bluuebunny/crossref_metadata_2025 huggingface dataset:
Is There an Age Cutoff for Intracranial Pressure Monitoring?: A Propensity Score Matched Analysis of the National Trauma Data Bank
Authors: Liveris Anna , Parsikia Afshin , Melvin Jeffrey , Chao Edward , Reddy Srinivas H , Teperman Sheldon , Stone Melvin E
Published: January 2021

Background

Despite mostly favorable past evidence for use of intracranial pressure monitoring (ICPM), more recent data question not only the indications but also the utility of ICPM. The Fourth Edition Brain Trauma Foundation guidelines offer limited indications for ICPM. Evidence supports ICPM for reducing mortality in patients with severe traumatic brain injury (TBI) and cites decreased survival in elderly patients.

Methods

All patients ≥ 18 years of age with isolated TBI, head Abbreviated Injury Scale (AIS) ≥ 3, and a Glasgow Coma Scale (GCS) ≤ 8 between 2008 and 2014 were included from the National Trauma Data Bank. Exclusion criteria were head AIS = 6 and death within 24 hours. Patients with and without ICPM were compared using TBI-specific variables. Patients were then matched via propensity-score matching (PSM), and the odds ratio (OR) of death with ICPM was determined using logistic regression modeling for 8 different age strata.

Results

A total of 23,652 patients with a mean age of 56 years, median head AIS of 4, median GCS of 3, and overall mortality of 29.2% were analyzed. After PSM, ICPM was associated with death beginning at the age stratum of 56-65 years. Intracranial pressure monitoring was associated with survival beginning at the age-group 36-45 years.

Discussion

Based on a large propensity-matched sample of TBI patients, ICPM was not associated with improved survival for TBI patients above 55 years of age. Until level 1 evidence is available, this age threshold should be considered for further prospective study in determining indications for ICPM.
“Problem Free is Not Fully Prepared”: Exploring the Difference Between Prevention and Promotion Oriented Educational Indicators as Related to U.S. State Demographic Characteristics
Authors: Ilakkuvan Vinu , Price Olga A.
Published: January 2021

This study assessed whether U.S. state-level prevention- and promotion-oriented indicators of student success are differentially associated with state-level demographic characteristics. Correlation and regression analyses were used to assess the relationship between state-level demographics and promotion-oriented (school engagement, extracurricular involvement, and feeling safe at school) and prevention-oriented indicators (high school dropout and grade 4 chronic absenteeism). State demographic factors were more strongly correlated with—and more predictive of—involvement in extracurricular activities and feeling safe at school, as compared to school engagement or the prevention-oriented indicators. That is, promotion-oriented indicators appear to be substantively different than prevention-oriented indicators in terms of their relationship to state socioeconomic and racial/ethnic characteristics. This suggests current overreliance on prevention-oriented indicators may fail to fully capture student well-being and differential access to effective policies and supports between states. States should include promotion-oriented measures in their educational assessments, reporting, and accountability systems to more comprehensively understand student success and what can be done to improve student well-being and related socioeconomic conditions—particularly through state-level policies and school‐community partnerships.
The Cross-Lagged Panel Analysis between Frailty and Physical Activity among Community-Dwelling Older Adults by Age Groups
Authors: Sagong Hae , Jang Ah Ram , Kim Da Eun , Won Chang Won , Yoon Ju Young
Published: January 2021

Objectives: This study was to investigate the reciprocal relationship between frailty and physical activity among older adults by age group (middle-old: 70–79 years; oldest-old: 80–84 years) within 2 years using cross-lagged panel analysis. Methods: The study data were derived from the Korean Frailty and Aging Cohort Study, and a total of 1092 participants were included. Results: Frailty and high physical activity had significant reciprocal relationships in the middle-old group, which indicates that frailty was associated with less high physical activity, and high physical activity predicts less frailty after 2 years. In the oldest-old group, there was no statistically significant reciprocal relationship between frailty and any level of physical activity reference to low physical activity and vice versa after 2 years. Discussion: Further studies on the relationship between frailty and physical activity of the oldest-old population and specific physical activity guidelines for older adults are needed.
Association of Physical Activity and Physical Functioning Phenotypes With Fall Risk Among Women
Authors: Ylitalo Kelly R. , Karvonen-Gutierrez Carrie A. , Sternfeld Barbara , Pettee Gabriel Kelley
Published: January 2021

