bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hormone replacement therapy on amyloid beta (Aβ) plaque density in the rhesus macaque amygdala
Authors: Appleman Maria-Luisa , Thomas Jeremy L. , Weiss Alison R. , Nilaver Benjamin I. , Cervera-Juanes Rita , Kohama Steven G. , Urbanski Henryk F.
Published: January 2024

Background

Amyloid beta (Aβ) plaque density was examined in the amygdala of rhesus macaques, to elucidate the influence of age, diet and hormonal environment.

Methods

Luminex technology was used to measure cerebrospinal fluid (CSF) concentrations of Aβ40 and Aβ42 across three decades, while immunohistochemistry was used to examine Aβ plaque density in the amygdala.

Results

Aβ40 was found to be the predominant isoform of Aβ in the CSF, but neither Aβ40 or Aβ42 concentrations showed an age-related change, and the ratio of Aβ42 to Aβ40 showed only a marginal increase. Significantly fewer Aβ plaques were detected in the amygdala of old ovariectomized animals if they received estradiol HRT (p < 0.001); similar results were obtained regardless of whether they had been maintained on a regular monkey chow for ∼48 months or on a high-fat, high-sugar, Western-style diet for ∼30 months.

Conclusion

The results demonstrate that HRT involving estrogen can reduce Aβ plaque load in a cognitive brain region of aged non-human primates. The results from this translational animal model may therefore have clinical relevance to the treatment of AD in post-menopausal women, whether used alone, or as a supplement to current pharmacological and monoclonal antibody-based interventions.
Estimating dementia risk in an African American population using the DCTclock
Authors: Ciesla Marissa , Pobst Jeff , Gomes-Osman Joyce , Lamar Melissa , Barnes Lisa L. , Banks Russell , Jannati Ali , Libon David , Swenson Rodney , Tobyne Sean , Bates David , Showalter John , Pascual-Leone Alvaro
Published: January 2024

The prevalence of Alzheimer’s disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer’s Disease Research Center Minority Aging Research Study (MARS) and African American Clinical Core (AACORE). We assessed baseline DCTclock scores in 646 participants (baseline median age = 78.0 ± 6.4, median years of education = 14.0 ± 3.2, 78% female) and found significantly lower baseline DCTclock scores in those who received a dementia diagnosis within 3 years. We also found that 16.4% of participants with a baseline DCTclock score less than 60 were significantly more likely to develop dementia in 5 years vs. those with the highest DCTclock scores (75–100). This research demonstrates the DCTclock’s ability to estimate the 5-year risk of developing dementia in an African American population. Early detection of elevated dementia risk using the DCTclock could provide patients, caregivers, and clinicians opportunities to plan and intervene early to improve cognitive health trajectories. Early detection of dementia risk can also enhance participant selection in clinical trials while reducing screening costs.
The effect of complex cognitive context on the dynamic stability during gait initiation in older women
Authors: Chen Yuxia , Tang Hongyuan , Wang Yuanxin , Jin Chunxia , Wang Lihong , Miao Wensheng , Wang Xiangdong
Published: January 2024

Background

Changes in cognitive control are considered potential factors affecting voluntary motor movements during gait initiation (GI). Simulating environments with higher cognitive resource demands have an effect on the stability of GI task performance, which is of significant importance for assessing fall risk in the older adults and devising fall risk management measures in multiple environments. This study aims to reveal the influence of complex cognitive competitive environment with increased cognitive demands on the dynamic stability during GI in the older women.

Methods

Twenty-three older females and twenty-three younger females performed walking tests under three conditions: voluntary initiation (SI), visual light reaction time task (LRT), and cognitive interference + visual light reaction time task (C + LRT). Eight cameras (Qualisys, Sweden, model: Oqus 600) and three force plates (Kistler, Switzerland, model: 9287C) are used to obtain kinematic and kinetic data. To recorde the trajectory of center of pressure (CoP) and the position of the foot placement, and compute the anterior–posterior (A-P) and medio-lateral (M-L) dynamic stability at the onset and end moments of the single-leg support by means of center of mass (CoM) and gait spatiotemporal parameters.

Results

Older women responded to the effect of complex environments involving cognitive competition on body stability by prolonging the lateral displacement time of the CoP during the anticipatory postural adjustments (APAs) phase, reducing step length and velocity, and increasing step width and foot inclination angle.

