bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized Method for Pseudomonas aeruginosa Integrative Filamentous Bacteriophage Propagation
Authors: Gavric Damir , Knezevic Petar
Published: January 2022

Filamentous bacteriophages frequently infect Pseudomonas aeruginosa and alter its phenotypic traits, including virulence factors. The first step in examination of these phages is to obtain suspensions with high virus titer, but as there are no methods for integrative filamentous phage multiplication, the aim was to design, describe, and compare two methods for this purpose. As models, three strains of Pseudomonas aeruginosa, containing (pro)phages Pf4, Pf5, and PfLES were used (PAO1, UCBPP-PA14, and LESB58, respectively). Method 1 comprised propagation of phages in 6 L of bacterial culture for 48 h, and method 2 applied 600 mL culture and incubation for 6 days with centrifugation and addition of new medium and inoculum at 2-day intervals. In method 1, phages were propagated by culture agitation, followed by centrifugation and filtration (0.45 and 0.22 μm), and in method 2, cultures were agitated and centrifuged several times to remove bacteria without filtration. Regardless of the propagation method, supernatants were subjected to concentration by PEG8000 and CsCl equilibrium density gradient centrifugation, and phage bands were removed after ultracentrifugation and dialyzed. In the obtained suspensions, phage titer was determined, and concentration of isolated ssDNA from virions was measured. When propagation method 2 was compared with method 1, the phage bands in CsCl were much thicker, phage number was 3.5–7.4 logs greater, and concentration of ssDNA was 7.6–22.4 times higher. When phage count was monitored from days 2 to 6, virion numbers increased for 1.8–5.6 logs, depending on phage. We also observed that filamentous phage plaques faded after 8 h of incubation when the double layer agar spot method was applied, whereas the plaques were visible for 24 h on single-layer agar. Finally, for the first time, we confirmed existence of replicative form and virions of PfLES (pro)phage as well as its ability to produce plaques. Similarly, for the first time, we confirmed plaque production of Pf5 (pro)phage present in P. aeruginosa strain UCBPP-PA14. The described method 2 has many advantages and can be further improved and adopted for filamentous phages of other hosts.
Activity-Based Protein Profiling for the Identification of Novel Carbohydrate-Active Enzymes Involved in Xylan Degradation in the Hyperthermophilic Euryarchaeon Thermococcus sp. Strain 2319x1E
Authors: Klaus Thomas , Ninck Sabrina , Albersmeier Andreas , Busche Tobias , Wibberg Daniel , Jiang Jianbing , Elcheninov Alexander G. , Zayulina Kseniya S. , Kaschani Farnusch , Bräsen Christopher , Overkleeft Herman S. , Kalinowski Jörn , Kublanov Ilya V. , Kaiser Markus , Siebers Bettina
Published: January 2022

Activity-based protein profiling (ABPP) has so far scarcely been applied in Archaea in general and, especially, in extremophilic organisms. We herein isolated a novel Thermococcus strain designated sp. strain 2319x1E derived from the same enrichment culture as the recently reported Thermococcus sp. strain 2319x1. Both strains are able to grow with xylan as the sole carbon and energy source, and for Thermococcus sp. strain 2319x1E (optimal growth at 85°C, pH 6–7), the induction of xylanolytic activity in the presence of xylan was demonstrated. Since the solely sequence-based identification of xylanolytic enzymes is hardly possible, we established a complementary approach by conducting comparative full proteome analysis in combination with ABPP using α- or β-glycosidase selective probes and subsequent mass spectrometry (MS)-based analysis. This complementary proteomics approach in combination with recombinant protein expression and classical enzyme characterization enabled the identification of a novel bifunctional maltose-forming α-amylase and deacetylase (EGDIFPOO_00674) belonging to the GH57 family and a promiscuous β-glycosidase (EGIDFPOO_00532) with β-xylosidase activity. We thereby further substantiated the general applicability of ABPP in archaea and expanded the ABPP repertoire for the identification of glycoside hydrolases in hyperthermophiles.
The Role of nmcR, ampR, and ampD in the Regulation of the Class A Carbapenemase NmcA in Enterobacter ludwigii
Authors: Nakano Ryuichi , Yamada Yuki , Nakano Akiyo , Suzuki Yuki , Saito Kai , Sakata Ryuji , Ogawa Miho , Narita Kazuya , Kuga Akio , Suwabe Akira , Yano Hisakazu
Published: January 2022

