bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectin-3 inhibition reduces fibrotic scarring and promotes functional recovery after spinal cord injury in mice
Authors: Shan Fangli , Ye Jianan , Xu Xinzhong , Liang Chao , Zhao Yuanzhe , Wang Jingwen , Ouyang Fangru , Li Jianjian , Lv Jianwei , Wu Zhonghan , Yao Fei , Jing Juehua , Zheng Meige
Published: January 2024

Background In the context of spinal cord injury (SCI), infiltrating macrophages assume prominence as the primary inflammatory cells within the lesion core, where the fibrotic scar is predominantly orchestrated by platelet-derived growth factor receptor beta (PDGFRβ+) fibroblasts. Galectin-3, a carbohydrate-binding protein of the lectin family, is notably expressed by infiltrating hematogenous macrophages and mediates cell-cell interactions. Although Galectin-3 has been shown to contribute to the endocytic internalization of PDGFRβ in vitro, its specific role in driving fibrotic scar formation after SCI has not been determined. Methods We employed a crush mid-thoracic (T10) SCI mouse model. Galectin-3 inhibition after SCI was achieved through intrathecal injection of the Galectin-3 inhibitor TD139 or in situ injection of lentivirus carrying Galectin-3-shRNA (Lv-shLgals3). A fibrosis-induced mice model was established by in situ injection of platelet derived growth factor D (PDGFD) or recombinant Galectin-3 (rGalectin-3) into the uninjured spinal cord. Galectin-3 internalization experiments were conducted in PDGFRβ+fibroblasts cocultured in conditioned medium in vitro. Results We identified the spatial and temporal correlation between macrophage-derived Galectin-3 and PDGFRβ in fibroblasts from 3 to 56 days post-injury (dpi). Administration of TD139 via intrathecal injection or in situ injection of Lv-shLgals3 effectively mitigated fibrotic scar formation and extracellular matrix deposition within the injured spinal cord, leading to enhanced neurological outcomes and function recovery after SCI. Furthermore, the fibrosis-inducing effects of exogenous PDGFD in the uninjured spinal cord could be blocked by TD139. In vitro experiments further demonstrated the ability of PDGFRβ+fibroblasts to internalize Galectin-3, with Galectin-3 inhibition resulting in reduced PDGFRβ expression. Conclusions Our findings underscore the pivotal role of macrophage-derived Galectin-3 in modulating the sustained internalized activation of PDGFRβ within fibroblasts, providing a novel mechanistic insight into fibrotic scarring post-SCI.
The relationship between chronotype, insomnia and depressive symptoms in Chinese male prisoners
Authors: He Jin , Zhang Shuqi , Yang Qingzhen , Liu Daoli , Xiao Weixia , Li Hengfen
Published: January 2024

Purpose: The aim of the study was to estimate the distribution and prevalence of chronotypes among prisoners who are forced to follow a uniform routine, and to examine the relationship between chronotype, insomnia, and depressive symptoms in a cross-sectional sample of male prisoners in China.
Methods: A total of 1609 male inmates from a men’s prison in Hebei Province, China, participated in this study by completing the Morning and Evening Questionnaire-5 (MEQ-5), Insomnia Index (ISI), and Depression Scale-9 (PHQ-9). Age, time served, insomnia, and depressive symptoms were compared among chronotypes. Binary logistic stepwise regression was used to analyze the factors influencing depression. Additionally, a simple mediation model which included MEQ-5, ISI, and PHQ-9, was analyzed while controlling for age as a covariate.
Results: The prevalence of morning types (MT), neutral types (NT), and evening types (ET) was 47.1%, 46.8%, and 6.1%. Being an ET was significantly associated with younger age and increased symptoms of insomnia and depression (P < 0.05). The relative risk of depression was 2.970-fold (95%CI, 1.724 to 5.116; P < 0.001) higher for ET compared to MT. Mediation analysis showed that insomnia partially mediated the relationship (effect=-0.242, SE=0.030, CI: -0.301 to -0.183) between chronotype and depression and that the direct effect of chronotype on depression was also significant (effect=-0.247, SE=0.034, CI:-0.314 to -0.180).
Conclusions: The prevalence of ET is relatively low in male prisoners. Chronotype have direct effect on depressive symptoms, resetting the late timing of ET may have a positive impact on depression.
RB-based: Link prediction based on the resource broadcast of nodes for complex networks
Authors: Liu zeguang , Yao Yabing , Xu Zhipeng
Published: January 2024

During the process of link prediction, traditional resource allocation methods only consider the influence of common neighbor nodes as transmission paths, while ignoring the impact of the effective resource amount of the topology structure surrounding these common neighbor nodes on link prediction performance. To address this limitation, this paper proposes a complex network link prediction method based on resource broadcast. Firstly, the paper provides a detailed analysis of the topology structure between the source node and the target node, presenting four different transmission paths. Secondly, in order to characterize the initial resources, the paper defines the effective resource amount after transmission through these four paths as the resource broadcast amount between nodes. Lastly, the similarity between nodes is characterized bidirectionally by considering the resource broadcast amount between nodes.Experiments conducted on 9 real network datasets demonstrate that, when compared with 8 other similarity-based indicators, this method achieves better prediction results according to benchmark evaluation indicators.
Vertical Distribution Characteristics and Potential Sources of Atmospheric Pollutants in the North China Plain, China, During the Summer of 2020
Authors: Liu Guohua , Wang Yu
Published: January 2024

