bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Organizational and Individual Factors on Knowledge Sharing Behavior: Social Capital Perspective
Authors: Abbasi Saliha Gul , Abbas Mazhar , Pradana Mahir , Al-Shammari Serhan Abdullah Salem , Zaman Umer , Nawaz Muhammad Shahid
Published: October 2021

This study aims to develop, examine, and test organizational and individual predictors of knowledge sharing behavior of teachers in the higher education sector in Pakistan. The study examined the direct and indirect effects of organizational factors on knowledge sharing behavior (KSB) through individual factors. The social capital theory has been utilized to explain the premise of this research. This study uses a survey design. Data has been collected from 269 university teachers in Pakistan. A Structural equation modeling has been used to test the hypotheses using SPSS and Amos. The Data supported the hypotheses. This Study concludes that organizational and individual are important for enhancing KSB as organizational factors work through individual factors to influence the KSB of faculty members.
Waqf and Authority Dynamics: Reconfigurations of a Pious Institution in Colonial Malabar, South India
Authors: Naseef M.K.  , Santhosh R.
Published: October 2021

The formative years of Darul Uloom, Vazhakkad, a well-known Muslim waqf institution in northern Kerala in India established in the late nineteenth century for imparting religious education, is examined in this article. Darul Uloom is probably the first registered waqf in Kerala and by analysing the registered waqf deeds of this institution, we seek to understand the operation of authority and management in the initial years of this institution, especially in the background of contestations between emergent Islamic reformists and traditionalists. We trace the significant reformulation of the foundational intent evident in the subsequent deeds by later custodians and the intervention of various social groups, particularly the local community, in refashioning the trajectory of the waqf. A shift in authority—a complex product of theological, political and economic contestations emerged in the context of transformations brought by British Colonialism in Malabar—is evident in this process. Through our analysis, we suggest that waqf institutions and its legal foundations were highly dynamic and adaptive to their changing social contexts as against the portrayal of these Islamic institutions as stagnant and inflexible.
Orbitozygomatic Transmandibular Approach to the Infratemporal Fossa in Pediatric Patients: Use of the Craniofacial Armamentarium
Authors: Neimanis Sara A. , Nguyen Jonathan , Brady Colin M.
Published: October 2021

The infratemporal fossa is an anatomically complex space at the intersection between the face, neck, and intracranial space. Tumors of the infratemporal fossa are rare, especially in the pediatric population, but when present their pathologies are often such that they benefit from surgical ablation prior to adjuvant chemo- and radio-therapies. Consequent to their training and surgical armamentarium, craniofacial surgeons have an intimate knowledge of this anatomy, and a unique skill set to approach and access this area. In this case series we present 2 pediatric patients with infratemporal fossa tumors which were successfully resected via a lateral orbitozygomatic transmandibular approach.
Primary central nervous system lymphoma
Authors: Schaff Lauren R. , Grommes Christian
Published: October 2021

Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or vitreoretinal space, without evidence of systemic involvement. The diagnosis of PCNSL requires a high level of suspicion because clinical presentation varies depending upon involved structures. Initiation of treatment is time sensitive for optimal neurologic recovery and disease control. In general, the prognosis of PCNSL has improved significantly over the past few decades, largely as a result of the introduction and widespread use of high-dose methotrexate (MTX) chemotherapy, which is considered the backbone of first-line polychemotherapy treatment. Upon completion of MTX-based treatment, a consolidation strategy is often required to prolong duration of response. Consolidation can consist of radiation, maintenance therapy, nonmyeloablative chemotherapy, or myeloablative treatment followed by autologous stem cell transplant. Unfortunately, even with consolidation, relapse is common, and 5-year survival rates stand at only 30% to 40%. Novel insights into the pathophysiology of PCNSL have identified key mechanisms in tumor pathogenesis, including activation of the B-cell receptor pathway, immune evasion, and a suppressed tumor immune microenvironment. These insights have led to the identification of novel small molecules targeting these aberrant pathways. The Bruton tyrosine kinase inhibitor ibrutinib and immunomodulatory drugs (lenalidomide or pomalidomide) have shown promising clinical response rates for relapsed/refractory PCNSL and are increasingly used for the treatment of recurrent disease. This review provides a discussion of the clinical presentation of PCNSL, the approach to work-up and staging, and an overview of recent advancements in the understanding of the pathophysiology and current treatment strategies for immunocompetent patients.
Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL
Authors: Siddiqi Tanya , Soumerai Jacob D. , Dorritie Kathleen A. , Stephens Deborah M. , Riedell Peter A. , Arnason Jon , Kipps Thomas J. , Gillenwater Heidi H. , Gong Lucy , Yang Lin , Ogasawara Ken , Thorpe Jerill , Wierda William G.
Published: October 2021

