bluuebunny/crossref_metadata_2025 huggingface dataset:
USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4
Authors: Pan Tingzheng , Li Xuetao , Li Yanyan , Tao Zhennan , Yao Hui , Wu Yue , Chen Guangliang , Zhang Kai , Zhou Youxin , Huang Yulun
Published: September 2021

Background

Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a short median overall survival. Effective induction of GBM cell death is difficult because the GBM cell population is genetically unstable, resistant to chemotherapy and highly angiogenic. In recent studies, ubiquitin-specific protease 7 (USP7) is shown to scavenge ubiquitin from oncogenic protein substrates, so effective inhibition of USP7 may be a potential key treatment for GBM.

Methods

Immunohistochemistry and western blotting were used to detect the expression of USP7 in GBM tissues. In vitro apoptosis assay of USP7 inhibition was performed by western blotting, immunofluorescence, and flow cytometry. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Western blotting and IP were used to verify the relationship between USP7 and its substrate. In an in vivo experiment using an intracranial xenograft model in nude mice was constructed to assess the therapeutic effect of target USP7.

Results

Immunohistochemistry and western blotting confirmed that USP7 was significantly upregulated in glioblastoma samples. In in vitro experiments, inhibition of USP7 in GBM induced significant apoptosis. Co-IP and TMT proteomics identified a key anti-apoptotic substrate of USP7, ADP-ribosylation factor 4 (ARF4). Western blotting and IP confirmed that USP7 interacted directly with ARF4 and catalyzed the removal of the K48-linked polyubiquitinated chain that binded to ARF4. In addition, in vivo experiments revealed that USP7 inhibition significantly suppressed tumor growth and promoted the expression of apoptotic genes.

Conclusions

Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a novel specific inhibitor of USP7 may be an effective approach for the treatment of GBM.
Extended classifier system with continuous real-coded variables for feature extraction of instantaneous pulse-rate variability and respiration of individuals with gaming disorder
Authors: Chi Hung-Ming , Hsiao Tzu-Chien
Published: September 2021

Background

Individuals with gaming disorder (GD) exhibit autonomic nervous system responses that indicate dysfunctional emotion regulation. Pulse rate variability (PRV) is a valuable biomarker for investigating the autonomic function of patients with mental disorders. Because individuals with GD dynamically regulate emotions during gaming, the PRV response relating to GD is not well understood. To investigate the dynamic PRV responses of individuals with GD, this study proposed the indexes of instantaneous PRV (iPRV) and instantaneous respiratory frequency (IFresp) of arterial blood pressure signals using empirical mode decomposition and normalized direct-quadrature algorithms. iPRV consists of low-frequency (LF), high-frequency (HF), and very high-frequency (VHF) bands. Moreover, a novel method of extended classifier system with continuous real-coded variables (XCSR) was used to detect GD and extract GD-related iPRV features using iPRV and IFresp as input data.

Results

A total of 32 college students without depressive and anxiety symptoms or cardiovascular diseases were recruited in this study. Participants were grouped into the high-risk GD and low-risk GD using both Chen Internet Addiction Scale and Internet Gaming Disorder Questionnaire. Their arterial blood pressures signals were measured while they watched gameplay videos with negative or positive emotional stimuli. Seven participants with high-risk GD exhibited significantly increased normalized VHF (nVHF) PRV and IFresp readings and significantly decreased normalized LF (nLF) PRV readings and LF/HF PRV ratios (from baseline) during negative or positive gameplay videos stimuli. These participants also exhibited higher nVHF PRV and lower nLF PRV readings and LF/HF PRV ratios when they experienced negative gameplay video stimuli relative to 17 participants with low-risk GD. The classification accuracy of the XCSR reached 90% for both negative and positive video stimuli, and nVHF PRV was most frequently used to detect GD risk.

Conclusions

iPRV and IFresp can be used to detect GD and analyze the autonomic mechanism of individuals with GD.
‘It was hell in the community’: a qualitative study of maternal and child health care during health care worker strikes in Kenya
Authors: Scanlon Michael L. , Maldonado Lauren Y. , Ikemeri Justus E. , Jumah Anjellah , Anusu Getrude , Chelagat Sheilah , Keter Joann Chebet , Songok Julia , Ruhl Laura J. , Christoffersen-Deb Astrid
Published: September 2021

Background

Health care workers in Kenya have launched major strikes in the public health sector in the past decade but the impact of strikes on health systems is under-explored. We conducted a qualitative study to investigate maternal and child health care and services during nationwide strikes by health care workers in 2017 from the perspective of pregnant women, community health volunteers (CHVs), and health facility managers.

Methods

We conducted in-depth interviews and focus group discussions (FGDs) with three populations: women who were pregnant in 2017, CHVs, and health facility managers. Women who were pregnant in 2017 were part of a previous study. All participants were recruited using convenience sampling from a single County in western Kenya. Interviews and FGDs were conducted in English or Kiswahili using semi-structured guides that probed women’s pregnancy experiences and maternal and child health services in 2017. Interviews and FGDs were audio-recorded, translated, and transcribed. Content analysis followed a thematic framework approach using deductive and inductive approaches.

