bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets
Authors: Boo Yong Chool
Published: January 2024

Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease. I introduce well-established therapeutic targets for this disease and various other emerging therapeutic targets that have been proposed based on the phenotypic difference between keloid-derived fibroblasts (KFs) and normal epidermal fibroblasts (NFs). We then present recent studies on the biological effects of various plant-derived extracts and compounds on KFs and NFs. Associated ex vivo, in vivo, and clinical studies are also presented. Finally, we discuss the mechanisms of action of the plant-derived extracts and compounds, the pros and cons, and the future tasks for natural product-based therapy for keloid disease, as compared with existing other therapies. Extracts of Astragalus membranaceus, Salvia miltiorrhiza, Aneilema keisak, Galla Chinensis, Lycium chinense, Physalis angulate, Allium sepa, and Camellia sinensis appear to modulate cell proliferation, migration, and/or extracellular matrix (ECM) production in KFs, supporting their therapeutic potential. Various phenolic compounds, terpenoids, alkaloids, and other plant-derived compounds could modulate different cell signaling pathways associated with the pathogenesis of keloids. For now, many studies are limited to in vitro experiments; additional research and development are needed to proceed to clinical trials. Many emerging therapeutic targets could accelerate the discovery of plant-derived substances for the prevention and treatment of keloid disease. I hope that this review will bridge past, present, and future research on this subject and provide insight into new therapeutic targets and pharmaceuticals, aiming for effective keloid treatment.
Uncovering Novel Extracellular Matrix Transcriptome Alterations in Lesions of Multiple Sclerosis
Authors: Stephenson Erin Laurel , Jain Rajiv William , Ghorbani Samira , Gorter Rianne Petra , D’Mello Charlotte , Yong Voon Wee
Published: January 2024

The extracellular matrix (ECM) of the central nervous system (CNS) is an interconnected network of proteins and sugars with critical roles in both homeostasis and disease. In neurological diseases, excessive ECM deposition and remodeling impact both injury and repair. CNS lesions of multiple sclerosis (MS), a chronic inflammatory and degenerative disease, cause prominent alterations of the ECM. However, there are a lack of data investigating how the multitude of ECM members change in relation to each other and how this affects the MS disease course. Here, we evaluated ECM changes in MS lesions compared to a control brain using databases generated in-house through spatial mRNA-sequencing and through a public resource of single-nucleus RNA sequencing previously published by Absinta and colleagues. These results underline the importance of publicly available datasets to find new targets of interest, such as the ECM. Both spatial and public datasets demonstrated widespread changes in ECM molecules and their interacting proteins, including alterations to proteoglycans and glycoproteins within MS lesions. Some of the altered ECM members have been described in MS, but other highly upregulated members, including the SPARC family of proteins, have not previously been highlighted. SPARC family members are upregulated in other conditions by reactive astrocytes and may influence immune cell activation and MS disease course. The profound changes to the ECM in MS lesions deserve more scrutiny as they impact neuroinflammation, injury, and repair.
Integration of Cell-Free DNA End Motifs and Fragment Lengths Can Identify Active Genes in Liquid Biopsies
Authors: Maansson Christoffer Trier , Thomsen Louise Skov , Meldgaard Peter , Nielsen Anders Lade , Sorensen Boe Sandahl
Published: January 2024

Multiple studies have shown that cell-free DNA (cfDNA) from cancer patients differ in both fragment length and fragment end motif (FEM) from healthy individuals, yet there is a lack of understanding of how the two factors combined are associated with cancer and gene transcription. In this study, we conducted cfDNA fragmentomics evaluations using plasma from lung cancer patients (n = 12) and healthy individuals (n = 7). A personal gene expression profile was established from plasma using H3K36me3 cell-free chromatin immunoprecipitation sequencing (cfChIP-seq). The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94–27.13%, p < 0.0001) compared to the genes with low expression. Furthermore, distinct GC-rich FEMs were enriched after cfChIP. Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10–39.49%, p < 0.0001). An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499–0.882, p < 0.0001). This study expands the knowledge regarding cfDNA fragmentomics and sheds new light on how gene activity is associated with both cfDNA fragment lengths and distinct FEMs.
Serum Neurofilament and Free Light Chain Levels in Patients Undergoing Treatment for Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Luigetti Marco , Primiano Guido , Basile Valerio , Vitali Francesca , Pignalosa Stefano , Romano Angela , Sabino Andrea , Marino Mariapaola , Di Santo Riccardo , Ciasca Gabriele , Basile Umberto
Published: January 2024

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.
Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma
Authors: Sadagopan Narayanan , He Aiwu Ruth
Published: January 2024

