bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular Reprogramming and Its Potential Application in Alzheimer’s Disease
Authors: Zhou Chao , Ni Wanyan , Zhu Taiyang , Dong Shuyu , Sun Ping , Hua Fang
Published: April 2022

Alzheimer’s disease (AD) has become the most common age-related dementia in the world and is currently incurable. Although many efforts have been made, the underlying mechanisms of AD remain unclear. Extracellular amyloid-beta deposition, intracellular tau hyperphosphorylation, neuronal death, glial cell activation, white matter damage, blood–brain barrier disruption, and other mechanisms all take part in this complicated disease, making it difficult to find an effective therapy. In the study of therapeutic methods, how to restore functional neurons and integrate myelin becomes the main point. In recent years, with the improvement and maturity of induced pluripotent stem cell technology and direct cell reprogramming technology, it has become possible to induce non-neuronal cells, such as fibroblasts or glial cells, directly into neuronal cells in vitro and in vivo. Remarkably, the induced neurons are functional and capable of entering the local neural net. These encouraging results provide a potential new approach for AD therapy. In this review, we summarized the characteristics of AD, the reprogramming technique, and the current research on the application of cellular reprogramming in AD. The existing problems regarding cellular reprogramming and its therapeutic potential for AD were also reviewed.
LIS1 and NDEL1 Regulate Axonal Trafficking of Mitochondria in Mature Neurons
Authors: Pandey Jai P. , Shi Liang , Brebion Remi A. , Smith Deanna S.
Published: April 2022

Defective mitochondrial dynamics in axons have been linked to both developmental and late-onset neurological disorders. Axonal trafficking is in large part governed by the microtubule motors kinesin-1 and cytoplasmic dynein 1 (dynein). Dynein is the primary retrograde transport motor in axons, and mutations in dynein and many of its regulators also cause neurological diseases. Depletion of LIS1, famous for linking dynein deregulation to lissencephaly (smooth brain), in adult mice leads to severe neurological phenotypes, demonstrating post-developmental roles. LIS1 stimulates retrograde transport of acidic organelles in cultured adult rat dorsal root ganglion (DRG) axons but findings on its role in mitochondrial trafficking have been inconsistent and have not been reported for adult axons. Here we report that there is an increased number of mitochondria in cross-sections of sciatic nerve axons from adult LIS1+/– mice. This is probably related to reduced dynein activity as axons from adult rat nerves exposed to the dynein inhibitor, ciliobrevin D also had increased numbers of mitochondria. Moreover, LIS1 overexpression (OE) in cultured adult rat DRG axons stimulated retrograde mitochondrial transport while LIS1 knockdown (KD) or expression of a LIS1 dynein-binding mutant (LIS1-K147A) inhibited retrograde transport, as did KD of dynein heavy chain (DHC). These findings are consistent with our report on acidic organelles. However, KD of NDEL1, a LIS1 and dynein binding protein, or expression of a LIS1 NDEL1-binding mutant (LIS1-R212A) also dramatically impacted retrograde mitochondrial transport, which was not the case for acidic organelles. Manipulations that disrupted retrograde mitochondrial transport also increased the average length of axonal mitochondria, suggesting a role for dynein in fusion or fission events. Our data point to cargo specificity in NDEL1 function and raise the possibility that defects in the LIS1/NDEL1 dynein regulatory pathway could contribute to mitochondrial diseases with axonal pathologies.
Validation of Candidate Sleep Disorder Risk Genes Using Zebrafish
Authors: Tran Steven , Prober David A.
Published: April 2022

Sleep disorders and chronic sleep disturbances are common and are associated with cardio-metabolic diseases and neuropsychiatric disorders. Several genetic pathways and neuronal mechanisms that regulate sleep have been described in animal models, but the genes underlying human sleep variation and sleep disorders are largely unknown. Identifying these genes is essential in order to develop effective therapies for sleep disorders and their associated comorbidities. To address this unmet health problem, genome-wide association studies (GWAS) have identified numerous genetic variants associated with human sleep traits and sleep disorders. However, in most cases, it is unclear which gene is responsible for a sleep phenotype that is associated with a genetic variant. As a result, it is necessary to experimentally validate candidate genes identified by GWAS using an animal model. Rodents are ill-suited for this endeavor due to their poor amenability to high-throughput sleep assays and the high costs associated with generating, maintaining, and testing large numbers of mutant lines. Zebrafish (Danio rerio), an alternative vertebrate model for studying sleep, allows for the rapid and cost-effective generation of mutant lines using the CRISPR/Cas9 system. Numerous zebrafish mutant lines can then be tested in parallel using high-throughput behavioral assays to identify genes whose loss affects sleep. This process identifies a gene associated with each GWAS hit that is likely responsible for the human sleep phenotype. This strategy is a powerful complement to GWAS approaches and holds great promise to identify the genetic basis for common human sleep disorders.
Sustainable Use of Greek Herbs By-Products, as an Alternative Source of Biologically Active Ingredients for Innovative Products
Authors: Dina Evanthia , Vontzalidou Argyro , Cheilari Antigoni , Bagatzounis Panagiotis , Agapidou Eftyxia , Giannenas Ilias , Grigoriadou Katerina , Aligiannis Nektarios
Published: April 2022