Results

Forty-three women and 22 CHVs participated in 4 FGDs and 3 FGDs, respectively, and 8 health facility managers participated in interviews. CHVs and health facility managers were majority female (80%). Participants reported that strikes by health care workers significantly impacted the availability and quality of maternal and child health services in 2017 and had indirect economic effects due to households paying for services in the private sector. Participants felt it was the poor, particularly poor women, who were most affected since they were more likely to rely on public services, while CHVs highlighted their own poor working conditions in response to strikes by physicians and nurses. Strikes strained relationships and trust between communities and the health system that were identified as essential to maternal and child health care.

Conclusion

We found that the impacts of strikes by health care workers in 2017 extended beyond negative health and economic effects and exacerbated fundamental inequities in the health system. While this study was conducted in one County, our findings suggest several potential avenues for strengthening maternal and child health care in Kenya that were highlighted by nationwide strikes in 2017.
Valuing child and adolescent health: a qualitative study on different perspectives and priorities taken by the adult general public
Authors: Powell Philip A. , Rowen Donna , Rivero-Arias Oliver , Tsuchiya Aki , Brazier John E.
Published: September 2021

Background

Quantitative health preference research has shown that different “perspectives”, defined here as who is imagined to be experiencing particular health states, impact stated preferences. This qualitative project aimed to elucidate this phenomenon, within the context of adults’ valuation of child and adolescent health states.

Methods

Six focus groups with 30 members of the UK adult public were conducted between December 2019 and February 2020 and analysed using framework analysis. Each focus group had two stages. First, participants individually completed time trade-off tasks and a pairwise task (mirroring a discrete choice experiment without duration) for two EQ-5D-Y health states, assuming a series of perspectives: (a) themselves at current age; (b) another adult; (c) 10-year old child; (d) themselves as a 10-year old child. Second, a semi-structured discussion explored their responses.

Results

Participants’ views were often heterogeneous, with some common themes. Qualitatively, participants expressed a different willingness to trade-off life years for a 10-year old child versus themselves or another adult, and this differed by the health profile and child imagined. The same health states were often viewed as having a different impact on utility for a 10-year old child than adults. Imagining a 10-year old child is difficult and there is variation in who is imagined. Participants found answering based on their own—adult perspective most acceptable. There were no strong preferences for prioritising child health over working-age adults’ health.

Conclusions

If an adult sample is used to value child- and adolescent-specific health states it is important to consider the perspective employed. Members of the adult public provide different responses when different perspectives are used due to differences in the perceived impact of the same health states. If adults are asked to imagine a child, we recommend that sampling is representative for parental status, since this can affect preferences.
Cytometric analysis of patients with COVID-19: what is changed in the second wave?
Authors: Scalia Giulia , Raia Maddalena , Gelzo Monica , Cacciapuoti Sara , De Rosa Annunziata , Pinchera Biagio , Scotto Riccardo , Giaccone Agnese , Mormile Mauro , Fabbrocini Gabriella , Gentile Ivan , Parrella Roberto , Castaldo Giuseppe
Published: September 2021

Background

Coronavirus disease 2019 (COVID-19) pandemic had a 1st wave in Europe from March to May 2020 and a 2nd wave since September 2020. We previously studied 35 hospitalized COVID-19 patients of the 1st wave demonstrating a cytokine storm and the exhaustion of most lymphocyte subpopulations. Herein, we describe the results obtained from COVID-19 patients of the 2nd wave.

Methods

We analyzed interleukin (IL)-6 by human-specific enzyme-linked immunosorbent assay and a large set of lymphocyte subpopulations by flow cytometry in 274 COVID-19 patients hospitalized from September 2020 to May 2021.

Results

Patients of 2nd wave compared with those of 1st wave showed lower serum IL-6 levels and a higher number of B and most T lymphocyte subpopulations in advanced stages, in relation with the age and the gender. On the other hand, we observed in 2nd wave patients: (i) a reduction of most lymphocyte subpopulations at mild and moderate stages; (ii) a reduction of natural killer cells and T regulatory cells together with a higher number of activated T helper (TH) 17 lymphocytes in all stages, which were mainly related to steroid and azithromycin therapies before hospitalization.

Conclusions

COVID-19 had a less severe impact in patients of the 2nd wave in advanced stages, while the impact appeared more severe in patients of mild and moderate stages, as compared with 1st wave patients. This finding suggests that in COVID-19 patients with milder expression at diagnosis, steroid and azithromycin therapies appear to worsen the immune response against the virus. Furthermore, the cytometric profile may help to drive targeted therapies by monoclonal antibodies to modulate specific IL/lymphocyte inhibition or activation in COVID-19 patients.
Rapid generation of conditional knockout mice using the CRISPR-Cas9 system and electroporation for neuroscience research
Authors: Nishizono Hirofumi , Hayano Yuki , Nakahata Yoshihisa , Ishigaki Yasuhito , Yasuda Ryohei
Published: September 2021