Patients with advanced hepatocellular carcinoma (HCC) have several systemic treatment options. There are many known risk factors for HCC, and although some, such as hepatitis C, are now treatable, others are not. For example, metabolic dysfunction-related chronic liver disease is increasing in incidence and has no specific treatment. Underlying liver disease, drug resistance, and an increasing number of treatment options without specific biomarkers are all challenges in selecting the best treatment for each patient. Conventional chemotherapy is almost never used for advanced-stage disease, which instead is treated with immunotherapy, tyrosine kinase inhibitors, and VEGF inhibitors. Immune checkpoint inhibitors targeting various receptors have been or are currently undergoing clinical evaluation. Ongoing trials with three-drug regimens may be the future of advanced-stage HCC treatment. Other immune-modulatory approaches of chimeric antigen receptor-modified T cells, bispecific antibodies, cytokine-induced killer cells, natural killer cells, and vaccines are in early-stage clinical trials. Targeted therapies remain limited for HCC but represent an area of potential growth. As we shift away from first-line sorafenib for advanced HCC, clinical trial control arms should comprise a standard treatment other than sorafenib, one that is a better comparator for advancing therapies.
Examining the Efficacy of ChatGPT in Marking Short-Answer Assessments in an Undergraduate Medical Program
Authors: Morjaria Leo , Burns Levi , Bracken Keyna , Levinson Anthony J. , Ngo Quang N. , Lee Mark , Sibbald Matthew
Published: January 2024

Traditional approaches to marking short-answer questions face limitations in timeliness, scalability, inter-rater reliability, and faculty time costs. Harnessing generative artificial intelligence (AI) to address some of these shortcomings is attractive. This study aims to validate the use of ChatGPT for evaluating short-answer assessments in an undergraduate medical program. Ten questions from the pre-clerkship medical curriculum were randomly chosen, and for each, six previously marked student answers were collected. These sixty answers were evaluated by ChatGPT in July 2023 under four conditions: with both a rubric and standard, with only a standard, with only a rubric, and with neither. ChatGPT displayed good Spearman correlations with a single human assessor (r = 0.6–0.7, p < 0.001) across all conditions, with the absence of a standard or rubric yielding the best correlation. Scoring differences were common (65–80%), but score adjustments of more than one point were less frequent (20–38%). Notably, the absence of a rubric resulted in systematically higher scores (p < 0.001, partial η2 = 0.33). Our findings demonstrate that ChatGPT is a viable, though imperfect, assistant to human assessment, performing comparably to a single expert assessor. This study serves as a foundation for future research on AI-based assessment techniques with potential for further optimization and increased reliability.
An ART Tour de Force on Mental Imagery: Vividness, Individual Bias Differences, and Complementary Visual Processing Streams
Authors: D’Angiulli Amedeo , Laarakker Christy , Buchanan Derrick Matthew
Published: January 2024

Grossberg’s adaptive resonance theory (ART) provides a framework for understanding possible interactions between mental imagery and visual perception. Our purpose was to integrate, within ART, the phenomenological notion of mental image vividness and thus investigate the possible biasing effects of individual differences on visual processing. Using a Vernier acuity task, we tested whether indirect estimation of relative V1 size (small, medium, large) and self-reported vividness, in three subgroups of 53 observers, could predict significant effects of priming, interference, or more extreme Perky effects (negative and positive), which could be induced by imagery, impacting acuity performance. The results showed that small V1 was correlated with priming and/or negative Perky effects independently of vividness; medium V1 was related to interference at low vividness but priming at high vividness; and large V1 was related to positive Perky effects at high vividness but negative Perky effects at low vividness. Our interpretation of ART and related modeling based on ARTSCAN contributes to expanding Grossberg’s comprehensive understanding of how and why individually experienced vividness may drive the differential use of the dorsal and ventral complementary visual processing pathways, resulting in the observed effects of imagery on concurrent perception.
Diagnosis and Therapy of Community-Acquired Pneumonia in the Emergency Department: A Retrospective Observational Study and Medical Audit
Authors: Lüthi-Corridori Giorgia , Roth Andrea I. , Boesing Maria , Jaun Fabienne , Tarr Philip E. , Leuppi-Taegtmeyer Anne B. , Leuppi Jörg D.
Published: January 2024