Various carbapenemases have been identified in the Enterobacteriaceae. However, the induction and corresponding regulator genes of carbapenemase NmcA has rarely been detected in the Enterobacter cloacae complex (ECC). The NmcA-positive isolate ECC NR1491 was first detected in Japan in 2013. It was characterized and its induction system elucidated by evaluating its associated regulator genes nmcR, ampD, and ampR. The isolate was highly resistant to all β-lactams except for third generation cephalosporins (3GC). Whole-genome analysis revealed that blaNmcA was located on a novel 29-kb putatively mobile element called EludIMEX-1 inserted into the chromosome. The inducibility of β-lactamase activity by various agents was evaluated. Cefoxitin was confirmed as a strong concentration-independent β-lactamase inducer. In contrast, carbapenems induced β-lactamase in a concentration-dependent manner. All selected 3GC-mutants harboring substitutions on ampD (as ampR and nmcR were unchanged) were highly resistant to 3GC. The ampD mutant strain NR3901 presented with a 700 × increase in β-lactamase activity with or without induction. Similar upregulation was also observed for ampC and nmcA. NR1491 (pKU412) was obtained by transforming the ampR mutant (135Asn) clone plasmid whose expression increased by ∼100×. Like NR3901, it was highly resistant to 3GC. Overexpression of ampC, rather than nmcA, may have accounted for the higher MIC in NR1491. The ampR mutant repressed nmcA despite induction and it remains unclear how it stimulates nmcA transcription via induction. Future experiments should analyze the roles of nmcR mutant strains.
Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Uryga Agnieszka , Nasr Nathalie , Kasprowicz Magdalena , Budohoski Karol , Sykora Marek , Smielewski Peter , Burzyńska Małgorzata , Czosnyka Marek
Published: January 2022

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH.

Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal.

Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50–67). WFNS scale was 2 (1–4) and the modified Fisher scale was 3 (1–3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (Rp = −0.42; p < 0.001).

Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.
The Role of Microtubule Associated Serine/Threonine Kinase 3 Variants in Neurodevelopmental Diseases: Genotype-Phenotype Association
Authors: Shu Li , Xiao Neng , Qin Jiong , Tian Qi , Zhang Yanghui , Li Haoxian , Liu Jing , Li Qinrui , Gu Weiyue , Wang Pengchao , Wang Hua , Mao Xiao
Published: January 2022

Objective: To prove microtubule associated serine/threonine kinase 3 (MAST3) gene is associated with neurodevelopmental diseases (NDD) and the genotype-phenotype correlation.

Methods: Trio exome sequencing (trio ES) was performed on four NDD trios. Bioinformatic analysis was conducted based on large-scale genome sequencing data and human brain transcriptomic data. Further in vivo zebrafish studies were performed.

Results: In our study, we identified four de novo MAST3 variants (NM_015016.1: c.302C > T:p.Ser101Phe; c.311C > T:p.Ser104Leu; c.1543G > A:p.Gly515Ser; and c.1547T > C:p.Leu516Pro) in four patients with developmental and epileptic encephalopathy (DEE) separately. Clinical heterogeneities were observed in patients carrying variants in domain of unknown function (DUF) and serine-threonine kinase (STK) domain separately. Using the published large-scale exome sequencing data, higher CADD scores of missense variants in DUF domain were found in NDD cohort compared with gnomAD database. In addition, we obtained an excess of missense variants in DUF domain when compared autistic spectrum disorder (ASD) cohort with gnomAD database, similarly an excess of missense variants in STK domain when compared DEE cohort with gnomAD database. Based on Brainspan datasets, we showed that MAST3 expression was significantly upregulated in ASD and DEE-related brain regions and was functionally linked with DEE genes. In zebrafish model, abnormal morphology of central nervous system was observed in mast3a/b crispants.

Conclusion: Our results support the possibility that MAST3 is a novel gene associated with NDD which could expand the genetic spectrum for NDD. The genotype-phenotype correlation may contribute to future genetic counseling.
Association Between Vitamin D and Influenza: Meta-Analysis and Systematic Review of Randomized Controlled Trials
Authors: Zhu Zhixin , Zhu Xiaoxia , Gu Lanfang , Zhan Yancen , Chen Liang , Li Xiuyang
Published: January 2022

Background: Vitamin D supplementation improves the immune function of human body and can be a convenient way to prevent influenza. However, evidence on the protective effect of vitamin D supplementation on influenza from Randomized Controlled Trials (RCTs) is inconclusive.

Methods: RCTs regarding the association between vitamin D supplementation and influenza were identified by searching PubMed, Cochrane library, Embase and Chinese Biomedical Database (CBM) from inception until present (last updated on 10 November 2021). Studies that reported dosages and durations of vitamin D supplementation and number of influenza infections could be included. Heterogeneity was assessed using Cochran's Q test and I2 statistics, the meta-analysis was conducted by using a random-effects model, the pooled effects were expressed with risk ratio (RR) with 95% confidence interval (95% CI).

Results: 10 trials including 4859 individuals were ultimately eligible after scanning. There was no evidence of a significant heterogeneity among studies (I2 = 27%, P = 0.150). Meta-regression analysis finding indicated that country, latitude, average age, economic level, follow-up period and average daily vitamin D intake did not cause the statistical heterogeneity. The study finding indicates that substitution with vitamin D significantly reduces the risk of influenza infections (RR = 0.78, 95% CI:0.64–0.95). No evidence of publication bias was observed. Omission of any single trial had little impact on the pooled risk estimates.