Conclusion

Complex initiation environments lead to competition for cognitive resources in the brain, resulting in decreased stability of GI motor control in older adults. The higher the complexity of the cognitive resource demands environment, the lower the stability of GI in older adults, and the greater the effect on their M-L stability at the onset of stepping.
Hippocampal neurogenesis facilitates cognitive flexibility in a fear discrimination task
Authors: Martínez-Canabal Alonso , López-Oropeza Grecia , Sotres-Bayón Francisco
Published: January 2024

Hippocampal neurogenesis, the continuous creation of new neurons in the adult brain, influences memory, regulates the expression of defensive responses to threat (fear), and cognitive processes like pattern separation and behavioral flexibility. One hypothesis proposes that neurogenesis promotes cognitive flexibility by degrading established memories and promoting relearning. Yet, empirical evidence on its role in fear discrimination tasks is scarce. In this study, male rats were initially trained to differentiate between two similar environments, one associated with a threat. Subsequently, we enhanced neurogenesis through environmental enrichment and memantine treatments. We then reversed the emotional valence of these contexts. In both cases, neurogenesis improved the rats’ ability to relearn the aversive context. Interestingly, we observed increased hippocampal activity, and decreased activity in the prelimbic cortex and lateral habenula, while the infralimbic cortex remained unchanged, suggesting neurogenesis-induced plasticity changes in this brain network. Moreover, when we pharmacologically inhibited the increased neurogenesis with Methotrexate, rats struggled to relearn context discrimination, confirming the crucial role of neurogenesis in this cognitive process. Overall, our findings highlight neurogenesis’s capacity to facilitate changes in fear discrimination and emphasize the involvement of a prefrontal-hippocampal-habenula mechanism in this process. This study emphasizes the intricate relationship between hippocampal neurogenesis, cognitive flexibility, and the modulation of fear-related memories.
Diagnostic challenges of neurosarcoidosis in non-endemic areas
Authors: Shrestha Keshari , Kleinschmidt-DeMasters B. K. , Ormond D. Ryan
Published: January 2024

Background

Neurosarcoidosis (NS) is a challenging diagnosis, particularly when cases occur in low-prevalence, non-endemic geographic regions. In the United States, the highest incidence is in the Midwest and Northeast, compared to our Southwest location. While it is well known that NS may clinically and neuroradiographically mimic meningeal carcinomatosis, autoimmune or infectious pachymeningitis, neurosyphilis, or tuberculosis, diagnosis may be particularly challenging if systemic signs of sarcoidosis are lacking or unconfirmed or if dural-based masses are present. We reviewed our Colorado experience with NS cases, focusing our study on cases where NS represented the first histological confirmation of disease.

Methods

A search of departmental databases was conducted with the search term “neurosarcoidosis” to identify cases 1-2008 to 12-2019, inclusive of the given case numbers. Patients were only included if their clinical and neuroimaging features were unusual and only when a biopsy of the central nervous system (CNS) represented the first confirmed diagnosis of sarcoidosis.

Results

A total of 17 cases were identified, of which the biopsy of the CNS was used for the initial confirmation of the disease in 9 of them. The most unusual findings were two patients with dural-based masses, one of which had pure NS as the cause of meningioma-like lesions and the second of which had coexistent meningioma and intimately admixed non-necrotizing granulomas of NS.

Conclusion

NS with unusual features, especially in non-endemic areas, continues to yield diagnostic challenges for neurologists, neuroradiologists, and pathologists.
Influence of mild cognitive impairment on clinical and functional prognosis in older candidates for cardiac surgery
Authors: Harmand Magali González-Colaço , Mata María , Prada-Arrondo Pablo César , Domínguez-Rodríguez Alberto , Barroso José , Galtier Ivan
Published: January 2024

Introduction

In this study, we analyzed the prognostic impact of mild cognitive impairment (MCI) prior to cardiac surgery on 12-month clinical outcomes in older patients.

Method

We performed a longitudinal prospective study of 48 patients undergoing cardiac surgery and 26 neurologically healthy participants aged 65 years or older. All participants underwent a neuropsychological assessment. Functional status, quality of life and frailty were assessed in candidates for surgery. One year after surgery, 24 patients remained in the study.

Results

Mild cognitive impairment (MCI) was diagnosed in 35% of the patients at baseline. Postsurgical changes in functionality consisted of a tendency toward impaired basic activities of daily living (BADL) in the MCI group and a statistically significant worsening in instrumental activities of daily living (IADL) in women with MCI. Changes in quality of life consisted of a significant improvement in anxiety-depression in the MCI group and a tendency toward greater pain-discomfort in the non-MCI group. Cognitive status significantly declined only in the non-MCI group. Neither group showed significant changes in frailty. Relative risk analysis showed that patients with a diagnosis of MCI at baseline had a higher risk of cognitive decline at follow-up, while those without a diagnosis of MCI at baseline had a lower risk of impaired IADL. No association was found between MCI and resource use. Preoperative impairment in memory, visuospatial and executive functions was significantly associated with loss of quality of life at follow-up. Impairment of memory and visuospatial function was significantly associated with cognitive decline. Preserved memory was associated with a lower risk of impaired BADL at follow-up.