The Cre/LoxP-based conditional knockout technology is a powerful tool for gene function analysis that allows region- and time-specific gene manipulation. However, inserting a pair of LoxP cassettes to generate conditional knockout can be technically challenging and thus time- and resource-consuming. This study proposes an efficient, low-cost method to generate floxed mice using in vitro fertilization and the CRISPR-Cas9 system over two consecutive generations. This method allowed us to produce floxed mice targeting exons 5 and 6 of CaMK1 in a short period of 125 days, using only 16 mice. In addition, we directly edited the genome of fertilized eggs of mice with our target genetic background, C57BL/6 N, to eliminate additional backcrossing steps. We confirmed that the genome of the generated floxed mice was responsive to the Cre protein. This low-cost, time-saving method for generating conditional knockout will facilitate comprehensive, tissue-specific genome analyses.
Targeting the DNA damage response enhances CD70 CAR-T cell therapy for renal carcinoma by activating the cGAS-STING pathway
Authors: Ji Feng , Zhang Fan , Zhang Miaomiao , Long Kaili , Xia Mingyue , Lu Fei , Li Enjie , Chen Jiannan , Li Jun , Chen Zhengliang , Jing Li , Jia Shaochang , Yang Rong , Hu Zhigang , Guo Zhigang
Published: September 2021

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.
The pattern of health insurance economic resilience in the Covid 19 pandemic shock
Authors: Kharazmi Erfan , Bordbar Shima , Gholampoor Hanie
Published: September 2021

Objective

Health insurance is based on people’s significant risks in receiving health services that they cannot afford alone. Since the outbreak of the corona epidemic, the health insurance system has suffered many economic problems. Designing a model of a health insurance system based on the requirements of a resilient economy can improve the functions of this system in the corona crisis.

Results

In this research 12, structural components were obtained in the form of 4 conceptual components. The 4 main conceptual components are Knowledge-based economy, Economic stability, Economic resilience, and justice. The knowledge-based economy is the basis for the formation of economic resilience in the health insurance systems. Health insurance systems will achieve two crucial intermediate results, namely economic resilience, and economic stability, by building the basic infrastructure of a knowledge-based economy. In the long run, maintaining such intermediate results is the foundation of justice in the health insurance system.
Evaluating context and interest in training in evidence-based mental health care: a qualitative investigation among healthcare providers in Kyiv, Ukraine
Authors: Hook Kimberly , Kozishkurt Julia , Kovalchuk Olga , Goncharenko Evelina , Kodovbetskyi Vitalii , Opanasenko Milana , Kopytko Andrii , Girnyk Andriy , Kliuzko Kateryna , Drainoni Mari-Lynn , Bogdanov Sergiy
Published: September 2021

Objective

Increasing access to quality, evidence-based mental health treatments, including psychotherapy, is a global priority. Knowledge of factors associated with delivery settings is critical to ensure that new practices are appropriate and effectively adapted for novel settings. Understanding perceived needs for training and interest in ongoing education is one key factor. This qualitative study aimed to identify perspectives on contemporary evidence-based psychotherapies, perceived needs for mental health training, and existing barriers and facilitators to provision of mental health services in community clinics in Ukraine. Purposive and snowball sampling was used to recruit 18 physicians and psychologists employed in community clinics in Kyiv. A combination of free-listing and semi-structured interviews was used to collect data, which were thematically coded using emergent coding.

Results

Findings from this study indicated that participants recognize a need for improved mental health knowledge and training, as well as suggested interest and openness to learning short-term, structured psychological interventions. Additional barriers and existing strengths described by participants provide insight into possible factors that may impact future trainings in and implementation of modern mental health approaches.
Organizational knowledge translation strategies for allied health professionals in traumatology settings: realist review protocol
Authors: Latulippe Karine , LeBlanc Annie , Gagnon Marie-Pierre , Boivin Katia , Lavoie Pascale , Dufour Joëlle , Raynard Emmanuelle Paquette , Richard Eve , Lamontagne Marie-Ève
Published: September 2021

Background

Knowledge translation (KT) is an important means of improving the health service quality. Most research on the effectiveness of KT strategies has focused on individual strategies, i.e., those directly targeting the modification of allied health professionals’ knowledge, attitudes, and behaviors, for example. In general, these strategies are moderately effective in changing practices (maximum 10% change). Effecting change in organizational contexts (e.g., change readiness, general and specific organizational capacity, organizational routines) is part of a promising new avenue to service quality improvement through the implementation of evidence-based practices. The objective of this study will be to identify why, how, and under what conditions organizational KT strategies have been shown to be effective or ineffective in changing the (a) knowledge, (b) attitudes, and (c) clinical behaviors of allied health professionals in traumatology settings.

Methods

This is a realist review protocol involving four iterative steps: (1) Initial theory formulation, (2) search for Evidence search, (3) knowledge extraction and synthesis, and (4) recommendations. We will search electronic databases such as PubMed, Embase, CINHAL, Cochrane Library, and Conference Proceedings Citation Index - Science. The studies included will be those relating to the use of organizational KT strategies in trauma settings, regardless of study designs, published between January 1990 and October 2020, and presenting objective measures that demonstrate change in allied health professionals’ knowledge, attitudes, and clinical behaviors. Two independent reviewers will select, screen, and extract the data related to all relevant sources in order to refine or refute the context-mechanism-outcome (CMO) configurations developed in the initial theory and identify new CMO configurations.

