bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Profiling of Dietary Carbohydrate Digestion in Piglets
Authors: Gao Xiaoqian , Yu Bing , Yu Jie , Mao Xiangbing , Huang Zhiqing , Luo Yuheng , Luo Junqiu , Zheng Ping , Yan Hui , He Jun , Chen Daiwen
Published: April 2022

Carbohydrates are the main source of energy in the diet, accounting for the largest proportion in the diets of humans and monogastric animals. Although recent progress has been made in the study of intestinal carbohydrate digestion in piglets, there is a lack of comprehensive study on the dynamic changes in intestinal carbohydrate digestion with age in the early growth stage of piglets. To fill in this gap of knowledge, we collected samples of the small intestine, pancreatic tissues, and colonic digesta from 42 piglets during newborn [day (d) 0], lactation (d 7, 14), weaning (d 21), and nursery (d 28, 35, and 42) stages. Intestinal and pancreatic tissues and colonic digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, short-chain fatty acids (SCFA), and microbial abundance. Villus height reached a maximum at 1 week (d 7) in the duodenum and jejunum (P <0.01), and a higher ratio of villus height to crypt depth and lactase activity were observed on d 0 and 7 (P < 0.001) compared to other ages. However, the sucrase and maltase activities were increased with piglets' age. Similar activities of sucrase and maltase were found in the small intestine. In addition, amylase, lipase, and protease activities were assayed in the pancreas. The activity of amylase increased with age, while lipase and protease decreased gradually from birth to weaning (d 21, 28) and then increased after weaning (d 35, 42). Compared with d 0, d 42 increased the abundance of Firmicutes and Bacteroidetes with a higher concentration of total SCFA (P < 0.001) and decreased the abundance of Proteobacteria, but weaning (d 21, 28) increased the abundance of Proteobacteria in the colon. These results indicate that with the increase in piglet age, the carbohydrate digestive function gradually increased, but weaning hindered the development of intestinal function. These results provide us with new insights into the healthy development of piglets' intestines, which may help us to better regulate the physiological health of piglets in the future.
A Systematic Pan-Cancer Analysis of CASP3 as a Potential Target for Immunotherapy
Authors: Zhou Zheng , Xu Shiying , Jiang Liehao , Tan Zhuo , Wang Jiafeng
Published: April 2022

CASP3 is the gene encoding caspase-3, a specific protease that cleaves substrates such as poly-ADP ribose polymerase and acetyl-DEVD-7-amino-4-methylcoumarin. This enzymatic activity leads to DNA fragmentation, which is a hallmark of apoptosis. Although recent studies have demonstrated that CASP3 plays a vital role in tumour suppression by promoting apoptosis, these reports did not consider systematic pan-cancer analyses. Therefore, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse CASP3 expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden (TMB), and microsatellite instability (MSI), as well as immune cell infiltration in different tumours and the molecular mechanisms underlying these. We found that CASP3 expression was significantly associated with the prognosis of most tumours. Additionally, promoter methylation status was associated with CASP3 expression in bladder urothelial carcinoma, oesophageal carcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, sarcoma, testicular germ cell tumours, and uterine corpus endometrial carcinoma. TMB and MSI were associated with CASP3 expression in 15 tumours. Moreover, CASP3 expression was correlated with the tumour microenvironment in nearly all tumour types. Further, we observed that in addition to apoptosis, CASP3 action plausibly involves B cell activation, antigen presentation, immune responses, chemokine receptors, and inflammatory function. Our study thus provides a relatively comprehensive understanding of the carcinogenicity of CASP3 in different tumours and suggests that CASP3 is a potential prognostic marker.
Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons Cultured in vitro
Authors: Diaz Jenny R. , Martá-Ariza Mitchell , Khodadadi-Jamayran Alireza , Heguy Adriana , Tsirigos Aristotelis , Pankiewicz Joanna E. , Sullivan Patrick M. , Sadowski Martin J.
Published: April 2022

The APOE gene is diversified by three alleles ε2, ε3, and ε4 encoding corresponding apolipoprotein (apo) E isoforms. Possession of the ε4 allele is signified by increased risks of age-related cognitive decline, Alzheimer’s disease (AD), and the rate of AD dementia progression. ApoE is secreted by astrocytes as high-density lipoprotein-like particles and these are internalized by neurons upon binding to neuron-expressed apoE receptors. ApoE isoforms differentially engage neuronal plasticity through poorly understood mechanisms. We examined here the effects of native apoE lipoproteins produced by immortalized astrocytes homozygous for ε2, ε3, and ε4 alleles on the maturation and the transcriptomic profile of primary hippocampal neurons. Control neurons were grown in the presence of conditioned media from Apoe–/– astrocytes. ApoE2 and apoE3 significantly increase the dendritic arbor branching, the combined neurite length, and the total arbor surface of the hippocampal neurons, while apoE4 fails to produce similar effects and even significantly reduces the combined neurite length compared to the control. ApoE lipoproteins show no systemic effect on dendritic spine density, yet apoE2 and apoE3 increase the mature spines fraction, while apoE4 increases the immature spine fraction. This is associated with opposing effects of apoE2 or apoE3 and apoE4 on the expression of NR1 NMDA receptor subunit and PSD95. There are 1,062 genes differentially expressed across neurons cultured in the presence of apoE lipoproteins compared to the control. KEGG enrichment and gene ontology analyses show apoE2 and apoE3 commonly activate expression of genes involved in neurite branching, and synaptic signaling. In contrast, apoE4 cultured neurons show upregulation of genes related to the glycolipid metabolism, which are involved in dendritic spine turnover, and those which are usually silent in neurons and are related to cell cycle and DNA repair. In conclusion, our work reveals that lipoprotein particles comprised of various apoE isoforms differentially regulate various neuronal arbor characteristics through interaction with neuronal transcriptome. ApoE4 produces a functionally distinct transcriptomic profile, which is associated with attenuated neuronal development. Differential regulation of neuronal transcriptome by apoE isoforms is a newly identified biological mechanism, which has both implication in the development and aging of the CNS.
Centrin 2: A Novel Marker of Mature and Neoplastic Human Astrocytes
Authors: Degl’Innocenti Elisa , Poloni Tino Emanuele , Medici Valentina , Recupero Luca , Dell’Amico Claudia , Vannini Eleonora , Borello Ugo , Mazzanti Chiara Maria , Onorati Marco , Dell’Anno Maria Teresa
Published: April 2022

