bluuebunny/crossref_metadata_2025 huggingface dataset:
Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study
Authors: McAllister Peter , Winner Paul K. , Ailani Jessica , Buse Dawn C. , Lipton Richard B. , Chakhava George , Josiassen Mette Krog , Lindsten Annika , Mehta Lahar , Ettrup Anders , Cady Roger
Published: February 2022

Background

Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack.

Methods

RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4–15 migraine days per month in the 3 months prior to screening. Patients were randomized (1:1) to a 30-min infusion of eptinezumab 100 mg or placebo within 1–6 h of a qualifying migraine attack onset. The 6-item Headache Impact Test (HIT-6) and 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) were administered at baseline and week 4, and the Patient Global Impression of Change (PGIC) at week 4. A post hoc analysis of these measures was conducted in patients who reported headache pain freedom at 2 h after infusion start.

Results

Of 480 patients enrolled and treated, 476 completed the study and are included in this analysis. Mean baseline HIT-6 total scores indicated severe headache impact (eptinezumab, 65.1; placebo, 64.8). At week 4, the eptinezumab-treated group demonstrated clinically meaningful improvement in HIT-6 total score compared with placebo (mean change from baseline: eptinezumab, − 8.7; placebo, − 4.5; mean [95% CI] difference from placebo: − 4.2 [− 5.75, − 2.63], P < .0001), with greater reductions in each item score vs placebo (P < .001 all comparisons). Change in HIT-6 total score in the subgroup with 2-h headache pain freedom was − 13.8 for the eptinezumab group compared with − 4.9 for the placebo group. mTOQ-6 total score mean change from baseline favored eptinezumab (change, 2.1) compared with placebo (1.2; mean [95% CI] difference: 0.9 [0.3, 1.5], P < .01). More eptinezumab-treated patients rated PGIC as much or very much improved than placebo patients (59.3% vs 25.9%).

Conclusions

When administered during a migraine attack, eptinezumab significantly improved patient-reported outcomes after 4 weeks compared with placebo, with particularly pronounced effects in patients reporting headache pain freedom at 2 h after infusion start.

Trial registration

ClinicalTrials.gov Identifier: NCT04152083. November 5, 2019.
Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a ≥ 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials
Authors: Lipton Richard B. , Charleston Larry , Tassorelli Cristina , Brevig Thomas , Hirman Joe , Cady Roger
Published: February 2022

Background

PROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide–targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50– < 75% MRR.

Methods

PROMISE-1 and PROMISE-2 were phase 3, randomized, double-blind, placebo-controlled studies. This analysis included patients from both studies treated with eptinezumab 100 mg or 300 mg who experienced ≥ 75% and ≥ 50–< 75% MRR over Weeks 1–12 (wks1–12). In both studies, HRQoL was measured by the 36-item Short-Form Health Survey (SF-36) and acute medication usage. PROMISE-2 also included the 6-item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC).

Results

In PROMISE-1, a total of 115/443 (26.0%; 100 mg,n = 49, 300 mg,n = 66) and 120/443 (27.0%; 100 mg,n = 61, 300 mg,n = 59) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. In PROMISE-2, a total of 211/706 (30.0%; 100 mg,n = 95; 300 mg,n = 116) and 209/706 (29.6%; 100 mg,n = 110, 300 mg,n = 99) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. EM and CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12 showed reduced use of acute headache medication and increased HRQoL to normative levels across SF-36 domains of bodily pain, social functioning, and physical functioning. In CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12, the mean change in HIT-6 total score with eptinezumab (pooled) was − 11.7 and − 7.6, respectively. “Very much” or “much” improvement responses were reported in 41.8% and 16.5% on PI-MBS and 36.2% and 20.0% on PGIC in ≥ 75% and ≥ 50–< 75% MRR, respectively.

Conclusion

Eptinezumab treatment induced a ≥ 75% MRR over wks1–12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50–< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM.

Trial registration

ClinicalTrials.govidentifiers: NCT02559895 (PROMISE-1), NCT02974153 (PROMISE-2).
The potential use of mitochondrial ribosomal genes (12S and 16S) in DNA barcoding and phylogenetic analysis of trematodes
Authors: Chan Abigail Hui En , Saralamba Naowarat , Saralamba Sompob , Ruangsittichai Jiraporn , Thaenkham Urusa
Published: February 2022

Background

Genetic markers like the nuclear ribosomal RNA (rRNA) genes, internal transcribed spacer regions, mitochondrial protein-coding genes, and genomes have been utilized for molecular identification of parasitic trematodes. However, challenges such as the design of broadly applicable primers for the vast number of species within Digenea and the genetic markers’ ability to provide sufficient species-level resolution limited their utility. This study presented novel and broadly applicable primers using the mitochondrial 12S and 16S rRNA genes for Digenea and aimed to show their suitability as alternative genetic markers for molecular identification of orders Plagiorchiida, Echinostomida, and Strigeida.