Discussion

Using a systematic and rigorous method, this review will help guide decision-makers and researchers in choosing the best organizational strategies to optimize the implementation of evidence-based practices.

Systematic review registration

PROSPERO CRD42020216105
The GAD-7 and the PHQ-8 exhibit the same mathematical pattern of item responses in the general population: analysis of data from the National Health Interview Survey
Authors: Tomitaka Shinichiro , Furukawa Toshiaki A.
Published: September 2021

Background

Recent studies have shown that, among the general population, responses to depression-rating scales follow a common mathematical pattern. However, the mathematical pattern among responses to the items of the Generalized Anxiety Disorder-7 (GAD-7) is currently unknown. The present study investigated whether item responses to the GAD-7, when administered to the general population, follow the same mathematical distribution as those of depression-rating scales.

Methods

We used data from the 2019 National Health Interview Survey (31,997 individuals), which is a nationwide survey of adults conducted annually in the United States. The patterns of item responses to the GAD-7 and the Patient Health Questionnaire-8 (PHQ-8), respectively, were analyzed inductively.

Results

For all GAD-7 items, the frequency distribution for each response option (“not at all,” “several days,” “more than half the days,” and “nearly every day,” respectively) was positively skewed. Line charts representing the responses to each GAD-7 item all crossed at a single point between “not at all” and “several days” and, on a logarithmic scale, showed a parallel pattern from “several days” to “nearly every day.” This mathematical pattern among the item responses was identical to that of the PHQ-8. This characteristic pattern of the item responses developed because the values for the “more than half the days” to “several days” ratio were similar across all items, as were the values for the “nearly every day” to “more than half the days” ratio.

Conclusions

Our results suggest that the symptom criteria of generalized anxiety disorder and major depression have a common distribution pattern in the general population.
Enhanced osteogenic differentiation of alendronate-conjugated nanodiamonds for potential osteoporosis treatment
Authors: Ahn Guk Young , Kim Sung-Eun , Yun Tae Hoon , Choi Inseong , Park Daewon , Choi Sung-Wook
Published: September 2021

Background

Alendronate (Alen) is promising material used for bone-targeted drug delivery due to its high bone affinity and therapeutic effects on bone diseases. In addition, Alen can enhance the osteogenic differentiation of osteoblastic cell. Recently, nanodiamonds (NDs) with hardness, non-toxicity, and excellent biocompatibility are employed as promising materials for carrier systems and osteogenic differentiation. Therefore, we prepared Alen-conjugated NDs (Alen-NDs) and evaluated their osteogenic differentiation performances.

Methods

Alen-NDs were synthesized using DMTMM as a coupling reagent. Morphological change of Mouse calvaria-derived preosteoblast (MC3T3-E1) treated with Alen-NDs was observed using the confocal microscope. The osteogenic differentiation was confirmed by cell proliferation, alkaline phosphatase (ALP), calcium deposition, and real-time polymerase chain reaction assay.

Results

Alen-NDs were prepared to evaluate their effect on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. The Alen-NDs had a size of about 100 nm, and no cytotoxicity at less than 100 μg/mL of concentration. The treatment of NDs and Alen-NDs reduced the proliferation rate of MC3T3-E1 cells without cell death. Confocal microscopy images confirmed that the treatment of NDs and Alen-NDs changed the cellular morphology from a fibroblastic shape to a cuboidal shape. Flow cytometry, alkaline phosphatase (ALP) activity, calcium deposition, and real-time polymerase chain reaction (RT-PCR) confirmed the higher differentiation of MC3T3-E1 cells treated by Alen-NDs, compared to the groups treated by osteogenic medium and NDs. The higher concentration of Alen-ND treated in MC3T3-E1 resulted in a higher differentiation level.

Conclusions

Alen-NDs can be used as potential therapeutic agents for osteoporosis treatment by inducing osteogenic differentiation.
Assessment of carpal tunnel syndrome via ultrasonography among hospital workers: a screening study
Authors: Fathy Mai , ElSadek Ahmed , Hamid Eman , AbdElMoneim Amr
Published: September 2021

Background

Carpal tunnel syndrome is a reasonably common disorder among working individuals. It may also be a cause of functional impairment. The aim of the study was to screen for the presence of carpal tunnel syndrome among hospital workers by non-invasive ultrasound.

Results

The prevalence of carpal tunnel syndrome diagnosed by ultrasound among hospital workers was 21.5%. Age and Boston carpal tunnel questionnaire scale were positively correlated to median nerve cross sectional area.