As microtubule-organizing centers (MTOCs), centrosomes play a pivotal role in cell division, neurodevelopment and neuronal maturation. Among centrosomal proteins, centrin-2 (CETN2) also contributes to DNA repair mechanisms which are fundamental to prevent genomic instability during neural stem cell pool expansion. Nevertheless, the expression profile of CETN2 in human neural stem cells and their progeny is currently unknown. To address this question, we interrogated a platform of human neuroepithelial stem (NES) cells derived from post mortem developing brain or established from pluripotent cells and demonstrated that while CETN2 retains its centrosomal location in proliferating NES cells, its expression pattern changes upon differentiation. In particular, we found that CETN2 is selectively expressed in mature astrocytes with a broad cytoplasmic distribution. We then extended our findings on human autoptic nervous tissue samples. We investigated CETN2 distribution in diverse anatomical areas along the rostro-caudal neuraxis and pointed out a peculiar topography of CETN2-labeled astrocytes in humans which was not appreciable in murine tissues, where CETN2 was mostly confined to ependymal cells. As a prototypical condition with glial overproliferation, we also explored CETN2 expression in glioblastoma multiforme (GBM), reporting a focal concentration of CETN2 in neoplastic astrocytes. This study expands CETN2 localization beyond centrosomes and reveals a unique expression pattern that makes it eligible as a novel astrocytic molecular marker, thus opening new roads to glial biology and human neural conditions.
Functional Organisation of the Mouse Superior Colliculus
Authors: Wheatcroft Thomas , Saleem Aman B. , Solomon Samuel G.
Published: April 2022

The superior colliculus (SC) is a highly conserved area of the mammalian midbrain that is widely implicated in the organisation and control of behaviour. SC receives input from a large number of brain areas, and provides outputs to a large number of areas. The convergence and divergence of anatomical connections with different areas and systems provides challenges for understanding how SC contributes to behaviour. Recent work in mouse has provided large anatomical datasets, and a wealth of new data from experiments that identify and manipulate different cells within SC, and their inputs and outputs, during simple behaviours. These data offer an opportunity to better understand the roles that SC plays in these behaviours. However, some of the observations appear, at first sight, to be contradictory. Here we review this recent work and hypothesise a simple framework which can capture the observations, that requires only a small change to previous models. Specifically, the functional organisation of SC can be explained by supposing that three largely distinct circuits support three largely distinct classes of simple behaviours–arrest, turning towards, and the triggering of escape or capture. These behaviours are hypothesised to be supported by the optic, intermediate and deep layers, respectively.
Strategies for Targeting Neural Circuits: How to Manipulate Neurons Using Virus Vehicles
Authors: Hui Yuqing , Zheng Xuefeng , Zhang Huijie , Li Fang , Yu Guangyin , Li Jiong , Zhang Jifeng , Gong Xiaobing , Guo Guoqing
Published: April 2022

Viral strategies are the leading methods for mapping neural circuits. Viral vehicles combined with genetic tools provide the possibility to visualize entire functional neural networks and monitor and manipulate neural circuit functions by high-resolution cell type- and projection-specific targeting. Optogenetics and chemogenetics drive brain research forward by exploring causal relationships among different brain regions. Viral strategies offer a fresh perspective for the analysis of the structure-function relationship of the neural circuitry. In this review, we summarize current and emerging viral strategies for targeting neural circuits and focus on adeno-associated virus (AAV) vectors.
Prediction of Freezing of Gait in Parkinson's Disease Using Unilateral and Bilateral Plantar-Pressure Data
Authors: Pardoel Scott , Nantel Julie , Kofman Jonathan , Lemaire Edward D.
Published: April 2022

Background

Freezing of gait (FOG) is an intermittent walking disturbance experienced by people with Parkinson's disease (PD). FOG has been linked to falling, injury, and overall reduced mobility. Wearable sensor-based devices can detect freezes already in progress and provide a cue to help the person resume walking. While this is helpful, predicting FOG episodes before onset and providing a timely cue may prevent the freeze from occurring. Wearable sensors mounted on various body parts have been used to develop FOG prediction systems. Despite the known asymmetry of PD motor symptom manifestation, the difference between the most affected side (MAS) and least affected side (LAS) is rarely considered in FOG detection and prediction studies.