Conclusion

The present study provides clue on the impact of MCI in candidates for cardiac surgery. Preoperative detection of cognitive impairment could be highly valuable to help guide pre- and post-operative management.
Alterations of spontaneous brain activity in type 2 diabetes mellitus without mild cognitive impairment: a resting-state functional magnetic resonance study
Authors: Wang Qianru , Hou Chuanke , Jiang Xingyuan , Li Hongjun
Published: January 2024

Background

Type 2 diabetes mellitus (T2DM) has been demonstrated an increased risk factor of cognitive impairment or even dementia. Kinds of resting-state functional magnetic resonance imaging indices have been proposed and used to investigate the brain mechanism underlying diabetic cognitive impairment. This study aimed to explore the early changes in spontaneous neural activity among T2DM patients without cognitive impairment by means of multiple rs-fMRI indices.

Methods

T2DM patients without cognitive impairment and age-, sex-, and education matched control subjects were included in this study. Three rs-fMRI indices, namely amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC) were computed after image pre-processing. The Montreal Cognitive Assessment (MoCA) was performed to distinguish normal cognition. Brain volume was also evaluated. Correlation analyses were conducted to explore any relationship among rs-fMRI indices and clinical characteristics.

Results

The T2DM patients were detected significantly decreased neural activity in right angular and left prefrontal gyrus including middle and superior frontal gyrus. Increased activities were also observed in left caudate and the supplementary motor area. No correlation between rs-fMRI indices and clinical characteristics was survived after multiple comparison correction. But we observed a significant, but decreased correlation between ALFF and ReHo values in the reported brain areas.

Conclusion

The combination of ALFF, ReHo and VMHC analyses demonstrated abnormal spontaneous neural activity in brain regions which were reported in T2DM patients without cognitive impairment. These results may enhance our understanding of the diabetic brain changes at the early stage.
Siamese model for collateral score prediction from computed tomography angiography images in acute ischemic stroke
Authors: Fortunati Valerio , Su Jiahang , Wolff Lennard , van Doormaal Pieter-Jan , Hofmeijer Jeanette , Martens Jasper , Bokkers Reinoud P. H. , van Zwam Wim H. , van der Lugt Aad , van Walsum Theo
Published: January 2024

Introduction

Imaging biomarkers, such as the collateral score as determined from Computed Tomography Angiography (CTA) images, play a role in treatment decision making for acute stroke patients. In this manuscript, we present an end-to-end learning approach for automatic determination of a collateral score from a CTA image. Our aim was to investigate whether such end-to-end learning approaches can be used for this classification task, and whether the resulting classification can be used in existing outcome prediction models.

Methods

The method consists of a preprocessing step, where the CTA image is aligned to an atlas and divided in the two hemispheres: the affected side and the healthy side. Subsequently, a VoxResNet based convolutional neural network is used to extract features at various resolutions from the input images. This is done by using a Siamese model, such that the classification is driven by the comparison between the affected and healthy using a unique set of features for both hemispheres. After masking the resulting features for both sides with the vascular region and global average pooling (per hemisphere) and concatenation of the resulting features, a fully connected layer is used to determine the categorized collateral score.

Experiments

Several experiments have been performed to optimize the model hyperparameters and training procedure, and to validate the final model performance. The hyperparameter optimization and subsequent model training was done using CTA images from the MR CLEAN Registry, a Dutch multi-center multi-vendor registry of acute stroke patients that underwent endovascular treatment. A separate set of images, from the MR CLEAN Trial, served as an external validation set, where collateral scoring was assessed and compared with both human observers and a recent more traditional model. In addition, the automated collateral scores have been used in an existing functional outcome prediction model that uses both imaging and non-imaging clinical parameters.

Conclusion

The results show that end-to-end learning of collateral scoring in CTA images is feasible, and does perform similar to more traditional methods, and the performance also is within the inter-observer variation. Furthermore, the results demonstrate that the end-to-end classification results also can be used in an existing functional outcome prediction model.
Post-translational modification and mitochondrial function in Parkinson’s disease
Authors: Luo Shishi , Wang Danling , Zhang Zhuohua
Published: January 2024

Parkinson’s disease (PD) is the second most common neurodegenerative disease with currently no cure. Most PD cases are sporadic, and about 5–10% of PD cases present a monogenic inheritance pattern. Mutations in more than 20 genes are associated with genetic forms of PD. Mitochondrial dysfunction is considered a prominent player in PD pathogenesis. Post-translational modifications (PTMs) allow rapid switching of protein functions and therefore impact various cellular functions including those related to mitochondria. Among the PD-associated genes, Parkin, PINK1, and LRRK2 encode enzymes that directly involved in catalyzing PTM modifications of target proteins, while others like α-synuclein, FBXO7, HTRA2, VPS35, CHCHD2, and DJ-1, undergo substantial PTM modification, subsequently altering mitochondrial functions. Here, we summarize recent findings on major PTMs associated with PD-related proteins, as enzymes or substrates, that are shown to regulate important mitochondrial functions and discuss their involvement in PD pathogenesis. We will further highlight the significance of PTM-regulated mitochondrial functions in understanding PD etiology. Furthermore, we emphasize the potential for developing important biomarkers for PD through extensive research into PTMs.
A comprehensive review of Cornus officinalis: health benefits, phytochemistry, and pharmacological effects for functional drug and food development
Authors: Deng Wenhui , Liu Yuchen , Guo Yaodong , Chen Jie , Abdu Hassan Idris , Khan Muhmmad R. U. , Palanisamy Chella Perumal , Pei Jinjin , Abd El-Aty A. M.
Published: January 2024

