bluuebunny/crossref_metadata_2025 huggingface dataset:
Unwelcome Companions: Loneliness Associates with the Cluster of Pain, Fatigue, and Depression in Older Adults
Authors: Powell Victoria D. , Abedini Nauzley C. , Galecki Andrzej T. , Kabeto Mohammed , Kumar Navasuja , Silveira Maria J.
Published: February 2021

Objective: Pain, fatigue, and depression commonly co-occur as a symptom cluster in pathological inflammatory states. Psychosocial stressors such as loneliness may lead to similar states through shared mechanisms. We investigated the association of loneliness with pain, fatigue, and depression in older adults. Methods: Using Health and Retirement Study data ( N = 11,766), we measured cross-sectional prevalence of frequent, moderate to severe pain; severe fatigue; depressive symptoms; and co-occurrence of symptoms surpassing threshold levels (i.e., symptom cluster). Logistic regression models evaluated associations with loneliness. Results: Pain, fatigue, and depression were reported in 19.2%, 20.0%, and 15.3% of the total sample, respectively. The symptom cluster was seen in 4.9% overall; prevalence in lonely individuals was significantly increased (11.6% vs. 2.3%, p < .0001). After adjusting for demographic variables, loneliness associated with the symptom cluster (adjusted OR = 3.39, 95% CI = 2.91, 3.95) and each symptom (pain adjusted OR = 1.61, 95% CI = 1.48, 1.76; fatigue adjusted OR = 2.02, 95% CI = 1.85, 2.20; depression adjusted OR = 4.34, 95% CI = 3.93, 4.79). Discussion: Loneliness strongly associates with the symptom cluster of pain, fatigue, and depression. Further research should examine causal relationships and investigate whether interventions targeting loneliness mitigate pain, fatigue, and depression.
Lingering Identity as Chronically Ill and the Unanticipated Effects of Life-Changing Precision Medicine in Cystic Fibrosis: A Case Report
Authors: Ladores Sigrid , Polen Morgan
Published: February 2021

Cystic fibrosis (CF) is the leading genetic disease among Caucasians; however, advances in diagnosis and treatment have improved both quality and quantity of life for those affected. A remarkable recent discovery is the triple-drug combination, elexacaftor/tezacaftor/ivacaftor, which has been touted as a “miracle drug” for CF because of its demonstrated efficacy and safety. This case study reports on an adult woman with CF who experienced positive life-changing results from elexacaftor/tezacaftor/ivacaftor, and yet discovered that she lived in fear that its effectiveness would diminish, and her debilitating symptoms would return. Her lingering identity as chronically ill tainted her view of her new life with skepticism and pervasive anxiety. This case highlights a critical need to engage in early, regular and sensitive discussions with patients before initiating treatments that may affect their emotional and mental health and provide referrals or services to meet those emergent needs.
Prognostic rules for predicting cognitive syndromes following stroke: A systematic review
Authors: Drozdowska Bogna A , McGill Kris , McKay Michael , Bartlam Roisin , Langhorne Peter , Quinn Terence J
Published: February 2021

Purpose

Stroke survivors are at high risk of developing cognitive syndromes, such as delirium and dementia. Accurate prediction of future cognitive outcomes may aid timely diagnosis, intervention planning, and stratification in clinical trials. We aimed to identify, describe and appraise existing multivariable prognostic rules for prediction of post-stroke cognitive status.

Method

We systematically searched four electronic databases from inception to November 2019 for publications describing a method to estimate individual probability of developing a cognitive syndrome following stroke. We extracted data from selected studies using a pre-specified proforma and applied the Prediction model Risk Of Bias Assessment Tool (PROBAST) for critical appraisal.

Findings

Of 17,390 titles, we included 10 studies (3143 participants), presenting the development of 11 prognostic rules – 7 for post-stroke cognitive impairment and 4 for delirium. Most commonly incorporated predictors were: demographics, imaging findings, stroke type and symptom severity. Among studies assessing predictive discrimination, the area under the receiver operating characteristic (AUROC) in apparent validation ranged from 0.80 to 0.91. The overall risk of bias for each study was high. Only one prognostic rule had been externally validated. Discussion/conclusion: Research into the prognosis of cognitive outcomes following stroke is an expanding field, still at its early stages. Recommending use of specific prognostic rules is limited by the high risk of bias in all identified studies, and lack of supporting evidence from external validation. To ensure the quality of future research, investigators should adhere to current, endorsed best practice guidelines for conduct of prediction model studies.
Choroidal Neovascularization and Macular Hemorrhage: Real-World Experience During the New York City COVID-19 Lockdown
Authors: Kovacs Kyle D. , Gonzalez Luis A. , Mahrous M. Abdallah , Orlin Anton , Papakostas Thanos D. , D’Amico Donald J. , Kiss Szilárd
Published: February 2021

Purpose:

This work reviews ocular, systemic, and demographic factors contributing to presentation of choroidal neovascular membrane (CNVM)–associated macular hemorrhage after the New York City coronavirus disease 2019 (COVID-19) lockdown.

