bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Awareness of a Provincial Mental Health Resource for Boys and Young Men 12 to 17 Years: Reflections From Foundry’s Province-Wide Campaign
Authors: Zenone Marco , Irving Paul , Cianfrone Michelle , Lockhart Leah , Costales Stefanie , Cruz Kathryn , Ignacio Jamie
Published: March 2020

Foundry empowers youth and young adults aged 12 to 24 years to lead healthy lives through a province-wide network of centers and online resources in British Columbia, Canada. However, initial evaluation data gathered from Foundry centers have shown that boys and young men are half as likely to access Foundry compared to girls and young women. To address this need, we set out to understand why boys and young men aged 12 to 17 years aren’t accessing mental health supports and to develop a promotional campaign to connect them with the resources available through Foundry. A campaign concept called “Everything Is Fine” was chosen; the campaign depicts boys and young men trying to appear as if they are OK, even though their facial expressions clearly show they are holding back stress. The campaign concept was chosen through an iterative process of research and testing. Promotion materials were created for social media (Instagram, Snapchat) and school posters, which were distributed across British Columbia, Canada . Evaluation was conducted through social media analytics and google analytics. Pre- and postsurveys were also distributed to two school districts to assess recognition of Foundry. Approximately 160,000+ persons viewed the media on Instagram, while 170,000+ viewed on Snapchat. There was a 70% increase in website traffic compared with the 3 months prior (18,881 vs. 11,126). In the surveyed school districts, Foundry awareness increased by 10% and 15%. The lessons learned from our campaign were to prioritize research and to leverage media agency experience for large campaigns.
Comparative Evaluation of Clinical Efficacy and Safety of Collagen Laminin–Based Dermal Matrix Combined With Resveratrol Microparticles (Dermalix) and Standard Wound Care for Diabetic Foot Ulcers
Authors: Çetinkalp Şevki , Gökçe Evren Homan , Şimşir IlgınYıldırım , Tuncay Tanrıverdi Sakine , Doğan Fatma , Biray Avcı Çığır , Eroğlu İpek , Utku Tülün , Gündüz Cumhur , Özer Özgen
Published: March 2020

This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. The aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. The wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile.
Zulu Men’s Conceptions, Understanding, and Experiences of Voluntary Medical Male Circumcision in KwaZulu-Natal, South Africa
Authors: Nxumalo Celenkosini Thembelenkosini , Mchunu Gugu Gladness
Published: March 2020

Voluntary Medical Male Circumcision (VMMC) is proven to reduce transmission of HIV/AIDS. Despite concerted efforts to scale up VMMC in men aged 18–49, the number of medically circumcised men in this age group remains suboptimal. Research has shown that several individual factors hinder and promote uptake of VMMC. The nature of these factors is not clearly understood within the dimensions of religion, culture and tradition, particularly in a low-income rural setting. This study aimed to analyze Zulu men’s conceptions, understanding and experiences regarding VMMC in KwaZulu-Natal (KZN), South Africa. A qualitative phenomenographic study approach was used to collect data from 20 uncircumcised males at six different clinics that provide VMMC services. Ethical approval to collect data was obtained from the Biomedical Research Ethics Committee of the University of KZN (BREC – BE627/18). Individual in-depth face to face interviews were conducted using a semistructured interview guide. Audiotapes were used to record interviews which were transcribed verbatim and then analyzed manually. The conceptions regarding medical circumcision appeared to be related to religious and cultural beliefs surrounding circumcision and the historical traditional practice thereof. The understanding of males regarding VMMC was mainly attributed to HIV prevention; however, knowledge on the degree of partial protection appeared to be limited. An array of negative accounted in the form of complications such as poor wound healing and postoperative pain undergone by peers and other close influencers’ accounted for participants’ experiences of VMMC. Poor knowledge and negative experiences relating to VMMC could account for reasons why men choose not to undergo VMMC.
Development and validation of an acoustic-electrical joint testing system for hydrate-bearing porous media
Authors: Xing Lanchang , Zhu Tai , Niu Jiale , Liu Changling , Wang Bin
Published: March 2020