Introduction

Cornus officinalis sieb. et zucc, a deciduous tree or shrub, is renowned for its “Cornus flesh” fruit, which is widely acknowledged for its medicinal value when matured and dried. Leveraging C. officinalis as a foundational ingredient opens avenues for the development of environmentally friendly health foods, ranging from beverages and jams to preserves and canned products. Packed with diverse bioactive compounds, this species manifests a spectrum of pharmacological effects, including anti-inflammatory, antioxidant, antidiabetic, immunomodulatory, neuroprotective, and cardiovascular protective properties.

Methods

This study employs CiteSpace visual analysis software and a bibliometric analysis platform, drawing upon the Web of Science (WOS) database for literature spanning the last decade. Through a comprehensive analysis of available literature from WOS and Google Scholar, we present a thorough summary of the health benefits, phytochemistry, active compounds, and pharmacological effects of C. officinalis. Particular emphasis is placed on its potential in developing functional drugs and foods.

Results and Discussion

While this review enhances our understanding of C. officinalis as a prospective therapeutic agent, its clinical applicability underscores the need for further research and clinical studies to validate findings and establish safe and effective clinical applications.
Pathogen presence, prevalence, and diversity in Ixodes scapularis and mammal hosts at their expanding northern range limits
Authors: Crandall Kirsten E. , Kerr Jeremy T. , Millien Virginie
Published: January 2024

With climate and land use changes, tick-borne pathogens are expected to become more widely distributed in Canada. Pathogen spread and transmission in this region is modulated by changes in the abundance and distribution of tick and host populations. Here, we assessed the relationships between pathogens detected in Ixodes scapularis and mammal hosts at sites of different levels of disease risk using data from summer field surveys in Ontario and Quebec, Canada. Generalized linear mixed models and ordinal logistic regressions were used to determine the influence of the abundance of I. scapularis and the abundance and diversity of mammal hosts on pathogen presence, prevalence, and diversity. We detected three pathogen species in I. scapularis and small mammals using nested PCRs, namely Borrelia burgdorferi sensu stricto, Babesia odocoilei, and Babesia microti. Depending on the analyzed pathogen, local infection prevalence ranged from 0% to 25.4% in questing ticks and from 0% to 16.7% in small mammal hosts. We detected B. odocoilei in localities beyond its known range limits in southeastern Quebec suggesting ongoing range expansion of this pathogen. Neither the abundance of I. scapularis nor the abundance and diversity of mammal hosts altered local pathogen presence and prevalence, contrary to expectations. However, mammal species richness was a key predictor of the number of pathogen species. Our study demonstrates the need for future surveillance efforts that test questing and feeding I. scapularis of all life stages, as well as their hosts to better determine the spread, transmission, and co-occurrence of tick-borne pathogens in Canada.
Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase
Authors: Rehan Mohd , Ahmed Firoz , Khan Mohammad Imran , Ansari Hifzur Rahman , Shakil Shazi , El-Araby Moustafa E. , Hosawi Salman , Saleem Mohammad
Published: January 2024

The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR. Catechins, characterized by two chiral centers and stereoisomerism, demonstrate variations in chemical and physical properties due to differences in the spatial orientation of atoms. Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored. In this study, we investigated the stereo-selectivity of catechins in inhibiting EGFR kinase, both in its wild-type and in the prevalent L858R mutant. Computational analyses indicated that all stereoisomers, including the extensively studied catechin (−)-EGCG, effectively bound within the ATP-binding site, potentially inhibiting EGFR kinase activity. Notably, gallated catechins emerged as superior EGFR inhibitors to their non-gallated counterparts, revealing intriguing binding trends. The top four stereoisomers exhibiting high dock scores and binding energies with wild-type EGFR comprise (−)-CG (−)-GCG (+)-CG, and (−)-EGCG. To assess dynamic behavior and stability, molecular dynamics simulations over 100 ns were conducted for the top-ranked catechin (−)-CG and the widely investigated catechin (−)-EGCG with EGFR kinase. This study enhances our understanding of how the stereoisomeric nature of a drug influences inhibitory potential, providing insights that could guide the selection of specific stereoisomers for improved efficacy inexisting drugs.
Tumor risks of finerenone in patients with type 2 diabetes mellitus complicated with chronic kidney disease: a meta-analysis and systematic review of randomized controlled trials
Authors: Du Yue , Cao Gui , Gu Linlin , Chen Yuehong , Liu Jingyu
Published: January 2024

Introduction: This study aimed to assess the tumor risk of finerenone in individuals with type 2 diabetes mellitus (T2DM) aggravated by chronic kidney disease (CKD).