The processing of medicinal and aromatic plants (MAPs) results in the production of a significant amount of plant by-products; herbal material of inferior quality and/or unusable plant parts that are not commercially exploitable. An extensive study of Greek native species was performed toward the production of innovative bioactive products using as raw materials the by-products obtained from the processing of cultivated MAPs. Origanum vulgare subsp. hirtum (oregano), Sideritis scardica (Greek mountain tea), Thymus vulgaris (thyme), and Matricaria recutita (chamomile) were selected due to their wide use for the preparation of beverages and culinary purposes. The determination of the percentage of the post-harvest processing by-products was performed for a 3 years period (2018–2020). Results showed that by-products derived from the above-mentioned species' processing constitute 64% (thyme), 54% (oregano), 37% (Greek mountain tea), and 24% (chamomile) of the total processed mass. To value the by-products as a potent source of bioactive ingredients, superior and inferior quality herbal material of the aforementioned plant species were extracted by an ultrasonic assisted extraction method. Hydroalcoholic extracts were chemically investigated using high-performance thin layer chromatography (HPTLC) and liquid chromatography-mass spectrometry (LC-MS) techniques. In addition, their free radical scavenging activity and total phenolic content (TPC) were estimated. Based on the results, herbs by-products revealed similar chemical content to the superior herbal material by the means of HPTLC and LC-MS analysis. In addition, strong free radical scavenging related to a high phenolic content was detected in the case of thyme, oregano, and Greek mountain tea. Moreover, the gas chromatography-mass spectrometry (GC-MS) analyses of the essential oils (EOs) of oregano and thyme by-products revealed the presence of carvacrol, thymol, γ-terpinene, and p-cymene among the major constituents. Finally, the LC-MS analyses of aqueous extracts of Greek mountain tea and chamomile by-products led to the identification of several bioactive compounds, such as flavonoids and phenylpropanoids. Overall, the presence of bioactive constituents in by-products, such as terpenes, phenolic compounds, and flavonoids underly their potent use as food antimicrobial and antioxidant additives, in the preparation of high added-value products, such as enriched aromatic edible oils, and innovative herbal teas, such as instant beverages.
Diabetes and Risks of Right-Sided and Left-Sided Colon Cancer: A Meta-Analysis of Prospective Cohorts
Authors: Xiao Wenxuan , Huang Jinglong , Zhao Chuanyi , Ding Lu , Wang Xuan , Wu Bian
Published: April 2022

Background and Aims

Diabetes is associated with an increased risk of colon cancer (CC). Epidemiologic studies previously reported a higher risk for right-sided colon cancer (RCC) compare to left-sided colon cancer (LCC), although data are conflicting. We performed a meta-analysis to investigate this issue.

Methods

We systematically searched the PubMed, EMBASE, Web of Science and Cochrane Library database for prospective cohort studies published up to June 2021. Studies were included if they reported site-specific estimates of the relative risk (RR) between diabetes and the risks of RCC and LCC. Random effects meta-analyses with inverse variance weighting were used to estimate the pooled site-specific RRs and the RCC-to-LCC ratio of RRs (RRRs).

Results

Data from 10 prospective cohort studies, representing 1,642,823 individuals (mainly white) and 17,624 CC patients, were included in the analysis. Diabetes was associated with an increased risk of both RCC (RR =1.35, 95% CI = 1.24-1.47) and LCC (RR = 1.18, 95% CI = 1.08-1.28). After adjusting for major risk factors, individuals with diabetes had a greater risk for RCC than for LCC (RRR = 1.13, 95% CI = 1.02-1.26), with no significant heterogeneity between studies (I2 = 0%).

Conclusions

This meta-analysis indicates that diabetes is associated with a higher risk for RCC than for LCC. Our findings suggest that colonoscopic surveillance in diabetic patients with careful examination of the right colon is warranted.
Neurocognitive Outcome and Seizure Freedom After Awake Surgery of Gliomas
Authors: Reitz Sarah Christina , Behrens Marion , Lortz Irina , Conradi Nadine , Rauch Maximilian , Filipski Katharina , Voss Martin , Kell Christian , Czabanka Marcus , Forster Marie-Therese
Published: April 2022

Objectives

Gliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficits. First treatment choice for patients with gliomas in speech-related areas is awake surgery, which aims at maximizing tumor resection while preserving or improving patient’s neurological status. The present study aimed at evaluating neurocognitive functioning and occurrence of epileptic seizures in patients suffering from gliomas located in language-related areas before and after awake surgery as well as during their follow up course of disease.

Materials and Methods

In this prospective study we included patients who underwent awake surgery for glioma in the inferior frontal gyrus, superior temporal gyrus, or anterior temporal lobe. Preoperatively, as well as in the short-term (median 4.1 months, IQR 2.1-6.0) and long-term (median 18.3 months, IQR 12.3-36.6) postoperative course, neurocognitive functioning, neurologic status, the occurrence of epileptic seizures and number of antiepileptic drugs were recorded.