Methods:

A retrospective, consecutive case series was conducted of all established patients presenting with macular hemorrhage between March 22, 2020, and August 10, 2020.

Results:

Fourteen patients (mean age 82.2 years) were evaluated. Ten patients had active CNVMs, 1 had an inactive lesion that was last injected 2 years prior, and 3 had new conversions from nonexudative age-related macular degeneration. In the actively treated CNVM group there was a delay in expected follow-up from 50.4 days to 125 days. Eight patients with previously active CNVM (73%) had a history of prior macular hemorrhage. Eight patients (57%) were on some form of antiplatelet or anticoagulation therapy. Twelve patients (86%) had COVID-19–specific risk factors besides age, and all but 1 patient (93%) delayed care without discussion with a physician. Ten patients (71%) had more than 1 week of symptoms prior to presentation. Twelve patients (86%) had signs of CNVM on prior optical coherence tomography.

Conclusions:

Adequate documentation of potential risks for hemorrhage (particularly prior hemorrhage or presence of subclinical type 1 CNVM), as well as COVID-19–specific risk factors, would aid triage of clinic appointments in future lockdowns. High-risk patients would likely benefit from direct physician communication discussing their individual risk profiles to alleviate anxiety over clinic visits and communicate their risk of severe vision loss.
Rationale and Surgical Technique of Ramp Lesion Repair Through an Additional Posteromedial Portal
Authors: Thaunat Mathieu , Fayard Jean-Marie , Freychet Benjamin , Vieira Thais Dutra , Sonnery-Cottet Bertrand
Published: February 2021

Background:

Ramp lesions are longitudinal lesions of the meniscocapsular complex of the posterior horn of the medial meniscus. These lesions are poorly recognized, difficult to diagnose, and require specific arthroscopic exploration. Ramp lesions are typically associated with anterior cruciate ligament rupture and have important biomechanical consequences as they result in increased anterior tibial translation and external rotation. Suture hook repair through the posteromedial portal is safe and provides a high healing rate.

Indications:

Spontaneous healing of ramp lesions is rarely observed, and repair is indicated for all lesions with the involvement of meniscotibial ligament. The choice of a posteromedial repair technique with vertical suture performed under visual control allows restoration of the continuity of meniscotibial ligament and effective healing of these lesions.

Technique Description:

Standardized arthroscopic exploration with systematic visualization of the posteromedial compartment using the transnotch technique is a crucial point to diagnose these lesions. The use of transillumination and a needle allows to palpate the lesion with the tip of the needle in case of doubt (hidden lesion) before performing the posteromedial portal safely. By using the transnotch vision and by introducing the instruments through the posteromedial portal, debridement with the shaver and repair with the hook of the lesion are performed under visual control. Vertical repair is performed by taking care to pass the hook through the meniscotibial ligament by perforating the deep face of the capsular portion and anterior portion of the ramp lesion. Similarly, it is recommended not to catch too much meniscal tissue on the anterior margin side to remain in the red zone and not to perforate the meniscus in the avascular zone to avoid secondary lesions caused by the “cheese wire” effect of the sutures in the white zone.

Results:

This technique has allowed us to reduce our percentage of secondary meniscectomy after ramp lesion repair from 25% using a standard arthroscopic exploration and meniscal repair technique through the anterior portal to 11.3% using a arthroscopic exploration and repair technique through the posteromedial portal at 4 years of follow-up.

Discussion/Conclusion:

Systematic use of the transnotch vision and repair through the posteromedial portal are recommended for the management of these lesions, which demonstrate serious mechanical and clinical consequences.
Fabrication of Carbon Nanotubes and Rare Earth Pr Reinforced AZ91 Composites by Powder Metallurgy
Authors: Li Ning , Yan Hong , Wu Qingjie , Cao Zeyu
Published: February 2021