Acoustic and electrical properties are fundamental and important physical properties to characterize hydrate-bearing sediments. A new experimental system called Ultrasound Combined with Electrical Impedance was developed for jointly testing the ultrasonic wave parameters and electrical impedance of hydrate-bearing porous media in the hydrate formation and decomposition processes. The Ultrasound Combined with Electrical Impedance system features its novel ultrasonic-electrical compound sensors and sensor array, fully controllable instruments, variety of sampled data, and flexible working modes. Experiment was carried out with methane gas as the hydrate former, meanwhile the acoustic/electrical parameters were derived. The acoustic/electrical properties were characterized with the aid of typical models such as the time-average equation, Wood’s equation, weighted equation, and Archie’s formula. It has been shown by the results that key parameters such as the sound velocity and electrical impedance can be used to characterize the acoustic and electrical properties of hydrate-bearing sediments conjointly, demonstrating the applicability of the proposed Ultrasound Combined with Electrical Impedance system. The wavelet-analysis based denoising approach and singularity detection method are effective denoising methods to filter the ultrasound signals and to identify the arriving time of the ultrasonic wave. The weighted equation and Archie’s formula with a segmented regression method are recommended for modeling the relations between the hydrate saturation and sound velocity/impedance modulus, respectively.
Reporting on sexual violence ‘inside the closet’: Masculinity, homosexuality and #MeToo
Authors: Hindes Sophie , Fileborn Bianca
Published: March 2020

Media representation of sexual violence and sexual consent communication in cases involving queer people is an area that has been overwhelmingly overlooked by research thus far. Research looking at heterosexual instances of sexual violence has given us valuable insights into how (hetero)normative gender roles are constructed in news media, and how these work to excuse and minimise the actions of heterosexual men. But how does this change when at least one of the men involved is queer or homosexual and does not fit into the (hetero)normative gender role paradigm which is commonly used to excuse men’s sexually violent behaviours? This research examined three celebrity cases of alleged sexual violence from the #MeToo movement where the communication of sexual consent (or lack thereof) played a primary role in media reporting. This includes the heteronormative case of Aziz Ansari, and two cases involving homosexual men including Kevin Spacey and Tom Ballard. Our research found that with an absence of cultural intelligibility around queer sex and queer negotiations of consent, problematic and damaging stereotypes about homosexual ‘deviancy’ were instead used by news media in attempts to make sense of these cases. It ultimately found that in both the heterosexual and homosexual cases that news media reporting was overwhelmingly protecting and perpetuating norms of hegemonic masculinity, namely through legitimising any homosexual advance on a heterosexual man as violence, and any heterosexual male advance on a woman as non-violence.
Bone cancer-induced pain is associated with glutamate signalling in peripheral sensory neurons
Authors: Zhu Yong Fang , Linher-Melville Katja , Wu Jianhan , Fazzari Jennifer , Miladinovic Tanya , Ungard Robert , Zhu Kan Lun , Singh Gurmit
Published: March 2020

We previously identified that several cancer cell lines known to induce nociception in mouse models release glutamate in vitro. Although the mechanisms of glutamatergic signalling have been characterized primarily in the central nervous system, its importance in the peripheral nervous system has been recognized in various pathologies, including cancer pain. We therefore investigated the effect of glutamate on intracellular electrophysiological characteristics of peripheral sensory neurons in an immunocompetent rat model of cancer-induced pain based on surgical implantation of mammary rat metastasis tumour-1 cells into the distal epiphysis of the right femur. Behavioural evidence of nociception was detected using von Frey tactile assessment. Activity of sensory neurons was measured by intracellular electrophysiological recordings in vivo. Glutamate receptor expression at the mRNA level in relevant dorsal root ganglia was determined by reverse transcription polymerase chain reaction using rat-specific primers. Nociceptive and non-nociceptive mechanoreceptor neurons exhibiting changes in neural firing patterns associated with increased nociception due to the presence of a bone tumour rapidly responded to sulphasalazine injection, an agent that pharmacologically blocks non-vesicular glutamate release by inhibiting the activity of the system xC− antiporter. In addition, both types of mechanoreceptor neurons demonstrated excitation in response to intramuscular glutamate injection near the femoral head, which corresponds to the location of cancer cell injection to induce the bone cancer-induced pain model. Therefore, glutamatergic signalling contributes to cancer pain and may be a factor in peripheral sensitization and induced tactile hypersensitivity associated with bone cancer-induced pain.
Do-It-Yourself (DIY) Systems in Diabetes: A Family and Provider Perspective
Authors: Duke Malinda D. , Fredlock Ashley A.
Published: March 2020

Type 1 diabetes is a unique disorder, requiring constant and vigilant assessment of glucose levels, food/snacks consumed, activities and exercise, emotions and stress, hormonal influence, and illness. No other diagnosis is as intensive in terms of the “burden” of care that impacts the patient/family physiologically, cognitively, and psychologically. Several Do-It-Yourself (DIY) closed-loop systems currently exist and can provide options for patients and families looking to reduce the burden of type 1 diabetes. However, as the systems are not Food and Drug Administration approved, healthcare providers are faced with the decision of whether to support patients using DIY systems. This manuscript discusses the ethics of choice and patient autonomy from the perspective of patient/family and healthcare provider. A set of proposed guidelines for healthcare providers are also presented for consideration when interacting with a patient or family who desires to use a DIY system to help manage type 1 diabetes.
Transformation of Mangiferin to Norathyriol by Human Fecal Matrix in Anaerobic Conditions: Comprehensive NMR of the Xanthone Metabolites, Antioxidant Capacity, and Comparative Cytotoxicity Against Cancer Cell Lines
Authors: Souza José R. R. , Trevisan Maria Teresa Salles , Feitosa Judith P. A. , Ricardo Nágila M. P. S. , Hull William E. , Erben Gerhard , Würtele Gerd , Breuer Andrea , Frei Eva , Ulrich Cornelia M. , Owen Robert W.
Published: March 2020

