bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired immune responses in the airways are associated with poor outcome in critically ill COVID-19 patients
Authors: Barnett Clea R. , Krolikowski Kelsey , Postelnicu Radu , Mukherjee Vikramjit , Sulaiman Imran , Chung Matthew , Angel Luis , Tsay Jun-Chieh J. , Wu Benjamin G. , Yeung Stephen T. , Duerr Ralf , Desvignes Ludovic , Khanna Kamal , Li Yonghua , Schluger Rosemary , Rafeq Samaan , Collazo Destiny , Kyeremateng Yaa , Amoroso Nancy , Pradhan Deepak , Das Sanchita , Evans Laura , Uyeki Timothy M. , Ghedin Elodie , Silverman Gregg J. , Segal Leopoldo N. , Brosnahan Shari B.
Published: March 2024

Introduction

Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study.

Material and methods

We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load.

Results

While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p<0.05), while there was no such association with antibody levels in the systemic circulation.

Discussion

Our data highlight the critical role of local adaptive immunity in the airways as a key defence mechanism against primary SARS-CoV-2 infection.
Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation
Authors: Wu Siqi , Tang Wenjing , Liu Ling , Wei Ke , Tang Yin , Ma Jingyue , Li Hongbin , Ao Yichan
Published: March 2024

Background

Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity.

Methods

Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5–24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192.

Results

In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge.

Conclusions

Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Graphical Abstract
Development of excitation power-responsive anti-stokes emission wavelength switching and their energy saving induced by localized surface plasmon resonance
Authors: Honda Jotaro , Sugawa Kosuke , Honma Koki , Fukumura Seiya , Katoh Ryuzi , Tahara Hironobu , Otsuki Joe
Published: March 2024

We designed an external stimulus-responsive anti-Stokes emission switching using dual-annihilator-based triplet–triplet annihilation upconversion systems. This system, which was constructed by incorporating a palladium porphyrin derivative as a sensitizer and 9,10-diphenylanthracene (DPA) and 9,10-bis(triisopropylsilyl)ethynylanthracene (TIPS) as annihilators into polymer thin films, produced TIPS- and DPA-based anti-Stokes emission under low and high excitation powers, respectively. The mechanism involves the following: under low excitation power, triplet energy transfer from triplet-excited PdOEP to DPA is induced, followed by relay to TIPS. This results in the generation of triplet-excited TIPS, and the subsequent triplet–triplet annihilation between them produces TIPS-based anti-Stokes emission. Conversely, under high excitation power, the high-density triplet-excited DPA, generated through triplet energy transfer from PdOEP, undergoes triplet–triplet annihilation among themselves, resulting in the generation of DPA-based anti-Stokes emission. Additionally, we achieved energy savings by reducing the required excitation power for switching through the utilization of plasmonic metal nanoparticles. The strong local electromagnetic fields associated with the localized surface plasmon resonance of metal nanoparticles enhance the photoexcitation efficiency of PdOEP, subsequently increasing the density of triplet-excited DPA. As a result, anti-Stokes emission switching becomes feasible at lower excitation powers.
Update on known and emergent viruses affecting human male genital tract and fertility
Authors: Dabizzi Sara , Maggi Mario , Torcia Maria Gabriella
Published: March 2024

Many viruses infect the male genital tract with harmful consequences at individual and population levels. In fact, viral infections may induce damage to different organs of the male genital tract (MGT), therefore compromising male fertility. The oxidative stress, induced during viral-mediated local and systemic inflammation, is responsible for testicular damage, compromising germinal and endocrine cell functions. A reduction in sperm count, motility, number of normal sperm and an increase in DNA fragmentation are all common findings in the course of viral infections that, however, generally regress after infection clearance. In some cases, however, viral shedding persists for a long time leading to unexpected sexual transmission, even after the disappearance of the viral load from the blood.

The recent outbreak of Zika and Ebola Virus evidenced how the MGT could represent a reservoir of dangerous emergent viruses and how new modalities of surveillance of survivors are strongly needed to limit viral transmission among the general population.

Here we reviewed the evidence concerning the presence of relevant viruses, including emergent and re-emergent, on the male genital tract, their route of entry, their adverse effects on male fertility and the pattern of viral shedding in the semen.

We also described laboratory strategies to reduce the risk of horizontal or vertical cross-infection in serodiscordant couples undergoing assisted reproductive technologies.
StackDPP: a stacking ensemble based DNA-binding protein prediction model
Authors: Ahmed Sheikh Hasib , Bose Dibyendu Brinto , Khandoker Rafi , Rahman M Saifur
Published: March 2024

Background

DNA-binding proteins (DNA-BPs) are the proteins that bind and interact with DNA. DNA-BPs regulate and affect numerous biological processes, such as, transcription and DNA replication, repair, and organization of the chromosomal DNA. Very few proteins, however, are DNA-binding in nature. Therefore, it is necessary to develop an efficient predictor for identifying DNA-BPs.