Bruton tyrosine kinase inhibitors (BTKi) and venetoclax are currently used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually develop resistance to these therapies, underscoring the need for effective new therapies. We report results of the phase 1 dose-escalation portion of the multicenter, open-label, phase 1/2 TRANSCEND CLL 004 (NCT03331198) study of lisocabtagene maraleucel (liso-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory CLL/SLL. Patients with standard- or high-risk features treated with ≥3 or ≥2 prior therapies, respectively, including a BTKi, received liso-cel at 1 of 2 dose levels (50 × 106 or 100 × 106 CAR+ T cells). Primary objectives included safety and determining recommended dose; antitumor activity by 2018 International Workshop on CLL guidelines was exploratory. Minimal residual disease (MRD) was assessed in blood and marrow. Twenty-three of 25 enrolled patients received liso-cel and were evaluable for safety. Patients had a median of 4 (range, 2-11) prior therapies (100% had ibrutinib; 65% had venetoclax) and 83% had high-risk features including mutated TP53 and del(17p). Seventy-four percent of patients had cytokine release syndrome (9% grade 3) and 39% had neurological events (22% grade 3/4). Of 22 efficacy-evaluable patients, 82% and 45% achieved overall and complete responses, respectively. Of 20 MRD-evaluable patients, 75% and 65% achieved undetectable MRD in blood and marrow, respectively. Safety and efficacy were similar between dose levels. The phase 2 portion of the study is ongoing at 100 × 106 CAR+ T cells. This trial was registered at clinicaltrials.gov as NCT03331198.
Perturbed NK-cell homeostasis associated with disease severity in chronic neutropenia
Authors: Sohlberg Ebba , Pfefferle Aline , Heggernes Ask Eivind , Tschan-Plessl Astrid , Jacobs Benedikt , Netskar Herman , Lorenz Susanne , Kanaya Minoru , Kosugi-Kanaya Mizuha , Meinke Stephan , Mörtberg Anette , Höglund Petter , Sundin Mikael , Carlsson Göran , Palmblad Jan , Malmberg Karl-Johan
Published: October 2021

Neutrophils have been thought to play a critical role in terminal differentiation of NK cells. Whether this effect is direct or a consequence of global immune changes with effects on NK-cell homeostasis remains unknown. In this study, we used high-resolution flow and mass cytometry to examine NK-cell repertoires in 64 patients with neutropenia and 27 healthy age- and sex-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK-cell homeostasis manifesting as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These immature NK-cell repertoires were characterized by expression of the proliferation/exhaustion markers Ki-67, Tim-3, and TIGIT and displayed blunted tumor target cell responses. Systems-level immune mapping revealed that the changes in immunophenotypes were confined to NK cells, leaving T-cell differentiation intact. RNA sequencing of NK cells from these patients showed upregulation of a network of genes, including TNFSF9, CENPF, MKI67, and TOP2A, associated with apoptosis and the cell cycle, but different from the conventional CD56bright signatures. Profiling of 249 plasma proteins showed a coordinated enrichment of pathways related to apoptosis and cell turnover, which correlated with immature NK-cell repertoires. Notably, most of these patients exhibited severe-grade neutropenia, suggesting that the profoundly altered NK-cell homeostasis was connected to the severity of their underlying etiology. Hence, although our data suggest that neutrophils are dispensable for NK-cell development and differentiation, some patients displayed a specific gap in the NK repertoire, associated with poor cytotoxic function and more severe disease manifestations.
piRNA-IPdb: a PIWI-bound piRNAs database to mining NGS sncRNA data and beyond
Authors: Barreñada Odei , Larriba Eduardo , Brieño-Enriquez Miguel A. , Mazo Jesús del
Published: October 2021

Background

PIWI-interacting RNAs (piRNAs) are an abundant single-stranded type of small non-coding RNAs (sncRNAs), which initially were discovered in gonadal cells, with a role as defenders of genomic integrity in the germline, acting against the transposable elements. With a regular size range of 21-35 nt, piRNAs are associated with a PIWI-clade of Argonaute family proteins. The most widely accepted mechanisms of biogenesis for piRNAs involve the transcription of longer precursors of RNAs to be processed, by complexes of proteins, to functional size, preferentially accommodating uridine residues at the 5’ end and 3’ methylation to increase the stability of these molecules. piRNAs have also been detected in somatic cells, with diverse potential functions, indicating their high plasticity and pleiotropic activity. Discovered about two decades ago, piRNAs are a large and versatile type of sncRNA and that remain insufficiently identified and analyzed, through next-generation sequencing (NGS), to evaluate their processing, functions, and biogenesis in different cell types and during development. piRNAs’ distinction from other sncRNAs has led to controversial results and interpretation difficulties when using existing databases because of the heterogeneity of the criteria used in making the distinction.