The source generation mechanism of air pollutants can be studied more in depth by characterizing their evolution and spread. The authors of this study conducted a three-month MAX-DOAS vertical observation in Shijiazhuang City, North China Plain, in the summer of 2020 in response to the long-standing air pollution issues in the region. The vertical distribution profiles of aerosol, NO2, HCHO, and CHOCHO were generated, and the inversion findings showed good agreement with the TROPOMI satellite remote sensing validation, demonstrating the validity and accuracy of the observations. The near-surface boundary layer is home to the majority of the NO2, HCHO, and CHOCHO species. The species' daytime evolution trends varied, with the highest NO2 peaks occurring in the morning and evening commute, the highest HCHO peaks occurring in the morning at 10:00 a.m., and CHOCHO's concentration during the day declined. Two minor aerosol pollution processes took place in Shijiazhuang City during the summer observation period. The elevated concentrations of NO2, CO, and the PM2.5/PM10 ratio during the pollution processes suggest that anthropogenic emissions, particularly the burning of biomass, were responsible for the large number of fine particles generated during the pollution events. Based on the examination of pollutant concentration profiles and meteorological data, it was determined that local emissions and north wind transport were the primary causes of Shijiazhuang's high NO2 values. Meanwhile, the southern region of Shijiazhuang was primarily responsible for the majority of the potential sources of atmospheric HCHO, and local emissions were also a major factor affecting the high CHOCHO values. Shijiazhuang's local near-surface volatile organic compounds (VOCs) are mostly caused by human emissions, although burning biomass and its regional transportation have a greater influence on the middle and upper boundary layers. This study systematically sorted the evolution characteristics and potential sources of pollutants in Shijiazhuang City during the summer based on the joint observations of various pollutants, including NO2, HCHO, and CHOCHO. These results can be used to support the development of appropriate policies for the prevention and control of pollutants in the Shijiazhuang local area of the North China Plain.
Prognostic Analysis of Radiation-Induced Liver Damage Following Carbon- Ion Radiotherapy for Hepatocellular Carcinoma
Authors: Hayashi Kazuhiko , Suzuki Osamu , Wakisaka Yushi , Ichise Koji , Uchida Hirofumi , Anzai Makoto , Hasegawa Azusa , Seo Yuji , Shimizu Shinichi , Ishii Takayoshi , Teshima Teruki , Fujimoto Jiro , Ogawa Kazuhiko
Published: January 2024

Background: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT.
Methods: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child–Pugh score following CIRT. The median age of the patients was 76 years (range: 47–95 years), and the median tumor diameter was 41 mm (range: 5–160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child–Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range: 2.3–41.1 months), and RILD was observed in 11 patients (10.1%).
Results: Multivariate analysis showed that pretreatment Child–Pugh score B (p=0.003, hazard ratio [HR]=6.90) and normal liver volume spared from <30 Gy RBE (VS30 <739 cm3) (p=0.009, HR=5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child–Pugh class A or B and VS30 <739 cm3 or ≥739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively.
Conclusion: In conclusion, the pretreatment Child–Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.
ConIS: Controllable Text-Driven Image Stylization with Semantic Intensity
Authors: Yang Gaoming Yang , Li Changgeng Li , Zhang Ji Zhang
Published: January 2024

Text-driven image stylization aims to synthesize content images with learned textual styles. Recent studies have shown the potential of the diffusion model for producing rich stylizations. However, existing approaches inefficiently control the degree of stylization, which hinders the balance between style and content in generated images. In this paper, we propose a Controllable Text-Driven Image Stylization (ConIS) Framework based on the diffusion model. The proposed framework introduces two modules into the pre-trained text-to-image model. The first is an Unconditional Null-text Inversion (UNTI) module, which optimizes null-text embedding to reduce the bias between inversion and sampling in the diffusion model. Given a content image, this module is able to reconstruct it without semantic guidance. The second is a Null-text Dilution (NTD) module. We design a parameterization mechanism for the semantic intensity of textual conditions, which indirectly controls the degree of stylization through the style degree factor. Finally, we replace the attention maps used in the sampling process with those from the UNTI module to constrain the structure of content images. Experiments have shown that the proposed method enables fine-grained control over the degree of stylization without retraining or fine-tuning the network. Both qualitative and quantitative results indicate that the ConIS framework outperforms state-of-the-art methods in balancing artistic detail and content structure.
Extremity fractures, attempted suicide, blood transfusion and thromboembolic events are independent risk factors for a prolonged hospital stay in severely injured elderly
Authors: Störmann Philipp , Hörauf Jason A. , Sturm Ramona , Zankena Lara , Zumsteg Jonin Serafin , Lefering Rolf , Marzi Ingo , Pape Hans-Christoph , Jensen Kai Oliver
Published: January 2024

