bluuebunny/crossref_metadata_2025 huggingface dataset:
New answers to the old RIDDLE: RNF168 and the DNA damage response pathway
Authors: Kelliher Jessica , Ghosal Gargi , Leung Justin Wai Chung
Published: April 2021

The chromatin‐based DNA damage response pathway is tightly orchestrated by histone post‐translational modifications, including histone H2A ubiquitination. Ubiquitination plays an integral role in regulating cellular processes including DNA damage signaling and repair. The ubiquitin E3 ligase RNF168 is essential in assembling a cohort of DNA repair proteins at the damaged chromatin via its enzymatic activity. RNF168 ubiquitinates histone H2A(X) at the N terminus and generates a specific docking scaffold for ubiquitin‐binding motif‐containing proteins. The regulation of RNF168 at damaged chromatin and the mechanistic implication in the recruitment of DNA repair proteins to the damaged sites remain an area of active investigation. Here, we review the function and regulation of RNF168 in the context of ubiquitin‐mediated DNA damage signaling and repair. We will also discuss the unanswered questions that require further investigation and how understanding RNF168 targeting specificity could benefit the therapeutic development for cancer treatment.
Inverse hydrogen isotope fractionation indicates heterotrophic microbial production of long‐chain n‐alkyl lipids in desolate Antarctic ponds
Authors: Chen Xin , Liu Xiaodong , Jia Hongzeng , Jin Jing , Kong Weidong , Huang Yongsong
Published: April 2021

Long‐chain (>C25) n‐alkyl lipids have long been considered biomarkers for higher plant leaf waxes and widely applied for paleoclimate and paleoenvironmental reconstructions. However, recent experimental and lacustrine sediment studies suggest long‐chain n‐alkanes and n‐alkanoic acids can also be produced by aerobic microbes, probably heterotrophic microbes based on carbon isotope data. Here we show that sedimentary long‐chain n‐alkanes and n‐alkanoic acids in two desolate Antarctic ponds where vascular plants are absent in the surroundings display hydrogen isotopic values up to 300 per mil higher than those of lake water. It is the first time that such strongly inverse or reduced hydrogen isotopic fractionation of lipid biomarkers is observed in natural sediment samples. Based on recent extensive experimental data on microbial hydrogen isotopic fractionation, our data can only be explained by the predominant production of long‐chain n‐alkanes and n‐alkanoic acids from heterotrophic micro‐organisms. Together with preliminary 16S rRNA gene sequencing data, our results represent the first unambiguous example of predominant heterotrophic microbial production of long‐chain n‐alkyl waxes in a natural environment.
The ecological impacts of multiple environmental stressors on coastal biofilm bacteria
Authors: Ferguson Robert M. W. , O’Gorman Eoin J. , McElroy David J. , McKew Boyd A. , Coleman Ross A. , Emmerson Mark C. , Dumbrell Alex J.
Published: April 2021

Ecological communities are increasingly exposed to multiple interacting stressors. For example, warming directly affects the physiology of organisms, eutrophication stimulates the base of the food web, and harvesting larger organisms for human consumption dampens top‐down control. These stressors often combine in the natural environment with unpredictable results. Bacterial communities in coastal ecosystems underpin marine food webs and provide many important ecosystem services (e.g. nutrient cycling and carbon fixation). Yet, how microbial communities will respond to a changing climate remains uncertain. Thus, we used marine mesocosms to examine the impacts of warming, nutrient enrichment, and altered top‐predator population size structure (common shore crab) on coastal microbial biofilm communities in a crossed experimental design. Warming increased bacterial α‐diversity (18% increase in species richness and 67% increase in evenness), but this was countered by a decrease in α‐diversity with nutrient enrichment (14% and 21% decrease for species richness and evenness, respectively). Thus, we show some effects of these stressors could cancel each other out under climate change scenarios. Warming and top‐predator population size structure both affected bacterial biofilm community composition, with warming increasing the abundance of bacteria capable of increased mineralization of dissolved and particulate organic matter, such as Flavobacteriia, Sphingobacteriia, and Cytophagia. However, the community shifts observed with warming depended on top‐predator population size structure, with Sphingobacteriia increasing with smaller crabs and Cytophagia increasing with larger crabs. These changes could alter the balance between mineralization and carbon sequestration in coastal ecosystems, leading to a positive feedback loop between warming and CO2 production. Our results highlight the potential for warming to disrupt microbial communities and biogeochemical cycling in coastal ecosystems, and the importance of studying these effects in combination with other environmental stressors.
A prospective, randomized, double‐blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department
Authors: Hodgson Sarah E. , Harding Andrew M. , Bourke Elyssia M. , Taylor David M. , Greene Shaun L.
Published: April 2021

Objective

To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED).

Background

Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared.

Design

We performed a prospective, randomized, double‐blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18–65 years, who presented with migraine, were eligible for recruitment. Sixty‐six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post‐commencement of the study medicine infusion.

Results

Sixty‐five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0–4.0) in the chlorpromazine arm versus 2.0 (1.0–4.0) in the prochlorperazine arm (median difference −0.5 (95% confidence interval, −1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277).