Background: Despite advances in therapy, community-acquired pneumonia (CAP) is still associated with significant morbidity and mortality. Several studies conducted in different countries have reported suboptimal adherence to the guidelines. However, there are currently no available data on adherence to CAP guidelines specifically in Switzerland. Objectives: The aim of this study was to audit the quality of diagnosis and therapy of CAP at a Swiss general hospital. Methods: A retrospective, observational, single-center cohort study was conducted, including patients older than 18 years diagnosed with CAP and admitted to a medical ward throughout 2019 without prior antibiotic therapy prescribed by their general practitioner (GP). The baseline characteristics of the patients were analyzed, and the diagnostic workup and treatment were compared to the Swiss guidelines for CAP. Results: A total of 254 patients diagnosed with CAP were included in this study (median age 78 years, 51.6% males). Atypical pneumonia was diagnosed in 4% of patients, while an organism was identified in 33% of cases, with Streptococcus pneumoniae being the most frequently detected pathogen (57%). A chest image was taken in almost all patients. Documentation of respiratory rate was missing in 23% of cases. Procalcitonin was measured in 23.2% of cases. Pneumococcal and legionella urinary antigen testing was performed on approximately 90% of all patients and blood cultures were drawn in approximately 80% of patients. In 39% of cases, arterial blood gas analysis was performed. Guideline adherence for the administration of empiric antibiotics was documented/recorded in 75% of cases. Twelve different antibiotic regimens were administered, and they were mostly amoxicillin/clavulanate with or without macrolides, as suggested by the guidelines. In particular, the use of ceftriaxone was higher (19.7%) compared to the Swiss guidelines. The average length of antibiotic therapy was longer (8.2 days) compared to the guidelines (5–7 days). Oral steroid therapy was administered to 29.1% of patients, including to 75% of those diagnosed with COPD. Conclusion: Overall, guideline adherence was moderately low, especially with regards to the assessment of respiratory rate, performance of arterial blood gas analysis, and sputum collection. Regarding antibiotic therapy, the use of ceftriaxone and the length of antibiotic therapy should be reduced. Further research is needed to identify the reasons for guideline non-adherence, and to find effective measures for the improvement of guideline adherence.
Focal Pulsed Field Ablation for Atrial Arrhythmias: Efficacy and Safety under Deep Sedation
Authors: Weyand Sebastian , Adam Viola , Biehler Paloma , Hägele Patricia , Hanger Simon , Heinzmann David , Löbig Stephanie , Pinchuk Andrei , Waechter Christian , Seizer Peter
Published: January 2024

Focal pulsed field ablation (PFA) is a novel technique for treating cardiac arrhythmias. It has demonstrated positive results in initial studies and has a good safety profile. In recent studies, PFA was often utilized for first-time pulmonary vein isolation (PVI) and was performed under general anesthesia. In our study, we assessed the feasibility, safety, acute procedural efficacy, and efficiency of focal PFA under deep sedation in patients, 80% of whom had undergone at least one left atrial ablation previously. We treated 30 patients (71 ± 7, 46% male) using the CENTAURI system for various atrial arrhythmias, including atrial fibrillation, typical and atypical atrial flutter, and focal atrial tachycardia. The average procedure and fluoroscopy times were 122 ± 43 min and 9 ± 7 min, respectively. A total of 83.33% of patients received additional line ablations beyond PVI, specifically targeting the posterior box and anterior mitral line. All ablations were successfully performed in deep sedation with only one major and one minor complication observed. The major complication was a vasospasm of the right coronary artery during ablation of the cavotricuspid isthmus, which was treated successfully with intracoronary nitroglycerin. All patients could be discharged in sinus rhythm. Moreover, adenosine appears effective in identifying dormant conduction in some patients after focal PFA. In conclusion, focal PFA is an effective approach for complex left atrial ablations under deep sedation, offering both high efficacy and efficiency with a reliable safety profile. Studies on long-term outcomes are needed.
Dermoscopy for the Differentiation of Subacute Cutaneous Lupus Erythematosus from Other Erythematous Desquamative Dermatoses—Psoriasis, Nummular Eczema, Mycosis Fungoides and Pityriasis Rosea
Authors: Żychowska Magdalena , Kołcz Kinga
Published: January 2024

Subacute cutaneous lupus erythematosus (SCLE) is a condition that might pose a diagnostic challenge. The aim of this study was to assess the usefulness of videodermoscopy in the differentiation of SCLE from other erythematous-desquamative dermatoses. Consecutive patients with SCLE (n = 27), psoriasis (n = 36), nummular eczema (n = 30), mycosis fungoides (n = 26), and pityriasis rosea (n = 20) referred to our Department of Dermatology were recruited for this study. A representative lesion was visualized using a Canfield D200EVO Videodermatoscope (Canfield Scientific GmbH, Bielefeld, Germany) and evaluated for the following parameters: vessels (morphology and distribution), scales (color and distribution), follicular findings, colors and morphologies, and presence of specific clues. SCLE was predominantly characterized by a polymorphous vascular pattern (92.6%) of unspecific distribution (92.6%) over a pink-red background (74.1%). Gray-brown dots were present in 10 (37.0%) cases, and pigmentation was noted in 15 (55.6%) patients, including peripheral pigmentation in 7 (25.9%) patients. Videodermoscopic evaluation showed significant differences between SCLE and psoriasis, which was characterized by regularly distributed dotted vessels. Although some common dermoscopic features with MF were noted, the presence of yellow structureless areas and red dots/globules favored the diagnosis of MF. In conclusion, a polymorphic vascular pattern, especially in association with gray-brown dots and/or peripheral pigmentation, is a valuable clue for the differentiation of SCLE from other erythematous-desquamative dermatoses.
A Retrospective Observational Study to Evaluate Adjacent Segmental Degenerative Change with the Dynesys-Transition-Optima Instrumentation System
Authors: Li Chi-Ruei , Chen Shih-Hao , Chen Wen-Hsien , Tsou Hsi-Kai , Tzeng Chung-Yuh , Chen Tse-Yu , Lin Mao-Shih
Published: January 2024

