bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and measurement properties of the AxEL (attitude toward education and advice for low-back-pain) questionnaire
Authors: O’Hagan Edel T. , Skinner Ian W. , Jones Matthew D. , Karran Emma L. , Traeger Adrian C. , Cashin Aidan G. , Wand Benedict M. , Schabrun Siobhan M. , O’Neill Sean , Harris Ian A. , McAuley James H.
Published: January 2022

Introduction

Clinician time and resources may be underutilised if the treatment they offer does not match patient expectations and attitudes. We developed a questionnaire (AxEL-Q) to guide clinicians toward elements of first-line care that are pertinent to their patients with low back pain.

Methods

We used guidance from the COSMIN consortium to develop the questionnaire and evaluated it in a sample of people with low back pain of any duration. Participants were recruited from the community, were over 18 years and fluent in English. Statements that represented first-line care were identified. Semantic scales were used to measure attitude towards these statements. These items were combined to develop the questionnaire draft. Construct validity was evaluated with exploratory factor analysis and hypotheses testing, comparing to the Back Beliefs Questionnaire and modified Pain Self-Efficacy Questionnaire. Reliability was evaluated and floor and ceiling effects calculated.

Results

We recruited 345 participants, and had complete data for analysis for 313 participants. The questionnaire draft was reduced to a 3-Factor questionnaire through exploratory factor analysis. Factor 1 comprised 9 items and evaluated Attitude toward staying active, Factor 2 comprised 4 items and evaluated Attitude toward low back pain being rarely caused by a serious health problem, Factor 3 comprised 4 items and evaluated Attitude toward not needing to know the cause of back pain to manage it effectively. There was a strong inverse association between each factor and the Back Beliefs Questionnaire and a moderate positive association with the modified Pain Self-Efficacy Questionnaire. Each independent factor demonstrated acceptable internal consistency; Cronbach α Factor 1 = 0.92, Factor 2 = 0.91, Factor 3 = 0.90 and adequate interclass correlation coefficients; Factor 1 = 0.71, Factor 2 = 0.73, Factor 3 = 0.79.

Conclusion

This study demonstrates acceptable construct validity and reliability of the AxEL-Q, providing clinicians with an insight into the likelihood of patients following first-line care at the outset.
The role of vascular invasion and lymphatic invasion in predicting recurrent thoracic oesophageal squamous cell carcinoma
Authors: Ma Yu , Yao Xi , Li Zhenzhen , Chen Jie , Li Wensheng , Wang Hongtao , Zhang Lanjun , Zhu Jianfei
Published: January 2022

Background

Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre.

Methods

This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics.

Results

Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P<0.001) and pTNM stage (P<0.001), and similar results were found in VI. Moreover, survival analysis showed that pT stage (P<0.001), pN stage (P=0.001), pTNM stage (p<0.001), VI (P=0.001) and LI (P<0.001) were associated with DFS in ESCC. Furthermore, multivariate analysis suggested that pT stage (RR=1.4, P =0.032), pN stage (RR=1.9, P<0.001) and LI (RR=1.5, P=0.008) were independent predictive factors for DFS. Finally, relapse was observed in 110 patients (lymph node metastasis, 78 and distant, 32) and 147 patients with cancer-related deaths. Subanalysis showed that LI-positive patients had higher lymph node metastasis, although there was no significant difference (32.1% vs. 15.6%, P=0.100).

Conclusions

LI and VI were common in ESCC; they were all survival predictors for patients with ESCC, and LI was independent. Patients with positive LI were more likely to suffer lymph node metastasis.
Endometrial injury concurrent with hysteroscopy increases the expression of Leukaemia inhibitory factor: a preliminary study
Authors: Ersahin Suat Suphan , Ersahin Aynur
Published: January 2022

Objective

It is not known by which mechanism endometrial injury increases pregnancy rates. Leukaemia inhibitory factor (LIF) is a cytokine involved in wound healing and implantation. The aim of this study was to determine the change in endometrial LIF mRNA expression before and after mechanical injury during hysteroscopy.

Methods

Forty patients with a history of two or more unsuccessful implantations who decided to undergo hysteroscopy in the proliferative phase were divided into two equal groups: one with endometrial injury (scratching group) and the other with noninjury (control group). Endometrial sampling was conducted before injury on the patients in the scratching group, and then injury was performed with monopolar needle forceps. Only diagnostic hysteroscopy was performed on the patients in the control group. Endometrial tissues were collected using a Pipelle catheter between Days 20 and 23 of the mid-luteal phase of the next cycles in both the scratching and control groups. Endometrial LIF mRNA expression was evaluated with the use of reverse-transcription polymerase chain reactions.

