bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic potential of ultrasound in carpal tunnel syndrome with different etiologies: correlation of sonographic median nerve measures with electrodiagnostic severity
Authors: Elnady Basant , Rageh Elsayed M. , Ekhouly Tohamy , Fathy Sabry M. , Alshaar Mohamed , Fouda El Saeed , Attar Mohammed , Abdelaal Ahmed M. , El Tantawi Ahmed , Algethami Mohammed M. , Bong David
Published: December 2019

Background

Carpal tunnel syndrome (CTS) is the commonest entrapment neuropathy. The aim of this study was to assess the accuracy and validity of high resolution musculoskeletal ultrasound (US) in the diagnosis of CTS in the Saudi population.

Methods

Sixty patients were diagnosed clinically to have CTS involving 89 wrists that were confirmed by neurophysiologic studies. Each affected wrist was characterized as idiopathic or associated with either diabetes mellitus or hypothyroidism and were assigned a severity grade based on results of neurophysiologic studies. Seventy-six healthy wrists from fifty age, sex and BMI matched healthy subjects were included in the control group. High resolution ultrasound (US) was performed to assess median nerve cross sectional area distal (CSAd) at the entry to the carpal tunnel and proximally (CSAp) at the level of pronator quadratus muscle with a further calculation of their difference (ΔCSA) and their mean average or CSAd+CSAp/2 (CSApd).

Results

There was a significant difference between both groups regarding mean ± SD of CSAd, CSAp, ∆CSA, and CSApd (p = 0.0001). A positive significant correlation was also found between the CSAd, ∆ CSA and the CSApd measurements with neurophysiologic severity grade of CTS (P = 0.001). A ∆CSA threshold of 2.5 mm2 showed the highest sensitivity and specificity to diagnose CTS in Saudis.

Conclusion

High resolution ultrasound is a valid and accurate diagnostic modality in carpal tunnel syndrome and correlated to CTS severity. A ∆CSA greater than 2.5 mm2 is considered a valid diagnostic value for CTS in our Saudi population. CTS in our patients with diabetes tend to have greater median nerve US measurement values.
Navigation-assisted suture anchor insertion for arthroscopic rotator cuff repair
Authors: Micic Ivan , Kholinne Erica , Hong Hanpyo , Choi Hyunseok , Kwak Jae-Man , Sun Yucheng , Hong Jaesung , Koh Kyoung-Hwan , Jeon In-Ho
Published: December 2019

Background

Suture anchor placement for subscapularis repair is challenging. Determining the exact location and optimum angle relative to the subscapularis tendon direction is difficult because of the mismatch between a distorted arthroscopic view and the actual anatomy of the footprint. This study aimed to compare the reliability and reproducibility of the navigation-assisted anchoring technique with conventional arthroscopic anchor fixation.

Methods

Arthroscopic shoulder models were tested by five surgeons. The conventional and navigation-assisted methods of suture anchoring in the subscapularis footprint on the humeral head were tested by each surgeon seven times. Angular results and anchor locations were measured and compared using the Wilcoxon signed rank test. Interobserver intraclass correlation coefficients (ICCs) were analyzed among the surgeons.

Results

The mean angular errors of the targeted anchor fixation guide without and with navigation were 17° and 2° (p < 0.05), respectively, and the translational errors were 15 and 3 mm (p < 0.05), respectively. All participants showed a narrow range of anchor fixation angular and translational errors from the original target. Among the surgeons, the interobserver reliabilities of angular errors for ICCs of the navigation-assisted and conventional methods were 0.897 and 0.586, respectively, and the interobserver ICC reliabilities for translational error were 0.938 and 0.619, respectively.

Conclusions

The navigation system may help surgeons be more aware of the surrounding anatomy and location, providing better guidance for anchor orientation, including footprint location and anchor angle.
Study protocol of coaching end-of-life palliative care for advanced heart failure patients and their family caregivers in rural appalachia: a randomized controlled trial
Authors: Piamjariyakul Ubolrat , Petitte Trisha , Smothers Angel , Wen Sijin , Morrissey Elizabeth , Young Stephanie , Sokos George , Moss Alvin H. , Smith Carol E.
Published: December 2019

Background

Heart failure (HF) afflicts 6.5 million Americans with devastating consequences to patients and their family caregivers. Families are rarely prepared for worsening HF and are not informed about end-of-life and palliative care (EOLPC) conservative comfort options especially during the end stage. West Virginia (WV) has the highest rate of HF deaths in the U.S. where 14% of the population over 65 years have HF. Thus, there is a need to investigate a new family EOLPC intervention (FamPALcare), where nurses coach family-managed advanced HF care at home.

Methods

This study uses a randomized controlled trial (RCT) design stratified by gender to determine any differences in the FamPALcare HF patients and their family caregiver outcomes versus standard care group outcomes (N = 72). Aim 1 is to test the FamPALcare nursing care intervention with patients and family members managing home supportive EOLPC for advanced HF. Aim 2 is to assess implementation of the FamPALcare intervention and research procedures for subsequent clinical trials. Intervention group will receive routine standard care, plus 5-weekly FamPALcare intervention delivered by community-based nurses. The intervention sessions involve coaching patients and family caregivers in advanced HF home care and supporting EOLPC discussions based on patients’ preferences. Data are collected at baseline, 3, and 6 months. Recruitment is from sites affiliated with a large regional hospital in WV and community centers across the state.