Results

Between 09/2012 and 09/2019, a total of 27 glioma patients, aged 36.1 ± 11.8 years, were included. Tumor resection was complete in 15, subtotal in 6 and partial in 6 patients, respectively. While preoperatively impairment in at least one neurocognitive domain was found in 37.0% of patients, postoperatively, in the short-term, 36.4% of patients presented a significant deterioration in word fluency (p=0.009) and 34.8% of patients in executive functions (p=0.049). Over the long-term, scores improved to preoperative baseline levels. The number of patients with mood disturbances significantly declined from 66.7% to 34.8% after surgery (p=0.03). Regarding seizures, these were present in 18 (66.7%) patients prior to surgery. Postoperatively, 22 (81.5%) patients were treated with antiepileptic drugs with all patients presenting seizure-freedom.

Conclusions

In patients suffering from gliomas in eloquent areas, the combination of awake surgery, regular neurocognitive assessment - considering individual patients´ functional outcome and rehabilitation needs – and the individual adjustment of antiepileptic therapy results in excellent patient outcome in the long-term course.
ERBB2D16 Expression in HER2 Positive Gastric Cancer Is Associated With Resistance to Trastuzumab
Authors: Wang Shuo , Zhao Yuze , Song Yuguang , Qiao Guoliang , Di Yan , Zhao Jing , Sun Pingping , Zheng Huixia , Huang He , Huang Hongyan
Published: April 2022

The human epidermal growth factor receptor-2 (ERBB2; formerly HER2)isoform ERBB2ΔEx16 (ERBB2d16) was oncogenic by mediating epithelial-mesenchymal transition (EMT), immune evasion, and resistance cell death to the anti-HER2 (trastuzumab) therapy. However, its physiological implications in gastric cancer were unclear. In this study, we examined a total of 110 patients with either locally advanced or metastatic HER2+ gastric cancer for the expression of ERBB2d16 and EMT markers, and the infiltration of CD3+ T cells in tumor tissues, and evaluated their relevance with the responses to the standard chemotherapy plus trastuzumab according to the RECIST criteria. We found that the ERBB2d16 isoform was present at a relatively high level in about half of the tumor samples examined (53/110) and an elevated ERBB2d16/ERBB2 ratio was positively associated with the expression of high E-cadherin and low vimentin indicating EMT, and with poor CD3+ T cell infiltration and strong intratumoral expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) as well as reduced diversity of T cell receptor clones. Moreover, the progression-free survival and overall survival of patients treated with trastuzumab were substantially shorter in those with a high ERBB2d16/ERBB2 ratio. In agreement, analysis by Cox proportional hazards models confirmed that high ERBB2d16 expression was a risk factor associated with an adverse prognosis. Thus, our data fit well with an oncogenic role of ERBB2d16 in gastric cancer by promoting EMT and immunosuppression. We also found that ERBB2d16 expression resists gastric cell death in patients treated with trustuzumab, and the ERBB2d16/ERBB2 ratio may serve as a novel prognostic maker for patients with gastric cancer that receive trastuzumab therapy.
Chemotherapy-Induced Amenorrhea and Its Prognostic Significance in Premenopausal Women With Breast Cancer: An Updated Meta-Analysis
Authors: Wang Yifei , Li Yaming , Liang Jingshu , Zhang Nan , Yang Qifeng
Published: April 2022

Objective

Chemotherapy-induced amenorrhea (CIA) is one of the most common side effects in premenopausal patients with breast cancer, and several factors may contribute to the incidence of CIA. In this meta-analysis, we aimed to summarize clinical risk factors associated with CIA incidence and to evaluate their prognostic effects in patients with breast cancer.

Methods

Three electronic databases (Cochrane Library, EMBASE, and MEDLINE) were systematically searched for articles published up to October 2021. The articles included clinical trials that evaluated risk factors associated with CIA and their prognostic value in treatment. For the meta-analysis, pooled odds ratio estimates (ORs) and 95% confidence intervals (CIs) were calculated using the inverse variance-weighted approach, in addition to publication bias and the chi-square test.

Results

A total of 68 studies involving 26,585 patients with breast cancer were included in this meta-analysis, and 16,927 patients developed CIA. From the 68 studies, 7 risk factors were included such as age group, hormone receptor (HR) status, estrogen receptor (ER) status, progesterone receptor (PR) status, tamoxifen administration, chemotherapeutic regimen, and tumor stage. Based on our results, patients with age of ≤40, HR-negative status, ER-negative status, PR-negative status, no use of tamoxifen, and use of anthracycline-based regimen (A) compared with anthracycline-taxane-based regimen (A+T) were associated with less incidence of CIA in patients with breast cancer. Moreover, CIA was associated with favorable disease-free survival (OR = 0.595, 95% CI = 0.537 to 0.658, p < 0.001) and overall survival (OR = 0.547, 95% CI = 0.454–0.660, p < 0.001) in premenopausal patients with breast cancer.