Conclusions

Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.
Barriers to care in episodic and chronic migraine: Results from the Chronic Migraine Epidemiology and Outcomes Study
Authors: Buse Dawn C. , Armand Cynthia E. , Charleston Larry , Reed Michael L. , Fanning Kristina M. , Adams Aubrey Manack , Lipton Richard B.
Published: April 2021

Objective

To assess rates of and factors associated with traversing fundamental barriers to good medical outcomes and pharmacologic care in individuals with episodic migraine (EM) and chronic migraine (CM), including socioeconomic status and race.

Background

Barriers to good outcomes in migraine include the lack of appropriate medical consultation, failure to receive an accurate diagnosis, not being offered a regimen with acute and preventive pharmacologic treatments (if indicated), and not avoiding medication overuse.

Methods

The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal Internet‐based survey. Respondents who met criteria for migraine consistent with the International Classification of Headache Disorders, 3rd edition, had a Migraine Disability Assessment score ≥ 6, and provided health insurance coverage status were included in this analysis. Successfully traversing each barrier to care and the effects of sociodemographic characteristics were examined.

Results

Among 16,789 respondents with migraine, 9184 (54.7%; EM: 7930; CM: 1254) were eligible. Current headache consultation was reported by 27.6% (2187/7930) of EM and 40.8% (512/1254) of CM respondents. Among consulters, 75.7% (1655/2187) with EM and 32.8% (168/512) with CM were accurately diagnosed. Among diagnosed consulters, 59.9% (992/1655) with EM and 54.2% (91/168) with CM reported minimally appropriate acute and preventive pharmacologic treatment. Among diagnosed and treated consulters, in the EM group 31.8% (315/992) and in the CM group 74.7% (68/91) met medication overuse criteria. Only 8.5% (677/7930) of EM and 1.8% (23/1254) of CM respondents traversed all four barriers. Higher income was positively associated with likelihood of traversing each barrier. Blacks and/or African Americans had higher rates of consultation than other racial groups. Blacks and/or African Americans and multiracial people had higher rates of acute medication overuse.

Conclusions

Efforts to improve care should focus on increasing consultation and diagnosis rates, improving the delivery of all appropriate guideline‐based treatment, and avoidance of medication overuse.
Accuracy of carbohydrate‐deficient transferrin as a biomarker of chronic alcohol abuse during treatment for alcoholism
Authors: Suzuki Tatsuya , Eguchi Akiko , Shigefuku Ryuta , Nagao Saeko , Morikawa Masayuki , Sugimoto Kazushi , Iwasa Motoh , Takei Yoshiyuki
Published: April 2021

Aim

Clinical evaluations are generally used to verify the effectiveness of detoxification treatments for alcohol dependence, but new objective biomarkers are essential for accurate diagnosis. We aim to assess the accuracy of carbohydrate‐deficient transferrin (%CDT) in a cohort of Japanese patients admitted to a psychiatric hospital specializing in alcohol dependence. In addition, we investigated the kinetics of %CDT during alcohol moderation or cessation.

Methods

The study cohort consisted of 126 alcohol‐dependent patients. The levels of serum %CDT were assessed by the N Latex CDT direct immunonephelometric assay.

Results

Alcohol consumption was significantly correlated with %CDT. The only independent predictive factor of alcohol consumption was %CDT, with glutamyltranspeptidase (GGT) and albumin–bilirubin score proving insufficient. The cut‐off value of %CDT was 1.9% with high sensitivity and specificity in detecting alcohol abstinence beyond 30 days (68.6% sensitivity, 91.8% specificity) and excessive alcohol drinking (77.9% sensitivity, 77.1% specificity). The %CDT levels were significantly decreased at 30 days of abstinence when compared with baseline. Notably, %CDT values were significantly changed even in the light alcohol drinking cohort (p = 0.0009), whereas GGT levels were not significantly changed.

Conclusions

Our results indicate that %CDT is an accurate and specific biomarker of alcohol consumption and is useful in detecting alcohol abstinence even in a low alcohol intake patient cohort. These results suggest that %CDT could be a useful objective biomarker of chronic alcohol abuse during clinical treatment for alcoholism.
Evaluation of the effect of periodontitis on quality of life using Oral‐Dental Health‐Related Quality of Life‐United Kingdom scale
Authors: Kutsal Derya , Bilgin Çetin Mehtap , Durukan Elif , Bulut Şule
Published: April 2021

Objective

The aim of this study was to investigate the impact of periodontitis on oral health‐related quality of life (OHQoL) using Oral‐Dental Health‐Related Quality of Life‐United Kingdom (OHRQoL‐UK) scale and evaluate the contributing factors.

Methods

50 patients with untreated periodontitis and 50 individuals without periodontitis were enrolled in the study. All subjects received detailed periodontal examination. Plaque index (PI), gingival index (GI), probing depth (PD) and clinical attachment level (CAL) measurements were examined. OHRQoL was assessed by the Oral Health Quality of Life‐United Kingdom (OHRQoL‐UK) scale. Symptoms of periodontitis were monitored by visual analogue scale (VAS). Socio‐demographic characteristics, medical history, smoking status, hygiene habits of the participants were recorded. This study is registered at ClinicalTrials.gov as NCT04240014.