Discussion

The outcomes of this clinical trial will result in new knowledge on coaching techniques for EOLPC and approaches to palliative and end-of-life rural home care. The HF population in WV will benefit from a reduction in suffering from the most common advanced HF symptoms, selecting their preferred EOLPC care options, determining their advance directives, and increasing skills and resources for advanced HF home care. The study will provide a long-term collaboration with rural community leaders, and collection of data on the implementation and research procedures for a subsequent large multi-site clinical trial of the FamPALcare intervention. Multidisciplinary students have opportunity to engage in the research process.

Trial registration

ClinicalTrials.gov NCT04153890, Registered on 4 November 2019
A qualitative study on reasons for early removal of Implanon among users in Arba Minch town, Gamo Goffa zone, South Ethiopia: a phenomenological approach
Authors: Utaile Mesfin Mamo , Debere Mesfin Kote , Nida Etsehiwot Tilahun , Boneya Dube Jara , Ergano Amsale Tekle
Published: January 2020

Background

Implanon is one of the cost - effective long acting reversible contraceptive methods used for spacing and limiting births in Ethiopia. Despite the scaling up initiative undertaken by the Ethiopian Government, Implanon uptake is very low compared to short acting contraceptive methods. There is low utilization of Implanon with high level of discontinuation in Ethiopia. Therefore, this study was conducted to explore the reasons for early removal of Implanon among users in Arba Minch town, South Ethiopia.

Methods

A community-based qualitative exploratory study using phenomenological approach was conducted. In-depth and key informant interviews were used to collect data from April 20–27, 2018 in Arba Minch town. Convenient sampling was employed to recruit participants from the households of targeted villages. A total of 10 in-depth interviews with women who recently removed Implanon and 5 key informant interviews with health extension workers were conducted. The sample size was determined based on the concept of saturation. The collected data were analyzed using thematic content analysis technique. Data coding and analysis were facilitated by using Open code version 4.0 software.

Results

This study revealed that majority of participants were able to mention at least three types of contraceptive methods available in the nearby health facilities. The study underlined that side effect of the method, husband opposition, seeking more children, and method failure were the common reasons for early removal of Implanon, in which side effect of the method was the main reason. Among various forms of side effects of Implanon identified by users, heavy and irregular bleeding was mentioned as the most frequently occurring side effect.

Conclusion

Our result indicated that heavy and irregular bleeding was the main reason for early removal of Implanon. Therefore it suggests improvement in the service delivery system. Improving client’s education and counseling service program could contribute much to avoid unreasonable and untimely removal of Implanon.
Drug prescription goals in primary care: a cross-sectional study
Authors: Bernard Louis , Ecochard René , Gueyffier François , Letrilliart Laurent
Published: January 2020

Background

Care goals are often implicit, although their identification is a key element of any prescription process. This study aimed to describe the clinical goals of drug prescriptions in general practice, their determinants and the agreement between physicians and patients.

Methods

This was a cross-sectional study conducted by 11 resident trainees acting as observers in 23 general practices. The residents recorded the indication and main physician’s goal for all drugs prescribed during five consultation days in each practice in December 2015, and the main patient’s goal for a sub-sample of consultations. We used an eight-category generic classification of prescription goals, including three specific (mortality, morbidity and cure), three non-specific (symptoms, quality of life, functioning) and two non-specified (other goal, no goal) categories. Analyses were based on a multivariable, multilevel model and on the kappa statistic applied to the sub-sample of consultations.

Results

The sample encompassed 2141 consultations and 5036 drugs. The main physicians’ goal of drug prescriptions was to relieve symptoms (43.3%). The other goals were to decrease the risk of morbidity (22.4%), to cure disease (11.7%), to improve quality of life (10.6%), to decrease the risk of mortality (8.5%) and to improve functioning (1.8%). The choice of a specific goal was more frequent in patients with the following characteristics: over 50 (OR [1.09;1.15]), of male gender (OR [1.09;1.39]), with full financial coverage for a long-term condition (OR [1.47;1.97]), known by the physician (OR [1.19;2.23]), or with a somatic health problem (OR [2.56;4.17]). Cohen’s kappa for drug prescription goals between the patients and the physicians was 0.26 (0.23–0.30).

Conclusions

Physicians’ goals are poorly shared with patients. It remains to be assessed whether it is possible to collect and discuss information on prescription goals on a daily basis.
Functional architecture underlying binocular coordination of eye position and velocity in the larval zebrafish hindbrain
Authors: Brysch Christian , Leyden Claire , Arrenberg Aristides B.
Published: December 2019

Background

The oculomotor integrator (OI) in the vertebrate hindbrain transforms eye velocity input into persistent position coding output, which plays a crucial role in retinal image stability. For a mechanistic understanding of the integrator function and eye position control, knowledge about the tuning of the OI and other oculomotor nuclei is needed. Zebrafish are increasingly used to study integrator function and sensorimotor circuits, yet the precise neuronal tuning to motor variables remains uncharacterized.