Description

We present “piRNA-IPdb”, a database based uniquely on datasets obtaining after the defining characteristic of piRNAs: those small RNAs bound to PIWI proteins. We selected and analyzed sequences from piRBase that exclusively cover the binding to PIWI. We pooled a total of 18,821,815 sequences from RNA-seq after immunoprecipitation that included the binding to any of the mouse PIWI proteins (MILI, MIWI, or MIWI2).

Conclusions

In summary, we present the characteristics and potential use of piRNA-IPdb database for the analysis of bona fide piRNAs.
Circadian miR-449c-5p regulates uterine Ca2+ transport during eggshell calcification in chickens
Authors: Cui Zhifu , Zhang Zhichao , Amevor Felix Kwame , Du Xiaxia , Li Liang , Tian Yaofu , Kang Xincheng , Shu Gang , Zhu Qing , Wang Yan , Li Diyan , Zhang Yao , Zhao Xiaoling
Published: October 2021

Background

miRNAs regulate circadian patterns by modulating the biological clocks of animals. In our previous study, we found that the clock gene exhibited a cosine expression pattern in the fallopian tube of chicken uterus. Clock-controlled miRNAs are present in mammals and Drosophila; however, whether there are clock-controlled miRNAs in the chicken uterus and, if so, how they regulate egg-laying rhythms is unclear. In this study, we selected 18 layer hens with similar ovipositional rhythmicity (each of three birds were sacrificed for study per 4 h throughout 24 h); their transcriptomes were scanned to identify the circadian miRNAs and to explore regulatory mechanisms within the uterus of chickens.

Results

We identified six circadian miRNAs that are mainly associated with several biological processes including ion trans-membrane transportation, response to calcium ion, and enrichment of calcium signaling pathways. Verification of the experimental results revealed that miR-449c-5p exhibited a cosine expression pattern in the chicken uterus. Ca2+-transporting ATPase 4 (ATP2B4) in the plasma membrane is the predicted target gene of circadian miR-449c-5p and is highly enriched in the calcium signaling pathway. We speculated that clock-controlled miR-449c-5p regulated Ca2+ transportation during eggshell calcification in the chicken uterus by targeting ATP2B4. ATP2B4 mRNA and protein were rhythmically expressed in the chicken uterus, and dual-luciferase reporter gene assays confirmed that ATP2B4 was directly targeted by miR-449c-5p. The expression of miR-449c-5p showed an opposite trend to that of ATP2B4 within a 24 h cycle in the chicken uterus; it inhibited mRNA and protein expression of ATP2B4 in the uterine tubular gland cells. In addition, overexpression of ATP2B4 significantly decreased intracellular Ca2+ concentration (P < 0.05), while knockdown of ATP2B4 accelerated intracellular Ca2+ concentrations. We found similar results after ATP2B4 knockdown by miR-449c-5p. Taken together, these results indicate that ATP2B4 promotes uterine Ca2+ trans-epithelial transport.

Conclusions

Clock-controlled miR-449c-5p regulates Ca2+ transport in the chicken uterus by targeting ATP2B4 during eggshell calcification.
“PrEP’s just to secure you like insurance”: a qualitative study on HIV pre-exposure prophylaxis (PrEP) adherence and retention among black cisgender women in Mississippi
Authors: Willie Tiara C. , Monger Mauda , Nunn Amy , Kershaw Trace , Stockman Jamila K. , Mayer Kenneth H. , Chan Philip A. , Adimora Adaora A. , Mena Leandro A. , Knight Deja , Philllips Karlye A. , Baral Stefan D.
Published: October 2021

Background

Pre-exposure prophylaxis (PrEP) has the potential to reduce transmission of HIV among Black cisgender women in the Southern United States (U.S.); however, national data suggests that PrEP initiation is lowest in the South and among Black women compared to other U.S. regions and white women. This study applied intersectionality and PrEP multilevel resilience frameworks to assess how socio-structural and clinical contexts shaped PrEP persistence among Black cisgender women in Mississippi.

Methods

Semi-structured interviews were conducted with eight Black cisgender women in Jackson, Mississippi. This sample was purposively recruited to include PrEP-initiated Black cisgender women.

