bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of asthma on the oxidative stress, inflammation, and endothelial dysfunction in children with pneumonia
Authors: Shabestari Ali Arjmand , Imanparast Fatemeh , Mohaghegh Pegah , Kiyanrad Habibeh
Published: September 2022

Background

In community-acquired pneumonia (CAP), pulmonary vascular endothelial dysfunction, inflammation, and oxidative stress (OS) are prominent and interesting as the unfavorable clinical outcomes of it. Asthma as a common chronic respiratory disease may affect the clinical outcomes of pneumonia, but the exact mechanism of this effect remains unclear. The present study aimed to assess the effects of asthma on the OS, inflammation, and endothelial dysfunction biomarkers in the children pneumonia.

Methods

A cross-sectional study designed with a total of 75 children including both severe CAP and asthma (as group I), severe CAP alone (as group II), and healthy children (as group III) was conducted. Fasting blood samples were taken to the assay of serum malondialdehyde (MDA), total antioxidant capacity (TAC), tumor necrosis factor-alpha (TNF-α), soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasminogen activator inhibitor-1 (PAI-1). The mean of anthropometric and biochemical parameters was compared by ANOVA and Tukey post-hoc test between groups.

Results

We observed TAC levels in groups I and II (0.997 ± 0.22 and 1.23 ± 0.21 mmol/l, respectively) were significantly lower compared with group III (1.46 ± 0.19 mmol/l, P value < 0.001). It was significantly higher in group II than in group I (P value < 0.001). Also, we observed MDA and TNF-α levels in groups I (6.94 ± 1.61 μmol/l, 7.34 ± 2.23 pg/ml, respectively) and II (2.57 ± 0.40 μmol/l, 5.54 ± 1.84 pg/ml, respectively) were significantly higher compared with group III (1.89 ± 0.27 μmol/l, 3.42 ± 1.32 pg/ml, P value < 0.001, P value < 0.001, respectively).

VCAM-1 and PAI-1 levels as the endothelial dysfunction biomarkers were significantly higher in group I (1.5 ± 0.62 mmol/l, 10.52 ± 3.2 AU/ml, respectively) compared with groups II (1.06 ± 0.53 mmol/l and 8.23 ± 3.4 AU/ml; P value < 0.001, P value < 0.001, respectively) and III (0.6 ± 0.35 mmol/l and 2.39 ± 0.83 AU/ml; P value < 0.001, P value < 0.001, respectively). Also, VCAM-1 and PAI-1 levels were significantly higher in group II compared with groups III (P value < 0.001, P value < 0.001).

Conclusions

Asthma can exacerbate the vascular dysfunction of pneumonia in children by increasing oxidative stress, inflammation, and endothelial dysfunction.
Cementless curved endoprosthesis stem for distal femoral reconstruction in a Chinese population: a combined anatomical & biomechanical study
Authors: Hu Xin , Lu Minxun , Wang Yitian , Wen Yang , Tan Linyun , Du Guifeng , Zhou Yong , Luo Yi , Min Li , Tu Chongqi
Published: September 2022

Background

The endoprosthetic knee reconstruction using a current universal femoral stem might not be suitable for local population due to the anatomical difference between Chinese and Western populations. We measured the anatomical parameters of Chinese femurs as reference for stem design, and proposed a cementless, curved, short endoprosthesis stem for the reconstruction of distal femur. This study analyzed the biomechanical performance of the newly designed stem aimed at the identification of better operative strategy.

Methods

The CT–scanning data of femurs derived from 96 healthy Chinese volunteers were imported into the Mimics software, and a segmental measurement strategy was applied to evaluate the radius of curvature (ROC) of the femoral medullary cavity. Then, 4 kinds of endoprosthetic replacement models were created based on the measurement results. Model A: the distal tumor resected femora + straight stem A; Model B: the distal tumor resected femora + curved stem B; Model C: the distal tumor resected femora + curved stem C; Model D: the distal tumor resected femora + curved stem D. Finally, the mechanical difference among these models were compared by finite element analysis.

Results

The mean femoral ROC of Segment1, 2, 3, 4, 5 measured in the present study was 724.5 mm, 747.5 mm, 1016.5 mm, 1286.5 mm, and 1128 mm, respectively. Based on the femoral ROC of Segment2, the stem ROC of the curved stem B, C, and D was designed as 475 mm, 700 mm, and 1300 mm, respectively. Generally, all endoprosthetic replacement models showed a normal–like stress distribution on the femurs. However, compared to the straight stem, the biomimetic curved stem showed better biomechanical performance both in terms of reducing the extent of the stress shielding of the femur and in terms of minimizing the stress distribution of the implant.

