bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributing to collaborative health governance in Africa: a realist evaluation of the Universal Health Coverage Partnership
Authors: Robert Emilie , Zongo Sylvie , Rajan Dheepa , Ridde Valéry
Published: June 2022

Background

Policy dialogue, a collaborative governance mechanism, has raised interest among international stakeholders. They see it as a means to strengthen health systems governance and to participate in the development of health policies that support universal health coverage. In this context, WHO has set up the Universal Health Coverage Partnership. This Partnership aims to support health ministries in establishing inclusive, participatory, and evidence-informed policy dialogue. The general purpose of our study is to understand how and in what contexts the Partnership may support policy dialogue and with what outcomes. More specifically, our study aims to answer two questions: 1) How and in what contexts may the Partnership initiate and nurture policy dialogue? 2) How do collaboration dynamics unfold within policy dialogue supported by the Partnership? 

Methods

We conducted a multiple-case study realist evaluation based on Emerson’s integrative framework for collaborative governance to investigate the role of the Partnership in policy dialogue on three policy issues in six sub-Saharan African countries: health financing (Burkina Faso and Democratic Republic of Congo), health planning (Cabo Verde, Niger, and Togo), and aid coordination for health (Liberia). We interviewed 121 key informants, analyzed policy documents, and observed policy dialogue events.

Results

The Partnership may facilitate the initiation of policy dialogue when: 1) stakeholders feel uncertain about health sector issues and acknowledge their interdependence in responding to such issues, and 2) policy dialogue coincides with their needs and interests. In this context, policy dialogue enables stakeholders to build a shared understanding of issues and of the need for action and encourages collective leadership. However, ministries’ weak ownership of policy dialogue and stakeholders’ lack of confidence in their capacity for joint action hinder their engagement and curb the institutionalization of policy dialogue.

Conclusions

Development aid actors wishing to support policy dialogue must do so over the long term so that collaborative governance becomes routine and a culture of collaboration has time to grow. Public administrations should develop collaborative governance mechanisms that are transparent and intelligible in order to facilitate stakeholder engagement.
A novel missense variant in the CASK gene causes intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia
Authors: Wu Sixian , Jiang Chuan , Li Jiaman , Zhang Guohui , Shen Ying , Wang Jing
Published: June 2022

Background

Variants in the CASK gene result in a wide range of observed phenotypes in humans, such as FG Syndrome 4 and intellectual disabilities. Intellectual developmental disorder with microcephaly and pontine and cerebellar hypoplasia (MICPCH) is an X-linked disorder that affects females and is characterized by severely impaired intellectual development and variable degrees of pontocerebellar hypoplasia. Variants in CASK are the main genetic cause of MICPCH. Variants in CASK can explain most patients with MICPCH, but there are still some patients whose disease aetiology cannot be explained.

Case presentation

An 11-month-old female diagnosed with MICPCH exhibited general developmental delays, microcephaly, and cerebellar hypoplasia. Whole-exome sequencing (WES) was used to find a novel heterozygous missense variant (NM_003688.3: c.638T>G) of CASK in this patient. Strikingly, this variant reduced the expression of CASK at the protein level but not at the mRNA level. By using protein structure prediction analysis, this study found that the amino acid change caused by the variant resulted in further changes in the stability of the protein structure, and these changes caused the downregulation of protein expression and loss of protein function.

Conclusion

In this study, we first reported a novel heterozygous pathogenic variant and a causative mechanism of MICPCH. The amino acid change cause by this variant led to changes in the protein structure and a decrease in its stability, which caused a loss of protein function. This study could be helpful to the genetic diagnosis of this disease.
Triglyceride glucose index for the detection of the severity of coronary artery disease in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China
Authors: Su Jinyu , Li Zhu , Huang Mengnan , Wang Yang , Yang Tong , Ma Mei , Ni Tongyao , Pan Guangwei , Lai Ziqin , Li Chunjie , Li Lin , Yu Chunquan
Published: June 2022

Background

Triglyceride glucose (TyG) index is a new marker associated with atherosclerosis. This study aimed to assess the association between TyG index and the severity of coronary artery disease (CAD) in patients with coronary heart disease (CHD) and further explore the association between TyG index and CAD severity in different glucose metabolic states.

Methods

This multi-centre retrospective study included 731 patients with CHD between January 1, 2014 and September 30, 2020 in China. All patients were stratified into groups based on the tertiles of TyG index (T1: 5.48 ≤ TyG index ≤ 7.17; T2: 7.18 ≤ TyG index ≤ 7.76; T3: 7.77 ≤ TyG index ≤ 10.82). The number of diseased vessels [single-vessel and multi-vessel CAD (≥ 50% stenosis in ≥ 2 large vessels)] represented the severity of CAD, which was measured using coronary angiography (CAG). Glucose metabolic states were defined by the American Diabetes Association as normal glucose regulation (NGR), prediabetes mellitus (Pre-DM), and diabetes mellitus (DM).

