bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile health apps for systemic lupus erythematosus and lupus nephritis: a critical appraisal
Authors: Ramasamy Akshara , Dugyala Poojitha , Mohan Chandra
Published: May 2022

Objectives

To critically assess the quality and functionality of the available mobile apps for systemic lupus erythematosus and lupus nephritis patients.

Methods

Two reviewers independently searched the App Store and Google Play Store for eligible mobile health (mHealth) apps. Two separate searches were done: one for systemic lupus erythematosus (SLE) and the other for lupus nephritis (LN). The Mobile App Rating Scale (MARS) was used to rate the quality of all selected apps.

Results

From the systemic lupus erythematosus screening, our search yielded 841 apps. Within these 841 apps, 17 of them were ultimately included. From the lupus nephritis screening, our search returned 1152 apps. Of the 1152 apps, 2 were ultimately included. Our search strategy included apps specifically designed for patients with SLE and LN. The MARS average of all the systemic lupus erythematosus apps was 2.7 out of 5. The MARS average of the two lupus nephritis apps was 2.6 out of 5.

Conclusion

Mobile health apps can serve as an effective tool for telehealth, engaging patients in self-care and for increasing the quality of life of lupus patients. While several mobile health technologies exist for patients with SLE and LN, there is still a significant need for app quality improvement and expanding the comprehensiveness of offered functions.
Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array
Authors: Grant Olivia A. , Wang Yucheng , Kumari Meena , Zabet Nicolae Radu , Schalkwyk Leonard
Published: May 2022

Background

Sex differences are known to play a role in disease aetiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using the Illumina EPIC array in human whole blood by performing a discovery (n = 1171) and validation (n = 2471) analysis.

Results

We identified and validated 396 sex-associated differentially methylated CpG sites (saDMPs) with the majority found to be female-biased CpGs (74%). These saDMP’s are enriched in CpG islands and CpG shores and located preferentially at 5’UTRs, 3’UTRs and enhancers. Additionally, we identified 266 significant sex-associated differentially methylated regions overlapping genes, which have previously been shown to exhibit epigenetic sex differences, and novel genes. Transcription factor binding site enrichment revealed enrichment of transcription factors related to critical developmental processes and sex determination such as SRY and ESR1.

Conclusion

Our study reports a reliable catalogue of sex-associated CpG sites and elucidates several characteristics of these sites using large-scale discovery and validation data sets. This resource will benefit future studies aiming to investigate sex specific epigenetic signatures and further our understanding of the role of DNA methylation in sex differences in human whole blood.
Diagnostic and prognostic performance to detect Alzheimer’s disease and clinical progression of a novel assay for plasma p-tau217
Authors: Groot Colin , Cicognola Claudia , Bali Divya , Triana-Baltzer Gallen , Dage Jeffrey L. , Pontecorvo Michael J. , Kolb Hartmuth C. , Ossenkoppele Rik , Janelidze Shorena , Hansson Oskar
Published: May 2022

Background

Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer’s disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217Lilly, within two independent cohorts.

Methods

The study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/−) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays.

Results

Both assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+JanssenAUC = 0.91 vs plasma p-tau217LillyAUC = 0.89), distinguishing MCI from controls (plasma p-tau217+JanssenAUC = 0.91 vs plasma p-tau217LillyAUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+JanssenAUC = 0.88 vs p-tau217LillyAUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+Janssenrho = −0.39 vs p-tau217Lillyrho = −0.35), and annual change in MMSE scores (plasma p-tau217+Janssenr= −0.45 vs p-tau217Lillyr= −0.41). Correlations between the two plasma measures were rho = 0.69,p< 0.001 in cohort 1 and rho = 0.70,p< 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+Janssenand plasma p-tau217Lillyin both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI).

Conclusions

Taken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+Janssenassay, similar to the p-tau217Lillyassay.
Idiopathic combined retinal vessels occlusion in a pregnant woman: a case report
Authors: Bahar Mohammadreza Mehrabi , Ghalandarpoor-Attar Seyedeh Noushin , Shabani Azadeh , Hantoushzadeh Sedigheh , Tabatabaei Seyed Ali , Ghalandarpoor-Attar Seyedeh Mojgan
Published: May 2022

Background

Ocular vascular occlusion is an extremely rare event, especially in the young population. This diagnosis is always associated with active systemic diseases in young adults and needs thrombophilia workup. Nevertheless, we present the case of a pregnant woman suffering from idiopathic combined central retinal vein and cilioretinal artery occlusion.