Results

Total OHRQoL‐UK scores were 38.24±6.47 in periodontitis patients and 55.88±9.38 in non‐periodontitis individuals (p < 0.001). The scores of all 4 parameters were significantly lower in patients with periodontitis compared to healthy individuals (p <0.001). Higher PI, GI, PD and CAL values were associated with extensive negative impacts of periodontitis on OHRQoL (p < 0.001). According to the results of linear regression analysis, only periodontitis was found to associate with OHRQoL. Periodontal disease reduces the total quality of life score by 15.087 (ß= −15.087; 95% CI = [(−18.934)‐(−11.240)].

Conclusions

Individuals with periodontitis has diminished OHRQoL compared to healthy individuals.
Oral health awareness, attitude towards dental treatment, fear of infection and economic impact during COVID‐19 pandemic in the Middle East
Authors: Abdulkareem Ali A , Abdulbaqi Hayder R , Alshami Muhanad L , Al‐Rawi Natheer H
Published: April 2021

Objectives

To assess the impact of COVID‐19 on oral hygiene (OH) awareness, attitude towards dental treatment, fear of infection and economic impact in the Middle East.

Methods

This survey was performed by online distribution of questionnaires in three countries in the Middle East (Jordan, Iraq and Egypt). The questionnaire consisted of five sections: the first section was aimed at collecting demographic data and the rest sections used to assess OH awareness, attitude towards dental treatment, degree of fear and economic impact of COVID‐19. The answers were either multiple choice, closed‐end (Yes or No) or 5‐point Likert scale for the last four sections.

Results

A total of 3782 respondents completed the questionnaire. Overall, OH awareness was low (mean ±SD; 1.84 ± 1.03), while attitude towards dental treatment (5.04 ± 1.68) and economic impact (11.29 ± 4.37) were moderately affected. In addition, fear of infection showed moderately high level (14.04 ± 4.11). All subgroups of the demographic variables showed significant differences among them in relation to OH awareness and attitude towards dental treatment. The regression model suggested country, gender, age, education level, income level and fear as predictors for OH awareness (R2 0.036) and attitude towards dental care (R2 0.141).

Conclusions

The pandemic negatively impacted the level of OH awareness. However, the attitude towards dental treatment was moderately affected. Increasing public fear and compromised economy influenced OH awareness and the attitude towards dental treatment.
Influence of γ‐irradiation on antioxidant, thermal and rheological properties of native and irradiated whole grain millet flours
Authors: Wani Haroon Maqbool , Sharma Paras , Wani Idrees Ahmed , Kothari Shanker Lal , Wani Ali Abas
Published: April 2021

Millets of different types like Barnyard (Echinochloa utilis), Finger (Eleusine coracana), Foxtail (Setaria italic), Kodo (Paspalum setaceum) Little (Panicum sumatrense), Pearl (Pennisetum glaucum) and Proso millets (Penicum miliaceum) are staple foods for Indian and African diets. The germination, fungal and microbial contamination leads to postharvest losses mainly due to poor warehouse storage in Asia and Africa. Six millet varieties conditioned at 12% and 14% moisture content and irradiated at a dosage of 2.5 and 5 kGy and then milled into flours. The flour was analysed for composition, antioxidant and the rheological and thermal properties. Pearl, Proso, Finger Kodo at 12% moisture contents showed significant (P ≤ 0.05) increase in Phenolic contents at 2.5 kGy level of irradiation treatments compared with native and 5% irradiation treatment level. The DPPH activity showed an interesting results (42.77–72.65%) with wide variation and a mixed trend of high and low results with irradiation. Thermal transition temperatures showed that the irradiation decreased the transition temperatures primarily due to loss of the crystalline and amorphous starch structure due to radiation that lead to rapid water uptake and shorter time to reach peak viscosity. We are further studying the application of the irradiated flours in different food products to understand the influence of irradiation on nutritional, sensory and functional properties in cereal‐based products.
Sexual reproduction in the soft coralLobophytum schoedeiin Bolinao‐Anda Reef Complex, Pangasinan, northwestern Philippines
Authors: Baran Christine C. , Baria‐Rodriguez Maria Vanessa
Published: April 2021