Result

In this work, we have proposed new benchmark datasets for the DNA-binding protein prediction problem. We discovered several quality concerns with the widely used benchmark datasets, PDB1075 (for training) and PDB186 (for independent testing), which necessitated the preparation of new benchmark datasets. Our proposed datasets UNIPROT1424 and UNIPROT356 can be used for model training and independent testing respectively. We have retrained selected state-of-the-art DNA-BP predictors in the new dataset and reported their performance results. We also trained a novel predictor using the new benchmark dataset. We extracted features from various feature categories, then used a Random Forest classifier and Recursive Feature Elimination with Cross-validation (RFECV) to select the optimal set of 452 features. We then proposed a stacking ensemble architecture as our final prediction model. Named Stacking Ensemble Model for DNA-binding Protein Prediction, or StackDPP in short, our model achieved 0.92, 0.92 and 0.93 accuracy in 10-fold cross-validation, jackknife and independent testing respectively.

Conclusion

StackDPP has performed very well in cross-validation testing and has outperformed all the state-of-the-art prediction models in independent testing. Its performance scores in cross-validation testing generalized very well in the independent test set. The source code of the model is publicly available at https://github.com/HasibAhmed1624/StackDPP. Therefore, we expect this generalized model can be adopted by researchers and practitioners to identify novel DNA-binding proteins.
The application of lasers in vital pulp therapy: clinical and radiographic outcomes
Authors: Afkhami Farzaneh , Rostami Golriz , Xu Chun , Peters Ove A.
Published: March 2024

The main purpose of vital pulp therapy (VPT) is to preserve the integrity and function of the pulp. A wide variety of materials and techniques have been proposed to improve treatment outcomes, and among them, the utilization of lasers has gained significant attention. The application of lasers in different stages of VPT has witnessed remarkable growth in recent years, surpassing previous approaches.

This study aimed to review the applications of lasers in different steps of VPT and evaluate associated clinical and radiographic outcomes. An electronic search using Scopus, MEDLINE, Web of Science and Google Scholar databases from 2000 to 2023 was carried out by two independent researchers. The focus was on human studies that examined the clinical and/or radiographic effects of different laser types in VPT. A total of 4243 studies were included in this narrative review article. Based on the compiled data, it can be concluded that although current literature suggests laser may be proposed as an adjunct modality for some procedural steps in VPT, more research with standardized methodologies and criteria is needed to obtain more reliable and conclusive results.
Analysis of drug-induced interstitial lung disease caused by herbal medicine using the Japanese Adverse Drug Event Report database
Authors: Oura Keita , Tanaka Mizuki , Matsumoto Kiyoka , Satake Riko , Inoue Misaki , Yoshida Yu , Wakabayashi Wataru , Hasegawa Shiori , Iwata Mari , Suzuki Takaaki , Maezawa Mika , Nakao Satoshi , Liao Jun , Iguchi Kazuhiro , Nakamura Mitsuhiro
Published: March 2024

Background

Drug-induced interstitial lung disease (DIILD) is a severe adverse event leading to morbidity and mortality. This study evaluated the adverse event indicators of DIILD and time-to-onset profiles following the daily intake of herbal drugs (Scutellariae radix [“ogon” in Japanese], Bupleuri radix [“saiko” in Japanese], and Pinelliae tuber [“hange” in Japanese]) using the Japanese Adverse Drug Event Report database. DIILD was defined in accordance with the Medical Dictionary for Regulatory Activities.

Methods

The Japanese Adverse Drug Event Report database contained 830,079 reports published between April 2004 and April 2023. The association between herbal medicines and DILLD was evaluated using the pharmacovigilance index as the reporting odds ratio (ROR), logistic regression models, propensity score-matching techniques, and Weibull shape parameters.

Results

The adjusted RORs using multivariate logistic regression models for Scutellariae radix (daily intake), Pinelliae tuber (daily intake), sex (male), age (≥ 60 years), Scutellariae radix (daily intake)*age (≥ 60 years), and Scutellariae radix (daily intake)* Pinelliae tuber (daily intake) were 1.47 (1.36 − 1.59), 1.05 (1.01 − 1.10), 1.45 (1.34 − 1.57), 1.92 (1.74 − 2.11), 3.35 (3.12 − 3.60), and 1.49 (1.46 − 1.53), respectively. DIILD onset profiles were evaluated using the Weibull shape parameter. A logistic plot of daily intake and onset of DIILD was drawn. ROR signals were detected in 32 of 54 herbal medicines, including Scutellariae radix, Bupleuri radix, and Pinelliae tuber. The median duration (days) (interquartile range) to DIILD onset was 36.0 (27.0–63.0) for Saikokaryukotsuboreito, 35.0 (21.0–55.0) for Saireito, and 31.0 (13.5–67.5) for Shosaikoto. The Weibull shape parameter beta (95% confidence interval) values for Saikokaryukotsuboreito, Saireito, and Shosaikoto were 1.36 (1.08–1.67), 1.36 (1.20–1.52), and 1.31 (0.98–1.68), respectively.