Results

Six themes identified that shaped PrEP care among Black cisgender women: (1) internal assets, (2) sole responsibility to HIV prevention, (3) added protection in HIV serodifferent relationships, (4) financial issues, (5) trust and distrust in the medical system, and (6) side effects. Black cisgender women reported that PrEP persistence increased control over their sexual health, reduced anxiety about HIV, and promoted self-care. Black cisgender women also indicated that medication assistance programs increased PrEP affordability resulting in continued persistence.

Conclusions

In addition to preventing HIV, PrEP may yield secondary positive impacts on the health and relationships of Black cisgender women. However, very few Black cisgender women in the South are using PrEP given intersectional barriers and thus necessitates adaptive strategies to support PrEP initiation and persistence. Efforts aimed at increasing the coverage of PrEP among Black cisgender women should consider implementation strategies responsive to lived realities of Black women.
Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe
Authors: Robbins Tanya , Hanlon Charlotte , Kelly Ann H. , Gidiri Muchabayiwa Francis , Musiyiwa Mickias , Silverio Sergio A. , Shennan Andrew H. , Sandall Jane
Published: October 2021

Background

Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care.

Methods

We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model.

Results

Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy.

Conclusions

Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care.
Association between health locus of control and perceived stress in college student during the COVID-19 outbreak: a cross-sectional study in Iran
Authors: Ganjoo Mahasty , Farhadi Akram , Baghbani Reza , Daneshi Safieh , Nemati Reza
Published: October 2021

Background

The COVID-19 pandemic as a global mental health crisis has affected everyone, including students. The present study aimed to determine and investigate the relationship between health locus of control and perceived stress in students of Bushehr University of Medical Sciences (southern Iran) during the outbreak of COVID-19.

Methods

The present cross-sectional study examined 250 students of Bushehr University of Medical Sciences. We performed simple random sampling and utilized the demographic information form, Multidimensional Health Locus of Control scale (MHLCS) by Wallston, and Perceived Stress Scale (PSS) by Cohen to collect data. We analyzed data using the SPSS, Pearson correlation coefficient, and the hierarchical regression model with an error level of 5%.

Results

The mean perceived stress was 30.74 ± 8.09, and 92.4% of the students had moderate and high stress levels. Among the components of the health locus of control, the internal health locus of control (IHLC) had the highest mean in students (27.55 ± 3.81). Furthermore, the internal health locus of control (R = − 0.30, P < 0.001) had a significant inverse relationship, with perceived stress and the chance health locus of control (CHLC) (R = 0.30, P < 0.001) had a significant direct relationship. In the final regression model, the health locus of control and all the variables predicted 22.7% of the perceived stress variation in students during the COVID-19 period.

Conclusion

The results indicated that the internal health locus of control was associated with a reduction of perceived stress, and the powerful others health locus of control (PHLC) was related to its increase in students during the COVID-19 pandemic. Given the uncertain future, in the present work, universities are suggested to design web-based educational interventions alongside the curriculum to further strengthen the internal health locus of control and thus help reduce their perceived stress.
Impact of surgery on survival in breast cancer with bone metastases only: a SEER database retrospective analysis
Authors: Peng Pai , Chen Jiang-Yuan , Han Yun-Tao , Chen Xin , Li Hong-Yuan , Hu Chao-Hua , Wang Jin-Li
Published: October 2021

Background

It was controversial to operate on the primary site of breast cancer (BC) with bone metastasis only. We investigated the impact of surgery on BC patients with bone metastases via a SEER database retrospective analysis.

Methods

A total of 2917 BC cases with bone metastasis, first diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and Results Database (SEER) of National Cancer Institute were selected. We assessed the effect of different surgical procedures on survival and prognosis.

Results

Compared with the non-surgical group, the primary tumor surgical group showed longer median survival time (χ2 = 146.023, P < 0.001), and the breast-conserving subgroup showed the highest median survival time of 70 months (χ2 = 157.117, P < 0.001). Compared with the non-surgery group, the median overall survival (OS) of primary surgery group was longer (HR = 0.525, 95%CI = 0.467–0.590, P < 0.001), and the breast-conserving subgroup showed the longest median operative OS (HR = 0.394, 95%CI = 0.325–0.478, P < 0.001).

Conclusion

This study showed that primary surgery could improve the median survival time and OS of BC patients with bone metastasis. Moreover, under the condition of low tumor burden, breast conserving surgery was a better choice.
Knowledge, attitudes, and beliefs regarding molar incisor hypomineralisation amongst Swiss dental students
Authors: Hamza Blend , Elhennawy Karim , van Waes Hubertus , Papageorgiou Spyridon N.
Published: October 2021

Background

Knowledge obtained at the undergraduate level regarding molar incisor hypomineralisation (MIH) has an impact on future practice of dentists and paediatric dentists. This cross-sectional study aimed to assess final-year dental students’ knowledge, attitudes and beliefs towards MIH in all Swiss universities.

