bluuebunny/crossref_metadata_2025 huggingface dataset:
ScanGrow: Deep Learning-Based Live Tracking of Bacterial Growth in Broth
Authors: Worth Ross Michael , Espina Laura
Published: July 2022

Monitoring the growth of bacterial cultures is one of the most common techniques in microbiology. This is usually achieved by using expensive and bulky spectrophotometric plate readers which periodically measure the optical density of bacterial cultures during the incubation period. In this study, we present a completely novel way of obtaining bacterial growth curves based on the classification of scanned images of cultures rather than using spectrophotometric measurements. We trained a deep learning model with images of bacterial broths contained in microplates, and we integrated it into a custom-made software application that triggers a flatbed scanner to timely capture images, automatically processes the images, and represents all growth curves. The developed tool, ScanGrow, is presented as a low-cost and high-throughput alternative to plate readers, and it only requires a computer connected to a flatbed scanner and equipped with our open-source ScanGrow application. In addition, this application also assists in the pre-processing of data to create and evaluate new models, having the potential to facilitate many routine microbiological techniques.
Impact of Putative Probiotics on Growth, Behavior, and the Gut Microbiome of Farmed Arctic Char (Salvelinus alpinus)
Authors: Knobloch Stephen , Skírnisdóttir Sigurlaug , Dubois Marianne , Kolypczuk Laetitia , Leroi Françoise , Leeper Alexandra , Passerini Delphine , Marteinsson Viggó Þ.
Published: July 2022

Beneficial bacteria promise to promote the health and productivity of farmed fish species. However, the impact on host physiology is largely strain-dependent, and studies on Arctic char (Salvelinus alpinus), a commercially farmed salmonid species, are lacking. In this study, 10 candidate probiotic strains were subjected to in vitro assays, small-scale growth trials, and behavioral analysis with juvenile Arctic char to examine the impact of probiotic supplementation on fish growth, behavior and the gut microbiome. Most strains showed high tolerance to gastric juice and fish bile acid, as well as high auto-aggregation activity, which are important probiotic characteristics. However, they neither markedly altered the core gut microbiome, which was dominated by three bacterial species, nor detectably colonized the gut environment after the 4-week probiotic treatment. Despite a lack of long-term colonization, the presence of the bacterial strains showed either beneficial or detrimental effects on the host through growth rate enhancement or reduction, as well as changes in fish motility under confinement. This study offers insights into the effect of bacterial strains on a salmonid host and highlights three strains, Carnobacterium divergens V41, Pediococcus acidilactici ASG16, and Lactiplantibacillus plantarum ISCAR-07436, for future research into growth promotion of salmonid fish through probiotic supplementation.
Shared Species Analysis, Augmented by Stochasticity Analysis, Is More Effective Than Diversity Analysis in Detecting Variations in the Gut Microbiomes
Authors: Ma Zhanshan (Sam)
Published: July 2022

Diversity analysis is a de facto standard procedure for most existing microbiome studies. Nevertheless, diversity metrics can be insensitive to changes in community composition (identities). For example, if species A (e.g., a beneficial microbe) is replaced by equal number of species B (e.g., an opportunistic pathogen), the diversity metric may not change, but the community composition has changed. The shared species analysis (SSA) is a computational technique that can discern changes of community composition by detecting the increase/decrease of shared species between two sets of microbiome samples, and it should be more sensitive than standard diversity analysis in discerning changes in microbiome structures. Here, we investigated the effects of ethnicity and lifestyles in China on the structure of Chinese gut microbiomes by reanalyzing the datasets of a large Chinese cohort with 300+ individuals covering 7 biggest Chinese ethnic groups (>95% Chinese population). We found: (i) Regarding lifestyles, SSA revealed significant differences between 100% of pair-wise comparisons in community compositions across all but phylum taxon levels (phylum level = 29%), but diversity analysis only revealed 14–29% pair-wise differences in community diversity across all four taxon levels. (ii) Regarding ethnicities, SSA revealed 100% pair-wise differences in community compositions across all but phylum (phylum level = 48–62%) levels, but diversity analysis only revealed 5–57% differences in community diversity across all four taxon levels. (iii) Ethnicity seems to have more prevalent effects on community structures than lifestyle does (iv) Community structures of the gut microbiomes are more stable at the phylum level than at the other three levels. (v) SSA is more powerful than diversity analysis in detecting the changes of community structures; furthermore, SSA can produce lists of unique and shared OTUs. (vi) Finally, we performed stochasticity analysis to mechanistically interpret the observed differences revealed by the SSA and diversity analyses.
Low-to-Moderate Dosage and Short-Term Use of Corticosteroids Benefit Patients With Severe COVID-19 Infections
Authors: Yang Liuqing , Peng Ling , Wu Weibo , Cao Mengli , Chen Chuming , Wang Fuxiang , Sauver Jennifer St. , Liu Yingxia
Published: July 2022