Conclusions

Ultrasound can be used as a non-invasive and convenient method for screening for carpal tunnel syndrome.
Outcomes of pregnancy in Egyptian women with multiple sclerosis in the new treatment era: a multi-center retrospective observational study
Authors: Ahmed Ali Mahmoud , Reda Mohamed Al-Bahay M. G. , Elsheshiny Ahmed Hassan
Published: September 2021

Background

Pregnancy is a recent growing issue in multiple sclerosis (MS) and the update in the diagnostic criteria of MS and introduction of many disease-modifying therapies (DMTs) may cause changes in the relationship between MS, pregnancy, and breastfeeding. This study aimed to investigate the effect of pregnancy and breastfeeding on MS and vice versa. A retrospective observational study was conducted to include MS women with a history of at least one pregnancy during the last 7 years. Data were collected from the archived files in addition to a self-administrating questionnaire. The annualized relapsing rate (ARR) was calculated before, during, and after pregnancy.

Results

We included 116 successful pregnancies from 93 MS women with mean age 32.74 ± 5.12 years. Interferon-beta was the commonly used DMT during and after pregnancy. Despite the ARR during the two years preceding the conception was 0.36 (95% CI 0.32–0.41), this rate was significantly decreased during first, second, and third trimester (0.07; 95% CI 0.04–0.15, 0.10; 95% CI 0.03–0.17, and 0.15; 95% CI 0.08–0.24, respectively; P-value < 0.001 in all). Furthermore, this ARR was significantly decreased during the first and last three months after delivery (0.27; 95% CI 0.16–0.39; P-value = 0.037, and 0.24; 95% CI 0.17–0.38; P-value = 0.023). Exclusive breastfeeding was associated with deceased risk of postpartum relapse, with HR 0.31 (95% CI 0.12–0.67; P = 0.002).

Conclusions

Pregnancy is protective from MS relapse, with a significant decrease of ARR from the pre-pregnancy period. Postpartum reactivation of the disease occurs from the third month after labor, rather than the early postpartum period. Exclusive breastfeeding for at least 2 months decreased the risk of postpartum relapse.
Exploring culinary heritage practices among the younger Chetti generations in Melaka
Authors: Mohd Fikri Nurul Hanis , Abdul Rahman Ahmad Esa , Noh Ismayaza
Published: September 2021

Chetti or Peranakan Indian cuisine is a historical creolized minority ethnic cuisine of Malaysia that carries the gene of the country’s multi-ethnic sociocultural development. Its culinary heritage is a unique blend of South Indian, Malay, and Nyonya cuisines. Despite its unique role in symbolizing Malaysia’s status as a multicultural nation, little is documented about the ethnic cuisine. The fact that the Chetti ethnic population is extremely small and continually shrinking means that the future of Chetti cuisine is uncertain. In this context, this paper aims to investigate the role of the younger Chetti generation in reviving the ethnic culinary heritage and the transmission of Chetti traditional food knowledge (TFK) in the contemporary setting. There is evidence that the younger Chetti generation are straying from their culture’s traditional cuisine due to migration, modernization, and urbanization, among other reasons. There are concerns that this may lead to the extinction of Chetti culinary heritage. Semi-structured interviews were conducted with eight younger Chetti participants in the Chetti village of Gajah Berang, Melaka. The qualitative data obtained from the interviews was analyzed using thematic analysis and revealed four relevant themes. The study found that the younger Chetti generation is relatively knowledgeable about their ethnic culinary heritage but overall unskilled. Whilst they predominantly learn about their culture’s cuisine from their mothers, it was found that Chetti ceremonies and festivals, as well as participation in other cultural events, also contribute to TFK transfer among the younger Chetti generation.
Hearing loss and hypertension: exploring the linkage
Authors: Babarinde John Adekunle , Adeyemo Adebolajo A. , Adeoye Abiodun Moshood
Published: September 2021

Background

The inner ear vascular system may be disrupted by systemic hypertension causing inner ear hemorrhage and resulting in progressive or sudden hearing loss. Constriction of the labyrinthine artery secondary to atherosclerosis seen in high BMI and waist/hip circumference—risk factors of hypertension—could also occur with resultant hearing loss. Thus, hypertension could predispose to increased risk of hearing loss. This cross-sectional study assessed the hearing thresholds of hypertensive patients and sought to determine the association between hypertension and hearing loss among patients attending cardiology clinic in tertiary hospital in Nigeria.

Results

The study population was 500 individuals equally divided into subject and control arms. The mean age of the subjects and controls was 47.2 ± 7.4 years and 46.9 ± 7.5 years respectively. Hearing loss—mainly mild sensorineural hearing loss—was seen in 30% of the subjects and 0.4% of the controls. The hearing loss was bilateral in all subjects and slightly worse in the right ears. The hearing loss worsened with increased age, severity, and duration of hypertension; however, there was no association between the hearing loss and body mass index.