Conclusion

Age, HR status, ER status, PR status, tamoxifen administration, and chemotherapeutic regimen can be considered independent factors to predict the occurrence of CIA. CIA is a favorable prognostic factor in premenopausal patients with breast cancer. CIA should be a trade-off in the clinical management of premenopausal patients with breast cancer, and further large cohort studies are necessary to confirm these results.
A Prospective Study of High Dose-Rate Brachytherapy or Stereotactic Body Radiotherapy of Intra-Prostatic Recurrence: Toxicity and Long Term Clinical Outcome
Authors: Ryg Una , Seierstad Therese , Nilsen Line Brennhaug , Hellebust Taran Paulsen , Djupvik Linda Holth , Gustafson Hilde , Hydal Jørgen , Kishan Amar U. , Hole Knut Håkon , Lilleby Wolfgang
Published: April 2022

Background

Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy.

Methods and Material

Thirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival.

Results

Median follow-up time was 81 months (range 21–115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years.

Conclusion

The toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation.
Concurrent RAS and RAS/BRAF V600E Variants in Colorectal Cancer: More Frequent Than Expected? A Case Report
Authors: Zelli Veronica , Parisi Alessandro , Patruno Leonardo , Cannita Katia , Ficorella Corrado , Luzi Carla , Compagnoni Chiara , Zazzeroni Francesca , Alesse Edoardo , Tessitore Alessandra
Published: April 2022

The assessment of RAS and BRAF mutational status is one of the main steps in the diagnostic and therapeutic algorithm of metastatic colorectal cancer (mCRC). Multiple mutations in the BRAF and RAS pathway are described as a rare event, with concurrent variants in KRAS and BRAF genes observed in approximately 0.05% of mCRC cases. Here, we report data from a case series affected by high-risk stage III and stage IV CRC and tested for RAS and BRAF mutation, treated at our Medical Oncology Unit. The analysis of KRAS, NRAS (codons 12, 13, 59, 61, 117, 146), and BRAF (codon 600) hotspot variants was performed in 161 CRC tumors from August 2018 to September 2021 and revealed three (1.8%) patients showing mutations in both KRAS and BRAF (V600E), including two cases with earlier CRC and one with metastatic disease. We also identified one patient (0.6%) with a mutation in both KRAS and NRAS genes and another one (0.6%) with a double KRAS mutation. Notably, the latter was characterized by aggressive behavior and poor clinical outcome. The mutational status, pathological features, and clinical history of these five CRC cases are described. Overall, this study case series adds evidence to the limited available literature concerning both the epidemiological and clinical aspects of CRC cases characterized by the presence of concurrent RAS/BRAF variants. Future multicentric studies will be required to increase the sample size and provide additional value to results observed so far in order to improve clinical management of this subgroup of CRC patients.
LncRNA HCG11 Facilitates Nasopharyngeal Carcinoma Progression Through Regulating miRNA-490-3p/MAP3K9 Axis
Authors: Zheng Jian , Zhao Zhuochen , Ren Huijun , Wang Yongfeng , Meng Xianchun , Zhang Wenjing , Zhang Cai , Ming Liang , Lu Xiubo
Published: April 2022

Purpose

Long noncoding RNAs (LncRNAs) play complex but important roles in the progression of various tumors. This study aimed to elucidate the functional mechanisms of the HLA complex group 11 (HCG11) in nasopharyngeal carcinoma (NPC).

Patients and Methods

HCG11 levels in NPC specimens were determined by fluorescence in situ hybridization (FISH) and qPCR. Proliferation, apoptosis, and metastasis of NPC cells were determined using CCK8, colony formation, annexin V-PI, and transwell assays. A murine tumor xenograft model was used to investigate the regulatory function of HCG11 in NPC in vivo, and immunohistochemical staining was used to determine the Ki-67 level in tumors. The target relationships between HCG11, microRNA miR-490-3p, and MAPK kinase kinase 9 (MAP3K9) were detected using bioinformatics, qPCR, western blotting, and luciferase reporter assays.

Results

HCG11 was highly expressed in NPC tissues and was positively associated with tumor stage, lymphatic metastasis, and poor prognosis. Functionally, HCG11 knockdown inhibited proliferation and migration and induced apoptosis of NPC cells. Mechanistically, miR-490-3p is a direct target of HCG11, oncogenic functions of HCG11 in NPC cell proliferation and migration can be partially reversed by the miR-490-3p inhibitor. HCG11 significantly increased mitogen-activated protein kinase MAPK kinase 9 (MAP3K9) levels by inhibiting miR-490-3p.

Conclusion

HCG11 facilitates NPC progression via MAP3K9 signaling by sponging miRNA-490-3p, which may contribute to new prognostic markers and promising therapeutic targets.
Intrafraction Prostate Motion Management During Dose-Escalated Linac-Based Stereotactic Body Radiation Therapy
Authors: Panizza Denis , Faccenda Valeria , Lucchini Raffaella , Daniotti Martina Camilla , Trivellato Sara , Caricato Paolo , Pisoni Valerio , De Ponti Elena , Arcangeli Stefano
Published: April 2022

Background

Extreme hypofractionation requires tight planning margins, high dose gradients, and strict adherence to planning criteria in terms of patient positioning and organ motion mitigation. This study reports the first clinical experience worldwide using a novel electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated linac-based stereotactic body radiation therapy (SBRT).