Methods

A previously utilised survey (in both English and German) was distributed among final-year dental students in all Swiss dental schools (Basel, Bern, Geneva and Zurich). It probed students’ knowledge, attitudes and beliefs regarding the diagnosis, prevalence, aetiology, and management of MIH, and was structured in two parts: knowledge/perception and clinical application. The students’ responses were analysed statistically with descriptive statistics.

Results

113 out of 133 final-year Swiss dental students took part in the study (85%). Nearly all students were familiar with MIH (99%), but only 12% of them felt confident when diagnosing MIH clinically. Direct composite fillings (66%), indirect restorations (28%) and preformed stainless-steel crowns (26%) were chosen as most suitable treatment options for MIH-affected teeth.

Conclusion

Final-year Swiss dental students are well informed about MIH. However, they report low level of confidence when clinically confronted with MIH-affected teeth regarding its diagnosis and treatment. Swiss Universities curricula should be revisited accordingly.
Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages
Authors: Sayre Dean , Steinhardt Laura C. , Irinantenaina Judickaelle , Dentinger Catherine , Rasoanaivo Tsinjo Fehizoro , Kapesa Laurent , Razafindrakoto Jocelyn , Legrand Agathe , Prada Nicole , Gutman Julie , Lewis Lauren , Mangahasimbola Reziky Tiandraza , Andriamananjara Mauricette , Ravaoarinosy Aimée Vololoniala , Ralemary Nicolas , Garchitorena Andres , Harimanana Aina
Published: October 2021

Background

Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours.

Methods

Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns.

Results

Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5–29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5–14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5–14-year-olds reported fever in the two weeks prior to survey (p = 0.044).

Conclusions

The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.
CircRNF220, not its linear cognate gene RNF220, regulates cell growth and is associated with relapse in pediatric acute myeloid leukemia
Authors: Liu Xiaodan , Liu Xiaoping , Cai Mansi , Luo Ailing , He Yingyi , Liu Sha , Zhang Xiaohong , Yang Xu , Xu Ling , Jiang Hua
Published: October 2021

Background

Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and have been confirmed to be critical in tumorigenesis and to be potential biomarkers or therapeutic targets. However, only a few circRNAs have been functionally characterized in pediatric acute myeloid leukemia (AML).

Methods

Here, we investigated the expression pattern of circRNAs in pediatric AML using a circRNA microarray. The characteristics, potential diagnostic value, and prognostic significance of circRNF220 were evaluated. A series of functional experiments were performed to investigate the role of circRNF220 in primary pediatric AML cells. Then we investigated the aberrant transcriptional networks regulated by circRNF220 in primary AML cells by RNA-seq. Furthermore, biotin RNA pulldown assays were implemented to verify the relationship between circRNF220 and miR-30a.

Results

We identified a circRNA, circRNF220, which was specifically abundant in and accumulated in the peripheral blood and bone marrow of pediatric patients with AML. It could distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity. Significantly, circRNF220 expression independently predicted prognosis, while high expression of circRNF220 was an unfavorable prognostic marker for relapse. Furthermore, we characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibited proliferation and promoted apoptosis in AML cell lines and primary cells. Mechanistically, circRNF220 may act as an endogenous sponge of miR-30a to sequester miR-30a and inhibit its activity, which increases the expression of its targets MYSM1 and IER2 and implicated in AML relapse.

Conclusions

Collectively, these findings demonstrated that circRNF220 could be highly efficient and specific for the accurate diagnosis of pediatric AML, with implications for relapse prediction.
Celastrol-based nanomedicine promotes corneal allograft survival
Authors: Li Zhanrong , Liu Ruixing , Guo Zhihua , Chu Dandan , Zhu Lei , Zhang Junjie , Shuai Xintao , Li Jingguo
Published: October 2021

Effectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases.

Graphical Abstract
From policy to practice: prioritizing person-centred healthcare actions in the state of Victoria
Authors: Bragge Peter , Horvat Lidia , Mckinlay Louise , Borg Kim , Macleod-Smith Belinda , Wright Breanna
Published: October 2021

Background

Meaningful involvement of consumers in healthcare is a high priority worldwide. In Victoria, Australia, a Partnering in Healthcare (PiH) policy framework was developed to guide health services in addressing consumer-focused healthcare improvements. The aim of this project was to identify priorities for improvement relating to the framework from the perspective of Victorian healthcare consumers and those who work in the healthcare sector.