Conclusions

The uncemented, curved, short stem with suitable ROC can perfectly match the Chinese femoral canal morphology which has better mechanical properties than the conventional femoral stem. Thus, this newly designed femoral stem might be an optimized method for treatment of malignant femoral tumours in the Chinese populations in the case that the numerical results are supported by future experimental studies.
Biomechanical behaviour of tension-band-reconstruction titanium plate in open-door laminoplasty: a study based on finite element analysis
Authors: Xu Hanpeng , Wu Jincheng , Xie Hongru , Wen Wangqiang , Xu Haoxiang , Du Juan , Miao Jun
Published: September 2022

Objective

To investigate and evaluate the biomechanical behaviour of tension-band-reconstruction (TBR) and ordinary titanium plates in open-door laminoplasty by finite element (FE) analysis.

Methods

TBR titanium plate and ordinary titanium plate were implanted into a validated finite element model of healthy adult cervical vertebrae. Among them, 5 ordinary titanium plate were used in model A, 2 TBR titanium plates and 3 ordinary titanium plates were used in model B, and 5 TBR titanium plates were used in model C. The same loading conditions was applied identically to all models. Range of motion (ROM) of the vertebral body, stress distribution of the titanium plate and intradiscal pressure (IDP) were compared in flexion, extension, lateral bending and rotation.

Results

The ROM of model B and C was similar in flexion and extension, and both were smaller than that of model A. The highest von Mises stress in the titanium plate appears is in model C. The IDP in C2/3 was significantly higher than that in other segments in flexion. There was no significant difference in IDP among three models in left lateral bending and left axial rotation.

Conclusion

Application of TBR titanium plate in open-door laminoplasty can reduced ROM in flexion, extension and axial rotation of the cervical vertebrae. But the increase of stress in TBR titanium plate could lead to higher risk of adverse events such as titanium plate deformation. Moreover, compared with complete TBR titanium plate, the combination of TBR titanium plate for C3 and C7 with ordinary titanium plate for the other vertebrae largely reduce the stress of the titanium plates by ensuring stability. The proposed FE model (C2-T1) exhibits a great potential in evaluating biomechanical behaviour of TBR titanium plate for open-door laminoplasty.
Factors influencing physical activity in postpartum women during the COVID-19 pandemic: a cross-sectional survey in Japan
Authors: Nomura Yumi , Araki Tomoko
Published: September 2022

Background

The aim of this study was to investigate factors influencing postpartum physical activity (PA), taking into consideration psychosocial perceptions during the coronavirus disease 2019 (COVID-19) pandemic by comparing health-related quality of life (HRQoL) scores.

Methods

A web-based cross-sectional survey of 787 postpartum women was conducted between March and October 2021. After applying the exclusion criteria, 590 women were analyzed. The International Physical Activity Questionnaire Short Form, was used to assess the level and amount of PA. The Short Form-12 Health Survey version 2 (SF-12v2) was used to measure HRQoL. Logistic regression analyses were used to determine whether sociodemographic factors and psychosocial perceptions during the COVID-19 pandemic were associated with the level of PA. Based on the current national guidelines for exercise in Japan, respondents were classified by weekly PA level as an Inactive group and an Active group to assess the influence of PA on HRQoL.

Results

Mean total PA was 19.3 total metabolic equivalents hour/week, and the prevalence of an inactive lifestyle was 45.9% among respondents. Each year of age was associated with an odds ratio (OR) of 0.92 (95% CI 0.87–0.97) for becoming physical inactivity during postpartum. Factors positively associated with more active levels were greater number of days for delivery (OR = 1.00; 95% CI 1.00–1.01), multiparity (OR = 1.50; 95% CI 1.00–2.23), having someone to talk about childcare and the individual’s partner (OR = 2.04; 95% CI 0.96–4.36) and not having anxiety symptoms (OR = 0.58; 95% CI 0.35–0.97). The Active group had significantly higher HRQoL scores than the Inactive group in the following scales: physical component summary (p < 0.001), mental component summary (p = 0.041).

Conclusions

The influential factors for postpartum PA level were younger age, longer duration after childbirth, multiparity and not having anxiety symptoms, which correlated positively with PA. The presence of someone with whom can talk to about childcare and partner issues was associated with the maintenance of higher PA among postpartum women, suggesting that factor as a positive influence on PA under unsettled conditions.
Interdisciplinary clinicians’ attitudes, challenges, and success strategies in providing care to transgender people: a qualitative descriptive study
Authors: Soled Kodiak Ray Sung , Dimant Oscar E. , Tanguay Jona , Mukerjee Ronica , Poteat Tonia
Published: September 2022

Background

Access to clinicians competent in transgender health remains a significant barrier and contributor toward health inequity for transgender people. Studies on access and barriers to care have predominantly evaluated transgender patients’ perceptions, but scant research has included the perspectives of clinicians.

Aims

We conducted a qualitative study to explore how clinicians (meaning physicians and advanced practice providers, in this paper) in the United States: (1) attain and utilize information, (2) perceive barriers and facilitators, and (3) understood gaps in their professional training, in regard to practicing transgender health care.

