bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Very Low-Level Somatic Mosaic COL4A5 Splicing Variant in Asymptomatic Female Using Droplet Digital PCR
Authors: Deng Haiyue , Zhang Yanqin , Ding Jie , Wang Fang
Published: March 2022

Background

Alport syndrome is a hereditary glomerulopathy featured by haematuria, proteinuria, and progressive renal failure. X-linked Alport syndrome (XLAS) due to COL4A5 disease-causing variants is the most common form. In the case of XLAS resulting from 10–18% presumed de novo COL4A5 disease-causing variants, there are only a few studies for mosaicism in the probands or parents. Very low-level (<1.0%) somatic mosaicism for COL4A5 disease-causing variants has not been published.

Materials and Methods

Chinese XLAS families with suspected parental mosaicism were enrolled in the present study to evaluate the forms of mosaicism, to offer more appropriate genetic counseling. PCR and direct sequencing were used to detect COL4A5 disease-causing variants harbored by the affected probands in parental multi-tissue DNAs (peripheral blood, urine sediments, saliva, hair), and droplet digital PCR (ddPCR) was used to quantify the mutant COL4A5 allelic fractions in parental different samples such as peripheral blood, saliva, and urine sediments.

Results

A Chinese asymptomatic female with suspected somatic and germline mosaicism was enrolled in the present study. She gave birth to two boys with XLAS caused by a hemizygous disease-causing variant c. 2245-1G>A in COL4A5 (NM_033380) intron 28, whereas this disease-causing variant was not detected in genomic DNA extracted from peripheral blood leukocytes in the woman using Sanger sequencing. She had multiple normal urine test results, and continuous linear immunofluorescence staining of α2 (IV) and α5 (IV) chains of skin tissue. Sanger sequencing demonstrated that COL4A5 disease-causing variant c. 2245-1G>A was not detected in her genomic DNAs isolated from urine sediments, saliva, and hair roots. Using ddPCR, the wild-type and mutant-type (c.2245-1G>A) COL4A5 was identified in the female's genomic DNAs isolated from peripheral blood, saliva, and urine sediments. The mutant allelic fractions in these tissues were 0.26% (peripheral blood), 0.73% (saliva), and 1.39% (urine), respectively.

Conclusions

Germline and very low-level somatic mosaicism for a COL4A5 splicing variant was detected in an asymptomatic female, which highlights that parental mosaicism should be excluded when a COL4A5 presumed de novo disease-causing variant is detected.
Lung Ventilation/Perfusion Scintigraphy for the Screening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Which Criteria to Use?
Authors: Le Pennec Romain , Tromeur Cécile , Orione Charles , Robin Philippe , Le Mao Raphaël , De Moreuil Claire , Jevnikar Mitja , Hoffman Clément , Savale Laurent , Couturaud Francis , Sitbon Olivier , Montani David , Jaïs Xavier , Le Gal Grégoire , Salaün Pierre Yves , Humbert Marc , Le Roux Pierre Yves
Published: March 2022

Objective

The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation. The aim of this study was to assess the accuracy of various interpretation criteria of planar V/Q scintigraphy for the screening of CTEPH in patients with PH.

Methods

The eligible study population consisted of consecutive patients with newly diagnosed PH in the Brest University Hospital, France. Final diagnosis (CTEPH or non-CTEPH) was established in a referential center on the management of PH, based on the ESC/ERS guidelines and a minimum follow-up of 3 years. A retrospective central review of planar V/Q scintigraphy was performed by three nuclear physicians blinded to clinical findings and to final diagnosis. The number, extent (sub-segmental or segmental) and type (matched or mismatched) of perfusion defects were reported. Sensitivity and specificity were evaluated for various criteria based on the number of mismatched perfusion defects and the number of perfusion defects (regardless of ventilation). Receiver operating characteristic (ROC) curves were generated and areas under the curve (AUC) were calculated for both.

Results

A total of 226 patients with newly diagnosed PH were analyzed. Fifty six (24.8%) were diagnosed with CTEPH while 170 patients (75.2%) were diagnosed with non-CTEPH. The optimal threshold was 2.5 segmental mismatched perfusion defects, providing a sensitivity of 100 % (95% CI 93.6–100%) and a specificity of 94.7% (95%CI 90.3–97.2%). Lower diagnostic cut-offs of mismatched perfusion defects provided similar sensitivity but lower specificity. Ninety five percent of patients with CTEPH had more than 4 segmental mismatched defects. An interpretation only based on perfusion provided similar sensitivity but a specificity of 81.8% (95%CI 75.3–86.9%).