Although the FDA has given emergency use authorization (EUA) for some antiviral drugs for the treatment of COVID-19, no direct antiviral drugs have been identified for the treatment of critically ill patients, the most important treatment is suppression of the hyperinflammation. The purpose of this study was to evaluate the role of corticosteroids in hospitalized severe or critical patients positive for COVID-19. This is a retrospective single-center descriptive study. Patients classified as having severe or critical COVID-19 infections with acute respiratory dysfunction syndrome in Shenzhen Third People’s Hospital were enrolled from January 11th to March 30th, 2020. Ninety patients were classified as having severe or critical COVID-19 infections. The patients were treated with methylprednisolone with a low-to-moderate dosage and short duration. The days from the symptom onset to methylprednisolone were about 8 days. Eighteen patients were treated with invasive ventilation and intensive care unit (ICU) care. All the patients in the severe group and ten in the critical group recovered and were discharged. Three critical cases with invasive ventilation died. Although cases were much more severe in the corticosteroid-treated group, the mortality was not significantly increased. Early use of low-to-moderate dosage and short duration of corticosteroid may be the more accurate immune-modulatory treatment and brings more benefits to severe patients with COVID-19.
Effect of Cholesterol on C99 Dimerization: Revealed by Molecular Dynamics Simulations
Authors: Li Cheng-Dong , Junaid Muhammad , Shan Xiaoqi , Wang Yanjing , Wang Xiangeng , Khan Abbas , Wei Dong-Qing
Published: July 2022

C99 is the immediate precursor for amyloid beta (Aβ) and therefore is a central intermediate in the pathway that is believed to result in Alzheimer’s disease (AD). It has been suggested that cholesterol is associated with C99, but the dynamic details of how cholesterol affects C99 assembly and the Aβ formation remain unclear. To investigate this question, we employed coarse-grained and all-atom molecular dynamics simulations to study the effect of cholesterol and membrane composition on C99 dimerization. We found that although the existence of cholesterol delays C99 dimerization, there is no direct competition between C99 dimerization and cholesterol association. In contrast, the existence of cholesterol makes the C99 dimer more stable, which presents a cholesterol binding C99 dimer model. Cholesterol and membrane composition change the dimerization rate and conformation distribution of C99, which will subsequently influence the production of Aβ. Our results provide insights into the potential influence of the physiological environment on the C99 dimerization, which will help us understand Aβ formation and AD’s etiology.
Effects of PCSK9 inhibitors on HDL cholesterol efflux and serum cholesterol loading capacity in familial hypercholesterolemia subjects: a multi-lipid-center real-world evaluation
Authors: Palumbo Marcella , Giammanco Antonina , Purrello Francesco , Pavanello Chiara , Mombelli Giuliana , Di Pino Antonino , Piro Salvatore , Cefalù Angelo Baldassare , Calabresi Laura , Averna Maurizio , Bernini Franco , Zimetti Francesca , Adorni Maria Pia , Scicali Roberto
Published: July 2022

Proprotein convertase subtilisin/kexin type 9 (PCSK9), beyond regulating LDL cholesterol (LDL-c) plasma levels, exerts several pleiotropic effects by modulating lipid metabolism in extrahepatic cells such as macrophages. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, including the HDL capacity to promote cell cholesterol efflux (CEC) and the serum capacity to promote cell cholesterol loading (CLC). The aim of this observational study was to investigate the effect of PCSK9 inhibitors (PCSK9-i) treatment on HDL-CEC and serum CLC in patients with familial hypercholesterolemia (FH). 31 genetically confirmed FH patients were recruited. Blood was collected and serum isolated at baseline and after 6 months of PCSK9-i treatment. HDL-CEC was evaluated through the main pathways with a radioisotopic cell-based assay. Serum CLC was assessed fluorimetrically in human THP-1 monocyte-derived macrophages. After treatment with PCSK9-i, total cholesterol and LDL-c significantly decreased (−41.6%, p < 0.0001 and −56.7%, p < 0.0001, respectively). Total HDL-CEC was not different between patients before and after treatment. Conversely, despite no changes in HDL-c levels between the groups, ABCG1 HDL-CEC significantly increased after treatment (+22.2%, p < 0.0001) as well as HDL-CEC by aqueous diffusion (+7.8%, p = 0.0008). Only a trend towards reduction of ABCA1 HDL-CEC was observed after treatment. PCSK9-i significantly decreased serum CLC (−6.6%, p = 0.0272). This effect was only partly related to the reduction of LDL-c levels. In conclusion, PCSK9-i treatment significantly increased HDL-CEC through ABCG1 and aqueous diffusion pathways and reduced the serum CLC in FH patients. The favorable effect of PCSK9-i on functional lipid profile could contribute to the cardiovascular benefit of these drugs in FH patients.
Nanodelivery Systems Delivering Hypoxia-Inducible Factor-1 Alpha Short Interfering RNA and Antisense Oligonucleotide for Cancer Treatment
Authors: Yan Yan , Li Houli , Yao Hongping , Cheng Xiaoliang
Published: July 2022