Conclusions

DIILD demonstrated a dose-dependent to crude drugs. Clinicians should strive for the early detection of DIILD and avoid the inadvertent administration of herbal medicines.
Aligning organisational priorities and implementation science for cancer research
Authors: Best Stephanie , Thursky Karin , Buzza Mark , Klaic Marlena , Peters Sanne , Guccione Lisa , Trainer Alison , Francis Jillian
Published: March 2024

Background

The challenge of implementing evidence into routine clinical practice is well recognised and implementation science offers theories, models and frameworks to promote investigation into delivery of evidence-based care. Embedding implementation researchers into health systems is a novel approach to ensuring research is situated in day-to-day practice dilemmas. To optimise the value of embedded implementation researchers and resources, the aim of this study was to investigate stakeholders’ views on opportunities for implementation science research in a cancer setting that holds potential to impact on care. The research objectives were to: 1) Establish stakeholder and theory informed organisation-level implementation science priorities and 2) Identify and prioritise a test case pilot implementation research project.

Methods

We undertook a qualitative study using semi-structured interviews. Participants held either a formal leadership role, were research active or a consumer advocate and affiliated with either a specialist cancer hospital or a cancer alliance of ten hospitals. Interview data were summarised and shared with participants prior to undertaking both thematic analysis, to identify priority areas for implementation research, and content analysis, to identify potential pilot implementation research projects. The selected pilot Implementation research project was prioritised using a synthesis of an organisational and implementation prioritisation framework – the organisational priority setting framework and APEASE framework.

Results

Thirty-one people participated between August 2022 and February 2023. Four themes were identified: 1) Integration of services to address organisational priorities e.g., tackling fragmented services; 2) Application of digital health interventions e.g., identifying the potential benefits of digital health interventions; 3) Identification of potential for implementation research, including deimplementation i.e., discontinuing ineffective or low value care and; 4) Focusing on direct patient engagement e.g., wider consumer awareness of the challenges in delivering cancer care. Six potential pilot implementation research projects were identified and the EMBED project, to support clinicians to refer appropriate patients with cancer for genetic testing, was selected using the synthesised prioritisation framework.

Conclusions

Using a theory informed and structured approach the alignment between strategic organisational priorities and implementation research priorities can be identified. As a result, the implementation research focus can be placed on activities with the highest potential impact.
Effects of changes in residential fast-food outlet exposure on Body Mass Index change: longitudinal evidence from 92,211 Lifelines participants
Authors: van Erpecum Carel-Peter L. , van Zon Sander K.R. , Bültmann Ute , Smidt Nynke
Published: March 2024

Background

Evidence on the association between fast-food outlet exposure and Body Mass Index (BMI) remains inconsistent and is primarily based on cross-sectional studies. We investigated the associations between changes in fast-food outlet exposure and BMI changes, and to what extent these associations are moderated by age and fast-food outlet exposure at baseline.

Methods

We used 4-year longitudinal data of the Lifelines adult cohort (N = 92,211). Participant residential addresses at baseline and follow-up were linked to a register containing fast-food outlet locations using geocoding. Change in fast-food outlet exposure was defined as the number of fast-food outlets within 1 km of the residential address at follow-up minus the number of fast-food outlets within 1 km of the residential address at baseline. BMI was calculated based on objectively measured weight and height. Fixed effects analyses were performed adjusting for changes in covariates and potential confounders. Exposure-moderator interactions were tested and stratified analyses were performed if p < 0.10.

Results

Participants who had an increase in the number of fast-food outlets within 1 km had a greater BMI increase (B(95% CI): 0.003 (0.001,0.006)). Decreases in fast-food outlet exposure were not associated with BMI change (B(95% CI): 0.001 (-0.001,0.004)). No clear moderation pattern by age or fast-food outlet exposure at baseline was found.