Background: This study evaluates the impact of hybrid dynamic stabilization using the Dynesys-Transition-Optima (DTO) system on adjacent segment disease (ASD) in lumbar spinal stenosis patients with spondylolisthesis. Methods: From 2012 to 2020, 115 patients underwent DTO stabilization at a single center by a single neurosurgeon. After exclusions for lack of specific stabilization and incomplete data, 31 patients were analyzed. Follow-up was conducted at 6, 12, and 24 months postoperatively, assessing disc height, listhesis distance, and angular motion changes at L2–L3, L3–L4, and L5–S1. Results: L3–L4 segment (the index level), demonstrated a delayed increase in listhesis distance, contrasting with earlier changes in other segments. At two years, L3–L4 exhibited less increase in listhesis distance and less disc height reduction compared to L2–L3 and L5–S1. Notably, the L3–L4 segment showed a significant reduction in angular motion change over two years. Conclusions: In conclusion, while ASD was not significantly prevented, the study indicates minor and delayed degeneration at the index level. The L3–L4 segment experienced reduced angular change in motion, suggesting a potential benefit of DTO in stabilizing this specific segment.
Real-Life Multicenter Experience of Venetoclax in Combination with Hypomethylating Agents in Previously Untreated Adult Patients with Acute Myeloid Leukemia in Greece
Authors: Chatzilygeroudi Theodora , Darmani Ismini , El Gkotmi Natali , Vryttia Pinelopi , Douna Stavroula , Bouchla Anthi , Labropoulou Vasiliki , Kotsopoulou Maria , Symeonidis Argiris , Pagoni Maria , Pappa Vasiliki , Papageorgiou Sotirios G.
Published: January 2024

Background: The landscape of first-line treatment for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy has changed remarkably after venetoclax approval. Accumulating real-world data further apprises us with more knowledgeable use. To assess the efficacy and safety challenges in the real-life setting of the combination of hypomethylated agent (HMA) and venetoclax, we conducted a multi-center retrospective study. Methods: Forty adult AML patients treated with the combination of HMA and venetoclax as a first-line treatment after full approval (2020) were included. To confirm VIALE-A results, this group was compared to a historical cohort of 17 chemotherapy-ineligible AML patients treated with HMA monotherapy before 2020. Results: The combination of HMA-venetoclax achieved a composite complete response rate of 86.8% (p < 0.001), median overall survival, and event-free survival of 33.8 and 19.7 months, respectively, in a median follow-up of 17.8 months (pos < 0.001, HR = 0.276, CI: 0.132–0.575, pEFS = 0.004, HR = 0.367, CI: 0.174–0.773). High rates of neutropenia (90%) and consequent infection rates (57.5%) were noted. Only 55% of our patients received antifungal prophylaxis, as its use remains controversial, and invasive fungal infections were presented in 7.5%. Conclusions: Evidently, venetoclax-HMA yields high response rates and profound survival benefits in real life and has changed our approach to alternative chemotherapy options.
Cystic Fibrosis in Adults: A Paradigm of Frailty Syndrome? An Observational Study
Authors: Iacotucci Paola , Carnovale Vincenzo , Ferrillo Lorenza , Somma Jolanda , Bocchino Marialuisa , D’Ippolito Marcella , Sanduzzi Zamparelli Alessandro , Rengo Giuseppe , Ferrara Nicola , Conti Valeria , Corbi Graziamaria
Published: January 2024