Conclusion

Our study confirmed the high diagnostic performance of planar V/Q scintigraphy for the screening of CTEPH in patients with PH. The optimal diagnostic cut-off for interpretation was 2.5 segmental mismatched perfusion defects. An interpretation only based on perfusion defects provided similar sensitivity but lower specificity.
Two Faces of Fermented Foods—The Benefits and Threats of Its Consumption
Authors: Skowron Krzysztof , Budzyńska Anna , Grudlewska-Buda Katarzyna , Wiktorczyk-Kapischke Natalia , Andrzejewska Małgorzata , Wałecka-Zacharska Ewa , Gospodarek-Komkowska Eugenia
Published: March 2022

In underdeveloped and developing countries, due to poverty, fermentation is one of the most widely used preservation methods. It not only allows extending the shelf life of food, but also brings other benefits, including inhibiting the growth of pathogenic microorganisms, improving the organoleptic properties and product digestibility, and can be a valuable source of functional microorganisms. Today, there is a great interest in functional strains, which, in addition to typical probiotic strains, can participate in the treatment of numerous diseases, disorders of the digestive system, but also mental diseases, or stimulate our immune system. Hence, fermented foods and beverages are not only a part of the traditional diet, e.g., in Africa but also play a role in the nutrition of people around the world. The fermentation process for some products occurs spontaneously, without the use of well-defined starter cultures, under poorly controlled or uncontrolled conditions. Therefore, while this affordable technology has many advantages, it can also pose a potential health risk. The use of poor-quality ingredients, inadequate hygiene conditions in the manufacturing processes, the lack of standards for safety and hygiene controls lead to the failure food safety systems implementation, especially in low- and middle-income countries or for small-scale products (at household level, in villages and scale cottage industries). This can result in the presence of pathogenic microorganisms or their toxins in the food contributing to cases of illness or even outbreaks. Also, improper processing and storage, as by well as the conditions of sale affect the food safety. Foodborne diseases through the consumption of traditional fermented foods are not reported frequently, but this may be related, among other things, to a low percentage of people entering healthcare care or weaknesses in foodborne disease surveillance systems. In many parts of the world, especially in Africa and Asia, pathogens such as enterotoxigenic and enterohemorrhagic Escherichia coli, Shigella spp., Salmonella spp., enterotoxigenic Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus have been detected in fermented foods. Therefore, this review, in addition to the positive aspects, presents the potential risk associated with the consumption of this type of products.
Systematic Analysis and Validation of the Prognosis, Immunological Role and Biology Function of the Ferroptosis-Related lncRNA GSEC/miRNA-101-3p/CISD1 Axis in Lung Adenocarcinoma
Authors: Jiang Xiulin , Yuan Yixiao , Tang Lin , Wang Juan , Zhang Dahang , Duan Lincan
Published: March 2022

Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for approximately 85% of pulmonary malignancies. Emerging evidence has demonstrated that ferroptosis plays a central role in both immunities as well as tumor proliferation. However, the clinical significance, immunological function, and upstream modulatory mechanism of ferroptosis-related genes in LUAD remain unclear. Here, we utilized various bioinformatics data to identify differentially expressed (DEGs) and prognosis-related ferroptosis (FRGs) genes in LUAD. Based upon identified DEGs, FRG, and ceRNA modulatory networks were constructed. Pearson’s correlation analysis was used to evaluate the correlation between FRGs and the tumor mutational burden, microsatellite instability, tumor-infiltrating immunity, cellular checkpoint control, and drug sensitivity in LUAD. A loss-of-function analysis was performed to verify the function of CISD1 in LUAD progression. Our findings revealed that certain FRGs (CISD1, ATP5MC3, PGD, SLC7A11, ACSL3, and FANCD2) are significantly upregulated in LUAD and that their elevated expression is associated with both advanced tumor stage and unfavorable prognosis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results revealed these FRGs to be primarily involved in ferroptosis and glutathione metabolism in LUAD. We constructed a prognostic FRG-based model capable of accurately predicting LUAD patient overall survival with high specificity. The upstream lncRNA GSEC/miRNA-101-3p regulatory axis involving CISD1, ATP5MC3, and PGD was identified to be relevant in tumor progression. We also found GSEC, CISD1, ATP5MC3, and PGD to be upregulated, with miRNA-101-3p downregulated, in the setting of LUAD. Immunohistochemical analysis revealed CISD1, ATP5MC3, and PGD overexpression in LUAD tissue samples; CISD1 knockdown was noted to significantly inhibit LUAD proliferation and migration. In summary, this study characterizes relevant functional roles of the lncRNA GSEC/miR-101-3p axis in the setting of LUAD and suggests diagnostic and therapeutic biomarkers potentially useful in the clinical management of this illness.
Concurrent Training Increases Serum Brain-Derived Neurotrophic Factor in Older Adults Regardless of the Exercise Frequency
Authors: Canton-Martínez Ermilo , Rentería Iván , García-Suárez Patricia C. , Moncada-Jiménez José , Machado-Parra Juan Pablo , Lira Fabio Santos , Johnson David K. , Jiménez-Maldonado Alberto
Published: March 2022

Background

Human brain function declines with aging. In this sense, exercise-based interventions has a promising effect on brain plasticity for older adults. Serum brain-derived neurotrophic factor (BDNF) is a positive biomarker for brain neuroplasticity in healthy older adults also modified by exercise training. Selected features of the exercise prescription for improving brain health are missing; therefore, the aim of this study was to determine the effects of concurrent exercise training frequency on serum BDNF levels in healthy older adults.

Methods

Nineteen volunteers (age: 65 ± 4 year; body mass index: 28.0 ± 4.5 kg/m2) completed either a three times/week (3-t/w) (n = 8) or five times/week (5-t/w) (n = 11) concurrent exercise program. The exercise program lasted 11 weeks and all exercise sessions were performed for 50 min at moderate intensity. Serum BDNF, body composition, cardiovascular, and physical fitness variables were assessed before and after the exercise training program.