Objective: Physical activity (PA) may slow aging-related declines in physical functioning (PF), but the relationship of PA and falls is not well understood. This study examined the association of PA and PF with falls. Methods: The Study of Women’s Health Across the Nation participants ( n = 1597; age: 65.1 years ± 2.7) reported PF and PA in 2012–2013 and falls in 2016–2017. Four phenotypes were identified: high PA–high PF, high PA–low PF, low PA–high PF, and low PA–low PF. Results: One-third (29.3%) reported ≥1 fall. Women with low PA–low PF (RR = 1.32; 95% CI: 1.06, 1.66) and with high PA–low PF (RR = 1.37; 95% CI: 1.07, 1.74) were more likely to fall than high PA–high PF. Over time, women with worsening PF had increased fall risk (RR = 1.43; 95% CI: 1.17, 1.74), but women who increased PA did not. Discussion: Poor PF increases the risk of falls, regardless of PA. However, increasing PA does not necessarily increase fall risk, reinforcing the importance of PA engagement.
Waiting and temporal control: The temporal experience of long-term unemployment
Authors: Nielsen Louise Overby , Danneris Sophie , Monrad Merete
Published: January 2021

This article analyses how long-term unemployed persons experience time during their unemployment trajectories. This article uses a combination of interviewing and participant drawings to study the experience of time passing during the unemployment trajectory. We focus on the experience of wait time and find that the wait experience varies with control: some clients experience temporal agency and others a loss of control over time. When the wait time is characterised by uncertainty and a loss of control over time, it reinforces an experience of stagnation in the unemployment trajectory and a feeling of being a temporal outsider, living a life on hold, in comparison to societal norms of a working life. For these clients, wait time adds to the burden of unemployment. For clients experiencing temporal agency, wait time is experienced as meaningful, even useful. These clients experience control over the wait time or that the wait time has a fortunate timing in relation to other things happening in the clients’ lives. Based on the analysis, temporal control is decisive for the long-term unemployed, and therefore, a focus on time is crucial both in research on social and employment services for vulnerable clients and in the practice field.
The experiences of those affected by parental young onset dementia: A qualitative systematic literature review
Authors: Cartwright Anna V , Stoner Charlotte R , Pione Richard D , Spector Aimee
Published: January 2021

Aim

To develop understanding of the lived experiences of children of people living with young onset dementia, defined as individuals both under and over the age of 18 years whose parent was diagnosed with dementia before the age of 65 years.

Method

A critical appraisal and thematic synthesis of the available qualitative literature regarding the lived experience of individuals whose parent has a diagnosis of young onset dementia. A three-stage approach for conducing thematic synthesis was followed.

Results

15 articles were included in the review. Four analytical themes and 11 subthemes were found. The analytical themes were ‘making sense of dementia’, ‘impact of dementia’, ‘coping’ and ‘support’.

Conclusions

The experiences of those affected by parental young onset dementia vary widely. There is a lack of knowledge and understanding of young onset dementia by professionals and the public, and a scarcity of appropriate support. This has clinical implications for professionals working with families affected by young onset dementia, in particular with regards to service design and delivery.
Minute ventilation/carbon dioxide production in chronic heart failure
Authors: Agostoni Piergiuseppe , Sciomer Susanna , Palermo Pietro , Contini Mauro , Pezzuto Beatrice , Farina Stefania , Magini Alessandra , De Martino Fabiana , Magrì Damiano , Paolillo Stefania , Cattadori Gaia , Vignati Carlo , Mapelli Massimo , Apostolo Anna , Salvioni Elisabetta
Published: February 2021

In chronic heart failure, minute ventilation (V′E) for a given carbon dioxide production (V′CO2) might be abnormally high during exercise due to increased dead space ventilation, lung stiffness, chemo- and metaboreflex sensitivity, early metabolic acidosis and abnormal pulmonary haemodynamics. TheV′Eversus V′CO2relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of theV′E/perfusion mismatch. Moreover, theV′Eaxis intercept,i.e.whenV′CO2is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO2pressures provides knowledge about reflex activities. TheV′Eversus V′CO2relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. TheV′Eversus V′CO2slope is reported as an absolute number with a recognised cut-off prognostic value of 35, except for specific diseases such as hypertrophic cardiomyopathy and idiopathic cardiomyopathy, where a lower cut-off has been suggested. However, nowadays, it is more appropriate to reportV′Eversus V′CO2slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed inV′Eversus V′CO2analysis in the presence of heart failure comorbidities. Finally,V′Eversus V′CO2abnormalities are relevant targets for treatment in heart failure.
The role of mucin 1 in respiratory diseases
Authors: Ballester Beatriz , Milara Javier , Cortijo Julio
Published: February 2021