Results

Our results revealed that the mitochondrial 12S and 16S rRNA genes are suitable for trematode molecular identification, with sufficient resolution to discriminate closely related species and achieve accurate species identification through phylogenetic placements. Moreover, the robustness of our newly designed primers to amplify medically important parasitic trematodes encompassing three orders was demonstrated through successful amplification. The convenience and applicability of the newly designed primers and adequate genetic variation of the mitochondrial rRNA genes can be useful as complementary markers for trematode molecular-based studies.

Conclusions

We demonstrated that the mitochondrial rRNA genes could be alternative genetic markers robust for trematode molecular identification and potentially helpful for DNA barcoding where our primers can be widely applied across the major Digenea orders. Furthermore, the potential of the mitochondrial rRNA genes for molecular systematics can be explored, enhancing their appeal for trematode molecular-based studies. The novelty of utilizing the mitochondrial rRNA genes and the designed primers in this study can potentially open avenues for species identification, discovery, and systematics in the future.
Exploring health provider’s knowledge on the home-based maternal and neonatal health care package in Rwanda
Authors: Nishimwe Clemence , Mchunu Gugu G.
Published: February 2022

Background

Rwanda implemented post-natal care home visits by maternal community health workers (M-CHWs) in charge of maternal and newborn health care in 2010 as a component of a home–based maternal and neonatal health care package (HB-MNHCP), this being a complementary strategy to facility-based postnatal care to improve survival. The country has not met its Sustainable Development Goal (SDG) 3 target of less than 70 maternal mortalities per 100,000 live births and less than 12 neonatal deaths per 1,000 live births. This study therefore aimed to establish the knowledge of the health providers, providing HB-MNHC services as part of their antenatal, delivery and postnatal care program, specifically the M-CHWs services.

Methods

The cross-sectional descriptive study included 79 purposively sampled health care providers who were directly involved in the various components of the HB-MNHCP, namely: professional nurses, midwives, M-CHW, social workers, supervisors and data managers. The Kibogora, Muhima and Nyamata District Hospitals and two rural, semi-urban and urban health facility were included. Data was collected using questionnaires from April to July 2018. This study followed the STROBE checklist form: Cross –sectional studies.

Results

Overall, 88.6% (n=70/79) of participants knew about the M-CHW three home visits scheduled during pregnancy, 73.4% (n=58/79) about the three postnatal home visits after birth when the weight was normal, and 64.6% (n=51/79) about the five PNC home visits for low birth weights. Most (97.5%, n=77/79) knew that the mother and newborn should be screened during the same M-CHW home visits, and 87.2% (n= 68/79) were aware of the seven postnatal core competencies of delivering key maternal and newborn interventions during PNC home visits.

Conclusions

There were varying levels of knowledge among the HB-MNHCP staff, indicating the need for ongoing monitoring and training to ensure that the correct information is provided to the mothers throughout the antenatal and postnatal periods. While most of the M-CHWs appear to have had the correct knowledge, their executing of some activities needs to be monitored to ensure that they provide the required services, as this is an important step in lowering the maternal and infant mortality and enabling Rwanda to meet its SDG 3. Home visits by the M-CHWs could increase referrals and reduce maternal and newborn mortality.
Are human resource managers with good listening competency more likely to avoid job burnout?
Authors: Wang Yanqing , Chen Hong
Published: February 2022

Background

Listening is an important responsibilities of human resource managers, whether it will bring role stress to human resource managers, or lead to the risk of job burnout. This study aims to analyze the impact of listening competency on job burnout among human resource managers, and examine the mediating effect of role stress.

Methods

This study adopted a cross-sectional method to randomly select 500 human resource managers from China’s top ten human resource management cities to conduct an online questionnaire survey, and 232 valid samples were obtained. Descriptive statistical and one-way ANOVA were used to explore the status of job burnout among human resource managers in China. Correlation analysis, multiple linear regression and mediating effect analysis were employed to test the relationship between listening competency and job burnout, as well as the mediating effect of role stress.

Results

(1) 34.5% of the respondents reported mild burnout, while 3.0% respondents showed serious burnout. Emotional exhaustion was the most serious. (2) Those are good at listening could easily avoid job burnout. Among them, listening skills were conducive to reducing the degree of depersonalization of human resource managers, and empathy was more conducive to improving their personal sense of accomplishment. (3) The role stress had a significant mediating role in the relationship between listening competency and job burnout. Which means that listening competency can avoid job burnout by reducing role stress of human resource managers.

Conclusions

This study revealed the current situation of job burnout among human resource managers in China, and explored the influence of listening competency on job burnout. This study enriched the research content of job burnout, and provided references for preventing and intervening job burnout of human resource managers.
The predictive ability of occipital to C3 angle for dysphagia after occipitocervical fusion in patients with combined C2–3 Klippel-Feil syndrome
Authors: Zou Qiang , Wang Linnan , Yang Xi , Song Yueming , Liu Limin , Wang Lei , Zhou Zhongjie , Hu Bowen , Chen Taiyong , Liu Hao
Published: February 2022

Background

Improper occipitocervical alignment after occipitocervical fusion (OCF) may lead to devastating complications, such as dysphagia and/or dyspnea. The occipital to C2 angle (O-C2a), occipital and external acoustic meatus to axis angle (O-EAa) have been used to evaluate occipitospinal alignment. However, it may be difficult to identify the inferior endplate of the C2 vertebra in patients with C2–3 Klippel-Feil syndrome (KFS). The purpose of this study aimed to compare four different parameters for predicting dysphagia after OCF in patients with C2–3 KFS.