Results

The baseline analysis results showed significant differences in the clinical and biological characteristics of CHD patients according to TyG index tertiles (P < 0.05 to < 0.001). Logistic regression analysis showed that the TyG index was significantly related to the risk of multi-vessel CAD (odds ratio [OR]: 1.715; 95% confidence interval [CI] 1.339–2.197; P < 0.001). The OR for multi-vessel CAD in TyG index T3 compared to that of T1 was 2.280 (95% CI 1.530–3.398; P < 0.001). Receiver operating characteristic (ROC) curve was generated to evaluate the accuracy of the TyG index in detecting the CAD severity, and the area under the curve (AUC) of the ROC plots was 0.601 (95% CI 0.559–0.643). The association between TyG index and multi-vessel CAD was significant in patients with DM, achieving the highest OR among the different glucose metabolic states (OR: 1.717; 95% CI 1.161–2.539; P < 0.05).

Conclusion

TyG index was associated with CAD severity in patients with CHD, and an increased TyG index could identify patients with a high risk of multi-vessel CAD. There was an association between TyG index and CAD severity for the condition of DM.
Knockdown of ENTPD5 inhibits tumor metastasis and growth via regulating the GRP78/p-eIF-2α/CHOP pathway in serous ovarian cancer
Authors: Chen Xueping , Zha Zhiqiang , Wang Yu , Chen Yun , Pang Menglan , Huang Liping , Chen Yao
Published: June 2022

Background

Dysregulation of Ectonucleoside Triphospahate Diphosphohydrolase 5 (ENTPD5) in tumors might be associated with tumor progression, while the role of ENTPD5 in the growth and metastasis of serous ovarian cancer (SOC) is still unclear.

Methods

ENTPD5 expression patterns in ovarian cancer tissues were analyzed by qRT-PCR and immunohistochemistry assay (IHC). Two SOC cell lines, SKOV3 and OVCAR8, were stably transfected with lentivirus to build knockdown and overexpression cell lines. Clone formation assay, collagen gel droplet culture technology, wound healing assay and flow cytometry were used to assess the migration and growth traits of SOC cells. Expression levels of ENTPD5, glucose regulated protein 78 (GRP78), eukaryotic translation initiation factor 2 alpha (eIF-2α), phosphorylated -eIF-2α and, C/EBP homologous protein (CHOP) in SOC cells were detected by Western blot.

Results

Compared to fallopian tube tissues, the expression of ENTPD5 was significantly higher in tumor tissues obtained from SOC patients, and positively correlated with clinical stage and metastasis. ENTPD5 knockdown robustly inhibited cell proliferation, migration, whereas ENTPD5 overexpression elicited the opposite effect on SOC cells. ENTPD5 knockdown arrested cell cycle in G0/G1 phase and increased apoptosis. Importantly, ENTPD5 knockdown was associated with significantly decreased protein levels for GRP78, CHOP, and p-eIF-2α, suggesting possible involvement of ENTPD5 in endoplasmic reticulum stress (ERS).

Conclusions

Our study demonstrates that ENTPD5 knockdown inhibited SOC cell proliferation, migration and restrained the activation of the GRP78/p-eIF-2α/CHOP pathway, which provides a potentially effective therapeutic target for the treatment of SOC.
Prohibitin 1 interacts with p53 in the regulation of mitochondrial dynamics and chemoresistance in gynecologic cancers
Authors: Kong Bao , Han Chae Young , Kim Se Ik , Patten David A. , Han Youngjin , Carmona Euridice , Shieh Dar-Bin , Cheung Annie C. , Mes-Masson Anne-Marie , Harper Mary-Ellen , Song Yong Sang , Tsang Benjamin K.
Published: June 2022

Background

Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients.

Methods

We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome.

Results

We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer.

Conclusion

Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer.
Respiratory distress observation scales to predict weaning outcome
Authors: Decavèle Maxens , Rozenberg Emmanuel , Niérat Marie-Cécile , Mayaux Julien , Morawiec Elise , Morélot-Panzini Capucine , Similowski Thomas , Demoule Alexandre , Dres Martin
Published: June 2022

Background

Whether dyspnea is present before starting a spontaneous breathing trial (SBT) and whether it may affect the outcome of the SBT is unknown. Mechanical Ventilation—Respiratory Distress Observation Scale (MV-RDOS) has been proposed as a reliable surrogate of dyspnea in non-communicative intubated patients. In the present study, we sought (1) to describe the evolution of the MV-RDOS during a SBT and (2) to investigate whether MV-RDOS can predict the outcome of the SBT.

Methods

Prospective, single-center study in a twenty-two bed ICU in a tertiary center. Patients intubated since more 48 h who had failed a first SBT were eligible if they meet classical readiness to wean criteria. The MV-RDOS was assessed before, at 2-min, 15-min and 30-min (end) of the SBT. The presence of clinically important dyspnea was inferred by a MV-RDOS value ≥  2.6.