The characterization of early life‐history strategies of soft corals is important in understanding population maintenance, replenishment, and recovery in disturbed coral reefs. This study examined the sexual reproduction of the soft coralLobophytum schoedeiin the Bolinao‐Anda Reef Complex (BARC), a degraded reef in northwestern Philippines. Reproductive strategies such as sexuality, sex ratio, fecundity, and reproductive timing were examined. Random colonies ofL. schoedeiwere sampled a few weeks before the predicted time of spawning to assess fecundity (n = 73 colonies), and sexuality and sex ratio (n = 221 colonies). Monthly sampling of tagged colonies ofL. schoedei(n = 20) was done over 13 months to determine the reproductive timing through polyp dissection. Peak of annual spawning was inferred based on the presence of large gametes and their absence in the next sampling period. Results showed thatL.schoedeiis a gonochoric broadcast spawner with 1:1.1 sex ratio. Although oogenesis and spermatogenesis exhibited overlapping cycles, both gametes matured and spawned in April, coinciding with increasing sea surface temperature. Prior to spawning, oocytes and spermaries ranged 300–633 µm and 150–337 µm in diameter, respectively. Mean female fecundity was 6.7 ± 3.9 oocytes per polyp and male fecundity was 39.2 ± 22.5 (±SD) spermaries per polyp. Some of these results, including the low number of oocytes produced by female polyps, may be caused by sexual reproduction in a degraded reef environment. Understanding these reproductive traits may be useful for predicting the resiliency of populations ofL. schoedeiin response to ongoing and future environmental change.
ISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell‐like features in cisplatin‐resistant ovarian cancer
Authors: Zhang Qi , Wang Jiamei , Qiao Huaiyu , Huyan Lingyue , Liu Baoqin , Li Chao , Jiang Jingyi , Zhao Fuying , Wang Huaqin , Yan Jing
Published: April 2021

Drug resistance is often developed during clinical chemotherapy of ovarian cancers. The ubiquitin‐like protein interferon‐stimulated gene 15 (ISG15) is possibly dependent on tumour context to promote or suppress progression of various tumours. The ubiquitin‐like protein interferon‐stimulated gene 15 (ISG15) was decreased in cisplatin‐resistant ovarian cancer cells. The current study identified that both ectopic wild type and nonISGylatable mutant ISG15 expression inhibited CSC‐like phenotypes of cisplatin‐resistant ovarian cancer cells. Moreover, ectopic ISG15 expression suppressed tumour formation in nude mice. In addition, ISG15 downregulation promoted CSC‐like features of cisplatin‐sensitive ovarian cancer cells. Furthermore, low ISG15 expression was associated with poor prognosis in patients with ovarian cancer. Transcriptional repressor Krüppel‐like factor 12 (KLF12) downregulated ISG15 in cisplatin‐resistant cells. Our data indicated that downregulating ISG15 expression, via weakening effect of KLF12, might be considered as new therapeutic strategy to inhibit CSC phenotypes in the treatment of cisplatin‐resistant ovarian cancer.
Anal cancer screening and prevention: a review for dermatologists
Authors: McGovern J. , Fuller C. , Burris K.
Published: April 2021

The incidence of and mortality from anal cancer, predominantly squamous cell carcinoma (SCC), have been increasing since the 1980s, during an era when many common malignancies have seen decreases in mortality. Dermatologists may be more likely to see patients at an increased risk for anal SCC, such as those living with HIV, MSM and those presenting for management of anogenital warts, yet there is little guidance in the field on how to manage these patients. We underwent a project to review the evidence surrounding screening and prevention of anal SCC. HPV vaccination, the main preventative measure for anal SCC, is often underutilized and may not be effective for those most at risk. Screening methods currently include high‐risk HPV and anal cytology testing, with high‐resolution anoscopy (HRA) reserved for biopsy and confirmatory testing. High‐risk HPV testing has been associated with high sensitivity for intraepithelial neoplasia, but low specificity in high‐risk groups. Recent meta‐analyses examining AIN detection using anal cytology estimate a similarly high sensitivity of 74–87%, with a relatively higher specificity (44–66%) for identifying high‐grade AIN. HRA is the gold standard for diagnosis, but its accessibility and cost are deterrents from its use as a screening tool. Cervical cancer screening, initially adopted without significant evidence of its impact, has significantly decreased cervical cancer rates. The argument can be made that rates of anal SCC may also benefit from appropriate screening methods, particularly anal cytology. It is prudent for dermatologists to be aware of the methods available to them in the management of at‐risk patients, the data supporting them, and the potential benefits of screening in order to counsel patients appropriately and address the increasing burden of disease.
Acceptability of an online relational intimacy and sexual enhancement (iRISE) intervention after breast cancer
Authors: Cullen Kimberley , Fergus Karen
Published: April 2021

The purpose of this study was to develop and evaluate an online relational intimacy and sexual enhancement (iRISE) intervention for couples experiencing sexual difficulties following breast cancer (BC). The acceptability of iRISE was evaluated using a single‐arm, qualitative design, with 14 couples completing satisfaction surveys and posttreatment interviews. The intervention was found to be acceptable, as demonstrated by high satisfaction ratings and qualitative feedback regarding iRISE and its online delivery. Couples spoke about the helpfulness of iRISE and how the intervention improved their sexual relationship. The use of video conferencing (eTherapy) was widely accepted by participants, who highlighted several advantages of this modality. Overall, the results support the acceptability of this online psychosexual intervention for couples affected by BC. The empirical and theoretical basis for the design of iRISE along with findings from a qualitative analysis of couples’ experiences of the intervention's helpfulness to them is discussed.
Convolutional neural networks for segmentation of FIB‐SEM nanotomography data from porous polymer films for controlled drug release
Authors: Skärberg Fredrik , Fager Cecilia , Mendoza‐Lara Francisco , Josefson Mats , Olsson Eva , Lorén Niklas , Röding Magnus
Published: April 2021