Results

Relative changes in mRNA expression levels of the LIF gene in endometrial samples taken before and after injury were calculated using the 2-ΔΔCt method, and the fold changes obtained were compared between and within the groups. Compared with preinjury values, an 11.1-fold increase was found in postinjury LIF mRNA expression in patients with monopolar forceps injury (p < 0.001). There was a 3.9-fold significant increase in postinjury LIF mRNA levels compared with those in the control group (p < 0.02).

Conclusions

The fertility-promoting effect of hysteroscopy-guided mechanical endometrial injury may be mediated by LIF mRNA.
GqPCR-stimulated dephosphorylation of AKT is induced by an IGBP1-mediated PP2A switch
Authors: Nadel Guy , Yao Zhong , Wainstein Ehud , Cohen Izel , Ben-Ami Ido , Schajnovitz Amir , Maik-Rachline Galia , Naor Zvi , Horwitz Benjamin A. , Seger Rony
Published: January 2022

Background

G protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH.

Methods

Here we used kinase activity assays of PI3K and followed phosphorylation state of proteins using specific antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by TUNEL assay and PARP1 cleavage.

Results

We identified the mechanism that allows the unique stimulated inactivation of AKT and show that the main regulator of this process is the phosphatase PP2A, operating with the non-canonical regulatory subunit IGBP1. In resting cells, an IGBP1-PP2Ac dimer binds to PI3K, dephosphorylates the inhibitory pSer608-p85 of PI3K and thus maintains its high basal activity. Upon GqPCR activation, the PP2Ac-IGBP1 dimer detaches from PI3K and thus allows the inhibitory dephosphorylation. At this stage, the free PP2Ac together with IGBP1 and PP2Aa binds to AKT, causing its dephosphorylation and inactivation.

Conclusion

Our results show a stimulated shift of PP2Ac from PI3K to AKT termed “PP2A switch” that represses the PI3K/AKT pathway, providing a unique mechanism of GPCR-stimulated dephosphorylation.
A prospective cohort study on lactation status and breastfeeding challenges in mothers giving birth to preterm infants
Authors: Dong Dingding , Ru Xifang , Huang Xiaofang , Sang Tian , Li Shan , Wang Ying , Feng Qi
Published: January 2022

Background

Mothers of preterm infants face many challenges in breastfeeding, especially regarding lactation. This study aimed to investigate the lactation status and challenges in breastfeeding faced by preterm infants’ mothers.

Methods

We approached 124 mothers who gave birth to preterm infants between 26 May and 31 October 2018 in a tertiary hospital in China. Lactation status and challenges in breastfeeding on day 7 postpartum, at discharge of infants, 2 weeks post-discharge, and 3 months of corrected age were collected using questionnaires. The area under the receiver operating characteristic (ROC) curve for expressed milk volume on day 7 postpartum for predicting expressed milk volume ≥ 300 mL/d at discharge was calculated. Logistic regression analyses were performed to identify factors associated with delayed lactogenesis II onset and continuation of breastfeeding at 3 months of corrected age.

Results

Seventy mothers were enrolled, and 51.4% had delayed lactogenesis II. Multivariate logistic regression analysis revealed that older maternal age (aOR = 1.19; 95% CI: 1.01, 1.40) and first live birth (aOR = 4.81; 95% CI 1.43, 16.18) were significant independent predictors of delayed lactogenesis II. Mothers with delayed lactogenesis II had significantly lower expressed milk volume (day 7 postpartum: 160.0 mL vs. 300.0 mL, U = 328.50, p = 0.001; at discharge: 425.0 mL vs. 612.5 mL, U = 372.00, p = 0.005), with a lower proportion of exclusive breastfeeding in their infants (at discharge: 33.3% vs. 69.8%, χ2 = 12.39, df = 1, p < 0.001; 3 months of corrected age: 17.8% vs. 52.8%, χ2 = 11.03, df = 1, p = 0.001). The ROC showed that expressed milk volume > 190 mL/d on day 7 postpartum significantly predicted expressed milk volume ≥ 300 mL/d at discharge. Insufficient human milk was the main reason for breastfeeding discontinuation at 3 months of corrected age. Twins were less likely to continue breastfeeding at 3 months of corrected age (aOR = 0.27; 95% CI 0.09, 0.86). In singleton infants, mother’s own milk ≥50% of total milk uptake at 2 weeks post-discharge (aOR = 32.66; 95% CI 3.00, 355.25) was an independent predictor of continuous breastfeeding at 3 months of corrected age. Feeding complications in infants, poor breastfeeding technique, and low milk output are the main challenges in breastfeeding.