Results

Fifty-eight patients (age 63 [51–70], SAPS II 66 [51–76]; med [IQR]) were included. Thirty-three (57%) patients failed the SBT, whose 18 (55%) failed before 15-min. Twenty-five (43%) patients successfully passed the SBT. A MV-RDOS ≥ 2.6 was present in ten (17%) patients before to start the SBT. All these ten patients subsequently failed the SBT. A MV-RDOS ≥ 2.6 at 2-min predicted a SBT failure with a 51% sensibility and a 88% specificity (AUC 0.741 95% confidence interval [CI] 0.616–0.866, p = 0.002). Best cut-off value at 2-min was 4.3 and predicted SBT failure with a 27% sensibility and a 96% specificity.

Conclusion

Despite patients met classical readiness to wean criteria, respiratory distress assessed with the MV-RDOS was frequent at the beginning of SBT. Measuring MV-RDOS before to initiate a SBT could avoid undue procedure and reduce patient’s exposure to unnecessary mechanical ventilation weaning failure and distress.
The current state of molecular profiling in gastrointestinal malignancies
Authors: Mukherji Reetu , Yin Chao , Hameed Rumaisa , Alqahtani Ali Z. , Kulasekaran Monika , He Aiwu R. , Weinberg Benjamin A. , Marshall John L. , Hartley Marion L. , Noel Marcus S.
Published: June 2022

This is a review of the current state of molecular profiling in gastrointestinal (GI) cancers and what to expect from this evolving field in the future. Individualized medicine is moving from broad panel testing of numerous genes or gene products in tumor biopsy samples, identifying biomarkers of prognosis and treatment response, to relatively noninvasive liquid biopsy assays, building on what we have learned in our tumor analysis and growing into its own evolving predictive and prognostic subspecialty. Hence, the field of GI precision oncology is exploding, and this review endeavors to summarize where we are now in preparation for the journey ahead.
CFTR heterozygosity in severe asthma with recurrent airway infections: a retrospective review
Authors: Priel Eldar , Adatia Adil , Kjarsgaard Melanie , Nair Parameswaran
Published: June 2022

Rationale

Patients with asthma who have neutrophilic bronchitis may have an underlying cause leading to increased susceptibility to airway infections.

Methods

Retrospective review of patients with asthma who had a previous history of recurrent exacerbations that had been associated with airway or sinus infections referred to a tertiary asthma center between 2005 and 2020. Demographics, clinical features, and airway inflammation type determined by sputum cytometry were compared between CFTR carriers and non-carriers. Multiple linear regression was used to identify clinical predictors of CFTR carrier status. Response to nebulized hypertonic saline was assessed by comparing the number of infective exacerbations before and after its initiation.

Results

75 patients underwent CFTR mutation testing. Of these, 13 (17%) were CFTR carriers. The most common mutation was $$\Delta$$
Δ
F508. CFTR carriers were older (adjusted odds ratio 1.06 (CI 95% 1.01, 1.13)) and had more frequent flares requiring hospitalization (4.19 (1.34, 24.74)). Neutrophilic airway inflammation was the most common inflammatory subtype in CFTR carriers, though 8/13 also had eosinophilic bronchitis. Nebulized hypertonic saline was well tolerated by most and reduced the frequency of infective exacerbations.

Conclusions

The prevalence of CFTR heterozygosity in this cohort with recurrent neutrophilic bronchitis is higher than in the general population. Respiratory disease in CFTR carriers is associated with older age and may cause significant morbidity. Airway neutrophilia is the most common inflammatory subtype, but > 50% had eosinophilic bronchitis requiring treatment. Hypertonic saline appears to be well tolerated and effective in reducing the number of infective exacerbations.
Pastoralists' perceptions on the impact of Rift valley fever disease following an outbreak in North Eastern Kenya
Authors: Mburu Caroline M. , Bukachi Salome A. , Bett Bernard
Published: June 2022

Rift Valley fever (RVF) is a zoonotic disease which leads to livestock losses and human fatalities, thus impoverishing pastoralists who largely depend on livestock for their livelihood. These losses lead to both short- and long-term effects that perpetuate poverty and disrupt family order and structure. We used qualitative methods to understand the lived experiences of pastoralists with RVF after a major outbreak in Kenya. Using narratives, we identified the social, economic and psychological effects of this disease, while focus group discussions helped us to understand the experiences of the pastoralists during and after an outbreak. The major impacts were deprivation and impoverishment, abrupt disruption to their way of life and family dynamics and mistrust of the formal healthcare system. The latter was related to the isolation of patients and the presence of foreign medical personnel in the area that fueled mistrust. Efforts need to be made by public health practitioners and policy-makers to enhance dialogue between clinicians and pastoralists and to come up with practical ways of improving local people’s livelihoods during and after an RVF epidemic.
Efficacy of epidural blood patching or surgery in spontaneous intracranial hypotension: an evidence map protocol
Authors: Amrhein Timothy J. , Kranz Peter G. , Cantrell Sarah , Deline Constance R. , Carr Carrie M. , Kim Dong Kun , Goldstein Karen M. , Williams John W.
Published: June 2022

Background

Spontaneous intracranial hypotension (SIH) is a debilitating disorder caused by non-iatrogenic spinal cerebrospinal fluid leaks. SIH is increasingly recognized as an important treatable cause of secondary headaches. Treatment involves either epidural blood patching or surgery, which have considerable differences in their adverse event rates, recovery times, and cost. The objective of this evidence map is to understand the breadth of studies that investigate SIH treatment efficacy and to identify knowledge gaps to inform future research.