Methods

To examine the effect of using data from the MAS, LAS, or both limbs for FOG prediction, plantar pressure data were collected during a series of walking trials and used to extract time and frequency-based features. Three datasets were created using plantar pressure data from the MAS, LAS, and both sides together. ReliefF feature selection was performed. FOG prediction models were trained using the top 5, 10, 15, 20, 25, or 30 features for each dataset.

Results

The best models were the MAS model with 15 features and the LAS and bilateral models with 5 features. The LAS model had the highest sensitivity (79.5%) and identified the highest percentage of FOG episodes (94.9%). The MAS model achieved the highest specificity (84.9%) and lowest false positive rate (1.9 false positives/walking trial). Overall, the bilateral model was best with 77.3% sensitivity and 82.9% specificity. In addition, the bilateral model identified 94.2% of FOG episodes an average of 0.8 s before FOG onset. Compared to the bilateral model, the LAS model had a higher false positive rate; however, the bilateral and LAS models were similar in all the other evaluation metrics.

Conclusion

The LAS model would have similar FOG prediction performance to the bilateral model at the cost of slightly more false positives. Given the advantages of single sensor systems, the increased false positive rate may be acceptable to people with PD. Therefore, a single plantar pressure sensor placed on the LAS could be used to develop a FOG prediction system and produce performance similar to a bilateral system.
Safety and Efficacy of Tirofiban During Intravenous Thrombolysis Bridging to Mechanical Thrombectomy for Acute Ischemic Stroke Patients: A Meta-Analysis
Authors: Li Wei , Lin Guohui , Xiao Zaixing , Zhang Yichuan , Li Bin , Zhou Yu , Chai Erqing
Published: April 2022

Introduction

The safety and efficacy of tirofiban in intravenous thrombolysis (IVT) bridging to mechanical thrombectomy in patients with acute ischemic stroke (AIS) is unknown. The purpose of this meta-analysis was to evaluate the safety and efficacy of tirofiban in IVT bridging to mechanical thrombectomy in acute ischemic stroke.

Methods

We systematically searched PubMed, EMBASE, Web of Science, and The Cochrane Library, CNKI, and Wan Fang databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the tirofiban and non-tirofiban groups in AIS intravenous thrombolysis bridging to mechanical thrombectomy (Published by November 20, 2021). Our primary safety endpoints were symptomatic cerebral hemorrhage (sICH), intracranial hemorrhage (ICH), postoperative re-occlusion, and 3-month mortality; the efficacy endpoints were 3-month favorable functional outcome (MRS ≤ 2) and successful recanalization rate (modified thrombolytic therapy in cerebral infarction (mTICI) 2b or 3).

Results

A total of 7 studies with 1,176 patients were included in this meta-analysis. A comprehensive analysis of the included literature showed that the difference between the tirofiban and non-tirofiban groups in terms of successful recanalization (OR = 1.19, 95% Cl [0.69, 2.03], p = 0.53, I2 = 22%) and favorable functional outcome at 3 months (OR = 1.13, 95% Cl [0.81, 1.60], p = 0.47, I2 = 17%) in patients with IVT bridging mechanical thrombectomy of AIS was not statistically significant. Also, the differences in the incidence of sICH (OR = 0.97, 95% Cl [0.58, 1.62], p = 0.89) and ICH (OR = 0.83, 95% Cl [0.55, 1.24], p = 0.36) between the two groups were not statistically significant. However, the use of tirofiban during IVT bridging mechanical thrombectomy reduced the rate of postoperative re-occlusion (OR = 0.36, 95% Cl [0.14, 0.91], p = 0.03) and mortality within 3 months (OR = 0.54, 95% Cl [0.33, 0.87], p = 0.01) in patients.

Conclusion

The use of tirofiban during IVT bridging mechanical thrombectomy for AIS does not increase the risk of sICH and ICH in patients and reduces the risk of postoperative re-occlusion and mortality in patients within 3 months. However, this result needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022297441.
Age-Related Tortuosity of Carotid and Vertebral Arteries: Quantitative Evaluation With MR Angiography
Authors: Sun Zhe , Jiang Dengrong , Liu Peiying , Muccio Marco , Li Chenyang , Cao Yan , Wisniewski Thomas M. , Lu Hanzhang , Ge Yulin
Published: April 2022

Background and Purpose

The vascular tortuosity (VT) of the internal carotid artery (ICA), and vertebral artery (VA) can impact blood flow and neuronal function. However, few studies involved quantitative investigation of VT based on magnetic resonance imaging (MRI). The main purpose of our study was to evaluate the age and gender effects on ICA and VA regarding the tortuosity and flow changes by applying automatic vessel segmentation, centerline tracking, and phase mapping on MR angiography.

Methods

A total of 247 subjects (86 males and 161 females) without neurological diseases participated in this study. All subjects obtained T1-weighted MRI, 3D time-of-flight MR angiography, and 2D phase-contrast (PC) MRI scans. To generate quantitative tortuosity metrics from TOF images, the vessel segmentation and centerline tracking were implemented based on Otsu thresholding and fast marching algorithms, respectively. Blood flow and velocity were measured using PC MRI. Among the 247 subjects, 144 subjects (≤ 60 years, 49 males/95 females) were categorized as the young group; 103 subjects (>60 years, 37 males/66 females) were categorized as the old group.

Results

Independent t-test showed that older subjects had higher tortuosity metrics, whereas lower blood flow and velocity than young subjects (p < 0.0025, Bonferroni-corrected). Cerebral blood flow calculated using the sum flux of four target arteries normalized by the brain mass also showed significantly lower values in older subjects (p < 0.001). The age was observed to be positively correlated with the VT metrics. Compared to the males, the females demonstrated higher geometric indices within VAs as well as faster age-related vascular profile changes. After adjusting age and gender as covariates, maximum blood velocity is negatively correlated with geometric measurements. No association was observed between blood flux and geometric measures.