Case presentation

A 36-year-old pregnant Iranian woman at the 36th week of her second pregnancy complained of subacute unilateral painless decreased vision of her left eye. She had experienced a transient vision loss that lasted several minutes, but attacks gradually became more frequent and finally persistent over a several-day period. Finally combined central retinal vein and cilioretinal artery occlusion was established. Her visual acuity improved to 4/10 in a month without any ocular intervention except for a short duration of prophylactic dose enoxaparin, and the acuity reached 8/10 without any complications in the third month follow-up visit. At 1 year follow-up, the visual acuity had not changed and no macular edema was seen.

Conclusions

Ocular vascular occlusion is extremely rare among young adults, and even rarer among pregnant women. According to this, any suspected retinal vascular event in this population should raise suspicion for underlying diseases such as hypertension, diabetes, autoimmune diseases, migraine, preeclampsia syndrome, and thrombophilia. However, as seen in this presented case, idiopathic ocular vascular occlusion events can occur also.
Butanol–isopropanol fermentation with oxygen-tolerant Clostridium beijerinckii XH29
Authors: Yao Xiuqing , Zhang Quan , Fan Yixuan , Xu Xinyang , Liu Ziyong
Published: May 2022

Acetone–butanol–ethanol (ABE) fermentation is a traditional way for solvents production through bioconversion by Clostridium species. It is still a challenge to obtain metabolic engineering strains with high ABE yield. Screening strains with remarkable characteristics from nature and improving ABE yield by mutation are viable approaches. Clostridium beijerinckii XH 0906, a newly isolated strain, produces butanol and isopropanol (BI) as the main end-products (9.1 g/L BI) during fermentation with glucose as the sole carbon source. The screening process for this strain was performed under aerobic conditions rather than anaerobic environment. Thus, it is a robust stain capable of oxygen-tolerant BI fermentation. Furthermore, C. beijerinckii XH 0906 fermented xylose and glucose simultaneously to produce BI. A mutant strain obtained by ultraviolet (UV) mutagenesis, C. beijerinckii XH 29, had improved BI production capacity and could produce 17.0 g/L BI and 18.4 g/L BI using glucose or corn stover hydrolysate, respectively as the carbon source. Interestingly, C. beijerinckii XH 29 also produced up to 19.3 g/L isopropanol through fermentation of a glucose–acetone mix. These results indicate that C. beijerinckii XH 29 is an excellent BI producer with great potential for industrial applications.

Graphical Abstract
Nanotechnological engineering of extracellular vesicles for the development of actively targeted hybrid nanodevices
Authors: Dumontel Bianca , Susa Francesca , Limongi Tania , Vighetto Veronica , Debellis Doriana , Canta Marta , Cauda Valentina
Published: May 2022

Background

We propose an efficient method to modify B-cell derived EVs by loading them with a nanotherapeutic stimuli-responsive cargo and equipping them with antibodies for efficient targeting of lymphoma cells.

Results

The post-isolation engineering of the EVs is accomplished by a freeze–thaw method to load therapeutically-active zinc oxide nanocrystals (ZnO NCs), obtaining the so-called TrojanNanoHorse (TNH) to recall the biomimetism and cytotoxic potential of this novel nanoconstruct. TNHs are further modified at their surface with anti-CD20 monoclonal antibodies (TNHCD20) achieving specific targeting against lymphoid cancer cell line. The in vitro characterization is carried out on CD20+ lymphoid Daudi cell line, CD20-negative cancerous myeloid cells (HL60) and the healthy counterpart (B lymphocytes). The TNH shows nanosized structure, high colloidal stability, even over time, and good hemocompatibility. The in vitro characterization shows the high biocompatibility, targeting specificity and cytotoxic capability. Importantly, the selectivity of TNHCD20 demonstrates significantly higher interaction towards the target lymphoid Daudi cell line compared to the CD20-negative cancerous myeloid cells (HL60) and the healthy counterpart (lymphocytes). An enhanced cytotoxicity directed against Daudi cancer cells is demonstrated after the TNHCD20 activation with high-energy ultrasound shock-waves (SW).

Conclusion

This work demonstrates the efficient re-engineering of EVs, derived from healthy cells, with inorganic nanoparticles and monoclonal antibodies. The obtained hybrid nanoconstructs can be on-demand activated by an external stimulation, here acoustic pressure waves, to exploit a cytotoxic effect conveyed by the ZnO NCs cargo against selected cancer cells.

Graphical Abstract
RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence
Authors: Sun Yanan , Yu Xiao , Gao Xingyu , Zhang Chang , Sun Hui , Xu Kaiyi , Wei Dongxu , Wang Qianwen , Zhang Haiying , Shi Yingai , Li Lisha , He Xu
Published: May 2022

Background

Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined.

Results

In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence.