Results

Here, we recorded cellular calcium signals while evoking monocular and binocular optokinetic eye movements at different slow-phase eye velocities. Our analysis reveals the anatomical distributions of motoneurons and internuclear neurons in the nucleus abducens as well as those of oculomotor neurons in caudally adjacent hindbrain volumes. Each neuron is tuned to eye position and/or velocity to variable extents and is only activated after surpassing particular eye position and velocity thresholds. While the abducens (rhombomeres 5/6) mainly codes for eye position, in rhombomeres 7/8, a velocity-to-position coding gradient exists along the rostro-caudal axis, which likely corresponds to the oculomotor structures storing velocity and position, and is in agreement with a feedforward mechanism of persistent activity generation. Position encoding neurons are recruited at eye position thresholds distributed across the behaviourally relevant dynamic range, while velocity-encoding neurons have more centred firing thresholds for velocity. In the abducens, neurons coding exclusively for one eye intermingle with neurons coding for both eyes. Many of these binocular neurons are preferentially active during conjugate eye movements and less active during monocular eye movements. This differential recruitment during monocular versus conjugate tasks represents a functional diversification in the final common motor pathway.

Conclusions

We localized and functionally characterized the repertoire of oculomotor neurons in the zebrafish hindbrain. Our findings provide evidence for a mixed but task-specific binocular code and suggest that generation of persistent activity is organized along the rostro-caudal axis in the hindbrain.
Charting the diversity of uncultured viruses of Archaea and Bacteria
Authors: Coutinho F. H. , Edwards R. A. , Rodríguez-Valera F.
Published: December 2019

Background

Viruses of Archaea and Bacteria are among the most abundant and diverse biological entities on Earth. Unraveling their biodiversity has been challenging due to methodological limitations. Recent advances in culture-independent techniques, such as metagenomics, shed light on the unknown viral diversity, revealing thousands of new viral nucleotide sequences at an unprecedented scale. However, these novel sequences have not been properly classified and the evolutionary associations between them were not resolved.

Results

Here, we performed phylogenomic analysis of nearly 200,000 viral nucleotide sequences to establish GL-UVAB: Genomic Lineages of Uncultured Viruses of Archaea and Bacteria. The pan-genome content of the identified lineages shed light on some of their infection strategies, potential to modulate host physiology, and mechanisms to escape host resistance systems. Furthermore, using GL-UVAB as a reference database for annotating metagenomes revealed elusive habitat distribution patterns of viral lineages and environmental drivers of community composition.

Conclusions

These findings provide insights about the genomic diversity and ecology of viruses of prokaryotes. The source code used in these analyses is freely available at https://sourceforge.net/projects/gluvab/.
Proteoglycan serglycin promotes non-small cell lung cancer cell migration through the interaction of its glycosaminoglycans with CD44
Authors: Guo Jing-You , Chiu Chu-Hsuan , Wang Mei-Jung , Li Fu-An , Chen Jeou-Yuan
Published: January 2020

Background

Serglycin (SRGN), previously recognized as an intracellular proteoglycan involved in the storage processes of secretory granules, has recently been shown to be upregulated in several solid tumors. We have previously shown that SRGN in non-small cell lung cancer (NSCLC) promotes malignant phenotypes in a CD44-dependent manner and increased expression of SRGN predicts poor prognosis of primary lung adenocarcinomas. However, the underlying mechanism remains to be defined.

Methods

Overexpression, knockdown and knockout approaches were performed to assess the role of SRGN in cell motility using wound healing and Boyden chamber migration assays. SRGN devoid of glycosaminoglycan (GAG) modification was produced by site-directed mutagenesis or chondroitinase treatment. Liquid chromatography/tandem mass spectrometry was applied for quantitative analysis of the disaccharide compositions and sulfation extent of SRGN GAGs. Western blot and co-immunoprecipitation analyses were performed to determine the expression and interaction of proteins of interest. Actin cytoskeleton organization was monitored by immunofluorescence staining.

Results

SRGN expressed by NSCLC cells is readily secreted to the extracellular matrix in a heavily glycosylated form attached with mainly chondroitin sulfate (CS)-GAG chains, and to a lesser extent with heparin sulfate (HS). The CS-GAG moiety serves as the structural motif for SRGN binding to tumor cell surface CD44 and promotes cell migration. SRGN devoid of CS-GAG modification fails to interact with CD44 and has lost the ability to promote cell migration. SRGN/CD44 interaction promotes focal adhesion turnover via Src-mediated paxillin phosphorylation and disassembly of paxillin/FAK adhesion complex, facilitating cell migration. In support, depletion of Src activity or removal of CS-GAGs efficiently blocks SRGN-mediated Src activation and cell migration. SRGN also promotes cell migration via inducing cytoskeleton reorganization mediated through RAC1 and CDC42 activation accompanied with increased lamellipodia and filopodia formation.