Results

Regardless of the group, the serum BDNF increased following the intervention (p < 0.001), and there were no significant group (p = 0.827) or interaction (p = 0.063) effects. The maximal oxygen consumption (VO2max) increased regardless of the group (p = 0.007), with a non-significant group (p = 0.722) or interaction (p = 0.223) effects. Upper- and lower-body strength increased in both groups (p = 0.003); however, there was no effect of the training frequency (p = 0.53). For the skeletal muscle mass, there was a trend in the interaction effect (p = 0.053). Finally, the body fat percentage was unchanged.

Conclusion

Eleven weeks of combined exercise training increased serum BDNF levels in healthy older adults, a response independent of the training frequency. The overall fitness level improved similarly in both exercise groups. These data reveal that a minimal dosage of concurrent exercise enhance functional capacity and a brain health biomarker in older adults.
Early Event-Related Potential During Figure and Object Perception of Abacus Mental Calculation Training Children: A Randomized Controlled Trial
Authors: Wang Dong , Zhu Kongmei , Cui Jiacheng , Wen Jianglin
Published: March 2022

The aim of this study was to discuss the effect of abacus mental calculation (AMC) on the early processing of children’s perception on numbers and objects. We designed a randomized controlled trial, and a total of 28 subjects were randomly distributed into two groups of equal numbers, namely, one group that received AMC training (training group) and the other group that did not receive training (non-training group). The subjects were asked to determine the figures and objects shown on the computer screen and were recorded on the computer. The event-related potential (ERP) component (N1, N170, P1, and P2) of different brain areas between the two subject groups was compared. Compared with the non-training group, the training group’s P1 in the occipital region showed a larger amplitude and a longer potential period. For N1, the training group showed a longer potential period. Additionally, for N170, the training group showed a smaller amplitude. Finally, the observation of P2 showed a smaller amplitude in the training group and a longer potential period in the condition of object stimulus. Overall, the activated degree of the occipital region of children who received AMC training was enhanced, while the activated degree of the central region of the forehead and temporal occipital region was slightly down. Meanwhile, the potential periods of all components were extended. Therefore, long-term AMC training can change children’s cortical function activities.
Cerebral Autoregulation Indices Are Not Interchangeable in Patients With Sepsis
Authors: Caldas Juliana , Quispe-Cornejo Armin Alvaro , Crippa Ilaria Alice , Subira Carles , Creteur Jacques , Panerai Ronney , Taccone Fabio Silvio
Published: March 2022

Introduction

Dynamic cerebral autoregulation (dCA) is frequently altered in patients with sepsis and may be associated with sepsis-associated brain dysfunction. However, the optimal index to quantify dCA in patients with sepsis is currently unknown.

Objective

To assess the agreement between two validated dCA indices in patients with sepsis.

Methods

Retrospective analysis of prospectively collected data in patients with sepsis; those with acute or chronic intracranial disease, arrhythmias, mechanical cardiac support, or history of supra-aortic vascular disease were excluded. Transcranial Doppler was performed on the right or left middle cerebral artery (MCA) with a 2-MHz probe, and MCA blood flow velocity (FV) and arterial pressure (BP) signals were simultaneously recorded. We calculated two indices of dCA: the mean flow index (Mxa), which is the Pearson correlation coefficient between BP and FV (MATLAB, MathWorks), and the autoregulation index (ARI), which is the transfer function analysis of spontaneous fluctuations in BP and FV (custom-written FORTRAN code). Impaired dCA was defined as Mxa >0.3 or ARI ≤ 4. The agreement between the two indices was assessed by Cohen's kappa coefficient.

Results

We included 95 patients (age 64 ± 13 years old; male 74%); ARI was 4.38 [2.83–6.04] and Mxa was 0.32 [0.14–0.59], respectively. There was no correlation between ARI and Mxa (r = −0.08; p = 0.39). dCA was altered in 40 (42%) patients according to ARI and in 50 (53%) patients according to Mxa. ARI and Mxa were concordant in classifying 23 (24%) patients as having impaired dCA and 28 (29%) patients as having intact dCA. Cohen's kappa coefficient was 0.08, suggesting poor agreement. ARI was altered more frequently in patients on mechanical ventilation than others (27/52, 52% vs. 13/43, 30%, p = 0.04), whereas Mxa did not differ between those two groups. On the contrary, Mxa was altered more frequently in patients receiving sedatives than others (23/34, 68% vs. 27/61, 44%, p = 0.03), whereas ARI did not differ between these two groups.

Conclusions

Agreement between ARI and Mxa in assessing dCA in patients with sepsis was poor. The identification of specific factors influencing the dCA analysis might lead to a better selection of the adequate cerebral autoregulation (CAR) index in critically ill patients with sepsis.
Early Neurological Improvement Predicts Clinical Outcome After Thrombectomy for Distal Medium Vessel Occlusions
Authors: Wang Maud , Farouki Yousra , Hulscher Franny , Mine Benjamin , Bonnet Thomas , Elens Stephanie , Vazquez Suarez Juan , Jodaitis Lise , Ligot Noémie , Naeije Gilles , Lubicz Boris , Guenego Adrien
Published: March 2022

Background and Purpose

Good clinical outcome predictors have been established in mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). An early neurological improvement (ENI), defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale (NIHSS), compared with the baseline score or an NIHSS of 0 or 1 at 24 h after MT, is a strong predictor of favorable outcome. We aimed to study the impact of ENI after MT for distal medium vessel occlusions (DMVO).