Phase‐separated polymer films are commonly used as coatings around pharmaceutical oral dosage forms (tablets or pellets) to facilitate controlled drug release. A typical choice is to use ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. When an EC/HPC film is in contact with water, the leaching out of the water‐soluble HPC phase produces an EC film with a porous network through which the drug is transported. The drug release can be tailored by controlling the structure of this porous network. Imaging and characterization of such EC porous films facilitates understanding of how to control and tailor film formation and ultimately drug release. Combined focused ion beam and scanning electron microscope (FIB‐SEM) tomography is a well‐established technique for high‐resolution imaging, and suitable for this application. However, for segmenting image data, in this case to correctly identify the porous network, FIB‐SEM is a challenging technique to work with. In this work, we implement convolutional neural networks for segmentation of FIB‐SEM image data. The data are acquired from three EC porous films where the HPC phases have been leached out. The three data sets have varying porosities in a range of interest for controlled drug release applications. We demonstrate very good agreement with manual segmentations. In particular, we demonstrate an improvement in comparison to previous work on the same data sets that utilized a random forest classifier trained on Gaussian scale‐space features. Finally, we facilitate further development of FIB‐SEM segmentation methods by making the data and software used open access.
Florence Nightingale's legacy for clinical academics: A framework analysis of a clinical professorial network and a model for clinical academia
Authors: Pattison Natalie , Deaton Christi , McCabe Candy , Coates Vivien , Johnston Bridget , Nolan Fiona , Whiting Lisa , Briggs Michelle
Published: April 2021

Background

Clinical academic nursing roles are rare, and clinical academic leadership positions even more scarce. Amongst the United Kingdom (UK) academia, only 3% of nurses who are employed within universities are clinically active. Furthermore, access to research fellowships and research grant funding for nurses in clinical or academic practice is also limited. The work of Florence Nightingale, the original role model for clinical academic nursing, is discussed in terms of how this has shaped and influenced that of clinical academic nurse leaders in modern UK healthcare settings. We analysed case studies with a view to providing exemplars and informing a new model by which to visualise a trajectory of clinical academic careers.

Methods

A Framework analysis of seven exemplar cases was conducted for a network of Clinical Academic Nursing Professors (n = 7), using a structured template. Independent analysis highlighted shared features of the roles: (a) model of clinical academic practice, (b) infrastructure for the post, (c) capacity‐building initiatives, (d) strategic influence, (e) wider influence, (f) local and national implementation initiatives, (g) research area and focus and (h) impact and contribution.

Findings

All seven of the professors of nursing involved in this discourse were based in both universities and healthcare organisations in an equal split. All had national and international profiles in their specialist clinical areas and were implementing innovation in their clinical and teaching settings through boundary spanning. We outline a model for career trajectories in clinical academia, and how leadership is crucial.

Conclusion

The model outlined emphasises the different stages of clinical academic roles in nursing. Nursing as a discipline needs to embrace the value of these roles, which have great potential to raise the standards of healthcare and the status of the profession.
From open to locked doors – From dependent to independent: Patient narratives of participation in their rehabilitation processes
Authors: Aasen Elin M. , Nilsen Halvard K. , Dahlborg Elisabeth , Helberget Lindis K. , Kjelsvik Marianne
Published: April 2021

Aims and objectives

The present study aimed to explore patients' experiences of participating in their rehabilitation process in the context of specialised rehabilitation in Norway.

Background

The rights of patients to participate in their care and treatment is an ideology that underlines newer international and Norwegian public documents. However, there is a gap between policy statements and clinical practice, and a discrepancy between patients' and professionals' statements about patient participation in rehabilitation.

Design

A qualitative approach with a narrative design.

Methods

Eleven patients were individually interviewed to tell their stories about the rehabilitation processes. We utilised narrative analysis with a three‐dimensional space narrative structure including temporality, sociality and spatiality. This study followed the COREQ checklist.

Results

The analysis identified two throughout plots: ‘person‐centred culture’ and ‘time’, and three plots which constructed how the patients participate in change through the rehabilitation process: (a) dependent—‘open doors’; (b) motivation from within; and (c) independence—‘locked doors’.

Conclusions

Patient participation in rehabilitation was dependent on person‐centred cultures in the unit and on different aspects of time. The dialogue and the power balance between the patients and the health personnel changed as the rehabilitation progressed. Motivation for rehabilitation had to come from within patients. The paternalistic ideology did not seem to dominate the specialised rehabilitation unit in the present study.

Relevance to clinical practice

This study gives new insight into how patients participate in change in the rehabilitation process. This can be valuable for healthcare professionals and governments. Insight into how the lack of person‐centred focus can harm the rehabilitation process, and a deeper understanding of the meaning of time in the rehabilitation process is essential. These results may provide a stimulus for discussions on how patients might participate in their rehabilitation process.
CDK4 and TERT amplification in head and neck mucosal melanoma
Authors: Lyu Jiong , Miao Yuwen , Yu Fang , Chang Chengdong , Guo Wei , Zhu Huiyong
Published: April 2021

Background

Recent high‐throughput sequencing studies have revealed frequent CDK4 and TERT amplification in mucosal melanoma, suggesting that they are potential therapeutic targets. In this study, we investigated the statuses of CDK4 and TERT in head and neck mucosal melanoma (HNMM) with the aim of providing preclinical data to support future clinical trials.

