bluuebunny/crossref_metadata_2025 huggingface dataset:
No Evidence That Music Training Benefits Speech Perception in Hearing-Impaired Listeners: A Systematic Review
Authors: McKay Colette M.
Published: February 2021

As musicians have been shown to have a range of superior auditory skills to non-musicians (e.g., pitch discrimination ability), it has been hypothesized by many researchers that music training can have a beneficial effect on speech perception in populations with hearing impairment. This hypothesis relies on an assumption that the benefits seen in musicians are due to their training and not due to innate skills that may support successful musicianship. This systematic review examined the evidence from 13 longitudinal training studies that tested the hypothesis that music training has a causal effect on speech perception ability in hearing-impaired listeners. The papers were evaluated for quality of research design and appropriate analysis techniques. Only 4 of the 13 papers used a research design that allowed a causal relation between music training and outcome benefits to be validly tested, and none of those 4 papers with a better quality study design demonstrated a benefit of music training for speech perception. In spite of the lack of valid evidence in support of the hypothesis, 10 of the 13 papers made claims of benefits of music training, showing a propensity for confirmation bias in this area of research. It is recommended that future studies that aim to evaluate the association of speech perception ability and music training use a study design that differentiates the effects of training from those of innate perceptual and cognitive skills in the participants.
Dental Restrictions to Clinical Practice during the COVID-19 Pandemic: An Australian Perspective
Authors: Nguyen T.M. , Tonmukayakul U. , Calache H.
Published: February 2021

The coronavirus disease 2019 (COVID-19) has disrupted essential oral healthcare in Australia. Sources for COVID-19 transmission via dental settings is considered to have high potential due to the production of aerosols and because transmission can occur through the airborne route. However, COVID-19 cases in dentistry is reportedly low. Delayed timely dental care, where severe oral diseases remain undetected, untreated, or asymptomatic such as advanced dental caries, periodontitis, and head and neck cancer, can have detrimental consequences for individuals at increased risk for oral diseases. The dental profession should remain vigilant and advocate for the continuation of essential oral healthcare even in times of uncertainty.

Knowledge Transfer Statement:

The reportedly low COVID-19 transmission occurring in dental settings highlight achievements made by the dental profession. There are valid reasons to reconsider risk-based essential oral healthcare during the COVID-19 pandemic.
Does gender diversity in supervisory boards affect gender diversity in management boards in Germany? An empirical analysis
Authors: Fleischer Dennis
Published: February 2021

Social aspects like gender diversity in the boardroom are becoming increasingly relevant and are a popular topic of public debate in the context of gender equality in business. However, there is little clarity about the potential spill-over effects of gender diversity. Both theory and empirical results have led to ambiguous conclusions with respect to the effect of gender diversity in the supervisory board on gender diversity in the management board. In addition, it is not clear whether the German gender quota legislation positively affects this relationship. This study analyses whether gender diversity in the supervisory board supports the gender diversity of the management board, and whether this relationship is affected by the gender quota legislation, focusing on the unique case of Germany. To cope with endogeneity concerns, this study employs a cross-lagged panel model with fixed effects using maximum likelihood structural equation modelling. The results of the analysis of the impact of the number of female supervisory board members on the number of female management board members do not support the view of positive spill-over effects of gender diversity in the environment of the German two-tier corporate governance system. Furthermore, this study finds no evidence of an effect of the German gender quota on this relationship.

JEL Codes

G38, M12, M14, M51
Looking Beyond the Mask: Evolution of Well-being Plans in Corporate India During the Pandemic of 2020
Authors: Krishnan Arvind
Published: February 2021

The coronavirus has altered the well-being efforts in corporate India irrevocably. By altering the working construct from office to home to (possibly) a hybrid, the pandemic has changed the base assumptions of what initiatives are needed by employees, how and where they consume it and how important it has become to the organisations. Like most swords, this has more than one edge. In this article, we attempt to find out, by asking people in industry, what the next year is likely to bring by way of changes in the focus, roll out, funding and measurement of well-being plans in corporate India. The survey indicates a sea change is afoot in how important these programs are, who is responsible for them and what they cover.
Wellness Lessons from Wellness Coaching
Authors: S. Vijayalakshmi
Published: February 2021

Wellness coaching is all about partnering with individuals in a thought-provoking and creative process to enable them to live life to their full potential. A life that is built upon self-awareness and choice; and is self-directed and active. As a wellness coach and mentor, there is a meaningful sense of contribution I experience towards creating a healthier planet, one conversation at a time. Equally so, in this journey of contribution, there is much more I have learnt and gained from my clients—knowledge, insight and deepening of real-life perspectives about wellness!