Conclusion

There is an association between hypertension and hearing loss, though most of the hypertensive subjects had mild sensorineural hearing loss. The prevalence and severity of the hearing loss worsens with the degree of hypertension. Incorporating regular audiological assessment for hypertensive patients could improve the quality of care for hypertension and quality of life for hypertensive patients.
Memory-efficient source wavefield reconstruction and its application to 3D reverse time migration
Authors: Ren Zhiming , Bao Qianzong , Xu Shigang
Published: September 2021

Reverse time migration (RTM) generally uses the zero-lag crosscorrelation imaging condition, requiring the source and receiver wavefields to be known at the same time step. However, the receiver wavefield is calculated in time-reversed order, opposite to the order of the forward-propagated source wavefield. The inconvenience can be resolved by storing the source wavefield on a computer memory/disk or by reconstructing the source wavefield on the fly for multiplication with the receiver wavefield. The storage requirements for the former approach can be very large. Hence, we have followed the latter route and developed an efficient source wavefield reconstruction method. During forward propagation, the boundary wavefields at N layers of the spatial grid points and a linear combination of wavefields at [Formula: see text] layers of the spatial grid points are stored. During backward propagation, it reconstructs the source wavefield using the saved wavefields based on a new finite-difference stencil ( M is the operator length parameter, and [Formula: see text]). Unlike existing methods, our method allows a trade-off between accuracy and storage by adjusting N. A maximum-norm-based objective function is constructed to optimize the reconstruction coefficients based on the minimax approximation using the Remez exchange algorithm. Dispersion and stability analyses reveal that our method is more accurate and marginally less stable than the method that requires storage of a combination of boundary wavefields. Our method has been applied to 3D RTM on synthetic and field data. Numerical examples indicate that our method with [Formula: see text] can produce images that are close to those obtained using a conventional method of storing M layers of boundary wavefields. The memory usage of our method is [Formula: see text] times that of the conventional method.
Data Matching to Support Analysis of Cancer Epidemiology Among Veterans Compared With Non-Veteran Populations—An Exemplar in Brain Tumors
Authors: Woo Christine , Cioffi Gino N. , Bej Taissa A. , Wilson Brigid , Briggs Janet M. , Markt Sarah C. , Schumacher Fredrick R. , Kruchko Carol , Waite Kristin A. , Nabors L. Burt , Nock Charles J. , Jump Robin L. P. , Barnholtz-Sloan Jill S.
Published: September 2021

PURPOSE

State and national cancer registries do not systematically include Veteran data, which hinders analysis of the diagnosis patterns, treatment trajectories, and clinical outcomes of Veterans compared with non-Veteran populations. This study used data matching approaches to compare cases included in the Oncology Domain of the Veterans Affairs (VA) Corporate Data Warehouse and the Ohio Cancer Incidence Surveillance System, using brain tumors as an exemplar.

METHODS

We used direct data matching, on the basis of protected health information (PHI) common to both databases, to compare primary brain tumors from Veterans and non-Veterans diagnosed from 2000 to 2016. Working with this matched data set, we used six data elements that did not contain PHI, to assess the feasibility of using deterministic data matching to compare Veterans and non-Veterans.

RESULTS

Between 2000 and 2016, 223 Veterans from Ohio had a primary brain tumor; of those, 55 (25%) were not included in Ohio Cancer Incidence Surveillance System. Direct data matching showed that Veterans experienced a greater proportion of glioblastomas (41%) compared with non-Veterans (21%). Sex did not account for this difference. Deterministic data matching within the matched data set found that 75% (126 of 168) of Veterans had exact matches for at least five of six non-PHI variables common to both databases.

CONCLUSION

This study indicated that direct and deterministic data matching approaches to compare brain tumors in Veterans and in non-Veterans is feasible. This approach has the potential to promote comparisons of the distribution of tumors, the impact of chemical and environmental exposures, treatment trajectories, and clinical outcomes among Veteran and non-Veteran populations with brain tumors as well as other cancers and rare diseases.
The Drosophila orthologue of the primary ciliary dyskinesia-associated gene, DNAAF3, is required for axonemal dynein assembly
Authors: zur Lage Petra , Xi Zhiyan , Lennon Jennifer , Hunter Iain , Chan Wai Kit , Bolado Carrancio Alfonso , von Kriegsheim Alex , Jarman Andrew P.
Published: September 2021

Ciliary motility is powered by a suite of highly conserved axoneme-specific dynein motor complexes. In humans, the impairment of these motors through mutation results in the disease primary ciliary dyskinesia (PCD). Studies in Drosophila have helped to validate several PCD genes whose products are required for cytoplasmic pre-assembly of axonemal dynein motors. Here we report the characterisation of the Drosophila orthologue of the less-known assembly factor DNAAF3. This gene, CG17669 (Dnaaf3), is expressed exclusively in developing mechanosensory chordotonal (Ch) neurons and the cells that generate spermatozoa, The only two Drosophila cell types bearing cilia/flagella containing dynein motors. Mutation of Dnaaf3 results in larvae that are deaf and adults that are uncoordinated, indicating defective Ch neuron function. The mutant Ch neuron cilia of the antenna specifically lack dynein arms, while Ca imaging in larvae reveals a complete loss of Ch neuron response to vibration stimulus, confirming that mechanotransduction relies on ciliary dynein motors. Mutant males are infertile with immotile sperm whose flagella lack dynein arms and show axoneme disruption. Analysis of proteomic changes suggest a reduction in heavy chains of all axonemal dynein forms, consistent with an impairment of dynein pre-assembly.
THSC/TREX-2 deficiency causes replication stress and genome instability in Caenorhabditis elegans
Authors: Zheleva Angelina , Camino Lola P. , Fernández-Fernández Nuria , García-Rubio María , Askjaer Peter , García-Muse Tatiana , Aguilera Andrés
Published: September 2021