Methods

In total, 29 HNMM samples were collected, including 16 oral mucosal melanoma (OMM) samples and 13 nasal cavity/sinuses melanoma (SNMM) samples. Fluorescence in situ hybridization was used to analyze CDK4 and TERT amplification, and immunohistochemistry was used to analyze CDK4 and TERT protein expression patterns. CDK4 expression was knocked down in the ME cells (an OMM cell line), and changes in cell cycle were analyzed. Cell viability assays were performed to determine the sensitivity of ME to abemaciclib (a CDK4 inhibitor) combined with dacarbazine (an anti‐melanoma chemotherapy drug).

Results

We detected five samples exhibited CDK4 amplifications and nine samples exhibited TERT amplifications in our HNMM series, and found that CDK4 amplification tended to occur in combination with TERT amplification. Amplifications of CDK4 and TERT were more common in OMM than in SNMM. Amplifications of CDK4 and TERT were associated with greater CDK4 and TERT protein expression levels. CDK4 knockdown led to delayed G1/S phase transition in ME cells. Furthermore, ME cells were sensitive to abemaciclib (IC50 = 5.23 nM). Abemaciclib and dacarbazine synergistically inhibited ME cells’ viability.

Conclusion

We confirmed high frequencies of CDK4 and TERT amplification in OMM. Combined therapy with a CDK4/6 inhibitor and anti‐melanoma chemotherapeutic agents will be a reasonable strategy for future clinical trials concerning unresectable or metastatic OMM.
Aromatase inhibitor anastrozole modifies cellular functions in gingival fibroblasts and endothelial cells: possible periodontal complications of aromatase inhibitor treatment
Authors: Hasegawa Shiori , Yanagita Manabu , Tatsumi Mari , Yamashita Motozo , Kitamura Masahiro , Murakami Shinya
Published: April 2021

Background

Recent studies have shown that treatment with aromatase inhibitors contributes to an increased prevalence of periodontitis.

Objective

In this study, we assessed effects of the aromatase inhibitor anastrozole on cellular function of human gingival fibroblasts (HGFs) and endothelial cells.

Methods

Expression levels of collagen, extracellular matrix (ECM) proteins, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were examined in HGFs exposed to anastrozole. Furthermore, inflammatory responses in HGFs cultured with anastrozole were evaluated in the presence of Porphyromonas gingivalis lipopolysaccharide. We also evaluated the vascular permeability and vascular endothelial (VE)‐cadherin expression of endothelial cells exposed to anastrozole.

Results

Anastrozole enhanced expression levels of collagen, ECM proteins, TIMPs, and inflammatory cytokines in HGFs, as well as vascular permeability of endothelial cells. In addition, anastrozole reduced expression levels of MMPs in HGFs and VE‐cadherin in endothelial cells.

Conclusion

These results suggest that anastrozole modulates various cellular functions in HGFs and endothelial cells.
Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone
Authors: Yao Kefang , Liu Jiacheng , Wang Jian , Yan Xiaomin , Xia Juan , Yang Yue , Wu Weihua , Liu Yong , Chen Yuxin , Zhang Zhaoping , Li Jie , Huang Rui , Wu Chao
Published: April 2021

A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the ‘grey zone (GZ)’. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty‐nine consecutive treatment‐naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106 IU/ml (GZ‐A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2 × 103 IU/ml (GZ‐C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2 × 103 IU/ml (GZ‐D). The distributions of different immune states were: 233 (4.90%) patients in immune‐tolerant phase, 941 (19.77%) patients in HBeAg‐positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg‐negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ‐B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg‐positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ‐B had advanced fibrosis or even cirrhosis.
Expression of epidermal antimicrobial peptides is increased in tinea pedis
Authors: Pham Christina Van Anh , Rademacher Franziska , Hinrichs Heilwig , Beck‐Jendroschek Vera , Harder Melanie , Brasch Jochen , Gläser Regine , Harder Jürgen
Published: April 2021

Background

Tinea pedis is often chronic or recurrent, but not all individuals are equally susceptible to this infection. Dermatophytes are able to induce the expression of antimicrobial peptides and proteins (AMPs) in human keratinocytes and certain AMPs can inhibit the growth of dermatophytes.

Objective

The focus of this study was to analyse the secretion of relevant AMPs, especially RNase 7, human beta‐defensin‐2 (hBD‐2) and the S‐100 protein psoriasin (S100A7), in patients with confirmed tinea pedis.

Methods

To verify the diagnosis, skin scales were obtained from all patients (n = 13) and the dermatophytes were identified by potassium hydroxide mount, culture and molecular analysis. To determine the AMP concentrations, the lesional skin area of the foot was rinsed with a buffer that was subsequently analysed by ELISA. The corresponding area of the other unaffected foot as well as defined healthy skin areas of the forearm and forehead and samples from age and gender‐matched healthy volunteers served as controls.