Conclusions

Proteoglycan SRGN promotes NSCLC cell migration via the binding of its GAG motif to CD44. SRGN/CD44 interaction induces Rho-family GTPase-mediated cytoskeleton reorganization and facilitates Src-mediated focal adhesion turnover, leading to increased cell migration. These findings suggest that targeting specific glycans in tumor microenvironment that serve as ligands for oncogenic pathways may be a potential strategy for cancer therapy.
Correction to: Production efficiency of the bacterial non-ribosomal peptide indigoidine relies on the respiratory metabolic state in S. cerevisiae
Authors: Wehrs Maren , Prahl Jan-Philip , Moon Jadie , Li Yuchen , Tanjore Deepti , Keasling Jay D. , Pray Todd , Mukhopadhyay Aindrila
Published: December 2019

Following publication of the original article [1], the authors have noted that the standard curve in Additional file 1: Figure S7 is incorrect.
Adherence to malaria rapid diagnostic test result among healthcare workers in Sokoto metropolis, Nigeria
Authors: Na’uzo Aliyu Mamman , Tukur Dahiru , Sufiyan Mu’awiyyah Babale , Stephen Adebowale Ayo , Ajayi IkeOluwapo , Bamgboye Eniola , Gobir Abdulrazaq Abdullahi , Umeokonkwo Chukwuma David , Abdullahi Zainab , Ajumobi Olufemi
Published: January 2020

Background

Presumptive diagnosis and prescription of anti-malarial medicines to malaria rapid diagnostic test (RDT)-negative patients is a common practice among health care workers (HCWs) in Nigeria. There is paucity of data on HCWs adherence to RDT result in Sokoto metropolis, Nigeria. The study was conducted to determine HCWs adherence to malaria test result and the influencing factors.

Methods

A cross-sectional study was conducted among 262 HCWs selected by multistage sampling technique from primary and secondary health facilities in Sokoto metropolis. Data on demographic characteristics, adherence to RDT result and its influencing factors were collected from the HCWs. Adherence was categorized into good if adherence score is ≥ 4 and poor if otherwise. Chi-squared test was used to test association between adherence to test results and patients’ fever presentation, expectation to be given anti-malarials, prior HCWs’ case management training, among others. Independent predictors of adherence to RDT results were ascertained.

Results

Respondents’ mean age was 33.5 ± 7.9 years, 190 (72.5%) worked in Primary Health Care facilities, 112 (42.8%) were Community Health Workers, 178 (67.9%) had National Diploma Certificate. The median years of practice was 5.0 (IQR: 3–10) years, while 118 (45.0%) had at most 4 years of practice. Overall, 211 (80.5%) had good adherence to RDT results. About 108 (89.3%) of HCWs who had training on malaria case management and 35 (89.7%) certificate holders had good adherence to RDT results. Predictors of adherence to test results were presence of fever in the patient [adjusted odds ratio (aOR): 2.53, 95% confidence interval (CI) 1.18–5.43], patients’ expectation to be given anti-malarial medicines by the HCW (aOR: 3.06, 95% CI 1.42–6.58) and having been trained on malaria case management (aOR: 2.63; 95% CI 1.26–5.44).

Conclusion

High level of adherence to RDT results among HCWs in Sokoto metropolis could be attributed to prior malaria case management training and HCWs’ confidence in the national treatment guidelines. Continual training and supportive supervision of HCWs on malaria case management might optimize the current level of adherence to RDT results in Sokoto metropolis, Nigeria. Similarly, patients/caregivers’ health education could aid better understanding of the need for anti-malarials thus reducing unnecessary demand.
The interactome and proteomic responses of ALKBH7 in cell lines by in-depth proteomics analysis
Authors: Meng Shu , Zhan Shaohua , Dou Wanchen , Ge Wei
Published: December 2019

Background

ALKBH7 is a mitochondrial protein, involved in programmed necrosis, fatty acid metabolism, cell cycle regulation, and prostate cancer disease. However, the exact roles of ALKBH7 and the underlying molecular mechanisms remain mysterious. Thus, investigations of the interactome and proteomic responses of ALKBH7 in cell lines using proteomics strategies are urgently required.

Methods

In the present study, we investigated the interactome of ALKBH7 in mitochondria through immunoprecipitation-mass spectrometry/mass spectrometry (IP-MS/MS). Additionally, we established the ALKBH7 knockdown and overexpression cell lines and further identified the differentially expressed proteins (DEPs) in these cell lines by TMT-based MS/MS. Two DEPs (UQCRH and HMGN1) were validated by western blotting analysis.

Results

Through bioinformatic analysis the proteomics data, we found that ALKBH7 was involved in protein homeostasis and cellular immunity, as well as cell proliferation, lipid metabolism, and programmed necrosis by regulating the expression of PTMA, PTMS, UQCRH, HMGN1, and HMGN2. Knockdown of ALKBH7 resulted in upregulation of UQCRH and HMGN1 expression, and the opposite pattern of expression was detected in ALKBH7 overexpression cell lines; these results were consistent with our proteomics data.

Conclusion

Our findings indicate that the expression of UQCRH and HMGN1 is regulated by ALKBH7, which provides potential directions for future studies of ALKBH7. Furthermore, our results also provide comprehensive insights into the molecular mechanisms and pathways associated with ALKBH7.
Assessing quality of life in older adults: psychometric properties of the OPQoL-brief questionnaire in a nursing home population
Authors: Haugan Gørill , Drageset Jorunn , André Beate , Kukulu Kamile , Mugisha James , Utvær Britt Karin S.
Published: January 2020

Background

Well-adapted and validated quality-of-life measurement models for the nursing home population are scarce. Therefore, the aim of this study was to test the psychometrical properties of the OPQoL-brief questionnaire among cognitively intact nursing home residents. The research question addressed evidence related to the dimensionality, reliability and construct validity, all of which considered interrelated measurement properties.