Conclusions

Vascular auto-segmentation, centerline tracking, and phase mapping provide promising quantitative assessments of tortuosity and its effects on blood flow. The neck arteries demonstrate quantifiable and significant age-related morphological and hemodynamic alterations. Moreover, females showed more distinct vascular changes with age. Our work is built upon a comprehensive quantitative investigation of a large cohort of populations covering adult lifespan using MRI, the results can serve as reference ranges of each decade in the general population.
Post-Stroke Administration of L-4F Promotes Neurovascular and White Matter Remodeling in Type-2 Diabetic Stroke Mice
Authors: Zhou Min , Li Rongwen , Venkat Poornima , Qian Yu , Chopp Michael , Zacharek Alex , Landschoot-Ward Julie , Powell Brianna , Jiang Quan , Cui Xu
Published: April 2022

Patients with type 2 diabetes mellitus (T2DM) exhibit a distinct and high risk of ischemic stroke with worse post-stroke neurovascular and white matter (WM) prognosis than the non-diabetic population. In the central nervous system, the ATP-binding cassette transporter member A 1 (ABCA1), a reverse cholesterol transporter that efflux cellular cholesterol, plays an important role in high-density lipoprotein (HDL) biogenesis and in maintaining neurovascular stability and WM integrity. Our previous study shows that L-4F, an economical apolipoprotein A member I (ApoA-I) mimetic peptide, has neuroprotective effects via alleviating neurovascular and WM impairments in the brain of db/db-T2DM stroke mice. To further investigate whether L-4F has neurorestorative benefits in the ischemic brain after stroke in T2DM and elucidate the underlying molecular mechanisms, we subjected middle-aged, brain-ABCA1 deficient (ABCA1−B/−B), and ABCA1-floxed (ABCA1fl/fl) T2DM control mice to distal middle cerebral artery occlusion. L-4F (16 mg/kg, subcutaneous) treatment was initiated 24 h after stroke and administered once daily for 21 days. Treatment of T2DM-stroke with L-4F improved neurological functional outcome, and decreased hemorrhage, mortality, and BBB leakage identified by decreased albumin infiltration and increased tight-junction and astrocyte end-feet densities, increased cerebral arteriole diameter and smooth muscle cell number, and increased WM density and oligodendrogenesis in the ischemic brain in both ABCA1−B/−B and ABCA1fl/fl T2DM-stroke mice compared with vehicle-control mice, respectively (p < 0.05, n = 9 or 21/group). The L-4F treatment reduced macrophage infiltration and neuroinflammation identified by decreases in ED-1, monocyte chemoattractant protein-1 (MCP-1), and toll-like receptor 4 (TLR4) expression, and increases in anti-inflammatory factor Insulin-like growth factor 1 (IGF-1) and its receptor IGF-1 receptor β (IGF-1Rβ) in the ischemic brain (p < 0.05, n = 6/group). These results suggest that post-stroke administration of L-4F may provide a restorative strategy for T2DM-stroke by promoting neurovascular and WM remodeling. Reducing neuroinflammation in the injured brain may contribute at least partially to the restorative effects of L-4F independent of the ABCA1 signaling pathway.
Transcranial Doppler Ultrasonography as a Diagnostic Tool for Cerebrovascular Disorders
Authors: Pan Yuanmei , Wan Wenbin , Xiang Minjie , Guan Yangtai
Published: April 2022

Imaging techniques including transcranial Doppler (TCD), magnetic resonance imaging (MRI), computed tomography (CT), and cerebral angiography are available for cerebrovascular disease diagnosis. TCD is a less expensive, non-invasive, and practically simpler approach to diagnosing cerebrovascular disorders than the others. TCD is a commonly available and inexpensive diagnostic tool. However, owing to its large operator dependency, it has a narrow application area. Cerebrovascular disease indicates a group of disorders that alter the flow of blood in the brain. The brain’s functions can be temporarily or permanently impaired as a result of this change in blood flow. Timely diagnosis and treatment can restore the brain-impaired functions, resulting in a much-improved prognosis for the patients. This review summarizes the basic principles underlying the TCD imaging technique and its utility as a diagnostic tool for cerebrovascular disease.
Decreased Postural Complexity in Overweight to Obese Children and Adolescents: A Cross-Sectional Study
Authors: Wiesinger Hans-Peter , Buchecker Michael , Müller Erich , Stöggl Thomas , Birklbauer Jürgen
Published: April 2022

Introduction

Although a few studies suggest that young overweight to obese children and adolescents (YO) may have impaired postural control compared to young normal-weight (YN) peers, little information exists about how these two groups differ in the quality of the underlying balance strategies employed. Hence, the aim of the present study was a first comprehensive examination of the structural complexity of postural sways in these two cohorts during quiet bilateral standing.

Methods

Nineteen YO secondary school students (13.0 ± 1.4 years; male = 10, female = 9) were carefully matched to YN controls (13.0 ± 1.5 years) for age, sex, height, and school. Mediolateral (ML) and anteriorposterior (AP) acceleration signals were recorded with an inertial measurement unit (IMU) positioned at the trunk while standing barefoot in two conditions: firm and foam support surface. The magnitude of postural fluctuations was obtained using the root mean square (RMS). The temporal structure of the signals was analyzed via sample entropy (SEn), largest Lyapunov exponent (LyE), and detrended fluctuation analysis (α-DFA) algorithm. Reliability was assessed using a test–retest design.