Methods:
Due to demographic change, the number of polytraumatized geriatric patients (> 64 years) is expected to further increase in the coming years. In addition to the particularities of the accident and the associated injury patterns, prolonged inpatient stays are regularly observed in this group. The aim of the evaluation is to identify further factors that cause prolonged inpatient stays.
A study of the data from the TraumaRegister DGU® from 2016-2020 was performed. Inclusion criteria were an age of over 64 years, intensive care treatment in the GAS-region, and an Injury Severity Score (ISS) of at least 16 points. All patients who were above the 80th percentile for the average length of stay or average intensive care stay of the study population were defined as so-called long-stay patients. This resulted in a prolonged inpatient stay of > 25 days and an intensive care stay of > 13 days. Among other, the influence of the cause of the accident, injury patterns according to body regions, the occurrence of complications, and the influence of numerous clinical parameters were examined.
Results:
A total of 23,026 patients with a mean age of 76.6 years and a mean ISS of 24 points were included. Mean ICU length of stay was 11 +/- 12.9 days (regular length of stay: 3.9 +/- 3.1d vs. prolonged length of stay: 12.8 +/- 5.7d) and mean inpatient stay was 22.5 +/- 18.9 days (regular length of stay: 20.7 +/- 15d vs. 35.7 +/- 22.3d). A total of n=6,447 patients met the criteria for a prolonged length of stay. Among these, patients had one more diagnosis on average (4.6 vs. 5.8 diagnoses) and had a higher ISS (21.8 +/- 6 pts. vs. 26.9 +/- 9.5 pts.)
Independent risk factors for prolonged length of stay were intubation duration greater than 6 days (30-fold increased risk), occurrence of sepsis (4x), attempted suicide (3x), presence of extremity injury (2.3x), occurrence of a thromboembolic event (2.7x), and administration of red blood cell concentrates in the resuscitation room (1.9x).
Conclusions:
The present analysis identified numerous independent risk factors for significantly prolonged hospitalization of the geriatric polytraumatized patient, which should be given increased attention during treatment. In particular, the need for a smooth transition to psychiatric follow-up treatment or patient-adapted rehabilitative care for geriatric patients with prolonged immobility after extremity injuries is emphasized by these results.
Long-term outcomes of computer-navigation assisted geographic resection for primary bone tumors in lower extremities - when less is more
Authors: Li Zhuoyu , Liu Weifeng , Deng Zhiping , Yang Yongkun , Jin Tao , Sun Yang , Li Yuan , Hao Lin , Zhang Qing , Niu Xiaohui
Published: January 2024

Objectives The aim of this study was to to investigate the outcomes of geographic resections with computer navigation for treatment of bone tumors in lower extremities.
Methods A retrospective cohort analysis was conducted on 51 patients who underwent computer-navigation assisted (25 cases) and free-hand (26 cases) geographic resections of bone tumors in lower extremities between September 2010 and Feburary 2022. All patients’ bone defects were reconstructed by allograft bones. The oncological outcomes, functional outcomes, resection accuracy and complications were compared between these two groups in this study.The oncological outcomes comparasion included the local control,metastasis and 3-year and 5-year overall survival differences between the navigation-assisted (NA) group and the free-hand (FH) group. The oncological outcomes were evaluated by Musculoskeletal Tumor Society (MSTS) scores. The resection accuracy was evaluated by indicators such as the major-axis length,the minor-axis length and maximal gap. The resection error (RE) was defined as the resected specimen length minus the planned resection length and were compared between the two groups. The maximal gap error (MGE) was defined as the length between the margin of allograft bones and the host bones at the bone cutting sites.
Results 51 consecutive patients was included in this retrosepective cohort and there were no patients lost in the follow-up period. The mean follow-up time was 93.76+38.49 (22-179) months. No navigation-related surgical complications were observed. The resection errors between the postoperative specimen length and the preoperative planned length were compared to evaluate the resection accuracy after surgery. In the navigation group, the resected errors of the long axis, short axis and depth were 1.760±1.109 (-3.9 to 3.8) mm, 1.32±0.571 (-2.3 to 2.3) mm and 1.58±0.360 (-2.1 to 2.3) mm in the navigation group and 3.67±1.829 (-4.2 to 3.4) mm, 4.61±2.488 (-9.4 to 10.4) mm and 4.21±1.902 (-7.1 to 9.5) mm in the free-hand group, respectively(p<0.001). While the comparasion of oncological, functional outcomes and complications between the groups didn’t show statistical difference (p>0.05).
Conclusions These resection accuracy of computer-navigation assisted surgery is better than free-hand group for bone tumors in lower extremities, and does not affect the oncological outcomes, functional outcomes and complications compared to the control group.
Level of evidence: level III Therapeutic.
How to disentangle sea level rise and a number of other processes influencing coastal floods?
Authors: Orlić Mirko , Pasarić Miroslava
Published: January 2024