Conclusion

Interventions to improve early postpartum lactation and breastfeeding techniques may increase breastfeeding adoption in mothers of preterm infants.
Lung stereotactic body radiation therapy: personalized PTV margins according to tumor location and number of four-dimensional CT scans
Authors: Trémolières Pierre , Gonzalez-Moya Ana , Paumier Amaury , Mege Martine , Blanchecotte Julien , Theotime Christelle , Autret Damien , Dufreneix Stéphane
Published: January 2022

Objectives

To characterise the motion of pulmonary tumours during stereotactic body radiation therapy (SBRT) and to evaluate different margins when creating the planning target volume (PTV) on a single 4D CT scan (4DCT).

Methods

We conducted a retrospective single-site analysis on 30 patients undergoing lung SBRT. Two 4DCTs (4DCT1 and 4DCT2) were performed on all patients. First, motion was recorded for each 4DCT in anterior–posterior (AP), superior-inferior (SI) and rightleft (RL) directions. Then, we used 3 different margins (3,4 and 5 mm) to create the PTV, from the internal target volume (ITV) of 4DCT1 only (PTV D1 + 3, PTV D1 + 4, PTV D1 + 5). We compared, using the Dice coefficient, the volumes of these 3 PTVs, to the PTV actually used for the treatment (PTVttt). Finally, new treatment plans were calculated using only these 3 PTVs. We studied the ratio of the D2%, D50% and D98% between each new plan and the plan actually used for the treatment (D2% PTVttt, D50% PTVttt, D50% ITVttt D98% PTVttt).

Results

30 lesions were studied. The greatest motion was observed in the SI axis (8.8 ± 6.6 [0.4–25.8] mm). The Dice index was higher when comparing PTVttt to PTV D1 + 4 mm (0.89 ± 0.04 [0.82–0.98]). Large differences were observed when comparing plans relative to PTVttt and PTV D1 + 3 for D98% PTVttt (0.85 ± 0.24 [0.19–1.00]).

and also for D98% ITVttt (0.93 ± 0.12 [0.4–1.0]).D98% PTVttt (0.85 ± 0.24 [0.19–1.00], p value = 0.003) was statistically different when comparing plans relative to PTVttt and PTV D1 + 3. No stastistically differences were observed when comparing plans relative to PTVttt and PTV D1 + 4. A difference greater than 10% relative to D98% PTVttt was found for only in one UL lesion, located under the carina.

Conclusion

A single 4DCT appears feasible for upper lobe lesions located above the carina, using a 4-mm margin to generate the PTV.

Advance in knowledge

Propostion of a personalized SBRT treatment (number of 4DCT, margins) according to tumor location (above or under the carina).
Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience
Authors: Badilla-Porras R. , Echeverri-McCandless A. , Weimer J. M. , Ulate-Campos A. , Soto-Rodríguez A. , Gutiérrez-Mata A. , Hernández-Con L. , Bogantes-Ledezma S. , Balmaceda-Meza A. , Brudvig J. , Sanabria-Castro A.
Published: January 2022

Background

Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population.

Objective

To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations.

Methods

DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records.

Results

Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens.

Conclusions

This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.
Whose responsibility? Part 2 of 2: views of patients, families, and clinicians about responsibilities for addressing the needs of persons with mental health problems in Chennai, India and Montreal, Canada
Authors: Iyer Srividya N. , Malla Ashok , Pope Megan , Mustafa Sally , Mohan Greeshma , Rangaswamy Thara , Schmitz Norbert , Joober Ridha , Shah Jai , Margolese Howard C. , Ramachandran Padmavati
Published: January 2022

Background

Individuals with mental health problems have many insufficiently met support needs. Across sociocultural contexts, various parties (e.g., governments, families, persons with mental health problems) assume responsibility for meeting these needs. However, key stakeholders' opinions of the relative responsibilities of these parties for meeting support needs remain largely unexplored. This is a critical knowledge gap, as these perceptions may influence policy and caregiving decisions.

Methods

Patients with first-episode psychosis (n = 250), their family members (n = 228), and clinicians (n = 50) at two early intervention services in Chennai, India and Montreal, Canada were asked how much responsibility they thought the government versus persons with mental health problems; the government versus families; and families versus persons with mental health problems should bear for meeting seven support needs of persons with mental health problems (e.g., housing; help covering costs of substance use treatment; etc.). Two-way analyses of variance were conducted to examine differences in ratings of responsibility between sites (Chennai, Montreal); raters (patients, families, clinicians); and support needs.