Methods

There were 40 patients with C2–3 KFS undergoing OCF between 2010 and 2019. Radiographs of these patients were collected to measure the occipital to C3 angle (O-C3a), O-C2a, occipito-odontoid angle (O-Da), occipital to axial angle (Oc-Axa), and narrowest oropharyngeal airway space (nPAS). The presence of dysphagia was defined as the patient complaining of difficulty or excess endeavor to swallow. Patients were divided into two groups according to whether they had postoperative dysphagia. We evaluated the relationship between each of the angle parameters and nPAS and analyzed their influence to the postoperative dysphagia.

Results

The incidence of dysphagia after OCF was 25% in patients with C2–3 KFS. The Oc-Axa, and nPAS were smaller in the dysphagia group compared to non-dysphagia group at the final follow-up (p < 0.05). Receiver-operating characteristic (ROC) curves showed that dO-C3a had the highest accuracy as a predictor of the dysphagia with an area under the curve (AUC) of 0.868. The differences in O-C3a, O-C2a, O-Da, and Oc-Axa were all linearly correlated with nPAS scores preoperatively and at the final follow-up within C2–3 KFS patients, while there was a higher R2 value between the dO-C3a and dnPAS. Multiple linear regression analysis showed that the difference of O-C3a was the only significant predictor for dnPAS (β = 0.670, p < 0.001).

Conclusions

The change of O-C3a (dO-C3a) is the most reliable indicator for evaluating occipitocervical alignment and predicting postoperative dysphagia in C2–3 KFS patients. Moreover, dO-C3a should be more than − 2° during OCF to reduce the occurrence of postoperative dysphagia.
Chemotherapy during the last 30 days of life and the role of palliative care referral, a single center experience
Authors: Woldie Indryas , Elfiki Tarek , Kulkarni Swati , Springer Colvin , McArthur Eric , Freeman Nicole
Published: February 2022

Background

Chemotherapy use closer to the end of life is a marker of poor-quality care. There are now multiple studies and local reviews addressing this issue. Understanding the practice locally will give valuable insight and opportunity for improvement.

Methods

The study is a retrospective chart review of patients on chemotherapy at the Windsor Regional Cancer Center who died between April 1st, 2016 to December 31st, 2018. Information on demographics, type of cancer, type, intent and route of chemotherapy, line of chemotherapy, referral to hospice and palliative care services was collected.

Results

A total of 681 patients on chemotherapy died between April 1st, 2016 to Dec 13th, 2018. Of these, 119 (17.4 %) died within 30 days following chemotherapy. Chemotherapy was parenteral (Intravenous and Subcutaneous) for the majority (75.2%) of the patients. Most (66.4%) of the patients died of disease progression. Intent for chemotherapy was palliative in 85% of patients, adjuvant/neoadjuvant in 6.6% and curative in 8.4% of the patients. Chemotherapy was 1st, 2nd, 3rd line or more in 67.4%, 21.3% and 11.3% of the patients respectively. The type of chemotherapy was conventional in 74.3% of patients and targeted/immunotherapy in 25.7% of patients.

Of the variables studied, lack of palliative referral and having lung cancer or melanoma were significantly associated with higher risk of getting chemotherapy within the last 30 days of life. The odds of getting chemotherapy within the last 30 days of life was 0.35, 95% CI (0.24-0.53), P <0.001 for those who were referred to palliative care. On the other hand, the odds of getting chemotherapy were 4.18, 95% CI (1.17-13.71), P = 0.037 and 2.21, 95% CI (1.24-4.01), P = 0.037 for those with melanoma and lung cancer respectively. In addition, those with early referral to palliative care (90 days or more prior to death) were least likely to receive chemotherapy within the last 30 days of life.

Conclusion

Administration of chemotherapy within the last 30 days of life could cause unnecessary suffering to patients and cost to society. Early referral to palliative care was significantly associated with reduced risk of getting chemotherapy within the last 30 days of life in this study. Prospective study is recommended to further investigate the role of early palliative referral on use of chemotherapy during the last 30 days of life.
Stay mindfully active during the coronavirus pandemic: a feasibility study of mHealth-delivered mindfulness yoga program for people with Parkinson’s disease
Authors: Kwok Jojo Yan Yan , Lee Jung Jae , Choi Edmond Pui Hang , Chau Pui Hing , Auyeung Man
Published: February 2022

Importance

Patients with long-term neurological conditions, such as Parkinson’s disease (PD), are particularly vulnerable to the public health measures taken to combat the COVID-19 pandemic. The inaccessibility of center-based rehabilitation further aggravated their motor dysfunctions as well as mental distress, leading to exacerbation of motor and non-motor symptoms, high healthcare utilization and worsened health-related quality of life (HRQOL).

