bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular studies of Iranian populations support the morphology-based taxonomic separation of Medicago rigidula and M. rigiduloides
Authors: BAYAT MITRA , ASSADI MOSTAFA , SMALL ERNEST , MEHREGAN IRAJ
Published: September 2021

A comprehensive study was undertaken to understand the genetic status and help to clarify the division of Medicago rigidula (largely European) and Medicago rigiduloides (largely Asian). Genetic diversity parameters collectively suggested a low genetic diversity (avg. Ho, 0.073; He, 0.374) accompanied by high population differentiation (avg. F, 0.832; Gst, 0.362).  Structure analysis divided 71 individuals (14 Iranian populations) into two highly distinct genetic groups (K=2) with significant genetic homogeneity. It also indicated the strong effect of the selfing mating-system as the main reason for the genetic diversity status and population structure. The population grouping was strongly confirmed by various clustering methods. Populations from north and northwestern Iran made up a distinctive genetic group corresponding to M. rigidula while the second group corresponding to M. rigiduloides harboured the western and two of the northwestern populations. The outcomes of this study provide the first reliable molecular evidence supporting the M. rigidula-M. rigiduloides separation previously suggested by morphology.
New basal taxa of South African Apioninae (Coleoptera: Curculionoidea: Brentidae)
Authors: WANAT MAREK
Published: September 2021

Four new genera, six new species and one new subspecies of the brentid subfamily Apioninae are described from the Republic of South Africa (R.S.A.), all representing ancient fauna with Gondwanan roots. The new genera are: Rhynchitapion gen. n., with Rh. variiforme sp. n. (the type-species) and Rh. pallidum sp. n., Apodytapion gen. n., with A. stepniewskii sp. n., Turnerapion gen. n., with T. pondoense sp. n., and Lepanomidius gen. n., with L. ruthmuellerae sp. n. (the type-species) and L. magdaloides sp. n. The primitive genus Lepanomus Balfour-Browne is re-described and a new subspecies of its type species, Lepanomus crinalis zuluensis ssp. n., is described from north-eastern R.S.A. In addition, Rhynchitapion usambarense sp. n. is described from Tanzania. An identification key to all 12 basal genera of South African Apioninae is presented and their higher systematics is discussed. Three new tribes are proposed in South African Apioninae: Rhynchitapiini trib. n., Apodytapiini trib. n., and Lepanomini trib. n., in addition to the existing basal Antliarhinini Schoenherr, 1823, Tanaini Schoenherr, 1839, Mecolenini Wanat, 2001, Apiomorphini Legalov, 2018, Setapiini Legalov, 2018, and derived Apionini Schoenherr, 1823. A temporary resignation from supertribal division of the subfamily is recommended after discussion.
Time scales of the Greenland Freshwater Anomaly in the Subpolar North Atlantic
Authors: Dukhovskoy D.S. , Yashayaev I. , Chassignet E.P. , Myers P.G. , Platov G. , Proshutinsky A.
Published: September 2021

The impact of increasing Greenland freshwater discharge on the subpolar North Atlantic (SPNA) remains unknown as there are uncertainties associated with the time scales of the Greenland freshwater anomaly (GFWA) in the SPNA. Results from numerical simulations tracking GFWA and an analytical approach are employed to estimate the response time suggesting a decadal time scale (13 years) required for the SPNA to adjust for increasing GFWA. Analytical solutions obtained for a long-lasting increase of freshwater discharge show a non-steady state response of the SPNA with increasing content of the GFWA. In contrast, solutions for a short-lived pulse of freshwater demonstrate different responses of the SPNA with a rapid increase of freshwater in the domain followed by an exponential decay after the pulse has passed. Derived theoretical relation between time scales show that residence time scales are time-dependent for a non-steady state case and asymptote the response time scale with time. Residence time of the GFWA deduced from Lagrangian experiments is close to and smaller than the response time, in agreement with the theory. The Lagrangian analysis shows dependence of the residence time on the entrance route of the GFWA and on the depth. The fraction of the GFWA exported through Davis Strait has limited impact on the interior basins, whereas the fraction entering the SPNA from the southwest Greenland shelf spreads into the interior regions. In both cases, the residence time of the GFWA increases with depth demonstrating long persistence of the freshwater anomaly in the subsurface layers.
A prognostic model (BATAP) with external validation for patients with transplant-associated thrombotic microangiopathy
Authors: Zhao Peng , Wu Ye-jun , He Yun , Chong Shan , Qu Qing-yuan , Deng Rui-xin , Sun Xiao-wan , Huang Qiu-sha , Liu Xiao , Zhu Xiao-lu , Wang Feng-rong , Zhang Yuan-yuan , Mo Xiao-dong , Han Wei , Wang Jing-zhi , Wang Yu , Chen Huan , Chen Yu-hong , Zhao Xiang-yu , Chang Ying-jun , Xu Lan-ping , Liu Kai-yan , Huang Xiao-jun , Zhang Xiao-hui
Published: September 2021

Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempted to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort, according to the time of transplantation, to perform external temporal validation. Patient age (odds ratio [OR], 2.371; 95% confidence interval [CI], 1.264-4.445), anemia (OR, 2.836; 95% CI, 1.566-5.138), severe thrombocytopenia (OR, 3.871; 95% CI, 2.156-6.950), elevated total bilirubin (OR, 2.716; 95% CI, 1.489-4.955), and proteinuria (OR, 2.289; 95% CI, 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was constructed according to the regression coefficients. The validated c-statistic was 0.816 (95%, CI, 0.766-0.867) and 0.756 (95% CI, 0.696-0.817) for the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.
Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis
Authors: Fanikos John , Marquis Kathleen , Buckley Leo , Tran Lena K. , McLaughlin Kevin , Golash Abby Jane , Campia Umberto , Piazza Gregory , Connors Jean M. , Goldhaber Samuel Z.
Published: September 2021

Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the risk of bleeding that accompanies systemic administration of higher alteplase doses. Some studies suggest that alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of alteplase under these conditions. Therefore, we undertook this in vitro study to determine the duration of alteplase stability. Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonic Endovascular System (with and without ultrasound) to simulate administration over 2, 4, and 6 hours. Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An enzyme-linked immunosorbent assay was used to measure alteplase concentrations at time 0 and at 15-minute intervals during simulated infusion. By using RP-HPLC in the absence of ultrasound, the alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. By using RP-HPLC for measurement, alteplase in the presence of ultrasound degraded steadily over time to ∼90% of its original amount in 120 minutes, ∼80% in 240 minutes, and ∼70% in 360 minutes. The remaining alteplase was available for enzymatic activity. Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated catheter-directed administration. Alteplase that did not degrade remained available for enzymatic activity.
Multisystem inflammatory syndrome in children (MIS-C): a mini-review
Authors: Giacalone Martina , Scheier Eric , Shavit Itai
Published: September 2021

Multisystem inflammatory syndrome in children (MIS-C) is a novel, life-threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This disease has created a diagnostic challenge due to overlap with Kawasaki disease (KD) and KD shock syndrome. The majority of patients with MIS-C present with the involvement of at least four organ systems, and all have evidence of a marked inflammatory state. Most patients show an increase in the level of at least four inflammatory markers (C-reactive protein, neutrophil count, ferritin, procalcitonin, fibrinogen, interleukin-6, and triglycerides). Therapy is primarily with immunomodulators, suggesting that the disease is driven by post-infectious immune dysregulation. Most patients, even those with severe cardiovascular involvement, recover without sequelae. Since coronary aneurysms have been reported, echocardiographic follow-up is needed.

Further study is needed to create uniform diagnostic criteria, therapy, and follow-up protocols.
A big white dot after CPR
Authors: Kola Sushma , Ginsburg Alexander D. , Harper Laura , Walker Laura E. , Braksick Sherri , Wijdicks Eelco F. M.
Published: September 2021

Introduction

Patients may remain comatose after the resumption of spontaneous circulation with cardiopulmonary resuscitation. A primary neurologic event may precede a cardiac standstill.

Case report

We present a 33-year-old patient with successful resuscitation for pulseless electrical activity and a “normal computed tomography (CT) scan.” Further scrutiny showed a hyperdense basilar artery sign (‘big white dot’) that led to a CT angiogram confirming an embolus to the proximal basilar artery. His examination showed fixed and dilated midsize (mesencephalic) pupils and extensor posturing. Endovascular retrieval of the clot was successful, but there was a devastating ischemic injury to the brainstem.

Conclusion

This case reminds us to consider neurologic causes of cardiac arrest.
Mining microbe–disease interactions from literature via a transfer learning model
Authors: Wu Chengkun , Xiao Xinyi , Yang Canqun , Chen JinXiang , Yi Jiacai , Qiu Yanlong
Published: September 2021

Background

Interactions of microbes and diseases are of great importance for biomedical research. However, large-scale of microbe–disease interactions are hidden in the biomedical literature. The structured databases for microbe–disease interactions are in limited amounts. In this paper, we aim to construct a large-scale database for microbe–disease interactions automatically. We attained this goal via applying text mining methods based on a deep learning model with a moderate curation cost. We also built a user-friendly web interface that allows researchers to navigate and query required information.

Results

Firstly, we manually constructed a golden-standard corpus and a sliver-standard corpus (SSC) for microbe–disease interactions for curation. Moreover, we proposed a text mining framework for microbe–disease interaction extraction based on a pretrained model BERE. We applied named entity recognition tools to detect microbe and disease mentions from the free biomedical texts. After that, we fine-tuned the pretrained model BERE to recognize relations between targeted entities, which was originally built for drug–target interactions or drug–drug interactions. The introduction of SSC for model fine-tuning greatly improved detection performance for microbe–disease interactions, with an average reduction in error of approximately 10%. The MDIDB website offers data browsing, custom searching for specific diseases or microbes, and batch downloading.