Conclusions: The meta-analysis produced a corroboration that vitamin D supplement has a preventive effect on influenza. Strategies for preventing influenza can be optimized by vitamin D supplementation.
Multi-Parametric Magnetic Resonance Imaging-Based Radiomics Analysis of Cervical Cancer for Preoperative Prediction of Lymphovascular Space Invasion
Authors: Huang Gang , Cui Yaqiong , Wang Ping , Ren Jialiang , Wang Lili , Ma Yaqiong , Jia Yingmei , Ma Xiaomei , Zhao Lianping
Published: January 2022

Background

Detection of lymphovascular space invasion (LVSI) in early cervical cancer (CC) is challenging. To date, no standard clinical markers or screening tests have been used to detect LVSI preoperatively. Therefore, non-invasive risk stratification tools are highly desirable.

Objective

To train and validate a multi-parametric magnetic resonance imaging (mpMRI)-based radiomics model to detect LVSI in patients with CC and investigate its potential as a complementary tool to enhance the efficiency of risk assessment strategies.

Materials and Methods

The model was developed from the tumor volume of interest (VOI) of 125 patients with CC. A total of 1037 radiomics features obtained from conventional magnetic resonance imaging (MRI), including a small field-of-view (sFOV) high-resolution (HR)-T2-weighted MRI (T2WI), apparent diffusion coefficient (ADC), T2WI, fat-suppressed (FS)-T2WI, as well as axial and sagittal contrast-enhanced T1-weighted MRI (T1c). We conducted a radiomics-based characterization of each tumor region using pretreatment image data. Feature selection was performed using the least absolute shrinkage and selection operator method on the training set. The predictive performance was compared with single variates (clinical data and single-layer radiomics signatures) analyzed using a receiver operating characteristic (ROC) curve. Three-fold cross-validation performed 20 times was used to evaluate the accuracy of the trained classifiers and the stability of the selected features. The models were validated by using a validation set.

Results

Feature selection extracted the six most important features (3 from sFOV HR-T2WI, 1 T2WI, 1 FS-T2WI, and 1 T1c) for model construction. The mpMRI-combined radiomics model (area under the curve [AUC]: 0.940) reached a significantly higher performance (better than the clinical parameters [AUC: 0.730]), including any single-layer model using sFOV HR-T2WI (AUC: 0.840), T2WI (AUC: 0.770), FS-T2WI (AUC: 0.710), ADC maps (AUC: 0.650), sagittal, and axial T1c values (AUC: 0.710, 0.680) in the validation set.

Conclusion

Biomarkers using multi-parametric radiomics features derived from preoperative MR images could predict LVSI in patients with CC.
Self-Expandable Metallic Stent Implantation Combined With Bronchial Artery Infusion Chemoembolization in the Treatment of Lung Cancer With Complete Atelectasis
Authors: Li Xiaobing , Yin Meipan , Xie Pengfei , Liu Ying , Li Xiangnan , Qi Yu , Ma Yaozhen , Li Chunxia , Wu Gang
Published: January 2022

Background

Atelectasis is a common complication of lung cancer, and there are few reports about the treatment methods. This study retrospectively analyzed the safety and effectiveness of endotracheal metal stent implantation combined with arterial infusion chemoembolization in the treatment of non-small cell lung cancer with complete atelectasis.

Methods

The clinical data of patients with non-small cell lung cancer and complete atelectasis treated by self-expandable metallic stent implantation combined with arterial infusion chemotherapy were retrospectively analyzed. The clinical efficacy was evaluated and postoperative adverse reactions were observed. Progression-free survival and overall survival were analyzed by Kaplan-Meier method.

Results

In all, 42 endotracheal metallic stents were implanted in 42 patients under fluoroscopy. 5–7 days after stent implantation, CT showed that 24 patients (57.1%) had complete lung recruitment, and that 13 (31.0%) had partial lung recruitment. The technical success rate was 100%, and the clinical success rate was 88.1% (37/42). 5–7 days after stent implantation, bronchial artery infusion chemoembolization was performed in all patients. The median progression-free survival and overall survival were 6 months (95% CI: 2.04-9.66) and 10 months (95% CI: 7.22-12.79), respectively.

Conclusion

Self-expandable metallic stent implantation combined with arterial infusion chemoembolization may be an effective and safe strategy in the treatment of lung cancer with atelectasis clinically.
Comparative Effectiveness of Enhanced Recovery After Surgery Program Combined With Single-Incision Laparoscopic Surgery in Colorectal Cancer Surgery: A Retrospective Analysis
Authors: Wang Changgang , Feng Haoran , Zhu Xiaoning , Song Zijia , Li You , Shi Yiqing , Jiang Yimei , Chen Xianze , Zhang Tao , Zhao Ren , Liu Kun
Published: January 2022

Background

Recently, enhanced recovery after surgery (ERAS) has been widely used in the perioperative management of colorectal cancer (CRC). This study aimed to evaluate the safety and feasibility of ERAS combined with single-incision laparoscopic surgery (SILS) in CRC surgery.

Methods

This was a retrospective study of patients with CRC who underwent surgery between April 2018 and April 2020 in Ruijin Hospital(North), Shanghai Jiaotong University School of Medicine. The patients were divided into three groups: group A (n=138), patients who underwent traditional multiport laparoscopic colectomy with conventional perioperative management; group B (n=63), patients who underwent SILS; and group C (n=51), patients who underwent SILS with ERAS.