It can be known from a large number of research results that improving the dispersibility of CNTs can effectively optimize the mechanical properties of the corresponding metal matrix composites. However, the crucial issue of increasing the bonding of CNTs and the matrix is still unsolved. In this paper, a novel method was developed to increase interfacial bonding strength by coating titanium oxide (TiO2) on the surface of CNTs. The rare earth Pr and TiO2@CNTs-reinforced AZ91matrix composites were successfully fabricated by powder metallurgy. Hot press sintering and hot extrusion of the milled powder was performed. After hot extrusion, the influence of TiO2@CNTs on the microstructure and mechanical properties of the composites were investigated. The results showed that the coating process can improve the distribution of CNTs in Mg alloy. The CNTs refined the grains of the matrix, and the CNTs were presented throughout the extrusion direction. When the TiO2@CNTs content was 1.0 wt.%, the yield strength (YS), ultimate tensile strength (UTS), and elongation of the alloy attained maximum values. The values were improved by 23.5%, 82.1%, and 40.0%, respectively, when compared with the AZ91 alloy. Good interfacial bonding was achieved, which resulted in an effective tensile loading transfer at the interface. CNTs carried the tensile stress and were observed on the tensile fracture.
Evaluation of FindMyApps: protocol for a randomized controlled trial of the effectiveness and cost-effectiveness of a tablet-based intervention to improve self-management and social participation of community-dwelling people with mild dementia, compared to usual tablet use
Authors: Neal David Peter , Kerkhof Yvonne J. F. , Ettema Teake P. , Muller Majon , Bosmans Judith , Finnema Evelyn , Graff Maud , Dijkstra Karin , Stek Max L. , Dröes Rose-Marie
Published: February 2021

Background

For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps intervention has been developed with and for people with dementia and their caregivers, to help them use tablets to facilitate self-management and engagement in meaningful social activities. A feasibility study and exploratory pilot trial evaluating FindMyApps have been carried out. This definitive trial further evaluates the effectiveness of the intervention and, for the first time, the cost-effectiveness.

Methods

A randomized controlled non-blinded single-center two-arm superiority trial will be conducted. Community-dwelling people with Mild Cognitive Impairment (MCI), or dementia with a Mini Mental-State Examination (MMSE) of > 17 and < 26, or Global Deterioration Scale 3 or 4, with an informal caregiver and access to a wireless internet connection will be included. In total, 150 patient-caregiver dyads will be randomly allocated to receive either usual care (control arm – tablet computer; n = 75 dyads) or usual care and the FindMyApps intervention (experimental arm – tablet computer and FindMyApps; n = 75 dyads). The primary outcomes are: for people with dementia, self-management and social participation; for caregivers, sense of competence. In addition to a main effect analysis, a cost-effectiveness analysis will be performed. In line with MRC guidance for evaluation of complex interventions a process evaluation will also be undertaken.

Discussion

Results of the trial are expected to be available in 2023 and will be submitted for publication in international peer-reviewed scientific journals, in addition to conference presentations and reporting via the EU Marie Sklodowska-Curie DISTINCT ITN network. By providing evidence for or against the effectiveness and cost-effectiveness of the FindMyApps intervention, the results of the trial will influence national implementation of FindMyApps. We hope that the results of the trial will further stimulate research and development at the intersection of technology and psycho-social care in dementia. We hope to further demonstrate that the randomized controlled trial is a valuable and feasible means of evaluating new digital technologies, to stimulate further high-quality research in this growing field.

Trial registration number

Netherlands Trial Register: NL8157; registered 15th November 2019.
Changes in the cortisol and oxytocin levels of first-time pregnant women during interaction with an infant: a randomized controlled trial
Authors: Sonoda Nozomi , Takahata Kaori , Tarumi Wataru , Shinohara Kazuyuki , Horiuchi Shigeko
Published: February 2021

Background

During pregnancy, physiological, psychological, and social changes affect pregnant women’s childcare anxiety and childrearing behavior. However, there are scarce reports on hormonal evaluation related to such anxiety and behavior. Herein, we evaluated changes in salivary cortisol (primary outcome) and oxytocin (secondary outcome) levels of first-time pregnant women when interacting with an infant and discussed the relation of these changes to the women’s stress level.

Methods

This was a two-arm randomized controlled trial. Participants were randomly assigned using a web-based randomization system. The experimental group involved interaction with an infant for 30 min. The control group involved watching a DVD movie of an infant for 30 min. Saliva samples were collected at preintervention and postintervention. Saliva samples were assayed, and all data were compared between and within the groups using independent t-test and paired t-test with a two-sided 5% significance level. This study was approved by the Research Ethics Committee of St. Luke’s International University.

Results

A total of 102 women were randomly assigned to the experimental (n = 51) and control (n = 51) groups. Finally, 38 women in the experimental group and 42 women in the control group were analyzed. The salivary cortisol level significantly decreased after the interventions in both groups (t = 4.57, p = 0.00; t = 5.01, p = 0.00). However, there were no significant differences in the salivary cortisol (t = 0.349, p = 0.73) and oxytocin (t = − 1.945, p = 0.58) levels between the two groups.