Conclusions

Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.
m6A demethylase FTO promotes tumor progression via regulation of lipid metabolism in esophageal cancer
Authors: Duan Xiaoran , Yang Li , Wang Liuya , Liu Qinghua , Zhang Kai , Liu Shasha , Liu Chaojun , Gao Qun , Li Lifeng , Qin Guohui , Zhang Yi
Published: May 2022

Background

Epitranscriptomics studies have contributed greatly to the development of research on human cancers. In recent years, N6-methyladenosine (m6A), an RNA modification on the N-6 position of adenosine, has been found to play a potential role in epigenetic regulation. Therefore, we aimed to evaluate the regulation of cancer progression properties by m6A.

Results

We found that m6A demethylase fat mass and obesity-associated protein (FTO) was highly expressed in esophageal cancer (EC) stem-like cells, and that its level was also substantially increased in EC tissues, which was closely correlated with a poor prognosis in EC patients. FTO knockdown significantly inhibited the proliferation, invasion, stemness, and tumorigenicity of EC cells, whereas FTO overexpression promoted these characteristics. Furthermore, integrated transcriptome and meRIP-seq analyses revealed that HSD17B11 may be a target gene regulated by FTO. Moreover, FTO promoted the formation of lipid droplets in EC cells by enhancing HSD17B11 expression. Furthermore, depleting YTHDF1 increased the protein level of HSD17B11.

Conclusions

These data indicate that FTO may rely on the reading protein YTHDF1 to affect the translation pathway of the HSD17B11 gene to regulate the formation of lipid droplets in EC cells, thereby promoting the development of EC. The understanding of the role of epitranscriptomics in the development of EC will lay a theoretical foundation for seeking new anticancer therapies.
Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis
Authors: Machin Jacob , Brewer Kimberly , Morales-Briceno Abelardo , Fenger Clara , Maylin George , Tobin Thomas
Published: May 2022

Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary “identifications” of Zilpaterol. These “identifications” occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.

In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presents in horse urine, yielding clusters of feed related Zilpaterol identifications in racehorses. The first cluster, April 2013, involved 48 racehorses in California; the second cluster, July 2013, involved 15 to 80 racehorses in Hong Kong. The third cluster, March 2019, involved 24 racehorses in Mauritius; this cluster traced to South African feedstuffs, triggering an alert concerning possible Zilpaterol feed contamination in South African racing. The fourth cluster, September/October 2020 involved 18 or so identifications in French racing, reported by the French Laboratories des Courses Hippiques, (LCH), and in July 2021, a fifth cluster of 10 Zilpaterol identifications in South Africa.

The regulatory approach to these identifications has been to alert horsemen and feed companies and penalties against horsemen are generally not implemented. Additionally, given their minimal exposure to Zilpaterol, there is little likelihood of Zilpaterol effects on racing performance or adverse health effects for exposed horses.

The driving factor in these events is that Zilpaterol is dissolved in molasses for incorporation into cattle feed. Inadvertent incorporation of Zilpaterol containing molasses into horse feed was the source of the California and Hong Kong Zilpaterol identifications. A second factor in the 2019 Mauritius and 2020 French identifications was the sensitivity of testing for Zilpaterol in Mauritius and France, with the French laboratory reportedly testing at a “more sensitive level for Zilpaterol”. As of January 1st, 2021, the new FEI Atypical Finding (ATF) policy specifies Zilpaterol as a substance to be treated as an Atypical Finding (ATF), allowing consideration of inadvertent feed contamination in the regulatory evaluation of Zilpaterol identifications.
Do social relationships mediate or moderate social inequalities in health? A systematic review protocol
Authors: Khaliq Nadia , McMunn Anne , Machuca-Vargas Carolina , Heilmann Anja
Published: May 2022

Introduction

Explanations for health inequalities include material, behavioural and psychosocial pathways. Social relationships are an important determinant of health, and research has consistently found that a lack of support networks may diminish favourable health outcomes. There is some evidence that social network structures, partly shaped by socioeconomic factors, contribute to health inequalities. This protocol will summarise the systematic review process.

Methods and analyses

The Systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An electronic database search of MEDLINE, Embase Classic + Embase and PsychINFO using the OvidSP platform will be undertaken. Databases will be searched from the earliest date of entry until 10 June 2022. Articles that have quantitatively assessed the role of social relationships in mediating or moderating health inequalities will be included and any health outcome (mental/physical) will be considered. The database search will be supplemented by reference list screening of all relevant full-text articles identified through the search. Two independent reviewers will be responsible for screening of articles, data extraction and assessment of bias. Observational studies will be risk assessed for bias using a modified version of the Newcastle-Ottawa Quality Assessment Scale, and intervention studies will be assessed using the revised Cochrane risk-of-bias tool. It is anticipated that the eligible studies will be highly variable; therefore, a meta-analysis will only be considered if the available data of the selected studies are similar. If the studies are too heterogeneous, a narrative synthesis of the extracted data will be presented.