Results

Overall, 252 participants were included in the retrospective study. The median operation time (min) in group B and group C was shorter than that in group A (group A 134.0 ± 42.5; group B 117 ± 38.9; group C 111.7 ± 35.4, p=0.004). The estimated surgical blood loss (ml) was lower in groups B and C than in group A (group A 165.1 ± 142.2; group B 122.0 ± 79.4; group C 105.2 ± 55.8, p=0.011). The length of surgical incision (cm) was shorter in groups B and C than in group A (group A 7.34 ± 1.05; group B 5.60 ± 0.80; group C 5.28 ± 0.52, p<0.001). The time before first flatus (hours) in group C was shorter than in groups A and B (group A 61.85 ± 21.14; group B 58.30 ± 20.08; group C 42.06 ± 23.72; p<0.001). The days prior to the administration of free oral fluids in group C was shorter than in groups A and B (group A 4.79 ± 1.28; group B 4.67 ± 1.11; group C 2.62 ± 0.64; p<0.001). The days of prior solid diet was less in group C than in groups A and B (group A 7.22 ± 3.87; group B 7.08 ± 3.18; group C 5.75 ± 1.70; p=0.027). The postoperative length of stay (LOS) was less in group C compared with that in groups A and B (group A 9.46 ± 4.84 days; group B 9.52 ± 7.45 days; group C 7.20 ± 2.37 days; p=0.023). The visual analog scale (VAS) scores on day 0, 1, and 2 in groups B and C were lower than those in group A (day 0, p<0.001; day 1, p<0.001; day 2, p=0.002), while the VAS score on day 3 showed no differences in the three groups (group A 1.29 ± 1.38; group B 0.98 ± 1.24; group C 0.75 ± 0.64, p=0.018).

Conclusion

The findings suggest that SILS combined with ERAS may be a feasible and safe procedure for CRC surgery because it provides favorable cosmetic results, early dietary resumption, shorter hospital stays, and appropriate control of postoperative pain without increases in complications or readmission rates compared to conventional perioperative care with SILS or conventional laparoscopic surgery(CLS) of CRC. Further prospective randomized controlled studies are needed to enhance evidence-based medical evidence.
Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy
Authors: Burke Aidan M. , Carrasquilla Michael , Jean Walter C. , Collins Brian T. , Anaizi Amjad N. , Atkins Michael B. , Gibney Geoffrey T. , Collins Sean P.
Published: January 2022

Purpose/Objectives

Clinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes.

Materials and Methods

Patients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated.

Results

Twenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated.

Conclusions

In our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.
Challenges and Advances in Diagnosis and Treatment of Leptomeningeal Disease (LMD)
Authors: Ferguson Sherise D. , Fomchenko Elena I. , Guerrieri Renato A. , Glitza Oliva Isabella C.
Published: January 2022

Leptomeningeal disease (LMD) is a devastating category of CNS metastasis with a very poor prognosis and limited treatment options. With maximal aggressive therapy, survival times remain short and, without treatment, prognosis is measured in weeks. Both LMD diagnosis and treatment are challenging topics within neuro-oncology. In this review, we discuss the advances in LMD diagnosis with a focus on the role of circulating tumor DNA (ctDNA) and discuss the role of targeted and immunotherapy in LMD treatment.
Pattern of Time-to-Surgery in Patients With Breast Cancer at Different Stages of the COVID-19 Pandemic
Authors: Chen Ruixian , Yang Jiqiao , Zhao Xin , Fu Zhoukai , Wang Zhu , Qiu Changjian , Wu Yunhao , Yang Ruoning , Liu Weijing , Huang Ya , Chen Jie
Published: January 2022

Background

The management of cancer surgeries is under unprecedented challenges during the COVID-19 pandemic, and the breast cancer patients may face a time-delay in the treatment. This retrospective study aimed to present the pattern of time-to-surgery (TTS) and analyze the features of breast cancer patients under the different stages of the COVID-19 pandemic.

Methods

Patients who received surgeries for breast cancers at West China Hospital between February 15, 2020 and April 30, 2020 (the outbreak and post-peak stages), and between March 10, 2021 and May 25, 2021 (the normalization stage) were included. TTS was calculated as the time interval between the pathological diagnosis and surgical treatment of breast cancer patients. And the pandemic was divided into three stages based on the time when the patients were pathologically diagnosed and the severity of pandemic at that time point. TTS, demographic and clinicopathological features were collected from medical records.

Results

A total of 367 patients were included. As for demographic features, it demonstrated statistically significant differences in insurance type (p<0.001) and regular screening (p<0.001), as well as age (p=0.013) and menstrual status (p=0.004). As for clinicopathological features, axillary involvement (p=0.019) was a factor that differed among three stages. The overall TTS was 23.56 ± 21.39 days. TTS for patients who were diagnosed during the outbreak of COVID-19 were longer than those diagnosed during pandemic post-peak and normalization stage (p<0.001). Pandemic stage (p<0.001) and excision biopsy before surgery (OR, 6.459; 95% CI, 2.225-18.755; p=0.001) were markedly correlated with the TTS of patients.