Methods

We retrospectively analyzed the data of consecutive patients who underwent MT for a primary DMVO in one large academic center. We compared clinical outcomes between patients with DMVO stratified by ENI. Multivariate analyses were performed to determine the impact of ENI on good 90-day outcome (modified Rankin scale of 0–2) and identify factors contributing to ENI.

Results

Between January 2018 and January 2021, 61 patients underwent an MT for an AIS with a primary DMVO. An ENI was seen in 24 (39%) patients (ENI+). Outcomes were significantly better in ENI+ patients, with 83% achieving a good outcome at 3 months vs. 43% for patients without ENI (ENI–; p = 0.019). ENI was an independent predictive factor of good clinical outcome even after adjusting for potential confounding factors [odds ratio 12.49 (1.49–105.01), p = 0.020]. The use of intravenous tissue plasminogen activator [IVtPA; Odds-ratio 6.59 (1.82–23.89), p = 0.004] was a positive predictor of ENI.

Conclusion

ENI at day 1 following MT for DMVO stroke is a strong independent predictor of good to excellent 3-month clinical outcome.
Novel Frameshift Heterozygous Mutation in UBAP1 Gene Causing Spastic Paraplegia-80: Case Report With Literature Review
Authors: Zhang Chao , Zhu Xiaowei , Zhu Zeyu , Ni Ruilong , Liu Taotao , Zheng Haoran , Liu Shihua , Cao Li , Zhong Ping , Tian Wotu
Published: March 2022

Hereditary spastic paraplegia (HSP) represents a group of rare inherited neurodegenerative conditions and is characterized by progressive lower limb spasticity. Ubiquitin-associated protein 1 (UBAP1)-related HSP is classified as spastic paraplegia-80 (SPG80), which is an autosomal-dominant (AD) juvenile-onset neurologic disorder and mainly affects the lower limbs. We described the clinical and genetic features of two patients in the same family caused by heterozygous mutation of the UBAP1 gene. The proband was a 34-year-old woman with progressive spasticity and hyperreflexia in the lower limbs for 26 years. Her mother also had similar symptoms since the age of 6. The proband and her mother only had motor dysfunctions, such as unsteady gait, hypertonia, and hyperreflexia of lower limbs. Other system functions (sensory, urinary, visual, and cognitive impairments) were not involved. WES disclosed a frameshift mutation (c.371dupT) in the UBAP1 gene, which was predicted to be “likely pathogenic” and was co-segregated in the pedigree. c.371dupT, encoding the truncated UBAP1 protein with 72.6% missing of the normal amino acid sequence, is responsible for the spastic paraplegia (SPG) in this family. In combination with clinical characteristics, genetic testing results, and co-segregation analysis, the diagnosis is considered to be pure spastic paraplegia-80 (SPG80), which is an AD disease. By retrospectively analyzing the documented cases, we comprehensively review the phenotypic features and summarize the genotype spectrum of SPG80 to enhance earlier recognition and therapeutic strategies.
Psychiatric and Behavioural Side Effects Associated With Perampanel in Patients With Temporal Lobe Epilepsy. A Real-World Experience
Authors: Mammì Anna , Ferlazzo Edoardo , Gasparini Sara , Bova Valentina , Neri Sabrina , Labate Angelo , Mastroianni Giovanni , Bianco Concetta Lo , Cianci Vittoria , Aguglia Umberto
Published: March 2022

Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were “irritability” for both groups and “aggression” for patients with other focal epilepsies.
Treatment of Focal-Onset Seizures in Children: Should This Be More Etiology-Driven?
Authors: Aeby Alec , Ceulemans Berten , Lagae Lieven
Published: March 2022

To accelerate the process of licensing antiseizure medication (ASM) in children, extrapolation of efficacy data for focal-onset seizures from adults to children ≥2 or ≥4 years of age is now accepted. We summarized the efficacy evidence from randomized, controlled trials that was used to grant approval for the pediatric indication of focal-onset seizures for the different ASMs available in Europe. Data from high-quality randomized, controlled trials in young children are limited, especially on the use of ASMs in monotherapy. Licensure trials are typically focused on seizure type irrespective of etiology or epilepsy syndrome. We elaborate on the importance of etiology- or syndrome-driven research and treatment, illustrating this with examples of childhood epilepsy syndromes characterized by predominantly focal-onset seizures. Some of these syndromes respond well to standard ASMs used for focal-onset seizures, but others would benefit from a more etiology- or syndrome-driven approach. Advances in molecular genetics and neuroimaging have made it possible to reveal the underlying cause of a child's epilepsy and tailor research and treatment. More high-quality randomized, controlled trials based on etiology or syndrome type are needed, including those assessing effects on cognition and behavior. In addition, study designs such as “N-of-1 trials” could elucidate possible new treatment options in rare epilepsies. Broadening incentives currently in place to stimulate the development and marketing of drugs for rare diseases (applicable to some epilepsy syndromes) to more common pediatric epilepsy types and syndromes might be a means to enable high-quality trials, and ultimately allow more evidence-based treatment in children.
A Waveform-Independent Measure of Recurrent Neural Activity
Authors: Weber Immo , Oehrn Carina Renate
Published: March 2022