Conclusion

The results of the systematic review will examine the link between social relationships and health inequalities. The findings of the review will identify gaps in knowledge where further research is needed.

Systematic review registration

PROSPERO CRD42020181706
Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells
Authors: Guo Rongqun , Li Wei , Li Yadan , Li Yingmei , Jiang Zhongxing , Song Yongping
Published: May 2022

Engineered T cells have been shown to be highly effective in cancer immunotherapy, although T cell exhaustion presents a challenge for their long-term function. Additional T-cell sources must be exploited to broaden the application of engineered T cells for immune defense and reconstitution. Unlimited sources of pluripotent stem cells (PSCs) have provided a potential opportunity to generate precise-engineered therapeutic induced T (iT) cells. Single-cell transcriptome analysis of PSC-derived induced hematopoietic stem and progenitor cells (iHSPC)/iT identified the developmental pathways and possibilities of generating functional T cell from PSCs. To date, the PSC-to-iT platforms encounter several problems, including low efficiency of conventional T subset specification, limited functional potential, and restrictions on large-scale application, because of the absence of a thymus-like organized microenvironment. The updated PSC-to-iT platforms, such as the three-dimensional (3D) artificial thymic organoid (ATO) co-culture system and Runx1/Hoxa9-enforced iT lymphopoiesis, provide fresh perspectives for coordinating culture conditions and transcription factors, which may greatly improve the efficiency of T-cell generation greatly. In addition, the improved PSC-to-iT platform coordinating gene editing technologies will provide various functional engineered unconventional or conventional T cells. Furthermore, the clinical applications of PSC-derived immune cells are accelerating from bench to bedside.
Integrative analysis of multi-omics data to detect the underlying molecular mechanisms for obesity in vivo in humans
Authors: Zhang Qiang , Meng Xiang-He , Qiu Chuan , Shen Hui , Zhao Qi , Zhao Lan-Juan , Tian Qing , Sun Chang-Qing , Deng Hong-Wen
Published: May 2022

Background

Obesity is a complex, multifactorial condition in which genetic play an important role. Most of the systematic studies currently focuses on individual omics aspect and provide insightful yet limited knowledge about the comprehensive and complex crosstalk between various omics levels.

Subjects and methods

Therefore, we performed a most comprehensive trans-omics study with various omics data from 104 subjects, to identify interactions/networks and particularly causal regulatory relationships within and especially those between omic molecules with the purpose to discover molecular genetic mechanisms underlying obesity etiology in vivo in humans.

Results

By applying differentially analysis, we identified 8 differentially expressed hub genes (DEHGs), 14 differentially methylated regions (DMRs) and 12 differentially accumulated metabolites (DAMs) for obesity individually. By integrating those multi-omics biomarkers using Mendelian Randomization (MR) and network MR analyses, we identified 18 causal pathways with mediation effect. For the 20 biomarkers involved in those 18 pairs, 17 biomarkers were implicated in the pathophysiology of obesity or related diseases.

Conclusions

The integration of trans-omics and MR analyses may provide us a holistic understanding of the underlying functional mechanisms, molecular regulatory information flow and the interactive molecular systems among different omic molecules for obesity risk and other complex diseases/traits.
Slow motor neurons resist pathological TDP-43 and mediate motor recovery in the rNLS8 model of amyotrophic lateral sclerosis
Authors: Hur Seong Kwon , Hunter Mandana , Dominique Myrna A. , Farag Madona , Cotton-Samuel Dejania , Khan Tahiyana , Trojanowski John Q. , Spiller Krista J. , Lee Virginia M.-Y.
Published: May 2022