Conclusions

Evaluation results demonstrate that our method outperform the baseline model (rule-based PKDE4J) with an average $$F_1$$

F
1

-score of 73.81%. For further validation, we randomly sampled nearly 1000 predicted interactions by our model, and manually checked the correctness of each interaction, which gives a 73% accuracy. The MDIDB webiste is freely avaliable throuth http://dbmdi.com/index/
Effects of the COVID-19 pandemic on trauma-related emergency medical service calls: a retrospective cohort study
Authors: Azbel Michael , Heinänen Mikko , Lääperi Mitja , Kuisma Markku
Published: September 2021

Background

The COVID-19 pandemic has had profound effects on the utilization of health care services, including Emergency Medical Services (EMS). Social distancing measures taken to prevent the spread of the disease have greatly affected the functioning of societies and reduced or halted many activities with a risk of injury. The aim of this study was to report the effects of lockdown measures on trauma-related EMS calls in the Finnish capital area.

Methods

We conducted a retrospective cohort study of all EMS calls in the Helsinki University Hospital (HUH) catchment area between 1 January and 31 July 2020. Calls were identified from the HUH EMS database. Calls were grouped into pre-lockdown, lockdown, and post-lockdown periods according to the restrictions set by the Finnish government and compared to the mean number of calls for the corresponding periods in 2018 and 2019. Statistical comparisons were performed using Mann-Whitney U-test for weekly numbers and percentages.

Results

During the study period there was a total of 70,705 EMS calls, of which 14,998 (21.2%) were related to trauma; 67,973 patients (median age 61.6 years; IQR 35.3–78.6) were met by EMS. There was no significant change in the weekly number of total or trauma-related EMS calls during the pre-lockdown period. During the lockdown period, the number of weekly total EMS calls was reduced by 12.2% (p = 0.001) and the number of trauma-related calls was reduced by 23.3% (p = 0.004). The weekly number of injured patients met by EMS while intoxicated with alcohol was reduced by 41.8% (p = 0.002). During the post-lockdown period, the number of total and trauma-related calls and the number of injured patients intoxicated by alcohol returned to previous years’ levels.

Conclusions

The COVID-19 pandemic and social distancing measures reduced the number of trauma-related EMS calls. Lockdown measures had an especially significant effect on the number of injured patients intoxicated by alcohol met by the EMS.

Trial registration

Not applicable.
The effect of COVID-19 on mental well-being in Switzerland: a cross-sectional survey of the adult Swiss general population
Authors: Diaz Hernandez Laura , Giezendanner Stéphanie , Fischer Roland , Zeller Andreas
Published: September 2021

Background

In addition to the threat of the COVID-19 pandemic to physical health, mental health is challenged by the emotional response to the situation and the official measures taken to stop the pandemic. This study aimed to assess the prevalence of impaired mental well-being due to COVID-19 and explore associated factors.

Methods

The study was an observational, population-based, nationwide, cross-sectional online survey of a representative sample of the general Swiss population performed between March and April 2020. Participants reported on mental well-being, self-isolation/quarantine, their risk for developing severe COVID-19, and their work situation. Multivariable logistic regression analyses assessed risk factors for impaired mental well-being due to the pandemic.

Results

Data from 1022 individuals were analysed. The median age was 44 years (range 18 to 78) and 49% were women. A third of respondents reported that the COVID-19 pandemic impaired their mental well-being and almost half reported specific mental health concerns. Impaired mental well-being was associated with having health problems (OR = 1.88, 95% CI: 1.29–2.74, vs no problems), being or living with someone at risk for severe COVID-19 (OR = 1.38, 95% CI: 1–1.9,), smoking (OR = 1.8, 95% CI: 1.24–2.61), living in urban residential environments (OR = 1.62, 95% CI: 1.13–2.32, vs rural), not being able to work due to closed workplace (OR = 1.66, 95% CI: 1.04–2.67), aged between 18 and 29 years old (OR = 1.99, 95% CI: 1.32–3.01, vs 45 to 59 years old), and living in a single household (living with someone, OR = 0.65, 95% CI: 0.44–0.97,vs single household). Overall, the most significant covariates of impaired mental well-being were specific mental health concerns: feeling depressed (OR = 7.21, 95% CI: 4.5–11.55), feeling less pleasure in doing things than before (OR = 6.28, 95% CI: 4.1–9.62), feeling anxious (OR = 6.13, 95% CI: 3.91–9.59) and feeling lonely (OR = 4.08, 95% CI: 2.53–6.58).

Conclusion

Impaired mental well-being can carry long-term consequences. We encourage policymakers to implement strategies to promote mental health during this pandemic situation. Special attention should be addressed to the youngest, those at risk for severe COVID-19 and those with government-imposed work restrictions.
Epidemiology and risk factors for pyogenic liver abscess in the Calgary Health Zone revisited: a population-based study
Authors: Losie Jennifer A. , Lam John C. , Gregson Daniel B. , Parkins Michael D.
Published: September 2021

Background

Pyogenic liver abscess (PLA), although uncommon in North America, is associated with significant morbidity and mortality. We sought to re-examine the epidemiology, risk factors, and outcomes of PLA in a large, diverse Canadian health zone.