Results

In both groups, foam standing caused higher postural fluctuations (higher RMS values) and reduced structural complexity (lower SEn values, higher LyE values, higher α-DFA values). In comparison to YN, YO exhibited a higher RMSAP. Especially in ML direction, the acceleration signals of the YO had higher repeatability (smaller SEn values), greater long-range correlations (higher α-DFA values), and lower local stability (higher LyE values). However, these observations were largely independent of the task difficulty. Except for α-DFAAP, the IMU approach proved reliable to characterize posture control.

Discussion

Our outcomes confirm postural control deficits in YO compared to their YN peers and indicate impaired regulatory mechanisms reflected as rigidity. Such less complex patterns usually reflect diverse pathologies, are detrimental to compensate for internal or external perturbations, and are attributed to lower adaptability and task performance. Without targeted balance stimuli, YO likely end in a lifelong vicious circle of mutually dependent poor balance regulation and low physical activity.
Cochlear Implant Awareness: Development and Validation of a Patient Reported Outcome Measure
Authors: Markodimitraki Laura M. , Stegeman Inge , Thomeer Hans G. X. M.
Published: April 2022

Background

Surgical success of cochlear implantation is usually measured through speech perception and quality of life questionnaires. Although these questionnaires cover a broad spectrum of domains, they do not evaluate the consciousness of wearing a cochlear implant (CI) and how this impacts the daily life of patients. To evaluate this concept we aimed to develop and validate a standardized patient reported outcome measure (PROM) for use in cochlear implant users.

Methods

Development and evaluation of the COchlear iMPlant AwareneSS (COMPASS) questionnaire was realized following the COSMIN guidelines in three phases: (1) item generation, (2) qualitative pilot study to ensure relevance, comprehensiveness, comprehensibility, and face validity, and (3) quantitative survey study for the assessment of reliability (test-retest) with 54 participants.

Results

Nine domains of CI awareness were identified through literature research and interviews with experts and patients. These resulted in the formulation of 18 items which were tested with a pilot study, after which 3 items were deleted. The final 15-item COMPASS questionnaire proved to have good validity and satisfactory reliability. The intraclass correlation coefficient calculated for items with continuous variables ranged from 0.66 to 0.89 with seven out of eight items scoring above the acceptable level of 0.7. The Cohen’s kappa calculated for items with nominal variables ranged from −0.4 to 0.78 with 11 (sub)items out of 15 scoring above fair to good agreement. Measurement error analysis for items with continuous variables showed a mean difference of −2.18 to 0.22. The calculated 95% limits of agreement for these items revealed no statistically significant difference between the two administered questionnaires. For items with nominal variables, the percentages of agreement calculated, ranged between 0 and 95%, and 83.3 and 96.6% for positive and negative agreement, respectively.

Conclusion

The COMPASS questionnaire is a valid and reliable PROM for evaluating the cochlear implant awareness, and it can be easily used in routine clinical practice.
Lipid-Lowering Efficacy of Kuding Tea in Patients With Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jiang Zhonghui , Lu Zhuqing , Wang Tianyi , Wang Yilian , Chu Jianfeng , Chen Keji , Gao Zhuye
Published: April 2022

Background

Kuding tea (KT), traditional tea material and widely used in China, has been found to have lipid-lowering effect in clinical and experimental studies. However, there has been no systematic review of the evidence on this subject.

Methods

Eight electronic databases were searched from database inception until September 2021 for relevant randomized controlled trials (RCTs). We used the Cochrane Reviewer’s Handbook to assess the quality of the included studies. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to measure the pooled effect size by random-effects model. Funnel plot, Egger regression test, and the Begg’s test was used to assess publication bias.

Results

Eight RCTs involving 716 patients were included in our meta-analysis. Comparing with the control group, KT group reduced serum total cholesterol (TC) levels (WMD: −0.56 mmol/L; 95% CI: −0.64, −0.47; I2 = 56.56%; P = 0.00), triglyceride (TG) levels (WMD: −0.30 mmol/L; 95% CI: −0.35, −0.24; I2 = 88.60%; P = 0.00), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: −0.29 mmol/L; 95% CI: −0.37, −0.21; I2 = 89.43%; P = 0.00), but no significant effects on high-density lipoprotein cholesterol (HDL-C) (WMD: 0.07 mmol/L; 95% CI: −0.02, 0.16; I2 = 93.92%; P = 0.12). The results of sensitivity analysis were not altered after removing each study in turn. Subgroup analyses showed that KT intervention period was the source of heterogeneity. Following analysis, results revealed that long-term (>4 weeks and ≤8 weeks) use of KT increased HDL-C levels (WMD: 0.19; 95% CI: 0.13, 0.25). In addition, both the sensitivity analysis and subgroup analysis showed that our results were robust. No potentially significant publication bias was found from the funnel plot, Begg-Mazumdar correlation test and Egger regression test.

Conclusion

KT supplementation can effectively improve lipid profile and KT is a promising approach to reduce blood lipid level in patients with metabolic disorders.