Methods

Thirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The EM tracking device consisted of an integrated Foley catheter with a transmitter. Patients were simulated and treated with a filled bladder and an empty rectum. Setup accuracy was achieved by ConeBeam-CT (CBCT) matching, and motion was tracked during all the procedure. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, the displacements that would have occurred without any intrafraction organ motion management (i.e. no interruptions and repositionings) were simulated.

Results

In 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position. In 25 (45%) a correction was mandated, but only in 10 (18%), the beam delivery was interrupted. Total treatment time lasted on average 10.2 minutes, 6.7 minutes for setup, and 3.5 minutes for beam delivery. Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would have been 6.9 minutes and 3.2 minutes, respectively. The prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during the beam-on phase. Predominant motion pattern was posterior and its probability increased with time, with a mean motion ≤ 2 mm occurring within 10 minutes.

Conclusions

EM real-time tracking was successfully implemented for intrafraction motion management during dose-escalated prostate SBRT. Results showed that most of the observed displacements were < 2 mm in any direction; however, there were a non-insignificant number of fractions with motion exceeding the predefined threshold, which would have otherwise gone undetected without intrafraction motion management.
Use of Prophylactic Indomethacin in Preterm Infants: A Systematic Review and Meta-Analysis
Authors: Al-matary Abdulrahman , Abu Shaheen Amani , Abozaid Sameh
Published: April 2022

Background

Prophylactic indomethacin has been widely used as an effective intervention for reducing mortalities and morbidities in preterm infants including the cardiopulmonary and neurodevelopmental morbidities such as intraventricular hemorrhage (IVH), but many studies have reported contradictory outcomes regarding its significance. Therefore, we aim to systematically review and meta-analyze the data of prophylactic indomethacin on preterm infants.

Methods

Our systematic search included the following databases: Pubmed, Google Scholar, Scopus, Web of Science, The New York Academy of Medicine (NYAM), Virtual health library (VHL), and the System for Information on Grey Literature in Europe (SIGLE) to include studies that assessed the use of prophylactic indomethacin in preterm infants until 12 August 2021.

Results

The final list of our included studies is comprised of 23 randomized trials and cohort studies. Among all the studies outcomes, significant favorable outcome was lowering the rate of PDA, surgical PDA ligation (P < 0.001) and severe IVH (P = 0.008) while no significance was recorded with BPD, pulmonary hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, intestinal perforation, mortality, and length of hospital stay.

Conclusion

Since the meta-analysis results regarding effectiveness of prophylactic indomethacin varied based on the study design particularly with regard to outcomes such as surgical PDA ligation and severe IVH, this warrants the need for more evidence regarding the effectiveness of prophylactic indomethacin in very low birth weight infants.
Clostridioides difficile Infection in Children: A 5-Year Multicenter Retrospective Study
Authors: Buonsenso Danilo , Graffeo Rosalia , Pata Davide , Valentini Piero , Palumbo Carla , Masucci Luca , Ruggiero Antonio , Attinà Giorgio , Onori Manuela , Lancella Laura , Lucignano Barbara , Giuseppe Martina Di , Bernaschi Paola , Cursi Laura
Published: April 2022

While there are numerous studies regarding Clostridioides difficile infection (CDI) in adults, literature on the pediatric population is scarce. Therefore, we performed a 5-year retrospective study between January 2014 and December 2018 in two referral centers in Rome, Italy. There were 359 patients tested for CDI who were enrolled: 87 resulted in positive and 272 in negative. CDI children had a higher number of previous-day hospital admissions (p = 0.024), hospitalizations (p = 0.001), and total hospital admissions (p = 0.008). Chronic comorbidities were more frequent in the CDI group (66.7% vs. 33.3%). Previous use of proton pump inhibitors and antibiotics was associated with CDI (p < 0.001). Among the antibiotics, only fluoroquinolones were significantly associated with CDI. Also, CDI children were more frequently exposed to antibiotics during the episode of hospitalization when children were tested. Our study provides an updated clinical and epidemiological analysis of children with CDI compared with a control group of children who tested negative. Further prospective studies could better define risk factors and preventive methods.
The Relationship Between Cord Blood Cytokine Levels and Perinatal Characteristics and Bronchopulmonary Dysplasia: A Case–Control Study
Authors: Wang Mengmeng , Luo Chenghan , Shi Zanyang , Cheng Xinru , Lei Mengyuan , Cao Wenjun , Zhang Jingdi , Ge Jian , Song Min , Ding Wenqian , Zhang Yixia , Zhao Min , Zhang Qian
Published: April 2022

Objective

To establish the association between serial levels of inflammatory cytokines in cord blood and perinatal characteristics and bronchopulmonary dysplasia (BPD) in preterm infants.

Methods

147 premature infants with gestational age ≤32 weeks who were born and hospitalized in the First Affiliated Hospital of Zhengzhou University between July 2019 and August 2021 were enrolled in this retrospective case–control study. Multiple microsphere flow immunofluorescence was used to detect seven cytokines in cord blood collected within 24 h of birth. Demographics, delivery characteristics, maternal factors, neonatal characteristics, and clinical outcomes were collected for the two groups. An unconditional logistic regression model was used in this study to assess the clinical variables.