Transcription is an essential process of DNA metabolism, yet it makes DNA more susceptible to DNA damage. THSC/TREX-2 is a conserved eukaryotic protein complex with a key role in mRNP biogenesis and maturation that prevents genome instability. One source of such instability is linked to transcription, as shown in yeast and human cells, but the underlying mechanism and whether this link is universal is still unclear. To obtain further insight into the putative role of the THSC/TREX-2 complex in genome integrity, we have used Caenorhabditis elegans mutants of the thp-1 and dss-1 components of THSC/TREX-2. These mutants show similar defective meiosis, DNA damage accumulation and activation of the DNA damage checkpoint. However, they differ from each other regarding replication defects, as determined by measuring dUTP incorporation in the germline. Interestingly, this specific thp-1 mutant phenotype can be partially rescued by overexpression of RNase H. Furthermore, both mutants show a mild increase in phosphorylation of histone H3 at Ser10 (H3S10P), a mark previously shown to be linked to DNA–RNA hybrid-mediated genome instability. These data support the view that both THSC/TREX-2 factors prevent transcription-associated DNA damage derived from DNA–RNA hybrid accumulation by separate means.
The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair
Authors: Wilson Patricia , Abdelmoti Lina , Norcross Rebecca , Jang Eun Ryoung , Palayam Malathy , Galperin Emilia
Published: September 2021

The ERK1/2 (also known as MAPK3 and MAPK1, respectively) signaling pathway is critical in organismal development and tissue morphogenesis. Deregulation of this pathway leads to congenital abnormalities with severe developmental dysmorphisms. The core ERK1/2 cascade relies on scaffold proteins, such as Shoc2 to guide and fine-tune its signals. Mutations in SHOC2 lead to the development of the pathology termed Noonan-like Syndrome with Loose Anagen Hair (NSLAH). However, the mechanisms underlying the functions of Shoc2 and its contributions to disease progression remain unclear. Here, we show that ERK1/2 pathway activation triggers the interaction of Shoc2 with the ubiquitin-specific protease USP7. We reveal that, in the Shoc2 module, USP7 functions as a molecular ‘switch’ that controls the E3 ligase HUWE1 and the HUWE1-induced regulatory feedback loop. We also demonstrate that disruption of Shoc2-USP7 binding leads to aberrant activation of the Shoc2-ERK1/2 axis. Importantly, our studies reveal a possible role for USP7 in the pathogenic mechanisms underlying NSLAH, thereby extending our understanding of how ubiquitin-specific proteases regulate intracellular signaling.
Laser ablation of the apical sensory organ ofHydroides elegans(Polychaeta) does not inhibit detection of metamorphic cues
Authors: Nedved Brian T. , Freckelton Marnie L. , Hadfield Michael G.
Published: September 2021

Larvae of many marine invertebrates bear an anteriorly positioned apical sensory organ (ASO) presumed to be the receptor for settlement- and metamorphosis-inducing environmental cues, based on its structure, position and observed larval behavior. Larvae of the polychaete Hydroides elegans are induced to settle by bacterial biofilms, which they explore with their ASO and surrounding anteroventral surfaces. A micro-laser was utilized to destroy the ASO and other anterior ciliary structures in competent larvae of H. elegans. After ablation, larvae were challenged with bacterial biofilmed or clean surfaces and percentage metamorphosis was determined. Ablated larvae were also assessed for cellular damage by applying fluorescently tagged FMRF-amide antibodies and observing the larvae by laser-scanning confocal microscopy. While the laser pulses caused extensive damage to the ASO and surrounding cells, they did not inhibit metamorphosis. We conclude that the ASO is not a required receptor site for cues that induce metamorphosis.
Stress in paradise: effects of elevated corticosterone on immunity and avian malaria resilience in a Hawaiian passerine
Authors: Names Gabrielle R. , Schultz Elizabeth M. , Krause Jesse S. , Hahn Thomas P. , Wingfield John C. , Heal Molly , Cornelius Jamie M. , Klasing Kirk C. , Hunt Kathleen E.
Published: September 2021