Results

Across sites and raters, governments were held most responsible for meeting each support need and all needs together. Montreal raters assigned more responsibility to the government than did Chennai raters. Compared to those in Montreal, Chennai raters assigned more responsibility to families versus persons with mental health problems, except for the costs of substance use treatment. Family raters across sites assigned more responsibility to governments than did patient raters, and more responsibility to families versus persons with mental health problems than did patient and clinician raters. At both sites, governments were assigned less responsibility for addressing housing- and school/work reintegration-related needs compared to other needs. In Chennai, the government was seen as most responsible for stigma reduction and least for covering substance use services.

Conclusions

All stakeholders thought that governments should have substantial responsibility for meeting the needs of individuals with mental health problems, reinforcing calls for greater government investment in mental healthcare across contexts. The greater perceived responsibility of the government in Montreal and of families in Chennai may both reflect and influence differences in cultural norms and healthcare systems in India and Canada.
Polymorphisms in the mTOR-PI3K-Akt pathway, energy balance-related exposures and colorectal cancer risk in the Netherlands Cohort Study
Authors: Simons Colinda C.J.M. , Schouten Leo J. , Godschalk Roger W.L. , van Schooten Frederik-Jan , Stoll Monika , Van Steen Kristel , van den Brandt Piet A. , Weijenberg Matty P.
Published: January 2022

Background

The mTOR-PI3K-Akt pathway influences cell metabolism and (malignant) cell growth. We generated sex-specific polygenic risk scores capturing natural variation in 7 out of 10 top-ranked genes in this pathway. We studied the scores directly and in interaction with energy balance-related factors (body mass index (BMI), trouser/skirt size, height, physical activity, and early life energy restriction) in relation to colorectal cancer (CRC) risk in the Netherlands Cohort Study (NLCS) (n=120,852). The NLCS has a case-cohort design and 20.3 years of follow-up. Participants completed a baseline questionnaire on diet and cancer in 1986 when 55–69 years old. ~75% of the cohort returned toenail clippings used for DNA isolation and genotyping (n subcohort=3,793, n cases=3,464). To generate the scores, the dataset was split in two and risk alleles were defined and weighted based on sex-specific associations with CRC risk in the other dataset half, because there were no SNPs in the top-ranked genes associated with CRC risk in previous genome-wide association studies at a significance level p<1*10−5.

Results

Cox regression analyses showed positive associations between the sex-specific polygenic risk scores and colon but not rectal cancer risk in men and women, with hazard ratios for continuously modeled scores close to 1.10. There was no modifying effect observed of the scores on associations between the energy balance-related factors and CRC risk. However, BMI (in men), non-occupational physical activity (in women), and height (in men and women) were associated with the risk of CRC, in particular (proximal and distal) colon cancer, in the direction as expected in the lower tertiles of the sex-specific polygenic risk scores.

Conclusions

Current data suggest that the mTOR-PI3K-Akt pathway may be involved in colon cancer development. This study thereby sheds more light on colon cancer etiology through use of genetic variation in the mTOR-PI3K-Akt pathway.
Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology
Authors: Song No-Joon , Allen Carter , Vilgelm Anna E. , Riesenberg Brian P. , Weller Kevin P. , Reynolds Kelsi , Chakravarthy Karthik B. , Kumar Amrendra , Khatiwada Aastha , Sun Zequn , Ma Anjun , Chang Yuzhou , Yusuf Mohamed , Li Anqi , Zeng Cong , Evans John P. , Bucci Donna , Gunasena Manuja , Xu Menglin , Liyanage Namal P. M. , Bolyard Chelsea , Velegraki Maria , Liu Shan-Lu , Ma Qin , Devenport Martin , Liu Yang , Zheng Pan , Malvestutto Carlos D. , Chung Dongjun , Li Zihai
Published: January 2022

Background

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain–containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy.

Methods

Using a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19.

Results

Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8+T cells, CD4+T cells, and CD56+natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis.

Conclusions

Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.
Glycopyrrolate for drooling in children with medical complexity under three years of age
Authors: Lovardi Eleonora , De Ioris Maria Antonietta , Lettori Donatella , Geremia Caterina , Staccioli Susanna , Bella Gessica Della , Scrocca Raffaella , Scarselli Alessia , Aversa Marcella , De Peppo Francesco , Campana Andrea , Castelli Enrico
Published: January 2022

Background

The aim of the study is to determine that Glycopirrolate is safe and effective in decreasing drooling in children with medical complexity under 3 years of age. Medical treatment is based on anticholinergic drugs as transdermal scopolamine, benzotropine and GLY. GLY (Glycopyrronium bromide) is a synthetic quaternary ammonium anticholinergic agent with poor blood–brain barrier penetration and consequently has limited central effects. Actually, the oral GLY formulation was approved by the United States Food and Drug Administration (FDA) to treat drooling in children aged 3–16 years. Five studies reported on GLY use for the treatment of drooling in children with cerebral palsy and other conditions with neurological impairment; four are prospective studies while one a retrospective review.