Several natural drugs (termed prodrugs) when administered orally undergo transformation by intestinal bacteria, producing metabolites, which may be more active than the parent compound. Mangiferin (I) is reported to have very low bioavailability in the upper gastrointestinal tract and reaches the large intestine, where it may be metabolized by the indigenous bacteria. Therefore, the aim of this study was to conduct pilot anaerobic fermentation studies with fecal inocula from human volunteers ( n = 3) to identify possible metabolic end products of mangiferin by the gastrointestinal metabolome. The major metabolite identified was deglycosylated mangiferin, namely, norathyriol (II) with an increase in homomangiferin (III) which was a minor contaminant of I. Mangiferin metabolites were identified and quantitated in the fermentation broths by high performance liquid chromatography (HPLC)–diode array detection–electrospray ionization-mass spectrometry, and structures confirmed unequivocally by nuclear magnetic resonance, after purification by semipreparative HPLC. Cell culture assays with 2 human cancer cell lines Caco-2 (colon cancer) and A240286S (non-small lung adenocarcinoma) showed that while the substrate mangiferin (I) and homomangiferin (III), a minor metabolite, are non-cytotoxic (half-maximal inhibitory concentration [IC50] ≥ 100 µM), the major metabolite norathyriol (II) is cytotoxic against Caco-2 cells (IC50 = 51.0 µM), whereas it is cytostatic against A240286S cells with a similar IC50 (51.1 µM).
Icon Familiarity Affects the Performance of Complex Cognitive Tasks
Authors: Shen Zhangfan , Zhang Linghao , Xiao Xing , Li Rui , Liang Ruoyu
Published: March 2020

The purpose of this study was to investigate whether and how users’ familiarity with symbols affects the performance of complex cognitive tasks which place considerable demands on working memory resources. We combined a modified math task paradigm with our previous icon familiarity training paradigm. Participants were required to complete a mathematical task involving icons to test their ability to perform complex cognitive tasks. The complexity of the task was manipulated using three independent variables: icon familiarity (high-frequency vs. low-frequency), whether or not the equation requires substitution (substitution vs. no-substitution), and the number of steps required for solution (one step vs. two steps). The results showed that participants performed better on the equation-solving task when it used icons they were more extensively trained on. Importantly, icon familiarity interacted with the complexity of the task and the familiarity effect on performance (accuracy and response time) became greater when the complexity increased. These findings provide evidence that familiarity affects not only the ease of information retrieval but also the ease of subsequent processing activities associated with these information, which extends our understanding of how familiarity affects working memory. Moreover, our findings have practical implications for improving interaction efficiency. Before the operators formally use a digital system, they need to learn the precise meaning of those complex or unfamiliar symbols in a certain context as much as possible.
Verdict 2019: The expanded support base of the Bharatiya Janata Party
Authors: Kumar Sanjay
Published: March 2020

The verdict of 2019 indicates that the Bharatiya Janata Party (BJP) not only managed to retain its support base which it built in 2014, but also expanded it both geographically and socially. It managed to win seats in states where it had not performed well in earlier elections, and to get more votes amongst communities which had not voted for it earlier. The Congress could not improve upon its 2014 performance, but it is important to note that neither its votes nor its tally of seats decreased. The BJP improved upon its performance of 2014 largely at the cost of regional parties. The combined vote share of the regional parties witnessed a decline. Some regional parties did manage to hold onto their support base but others could not secure the support base they had held in 2014. In states like Bihar, Jharkhand, Uttar Pradesh (UP), Karnataka and Maharashtra, the regional parties performed badly despite some of them having formed an anti-BJP alliance. The BJP’s gain in terms of vote share and seats, largely at the expense of regional parties in many states, begins a new debate about whether this is the beginning of the end of the dominance of regional parties in the North Indians states, or if it is a passing phase in Indian elections. If this decline in the importance of the regional parties is largely in respect of national elections, could there be a reversal in the trend during state assembly elections?
Homeless Patients Associate Clinician Bias With Suboptimal Care for Mental Illness, Addictions, and Chronic Pain
Authors: Gilmer Cyndi , Buccieri Kristy
Published: March 2020