Objective

This study aimed to evaluate the feasibility, safety, and preliminary effects of the mHealth-delivered home-based mindfulness yoga program on functional balance, motor symptoms, mental health and HRQOL in patients with PD.

Design, setting and participants

This prospective, single-arm, non-randomized feasibility study adopted a sequential explanatory mixed-method design. Adults (aged ≥ 18) with a clinical diagnosis of idiopathic Parkinson’s disease (Hoehn and Yahr stage I to III) who were able to stand unaided and walk with or without an assistive device were enrolled via convenience sampling.

Intervention

Home-based mindfulness yoga training were delivered via video-conferencing software (Zoom) in eight bi-weekly 90-min sessions.

Main outcomes and measures

This current study measured functional balance, motor symptoms, perceived balance confidence, perceived freezing of gait symptoms, anxiety and depression, mindfulness and HRQOL using a tele-assessment approach at baseline and 1-week post-intervention. All participants were invited to attend qualitative individual interviews to explore their experience of using online mindfulness yoga program as a lifestyle intervention for PD rehabilitation.

Results

Among the ten patients, 80% completed the program with an adherence rate of 98.4%. All participants were able to learn and practice mindfulness yoga following the eight bi-weekly online mindfulness yoga training sessions, without any significant adverse events. Tele-assessment of outcomes were feasible and uneventful. Qualitative feedback revealed participants had a high preference of using the tele-rehabilitation approach to stay mindful and being active, both physically and socially, while confronting the changes brought by COVID-19 pandemic.

Conclusions and relevance

The mHealth-delivered home-based mindfulness yoga intervention was feasible, safe, and well-accepted among people with PD to relieve the burden brought by COVID-19 pandemic. Future studies should adopt a design with enhanced rigor, a comparison group, and enlarged sample size to evaluate the efficacy of the program in patients with long-term neurological conditions and/or physical impairments. We recommend a longer intervention duration of at least 8 weeks to enhance the psychophysiological effects.
Burnout and dropout intention in medical students: the protective role of academic engagement
Authors: Abreu Alves Sara , Sinval Jorge , Lucas Neto Lia , Marôco João , Gonçalves Ferreira António , Oliveira Pedro
Published: February 2022

Introduction

The influence of burnout, academic engagement, and their interaction in dropout intention among medical students should be further studied. Current research shows its consequences are relevant, however, there is little understanding on burnout and academic engagement moderation in dropout intention. The current study tested a model that relates the effects of coping strategies, social support satisfaction, general distress on academic engagement, burnout, and dropout intention, on medical students.

Methods

Through an online survey a non-probabilistic sample of one Medical Faculty's 1st- and 2nd-year students was recruited. Cross-sectional data were collected using psychometric instruments (Maslach Burnout Inventory – Student Survey, Social Support Satisfaction Scale for College Students, Brief COPE Scale for College Students, University Student Engagement Inventory, and Depression, Anxiety and Stress Scale), sociodemographic and academic variables, and analyzed using structural equation modeling.

Results

532 students (76% response rate) enrolled in the study. Latent variables structural model presented a satisfactory fit to the data and confirmed the expected negative path between burnout and dropout intention (βDI<-SB=0.430;p<.001) and the latent moderation burnout x engagement (βDI<-SB*SE=-0.218;p<.001).

Conclusion

Academic engagement attenuates the impact of burnout on dropout intention, working as a protective factor. Social support satisfaction and adaptive coping are associated with increased levels of academic engagement, and general distress and maladaptive coping are associated with burnout. Medical Schools should develop interventions to prevent dropout intention, tackle students' stress and academic challenges, and develop their academic engagement levels.
Matrix analyses of pharmaceutical products for the years 2017 to 2019 among public health facilities in Hadiya zone, Ethiopia: a cross-sectional descriptive study
Authors: Yohannes Tamirat , Boche Bekele , Birhanu Nimona , Gudeta Tadesse
Published: February 2022

Background

To date, global healthcare spending becomes a primary concern, and pharmaceutical costs are the main drivers. The issue is more pressing in developing countries like Ethiopia. However, there is a scantiness of comprehensive data on inventory control practices in health facilities. This study, therefore, aimed to assess the criticality, financial value, and consumption patterns of pharmaceuticals using inventory matrix analyses and explore the related challenges.

Methods

A cross-sectional study supplemented with qualitative assessments was carried out from December 2020 to January 2021 in public health facilities. Three hospitals and 14 health centers were proportionally selected using a simple random sampling technique. Self-administered questionnaires and review of logistics documents and databases like Dagu-Facility were used to obtain the quantitative data. The data were analyzed using excel spreadsheets and SPSS version 23. We gathered the qualitative data through face-to-face in-depth interviews.