Methods

this is a case report of eighteen children (sex ratio 11/8, median age 17 months, range 2–36 months) under three years of age, followed by a multidisciplinary team at the Bambino Gesù Children Hospital. The median follow-up was of 31.5 months (range 1–69 months). Response to treatment was assessed according to the Drooling Impact Scale administered at time 0 and after 1 month. All patients have an important neurological impairment: nine patients have a cerebral palsy (Gross Motor Function Classification System class V) and nine a genetic/malformative syndrome. Twelve patients have a tracheostomy and two need mechanical ventilation. Gastrostomy is present in 16 out of 18 patients. All patients received Glycopirrolate. The median starting daily dose was 0.065 mg/kg/die (range 0.02–0.21 mg/kg/die) three times a day. The drooling impact scale was administered at time O and after 1 month.

Results

Four out 18 patients stopped treatment for adverse event, lack of efficacy or parental decision. The mean Drooling Impact Scale at time 0 was 89 (range 81–100) and after 1 month 61(range 43–78); the difference was statistically significant (P < 0.001). The overall response to treatment was 94%.

Conclusions

This is the first study to determine the safety and effectiveness of Glycopyrrolate in decreasing drooling in a specific subset of patients. No major side effects were observed. Further comparative studies are needed to confirm our results.
Temporal transcriptomic changes in long non-coding RNAs and messenger RNAs involved in the host immune and metabolic response during Toxoplasma gondii lytic cycle
Authors: Wang Sha-Sha , Zhou Chun-Xue , Elsheikha Hany M. , He Jun-Jun , Zou Feng-Cai , Zheng Wen-Bin , Zhu Xing-Quan , Zhao Guang-Hui
Published: January 2022

Background

Long non-coding RNAs (lncRNAs) are important regulators of various biological and pathological processes, in particular the inflammatory response by modulating the transcriptional control of inflammatory genes. However, the role of lncRNAs in regulating the immune and inflammatory responses during infection with the protozoan parasite Toxoplasma gondii remains largely unknown.

Methods

We performed a longitudinal RNA sequencing analysis of human foreskin fibroblast (HFF) cells infected by T. gondii to identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs), and dysregulated pathways over the course of T. gondii lytic cycle. The transcriptome data were validated by qRT-PCR.

Results

RNA sequencing revealed significant transcriptional changes in the infected HFFs. A total of 697, 1234, 1499, 873, 1466, 561, 676 and 716 differentially expressed lncRNAs (DElncRNAs), and 636, 1266, 1843, 2303, 3022, 1757, 3088 and 2531 differentially expressed mRNAs (DEmRNAs) were identified at 1.5, 3, 6, 9, 12, 24, 36 and 48 h post-infection, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DElncRNAs and DEmRNAs revealed that T. gondii infection altered the expression of genes involved in the regulation of host immune response (e.g., cytokine–cytokine receptor interaction), receptor signaling (e.g., NOD-like receptor signaling pathway), disease (e.g., Alzheimer's disease), and metabolism (e.g., fatty acid degradation).

Conclusions

These results provide novel information for further research on the role of lncRNAs in immune regulation of T. gondii infection.

Graphical Abstract
Proof-of-concept and concurrent validity of a prototype headset to assess peak oxygen uptake without a face mask
Authors: Düking Peter , Kunz Philipp , Engel Florian A. , Mastek Helena , Sperlich Billy
Published: January 2022

Objective

Portable gas exchange instruments allow the assessment of peak oxygen uptake (V̇O2peak) but are often bulky, expensive and require wearing a face mask thereby limiting their routine application. A newly developed miniaturized headset (VitaScale, Nuremberg, Germany) may overcome these barriers and allow measuring V̇O2peak without applying a face mask. Here we aimed (i) to disclose the technical setup of a headset incorporating a gas and volume sensor to measure volume flow and expired oxygen concentration and (ii) to assess the concurrent criterion-validity of the headset to measure V̇O2peak in 44 individuals exercising on a stationary cycle ergometer in consideration of the test–retest reliability of the criterion measure.