Systematic Review Registration

[www.crd.york.ac.uk/prospero], identifier [CRD42020221850].
Acute Effects of Milk vs. Carbohydrate on Bone Turnover Biomarkers Following Loading Exercise in Young Adult Females
Authors: Prowting Joel L. , Skelly Lauren E. , Kurgan Nigel , Fraschetti Emily C. , Klentrou Panagiota , Josse Andrea R.
Published: April 2022

Dairy products and impact exercise have previously been identified to be independently beneficial for bone mineral properties, however, it is unknown how the combination of these two osteogenic interventions may alter acute bone turnover. Using a randomized crossover design, we compared the acute effects of consuming milk vs. an isoenergetic carbohydrate control beverage on bone biomarkers following loading exercise. Thirteen healthy female participants (Age = 20.3 ± 2.3y; BMI = 21.0 ± 1.1 kg/m2) consumed either 550 mL of 0% skim white milk (MILK) or 52.7 g of maltodextrin in 550 mL of water (CHO), both 5 min and 1 h following completion of a combined plyometric (198 impacts) and resistance exercise (3–4 sets/exercise, 8–12 reps/set, ∼75% 1-RM) bout. Venous blood samples were obtained pre-exercise, and 15 min, 75 min, 24 h and 48 h post-exercise to assess serum concentrations of bone resorption biomarkers, specifically carboxyl-terminal crosslinking telopeptide of type I collagen (CTX), receptor activator nuclear factor kappa-β ligand (RANKL), and sclerostin (SOST), as well as bone formation biomarkers, specifically osteoprotegerin (OPG) and osteocalcin (OC). When absolute biomarker concentrations were examined, there were no interaction or group effects for any biomarker, however, there were main time effects (p < 0.05) for RANKL, SOST, and OC, which were lower, and the OPG: OPG/RANKL ratio, which was higher at 75 min post-exercise compared with baseline in both conditions. In addition to assessing absolute biomarker concentrations at specific timepoints, we also evaluated the relative (% change) cumulative post-exercise response (75 min to 48 h) using an area under the curve (AUC) analysis. This analysis showed that the relative post-exercise CTX response was significantly lower in the MILK compared to the CHO condition (p = 0.03), with no differences observed in the other biomarkers. These results show that while milk does not appear to alter absolute concentrations of bone biomarkers compared to CHO, it may attenuate relative post-exercise bone resorption (i.e., blunt the usual catabolic response to exercise).
Curcumin and Intestinal Oxidative Stress of Pigs With Intrauterine Growth Retardation: A Review
Authors: Tang Xiaopeng , Xiong Kangning , Wassie Teketay , Wu Xin
Published: April 2022

Intrauterine growth restriction (IUGR) refers to the slow growth and development of a mammalian embryo/fetus or fetal organs during pregnancy, which is popular in swine production and causes considerable economic losses. Nutritional strategies have been reported to improve the health status and growth performance of IUGR piglets, among which dietary curcumin supplementation is an efficient alternative. Curcumin is a natural lipophilic polyphenol derived from the rhizome of Curcuma longa with many biological activities. It has been demonstrated that curcumin promotes intestinal development and alleviates intestinal oxidative damage. However, due to its low bioavailability caused by poor solubility, chemical instability, and rapid degradation, the application of curcumin in animal production is rare. In this manuscript, the structural-activity relationship to enhance the bioavailability, and the nutritional effects of curcumin on intestinal health from the aspect of protecting piglets from IUGR associated intestinal oxidative damage were summarized to provide new insight into the application of curcumin in animal production.
Bioactive Compounds and Antioxidant Activity of Lettuce Grown in Different Mixtures of Monogastric-Based Manure With Lunar and Martian Soils
Authors: Duri Luigi G. , Pannico Antonio , Petropoulos Spyridon A. , Caporale Antonio G. , Adamo Paola , Graziani Giulia , Ritieni Alberto , De Pascale Stefania , Rouphael Youssef
Published: April 2022

The supplementation of bioactive compounds in astronaut’s diets is undeniable, especially in the extreme and inhospitable habitat of future space settlements. This study aims to enhance the Martian and Lunar regolith fertility (testing two commercial simulants) through the provision of organic matter (manure) as established by in situ resource utilization (ISRU) approach. In this perspective, we obtained 8 different substrates after mixing Mojave Mars Simulant (MMS-1) or Lunar Highlands Simulant (LHS-1), with four different rates of manure (0, 10, 30, and 50%, w/w) from monogastric animals. Then, we assessed how these substrates can modulate fresh yield, organic acid, carotenoid content, antioxidant activity, and phenolic profile of lettuce plants (Lactuca sativa L.). Regarding fresh biomass production, MMS-1-amended substrates recorded higher yields than LHS-1-ones; plants grown on a 70:30 MMS-1/manure mixture produced the highest foliar biomass. Moreover, we found an increase in lutein and β-carotene content by + 181 and + 263%, respectively, when applying the highest percentage of manure (50%) compared with pure simulants or less-amended mixtures. The 50:50 MMS-1/manure treatment also contained the highest amounts of individual and total organic acids, especially malate content. The highest antioxidant activity for the ABTS assay was recorded when no manure was added. The highest content of total hydroxycinnamic acids was observed when no manure was added, whereas ferulic acid content (most abundant compound) was the highest in 70:30 simulant/manure treatment, as well as in pure LHS-1 simulant. The flavonoid content was the highest in pure-simulant treatment (for most of the compounds), resulting in the highest total flavonoid and total phenol content. Our findings indicate that the addition of manure at specific rates (30%) may increase the biomass production of lettuce plants cultivated in MMS-1 simulant, while the phytochemical composition is variably affected by manure addition, depending on the stimulant. Therefore, the agronomic practice of manure amendment showed promising results; however, it must be tested with other species or in combination with other factors, such as fertilization rates and biostimulants application, to verify its applicability in space colonies for food production purposes.
Improvement in Mung Bean Peptide on High-Fat Diet-Induced Insulin Resistance Mice Using Untargeted Serum Metabolomics
Authors: Li Lina , Tian Yu , Feng Yuchao , Zhang Shu , Jiang Yingjun , Zhang Yiwei , Zhan Yuanyuan , Wang Changyuan
Published: April 2022