Results

The facilities spent 66,312,277.0 Ethiopian birrs to procure 518 pharmaceuticals between 2017 and 2019. Of the total products, 68 (13.1%) belonged to class A and 353 (68.1%) belonged to class C. Among 427 items identified by VEN analysis, 202 (47.3%) were vitals, and 201 (47.1%) were essential products making the highest proportions. Cross-tabulations of ABC and VEN showed that 230 (53.9%) items formed category I, representing 84.3% of total expenditures. Sterile surgical gloves #7.5, amoxicillin capsules, examination gloves, and 40% dextrose injection were among the top-ten high-value closing inventories, accounting for 21% of class X items. The fast-moving items were the most prevalent in all years, accounting for more than 45%, and shared the maximum expenditure, up to 90%. Scarcity of infrastructure and skilled human resources, shortage of pharmaceuticals and problems with suppliers, and management issues were the major challenges in the health facilities.

Conclusion

Most of the items identified by ABC-VEN and FSN-XYZ were Category one, i.e., mainly vital costly products and a few fast-moving items with high closing inventory values, respectively, suggesting close supervision. However, several issues became impediments. Hence, facilities should alleviate the bottlenecks and monitor the stock status to prevent theft and stock out.
Satellitome comparison of two oedipodine grasshoppers highlights the contingent nature of satellite DNA evolution
Authors: Camacho Juan Pedro M. , Cabrero Josefa , López-León María Dolores , Martín-Peciña María , Perfectti Francisco , Garrido-Ramos Manuel A. , Ruiz-Ruano Francisco J.
Published: February 2022

Background

The full catalog of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago.

Results

We found that about one third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species.

Conclusions

Our analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.
Ex vivo observation of granulocyte activity during thrombus formation
Authors: Morozova Daria S. , Martyanov Alexey A. , Obydennyi Sergei I. , Korobkin Julia-Jessica D. , Sokolov Alexey V. , Shamova Ekaterina V. , Gorudko Irina V. , Khoreva Anna L. , Shcherbina Anna , Panteleev Mikhail A. , Sveshnikova Anastasia N.
Published: February 2022

Background

The process of thrombus formation is thought to involve interactions between platelets and leukocytes. Leukocyte incorporation into growing thrombi has been well established in vivo, and a number of properties of platelet-leukocyte interactions critical for thrombus formation have been characterized in vitro in thromboinflammatory settings and have clinical relevance. Leukocyte activity can be impaired in distinct hereditary and acquired disorders of immunological nature, among which is Wiskott-Aldrich Syndrome (WAS). However, a more quantitative characterization of leukocyte behavior in thromboinflammatory conditions has been hampered by lack of approaches for its study ex vivo. Here, we aimed to develop an ex vivo model of thromboinflammation, and compared granulocyte behavior of WAS patients and healthy donors.

Results

Thrombus formation in anticoagulated whole blood from healthy volunteers and patients was visualized by fluorescent microscopy in parallel-plate flow chambers with fibrillar collagen type I coverslips. Moving granulocytes were observed in hirudinated or sodium citrate-recalcified blood under low wall shear rate conditions (100 s−1). These cells crawled around thrombi in a step-wise manner with an average velocity of 90–120 nm/s. Pre-incubation of blood with granulocyte priming agents lead to a significant decrease in mean-velocity of the cells and increase in the number of adherent cells. The leukocytes from patients with WAS demonstrated a 1.5-fold lower mean velocity, in line with their impaired actin polymerization. It is noteworthy that in an experimental setting where patients’ platelets were replaced with healthy donor’s platelets the granulocytes’ crawling velocity did not change, thus proving that WASP (WAS protein) deficiency causes disruption of granulocytes’ behavior. Thereby, the observed features of granulocytes crawling are consistent with the neutrophil chemotaxis phenomenon. As most of the crawling granulocytes carried procoagulant platelets teared from thrombi, we propose that the role of granulocytes in thrombus formation is that of platelet scavengers.

Conclusions

We have developed an ex vivo experimental model applicable for observation of granulocyte activity in thrombus formation. Using the proposed setting, we observed a reduction of motility of granulocytes of patients with WAS. We suggest that our ex vivo approach should be useful both for basic and for clinical research.
Translating research into practice—implementation recommendations for pediatric rheumatology; Proceedings of the childhood arthritis and rheumatology research alliance 2020 implementation science retreat
Authors: Yildirim-Toruner Cagri , Pooni Rajdeep , Goh Y. Ingrid , Becker-Haimes Emily , Dearing James W. , Fernandez Maria E. , Morgan Esi M. , Parry Gareth , Burnham Jon M. , Ardoin Stacy P. , Barbar-Smiley Fatima , Chang Joyce C. , Chiraseveenuprapund Peter , Del Gaizo Vincent , Eakin Guy , Johnson Lisa C. , Kimura Yukiko , Knight Andrea M. , Kohlheim Melanie , Lawson Erica F. , Lo Mindy S. , Pan Nancy , Ring Andrea , Ronis Tova , Sadun Rebecca E. , Smitherman Emily A. , Taxter Alysha J. , Taylor Janalee , Vehe Richard K. , Vora Sheetal S. , Weiss Jennifer E. , von Scheven Emily ,   MAS for the CARRA Implementation Science Workgroup
Published: February 2022