Methods

A survey of Victorians representing key stakeholder groups was used to identify a “long list” of potential priorities, followed by a day-long summit to reduce this to a “short list” using explicit prioritization criteria. The survey was piloted prior to implementation, and diverse consumer groups and key health service providers were purposefully sampled for the summit.

Results

The survey (n = 680 respondents) generated 14–20 thematic categories across the proposed framework’s five domains. The summit (n = 31 participants, including n = 21 consumer representatives) prioritized the following five areas based on the survey findings: communication, shared decision-making, (shared) care planning, health (system) literacy and people (not) around the patient. These priorities were underpinned by three cross-cutting principles: care/compassion/respect, accountability and diversity.

Conclusion

Few studies have explicitly sought consumer input on health policy implementation. Adopting a codesign approach enabled the framework to be a shared foundation of healthcare improvement. The framework was subsequently launched in 2019. All Victorian health services are required to commit annually to improvement priorities against at least two framework domains.
Development and validation of new screening tool for predicting dementia risk in community-dwelling older Japanese adults
Authors: Makino Keitaro , Lee Sangyoon , Bae Seongryu , Chiba Ippei , Harada Kenji , Katayama Osamu , Shinkai Yohei , Shimada Hiroyuki
Published: October 2021

Background

Established clinical assessments for detecting dementia risk often require time, cost, and face-to-face meetings. We aimed to develop a Simplified Telephone Assessment for Dementia risk (STAD) (a new screening tool utilizing telephonic interviews to predict dementia risk) and examine the predictive validity of the STAD for the incidence of dementia.

Methods

We developed STAD based on a combination of literature review, statistical analysis, and expert opinion. We selected 12 binary questions on subjective cognitive complaints, depressive symptoms, and lifestyle activities. In the validation study, we used STAD for 4298 community-dwelling older adults and observed the incidence of dementia during the 24-month follow-up period. The total score of STAD ranging from 0 to 12 was calculated, and the cut-off point for dementia incidence was determined using the Youden index. The survival rate of dementia incidence according to the cut-off points was determined. Furthermore, we used a decision-tree model (classification and regression tree, CART) to enhance the predictive ability of STAD for dementia risk screening.

Results

The cut-off point of STAD was set at 4/5. Participants scoring ≥ 5 points showed a significantly higher risk of dementia than those scoring ≤ 4 points, even after adjusting for covariates (hazard ratio [95% confidence interval], 2.67 [1.40–5.08]). A decision tree model using the CART algorithm was constructed using 12 nodes with three STAD items. It showed better performance for dementia prediction in terms of accuracy and specificity as compared to the logistic regression model, although its sensitivity was worse than the logistic regression model.

Conclusions

We developed a 12-item questionnaire, STAD, as a screening tool to predict dementia risk utilizing telephonic interviews and confirmed its predictive validity. Our findings might provide useful information for early screening of dementia risk and enable bridging between community and clinical settings. Additionally, STAD could be employed without face-to-face meetings in a short time; therefore, it may be a suitable screening tool for community-dwelling older adults who have negative attitudes toward clinical examination or are non-adherent to follow-up assessments in clinical trials.
Exploring biological basis of Syndrome differentiation in coronary heart disease patients with two distinct Syndromes by integrated multi-omics and network pharmacology strategy
Authors: Wu Gaosong , Zhao Jing , Zhao Jing , Song Nixue , Zheng Ningning , Zeng Yuanyuan , Yao Tingting , Zhang Jingfang , Weng Jieqiong , Yuan Mengfei , Zhou Hu , Shen Xiaoxu , Li Houkai , Zhang Weidong
Published: October 2021

Background

Traditional Chinese Medicine (TCM) is distinguished by Syndrome differentiation, which prescribes various formulae for different Syndromes of same disease. This study aims to investigate the underlying mechanism.

Methods

Using a strategy which integrated proteomics, metabolomics study for clinic samples and network pharmacology for six classic TCM formulae, we systemically explored the biological basis of TCM Syndrome differentiation for two typical Syndromes of CHD: Cold Congealing and Qi Stagnation (CCQS), and Qi Stagnation and Blood Stasis (QSBS).

Results

Our study revealed that CHD patients with CCQS Syndrome were characterized with alteration in pantothenate and CoA biosynthesis, while more extensively altered pathways including D-glutamine and D-glutamate metabolism; alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism, were present in QSBS patients. Furthermore, our results suggested that the down-expressed PON1 and ADIPOQ might be potential biomarkers for CCQS Syndrome, while the down-expressed APOE and APOA1 for QSBS Syndrome in CHD patients. In addition, network pharmacology and integrated analysis indicated possible comorbidity differences between the two Syndromes, that is, CCQS or QSBS Syndrome was strongly linked to diabetes or ischemic stroke, respectively, which is consistent with the complication disparity between the enrolled patients with two different Syndromes. These results confirmed our assumption that the molecules and biological processes regulated by the Syndrome-specific formulae could be associated with dysfunctional objects caused by the Syndrome of the disease.