Methods: A thorough search in the OVID Medline, OVID EMBASE, and Cochrane Library databases from their creation through 2 November 2022 yielded randomized controlled trials (RCTs) reporting on the tumor risks of finerenone in patients with T2DM complicated with CKD. A pair of reviewers selected the relevant studies based on selection criteria, collected data, and assessed the methodological quality of eligible RCTs. The Peto odds ratio (OR) with a 95% confidence interval (CI) was calculated, and subgroup analysis of tumor nature, tumor origin system, tumor origin organ, and follow-up time was performed. Furthermore, Egger’s test was implemented to determine publication bias.

Results: Four RCTs with 14,875 participants who had a low-to-moderate risk of bias were included. Compared with placebo treatment, finerenone did not increase the risk of overall neoplasms (Peto OR = 0.97; 95% CI, 0.83–1.14), malignant neoplasms (Peto OR = 1.03; 95% CI, 0.86–1.23), benign neoplasms (Peto OR = 0.94; 95% CI, 0.50–1.80), or in situ neoplasms (Peto OR = 0.14; 95% CI, 0.01–2.17). Subgroup analysis of the tumor origin system showed that finerenone was associated with an increased risk of malignant neoplasms of urinary tract compared with placebo treatment (Peto OR = 1.69; 95% CI, 1.07–2.67). The results were found to be robust in sensitivity analysis, and there was no indication of publication bias.

Discussion: Finerenone is not associated with an increased risk of overall tumors, but it may be linked to an increased risk of malignant neoplasms in urinary tract. Additional well-planned cohort studies in larger research populations are needed to corroborate these findings.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022374101, Identifier CRD42022374101.
Comparative price analysis of biological medicines: disparities generated by different pricing policies
Authors: Pontes Marcela Amaral , Ribeiro Alane Andrelino , Albuquerque Flávia Caixeta , Leite Cotenzini Silvana Nair
Published: January 2024

Introduction: Biological medicines have been assuming an important role among the therapeutic options for several diseases, however, due to their complex production process, the products obtained from this technology have a high added value and do not reach the purchasing power of most patients, which overwhelms the budget of health systems. With the development of biosimilars, which have reduced production costs, it is expected that access to biological medicines will become broader. However, in Brazil, the criteria for determining the price of biosimilars, unlike the generic policy in the country, do not foresee a price reduction due to the reduction of development costs.

Objective: To understand the impact of the current model of economic regulation on the availability and access of these products in the country, based on a comparative analysis in selected countries, and identify trends that can help to expand the availability and access to biological medicines.

Method: Quantitative and qualitative study, to identify the variation between the entry prices of biological medicines in Brazil and in selected countries, as well as the differences in the economic regulation policies established in these countries.

Results: The results demonstrate that the current pricing model in Brazil has generated distortions in the prices of biosimilars in the market, which, consequently, makes it difficult for the population to access this category of products, in addition to allowing unsustainable market practices for the systems of public and private health in Brazil. It was also found that most of the analyzed countries, unlike Brazil, seek to harmonize the prices of different brands of the same molecule marketed in the country and with the international market, in addition to establishing incentive policies for indication and replacement by biosimilars, which expands the participation of biosimilars in the market significantly.

Conclusion: Based on the data presented, it is concluded that it is essential to build a broader political and regulatory debate on the market for biologicals and biosimilars in the country to guarantee the access of the Brazilian population to more cost-effective technologies, generate a more competitive market and consequently contribute to the financial sustainability of health systems.
Efficacy of inhaled nitric oxide in preterm infants ≤ 34 weeks: a systematic review and meta—analysis of randomized controlled trials
Authors: Feng Zhoushan , Wu Xiaohong , Xu Xiaona , Cui Qiliang , Wu Fan
Published: January 2024

Background: The effect of inhaled nitric oxide (iNO) in neonates >34 weeks on improving respiration is well documented. However, the efficacy of iNO in preterm infants ≤34 weeks remains controversial.

Objectives: The main purpose of this review is to assess the effectiveness and safety of iNO treatment in preterm infants ≤34 weeks.

Search methods: We systematically searched PubMed, Embase and Cochrane Libraries from their inception to 1 June 2023. We also reviewed the reference lists of retrieved studies.

Selection criteria: Our study involved randomized controlled trials on preterm infants ≤34 weeks, especially those receiving iNO treatment, and mainly assessed outcomes such as bronchopulmonary dysplasia (BPD) and mortality. Two authors independently reviewed these trials, extracted data, and evaluated study biases. Disagreements were resolved by consensus. We used the GRADE method to assess evidence quality.