Conclusions

Increases in residential fast-food outlet exposure are associated with BMI gain, whereas decreases in fast-food outlet exposure are not associated with BMI loss. Effect sizes of increases in fast-food outlet exposure on BMI change were small at individual level. However, a longer follow-up period may have been needed to fully capture the impact of increases in fast-food outlet exposure on BMI change. Furthermore, these effect sizes could still be important at population level considering the rapid rise of fast-food outlets across society. Future studies should investigate the mechanisms and changes in consumer behaviours underlying associations between changes in fast-food outlet exposure and BMI change.
Harmony in nature: understanding the cultural and ecological aspects of plant use in Ladakh
Authors: Angmo Kunzes , Adhikari Bhupendra S. , Bussmann Rainer W. , Rawat Gopal S.
Published: March 2024

Background

Traditional knowledge (TK) in Ladakh encapsulates a repository of experimental wisdom cultivated over millennia. Despite this cultural wealth, dwindling interest among the younger generations in the region’s age-old practices underscores the urgency to document TK. The current study investigates the diverse usage of plants in Surru, Wakha and Lower Indus valleys of Western Ladakh exploring the influence of socioeconomic and ecological factors.

Methods

A stratified random sample approach was adopted to select 540 respondents for gathering information of useful plants through interviews and questionnaires. Participant observation, questionnaires, open-ended and semi-structured interviews were conducted for data collection. Free listing was done to create an extensive list of plants and their uses. Ethnobotanical metrics such as relative frequency of citation (RFC), relative importance index (RI), cultural value (CV) index and cultural importance (CI) index were computed to assess species applicability. Additionally, one-way analysis of variance (ANOVA) was utilized to discern significant differences in knowledge levels based on valleys, gender, education and religion using TK as a response variable.

Results

Altogether, we recorded 246 plant species under various ethnobotanical uses from Western Ladakh. These include medicinal (126), fodder (124), wild ornamentals (86), food (81), fuel wood (54), dye (20), religious (31) and others (34). Novel plant reports include Berberis brandisiana Ahrendt and Dactylorhiza kafiriana Renz. The dominant plant family is Asteraceae with 35 species. Suru valley exhibits the highest number of cited plants followed by Wakha-chu and Lower Indus valleys (192, 168 and 152 species, respectively).

Conclusion

Disparities in plant use understanding are evident among different groups, prompting further investigation through intercultural comparisons. Plants such as Arnebia euchroma, Juniperus semiglobosa, and Artemisia species emerge with cultural importance. Gender, valley affiliation, religious background and the remoteness of a village all influence local plant knowledge. These variations are linked to socioeconomic disparities among communities.
Channel-wise attention enhanced and structural similarity constrained cycleGAN for effective synthetic CT generation from head and neck MRI images
Authors: Gong Changfei , Huang Yuling , Luo Mingming , Cao Shunxiang , Gong Xiaochang , Ding Shenggou , Yuan Xingxing , Zheng Wenheng , Zhang Yun
Published: March 2024

Background

Magnetic resonance imaging (MRI) plays an increasingly important role in radiotherapy, enhancing the accuracy of target and organs at risk delineation, but the absence of electron density information limits its further clinical application. Therefore, the aim of this study is to develop and evaluate a novel unsupervised network (cycleSimulationGAN) for unpaired MR-to-CT synthesis.

Methods

The proposed cycleSimulationGAN in this work integrates contour consistency loss function and channel-wise attention mechanism to synthesize high-quality CT-like images. Specially, the proposed cycleSimulationGAN constrains the structural similarity between the synthetic and input images for better structural retention characteristics. Additionally, we propose to equip a novel channel-wise attention mechanism based on the traditional generator of GAN to enhance the feature representation capability of deep network and extract more effective features. The mean absolute error (MAE) of Hounsfield Units (HU), peak signal-to-noise ratio (PSNR), root-mean-square error (RMSE) and structural similarity index (SSIM) were calculated between synthetic CT (sCT) and ground truth (GT) CT images to quantify the overall sCT performance.

Results

One hundred and sixty nasopharyngeal carcinoma (NPC) patients who underwent volumetric-modulated arc radiotherapy (VMAT) were enrolled in this study. The generated sCT of our method were more consistent with the GT compared with other methods in terms of visual inspection. The average MAE, RMSE, PSNR, and SSIM calculated over twenty patients were 61.88 ± 1.42, 116.85 ± 3.42, 36.23 ± 0.52 and 0.985 ± 0.002 for the proposed method. The four image quality assessment metrics were significantly improved by our approach compared to conventional cycleGAN, the proposed cycleSimulationGAN produces significantly better synthetic results except for SSIM in bone.