This study aimed to assess the main clinical and anamnestic characteristics of adult Cystic Fibrosis (CF) patients and to evaluate the association of frailty with the CF genotyping classification. In an observational cross-sectional study, all ambulatory CF patients over 18 years old who received a diagnosis at the Regional Cystic Fibrosis Center for adults were enrolled and assessed by spirometry for respiratory function, by ADL and IADL for functional status, and by the Study of Osteoporotic Fractures (SOF) Index for frailty. The study population consisted of 139 CF patients (mean age 32.89 ± 10.94 years old, 46% women). Most of the subjects were robust (60.4%). The pre-frail/frail group was more frequently females (p = 0.020), had a lower BMI (p = 0.001), worse respiratory function, a higher number of pulmonary exacerbations/years, cycles of antibiotic therapy, and hospitalization (all p < 0.001) with respect to robust patients. The pre-frail/frail subjects used more drugs and were affected by more CF-related diseases (all p < 0.001). In relation to logistic regression, the best predictor of the pre-frail/frail status was a low FEV1 level. The CF patients show similarities to older pre-frail/frail subjects, suggesting that CF might be considered an early expression of this geriatric syndrome. This finding could help to better define the possible progression of CF, but overall, it could also suggest the usefulness employing of some tools used in the management and therapy of frailty subjects to identify the more severe CF subjects.
Safety, Efficacy, and Visual Performance of an Orthokeratology Lens with Increased Compression Factor
Authors: Martínez-Plaza Elena , Zamora Castro Cecilia , Molina-Martín Ainhoa , Piñero David P.
Published: January 2024

The aim was to evaluate the safety, efficacy, and visual performance of an orthokeratology lens with an increased compression factor (ICF) of 1.25 D in a 3-month follow-up. Thirty-six myopic patients (5 males and 31 females; 24.2 ± 5.8 years) were fitted with Alexa AR (Tiedra Farmacéutica S.L., Madrid, Spain) contact lenses (CLs) and twenty participants finished the follow-up. Visual acuity (VA), subjective refraction, primary spherical and primary coma aberrations, keratometry, central pachymetry, and ocular surface evaluation were performed at baseline and after 1 night, 1 week, 1 month, and 3 months of CL wear. The differences among visits were analyzed using a repeated-measures analysis of variance or the Friedman test. The spherical equivalent decreased (p ≤ 0.005), and the uncorrected VA improved (p < 0.001) until the first week. Corneal and ocular aberrations showed a significant increase (p ≤ 0.02). A significant decrease (p < 0.001) was found for keratometry values. No significant changes were observed in either central pachymetry or ocular surface parameters among study visits. In conclusion, an orthokeratology CL with an ICF of 1.25 D provides good safety, efficacy, and visual performance in a 3-month follow-up. Seven days of orthokeratology wear are enough to achieve the full myopic compensation, resulting in satisfactory VA.
Association between Asthma and Lower Levels of Physical Activity: Results of a Population-Based Case–Control Study in Spain
Authors: De-Miguel-Diez Javier , Llamas-Saez Carlos , Vaquero Teresa Saez , Jiménez-García Rodrigo , López-de-Andrés Ana , Carabantes-Alarcón David , Carricondo Francisco , Romero-Gómez Barbara , Pérez-Farinos Napoleón
Published: January 2024

(1) Background: Our aim was to determine changes in the prevalence of physical activity (PA) in adults with asthma between 2014 and 2020 in Spain, investigate sex differences and the effect of other variables on adherence to PA, and compare the prevalence of PA between individuals with and without asthma. (2) Methods: This study was a cross-sectional, population-based, matched, case–control study using European Health Interview Surveys for Spain (EHISS) for 2014 and 2020. (3) Results: We identified 1262 and 1103 patients with asthma in the 2014 and 2020 EHISS, respectively. The prevalence of PA remained stable (57.2% vs. 55.7%, respectively), while the percentage of persons who reported walking continuously for at least 2 days a week increased from 73.9% to 82.2% (p < 0.001). Male sex, younger age, better self-rated health, and lower body mass index (BMI) were significantly associated with greater PA. From 2014 to 2020, the number of walking days ≥2 increased by 64% (OR1.64 95%CI 1.34–2.00). Asthma was associated with less PA (OR0.87 95%CI 0.47–0.72) and a lower number of walking days ≥2 (OR0.84 95%0.72–0.97). (4) Conclusions: Walking frequency improved over time among people with asthma. Differences in PA were detected by age, sex, self-rated health status, and BMI. Asthma was associated with less LTPA and a lower number of walking days ≥2.
Transcatheter Aortic Valve Implantation to Treat Degenerated Aortic, Mitral and Tricuspid Bioprosthesis
Authors: Khokhar Arif A. , Curio Jonathan , Sticchi Alessandro , Hartley Adam , Demir Ozan M. , Ruparelia Neil
Published: January 2024