Methods

This review will consider experimental, observational, and systematic review studies that assess the efficacy of epidural blood patching and surgery for the treatment of patients with SIH. Individual case studies, clinical guidelines, editorials, protocols, and studies that do not assess an intervention will not be included. English language studies will be included without limitation based on the date of publication. Databases to be searched include MEDLINE® (via Ovid), EMBASE (via Elsevier), and Web of Science™ (via Clarivate). Study selection will be performed independently by two investigators with extracted data to include study type, the number of patients included, patient descriptors, intervention characteristics, and outcome measure used. Data will be presented through a narrative summary aided by tabular and graphical formats in a manner that aligns with the objective of the evidence mapping review.

Discussion

The overarching goal of this evidence map is to provide an improved understanding of the breadth of studies investigating SIH treatment efficacy in the literature and to thereby identify knowledge gaps that can inform future research directions.

Trial registration

OSF Registry https://osf.io/nwju7.
Comparison of non-tidal loading data for application in a secular terrestrial reference frame
Authors: Glomsda Matthias , Bloßfeld Mathis , Seitz Manuela , Angermann Detlef , Seitz Florian
Published: June 2022

The Deutsches Geodätisches Forschungsinstitut der Technischen Universität München (DGFI-TUM) is one of the three Combination Centres of the International Earth Rotation and Reference Systems Service for the International Terrestrial Reference System (ITRS). In its upcoming realization of the ITRS, the DTRF2020, DGFI-TUM will again correct for non-tidal loading (NTL) effects at the normal equation level. Next to the dedicated NTL data set for the ITRS 2020 realization provided by the Global Geophysical Fluid Center (GGFC), we also considered the data provided by the Earth System Modelling group of the Deutsches GeoForschungsZentrum (ESMGFZ). Besides also comprising all NTL components (atmospheric, oceanic, hydrological) and being mass conserving, the ESMGFZ data has the advantage of daily availability and is already in use at DGFI-TUM. The decision for one or the other data set depends on their suitability for a secular terrestrial reference frame like the DTRF2020, which will be assessed in this work. Although we also compare the site displacements induced by NTL to the residuals of station positions of the Global Navigation Satellite Systems, we will not evaluate the quality of the underlying geophysical models per se. The two data sets differ w.r.t. the underlying hydrological models and the treatment of non-tidal oceanic loading, but the most relevant difference is given in terms of trends in the displacement time-series. After a close investigation of the latter, we finally decided to apply the GGFC contribution to the ITRS 2020 realization in the DTRF2020.

Graphical Abstract
A case of radical resection for brain metastases of pancreatic cancer after curative chemotherapy for para-aortic lymph node metastases
Authors: Utsunomiya Takeshi , Funamizu Naotake , Ozaki Erina , Tamura Kei , Sakamoto Katsunori , Ogawa Kohei , Kusakabe Kosuke , Suehiro Satoshi , Yamashita Daisuke , Kurata Mie , Kitazawa Riko , Takada Yasutsugu
Published: June 2022

Background

The incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood–brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature.

Case presentation

A 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors.

Conclusions

Aggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.
Microscopic Observations on Form and Structure of the Worm Enchytraeus buchholzi (Clitellata: Enchytraeidae)
Authors: Zhao Limin , Xie Xiuchao , Chen Dejing , Ma Guilan , Sun Ya
Published: June 2022

Background

The worm Enchytraeus buchholzi is a new record species for Shaanxi, China, and a key pest on American ginseng Panax quinquefolium. To distinguish the species, the authors prepared its whole mounts and paraffin-embedded sections, and microscopically observed, photographed and measured. Besides, we conducted an experimental study on its DNA barcode. 

Results

Cells, tissues and organs related to nervous, digestive, circulatory, excretory and reproductive systems were found, photomicrographed and described, including: prostomium, peristomium, segments, clitellum, pygidium, lateral and ventral chaetae; brain, cranial nerves, sensory papillae, ventral nerve cord; pharyngeal pad and glands, retractor muscles and muscular bundles, peptonephridia, esophagus, intestine; dorsal, lateral, ventral and intestinal parietal vessels, coelomocytes, coelomic cavity; nephridia, chloragogen cells; ovaries, groups of germ cells with developing oocytes, mature eggs, spermathecae; testes, seminal vesicles, sperm funnels, penial bulbs. Their shapes and sizes were given, and functions discussed briefly. The visual effect of staining specimens with hematoxylin plus eosin ranked the first, and that with acetocarmine the second. 

