bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging web-based prediction calculators to set patient expectations for elective spine surgery: a qualitative study to inform implementation
Authors: Lentz Trevor A. , Stephens Byron F. , Abtahi Amir M. , Schwarz Jacob , Schoenfeld Andrew J. , Rhoten Bethany A. , Block Shannon , O’Brien Alex , Archer Kristin R.
Published: August 2023

Background

Prediction calculators can help set outcomes expectations following orthopaedic surgery, however effective implementation strategies for these tools are unknown. This study evaluated provider and patient perspectives on clinical implementation of web-based prediction calculators developed using national prospective spine surgery registry data from the Quality Outcomes Database.

Methods

We conducted semi-structured interviews in two health systems, Vanderbilt University Medical Center (VUMC) and Duke University Health System (DUHS) of orthopedic and neurosurgery health care providers (VUMC: n = 19; DUHS: n = 6), health care administrators (VUMC: n = 9; DUHS: n = 9), and patients undergoing elective spine surgery (VUMC: n = 16). Qualitative template analysis was used to analyze interview data, with a focus on end-user perspectives regarding clinical implementation of web-based prediction tools.

Results

Health care providers, administrators and patients overwhelmingly supported the use of the calculators to help set realistic expectations for surgical outcomes. Some clinicians had questions about the validity and applicability of the calculators in their patient population. A consensus was that the calculators needed seamless integration into clinical workflows, but there was little agreement on best methods for selecting which patients to complete the calculators, timing, and mode of completion. Many interviewees expressed concerns that calculator results could influence payers, or expose risk of liability. Few patients expressed concerns over additional survey burden if they understood that the information would directly inform their care.

Conclusions

Interviewees had a largely positive opinion of the calculators, believing they could aid in discussions about expectations for pain and functional recovery after spine surgery. No single implementation strategy is likely to be successful, and strategies vary, even within the same healthcare system. Patients should be well-informed of how responses will be used to deliver better care, and concerns over how the calculators could impact payment and liability should be addressed prior to use. Future research is necessary to determine whether use of calculators improves management and outcomes for people seeking a surgical consult for spine pain.
Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation
Authors: Wang Jing , Ji Yanchun , Ai Cheng , Chen Jia-Rong , Gan Dingyi , Zhang Juanjuan , Mo Jun Q. , Guan Min-Xin
Published: August 2023

Background

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited eye disease due to mutations in mitochondrial DNA. However, there is no effective treatment for this disease. LHON-linked ND6 14484T > C (p.M64V) mutation caused complex I deficiency, diminished ATP production, increased production of reactive oxygen species (ROS), elevated apoptosis, and impaired mitophagy. Here, we investigated if the allotopic expression of human mitochondrial ND6 transgene corrected the mitochondrial dysfunctions due to LHON-associated m.14484T > C mutation.

Methods

Nucleus-versions of ND6 was generated by changing 6 non-universal codons with universal codons and added to mitochondrial targeting sequence of COX8. Stable transfectants were generated by transferring human ND6 cDNA expressed in a pCDH-puro vector into mutant cybrids carrying the m.14484T > C mutation and control cybrids. The effect of allotopic expression of ND6 on oxidative phosphorylation (OXPHOS) was evaluated using Blue Native gel electrophoresis and extracellular flux analyzer. Assessment of ROS production in cell lines was performed by flow cytometry with MitoSOX Red reagent. Analyses for apoptosis and mitophagy were undertaken via flow cytometry, TUNEL and immunofluorescence assays.

Results

The transfer of human ND6 into the cybrids carrying the m.14484T > C mutation raised the levels of ND6, ND1 and ND4L but did not change the levels of other mitochondrial proteins. The overexpression of ND6 led to 20~23% increases in the assembly and activity of complex I, and ~ 53% and ~ 33% increases in the levels of mitochondrial ATP and ΔΨm in the mutant cybrids bearing m.14484T > C mutation. Furthermore, mutant cybrids with overexpression of ND6 exhibited marked reductions in the levels of mitochondrial ROS. Strikingly, ND6 overexpression markedly inhibited the apoptosis process and restored impaired mitophagy in the cells carrying m.14484T > C mutation. However, overexpression of ND6 did not affect the ND6 level and mitochondrial functions in the wild-type cybrids, indicating that this ND6 level appeared to be the maximum threshold level to maintain the normal cell function.

Conclusion

We demonstrated that allotopic expression of nucleus-versions of ND6 restored complex I, apoptosis and mitophagy deficiencies caused by the m.14484T > C mutation. The restoration of m.14484T > C mutation-induced mitochondrial dysfunctions by overexpression of ND6 is a step toward therapeutic interventions for LHON and mitochondrial diseases.
Interleukin-5 levels in relation to malaria severity: a systematic review
Authors: Kotepui Manas , Duangchan Thitinat , Mahittikorn Aongart , Mekhora Chusana , Anabire Nsoh Godwin , Kotepui Kwuntida Uthaisar
Published: August 2023

Background

The role of cytokines such as interleukin-5 (IL-5) in the pathogenesis of malaria remains unclear. This systematic review sought to synthesize variations in IL-5 levels between severe and uncomplicated malaria, as well as between malaria and controls not afflicted with the disease.