Conclusions

The salivary cortisol level of first-time pregnant women significantly decreased in the experimental and control groups postintervention, although no significant difference was found between the two groups. Such decrease indicates stress reduction and release among these women. The absence of a significant increase in salivary oxytocin level in both groups may be related to the limitations of an insufficient number of samples that could be analyzed owing to the small saliva volume in some samples and the lack of adequate tactile stimulation of the intervention protocol. These results and procedural limitations provide useful insights into approaching subsequent studies aiming at continuously optimizing detection procedures.

Trial registration

UMIN000028471 (Clinical Trials Registry of University Hospital Information Network. July 31, 2017- Retrospectively registered.
The effects of transcutaneous electrical nerve stimulation during the first stage of labor: a randomized controlled trial
Authors: Njogu Anne , Qin Si , Chen Yujie , Hu Lizhen , Luo Yang
Published: February 2021

Background

Labor pain during childbirth can have devastating effects on the progress of labor, mother, and fetus. Consequently, the management of labor pain is crucial for the well-being of the mother and fetus. Transcutaneous electrical nerve stimulation (TENS) is a non -pharmacological analgesic technique. It uses a low-voltage electrical current to activate descending inhibitory systems in the central nervous system to relieve pain. This study aimed to determine the effects of TENS therapy in the first stage of labor.

Methods

In this single-blind randomized controlled trial, we screened low-risk pregnant women who anticipated spontaneous vaginal delivery. Women were assigned (1:1) to either the experimental group (received TENS therapy in the first stage of labor) or the control group (received routine obstetric care). The women, midwives, and researchers working in the gynecology and obstetric department were aware of the treatment group, but statisticians analysis the data were blinded. The primary outcome was labor pain intensity, assessed by visual analog scale (VAS) immediately after the randomization, at 30, 60, and 120 min after TENS therapy, and 2–24 h post-delivery. We used SPSS 21.0 software in data analysis. An independent sample t-test compared the mean VAS scores and labor duration between groups. A Chi-square test was employed to compare categorical variables between the groups. A significant level of ≤0.05 was statistically significant.

Results

A total of 326 pregnant women were eligible: experimental group (n = 161) and control group (n = 165). The experimental group had statistically significantly lower mean VAS scores at a different time (30, 60, and 120 min post-intervention and 2–24 h post-delivery) than the control group (p < 0.001). The experimental group demonstrated a statistically significant shorter duration of the active labor phase than the control group (p < 0.001).

Conclusion

This study indicates that TENS can be used as a non-pharmacological therapy to reduce pain and shorten the active labor phase.

Trial registration

ISRCTN registry, ISRCTN23857995. Registered on 11/12/2020, ‘retrospectively registered.
Variation rs9929218 and risk of the colorectal Cancer and adenomas: A meta-analysis
Authors: Wang Huiyan , Gu Dongying , Yu Miao , Hu Yanjun , Chen Zhe , Huo Xinying , Yu Tao , Chen Jinfei , Zheng Yang
Published: February 2021

Backgrounds

Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations.

Methods

To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations’ strength.

Results

Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04–1.42 for GG versus AA; OR = 1.22, 95%CI 1.05–1.42 for GG/AG versus AA). In the subgroup analyses, significantly increased risks were found among Europeans.

Conclusions

In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.
Association between ambient temperature, particulate air pollution and emergency room visits for conjunctivitis
Authors: Khalaila S. , Coreanu T. , Vodonos A. , Kloog I. , Shtein A. , Colwell L. E. , Novack V. , Tsumi E.
Published: February 2021

Background

Numerous studies have confirmed the association of ambient temperature and air pollution with a higher risk of morbidities, yet few have addressed their effect on the ocular system. The purpose of this study was to assess the association between temperature, air pollution, and emergency room visits for conjunctivitis.

Methods

In this case-crossover study, the records of all emergency room visits to Soroka University Medical Center (SUMC) from 2009 to 2014 were reviewed for patients with conjunctivitis. Daily exposure to fine and coarse particulate matter and temperature were determined by a hybrid model involving satellite sensors. Mean relative humidity was obtained from the Ministry of Environmental Protection meteorological monitoring station located in Beer-Sheva.

Results

Six hundred one patients were diagnosed with conjunctivitis in the SUMC emergency room. We discovered a positive association between temperature increments and incidence of conjunctivitis. The strongest effect was found during summer and autumn, with an immediate (lag0) incidence increase of 8.1% for each 1 °C increase in temperature (OR = 1.088, 95%CI: 1.046–1.132) between 24 and 28 °C in the summer and 7.2% for each 1 °C increase in temperature (OR = 1.072, 95%CI: 1.036–1.108) between 13 and 23 °C in the autumn. There was no statistically significant association between fine and coarse particulate matter and conjunctivitis incidence.