Conclusions

The supplementary and objective descriptions, with the microphotographs as forceful pieces of evidence, have expanded biological knowledge in aspects of the form, structure and function of the worm, which is helpful for professionals to recognize and understand this species and provide a solid basis for its integrated pest management.
Promoting medical student engagement through co-development and peer-assisted learning: a new patient safety course as a case study
Authors: Kayser Jesper Dybdal , Mielke-Christensen Anne , Østergaard Doris , Dieckmann Peter
Published: June 2022

Introduction

Peer-assisted learning programs have been focused on providing students with competencies to deliver lectures and facilitate workshops, whereas involvement of students as co-developers of educational programmes has been relatively under-described in the literature. Likewise, the use of students as facilitators in simulation-based training and debriefing is also scarce.

In this paper, we describe how medical students were co-developers of a novel course on patient safety and how they were trained as student facilitators to conduct simulation-based training and debriefing, as well as workshops.

Methods

Medical students co-developed a course in patient safety consisting of three simulation-based scenarios and three workshops. The students were educated in relevant patient safety topics. They were trained to become student facilitators to conduct workshops, simulations and debriefings at a patient safety course for medical students. A questionnaire was developed to evaluate the course participants´ perception of the learning objectives and the student facilitators following the latest course in 2020. In addition, semi-structured interviews with the student facilitators were conducted to explore their perceptions of being part of the course.

Results

A total of 92% of the course participants completed the evaluation of the course. The majority of the course participants found that the student facilitators created a safe learning environment and had the necessary skills to teach. The learning objectives for the course were found to be useful. A total of 10 interviews with the student facilitators were conducted. We found that the student facilitators were motivated to teach in the course, as a way of improving their teamwork, leadership qualities and communication skills, as well as their resume. Some of the student facilitators mentioned that they were able to create a safe learning environment, whereas others mentioned a feeling of inadequacy for their teacher role. In addition to developing their teaching skills, they mentioned that they developed their medical expertise, alongside their communication-, collaboration-, leadership- and professional skills.

Conclusion

This study illustrates how medical students were involved in the co-development, delivery and implementation of a course in patient safety. The evaluation of the course shows that student facilitators succeeded in creating a safe learning environment. The interviews of the student facilitators reveal their various motivations for teaching, in addition to different perceptions of their experience as a student facilitator. Some expressed a positive feeling of being able to establish a safe learning environment, whilst others expressed a feeling of inadequacy when facilitating peers. In addition, the student facilitators indicated that they developed themselves both professionally and personally.
Treatment of arterial calcification in patients with chronic limb threatening ischemia with etidronate: protocol of an investigator-initiated multicenter, double blind, placebo-controlled, randomized clinical trial
Authors: Hoogervorst R. , van Overhagen H. , de Jong P. A. , Spiering W. , de Borst G. J. , Veger H. T. C. , Mairuhu A. T. A. , Mali W. P. T. M.
Published: June 2022

Background

Pathologic studies have shown that in patients with critical limb threatening ischaemia (CLTI) medial arterial calcifications are frequently found and may be responsible for aggravating the disease. These extensive calcifitcations are found not only in arteries of the leg but also in the coronary arteries and the aorta. The progression of these calcifications is fast and they stiffen the vessel wall and may thus increase the cardiovascular risk.

Reduction of progression of calcification may not only reduce the burden of CLTI but may also reduce the high residual cardiovascular risk. Medial calcifications have been halted by etidronate in other trials. Its potential to reduce the burden from peripheral vascular disease in CLTI and residual cardiovascular risk remains to be established.

Methods

This is an investigator-initiated multicenter, double blind, placebo-controlled, randomized trial comparing the effects of etidronate versus placebo in patients with CLTI.

Subjects will be randomized to either treatment with etidronate for 12 months (cyclical 20 mg/kg for 2 weeks on and 10 weeks off) orally or placebo for 12 months (in a similar routine).

The primary endpoint is the change in arterial calcification as quantified by CT-scan.

Secondary endpoints are the number of amputations above and below the ankle, mortality, number of vascular interventions and quality of life.

