisfaction Questionnaire (LMSQ) for that purpose. Here, we present its content and psychometric properties. Methods: The LMSQ was validated on 86 patients in a single center study. The Kaiser-Meyer-Olkin test, confirmatory factor analysis, covariance analysis, and a test of exact fit were performed. Reliability was tested using Cronbach’s α and McDonald’s ω. The relationship to other patient-reported outcomes was tested using Pearson’s correlation. Results: Confirmatory factors analysis yielded moderate factor loadings with p < 0.001 in all subscales. Reliability was adequate (α = 0.857 and ω = 0.872). Model fitness was excellent in all tests. The LMSQ was positively correlated with medication adherence (r = 0.603, p < 0.001) and most dimensions of health literacy. Conclusions: The LMSQ possesses adequate psychometric properties for its purpose. We recommend further validation in a more diverse patient collective.
Enhancement of Immune Response of Bioconjugate Nanovaccine by Loading of CpG through Click Chemistry
Authors: Mo Mengting , Li Xiang , Li Caixia , Wang Kangfeng , Li Shulei , Guo Yan , Sun Peng , Wu Jun , Lu Ying , Pan Chao , Wang Hengliang
Published: March 2023

CpG is a widely used adjuvant that enhances the cellular immune response by entering antigen-presenting cells and binding with receptors. The traditional physical mixing of the antigen and CpG adjuvant results in a low adjuvant utilization rate. Considering the efficient delivery capacity of nanovaccines, we developed an attractive strategy to covalently load CpG onto the nanovaccine, which realized the co-delivery of both CpG and the antigen. Briefly, the azide-modified CpG was conjugated to a bioconjugate nanovaccine (NP-OPS) against Shigella flexneri through a simple two-step reaction. After characterization of the novel vaccine (NP-OPS-CpG), a series of in vitro and in vivo experiments were performed, including in vivo imaging, lymph node sectioning, and dendritic cell stimulation, and the results showed that more CpG reached the lymph nodes after covalent coupling. Subsequent flow cytometry analysis of lymph nodes from immunized mice showed that the cellular immune response was greatly promoted by the nanovaccine coupled with CpG. Moreover, by analyzing the antibody subtypes of immunized mice, NP-OPS-CpG was found to further promote a Th1-biased immune response. Thus, we developed an attractive method to load CpG on a nanovaccine that is simple, convenient, and is especially suitable for immune enhancement of vaccines against intracellular bacteria.
Targeting FGFR Pathway Is Not an Effective Therapeutic Strategy in Patients with Unselected Metastatic Esophagogastric Cancer Resistant to Trastuzumab
Authors: Zecchetto Camilla , Quinzii Alberto , Casalino Simona , Gaule Marina , Pesoni Camilla , Merz Valeria , Pietrobono Silvia , Mangiameli Domenico , Pasquato Martina , Milleri Stefano , Giacopuzzi Simone , Bencivenga Maria , Tomezzoli Anna , de Manzoni Giovanni , Melisi Davide
Published: March 2023

Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a mechanism potentially involved in trastuzumab-acquired resistance. FGFR inhibition could be a potential mechanism as a second-line treatment. In this Simon’s two-stage phase 2, single arm study, patients with advanced EG cancer refractory to trastuzumab-containing therapies received pemigatinib, an inhibitor of FGFR. The primary end point was the 12-week progression-free survival rate. Translational analyses were performed on tissue and plasma samples. Eight patients were enrolled in the first stage. Although the 6-week disease control rate was 25%, only one patient achieved a stable disease after 12 weeks of treatment. The trial was discontinued before the second stage. Two out of six evaluable tumor samples expressed FGFR3. No FGFRs amplification was detected. HER2 amplification was lost in three out of eight patients. Three patients had an high Tumor Mutational Burden, and two of them are significantly long-term survivors. These results do not support the therapeutic efficacy of targeting FGFR in unselected patients with advanced EG cancer, who are refractory to trastuzumab-containing therapies.
Total Cholesterol Variability and the Risk of Osteoporotic Fractures: A Nationwide Population-Based Cohort Study
Authors: Kim Dongyeop , Kim Jee Hyun , Song Tae-Jin
Published: March 2023

Several risk factors for osteoporotic fractures have been identified but reports of the association of lipid parameters with the occurrence of osteoporotic fractures have been limited. We aimed to examine whether serum total cholesterol (TC) variability is associated with osteoporotic fractures. The study included 3,00,326 subjects who had undergone three or more health examinations between 2003 and 2008. The primary endpoint was the incidence of osteoporotic fractures, including vertebral, hip, distal radius, and humerus fractures. TC variability was evaluated based on the following three parameters: coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). A total of 29,044 osteoporotic fracture events (9.67%) were identified during a median of 11.6 years of follow-up. The risk of osteoporotic fractures in the highest quartile was significantly higher compared with the lowest quartile according to the three indices of TC variability with adjusted hazard ratios (HR) and 95% confidence intervals (CI) as follows: CV (HR 1.11, 95% CI [1.08–1.15]), SD (HR 1.07, 95% CI [1.04–1.11]) and VIM (HR 1.07, 95% CI [1.04–1.11]). The Kaplan–Meier curves showed a significantly positive relationship between the higher quartile of TC variability and overall osteoporotic fractures. The association remained significant in subgroup analyses of vertebral and hip fractures, regardless of the indices of TC variability. Our study showed that visit-to-visit TC variability was found to be associated with osteoporotic fracture risk. Maintaining TC levels stable may help attenuate the osteoporotic fracture risk in the future.