Recent evidence has demonstrated that mucin 1 (MUC1) is involved in many pathological processes that occur in the lung. MUC1 is a transmembrane protein mainly expressed by epithelial and hematopoietic cells. It has a receptor-like structure, which can sense the external environment and activate intracellular signal transduction pathways through its cytoplasmic domain. The extracellular domain of MUC1 can be released to the external environment, thus acting as a decoy barrier to mucosal pathogens, as well as serving as a serum biomarker for the diagnosis and prognosis of several respiratory diseases such as lung cancer and interstitial lung diseases. Furthermore, bioactivated MUC1-cytoplasmic tail (CT) has been shown to act as an anti-inflammatory molecule in several airway infections and mediates the expression of anti-inflammatory genes in lung diseases such as chronic rhinosinusitis, chronic obstructive pulmonary disease and severe asthma. Bioactivated MUC1-CT has also been reported to interact with several effectors linked to cellular transformation, contributing to the progression of respiratory diseases such as lung cancer and pulmonary fibrosis. In this review, we summarise the current knowledge of MUC1 as a promising biomarker and drug target for lung disease.
Systematic review and meta-analysis of residential radon and lung cancer in never-smokers
Authors: Cheng Elvin S. , Egger Sam , Hughes Suzanne , Weber Marianne , Steinberg Julia , Rahman Bayzidur , Worth Heather , Ruano-Ravina Alberto , Rawstorne Patrick , Yu Xue Qin
Published: February 2021

Background

Globally, radon is the leading risk factor for lung cancer in never-smokers (LCINS). In this study, we systematically reviewed and meta-analysed the evidence of the risk of LCINS associated with residential radon exposure.

Methods

Medline and Embase databases were searched using predefined inclusion and exclusion criteria to identify relevant studies published from 1 January 1990 to 5 March 2020 focused on never-smokers. We identified four pooled collaborative studies (incorporating data from 24 case–control studies), one case–control study and one cohort study for systematic review. Meta-analysis was performed on the results of the four pooled studies due to different measures of effect and outcome reported in the cohort study and insufficient information reported for the case–control study. In apost hocanalysis, the corresponding risk for ever-smokers was also examined.

Results

Risk estimates of lung cancer from residential radon exposure were pooled in the meta-analysis for 2341 never-smoker cases, 8967 never-smoker controls, 9937 ever-smoker cases and 12 463 ever-smoker controls. Adjusted excess relative risks (aERRs) per 100 Bq·m−3of radon level were 0.15 (95% CI 0.06–0.25) for never-smokers and 0.09 (95% CI 0.03–0.16) for ever-smokers, and the difference between them was statistically insignificant (p=0.32). The aERR per 100 Bq·m−3was higher for men (0.46; 95% CI 0.15–0.76) than for women (0.09; 95% CI −0.02–0.20) among never-smokers (p=0.027).

Conclusion

This study provided quantified risk estimates for lung cancer from residential radon exposure among both never-smokers and ever-smokers. Among never-smokers in radon-prone areas, men were at higher risk of lung cancer than women.
Morphological characterization and genetic diversity analysis of Tunisian durum wheat (Triticum turgidum var. durum) accessions
Authors: Ouaja Maroua , Bahri Bochra A. , Aouini Lamia , Ferjaoui Sahbi , Medini Maher , Marcel Thierry C. , Hamza Sonia
Published: February 2021

Background

Tunisia is considered a secondary center of diversification of durum wheat and has a large number of abandoned old local landraces. An accurate investigation and characterization of the morphological and genetic features of these landraces would allow their rehabilitation and utilization in wheat breeding programs. Here, we investigated a diverse collection of 304 local accessions of durum wheat collected from five regions and three climate stages of central and southern Tunisia.

Results

Durum wheat accessions were morphologically characterized using 12 spike- and grain-related traits. A mean Shannon-Weaver index (H′) of 0.80 was obtained, indicating high level of polymorphism among accessions. Based on these traits, 11 local landraces including Mahmoudi, Azizi, Jneh Khotifa, Mekki, Biskri, Taganrog, Biada, Badri, Richi, Roussia and Souri were identified. Spike length (H′ = 0.98), spike shape (H′ = 0.86), grain size (H′ = 0.94), grain shape (H′ = 0.87) and grain color (H′ = 0.86) were the most polymorphic morphological traits. The genetic diversity of these accessions was assessed using 10 simple sequence repeat (SSR) markers, with a polymorphic information content (PIC) of 0.69. Levels of genetic diversity were generally high (I = 0.62;He = 0.35). In addition, population structure analysis revealed 11 genetic groups, which were significantly correlated with the morphological characterization. Analysis of molecular variance (AMOVA) showed high genetic variation within regions (81%) and within genetic groups (41%), reflecting a considerable amount of admixture between landraces. The moderate (19%) and high (59%) levels of genetic variation detected among regions and among genetic groups, respectively, highlighted the selection practices of farmers. Furthermore, Mahmoudi accessions showed significant variation in spike density between central Tunisia (compact spikes) and southern Tunisia (loose spikes with open glume), may indicate an adaptation to high temperature in the south.