Methods

A Qualitative Descriptive approach guided our conventional content analysis of field notes and interviews with clinicians within a parent study that explored health care access among transgender adults. Transcripts were coded into meaning units that were iteratively abstracted into themes. Standard measures were performed to promote the trustworthiness of the analysis and reduce bias.

Results

Participants (n = 13) consisted of physicians (n = 8), physician assistants (n = 3), and nurse practitioners (n = 2). The majority were women (n = 11), identified as White (n = 9), cisgender (n = 13), and ages ranged from 31 – 58 years. Five main themes were identified: (1) Knowledge Acquisition: Formal and Informal Pathways to Competency; (2) Perceived Challenges and Barriers: I didn’t know what I was doing; (3) Power to Deny: Prescriptive Authority and Gatekeeping; (4) Stigma: This is really strange, and I can’t really understand it; (5) Reflections: Strategies for Success, Rewards, and Personal Motivations.

Discussion

Clinicians gained a sense of comfort and competence with mentorship, self-directed learning, clinical experience, and person-centered, harm-reduction approaches. Stigma, bias, and structural-level factors were barriers to providing care. This study offers a unique perspective of clinicians’ motivations and strategies for providing gender-affirming care and elucidates how stigma impacts the delivery of gender-affirming care.
Establishment and genetically characterization of patient-derived xenograft models of cervical cancer
Authors: Zou Shuangwei , Ye Miaomiao , Zhang Jian-an , Ji Huihui , Chen Yijie , Zhu Xueqiong
Published: September 2022

Purpose

Patient-derived xenograft (PDX) models were established to reproduce the clinical situation of original cancers and have increasingly been applied to preclinical cancer research. Our study was designed to establish and genetically characterize cervical cancer PDX models.

Methods

A total of 91 fresh fragments obtained from 22 surgically resected cervical cancer tissues were subcutaneously engrafted into female NOD-SCID mice. Hematoxylin and eosin (H&E) staining was performed to assess whether the established PDX models conserved the histological features of original patient cervical cancer tissues. Moreover, a Venn diagram was applied to display the overlap of all mutations detected in whole-genome sequencing (WGS) data from patient original cervical cancer (F0) and F2-, F3-PDX models. The whole exome sequencing (WES) and the “maftools” package were applied to determine the somatic mutations among primary cervical cancers and the established PDX models.

Results

Our study successfully developed a panel of cervical cancer PDX models and the latency time of cervical cancer PDX model establishment was variable with a progressive decrease as the passage number increased, with a mean time to initial growth of 94.71 days in F1 engraftment to 40.65 days in F3 engraftment. Moreover, the cervical cancer PDX models preserved the histological features of their original cervical cancer. WGS revealed that the genome of original cervical cancer was preserved with high fidelity in cervical cancer PDX models throughout the xenografting and passaging process. Furthermore, WES demonstrated that the cervical cancer PDX models maintained the majority somatic mutations of original cervical cancer, of which the KMT2D, LRP1B, NAV3, TP53, FAT1, MKI67 and PKHD1L1 genes were identified as the most frequently mutated genes.

Conclusions

The cervical cancer PDX models preserved the histologic and genetic characteristics of their original cervical cancer, which helped to gain a deeper insight into the genetic alterations and lay a foundation for further investigation of the molecular targeted therapy of cervical cancer.
Valorization of cheese whey to lactobionic acid by a novel strain Pseudomonas fragi and identification of enzyme involved in lactose oxidation
Authors: Wu Jiawei , Liu Peng , Zheng Zhaojuan , Ouyang Jia
Published: September 2022

Background

Efficient upgrading of inferior agro-industrial resources and production of bio-based chemicals through a simple and environmentally friendly biotechnological approach is interesting Lactobionic acid is a versatile aldonic acid obtained from the oxidation of lactose. Several microorganisms have been used to produce lactobionic acid from lactose and whey. However, the lactobionic acid production titer and productivity should be further improved to compete with other methods.

Results

In this study, a new strain, Pseudomonas fragi NL20W, was screened as an outstanding biocatalyst for efficient utilization of waste whey to produce lactobionic acid. After systematic optimization of biocatalytic reactions, the lactobionic acid productivity from lactose increased from 3.01 g/L/h to 6.38 g/L/h in the flask. In batch fermentation using a 3 L bioreactor, the lactobionic acid productivity from whey powder containing 300 g/L lactose reached 3.09 g/L/h with the yield of 100%. Based on whole genome sequencing, a novel glucose dehydrogenase (GDH1) was determined as a lactose-oxidizing enzyme. Heterologous expression the enzyme GDH1 into P. putida KT2440 increased the lactobionic acid yield by 486.1%.

Conclusion

This study made significant progress both in improving lactobionic acid titer and productivity, and the lactobionic acid productivity from waste whey is superior to the ever reports. This study also revealed a new kind of aldose-oxidizing enzyme for lactose oxidation using P. fragi NL20W for the first time, which laid the foundation for further enhance lactobionic acid production by metabolic engineering.