On 12 November 2019 at 21:50 UTC about 85% of the city of Venice was flooded, due to the sea level height reaching 189 cm – the second largest value ever recorded there. Both the operational modeling system and the machine learning system underestimated the event by about 40 cm. In order to explain the underestimation, the sea level data recorded in the area were subjected to the decomposition method that had been gradually developed at the Andrija Mohorovičić Geophysical Institute over the last forty or so years. The procedure revealed eight phenomena contributing to the sea level maximum: vertical land motion, sea level rise, variable annual change, surge caused by planetary atmospheric waves, tide, storm surge, meteotsunami and wind set-up inside the lagoon. It turned out that a combined contribution of the last two phenomena was almost equal to the difference between observed sea level height and forecasted/hindcasted values. Consequently, the difference was related to a secondary atmospheric depression, which had caused both meteotsunami and wind set-up inside the lagoon but was not adequately captured by the operational modeling system nor was it allowed for by the machine learning system. Since the decomposition method proved to be useful in the Adriatic Sea, it is expected that the method could be applicable in other basins around the world if they are prone to strong and multifaceted atmospheric forcing.
Constructing genotype and phenotype network helps reveal
Authors: Cao Xuewei , Zhu Lirong , Liang Xiaoyu , Zhang Shuanglin , Sha Qiuying
Published: January 2024

Background. Analyses of a bipartite Genotype and Phenotype Network (GPN), linking the genetic variants and phenotypes based on statistical associations, provide an integrative approach to elucidate the complexities of genetic relationships across diseases and identify pleiotropicloci. In this study, we assess contributions to constructing a well-defined GPN with a clear representation of genetic associations by comparing the network properties with a random network, including connectivity, centrality, and community structure. Then, we extend our discussion to include two applications of bipartite GPN in disease heritability enrichment analysis and phenome-wide association studies (PheWAS).
Results. We construct network topology annotations of genetic variants that quantify the possibility of pleiotropy and apply stratified linkage disequilibrium (LD) score regression to 12 highly genetically correlated phenotypes to identify enriched annotations. The constructed network topology annotations are informative for disease heritability after conditioning on a broad set of functional annotations from the baseline-LD model. In application of PheWAS, the community detection method can be used to obtain a priori grouping of phenotypes detected from GPN based on the shared genetic architecture, then jointly test the association between multiple phenotypes in each network module and one genetic variant to discover the cross-phenotype associations and pleiotropy. Significance thresholds for PheWAS are adjusted for multiple testing by applying the false discovery rate (FDR) control approach. Extensive simulation studies and analyses of 633 electronic health record (EHR)-derived phenotypes in the UK Biobank GWAS summary dataset reveal that most multiple phenotype association tests based on GPN can well-control FDR and identify more significant genetic variants compared with the tests based on UK Biobank categories.
Conclusions. The construction and integration of the bipartite GPNs enhance our understanding of disease heritability, genetic architecture between phenotypes, and pleiotropy.
Application of Graphical Analysis and Principal Components in Investigating the Effect of Genotype × Trait (GT) in Maize Hybrids
Authors: Shojaei Seyed Habib , Bihamta Mohammad Reza , Mousavi Seyed Mohammad Nasir , Qasemi Seyed Hamed , keshavarzi Mohammad Hossein Bijeh , Omrani Ali
Published: January 2024

In order to investigate the effect of genotype x trait and investigate grain yield and yield components and to select the most suitable hybrid in terms of traits, 20 maize hybrids were cultivated and investigated in the form of randomized complete block design (RCBD) in three replications in Karaj region. The results of the analysis of variance at the probability level of 0.01 showed that the effect of genotype in terms of all traits except for the traits of days until tassel dries, peduncle outside the flag leaf, tassel length, the number of fill seeds and the depth of the seeds are significantly different. Based on the mean comparison done by Duncan's method, G3, G6, G7 and G4 genotypes were identified as favorable hybrids and G17, G20, G19 and G18 hybrids were identified as unfavorable hybrids in terms of all evaluated traits. Based on the graphic analysis done on the data, the genotypes G5, G4, G6, G3, G9 and G14 can be identified as desirable hybrids. Also, based on the genotypes grouping diagram, the hybrids were grouped into 9 groups in terms of traits. The correlation diagram between the traits also indicated that the grain yield trait has a positive correlation with tassel length, leaf length, leaf width, and leaf surface traits. Based on the principal components analysis, the traits were named into 10 components, which are respectively: components of ear characteristics, time characteristics in terms of maturity, leaf characteristics, Characteristics of maize plant 1, characteristics of maize plant 2, physiological characteristics and germination, the crown part of the ear characteristics, grain characteristics, grain yield and characteristics of the ear head.
The Association between Intracranial Atherosclerotic Stenosis and Post- stroke Mild Behavioral Impairment
Authors: Liu Zhengxin , Wei Wenshi
Published: January 2024

Purpose
The aim of this study was to analyze the association between Intracranial atherosclerotic stenosis (ICAS) and post-stroke mild behavioral impairment (MBI) in patients with minor stroke.
Methods
A total of 121 patients underwent high-resolution 3T magnetic resonance angiography and MBI checklist (MBI-C) assessment. We adjusted for demographic and vascular risk factors in logistic regression analysis, to determine the association of ICAS with MBI.
Results
Of the 121 patients with minor stroke in this study, 52 (42.98%) were diagnosed with ICAS. After adjusting for potential confounders, we found that patients with ICAS were more likely to develop MBI after an acute, non-disabling ischemic stroke compared to patients without ICAS (Odds Ratio:5.28; 95% Confidence Interval: 2.27-13.0)
Conclusions
Our study demonstrated a positive association between ICAS and post-stroke MBI in patients with minor stroke. Furthermore, the inverse correlation between precuneus cortical thickness and MBI scores provides a new insight into further diagnosing MBI through imaging. Our findings suggest that early detection and treatment of ICAS may help prevent the development of MBI in patients with minor stroke.
Selection bias risk in randomised control trials rated as of “low bias” risk according to Cochrane’s Risk of Bias 2 tool (Protocol)
Authors: Mickenautsch Steffen , Yengopal Veerasamy
Published: January 2024