Conclusion

Overall, this study demonstrates the genetic richness of local durum wheat germplasm for better in situ and ex situ conservation and for the subsequent use of these accessions in wheat breeding programs.
Helicobacter pylori 23S rRNA gene A2142G, A2143G, T2182C, and C2195T mutations associated with clarithromycin resistance detected in Sudanese patients
Authors: Albasha Aalaa Mahgoub , Elnosh Maram M. , Osman Esraa Hassan , Zeinalabdin Duha M. , Fadl Amira A. M. , Ali Musa Abdalla , Altayb Hisham N.
Published: February 2021

Background

Clarithromycin resistant Helicobacter pylori (H. pylori) strains represent a worldwide health problem. These stains are usually carrying mutations within the 23S rRNA gene associated with clarithromycin resistance. This study aimed to detect H. pylori and clarithromycin resistant associated mutations from Sudanese patients with gastritis symptoms.

Materials and methods

Two hundred and eighty-eight gastric biopsies were collected using gastrointestinal endoscopy from patients with gastritis symptoms in different hospitals in Khartoum state. H. pylori was detected by PCR using primer targeting 16S rRNA. Then allele-specific PCR and DNA sequencing were used to screen for the presence of A2142G and A2143G point mutations.

Results

Out of 288 samples, H. pylori was detected in 88 (~ 30.6%) samples by 16 s RNA. Allele-specific PCR detected the variant A2142G in 9/53 (~ 17%) sample, while A2143G mutation was not found in any sample. The DNA sequencing revealed the presence of mutations associated with clarithromycin-resistance in 36% (9/25) of samples; the A2142G was present in one sample, A2143G in 5 samples and T2182C in 4 samples. Additionally, another point mutation (C2195T) was detected in 3 samples. There was no association of 23S rRNA gene point mutations with gender, age group, and patients’ geographical distribution.

Conclusion

This study revealed a high frequency (36%) of mutations associated with clarithromycin resistance using DNA sequencing of the 23S rRNA gene’s V domain. This information should be taken into consideration to avoid eradication therapy failing.
Group cognitive behavioural therapy (GCBT) versus treatment as usual (TAU) in the treatment of irritable bowel syndrome (IBS): a study protocol for a randomized controlled trial
Authors: Kikuchi Shino , Oe Yuki , Sasaki Yohei , Ishii Hirono , Ito Yuri , Horikoshi Masaru , Sozu Takashi , Seno Hiroshi , Furukawa Toshi A.
Published: February 2021

Background

Irritable bowel syndrome (IBS) is a common disease that affects the quality of life (QOL) and social functioning of sufferers. Visceral anxiety is currently considered a key factor in the onset and exacerbation of IBS, and cognitive-behavioural therapy (CBT) targeting visceral anxiety is thought to be effective. However, access to CBT is limited due to the lack of trained therapists, the substantial time required for therapy and the associated costs. Group CBT (GCBT) may solve some of these problems. We have therefore planned this trial to examine the efficacy of GCBT for IBS.

Methods

The trial is a two-armed, parallel group, open label, stratified block randomized superiority trial. The study group will consist of 112 participants (aged 18–75 years) with IBS (Rome-III or IV criteria). Participants will be randomly allocated 1:1 to (i) the intervention group: ten-week GCBT plus treatment as usual (TAU) or (ii) the control group: waiting list (WL) plus TAU. The co-primary outcomes are the change in IBS severity or disease-specific quality of life from baseline to week 13 which is 1 month after the end of treatment. The efficacy of GCBT for IBS will be examined through mixed-effects repeated-measures analysis.

Discussion

GCBT, if found effective, can address the issues of the shortage of therapists as well as the time required and the costs associated with individual CBT. Clinically, the findings will help make effective CBT programmes accessible to a large number of distressed IBS patients at lower costs. Theoretically, the results will clarify the relationship between IBS and psychological stress and will help elucidate the underlying mechanisms of IBS.

Trial registration

UMIN, CTR-UMIN000031710. Registered on March 13, 2018.
A review of the quantitative effectiveness evidence synthesis methods used in public health intervention guidelines
Authors: Smith Ellesha A. , Cooper Nicola J. , Sutton Alex J. , Abrams Keith R. , Hubbard Stephanie J.
Published: February 2021

Background

The complexity of public health interventions create challenges in evaluating their effectiveness. There have been huge advancements in quantitative evidence synthesis methods development (including meta-analysis) for dealing with heterogeneity of intervention effects, inappropriate ‘lumping’ of interventions, adjusting for different populations and outcomes and the inclusion of various study types. Growing awareness of the importance of using all available evidence has led to the publication of guidance documents for implementing methods to improve decision making by answering policy relevant questions.

Methods

The first part of this paper reviews the methods used to synthesise quantitative effectiveness evidence in public health guidelines by the National Institute for Health and Care Excellence (NICE) that had been published or updated since the previous review in 2012 until the 19th August 2019.The second part of this paper provides an update of the statistical methods and explains how they address issues related to evaluating effectiveness evidence of public health interventions.