Objective: To determine how accessible health care services are for people who are experiencing homelessness and to understand from their perspectives what impact clinician bias has on the treatment they receive. Methods: Narrative interviews were conducted with 53 homeless/vulnerably housed individuals in Ontario, Canada. Visit history records were subsequently reviewed at 2 local hospitals, for 52 of the interview participants. Results: Of the 53 participants only 28% had a primary care provider in town, an additional 40% had a provider in another town, and 32% had no access to a primary care provider at all. A subset of the individuals were frequent emergency department users, with 15% accounting for 75% of the identified hospital visits, primarily seeking treatment for mental illness, pain, and addictions. When seeking primary care for these 3 issues participants felt medication was overprescribed. Conversely, in emergency care settings participants felt prejudged by clinicians as being drug-seekers. Participants believed they received poor quality care or were denied care for mental illness, chronic pain, and addictions when clinicians were aware of their housing status. Conclusion: Mental illness, chronic pain, and addictions issues were believed by participants to be poorly treated due to clinician bias at the primary, emergency, and acute care levels. Increased access to primary care in the community could better serve this marginalized population and decrease emergency department visits but must be implemented in a way that respects the rights and dignity of this patient population.
Challenging Management of a Patient With Severe Bilateral Deep Vein Thrombosis
Authors: Hamandi Mohanad , Lanfear Allison T. , Woolbert Seth , Bolin Madison L. , Fan Joy , William Michael , Khan Zoheb , DiMaio J. Michael , Dib Chadi
Published: March 2020

Among patients with proximal iliofemoral deep vein thrombosis (DVT) and an elevated Villalta score, anticoagulation therapy alone may not be a sufficient management strategy in select cases. In this article, we report a case of severe bilateral iliofemoral DVT that resisted the standard treatment for DVT, requiring catheter-directed thrombolysis and subsequent mechanical thrombectomy.
Comparison Between Autografts and Allografts in Superior Capsular Reconstruction: A Systematic Review of Outcomes
Authors: Kim Dong Min , Shin Myung Jin , Kim Hyojune , Park Dongjun , Jeon In-Ho , Kholinne Erica , Koh Kyoung Hwan
Published: March 2020

Background:

The treatment of irreparable rotator cuff tears (IRCTs) is a significant challenge, and various treatment options have emerged. Superior capsular reconstruction (SCR) is a promising procedure for patients with IRCTs.

Purpose:

To investigate the clinical outcomes of SCR and compare allografts with autografts.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A search for relevant articles was carried out using the PubMed, Cochrane Library, Embase, Scopus, and Google Scholar databases. We used medical subject heading (MeSH) terms and natural keywords (superior AND (capsule OR capsular) AND reconstruction). Also, we filtered for high-quality articles using the Methodological Index for Non-Randomized Studies (MINORS). We summarized the characteristic data and commonly used outcome measures of each included study and performed a descriptive analysis using an evidence-based tendency concept as proposed by Huisstede et al (2013).

Results:

A total of 10 articles (374 shoulders) with a mean follow-up of 27.2 months were selected and analyzed. There were 4 articles on SCR with an autograft, 4 on SCR with an allograft, and 2 on SCR with both an autograft and allograft. For autografts and allografts, respectively, the mean gain in forward elevation (FE) was 48.7° and 33.3°, the visual analog scale for pain score improved by 3.5 and 3.3, the American Shoulder and Elbow Surgeons (ASES) score increased by 47.3 and 31.9, and the acromiohumeral distance increased by 1.2 and 1.8 mm. In addition, the number of graft tears was 16 (10.0%) and 17 (12.9%), the number of other complications was 12 (7.5%) and 6 (3.9%), and the number of reoperations was 5 (3.1%) and 14 (8.2%) for autografts and allografts, respectively.

Conclusion:

Both autografts and allografts improved clinical outcomes. Although the graft tear rate appeared similar between the autograft and allograft groups, the autograft group had no cases of conversion to reverse total shoulder arthroplasty. In addition, we found 3 evidence-based tendencies: (1) a tendency for both autografts and allografts to have significantly improved FE and clinical scores, (2) a tendency that autografts improved internal rotation and allografts improved abduction, and (3) a weak tendency that autografts improved abduction and allografts improved internal and external rotation. Although it was not possible to compare the groups statistically, the differences in ASES scores might be clinically important and will need to be explored in future comparative studies.
Current Best Clinical Practices—Management of Retinal Vein Occlusion
Authors: Modi Yasha S. , Klufas Michael A. , Sridhar Jayanth , Singh Rishi P. , Yonekawa Yoshihiro , Pecen Paula
Published: March 2020