Aim: To investigate the risk of selection bias in “low bias” risk rated randomised control trials (RCT).
Methods: A systematic literature search of current systematic reviews of RCTs will be conducted. From the identified reviews, RCTs with overall “high bias” and “low bias” RoB 2 risk ratings will be extracted. All RCTs will be statistically tested for selection bias risk. From the test results true positive, true negative, false positive or false negative ratings will be established and the negative and positive likelihood ratios with 95% Confidence interval computed. From the likelihood ratios the likelihood that RCTs with “low bias” RoB 2 risk ratings are at actual risk of selection bias will be inferred.
Ethics and dissemination: Ethical approval is not required for methodological studies. The results will be disseminated as a prior preprint version and subsequent peer-reviewed publication.
Digitale Zwillinge in der naturwissenschaftlichen Bildung
Authors: Geuer Lena , Ulber Roland
Published: January 2024

Digitale Medien sind elementarer Bestandteil in Lehr-Lern-Prozessen und stehen im Einklang mit den physischen, medialen und virtuellen Lebensräumen der Schüler:innen indem sie Gegenwarts- und insbesondere auch eine Zukunftsbedeutung für die Heranwachsenden haben. Die didaktisch-methodische Reflektion und Bewertung von technologischen Innovationen aus dem Internet of Things (IoT) oder der Industrie 4.0 ermöglichen es, grundlegende Aussagen zu fächerspezifischen sowie fächerübergreifenden Potentialen zum Einsatz im schulischen Kontext zu formulieren.
In diesem Beitrag werden die Potentiale für ein gelingendes Lehren und Lernen in der naturwissenschaftlichen Bildung von digitalen Zwillingen zusammenfassend betrachtet. Digitale Zwilling sind bereits in der industriellen Prozessentwicklung und -optimierung implementiert. Grundsätzlich nehmen die, in digitalen Zwillingen, repräsentierten Vernetzungsstrukturen zwischen digitaler und realer Welt und deren Potential in den Bereichen künstliche Intelligenz, maschinelles Lernen und Data-Mining-Prozessen einen wesentlichen Fokus ein. Um Bildungsperspektiven für den naturwissenschaftlichen Unterricht abzuleiten, werden die eingehenden und ausgehenden Datenstrukturen und deren Funktionsweisen in digitalen Zwillingen näher betrachtet.
Der Beitrag thematisiert den Blick auf digitale Zwillinge als intelligente neue Bildungstechnologie in Lehr-Lern-Prozessen, welche auch im industriellen Sektor noch nicht an ihrem Entwicklungsendpunkt steht und vielfältige Anwendungspotentiale im Schulkontext, viele offene Forschungsfragen und Entwicklungspotentiale im Rahmen der Bildungsforschung bereithalten.
Student engagement with a novel online assessment strategy
Authors: JORDAN Sally E. , BOLTON John P.r.
Published: January 2024

The study investigated the impact on student engagement and achievement of a "formative thresholded" continuous assessment strategy in which students had to meet a modest threshold, but their continuous assessment marks did not contribute to their final grade. Students were free to choose their own blend of tutor-marked and computer-marked assignments provided they met the threshold in a minimum number of assignments. For students reaching this threshold, the final grade was determined solely by an end-of-year examination. This assessment strategy was compared with one in which summative assignments contributed to the final grade alongside the final examination. The methodology took the form of data analysis of assessment records from more than 3500 anonymized students over a period of 7 years. Evidence was found for improved student engagement under the formative thresholded assessment strategy, with students choosing to complete many more computer-marked assignments, balanced by slightly fewer tutor-marked assignments. There was no change in overall retention. Many students made use of the capability to repeat different versions of the computer-marked questions. There was some evidence of students gaming the system (repeating questions until they obtained a version they had seen before), though most students did not do this at all and only a small number did so regularly. Students appeared to make better use of model answers, provided in response to three incorrect tries at a question, than of hints provided after each try. It was noted that the formative thresholded assessment strategy has potential for wider use.
Estimation of irrigation water requirements in the Gharb-irrigated perimeter (north-western Morocco)
Authors: Cheikhaoui Yousra , Sadiki Mohamed , Allouza Mohamed , Chakiri Saïd , Bouabdli Abdelahek
Published: January 2024