Results

The proportion of NICE public health guidelines that used a meta-analysis as part of the synthesis of effectiveness evidence has increased since the previous review in 2012 from 23% (9 out of 39) to 31% (14 out of 45). The proportion of NICE guidelines that synthesised the evidence using only a narrative review decreased from 74% (29 out of 39) to 60% (27 out of 45).An application in the prevention of accidents in children at home illustrated how the choice of synthesis methods can enable more informed decision making by defining and estimating the effectiveness of more distinct interventions, including combinations of intervention components, and identifying subgroups in which interventions are most effective.

Conclusions

Despite methodology development and the publication of guidance documents to address issues in public health intervention evaluation since the original review, NICE public health guidelines are not making full use of meta-analysis and other tools that would provide decision makers with fuller information with which to develop policy. There is an evident need to facilitate the translation of the synthesis methods into a public health context and encourage the use of methods to improve decision making.
A qualitative meta-synthesis of facilitators and barriers to tuberculosis diagnosis and treatment in Nigeria
Authors: Oga-Omenka Charity , Wakdet Lawrence , Menzies Dick , Zarowsky Christina
Published: February 2021

Background

Despite progress in tuberculosis (TB) control globally, TB continues to be a leading cause of death from infectious diseases, claiming 1.2 million lives in 2018; 214,000 of these deaths were due to drug resistant strains. Of the estimated 10 million cases globally in 2018, 24% were in Africa, with Nigeria and South Africa making up most of these numbers.

Nigeria ranks 6th in the world for TB burden, with an estimated 4.3% multi-drug resistance in new cases. However, the country had one of the lowest case detection rates, estimated at 24% of incident cases in 2018 - well below the WHO STOP TB target of 84%. This rate highlights the need to understand contextual issues influencing tuberculosis management in Nigeria. Our synthesis was aimed at synthesizing qualitative evidence on factors influencing TB care in Nigeria.

Methods

A three-stage thematic meta-synthesis of qualitative studies was used to identify barriers and facilitators to tuberculosis case finding and treatment in Nigeria. A search of eleven databases was conducted. The date of publication was limited to 2006 to June 2020. We analyzed articles using a three-stage process, resulting in coding, descriptive subthemes and analytical themes.

Results

Our final synthesis of 10 articles resulted in several categories including community and family involvement, education and knowledge, attitudes and stigma, alternative care options, health system factors (including coverage and human resource), gender, and direct and indirect cost of care. These were grouped into three major themes: individual factors; interpersonal influences; and health system factors.

Conclusion

Case finding and treatment for TB in Nigeria currently depends more on individual patients presenting voluntarily to the hospital for care, necessitating an understanding of patient behaviors towards TB diagnosis and treatment. Our synthesis has identified several related factors that shape patients’ behavior towards TB management at individual, community and health system levels that can inform future interventions.
Media representations of COVID-19 public health policies: assessing the portrayal of essential health services in Canadian print media
Authors: Ogbogu Ubaka , Hardcastle Lorian
Published: February 2021

Aims

The study assessed how the Canadian print media represented essential healthcare services during the COVID-19 pandemic, including the controversial decision to include liquor and cannabis stores in essential services lists.

Methods

Mixed-method content analysis of 67 articles published in major Canadian English language newspapers between March 23 and April 1, 2020. Articles were analyzed and coded by two raters. Ratings were analyzed in SPSS.

Results

Few articles in the sample discussed essential healthcare services and the inclusion of liquor and cannabis stores in essential services lists. Majority of the articles that discussed both topics framed the discussion positively and consistently with current knowledge and evidence.

Conclusion

Canadian print media representations of essential healthcare services and associated public debate are largely descriptive and, therefore, fail to engage critically with or advance public understanding of an important health policy issue.
Anterior cruciate ligament remnant‐preserving and re‐tensioning reconstruction: a biomechanical comparison study of three different re‐tensioning methods in a porcine model
Authors: Ryu Dong Jin , Kwon Kyeu Back , Hong Da Hee , Park Sang Jun , Park Jae Sung , Wang Joon Ho
Published: February 2021

Background

With the developments in the arthroscopic technique, anterior cruciate ligament (ACL) remnant-preserving reconstruction is gradually gaining attention with respect to improving proprioception and enhancing early revascularization of the graft. To evaluate the mechanical pull-out strength of three different methods for remnant-preserving and re-tensioning reconstruction during ACL reconstruction.

Methods

Twenty-seven fresh knees from mature pigs were used in this study. Each knee was dissected to isolate the femoral attachment of ACL and cut the attachment. An MTS tensile testing machine with dual-screw fixation clamp with 30° flexion angle was used. The 27 specimens were tested after applying re-tensioning sutures with No. 0 polydioxanone (PDS), using the single stitch (n = 9), loop stitch (n = 9), and triple stitch (n = 9) methods. We measured the mode of failure, defined as (1) ligament failure (longitudinal splitting of the remnant ACL) or (2) suture failure (tearing of the PDS stitch); load-to-failure strength; and stiffness for the three methods. Kruskal-Wallis test and Mann-Whitney U-test were used to compare the variance of load-to-failure strength and stiffness among the three groups.