Graphical Abstract
A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer
Authors: Schinke Henrik , Shi Enxian , Lin Zhongyang , Quadt Tanja , Kranz Gisela , Zhou Jiefu , Wang Hongxia , Hess Julia , Heuer Steffen , Belka Claus , Zitzelsberger Horst , Schumacher Udo , Genduso Sandra , Riecken Kristoffer , Gao Yujing , Wu Zhengquan , Reichel Christoph A. , Walz Christoph , Canis Martin , Unger Kristian , Baumeister Philipp , Pan Min , Gires Olivier
Published: September 2022

Background

Epidermal growth factor receptor (EGFR) is both a driver oncogene and a therapeutic target in advanced head and neck squamous cell carcinoma (HNSCC). However, response to EGFR treatment is inconsistent and lacks markers for treatment prediction. This study investigated EGFR-induced epithelial-to-mesenchymal transition (EMT) as a central parameter in tumor progression and identified novel prognostic and therapeutic targets, and a candidate predictive marker for EGFR therapy response.

Methods

Transcriptomic profiles were analyzed by RNA sequencing (RNA-seq) following EGFR-mediated EMT in responsive human HNSCC cell lines. Exclusive genes were extracted via differentially expressed genes (DEGs) and a risk score was determined through forward feature selection and Cox regression models in HNSCC cohorts. Functional characterization of selected prognostic genes was conducted in 2D and 3D cellular models, and findings were validated by immunohistochemistry in primary HNSCC.

Results

An EGFR-mediated EMT gene signature composed of n = 171 genes was identified in responsive cell lines and transferred to the TCGA-HNSCC cohort. A 5-gene risk score comprising DDIT4, FADD, ITGB4, NCEH1, and TIMP1 prognosticated overall survival (OS) in TCGA and was confirmed in independent HNSCC cohorts. The EGFR-mediated EMT signature was distinct from EMT hallmark and partial EMT (pEMT) meta-programs with a differing enrichment pattern in single malignant cells. Molecular characterization showed that ITGB4 was upregulated in primary tumors and metastases compared to normal mucosa and correlated with EGFR/MAPK activity in tumor bulk and single malignant cells. Preferential localization of ITGB4 together with its ligand laminin 5 at tumor-stroma interfaces correlated with increased tumor budding in primary HNSCC tissue sections. In vitro, ITGB4 knock-down reduced EGFR-mediated migration and invasion and ITGB4-antagonizing antibody ASC8 impaired 2D and 3D invasion. Furthermore, a logistic regression model defined ITGB4 as a predictive marker of progression-free survival in response to Cetuximab in recurrent metastatic HNSCC patients.

Conclusions

EGFR-mediated EMT conveyed through MAPK activation contributes to HNSCC progression upon induction of migration and invasion. A 5-gene risk score based on a novel EGFR-mediated EMT signature prognosticated survival of HNSCC patients and determined ITGB4 as potential therapeutic and predictive target in patients with strong EGFR-mediated EMT.
Efficacy of conservative treatment for spastic cerebral palsy children with equinus gait: a systematic review and meta-analysis
Authors: Klaewkasikum Krongkaew , Patathong Tanyaporn , Woratanarat Patarawan , Woratanarat Thira , Thadanipon Kunlawat , Rattanasiri Sasivimol , Thakkinstian Ammarin
Published: September 2022

Background

Comparisons between various conservative managements of spastic equinus deformity in cerebral palsy demonstrated limited evidences, to evaluate the efficacy of conservative treatment among cerebral palsy children with spastic equinus foot regarding gait and ankle motion.

Methods

Studies were identified from PubMed and Scopus up to February 2022. Inclusion criteria were randomized controlled trial (RCT), conducted in spastic cerebral palsy children with equinus deformity, aged less than 18 years, compared any conservative treatments (Botulinum toxin A; BoNT-A, casting, physical therapy, and orthosis), and evaluated gait improvement (Physician Rating Scale or Video Gait Analysis), Observational Gait Scale, Clinical Gait Assessment Score, ankle dorsiflexion (ankle dorsiflexion at initial contact, and passive ankle dorsiflexion), or Gross Motor Function Measure. Any study with the participants who recently underwent surgery or received BoNT-A or insufficient data was excluded. Two authors were independently selected and extracted data. Risk of bias was assessed using a revised Cochrane risk-of-bias tool for randomized trials. I2was performed to evaluate heterogeneity. Risk ratio (RR), the unstandardized mean difference (USMD), and the standardized mean difference were used to estimate treatment effects with 95% confidence interval (CI).