Methods

This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022368773). Searches for studies that reported IL-5 levels in patients with malaria (any severity) and/or uninfected individuals were performed in Web of Science, PubMed, EMBASE, Scopus, CENTRAL, and MEDLINE, between 1st and 10th October, 2022. The risk of bias among all included studies was minimized using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies. The differences in IL-5 levels between malaria and uninfected controls, and between severe and uncomplicated malaria were synthesized by narrative synthesis.

Results

Among 1177 articles identified in the databases, 23 matched the eligibility criteria and were included in this systematic review. Qualitative syntheses showed the heterogeneity of IL-5 levels between different severities of clinical malaria and uninfected controls. The majority of the included studies (12/15 studies, 80%) found no change in IL-5 levels between malaria cases and uninfected controls. Similarly, most studies found no difference in IL-5 levels between severe (regardless of complications) and uncomplicated malaria (4/8 studies, 50%). The qualitative syntheses revealed that most studies found no difference in IL-5 levels between severe and non-severe malaria.

Conclusions

The comprehensive review suggests that IL-5 levels are unchanged in patients with different levels of clinical severity of malaria and uninfected controls. Given the limited number of published studies on IL-5 levels in malaria, there is a need for additional research to determine the function of this cytokine in the pathogenesis of malaria.
ATRA sensitized the response of hepatocellular carcinoma to Sorafenib by downregulation of p21-activated kinase 1
Authors: Wang Kai , Qiu Xun , Zhang Zhensheng , Xu Hanzhi , Tan Yawen , Su Renyi , Gao Fengqiang , Zhuo Jianyong , Li Wangyao , Lian Zhengxing , He Hong , Xu Xiao
Published: August 2023

Background

Sorafenib resistance greatly reduces the efficacy of treatments in advanced hepatocellular carcinoma (HCC) patients, but the underlying mechanisms are not thoroughly understood. All-trans retinoic acid (ATRA), an anti-leukaemia agent, has attracted considerable attention due to its role in sensitizing cells to other anticancer treatments. We aimed to investigate the combined effect of ATRA and Sorafenib on HCC and the underlying mechanisms.

Methods

CCK-8, cell sphere formation, trans-well migration, and wound-healing assays were used to analyse the biological behaviours of HCC cells in vitro. Western blotting and qRT-PCR analysis were conducted to measure the expression of p21 activated kinase 1 (PAK1) and phospho-p21 activated kinase 1 (pPAK1). Xenograft models were established to confirm the synergistic effects of ATRA and Sorafenib in vivo. TUNEL assays and immunohistochemistry were utilized to determine apoptosis, proliferation, PAK1 and pPAK1 levels in tumour tissues.

Results

We observed that PAK1 was overexpressed in HCC, and its expression was negatively correlated with the survival of patients. PAK1 promoted the proliferation, self-renewal and epithelial-mesenchymal transition of HCC cells. Correlation analysis indicated that the IC50 of Sorafenib was positively correlated with the level of pPAK1 in HCC cell lines. ATRA inhibited the progression of HCC and sensitized HCC response to Sorafenib by downregulation of PAK1, as shown by the calculated coefficient of drug interaction and the data obtained from xenograft models.

Conclusions

Our findings indicated that instead of treatment with Sorafenib alone, the combination of ATRA and Sorafenib provides a more effective treatment for HCC patients.
Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized controlled trial
Authors: Akiba Christopher F. , Patel Sheila V. , Wenger Lynn D. , Morgan-Lopez Antonio , Zarkin Gary A. , Orme Stephen , Davidson Peter J. , Kral Alex H. , Lambdin Barrot H.
Published: August 2023

Background

More than half a million Americans died of an opioid-related overdose between 1999 and 2020, the majority occurring between 2015 and 2020. The opioid overdose mortality epidemic disproportionately impacts Black, Indigenous, and people of color (BIPOC): since 2015, overdose mortality rates have increased substantially more among Black (114%) and Latinx (97%) populations compared with White populations (32%). This is in part due to disparities in access to naloxone, an opioid antagonist that can effectively reverse opioid overdose to prevent death. Our recent pilot work determined that many barriers to naloxone access can be identified and addressed by syringe service programs (SSPs) using the Systems Analysis and Improvement Approach to Naloxone distribution (SAIA-Naloxone). This randomized controlled trial will test SAIA-Naloxone’s ability to improve naloxone distribution in general and among BIPOC specifically.

Methods

We will conduct a trial with 32 SSPs across California, randomly assigning 16 to the SAIA-Naloxone arm and 16 to receive implementation as usual. SAIA-Naloxone is a multifaceted, multilevel implementation strategy through which trained facilitators work closely with SSPs to (1) assess organization-level barriers, (2) prioritize barriers for improvement, and (3) test solutions through iterative change cycles until achieving and sustaining improvements. SSPs receiving SAIA-Naloxone will work with a trained facilitator for a period of 12 months. We will test SAIA-Naloxone’s ability to improve SSPs’ naloxone distribution using an interrupted time series approach. Data collection will take place during a 3-month lead-in period, the 12-month active period, and for an additional 6 months afterward to determine whether impacts are sustained. We will use a structured approach to specify SAIA-Naloxone to ensure strategy activities are clearly defined and to assess SAIA-Naloxone fidelity to aid in interpreting study results. We will also assess the costs associated with SAIA-Naloxone and its cost-effectiveness.