Results

Ligament failure occurred in all cases in the single stitch group and in all but one case in the triple stitch group. Suture failure occurred in all cases in the loop stitch group and in one case in the triple stitch group. The load-to-failure strength was significantly higher with loop stich (91.52 ± 8.19 N) and triple stitch (111.1 ± 18.15 N) than with single stitch (43.79 ± 11.54 N) (p = 0.002). With respect to stiffness, triple stitch (2.50 ± 0.37 N/mm) yielded significantly higher stiffness than the other methods (p = 0.001).

Conclusions

The results suggested that loop stitch or triple stitch would be a better option for increasing the mechanical strength when applying remnant-preserving and re-tensioning reconstruction during ACL reconstruction.
Long-term radiographic outcomes and functional evaluation of ulnar shortening osteotomy in patients with ulnar impaction syndrome and reverse oblique sigmoid notch: a retrospective case series study
Authors: Huang Hui-Kuang , Lee Steve K. , Huang Yi-Chao , Yin Cheng-Yu , Chang Ming-Chau , Wang Jung-Pan
Published: February 2021

Background

Ulnar shortening osteotomy (USO) is an effective treatment for ulnar impaction syndrome. However, there have been reports of osteoarthritis (OA) at the distal radioulnar joint (DRUJ) when USO was performed on patients with a reverse oblique sigmoid notch. This study aimed to evaluate the radiographic and functional outcomes following USO in patients with a reverse oblique sigmoid notch.

Methods

We retrospectively reviewed patients having a reverse oblique sigmoid notch who underwent USO for ulnar impaction syndrome between 2002 and 2013. We evaluated radiographic changes of the DRUJ and functional outcomes of patients.

Results

We enrolled 22 patients (22 wrists) with an average age of 49.6 years and a mean follow-up of 93.2 (range, 36–179; standard deviation [SD], 38.2) months. We found that there were changes in the inclination angle of the sigmoid notch, from an average reverse oblique of 14.9o(range, 11o–23o; SD, 3.4o) preoperatively to a more parallel 5.1o(range, 0o–11o; SD, 3.2o) at the final follow-up. The functional results at the final follow-up were good, with a mean visual analogue scale for pain of 0.2 (range, 0–1; SD, 0.4) at rest and 1.3 (range, 0–3; SD, 0.9) during activity, QuickDASH of 15.1 (range, 2.3–34.1; SD, 8.8), and modified Mayo Wrist Score of 91.6 (range, 70–100; SD, 6.4). Seven wrists (31.8%) had changes compatible with OA, but the wrists did not exhibit a significantly worse function when compared to wrists without OA changes, except for supination motion and grip strength.

Conclusions

For patients with a reverse oblique sigmoid inclination following USO, we observed that the inclination angle had a tendency to become parallel and some patients developed OA at the DRUJ. However, long-term functional outcomes could still be good. The reverse oblique sigmoid inclination does not seem to be an absolute contraindication for USO.
Helicobacter pylori-induced gastric cancer is orchestrated by MRCKβ-mediated Siah2 phosphorylation
Authors: Dixit Pragyesh , Kokate Shrikant B. , Poirah Indrajit , Chakraborty Debashish , Smoot Duane T. , Ashktorab Hassan , Rout Niranjan , Singh Shivaram P. , Bhattacharyya Asima
Published: February 2021

Background

Helicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression.

Methods

H. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay.

Results

Siah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine6 (Ser6) and threonine279 (Thr279). Phosphorylation of Siah2 was mediated by MRCKβ, a Ser/Thr protein kinase. MRCKβ was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCKβ could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCKβ and use of proteasomal inhibitor MG132 could rescue MRCKβ from Siah2-mediated degradation. Ser6 and Thr279 phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells.

Conclusions

Increased level of Ser6 and Thr279-phosphorylated-Siah2 and downregulated MRCKβ were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCKβ-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.
High GFPT1 expression predicts unfavorable outcomes in patients with resectable pancreatic ductal adenocarcinoma
Authors: Gong Yitao , Qian Yunzhen , Luo Guopei , Liu Yu , Wang Ruijie , Deng Shengming , Cheng He , Jin Kaizhou , Ni Quanxing , Yu Xianjun , Wu Weiding , Liu Chen
Published: January 2021

Background

Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC.

Methods

We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models.

Results

GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004).

Conclusions

GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.
Hsa_circ_0025202 suppresses cell tumorigenesis and tamoxifen resistance via miR-197-3p/HIPK3 axis in breast cancer
Authors: Li Hongjuan , Li Qing , He Shan
Published: February 2021

Background

The involvement of circular RNAs (circRNAs) in tamoxifen (TAM) resistance has been identified. Herein, we aimed to identify the role and novel mechanisms of hsa_circ_0025202 in tamoxifen resistance in breast cancer (BC).