Hypoxia-inducible factor (HIF), which plays a crucial role in oxygen homeostasis, contributes to immunosuppression, tumor angiogenesis, multidrug resistance, photodynamic therapy resistance, and metastasis. HIF as a therapeutic target has attracted scientists’ strong academic research interests. Short interfering RNA (siRNA) and antisense oligonucleotide (ASO) are the more promising and broadly utilized methods for oligonucleotide-based therapy. Their physicochemical characteristics such as hydrophilicity, negative charge, and high molecular weight make them impossible to cross the cell membrane. Moreover, siRNA and ASO are subjected to a rapid deterioration in circulation and cannot translocate into nuclear. Delivery of siRNA and ASO to specific gene targets should be realized without off-target gene silencing and affecting the healthy cells. Nanoparticles as vectors for delivery of siRNA and ASO possess great advantages and flourish in academic research. In this review, we summarized and analyzed regulation mechanisms of HIF under hypoxia, the significant role of HIF in promoting tumor progression, and recent academic research on nanoparticle-based delivery of HIF siRNA and ASO for cancer immunotherapy, antiangiogenesis, reversal of multidrug resistance and radioresistance, potentiating photodynamic therapy, inhibiting tumor metastasis and proliferation, and enhancing apoptosis are reviewed in this thesis. Furthermore, we hope to provide some rewarding suggestions and enlightenments for targeting HIF gene therapy.
Heterozygous Deletion of Epilepsy Gene KCNQ2 Has Negligible Effects on Learning and Memory
Authors: Tracy Gregory C. , Wilton Angelina R. , Rhodes Justin S. , Chung Hee Jung
Published: July 2022

Neuronal Kv7/Potassium Voltage-Gated Channel Subfamily Q (KCNQ) potassium channels underlie M-current that potently suppresses repetitive and burst firing of action potentials (APs). They are mostly heterotetramers of Kv7.2 and Kv7.3 subunits in the hippocampus and cortex, the brain regions important for cognition and behavior. Underscoring their critical roles in inhibiting neuronal excitability, autosomal dominantly inherited mutations in Potassium Voltage-Gated Channel Subfamily Q Member 2 (KCNQ2) and Potassium Voltage-Gated Channel Subfamily Q Member 3 (KCNQ3) genes are associated with benign familial neonatal epilepsy (BFNE) in which most seizures spontaneously remit within months without cognitive deficits. De novo mutations in KCNQ2 also cause epileptic encephalopathy (EE), which is characterized by persistent seizures that are often drug refractory, neurodevelopmental delay, and intellectual disability. Heterozygous expression of EE variants of KCNQ2 is recently shown to induce spontaneous seizures and cognitive deficit in mice, although it is unclear whether this cognitive deficit is caused directly by Kv7 disruption or by persistent seizures in the developing brain as a consequence of Kv7 disruption. In this study, we examined the role of Kv7 channels in learning and memory by behavioral phenotyping of the KCNQ2+/− mice, which lack a single copy of KCNQ2 but dos not display spontaneous seizures. We found that both KCNQ2+/− and wild-type (WT) mice showed comparable nociception in the tail-flick assay and fear-induced learning and memory during a passive inhibitory avoidance (IA) test and contextual fear conditioning (CFC). Both genotypes displayed similar object location and recognition memory. These findings together provide evidence that heterozygous loss of KCNQ2 has minimal effects on learning or memory in mice in the absence of spontaneous seizures.
Casein kinase 2 attenuates brain injury induced by intracerebral hemorrhage via regulation of NR2B phosphorylation
Authors: Sun Zhimin , Li Qiyao , Li Xiaopeng , Shi Yunpeng , Nan Chengrui , Jin Qianxu , Wang Xiaoyan , Zhuo Yayu , Zhao Zongmao
Published: July 2022

Objective

Intracerebral hemorrhage (ICH) is a common cerebrovascular disease with high incidence, disability, and mortality. Casein kinase 2 (CK2) is a serine/threonine kinase with hundreds of identified substrates and plays an important role in many diseases. This study aimed to explore whether CK2 plays protective roles in ICH-induced neuronal apoptosis, inflammation, and oxidative stress through regulation NR2B phosphorylation.

Methods

CK2 expression level of brain tissues taken from ICH patients was determined by immunoblotting. Neurons from embryonic rat and astrocytes from newborn rats were cultured and treated by Hemoglobin chloride (Hemin). The proliferation of astrocytes, the apoptosis and oxidative stress of neurons and the inflammatory factors of astrocytes were detected. CK2 expression was determined in ICH model rats. The effects of CK2 overexpression plasmid (pc-CK2) on neurobehavioral defects and brain water content in ICH rats were observed.

Results

CK2 expression in ICH patients was down-regulated. Overexpression of CK2 promoted the astrocyte proliferation, inhibited neuronal apoptosis, and reduced astrocyte-mediated inflammation. N-methyl-D-aspartate receptor 2B (NR2B) reversed the effects of pc-CK2 on neurons and astrocytes. CK2 phosphorylated NR2B at the S1480 site, down-regulated the expression of NR2B and interfered with the interaction between NR2B and postsynaptic density protein 95 (PSD95). In vivo experiments showed that the expression of CK2 decreased and the expression of NR2B increased in ICH rats. Furthermore, pc-CK2 attenuated neurobehavioral defects, brain water content and neuronal damage in ICH rats.