Retinal vein occlusion (RVO) is the second most common cause of vision loss from retinal vascular diseases in adults in the United States. Visual loss arises as a result of a host of factors, including macular ischemia and macular edema. Primary antivascular endothelial growth factor therapy is the current standard of care, with level I evidence demonstrating sustained visual gains up to 2 years after treatment in both branch and central RVO. Prompt antivascular endothelial growth factor therapy is important because delays in treatment yield lesser visual gains. Steroid therapy also improves visual outcomes in RVO but with higher rates of adverse effects, including cataract formation and ocular hypertension. Although the treatment burden can be high, these drugs have collectively revolutionized treatment outcomes in this disease state, providing improved visual outcomes over previous laser therapies.
Evaluation of a Genetic Risk Score for Diagnosis of Psoriatic Arthritis
Authors: Smith Mary Patricia , Ly Karen , Thibodeaux Quinn , Beck Kristen , Yang Eric , Sanchez Isabelle , Nititham Joanne , Bhutani Tina , Liao Wilson
Published: March 2020

Background:

Diagnosis of psoriatic arthritis (PsA) can be challenging, resulting in delays that contribute to irreversible joint damage, reduced quality of life, and increased mortality.

Objective:

Use genetic markers to develop and evaluate a PsA genetic risk score (GRS) for its ability to discriminate between psoriasis (PsO) only and PsO with PsA among a psoriatic cohort with full genome-wide genotype data.

Methods:

Genome-wide single-nucleotide polymorphism genotyping was performed on 724 psoriatic patients. A set of 11 candidate risk genes previously shown to be preferentially associated with PsO or PsA were selected. To evaluate the cumulative effects of these risk loci, a PsA GRS was developed using an unweighted risk allele count (cGRS) and a weighted (wGRS) approach. Additional analyses included only human leukocyte antigen (HLA) risk alleles.

Results:

The discriminative power attributable to each GRS was evaluated by calculating the areas under the receiver operator characteristic curve (AUROC). The AUROC for the wGRS is 56.2% versus 54.1% for the cGRS, and the AUROC for the HLA-only wGRS model was 56.9% versus 55.7% for the HLA-only cGRS.

Conclusion:

The AUROC of 56.9% for HLA-only wGRS indicates that this approach has the greatest power in discriminating PsA from PsO among these models. Given that an AUROC of 56.9% is quite modest, this study suggests that using a small number of well-validated genetic loci provides limited predictive power for PsA, and that future approaches may benefit from using a larger number of genetic loci.
Using fractional exhaled nitric oxide to guide step-down treatment decisions in patients with asthma: a systematic review and individual patient data meta-analysis
Authors: Wang Kay , Verbakel Jan Y. , Oke Jason , Fleming-Nouri Alexander , Brewin Josh , Roberts Nia , Harada Norihiro , Atsuta Ryo , Takahashi Kazuhisa , Mori Kazutaka , Fujisawa Tomoyuki , Shirai Toshihiro , Kawayama Tomotaka , Inoue Hiromasa , Lazarus Stephen , Szefler Stanley , Martinez Fernando , Shaw Dominick , Pavord Ian D. , Thomas Mike
Published: March 2020

Background

High exhaled nitric oxide fraction (FENO) levels are associated with greater risk of asthma exacerbation. However, it is not clear howFENOcan be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability ofFENOto guide ICS reductions.

Methods

Systematic searching of electronic databases identified prospective observational studies and randomised controlled trials which recruited participants with mild-to-moderate asthma aged ≥12 years and measuredFENObefore reducing ICS. We performed multilevel mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model.

Results

We included data from seven out of eight eligible studies, representing 384 participants. ICS doses were halved in four studies and withdrawn in three studies. A baselineFENOmeasurement of ≥50 ppb was associated with increased risk of exacerbations (crude OR 3.14, 95% CI 1.41–7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36–6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was <15%versus<10% would result in fewer patients remaining on the same ICS dose (40 (10.4%) out of 384versus141 (36.7%) out of 384), but similar proportions of patients avoiding exacerbations (222 (91.4%) out of 243, 95% CI 87.1–94.6%versus311 (90.4%) out of 344, 95% CI 86.8–93.3%).