Methods

All Calgary Health Zone (CHZ) residents aged ≥20 with PLA between 2015 and 2017 were identified. Incidence and mortality rates were calculated using census data. Risk factors for PLA were identified using a multivariate analysis. Data was compared to 1999–2003 data, also collected in the CHZ.

Results

There were 136 patients diagnosed with PLA between 2015 and 2017. Incidence rate during this period increased significantly relative to 1999–2003 (3.7 vs 2.3 cases/100,000 population, p < 0.01), however, mortality rates remained similar. The microbiological composition of PLA did not change over this 15-year time period but the number of antimicrobial resistant isolates did increase (8% vs 1%, p = 0.04). The greatest risk factors for PLA relative to general populations included current malignancy, liver-transplant, end-stage renal disease, and cirrhosis. Thirty-day mortality was 7.4% and independent risk factors included polymicrobial bacteremia, absence of abscess drainage, congestive-heart failure, a history of liver disease, and admission bilirubin.

Conclusions

Pyogenic liver abscess is a health concern with rising incidence rate. The increasing prevalence of comorbidities in our population and factors that are associated with risk of PLA suggests this will continue to be an emerging diagnosis of concern. Increasing prevalence of antibiotic resistant organisms compounding unclear optimal treatment regimens is an issue that requires urgent study.
Might life-threatening acute pulmonary edema occur after using recombinant tissue plasminogen activator? A case report
Authors: Chen Xue-Bing , Qu Dong , Zhang Qing , Yue Xia , Qiao Dong-Fang
Published: September 2021

Background

Recombinant tissue plasminogen activator (rt-pa) is the first-line drug for the treatment of acute ischemic stroke, and can lead to some complications.There were rare reports of death due to acute pulmonary edema during rt-pa thrombolysis treatment.

Case presentation

This study reports a 30-year-old man was diagnosed with acute ischemic stroke and underwent rt-pa thrombolytic therapy. Finally he died despite active rescue.

Conclusions

The autopsy revealed that he died of acute pulmonary edema. This case suggests that it is necessary to pay close attention to the changes of vital signs during thrombolysis and be aware of possibility of pulmonary edema during thrombolysis.
18F-FDG-PET-MRI for the assessment of acute intestinal graft-versus-host-disease (GvHD)
Authors: Roll Wolfgang , Schindler Philipp , Masthoff Max , Strotmann Rebecca , Albring Jörn , Reicherts Christian , Weckesser Matthias , Noto Benjamin , Stelljes Matthias , Schäfers Michael , Evers Georg
Published: September 2021

Background

Graft versus host disease (GvHD) is a frequent complication of allogeneic stem cell transplantation (alloSCT), significantly increasing mortality. Previous imaging studies focused on the assessment of intestinal GvHD with contrast-enhanced MRI/CT or 18F-FDG-PET imaging alone. The objective of this retrospective study was to elucidate the diagnostic value of a combined 18F-FDG-PET-MRI protocol in patients with acute intestinal GvHD.

Methods

Between 2/2015 and 8/2019, 21 patients with acute intestinal GvHD underwent 18F-FDG-PET-MRI. PET, MRI and PET-MRI datasets were independently reviewed. Readers assessed the number of affected segments of the lower gastrointestinal tract and the reliability of the diagnosis on a 5-point Likert scale and quantitative PET (SUVmax, SUVpeak, metabolic volume (MV)) and MRI parameter (wall thickness), were correlated to clinical staging of acute intestinal GvHD.

Results

The detection rate for acute intestinal GvHD was 56.8% for PET, 61.4% for MRI and 100% for PET-MRI. PET-MRI (median Likert-scale value: 5; range: 4–5) offers a significantly higher reliability of the diagnosis compared to PET (median: 4; range: 2–5; p = 0.01) and MRI alone (median: 4; range: 3–5; p = 0.03). The number of affected segments in PET-MRI (rs = 0.677; p <  0.001) and the MV (rs = 0.703; p <  0.001) correlated significantly with the clinical stage. SUVmax (rs = 0.345; p = 0.14), SUVpeak (rs = 0.276; p = 0.24) and wall thickening (rs = 0.174; p = 0.17) did not show a significant correlation to clinical stage.

Conclusion

18F-FDG-PET-MRI allows for highly reliable assessment of acute intestinal GvHD and adds information indicating clinical severity.
Mediation pathways for reduced substance use among parents in South Africa: a randomized controlled trial
Authors: Massarwi Adeem Ahmad , Cluver Lucie , Meinck Franziska , Doubt Jenny , Lachman Jamie M. , Shenderovich Yulia , Green Ohad
Published: September 2021

Background

Substance use is a major public health concern worldwide. Alcohol and drug use have increased during recent decades in many low- and middle-income countries, with South Africa, where this study was conducted, having among the highest rates in the world. Despite existing evidence on the effectiveness of family-based interventions in reducing substance use among parents and caregivers in low- and middle-income countries, little is known about the mechanism of change that contributes to the reduction. This study investigated mediators of change in a parenting programme (Parenting for Lifelong Health [PLH]) on reducing substance use among parents and caregivers of adolescents through three potential mediators: parental depression, parenting stress and family poverty.