Conclusion

Temperature increases during summer and autumn are significantly associated with an increased risk of conjunctivitis. Conjunctivitis is not associated with non-anthropogenic air pollution. These findings may help community clinics and hospital emergency rooms better predict conjunctivitis cases and will hopefully lead to improved prevention efforts that will lower the financial burden on both the individual and the public.
Effects of body size and load carriage on lower-extremity biomechanical responses in healthy women
Authors: Unnikrishnan Ginu , Xu Chun , Baggaley Michael , Tong Junfei , Kulkarni Sahil , Edwards W. Brent , Reifman Jaques
Published: February 2021

Background

Musculoskeletal injuries, such as stress fractures, are the single most important medical impediment to military readiness in the U.S. Army. While multiple studies have established race- and sex-based risks associated with a stress fracture, the role of certain physical characteristics, such as body size, on stress-fracture risk is less conclusive.

Methods

In this study, we investigated the effects of body size and load carriage on lower-extremity joint mechanics, tibial strain, and tibial stress-fracture risk in women. Using individualized musculoskeletal-finite-element-models of 21 women of short, medium, and tall statures (n = 7 in each group), we computed the joint mechanics and tibial strains while running on a treadmill at 3.0 m/s without and with a load of 11.3 or 22.7 kg. We also estimated the stress-fracture risk using a probabilistic model of bone damage, repair, and adaptation.

Results

Under all load conditions, the peak plantarflexion moment for tall women was higher than those in short women (p < 0.05). However, regardless of the load condition, we did not observe differences in the strains and the stress-fracture risk between the stature groups. When compared to the no-load condition, a 22.7-kg load increased the peak hip extension and flexion moments for all stature groups (p < 0.05). However, when compared to the no-load condition, the 22.7-kg load increased the strains and the stress-fracture risk in short and medium women (p < 0.05), but not in tall women.

Conclusion

These results show that women of different statures adjust their gait mechanisms differently when running with external load. This study can educate the development of new strategies to help reduce the risk of musculoskeletal injuries in women while running with external load.
Prioritization of predisposing factors of gingival hyperplasia during orthodontic treatment: the role of amount of biofilm
Authors: Vincent-Bugnas Séverine , Borsa Leslie , Gruss Apolline , Lupi Laurence
Published: February 2021

Background

The mechanism of gingival growth that may occur during fixed orthodontic treatment is not yet fully understood and the amount of dental plaque is often incriminated. The objective of this study was to evaluate the prevalence of gingival growth during multi-attachment orthodontic treatment and to prioritize its predicting factors, especially the quantity of biofilm.

Methods

This comprehensive cross-sectional descriptive study was conducted on orthodontic patients aged 9 to 30 years, in good health, treated by a fixed appliance. Periodontal clinical parameters such as plaque index, gingival index, probing pocket depth, periodontal phenotype and gingival enhancement index were recorded. Likewise, the brushing habits and the date of the last scaling were noted. The orthodontic parameters studied were the duration of the treatment, the type of bracket, the alloys used for the arches and the type of ligatures. Descriptive statistics were carried out, and variables presenting p value < 0.25 were included in a multivariate analysis to calculate the Odds Ratio (OR) of gingival enlargement”.

Results

A total of 193 patients were included (16.38 ± 4.89 years). Gingival growth occurred for 49.7% of patients included. The predisposing factors for this pathology during fixed orthodontic treatment were conventional metal brackets (p = 0.021), mouth breathing (p = 0.040), male gender (p = 0.035), thick periodontal phenotype (p = 0.043), elastomeric ligations (p = 0.007), duration of treatment (p = 0.022) and presence of plaque (p = 0.004). After achievement of the logistic regression, only two factors remained related to gingival enlargement: metallic brackets (OR: 3.5, 95% CI: 1.1–10.55) and duration of treatment (OR: 2.03, 95% CI: 1.01–4.08). The amount of plaque would not be directly related to the development of gingival increase during orthodontic treatment.

Conclusions

Among the predisposing factors that underlie gingival growth during multi-attachment therapy, the amount of plaque is not found. The qualitative assessment of the plaque and its evolution during treatment could clarify the role of the biofilm in the occurrence of gingival overgrowth.
Procyanidin B2 induces apoptosis and autophagy in gastric cancer cells by inhibiting Akt/mTOR signaling pathway
Authors: Li Yuqin , Lu Xiaolan , Tian Peiying , Wang Kai , Shi Jianping
Published: February 2021

Background

Procyanidin B2 (PB2), a unique component of the grape seed and other medicinal plants. PB2 has shown wide anticancer activity in various human cancer cells. However, it remains unclear about the biological effects and associated mechanisms of PB2 on gastric cancer cells.