Conclusions

We developed a novel cycleSimulationGAN model that can effectively create sCT images, making them comparable to GT images, which could potentially benefit the MRI-based treatment planning.
Engaging Fathers for Effective Child Nutrition and Development in Tanzania (EFFECTS): study protocol for a five-arm, cluster-randomized trial
Authors:   EFFECTS Study Investigators, Lyaatu Isaac , Mosha Dominic , Sando Mary Mwanyika , Jeong Joshua , Yousafzai Aisha , PrayGod George , Evarist Roman , Galvin Lauren , Kieffer Mary Pat , Kumalija Elfrida , Simpson Jennifer , Ambikapathi Ramya , Boncyk Morgan , Matangi Evidence , Gunaratna Nilupa S.
Published: March 2024

Background

Globally, 144 million children under 5 years are undernourished and 250 million do not meet their developmental potential. Multi-input interventions, such as bundled nutrition and parenting interventions, are designed to mitigate risks for multiple child outcomes. There is limited evidence that bundled interventions have additive benefits to nutrition, growth, or development outcomes. These outcomes share common risks; therefore, designing interventions to tackle these risks using a common theory of change may optimize effectiveness. Emerging evidence suggests explicit engagement of fathers may benefit child outcomes, but few trials have tested this or included data collected from fathers.

Methods

Engaging Fathers for Effective Child Nutrition and Development in Tanzania (EFFECTS) is a community-based cluster-randomized controlled trial that will be implemented in the rural Mara Region, Tanzania. The trial aims (1) to test a bundled nutrition and parenting program delivered to mothers’ groups, with or without fathers’ groups, over 12 months on child and caregiving outcomes compared to a nutrition program alone, and (2) to test nutrition or bundled nutrition and parenting programs delivered to mothers’ and fathers’ groups over 12 months on child and caregiving outcomes compared to programs delivered to mothers alone. The trial comprises five arms: (1) mothers’ groups receiving a nutrition program, (2) mothers’ groups receiving a bundled nutrition and parenting program, (3) mothers’ and fathers’ groups receiving a nutrition program, (4) mothers’ and fathers’ groups receiving a bundled nutrition and parenting program, and (5) control receiving standard of care health services. The primary outcomes are child dietary diversity and early child development (mental and motor development). Parents with a child under 18 months will be enrolled in peer groups and receive twice monthly intervention by trained community health workers. Data will be collected from mothers, fathers, and children at baseline (pre-intervention), midline, and endline (post-intervention).

Discussion

EFFECTS will generate evidence on the effects of bundled nutrition and parenting interventions on child nutrition, growth, and development outcomes; determine the benefits of engaging fathers on child, caregiving, and caregiver outcomes; and investigate common and unique pathways between treatments and child outcomes.

Trial registration

ClinicalTrials.gov NCT03759821. Registered on November 30, 2018
New thiazole, thiophene and 2-pyridone compounds incorporating dimethylaniline moiety: synthesis, cytotoxicity, ADME and molecular docking studies
Authors: Metwally Heba M. , Younis Norhan M. , Abdel-Latif Ehab , El-Rayyes Ali
Published: March 2024

Various sets of thiazole, thiophene, and 2-pyridone ring structures containing a dimethylaniline component were synthesized. Substituted thiazoles 2–3 and thiophenes 5–7 were produced by reacting thiocarbamoyl compound 4 with α-halogenated reagents in different basic conditions. Also, a series of 2-pyridone derivatives 9a–f substituted with dimethylaniline was synthesized through Michael addition of malononitrile to α,β-unsaturated nitrile derivatives 8a–f. The synthesized products were structurally proven by spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Furthermore, the anti-cancer efficacy of the compounds was assessed using the MTT assay on two cell lines: hepatocellular carcinoma (HepG-2) and breast cancer (MDA-MB-231). The results showed the highest growth inhibition for derivatives 2, 6, 7, and 9c, which were further examined for their IC50 values. The IC50 for compound 2 showed equipotent activity (IC50 = 1.2 µM) against the HepG-2 cell line compared to Doxorubicin (IC50 = 1.1 µM). Compounds 2, 6, 7 and 9c showed very good ADME assessments for further drug administration. Moreover, the PASS theoretical prediction for the compounds showed high antimitotic and antineoplastic activities for compounds 2, 6, 7, and 9c, as well as potent inhibition activity for the insulysin enzyme (IDE). Molecular docking stimulations were performed on CDK1/CyclinB1/CKS2 (PDB ID: 4y72) and BPTI (PDB ID: 2ra3). When docked into (PDB ID: 4y72), all of the tested compounds showed considerable inhibition, and the 2-pyridone derivative 9d had the maximum binding affinity (− 8.1223 kcal/mol). While thiophene derivative 6 offered the maximum binding affinity (− 7.5094 kcal/mol) when docked into (PDB ID: 2ra3).