In the intermediate stages of amyotrophic lateral sclerosis (ALS), surviving motor neurons (MNs) that show intrinsic resistance to TDP-43 proteinopathy can partially compensate for the loss of their more disease-susceptible counterparts. Elucidating the mechanisms of this compensation may reveal approaches for attenuating motor impairment in ALS patients. In the rNLS8 mouse model of ALS-like pathology driven by doxycycline-regulated neuronal expression of human TDP-43 lacking a nuclear localization signal (hTDP-43ΔNLS), slow MNs are more resistant to disease than fast-fatigable (FF) MNs and can mediate recovery following transgene suppression. In the present study, we used a viral tracing strategy to show that these disease-resistant slow MNs sprout to reinnervate motor endplates of adjacent muscle fibers vacated by degenerated FF MNs. Moreover, we found that neuromuscular junctions within fast-twitch skeletal muscle (tibialis anterior, TA) reinnervated by SK3-positive slow MNs acquire resistance to axonal dieback when challenged with a second course of hTDP-43ΔNLS pathology. The selective resistance of reinnervated neuromuscular junctions was specifically induced by the unique pattern of reinnervation following TDP-43-induced neurodegeneration, as recovery from unilateral sciatic nerve crush did not produce motor units resistant to subsequent hTDP-43ΔNLS. Using cross-reinnervation and self-reinnervation surgery in which motor axons are disconnected from their target muscle and reconnected to a new muscle, we show that FF MNs remain hTDP-43ΔNLS-susceptible and slow MNs remain resistant, regardless of which muscle fibers they control. Collectively, these findings demonstrate that MN identity dictates the susceptibility of neuromuscular junctions to TDP-43 pathology and slow MNs can drive recovery of motor systems due to their remarkable resilience to TDP-43-driven degeneration. This study highlights a potential pathway for regaining motor function with ALS pathology in the advent of therapies that halt the underlying neurodegenerative process.
Cloth face mask fit and function for children part one: design exploration
Authors: Du Puis Jenny Leigh , Forstenhausler Lauren , Goodge Katarina , Maher Mona , Frey Margaret , Baytar Fatma , Park Huiju
Published: May 2022

Commercially available children’s cloth masks range widely in material type and fabric structures, methods of construction, layering, and shape, and there is a lack of sizing systems, anthropometric data or guidelines specifically targeting the fit assessment and design of cloth face masks for children 4-6 years old. To better identify and understand the cloth face mask fit and functional needs of children ages 4-6 years old, the researchers embarked on interdisciplinary in-depth study to investigate commercial market offerings of children’s face masks, identify consumer perspectives, and explore mask design improvements through design research. By triangulating results from survey feedback, commercial market content analysis, and wear trial observations, the researchers were able to identify important design criteria that can be used in the improvement of children’s cloth face mask design: size, comfort, dexterity, movement, and thermal comfort. These criteria were used to iteratively develop new mask prototypes involving a 3D printed head form, traditional sewing and hand patternmaking skills, and the creation of multiple mask versions to explore the design criteria listed above. The designs were interpreted through Bye’s (2010) Problem-Based Design Research (PBDR) framework, which identifies common design research practices in the field on a spectrum and situates PBDR as a process centered on a problem as impetus for design through which artifacts are developed.
Responses of promyelocytic leukemia HL60 cells as an inflammatory cell lineage model to silica microparticles used to coat blood collection tubes
Authors: Masuki Hideo , Uematsu Takashi , Kawabata Hideo , Sato Atsushi , Watanabe Taisuke , Tsujino Tetsuhiro , Nakamura Masayuki , Okubo Masaya , Kawase Tomoyuki
Published: May 2022

Background

The preparation of platelet-rich fibrin (PRF) requires glass blood collection tubes, and thus, the shortage or unavailability of such tubes has driven clinicians to search for suitable substitutes, such as silica-coated plastic tubes. However, we have previously demonstrated the cytotoxicity of silica microparticles (MPs) used in plastic tubes to cultured human periosteal cells. To further establish the effects of silica MPs on inflammation, we examined silica MP-induced changes in a human promyelocytic cell model in vitro.

Methods

Human promyelocytic HL60 cells were used either without chemical induction or after differentiation induced using phorbol myristate acetate (PMA) or dimethyl sulfoxide. HL60 cells, osteoblastic MG63, and Balb/c mouse cells were treated with silica MPs, and their surface ultrastructure and numbers were examined using a scanning electron microscope and an automated cell counter, respectively. Differentiation markers, such as acid phosphatase, non-specific esterase, and CD11b, were visualized by cytochemical and immunofluorescent staining, and superoxide dismutase (SOD) activity was quantified.

Results

Regardless of SOD activity, silica cytotoxicity was observed in MG63 and Balb/c cells. At sub-toxic doses, silica MPs slightly or moderately upregulated the differentiation markers of the control, PMA-induced monocytic, and dimethyl sulfoxide-induced granulocytic HL60 cells. Although SOD activity was the highest (P < 0.05) in PMA-induced cells, a silica-induced reduction in cell adhesion was observed only in those cells (P < 0.05).

Conclusions

Silica MP contamination of PRF preparations can potentially exacerbate inflammation at implantation sites. Consequently, unless biomedical advantages can be identified, silica-coated plastic blood collection tubes should not be routinely used for PRF preparations.
Developing guideline-based key performance indicators for recurrent miscarriage care: lessons from a multi-stage consensus process with a diverse stakeholder group
Authors: Hennessy Marita , Linehan Laura , Dennehy Rebecca , Devane Declan , Rice Rachel , Meaney Sarah , O’Donoghue Keelin
Published: May 2022

Background

Standardised care pathways tailored to women/couples who experience recurrent miscarriage are needed; however, clinical practice is inconsistent and poorly organised. In this paper, we outline our processes and experiences of developing guideline-based key performance indicators (KPIs) for recurrent miscarriage care with a diverse stakeholder group which will be used to evaluate national services. To date, such exercises have generally only involved clinicians, with the need for greater stakeholder involvement highlighted.