Discussion

This trial takes a novel approach to improving equitable distribution of naloxone amid the ongoing epidemic and associated racial disparities. If successful, SAIA-Naloxone represents an important organizational-level solution to the multifaceted and multilevel barriers to equitable naloxone distribution.
Treatment progress of spinal metastatic cancer: a powerful tool for improving the quality of life of the patients
Authors: Zhao Yuliang , Liu Fei , Wang Wei
Published: August 2023

Spinal metastasis is a common secondary malignant tumor of the bone, often resulting in spinal cord and nerve root compression, leading to obvious pain and related compression symptoms. This condition has a high incidence and mortality rate. The treatment approach for most patients with spinal metastasis is primarily palliative. Consultation with a multidisciplinary team is widely accepted as a comprehensive treatment approach for patients with spinal metastases. With advancements in research and technology, the evaluation and treatment of spinal metastatic cancer are continuously evolving. This study provides an overview of surgical treatment, minimally invasive treatment, and radiotherapy for spinal metastatic cancer and also analyzes the clinical effects, advantages, and current limitations associated with various treatment approaches.
The performance of duplex ultrasonography for the assessment of renal artery stenosis in Takayasu’s arteritis patients
Authors: Wang Yahong , Wang Ying , Zhang Li , Ge Zhitong , Li Jing , Yang Yunjiao , Chen Yu , Yang Xiao , Li Jianchu , Tian Xinping
Published: August 2023

Background

This study intends to analyze the hemodynamic parameters of the renal artery in patients with Takayasu’s arteritis (TAK) to explore the diagnostic efficacy of duplex ultrasonography in assessing the involved renal artery in TAK patients.

Methods

One hundred fifteen TAK patients with 314 renal arteries were retrospectively analyzed, who were admitted to Peking Union Medical College Hospital between 2017 and 2022. These patients underwent both renal artery ultrasonography and angiography within a 4-week period. Specifically, the study compared seven ultrasonic parameters across groups categorized by the severity of renal artery stenosis (RAS), including noninvolvement, < 50% stenosis, 50–69% stenosis, and 70–99% stenosis. Receiver operating characteristic (ROC) curves were employed to determine the optimal threshold values for renal artery peak systolic velocity (RPSV), renal-aortic PSV ratio (RAR), and renal-interlobar PSV ratio (RIR) in order to diagnose various degrees of RAS in TAK patients.

Results

Statistically significant differences were observed in RAR and RIR among the four groups (all P < 0.05). However, no statistically significant differences were found in RPSV and AT between the moderate stenosis group (50–69% stenosis) and the severe stenosis group (70–99% stenosis). The discrimination of interlobar PSV (IPSV) and interlobar RI (IRI) was not significant, and IEDV did not show statistical significance among the four groups.

For TAK patients, the recommended thresholds of RPSV for the diagnosis of renal artery involvement (RAI), ≥ 50% RAS, and ≥ 70% RAS were determined to be 143 cm/s, 152 cm/s, and 183 cm/s, respectively. The sensitivities, specificities, and accuracies of these thresholds were all found to be greater than 80%. Additionally, the optimal thresholds of RIR for detecting RAI, ≥ 50% RAS, and ≥ 70% RAS were determined to be 4.6, 5.6, and 6.4, respectively, with satisfactory diagnostic efficiencies. The areas under the curve (AUCs) for RPSV and RIR were calculated to be 0.908 and 0.910, respectively, for the diagnosis of ≥ 50% RAS, and 0.876 and 0.882 for the diagnosis of ≥ 70% RAS. When the aortic PSV is greater than or equal to 140 cm/s, the RAR exhibits inadequate diagnostic efficacy. Conversely, when the aortic PSV is less than 140 cm/s, a RAR value of 2.2 or higher can be employed as the diagnostic threshold for identifying RAS of 70% or greater, with a sensitivity of 84.00%, specificity of 89.93%, and an overall accuracy of 89.08%.

Conclusion

In the present study, it has been demonstrated that RPSV and RIR possess substantial diagnostic value as ultrasonic parameters for diagnosing RAS in TAK patients. Furthermore, when assessing the diagnostic efficacy of RAR, it is crucial to consider the severity of aortic stenosis as a determining factor.
Mapping the effectiveness of the community tuberculosis care programs: a systematic review
Authors: Sejie Gabalape Arnold , Mahomed Ozayr H.
Published: August 2023

Background

Tuberculosis is a significant global public health threat, especially in countries with limited resources. To improve tuberculosis care, the World Health Organization emphasizes the importance of considering a TB patient’s journey across a variety of connected settings and facilities. A systematic review was conducted to map previously conducted studies to identify existing community TB implementation models, their effectiveness on cost, and treatment outcomes.

Methods

Systematic search through various electronic databases MEDLINE, EBSCO (PsycINFO and CINAHL), Cochrane Library, EMBASE, WHO Regional Databases, gray literature, and hand-searched bibliographies was performed. Articles published in English between the years 2000 and 2022 with a substantial focus on community TB implementation models were considered for inclusion. Studies were excluded if the intervention was purely facility-based and those focusing exclusively on qualitative assessments. Two reviewers used standardized methods to screen titles, abstracts, and data charting. Included studies were assessed for quality using ROBINS-I and ROB 2. Analysis of study results uses a PRISMA flow diagram and quantitative approach.