Conclusion

CK2 phosphorylated NR2B, down-regulated the expression of NR2B, interfered with the interaction between NR2B and PSD95, alleviated inflammatory reactions, inhibited neuronal apoptosis and oxidative stress after ICH. CK2 and NR2B may be new potential therapeutic targets for the treatment of ICH. However, the limitation of this study is that we only investigated the regulation of NR2B by CK2.
Non-invasive brain stimulation associated mirror therapy for upper-limb rehabilitation after stroke: Systematic review and meta-analysis of randomized clinical trials
Authors: Zhao Qingqing , Li Hong , Liu Yu , Mei Haonan , Guo Liying , Liu Xianying , Tao Xiaolin , Ma Jiang
Published: July 2022

Background

Non-invasive brain stimulation (NIBS) techniques and mirror therapy (MT) are promising rehabilitation measures for stroke. While the combination of MT and NIBS has been employed for post-stroke upper limb motor functional rehabilitation, its effectiveness has not been examined.

Objective

This study aimed to evaluate the effectiveness of combined MT and NIBS in the recovery of upper limb motor function in stroke patients.

Methods

The search was carried out in PubMed, EMBASE, Cochrane Library, Web of Science, Science Direct, CNKI, WANFANG and VIP until December 2021. Randomized clinical trials (RCTs) comparing MT or NIBS alone with the combination of NIBS and MT in improving upper extremity motor recovery after stroke were selected. A meta-analysis was performed to calculate the mean differences (MD) or the standard mean differences (SMD) and 95% confidence intervals (CI) with random-effect models. Subgroup analyses were also conducted according to the types of control group, the types of NIBS, stimulation timing and phase poststroke.

Results

A total of 12 articles, including 17 studies with 628 patients, were reviewed in the meta-analysis. In comparison with MT or NIBS alone, the combined group significantly improved body structure and function (MD = 5.97; 95% CI: 5.01–6.93; P < 0.05), activity levels (SMD = 0.82; 95% CI 0.61–1.02; P < 0.05). For cortical excitability, the motor evoked potential cortical latency (SMD = −1.05; 95% CI:−1.57–−0.52; P < 0.05) and the central motor conduction time (SMD=-1.31 95% CI:−2.02-−0.61; P < 0.05) of the combined group were significantly shortened. A non-significant homogeneous summary effect size was found for MEP amplitude (SMD = 0.47; 95%CI = −0.29 to 1.23; P = 0.23). Subgroup analysis showed that there is an interaction between the stimulation sequence and the combined treatment effect.

Conclusion

In this meta-analysis of randomized clinical trials, in comparison to the control groups, MT combined with NIBS promoted the recovery of upper extremity motor function after stroke, which was reflected in the analysis of body structure and function, activity levels, and cortical excitability.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022304455.
Neurological recovery and antioxidant effect of erythropoietin for spinal cord injury: A systematic review and meta-analysis
Authors: Zhang Ya-yun , Yao Min , Zhu Ke , Xue Rui-rui , Xu Jin-hai , Cui Xue-jun , Mo Wen
Published: July 2022

Background

To critically evaluate the neurological recovery effects and antioxidant effects of erythropoietin (EPO) in rat models of spinal cord injury (SCI).

Methods

The PubMed, EMBASE, MEDLINE, ScienceDirect, and Web of Science were searched for animal experiments applying EPO to treat SCI to January 2022. We included studies which examined neurological function by the Basso, Beattie, and Bresnahan (BBB) scale, as well as cavity area and spared area, and determining the molecular-biological analysis of antioxidative effects by malondialdehyde (MDA) levels in spinal cord tissues. Meta-analysis were performed with Review Manager 5.4 software.

Results

A total of 33 studies were included in this review. The results of the meta-analysis showed that SCI rats receiving EPO therapy showed a significant locomotor function recovery after 14 days compared with control, then the superiority of EPO therapy maintained to 28 days from BBB scale. Compared with the control group, the cavity area was reduced [4 studies, weighted mean difference (WMD) = −16.65, 95% CI (−30.74 to −2.55), P = 0.02] and spared area was increased [3 studies, WMD =11.53, 95% CI (1.34 to 21.72), P = 0.03] by EPO. Meanwhile, MDA levels [2 studies, WMD = −0.63 (−1.09 to −0.18), P = 0.007] were improved in the EPO treatment group compared with control, which indicated its antioxidant effect. The subgroup analysis recommended 5,000 UI/kg is the most effective dose [WMD = 4.05 (2.23, 5.88), P < 0.0001], although its effect was not statistically different from that of 1,000 UI/kg. Meanwhile, the different rat strains (Sprague-Dawley vs. Wistar), and models of animals, as well as administration method (single or multiple administration) of EPO did not affect the neuroprotective effect of EPO for SCI.