Results

The coefficient of variation (CV%) while measuring V̇O2peak during incremental cycling with the headset was 6.8%. The CV% for reliability of the criterion measure was 4.0% for V̇O2peak. Based on the present data, the headset might offer a new technology for V̇O2peak measurement due to its low-cost and mask-free design.
Identification of the role of oral health educators in elementary schools during COVID-19 pandemic: a competency framework
Authors: Khiami Adel , Dashash Mayssoon
Published: January 2022

Objective

Oral health educators should have the required knowledge, skills and attitude in order to meet the increased needs of the Ministry of Education in Syria as well as to perform their duties in promoting oral health in children appropriately during the COVID-19 pandemic. Therefore, this study was undertaken to identify core competencies required for oral health educators in elementary schools during the COVID-19 pandemic. Qualitative exploratory study was undertaken. A focus group which consisted of 5 Medical Education postgraduates and 3 oral health educators’ training team members were invited to formulate a preliminary list of basic competencies. Delphi technique was also adopted through inviting 12 experts in oral health education to evaluate and formulate a final list of elementary schools’ oral health educators’ competencies during the COVID-19 pandemic.

Results

A competency framework was developed. Fifty-five competencies were identified including 35 in cognitive domain, 12 skills and 8 attitude competencies. A list of essential competencies has been identified. These competencies should be addressed in training programs targeting oral health educators, which can consequently produce competent educators who can successfully promote and provide health care to all schoolchildren during the COVID-19 pandemic.
Survey participation among general practitioners: comparison between teaching physicians and a random sample
Authors: Pentzek Michael , Baumgart Verena , Hegerath Flora-Marie
Published: January 2022

Objective

Health scientists strive for a smooth recruitment of physicians for research projects like surveys. Teaching physicians are an easy to approach population that is already affiliated with a university by teaching students in their practice. How do response rates compare between a convenient online survey among teaching physicians and an elaborate postal survey in a random sample of unknown physicians? Data from the TMI-GP study on the use of memory tests in general practice were used.

Results

Physicians in the random sample responded to the postal survey more often than teaching physicians to the online survey (59.5% vs. 18.9%; odds ratio 7.06; 95% confidence interval 4.81–10.37; p < 0.001). Although it is unclear whether the sample, the survey mode (online vs. postal) or both account for this effect, it is noteworthy that even in such a convenience sample of known/committed physicians, an adequate response rate could not be reached without a tailored and elaborated survey technique. Responders in the two samples were comparable regarding a content-related item (use of memory tests; Χ2(df = 1) = 3.07; p = 0.080).
Carotid artery velocity time integral and corrected flow time measured by a wearable Doppler ultrasound detect stroke volume rise from simulated hemorrhage to transfusion
Authors: Kenny Jon-Émile S. , Barjaktarevic Igor , Mackenzie David C. , Elfarnawany Mai , Yang Zhen , Eibl Andrew M. , Eibl Joseph K. , Kim Chul-Ho , Johnson Bruce D.
Published: January 2022

Objective

Doppler ultrasonography of the common carotid artery is used to infer stroke volume change and a wearable Doppler ultrasound has been designed to improve this workflow. Previously, in a human model of hemorrhage and resuscitation comprising approximately 50,000 cardiac cycles, we found a strong, linear correlation between changing stroke volume, and measures from the carotid Doppler signal, however, optimal Doppler thresholds for detecting a 10% stroke volume change were not reported. In this Research Note, we present these thresholds, their sensitivities, specificities and areas under their receiver operator curves (AUROC).

Results

Augmentation of carotid artery maximum velocity time integral and corrected flowtime by 18% and 4%, respectively, accurately captured 10% stroke volume rise. The sensitivity and specificity for these thresholds were identical at 89% and 100%. These data are similar to previous investigations in healthy volunteers monitored by the wearable ultrasound.
The relationship between dietary sulfur amino acids intake and severity and frequency of pain in Iranian patients with musculoskeletal pains, 2020
Authors: Bahrampour Niki , Movahedi Ariyo , Djazayery Abolghassem , Clark Cain C. T.
Published: January 2022

Objective

Musculoskeletal pain conditions (MPs) are a widespread public problem that can affect 13.5% to 47% of the total population. Dietary changes can have strong effects on person’s health; for instance, Sulfur amino acids (SAAs) can act as a precursor of neurotransmitters, antioxidative metabolic intermediates, such as glutathione, impact inflammation, and play a role in severity and frequency of MPs. We evaluated the relationship between dietary SAAs intake with severity and frequency of pain in patients with MPs.

Results

This cross-sectional study consisted of 175 men and woman. Anthropometric measurements and pain assessments were conducted via questionnaires. Dietary data were collected using 7 days 24-h recall. ANOVA and Spearman correlation coefficients were used to examine the relationship and correlation, respectively, between exposure and outcome variables.