Transcatheter aortic valve implantation (TAVI) is now well established as the treatment of choice for patients with native aortic valve stenosis who are high or intermediate risk for surgical aortic valve replacement. Recent data has also supported the use of TAVI in patients at low surgical risk and also in anatomical subsets that were previously felt to be contra-indicated including bicuspid aortic valves and aortic regurgitation. With advancements and refinements in procedural techniques, the application of this technology has now been further expanded to include the management of degenerated bioprosthesis. After the demonstration of feasibility and safety in the management of degenerated aortic bioprosthetic valves, mitral and tricuspid bioprosthetic valve treatment is now also well-established and provides an attractive alternative to performing redo surgery. In this review, we appraise the latest clinical evidence and highlight procedural considerations when utilising TAVI technology in the management of degenerated aortic, mitral or tricuspid prosthesis.
Isolation and Identification of Pigment-Producing Endophytic Fungi from the Amazonian Species Fridericia chica
Authors: de Melo Pereira Dorothy Ívila , Gurgel Raiana Silveira , de Souza Anne Terezinha Fernandes , Matias Rosiane Rodrigues , de Souza Falcão Lucas , Chaves Francisco Celio Maia , da Silva Gilvan Ferreira , Martínez José Gregorio , de Lima Procópio Rudi Emerson , Fantin Cleiton , Albuquerque Patrícia Melchionna
Published: January 2024

Pigments of fungal origin have aroused increasing interest in the food dye and cosmetic industries since the global demand for natural dyes has grown. Endophytic microorganisms are a source of bioactive compounds, and Amazonian plant species can harbor fungi with a wide range of biotechnological applications. Popularly known in Brazil as crajiru, Fridericia chica is a medicinal plant that produces a red pigment. In this study, a total of 121 fungi were isolated in potato dextrose agar from three plants. We identified nine pigment-producing endophytic fungi isolated from branches and leaves of F. chica. The isolates that showed pigment production in solid media were molecularly identified via multilocus analysis as Aspergillus welwitschiae, A. sydowii, Curvularia sp., Diaporthe cerradensis (two strains), Hypoxylon investiens, Neoscytalidium sp. (two strains) and Penicillium rubens. These isolates were subjected to submerged fermentation in two culture media to obtain metabolic extracts. The extracts obtained were analyzed in terms of their absorbance between 400 and 700 nm. The pigmented extract produced by H. investiens in medium containing yeast extract showed maximum absorbance in the red absorption range (UA700 = 0.550) and significant antioxidant and antimicrobial activity. This isolate can thus be considered a new source of extracellular pigment.
Cladosporium—Insect Relationships
Authors: Nicoletti Rosario , Russo Elia , Becchimanzi Andrea
Published: January 2024

The range of interactions between Cladosporium, a ubiquitous fungal genus, and insects, a class including about 60% of the animal species, is extremely diverse. The broad case history of antagonism and mutualism connecting Cladosporium and insects is reviewed in this paper based on the examination of the available literature. Certain strains establish direct interactions with pests or beneficial insects or indirectly influence them through their endophytic development in plants. Entomopathogenicity is often connected to the production of toxic secondary metabolites, although there is a case where these compounds have been reported to favor pollinator attraction, suggesting an important role in angiosperm reproduction. Other relationships include mycophagy, which, on the other hand, may reflect an ecological advantage for these extremely adaptable fungi using insects as carriers for spreading in the environment. Several Cladosporium species colonize insect structures, such as galleries of ambrosia beetles, leaf rolls of attelabid weevils and galls formed by cecidomyid midges, playing a still uncertain symbiotic role. Finally, the occurrence of Cladosporium in the gut of several insect species has intriguing implications for pest management, also considering that some strains have proven to be able to degrade insecticides. These interactions especially deserve further investigation to understand the impact of these fungi on pest control measures and strategies to preserve beneficial insects.
Parkinson’s Disease and Photobiomodulation: Potential for Treatment
Authors: Bicknell Brian , Liebert Ann , Herkes Geoffrey
Published: January 2024

Parkinson’s disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson’s disease and their care givers. Parkinson’s disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome–gut–brain axis is also important in Parkinson’s disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson’s disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson’s disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson’s disease and may potentially slow its progression.
The Case for Pre-Emptive Pharmacogenetic Screening in South Africa
Authors: Hurrell Tracey , Naidoo Jerolen , Masimirembwa Collen , Scholefield Janine
Published: January 2024

Lack of equitable representation of global genetic diversity has hampered the implementation of genomic medicine in under-represented populations, including those on the African continent. Data from the multi-national Pre-emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study suggest that genotype guidance for prescriptions reduced the incidence of clinically relevant adverse drug reactions (ADRs) by 30%. In this study, hospital dispensary trends from a tertiary South African (SA) hospital (Steve Biko Academic Hospital; SBAH) were compared with the drugs monitored in the PREPARE study. Dispensary data on 29 drugs from the PREPARE study accounted for ~10% of total prescriptions and ~9% of the total expenditure at SBAH. VigiLyze data from the South African Health Products Regulatory Authority were interrogated for local ADRs related to these drugs; 27 were listed as being suspected, concomitant, or interacting in ADR reports. Furthermore, a comparison of pharmacogene allele frequencies between African and European populations was used to frame the potential impact of pre-emptive pharmacogenetic screening in SA. Enumerating the benefit of pre-emptive pharmacogenetic screening in SA will only be possible once we initiate its full application. However, regional genomic diversity, disease burden, and first-line treatment options could be harnessed to target stratified PGx today.
Study of the Impact of Rural Land Transfer on the Status of Women in Rural Households
Authors: Hong Mingyong , Zhou Donglai , Lou Lei
Published: January 2024