Results

A total of 6982 articles were identified with 36 meeting the eligibility criteria for analysis. Electronic medication monitors showed an increased probability of treatment success rate (RR 1.0–4.33 and the 95% CI 0.98–95.4) in four cohort studies in low- and middle-income countries with the incremental cost-effectiveness of $434. Four cohort studies evaluating community health worker direct observation therapy in low- and middle-income countries showed a treatment success risk ratio of up to 3.09 with a 95% CI of 0.06–7.88. (32,41,43,48) and incremental cost-effectiveness up to USS$410. Moreover, four comparative studies in low- and middle-income countries showed family directly observed treatment success risk ratio up to 9.07, 95% CI of 0.92–89.9. Furthermore, four short message service trials revealed a treatment success risk ratio ranging from 1.0 to 1.45 (95% CI fell within these values) with a cost-effectiveness of up to 350I$ compared to standard of care.

Conclusions

This review illustrates that community-based TB interventions such as electronic medication monitors, community health worker direct observation therapy, family directly observed treatment, and short message service can substantially bolster efficiency and convenience for patients and providers while reducing health system costs and improving clinical outcomes.
Global regularity of 2D MHD equations with almost Laplacian velocity dissipation
Authors: Li Linrui , Hong Mingli
Published: August 2023

We obtain the global existence and global regularity for the 2D MHD equations with almost Laplacian velocity dissipation, which require the dissipative operators weaker than any power of the fractional Laplacian. The result can be regarded as a further improvement and generalization of previous works.
How effective are perches in promoting bird-mediated seed dispersal for natural forest regeneration? A systematic review protocol
Authors: Gan Jelaine Lim , Grainger Matthew James , Shirley Mark David Foster , Pfeifer Marion
Published: August 2023

Background

Forest landscape restoration (FLR), often through tree planting, is one of the priorities in many global and national initiatives for carbon offsetting as part of climate change mitigation and biodiversity conservation. However, active efforts to meet FLR objectives entail substantial costs for the procurement of planting stocks and require an experienced workforce for planting and nurturing tree seedlings. Alternatively, restoration projects can be more cost-effective and potentially may have greater biodiversity gain through assisting and accelerating natural forest regeneration. The use of perches is one of the strategies under Assisted Natural Regeneration (ANR) and is used to attract avian seed dispersers to degraded habitats for increased tree seed supply and seedling establishment. This systematic review and potential meta-analysis aim to determine the effectiveness of artificial and natural perches in promoting natural forest regeneration. Specifically, we will evaluate their effectiveness in driving seed richness, seed density, seedling richness, and seedling density. The results will synthesize available evidence on the topic, identify knowledge gaps we need filling to upscale the strategy, and inform their use in concert with other ANR strategies.

Methods

The search strategy was informed through a literature scan and discussions with stakeholders and experts. A total of eight databases, which include an organizational library and a web-based search engine, will be searched using the refined search string in English. The search string was formed using keywords corresponding to the PICO structure of the research question, and its comprehensiveness was evaluated using 10 benchmark articles. The search results will be screened by the review team (composed of a primary and at least two secondary reviewers) using the set eligibility criteria at the title and abstract level, followed by the full-text screening. The screened studies will then undergo critical appraisal using the assessment criteria based on risk of bias and methods. Data from the accepted studies will be extracted to the standard data sheet for meta-analysis. Effect size (Hedges’ g) will be computed to determine whether perches are effective in increasing seed dispersal and seedling establishment in degraded sites. The effect of potential modifiers relating to the landscape will be explored via mixed models.
MicroRNA-144-3p protects against chemotherapy-induced apoptosis of ovarian granulosa cells and activation of primordial follicles by targeting MAP3K9
Authors: Liu Meng , Xiao Bang , Zhu Yiqing , Chen Meiting , Huang Jinfeng , Guo Haiyan , Wang Fang
Published: August 2023

Premature ovarian failure (POF) is defined by amenorrhea, ovarian atrophy, hypoestrogenism, elevated gonadotropin level, and infertility under the age of 40. POF is frequently induced by chemotherapeutic agents. However, the underlying mechanisms regarding chemotherapy-mediated damage to ovarian function are unclear. In this study, enhanced apoptosis of granulosa cells (GCs) and aberrant activation of primordial follicles were observed in a POF mouse model induced by cisplatin. We subsequently observed significant downregulation of miR-144-3p and upregulation of mitogen-activated protein kinase kinase kinase 9 (MAP3K9) in primary ovarian GCs from POF mice, as revealed by microarrays. Furthermore, MAP3K9 expression was higher in human ovarian granulosa cells (COV434) treated with cisplatin and was identified as a novel target of miR-144-3p. Functional analysis revealed that miR-144-3p attenuated cisplatin induced apoptosis of GCs via silencing MAP3K9 expression, which suppressed the activity of the downstream p38 mitogen activated protein kinase (MAPK) pathway. Meanwhile, miR-144-3p prevented premature primordial follicle depletion in cisplatin-induced POF mice through targeting Map3k9, which led to a decline in the phosphorylation and activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase b (AKT) pathway. Taken together, this study revealed the protective effects of miR-144-3p on ovarian function and shed light on the epigenetic regulatory mechanism in the development of POF, which might provide new biomarkers for the ovarian reserve.
The role of organoids in cancer research
Authors: Fang Zhen , Li Peijuan , Du Fengying , Shang Liang , Li Leping
Published: August 2023