Results: Our research included a total of 17 studies involving 4,080 neonates and 7 follow-up studies. The synthesis of results showed that in neonates, iNO treatment reduced the incidence of BPD (RR: 0.92; 95% CI: 0.86–0.98). It also decreased the composite outcome of death or BPD (RR: 0.94; 95% CI: 0.90–0.98), without increasing the risk of short-term (such as intraventricular hemorrhage, periventricular leukomalacia) and long-term neurological outcomes (including Bayley mental developmental index <70, cerebral palsy and neurodevelopmental impairment). Furthermore, iNO did not significantly affect other neonatal complications like sepsis, pulmonary hemorrhage, necrotizing enterocolitis, and symptomatic patent ductus arteriosus. Subgroup analysis revealed that iNO significantly reduced BPD incidence in neonates at 36 weeks under specific intervention conditions, including age less than 3 days, birth weight over 1,000 g, iNO dose of 10 ppm or higher, or treatment duration exceeding 7 days (p < 0.05).

Conclusion: Inhaled NO reduced the incidence of BPD in neonates at 36 weeks of gestation, and the effect of the treatment depended on neonatal age, birth weight, duration and dose of iNO. Therefore, iNO can be considered a promising treatment for the potential prevention of BPD in premature infants. More data, however, would be needed to support nitric oxide registration in this specific patient population, to minimize its off-label use.
Preparation and activity study of Ruoqiang jujube polysaccharide copper chelate
Authors: Moheteer Aierpati , Li Jianlong , Abulikemu Xireli , Lakho Shakeel Ahmed , Meng Yan , Zhang Jiayi , Khand Faiz Muhammad , Leghari Ambreen , Abula Saifuding , Guo Qingyong , Liu Dandan , Mai Zhanhai , Tuersong Waresi , Wusiman Adelijiang
Published: January 2024

Background: Polysaccharide metal chelate exhibit both immunoregulatory activity and metal element supplementation effects.

Methods: In this study, Ruoqiang jujube polysaccharide copper chelate (RJP-Cu) was prepared and the preparation conditions were optimized using the response surface method. Subsequently, RJP-Cu was administered to lambs to evaluate its impact on growth performance, copper ion (Cu2+) supplementation, immune enhancement, and intestinal flora was evaluated.

Results: The results indicated that optimal RJP-Cu chelation conditions included a sodium citrate content of 0.5 g, a reaction temperature of 50°C, and a solution pH of 8.0, resulting in a Cu2+ concentration of 583°mg/kg in RJP-Cu. Scanning electron microscopy (SEM) revealed significant structural changes in RJP before and after chelation. RJP-Cu displaying characteristic peaks of both polysaccharides and Cu2+ chelates. Blood routine indexes showed no significant differences among the RJP-Cu-High dose group (RJP-Cu-H), RJP-Cu-Medium dose group (RJP-Cu-M), RJP-Cu-low dose group (RJP-Cu-L) and the control group (p > 0.05). However, compared with the control group, the RJP-Cu-H, M, and L dose groups significantly enhanced lamb production performance (p < 0.05). Furthermore, RJP-Cu-H, M, and L dose groups significantly increased serum Cu2+ concentration, total antioxidant capacity (T-AOC), catalase (CAT), and total superoxide dismutase (T-SOD) contents compared with control group (p < 0.05). The RJP-Cu-H group exhibited significant increases in serum IgA and IgG antibodies, as well as the secretion of cytokines IL-2, IL-4, and TNF-α compared to the control group (p < 0.05). Furthermore, RJP-Cu-H group increased the species abundance of lamb intestinal microbiota, abundance and quantity of beneficial bacteria, and decrease the abundance and quantity of harmful bacteria. The RJP-Cu-H led to the promotion of the synthesis of various Short Chain Fatty Acids (SCFAs), improvements in atrazine degradation and clavulanic acid biosynthesis in lambs, while reducing cell apoptosis and lipopolysaccharide biosynthesis.

Conclusion: Thus, these findings demonstrate that RJP-Cu, as a metal chelate, could effectively promote lamb growth performance, increase Cu2+ content, and potentially induce positive immunomodulatory effects by regulating antioxidant enzymes, antibodies, cytokines, intestinal flora, and related metabolic pathways.
Hypergraph patterns and collaboration structure
Authors: Juul Jonas L. , Benson Austin R. , Kleinberg Jon
Published: January 2024

Humans collaborate in different contexts such as in creative or scientific projects, in workplaces and in sports. Depending on the project and external circumstances, a newly formed collaboration may include people that have collaborated before in the past, and people with no collaboration history. Such existing relationships between team members have been reported to influence the performance of teams. However, it is not clear how existing relationships between team members should be quantified, and whether some relationships are more likely to occur in new collaborations than others. Here we introduce a new family of structural patterns, m-patterns, which formalize relationships between collaborators and we study the prevalence of such structures in data and a simple random-hypergraph null model. We analyze the frequency with which different collaboration structures appear in our null model and show how such frequencies depend on size and hyperedge density in the hypergraphs. Comparing the null model to data of human and non-human collaborations, we find that some collaboration structures are vastly under- and overrepresented in empirical datasets. Finally, we find that structures of scientific collaborations on COVID-19 papers in some cases are statistically significantly different from those of non-COVID-19 papers. Examining citation counts for 4 different scientific fields, we also find indications that repeat collaborations are more successful for 2-author scientific publications and less successful for 3-author scientific publications as compared to other collaboration structures.
Research on the influence of gas ionization on pulse forming in linear transformer driver (LTD) electron beam generator
Authors: Li Qiang , Liu Dagang , Xiang Fei , Liu Laqun , Wang Huihui
Published: January 2024