Graphical Abstract
Biology of the non-parasitic phase of the cattle tick Rhipicephalus (Boophilus) microplus in an area of Amazon influence
Authors: Sales Daniela P. , Silva-Junior Marcelo H. S. , Tavares Caio P. , Sousa Isabella C. , Sousa Dauana M. , Brito Danilo R. B. , Camargo André M. , Leite Romário Cerqueira , Faccini J. L. H. , Lopes Welber D. Z. , Labruna Marcelo B. , Luz Hermes R. , Costa-Junior Livio M.
Published: March 2024

Background

Rhipicephalus (Boophilus) microplus is the most important tick species affecting cattle in the world. Under field conditions, the non-parasitic phase of R. (B.) microplus is unknown in the Amazon biome, including Brazil. The present study aimed to evaluate the non-parasitic phase of R. (B.) microplus in field (grass plots) and laboratory conditions.

Methods

The study was conducted from September 2020 to April 2022 in an Amazonian region (Maranhão State, Brazil). We evaluated the biological parameters of R. (B.) microplus under laboratory and field conditions. Engorged females were exposed to experimental conditions every 14 days, totaling 20 months of study. The following biological parameters were observed: pre-oviposition period, egg mass incubation period, and maximum larval survival period.

Results

Abiotic data (e.g., temperature and humidity) varied little throughout the year. Precipitation was the factor that varied the most throughout the year (dry ~ 30 mm3 and rain 400 mm3), and the parameters of pre-oviposition and pre-hatching are longer during the rainy season. A possible negative effect of the dry season on the percentage of hatched eggs was observed. Larval longevity in the plots of both control and free females was short (mean ~ 50–60 days), below that recorded for larvae under controlled conditions (mean ~ 95 days).

Conclusions

Rhipicephalus (Boophilus) microplus was able to complete its non-parasitic phase by producing host-seeking larvae in the pasture during all months of the study. The results indicate that R. (B.) microplus can complete up to six generations per year in biome Amazon. To our knowledge, this is the highest number of annual generations for R. (B.) microplus in Latin America.

Graphical Abstract
Sex matters in the association between cardiovascular health and incident dementia: evidence from real world data
Authors: Ponjoan Anna , Blanch Jordi , Fages-Masmiquel Ester , Martí-Lluch Ruth , Alves-Cabratosa Lia , Garcia-Gil María del Mar , Domínguez-Armengol Gina , Ribas-Aulinas Francesc , Zacarías-Pons Lluís , Ramos Rafel
Published: March 2024

Background

Cardiovascular health has been associated with dementia onset, but little is known about the variation of such association by sex and age considering dementia subtypes. We assessed the role of sex and age in the association between cardiovascular risk and the onset of all-cause dementia, Alzheimer’s disease, and vascular dementia in people aged 50–74 years.

Methods

This is a retrospective cohort study covering 922.973 Catalans who attended the primary care services of the Catalan Health Institute (Spain). Data were obtained from the System for the Development of Research in Primary Care (SIDIAP database). Exposure was the cardiovascular risk (CVR) at baseline categorized into four levels of Framingham-REGICOR score (FRS): low (FRS < 5%), low-intermediate (5% ≤ FRS < 7.5%), high-intermediate (7.5% ≤ FRS < 10%), high (FRS ≥ 10%), and one group with previous vascular disease. Cases of all-cause dementia and Alzheimer’s disease were identified using validated algorithms, and cases of vascular dementia were identified by diagnostic codes. We fitted stratified Cox models using age parametrized as b-Spline.

Results

A total of 51,454 incident cases of all-cause dementia were recorded over a mean follow-up of 12.7 years. The hazard ratios in the low-intermediate and high FRS groups were 1.12 (95% confidence interval: 1.08–1.15) and 1.55 (1.50–1.60) for all-cause dementia; 1.07 (1.03–1.11) and 1.17 (1.11–1.24) for Alzheimer’s disease; and 1.34 (1.21–1.50) and 1.90 (1.67–2.16) for vascular dementia. These associations were stronger in women and in midlife compared to later life in all dementia types. Women with a high Framingham-REGICOR score presented a similar risk of developing dementia — of any type — to women who had previous vascular disease, and at age 50–55, they showed three times higher risk of developing dementia risk compared to the lowest Framingham-REGICOR group.