Methods

Our study involved six stages: (i) identification and synthesis of recommendations for recurrent miscarriage care through a systematic review of clinical practice guidelines; (ii) a two-round modified e-Delphi survey with stakeholders to develop consensus on recommendations and outcomes; (iii) four virtual meetings to develop this consensus further; (iv) development of a list of candidate KPIs; (v) survey to achieve consensus on the final suite of KPIs and a (vi) virtual meeting to agree on the final set of KPIs. Through participatory methods, participants provided feedback on the process of KPI development.

Results

From an initial list of 373 recommendations and 14 outcomes, 110 indicators were prioritised for inclusion in the final suite of KPIs: (i) structure of care (n = 20); (ii) counselling and supportive care (n = 7); (iii) investigations (n = 30); treatment (n = 34); outcomes (n = 19). Participants’ feedback on the process comprised three main themes: accessibility, richness in diversity, streamlining the development process.

Conclusions

It is important and feasible to develop guideline-based KPIs with a diverse stakeholder group. One hundred and ten KPIs were prioritised for inclusion in a suite of guideline-based KPIs for recurrent miscarriage care. Insights into our experiences may help others undertaking similar projects, particularly those undertaken in the absence of a clinical guideline and/or involving a range of stakeholders.
Agreement between older adult patient and caregiver proxy symptom reports
Authors: Kroenke Kurt , Stump Timothy E. , Monahan Patrick O.
Published: May 2022

Background

Proxy report is essential for patients unable to complete patient-reported outcome (PRO) measures themselves and potentially beneficial when the caregiver perspective can complement patient report. In this study, we examine agreement between self-report by older adults and proxy report by their caregivers when completing PROs for pain, anxiety, depression, and other symptoms/impairments.

Methods

Four PROs were administered by telephone to older adults and their caregivers followed by re-administration within 24 h in a random subgroup. The PROs included the PHQ-9 depression, GAD-7 anxiety, PEG pain, and SymTrak multi-dimensional symptom and functional status scales.

Results

The sample consisted of 576 older adult and caregiver participants (188 patient-caregiver dyads, 200 patients without identified caregiver). The four measures had good internal (Cronbach’s alpha, 0.76 to 0.92) and test–retest (ICC, 0.63 to 0.92) reliability whether completed by patients or caregivers. Total score and item-level means were relatively similar for both patient and caregiver reports. Agreement for total score as measured by intraclass correlation coefficient (ICC) was better for SymTrak-23 (0.48) and pain (0.58) than for anxiety (0.28) and depression (0.25). Multinomial modeling showed higher (worse) patient-reported scale scores were associated with caregiver underreporting, whereas higher caregiver task difficulty was associated with overreporting.

Conclusion

When averaged over individuals at the group level, proxy reports of PRO scores by caregivers tend to approximate patient reports. For individual patients, proxy report should be interpreted more cautiously for psychological symptoms as well as when patient-reported symptoms are more severe, or caregiver task difficulty is high.
Maintaining Implementation through Dynamic Adaptations (MIDAS): protocol for a cluster-randomized trial of implementation strategies to optimize and sustain use of evidence-based practices in Veteran Health Administration (VHA) patients
Authors: Damschroder Laura J. , Sussman Jeremy B. , Pfeiffer Paul N. , Kurlander Jacob E. , Freitag Michelle B. , Robinson Claire H. , Spoutz Patrick , Christopher Melissa L.D. , Battar Saraswathy , Dickerson Kimberly , Sedgwick Christopher , Wallace-Lacey Ashleigh G. , Barnes Geoffrey D. , Linsky Amy M. , Ulmer Christi S. , Lowery Julie C.
Published: May 2022

Background

The adoption and sustainment of evidence-based practices (EBPs) is a challenge within many healthcare systems, especially in settings that have already strived but failed to achieve longer-term goals. The Veterans Affairs (VA) Maintaining Implementation through Dynamic Adaptations (MIDAS) Quality Enhancement Research Initiative (QUERI) program was funded as a series of trials to test multi-component implementation strategies to sustain optimal use of three EBPs: (1) a deprescribing approach intended to reduce potentially inappropriate polypharmacy; (2) appropriate dosing and drug selection of direct oral anticoagulants (DOACs); and (3) use of cognitive behavioral therapy as first-line treatment for insomnia before pharmacologic treatment. We describe the design and methods for a harmonized series of cluster-randomized control trials comparing two implementation strategies.