Conclusions

TTS of breast cancer patients significantly varied in different stages of the COVID-19 pandemic. And breast cancer patients’ daily lives and disease treatments were affected by the pandemic in many aspects, such as health insurance access, physical screening and change of therapeutic schedules. As the time-delay may cause negative influences on patients’ disease, we should minimize the occurrence of such time-delay. It is vital to come up with comprehensive measures to deal with unexpected situations in case the pandemic occurs.
mMCP7, a Mouse Ortholog of δ Tryptase, Mediates Pelvic Tactile Allodynia in a Model of Chronic Pelvic Pain
Authors: Pattabiraman Goutham , Liu Zhiqiang , Paul Madhumita , Schaeffer Anthony J. , Thumbikat Praveen
Published: January 2022

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a condition that affects a large number of men and has unknown etiology. We have previously demonstrated the presence of elevated levels of mast cell tryptase in expressed prostatic secretions (EPS) of CP/CPPS patients. In a murine model of CP/CPPS, we showed tryptase and its cognate receptor PAR2 as critical to the development of pelvic pain and lower urinary tract symptoms. Here, we extend these observations to demonstrate that an isoform of tryptase called delta (δ)-tryptase, is elevated in the EPS of patients with CP/CPPS and is correlated with pelvic pain symptoms. Using anEscherichia coli(CP1) -induced murine model of CP/CPPS, we demonstrated a differential response in C57BL/6J and NOD/ShiLtJ mice, with C57BL6/J mice being resistant to an increase in pelvic tactile allodynia, despite having equivalent levels of activated mast cells in the prostate. Activated tryptase+vemast cells were observed to be in closer apposition to PGP9.5+venerve fibers in the prostate stroma of NOD/ShiLtJ in comparison to C57BL/6J mice. The mouse ortholog of δ-tryptase, mouse mast cell protease 7 (mMCP7) has been reported to be unexpressed in C57BL/6J mice. We confirmed the absence of mMCP7 in the prostates of C57BL/6J and its presence in NOD/ShiLtJ mice. To evaluate a role for mMCP7 in the differential allodynia responses, we performed direct intra-urethral instillations of mMCP7 and the beta (β)-tryptase isoform ortholog, mMCP6 in the CP1-infection model. mMCP7, but not mMCP6 was able to induce an acute pelvic allodynia response in C57BL/6J mice.In-vitrostudies with mMCP7 on cultured mast cells as well as dissociated primary neurons demonstrated the ability to induce differential activation of pain and inflammation associated molecules compared to mMCP6. We conclude that mMCP7, and possibility its human ortholog δ-tryptase, may play an important role in mediating the development of pelvic tactile allodynia in the mouse model of pelvic pain and in patients with CP/CPPS.
Clinical Characteristics and the Risk Factors of Hepatic Injury in 221 Children With Infectious Mononucleosis
Authors: Zhang Chao , Cui Shu , Mao Guoshun , Li Guitao
Published: January 2022

Background: Infectious mononucleosis caused by Epstein-Barr Virus infection is a common acute infectious disease in children. About 40–80% of children with infectious mononucleosis have hepatic injury, and hepatic failure is one of the main causes of death in patients with fatal infectious mononucleosis. Identifying the demographics, presenting clinical characteristics and the risk factors of hepatic injury in infectious mononucleosis children are helpful to remind clinicians which patients are prone to have hepatic damage.

Methods: A descriptive, cross-sectional study with a 31-month retrospective review was performed on all infectious mononucleosis children hospitalized in the pediatric department of Fuyang People's Hospital. Demographic data, presenting features, radiology imaging, clinical and laboratory parameters, and clinical outcomes of infectious mononucleosis children were collected.

Results: Two-hundred twenty-one infectious mononucleosis inpatients were enrolled, and 43.9% (97/221) patients were considered to have a hepatic injury (defined as alanine amino transaminase > 40 U/L). Compared with patients without hepatic injury, hepatic injury patients were marked with a significantly higher percentage of hepatomegaly (31 vs. 49%), splenomegaly (58 vs. 81%) and palpebral edema (47 vs. 63%), higher age (3.05 ± 2.12 vs. 3.84 ± 2.44), hospitalization days (6.85 ± 2.64 vs. 8.08 ± 2.83), leukocyte (14.24 ± 5.32 vs. 18.53 ± 8.63), lymphocytes (9.48 ± 4.49 vs. 13.80 ± 7.47), the proportion of atypical lymphocytes (0.12 ± 0.07 vs. 0.15 ± 0.08) and aspartate aminotransferase (33.71 ± 10.94 vs. 107.82 ± 93.52). The results of correlation analysis and multiple linear regression analysis indicated that age (OR = 1.185; 95% CI = 1.035–1.357, p = 0.014), female (OR = 2.002, 95% CI: 0.261–0.955, p = 0.036) and splenomegaly (OR = 2.171, 95% CI: 1.018–4.628, p = 0.045) were independent risk factors of hepatic injury.