Methods

Cross-sectional data were collected during 2017–2018, in 27 nursing homes representing four different Norwegian municipalities, located in Western and Mid-Norway. The total sample comprised 188 of 204 (92% response rate) long-term nursing home residents who met the inclusion criteria: (1) municipality authority’s decision of long-term nursing home care; (2) residential time 3 months or longer; (3) informed consent competency recognized by responsible doctor and nurse; and (4) capable of being interviewed.

Results

Principal component analysis and confirmative factor analyses indicated a unidimensional solution. Five of the original 13 items showed low reliability and validity; excluding these items revealed a good model fit for the one-dimensional 8-items measurement model, showing good internal consistency and validity for these 8 items.

Conclusion

Five out of the 13 original items were not high-quality indicators of quality-of-life showing low reliability and validity in this nursing home population. Significant factor loadings, goodness-of-fit indices and significant correlations in the expected directions with the selected constructs (anxiety, depression, self-transcendence, meaning-in-life, nurse-patient interaction, and joy-of-life) supported the psychometric properties of the OPQoL-brief questionnaire. Exploring the essence of quality-of-life when residing in a nursing home is highly warranted, followed by development and validation of new tools assessing quality-of-life in this population. Such knowledge and well-adapted scales for the nursing home population are beneficial and important for the further development of care quality in nursing homes, and consequently for quality-of-life and wellbeing in this population.
Rabbit VX2 lung tumor models can form early nodal metastases
Authors: Gregor Alexander , Fujino Kosuke , Bernards Nicholas , Kinoshita Tomonari , Motooka Yamato , Inage Terunaga , Ishiwata Tsukasa , Chen Zhenchian , Ujiie Hideki , Lee Chang Young , Yasufuku Kazuhiro
Published: December 2019

Background

The rabbit squamous cell cancer line, VX2, has been used to generate various tumor models in rabbits. It is notable for its ability to generate nodal metastases. However, the timing and extent of nodal metastases vary by primary inoculation site and methodology. The development of metastases specifically in lung cancer models has not been well-described. We sought to characterize the generation of nodal metastases in rabbit transbronchial VX2 lung tumor models.

Methods

Rabbit VX2 lung tumor models were created in the right lung via transbronchial injection and serially imaged by computed tomography. Rabbits (n = 15) were sacrificed from between 5 and 24 days post-inoculation for collection of the ipsilateral and contralateral paratracheal lymph nodes. These underwent histopathological evaluation for metastases using hematoxylin and eosin as well as cytokeratin AE1/AE3 immunohistochemical staining.

Results

Nodal metastases were detectable as early as 1 week after inoculation but were more prevalent with longer inoculation; all rabbits at > 2 weeks post-inoculation had nodal metastases. Contralateral metastases were in general seen later than ipsilateral metastases. Lymph node volume did not predict the likelihood of nodal metastases (p = 0.4 and p = 0.07 for ipsilateral and contralateral nodal metastases, respectively), but primary tumor volume was significantly associated with the likelihood of nodal metastases (p = 0.001 and p = 0.005 for ipsilateral and contralateral nodal metastases, respectively). Ipsilateral metastases were detectable at a tumor diameter of 1 cm; contralateral metastases were more variable but in general required a tumor diameter of 2 cm.

Conclusions

Rabbit transbronchial VX2 lung tumor models generate nodal metastases relatively early after inoculation. These results suggest such models may be valuable tools in the investigation of novel therapeutic modalities relevant for the treatment of both early-stage and locally advanced lung cancer.
The importance of ultrasound in identifying and differentiating patients with early inflammatory arthritis: a narrative review
Authors: Kaeley Gurjit S. , Bakewell Catherine , Deodhar Atul
Published: January 2020

Early differentiation between different types of inflammatory arthritis and subsequent initiation of modern treatments can improve patient outcomes by reducing disease activity and preventing joint damage. Routine clinical evaluation, laboratory testing, and radiographs are typically sufficient for differentiating between inflammatory and predominantly degenerative arthritis (e.g., osteoarthritis). However, in some patients with inflammatory arthritis, these techniques fail to accurately identify the type of early-stage disease. Further evaluation by ultrasound imaging can delineate the inflammatory arthritis phenotype present. Ultrasound is a noninvasive, cost-effective method that enables the evaluation of several joints at the same time, including functional assessments. Further, ultrasound can visualize pathophysiological changes such as synovitis, tenosynovitis, enthesitis, bone erosions, and crystal deposits at a subclinical level, which makes it an effective technique to identify and differentiate most common types of inflammatory arthritis. Limitations associated with ultrasound imaging should be considered for its use in the differentiation and diagnosis of inflammatory arthritides.
Association of circulating microRNAs with prevalent and incident knee osteoarthritis in women: the OFELY study
Authors: Rousseau Jean-Charles , Millet Marjorie , Croset Martine , Sornay-Rendu Elisabeth , Borel Olivier , Chapurlat Roland
Published: January 2020

Objectives

In the context of the scarcity of biomarkers for knee osteoarthritis (OA), we examined the associations of prevalent and incident OA with the expression levels of serum miRNAs in subjects with and without OA.