Results

From 20 included studies (716 children), 15 RCTs were eligible for meta-analysis (35% had low risk of bias). BoNT-A had higher number of gait improvements than placebo (RR 2.64, 95% CI 1.71, 4.07,I2 = 0). Its combination with physical therapy yielded better passive ankle dorsiflexion at knee extension than physical therapy alone (USMD = 4.16 degrees; 95% CI 1.54, 6.78,I2 = 36%). Casting with or without BoNT-A had no different gait improvement and ankle dorsiflexion at knee extension when compared to BoNT-A. Orthosis significantly increased ankle dorsiflexion at initial contact comparing to control (USMD 10.22 degrees, 95 CI% 5.13, 15.31,I2 = 87%).

Conclusion

BoNT-A and casting contribute to gait improvement and ankle dorsiflexion at knee extension. BoNT-A specifically provided gait improvement over the placebo and additive effect to physical therapy for passive ankle dorsiflexion. Orthosis would be useful for ankle dorsiflexion at initial contact.

Trial registrationPROSPERO number CRD42019146373.
Do different multi‐segment foot models detect the same changes in kinematics when wearing foot orthoses?
Authors: Klein Tomas , Chapman Graham J. , Lastovicka Ondrej , Janura Miroslav , Richards Jim
Published: September 2022

Background

Different multi‐segment foot models have been used to explore the effect of foot orthoses. Previous studies have compared the kinematic output of different multi‐segment foot models, however, no study has explored if different multi‐segment foot models detect similar kinematic changes when wearing a foot orthoses. The aim of this study was to compare the ability of two different multi‐segment foot models to detect kinematic changes at the hindfoot and forefoot during the single and double support phases of gait when wearing a foot orthosis.

Methods

Foot kinematics were collected during walking from a sample of 32 individuals with and without a foot orthosis with a medial heel bar using an eight‐camera motion capture system. The Oxford Foot Model (OFM) and a multi‐segment foot model using the Calibrated Anatomical System Technique (CAST) were applied simultaneously. Vector field statistical analysis was used to explore the kinematic effects of a medial heel bar using the two models, and the ability of the models to detect any changes in kinematics was compared.

Results

For the hindfoot, both models showed very good agreement of the effect of the foot orthosis across all three anatomical planes during the single and double support phases. However, for the forefoot, the level of agreement between the models varied with both models showing good agreement of the effect in the coronal plane but poorer agreement in the transverse and sagittal planes.

Conclusions

This study showed that while consistency exists across both models for the hindfoot and forefoot in the coronal plane, the forefoot in the transverse and sagittal planes showed inconsistent responses to the foot orthoses. This should be considered when interpreting the efficacy of different interventions which aim to change foot biomechanics.
Effects of vitrified cryopreservation duration on IVF and neonatal outcomes
Authors: Mao Yuling , Tang Ni , Luo Yanfen , Yin Ping , Li Lei
Published: September 2022

Background

In this study, we aimed to evaluate the impact of the duration of cryopreservation storage on embryo viability, implantation competence, pregnancy outcome and neonatal outcomes.

Methods

We retrospectively evaluated the outcomes of patients who underwent IVF with vitrified cryopreserved embryos between January 2004 and August 2019 by following the first frozen embryo transfer cycles within the study period. A total of 31,143 patients met the inclusion criteria and were grouped according to the embryo storage time as follows: Group 1 (n = 20,926),1–90 days; Group 2 (n = 6,472), 91–180 days; Group 3 (n = 2,237), 181–365 days; Group 4 (n = 746), 366–730 days; and Group 5 (n = 762), > 731 days.

Results

The embryo survival rate decreased significantly with longer durations of cryopreservation. The highest and lowest survival rate was recorded in Group 1 and Group 5, respectively (34853/35338; 98.63% vs. 1281/1801; 71.13%;P < 0.01). The human chorionic gonadotropin (HCG) detection and clinical pregnancy rate was highest in Group 1 (57.85% and 55. 26%, respectively;P < 0.01). Short-term cryopreservation (≤ 3 months) is associated with higher rates of clinical pregnancy. There were no significant differences in neonatal birth weight, neonatal height and congenital anomalies among the groups (P > 0. 05).

Conclusion

The prolonged storage time of vitrified embryos negatively affected survival rate and clinical pregnancy rate. It did not have a significant influence on neonatal health. This study provides new findings about the relationship between prolonged storage time of vitrified embryos and clinical outcomes and offers evidence for the safety of using long-stored embryos after vitrification.
Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome
Authors: Serra Gregorio , Giambrone Clara , Antona Vincenzo , Cardella Francesca , Carta Maurizio , Cimador Marcello , Corsello Giovanni , Giuffrè Mario , Insinga Vincenzo , Maggio Maria Cristina , Pensabene Marco , Schierz Ingrid Anne Mandy , Piro Ettore
Published: September 2022

Background

Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2).

Case presentation

We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma andostium secundumtype atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis.