Results

IL-6 cord blood levels at birth were significantly higher in the BPD group than in the non-BPD group, but the odds ratio (OR) was very small (OR = 1). No differences in other cytokine concentrations were observed between the two groups. Multivariable logistic regression analysis demonstrated that increased maternal white blood cell (WBC) count on admission and lower birth weight increased the risk of BPD progression.

Conclusions

Increased IL-6 cord blood levels at birth in preterm infants may have trivial significance for predicting BPD. Furthermore, higher maternal WBC count on admission and lower birth weight increased the risk of BPD.
Relationship Between Vitamin D Level and Platelet Parameters in Children With Viral Respiratory Infections
Authors: Feketea Gavriela , Vlacha Vasiliki , Pop Raluca Maria , Bocsan Ioana Corina , Stanciu Luminita Aurelia , Buzoianu Anca Dana , Zdrenghea Mihnea
Published: April 2022

Apart from their classical roles, both platelets and vitamin D play important roles in inflammation and infectious diseases. This study evaluated the platelet response to viral respiratory tract infection in children aged 4–16 years, 32 with influenza, 27 with non-influenza viral infection tested by nasopharyngeal swab and 21 healthy children of the same age. Blood count, including platelet count (PLT), mean platelet volume (MPV) and other platelet indices, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and vitamin D (vit D) levels were compared. The influenza group showed lower PLT and platelet mass (PLT*MPV), and the non-influenza group showed significantly lower MPV, which was correlated with the vit D levels, but not CRP or ESR, and the value vit D*MPV was significantly lower in this group. These results revealed that platelet activation in viral respiratory tract infections in children, as measured by MPV, is related to the vit D level, with differences between influenza and non-influenza infection.

Conclusions

Viral respiratory tract infection in children can diminish the platelet size most likely by suppressing the platelet activation. This response is associated with low levels of vit D. Whether the vit D status is associated with the virus-platelet immune/inflammatory process needs further investigation.
Distribution of HbS Allele and Haplotypes in a Multi-Ethnic Population of Guinea Bissau, West Africa: Implications for Public Health Screening
Authors: Martella Maddalena , Campeggio Mimma , Pulè Gift , Wonkam Ambroise , Menzato Federica , Munaretto Vania , Viola Giampietro , Da Costa Sabado P. , Reggiani Giulia , Araujo Antonia , Cumbà Dionisio , Liotta Giuseppe , Sainati Laura , Riccardi Fabio , Colombatti Raffaella
Published: April 2022

Background

Sickle Cell Disease (SCD) is an inherited condition that is widespread globally and especially in malaria-endemic West African countries. Limited epidemiological data on SCD are available for Guinea Bissau, where newborn screening is not yet implemented, routine diagnosis is not available, and care is case directed.

Methods

Dried blood spots were collected from children accessing two hospitals managed by Italian Non-Governmental Organizations in the capital city of Bissau and sent to Padova for Hemoglobin (Hb) quantification through HPLC and molecular analysis. Beta globin gene analysis was performed in all; and Hb haplotype of the HbSS and HbSA patients was performed in South Africa. One hundred samples belonging to the most frequent ethnic groups were randomly selected for detection of G6PD mutations.

Results

Samples from 848 consecutive children (498 males and 350 females, mean age 6.8 years) accessing the two hospitals were analyzed: 6.95% AS (4.42% allelic frequency), 0.94% SS, and 0.23% AC. 376G G6PD allelic frequency was 24%; 14.8% in AS individuals. The Senegal haplotype was the most prevalent (31%), and the proposition of chromosomes with the atypical haplotype was surprisingly high (56%).

Conclusion

Our study demonstrates a significant frequency of the HbS allele in the population of Guinea Bissau supporting the implementation of screening strategies. The differences among ethnic groups can help guide targeted interventions for SCD awareness campaigns and determine priority areas for public health interventions. The pilot analysis on haplotypes reveals a large proportion of the atypical haplotype, which may be indicative of a genetically heterogeneous population.
Persistent Pulmonary Interstitial Emphysema With Respiratory Infection: A Clinicopathological Analysis of Six Cases and Detection of Infectious Pathogens by Metagenomic Next-Generation Sequencing (mNGS)
Authors: Zhou Ping , Wang Weiya , Fu Yiyun , Zhang Ying , Liang Zuoyu , Tang Yuan , Jiang Lili
Published: April 2022

Background

Persistent pulmonary interstitial emphysema (PPIE) is known to be related to mechanical ventilation and preterm. However, PPIE is also reported rarely in non-ventilated and full-term infants. Its relationship with respiratory infection is rarely reported in the literature. PPIE is difficult to diagnose and always mimics other congenital thoracic malformations (CTMs), such as congenital cystic adenomatoid malformation (CCAM).

Objective

The objective of this study was to evaluate clinicopathological and radiographic features of PPIE with respiratory infection and to detect the possible infectious pathogens.

Methods

From January 2011 to December 2019, six cases were confirmed pathologically with PPIE from a large cohort of 477 resected CTMs in West China Hospital of Sichuan University. Clinical and radiographic features were obtained from patients' medical records and follow-up. The present study aimed to analyze clinicopathological and radiographic features and to detect the infectious pathogens by metagenomic next-generation sequencing (mNGS).