Methods

With a next-generation sequencing approach, we compared the miRome expression of 10 women with knee OA and 10 age-matched healthy subjects. By real-time qPCR, we analyzed the expression levels of 19 miRNAs at baseline selecting 43 women with prevalent knee OA (Kellgren Lawrence score of 2/3), 23 women with incident knee OA over a 4-year follow-up and 67 healthy subjects without prevalent or incident OA matched for age and body mass index.

Results

Serum miR-146a-5p was significantly increased in the group of prevalent knee OA compared with controls (relative quantification (RQ); median [Interquartile range] 1.12 [0.73; 1.46] vs 0.85 [0.62; 1.03], p = 0.015). The likelihood of prevalent knee OA was significantly increased (odds ratio [95% confidence interval (CI)] 1.83 [1.21–2.77], p = 0.004) for each quartile increase in serum miR-146a-5p. The women with miR-146a-5p levels above the median (0.851) had a higher risk of prevalent knee OA compared to those below the median [95% CI] 4.62 [1.85–11.5], p = 0.001. Moreover, we found a significant association between the baseline level of serum miR-186-5p and the risk of incident knee OA (Q4 vs Q1–3; odds ratio [95% CI] 6.13 [1.14–32.9], p = 0.034).

Conclusion

We showed for the first time that miR-146a-5p and miR-186-5p are significantly associated with prevalent and incident knee OA, respectively.
A re-evaluation of LINE-1 ORF2 expression in LNCaP prostate cancer cells
Authors: Briggs Erica M. , Spadafora Corrado , Logan Susan K.
Published: December 2019

Background

We previously examined expression of Long Interspersed Element-1 (LINE-1) in a variety of prostate cancer cells including hormone-dependent LNCaP cells. These studies demonstrated expression and sub-cellular localization of LINE-1 proteins, ORF1p, with antibody 4H1, and ORF2p, with antibody chA1-L1.

Results

Here we conduct immunoprecipitation/mass spectrometry analysis using chA1-L1 antibody against ORF2p in LNCaP cells. Our results indicate that antigens detected by the antibody include the transcriptional regulator BCLAF1. We show that chA1-L1 recognizes BCLAF1 using siRNA knockdown and overexpression of a tagged BCLAF1. We also show that chA1-L1 antibody recognizes ORF2p in HEK293 cells overexpressing LINE-1. Further, analysis of ORF2p (chA1-L1) and BCLAF1 foci using immunofluorescence in LNCaP cells showed significant colocalization.

Conclusions

Overall, our findings indicate that chA1-L1 antibody recognizes both BCLAF1 and ORF2p but the majority of antigen recognized in LNCaP cells is BCLAF1.
One-month-old girl presenting with pseudohypoaldosteronism leading to the diagnosis of CDK13-related disorder: a case report and review of the literature
Authors: Yakubov Renata , Ayman Asaly , Kremer Adi Klein , van den Akker Machiel
Published: December 2019

Background

It is not uncommon that an infant with a disease of unknown etiology is presented to a physician. Facial dysmorphic features lead to a different diagnosis. It is a challenge to link the presentation to the newfound diagnosis.

Case presentation

A 37-day-old Yemenite Jewish girl was presented to our institution with a clinical picture of pseudohypoaldosteronism due to abnormal facial features and a psychomotor developmental delay. Further investigation led to the diagnosis of CDK13-related disorder. According to the literature, CDK13 has a key role in the cell cycle, but no interference with the aldosterone signaling pathway or electrolyte balance was described. No mutations in the previously described gene NR3C2 (cytogenetic location 4q31.23), encoding the mineralocorticoid receptor, were found. Although the clinical presentation corresponded to pseudohypoaldosteronism type 1, we could not genetically confirm this.

Conclusions

Probably pseudohypoaldosteronism was a coincidental finding in this girl with a CDK13 mutation, but because only limited information is known about CDK13-related disorders, further investigation could be more informative to clarify this presentation.
Health insurance coverage, type of payment for health insurance, and reasons for not being insured under the National Health Insurance Scheme in Ghana
Authors: Ayanore Martin Amogre , Pavlova Milena , Kugbey Nuworza , Fusheini Adam , Tetteh John , Ayanore Augustine Adoliba , Akazili James , Adongo Philip Baba , Groot Wim
Published: December 2019

Background

Ghana’s National Health Insurance Scheme has improved access to care, although equity and sustainability issues remain. This study examined health insurance coverage, type of payment for health insurance and reasons for being uninsured under the National Health Insurance Scheme in Ghana.

Methods

The 2014 Ghana Demographic Health Survey datasets with information for 9396 women and 3855 men were analyzed. The study employed cross-sectional national representative data. The frequency distribution of socio-demographics and health insurance coverage differentials among men and women is first presented. Further statistical analysis applies a two-stage probit Hackman selection model to determine socio-demographic factors associated with type of payment for insurance and reasons for not insured among men and women under the National Health insurance Scheme in Ghana. The selection equation in the Hackman selection model also shows the association between insurance status and socio-demographic factors.