Rhythmic neural activity, so-called oscillations, plays a key role in neural information transmission, processing, and storage. Neural oscillations in distinct frequency bands are central to physiological brain function, and alterations thereof have been associated with several neurological and psychiatric disorders. The most common methods to analyze neural oscillations, e.g., short-time Fourier transform or wavelet analysis, assume that measured neural activity is composed of a series of symmetric prototypical waveforms, e.g., sinusoids. However, usually, the models generating the signal, including waveform shapes of experimentally measured neural activity are unknown. Decomposing asymmetric waveforms of nonlinear origin using these classic methods may result in spurious harmonics visible in the estimated frequency spectra. Here, we introduce a new method for capturing rhythmic brain activity based on recurrences of similar states in phase-space. This method allows for a time-resolved estimation of amplitude fluctuations of recurrent activity irrespective of or specific to waveform shapes. The algorithm is derived from the well-established field of recurrence analysis, which, in comparison to Fourier-based analysis, is still very uncommon in neuroscience. In this paper, we show its advantages and limitations in comparison to short-time Fourier transform and wavelet convolution using periodic signals of different waveform shapes. Furthermore, we demonstrate its application using experimental data, i.e., intracranial and noninvasive electrophysiological recordings from the human motor cortex of one epilepsy patient and one healthy adult, respectively.
Whey Protein Supplementation Effects on Body Composition, Performance, and Blood Biomarkers During Army Initial Entry Training
Authors: McAdam Jeremy S. , Lyons Kaitlin D. , Beck Darren T. , Haun Cody T. , Romero Matthew A. , Mumford Petey W. , Roberson Paul A. , Young Kaelin C. , Lohse Keith R. , Roberts Michael D. , Sefton JoEllen M.
Published: March 2022

This study assesses if a lower dose of whey protein can provide similar benefits to those shown in previous work supplementing Army Initial Entry Training (IET) Soldiers with two servings of whey protein (WP) per day. Eighty-one soldiers consumed one WP or a calorie matched carbohydrate (CHO) serving/day during IET (WP: n = 39, height = 173 ± 8 cm, body mass = 76.8 ± 12.8 kg, age = 21 ± 3 years; CHO: n = 42, 175 ± 8 cm, 77.8 ± 15.3 kg, 23 ± 4 years). Physical performance (push-ups, sit-ups, and a two-mile run) was assessed during weeks two and eight. All other measures (dietary intake, body composition, blood biomarkers) at weeks one and nine. There was a significant group difference for fat mass (p = 0.044) as WP lost 2.1 ± 2.9 kg and had a moderate effect size (Cohen's d: −0.24), whereas the CHO group lost 0.9 ± 2.5 kg and had only a small effect size (d: −0.1). There was no significant group-by-time interaction on fat-free mass (p = 0.069). WP gained 1.2 ± 2.4 (d: 0.1) and CHO gained 0.1 ± 3 (d: 0) kg of FFM on average. There was a significant group by week 1-fat free mass interaction (p = 0.003) indicating individuals with higher initial fat-free mass benefitted more from WP. There were no group differences for push-up (p = 0.514), sit-up (p = 0.429) or run (p = 0.313) performance. For all biomarkers there was a significant effect of time as testosterone (p < 0.01), testosterone to cortisol ratio (p = 0.39), and IGF-1 (p < 0.01) increased across training and cortisol (p = 0.04) and IL-6 (p < 0.01) decreased. There were no differences in groups across IET for any of the biomarkers. We conclude one WP serving is beneficial for FM and for FFM in soldiers with high baseline FFM but may not significantly alter biomarker response or physical performance of IET soldiers who have high relative dietary protein intakes.
Structural Elucidation and Antioxidant Activities of a Neutral Polysaccharide From Arecanut (Areca catechu L.)
Authors: Ji Xiaolong , Guo Jianhang , Pan Feibing , Kuang Fengjun , Chen Haiming , Guo Xudan , Liu Yanqi
Published: March 2022

A novel neutral polysaccharide designated as PAP1b was isolated from Areca catechu L. by hot water extraction, ethanol precipitation, and column chromatography. PAP1b was mainly composed of mannose, galactose, xylose, and arabinose in a ratio of 4.1:3.3:0.9:1.7, with an average molecular weight of 37.3 kDa. Structural characterization indicated that the backbone of PAP1b appeared to be composed mainly of → 6-β-Manp-(1 →, → 4)-α-Galp-(1 → and → 3,6)-β-Manp-(1 →) residues with some branches, and terminal of (1 →)-linked-β-Manp residues. The results of bioactivity experiments showed that PAP1b had antioxidant in vitro, esspecially on scavenging DPPH and hydroxyl radicals. Therefore, the polysaccharide from Areca catechu L. could be used as a potential antioxidant in functional food.
Algae Supplementation for Exercise Performance: Current Perspectives and Future Directions for Spirulina and Chlorella
Authors: Gurney Tom , Spendiff Owen
Published: March 2022