Discussion

Up to now, the inert end stage of vascular disease in patients with CLTI, has been considered calcification of vessel walls. We believe there is reason to reverse causation and hypothesize that calcification causes vascular disease. This reversal can be proven in a clinical trial if halting the calcification process improves the outcome of the patient. Therefore we use etidronate, a bisphosphate that has proven to stop the calcification in several rare monogenetic calcifying diseases. We aim to perform this mechanistic proof-of-concept study hopefully leading to a clinical outcome study later on.
RF performance evaluation of the nRF24L01+ based wireless water quality monitoring sensor node: Khartoum city propagation scenario
Authors: Abdelrahim Sami Omer Osman , Hassan Mohamed Zakria Mohamed , Salih Alzain Mohamed Suliman , Abdo-Alrahiem Amjed Abubaker Mohamed , Abdelgadir Mohamed Mayada
Published: June 2022

Recently, and to cater to increased needs of Drinking Water Quality Monitoring (DWQM) and data management, there has been a growing interest in the marketplace as well as in the research community to develop advanced water quality monitoring systems utilizing modern information and communications technologies (ICT) such as wireless sensor networks (WSN) and Internet of Things (IoT). The application of the wireless-sensing paradigm is becoming a common trend in water quality monitoring systems. In fact, a growing body of the literature has focused on developing wireless sensing-enabled water quality monitoring systems. However, previous studies have not dealt with the radio performance evaluation of modern wireless water quality monitoring systems deployed in urban city scenarios. The present paper seeks to address the radio frequency (RF) performance evaluation for a developed modern wireless Drinking Water Quality Monitoring System (DWQMS) based on the commercial nRF24L01+ RF module. This research study is based on three city propagation scenarios as case studies. The obtained experimental data suggested that the nRF24L01+ module can provide relatively acceptable RF performance under less favorable and hostile city propagation environments.
Optimization of cold-formed lipped C-section under bending using prediction equations as objective functions
Authors: Swelem Sherine , Fahmy Ahmed , Ellafy Heba
Published: June 2022

The use of cold-formed sections (CFS) in construction is growing quickly in spite of the difficulty facing the designer in choosing the optimum sections’ proportions of any CFS in order to acquire the most economical section. In this paper, the optimization of CFS C-lipped channel beam will be carried out with respect to their flexural strength calculated using the direct strength method (DSM) given by the American specifications (AISI). The optimization will be carried out by developing an accurate and effective optimization code using particle swarm optimization (PSO). The mathematical model and the optimization technique used in this paper will help in finding the most optimum ratios between the different elements of the C-lipped channel beam that are studied in three groups. Nonlinear regression analysis is performed to obtain proposed equations that predict the flexural capacity of the cross section in two modes of failure: the local buckling mode and the distortional buckling mode. These proposed equations are used as objective functions in the optimization process as they showed that they are capable of predicting the moment capacity of the C-lipped channel effectively. It was found that the most suitable group of the three studied groups is the ratios between different elements of the cross section lies between 15 and 50%.
Barriers to effective childhood cancer control in Kenya (BECK) study, 2019-2020: A mixed methods study in a national tertiary facility and 10 regional cancer treatment centers.
Authors: Mwenda Valerian , Karagu Alfred , Githanga Jessie Nyokabi , Nyangasi Mary
Published: June 2022

10018

Background: Globally, 80,000 children die from cancer annually; 80% in low- and middle-income countries (LMICs). Childhood cancer cure is possible in more than 80% of cases, in all economic settings. This study aimed to identify barriers to effective management of childhood cancers in Kenya, for program and policy intervention. Methods: We reviewed childhood cancer cases diagnosed at Kenyatta National Hospital in the period 2015-2019. We also assessed capacity of ten recently established regional cancer centres for childhood cancer diagnosis and treatment. We conducted focused group discussions among childhood cancer survivors’ caregivers and key informant interviews among childhood cancer specialists and policy makers from the Ministry of Health and the National Cancer Institute of Kenya. We estimated diagnostic delays, mapped service availability and deductively summarized the qualitative data into main themes. Results: We abstracted 1,764 cases; median age 6 years (IQR 9); 1013 (57.5%) were male. Most affected age group was 0-4 years (47.3%). Most common cancer types were retinoblastoma (23.3%), nephroblasoma (10.4%) and acute lymphoblastic leukaemia 10.3%). Cases managed at KNH decreased between 2015 and 2017, and then recovered. The median total delay (symptoms onset to treatment initiation) was 32 days (range 0-3666). Regional cancer centres lacked specialized workforce for childhood cancer care. Caregivers identified inadequate cover by National Health Insurance and disorganized care process as major challenges. At health system and policy level, low awareness, fragmented referral systems and in-effective policy implementation are major challenges to childhood cancer control. Conclusions: Increasing number of specialized personnel, creation of a differentiated financing package for childhood cancer and restructuring of referral and the care process can improve childhood cancer outcomes in Kenya.
Patterns of relapse after immunotherapy in patients with high-risk neuroblastoma.
Authors: Moerdler Scott , Naranjo Arlene , Tenney Sheena , Bagatell Rochelle , Yu Alice L. , London Wendy B.
Published: June 2022