Conclusions

CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.
Scalable, ultra-fast, and low-memory construction of compacted de Bruijn graphs with Cuttlefish 2
Authors: Khan Jamshed , Kokot Marek , Deorowicz Sebastian , Patro Rob
Published: September 2022

The de Bruijn graph is a key data structure in modern computational genomics, and construction of its compacted variant resides upstream of many genomic analyses. As the quantity of genomic data grows rapidly, this often forms a computational bottleneck. We present Cuttlefish 2, significantly advancing the state-of-the-art for this problem. On a commodity server, it reduces the graph construction time for 661K bacterial genomes, of size 2.58Tbp, from 4.5 days to 17–23 h; and it constructs the graph for 1.52Tbp white spruce reads in approximately 10 h, while the closest competitor requires 54–58 h, using considerably more memory.
Performance of model-based vs. permutation tests in the HEALing (Helping to End Addiction Long-termSM) Communities Study, a covariate-constrained cluster randomized trial
Authors: Tang Xiaoyu , Heeren Timothy , Westgate Philip M. , Feaster Daniel J. , Fernandez Soledad A. , Vandergrift Nathan , Cheng Debbie M.
Published: September 2022

Background

The HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate-constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests.

Methods

The primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups.

Results

Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA).

Conclusions

Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study.

Trial registration

ClinicalTrials.gov http://www.clinicaltrials.gov; Identifier: NCT04111939
Empowering the willing: the feasibility of tele-mentored self-performed pleural ultrasound assessment for the surveillance of lung health
Authors: Kirkpatrick Andrew W. , McKee Jessica L. , Ball Chad G. , Ma Irene W. Y. , Melniker Lawrence A.
Published: September 2022

Background

SARS-CoV-2 infection, manifesting as COVID-19 pneumonia, constitutes a global pandemic that is disrupting health-care systems. Most patients who are infected are asymptomatic/pauci-symptomatic can safely self-isolate at home. However, even previously healthy individuals can deteriorate rapidly with life-threatening respiratory failure characterized by disproportionate hypoxemic failure compared to symptoms. Ultrasound findings have been proposed as an early indicator of progression to severe disease. Furthermore, ultrasound is a safe imaging modality that can be performed by novice users remotely guided by experts. We thus examined the feasibility of utilizing common household informatic-technologies to facilitate self-performed lung ultrasound.

Methods

A lung ultrasound expert remotely mentored and guided participants to image their own chests with a hand-held ultrasound transducer. The results were evaluated in real time by the mentor, and independently scored by three independent experts [planned a priori]. The primary outcomes were feasibility in obtaining good-quality interpretable images from each anatomic location recommended for COVID-19 diagnosis.

Results

Twenty-seven adults volunteered. All could be guided to obtain images of the pleura of the 8 anterior and lateral lung zones (216/216 attempts). These images were rated as interpretable by the 3 experts in 99.8% (647/648) of reviews. Fully imaging one’s posterior region was harder; only 108/162 (66%) of image acquisitions was possible. Of these, 99.3% of images were interpretable in blinded evaluations. However, 52/54 (96%) of participants could image their lower posterior lung bases, where COVID-19 is most common, with 99.3% rated as interpretable.

Conclusions

Ultrasound-novice adults at risk for COVID-19 deterioration can be successfully mentored using freely available software and low-cost ultrasound devices to provide meaningful lung ultrasound surveillance of themselves that could potentially stratify asymptomatic/paucisymptomatic patients with early risk factors for serious disease. Further studies examining practical logistics should be conducted.

Trial Registration: ID ISRCTN/77929274 on 07/03/2015.
Discovery and characterization of heterogeneous and multipotent fibroblast populations isolated from excised cleft lip tissue
Authors: Parisi Ludovica , Rihs Silvia , La Scala Giorgio C. , Schnyder Isabelle , Katsaros Christos , Degen Martin
Published: September 2022

Background

Regularly discarded lip tissue obtained from corrective surgeries to close the cleft lip represents an easily accessible and rich source for the isolation of primary fibroblasts. Primary fibroblasts have been described to show compelling similarities to mesenchymal stem cells (MSCs). Hence, cleft lip and palate (CLP) lip-derived fibroblasts could be thought as an intriguing cell source for personalized regenerative therapies in CLP-affected patients.

Methods

Initially, we thoroughly characterized the fibroblastic nature of the lip-derived mesenchymal outgrowths by molecular and functional assays. Next, we compared their phenotype and genotype to that of bone marrow-mesenchymal stem cells (BM-MSCs) and of human lung-derived fibroblasts WI38, by assessing their morphology, surface marker expression, trilineage differentiation potential, colony-forming (CFU) capacity, and immunomodulation property. Finally, to better decipher the heterogeneity of our CLP cultures, we performed a single cell clonal analysis and tested expanded clones for surface marker expression, as well as osteogenic and CFU potential.