Results

In tinea pedis patients the AMP concentrations were higher in lesional skin than in non‐lesional skin and in healthy skin of controls. In particular, concentrations of hBD‐2 and psoriasin were significantly elevated.

Conclusions

The induction of AMPs in tinea pedis might be triggered directly by the dermatophytes; furthermore, attendant inflammation and/or differentiation processes may play a role. Our results indicate that there is no defect in the constitutive expression and induction of the analysed AMPs by dermatophytes in the epidermis of affected patients. However, it is not known why the elevated AMP concentrations fail to efficiently combat dermatophyte growth.
Identifying cellular signalling molecules in developmental disorders of the brain: Evidence from focal cortical dysplasia and tuberous sclerosis
Authors: Li Yao‐Feng , Scerif Fatma , Picker Simon R. , Stone Thomas J. , Pickles Jessica C. , Moulding Dale A. , Avery Aimee , Virasami Alex , Fairchild Amy R. , Tisdall Martin , Harkness William , Cross J Helen , Hargrave Darren , Guillemot Francois , Paine Simon M. , Yasin Shireena A. , Jacques Thomas S.
Published: April 2021

Aims

We understand little of the pathogenesis of developmental cortical lesions, because we understand little of the diversity of the cell types that contribute to the diseases or how those cells interact. We tested the hypothesis that cellular diversity and cell–cell interactions play an important role in these disorders by investigating the signalling molecules in the commonest cortical malformations that lead to childhood epilepsy, focal cortical dysplasia (FCD) and tuberous sclerosis (TS).

Methods

Transcriptional profiling clustered cases into molecularly distinct groups. Using gene expression data, we identified the secretory signalling molecules in FCD/TS and characterised the cell types expressing these molecules. We developed a functional model using organotypic cultures.

Results

We identified 113 up‐regulated secretory molecules in FCDIIB/TS. The top 12 differentially expressed genes (DEGs) were validated by immunohistochemistry. This highlighted two molecules, Chitinase 3‐like protein 1 (CHI3L1) and C‐C motif chemokine ligand 2 (CCL2) (MCP1) that were expressed in a unique population of small cells in close proximity to balloon cells (BC). We then characterised these cells and developed a functional model in organotypic slice cultures. We found that the number of CHI3L1 and CCL2 expressing cells decreased following inhibition of mTOR, the main aberrant signalling pathway in TS and FCD.

Conclusions

Our findings highlight previously uncharacterised small cell populations in FCD and TS which express specific signalling molecules. These findings indicate a new level of diversity and cellular interactions in cortical malformations and provide a generalisable approach to understanding cell–cell interactions and cellular heterogeneity in developmental neuropathology.
A comparison of rectoanal pressures during Valsalva maneuver and evacuation uncovers rectoanal discoordination in defecatory disorders
Authors: Srinivasan Sushmitha Grama , Sharma Mayank , Feuerhak Kelly , Bailey Kent R. , Bharucha Adil E.
Published: April 2021

Background

It is suggested that patients with defecation disorders (DD) strain excessively or do a Valsalva maneuver (VM) during evacuation, resulting in rectoanal discoordination, which hinders rectal evacuation. However, definitive data are lacking.

Methods

Rectoanal pressures during evacuation and a VM were measured with seated high‐resolution manometry (HRM) in 64 healthy and 136 constipated women with a normal (84 women, C‐normal) or prolonged (52 women, C‐abnormal) balloon expulsion time (BET). The number of abnormal rectoanal parameters during evacuation and the joint distribution of pressures during evacuation and a VM were used to discriminate between controls and C‐abnormal BET patients.

Key Results

The peak anal pressure (5 s) during a VM accounted for 0%, 26%, and 49% of the variance in anal pressure during evacuation in healthy women, C‐normal BET, and C‐abnormal BET. The association between anal pressure during a VM and evacuation was stronger in C‐abnormal BET than in healthy women and C‐normal BET (p for interaction <0.001). Fifty‐eight of 64 controls and 33 of 52 C‐abnormal BET patients had no or one abnormal parameter during evacuation; hence, the probability of C‐abnormal BET was 33/91 (36%). In patients with no or one abnormal parameter during evacuation, a logistic model based on anal pressures during evacuation and a VM discriminated between controls and patients with C‐abnormal BET with a sensitivity and a specificity of 67% and 75%.