Conclusions

This systematic review indicated that EPO can promote the recovery of the locomotor function of SCI rats. The mechanism exploration of EPO needs to be verified by experiments, and then carefully designed randomized controlled trials are needed to explore its neural recovery effects.
Disrupted Brain Structural Network Connection in de novo Parkinson's Disease With Rapid Eye Movement Sleep Behavior Disorder
Authors: Chen Amei , Li Yuting , Wang Zhaoxiu , Huang Junxiang , Ruan Xiuhang , Cheng Xiaofang , Huang Xiaofei , Liang Dan , Chen Dandan , Wei Xinhua
Published: July 2022

Objective

To explore alterations in white matter network topology in de novo Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD).

Materials and Methods

This study included 171 de novo PD patients and 73 healthy controls (HC) recruited from the Parkinson's Progression Markers Initiative (PPMI) database. The patients were divided into two groups, PD with probable RBD (PD-pRBD, n = 74) and PD without probable RBD (PD-npRBD, N = 97), according to the RBD screening questionnaire (RBDSQ). Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group.

Results

All three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency (Ne) were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients.

Conclusions

PD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD.
Impact of brain overgrowth on sensorial learning processing during the first year of life
Authors: López-Arango Gabriela , Deguire Florence , Agbogba Kristian , Boucher Marc-Antoine , Knoth Inga S. , El-Jalbout Ramy , Côté Valérie , Damphousse Amélie , Kadoury Samuel , Lippé Sarah
Published: July 2022

Macrocephaly is present in about 2–5% of the general population. It can be found as an isolated benign trait or as part of a syndromic condition. Brain overgrowth has been associated with neurodevelopmental disorders such as autism during the first year of life, however, evidence remains inconclusive. Furthermore, most of the studies have involved pathological or high-risk populations, but little is known about the effects of brain overgrowth on neurodevelopment in otherwise neurotypical infants. We investigated the impact of brain overgrowth on basic perceptual learning processes (repetition effects and change detection response) during the first year of life. We recorded high density electroencephalograms (EEG) in 116 full-term healthy infants aged between 3 and 11 months, 35 macrocephalic (14 girls) and 81 normocephalic (39 girls) classified according to the WHO head circumference norms. We used an adapted oddball paradigm, time-frequency analyses, and auditory event-related brain potentials (ERPs) to investigate differences between groups. We show that brain overgrowth has a significant impact on repetition effects and change detection response in the 10–20 Hz frequency band, and in N450 latency, suggesting that these correlates of sensorial learning processes are sensitive to brain overgrowth during the first year of life.
A data-driven machine learning approach for brain-computer interfaces targeting lower limb neuroprosthetics
Authors: Dillen Arnau , Lathouwers Elke , Miladinović Aleksandar , Marusic Uros , Ghaffari Fakhreddine , Romain Olivier , Meeusen Romain , De Pauw Kevin
Published: July 2022

Prosthetic devices that replace a lost limb have become increasingly performant in recent years. Recent advances in both software and hardware allow for the decoding of electroencephalogram (EEG) signals to improve the control of active prostheses with brain-computer interfaces (BCI). Most BCI research is focused on the upper body. Although BCI research for the lower extremities has increased in recent years, there are still gaps in our knowledge of the neural patterns associated with lower limb movement. Therefore, the main objective of this study is to show the feasibility of decoding lower limb movements from EEG data recordings. The second aim is to investigate whether well-known neuroplastic adaptations in individuals with an amputation have an influence on decoding performance. To address this, we collected data from multiple individuals with lower limb amputation and a matched able-bodied control group. Using these data, we trained and evaluated common BCI methods that have already been proven effective for upper limb BCI. With an average test decoding accuracy of 84% for both groups, our results show that it is possible to discriminate different lower extremity movements using EEG data with good accuracy. There are no significant differences (p = 0.99) in the decoding performance of these movements between healthy subjects and subjects with lower extremity amputation. These results show the feasibility of using BCI for lower limb prosthesis control and indicate that decoding performance is not influenced by neuroplasticity-induced differences between the two groups.
Role of Real-World Data in Assessing Cardiac Toxicity After Lung Cancer Radiotherapy
Authors: Abravan Azadeh , Price Gareth , Banfill Kathryn , Marchant Tom , Craddock Matthew , Wood Joe , Aznar Marianne C. , McWilliam Alan , van Herk Marcel , Faivre-Finn Corinne
Published: July 2022

Radiation-induced heart disease (RIHD) is a recent concern in patients with lung cancer after being treated with radiotherapy. Most of information we have in the field of cardiac toxicity comes from studies utilizing real-world data (RWD) as randomized controlled trials (RCTs) are generally not practical in this field. This article is a narrative review of the literature using RWD to study RIHD in patients with lung cancer following radiotherapy, summarizing heart dosimetric factors associated with outcome, strength, and limitations of the RWD studies, and how RWD can be used to assess a change to cardiac dose constraints.
Update on Long-Acting Anticholinergics in Children and Adolescents With Difficult and Severe Asthma
Authors: Santamaria Francesca , Ziello Carla , Lorello Paola , Bouchè Cristina , Borrelli Melissa
Published: July 2022