Results

We identified intriguingly similar phenotypic and genotypic properties between CLP lip fibroblasts and BM-MSCs, which makes them distinct from WI38. Furthermore, our own data in combination with the complex anatomy of the lip tissue indicated heterogeneity in our CLP cultures. Using a clonal analysis, we discovered single cell-derived clones with increased levels of the MSC markers CD106 and CD146 and clones with variabilities in their commitment to differentiate into bone-forming cells and in their potential to form single cell-derived colonies. However, we were not able to gain clones possessing superior MSC-like capacities when compared to the heterogeneous parental CLP population. Additionally, all clones could still generate contractile forces and retained robust levels of the fibroblast specific marker FSP1, which was not detectable in BM-MSCs.

Conclusions

Our results suggest that we isolate heterogeneous populations of fibroblasts from discarded CLP lip tissue, which show a prominently multipotent character in their entirety avoiding the need for elaborate subpopulation selections in vitro. These findings suggest that CLP lip fibroblasts might be a novel potential cell source for personalized regenerative medicine of clinical benefit for CLP patients.
Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn’s colon fibrosis is improved by IFN-γ and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling
Authors: Ye Yixin , Zhang Xiaomei , Su Dongsheng , Ren Yushuang , Cheng Fuyi , Yao Yunqi , Shi Gang , Ji Yanhong , Chen Shuang , Shi Pengyi , Dai Lei , Su Xiaolan , Deng Hongxin
Published: September 2022

Background

Inflammatory bowel diseases (IBD) are chronic relapsing–remitting inflammatory diseases of the gastrointestinal tract that are typically categorized into two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although MSCs therapy has achieved encouraging outcomes in IBD therapy, objective responses are limited in colon fibrosis stenosis owing to the complicated microenvironment of CD and MSCs heterogeneity of quality. Here, we chose IFN-γ and kynurenic acid (KYNA) to overcome the low response and heterogeneity of human adipose-derived MSCs (hADSCs) to treat IBD and expand the therapeutic effects based on the excellent ability of IFN-γ and KYNA to promote indoleamine 2,3-dioxygenase-1 (IDO-1) signaling, providing a potential protocol to treat IBD and fibrosis disease.

Methods

hADSCs were isolated, cultured, and identified from human abdominal adipose tissue. The CD pathology-like acute colitis and chronic colon fibrosis rat model was induced by 2,4,6-trinitrobenzen sulfonic acid (TNBS). hADSCs were pretreated in vitro with IFN-γ and KYNA and then were transplanted intravenously at day 1 and 3 of TNBS administration in colitis along with at day 1, 15, and 29 of TNBS administration in chronic colonic fibrosis. Therapeutic efficacy was evaluated by body weights, disease activity index, pathological staining, real-time PCR, Western blot, and flow cytometry. For knockout of IDO-1, hADSCs were transfected with IDO-1-targeting small gRNA carried on a CRISPR-Cas9-lentivirus vector.

Results

hADSCs treated with IFN-γ and KYNA significantly upregulated the expression and secretion of IDO-1, which has effectively ameliorated CD pathology-like colitis injury and fibrosis. Notably, the ability of hADSCs with IDO-1 knockout to treat colitis was significantly impaired and diminished the protective effects of the primed hADSCs with IFN-γ and KYNA.

Conclusion

Inflammatory cytokines IFN-γ- and KYNA-treated hADSCs more effectively alleviate TNBS-induced colitis and colonic fibrosis through an IDO-1-dependent manner. Primed hADSCs are a promising new strategy to improve the therapeutic efficacy of MSCs and worth further research.
YAP and TAZ play a crucial role in human erythrocyte maturation and enucleation
Authors: Damkham Nattaya , Lorthongpanich Chanchao , Klaihmon Phatchanat , Lueangamornnara Usaneeporn , Kheolamai Pakpoom , Trakarnsanga Kongtana , Issaragrisil Surapol
Published: September 2022

Background

Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are two key transcription co-activators of the Hippo pathway. Both were originally characterized as organ size and cell proliferation regulators. Later studies demonstrated that the Hippo pathway may play a role in Drosophila and mammal hematopoiesis. However, the role of the Hippo pathway in human erythropoiesis has not yet been fully elucidated.

Methods

The role of YAP and TAZ was studied in human erythropoiesis and hematopoietic stem cell (HSC) lineage determination by using mobilized peripheral blood (PB) and cord blood (CB)-derived HSC as a model. HSCs were isolated and cultured in an erythroid differentiation medium for erythroid differentiation and culture in methylcellulose assay for HSC lineage determination study.

Results

YAP and TAZ were barely detectable in human HSCs, but became highly expressed in pro-erythroblasts and erythroblasts. Depletion or knockdown of YAP and/or TAZ did not affect the ability of HSC lineage specification to erythroid lineage in either methylcellulose assay or liquid culture. However, depletion of YAP and TAZ did impair erythroblast terminal differentiation to erythrocytes and their enucleation. Moreover, ectopic expression of YAP and TAZ in pro-erythroblasts did not exert an apparent effect on erythroid differentiation, expansion, or morphology.