Nutritional clinical trials have reported algae such as spirulina and chlorella to have the capability to improve cardiovascular risk factors, anemia, immune function, and arterial stiffness. With positive results being reported in clinical trials, researchers are investigating the potential for algae as an ergogenic aid for athletes. Initial studies found spirulina and chlorella supplementation to increase peak oxygen uptake and time to exhaustion, with the mechanistic focus on the antioxidant capabilities of both algae. However, a number of oxidative stress biomarkers reported in these studies are now considered to lack robustness and have consequently provided equivocal results. Considering the nutrient complexity and density of these commonly found edible algae, there is a need for research to widen the scope of investigation. Most recently algae supplementation has demonstrated ergogenic potential during submaximal and repeated sprint cycling, yet a confirmed primary mechanism behind these improvements is still unclear. In this paper we discuss current algae supplementation studies and purported effects on performance, critically examine the antioxidant and ergogenic differing perspectives, and outline future directions.
Scutellaria barbata Inhibits Hepatocellular Carcinoma Tumorigenicity by Inducing Ferroptosis of Hepatocellular Carcinoma Cells
Authors: Li Yue , Zhang Jiongshan , Zhang Kun , Chen Yan , Wang Wei , Chen Hongjie , Zou Zengcheng , Li Yongwei , Dai Min
Published: March 2022

Ferroptosis is caused by accumulation of iron-dependent lipid peroxidation, which is characterized by reduction in cell volume and increase in mitochondrial membrane density. Studies have shown that ferroptosis contributes to the development and progression of numerous major diseases, including hepatocellular carcinoma (HCC). As a unique biomedical resource, Traditional Chinese Medicine (TCM) has been widely used in the treatment of HCC. In this present study, Scutellaria barbata was used to treat HCC cells in vitro, and the results revealed that S. barbata suppressed HCC cell growth through inducing ferroptosis. Next, the exploration of the molecular mechanism on how S. barbata induced ferroptosis in HCC cells suggested that S. barbata may induce ferroptosis by promoting iron perioxidation and lipid ROS metabolism. Finally, S. barbata also inhibited HCC tumorigenicity in vivo by inducing ferroptosis of HCC cells. These results provided theoretical basis for explaining the mechanism of TCM treatment for HCC and offered therapeutic opportunities for HCC patients.
Roles of GFPT2 Expression Levels on the Prognosis and Tumor Microenvironment of Colon Cancer
Authors: Ding Xiaorong , Liu Hua , Yuan Ying , Zhong Qin , Zhong Xiaomin
Published: March 2022

Background

Recently, increasing evidence has suggested that Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is related to carcinogenesis. However, the potential roles of GFPT2 in colon cancer still need to be fully investigated.

Methods

We examined the protein levels of GFPT2 by immunohistochemistry (IHC) in tissues collected from 83 patients with colon cancer. We further detected GFBPT2 protein levels by Western Blot assay. We checked the relationship between GFPT2 expression levels and overall survival (OS), stromal and immune scores and immune components from The Cancer Gene Atlas (TCGA) database. GFBP2-related pathways were validated in the Cancer Cell Line Encyclopedia (CCLE) database. Expression of GFPT2 in single cell subpopulations was calculated from The Tumor Immune Single Cell Center (TISCH). The levels of GFPT2 and drug sensitivity data were performed from CellMiner dataset.

Results

GFPT2 was highly expressed and correlated with poor pathological features in 83 colon cancer patients. Moreover, increased GFPT2 expression was significantly associated with poorer OS in 329 colon adenocarcinoma (COAD) patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the differentially expressed genes of GFPT2 were mostly enriched in focal adhesion, ECM receptor interaction, JAK/STAT signaling pathway and immune related pathways. In addition, GFPT2 expression was correlated with the tumor microenvironment (TME). GFPT2 expression was linked to cancer-associated fibroblasts (CAFs)-associated factors and epithelial-mesenchymal transition (EMT)-related factors. GFPT2 was positively correlated with immunosuppressive cells and regulated immunosuppressive factors and T-cell exhaustion. Finally, our data suggested that the expression of GFPT2 may be a judgment of the sensitivity of a certain class of drugs.

Conclusions

Our work reveals the roles of GFPT2 in tumorigenesis, particularly in immune response, TME and drug resistance, which are crucial for the development of customized cancer therapies.
Development and Validation of Nomograms to Predict Overall Survival and Cancer-Specific Survival in Patients With Pancreatic Adenosquamous Carcinoma
Authors: Yang Zhen , Shi Guangjun , Zhang Ping
Published: March 2022

Background

Pancreatic adenosquamous carcinoma (PASC) is a heterogeneous group of primary pancreatic cancers characterized by the coexistence of both glandular and squamous differentiation. The aim of this study was to develop nomograms to predict survival outcomes in patients with PASC.

Methods

In this retrospective study, data on PASC, including clinicopathological characteristics, treatments, and survival outcomes, were collected from the SEER database between 2000 and 2018. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The eligible patients were randomly divided into development cohort and validation cohort in a 7:3 ratio. The nomograms for prediction of OS and CSS were constructed by the development cohort using a LASSO-Cox regression model, respectively. Besides the model performance was internally and externally validated by examining the discrimination, calibration, and clinical utility.