Methods

The current study used a pragmatic cluster randomized controlled trial design. The total sample comprised 552 parent and caregiver of adolescents M = 49.37(SD = 14.69) who were recruited from 40 communities in South Africa’s Eastern Cape. Participants completed a structured confidential self-report questionnaire at baseline and a follow-up test 5 to 9 months after the intervention. Structural equation modeling was conducted to investigate direct and indirect effects.

Results

Analyses indicated that the effect of the PLH intervention on reducing parental substance use was mediated in one indirect pathway: improvement in parental mental health (reduction in parental depression levels). No mediation pathways from the PLH intervention on parental substance use could be associated with parenting stress or family poverty.

Conclusions

The findings of the study suggest that intervention approaches targeting mental health among parents and caregivers have promise for reducing parental substance use. These findings emphasize the need to create supportive environments and systems for parents who suffer from emotional strain and mental health problems, particularly within families experiencing adversity.

Trial registration

Pan-African Clinical Trials Registry PACTR201507001119966. Registered on 27 April 2015. The trial can be found by searching for the key word ‘Sinovuyo’ on the Pan-African Clinical Trials Registry website or via the following link:
http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?_nfpb=true&_windowLabel=BasicSearchUpdateController_1&BasicSearchUpdateController_1_actionOverride=%2Fpageflows%2Ftrial%2FbasicSearchUpdate%2FviewTrail&BasicSearchUpdateController_1id=1119
Effectiveness of the World Health Organization Safe Childbirth Checklist (WHO-SCC) in preventing poor childbirth outcomes: a study protocol for a matched-pair cluster randomized control trial
Authors: Millogo Tieba , Kourouma Kadidiatou Raïssa , Diallo Aïssatou , Agbre-Yace Marie Laurette , Baldé Mamadou Diouldé , Kouanda Seni
Published: September 2021

Background

Women delivering in health facilities in sub-Saharan Africa and their newborns do not always receive proven interventions needed to prevent and/or adequately manage severe complications. The gaps in quality of care are increasingly pointed out as major contributing factor to the high and slow declining perinatal mortality rates. The World Health Organization Safe Childbirth Checklist (WHO-SCC), as a quality improvement strategy, targets low cost and easy to perform interventions and suits well with the context of limited resource settings. In this matched-pair cluster randomized controlled trial, we assess the effectiveness of the WHO-SCC in improving healthcare providers’ adherence to best practices and ultimately improving childbirth outcomes.

Methods

This is a multi-country study. In each country we will carry out a matched-pair cluster randomized controlled trial whereby four pairs of regional hospitals will be randomized on a 1:1 basis to either the intervention or control group. A context specific WHO-SCC will be implemented in the intervention facilities along with trainings of healthcare providers on best childbirth practices and ongoing supportive supervisions. The standard of care will prevail in the control group. The primary outcome is a summary composite metric that combine the following poor childbirth outcomes: stillbirths, maternal deaths, early neonatal deaths, severe postpartum hemorrhage, maternal infections, early neonatal infections, prolonged obstructed labor, severe pre-eclampsia, uterine rupture in the health facility, eclampsia and maternal near miss. The occurrence of these outcomes will be ascertained in a sample of 2530 childbirth events in each country using data extraction. A secondary outcome of interest is the adherence of healthcare providers to evidence best practices. This will be measured through direct observations of a sample of 620 childbirth events in each country.

Discussion

Our study has the potential to provide strong evidence on the effectiveness of the WHO-SCC, a low cost and easy to implement intervention that can be easily scaled up if found effective.

Trial registration

The trial was registered in the Pan-African Clinical Trials Registry on 21st January 2020 under the following number: PACTR202001484669907. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9662
A feedback journey: employing a constructivist approach to the development of feedback literacy among health professional learners
Authors: O’Connor Anne , McCurtin Arlene
Published: September 2021

Background

Feedback, if effectively provided by the teacher and utilised by the learner, enables improvement in academic performance. It is clear from current literature that the provision of feedback by teachers is not sufficient on its own to guarantee improvements as early university entrants may not be sufficiently equipped to effectively engage with feedback. Nonetheless, it is critical for health professional students to develop feedback literacy early, in order to prepare them for a professional career of lifelong learning and critical thinking. The overarching aim of this study was to identify a feasible, sustainable approach to improve feedback literacy among students on pre-qualifying health professional programmes.

Methods

The study was divided into two phases. A mixed-methods approach grounded in constructivism was employed. Participants included teachers and learners from the School of Allied Health at X University, and two internationally acclaimed educationalists. In phase 1, first year students were encouraged to use an established online platform to upload modular feedback and develop personal learning action plans aimed at improving academic performance. A follow-up survey highlighted poor engagement with this method. Thus, the second phase focused on the co-construction of a suite of modules to develop these skills, supported by academic staff. Interviews were conducted with participants to review and refine this initiative.