Results

About 66.0% of women and 52.6% of men were covered by health insurance. Wealth status determined insurance status, with poorest, poorer and middle-income groups being less likely to pay themselves for insurance. Women never in union and widowed women were less likely to be covered relative to married women although this group was more likely to pay NHIS premiums themselves. Wealth status (poorest, poorer and middle-income) was associated with non-affordability as a reason for being not insured. Geographic disparities were also found. Rural men and nulliparous women were also more likely to mention no need of insurance as a reason of being uninsured.

Conclusion

Tailored policies to reduce delays in membership enrolment, improve positive perceptions and awareness of National Health Insurance Scheme in reducing catastrophic spending and addressing financial barriers for enrolment among some groups can be positive precursors to improve trust and enrolments and address broad equity concerns regarding the National Health Insurance Scheme.
The cost-effectiveness of pegaspargase versus native asparaginase for first-line treatment of acute lymphoblastic leukaemia: a UK-based cost-utility analysis
Authors: Hu Xingdi , Wildman Kingsley P. , Basu Subham , Lin Peggy L. , Rowntree Clare , Saha Vaskar
Published: December 2019

Background

L-asparaginase is a key component of treatment for patients with acute lymphoblastic leukaemia (ALL) in the UK. Commonly used forms of asparaginase are native E. coli-derived asparaginase (native asparaginase) and pegaspargase in first-line combination therapy, and native Erwinia chrysanthemi-derived asparaginase (Erwinia asparaginase) as second-line treatment. The objective of this study was to evaluate the cost-effectiveness of pegaspargase versus native asparaginase in first-line combination therapy for patients with newly diagnosed ALL. A combined decision tree and health-state transition Markov cost-effectiveness model was developed to assess the relative costs and health outcomes of pegaspargase versus native asparaginase in the UK setting.

Results

In base case analyses, first-line pegaspargase (followed by Erwinia asparaginase in cases of hypersensitivity) dominated first-line native asparaginase followed by Erwinia asparaginase; i.e. resulted in lower costs and more quality-adjusted life year gain. The favourable hypersensitivity rates and administration profile of pegaspargase led to lifetime cost savings of £4741 versus native asparaginase. Pegaspargase remained cost-effective versus all treatment strategies in all scenario analyses, including use of the 2500 IU/m2 dose, recommended for patients ≤21 years of age.

Conclusions

Pegaspargase, as part of multi-drug chemotherapy, is a cost-effective option for the treatment of newly diagnosed ALL. Based on this study, The National Institute for Health and Care Excellence Technology Appraisal Committee concluded that it could recommend pegaspargase as a cost-effective use of National Health Service resources in England & Wales for treating ALL in children, young people and adults with untreated, newly diagnosed disease.

Trial registration

UKALL 2011, EudraCT number 2010-020924-22; UKALL 2003, EudraCT number 2007-004013-34; UKALL14, EudraCT number 2009-012717-22.
Case report: a rapid review approach used by the UK National Screening Committee to inform recommendations on general population screening for vasa praevia
Authors: Leonard Saoirse , Buchanan-Hughes Amy , Bobrowska Anna , Visintin Cristina , Marshall John
Published: December 2019

Background

The UK National Screening Committee (UK NSC) reviews evidence about existing or potential population screening programmes using rapid review products called evidence summaries. We provide a case report as an example of how rapid reviews are developed within the UK NSC’s process, consider how the quality of rapid reviews should be assessed and ask whether the rapid review was an appropriate tool to inform the UK NSC’s decision-making process.

Methods

We present the rapid review approach taken by the commissioner and the reviewers to develop an evidence summary for vasa praevia (VP), which the UK NSC reappraised as part of its 3-yearly cycle for conditions where screening is currently not recommended. We apply the AMSTAR 2 quality appraisal checklist for systematic reviews, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and a published checklist of items to consider with a rapid review approach. As UK NSC evidence summaries do not include meta-analyses, any related AMSTAR 2 or PRISMA checklist items were considered inapplicable.

Results

The evidence summary was available within the required timelines and highlighted little change from the previous review in terms of key evidence gaps relating to the epidemiology of VP, the screening test and the management pathway. Therefore, the UK NSC concluded that there was insufficient evidence to support a change in its previous recommendation against screening. The evidence summary scored moderately against the applicable AMSTAR 2 and PRISMA checklist items. Against the published checklist of items to consider with a rapid review approach, the evidence summary performed well.