Conclusions

This study demonstrated that YAP/TAZ plays important role in erythroid maturation and enucleation but is dispensable for lineage determination of human HSCs.
Short-time-window Patlak imaging using a population-based arterial input function and optimized Bayesian penalized likelihood reconstruction: a feasibility study
Authors: Tanaka Takato , Nakajo Masatoyo , Kawakami Hirofumi , Motomura Eriko , Fujisaka Tomofumi , Ojima Satoko , Saigo Yasumasa , Yoshiura Takashi
Published: September 2022

Background

To explore the feasibility of short-time-window Ki imaging using a population-based arterial input function (IF) and optimized Bayesian penalized likelihood (BPL) reconstruction as a practical alternative to long-time-window Ki imaging with an individual patient-based IF. Myocardial Ki images were generated from 73 dynamic 18F-FDG-PET/CT scans of 30 patients with cardiac sarcoidosis. For each dynamic scan, the Ki images were obtained using the IF from each individual patient and a long time window (10–60 min). In addition, Ki images were obtained using the normalized averaged population-based IF and BPL algorithms with different beta values (350, 700, and 1000) with a short time window (40–60 min). The visual quality of each image was visually rated using a 4-point scale (0, not visible; 1, poor; 2, moderate; and 3, good), and the Ki parameters (Ki-max, Ki-mean, Ki-volume) of positive myocardial lesions were measured independently by two readers. Wilcoxon’s rank sum test, McNemar’s test, or linear regression analysis were performed to assess the differences or relationships between two quantitative variables.

Results

Both readers similarly rated 51 scans as positive (scores = 1–3) and 22 scans as negative (score = 0) for all four Ki images. Among the three types of population-based IF Ki images, the proportion of images with scores of 3 was highest with a beta of 1000 (78.4 and 72.5%, respectively) and lowest with a beta of 350 (33.3 and 23.5%) for both readers (all p < 0.001). The coefficients of determination between the Ki parameters obtained with the individual patient-based IF and those obtained with the population-based IF were highest with a beta of 1000 for both readers (Ki-max, 0.91 and 0.92, respectively; Ki-mean, 0.91 and 0.92, respectively; Ki-volume, 0.75 and 0.60, respectively; and all p < 0.001).

Conclusions

Short-time-window Ki images with a population-based IF reconstructed using the BPL algorithm and a high beta value were closely correlated with long-time-window Ki images generated with an individual patient-based IF. Short-time-window Ki images using a population-based IF and BPL reconstruction might represent practical alternatives to long-time-window Ki images generated using an individual patient-based IF.
Existence of positive solutions for p-Laplacian boundary value problems of fractional differential equations
Authors: Chabane Farid , Benbachir Maamar , Hachama Mohammed , Samei Mohammad Esmael
Published: September 2022

In this paper, we study the existence and multiplicity of ρ-concave positive solutions for a p-Laplacian boundary value problem of two-sided fractional differential equations involving generalized-Caputo fractional derivatives. Using Guo–Krasnoselskii fixed point theorem and under some additional assumptions, we prove some important results and obtain the existence of at least three solutions. To establish the results, Green functions are used to transform the considered two-sided generalized Katugampola and Caputo fractional derivatives. Finally, applications with illustrative examples are presented to show the validity and correctness of the obtained results.
Discriminating seismic events using 1D and 2D CNNs: applications to volcanic and tectonic datasets
Authors: Nakano Masaru , Sugiyama Daisuke
Published: September 2022

Detecting seismic events, discriminating between different event types, and picking P- and S-wave arrival times are fundamental but laborious tasks in seismology. In response to the ever-increasing volume of seismic observational data, machine learning (ML) methods have been applied to try to resolve these issues. Although it is straightforward to input standard (time-domain) seismic waveforms into ML models, many studies have used time–frequency-domain representations because the frequency components may be effective for discriminating events. However, detailed comparisons of the performances of these two methods are lacking. In this study, we compared the performances of 1D and 2D convolutional neural networks (CNNs) in discriminating events in datasets from two different tectonic settings: tectonic tremor and ordinary earthquakes observed at the Nankai trough, and eruption signals and other volcanic earthquakes at Sakurajima volcano. We found that the 1D and 2D CNNs performed similarly in these applications. Half of the misclassified events were misassigned the same labels in both CNNs, implying that the CNNs learned similar features inherent to the input signals and thus misclassified them similarly. Because the first convolutional layer of a 1D CNN applies a set of finite impulse response (FIR) filters to the input seismograms, these filters are thought to extract signals effective for discriminating events in the first step. Therefore, because our application was the discrimination of signals dominated by low- and high-frequency components, we tested which frequency components were effective for signal discriminations based on the filter responses alone. We found that the FIR filters comprised high-pass and low-pass filters with cut-off frequencies around 7–9 Hz, frequencies at which the magnitude relations of the input signal classes change. This difference in the power of high- and low-frequency components proved essential for correct signal classifications in our dataset.

Graphical Abstract