10043

Background: While the addition of anti-GD2 immunotherapy led to improvement in outcomes in patients on the Children’s Oncology Group (COG) ANBL0032 study, relapse remains a concern. Prior studies demonstrated the prognostic importance of time to first relapse, however, the effect of immunotherapy on timing and patterns of relapse in neuroblastoma (NBL) have yet to be evaluated. The purpose of this exploratory analysis was to describe the impact of immunotherapy on patterns of relapse in patients with high-risk NBL, including a descriptive comparison of sites of relapse based on post-consolidation treatment received [dinutuximab with cytokines and isotretinoin (DIN) vs isotretinoin alone (ISO)]. Methods: A retrospective, descriptive analysis of patients on ANBL0032 was performed, including patients randomized to DIN or ISO and those non-randomly assigned to DIN after ISO arm closure. Pt characteristics including age, stage, MYCN amplification status, tumor grade, mitosis-karyorrhexis index (MKI) and ploidy were summarized descriptively and relapse sites were tabulated. For DIN patients who subsequently relapsed, overall survival (OS) was calculated starting from the time of first relapse after enrollment on ANBL0032 (“post-relapse OS”). Kaplan-Meier OS curves were generated based on site of relapse. Results: The analytic cohort included 1,431 (DIN = 1,327; ISO = 104) patients. Among DIN patients, 492 relapsed, many in > 1 site. In the randomized cohort (n = 248), 122 relapsed (DIN = 68/144; ISO = 54/104). The frequencies (DIN; ISO) by site of relapse in the randomized cohort were: bone (53%; 54%), CNS (16%; 11%), lymph node (13%; 17%), abdominal (10%; 17%), paraspinal (6%; 2%), liver (3%; 4%), other soft tissue (22%; 7%). A higher proportion of ISO patients had marrow relapse (29.4% DIN; 48.2% ISO); however, the proportion of DIN patients with lung relapses appeared higher (9% vs 2%). Among all relapsed patients, the proportion with bone relapse did not appear to differ between treatment groups, regardless of MYCN status. Among patients with MYCN amplified disease, the proportion with marrow relapse did not appear to differ based on treatment [21/149 (14.1%) DIN; 3/20 (15.0%) ISO]; however, among patients with MYCN non-amplified disease, the proportion with marrow relapse appeared higher in the ISO group [16/23; 69.6%] vs the DIN group [52/193 (26.9%)]. Conclusions: In this exploratory analysis of patients on COG ANBL0032, the pattern for site of relapse appears to differ between patients treated with DIN vs ISO. While immunotherapy remains the treatment of choice in this population, the findings from this retrospective exploratory analysis warrant further investigation to decrease the risk for post-immunotherapy relapse. Clinical trial information: NCT00026312.
Informatics tools to implement late cardiovascular risk prediction modeling for population health management of high-risk childhood cancer survivors.
Authors: Noyd David H , Janitz Amanda , Baker Ashley , Beasley William , Etzold Nancy , Kendrick David , Oeffinger Kevin C.
Published: June 2022

10048

Background: Marked improvements in outcomes for children with cancer and robust cohort studies with longitudinal follow-up inform evidence-based guidelines for survivors at risk for late cardiomyopathy. Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management. Methods: The Oklahoma Childhood Cancer Survivor cohort was constructed from an institutional cancer registry of survivors diagnosed between 2005 and 2014 (n=382). Data elements (cumulative anthracycline, cumulative chest-directed radiotherapy, alkylator, and platinum exposures) were extracted from Passport for Care (PFC) to implement previously validated late cardiovascular risk prediction modeling from the Childhood Cancer Survivor Study (CCSS) for cardiomyopathy. Risk groups were compared to the Children’s Oncology Group (COG) Long-Term Follow-up Guidelines. Standard query language facilitated extraction of echocardiogram data from the electronic health record to determine adherence, defined as an echocardiogram within 27 months and 63 months from the last day of therapy for high and moderate risk survivors, respectively. Results: Sixty-nine percent (n=264) of survivors from the cancer registry were documented in PFC, of whom 29%, 56%, and 15% were classified as low, moderate, high risk, respectively, based on the CCSS late cardiomyopathy risk calculator. Concordance was modest for high and moderate risk groups (Kappa = 0.42 and 0.46, respectively) and good for the low risk group (Kappa = 0.77) compared to COG risk groups. There was excellent adherence to echocardiogram guidelines with 93% and 81% of moderate and high-risk survivors, respectively. There were significant differences based on risk group (p=0.02) and age at diagnosis (p<0.01). Conclusions: Clinical informatics tools represent a feasible approach to leverage discrete data elements regarding key treatment exposures from PFC to successfully implement previously validated late cardiovascular risk prediction models on a population health level. PFC promotes adherence to echocardiogram surveillance and serves as a platform for future interoperability to generate real-world data to improve survivorship-focused care. [Table: see text]
Improvements in life expectancy among childhood cancer survivors: Uneven gains and remaining challenges.
Authors: Yeh Jennifer M , Ward Zachary J. , Stratton Kayla , Armstrong Gregory T. , Chow Eric Jessen , Hudson Melissa M. , Morton Lindsay M. , Oeffinger Kevin C. , Diller Lisa , Leisenring Wendy M.
Published: June 2022