There was a significant correlation between age, weight, waist circumference (WC), waist circumference to height (WHtR), body mass index (BMI), and severity and frequency of MPs among women. There was a correlation between age and severity of pain in men.

The present study highlights a positive association between the dietary SAAs and severity of pain, even after adjusting for confounding variables.
Expression of angiogenic markers in jawbones and femur in a rat model treated with zoledronic acid
Authors: Li Jing Wen , Wang Jing Yi , Yu Ru Qing , Huo Lei , Zheng Li Wu
Published: January 2022

Objectives

This study aimed to investigate the gene expression of angiogenic marker in surgically treated jawbones and femur on a rat model administrated with zoledronic acid.

Results

No soft tissue fenestration or bone exposure was found in femur. Delayed soft tissue healing was found in both ZA group (3 in mandible, 4 in maxilla) and control group (1 in mandible, 2 in maxilla), while exposed bone was found only in the ZA group (1 in maxilla, 2 in mandible). RT-PCR analysis demonstrated no significant difference in gene expression of angiogenetic markers between ZA-treated and control groups in femur and mandible. In the maxilla, the expression of VEGFA and VEGFR-2 in medium-term ZA group was significantly down-regulated compared with that in the control. The ZA treatment does not change significantly the expression of the angiogenic factors in femur and mandible, but significantly downregulates the expression in maxilla in this rat model. The angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.
Atypical and dual biotypes variant of virulent SA-NAG-Vibrio cholerae: an evidence of emerging/evolving patho-significant strain in municipal domestic water sources
Authors: Igere Bright E. , Okoh Anthony I. , Nwodo Uchechukwu U.
Published: January 2022

Introduction and purpose

The recent cholera spread, new cases, and fatality continue to arouse concern in public health systems; however, interventions on control is at its peak yet statistics show continuous report. This study characterized atypical and patho-significant environmentalVibrio choleraeretrieved from ground/surface/domestic water in rural-urban-sub-urban locations of Amathole District municipality and Chris Hani District municipality, Eastern Cape Province, South Africa.

Methods

Domestic/surface water was sampled and 759 presumptiveV. choleraeisolates were retrieved using standard microbiological methods. Virulence phenotypic test: toxin co-regulated pili (tcp), choleragen red, protease production, lecithinase production, and lipase test were conducted. Serotyping using polyvalent antisera (Bengal and Ogawa/Inaba/Hikojima) and molecular typing: 16SrRNA, OmpW, serogroup (Vc-O1/O139), biotype (tcpAClas/El Tor,HlyAClas/El Tor,rstRClas/El Tor,RS1,rtxA,rtxC), and virulence (ctxA,ctxB,zot,ace,cep,prt,toxR,hlyA) genes were targeted.

Result

Result of16SrRNAtyping confirmed 508 (66.9%) whileOmpWdetected/confirmed 61 (12.01%)V. choleraestrains. Phenotypic-biotyping scheme showed positive test to polymyxin B (68.9%), Voges proskauer (6.6%), and Bengal serology (11.5%). Whereas Vc-O1/O139 was negative, yet two of the isolates harbored the cholera toxin with a gene-typectxBandhlyAClas: 2/61, revealing atypical/unusual/dual biotype phenotypic/genotypic features. Other potential atypical genotypes detected includerstR: 7/61,Cep: 15/61,ace: 20/61,hlyAElTor: 53/61,rtxA: 30/61,rtxC: 11/61, andprtV: 15/61 respectively.

Conclusion

Although additional patho-significant/virulent genotypes associated with epidemic/sporadic cholera cases were detected, an advanced, bioinformatics, and post-molecular evaluation is necessary. Such stride possesses potential to adequately minimize future cholera cases associated with dynamic/atypical environmentalV. choleraestrains.
Research progress of the application of mesenchymal stem cells in chronic inflammatory systemic diseases
Authors: Huang Fangfang , Thokerunga Erick , He Fajian , Zhu Xinyu , Wang Zi , Tu Jiancheng
Published: January 2022

Chronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation.
Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
Authors: Da Ros Francesco , Persano Luca , Bizzotto Dario , Michieli Mariagrazia , Braghetta Paola , Mazzucato Mario , Bonaldo Paolo
Published: January 2022

Background

Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell–cell and cell–matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic malignancies. Here we describe Emilin-2 as an abundant extracellular matrix component of bone marrow stroma.

Methods

Immunodetection of Emilin-2 was performed in bone marrow sections of mice from 30 days to 6 months of age. Emilin-2 expression was monitored in vitro in primary and mesenchymal stem cell lines under undifferentiated and adipogenic conditions. Hematopoietic stem cells and progenitors in bone marrow of 3- to 10-month-old wild-type and Emilin-2 null mice were analyzed by flow cytometry.