Organoids are established through in vitro 3D culture, and they can mimic the structure and physiological functions of organs or tissues in vivo. Organoids have attracted much attention in recent years. They can provide a reliable technology platform for cancer research and treatment and are a valuable preclinical model for academic research and personalized medicine. A number of studies have confirmed that organoids have great application prospects in new drug development, drug screening, tumour mechanism research, and precision medicine. In this review, we mainly focus on recent advances in the application of organoids in cancer research. We also discussed the opportunities and challenges facing organoids, hoping to indicate directions for the development of organoids in the future.
The global prevalence of screen-based disordered eating and associated risk factors among high school students: systematic review, meta-analysis, and meta-regression
Authors: Ghazzawi Hadeel A. , Nimer Lana S. , Sweidan Dima H. , Alhaj Omar A. , Abulawi Duha , Amawi Adam T. , Levine Michael P. , Jahrami Haitham
Published: August 2023

Objective

Estimate the prevalence, and associated risk factors, of high school students who are considered at risk for an eating disorder based on screening measures.

Methods

An electronic search of nine databases was completed from their inception until 1st September 2022. A random-effects meta-analysis was conducted, and confounder (moderator) analyses and meta-regressions examined whether the overall prevalence estimate for of screen-based disordered eating (SBDE) was moderated by student age, BMI, or gender, as well as culture and type of SBDE assessment.

Results

The mean estimate of the prevalence of SBDE among high school students (K = 42 (66 datapoints), N = 56282] in the sample of 25 countries was 13% ([95% CI] = 10.0–16.8%, I2 = 99.0%, Cochran's Q p = 0.001). This effect was not moderated by features of the samples such as gender, BMI, or age. Among cultures, non-Western countries had a higher prevalence of SBDE prevalence than Western countries, but the difference was not significant. There was considerable variability in the prevalence estimates as a function of the assessment measure, but no meaningful pattern emerged.

Conclusion

The estimated figure of 1 in 8 high school students with SBDE—unmoderated by gender and BMI—stands out as a problem in need of attention from public health officials, psychologists, psychiatrists, pediatricians, parents, and educators. There is a great need for innovative, integrated policy and program development all along the spectrum of health promotion and universal, selective, and indicated prevention. Further research is also needed to validate and refine this estimate by (a) conducting basic research on the accuracy of eating disorder screening measurements in samples ages 14 through 17; (b) examining representative samples in more countries in general and Latin American countries in particular; (c) clarifying the relationships between SBDE and age throughout the different phases of late childhood, adolescence, and emerging adulthood; and (d) investigating whether there are meaningful forms of disordered eating and whether these are associated with variables such as gender, ethnicity, and BMI.
An investigation of Bellini’s Transfiguration in the Capodimonte museum by means of XRF and visible reflectance hyperspectral imaging: Bellini’s handling of materials in the head and figure of the transfigured Christ
Authors: de Viguerie Laurence , Glanville Helen , Radepont Marie , Cerasuolo Angela , Rullo Alessandra , Seccaroni Claudio , Walter Philippe
Published: August 2023

The Transfiguration by Giovanni Bellini in the Museo di Capodimonte (Naples) is an iconic image of a transcendental event at the heart of the Christian religion. Using non-destructive chemical imaging, and focusing on the central image of the transfigured Christ we have studied by what means and with what materials the artist represented this divine event. The results showed what is to date the earliest use of the pigment stibnite. The techniques employed demonstrate both continuity with Bellini’s earliest works (such as the combination of the use of shell-gold and organic, tinted layers), but also his knowledge of Netherlandish painting. This research has furthered our understanding of how he achieved the luminosity so characteristic of his translation of the divine into the materiality of paint.
How to insert visual information into a whiteboard animation with a human hand? Effects of different insertion styles on learning
Authors: Krieglstein Felix , Meusel Felicia , Rothenstein Eva , Scheller Nadine , Wesenberg Lukas , Rey Günter Daniel
Published: August 2023

Whiteboard animations have become very popular in recent years. They are mainly used in distance education, where learners can acquire knowledge individually and without the help of a teacher. However, there is little empirical evidence on how whiteboard animations should be designed to achieve learning-enhancing effects. Since the presentation of whiteboard animations is reminiscent of a teacher drawing or showing content on a whiteboard, the hand has been identified as an essential feature of this learning medium. Therefore, the aim of this experimental study was to investigate whether and how the human hand should be implemented in whiteboard animations for the presentation of visual content. University students (N = 84) watched a whiteboard animation in which the type of information insertion was manipulated (hand drawing content vs. hand pushing content in vs. no hand visible). Results revealed that the drawing hand on a whiteboard led to significantly higher intrinsic motivation than the hand pushing visual content onto the whiteboard. Contrary to assumptions derived from cognitive load theory, the implementation of a human hand did not cause extraneous cognitive load. However, no other effects on the perception of the instructor, cognitive load, and learning performance were found. The results are discussed in terms of both cognitive and social processes in multimedia learning.
Splanchnic sympathetic nerve denervation improves bacterial clearance and clinical recovery in established ovine Gram-negative bacteremia
Authors: Peiris Rachel M. , May Clive N. , Booth Lindsea C. , McAllen Robin M. , McKinley Michael J. , Hood Sally , Martelli Davide , Bellomo Rinaldo , Lankadeva Yugeesh R.
Published: August 2023

Background

The autonomic nervous system can modulate the innate immune responses to bacterial infections via the splanchnic sympathetic nerves. Here, we aimed to determine the effects of bilateral splanchnic sympathetic nerve denervation on blood pressure, plasma cytokines, blood bacterial counts and the clinical state in sheep with established bacteremia.

Methods

Conscious Merino ewes received an intravenous infusion of Escherichia coli for 30 h (1 × 109 colony forming units/mL/h) to induce bacteremia. At 24 h, sheep were randomized to have bilaterally surgically implanted snares pulled to induce splanchnic denervation (N = 10), or not pulled (sham; N = 9).

Results

Splanchnic denervation did not affect mean arterial pressure (84 ± 3 vs. 84 ± 4 mmHg, mean ± SEM; PGroup = 0.7) compared with sham treatment at 30-h of bacteremia. Splanchnic denervation increased the plasma levels of the pro-inflammatory cytokine interleukin-6 (9.2 ± 2.5 vs. 3.8 ± 0.3 ng/mL, PGroup = 0.031) at 25-h and reduced blood bacterial counts (2.31 ± 0.45 vs. 3.45 ± 0.11 log10 [CFU/mL + 1], PGroup = 0.027) at 26-h compared with sham treatment. Plasma interleukin-6 and blood bacterial counts returned to sham levels by 30-h. There were no differences in the number of bacteria present within the liver (PGroup = 0.3). However, there was a sustained improvement in clinical status, characterized by reduced respiratory rate (PGroup = 0.024) and increased cumulative water consumption (PGroup = 0.008) in splanchnic denervation compared with sham treatment.

Conclusion

In experimental Gram-negative bacteremia, interrupting splanchnic sympathetic nerve activity increased plasma interleukin-6, accelerated bacterial clearance, and improved clinical state without inducing hypotension. These findings suggest that splanchnic neural manipulation is a potential target for pharmacological or non-pharmacological interventions.
Does the use of pharmacotherapy interact with the effects of psychotherapy? A meta-analytic review
Authors: Cuijpers Pim , Miguel Clara , Harrer Mathias , Ciharova Marketa , Karyotaki Eirini
Published: August 2023

Background

It is not clear if there is an interaction between psychotherapy and pharmacotherapy. First, there may be no interaction at all, meaning that the effects of both are independent of each other. Second, antidepressants may reduce the effects of psychotherapy, and third, antidepressants may increase the effects of psychotherapy. We examined which of the three is correct.

Methods

We conducted random effects meta-analyses of randomized trials comparing psychotherapies for adult depression with control conditions. The proportion of users of antidepressants was used as a predictor of the effect size in a series of meta-regression analyses, while adjusting for relevant moderators, such as type of control group and baseline severity.

Results

We included 300 randomized controlled trials (353 comparisons between treatment and control; 32,852 participants). The main effect size of psychotherapy was g = 0.71 (95% CI: 0.64; 0.79) with high heterogeneity (I2 = 82; 95% CI: 80; 84). We found no significant association between the proportion of antidepressants users and effect size (p = .07). We did find a significant association with some other predictors, including the type of control group and risk of bias. The use of antidepressants was associated with higher response rates within the control conditions, but not with the relative effects of the treatments compared to the control groups.

Discussion

We found support for the independent effects of psychotherapy and pharmacotherapy, which is good news from a clinical perspective. Apparently, patients can start with psychotherapy and do not have to be afraid that this will reduce the effects of the therapy.
Diversity data in oncology electronic data capture and database design: A global overview, gap analysis and recommendations for industry from the imCORE network, a worldwide research network designed to connect members in an open environment of shared information, expertise, and decisions.
Authors: Helou Sarah , Vidhyarkorn Tanya , Russell Janice , Churchill Sarah
Published: August 2023

101

Background: The importance of enrolling diverse and inclusive patient populations in clinical trials has never been more critical however the implementation of measures to ensure inclusive clinical trials remains inconsistent and challenging industry wide. One key mechanism for tracking diversity in clinical trials is the database design of patient demographic classifications. Methods: In this paper we utilize the global reach of the imCORE network to explore the current trends in clinical trial database design for demographic data. We collect and review data on the design of electronic database systems from a diversity of sources including Roche Genentech clinical trial database frameworks and databases at our imCORE sites. We then provide a global electronic database demographic data classification overview and gap analysis. Results: Findings related to electronic database design, demographic data collection process, barriers to capturing diversity and demographic data are presented. Conclusions: Based on our findings we make recommendations from the site and sponsor perspective for an improved future state of electronic demographic diversity data collection in clinical trials with the goal of ultimately leading to meaningful change toward fully inclusive and equitable clinical trials.
Preclinical evaluation of JAK2 specific investigational oligonucleotide for the treatment of MDS/PV.
Authors: Przychodzen Bartlomiej , Smieszek Sandra Paulina
Published: August 2023

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Background: Myeloproliferative disorders (MPD) are clonal hematopoietic stem cell malignancies with cytokine independency or hypersensitivity. Polycythemia vera (PV), an acquired MPD characterized by increased blood cell mass and hematocrit and leukocyte count, is associated with incidental myelofibrosis (MF). MDS is characterized by cytopenia and the presence of morphological dysplasia of precursor and mature bone marrow blood cells. PV and MDS leave patients at risk for progression to acute myeloid leukemia. Abnormal cytokine signaling due to an aberrant JAK2-STAT pathway has a vital role in PV and MDS pathogenesis. JAK2 mutations can result in hematologic malignancies, where hyperactive signaling of the JAK2-STAT pathway promotes tumor cell proliferation, invasion, and angiogenesis. Increased JAK2 kinase activity is observed in hematologic malignancies; somatic JAK2 V617F gain-of-function mutations are found in at least 95% of PV patients and is implicated in MDS cases. We hypothesize that preventing JAK2 transcription by antisense oligonucleotide (ASO) mediated exon masking of the JAK2 intron-exon junction will result in reduced JAK2 mRNA, and thus JAK2 protein, by providing nonsense mediated decay (NMD) in the reading frame. This may alleviate disease manifestations of hematologic malignancies like PV and MDS. Methods: This study utilized a HEL cell line harboring the V617F JAK2 gain-of-function mutation. We designed a series 19mer ASO targeting JAK2 exon-intron junctions ( JAK2 intron-exon junction providing NMD in the reading frame, steric, non-RNAse H1) and tested these at a range of concentrations. The ASOs were designed with a phosphorothioate 2’-O-methoxyethyl backbone and prioritized based on in silico binding affinity and limited off-target binding. HEL cells underwent ASO treatment (1µM) and 72-hour incubation. Results: We observed significant JAK2 protein decrease (~50%) in ASO-treated samples compared to untreated samples. JAK2 qPCR results confirmed 40-60% of target transcript. STAT5 phosphorylation status further confirmed this effect, and we report a 35% pSTAT5 reduction. Furthermore, this ASO showed limited off-target effects in silico. siRNA and CRISPR knockout lysate were used as controls. Our preclinical data support this ASO as a highly specific JAK2 agent, affecting direct levels of JAK2 as well as downstream STAT signaling. Conclusions: Around 50-60% of primary MF patients harbor the JAK2 V617F gain-of-function mutation. ASOs offer the capability to directly target JAK2 mutations with high precision and effectively reduce JAK2 protein production, without off-target kinase effects. The ability to reduce JAK2 protein may alleviate the disease burden that patients with hematologic malignancies face, resulting in a higher quality of life through prevention and treatment.
Survival benefit of maintenance therapy in AML patients after complete remission in northeast Iran oncology centers with limited access to oral azacitidine.
Authors: Shariatmaghani Somayeh Sadat , Moeini Nodeh Mohammad , Emadzadeh Maryam , Allahyari Abollghasem , Rahimi Hossein , Mozaheb Zahra , Seddigh Shamsi Mohsen , ataei Azimi Sajad , Bary Alireza , Mohaddes Tahereh , Nazar Eisa , Davoudi Farnoush , Rezaei Borojerdi Zahra
Published: August 2023

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Background: Acute myeloid leukemia (AML) is associated with high relapse rates even in patients who achieve a complete remission with initial treatment. Maintenance therapy with cytotoxic agents has been considered a strategy to prolong disease-free survival (DFS) and overall survival (OS). The lack of availability of oral Azacitidine in some countries limits its use. This study aimed to compare the DFS and OS rates of AML patients with and without maintenance therapy using subcutaneous cytarabine or oral thioguanine. Methods: This retrospective cohort study reviewed the charts of non-m3 AML patients treated in oncology centers in northeast Iran from February 2015 to February 2021. The study included patients aged 15-60 who experienced complete remission following induction and then consolidation chemotherapy and did not receive Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). Patients were categorized based on receiving maintenance therapy (MT) after the first-line treatment and those who were only followed up (FU). Patients’ demographic information, pathology and lab findings, date of relapse and/or death, and first-line and maintenance treatments regimens were extracted. For each of the MT and FU groups, the frequency of main outcomes (death and/or relapse) was calculated, and the Median (95%CI) of DFS and OS was estimated. The log-rank test was used to compare the DFS and OS between groups. Results: A total of 100 patients (50 MT and 50 FU) met the study inclusion criteria. There were no significant differences between the two groups regarding patients’ demographic characteristics, pathology and lab findings, and ELN’s risk category. The relapse rate in the FU and MT groups was 76% (n=38) and 60% (n=30) respectively (p=0.09). 39 individuals (78%) in the FU group and 26 individuals (54.2%) in the MT group died between complete remission and Feb 2022(p=0.01). The Median (95% CI) of DFS in FU and MT groups were 11 (8.6-13.3) and 18 (7.3 -28.6) months respectively (P=0.03). The median OS (95% CI) was 16 (10.8 - 21.1) months in the FU group and 23 (10.8 - 35) months in the MT group (P=0.04). Further comparisons between patients who received subcutaneous cytarabine and oral thioguanine revealed no significant differences regarding DFS and OS. Conclusions: The study results suggest that maintenance therapy with subcutaneous cytarabine or oral thioguanine after complete remission in non-m3 AML patients is associated with improved DFS and OS. Further randomized controlled trials and cost-utility studies are recommended to consider these available cytotoxic agents as maintenance therapy alternatives in regions where Azacitidine is not available.
Global public health implications of social media engagement from a virtual education platform to combat oncology misinformation.
Authors: Wilkerson William B. , Pawar Shubhadarshini , Leyfman Yan , Menon Gayathri P. , Joshi Muskan , Balasubramanian Maduri , Van de Kieft Alexandra , Park Chandler H.
Published: August 2023

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Background: While the popularity of social media has grown as a source of healthcare news, studies have shown that one third of social media posts contain misinformation with 76.9% of them containing harmful information leading to adverse outcomes. As a result, MedNews Week (MNW), a digital platform dedicated to combating misinformation, was developed to contribute to global oncology education through its free programming. In its first year, MNW has connected 193,000 live viewers from 57 countries with opportunities to learn from and engage live with oncology’s global leaders during their Keynote Lectures. The goal of this study was to assess whether Twitter Impressions, LinkedIn Impressions and Speaker H-Index significantly predicted the number of live attendees at Keynote Lectures as a marker for the utilization of medical information resources by a global network of patients and patient advocates. Methods: In 2022, MNW hosted 32 distinguished physician-researchers as Keynote Speakers for live streamed virtual lectures of which 25 spoke on oncology topics. Twitter and LinkedIn promotional posts for each Keynote Lecture began one week before every event and the number of impressions were collected. The number of virtual attendees at each live lecture and speaker h-index (a common metric of scholarly impact) were recorded for each lecturer for statistical testing. Multiple linear regression was performed using R. Results: Results showed that the overall regression was statistically significant (R2 = 0.9977, F(3, 18) = 2650, p-value < 0.001). Twitter and LinkedIn Impressions significantly predicted the number of live attendees at Keynote Lectures (p-value < 0.001). However, the speaker H-index did not significantly predict the number of live Keynote attendees (p-value = 0.258 > 0.05). Conclusions: There is very strong evidence to support social media engagement as a predictor of health resource utilization as evident by Keynote Lecture attendance. However, a speaker’s H-index was not found to be a good predictor of health resource utilization by patients and patient advocates. The results of this analysis highlight the importance of traditional resources of medical knowledge adapting to the current digital climate, as platforms like MNW and COSMO demonstrate the growing impact of social media as an outlet for patient education and outreach – particularly in underserved regions globally.[Table: see text]
Impact of a digital education platform to combat global inequity in oncology education amongst healthcare professionals in lower socioeconomic areas.
Authors: Leyfman Yan , Pawar Shubhadarshini , Joshi Muskan , Van de Kieft Alexandra , Menon Gayathri P. , Wilkerson William B. , Balasubramanian Maduri , Jackewicz Sean , Azeez Ahmed , Chorya Harshal , Pai Pallavi , Coloma Helena S , Wilson Steven , Park Chandler H.
Published: August 2023

140

Background: Studies have shown that lower socioeconomic (LS) status contributes to heavier disease burden. While finances and infrastructural challenges have contributed to these inequities, access to the latest medical information has been cited as an equally important contributor. To address this, MedNews Week (MNW), a free, digital education platform was developed to provide global oncology education through its programming featuring Keynote presentations from oncology’s global leaders. To reach healthcare professionals (HCP), MNW has partnered with VuMedi, a global video education platform for physicians. The aim of this study was to assess the impact of MNW’s oncology programming on VuMedi’s education platform for HCP. Methods: From September 2022 to February 2023, MNW hosted 37 global oncology leaders and their Keynote Presentations were showcased on VuMedi. Data including viewership, global reach, page views, tumor subtype views, unique visits, and audience occupation demographics. In collaboration with VuMedi, descriptive analysis was performed, and a mixed-methods approach was employed to assess engagement. Results: During this 6-month period, the MNW channel on VuMedi demonstrated increased linear growth. Programming generated 4,387,213 total page views and 206 channel views with viewership from 22 countries— 12 of which are from LS areas, including Nigeria, Sudan, Georgia, and Bangladesh. Viewers were largely surgeons compared to Allied HCP (11:2). Solid tumors had high viewership [706 (0.012%) page views and 9717 (7%) impressions] compared with heme malignancies [689 (0.001%) page views and 1688 (1.22%) impressions]. Within solid tumors, GI oncology presentations were the most viewed— generating 3755 (0.06%) page views and 28067 (20%) impressions, and the highest number of registrations recorded for this category. During this period, the channel had 1,750,161 total visits with 44,982 new registrants. Conclusions: MNW has demonstrated an ability to attract and sustain a diverse, global, growing physician audience— especially within LE areas. While previous studies have identified internet access, cost, and infrastructural challenges as barriers to high-quality medical information, MNW has experienced steady growth and reachability especially within these limited areas. The platform’s ability to showcase global leaders to HCP offers an effective and practical approach to combat educational inequity, while positively impacting oncology education globally.[Table: see text]