Currently, there is limited research on the influence of gas ionization on the pulse formation process in pulse power source-driven loads. This paper introduces a road-field-Particle-In-Cell (PIC)/Monte Carlo Collision (MCC) collaborative simulation method that can accurately simulate gas ionization in Linear Transformer Driver (LTD) electron beam generation (EBG). The method couples the electromagnetic field and charged particle simulated through PIC/MCC with the circuit modules, and the load's voltammetry characteristics can real-time feedback to the Blumlein Pulse Forming Network (BPFN) of the LTD. In contrast to prior simulations that used fitted ideal T-shaped pulse input waveforms to model the load, this method provides a clearer depiction of the influence of gas ionization on the pulse shape. Additionally, the paper conducts simulation studies on LTD electron beam generator operating at different argon gas pressures. The findings indicate that introducing gas can effectively increase current while reducing voltage amplitude, thereby lowering the diode impedance. A small amount of gas can slightly enhance peak power, but excessive gas diminishes peak power and significantly shortens voltage pulse width. This is attributed to the beneficial effect of a small amount of gas ionization-produced plasma on the device. However, an excessive amount of gas ionization-generated plasma can lead to impedance mismatch in the device, even resulting in a load short circuit. This phenomenon causes a decrease in pressure drop at the top, consequently shortening the pulse width.
Data-limited and imbalanced bladder wall segmentation with confidence map-guided residual networks via transfer learning
Authors: Wang Mingqing , Yang Ruijie
Published: January 2024

Purpose: To develop an algorithm using a residual base network guided by the confidence map and transfer learning for limited dataset size and imbalanced bladder wall segmentation.

Methods: The geometric transformation was made to the training data for data augmentation, and a pre-trained Resnet50 model on ImageNet was also adopted for transfer learning. Three loss functions were put into the pre-trained Resnet50 network, they are the cross-entropy loss function (CELF), the generalized Dice loss function (GDLF) and the Tversky loss function (TLF). Three models were obtained through training, and three corresponding confidence maps were output after entering a new image. By selecting the point with the maximum confidence values at the corresponding position, we merged the three images into one figure, performed threshold filtering to avoid external anomalies, and finally obtained the segmentation result.

Results: The average Jaccard similarity coefficient of model training based on the CELF, GDLF and TLF is 0.9173, 0.8355, 0.8757, respectively, and the average Jaccard similarity coefficient of our algorithm can be achieved at 0.9282. In contrast, the classical 2D U-Net algorithm can only achieve 0.518. We also qualitatively give the reasons for the improvement of model performance.

Conclusion: Our study demonstrates that a confidence map-assisted residual base network can accurately segment bladder walls on a limited-size data set. Compared with the segmentation results of each model alone, our method originally improves the accuracy of the segmentation results by combining confidence map guidance with threshold filtering.
Integration of genome-wide association studies, metabolomics, and transcriptomics reveals phenolic acid- and flavonoid-associated genes and their regulatory elements under drought stress in rapeseed flowers
Authors: Salami Maryam , Heidari Bahram , Batley Jacqueline , Wang Jin , Tan Xiao-Li , Richards Christopher , Tan Helin
Published: January 2024

Introduction

Biochemical and metabolic processes help plants tolerate the adverse effects of drought. In plants accumulating bioactive compounds, understanding the genetic control of the biosynthesis of biochemical pathways helps the discovery of candidate gene (CG)–metabolite relationships.

Methods

The metabolic profile of flowers in 119 rapeseed (Brassica napus) accessions was assessed over two irrigation treatments, one a well-watered (WW) condition and the other a drought stress (DS) regime. We integrated information gained from 52,157 single-nucleotide polymorphism (SNP) markers, metabolites, and transcriptomes to identify linked SNPs and CGs responsible for the genetic control of flower phenolic compounds and regulatory elements.