10050

Background: Childhood cancer survivors are at risk for shortened lifespan. Projections of life expectancy (LE) by diagnosis can provide benchmarks for assessing improvements over time. Methods: We developed a simulation model to project risk for common, life-threatening chronic health conditions (CHCs; heart failure, myocardial infarction, valvular disease, stroke, secondary breast cancer, colorectal cancer, glial tumors, sarcomas) and excess mortality among 5-year survivors, based on patient characteristics (sex, age at diagnosis, diagnosis) and treatment exposures (chemotherapy, radiation dose). Risk was estimated using statistical models and Childhood Cancer Survivor Study data. Age-related CHC risks (SEER, NHLBI) and competing mortality (CDC Wonder) were based on national databases. We used model calibration to identify parameter sets that generated outcomes consistent with observed data. Model outcomes included conditional LE and 10-year survival probability at age 40. For comparisons to the general population, we simulated age-, sex-, and diagnosis year-matched individuals who faced only competing mortality rates. Results: Among a cohort representative of the CCSS (mean diagnosis age, 7.4 yrs), compared to the general population, the gap in LE among survivors diagnosed in the 1970s vs. 1990s decreased from 17 yrs (25%) to 11 yrs (17%). Changes in LE among survivors diagnosed in the 1990s vs. 1970s varied by diagnosis, with leukemia, lymphoma, and CNS tumor survivors estimated to live an additional 8 to 11 yrs (Table). In contrast, considerably smaller gains were estimated for sarcoma and renal tumor survivors (1–3 yrs) and a loss for neuroblastoma (-3 yrs). Among survivors who reached age 40, the probability of surviving an additional 10 years increased from 89% to 92% between 1970s vs. 1990s, with the greatest gains for lymphoma and CNS tumors. Conclusions: Although temporal changes in pediatric oncology are projected to result in LE gains among survivors, considerable variation is projected across diagnoses. These findings highlight the uneven success of improving treatments for all cancers. [Table: see text]
Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Biomarker (BM) analyses by next-generation sequencing (NGS) from the SOLAR-1 study.
Authors: Juric Dejan , Rugo Hope S. , Reising Albert , Ma Chong , Ciruelos Eva M. , Loibl Sibylle , Singer Christian F. , Sohn Joohyuk , Campone Mario , Conte Pierfranco , Iwata Hiroji , Ghaznawi Farhat , Miller Michelle Kristine , Taran Tetiana , Su Fei , Andre Fabrice
Published: June 2022

1006

Background: PIK3CA mutations (mut; ~40% of HR+, HER2– ABC) are linked to poor prognosis. In SOLAR-1, ALP (PI3Kα-selective inhibitor and degrader) + FUL improved progression-free survival (PFS) vs placebo (PBO) + FUL in pts with PIK3CA-mutated HR+, HER2– ABC. Here, we focus on efficacy data by gene alterations in SOLAR-1 PIK3CA-altered (alt) cohort. Methods: SOLAR-1 was a phase 3, randomized, double-blind study of ALP (or PBO) + FUL in HR+, HER2– ABC progressing on/after an aromatase inhibitor. Baseline tissue samples with enough quantity/quality (N = 398) were retrospectively tested by NGS (FoundationOne CDx 324-gene panel) and pts grouped by PIK3CA-alteration status. Clinical benefit was assessed using PFS and hazard ratio (HR) based on tumor mutational burden (TMB) and gene alteration status in the PIK3CA-alt cohort. No multiplicity adjustment was made. Results: PIK3CA-alt (ALP, n = 120; PBO, n = 117) and PI3KCA-non-alt (ALP, n = 81; PBO, n = 80) cohorts had differential gene alteration landscapes. In the PIK3CA-alt cohort, ALP + FUL clinical benefit was seen across TMB quartiles (Q1: 0 -<2.52, Q2: 2.52 -<3.78, Q3: 3.78 -<5.04, Q4: ≥ 5.04 mut/megabase). ALP + FUL had greater benefit in pts with alt vs non-alt FGFR1/ 2 (Table). ALP + FUL benefit was independent of alterations in TP53, ESR1, CCND1, MAP3K1, and ARID1A and limited in MYC- and RAD21-alt cohorts . ALP + FUL benefit was seen in pts with alt genes in the MAPK (HR [95% CI] vs PBO: alt 0.43 [0.23 - 0.80]; non-alt 0.56 [0.40 - 0.79]) and PI3K (in addition to PIK3CA; alt 0.68 [0.38 - 1.23]; non-alt 0.48 [0.34 - 0.68]) pathways, and implicated in CDK4/6i resistance (alt 0.52 [0.30 - 0.89]; non-alt 0.53 [0.37 - 0.76]). Conclusions: The unique mut profile of PIK3CA-alt tumors did not affect ALP + FUL benefit in pts with HR+, HER2– ABC. Clinical benefit was maintained regardless of alterations in most BMs, including ESR1 and genes implicated in CDK4/6i resistance, consistent with ALP targeting the PIK3CA driver oncogene. Clinical trial information: NCT#02437318; EUDRA CT#2015-000340-42. [Table: see text]