Methods

Cell proliferation was measured by CCK8 assay, and cellular lactate dehydrogenase (LDH) release was measured in the culture medium. Cellular apoptosis was observed via TUNEL staining assay and measured by caspase-3 and -9 activities. Autophagy was observed by LC3 staining. Western blot analysis was performed to verify autophagy-associated proteins (Beclin1 and Atg5) and Akt-mTOR pathway.

Results

PB2 reduced the viability of BGC-823 and SGC-7901 cells in a concentration-dependent manner. Furthermore, PB2 induced increased apoptosis rate of gastric cancer cells and enhanced caspase-3 and -9 activities. Simultaneously, PB2 triggered autophagy in gastric cancer cells, with enhanced LC3 staining and increased expression of Beclin1 and Atg5, while the inhibition of autophagy by 3-MA reversed the PB2-induced suppression on cell viability. In addition, PB2 significantly decreased p-Akt and p-mTOR protein expression of gastric cancer cells.

Conclusion

PB2 exerts anti-proliferative and apoptotic effects and induces autophagy by modulating Akt/mTOR signaling pathway. PB2 may be developed as a potential therapeutic drug for gastric cancer.
Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis
Authors: Hof Lotta , Moreth Till , Koch Michael , Liebisch Tim , Kurtz Marina , Tarnick Julia , Lissek Susanna M. , Verstegen Monique M. A. , van der Laan Luc J. W. , Huch Meritxell , Matthäus Franziska , Stelzer Ernst H. K. , Pampaloni Francesco
Published: February 2021

Background

Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days.

Results

We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures.

Conclusion

Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis.
Sputum sample positivity for Haemophilus influenzae or Moraxella catarrhalis in acute exacerbations of chronic obstructive pulmonary disease: evaluation of association with positivity at earlier stable disease timepoints
Authors: Malvisi Lucio , Taddei Laura , Yarraguntla Aparna , Wilkinson Tom M. A. , Arora Ashwani Kumar ,   the AERIS Study Group
Published: February 2021

Background

Infection with Haemophilus influenzae (Hi) or Moraxella catarrhalis (Mcat) is a risk factor for exacerbation in chronic obstructive pulmonary disease (COPD). The ability to predict Hi- or Mcat-associated exacerbations may be useful for interventions developed to reduce exacerbation frequency.

Methods

In a COPD observational study, sputum samples were collected at monthly stable-state visits and at exacerbation during two years of follow-up. Bacterial species (Hi, Mcat) were identified by culture and quantitative PCR assay. Post-hoc analyses were conducted to assess: (1) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at the screening visit (stable-state timepoint); (2) first Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days; (3) second Hi- or Mcat-positive exacerbations given presence or absence of Hi or Mcat at stable timepoints within previous 90 days. Percentages and risk ratios (RRs) with 95% confidence intervals were calculated.

Results

PCR results for analyses 1, 2 and 3 (samples from 84, 88 and 83 subjects, respectively) showed that the risk of an Hi- or Mcat-positive exacerbation is significantly higher if sputum sample was Hi- or Mcat-positive than if Hi- or Mcat-negative at previous stable timepoints (apart from Mcat in analysis 3); RRs ranged from 2.1 to 3.2 for Hi and 1.9 to 2.6 for Mcat.For all analyses, the percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-positive stable timepoints was higher than the percentage of Hi- or Mcat-positive exacerbations if Hi- or Mcat-negative at previous stable timepoints. Percentage of Hi- or Mcat-positive exacerbations given previous Hi- or Mcat-negative stable timepoints was 26.3%–37.0% for Hi and 17.6%–19.7% for Mcat.

Conclusions

Presence of Hi or Mcat at a stable timepoint was associated with a higher risk of a subsequent Hi- or Mcat-associated exacerbation compared with earlier absence. However, a large percentage of Hi- or Mcat-associated exacerbations was not associated with Hi/Mcat detection at an earlier timepoint. This suggests that administration of an intervention to reduce these exacerbations should be independent of bacterial presence at baseline.

Trial Registrationhttps://clinicaltrials.gov/; NCT01360398, registered May 25, 2011
Impulse oscillometry for detection of small airway dysfunction in subjects with chronic respiratory symptoms and preserved pulmonary function
Authors: Li Liang-Yuan , Yan Tian-Sheng , Yang Jing , Li Yu-Qi , Fu Lin-Xi , Lan Lan , Liang Bin-Miao , Wang Mao-Yun , Luo Feng-Ming
Published: February 2021

Background

Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF.