Conclusions

In this case report, the use of a rapid review as part of the UK NSC’s process enabled a pragmatic approach to assessing the overall volume, quality and direction of literature on key questions relating to the viability of a population screening programme for VP. Based on our assessments of this single evidence summary, systematic review quality appraisal tools may undervalue rapid reviews. The validity of the methods used in this case report, as well as the wider generalisability of our insights relating to rapid review practice, reporting and quality assessment, requires analysis of a larger sample of rapid reviews.
Inhibitory Interplay of SULT2B1b Sulfotransferase with AKR1C3 Aldo-keto Reductase in Prostate Cancer
Authors: Park Sulgi , Song Chung-Seog , Lin Chun-Lin , Jiang Shoulei , Osmulski Pawel A , Wang Chiou-Miin , Marck Brett T , Matsumoto Alvin M , Morrissey Colm , Gaczynska Maria E , Chen Yidong , Mostaghel Elahe A , Chatterjee Bandana
Published: January 2020

SULT2B1b (SULT2B) is a prostate-expressed hydroxysteroid sulfotransferase, which may regulate intracrine androgen homeostasis by mediating 3β-sulfation of dehydroepiandrosterone (DHEA), the precursor for 5α-dihydrotestosterone (DHT) biosynthesis. The aldo-keto reductase (AKR)1C3 regulates androgen receptor (AR) activity in castration-resistant prostate cancer (CRPC) by promoting tumor tissue androgen biosynthesis from adrenal DHEA and also by functioning as an AR-selective coactivator. Herein we report that SULT2B-depleted CRPC cells, arising from stable RNA interference or gene knockout (KO), are markedly upregulated for AKR1C3, activated for ERK1/2 survival signal, and induced for epithelial-to-mesenchymal (EMT)-like changes. EMT was evident from increased mesenchymal proteins and elevated EMT-inducing transcription factors SNAI1 and TWIST1 in immunoblot and single-cell mass cytometry analyses. SULT2B KO cells showed greater motility and invasion in vitro; growth escalation in xenograft study; and enhanced metastatic potential predicted on the basis of decreased cell stiffness and adhesion revealed from atomic force microscopy analysis. While AR and androgen levels were unchanged, AR activity was elevated, since PSA and FKBP5 mRNA induction by DHT-activated AR was several-fold higher in SULT2B-silenced cells. AKR1C3 silencing prevented ERK1/2 activation and SNAI1 induction in SULT2B-depleted cells. SULT2B was undetectable in nearly all CRPC metastases from 50 autopsy cases. Primary tumors showed variable and Gleason score (GS)-independent SULT2B levels. CRPC metastases lacking SULT2B expressed AKR1C3. Since AKR1C3 is frequently elevated in advanced prostate cancer, the inhibitory influence of SULT2B on AKR1C3 upregulation, ERK1/2 activation, EMT-like induction, and on cell motility and invasiveness may be clinically significant. Pathways regulating the inhibitory SULT2B-AKR1C3 axis may inform new avenue(s) for targeting SULT2B-deficient prostate cancer.
Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery
Authors: Smith Barbara L. , Lanahan Conor R. , Specht Michelle C. , Kelly Bridget N. , Brown Carson , Strasfeld David B. , Ferrer Jorge M. , Rai Upahvan , Tang Rong , Rice-Stitt Travis , Biernacka Anna , Brachtel Elena F. , Gadd Michele A.
Published: January 2020

Background

Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20–40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor.

Methods

Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology.

Results

In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal.

Conclusions

The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.
Unstained blood smear contrast enhancement using spectral time multiplexing super resolution
Authors: Yebouet Marie-Florence , Diby Ambroise , Kaduki Kenneth , Zoueu Jérémie
Published: January 2020

We report the use of Time Multiplexing Super Resolution (TMSR) to reduce significantly speckle noise in spectral
imaging microscopy of unstained thin blood smear samples of malaria-infected blood. The method is based on combining
speckle illumination with a moving array serving as an encoding mask. We propose the use of a new encoding mask to
improve the performance of the conventional TMSR method. The new mask is a two-dimensional generalisation of the one-
dimensional Ipatov code. The mask is projected on the object and 13 low-resolution images captured and subsequently
decoded properly using the same array. The low contrast images are added and extracted from the resulting
reconstruction, giving a super-resolved, high-contrast image. The Ipatov filter used in this work performs better than the
Barker filter.
Do Energy Efficiency Investments Deliver at the Right Time?
Authors: Boomhower Judson , Davis Lucas
Published: January 2020

Most analyses of energy efficiency investments ignore that the value of electricity varies widely across hours. We show how much timing matters. Using novel hourly consumption data from an air conditioner rebate program in California, we find that energy savings are concentrated in high-value hours. This significantly increases the value of these investments, especially after we account for the large capacity payments that electricity generators receive to guarantee supply in peak hours. We then use engineering predictions to calculate timing premiums for a wide range of energy efficiency investments, finding substantial variation in economic value across investments. (JEL L94, L98, Q41, Q48)
The Collateral Composition Channel
Authors: Boissay Frédéric , Cooper Russell
Published: January 2020

Wholesale financial markets reallocate deposits. Because of incentive problems, these flows are limited by endogenous collateral constraints. The composition of collateral matters. The use of inside collateral creates a “collateral pyramid”: cash flows from one loan are pledged to secure another. Outside collateral, such as treasuries, stabilizes the pyramid. Through collateral pyramids the financial sector sustains a large volume of reallocation across banks, but at the cost of systemic panics. During panics, the safe asset creation process stalls, the pyramid collapses, collateral becomes scarce. Markets are more fragile when loans are secured by inside collateral. (JEL E32, E44, G01, G21)