Conclusions

Assessment of rectoanal pressures during evacuation and a VM uncovers rectaoanal discoordination and facilitates the diagnosis of DD in selected patients.
The 14‐3‐3 proteins: regulators of plant metabolism and stress responses
Authors: Zhao X. , Li F. , Li K.
Published: April 2021

The 14‐3‐3 proteins bind to and modulate the activity of phosphorylated proteins that regulate a variety of metabolic processes in plants. Over the past decade interest in the plant 14‐3‐3 field has increased dramatically, mainly due to the vast number of mechanisms by which 14‐3‐3 proteins regulate metabolism. As this field develops, it is essential to understand the role of these proteins in metabolic and stress responses. This review summarizes current knowledge about 14‐3‐3 proteins in plants, including their molecular structure and function, regulatory mechanism and roles in carbon and nitrogen metabolism and stress responses. We begin with a molecular structural analysis of 14‐3‐3 proteins, which describes the basic principles of 14‐3‐3 function, and then discuss the regulatory mechanisms and roles in carbon and nitrogen metabolism of 14‐3‐3 proteins. We conclude with a summary of the 14‐3‐3 response to biotic stress and abiotic stress.
Transcript profiles analysis of citrus aquaporins in response to fruit water loss during storage
Authors: Zhang M. , Yang H. , Zhu F. , Xu R. , Cheng Y.
Published: April 2021

Water loss is an essential factor that affects the maintenance of quality of citrus fruit during postharvest handling and storage. Aquaporins (AQPs) play an important role in the transport of water across membranes. However, the expression profiling of AQPs is incomplete for citrus fruits during storage.

In this study, a post‐harvest storage experiment was performed using sweet orange fruits to determine changes in water loss and fruit quality. Also, genome‐wide expression analysis of CsAQP genes was carried out in fruit of different citrus varieties during storage.

Low humidity storage conditions accelerated the postharvest water loss and texture decline and increased the TSS content in the fruit. A total of 39 non‐redundant CsAQP genes were identified. A comprehensive analysis of these genes demonstrated that all AQPs had conserved filter motifs in the different citrus varieties examined. Moreover, multiple expression analysis revealed AQPs had complex expression profiles upon water loss in citrus fruit, being time‐specific in tight‐skin varieties (orange and pomelo varieties), tissue‐specific between peel and pulp, and variety‐specific between loose‐skin (mandarin varieties) and tight‐skin varieties (such as sweet orange and pummelo).

These results indicated that the relative humidity in storage environment affected the postharvest water loss and quality of citrus fruit. Besides, the alternation in AQPs expression may partially account for the different water loss ratio in citrus varieties and the transfer of water between the peel and the pulp of citrus fruit during storage.
Alone in the campaign: Distrust in regulators and the coping of front‐line workers
Authors: Davidovitz Maayan , Cohen Nissim
Published: April 2021

Trust is the “glue” connecting state and society and particularly relevant to how front‐line workers, who are the face of public administration vis‐à‐vis citizens, implement policy. Therefore, it is important to examine how front‐line workers' absence of trust in regulators influences the ways they cope with their clients. Our study investigates this question empirically through interviews and focus groups with 80 Israeli social service providers. Our results show that front‐line workers' distrust in regulators is a product of four factors: perceived lack of protection, clash of values, politicization in implementation processes, and regulators' “disconnection” from the field. It leads them to adopt two coping strategies: acts of self‐protection and deviation from formal policy. A further derivative is their turnover intention.
The effects of exergames on muscle strength: A systematic review and meta‐analysis
Authors: Viana Ricardo Borges , de Oliveira Vinnycius Nunes , Dankel Scott J. , Loenneke Jeremy P. , Abe Takashi , da Silva Wellington Fernando , Morais Naiane Silva , Vancini Rodrigo Luiz , Andrade Marília Santos , de Lira Claudio Andre Barbosa
Published: April 2021

This systematic review and meta‐analysis examined studies on the chronic effects of exergames on muscle strength in humans. PubMed, Scopus, CENTRAL, Web of Science, SciELO, Biblioteca Virtual em Saúde, and Google Scholar were searched, and manual searches of the reference lists of included studies and hand‐searches on Physiotherapy Evidence Database and ResearchGate were conducted from inception to August 10, 2020. Randomized and non‐randomized exergame intervention studies with or without a non‐exercise group and/or a “usual care intervention group” (any other intervention that did not incorporate exergames), which evaluated muscle strength through direct measurements, were included. Forty‐seven and 25 studies were included in the qualitative review and meta‐analysis, respectively. The between‐groups meta‐analyses showed no significant differences between exergames and non‐exercise control groups for handgrip strength in heathy/unhealthy middle‐aged/older adults or knee extension maximum voluntary isometric contraction (MVIC) in healthy older adults. However, exergames provided a greater increase in handgrip strength, knee flexion MVIC, and elbow extension MVIC, but not knee extension MVIC or elbow flexion MVIC, in individuals with different health statuses when compared to usual care interventions. Also, there was a greater increase in handgrip strength in children with hemiplegic cerebral palsy favouring usual care plus exergames compared to usual care interventions. These results suggest that exergames may improve upper and lower limb muscle strength in individuals with different heath statuses compared to usual care interventions, but not muscle strength in middle age/older adults after accounting for random error. Also, exergames appear to be a useful tool for improving handgrip strength in children with hemiplegic cerebral palsy when added to usual care. However, as the exergame interventions were applied in different populations and there currently are many different approaches to perform exergames, future randomized controlled trials with high methodological quality and large sample sizes are needed to provide more compelling evidence in favour of a specific exergame protocol, or to elucidate exergame protocol design principles that appear to strongly influence outcomes.