The translation of research findings into clinical practice is challenging, especially fields like in pediatric rheumatology, where the evidence base is limited, there are few clinical trials, and the conditions are rare and heterogeneous. Implementation science methodologies have been shown to reduce the research- to- practice gap in other clinical settings may have similar utility in pediatric rheumatology. This paper describes the key discussion points from the inaugural Childhood Arthritis and Rheumatology Research Alliance Implementation Science retreat held in February 2020. The aim of this report is to synthesize those findings into an Implementation Science Roadmap for pediatric rheumatology research. This roadmap is based on three foundational principles: fostering curiosity and ensuring discovery, integration of research and quality improvement, and patient-centeredness. We include six key steps anchored in the principles of implementation science. Applying this roadmap will enable researchers to evaluate the full range of research activities, from the initial clinical design and evidence acquisition to the application of those findings in pediatric rheumatology clinics and direct patient care.
Occupation and prostate Cancer risk: results from the epidemiological study of prostate cancer (EPICAP)
Authors: Bijoux Wendy , Cordina-Duverger Emilie , Balbolia Soumaya , Lamy Pierre-Jean , Rebillard Xavier , Tretarre Brigitte , Cenee Sylvie , Menegaux Florence
Published: February 2022

Background

Although prostate cancer (PCa) is the most frequent male cancer in industrialized countries, little is known about its aetiology. The literature has suggested an influence of the environment, including occupational exposures, but results are inconsistent. In this context, we investigated PCa risk associated to employment among several occupations using data from EPICAP study.

Methods

EPICAP is a French population-based case-control study including 819 PCa incident cases and 879 controls frequency-matched on age. In-person interviews gathered data on potential risk factors and lifetime occupational histories for each job held at least 6 months. Then, occupations were coded using ISCO 68. Unconditional logistic regressions were performed to assess the association between occupations (ever occupied and by duration) and PCa risk, whether all and aggressive, after adjusting for potential confounders.

Results

For ≥10 years of employment, we found positive associations with PCa, whether overall and aggressive, among Medical, Dental and Veterinary workers (OR (odds ratios) =5.01 [95% confidence interval] [1.27; 19.77]), Members of the armed forces (OR = 5.14 [0.99; 26.71]) and Fishermen, hunters and related workers (OR = 4.58 [1.33; 15.78]); whether overall and non-aggressive PCa, among Legislative officials and Government administrators (OR = 3.30 [1.10; 9.84]) or Managers (OR = 1.68 [1.18; 2.41]); however a negative association, whether overall and non-aggressive PCa, among Material-Handling and Related Equipment Operators, Dockers and Freight Handlers (OR = 0.40 [0.17; 0.97]).

Conclusion

Excess PCa risks were observed in the EPICAP study mostly among white collar workers exposed to several factors in their work environment. These emerging associations can be used to lead future research investigating specific occupational exposures.
HealthCare educational differences in pain management, adverse childhood experiences and their relationship to substance use disorder education
Authors: Ojeda Myriam Shaw , Chen Aleda M. H. , Miracle Tessa , Delaney Elizabeth , Freiermuth Caroline E. , Sprague Jon E.
Published: February 2022

Background

In order to assist the State of Ohio in the United States in addressing the opioid epidemic, the Ohio Attorney General appointed experts in a variety of academic disciplines to the Scientific Committee on Opioid Prevention and Education (SCOPE). The focus of SCOPE is the application of scientific principles in the development of prevention and educational strategies for reducing substance use disorder (SUD). One area of focus for SCOPE was SUD education of healthcare professionals. The objective of the present was to identify the content and extent to which future healthcare professionals are trained in pain management, SUD, and adverse childhood experiences (ACEs).

Methods

In December of 2019, a survey was distributed to 49 healthcare professional schools in Ohio that included the following disciplines: medicine, pharmacy, advanced practice registered nurse (APRN), physician assistant, dentistry, and optometry. The survey included four domains: initial screening of patients, training in SUD, training in care for patients at high risk for SUD, and education in evaluating patients for ACEs. Descriptive statistics were calculated.

Results

Thirty one of the forty-nine schools completed the survey. Most disciplines indicated that some form of basic training in the principles of SUD were taught in their core curriculum. The training on ethical issues surrounding SUD were not as widely covered (range 0-62.5%). Medicine, APRN, physician assistant, and pharmacy schools had a “moderate” to “great” extent of pharmacologic therapy curriculum integration. Other pain management strategies were “somewhat” to “moderately” integrated. There were variations seen in training on risk of medication misuse based on various contributors to health. At least 67.7% of medicine, APRN, physician assistant, and pharmacy programs included motivational interviewing training. The extent to which schools integrated education regarding ACEs into their curriculum varied from 0 to 66.7%.