Methods

The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed.

Results

209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5–R20 and Fres than those who didn’t. Subjects with dyspnea had higher R5, R5–R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5–R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5–R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002).

Conclusion

IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases.
Primary sacral non-Hodgkin’s lymphoma: report of a case and systematic review of literature
Authors: Chigurupati Satya Vijay , Shukla Mridula , Pandey Manoj
Published: February 2021

Introduction

Isolated primary sacral diffuse large B cell non-Hodgkin’s lymphoma is a very rare entity, and only 11 cases have been reported previously.

Case presentation

A 36-year-old man was referred with low backache and radiculopathy pain with a clinico-radiological and cytological diagnosis of sacral metastasis. Histopathological examination and immunohistochemistry of image-guided tissue core biopsy from the sacral mass confirmed it as high-grade diffuse large B cell lymphoma (DLBCL). With normal blood counts and bone marrow, and no lesions elsewhere on imaging, he was staged IAE and received 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen chemotherapy followed by radiotherapy. The patient has completed a 3-year follow-up and is doing well with yearly imaging showing no evidence of active disease or recurrence.

Conclusions

The case shows the importance of an image-guided core biopsy and immunohistochemistry over a fine needle aspiration cytology in select cases as it can alter the treatment and outcome in patients. Because of rarity, the treatment and prognosis in primary sacral NHL is not still very clear as it is treated as per the guidelines of treatment of bone lymphoma.
Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism
Authors: Schürmann Matthias , Oppel Felix , Shao Senyao , Volland-Thurn Verena , Kaltschmidt Christian , Kaltschmidt Barbara , Scholtz Lars-Uwe , Sudhoff Holger
Published: February 2021

Background

Cholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies.

Methods

We isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry.

Results

Under standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation.

Conclusion

We propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence.
Generation and immunogenicity analysis of recombinant classical swine fever virus glycoprotein E2 and Erns expressed in baculovirus expression system
Authors: Wei Qiang , Bai Yilin , Song Yapeng , Liu Yunchao , Yu Wei , Sun Yaning , Wang Li , Deng Ruiguang , Xing Guangxu , Zhang Gaiping
Published: February 2021

Classical swine fever (CSF) caused by the classical swine fever virus (CSFV) is a highly contagious swine disease resulting in large economical losses worldwide. The viral envelope glycoprotein E2 and Erns are major targets for eliciting antibodies against CSFV in infected animals. In this report, the glycoprotein E2 and Erns were expressed using the baculovirus system and their protective immunity in rabbits were tested. Twenty CSFV seronegative rabbits were randomly divided into five groups. Each rabbit was intramuscularly immunized with CSFV-E2, CSFV-Erns, or their combination (CSFV-E2 + Erns). Besides, a commercial CSFV vaccine (C-strain) and PBS were used as positive or negative controls, respectively. Four weeks after the second immunization, all the rabbits were challenged with 100 RID50 of CSFV C-strain. High levels of CSFV E2-specific antibody, neutralizing antibody and cellular immune responses to CSFV were elicited in the rabbits inoculated with C-strain, CSFV-E2, and CSFV-E2 + Erns. And the rabbits inoculated with the three vaccines received complete protection against CSFV C-strain. However, no neutralizing antibody was detected in the Erns vaccinated rabbits and the rabbits exhibited fever typical of CSFV, suggesting the Erns alone is not able to induce a protective immune response. Taken together, while the Erns could not confer protection against CSFV, E2 and E2 + Erns could not only elicit humoral and cell-mediated immune responses but also confer complete protection against CSFV C-strain in rabbits.
Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene
Authors: Rjiba Khouloud , Ayech Hédia , Kraiem Olfa , Slimani Wafa , Jelloul Afef , Ben Hadj Hmida Imen , Mahdhaoui Nabiha , Saad Ali , Mougou-Zerelli Soumaya
Published: February 2021

Background

Wolf–Hirschhorn (WHS) is a set of congenital physical anomalies and mental retardation associated with a partial deletion of the short arm of chromosome 4. To establish a genotype–phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients. Patient 1 was a boy of 1-year-old, presented a typical WHS phenotype while patient 2, is a boy of 2 days presented an hypospadias, a micropenis and a cryptorchidie in addition to the typical WHS phenotype. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used.