Tiotropium bromide is the only long-acting muscarinic antagonist (LAMA) approved for treatment of patients aged ≥6 years old who have symptoms of uncontrolled asthma. Results from several clinical trials have found that once-daily inhaled tiotropium bromide is safe and efficacious in 6- to 17-year-olds with symptomatic asthma despite treatment with inhaled corticosteroids, with or without other medications. There are still few available studies investigating the impact of tiotropium bromide treatment in preschool children with suboptimal control. In this narrative review, we summarize the pharmacological effects of the LAMA tiotropium bromide, provide an overview about current asthma studies at different pediatric ages, and describe future research needs.
Maternal Factors in Pregnancy and Ethnicity Influence Childhood Adiposity, Cardiac Structure, and Function
Authors: Khan Sophia , Whatmore Andrew , Perchard Reena , Khan Aysha , Vyas Avni , Dua Jaspal , Cruickshank J. Kennedy , Clayton Peter
Published: July 2022

Importance

The links between maternal and offspring adiposity and metabolic status are well established. There is much less evidence for the impact of these relationships combined with ethnic background on cardiac structure and function in childhood.

Objective

To test the hypothesis that ethnicity, maternal adiposity and glycemic status, and child adiposity affect cardiac structure and function.

Design

A prospective cohort study.

Setting

A single-center mother-child cohort study. The cohort is a subset of the international multi-center Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.

Participants

This study included 101 healthy pre-pubertal British-born children [56 White Europeans (WEs) and 45 South Asians (SAs)] with a median age of 9.1 years, range 6.0–12.2 years, at the time of the investigation.

Main Outcomes and Measures

Anthropometric and echocardiographic measurements were made on the cohort. Maternal pregnancy and birth data were available. Relationships between maternal parameters (BMI and glucose status), child adiposity, and echo measures were assessed.

Results

Despite no ethnic difference in BMI SDS at a median age of 9.1 years, SA children exhibited higher levels of body fat than WE children (whole body, right arm, and truncal fat all p < 0.001). SA children also exhibited greater changes in weight and height SDS but not BMI SDS from birth than WE children. As expected, maternal BMI correlated with child BMI (r = 0.28; p = 0.006), and body fat measures (e.g., whole body fat r = 0.25; p = 0.03). Maternal fasting glucose levels were associated with child body fat measures (r = 0.22–0.28; p = 0.02–0.05). Left ventricular (LV) indices were not different between SA and WE children, but E/A and E′/A′ (measures of diastolic function) were lower in SA when compared with WE children. LV indices correlated positively to BMI SDS and body fat markers only in SA children. Maternal fasting and 2-h glucose were negatively correlated with E′/A′ in SA children (r = −0.53, p = 0.015, and r = −0.49, p = 0.023, respectively) but not in WE children.

Conclusion and Relevance

SA and WE children exhibit differences in adiposity and diastolic function at a median age of 9.1 years. Novel relationships between maternal glycemia, child adiposity, and cardiac structure and function, present only in SA children, were identified.
TGF-β1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia
Authors: Zhao Jinfeng , Xu Xiaodan , Gou Qingyun , Zheng Qipeng , Ge Liang , Chen Lingzhi , Zhang Cong , Ma Hui , Lin Shuxiang , Hu Xiaoli , Zhan Jianghua
Published: July 2022

Objective

Biliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.

Methods

A total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.

Results

LECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; rs = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.

Conclusion

LECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.
Hermansky-Pudlak syndrome type 2: A rare cause of severe periodontitis in adolescents—A case study
Authors: Chen Jun , Yang Yifan , Liu Binjie , Xie Xiaoli , Li Wenjie
Published: July 2022

Background and aims

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA) and platelet storage pool deficiency. The HPS-2 subtype is distinguished by neutropenia, and little is known about its periodontal phenotype in adolescents. AP3B1 is the causative gene for HPS-2. A 13-year-old Chinese girl presented to our department suffering from gingival bleeding and tooth mobility. Her dental history was otherwise unremarkable. Suspecting some systemic diseases as the underlying cause, the patient was referred for medical consultation, a series of blood tests, and genetic tests. In this case study, periodontal status and mutation screening of one HPS-2 case are presented.

Methods

Blood analysis including a complete blood count (CBC) and glycated hemoglobin levels were measured. Platelet transmission electron microscopy (PTEM) was performed to observe the dense granules in platelets. Whole-exome sequencing (WES) and Sanger sequencing were performed to confirm the pathogenic variants.

Results

A medical diagnosis of HPS-2 was assigned to the patient. Following the medical diagnosis, a periodontal diagnosis of “periodontitis as a manifestation of systemic disease” was assigned to the patient. We identified novel compound heterozygous variants in AP3B1 (NM_003664.4: exon7: c.763C>T: p.Q255*) and (NM_003664.4: exon1: c.53_56dup: p.E19Dfs*21) in this Chinese pedigree with HPS-2.