Conclusions: In this study, the hepatic injury was associated with gender, age, and splenomegaly, which improved our understanding of risk factors about hepatic injury among infectious mononucleosis children.
Hospital Admissions for Respiratory Tract Infections in Children Aged 0–5 Years for 2017/2023
Authors: Methi Fredrik , Størdal Ketil , Telle Kjetil , Larsen Vilde Bergstad , Magnusson Karin
Published: January 2022

Aim: To compare hospital admissions across common respiratory tract infections (RTI) in 2017-21, and project possible hospital admissions for the RTIs among children aged 0–12 months and 1-5 years in 2022 and 2023.

Methods: In 644 885 children aged 0–12 months and 1–5 years, we plotted the observed monthly number of RTI admissions [upper- and lower RTI, influenza, respiratory syncytial virus (RSV), and COVID-19] from January 1st, 2017 until October 31st, 2021. We also plotted the number of RTI admissions with a need for respiratory support. We used the observed data to project four different scenarios of RTI admissions for the rest of 2021 until 2023, with different impacts on hospital wards: (1) “Business as usual,” (2) “Continuous lockdown,” (3) “Children's immunity debt,” and (4) “Maternal and child immunity debt.”

Results: By October 31st, 2021, the number of simultaneous RTI admissions had exceeded the numbers usually observed at the typical season peak in January, i.e., ~900. Based on our observed data and assuming that children and their mothers (who transfer antibodies to the very youngest) have not been exposed to RTI over the last one and a half years, our scenarios suggest that hospitals should be prepared to handle two to three times as many RTI admissions, and two to three times as many RTI admissions requiring respiratory support among 0–5-year-olds as normal, from November 2021 to April 2022.

Conclusion: Scenarios with immunity debt suggest that pediatric hospital wards and policy makers should plan for extended capacity.
Effect of Installation Platform on Bearing Capacity of an Offshore Monopile Foundation
Authors: Fabo Chen , Ben He , Peng Gao , Xiangming Ge , Yong Zhou , Weijiang Chu
Published: January 2022

An installation platform will disturb the natural seabed adjacent to a monopile and, consequently, affects the bearing capacity of the monopile foundation. Thus, consideration of the influence of installation disturbance is required in the monopile design, which can also save a fraction of the construction costs and avoid security risks. It was found in a sensitivity analysis, depending on the numerical simulations for an offshore monopile foundation installed using an installation platform, that the bearing capacities of the monopile were reduced by the penetration and extraction of the support legs of the installation platform, which were, a reduction of about 7% of the horizontal bearing capacity of the monopile (decreasing with a larger diameter of the monopile), about 2% of the ultimate bending moment, and almost no reduction of the vertical bearing capacity. For the monopile specifically subjected to the combined loads, it was found in SLS that horizontal displacement and rotation at the mudline increased by about 5.13% and 2.12%, respectively, and internal forces increased by about 3.29%–9.87%; and the horizontal displacement and the rotation at the mudline increased by about 4.56% and 2.79% in ULS, respectively, and the internal forces increased by about 3.49%–7.79% in the ULS. The study on the effects of the disturbance of the installation platform can be an important suggestion for the engineer in monopile design.
Mammalian Epidermis: A Compendium of Lipid Functionality
Authors: Vietri Rudan Matteo , Watt Fiona M.
Published: January 2022

Mammalian epidermis is a striking example of the role of lipids in tissue biology. In this stratified epithelium, highly specialized structures are formed that leverage the hydrophobic properties of lipids to form an impermeable barrier and protect the humid internal environment of the body from the dry outside. This is achieved through tightly regulated lipid synthesis that generates the molecular species unique to the tissue. Beyond their fundamental structural role, lipids are involved in the active protection of the body from external insults. Lipid species present on the surface of the body possess antimicrobial activity and directly contribute to shaping the commensal microbiota. Lipids belonging to a variety of classes are also involved in the signaling events that modulate the immune responses to environmental stress as well as differentiation of the epidermal keratinocytes themselves. Recently, high-resolution methods are beginning to provide evidence for the involvement of newly identified specific lipid molecules in the regulation of epidermal homeostasis. In this review we give an overview of the wide range of biological functions of mammalian epidermal lipids.
Stable Cu Isotope Ratios Show Changes in Cu Uptake and Transport Mechanisms in Vitis vinifera Due to High Cu Exposure
Authors: Blotevogel Simon , Oliva Priscia , Denaix Laurence , Audry Stéphane , Viers Jerome , Schreck Eva
Published: January 2022