While the status of rural women in the family has undergone changes, rural land transfer has brought about transformations in both rural production and daily life. This paper adopts the perspective of rural land transfer, follows the research track of Marx and Engels’s theory of women, and based on the theoretical research of the changes in the status of modern women in the family, constructs a framework for analyzing the status of women in rural families. Drawing on the data from the 2014 China Family Panel Studies (CFPS2014), this article utilizes OLS (Ordinary Least Square) and ordered logit models to explore the impact of rural land transfer on the status of women in rural households. The study reveals the following findings: Initially, rural land transfer-out improves women’s household decision-making power and enhances the status of women in rural households. The reliability of these results is further confirmed through robustness tests and endogeneity discussions. Secondly, the heterogeneity analysis indicates that the transfer of agricultural land promotes the status of women in rural households in nonmajor grain-producing areas more than women in major grain-producing areas. The reason is that women in major grain-producing areas lack off-farm employment opportunities compared with women in non-major grain-producing areas and the main grain producing areas may have a strong patriarchal cultural atmosphere. Thirdly, the analysis of mechanisms indicates that rural land transfer-out improves the status of women in rural households by augmenting their independent income. Conversely, rural land transfer-in increases women’s private labor and decreases their independent income without promoting their family status. The study sheds light on rural women’s empowerment, the improvement of intra-household bargaining power, and the comprehensive development of rural women. The conclusion of this paper provides a new understanding and some recommendations for us to explore the change of rural women’s status in the family.
Understanding Resource Recycling and Land Management to Upscale Zero-Tillage Potato Cultivation in the Coastal Indian Sundarbans
Authors: Goswami Rupak , Roy Riya , Gangopadhyay Dipjyoti , Sen Poulami , Roy Kalyan , Sarkar Sukamal , Misra Sanchayeeta , Ray Krishnendu , Monjardino Marta , Mainuddin Mohammed
Published: January 2024

Upscaling sustainable intensification (SI) technologies is crucial to enhancing the resilience of fragile farming systems and vulnerable livelihoods of smallholder farmers. It is also critical to shape the future land-use and land-cover changes in a region. Zero-tillage potato cultivation (ZTPC), introduced as an SI intervention in parts of the Indian Sundarbans, has demonstrated promises of rapid upscaling, and thus, changes in the seasonal land-use pattern in the region. This study aims to understand the socioecological complexity of farming systems to comprehend how the nascent stage of ZTPC thrives at the farm level and what preconditions are necessary to upscale them. The objectives are to analyse the farm resource recycling pattern in ZTPC, and map and simulate its system’s complexity to strategize ZTPC upscaling in the region. The analysis of farm resource recycling data reveals that ZTPC stability hinges on managing trade-offs in resource allocations, specifically involving straw, organic manure, sweet water, and family labour. The decision to manage such trade-offs depends on farm type characterizations by their landholdings, distance from the homestead, pond, and cattle ownership, competing crops, and family composition. Using a semiquantitative systems model developed through fuzzy cognitive mapping, the study underscores the significance of effective training, input support, enterprise diversification by introducing livestock, timely tuber supply, access to critical irrigation, and capacity building of local institutions as the essential preconditions to sustain and upscale ZTPC. This research contributes a systems perspective to predict agricultural land use within technology transfer initiatives, providing insights into how farm- and extra-farm factors influence resource allocations for ZTPC. Public extension offices must understand the trade-offs associated with straw, organic matter, and harvested water and design differentiated supports for different farm types. The most compelling interventions to upscale ZTPC includes farm diversification by introducing livestock through institutional convergence, pragmatic agroforestry initiatives to enhance on-farm biomass and fuel production, building awareness and integrating alternative energy use to save straw and cow dung, building social capital to ensure access to sweet irrigation water, and developing and/or strengthening farmer collectives to ensure the supply of quality tuber and marketing of farm produce.
Spatial and Temporal Variation Characteristics of Ecological Environment Quality in China from 2002 to 2019 and Influencing Factors
Authors: Li Junjie , Peng Xiangbin , Tang Ruomei , Geng Jing , Zhang Zipeng , Xu Dong , Bai Tingting
Published: January 2024