Conclusion

In patients with mild-to-moderate asthma, gradual ICS reduction whenFENOis <50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations.
Re-imagining cystic fibrosis care: next generation thinking
Authors: Rang Catherine , Keating Dominic , Wilson John , Kotsimbos Tom
Published: March 2020

Cystic fibrosis (CF) is a common multi-system genetically inherited condition, predominately found in individuals of Caucasian decent. Since the identification of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene in 1989, and the subsequent improvement in understanding of CF pathophysiology, significant increases in life-expectancy have followed. Initially this was related to improvements in the management and systems of care for treating the various affected organ systems. These cornerstone treatments are still essential for CF patients born today. However, over the last decade, the major advance has been in therapies that target the resultant genetic defect: the dysfunctional CFTR protein. Small molecule agents that target this dysfunctional proteinviaa variety of mechanisms have led to lung function improvements, reductions in pulmonary exacerbation rates and increases in weight and quality-of-life indices. As more patients receive these agents earlier and earlier in life, it is likely that general CF care will increasingly pivot around these specific therapies, although it is also likely that effects other than those identified in the initial trials will be discovered and need to be managed. Despite great excitement for modulator therapies, they are unlikely to be suitable or available for all; whether this is due to a lack of availability for specificCFTRmutations, drug-reactions or the health economic set-up in certain countries. Nevertheless, the CF community must be applauded for its ongoing focus on research and development for this life-limiting disease. With time, personalised individualised therapy would ideally be the mainstay of CF care.
MicroRNA-125b exerts antitumor functions in cutaneous squamous cell carcinoma by targeting the STAT3 pathway
Authors: Tian Ke , Liu Wanggen , Zhang Jing , Fan Xiaoyi , Liu Jingyuan , Zhao Nan , Yao Chunxia , Miao Guoying
Published: March 2020

Background

MicroRNA-125b (miR-125b) is downregulated in human cutaneous squamous cell carcinoma (CSCC). However, its function in CSCC has yet to be extensively explored. Here, we analyze the relationship between signal transducer and activator of transcription 3 (STAT3) and miR-125b in CSCC.

Methods

Western blotting and quantitative RT-PCR were used to determine the expression of the miR-125b–STAT3 axis in human CSCC tissues and cell lines. The direct regulatory effect of miR-125b on STAT3 expression was assessed using a luciferase reporter gene assay and RNA immunoprecipitation assay. The MTT assay and flow cytometry were used to determine the role of the miR-125b–STAT3 axis in CSCC cell proliferation and apoptosis.

Results

MiR-125b expression levels were significantly lower in CSCC cell lines and tissues than in normal cell lines and tissues. STAT3 was identified as the direct target of miR-125b. Upregulation of miR-125b and downregulation of STAT3 suppressed cell proliferation and promoted cell apoptosis. Cyclin D1 and Bcl2 were identified as the downstream targets of the miR-125–STAT3 axis.

Conclusions

Our findings indicate that miR-125b acts as a tumor suppressor in CSCC by targeting the STAT3 pathway. This observation increases our understanding of the molecular mechanisms of CSCC. Therapies aimed at activating miR-125b or inhibiting STAT3 signaling should be explored as potential treatments for CSCC.
Teleology’s long shadow
Authors: Werth A. , Allchin D.
Published: March 2020

We describe the ubiquity of teleological language and thinking throughout biology, as a context for understanding how students think about evolution, as well. Examples can be found in molecular biology, physiology, ecology, and taxonomy, at least. Recent research documents a deep human psychological tendency to attribute purpose or intent (and thus normative meaning) to natural phenomena. We present a possible evolutionary explanation. Still, these cognitive habits help foster scientific errors of projecting human norms onto natural phenomena (what we have elsewhere termed the naturalizing error). Subsequent appeals to “nature” are used (inappropriately) to justify cultural ideologies. Accordingly, we advocate explicit learning about teleological dispositions and their cultural consequences as an essential countermeasure.
Ancient evolutionary signals of protein-coding sequences allow the discovery of new genes in the Drosophila melanogaster genome
Authors: Casimiro-Soriguer Carlos S. , Rubio Alejandro , Jimenez Juan , Pérez-Pulido Antonio J.
Published: March 2020

Background

The current growth in DNA sequencing techniques makes of genome annotation a crucial task in the genomic era. Traditional gene finders focus on protein-coding sequences, but they are far from being exhaustive. The number of this kind of genes continuously increases due to new experimental data and development of improved bioinformatics algorithms.

Results

In this context, AnABlast represents a novel in silico strategy, based on the accumulation of short evolutionary signals identified by protein sequence alignments of low score. This strategy potentially highlights protein-coding regions in genomic sequences regardless of traditional homology or translation signatures. Here, we analyze the evolutionary information that the accumulation of these short signals encloses. Using the Drosophila melanogaster genome, we stablish optimal parameters for the accurate gene prediction with AnABlast and show that this new strategy significantly contributes to add genes, exons and pseudogenes regions, yet to be discovered in both already annotated and new genomes.