Results

A total of 632 consecutive patients who had been diagnosed with PASC were identified and randomly divided into development (n = 444) and validation (n = 188) cohorts. In the development cohort, the estimated median OS was 7.0 months (95% CI: 6.19–7.82) and the median CSS was 7.0 months (95% CI: 6.15–7.85). In the validation cohort, the estimated median OS was 6.0 months (95% CI: 4.46–7.54) and the median CSS was 7.0 months (95% CI: 6.25–7.75). LASSO-penalized COX regression analysis identified 8 independent predictors in the OS prediction model and 9 independent risk factors in the CSS prediction model: age at diagnosis, gender, year of diagnosis, tumor location, grade, stage, size, lymph node metastasis, combined metastasis, surgery, radiation, and chemotherapy. The Harrell C index and time-dependent AUCs manifested satisfactory discriminative capabilities of the models. Calibration plots showed that both models were well calibrated. Furthermore, decision curves indicated good utility of the nomograms for decision-making.

Conclusion

Nomogram-based models to evaluate personalized OS and CSS in patients with PASC were developed and well validated. These easy-to-use tools will be useful methods to calculate individualized estimate of survival, assist in risk stratification, and aid clinical decision-making.
Tumor-Educated Platelets as a Promising Biomarker for Blood-Based Detection of Renal Cell Carcinoma
Authors: Xiao Ruotao , Liu Cheng , Zhang Bo , Ma Lulin
Published: March 2022

Purpose

Tumor-educated platelets (TEPs) are a promising liquid biopsy in many cancers. However, their role in renal cell carcinoma (RCC) is unknown. Thus, this study explored the diagnostic value of TEPs in RCC patients.

Methods

Platelets were prospectively collected from 24 RCC patients and 25 controls. RNA-seq was performed to identify the differentially expressed genes (DEGs) between RCC patients and controls. Besides, RNA-seq data of pan-cancer TEPs were downloaded and randomly divided into training and validation sets. A pan-cancer TEP model was developed in the training set using the support vector machine (SVM) and validated in the validation set and our RCC dataset. Finally, an RCC-based TEP model was developed and optimized through the SVM algorithms and recursive feature elimination (RFE) method.

Result

Two hundred three DEGs, 64 (31.5%) upregulated and 139 (68.5%) downregulated, were detected in the platelets of RCC patients compared with controls. The pan-cancer TEP model had a high accuracy in detecting cancer in the internal validation (training set, accuracy 98.8%, AUC: 0.999; validation set, accuracy 95.4%, AUC: 0.972; different tumor subtypes, accuracy 86.6%–96.1%, AUC: 0.952–1.000). However, the pan-cancer TEP model in the external validation had a scarce diagnostic value in RCC patients (accuracy 48.7%, AUC: 0.615). Therefore, to develop the RCC-based TEP model, the gene biomarkers mostly contributing to the model were selected using the RFE method. The RCC-based TEP model containing 68 gene biomarkers reached a diagnostic accuracy of 100% (AUC: 1.000) in the training set, 88.9% (AUC: 0.963) in the validation set, and 95.9% (AUC: 0.988) in the overall cohort.

Conclusion

TEPs could function as a minimally invasive blood biomarker in the detection of RCC.
Successful Treatment of a Patient With Multiple-Line Relapsed Extensive-Stage Small-Cell Lung Cancer Receiving Penpulimab Combined With Anlotinib: A Case Report
Authors: Zhang Zibo , Li Yujun , Dong Yan , Li Jia , Zhang Bin , Zhang Chunxia , Cui Xiaonan
Published: March 2022

Small-cell lung cancer (SCLC) is a highly malignant, rapidly developing group of diseases with poor biological behavior. Most patients have extensive-stage SCLC (ES-SCLC) when they are first diagnosed. Standard chemotherapy is prone to relapse in a short period of time, and the patients’ median overall survival (OS) can reach only 13 months when chemotherapy is given in combination with PD-L1 inhibitors. To date, no studies have verified the efficacy and safety of the composite treatment of ES-SCLC with penpulimab and anlotinib despite some recognized data and advantages related to this regimen. Penpulimab, a novel PD-1 inhibitor with an IgG1 subtype, has a structural modification of the Fc segment which can prevent the immune cells from being phagocytosed or killed and can steadily avoid tumor immune escape. This case report describes a 71-year-old man who had ES-SCLC for 7 years which progressed after receiving standard systemic chemotherapy combined with radiotherapy. The third-line treatment of four cycles of anlotinib and carilizumab was discontinued because of grade 2 immune-related pneumonia despite the efficacy being evaluated as stable disease. After maintaining 22 months of progression-free survival, the patient relapsed and switched to a safer regimen of penpulimab combined with anlotinib to continue the treatment for four cycles. Partial response evaluation was confirmed twice, and the patient remained in good general condition. The combination of penpulimab and anlotinib can positively regulate the therapeutic effect by simultaneously acting on the tumor microenvironment and promoting blood vessel normalization. In general, this case provides support for the successful possibility of a rechallenge with immune checkpoint inhibitors, the better clinical efficacy of cross-line therapy with anlotinib, and the drug safety of penpulimab, suggesting a beneficial therapy for the clinical treatment of ES-SCLC.
Analysis of Gene Expression Profiles in the Liver of Rats With Intrauterine Growth Retardation
Authors: Shen Zheng , Zhu Weifen , Du Lizhong
Published: March 2022

Background

Intrauterine growth restriction (IUGR) is highly associated with fetal as well as neonatal morbidity, mortality, and an increased risk metabolic disease development later in life. The mechanism involved in the increased risk has not been established. We compared differentially expressed genes between the liver of appropriate for gestational age (AGA) and IUGR rat models and identified their effects on molecular pathways involved in the metabolic syndrome.