Since the beginning of the new century, there has been a notable enhancement in China’s ecological environment quality (EEQ), a development occurring in tandem with climate change and the extensive ecological restoration projects (ERPs) undertaken in the country. However, comprehensive insights into the spatial and temporal characteristics of China’s EEQ, and its responses to both climate change and human activities over the past two decades, have remained largely elusive. In this study, we harnessed a combination of multi-source remote-sensing data and reanalysis data. We employed Theil–Sen median trend analysis, multivariate regression residual analysis, and the Hurst index to examine the impacts and changing patterns of climatic factors and human activities on China’s EEQ during the past two decades. Furthermore, we endeavored to forecast the future trajectory of EEQ. Our findings underscore a significant improvement in EEQ across most regions of China between 2002 and 2019, with the most pronounced enhancements observed in the Loess Plateau, Northeast China, and South China. This transformation can be attributed to the combined influence of climatic factors and human activities, which jointly accounted for alterations in EEQ across 78.25% of China’s geographical expanse. Human activities (HA) contributed 3.93% to these changes, while climatic factors (CC) contributed 17.79%. Additionally, our projections indicate that EEQ is poised to continue improving in 56.70% of China’s territory in the foreseeable future. However, the Loess Plateau, Tarim Basin, and Inner Mongolia Plateau are anticipated to experience a declining trend. Consequently, within the context of global climate change, the judicious management of human activities emerges as a critical imperative for maintaining EEQ in China. This study, bridging existing gaps in the literature, furnishes a scientific foundation for comprehending the evolving dynamics of EEQ in China and informs the optimization of management policies in this domain.
Internal Rotation Measurement of the Knee with Polymer-Based Capacitive Strain Gauges versus Mechanical Rotation Measurement Taking Gender Differences into Account: A Comparative Analysis
Authors: Mayr Hermann O. , Rosenstiel Nikolaus , Prakash Karthika S. , Comella Laura Maria , Woias Peter , Schmal Hagen , Seidenstuecker Michael
Published: January 2024

With the conventional mechanical rotation measurement of joints, only static measurements are possible with the patient at rest. In the future, it would be interesting to carry out dynamic rotation measurements, for example, when walking or participating in sports. Therefore, a measurement method with an elastic polymer-based capacitive measuring system was developed and validated. In our system, the measurement setup was comprised of a capacitive strain gauge made from a polymer, which was connected to a flexible printed circuit board. The electronics integrated into the printed circuit board allowed data acquisition and transmission. As the sensor strip was elongated, it caused a change in the spacing between the strain gauge’s electrodes, leading to a modification in capacitance. Consequently, this alteration in capacitance enabled the measurement of strain. The measurement system was affixed to the knee by adhering the sensor to the skin in alignment with the anterolateral ligament (ALL), allowing the lower part of the sensor (made of silicone) and the circuit board to be in direct contact with the knee’s surface. It is important to note that the sensor should be attached without any prior stretching. To validate the system, an in vivo test was conducted on 10 healthy volunteers. The dorsiflexion of the ankle was set at 2 Nm using a torque meter to eliminate any rotational laxity in the ankle. A strain gauge sensor was affixed to the Gerdii’s tubercle along the course of the anterolateral ligament, just beneath the lateral epicondyle of the thigh. In three successive measurements, the internal rotation of the foot and, consequently, the lower leg was quantified with a 2 Nm torque. The alteration in the stretch mark’s length was then compared to the measured internal rotation angle using the static measuring device. A statistically significant difference between genders emerged in the internal rotation range of the knee (p = 0.003), with female participants displaying a greater range of rotation compared to their male counterparts. The polymer-based capacitive strain gauge exhibited consistent linearity across all measurements, remaining within the sensor’s initial 20% strain range. The comparison between length change and the knee’s internal rotation angle revealed a positive correlation (r = 1, p < 0.01). The current study shows that elastic polymer-based capacitive strain gauges are a reliable instrument for the internal rotation measurement of the knee. This will allow dynamic measurements in the future under many different settings. In addition, significant gender differences in the internal rotation angle were seen.
Bidirectional Regulation of GABAA Reversal Potential in the Adult Brain: Physiological and Pathological Implications
Authors: Kim Haram R. , Martina Marco
Published: January 2024

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABAA channels are permeable to anions, the reversal potential of GABAA is very close to that of Cl−, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl−, respectively. Due to the closeness between GABAA reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABAA a uniquely flexible signaling system. In most neurons of the adult brain, the GABAA reversal potential is slightly more negative than the resting membrane potential, which makes GABAA hyperpolarizing. Alterations in GABAA reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer’s disease, schizophrenia, and Down’s syndrome), GABAA becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABAA reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation.