bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effective clinical trial design: Application of a Bayesian sequential model to the ProFHER pragmatic trial
Authors: Forster Martin , Brealey Stephen , Chick Stephen , Keding Ada , Corbacho Belen , Alban Andres , Pertile Paolo , Rangan Amar
Published: August 2021

Background/Aims:

There is growing interest in the use of adaptive designs to improve the efficiency of clinical trials. We apply a Bayesian decision-theoretic model of a sequential experiment using cost and outcome data from the ProFHER pragmatic trial. We assess the model’s potential for delivering value-based research.

Methods:

Using parameter values estimated from the ProFHER pragmatic trial, including the costs of carrying out the trial, we establish when the trial could have stopped, had the model’s value-based stopping rule been used. We use a bootstrap analysis and simulation study to assess a range of operating characteristics, which we compare with a fixed sample size design which does not allow for early stopping.

Results:

We estimate that application of the model could have stopped the ProFHER trial early, reducing the sample size by about 14%, saving about 5% of the research budget and resulting in a technology recommendation which was the same as that of the trial. The bootstrap analysis suggests that the expected sample size would have been 38% lower, saving around 13% of the research budget, with a probability of 0.92 of making the same technology recommendation decision. It also shows a large degree of variability in the trial’s sample size.

Conclusions:

Benefits to trial cost stewardship may be achieved by monitoring trial data as they accumulate and using a stopping rule which balances the benefit of obtaining more information through continued recruitment with the cost of obtaining that information. We present recommendations for further research investigating the application of value-based sequential designs.
What kind of global citizen? A framework for best practices in world history civic education
Authors: Muetterties Carly C
Published: August 2021

Scholars have long identified fostering democratic citizenship as a primary purpose of public schooling in the United States, as schools should intentionally prepare students with the knowledge and skills needed for active, informed democratic citizenship. In addition, global interconnectedness has reshaped needed civic competencies to participate in civic life. This conceptual article considers the intersections between civic and world history education, assessing the relationship between the two disciplines in order to create a framework of best practices in world history civic education. Global citizenship discourse is analyzed using this framework, considering how different forms may reinforce or undermine world history’s purpose of preparing students with pluralist understandings for global democratic living. Drawing on components of history education, world history, and global citizenship education scholarship, this article seeks to establish epistemological clarity as to how world history can contribute to meaningful civic education and vice versa.
A real-time analysis of intraoperative interruptions in relation to use of simple preventive measures including a sign on the door and a checklist-based team brief
Authors: Aydin Mehmet Akif , Gul Gungor , Aydin Muhammet Fatih , Tunc Yesim
Published: August 2021

This study aimed to evaluate intraoperative interruptions by frequency, type, interference and source, and preventive measures. The interruptions in the operating theatre were evaluated for 52 surgical procedures based on real-time recordings and divided into routine operative procedures (ROP, n = 26, without intervention) and intervened operative procedures (IOP, n = 26, observed after team brief and placement of a warning sign for unnecessary door openings) groups. Intervened operative procedures vs. routine operative procedures was associated with a significantly lower number of interruptions (p = 0.014). Implementation of preventive measures was associated with a significantly lower number of entrances and exits (p = 0.001) and equipment issues (p = 0.003), interruptions that affected the circulating nurse or anaesthesia technician/associate (p = 0.003) and those caused by team members other than assisting surgeon and scrub nurse (p-value ranged from 0.015 to 0.009). Our findings revealed significantly reduced interruptions after a simple preventive measure including team brief and the placement of a warning sign for unnecessary door openings.
Computer-based three-dimensional measurement of carpal alignment: measurement techniques and normal ranges
Authors: Sippo Robert M. J. , Höglund Theresa E. K. , Waris Eero
Published: August 2021

The three-dimensional carpal alignment was measured in the neutral wrist position in 121 asymptomatic volunteers using computer-based cone-beam CT analysis. Normal values and the reliability of the automated analysis are reported. An analysis software based on segmentation of CT images and mathematical modelling was used to determine several axis variants based on different landmarks and to calculate the intercarpal angles automatically. Twenty wrists were imaged twice to determine intra-observer reliability. Mean values using the preferred axis variants were: scapholunate angle 57° (SD 9°), radiolunate angle 2° (SD 10°), lunocapitate angle –14° (SD 9°). Using alternate axis variants notably changed the angles produced. The intra-observer reliability of the analysis was excellent (mean intraclass correlation coefficient 0.97, SD 0.03). Computer-based CT analysis enables highly reproducible and automated assessment of carpal alignment. This study provides a reference database for measurement techniques and normal carpal angle values in three-dimensional imaging.
Does Diabetes Alter CSF Total Protein Levels? A Retrospective Cohort Study
Authors: Breiner Ari , Bourque* Pierre R. , Warman-Chardon Jodi , Brooks John , McCudden Christopher R.
Published: August 2021

Background and Purpose:

Elevation of total protein level in cerebrospinal fluid (CSF-TP) in diabetic patients is often disregarded by clinicians. However, existing studies on the topic have significant limitations, and therefore we aimed to explore the relationship between diabetes and CSF-TP in a large database of CSF samples.

Methods:

Retrospective review of all diagnostic lumbar punctures at the Ottawa Hospital between 1996-2016. Patients were excluded if they had elevated CSF cell counts, or a condition known to elevate CSF-TP. Multivariate linear regression modeling considered the effects of age, sex, and diabetes.

Results:

Among 6124 patients (746 with diabetes, 5378 without), mean CSF-TP did not differ significantly between groups (0.39 and 0.35 mmol/L, p = 0.2). When controlled for age and sex, there was no significant effect of diabetes on CSF-TP and no significant correlation between mean serum glucose and CSF-TP (R2 = 0.12).

Conclusions:

CSF-TP did not differ significantly between diabetic and non-diabetic groups, once the influence of age and sex was controlled. Elevated CSF-TP should be regarded as pathologic, even in the setting of diabetes.
We are in the “breakout room.” Now what? An e-portfolio study of virtual team processes involving undergraduate online learners
Authors: Ismailov Murod , Laurier Joël
Published: August 2021

The COVID-19 pandemic, resulting in unprecedented campus closures and social distancing, has reinforced the value of learning using a virtual teamwork format. While a large body of research focuses on the inputs (members’ skills, motivation, technology, and virtuality) and outcomes (satisfaction, performance, and learning) of virtual teamwork, to date, only a limited number of studies have explored virtual teamwork processes involving university students. By drawing on the team processes model ( Marks et al., 2001 ), in this qualitative study, we extend the scope of virtual team processes to a university online course. In addition, we explore transition, action, and interpersonal processes that undergraduate students experience when learning in virtual teams. The study participants included Japanese and international students ( N = 20) from three universities in Japan taking a synchronous online course in international organizations during the summer of 2020; 15 combinations of virtual teams were created. The study is based on the inductive content analysis of e-portfolios created and managed by students taking the online course. The findings show that virtual teams are multitasking entities that transition through multiple processes simultaneously and consequentially to achieve team goals. From the analyzed e-portfolios, it can be observed that across all themes, systems monitoring (action processes), affect management (interpersonal processes), and strategy formulation and planning (transition processes) have been crucial in invigorating virtual teams toward task accomplishment. Finally, the study discusses both theoretical and practical implications.
Fungal infections in hematopoietic stem-cell transplant patients: a review of epidemiology, diagnosis, and management
Authors: Rahi Mandeep Singh , Jindal Vishal , Pednekar Prachi , Parekh Jay , Gunasekaran Kulothungan , Sharma Sorabh , Stender Michael , Jaiyesimi Ishmael A.
Published: August 2021

The advent of bone marrow transplant has opened doors to a different approach and offered a new treatment modality for various hematopoietic stem-cell-related disorders. Since the first bone marrow transplant in 1957, there has been significant progress in managing patients who undergo bone marrow transplants. Plasma-cell disorders, lymphoproliferative disorders, and myelodysplastic syndrome are the most common indications for hematopoietic stem-cell transplant. Despite the advances, invasive fungal infections remain a significant cause of morbidity and mortality in this high-risk population. The overall incidence of invasive fungal infection in patients with hematopoietic stem-cell transplant is around 4%, but the mortality in patients with allogeneic stem-cell transplant is as high as 13% in one study. Type of stem-cell transplant, conditioning regimen, and development of graft- versus-host disease are some of the risk factors that impact the risk and outcomes in patients with invasive fungal infections. Aspergillus and candida remain the two most common organisms causing invasive fungal infections. Molecular diagnostic methods have replaced some traditional methods due to their simplicity of use and rapid turnaround time. Primary prophylaxis has undoubtedly shown to improve outcomes even though breakthrough infection rates remain high. The directed treatment has seen a significant shift from amphotericin B to itraconazole, voriconazole, and echinocandins, which have shown better efficacy and fewer adverse effects. In this comprehensive review, we aim to detail epidemiology, risk factors, diagnosis, and management, including prophylaxis, empiric and directed management of invasive fungal infections in patients with hematopoietic stem-cell transplant.
Persistent lymphopenia after diagnosis of COVID-19 predicts acute respiratory distress syndrome: A retrospective cohort study
Authors: Zou Zhi-ye , Ren Di , Chen Rong-ling , Yu Bao-jun , Liu Yan , Huang Jia-jia , Yang Zhen-jia , Zhou Zhi-peng , Feng Yong-wen , Wu Ming
Published: August 2021

Background

Lymphopenia is a marker of immunosuppression after severe coronavirus disease-2019 (COVID-19) which is characterized by acute respiratory distress syndrome (ARDS). This study aimed to evaluate the relationships between persistent lymphopenia and ARDS.

Methods

A retrospective cohort study of 125 patients with COVID-19 admitted to government-designated treatment center between 14 January 2020, and 20 March 2020 was conducted. We recorded all complete blood cell counts during the day 0th, 3rd, and 7th following the diagnosis of COVID-19. Patients were grouped based on the depression of the lymphocyte cell count, their return, or their failure to normal. The primary outcome was the occurrence of ARDS, and secondary outcomes included developing vital organ dysfunction and hospital lengths of stay.

Results

17.6% (22/125) patients developed ARDS. The lymphocyte counts with ARDS and non-ARDS were 0.94 × 109/L, 1.20 × 109/L at admission, respectively ( p = 0.02). On the 3rd and 7th day, the median of lymphocyte count in ARDS was significantly lower than that of non-ARDS. Multivariable logistic regression, which was adjusting for potentially confounding factors (including age, comorbidities, and APACHE II score), showed that persistent lymphopenia within the 7th day was independently associated with ARDS (OR, 3.94 [95% CI, 1.26–12.33, p = 0.018). Further, patients with persistent lymphopenia had longer hospital lengths of stay ( p < 0.001).

Conclusion

The results showed persistent lymphopenia predicted ARDS after COVID-19. Further studies are needed to investigate whether immunostimulation of lymphocytes within 1 week can reduce ARDS occurrence in patients with COVID-19.
Reversible temporal hypodensity on CT in a patient with minor head injury: Transient global amnesia or contusion?
Authors: Shah Basit , Poonja Sabrina , Hussain Mohammed Wasif
Published: August 2021

Transient global amnesia (TGA) is a condition characterized by a sudden, temporary lapse in memory without focal neurological deficits, usually in middle aged adults, sometimes precipitated by an inciting event. We describe a case of a young patient, who presented with a constellation of symptoms consistent with TGA post-concussion with a right temporal lobe hypodensity on CT head. This patient’s memory returned to baseline within 24 hours, with only a mild residual headache which resolved within the next day and no MRI findings 48 hours after, illustrating that his clinical trajectory favours TGA rather than post-concussive amnesia. While the pathophysiology of TGA is still a mystery, clinicians and researchers continue to hypothesize the anatomical basis of this condition.
Does Simultaneous Fixation of Both Distal Radius and Distal Ulnar Fractures Improve Outcomes? A Retrospective Cohort Study
Authors: Kurozumi Taketo , Miyamoto Hideaki , Suzuki Takashi , Watanabe Yoshinobu
Published: August 2021

Introduction: Distal metaphyseal ulnar fractures are often found in conjunction with distal radius fractures. However, there is no consensus on optimal management. The purpose of this study was to determine whether simultaneous fixation of both distal radius and distal ulnar fractures would improve outcomes. Materials and Methods: Patients treated for distal radial fractures over a 4-year period at our trauma center were identified, and their medical records were analyzed. Twenty-three patients met the inclusion criteria for this study. All radius fractures were fixed using a volar locking plate. Fourteen ulnar fractures were treated with surgical fixation, and nine were treated conservatively. Data were collected on patient demographics, mechanism of injury, whether it was a closed or open fracture, Gustilo classification, AO/OTA classification, immobilization period, follow-up period, and type of treatment. Physical findings comprising the active range of motion and grip strength and radiological findings, including the ulnar variance compared to the healthy side and bone union, were evaluated. Clinical outcomes were assessed using the quick Disabilities of the Arm, Shoulder, and Hand scores. Results: There was no significant difference between the groups in the quick Disabilities of the Arm, Shoulder, and Hand scores, but the arc of dorsi-palmar flexion was more restricted in the operative group than in the conservative group. Other results were not significantly different between the two groups. Discussion: Fixation of distal metaphyseal ulnar fractures can be challenging, and several studies have shown the validity of conservative treatments. This supports the view that if the distal radius fracture is anatomically and rigidly fixed, distal metaphyseal ulnar fractures can be successfully managed conservatively. Conclusion: Our results did not show any merit in the simultaneous fixation of both distal radius and distal ulnar fractures. Thus, needless surgery should be avoided.
A Review on the Malaysian and Indonesian Batik Production, Challenges, and Innovations in the 21st Century
Authors: Syed Shaharuddin Sharifah Imihezri , Shamsuddin Maryam Samirah , Drahman Mohd Hafiz , Hasan Zaimah , Mohd Asri Nurul Anissa , Nordin Ahmad Amri , Shaffiar Norhashimah Mohd
Published: August 2021

Malaysia and Indonesia are well known as prolific producers of batik in Southeast Asia. The history of batik in both countries is deeply intertwined for more than a century. Most available published works related to batik production, challenges, and innovations were discussed within the local batik context of each country. This study aims to identify collectively how far batik, as a creative industry in these countries has progressed since its establishment until the present 21st century. It was notable that batik craftsmanships have been mostly maintained as similar tools and techniques are persistently being used until today in both countries. Significant progress was observed in the design and stylization of the batik design with the use of digital approaches such as fractal geometry. Similar challenging problems faced by both nations were highlighted and clustered into internal and external issues. It was concluded that assimilations of Third Industrial Revolution technology (IR3.0) primarily centered on the use of computer-aided design and computer-aided manufacturing to improve existing batik production. Emerging studies have shown the positive impact of integrating Fourth Industrial Revolution (IR4.0) technology such as augmented reality (AR) in promoting batik knowledge and transmitting batik as an intangible cultural heritage. The transmission of batik skills to the young generation has been a persistent problem. Thus, a brief framework was proposed to exemplify how IR4.0 technology can innovatively be used to transmit the batik skills via education platform.
Labor Market Precarity Shapes Perception of the Public Sector in the Eurozone
Authors: Fernández Puente Adolfo C. , Sánchez-Sánchez Nuria
Published: August 2021

This study analyses the impact of working in the public sector on job satisfaction in Europe (19) through the European Working Condition Survey (EWCS). A grouping of countries is proposed based on the perception of workers regarding the functioning of the labor market. Econometric estimates show that public sector workers, at an aggregate level, are more satisfied than those in the private sector. The highest job satisfaction corresponds to permanent contract public sector workers, followed by temporary contract public sector employees, the permanent contract private sector, and the temporary contract private sector workers. The results confirm that in those countries with a higher proportion of individuals who consider losing their job a probability, public sector job satisfaction is higher. In addition, those countries where the proportion of individuals with low confidence in finding a new job with similar characteristics to the one they have, public sector job satisfaction is also higher.
Linkage, Leverage, and Authoritarianism: An Overview of the Collapse of Turkey’s EU Membership Prospect
Authors: Cop Burak , Kılıçdaroğlu Kerem
Published: August 2021

The effects of the linkage and the leverage over countries that either go through a democratic transition or further advance on the democratization path have been widely discussed by comparative democratization scholars. Western leverage designates governments’ level of vulnerability in the face of foreign pressure for democratization, while linkage is meant to be the intensity of the connections and the cross-border streams between a democratizing country and the Western world. It is generally acknowledged that the linkage is a more determinative factor than the leverage. On the contrary, the authoritarian shifts of many countries that took place during the first two decades of the 21st century challenged the optimistic and deterministic role assigned to linkage. Turkey is a noteworthy example in this regard since the intensity of its linkage to Europe could not compensate the negative effects of a declining leverage over Turkish democratization since 2006. The argument that linkage matters more than leverage does not apply to Turkey. The evolution of domestic political regimes in European Union candidate countries in parallel with their accession processes constitutes separate cases differing from one another. Turkey is not only a separate case for its part, but also a unique one.
Decomposing the Effect of Brand Image in Influencing Information Adoption: The Case of Online Travel Agents
Authors: Garg Prerna , Pandey Anoop
Published: August 2021

The availability of information in the form of online reviews offered by online travel agents (OTAs) is playing an important role in the travel decisions of today’s consumer. Considering the huge amount of attention given to behavioral dimension in decision making literature and the popularity of the information adoption model, the present study aims at exploring the direct and indirect effect of information quality (IQ) and information credibility (IC) on attitude toward information usefulness (AT). The study specifically bridges the gap in the literature of information adoption by using brand image (BI) of the OTA as a mediator. The research also examines the subsequent effect of attitude toward information usefulness on information adoption (IA). Convenience sampling technique has been used to gather responses and structural equation modeling has been used to analyze the data. The results confirm the presence of partial mediation effect in the proposed relationships between IQ, IC, BI, and AT and posit a significant effect of attitude toward information usefulness on the adoption of information. The study concludes that it is imperative for marketers in the travel industry to understand that perception of their brand plays a very important role in positioning their information as a useful one.
The prospects of antimicrobial coated medical implants
Authors: Shahid Aqsa , Aslam Bilal , Muzammil Saima , Aslam Nosheen , Shahid Muhammad , Almatroudi Ahmad , Allemailem Khaled S , Saqalein Muhammad , Nisar Muhammad Atif , Rasool Muhammad Hidayat , Khurshid Mohsin
Published: August 2021

The implants are increasingly being a part of modern medicine in various surgical procedures for functional or cosmetic purposes. The progressive use of implants is associated with increased infectious complications and prevention of such infections always remains precedence in the clinical settings. The preventive approaches include the systemic administration of antimicrobial agents before and after the surgical procedures as well as the local application of antibiotics. The relevant literature and existing clinical practices have highlighted the role of antimicrobial coating approaches in the prevention of implants associated infections, although the applications of these strategies are not yet standardized, and the clinical efficacy is not much clear. The adequate data from the randomized control trials is challenging because of the unavailability of a large sample size although it is compulsory in this context to assess the clinical efficacy of preemptive practices. This review compares the efficacy of preventive approaches and the prospects of antimicrobial-coated implants in preventing implant-related infections.
A Case of Disseminated Coccidioidomycosis: When the Treasure Chest Wall Opened
Authors: Dhital Sandhya , Raza Nadia , Heidari Arash
Published: August 2021

Coccidioidomycosis is an infection caused by soil-dwelling fungi, Coccidioides, that are endemic to the southwestern United States, northern Mexico, and scattered areas of Latin America. It typically presents with pulmonary manifestations that resemble symptoms of bronchitis, pneumonia, and the flu. Extrapulmonary manifestations that involve the skin, lymph nodes, bones, and joints have also been well described, but disseminated coccidioidomycosis initially presenting as chest wall infection without pulmonary symptoms is not. In this article, we present a case of a 33-year-old man who presented with chest wall swelling and eventually diagnosed with chest wall abscesses due to disseminated coccidioidomycosis. We propose that consideration of disseminated coccidioidomycosis in nonresolving swelling, mass, lesions, or abscess especially in endemic areas for coccidioidomycosis and in travelers to the endemic area may prevent the progression and further complications of coccidioidomycosis.
Is the Prognosis of Osgood-Schlatter Poorer Than Anticipated? A Prospective Cohort Study With 24-Month Follow-up
Authors: Holden Sinead , Olesen Jens Lykkegaard , Winiarski Lukasz M. , Krommes Kasper , Thorborg Kristian , Hölmich Per , Rathleff Michael Skovdal
Published: August 2021

Background:

Osgood-Schlatter disease (OSD), an apophyseal injury of the tibial tuberosity, affects up to 1 in 10 adolescents. This condition has previously been assumed to be innocuous and to self-resolve with limited intervention.

Purpose:

To investigate the 24-month prognosis of OSD and examine if ultrasound (US) classification is associated with outcomes.

Study Design:

Case series; Level of evidence, 4.

Methods:

This study included a preregistered prospective cohort of 51 adolescents (aged 10-14 years) diagnosed with OSD who were evaluated for 24 months. The primary outcome at 24-month follow-up was whether participants continued to experience OSD-related knee pain. Baseline US scans were collected and characterized by OSD type (De Flaviis classification) as well as maturation of the tibial tuberosity. Secondary outcomes included sports participation, Knee injury and Osteoarthritis Outcome Score (KOOS) Sport/Recreation subscale, and health-related quality of life (European Quality of Life–5 Dimensions–Youth [EQ-5D-Y]). All participants were invited for re-examination by US at follow-up.

Results:

A total of 51 patients preregistered for the study, with 90% (n = 46) available at follow-up. Of these 46 participants, 37% (n = 17) still reported knee pain due to OSD. In this subgroup, the median duration since symptom onset was 42 months (interquartile range, 38-51 months). More than 1 in 5 participants reported stopping sport due to knee pain, and those who continued to experience knee pain reported significantly worse KOOS Sport/Recreation scores at follow-up compared with patients with no knee pain (mean 74 [95% CI, 63-84] vs 91 [95% CI, 85-97]). Participants with continued OSD-related pain also had lower health-related quality of life (mean difference in EQ-5D-Y, 0.11 [95% CI, 0.06-0.13]). Higher De Flaviis classification at baseline was significantly associated with an increased risk of knee pain at 2 years. Diagnostic US at follow-up demonstrated primarily tendon changes (thickening, positive Doppler signal), as well as an ununited ossicle in 32% of participants who underwent US scanning at follow-up.

Conclusion:

Over one-third of the study participants had knee pain at 2-year follow-up, which was associated with lower sports related function and health related quality of life. This questions the assumption that all patients with OSD experience quick recovery. Participants without any changes on imaging at baseline were less likely to report pain at follow-up.
The ISIS Impacts on the Political Connections, Board Interlock, and Quality of Financial Reporting
Authors: Salehi Mahdi , Maalah Ali Zuhair , Nazaridavaji Hamideh
Published: August 2021

This research examines the relationship between political connections, board interlock, and the quality of financial reporting of the listed companies on the Iraq Stock Exchange (ISE) with ISIS's mediating role (the Islamic State of Iraq and Syria). This research is about the mediating part of ISIS in the relationship between board interlock, political connections, and financial reporting quality. The study attempts to reveal whether or not political connections and board interlock can improve financial reporting quality. A multiple regression model is used to test the research hypothesis. The samples consist of 245 (firm-year) companies listed on the ISE from 2012 to 2018, and the hypothesis is tested by multiple regression based on integrated data models. The results demonstrate a significant and negative relationship between political connections, board interlock, and financial reporting quality. Thus, higher political connections reduce the quality of financial reporting. The results also conveyed that ISIS contributes to the decline of this relationship. This research expands the literature review on ISIS’s impact on these engaged countries' economies.
Dutch Mental Health Patients’ and Significant Others’ Perspectives on Compulsory Treatment at Home: One Size Does Not Fit All
Authors: de Waardt DA , Meijnckens D , Wierdsma AI , Widdershoven GAM , Mulder CL
Published: August 2021

On January 1, 2020, the Compulsory Mental Health Care Act took effect in the Netherlands. It contains provisions for compulsory community treatment (CCT) and compulsory treatment at home (CTH). In this study, we collected the opinions of patients and their significant others on CTH and on their preferences regarding compulsory care in their homes. Patients and their significant others were involved in the experience-based co-design of a purpose-built online questionnaire. This questionnaire was completed by 624 patients and 531 significant others.

Sixty-one percent of the patients and 62% of the significant others did not want compulsory treatment to take place at home but in hospital or elsewhere. Patients’ and significant others’ opinion showed few differences, except with regard to the involvement of the significant others in CTH.

As the respective views of patients and significant others were mixed, we recommend that crisis plans and compulsory treatment plans should be individually tailored to the needs and wishes of patients and their significant others regarding CTH.
Keeping families afloat: Foster carer’s parenting experiences during COVID-19 in Ghana and implications for practice
Authors: Frimpong-Manso Kwabena , Cudjoe Ebenezer , Abdullah Alhassan , Deliege Antoine , Eshun Esther Kum-Tabia
Published: August 2021

Formal foster care is a relatively new phenomenon in Ghana. The practice is in conformity with international and national policy guidelines to deinstitutionalize and strengthen family-based care for children without adequate parental care. In addition to the known challenges of foster parenting in Ghana (stigma, financial challenges and emotional strain, inexperience of the foster parents), the socio-economic impacts of COVID-19 restrictions may worsen caregivers’ burden and negatively affect children in care. This study explored how foster parents are meeting their caregiving demands during the COVID-19 pandemic in the face of existing and new challenges. Following a participatory practice research approach, a co-constructed interview guide by the researchers and a practitioner was used to conduct in-depth telephone interviews with 13 foster parents. Findings from thematic analysis of the interviews showed challenges, including increased cost of caregiving and multiple caregiving duties as challenges facing foster parents whereas children’s knowledge about the virus, informal support and religious beliefs collectively enhanced caregiving during the pandemic. The findings provide learning about ways to alleviate parenting challenges for foster parents during and after the pandemic. Specifically, interventions that view children as actors for change and strengthen community and religious bodies to deliver psychosocial services would be useful to improve foster parenting.
Micromechanical analysis of effective mechanical properties of graphene/ZrO2-hybrid poly (methyl methacrylate) nanocomposites
Authors: Rathi Ankit , Kundalwal S. I.
Published: August 2021

In this study, the tensile properties of two-phase and three-phase graphene/ZrO2-hybrid poly (methyl methacrylate) (PMMA) nanocomposites are investigated by developing finite element model using ANSYS. Primarily, the effective elastic properties of two- and three-phase graphene/ZrO2-hybrid PMMA nanocomposites (GRPCs) are estimated by developing mechanics of material (MOM) model. Results indicated that the effective elastic properties of GRPCs increase with an increase in the volume fraction of graphene. Also, the stiffness of GRPCs is increased by 78.12% with increasing in the volume fraction of graphene from 0.1 to 0.5 Vf. The incorporation of an additional ZrO2 interphase significantly improved the mechanical performance of resulting GRPCs.
RARγ activation sensitizes human myeloma cells to carfilzomib treatment through the OAS-RNase L innate immune pathway
Authors: Wang Qiang , Lin Zhijuan , Wang Zhuo , Ye Lingqun , Xian Miao , Xiao Liuling , Su Pan , Bi Enguang , Huang Yung-hsing , Qian Jianfei , Liu Lintao , Ma Xingzhe , Yang Maojie , Xiong Wei , Zu Youli , Pingali Sai Ravi , Xu Bing , Yi Qing
Published: August 2021

Proteasome inhibitors (PIs) such as bortezomib (Btz) and carfilzomib (Cfz) are highly efficacious for patients with multiple myeloma (MM). However, relapses are frequent, and acquired resistance to PI treatment emerges in most patients. Here, we performed a high-throughput screen of 1855 Food and Drug Administration (FDA)-approved drugs and identified all-trans retinoic acid (ATRA), which alone has no antimyeloma effect, as a potent drug that enhanced MM sensitivity to Cfz-induced cytotoxicity and resensitized Cfz-resistant MM cells to Cfz in vitro. ATRA activated retinoic acid receptor (RAR)γ and interferon-β response pathway, leading to upregulated expression of IRF1. IRF1 in turn initiated the transcription of OAS1, which synthesized 2-5A upon binding to double-stranded RNA (dsRNA) induced by Cfz and resulted in cellular RNA degradation by RNase L and cell death. Similar to ATRA, BMS961, a selective RARγ agonist, could also (re)sensitize MM cells to Cfz in vitro, and both ATRA and BMS961 significantly enhanced the therapeutic effects of Cfz in established MM in vivo. In support of these findings, analyses of large datasets of patients’ gene profiling showed a strong and positive correlation between RARγ and OAS1 expression and patient’s response to PI treatment. Thus, this study highlights the potential for RARγ agonists to sensitize and overcome MM resistance to Cfz treatment in patients.
Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis
Authors: Semenza Gregg L.
Published: August 2021

Hypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and transcriptional activity, respectively. Mutations in genes encoding components of the O2-sensing pathway cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in bone marrow neoplasms, and the development of HIF inhibitors may improve outcomes in these disorders.
Incidence and mortality rates of intracranial hemorrhage in hemophilia: a systematic review and meta-analysis
Authors: Zwagemaker Anne-Fleur , Gouw Samantha C. , Jansen Julie S. , Vuong Caroline , Coppens Michiel , Hu Qun , Feng Xiaoqin , Kim Soon K. , Van der Bom Johanna G. , Fijnvandraat Karin
Published: August 2021

Intracranial hemorrhage (ICH) is a severe complication that is relatively common among patients with hemophilia. This systematic review aimed to obtain more precise estimates of ICH incidence and mortality in hemophilia, which may be important for patients, caregivers, researchers, and health policy makers. PubMed and EMBASE were systematically searched using terms related to “hemophilia” and “intracranial hemorrhage” or “mortality.” Studies that allowed calculation of ICH incidence or mortality rates in a hemophilia population ≥50 patients were included. We summarized evidence on ICH incidence and calculated pooled ICH incidence and mortality in 3 age groups: persons of all ages with hemophilia, children and young adults younger than age 25 years with hemophilia, and neonates with hemophilia. Incidence and mortality were pooled with a Poisson-Normal model or a Binomial-Normal model. We included 45 studies that represented 54 470 patients, 809 151 person-years, and 5326 live births of patients with hemophilia. In persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% confidence interval [CI], 1.2-4.8) and 0.8 (95% CI 0.5-1.2) per 1000 person-years, respectively. In children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI, 4.9-11.1) and 0.5 (95% CI, 0.3-0.9) per 1000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI, 1.5-2.8) per 100 live births. ICH was classified as spontaneous in 35% to 58% of cases. Our findings suggest that ICH is an important problem in hemophilia that occurs among all ages, requiring adequate preventive strategies.
CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro
Authors: Cheng Xiaoqiang , Lin Jiayi , Chen Zhanghuan , Mao Yubo , Wu Xiexin , Xu Congxin , Du Jiacheng , Dong Zhongchen , Yang Huilin , Zhou Feng , Geng Dechun
Published: August 2021

Background

Nucleus pulposus cell (NPC) degeneration is widely accepted as one of the major causes of intervertebral disc (IVD) degeneration (IVDD). The pathogenesis of IVDD is complex and consists of inflammation, oxidative stress, and the loss of extracellular matrix (ECM). Cannabinoid type 2 receptor (CB2) has been shown to be involved in the pathological mechanism of a variety of diseases due to its anti-inflammatory effects and antioxidative stress capacity.

Method

In Vitro, H2O2 was used to induce degeneration of nucleus pulposus cells, mRNA and protein expression level was determined by RT-PCR and Western Blot, and Immunocytochemical staining were used to detect expression of collagen II, aggrecan, MMP3/13, superoxide dismutase 2 (SOD2) and inducible nitric oxide synthase (iNOS). In vivo, the potential therapeutic effect of CB2 was detected in the rat acupuncture model.

Result

In vitro, we found that the CB2 agonist (JWH133) treatment reduced the oxidative stress level in NPCs induced by hydrogen peroxide (H2O2) treatment. Furthermore, the expression of inflammatory cytokines was also decreased by JWH133 treatment. We found that collagen II and aggrecan expression was preserved, whereas matrix metalloproteinase levels were reduced. In vivo, we established a rat model by needle puncture. Imaging assessment revealed that the disc height index (DHI) and morphology of IVD were significantly improved, and the disc degeneration process was delayed by treatment of JWH133. Furthermore, immunohistochemical (IHC) staining revealed that JWH133 could inhibit the degradation of collagen II and decrease the expression of MMP3.

Conclusions

The experiment indicates the oxidative stress and inflammatory response of rat NPCs induced by H2O2 could be inhibited by activating CB2. This study reveals that CB2 activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD.
Incidence of incidental cancer in transurethral resection of prostate specimens: a 10-year retrospective analysis
Authors: Nergiz Döndü , Yıldırım Hülya Tosun , Yıldırım Şenay
Published: August 2021

Background

Prostate cancer can be detected incidentally in patients undergoing transurethral resection of the prostate for benign prostatic hyperplasia. Therefore, it is very important that the transurethral resection of the prostate specimen is evaluated carefully for accurate grading and staging. The aim of this study was to investigate the frequency of incidental prostate cancer and its relationship with clinicopathological findings.

Methods

The study included a total of 900 patients, who underwent transurethral resection of the prostate for benign prostatic hyperplasia treatment between June 2010 and June 2020. Patient age, prostate-specific antigen (PSA) levels and resected prostate weight were assessed, and the tumor stage, Gleason grade group, lymphovascular and perineural invasion status were also evaluated in the incidental prostate cancer group. The association between these parameters and prostate cancer detection was analyzed.

Results

Incidental detection of prostate cancer was determined at the rate of 13.3%. The incidental prostate cancer group had a significantly higher mean age and PSA levels compared to the benign prostatic hyperplasia group. The weight of the resected specimen had no impact on the incidence of incidental prostate cancer. Of the total 120 incidental prostate cancer cases, 59 (49.2%) were stage T1a and 61 (50.8%) were stage T1b. No significant difference was determined between the T1 stages and age distribution, but a statistically significant difference was determined in the other clinicopathological parameters.

Conclusions

The results of this study demonstrated that the incidence of incidental prostate cancer detection was related to age and PSA levels and increased, especially in those aged ≥ 60 years and/or PSA level ≥ 4 ng/mL. To avoid overlooking incidental prostate cancer in these patients, it can be recommended that material is sufficiently sampled and carefully evaluated, and when necessary, all resected specimens are examined. Although no significant correlation was determined between specimen weight and the incidence of incidental prostate cancer, as a significant difference was determined in T1 stages, this suggests that the amount of material evaluated could change the sub-stage.
Greater morphological and primary metabolic adaptations in roots contribute to phosphate-deficiency tolerance in the bread wheat cultivar Kenong199
Authors: Zheng Lu , Karim Mohammad Rezaul , Hu Yin-Gang , Shen Renfang , Lan Ping
Published: August 2021

Background

Phosphate (Pi) deficiency severely affects crop growth and productivity, including wheat, therefore it is necessary to develop cultivars with enhanced Pi-deficiency tolerance. However, the underlying mechanism of Pi-deficiency tolerance in wheat is still elusive. Two contrasting wheat cultivars, low-Pi tolerant Kenong199 (KN199) and low-Pi sensitive Chinese Spring (CS) were used to reveal adaptations in response to Pi deficiency at the morphological, physiological, metabolic, and molecular levels.