This study aimed to elucidate the potential regulatory mechanism of mung bean peptides (MBPs) on glucolipid metabolism in insulin-resistant mice induced by high-fat diet (HFD) using untargeted serum metabolomics, enzyme linked immunosorbent assay (ELISA), intraperitoneal injection glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and hematoxylin-eosin staining (H&E). The regulatory effect of MBPs for alleviating insulin resistance was studied by measuring body weight, fasting blood glucose (FBG) and serum insulin levels, C-Peptide levels, inflammatory and antioxidant factors, and histopathological observation of C57BL/6 mice. The experimental results showed that dietary intervention with MBPs (245 mg/kg/d) for 5 weeks significantly relieved insulin resistance in HFD mice. The body weight, insulin resistance index, and the levels of FBG, C-Peptide, IL-6, TNF-α, and MDA in the serum of HFD mice significantly decreased (P < 0.05). Conversely, SOD content and pancreatic β cell function index significantly increased (P < 0.05), and the damaged pancreatic tissue was repaired. One biomarker associated with insulin resistance was glycine. In addition, there were four important differential metabolites: pyroglutamate, D-glutamine, aminoadipic acid, and nicotinamide, involved in 12 metabolic pathway changes. It was found that MBPs may regulate amino acid, glycerol phospholipid, fatty acid, alkaloid, and nicotinamide metabolism to regulate the metabolic profile of HFD mice in a beneficial direction.
Cerebrospinal Fluid Cell-Free DNA-Based Detection of High Level of Genomic Instability Is Associated With Poor Prognosis in NSCLC Patients With Leptomeningeal Metastases
Authors: Wu Xi , Xing Puyuan , Shi Min , Guo Weihua , Zhao Fangping , Zhu Honglin , Xiao Jianping , Wan Jinghai , Li Junling
Published: April 2022

Introduction

Leptomeningeal metastasis (LM) commonly occurs in non-small cell lung cancer (NSCLC) patients and has a poor prognosis. Due to limited access to leptomeningeal lesions, the genetic characteristics of LM have not been explored to date. Cerebrospinal fluid (CSF) may be the most representative liquid biopsy medium to obtain genomic information from LM in NSCLC.

Methods

CSF biopsies and matched peripheral blood biopsies were collected from 33 NSCLC patients with LM. We profiled genetic alterations from LM by comparing CSF cell-free DNA (cfDNA) with plasma cfDNA. Somatic mutations were examined using targeted sequencing. Genomic instability was analyzed by low-coverage whole-genome sequencing (WGS).

Results

Driver mutations were detected in 100% of CSF cfDNA with much higher variant allele frequency than that in matched plasma cfDNA (57.5%). Furthermore, we found that the proportions of CSF cfDNA fragments below 150 bp were significantly higher than those in plasma cfDNA. These findings indicate enrichment of circulating tumor DNA (ctDNA) in CSF and explain the high sensitivity of mutation detection in the CSF. The absence of some mutations in CSF cfDNA—especially the first-/second-generation mutation T790M, which confers resistance to epidermal growth factor receptor (EGFR)-Tyrosine kinase inhibitors (TKIs)—that were present in plasma cfDNA samples indicates different mechanisms of cancer evolution between LM and extracranial lesions. In addition, 86.6% of CSF ctDNA samples revealed high levels of genomic instability compared with 2.5% in plasma cfDNA samples. A higher number of large-scale state transitions (LSTs) in CSF cfDNA were associated with a shorter overall survival (OS).

Conclusion

Our results suggest that LM and extracranial lesions develop independently. Both CSF cfDNA genetic profiling and plasma cfDNA genetic profiling are necessary for clinical decision-making for NSCLC patients with LM. Through CSF-based low-coverage WGS, a high level of LSTs was identified as a potential biomarker of poor prognosis.
Radiation Induced Lymphopenia Is Associated With the Effective Dose to the Circulating Immune Cells in Breast Cancer
Authors: Chen Fang , Jin Jian-Yue , Hui Timothy S.K. , Jing Haiman , Zhang Hong , Nong Yaqing , Han Ying , Wang Weili , Ma Lingyu , Yi Fan , Chen Qingqing , Zhang Yongsheng , Fu Pingfu , Yang Li , Xu Zhiyuan , Kong Feng-Ming Spring
Published: April 2022

Background

Lymphopenia is a known significant factor for treatment outcome in cancer patients, with underlying risk factor poorly understood in breast cancer. We hypothesize that the effective dose to the circulating immune cells (EDIC) which was related with lymphopenia in lung cancer will also have significant effect for radiation induced lymphopenia (RIL) in patients with breast cancer.