Results

The six PPIE cases included four girls and two boys, ranging from 2 months to 5 years; 100% (5/5) of the available cases were full-term and without mechanical ventilation. CCAM were suspected in 66.7% (4/6) patients; 66.7% (4/6) cases affected a single lobe, and 33.3% (2/6) cases affected both lung lobes. Clinically, all six PPIEs were presented with symptoms of respiratory infection and diagnosed with pneumonia. All six patients were treated by surgery after anti-infective treatment. The pathologic characteristics showed lung cysts with variable size along the bronchovascular bundles, the cysts had a discontinuous fibrotic wall with a smooth inner surface lined with uninucleated and/or multinucleated macrophages. Streptococcus pneumoniae was detected in patient No. 1. Human beta-herpesvirus 5 was detected in patient No. 2. Neisseria mucosa, Neisseria sicca, Prevotella melaninogenica, Prevotella histicola, and Fusobacterium nucleatum were detected in patient No. 5, and no infectious pathogen was detected in 50% (3/6, No. 3, No. 4, and No. 6) of cases.

Conclusion

Six rare cases of PPIE with respiratory infection were treated by surgery after anti-infective treatment. All five available cases were full-term infants without mechanical ventilation. The histological characteristics of PPIE were the wall of cysts composed of a thin layer of discontinuous fibrous tissue and lined with uninucleated or/and multinucleated macrophages.
Challenges in Management of VTE in Children With Cancer: Risk Factors and Treatment Options
Authors: Samji Nasrin , Bhatt Mihir D. , Kulkarni Ketan
Published: April 2022

Venous thromboembolism (VTE) occurs in 2.1 to up to 50% of children with cancer and contributes to long term morbidity as well as early mortality in this population. Pediatric patients with malignancy are predisposed to VTE due to the prothrombotic nature of cancer and its associated coagulopathies as well as chemotherapeutic agents, use of central venous catheters, surgery, radiotherapy, and concomitant thrombophilia. Management of thrombosis in this population is challenging due to concomitant thrombocytopenia, associated bleeding risks, concurrent co-morbidities, and toxicities of therapy. The aim of this paper is to highlight clinically relevant issues and management dilemmas using clinical vignettes. We review the clinical significance of asymptomatic and symptomatic thrombosis, examine the various options for asparaginase-associated thrombosis, address the role and controversies of direct oral anticoagulants, and describe our approach to managing anticoagulation therapy in the context of chemotherapy-induced thrombocytopenia.
The First United Arab Emirates National Representative Birth Cohort Study: Study Protocol
Authors: Mutare Sharon , Feehan Jack , Cheikh Ismail Leila , Ali Habiba I. , Stojanovska Lily , Shehab Abdullah , Khair Howaida , Ali Raghib , Hwalla Nahla , Kharroubi Samer , Hills Andrew P. , Fernandes Michelle , Al Dhaheri Ayesha Salem
Published: April 2022

Background

In recent years, the prevalence of non-communicable diseases (NCDs) has escalated. Evidence suggests that there are strong associations between nutrition in early life and the risk of disease in adulthood. This manuscript describes the study protocol of the First United Arab Emirates National Representative Birth Cohort Study (UAE-BCS), with the objective of investigating nutrition and lifestyle factors in the first 1,000 days of life. The main aims of the study are (1) to address critical issues relating to mother and child nutrition and their effect on growth and development, (2) to profile maternal nutrition, child growth, health, and development outcomes in early life, and (3) to study the associations between these factors among the Emirati population in the UAE.

Methods/Design

In this study, a multidisciplinary team of researchers was established including credible researchers from the UAE, Lebanon, Australia, and the United Kingdom to launch the First United Arab Emirates 3-year birth cohort study. We aim to recruit 260 pregnant Emirati women within their first trimester, which is defined by the study as from 8 to 12 weeks pregnant, from obstetrics and gynecology clinics in the UAE. Participants will be recruited via face-to-face interviews and will receive a total of 11 visits with 1 visit in each trimester of pregnancy and 8 visits after delivery. Maternal data collection includes, socio-demographic and lifestyle factors, dietary intake, anthropometric measurements, physical activity, maternal psychological state, and blood samples for biochemical analysis. Post-partum, visits will take place when the child is 0.5, 4, 6, 9, 12, 18, and 24 months old, with data collection including infant anthropometric measurements, young child feeding practices, dietary intake, supplement use and the eating environment at home, as well as all maternal data collection described above, apart from blood samples. Additional data collection for the child includes early child developmental assessments taking place at three timepoints: (1) within 2 weeks of birth, (2) at 10–14 months and (3) at 22–26 months of age. Early child developmental assessments for the infant include vision, hearing, cognition, motor skills, social-emotional reactivity, neurodevelopmental, and sleep assessments.