Conclusion

This case study indicates the importance of periodontitis as a possible indicator of underlying systemic disease. Systemic disease screening is needed when a young patient presents with unusual, severe periodontitis, as the oral condition may be the first of a systemic abnormality. Our work also expands the spectrum of AP3B1 mutations and further provides additional genetic testing information for other HPS-2 patients.
Efficacy and safety of ultrasound-guided bleomycin combined with dexamethasone in the treatment of pediatric lymphangiomas
Authors: Zhang Yu-Tong , Zhang Chao , Wang Yu , Chang Jian
Published: July 2022

Purpose

This work aimed to report our experience with ultrasound-guided instillation for the treatment of lymphangiomas in children, so as to determine whether the combined use of bleomycin and dexamethasone achieved a higher response rate and a lower side effect rate.

Methods

The medical records from patients with lymphangiomas between January 1st, 2013 and September 31st, 2020, were reviewed. Patients who received bleomycin combined with dexamethasone sclerotherapy were classified as the dexamethasone group, while those receiving bleomycin without dexamethasone were classified as the control group.

Results

Altogether one hundred and twenty-seven patients were diagnosed with lymphangiomas. Among them, one hundred and five patients received bleomycin combined with dexamethasone injection, while the remaining twenty-two received bleomycin injection alone. The excellent rates were 89.52% [95% confidence interval (CI), 81.64–94.40%] in the dexamethasone group and 72.73% (95% CI, 52.51–92.94%) in the control group (p < 0.05). Additionally, the recurrence rates were 3.81% (95% CI, 1.22–10.03%) in the dexamethasone group and 13.64% (95% CI, 3.6–36.0%) in the control group (p > 0.05). After comparison between the two groups, the following risk factors were identified. These include >10 sacs at the initial stage of diagnosis, larger size after all injections, and response to the first injection.

Conclusions

Although there was no significant difference in the recurrence rate between the two groups, this retrospective study demonstrated that the excellent response rates were dramatically improved between the two groups, suggesting that bleomycin combined with DEX was an effective and highly safe treatment for all types of pediatric lymphangiomas. Moreover, this study also identified three novel features as the significant risk factors for recurrence.
Case report: Restrictive cardiomyopathy presenting with complete thromboembolism occlusion of the terminal part of the abdominal aorta in a preadolescent Saudi girl
Authors: Al-Shammari Ahmad A. , Muslim Rawan Al , Almuslim Jenan , Elashaal Ehab , Lardhi Haitham , AlQahtani Saleh A. , AlBassam Bassam N. , Lardhi Amer
Published: July 2022

Restrictive cardiomyopathy (RCM) is a rare disease in children, accounting for <5% of all pediatric cardiomyopathies. It may be idiopathic or may be a secondary to a systemic disease. The disease is characterized by normal systolic function with impaired ventricular filling caused by stiff ventricular walls. Children with RCM often present with symptoms of exercise intolerance, shortness of breath, weakness, and chest discomfort. Thromboembolism events are an unusual presentation of RCM. We are reporting a preadolescent female from the eastern province of Saudi Arabia who presented with sudden right lower limb swelling, paresthesia, and pain caused by a complete occlusion of the terminal part of the abdominal aorta and both common iliac arteries. Echocardiography revealed dilated atria, normal ventricle dimensions and two floating thrombi in the left atrium. The patient was successfully managed with an anticoagulant, surgical thrombectomy and cardiac transplantation.
Penta-O-Galloyl-β-D-Glucose in Pistacia integerrima Targets AMPK-ULK1 and ERK/STAT3 Signaling Axes to Induce ROS-Independent Autophagic Cell Death in Human Lung Cancer Cells
Authors: Balkrishna Acharya , Mulay Vallabh Prakash , Verma Sudeep , Srivastava Jyotish , Lochab Savita , Varshney Anurag
Published: July 2022

Natural molecules have promising perspectives as adjuvants to chemotherapies against cancer. Pistacia chinensis subsp. Integerrima (hereafter, Pistacia integerrima) traditionally known for medicinal values in respiratory disorders was tested for anti-lung cancer properties. The extract prepared from Pistacia integerrima (PI) selectively impaired the viability of lung cancer cells, A549 and NCI-H460, compared to non-cancer cells. At non-lethal concentrations, PI mitigated colony-forming, spheroid formations and metastatic properties of lung cancer cells. As a step toward identifying the phytomolecule that is imparting the anti-lung cancer properties in PI, we subjected the extract to extensive characterization through UPLC/QToF-MS and further validated the findings with UHPLC. The gallotannin, penta-O-galloyl-β-D-glucose (PGG), among others, was identified through UPLC/QToF-MS. PGG exhibits potential chemopreventive effects against various cancer types. However, a defined mechanism of action of PGG in restricting lung cancer progression is still unexplored. Bioactivity-guided column fractionations enabled the determination of PGG as the major phytochemical that governed PI-mediated AMPK-ULK1-dependent autophagy and apoptosis, albeit independent of intracellular ROS activation. Interestingly, the autophagy flux when inhibited restored the cell viability even in the presence of PI. The study further delineated that PI and PGG activated ERK and inhibited STAT3 to trigger apoptosis through caspase-3 and PARP 1 pathways. Collectively, the finding demonstrates that plant extract, PGG, in the PI extract effectively combats lung cancer progression through autophagic cell death by altering ERK/AMPK-ULK1/STAT3 signaling axes. The study proposes PGG as a potential AMPK activator and STAT3 inhibitor that can be exploited further in developing adjuvant chemotherapeutics against lung cancer.
Probiotics (Bacillus clausii and Lactobacillus fermentum NMCC-14) Ameliorate Stress Behavior in Mice by Increasing Monoamine Levels and mRNA Expression of Dopamine Receptors (D1 and D2) and Synaptophysin
Authors: Rehman Mujeeb Ur , Ghazanfar Shakira , Ul Haq Rizwan , Ullah Shakir , Khan Salman , Wu Jianbo , Ahmad Waqar , Tipu Muhammad Khalid
Published: July 2022