Conclusions

AnABlast can be freely used to analyze genomic regions of whole genomes where it contributes to complete the previous annotation.
Can microscopic ileitis in patients with clinically suspected inflammatory bowel disease predict the future?
Authors: Abu Baker Fadi , Z’cruz De La Garza Jesus Alonso , Nafrin Smadar , Mari Amir , Suki Muhammed , Ovadia Baruch , Gal Oren , Kopelamn Yael
Published: March 2020

Background

The implication of microscopic ileitis finding in patients referred for ileocolonoscopy for clinically suspected inflammatory bowel disease (IBD) is not well defined, and its correlation with clinical outcome has not been fully studied. The current study aims to determine the prognostic yield of biopsies in this setting, and to evaluate the correlation of microscopic ileitis with long-term clinical outcome.

Methods

We reviewed endoscopic reports of patients referred to our department for ileocolonoscopy in the years 2010–2016, as part of a diagnostic work-up for suspected IBD. Patients whose ileocolonoscopies proved normal were included, provided that terminal ileum biopsies had been performed. Accordingly, patients were divided into groups classified as normal (normal or reactive changes) and microscopic ileitis (inflammation or ileitis of any severity). Both groups were followed prospectively to determine clinical outcome.

Results

A total of 439 patients met the inclusion criteria. Sixty-four (14.6%) showed inflammation on biopsy and were included in the microscopic ileitis group. Age range and gender figures did not differ significantly between the groups. Overall follow-up period was 6.1 ± 2.3 years. Patients in the microscopic ileitis group were significantly associated with Crohn’s diagnosis during the follow-up period compared with the normal group (19% vs 2%, OR = 11.98, 95%CI = 4.48–32.01; p < 0.01). Patients with granuloma or moderate-severe ileitis on biopsy were significantly associated with Crohn’s development (100% vs 11%; P < 0.01) compared with mild or nonspecific inflammation.

Conclusion

The discovery of microscopic ileitis in clinically suspected IBD is associated with increased risk of future diagnosis of Crohn’s disease.
Stroke patients treated by thrombectomy in real life differ from cohorts of the clinical trials: a prospective observational study
Authors: Deb-Chatterji Milani , Pinnschmidt Hans , Flottmann Fabian , Leischner Hannes , Alegiani Anna , Brekenfeld Caspar , Fiehler Jens , Gerloff Christian , Thomalla Götz
Published: March 2020

Background

Randomized controlled trials (RCTs) demonstrated efficacy and safety of endovascular treatment (ET) in anterior circulation large vessel occlusions (LVO). We aimed at investigating how stroke patients treated by thrombectomy in clinical practice and their outcome compare to cohorts and results of thrombectomy trials.

Methods

In a prospective study, we consecutively included stroke patients treated by thrombectomy (2015–2017). Baseline characteristics, procedural and outcome data were analyzed. Outcome was assessed by modified Rankin Scale (mRS) at 90 days. Ordinal regression analysis was performed to identify predictors of outcome.

Results

Thrombectomy was applied in 264 patients (median 75 years, 49.6% female). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16, 58.0% received concomitant intravenous thrombolysis, 62.1% were referred from external hospitals. Median Alberta Stroke Program Early CT Score (ASPECTS) was 7. Successful recanalization (modified Thrombolysis in Cerebral Infarction Score, mTICI 2b/3) was achieved in 72.0%. Symptomatic intracranial hemorrhage (sICH) occurred in 4.5%. Independent outcome (mRS 0–2) was achieved in 26.2%, poor outcome (mRS 5–6) in 49.2%. Only 33.5% met the stringent enrolment criteria of previous RCTs. Lower age, baseline NIHSS, pre-stroke mRS, higher ASPECTS, and successful recanalization were independent predictors of favourable outcome.

Conclusions

The majority of stroke patients treated by ET in clinical practice would not have qualified for randomization in prior RCTs. Outcome in real-life patient cohorts is worse than in the highly selected cohorts from randomized trials, while rates of successful recanalization, sICH and outcome predictors are the same. Our findings support ET in broader patient populations than in the RCTs and may improve treatment decision in individual stroke patients with LVO in clinical practice.
Incidence and predictive factors of diaphragmatic dysfunction in acute stroke
Authors: Catalá-Ripoll José Vicente , Monsalve-Naharro José Ángel , Hernández-Fernández Francisco
Published: March 2020

Background

The most characteristic clinical signs of stroke are motor and/or sensory involvement of one side of the body. Respiratory involvement has also been described, which could be related to diaphragmatic dysfunction contralateral to the brain injury. Our objective is to establish the incidence of diaphragmatic dysfunction in ischaemic stroke and analyse the relationship between this and the main prognostic markers.

Methods

A prospective study of 60 patients with supratentorial ischaemic stroke in the first 48 h. Demographic and clinical factors were recorded. A diaphragmatic ultrasound was performed for the diagnosis of diaphragmatic dysfunction by means of the thickening fraction, during normal breathing and after forced inspiration. Diaphragmatic dysfunction was considered as a thickening fraction lower than 20%. The appearance of respiratory symptoms, clinical outcomes and mortality were recorded for 6 months. A bivariate and multivariate statistical analysis was designed to relate the incidence of respiratory involvement with the diagnosis of diaphragmatic dysfunction and with the main clinical determinants.