Methods

We extracted RNA from the liver of IUGR and AGA rats and profiled gene expression by microarray analysis. GO function and KEGG pathway enrichment analyses were conducted using the Search Tool for the Retrieval of Interacting Genes database. Then, the Cytoscape software was used to visualize regulatory interaction networks of IUGR-related genes. The results were further verified via quantitative reverse transcriptase PCR analysis.

Results

In this study, 815 genes were found to be markedly differentially expressed (fold-change >1.5, p < 0.05) between IUGR and AGA, with 347 genes elevated and 468 suppressed in IUGR, relative to AGA. Enrichment and protein–protein interaction network analyses of target genes revealed that core genes including Ppargc1a, Prkaa2, Slc2a1, Rxrg, and Gcgr, and pathways, including the PPAR signaling pathway and FoxO signaling pathway, had a potential association with metabolic syndrome development in IUGR. We also confirmed that at the mRNA level, five genes involved in glycometabolism were differentially expressed between IUGR and AGA.

Conclusion

Our findings elucidate on differential gene expression profiles in IUGR and AGA. Moreover, they elucidate on the pathogenesis of IUGR-associated metabolic syndromes. The suggested candidates are potential biomarkers and eventually intended to treat them appropriately.
Mycoplasma Pneumoniae Infection and Persistent Wheezing in Young Children: A Retrospective Case-Control Study
Authors: Sun Huiming , Li Shuxiang , Wang Ting , Chen Zhengrong
Published: March 2022

Background

To investigate the clinical characteristics of children with persistent wheezing (PW) with Mycoplasma pneumoniae (MP) DNA in bronchoalveolar lavage fluid (BALF).

Methods

This retrospective case-control study included consecutive admitted children under 3 years of age who were diagnosed with PW and had MP DNA detected in BALF. Patients with mycoplasma pneumoniae pneumonia (MPP) and foreign-body aspiration (FBA) were enrolled as controls. The clinical characteristics of the groups were compared.

Results

During the study period, there were 89 patients diagnosed with PW without structural anomalies of the conductive airways, and 30 of these patients (33.7%, 30/89) with MP DNA detected in the BALF were selected as the study group. We included 44 patients with MPP and 44 patients with FBA as controls. Patients with MPP were older and had a higher occurrence of fever and C-reactive protein (CRP) than patients with PW (all P < 0.001). The median MP DNA copy number in patients with MPP was higher than that of patients with PW (P = 0.004). The median level of MP IgG in patients with PW was lower than that of patients with MPP and higher than that of patients with FBA (all P < 0.001). MP DNA copy number positively correlated with age (r = 0.392, P = 0.001) and CRP (r = 0.235, P = 0.048).

Conclusions

Our study reveals that MP was highly detected in the BALF of PW patients. In addition, young patients with a low load of MP infection showed lower amounts of antibody, and a weak inflammatory response might be associated with PW.
Effect of Platelet Transfusions on Extracorporeal Life Support Oxygenator’s Function
Authors: Chegondi Madhuradhar , Vijayakumar Niranjan , Badheka Aditya , Karam Oliver
Published: March 2022

Objective

Bleeding is a common complication of extracorporeal membrane oxygenation (ECMO), leading to increased mortality. Since one of its main complications is bleeding, platelet transfusions are frequently prescribed for children on ECMO. However, there is currently very little information on the effect of platelet transfusions on the function of the ECMO oxygenator. Our objective was to describe the effect of platelet transfusions on oxygenator function.

Methods

In this retrospective study, we included all children (<18 years) who received ECMO support in our pediatric intensive care unit (PICU) between January 2017 and December 2019. Oxygenator function, measured before and after platelet transfusion, was assessed by post-oxygenator PECMOO2and the gradient in pre- post-oxygenator pressures (Delta Pressure).

Results

Over 3 years, we analyzed 235 platelet transfusions from 55 children who received ECMO support. Thirty-two (80%) of children were on veno-arterial ECMO and majority of them were peripherally cannulated. When looking at all transfusions, the post-transfusion change in delta-pressure was 0.1 mmHg (p= 0.69) and post-membrane PECMOO2was 6 mmHg (p= 0.49). However, in the subgroup with the lowest quartile of pre-transfusion oxygenator function, the post-transfusion change in delta-pressure was −5.2 ± 2.7 mmHg (p< 0.001) and the post-transfusion change in PECMOO2was −118 ± 49 (p< 0.001). The area under the ROC curve for the pre-transfusion delta-pressure and PECMOO2to predict a worsening of the oxygenator function were 0.72 (95%CI 0.63–0.81) and 0.71 (95%CI 0.64–0.78), respectively. Using regression models, pre-transfusion delta-pressure and PECMOO2were the only independent factors associated with oxygenator function worsening (p< 0.001).

Conclusion

Our study suggests that overall, platelet transfusions do not seem to impact the ECMO oxygenator’s function. However, in the subgroup of patients with the lowest pre-transfusion oxygenator function, platelet transfusions were independently associated with a worsening function. Future studies should investigate if this warrants adjustments of the anticoagulation strategy around the platelet transfusion, especially among patients with lower oxygenator function.