Conclusions

The study finding suggests a need for a unified, consistent, and expanded training requirement in the foundations of pain management, SUD, and ACEs in professional healthcare education.
Use of bronchoscopic steam thermal ablation (BTVA) in a clinically compromised patient
Authors: Marchese Roberto , Lo Nigro Chiara , Scaduto Federica
Published: February 2022

Background

Bronchoscopic lung volume reduction (BLVR) techniques improve lung function and increase exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) and BLVR treatment is included in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines for these patients. BTVA (Intervapor Uptake Medical, Tustin, CA, USA) represents a recent therapy of this group that allows to treat sublobar areas and for this reason is used clinically compromised patients, like in this case report.

Case presentation

In this paper we describe a case report of an 85-year-old male with severe respiratory failure and a diagnosis of emphysema presented with dyspnea and clinical worsening, despite the best medical therapy practiced. For comorbidity and pathology’s features he was excluded from surgical treatment options, like lung volume reduction surgical (LVRS) and from positioning of endobronchial valves (EBV) for the presence of collateral ventilation and he was addressed to BTVA. The procedure was successful for this patient.

Conclusions

This case supports recent suggestions that BTVA can be a good alternative treatment for patients properly selected.
Detection of cerebral hypoperfusion with a dynamic hyperoxia test using brain oxygenation pressure monitoring
Authors: Gargadennec Thomas , Ferraro Gioconda , Chapusette Rudy , Chapalain Xavier , Bogossian Elisa , Van Wettere Morgane , Peluso Lorenzo , Creteur Jacques , Huet Olivier , Sadeghi Niloufar , Taccone Fabio Silvio
Published: February 2022

Introduction

Brain multimodal monitoring including intracranial pressure (ICP) and brain tissue oxygen pressure (PbtO2) is more accurate than ICP alone in detecting cerebral hypoperfusion after traumatic brain injury (TBI). No data are available for the predictive role of a dynamic hyperoxia test in brain-injured patients from diverse etiology.

Aim

To examine the accuracy of ICP, PbtO2and the oxygen ratio (OxR) in detecting regional cerebral hypoperfusion, assessed using perfusion cerebral computed tomography (CTP) in patients with acute brain injury.

Methods

Single-center study including patients with TBI, subarachnoid hemorrhage (SAH) and intracranial hemorrhage (ICH) undergoing cerebral blood flow (CBF) measurements using CTP, concomitantly to ICP and PbtO2monitoring. Before CTP, FiO2was increased directly from baseline to 100% for a period of 20 min under stable conditions to test the PbtO2catheter, as a standard of care. Cerebral monitoring data were recorded and samples were taken, allowing the measurement of arterial oxygen pressure (PaO2) and PbtO2at FiO2100% as well as calculation of OxR (= ΔPbtO2/ΔPaO2). Regional CBF (rCBF) was measured using CTP in the tissue area around intracranial monitoring by an independent radiologist, who was blind to the PbtO2values. The accuracy of different monitoring tools to predict cerebral hypoperfusion (i.e., CBF < 35 mL/100 g × min) was assessed using area under the receiver-operating characteristic curves (AUCs).

Results

Eighty-seven CTPs were performed in 53 patients (median age 52 [41–63] years—TBI,n = 17; SAH,n = 29; ICH,n = 7). Cerebral hypoperfusion was observed in 56 (64%) CTPs: ICP, PbtO2and OxR were significantly different between CTP with and without hypoperfusion. Also, rCBF was correlated with ICP (r = − 0.27;p = 0.01), PbtO2(r = 0.36;p < 0.01) and OxR (r = 0.57;p < 0.01). Compared with ICP alone (AUC = 0.65 [95% CI, 0.53–0.76]), monitoring ICP + PbO2(AUC = 0.78 [0.68–0.87]) or ICP + PbtO2 + OxR (AUC = 0.80 (0.70–0.91) was significantly more accurate in predicting cerebral hypoperfusion. The accuracy was not significantly different among different etiologies of brain injury.

Conclusions

The combination of ICP and PbtO2monitoring provides a better detection of cerebral hypoperfusion than ICP alone in patients with acute brain injury. The use of dynamic hyperoxia test could not significantly increase the diagnostic accuracy.
Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation
Authors: Li Yangping , Wang Feng , Teng Peng , Ku Li , Chen Li , Feng Yue , Yao Bing
Published: February 2022

Background

Circular RNAs (circRNAs), a novel class of poorly conserved non-coding RNAs that regulate gene expression, are highly enriched in the human brain. Despite increasing discoveries of circRNA function in human neurons, the circRNA landscape and function in developing human oligodendroglia, the myelinating cells that govern neuronal conductance, remains unexplored. Meanwhile, improved experimental and computational tools for the accurate identification of circRNAs are needed.

Results

We adopt a published experimental approach for circRNA enrichment and develop CARP (CircRNA identification using A-tailing RNase R approach and Pseudo-reference alignment), a comprehensive 21-module computational framework for accurate circRNA identification and quantification. Using CARP, we identify developmentally programmed human oligodendroglia circRNA landscapes in the HOG oligodendroglioma cell line, distinct from neuronal circRNA landscapes. Numerous circRNAs display oligodendroglia-specific regulation upon differentiation, among which a subclass is regulated independently from their parental mRNAs. We find that circRNA flanking introns often containcis-regulatory elements for RNA editing and are predicted to bind differentiation-regulated splicing factors. In addition, we discover novel oligodendroglia-specific circRNAs that are predicted to sponge microRNAs, which co-operatively promote oligodendroglia development. Furthermore, we identify circRNA clusters derived from differentiation-regulated alternative circularization events within the same gene, each containing a common circular exon, achieving additive sponging effects that promote human oligodendroglia differentiation.