Climate change has significant implications in semi-arid regions, including the Gharb Plain in North-Western Morocco. The short- or long-term consequences can have serious impacts on the population and the ecosystem, and more particularly on agricultural activities. Addressing the challenges of sustainable food production within the existing agricultural land while minimizing ecological disruption poses a pressing concern. A key aspect in achieving this balance lies in accurately estimating water requirements and maintaining water balance in irrigated agricultural areas, thereby ensuring efficient allocation of water resources while minimizing the ecological footprint in arid and semi-arid regions. This study employs NASA POWER meteorological data, GIS technology, and the Penman–Monteith equation to estimate irrigation water requirements (IWRs) for rice, sugarcane, and citrus crops in the Gharb Plain. Our study shows a significant decrease in IWRs in the Gharb Plain region, due to improved agricultural practices and efficient irrigation techniques. The peak period for crop water needs is between May and September. Sugarcane has the highest water consumption compared to rice and citrus. Climate variables, irrigation efficiency, and changes in cultivation impact water requirements. Our findings aid in estimating irrigation needs for different crops in the Gharb Plain, promoting sustainable water management.
P53-induced GAP-43 Upregulation in Primary Cortical Neurons of Rats
Authors: Li Tianxia , Jia Yuexin , Fu Junxian , Fu Zhuo , Qiao Zhidong , Liu Xiaoyang , Lv Ting , Tang Rong , Yang Guanglu
Published: January 2024

Objective:

In this study, we employed an in vitro culturing technique to investigate the
impact of p53 on the modulation of growth-associated protein-43 (GAP-43) within the primary
cortical neurons of rat specimens.

Methods:

(1) Within the first 24 hours after birth, the bilateral cortex was extracted from newborn
Wistar rats and primary cortical neurons were cultured and identified. (2) The changes in the mRNA
and protein expressions of GAP-43 induced by p53 in rat primary cortical neurons cultured in
vitro were identified utilizing real-time polymerase chain reaction and western blot techniques.

Results:

(1) Lentiviral transfection of p53 within primary cortical neurons of rats elicited elevated
levels of both mRNA and protein expressions of GAP-43, consequently culminating in a noteworthy
augmentation of p53 expression. (2) The introduction of a p53 inhibitor in rat primary cortical
neurons resulted in a reduction in both mRNA and protein expressions of GAP-43.

Conclusion:

Within primary rat cortical neurons, p53 has the potential to prompt an augmentation
in both the transcriptional and protein expression levels of the GAP-43 protein.
Effect of chitosan coating on drug carrier capacity of metal organic framework MIL-100(Fe) contained cyclophosphamide
Authors: Tohidi S. , Aghaie-Khafri M. , Kadivar M.
Published: January 2024

Introduction:

Among the various investigated drug carriers, metal-organic
frameworks (MOFs) have recently gained attention due to their ability to adsorb different
drugs and compatibility with various surface modification strategies. In this study, molecular dynamic simulation was conducted to assess the effect of chitosan on the loading of
cyclophosphamide into MIL-100(Fe).

Methods:

The simulations provided insights into atomic interactions by determining the
coefficient of diffusion as mean squared displacement (MSD), resulting in values of 1.35
and 1.25 before and after chitosan coating, respectively. Experimental analysis of the chitosan-coated MIL-100(Fe) containing cyclophosphamide (MIL-100(Fe)/CS/CP) was performed using SEM, FTIR, BET, DLS, and powder X-ray diffraction. The drug loading
and release processes were evaluated using UV-spectroscopy. RESULT: In vivo-in vitro
studies were carried out to assess the performance of the system. The drug loading in chitosan-coated MIL-100(Fe) showed a significant increase compared to uncoated MIL100(Fe), with payloads of 32% and 26.41%, respectively.

Conclusion:

DLS analysis revealed that the presence of chitosan increased the particle
size of MIL-100(Fe) from 381 to 463 nm and altered the zeta potential from 18 to -17 mV.
The toxic impact of MIL-100(Fe)/CS/CP was evaluated on MCF-7 cells (human breast
cancer cells) through in vivo experimental analysis. In vivo images and H&E analysis
demonstrated the inhibitory effects of MIL-100(Fe)/CS/CP on tumor cells. Additionally,
the drug loading of MIL-100(Fe) particles and MIL-100(Fe)/CS was simulated using the
molecular dynamics software LAAMPS, providing further insights into the system's behavior and performance.
Tertiary Lymphoid Structures Gene Signature Predicts Prognosis
and Immune Infiltration Analysis in Head and Neck Squamous Cell
Carcinoma
Authors: Xing Aiyan , Lv Dongxiao , Wu Changshun , Zhou Kai , Zhao Tianhui , Zhao Lihua , Wang Huaqing , Feng Hong
Published: January 2024

Objectives:

This study aims to assess the prognostic implications of gene signature of
the tertiary lymphoid structures (TLSs) in head and neck squamous cell carcinoma (HNSCC) and
scrutinize the influence of TLS on immune infiltration.

Methods:

Patients with HNSCC from the Cancer Genome Atlas were categorized into high/low
TLS signature groups based on the predetermined TLS signature threshold. The association of the
TLS signature with the immune microenvironment, driver gene mutation status, and tumor mutational load was systematically analyzed. Validation was conducted using independent datasets
(GSE41613 and GSE102349).

Results:

Patients with a high TLS signature score exhibited better prognosis compared to those
with a low TLS signature score. The group with a high TLS signature score had significantly higher immune cell subpopulations compared to the group with a low TLS signature score. Moreover,
the major immune cell subpopulations and immune circulation characteristics in the tumor immune microenvironment were positively correlated with the TLS signature. Mutational differences in driver genes were observed between the TLS signature high/low groups, primarily in the
cell cycle and NRF2 signaling pathways. Patients with TP53 mutations and high TLS signature
scores demonstrated a better prognosis compared to those with TP53 wild-type. In the independent cohort, the relationship between TLS signatures and patient prognosis and immune infiltration was also confirmed. Additionally, immune-related biological processes and signaling pathways were activated with elevated TLS signature.