Material and Methods

Patients treated with adjuvant radiotherapy (RT) and with complete blood tests within one week from RT end/start (post/preRT) were eligible in this study. Radiation dosimetric factors were collected retrospectively, and EDIC for each patient was calculated based on the doses to lung, heart and total body according to the model description, as previously reported. RIL was defined by the CTCAE5.0 based on postRT peripheral lymphocyte count (PLC). Linear regression was first used to test the correlation between EDIC with post/preRT PLC ratio and postRT PLC, using all these as continuous variables. Normal tissue complication probability (NTCP) was used to develop models that predict the CTCAE graded RIL from EDIC.

Results

A total of 735 patients were eligible. The mean post/preRT PLC ratio was 0.66 (95% CI: 0.64-0.68) and mean EDIC of breast cancer was 1.70Gy (95% CI: 1.64-1.75). Both post/preRT PLC ratio and postRT PLC were significantly correlated with EDIC (P<0.001), with R2of 0.246. For patients with normal preRT PLC, the post/preRT PLC ratio was better associated with EDIC, and postRT PLC was expressed as PLCpreRT× (0.89 – 0.16 ×EDIC). For patients with preRT lymphopenia, postRT PLC was better associated with EDIC and it was 1.1 – 0.17 ×EDIC. Using binned EDIC as the dose variable, the bootstrap validated NTCPs fit the data nicely with R2of 0.93, 0.96, and 0.94 for grade-1, grade-2, and grade-3 RIL, respectively. The corresponding EDIC to induce 50% of grade-1, grade-2 and grade-3 RIL was 1.2, 2.1 and 3.7 Gy, respectively.

Conclusion

EDIC is a significant factor for RIL in patients with breast cancer, and may be used to compute the risk of lymphopenia in each individual patient with the use of the conventional NTCP modeling. External validation is needed before the EDIC can be used to guide RT plan.
Epidemiological Evidence Between Variants in Matrix Metalloproteinases-2, -7, and -9 and Cancer Risk
Authors: Huang Chenglu , Xu Suqin , Luo Zhilin , Li Dong , Wang Rui , Wang Tianhu
Published: April 2022

Background

Matrix metalloproteinases (MMPs), a kind of proteases, have a critical function in cancer occurrence, invasion, and migration. MMP gene variants (e.g., MMP-2, MMP-7, and MMP-9) can affect the biological functions of these enzymes and lead to the occurrence and progression of cancer, which has become a hot topic in recent years, but the corresponding results are still controversial. In this context, here, the meta-analysis was conducted for assessing the relations of variants in MMP-2, MMP-7, and MMP-9 with the risk of various cancers.

Methods

PubMed, Web of Science, and Medline were systemically searched, and data were extracted from all eligible studies so as to investigate the susceptibility of MMP-2, MMP-7, and MMP-9 to different types of cancers. The association between a variant in MMP and cancer susceptibility was analyzed through odds ratios (ORs) as well as 95% CIs. The Venice criteria and false-positive report probability (FPRP) were adopted to evaluate epidemiological evidence of significant associations discovered.

Results

The associations between the variants of MMPs and cancer risk in 36,530 cases and 41,258 controls were found, with 12 associations (MMP-2 rs243865 with esophageal cancer and lung cancer, MMP-7 rs11568818 with bladder and cervical cancer, and MMP-9 rs3918242 with breast cancer) rated as strong associations for cancer risk and 7 and 15 as moderate and weak associations, respectively. These significant associations were mostly found in Asians.

Conclusions

These findings support the relations between variants of MMP-2, MMP-7, and MMP-9 and various cancers risk, demonstrating the credibility of these relations.
Neoadjuvant Sintilimab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma
Authors: Lv Huilai , Tian Yang , Li Jiachen , Huang Chao , Sun Bokang , Gai Chunyue , Li Zhenhua , Tian Ziqiang
Published: April 2022

Background

Neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) are the standard treatments in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Adding PD-1 inhibitor to the chemotherapy has shown significant clinical benefits in first-line treatment of advanced ESCC. This study evaluated the efficacy and safety of neoadjuvant sintilimab plus chemotherapy in patients with resectable locally advanced ESCC.

Methods

The clinical data of 96 patients with resectable locally advanced ESCC, treated with sintilimab plus chemotherapy followed by esophagectomy, were reviewed. The pathologic complete response (pCR) rate, major pathological response (MPR) rate, R0 resection rate, tumor downstaging, survival, and safety were retrospectively analyzed.

Results

Patients were between the ages of 43 and 78 years (interquartile range [IQR], 60–69 years). Forty (41.7%) were diagnosed with stage II ESCC, 52 (54.2%) with stage III, and 4 (4.2%) with stage IVA. Sixty-seven (69.8%) were male, and 84 (87.5%) patients had an ECOG PS of ≤1. Forty-eight (50.0%) patients received 3–4 cycles of the neoadjuvant treatment. Twenty-nine (30.2%) patients obtained pCR, and MPR was achieved in 60 (62.5%) patients. The R0 resection rate was 99%. Eighty (83.3%) patients achieved clinical downstaging, and 71 (74.0%) achieved pathological downstaging. The median follow-up was 8.9 months, and 1-year DFS rate was 95.2% (95% CI, 88.8%–100%). Grade 3–4 TRAEs occurred in 12 (12.5%) patients, and the incidence of grade 3–4 surgical complications was 2.1%. No deaths were reported.

Conclusion

These real-world data revealed that neoadjuvant sintilimab plus chemotherapy could provide encouraging pCR with good tolerability for resectable locally advanced ESCC, and this regimen warrants further exploration in prospective clinical studies.