Results

Learners’ engagement with the first phase of the study was poor. Thus, the second phase provided all stakeholders with the opportunity to feed into the development of a suite of modules, designed to encourage teachers and learners to work in partnership to nurture these skills. All stakeholder groups reported short- and long-term benefits with this approach, but also highlighted challenges towards its implementation.

Conclusion

The development of feedback literacy among health professional learners is essential. The transferability of such skills has been highlighted in the literature and by all stakeholder groups involved in this study. Finding a balance between introducing these skills at a time early enough to highlight their importance among university entrants is challenging. Further balance must be achieved between the workload required to achieve these skills and current programme demands for both teachers and learners.
Psychometrics of the moral distress scale in Iranian mental health nurses
Authors: Ghafouri Raziyeh , Lotfi-Bajestani Sara , Nasiri Malihe , Ohnishi Kayoko , Atashzadeh-Shoorideh Foroozan
Published: September 2021

Background

One of the challenges that nurses often face in ethical decision-making situations is moral distress. Moral distress is caused by the conflict between professional and individual values in decision-making situations. Despite its importance, there is no reliable scale in Persian to measure it. Therefore, this study was conducted to validate the moral distress scale in mental health nurses in Iranian culture and Persian language.

Methods

This study was conducted in two parts: Translation and cross-cultural adaptation and psychometric analysis. The translation and cross-cultural adaptation process was conducted based on the Polit approach. Next, face validity (qualitative), content validity (quantitative and qualitative), and construct validity were examined. This part of the study was a cross-sectional study. In this step, a demographic questionnaire and the Moral Distress Scale were sent to 500 nurses working in selected educational and medical centers in Iran via online questionnaires. Then, the construct validity of the “Moral Distress Scale” was confirmed by confirmatory factor analysis and the reliability of the instrument was examined by studying the internal consistency with Cronbach’s alpha and the internal correlation of the AIC.

Results

The confirmatory factor analysis showed an acceptable ratio of the expressions in 15 items in three factors: Acquiescence to patients’ rights violations (6 items), Unethical conduct by caregivers (5 items), and low staffing (4 items) in the scale. The internal consistency of the instrument with Cronbach’s alpha was higher than 7.0.

Conclusion

The Persian version of moral distress with 15 items of the three factors had validity and reliability. According to the present findings, this scale can be used to study moral distress among nurses working in psychiatric wards. Moral distress leads to burnout, increases risks to patient safety and reduces quality of care. Nurses need to be able to assess and manage moral distress. Therefore, considering the side effects, it is necessary to have a reliable and valid scale that can be studied. Considering that culture has an impact on nurses’ moral distress, it is suggested that this instrument be studied in and tested in other languages and cultures.
Comprehensive analysis of the cancer driver genes in breast cancer demonstrates their roles in cancer prognosis and tumor microenvironment
Authors: Du Xiao-wei , Li Gao , Liu Juan , Zhang Chun-yan , Liu Qiong , Wang Hao , Chen Ting-song
Published: September 2021

Background

Breast cancer is the most common malignancy in women. Cancer driver gene-mediated alterations in the tumor microenvironment are critical factors affecting the biological behavior of breast cancer. The purpose of this study was to identify the expression characteristics and prognostic value of cancer driver genes in breast cancer.

Methods

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets are used as the training and test sets. Classified according to cancer and paracancerous tissues, we identified differentially expressed cancer driver genes. We further screened prognosis-associated genes, and candidate genes were submitted for the construction of a risk signature. Functional enrichment analysis and transcriptional regulatory networks were performed to search for possible mechanisms by which cancer driver genes affect breast cancer prognosis.

Results

We identified more than 200 differentially expressed driver genes and 27 prognosis-related genes. High-risk group patients had a lower survival rate compared to the low-risk group (P<0.05), and risk signature showed high specificity and sensitivity in predicting the patient prognosis (AUC 0.790). Multivariate regression analysis suggested that risk scores can independently predict patient prognosis. Further, we found differences in PD-1 expression, immune score, and stromal score among different risk groups.

Conclusion

Our study confirms the critical prognosis role of cancer driver genes in breast cancer. The cancer driver gene risk signature may provide a novel biomarker for clinical treatment strategy and survival prediction of breast cancer.
Interspecific attraction between ground-nesting songbirds and ants: the role of nest-site selection
Authors: Maziarz Marta , Broughton Richard K. , Casacci Luca Pietro , Hebda Grzegorz , Maák István , Trigos-Peral Gema , Witek Magdalena
Published: September 2021

Background

Interspecific interactions within ecological networks can influence animal fitness and behaviour, including nest-site selection of birds and ants. Previous studies revealed that nesting birds and ants may benefit from cohabitation, with interspecific attraction through their nest-site choice, but mutual interactions have not yet been tested. We explored a previously undescribed ecological link between ground-nesting birds and ants raising their own broods (larvae and pupae) within the birds’ nests in a temperate primeval forest of lowland Europe. We tested whether the occurrence of ant broods within bird nests resulted from a mutual or one-sided interspecific attraction that operated through nest-site choice and was modified by weather conditions.