Even though copper (Cu) is an essential plant nutrient, it can become toxic under certain conditions. Toxic effects do not only depend on soil Cu content, but also on environmental and physiological factors, that are not well understood. In this study, the mechanisms of Cu bioavailability and the homeostasis of Vitis vinifera L. cv. Tannat were investigated under controlled conditions, using stable Cu isotope analysis. We measured Cu concentrations and δ65Cu isotope ratios in soils, soil solutions, roots, and leaves of grapevine plants grown on six different vineyard soils, in a 16-week greenhouse experiment. The mobility of Cu in the soil solutions was controlled by the solubility of soil organic matter. No direct relationship between Cu contents in soils or soil solutions and Cu contents in roots could be established, indicating a partly homeostatic control of Cu uptake. Isotope fractionation between soil solutions and roots shifted from light to heavy with increasing Cu exposure, in line with a shift from active to passive uptake. Passive uptake appears to exceed active uptake for soil solution concentrations higher than 270 μg L–1. Isotope fractionation between roots and leaves was increasingly negative with increasing root Cu contents, even though the leaf Cu contents did not differ significantly. Our results suggest that Cu isotope analysis is a sensitive tool to monitor differences in Cu uptake and translocation pathways even before differences in tissue contents can be observed.
Domestication Impacts the Wheat-Associated Microbiota and the Rhizosphere Colonization by Seed- and Soil-Originated Microbiomes, Across Different Fields
Authors: Abdullaeva Yulduzkhon , Ratering Stefan , Ambika Manirajan Binoy , Rosado-Porto David , Schnell Sylvia , Cardinale Massimiliano
Published: January 2022

The seed-transmitted microorganisms and the microbiome of the soil in which the plant grows are major drivers of the rhizosphere microbiome, a crucial component of the plant holobiont. The seed-borne microbiome can be even coevolved with the host plant as a result of adaptation and vertical transmission over generations. The reduced genome diversity and crossing events during domestication might have influenced plant traits that are important for root colonization by seed-borne microbes and also rhizosphere recruitment of microbes from the bulk soil. However, the impact of the breeding on seed-transmitted microbiome composition and the plant ability of microbiome selection from the soil remain unknown. Here, we analyzed both endorhiza and rhizosphere microbiome of two couples of genetically related wild and cultivated wheat species (Aegilops tauschii/Triticum aestivum and T. dicoccoides/T. durum) grown in three locations, using 16S rRNA gene and ITS2 metabarcoding, to assess the relative contribution of seed-borne and soil-derived microbes to the assemblage of the rhizosphere microbiome. We found that more bacterial and fungal ASVs are transmitted from seed to the endosphere of all species compared with the rhizosphere, and these transmitted ASVs were species-specific regardless of location. Only in one location, more microbial seed transmission occurred also in the rhizosphere of A. tauschii compared with other species. Concerning soil-derived microbiome, the most distinct microbial genera occurred in the rhizosphere of A. tauschii compared with other species in all locations. The rhizosphere of genetically connected wheat species was enriched with similar taxa, differently between locations. Our results demonstrate that host plant criteria for soil bank’s and seed-originated microbiome recruitment depend on both plants’ genotype and availability of microorganisms in a particular environment. This study also provides indications of coevolution between the host plant and its associated microbiome resulting from the vertical transmission of seed-originated taxa.
Testing the Effectiveness of the Health Belief Model in Predicting Preventive Behavior During the COVID-19 Pandemic: The Case of Romania and Italy
Authors: Karl Johannes Alfons , Fischer Ronald , Druică Elena , Musso Fabio , Stan Anastasia
Published: January 2022

We use a cultural psychology approach to examine the relevance of the Health Belief Model (HBM) for predicting a variety of behaviors that had been recommended by health officials during the initial stages of the COVID-19 lockdown for containing the spread of the virus and not overburdening the health system in Europe. Our study is grounded in the assumption that health behavior is activated based on locally relevant perceptions of threats, susceptibility and benefits in engaging in protective behavior, which requires careful attention to how these perceptions might be structured and activated. We assess the validity of the HBM in two European countries that have been relatively understudied, using simultaneous measurements during acute periods of infection in Romania and Italy. An online questionnaire provided a total of (N = 1863) valid answers from both countries. First, to understand individual difference patterns within and across populations, we fit a General Linear Model in which endorsement was predicted by behavior, country, their interaction, and a random effect for participants. Second, we assess the effect of demographics and health beliefs on prevention behaviors by fitting a multi-group path model across countries, in which each behavior was predicted by the observed health belief variables and demographics. Health beliefs showed stronger relationships with the recommended behaviors than demographics. Confirming previously reported relationships, self-efficacy, perceived severity, and perceived benefits were consistently related to the greater adoption of individual behaviors, whereas greater perceived barriers were related to lower adoption of health behaviors. However, we also point to important location specific effects that suggest that local norms shape protective behavior in highly contextualized ways.
Visual and Hearing Sensitivity Affect Robot-Based Training for Children Diagnosed With Autism Spectrum Disorder
Authors: Chevalier P. , Ghiglino D. , Floris F. , Priolo T. , Wykowska A.
Published: January 2022