Results

An incidence of diaphragmatic dysfunction of 51.7% was observed. 70% (23 cases) of these patients developed symptoms of severe respiratory compromise during follow-up. Independent predictors were diaphragmatic dysfunction in basal respiration (p = 0.026), hemiparesis (p = 0.002) and female sex (p = 0.002). The cut-off point of the thickening fraction with greater sensitivity (75.75%) and specificity (62.9%) was 24% (p = 0.003).

Conclusions

There is a high incidence of diaphragmatic dysfunction in patients with supratentorial ischaemic stroke which can be studied by calculating the thickening fraction on ultrasound. Among these patients we have detected a higher incidence of severe respiratory involvement.
An efficient gene disruption method for the woody plant pathogen Botryosphaeria dothidea
Authors: Dong Bao-Zhu , Guo Li-Yun
Published: March 2020

Background

Botryosphaeria dothidea causes apple white rot and infects many tree plants. Genome data for B. dothidea are available and many pathogenesis-related genes have been predicted. However, a gene manipulation method is needed to study the pathogenic mechanism of B. dothidea.

Results

We established a gene disruption (GD) method based on gene homologous recombination (GHR) for B. dothidea using polyethylene glycol-mediated protoplast transformation. The results showed that a GHR cassette gave much higher GD efficiency than a GHR plasmid. A high GD efficiency (1.3 ± 0.14 per 106 protopasts) and low frequency of random insertions were achieved with a DNA cassette quantity of 15 μg per 106 protoplasts. Moreover, we successfully disrupted genes in two strains. Bdo_05381-disrupted transformants produced less melanin, whereas the Bdo_02540-disrupted transformant showed a slower growth rate and a stronger resistance to Congo red.

Conclusion

The established GD method is efficient and convenient and has potential for studying gene functions and the pathogenic mechanisms of B. dothidea and other coenocytic fungi.
Improving the healthcare response to domestic violence and abuse in UK primary care: interrupted time series evaluation of a system-level training and support programme
Authors: Sohal Alex Hardip , Feder Gene , Boomla Kambiz , Dowrick Anna , Hooper Richard , Howell Annie , Johnson Medina , Lewis Natalia , Robinson Clare , Eldridge Sandra , Griffiths Chris
Published: March 2020

Background

It is unknown whether interventions known to improve the healthcare response to domestic violence and abuse (DVA)—a global health concern—are effective outside of a trial.

Methods

An observational interrupted time series study in general practice. All registered women aged 16 and above were eligible for inclusion. In four implementation boroughs’ general practices, there was face-to-face, practice-based, clinically relevant DVA training, a prompt in the electronic medical record, reminding clinicians to consider DVA, a simple referral pathway to a named advocate, ensuring direct access for women to specialist services, overseen by a national, health-focused DVA organisation, fostering best practice. The fifth comparator borough had only a session delivered by a local DVA specialist agency at community venues conveying information to clinicians. The primary outcome was the daily number of referrals received by DVA workers per 1000 women registered in a general practice, from 205 general practices, in all five northeast London boroughs. The secondary outcome was recorded new DVA cases in the electronic medical record in two boroughs. Data was analysed using an interrupted time series with a mixed effects Poisson regression model.

Results

In the 144 general practices in the four implementation boroughs, there was a significant increase in referrals received by DVA workers—global incidence rate ratio of 30.24 (95% CI 20.55 to 44.77, p < 0.001). There was no increase in the 61 general practices in the other comparator borough (incidence rate ratio of 0.95, 95% CI 0.13 to 6.84, p = 0.959). New DVA cases recorded significantly increased with an incident rate ratio of 1.27 (95% CI 1.09 to 1.48, p < 0.002) in the implementation borough but not in the comparator borough (incidence rate ratio of 1.05, 95% CI 0.82 to 1.34, p = 0.699).

Conclusions

Implementing integrated referral routes, training and system-level support, guided by a national health-focused DVA organisation, outside of a trial setting, was effective and sustainable at scale, over four years (2012 to 2017) increasing referrals to DVA workers and new DVA cases recorded in electronic medical records.
Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram
Authors: Sun Ting , Yang Wei , Toprani Sneh M. , Guo Wei , He Lile , DeLeo Albert B. , Ferrone Soldano , Zhang Gong , Wang Enwen , Lin Zunwen , Hu Pan , Wang Xinhui
Published: March 2020

Background

The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response.

Methods

High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24−/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA).

Results

We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors.

Conclusion

DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.

Graphical abstract