Results

Results of the analysis showed that patient 2 had a greater deletion size (4.8 Mb) of chromosome 4 than patient 1 (3.4 Mb). Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. If we analyze the uncommon deleted region between patient1 and patient 2 we found that the Muscle Segment Homeobox (MSX1) gene is included in this region.MSX1is a critical transcriptional repressor factor, expressed in the ventral side of the developing anterior pituitary and implicated in gonadotrope differentiation.Msx1acts as a negative regulatory pituitary development by repressing the gonadotropin releasing hormone (GnRH) genes during embryogenesis. We hypothesized that the deletion ofMSX1in our patient may deregulate the androgen synthesis.

Conclusion

Based on theMSX1gene function, its absence might be indirectly responsible for the hypospadias phenotype by contributing to the spatiotemporal regulation ofGnRHtranscription during development.
Serum complement 3 is a potential biomarker for assessing disease activity in Takayasu arteritis
Authors: Chen Rongyi , Ma Lingying , Lv Peng , Lin Jiang , Li Chaolun , Yan Yan , Jin Xuejuan , Dai Xiaomin , Ji Zongfei , Chen Huiyong , Ma Lili , Sun Ying , Jiang Lindi
Published: February 2021

Background

Takayasu arteritis (TA) is a rare disease, lacking convenient and feasible biomarkers to identify disease activity. We aimed to evaluate the value of complements in distinguishing active TA.

Methods

Consecutive patients were enrolled from the prospective East China TA cohort from April 2008 to June 2019. Patients were divided into two groups according to their baseline Kerr score. The value of complements and other biomarkers in identifying disease activity were analysed with cluster analysis, ROC curves, and combined tests. An independent group of patients from July 2019 to December 2019 were employed to validate the results.

Results

Of the enrolled 519 patients, 406 (72.2%) cases were identified as active disease. Higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), and complement 3 (C3) levels were observed in the active group. Elevated C3 (≥ 1.085 g/L) had a high value to identify active TA with a sensitivity of 69.9%, specificity of 66.7%, and AUC of 0.715. Combining the CRP (≥ 10.65 g/L; sensitivity, 50.7%; specificity, 82.4%) and C3, the sensitivity could be improved to 85.1% in parallel test and the specificity could be improved to 94.1% in serial test. Validation was further performed to confirm the value of C3 for disease activity assessment. The accuracy of the parallel test of CRP and C3 in external validation with independent 53 TA cases was 72.73% with the AUC of 0.721.

Conclusion

Elevated C3 could effectively evaluate the disease activity of TA, and C3 combining with CRP could further improve the disease activity evaluation.
Clinical signs predictive of severe illness in young Pakistani infants
Authors: Shahid Shahira , Tikmani Shiyam Sunder , Nayani Kanwal , Munir Ayesha , Brown Nick , Zaidi Anita K. M. , Jehan Fyezah , Nisar Muhammad Imran
Published: February 2021

Objective

Early detection of specific signs and symptoms to predict severe illness is essential to prevent infant mortality. As a continuation of the results from the multicenter Young Infants Clinical Signs and Symptoms (YICSS) study, we present here the performance of the seven-sign algorithm in 3 age categories (0–6 days, 7–27 days and 28–59 days) in Pakistani infants aged 0–59 days.

Results

From September 2003 to November 2004, 2950 infants were enrolled (age group 0–6 days = 1633, 7–27 days = 817, 28–59 days = 500). The common reason for seeking care was umbilical redness or discharge (29.2%) in the 0–6 days group. Older age groups presented with cough (16.9%) in the 7–27 age group and (26.9%) infants in the 28–59 days group. Severe infection/sepsis was the most common primary diagnoses in infants requiring hospitalization across all age groups. The algorithm performed well in every age group, with a sensitivity of 85.9% and specificity of 71.6% in the 0–6 days age group and a sensitivity of 80.5% and specificity of 80.2% in the 28–59 days group; the sensitivity was slightly lower in the 7–27 age group (72.4%) but the specificity remained high (83.1%).
Are radiologists ready to evaluate true response to immunotherapy?
Authors: Yirgin Inci Kizildag , Erturk Sukru Mehmet , Dogan Izzet , Vatansever Sezai
Published: February 2021

Background

Standardized response criteria for evaluating patients radiological imaging have an essential role in oncological management. Immunotherapy, using immune checkpoint inhibitors (ICIs), including drugs targeting cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death protein 1 or its ligand, promise a new role that has demonstrated improvement management in cancers resistant to chemotherapy. This article reviews the literature to understand the most useful response evaluation criteria for optimal patient management under immunotherapy treatment. Areas that warrant further research are described.

Conclusion

In conclusion, ICIs have become more widely accepted and used by medical oncologists. Radiologists face challenges in assessing tumor response and becoming more involved in the management of treatment. The latest published immune-RECIST criteria can be used in response assessment, but further prospective evaluation is needed with registration clinical trials to be definitively validated.