Vertebrates confronted with challenging environments often experience an increase in circulating glucocorticoids, which result in morphological, physiological and behavioral changes that promote survival. However, chronically elevated glucocorticoids can suppress immunity, which may increase susceptibility to disease. Since the introduction of avian malaria to Hawaii a century ago, low-elevation populations of Hawaii Amakihi (Chlorodrepanis virens) have undergone strong selection by avian malaria and evolved increased resilience (the ability to recover from infection), while populations at high elevation with few vectors have not undergone selection and remain susceptible. We investigated how experimentally elevated corticosterone affects the ability of high- and low-elevation male Amakihi to cope with avian malaria by measuring innate immunity, hematocrit and malaria parasitemia. Corticosterone implants resulted in a decrease in hematocrit in high- and low-elevation birds but no changes to circulating natural antibodies or leukocytes. Overall, leukocyte count was higher in low- than in high-elevation birds. Malaria infections were detected in a subset of low-elevation birds. Infected individuals with corticosterone implants experienced a significant increase in circulating malaria parasites while untreated infected birds did not. Our results suggest that Amakihi innate immunity measured by natural antibodies and leukocytes is not sensitive to changes in corticosterone, and that high circulating corticosterone may reduce the ability of Amakihi to cope with infection via its effects on hematocrit and malaria parasite load. Understanding how glucocorticoids influence a host's ability to cope with introduced diseases provides new insight into the conservation of animals threatened by novel pathogens.
Single target acuity in the common sunfish (Lepomis gibbosus)
Authors: Spratte Caroline , Sandow Laura-Marie , Schnermann Julia S. , Hanke Frederike D.
Published: September 2021

Vision contributes to foraging, territorial and reproductive behavior in sunfish. In these contexts, sunfish need to perceive single targets, such as prey items or body markings from either conspecifics or individuals of other sunfish species, from some distance. We determined the single target acuity of six common sunfish in a behavioral experiment to assess whether the visual abilities of sunfish correspond with behavioral observations or reactive distance measures, and thus assessed the limits of vision for the mentioned behaviors. Single target acuity for full-contrast single targets amounted to 0.17 deg (0.13–0.32 deg). When contrast was reduced to Weber contrasts of 0.67 and 0.41, single target acuity dropped to 0.34 deg (0.31–0.37 deg), and finally to 0.42 deg (0.34–0.54 deg). Single target acuity would thus allow common sunfish to perceive biologically relevant stimuli at reasonable distances even when contrast is reduced.
Effectiveness of interventions to support the transition home after acute stroke: a protocol for a systematic review
Authors: O'Callaghan Geraldine , Fahy Martin , Murphy Paul , Langhorne Peter , Galvin Rose , Horgan Frances
Published: September 2021

Background

Despite advances in the quality of acute stroke management, there are gaps in knowledge about effective support interventions to better manage the transition of care to home for patients with this complex condition.  The goal of this systematic review is to explore the literature around support interventions available for patients as they navigate from acute hospital, rehabilitation or early supported discharge (ESD) services to independent living at home; and to establish if, in comparison with usual care or other comparative active interventions, support services offered to patients as they transition from acute hospital, inpatient rehabilitation/ESD to home, can achieve better patient and / or process outcomes.

Protocol 

In September 2021, we will carry out, on electronic peer-reviewed databases, a comprehensive literature search based on a pre-defined search strategy, developed and conducted in collaboration with an Information Specialist.   In an effort to identify all published trials we will perform citation tracking of included studies, check reference lists of relevant articles, review grey literature, and extend our search to google scholar.

We will include randomised controlled trials (including cluster and quasi-randomisation) recruiting stroke patients transitioning to home, to receive either usual care or any support intervention designed to improve outcomes after stroke.

The primary clinical outcome will be functional status.  Two review authors will scrutinise trials, categorise them on their eligibility, and extract data. We will analyse the results for all trials and perform meta-analyses where possible.  We will assess risk of bias for the included trials and use GRADE to assess the quality of the body of evidence.

Patient and public involvement (PPI) engaged in the development of the research questions, and will participate in co-design of a strategy for dissemination of findings.

Conclusions: The findings from this review will be used to identify knowledge gaps to direct future research.
Whole genome sequencing of two human rhinovirus A types (A101 and A15) detected in Kenya, 2016-2018
Authors: Luka Martha M. , Kamau Everlyn , de Laurent Zaydah R. , Morobe John Mwita , Alii Leonard K. , Nokes D. James , Agoti Charles N.
Published: September 2021

Background: Virus genome sequencing is increasingly utilized in epidemiological surveillance. Genomic data allows comprehensive evaluation of underlying viral diversity and epidemiology to inform control. For human rhinovirus (HRV), genomic amplification and sequencing is challenging due to numerous types, high genetic diversity and inadequate reference sequences.

Methods: We developed a tiled amplicon type-specific protocol for genome amplification and sequencing on the Illumina MiSeq platform of two HRV types, A15 and A101. We then assessed added value in analyzing whole genomes relative to the VP4/2 region only in the investigation of HRV molecular epidemiology within the community in Kilifi, coastal Kenya.

Results: We processed 73 nasopharyngeal swabs collected between 2016-2018, and 48 yielded at least 70% HRV genome coverage. These included all A101 samples (n=10) and 38 (60.3%) A15 samples.  Phylogenetic analysis revealed that the Kilifi A101 sequences interspersed with global A101 genomes available in GenBank collected between 1999-2016. On the other hand, our A15 sequences formed a monophyletic group separate from the global genomes collected in 2008 and 2019. An improved phylogenetic resolution was observed with the genome phylogenies compared to the VP4/2 phylogenies.

Conclusions: We present a type-specific full genome sequencing approach for obtaining HRV genomic data and characterizing infections.