Methods

For each trial, we will recruit 8–12 clinics (24–36 total). All will have access to relevant clinical data to identify patients who may benefit from the target EBP at that clinic and provider. For each trial, clinics will be randomized to one of two implementation strategies to improve the use of the EBPs: (1) individual-level academic detailing (AD) or (2) AD plus the team-based Learn. Engage. Act. Process. (LEAP) quality improvement (QI) learning program. The primary outcomes will be operationalized across the three trials as a patient-level dichotomous response (yes/no) indicating patients with potentially inappropriate medications (PIMs) among those who may benefit from the EBP. This outcome will be computed using month-by-month administrative data. Primary comparison between the two implementation strategies will be analyzed using generalized estimating equations (GEE) with clinic-level monthly (13 to 36 months) percent of PIMs as the dependent variable. Primary comparative endpoint will be at 18 months post-baseline. Each trial will also be analyzed independently.

Discussion

MIDAS QUERI trials will focus on fostering sustained use of EBPs that previously had targeted but incomplete implementation. Our implementation approaches are designed to engage frontline clinicians in a dynamic optimization process that integrates the use of actional clinical data and making incremental changes, designed to be feasible within busy clinical settings.

Trial registration

ClinicalTrials.gov: NCT05065502. Registered October 4, 2021—retrospectively registered.
Best–worst scaling methodology to evaluate constructs of the Consolidated Framework for Implementation Research: application to the implementation of pharmacogenetic testing for antidepressant therapy
Authors: Salloum Ramzi G. , Bishop Jeffrey R. , Elchynski Amanda L. , Smith D. Max , Rowe Elizabeth , Blake Kathryn V. , Limdi Nita A. , Aquilante Christina L. , Bates Jill , Beitelshees Amber L. , Cipriani Amber , Duong Benjamin Q. , Empey Philip E. , Formea Christine M. , Hicks J. Kevin , Mroz Pawel , Oslin David , Pasternak Amy L. , Petry Natasha , Ramsey Laura B. , Schlichte Allyson , Swain Sandra M. , Ward Kristen M. , Wiisanen Kristin , Skaar Todd C. , Van Driest Sara L. , Cavallari Larisa H. , Tuteja Sony
Published: May 2022

Background

Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best–worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use.

Methods

We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites.

Results

Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions.

Conclusions

This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.
Suppression of Pituitary Hormone Genes in Subjects Who Died From COVID-19 Independently of Virus Detection in the Gland
Authors: Poma Anello Marcello , Proietti Agnese , Macerola Elisabetta , Bonuccelli Diana , Conti Marco , Salvetti Alessandra , Dolo Vincenza , Chillà Andrea , Basolo Alessio , Santini Ferruccio , Toniolo Antonio , Basolo Fulvio
Published: May 2022

Context

Involvement of the pituitary gland in SARS-CoV-2 infection has been clinically suggested by pituitary hormone deficiency in severe COVID-19 cases, by altered serum adrenocorticotropic hormone (ACTH) levels in hospitalized patients, and by cases of pituitary apoplexy. However, the direct viral infection of the gland has not been investigated.

Objective

To evaluate whether the SARS-CoV-2 genome and antigens could be present in pituitary glands of lethal cases of COVID-19, and to assess possible changes in the expression of immune-related and pituitary-specific genes.

Methods

SARS-CoV-2 genome and antigens were searched in the pituitary gland of 23 patients who died from COVID-19 and, as controls, in 12 subjects who died from trauma or sudden cardiac death. Real-time reverse transcription polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry, and transmission electron microscopy were utilized. Levels of mRNA transcripts of immune-related and pituitary-specific genes were measured by the nCounter assay.

Results

The SARS-CoV-2 genome and antigens were detected in 14/23 (61%) pituitary glands of the COVID-19 group, not in controls. In SARS-CoV-2–positive pituitaries, the viral genome was consistently detected by PCR in the adeno- and the neurohypophysis. Immunohistochemistry, in situ hybridization, and transmission electron microscopy confirmed the presence of SARS-CoV-2 in the pituitary. Activation of type I interferon signaling and enhanced levels of neutrophil and cytotoxic cell scores were found in virus-positive glands. mRNA transcripts of pituitary hormones and pituitary developmental/regulatory genes were suppressed in all COVID-19 cases irrespective of virus positivity.