Results

We found a non-random occupation of bird nests by ants raising their own broods within them, which indicated interspecific attraction driven solely by the ants. The birds’ preference to nest near tussocks of vegetation showed little overlap with the most frequent placement of ant colonies among fallen deciduous tree-leaves, dead wood and moss. Additionally, birds did not appear to select forest localities with high densities of ant colonies. The occurrence of ant broods within bird nests was also unrelated to bird nest placement near to specific habitat features. The attractiveness of bird nests to ants appeared to increase with the thermal activity of the birds warming their nests, and also during cool and wet weather when the occurrence of ant broods within bird nests was most frequent. Ants often remained in the nests after the birds had vacated them, with only a slight reduction in the probability of ant brood occurrence over time.

Conclusions

The natural patterns of bird nest colonisation by ants support the hypothesis of ants’ attraction to warm nests of birds to raise their broods under advantageous thermal conditions. Similar relationships may occur between other warm-blooded, nest-building vertebrates and nest-dwelling invertebrates, which depend on ambient temperatures. The findings advance our understanding of these poorly recognised interspecific interactions, and can inform future studies of ecological networks.
Condylar erosion is predictive of painful closed lock of the temporomandibular joint: a magnetic resonance imaging study
Authors: Emshoff Rüdiger , Bertram Annika , Hupp Linus , Rudisch Ansgar
Published: September 2021

Background

To assess whether magnetic resonance imaging (MRI) findings of condylar erosion (CE) are predictive of a specific clinical diagnosis of painful closed lock of the temporomandibular joint (TMJ), and to determine the strength of association between CE and types of internal derangement (ID).

Methods

Based upon sample size estimation, this retrospective paired-design study involved 62 patients, aged between 18 and 67 years. Inclusion criteria were the presence of a unilateral clinical diagnosis of arthralgia coexisting with disk displacement without reduction (‘AR and DDwoR/wLO’), assigned according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I, and the absence of signs and symptoms of TMJ pain and dysfunction on the contralateral TMJ side. Bilateral sagittal and coronal MR images were obtained to establish the prevalence of CE and TMJ ID types of disk displacement with (DDR) and without reduction (DDNR). Logistic regression analysis was used to compute odds ratios for CE and ID types. Confounding variables adjusted for were age, sex, time since pain onset, pain intensity, and type of ID.

Results

In the regression analysis, the MRI items of DDR (p = 0.533) and DDNR (p = 0.204) dropped out as nonsignificant in the diagnostic clinical ‘AR and DDwoR/wLO’ group. Significant increases in the risk of ‘AR and DDwoR’ occurred with CE (3.1:1 odds ratio; p = 0.026). The presence of CE was significantly related to DDNR (adjusted OR = 43.9; p <  0.001).

Conclusions

The data suggest CE as a dominant factor in the definition of painful closed lock of the TMJ, support the view that joint locking needs to be considered as a frequent symptom of osteoarthritis, and emphasize a strong association between the MRI items of CE and DDNR.
PEGylated recombinant human hyaluronidase (PEGPH20) pre-treatment improves intra-tumour distribution and efficacy of paclitaxel in preclinical models
Authors: Morosi Lavinia , Meroni Marina , Ubezio Paolo , Fuso Nerini Ilaria , Minoli Lucia , Porcu Luca , Panini Nicolò , Colombo Marika , Blouw Barbara , Kang David W. , Davoli Enrico , Zucchetti Massimo , D’Incalci Maurizio , Frapolli Roberta
Published: September 2021

Background

Scarce drug penetration in solid tumours is one of the possible causes of the limited efficacy of chemotherapy and is related to the altered tumour microenvironment. The abnormal tumour extracellular matrix (ECM) together with abnormal blood and lymphatic vessels, reactive stroma and inflammation all affect the uptake, distribution and efficacy of anticancer drugs.

Methods

We investigated the effect of PEGylated recombinant human hyaluronidase PH20 (PEGPH20) pre-treatment in degrading hyaluronan (hyaluronic acid; HA), one of the main components of the ECM, to improve the delivery of antitumor drugs and increase their therapeutic efficacy. The antitumor activity of paclitaxel (PTX) in HA synthase 3-overexpressing and wild-type SKOV3 ovarian cancer model and in the BxPC3 pancreas xenograft tumour model, was evaluated by monitoring tumour growth with or without PEGPH20 pre-treatment. Pharmacokinetics and tumour penetration of PTX were assessed by HPLC and mass spectrometry imaging analysis in the same tumour models. Tumour tissue architecture and HA deposition were analysed by histochemistry.