Conclusion:

High TLS signature is a promising independent prognostic factor for HNSCC patients. Immunological analysis indicated a correlation between TLS and immune cell infiltration
in HNSCC. These findings provide a theoretical basis for future applications of TLS signature in
HNSCC prognosis and immunotherapy.
A Review of the Leishmanicidal Properties of Lectins
Authors: Grangeiro Yasmim A. , Santos Ana L.E. , Barbosa Flávia E.V. , Roma Renato R. , Souza Racquel O.S. , Silva Cláudio G.L , Teixeira Claudener S.
Published: January 2024

Lectins are proteins widely distributed among plants, animals and microorganisms that
have the ability to recognize and interact with specific carbohydrates. They have varied biological
activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses
and protozoa, which is related to the interaction of these proteins with the carbohydrates present in
the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases
caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and
amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates
present on the cell surface of the parasite, it prevents their development through various
mechanisms of action, such as the production of ROS and alteration of membrane integrity, and
can also interact with defense cells present in the human body, thus showing that these molecules
can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective
of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity,
emphasizing the advances and perspectives of research in this theme. Through the analysis
of the selected studies, we were able to conclude that lectins have great potential for inhibiting the
development of leishmaniasis. However, there are still few studies on this subject.
The Disulfide Bond-Mediated Cyclization of Oral Peptides
Authors: Yao Chenguang , Ye Guoguo , Yang Qin , Chen Zhenwang , Yang Minghui
Published: January 2024

‘Structure determines function’ is a consensus in the current biological community, but
the structural characteristics corresponding to a certain function have always been a hot field of
scientific exploration. A peptide is a bio-active molecule that is between the size of an antibody
and a small molecule. Still, the gastrointestinal barrier and the physicochemical properties of peptides
have always limited the oral administration of peptides. Therefore, we analyze the main
ways oral peptide conversion strategies of peptide modification and permeation enhancers. Based
on our analysis of the structure of natural oral peptides, which can be absorbed through the gastrointestinal
tract, we believe that the design strategy of natural stapled peptides based on disulfide
bonds is good for oral peptide design. This cannot only be used to identify anti-gastrointestinal digestive
structural proteins in nature but also provide a solid structural foundation for the construction
of new oral peptide drugs.
Anthriscus sylvestris: An overview on Bioactive Compounds and
Anticancer Mechanisms from a Traditional Medicinal Plant to Modern
Investigation
Authors: Zhang Mengyu , Ji Xiaoyun , Li Yuxin , Chen Xin , Wu Xiaoqing , Tan Rui , Jiang Hezhong
Published: January 2024

Anthriscus sylvestris (L.) Hoffm. Gen. is a biennial or perennial herb commonly found in
China. It has a long history of use in traditional Chinese medicine to treat various ailments such as
cough, gastric disorders, spleen deficiency, and limb weakness. Recently, its potential as an anticancer
agent has gained considerable attention and has been the subject of extensive research focusing
on extract efficacy, identification of active compounds, and proposed molecular mechanisms.
Nevertheless, further high-quality research is still required to fully evaluate its potential as an anticancer
drug.

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This review aims to comprehensively summarize the anticancer properties exhibited by the active
components found in Anthriscus sylvestris.

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We conducted a comprehensive search, collation, and analysis of published articles on anticancer
activity and active compounds of A. sylvestris using various databases that include, but are not limited
to, PubMed, Web of Science, Science Direct and Google Scholar.

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The primary chemical composition of A. sylvestris consists of phenylpropanoids, flavonoids, steroids,
fatty acids, and organic acids, showcasing an array of pharmacological activities like anticancer,
antioxidant, anti-aging, and immunoregulatory properties. Thus, this review highlights the
active compounds isolated from A. sylvestris extracts, which provide potential leads for the development
of novel anticancer drugs and a better understanding of the plant's pharmacological effects,
particularly its anticancer mechanism of action.
Current Landscape of Gene Therapy for the Treatment of Cardiovascular
Disorders
Authors: Wal Pranay , Aziz Namra , Singh Chetan Pratap , Rasheed Azhar , Tyagi Lalit Kumar , Agrawal Ankur , Wal Ankita
Published: January 2024

Cardiovascular disorders (CVD) are the primary cause of death worldwide. Multiple
factors have been accepted to cause cardiovascular diseases; among them, smoking, physical inactivity,
unhealthy eating habits, age, and family history are flag-bearers. Individuals at risk of developing
CVD are suggested to make drastic habitual changes as the primary intervention to prevent
CVD; however, over time, the disease is bound to worsen. This is when secondary interventions
come into play, including antihypertensive, anti-lipidemic, anti-anginal, and inotropic drugs. These
drugs usually undergo surgical intervention in patients with a much higher risk of heart failure.
These therapeutic agents increase the survival rate, decrease the severity of symptoms and the
discomfort that comes with them, and increase the overall quality of life. However, most individuals
succumb to this disease. None of these treatments address the molecular mechanism of the disease
and hence are unable to halt the pathological worsening of the disease. Gene therapy offers a
more efficient, potent, and important novel approach to counter the disease, as it has the potential
to permanently eradicate the disease from the patients and even in the upcoming generations. However,
this therapy is associated with significant risks and ethical considerations that pose noteworthy
resistance. In this review, we discuss various methods of gene therapy for cardiovascular disorders
and address the ethical conundrum surrounding it.
Hemophilia Healing with AAV: Navigating the Frontier of Gene Therapy
Authors: Khan Safir Ullah , Khan Munir Ullah , Suleman Muhammad , Inam Amrah , Din Muhammad Azhar Ud
Published: January 2024