Conclusion

Our study supports the tropism of SARS-CoV-2 for human pituitary and encourages exploration of pituitary dysfunction after COVID-19.
Comparative analysis of dental pulp stem cells and stem cells from human exfoliated teeth in terms of growth kinetics, immunophenotype, self-renewal and multi lineage differentiation potential for future perspective of calcified tissue regeneration
Authors: Naz Shagufta , Khan Farhan Raza , Khan Irfan , Zohra Raheela Rahmat , Salim Asmat , Mohammed Nuruddin , Ahmad Tashfeen
Published: May 2022

Background and Objectives: Owing to high proliferation rate, multipotency and self-renewal capability, dental pulp stem cells (DPSC) and stem cells from human exfoliated teeth (SHED) have become stem cell source of choice for cell based regenerative therapies. We aimed to compare DPSC and SHED as stem cell sources with a future use in regeneration of calcified tissue.

Methods: Explant derived human DPSC (n=9) and SHED (n=1) were cryopreserved, thawed and expanded for analysis of population doubling time, colony forming unit assay and efficiency. A growth curve was plotted to determine population doubling time, while colony forming numbers and efficiency was determined at plating cell densities of 5.6, 11.1 and 22.2 / cm2. The isolated cells were characterized for the presence of stem cell markers by immunophenotyping and immunofluorescence staining, and tri-lineage differentiation. Statistical analysis was performed by Pearson correlation, Exponential regression and two way Anova with Tukey test at p<0.05.

Results: DPSC and SHED exhibited spindle shaped fibroblast like morphology. SHED was found superior than DPSC in terms of proliferation and colony forming efficiency. Immunophenotypes showed that DPSC contain 62.6±26.3 %, 90.9±14.8% and 19.8±0.1%, while SHED contain 90.5%, 97.7% and 0.1% positive cells for CD90, CD73 and CD105. DPSC were strongly positive for vimentin, CD29, CD73, while reactivity was moderate to weak against CD44 and CD90. SHED expressed vimentin, CD29, CD105, CD90 and CD44. Both were negative for CD45. Upon induction, both cell types differentiated into bone, fat and cartilage like cells.

Conclusion: Cultured DPSC and SHED were proliferative and exhibited self-renewal property. Both DPSC and SHED expressed stem cell markers and were able to differentiate into bone, fat and cartilage like cells. Thus, these could be a suitable stem cell sources for cell based regenerative therapies.

doi: https://doi.org/10.12669/pjms.38.5.5187

How to cite this:Naz S, Khan FR, Khan I, Zohra RR, Salim A, Mohammed N, et al. Comparative analysis of dental pulp stem cells and stem cells from human exfoliated teeth in terms of growth kinetics, immunophenotype, self-renewal and multi lineage differentiation potential for future perspective of calcified tissue regeneration. Pak J Med Sci. 2022;38(5):---------.  doi: https://doi.org/10.12669/pjms.38.5.5187

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reliability of hand-held dynamometer in measuring gluteus medius isometric muscle strength in healthy population
Authors: Soomro Rabail Rani , Karimi Hossein , Gillani Syed Amir
Published: May 2022

Objectives: To determine the inter-rater and intra-rater reliability of the hand-held dynamometer in measuring isometric gluteus medius muscle strength in asymptomatic healthy population.

Methods: It was a cross sectional study conducted at the department of physiotherapy, Sindh Institute of Physical Medicine and Rehabilitation from March 2021 to April 2021. Thirty healthy subjects aged 18 to 25 years of both sexes and no previous or current complaints of hip or knee pain were included through non-probability purposive sampling technique. The strength of the unilateral isometric gluteus medius muscle was measured using a hand-held dynamometer by two raters at the same day and a week later. Pearson Correlation coefficient was calculated to see the relationship of muscle strength measured by each rater within and between day’s sessions. Intra–class correlation was calculated with 95% confidence interval and Standard error of measurements using reliability analysis.

Results: In the present study there were thirty participants studied by two raters, the mean age of participants was 21.53 (SD=±1.40) years, the mean BMI was 24.05 (SD=±1.12) kg/m2 and 70% participants were female and 30% were males. This study showed the mean muscle measurement of participants within days was 12.92 (SD=±0.94), with intra-class correlation ICC (2,2) 0.94 and SEM 0.12 and mean muscle measurement of patients between days was 12.99 (SD=±0.91), with intra-class correlation ICC (2,2) 0.90 and SEM 0.12.

Conclusion: Hand-held dynamometer has shown excellent inter-rater and intra-rater reliability in measuring isometric strength of Gluteus Medius muscle among healthy population. It is convenient to be used in clinical settings and can be a useful outcome tool to assess strength in interventional studies.

doi: https://doi.org/10.12669/pjms.38.5.5207

How to cite this:Soomro RR, Karimi H, Gillani SA. Reliability of hand-held dynamometer in measuring gluteus medius isometric muscle strength in healthy population. Pak J Med Sci. 2022;38(5):---------. doi: https://doi.org/10.12669/pjms.38.5.5207

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.