Results

KN199 was more tolerant to Pi deficiency than CS with significantly increased root biomass and R/S ratio. Root traits, the total root length, total root surface area, and total root volume, were remarkably enhanced by Pi deficiency in KN199. The shoot total P and soluble Pi concentrations of KN199 were significantly higher than those of CS, but not in roots. In KN199, high Pi level in shoots is a higher priority than that in roots under Pi deficiency. It was probably due to differentially regulation in the miR399-mediated signaling network between the shoots of the two cultivars. The Pi deficiency-induced root architecture adaptation in KN199 was attributed to the regulation of the hormone-mediated signaling (ethylene, gibberellin, and jasmonates). The expression of genes associated with root development and Pi uptake was enhanced in KN199. Some primary metabolites (amino acids and organic acids) were significantly accumulated in roots of KN199 under Pi deficiency.

Conclusions

The low-Pi tolerant wheat cultivar KN199 possessed greater morphological and primary metabolic adaptations in roots than CS under Pi deficiency. The adaption and the underlying molecular mechanisms in wheat provide a better understanding of the Pi-deficiency tolerance and the strategies for improving Pi efficiency in wheat.
Exosomal circEIF3K from cancer-associated fibroblast promotes colorectal cancer (CRC) progression via miR-214/PD-L1 axis
Authors: Yang Kaihua , Zhang Jie , Bao Chuanqing
Published: August 2021

Background

Tumor microenvironment (e.g., cancer-associated fibroblast) plays a key role in cancer tumorigenesis and metastasis. However, the detailed mechanism of whether hypoxia promotes CRC progression via tumor microenvironment remains unclear.

Methods

In this study, circEIF3K exosome was examined by NanoSight Tracking Analysis and RT-qPCR. We used cell colony formation assay, transwell assay and tube formation assay to determine proliferation, invasion and metastasis of HCT116 or SW620 cells. Xenograft tumor assay was employed to show in vivo tumor growth of HCT116 cells.

Results

We found that hypoxia could induce secretion of circEIF3K exosome. Conditioned medium (CM) and exosome from circEIF3K knockdown CAF significantly attenuated proliferation, invasion and tube formation of HCT116 or SW620 cells, which could be reverted by miR-214 under hypoxia treatment. Besides, we observed that circEIF3K knockdown evidently impaired tumor growth in mice. TCGA dataset analysis showed that low expression of circEIF3K was observed in normal tissues and associated with prolonged survival time. Finally, PD-L1 was confirmed as important target for miR-214 in CRC.

Conclusion

In conclusion, our study reveals that a novel axis circEIF3K/miR-214/PD-L1 mediates hypoxia-induced CRC progression via CAF, providing the rationale for developing new targeted therapeutics to treat CRC.
Prevalence of bone fractures among children and adolescents with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis
Authors: Seens Hoda , Modarresi Shirin , MacDermid Joy C , Walton David M , Grewal Ruby
Published: August 2021

Background

Attention-deficit/hyperactivity disorder (ADHD) is a significant neurodevelopment disorder among children and adolescents, with 5 % prevalence. Bone fractures account for 25 % of accidents and injuries among all children and adolescents. Considering the characteristics of inattention, hyperactivity, and impulsivity in children with ADHD, it is critical to examine bone fractures among these children. The objective of our meta-analysis was to determine the prevalence of bone fractures among children and adolescents with ADHD.

Methods

We completed a systematic review and meta-analysis using an electronic search of the following databases: CINAHL, EMBASE, PsycINFO, PubMed, and Scopus. The search terms used were: “attention deficit hyperactivity disorder OR attention deficit disorder” and “bone fracture*.” We included studies examining patients 18 years or younger who were diagnosed with ADHD and tracked (prospectively or retrospectively) for five or more years. Effect size (es), using a random effects model, was calculated. We registered the review protocol with PROSPERO (CRD42019119527).

Results

From 445 records retrieved, 31 full text articles were reviewed and 5 articles met inclusion criteria for meta-analysis. The summary es revealed the prevalence of bone fractures among children and adolescents with ADHD to be 4.83 % (95 % CI: 3.07–6.58 %). The location of bone fractures, using a subset of data, showed a distribution of 69.62 %, 22.85 %, and 7.53 % in the upper limbs, lower limbs, and other anatomical regions, respectively. Another subset of studies revealed a 2.55-fold increase in the prevalence of fractures among the children with ADHD compared to their counterparts.

Conclusions

Awareness of these findings is critical to physicians, parents, and policy makers to create safe environments and provide supports in order to optimize the health and safety of children and adolescents with ADHD.