Conclusion

This study provided evidence-based strategy for exploring the biological basis of Syndrome differentiation in TCM, which sheds light on the translation of TCM theory in the practice of precision medicine.
Self-reported experience of orofacial injury, preventive practice, and knowledge of Iranian adolescent martial art athletes towards sports-related orofacial injuries
Authors: Esmaeilpoor Ali , Mohebbi Simin Z. , Moghadam Navid , Ahmadian Mina , Razeghi Samaneh , Khami Mohammad R.
Published: October 2021

Background

Increased engagement of adolescents in martial arts exposes them to a relatively high risk of experiencing orofacial injuries. We evaluated self-reported experience of orofacial injuries, preventive practice, and knowledge of management of sport-related orofacial injuries and related factors in adolescent Karate and Taekwondo athletes in Iran.

Methods

This cross-sectional study was conducted on Iranian martial arts athletes including Karate and Taekwondo aged 11–17-year-old in 2020 via an online questionnaire. The anonymous self-administrated questionnaire had four parts: background (age, gender, duration of sports activity, training sessions per week, and previous education on orofacial injury); self-reported experience of orofacial injury; preventive practice including mouthguard and helmet use; and knowledge of emergency management of orofacial injuries. Preventive practice and knowledge scores were calculated by summing up the scores of corresponding questions (possibly range 0–7). A linear regression model and the Pearson correlation served for statistical analysis.

Results

Totally, 295 athletes with a mean age of 14.56 ± 1.91 years participated in the study. A quarter (n = 74, 25.1%) of athletes stated that they had received training on prevention of orofacial injuries. Only 3.7% (n = 11) of the participants reported the use of custom-made mouthguards, and 62% (n = 183) reported a positive history of orofacial injuries. A significant relationship existed between self-reported orofacial injury and age (β = − 0.32, p < 0.001), hours of training per week (β = 0.12, p = 0.037), type of sport (β = 0.11, p = 0.049), and previous training on orofacial injuries (β = − 0.14, p = 0.010). No difference existed in the history of orofacial injury between females (n = 114) and males (n = 69) (p = 0.374). The mean score of self-reported preventive practice and knowledge of management of orofacial injuries was 3.53 ± 1.82 (out of 7) and 1.67 ± 1.10 (out of 7), respectively. Age (β = 0.19, p = 0.002) and history of orofacial injury (β = − 0.15, p = 0.010) were associated with the score of self-reported preventive practice. Female athletes (β = 0.11, p = 0.048) and athletes who exercised more per week (β = 0.15, p = 0.012) had significantly more knowledge on management of orofacial injuries.

Conclusion

Adolescent athletes had relatively undesirable preventive practices and a distinct lack of knowledge. The high occurrence of self-reported orofacial injuries indicates the importance of more education and stricter rules for the athlete population.
Acute pancreatitis in a COVID-19 patient in Brazil: a case report
Authors: da Costa Ferreira Caroline Petersen , Marques Kalynne Rodrigues , de Mattos Gustavo Henrique Ferreira , de Campos Tércio
Published: October 2021

Background

The consequences of the coronavirus disease 2019 pandemic have already exceeded 10 million infected and more than 560,000 deaths worldwide since its inception. Currently, it is known that the disease affects mainly the respiratory system; however, recent studies have shown an increase in the number of patients with manifestations in other systems, including gastrointestinal manifestations. There is a lack of literature regarding the development of acute pancreatitis as a complication of coronavirus disease 2019.

Case report

We report a case of acute pancreatitis in a white male patient with coronavirus disease 2019. A 35-year-old man (body mass index 31.5) had acute epigastric pain radiating to his back, dyspnea, nausea, and vomiting for 2 days. The patient was diagnosed with severe acute pancreatitis (AP)-APACHE II: 5, SOFA: 3, Marshall: 0; then he was transferred from ED to the semi-intensive care unit. He tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcription-polymerase chain reaction, and his chest computed tomography findings were compatible with coronavirus disease 2019. Treatment was based on bowel rest, fluid resuscitation, analgesia, and empiric antibiotic therapy. At day 12, with resolution of abdominal pain and improvement of the respiratory condition, the patient was discharged.