Results

Emilin-2 is deposited in bone marrow extracellular matrix in an age-dependent manner, forming a meshwork that extends from compact bone boundaries to the central trabecular regions. Emilin-2 is expressed and secreted by both primary and immortalized bone marrow mesenchymal stem cells, exerting an inhibitory action in adipogenic differentiation. In vivo Emilin-2 deficiency impairs the frequency of hematopoietic stem/progenitor cells in bone marrow during aging.

Conclusion

Our data provide new insights in the contribution of bone marrow extracellular matrix microenvironment in the regulation of stem cell niches and hematopoietic progenitor differentiation.
Modification of mesenchymal stem cells by HMGB1 promotes the activity of Cav3.2 T-type calcium channel via PKA/β-catenin/γ-cystathionase pathway
Authors: Wu Hao , Xie Xiaodong , Sun Mingyang , Chen Min , Tao Xuan , Fang Xin , Meng Xiaohu , Wei Wei , Yu Min
Published: January 2022

Background

Mesenchymal stem cells (MSC) hold great promise for treating cardiovascular disease. Recently, we genetically modified MSCs with high mobility group box 1 (HMGB1), and these cells demonstrated high mobility by efficient migrating and homing to target neointima. The possible mechanism was investigated in the current study.

Methods

Rat MSCs were transfected with lentivirus containing HMGB1 cDNA to yield MSC-H cell line stably overexpressing HMGB1. The MSC-C cells which were transfected with empty lentivirus served as negative control, and the differentially expressed genes were analyzed by microarray. The cell mobility was determined by transwell migration assay. Intracellular free calcium and the expression of Cav3.2 T-type calcium channel (CACNA1H) were assayed to analyze activity of CACNA1H-mediated calcium influx. H2S production and γ-cystathionase expression were examined to assess the activity of γ-cystathionase/H2S signaling. The interaction of HMGB1 with γ-cystathionase in MSC-H cells was analyzed by co-immunoprecipitation. Luciferase reporter assay was performed to determine whether the promoter activity of γ-cystathionase was regulated by interaction of β-catenin and TCF/LEF binding site. Intercellular cAMP, PKA activity, phosphorylation of β-catenin, and GSK3β were investigated to reveal cAMP/PKA mediated β-catenin activation.

Result

Microarray analysis revealed that differentially expressed genes were enriched in cAMP signaling and calcium signaling. CACNA1H was upregulated to increase intracellular free calcium and MSC-H cell migration. Blockage of CACNA1H by ABT-639 significantly reduced intracellular free calcium and cell migration. The γ-cystathionase/H2S signaling was responsible for CACNA1H activation. H2S production was increased with high expression of γ-cystathionase in MSC-H cells, which was blocked by γ-cystathionase inhibitor DL-propargylglycine. Upregulation of γ-cystathionase was not attributed to interaction with HMGB1 overexpressed in MSC-H cells although γ-cystathionase was suggested to co-immunoprecipitate with oxidized HMGB1. Bioinformatics analysis identified a conserved TCF/LEF binding site in the promoter of γ-cystathionase gene. Luciferase reporter assay confirmed that the promoter had positive response to β-catenin which was activated in MSC-H cells. Finally, cAMP/PKA was activated to phosphorylate β-catenin at Ser657 and GSK3β, enabling persisting activation of Wnt/β-catenin signaling in MSC-H cells.

Conclusion

Our study revealed that modification of MSCs with HMGB1 promoted CACNA1H-mediated calcium influx via PKA/β-catenin/γ-cystathionase pathway. This was a plausible mechanism for high mobility of MSC-H cell line.
Human MuStem cells repress T-cell proliferation and cytotoxicity through both paracrine and contact-dependent pathways
Authors: Charrier Marine , Lorant Judith , Contreras-Lopez Rafael , Téjédor Gautier , Blanquart Christophe , Lieubeau Blandine , Schleder Cindy , Leroux Isabelle , Deshayes Sophie , Fonteneau Jean-François , Babarit Candice , Hamel Antoine , Magot Armelle , Péréon Yann , Viau Sabrina , Delorme Bruno , Luz-Crawford Patricia , Lamirault Guillaume , Djouad Farida , Rouger Karl
Published: January 2022

Background

Muscular dystrophies (MDs) are inherited diseases in which a dysregulation of the immune response exacerbates disease severity and are characterized by infiltration of various immune cell types leading to muscle inflammation, fiber necrosis and fibrosis. Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling.

Methods

The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-γ expression and lysis activity.

Results

Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one.

Conclusions

Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.