Results

In a genome-wide association study (GWAS), of the SNPs tested, 29,310 SNPs were qualified to assess the population structure and linkage disequilibrium (LD), of which several SNPs for radical scavenging activity (RSA) and total flavanol content (TFLC) were common between the two irrigation conditions and pleiotropic SNPs were found for chlorogenic and coumaric acids content. The principal component analysis (PCA) and stepwise regression showed that chlorogenic acid and epicatechin in WW and myricetin in DS conditions were the most important components for RSA. The hierarchical cluster analysis (HCA) showed that vanillic acid, myricetin, gallic acid, and catechin were closely associated in both irrigation conditions. Analysis of GWAS showed that 60 CGs were identified, of which 18 were involved in stress-induced pathways, phenylpropanoid pathway, and flavonoid modifications. Of the CGs, PAL1, CHI, UGT89B1, FLS3, CCR1, and CYP75B137 contributed to flavonoid biosynthetic pathways. The results of RNA sequencing (RNA-seq) revealed that the transcript levels of PAL, CHI, and CYP75B137 known as early flavonoid biosynthesis-related genes and FLS3, CCR1, and UGT89B1 related to the later stages were increased during drought conditions. The transcription factors (TFs) NAC035 and ERF119 related to flavonoids and phenolic acids were upregulated under drought conditions.

Discussion

These findings expand our knowledge on the response mechanisms to DS, particularly regarding the regulation of key phenolic biosynthetic genes in rapeseed. Our data also provided specific linked SNPs for marker-assisted selection (MAS) programs and CGs as resources toward realizing metabolomics-associated breeding of rapeseed.
Genomic prediction reveals unexplored variation in grain protein and lysine content across a vast winter wheat genebank collection
Authors: Berkner Marcel O. , Weise Stephan , Reif Jochen C. , Schulthess Albert W.
Published: January 2024

Globally, wheat (Triticum aestivum L.) is a major source of proteins in human nutrition despite its unbalanced amino acid composition. The low lysine content in the protein fraction of wheat can lead to protein-energy-malnutrition prominently in developing countries. A promising strategy to overcome this problem is to breed varieties which combine high protein content with high lysine content. Nevertheless, this requires the incorporation of yet undefined donor genotypes into pre-breeding programs. Genebank collections are suspected to harbor the needed genetic diversity. In the 1970s, a large-scale screening of protein traits was conducted for the wheat genebank collection in Gatersleben; however, this data has been poorly mined so far. In the present study, a large historical dataset on protein content and lysine content of 4,971 accessions was curated, strictly corrected for outliers as well as for unreplicated data and consolidated as the corresponding adjusted entry means. Four genomic prediction approaches were compared based on the ability to accurately predict the traits of interest. High-quality phenotypic data of 558 accessions was leveraged by engaging the best performing prediction model, namely EG-BLUP. Finally, this publication incorporates predicted phenotypes of 7,651 accessions of the winter wheat collection. Five accessions were proposed as donor genotypes due to the combination of outstanding high protein content as well as lysine content. Further investigation of the passport data suggested an association of the adjusted lysine content with the elevation of the collecting site. This publicly available information can facilitate future pre-breeding activities.
Accurate and fast detection of tomatoes based on improved YOLOv5s in natural environments
Authors: Touko Mbouembe Philippe Lyonel , Liu Guoxu , Park Sungkyung , Kim Jae Ho
Published: January 2024

Uneven illumination, obstruction of leaves or branches, and the overlapping of fruit significantly affect the accuracy of tomato detection by automated harvesting robots in natural environments. In this study, a proficient and accurate algorithm for tomato detection, called SBCS-YOLOv5s, is proposed to address this practical challenge. SBCS-YOLOv5s integrates the SE, BiFPN, CARAFE and Soft-NMS modules into YOLOv5s to enhance the feature expression ability of the model. First, the SE attention module and the C3 module were combined to form the C3SE module, replacing the original C3 module within the YOLOv5s backbone architecture. The SE attention module relies on modeling channel-wise relationships and adaptive re-calibration of feature maps to capture important information, which helps improve feature extraction of the model. Moreover, the SE module’s ability to adaptively re-calibrate features can improve the model’s robustness to variations in environmental conditions. Next, the conventional PANet multi-scale feature fusion network was replaced with an efficient, weighted Bi-directional Feature Pyramid Network (BiFPN). This adaptation aids the model in determining useful weights for the comprehensive fusion of high-level and bottom-level features. Third, the regular up-sampling operator is replaced by the Content Aware Reassembly of Features (CARAFE) within the neck network. This implementation produces a better feature map that encompasses greater semantic information. In addition, CARAFE’s ability to enhance spatial detail helps the model discriminate between closely spaced fruits, especially for tomatoes that overlap heavily, potentially reducing the number of merging detections. Finally, for heightened identification of occluded and overlapped fruits, the conventional Non-Maximum-Suppression (NMS) algorithm was substituted with the Soft-NMS algorithm. Since Soft-NMS adopts a continuous weighting scheme, it is more adaptable to varying object sizes, improving the handling of small or large fruits in the image. Remarkably, this is carried out without introducing changes to the computational complexity. The outcome of the experiments showed that SBCS-YOLOv5s achieved a mean average precision (mAP (0.5:0.95)) of 87.7%, which is 3.5% superior to the original YOLOv5s model. Moreover, SBCS-YOLOv5s has a detection speed of 2.6 ms per image. Compared to other state-of-the-art detection algorithms, SBCS-YOLOv5s performed the best, showing tremendous promise for tomato detection in natural environments.