Discussion

The United Arab Emirates Birth Cohort study protocol provides a standardized model of data collection methods for collaboration among the multisectoral teams within the United Arab Emirates to enrich the quality and research efficiency in early nutrition, thereby enhancing the health of mothers, infants, and children.
Caregivers' Attitudes Toward COVID-19 Vaccination in Children and Adolescents With a History of SARS-CoV-2 Infection
Authors: Buonsenso Danilo , Valentini Piero , Macchi Marina , Folino Francesco , Pensabene Carola , Patria Maria Francesca , Agostoni Carlo , Castaldi Silvana , Lecce Maurizio , Giannì Maria Lorella , Marchisio Paola , Milani Gregorio P. ,   The CHICO Study Group
Published: April 2022

Background

Limited data are available on the attitudes of caregivers toward COVID-19 vaccination in children and adolescents with a history of SARS-CoV-2 infection or Long Covid symptoms. The aim of this study was to investigate the vaccine hesitancy among caregivers of children and adolescents with a documented history of SARS-CoV-2 infection and to explore the possible associations between COVID-19 manifestations and the acceptance of the vaccine.

Methods

Caregivers of children or adolescents with a microbiologically confirmed diagnosis of SARS-CoV-2 infection evaluated in two University Hospitals were interviewed.

Results

We were able to contact 132 caregivers and 9 declined to participate. 68 caregivers (56%) were in favor of COVID-19 vaccination for their child. In the multiple logistic regression, child's age (OR 1.17, 95%CI 1.06–1.28) and hospitalization due to COVID-19 (OR 3.25, 95%CI 1.06–9.95) were positively associated with being in favor of COVID-19 vaccination. On the contrary, the occurrence of child's Long Covid was associated with a higher likelihood of being against the vaccination (OR 0.28, 95%CI 0.10–0.80).

Conclusions

This preliminary study shows that only about half of the interviewed parents of children and adolescents with a previous SARS-CoV-2 infection are willing to vaccinate them to prevent a repeated COVID-19 infection. These findings might help healthcare workers to provide tailored information to caregivers of children with a previous SARS-CoV-2 infection.
Plant Source Derived Compound Exhibited In Silico Inhibition of Membrane Glycoprotein In SARS-CoV-2: Paving the Way to Discover a New Class of Compound For Treatment of COVID-19
Authors: Mahanta Saurov , Naiya Tufan , Biswas Kunal , Changkakoti Liza , Mohanta Yugal Kishore , Tanti Bhaben , Mishra Awdhesh Kumar , Mohanta Tapan Kumar , Sharma Nanaocha
Published: April 2022

SARS-CoV-2 is the virus responsible for causing COVID-19 disease in humans, creating the recent pandemic across the world, where lower production of Type I Interferon (IFN-I) is associated with the deadly form of the disease. Membrane protein or SARS-CoV-2 M proteins are known to be the major reason behind the lower production of human IFN-I by suppressing the expression of IFNβ and Interferon Stimulated Genes. In this study, 7,832 compounds from 32 medicinal plants of India possessing traditional knowledge linkage with pneumonia-like disease treatment, were screened against the Homology-Modelled structure of SARS-CoV-2 M protein with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals against the SARS-CoV-2 M protein, a compound, ZIN1722 from Zingiber officinale showed the best binding affinity with the receptor with a Glide Docking Score of −5.752 and Glide gscore of −5.789. In order to study the binding stability, the complex between the SARS-CoV-2 M protein and ZIN1722 was subjected to 50 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 32 ns of MD Simulation. The molecule ZIN1722 also showed promising results during ADME-Tox analysis performed using Swiss ADME and pkCSM. With all the findings of this extensive computational study, the compound ZIN1722 is proposed as a potential inhibitor to the SARS-CoV-2 M protein, which may subsequently prevent the immunosuppression mechanism in the human body during the SARS-CoV-2 virus infection. Further studies based on this work would pave the way towards the identification of an effective therapeutic regime for the treatment and management of SARS-CoV-2 infection in a precise and sustainable manner.
Controlling Factors of Gas-Bearing Properties in Permian Tight Sandstone Based on Sealing Corings, Sulige Gas Field, Ordos Basin, Northern China
Authors: Wu Weitao , Wei Xinshan , Zhao Xiaohui , Li Ning , Lu Xiang , Chen Jiawei
Published: April 2022

Gas saturation (Sg) is an important parameter for studying the gas-bearing properties of tight sandstone; however, there has been limited research on gas-bearing properties based on sealing coring. This study determines the controlling factors of the gas-bearing properties of tight sandstone in the Permian He8 Member of the Sulige Gas Field, Ordos Basin, Northern China, based on sealing coring, logging, drilling, gas testing, and laboratory analysis. The He8 Member Sg distribution is 17.9–63.8% (main range: 30–45%) and shows a downward trend from bottom to top. The Ro and hydrocarbon generation intensity of the source rock, reservoir porosity, and permeability tend to control the Sg in stages. When these parameters are less than 1.8%, 17 × 108 m3/km2, 10%, and 0.5 × 10–3 μm2, respectively, Sg increases significantly. When each parameter is greater than the aove boundary value, the change in Sg is not obvious. Four types of gas-bearing patterns of tight sandstone can be observed according to the distribution of reservoir and source rock conditions: “upper and lower constant,” “upper low–lower high,” “upper high–medium low–lower high,” and “upper high–lower low”; these patterns are mainly controlled by high maturity source rocks, reservoir physical properties, reservoir physical properties and structure, and structure, respectively. The corresponding gas test results reveal the existence of pure gas, pure gas and gas–water, gas–water, and gas-bearing water and pure water layers, respectively.