Conclusion

Since there is still limited evidence of pancreatic involvement in severe acute respiratory syndrome coronavirus 2 infection, no definite conclusion can be made. Given the lack of other etiology, we consider the possibility that the patient’s acute pancreatitis could be secondary to coronavirus disease 2019 infection, and we suggest investigation of pancreas-specific plasma amylase in patients with coronavirus disease 2019 and abdominal pain.
Fatal large-vessel cerebrovascular infarct presenting with severe coronavirus disease 2019 in a 39-year-old patient: a case report
Authors: Koslover Nicolas , Hardwick Marc , Grundmann Alexander , Levene Tamara
Published: October 2021

Background

Emerging reports are describing stroke in young, otherwise healthy patients with coronavirus disease 2019, consistent with the theory that some of the most serious complications of coronavirus disease 2019 are due to a systemic coagulopathy. However, the relevance of both the severity of coronavirus disease 2019 illness and established vascular risk factors in these younger patients is unknown, as reports are inconsistent.

Case presentation

Here we describe a 39-year-old white male, who died after presenting simultaneously with a malignant large-vessel cerebrovascular infarct and a critical coronavirus disease 2019 respiratory illness. Doppler ultrasound revealed evidence of carotid plaque thrombosis. Blood tests revealed evidence of undiagnosed diabetes mellitus; however, the patient was otherwise healthy, fit, and active.

Conclusions

This unique case highlights a possible interaction between established risk factors and large-vessel thrombosis in young patients with coronavirus disease 2019, and informs future research into the benefits of anticoagulation in these patients.
Therapeutic activity of sarpogrelate and dopamine D2 receptor agonists on cardiovascular and renal systems in rats with alloxan-induced diabetes
Authors: Fouad Shalaby Mohammed Ahmed , Abd El Latif Hekma A. , El Yamani Mohamed , Galal May Ahmed , Kamal Sherifa , Sindi Ikhlas , Masaood Raneem
Published: October 2021

Background

Dopamine D2 receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia. An affiliation was found between the initiation of myocardial injury ailment and long term treatment with dopamine D2 agonist drugs identified with the partial activation of 5-hydroxytryptamine receptor 2 A (5-HT2A). The investigation aimed to examine the activity of sarpogrelate (a 5-HT2A receptor blocker) in reducing myocardial injury prompted by extended haul utilisation of D2 receptor agonists in rats with alloxan-induced diabetes.

Methods

Both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Both tail-cuff blood pressure and the BGL were recorded weekly. For all animals, the kidney hypertrophy index, serum creatinine, blood urea nitrogen, alanine transaminase, and aspartate transaminase levels were measured after one month of treatment. The severity of the cardiac injury was assessed by the estimation of lactate dehydrogenase-1 (LDH-1), cardiac troponin I, and tumor necrosis factor alpha 1 (TNF1). The triphenyltetrazolium chloride (TTC) staining method was used to determine the experimental myocardial infarction (MI) size.

Results

Bromocriptine and cabergoline created a significant reduction in BGL, BP, and kidney hypertrophy index in diabetic nephropathy rats. Administration of bromocriptine and cabergoline, alone, or in combination with sarpogrelate fundamentally diminished the blood concentrations of alkaline phosphatase (ALP), Aspartate aminotransferase (AST), urea, and creatinine. Bromocriptine and cabergoline alone showed a noteworthy increase in the LDH-1, Troponin I, and TNF1 levels in the serum (p < 0.05). Paradoxically, utilising bromocriptine or cabergoline with sarpogrelate treatment altogether decreased the levels of the myocardial biomarkers in the serum. A mix of bromocriptine or cabergoline with sarpogrelate diminished the level of the myocardial infarct size in the heart assessed through the TTC staining method.

Conclusions

The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these two drugs on the myocardial tissues.
Short-range Lidar SLAM utilizing localization data of monocular localization
Authors: Nakamura Sousuke , Muto Shunsuke , Takahashi Daichi
Published: October 2021

Simultaneous localization and mapping (SLAM) is a widely used technology in autonomous mobile robots, where sensors such as Lidar or cameras are typically used. Sensor fusion using multiple sensors has been employed to compensate for the shortcomings of each sensor in SLAM. However, the sensor cost cannot be ignored when considering its practical usage. Therefore, this study aims at realizing a high-precision SLAM using a sensor switching system, combining multiple low-cost sensors. The sensor switching system consists of a low-cost Lidar SLAM and a monocular localization. Since a low-cost Lidar has a short laser range, degeneracy often occurs due to the fact that they cannot capture features while building maps. The proposed system uses localization data from monocular localization to ensure precision in regions where degeneracy occurs. The proposed system was evaluated through the simulation assuming the museum environment where the degeneracy occurred. The accuracy of the robot trajectory and the built map proved the effectiveness of the proposed system.