Stress is a physiological consequence of the body to adversity. The gut–brain axis and probiotics are gaining interest to provide better treatment for stress and other neurological disorders. Probiotic (Lactobacillus fermentum NMCC-14 and Bacillus clausii, 1010 colony-forming unit/day/animal, per oral) effects were investigated in acute (up to day 7) and subacute (days 8–14) restraint-stressed and normal mice through behavioral paradigms (elevated plus maze: EPM, light dark box/dark light box: LDB, and open field test: OFT). Time spent in the open arms of the EPM, time spent in the light compartment of the LDB, and movable time and time spent in the center of the OFT were significantly (p ≤ 0.05, n = 5) increased in probiotic-treated restraint-stressed mice. Enzyme-linked immunoassay determined blood cortisol and adrenocorticotropic hormone (ACTH) levels, which were reduced significantly (p < 0.05, n = 5) in probiotic-treated restraint-stressed mice. Hematoxylin and eosin-stained hippocampal slides also showed less or no neurodegeneration in the probiotic-treated animals. High-performance liquid chromatography and quantitative polymerase chain reaction were performed to determine the monoamine levels and mRNA expression of dopamine receptor subtypes (D1 and D2) and synaptophysin in the mice hippocampus (HC) and prefrontal cortex (PFC). The dopamine, serotonin, and norepinephrine levels were also significantly (p < 0.05, n = 5) increased in the HC and PFC of probiotic-treated animal brains. Fold expression of mRNA of D1 and D2 (except HC, LF-S, day 14) receptors and synaptophysin was also significantly (p < 0.05, n = 5) increased in the same brain parts of probiotic-treated restraint-stressed mice. Comparing mice in the Lactobacillus fermentum NMCC-14 and Bacillus clausii groups to mice in the normal group, only a significant (p < 0.05, n = 5) decrease was observed in the serum ACTH and cortisol levels on day 14 in Bacillus clausii-treated mice, where all other parameters also showed improvement. In comparison, Bacillus clausii showed greater stress suppressant activity than Lactobacillus fermentum NMCC-14. However, both probiotic bacteria can be a better and safer therapeutic alternative for ailments than currently available drugs.
Efficacy and Safety of Iclaprim for the Treatment of Skin Structures and Soft Tissue Infections: A Methodological Framework
Authors: Wang Lian , Fan Jin , Zheng Linli , Chen Lingmin
Published: July 2022

Background: Skin and soft tissue infections (SSTIs) are among the most common infections worldwide. They manifest in a variety of forms, such as erysipelas, cellulitis, and necrotizing fasciitis. Antibiotics are the significant method for clinical treatment of SSTIs. This study reported a methodology framework to determine the efficacy and safety of iclaprim in treatment of SSTIs.

Methods: We will search the PubMed, EMbase, CNKI, WanFang Data, VIP, and ClinicalTrials.gov from their inception to June 2022 for randomized controlled trials and cohort studies on iclaprim with SSTIs. Two authors will independently screen the eligible studies, assess the quality of the included papers, and extract the required information. Randomized controlled trials will be assessed using the Cochrane risk-of-bias tool. The Newcastle–Ottawa Scale will be used to evaluate observational studies. The quality of the evidence will be evaluated using the Grading of Recommendations Assessment Development and Evaluation system. RevMan 5.3 will be used for the data synthesis and quantitative analysis.

Results and Discussions: This study will provide the clinicians with more high-quality evidence to choose iclaprim for patients with SSTIs.

Ethics and Dissemination: This systematic review and meta-analysis will be based on published data, so ethical approval is not necessary. The results of this meta-analysis will be published in a peer-reviewed journal.
Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism
Authors: He Rupu , Ma Ruyun , Jin Zheng , Zhu Yanning , Yang Fude , Hu Fangdi , Dai Jianye
Published: July 2022

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions.

Methods: First, we established the GPL rat model which was induced by N-methyl-N′-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR’s anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR’s anti-gastritis and anti-cancer phenotype in cell models.

Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells.

Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.