Conclusions

We found a dose‒response association between the Framingham-REGICOR score and the onset of all dementia types. Poor cardiovascular health in midlife increased the onset of all dementia types later in life, especially in women.
Trade openness and structural change dynamics in West African countries
Authors: Chabi Patrick , Saygılı Refik Fatih
Published: March 2024

In this study, we investigate the contribution of trade openness to the structural change process in ECOWAS countries. Our findings suggest that the production structural change process is significantly and positively affected by the extent of trade openness. Higher openness levels are associated with more production reshuffling between sectors. However, this impact is found to be nonlinear. After a threshold of 147.64% of trade openness, the effect reverses. Considering the labor structural change, results suggest that more openness tends to trigger the reshuffle of labor toward less productive sectors. This effect reverses after the openness reached a level of 152.42%. Moreover, exports contract, whereas imports trigger the reshuffling of domestic production factors. So, focusing on industrial-friendly import policies should be a priority for ECOWAS Countries. For labor, exports as well as imports trigger the reshuffling of labor towards less productive sectors. These findings emphasize the importance of external effects in the structural change process in ECOWAS countries. Our analysis suggests that given the basic structure of export products, as long as their increases would fail to develop manufacturing sectors, their ability to shift labor towards more productive sectors would be limited. Also, as imports promote the retail sector, which is less productive, this limits their effect to trigger a desirable labor structural change.
Determinants of household food expenditure in Tanzania: implications on food security
Authors: Rashid Furaha Ndakije , Sesabo Jennifer K. , Lihawa Robert Michael , Mkuna Eliaza
Published: March 2024

Background

Food expenditure in developing countries particularly those in sub-Saharan Africa constitutes about 65–70% of total household expenditure. Existing literature on the determinants of household food expenditure in developing countries have mixed results. Thus, this study aimed at examining the determinants of household food expenditure in Tanzania and their implications on food security using country representative data from the 2017/18 household budget survey. The Two-Stage least squares (2SLS) regression analysis was used as method of analysis.

Results

Results show that, on average, monthly household food expenditure in Tanzania is about TZS 159,072.80(≈ US $ 69.2). Food expenditure exhibited a non-linear relationship with age of household head with income elasticity of 0.72%. Expenditure also increases with household size, household head sex, education, asset ownership, group membership and marital status while being located in rural areas is negatively associated with food expenditure.

Conclusions

To increase household’s food expenditure with dietary diversity for improved health, strategies aiming at improving household income, family planning, gender equity, education and social cohesion are important which will further increase household’s food security.
Statistical methods for assessing the effects of de novo variants on birth defects
Authors: Xie Yuhan , Wu Ruoxuan , Li Hongyu , Dong Weilai , Zhou Geyu , Zhao Hongyu
Published: March 2024

With the development of next-generation sequencing technology, de novo variants (DNVs) with deleterious effects can be identified and investigated for their effects on birth defects such as congenital heart disease (CHD). However, statistical power is still limited for such studies because of the small sample size due to the high cost of recruiting and sequencing samples and the low occurrence of DNVs. DNV analysis is further complicated by genetic heterogeneity across diseased individuals. Therefore, it is critical to jointly analyze DNVs with other types of genomic/biological information to improve statistical power to identify genes associated with birth defects. In this review, we discuss the general workflow, recent developments in statistical methods, and future directions for DNV analysis.
Climate-influenced vector-borne diseases in Africa: a call to empower the next generation of African researchers for sustainable solutions
Authors: Obame-Nkoghe Judicaël , Agossou Adjoavi Esse , Mboowa Gerald , Kamgang Basile , Caminade Cyril , Duke Dawn C. , Githeko Andrew Karanja , Ogega Obed M. , Engone Elloué Nestor , Sarr Fatou Bintou , Nkoghe Dieudonné , Kengne Pierre , Ndam Nicaise T. , Paupy Christophe , Bockarie Moses , Voua Otomo Patricks
Published: March 2024

We look at the link between climate change and vector-borne diseases in low- and middle-income countries in Africa. The large endemicity and escalating threat of diseases such as malaria and arboviral diseases, intensified by climate change, disproportionately affects vulnerable communities globally. We highlight the urgency of prioritizing research and development, advocating for robust scientific inquiry to promote adaptation strategies, and the vital role that the next generation of African research leaders will play in addressing these challenges. Despite significant challenges such as funding shortages within countries, various pan-African-oriented funding bodies such as the African Academy of Sciences, the Africa Research Excellence Fund, the Wellcome Trust, the U.S. National Institutes of Health, and the Bill and Melinda Gates Foundation as well as initiatives such as the African Research Initiative for Scientific Excellence and the Pan-African Mosquito Control Association, have empowered (or are empowering) these researchers by supporting capacity building activities, including continental and global networking, skill development, mentoring, and African-led research. This article underscores the urgency of increased national investment in research, proposing the establishment of research government agencies to drive evidence-based interventions. Collaboration between governments and scientific communities, sustained by pan-African funding bodies, is crucial. Through these efforts, African nations are likely to enhance the resilience and adaptive capacity of their systems and communities by navigating these challenges effectively, fostering scientific excellence and implementing transformative solutions against climate-sensitive vector-borne diseases.
Haptic interface with multimodal tactile sensing and feedback for human–robot interaction
Authors: Kang Mingyu , Gang Cheol-Gu , Ryu Sang-Kyu , Kim Hyeon-Ju , Jeon Da-Yeon , Pyo Soonjae
Published: March 2024