In this paper, we investigate the impact of sensory sensitivity during robot-assisted training for children diagnosed with Autism Spectrum Disorder (ASD). Indeed, user-adaptation for robot-based therapies could help users to focus on the training, and thus improve the benefits of the interactions. Children diagnosed with ASD often suffer from sensory sensitivity, and can show hyper or hypo-reactivity to sensory events, such as reacting strongly or not at all to sounds, movements, or touch. Considering it during robot therapies may improve the overall interaction. In the present study, thirty-four children diagnosed with ASD underwent a joint attention training with the robot Cozmo. The eight session training was embedded in the standard therapy. The children were screened for their sensory sensitivity with the Sensory Profile Checklist Revised. Their social skills were screened before and after the training with the Early Social Communication Scale. We recorded their performance and the amount of feedback they were receiving from the therapist through animations of happy and sad emotions played on the robot. Our results showed that visual and hearing sensitivity influenced the improvements of the skill to initiate joint attention. Also, the therapists of individuals with a high sensitivity to hearing chose to play fewer animations of the robot during the training phase of the robot activity. The animations did not include sounds, but the robot was producing motor noise. These results are supporting the idea that sensory sensitivity of children diagnosed with ASD should be screened prior to engaging the children in robot-assisted therapy.
Selection and Characterization of Burkholderia spp. for Their Plant-Growth Promoting Effects and Influence on Maize Seed Germination
Authors: dos Santos Isaneli Batista , Pereira Arthur Prudêncio de Araújo , de Souza Adijailton José , Cardoso Elke Jurandy Bran Nogueira , da Silva Flaviana Gonçalves , Oliveira João Tiago Correia , Verdi Maria Carolina Quecine , Sobral Júlia Kuklinsky
Published: January 2022

Burkholderia sp. is a bacterial genus extremely versatile in the environment and has been reported for a great potential to promote plant growth via different mechanisms. Here we evaluate the plant growth-promoting mechanisms in twenty-six Burkholderia strains. Strains were evaluated for their ability to promote plant growth by means of: indole-3-acetic acid (IAA) production under different conditions of pH, salt stress and the presence or absence of L-tryptophan; exopolysaccharides (EPS) production and quorum sensing (ALH). The strains were also characterized in terms of their genetic variability and species identification through Sanger sequencing. Then, the bacteria most responsive in the greatest number of plant-growth promotion mechanisms were selected for a corn seed germination test. All bacteria synthesized IAA in medium with 0.0 or 5.0 mM of L-tryptophan in combination with either 1 or 5% of NaCl, and pH values of either 4.5 or 7.2. The EPS production was confirmed for 61.54% of the bacterial strains. Quorum sensing also occurred in 92.3% of the selected bacteria. The Jaccard similarity coefficient revealed 16 clusters with high genetic variability between bacterial strains. Bacterial strains were assigned to seven species: B. anthina, B. cepacia, B. gladioli, B. ambifaria, B. graminis, B. heleia, and Burkholderia spp. The corn seed bacterization did not affect the germination velocity index (GSI), as well as the first count of germinated seeds (FC). However, inoculations formulated with B. heleia strain G28, B. gladioli strain UAGC723, and B. graminis strain UAGC348 promoted significant increases in root length, seedling height and fresh and dry seedling phytomass, respectively. These results indicate the high biotechnological potential of several strains in the genus Burkholderia sp. as seed inoculants, favoring germination and seedling initial development.
The Relation of Accelerometer-Measured Physical Activity and Serum Uric Acid Using the National Health and Nutrition Survey (NHANES) 2003–2004
Authors: Smith Isaac D. , Ross Leanna M. , Gabaldon Josi R. , Holdgate Nicholas , Pieper Carl F. , Ning Tony C. , Kraus William E. , Huffman Kim M.
Published: January 2022

Objective: Gout is a crystal-induced inflammatory arthritis caused by elevated uric acid. Physical activity has the potential to reduce serum uric acid (SUA), thus improving the disease burden of gout. In this study, we examined the association of objectively-measured physical activity and SUA.

Methods: A cross-sectional study was conducted using survey, laboratory, and accelerometer data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES). SUA concentrations (mg/dL) were obtained during an initial exam, and then physical activity (kCal/day) was measured with 7 days of ActiGraph accelerometry in participants (n = 3,475) representative of the ambulatory, non-institutionalized US civilian population. Regression, including restricted cubic splines, was used to assess the relation of physical activity and SUA in bivariate and adjusted models. Covariates included age, gender, race/ethnicity, alcohol use, body mass index, renal function, and urate-lowering therapy.

Results: In the bivariate model, physical activity was correlated with SUA concentrations and included a non-linear component (p < 0.01). In the adjusted model, linear splines were employed with a node at the SUA nadir of 5.37mg/dL; this occurred at 703 kCal/day of physical activity. The association of physical activity and SUA was negative from 0 to 703 kCal/day (p = 0.07) and positive >703 kCal/day (p < 0.01 for the change in slope).

Conclusion: Physical activity and SUA are associated in a non-linear fashion, with a minimum estimated SUA at 703 kCal/day of objectively-measured physical activity. These findings raise intriguing questions about the use of physical activity as a potential adjunctive therapy in patients with gout, and further interventional studies are needed to elucidate the effects of moderate intensity exercise on SUA concentrations.