Methods

The levels of hsa_circ_0025202, microRNA (miR)-197-3p, and homeodomain-interacting protein kinase 3 (HIPK3) were tested using quantitative real-time polymerase chain reaction and western blot. IC50 value of TAM, cell proliferation, cell cycle, cell invasion, migration, apoptosis, western blot, and mouse xenograft assays was used to demonstrate the effects of hsa_circ_0025202, miR-197-3p, and HIPK3 on BC cell tumorigenesis and TAM resistance. Dual-luciferase report and RNA immunoprecipitation assays were applied to explore the potential interaction between miR-197-3p and hsa_circ_0025202 or HIPK3.

Results

Hsa_circ_0025202 was decreased in BC tissues and TAM resistant BC cells, and knockdown of hsa_circ_0025202 elevated the IC50 value of cells to TAM, led to the promotion of cell proliferation, invasion and migration, mediated cell cycle progression, and inhibited cell apoptosis in BC in vitro. Besides, the upregulation of hsa_circ_0025202 hindered tumor growth and promoted TAM sensitivity in vivo. In a mechanical study, hsa_circ_0025202 targeted miR-197-3p, and silencing of miR-197-3p reversed the regulatory effects of hsa_circ_0025202 knockdown on TAM resistance and malignant phenotypes. Additionally, HIPK3 was a target of miR-197-3p, and miR-197-3p overexpression enhanced TAM resistance and promoted cell malignant biological behaviors in BC by targeting HIPK3.

Conclusion

Hsa_circ_0025202 repressed cell tumorigenesis and TAM resistance via miR-197-3p/HIPK3 axis in BC, suggesting a potential therapeutic strategy to overcome chemoresistance in BC patients.
Neoadjuvant therapy of BRCA1-driven ovarian cancer by combination of cisplatin, mitomycin C and doxorubicin
Authors: Gorodnova Tatiana V. , Sokolenko Anna P. , Kotiv Khristina B. , Sokolova Tatiana N. , Ivantsov Alexandr O. , Guseynov Konstantin D. , Nekrasova Ekaterina A. , Smirnova Olga A. , Berlev Igor V. , Imyanitov Evgeny N.
Published: February 2021

Background

Cisplatin, mitomycin C and anthracyclines demonstrate high activity in BRCA1-deficient tumors. This study aimed to evaluate the efficacy of the triplet combination of these drugs in BRCA1-driven high-grade serous ovarian carcinomas (HGSOCs).

Methods

Ten HGSOC patients with germ-line BRCA1 mutation received neoadjuvant chemotherapy (NACT) consisting of mitomycin C 10 mg/m2 (day 1), doxorubicin 30 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1), given every 4 weeks (MAP regimen). The comparator group included 16 women, who received standard NACT combination of paclitaxel 175 mg/m2 and carboplatin (6 AUC), given every 3 weeks (TCbP scheme).

Results

None of the patients treated by the MAP scheme demonstrated complete pathologic response in ovaries, while 4 women showed absence of tumor cells in surgically excised omental specimens. When chemotherapy response scores (CRS) were considered, poor responsiveness (CRS 1) was not observed in the MAP group, but was common for the TCbP regimen (6/16 (38 %) for ovaries and 5/16 (31 %) for omentum; p = 0.05 and 0.12, respectively). Median treatment-free interval (TFI) was not reached in women treated by the MAP, but was 9.5 months for the TCbP scheme (p = 0.1). The rate of the recurrence within 1 year after the completion of the treatment was 4/10 (40 %) for the MAP and 10/13 (77 %) for the TCbP (p = 0.1).

Conclusions

The attempt to intensify NACT by administering combination of 3 drugs did not result in high rate of complete pathologic responses. However, there was a trend towards higher efficacy of the MAP regimen versus conventional TCbP scheme with regard to CRS and clinical outcomes.
Cannabinoid treatment for autism: a proof-of-concept randomized trial
Authors: Aran Adi , Harel Moria , Cassuto Hanoch , Polyansky Lola , Schnapp Aviad , Wattad Nadia , Shmueli Dorit , Golan Daphna , Castellanos F. Xavier
Published: February 2021

Background

Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5–21 years) with ASD.

Methods

We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and Δ9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and Δ9-tetrahydrocannabinol at the same ratio. Participants (N = 150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability.

Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI).

Results

Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n = 45) versus 21% on placebo (n = 47; p = 0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n = 34) versus 3.6 points after placebo (n = 36); p = 0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n = 95); 23% and 21% on pure-cannabinoids (n = 93), and 8% and 15% on placebo (n = 94).

Limitations

Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results.

Conclusions

This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended.

Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226
Mimickers of novel coronavirus disease 2019 (COVID-19) on chest CT: spectrum of CT and clinical features
Authors: Elmokadem Ali H. , Batouty Nihal M. , Bayoumi Dalia , Gadelhak Basma N. , Abdel-Wahab Rihame M. , Zaky Mona , Abo-Hedibah Sherif A. , Ehab Ahmed , El-Morsy Ahmed
Published: February 2021

COVID-19 (coronavirus disease 2019) is a recently emerged pulmonary infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). It started in Wuhan, China, in December 2019 and led to a highly contagious disease. Since then COVID-19 continues to spread, causing exponential morbidity and mortality and threatening economies worldwide. While the primary diagnostic test for COVID-19 is the reverse transcriptase–polymerase chain reaction (RT-PCR) assay, chest CT has proven to be a diagnostic tool of high sensitivity. A variety of conditions demonstrates CT features that are difficult to differentiate from COVID-19 rendering CT to be of low specificity. Radiologists and physicians should be aware of imaging patterns of these conditions to prevent an erroneous diagnosis that could adversely influence management and patients’ outcome. Our purpose is to provide a practical review of the conditions that mimic COVID-19. A brief description of the forementioned clinical conditions with their CT features will be included.
Chemotherapy-related striate melanonychia: a case report
Authors: Hussain Fazleenah , Gnanappiragasam Dushyanth , Shaffrali Freida
Published: January 2021

Background

Chemotherapy medications are reported to cause discoloration of the nails known as melanonychia. Depending on the nail structure affected and the severity of the insult, the clinical features can be variable. There are a great deal of unreported cases of pigmentary nail changes associated with chemotherapy treatment. By sharing our knowledge, we hope to raise the awareness of these nail changes amongst clinicians. Early recognition is crucial to allay anxiety among patients and avoid any unnecessary investigations.

Case presentation

We present a case of 36-year-old woman of south Asian origin, who developed dark pigmentation in the left thumb nail during neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, cyclophosphamide, and docetaxel (FEC-D) for triple negative breast cancer. Upon examination, the left thumb nail pigmentation was strikingly linear, uniform, and well demarcated extending from proximal nail fold to free margin. Despite the reassuring clinical features, the patient was understandably anxious that this could be a presentation of acral melanoma and was referred to the plastic surgeons for a nail matrix biopsy. Biopsy reassuringly was reported as melanosis and a diagnosis of striate melanonychia was made. The patient was discharged after 2-year follow-up.

Conclusion

Chemotherapy medications have improved survival rates and patient outcomes. It is important for clinicians to be aware of the association of melanonychia with certain chemotherapy medications to reduce anxiety and allow successful management of these patients without delay. Striate melanonychia in this patient was felt most likely due to the synergistic effect of chemotherapy drugs compounded with racial predisposition. Chemotherapy agents most likely to have contributed include cyclophosphamide, docetaxel, and 5-fluorouracil.
Electrospun fibers enhanced the paracrine signaling of mesenchymal stem cells for cartilage regeneration
Authors: Kadir Nurul Dinah , Yang Zheng , Hassan Afizah , Denslin Vinitha , Lee Eng Hin
Published: February 2021

Background

Secretome profiles of mesenchymal stem cells (MSCs) are reflective of their local microenvironments. These biologically active factors exert an impact on the surrounding cells, eliciting regenerative responses that create an opportunity for exploiting MSCs towards a cell-free therapy for cartilage regeneration. The conventional method of culturing MSCs on a tissue culture plate (TCP) does not provide the physiological microenvironment for optimum secretome production. In this study, we explored the potential of electrospun fiber sheets with specific orientation in influencing the MSC secretome production and its therapeutic value in repairing cartilage.

Methods

Conditioned media (CM) were generated from MSCs cultured either on TCP or electrospun fiber sheets of distinct aligned or random fiber orientation. The paracrine potential of CM in affecting chondrogenic differentiation, migration, proliferation, inflammatory modulation, and survival of MSCs and chondrocytes was assessed. The involvement of FAK and ERK mechanotransduction pathways in modulating MSC secretome were also investigated.

Results

We showed that conditioned media of MSCs cultured on electrospun fiber sheets compared to that generated from TCP have improved secretome yield and profile, which enhanced the migration and proliferation of MSCs and chondrocytes, promoted MSC chondrogenesis, mitigated inflammation in both MSCs and chondrocytes, as well as protected chondrocytes from apoptosis. Amongst the fiber sheet-generated CM, aligned fiber-generated CM (ACM) was better at promoting cell proliferation and augmenting MSC chondrogenesis, while randomly oriented fiber-generated CM (RCM) was more efficient in mitigating the inflammation assault. FAK and ERK signalings were shown to participate in the modulation of MSC morphology and its secretome production.

Conclusions

This study demonstrates topographical-dependent MSC paracrine activities and the potential of employing electrospun fiber sheets to improve the MSC secretome for cartilage regeneration.