Results

Pre-treatment with PEGPH20 modified tumour tissue architecture and improved the antitumor activity of paclitaxel in the SKOV3/HAS3 tumour model, favouring its accumulation and more homogeneous intra-tumour distribution, as assessed by quantitative and qualitative analysis. PEGPH20 also reduced HA content influencing, though less markedly, PTX distribution and antitumor activity in the BxPC3 tumour model.

Conclusion

Remodelling the stroma of HA-rich tumours by depletion of HA with PEGPH20 pre-treatment, is a potentially successful strategy to improve the intra-tumour distribution of anticancer drugs, increasing their therapeutic efficacy, without increasing toxicity.
Genome-wide association study and transcriptome analysis reveal key genes affecting root growth dynamics in rapeseed
Authors: Li Keqi , Wang Jie , Kuang Lieqiong , Tian Ze , Wang Xinfa , Dun Xiaoling , Tu Jinxing , Wang Hanzhong
Published: September 2021

Background

In terms of global demand, rapeseed is the third-largest oilseed crop after soybeans and palm, which produces vegetable oil for human consumption and biofuel for industrial production. Roots are vital organs for plant to absorb water and attain mineral nutrients, thus they are of great importance to plant productivity. However, the genetic mechanisms regulating root development in rapeseed remain unclear. In the present study, seven root-related traits and shoot biomass traits in 280 Brassica napus accessions at five continuous vegetative stages were measured to establish the genetic basis of root growth in rapeseed.

Results

The persistent and stage-specific genetic mechanisms were revealed by root dynamic analysis. Sixteen persistent and 32 stage-specific quantitative trait loci (QTL) clusters were identified through genome-wide association study (GWAS). Root samples with contrasting (slow and fast) growth rates throughout the investigated stages and those with obvious stage-specific changes in growth rates were subjected to transcriptome analysis. A total of 367 differentially expressed genes (DEGs) with persistent differential expressions throughout root development were identified, and these DEGs were significantly enriched in GO terms, such as energy metabolism and response to biotic or abiotic stress. Totally, 485 stage-specific DEGs with different expressions at specific stage were identified, and these DEGs were enriched in GO terms, such as nitrogen metabolism. Four candidate genes were identified as key persistent genetic factors and eight as stage-specific ones by integrating GWAS, weighted gene co-expression network analysis (WGCNA), and differential expression analysis. These candidate genes were speculated to regulate root system development, and they were less than 100 kb away from peak SNPs of QTL clusters. The homologs of three genes (BnaA03g52990D, BnaA06g37280D, and BnaA09g07580D) out of 12 candidate genes have been reported to regulate root development in previous studies.

Conclusions

Sixteen QTL clusters and four candidate genes controlling persistently root development, and 32 QTL clusters and eight candidate genes stage-specifically regulating root growth in rapeseed were detected in this study. Our results provide new insights into the temporal genetic mechanisms of root growth by identifying key candidate QTL/genes in rapeseed.
Limitations in representative sampling of unpaid caregivers from minority ethnocultural backgrounds in a population-based survey
Authors: Marani Husayn
Published: September 2021

Objective

Historically, persons from minority ethnic, religious and linguistic backgrounds have been un- or under-represented in population-based research studies. Emerging scholarship suggests challenges in representative sampling, particularly of minority ethnocultural groups, has been exacerbated by the COVID-19 pandemic. This research note offers additional insights concerning these challenges in the context of a population-based survey of unpaid caregivers conducted in Ontario, Canada, between August and December, 2020, the analysis of which is currently underway.

Results

Beyond limitations intrinsic to study design, including time and budget constraints, the study sample underrepresents unpaid caregivers from minority ethnocultural backgrounds due to differences in conceptions of caregiving across minority cultures, the time-consuming nature of caregiving that disproportionately affects minority groups, and a propensity to avoid research which is rooted in tokenism. These hypotheses are non-exhaustive, speculative and warrant further empirical investigation.
The addition of neoadjuvant pertuzumab for the treatment of HER2+ breast cancer: a cost estimate with real-world data
Authors: Borges Andreia , Pereira Filipa , Redondo Patrícia , Antunes Luís , Vieira Cláudia , Antunes Pedro , Bento Maria José , Sousa Susana , Lopes José Machado , Rocha-Gonçalves Francisco , de Sousa Joaquim Abreu , Pereira Deolinda Sousa , Borges Marina
Published: September 2021

Background

Breast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20–25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC).

Methods

Two retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012–2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015–2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed.

Results

AC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375€, with pertuzumab accounting for 13,978€ (24.79%) and increasing in 15,982€ the average cost/patient (p < 0.001). Clinical staging and hormone receptors (HR) were significantly associated with pCR. ICER was 1.370€ per percentage point of pCR.

Conclusions

ICER was more favourable in stage III HR negative BC patients compared to other patient profiles. Innovative treatments access is critical to deliver high-quality healthcare, but sustainability must be considered. These results suggest the importance of establishing a cost-effectiveness profile of Pertuzumab in NeoT for HER2-positive BC.