Novel sensing and actuation technologies have notably advanced haptic interfaces, paving the way for more immersive user experiences. We introduce a haptic system that transcends traditional pressure-based interfaces by delivering more comprehensive tactile sensations. This system provides an interactive combination of a robotic hand and haptic glove to operate devices within the wireless communication range. Each component is equipped with independent sensors and actuators, enabling real-time mirroring of user’s hand movements and the effective transmission of tactile information. Remarkably, the proposed system has a multimodal feedback mechanism based on both vibration motors and Peltier elements. This mechanism ensures a varied tactile experience encompassing pressure and temperature sensations. The accuracy of tactile feedback is meticulously calibrated according to experimental data, thereby enhancing the reliability of the system and user experience. The Peltier element for temperature feedback allows users to safely experience temperatures similar to those detected by the robotic hand. Potential applications of this system are wide ranging and include operations in hazardous environments and medical interventions. By providing realistic tactile sensations, our haptic system aims to improve both the performance and safety of workers in such critical sectors, thereby highlighting the great potential of advanced haptic technologies.
No substantive effects of school socioeconomic composition on student achievement in Australia: a response to Sciffer, Perry and McConney
Authors: Marks Gary N.
Published: March 2024

In this journal, Sciffer et al. (Large-scale Assessments in Education 10:1–22, 2022), hereafter SP&M, conclude that school socioeconomic compositional (SEC) or school socioeconomic status (school-SES) effects in Australia are substantial and substantively important for research and policy. This paper demonstrates that these claims are unwarranted. Their SEC estimates are much larger than estimates from comparable studies and a metastudy. Despite plausible theoretical reasons and empirical evidence, SP&M do not consider that school academic composition is a significant predictor of student achievement independent of SEC. SEC effects are confounded by academic composition and are typically trivial when considering academic composition. The second part of this paper compares SP&M’s estimates with analysis of the same data, from the Australian National Assessments in Performance—Literacy and Numeracy (NAPLAN). In a model corresponding to SP&M analyses comprising demographics, SES, school-SES, and student-level prior achievement, the effects of school-SES are small, with standardized effects mostly less than 0.10. With the addition of academic composition measured by school-level prior achievement, school-SES effects are effectively zero. In contrast, academic composition has significant, albeit small, impacts on student achievement. Therefore, contrary to SP&M’s (2022) conclusion, school-SES effects on student achievement in NAPLAN are negligible, whereas school-level prior achievement has small effects. That is not to say that school-SES is always irrelevant, but any assessment of its importance must consider both student- and school-level prior achievement.
Innovative approach for semi‐continuous production of puerarin palmitate via transesterification with novel immobilized lipase
Authors: Lee Hyeseon , Yang Eunjeong , Kwon Hyeok Ki , Kim Bo Kyeong , Lee Taek , Yoo Hah Young , Park Chulhwan
Published: March 2024

Background

Puerarin, a flavonoid abundantly found in the roots of Pueraria lobata, exhibits antioxidant, anti-cancer, anti-inflammatory, and anti-aging properties. Despite its numerous benefits, the low bioavailability of puerarin hinders its widespread industrial application. To improve this, flavonoid acylation is required. Lipase is a biocatalyst primarily used for flavonoid acylation; immobilized lipase is preferred given the limited stability of free lipase. Although research on flavonoid acylation for structural modification is actively being conducted, there is a need to explore continuous production for enhancing the industrial application of flavonoid esters. Therefore, in this study, we aimed to produce puerarin palmitate innovatively by selecting an effective lipase, developing an immobilized lipase, characterizing the enzymatic reaction, and designing a semi-continuous reactor system.

Results

Lipase from Thermomyces lanuginosus (TL) was found to be the most suitable for the synthesis of puerarin palmitate; it was successfully immobilized on glutaraldehyde-activated silica gel (GASG). TL GASG showed greater solvent, thermal, and operational stability than those of commercial immobilized lipases. Furthermore, TL GASG use resulted in a puerarin palmitate conversion rate of 97.17% within 3 h. Additionally, the reusability of TL GASG for this reaction was higher than that of commercially available immobilized lipases. Upon using a semi-continuous reactor, the cumulative conversion rate of puerarin palmitate remained above 85% after more than ten substrate injections.

Conclusions

The results support the feasibility of the continuous production of flavonoid esters, underscoring their diverse industrial applications. A biorefinery strategy is anticipated to be proposed to utilize P. lobata extract biomass for flavonoid ester production. Moreover, optimizing continuous reactors through statistical experimental design is expected to enhance flavonoid ester production efficiency; these aspects will be explored in future research.

Graphical Abstract