Gene therapy for hemophilia has advanced tremendously after thirty years of continual
study and development. Advancements in medical science have facilitated attaining normal levels
of Factor VIII (FVIII) or Factor IX (FIX) in individuals with haemophilia, thereby offering the potential for their complete recovery. Despite the notable advancements in various countries, there is
significant scope for further enhancement in haemophilia gene therapy. Adeno-associated virus
(AAV) currently serves as the primary vehicle for gene therapy in clinical trials targeting haemophilia. Subsequent investigations will prioritize enhancing viral capsid structures, transgene
compositions, and promoters to achieve heightened transduction efficacy, diminished immunogenicity, and more predictable therapeutic results. The present study indicates that whereas animal
models have transduction efficiency that is over 100% high, human hepatocytes are unable to express clotting factors and transduction efficiency to comparable levels. According to the current
study, achieving high transduction efficiency and high levels of clotting factor expression in human hepatocytes is still insufficient. It is also crucial to reduce the risk of cellular stress caused by
protein overload. Despite encountering various hurdles, the field of haemophilia gene therapy
holds promise for the future. As technology continues to advance and mature, it is anticipated that
a personalized therapeutic approach will be developed to cure haemophilia effectively.
Advances in Monoclonal Antibody Therapies for Triple-Negative
Breast Cancer: Immunotherapeutic and Targeted Strategies
Authors: Khalaji Amirreza , Hadad Sara , Jabbaripour Sarmadian Amirreza , Ojaghlou Fatemeh , Janagard Elham Mohebi , Baradaran Behzad
Published: January 2024

Triple-negative breast cancer (TNBC) presents considerable obstacles
because of its highly aggressive characteristics and limited availability of specific
therapeutic interventions. The utilization of monoclonal antibody (mAb)-based
immunotherapy is a viable approach to tackle these difficulties. This review aims to
examine the present state of mAb-based immunotherapy in TNBC, focusing on the
underlying mechanisms of action, clinical applications, and existing challenges. The
effectiveness of mAbs in reducing tumor development, regulating immune responses,
and changing the tumor microenvironment has been demonstrated in many clinical
investigations. The challenges encompass several aspects such as the discovery of
biomarkers, understanding resistance mechanisms, managing toxicity, considering
costs, and ensuring accessibility. The future is poised to bring forth significant
advancements in the field of biomedicine, particularly in the areas of new mAbs,
personalized medicine, and precision immunotherapy. In conclusion, mAb-based
immunotherapy has promise in revolutionizing the treatment of TNBC, hence providing
a possible avenue for enhanced patient outcomes and quality of life.
Smart Ultrasound-responsive Polymers for Drug Delivery: An Overview on Advanced Stimuli-sensitive Materials and Techniques
Authors: Yazdan Mostafa , Naghib Seyed Morteza
Published: January 2024

In recent years, a notable advancement has occurred in the domain of drug delivery systems
via the integration of intelligent polymers that respond to ultrasound. The implementation of
this groundbreaking methodology has significantly revolutionised the controlled and precise delivery
of therapeutic interventions. An in-depth investigation is conducted into the most recent developments
in ultrasonic stimulus-responsive materials and techniques for the purpose of accomplishing
precise medication administration. The investigation begins with an exhaustive synopsis of the foundational
principles underlying drug delivery systems that react to ultrasonic stimuli, focusing specifically
on the complex interplay between polymers and ultrasound waves. Significant attention is devoted
to the development of polymers that demonstrate tailored responsiveness to ultrasound, thereby
exemplifying their versatility in generating controlled drug release patterns. Numerous classifications
of intelligent polymers are examined in the discussion, including those that react to variations in temperature,
pH, and enzymes. When coupled with ultrasonic stimuli, these polymers offer a sophisticated
framework for the precise manipulation of drug release in terms of both temporal and spatial dimensions.
The present study aims to examine the synergistic effects of responsive polymers and ultrasound
in overcoming biological barriers such as the blood-brain barrier and the gastrointestinal
tract. By doing so, it seeks to shed light on the potential applications of these materials in intricate
clinical scenarios. The issues and future prospects of intelligent ultrasound-responsive polymers in
the context of drug delivery are critically analysed in this article. The objective of this study is to
offer valuable perspectives on the challenges that must be overcome to enable the effective implementation
of these technologies. The primary objective of this comprehensive review is to furnish
researchers, clinicians, and pharmaceutical scientists with a wealth of information that will serve as a
guide for forthcoming developments in the development and enhancement of intelligent drug delivery
systems that employ ultrasound-responsive polymers to attain superior therapeutic outcomes.