Conclusions

Our results reveal dynamic regulation of human oligodendroglia circRNA landscapes during early differentiation and suggest critical roles of the circRNA-miRNA-mRNA axis in advancing human oligodendroglia development.
Efficacy of cognitive behavioral therapy on aggressive behavior in children with attention deficit hyperactivity disorder and emotion dysregulation: study protocol of a randomized controlled trial
Authors: Vacher C. , Romo L. , Dereure M. , Soler M. , Picot M. C. , Purper-Ouakil D.
Published: February 2022

Background

Attention deficit hyperactivity disorder (ADHD) is frequently associated with emotional dysregulation (ED). ED is characterized by excessive and inappropriate emotional reactions compared to social norms, uncontrolled and rapid shifts in emotion, and attention focused on emotional stimuli. Few studies have evaluated non-pharmacological interventions to improve ED in children with ADHD. The current randomized controlled trial assesses the efficacy of a cognitive behavioral therapy (CBT) intervention compared with a theater-based intervention (TBI) in children with ADHD and ED.

Methods

Sixty-eight 7- to 13-year-old children with ADHD and ED will be recruited and randomly assigned to the CBT or TBI group. CBT aims to reduce ED by teaching anger management strategies. TBI seeks to reduce ED by improving emotion understanding and expression through mimics and movement. In both groups, children participate in 15 1-h sessions, and parents participate in 8 sessions of a parent management program. The primary outcome measure is the change in the “Aggression” sub-score of the Child Behavior Checklist (CBCL). Secondary outcome measures include overall impairment (Children’s Global Assessment Scale, Strengths and Difficulties Questionnaire), personality profile (Hierarchical Personality Inventory for Children), executive function (Behavioral Rating Inventory of Executive Function), quality of life (Kidscreen-27), parental stress (Parenting Stress Index, 4th edition), parental depression (Beck Depression Inventory-II), and impact of child disorders on the quality of the family life (Parental Quality of Life and Developmental Disorder).

Discussion

Children with ADHD and ED are at risk of functional impairment and poor outcomes and have specific therapeutic needs. This randomized controlled trial wants to assess non-pharmacological treatment options for this population.

Trial registration

Clinicaltrials.gov.NCT03176108. Registered on June 5, 2017.
Bottom-up synthetic ecology study of microbial consortia to enhance lignocellulose bioconversion
Authors: Lin Lu
Published: February 2022

Lignocellulose is the most abundant organic carbon polymer on the earth. Its decomposition and conversion greatly impact the global carbon cycle. Furthermore, it provides feedstock for sustainable fuel and other value-added products. However, it continues to be underutilized, due to its highly recalcitrant and heterogeneric structure. Microorganisms, which have evolved versatile pathways to convert lignocellulose, undoubtedly are at the heart of lignocellulose conversion. Numerous studies that have reported successful metabolic engineering of individual strains to improve biological lignin valorization. Meanwhile, the bottleneck of single strain modification is becoming increasingly urgent in the conversion of complex substrates. Alternatively, increased attention has been paid to microbial consortia, as they show advantages over pure cultures, e.g., high efficiency and robustness. Here, we first review recent developments in microbial communities for lignocellulose bioconversion. Furthermore, the emerging area of synthetic ecology, which is an integration of synthetic biology, ecology, and computational biology, provides an opportunity for the bottom-up construction of microbial consortia. Then, we review different modes of microbial interaction and their molecular mechanisms, and discuss considerations of how to employ these interactions to construct synthetic consortia via synthetic ecology, as well as highlight emerging trends in engineering microbial communities for lignocellulose bioconversion.
Genetic and molecular biology of gastric cancer among Iranian patients: an update
Authors: Abbaszadegan Mohammad Reza , Mojarrad Majid , Rahimi Hamid Reza , Moghbeli Meysam
Published: February 2022

Background

There is a declining trend of gastric cancer (GC) incidence in the world during recent years that is related to the development of novel diagnostic methods. However, there is still a high ratio of GC mortality among the Iranian population that can be associated with late diagnosis. Despite various reports about the novel diagnostic markers, there is not any general and standard diagnostic panel marker for Iranian GC patients. Therefore, it is required to determine an efficient and general panel of molecular markers for early detection.

Main body of the abstract

In the present review, we summarized all of the reported markers until now among Iranian GC patients to pave the way for the determination of a population-based diagnostic panel of markers. In this regard, we categorized these markers in different groups based on their involved processes to know which molecular process is more frequent during the GC progression among Iranians.

Conclusion

We observed that the non-coding RNAs are the main factors involved in GC tumorigenesis in this population.