In this article, I will reflect upon my coaching experiences, build on and outline my learnings regarding the following: How wellness manifests itself in the life of an individual and how wellness coaching can help holistically? Top 10 wellness lessons—that contribute to the success and sustainability of an individual’s wellness journey. These include what could be some of the derailers and challenges in embracing wellness. Insights (based on the above) that organisations and wellness champions could incorporate whilst building wellness programmes.
Health, Healing and Wellness: Combat Corona Initiatives at Mumbai Refinery of HPCL
Authors: Upadhyay Archana Yemeshvary Ashok , Sharma Dharmendra Kumar
Published: February 2021

The outbreak of COVID-19 pandemic during the year 2020 affected various facets of every business. Emphasis on employee health and wellness, digitalization, virtual workplaces and online business became the new normal. This article is a narrative about the multipronged approach adopted by Mumbai refinery of Hindustan Petroleum Corporation Limited (HPCL), an Oil & Gas Central Public Sector Enterprise, towards ensuring continuity of business as well as the health and well-being of its employees and their family members during COVID-19 pandemic. HPCL being in oil and gas sector, which is categorized as ‘essential goods and services’, continued all business as usual even during the nationwide lockdown to ensure uninterrupted supply of petroleum products. The management of the refinery showed exceptional agility and resilience in responding to the challenge and connecting with employees to meet the objective of enhanced employee engagement. Existing policies, systems and procedures were remodelled, and several additional measures were taken to upskill employees to work and perform in the new scenario. The HR team demonstrated sensitivity in curating initiatives towards ensuring health and well-being of employees and their family members as well. The happiness and mindfulness activities organized by HR team helped them overcome fear and anxiety, bond together and connect. Patriotism that stirred out of all these activities kept their spirit high to ensure business continuity. Consequently, Mumbai refinery not only maintained the productivity to serve the nation during the critical period but also witnessed a cultural transition into a ‘caring culture’ focused on employee health, healing and well-being.
Management of Primary Plasma Cell Leukemia Remains Challenging Even in the Era of Novel Agents
Authors: Chaulagain Chakra P , Diacovo Maria-Julia , Van Amy , Martinez Felipe , Fu Chieh-Lin , Jimenez Jimenez Antonio Martin , Ahmed Wesam , Anwer Faiz
Published: February 2021

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of multiple myeloma (MM). PCL is characterized by peripheral blood involvement by malignant plasma cells and an aggressive clinical course leading to poor survival. There is considerable overlap between MM and PCL with respect to clinical, immunophenotypic, and cytogenetic features, but circulating plasma cell count exceeding 20% of peripheral blood leukocytes or an absolute plasma cell count of >2000/mm3 distinguishes it from MM. After initial stabilization and diagnosis confirmation, treatment of PCL in a fit patient typically includes induction combination chemotherapy containing novel agents typically, with proteasome inhibitors (such as bortezomib) and immunomodulatory drugs (eg, lenalidomide), followed by autologous hematopoietic stem cell transplant (HSCT) and multidrug maintenance therapy using novel agents post-HSCT. Long-term outcomes have improved employing this strategy but the prognosis for non-HSCT candidates remains poor and new approaches are needed for such PCL patients not eligible for HSCT. Here, we report a case of primary PCL, and a comprehensive and up to date review of the literature for diagnosis and management of PCL. We also present the findings of Positron Emission Tomography (PET) scan. Since PCL is often associated with extra-medulary disease, including PET scan at the time of staging and restaging may be a novel approach particularly to evaluate the extra-medullary disease sites.
Microbial dysbiosis is associated with aggressive histology and adverse clinical outcome in B-cell non-Hodgkin lymphoma
Authors: Diefenbach Catherine S. , Peters Brandilyn A. , Li Huilin , Raphael Bruce , Moskovits Tibor , Hymes Kenneth , Schluter Jonas , Chen J. , Bennani N. Nora , Witzig Thomas E. , Ahn Jiyoung
Published: February 2021

B-cell non-Hodgkin lymphoma cell survival depends on poorly understood immune evasion mechanisms. In melanoma, the composition of the gut microbiota (GMB) is associated with immune system regulation and response to immunotherapy. We investigated the association of GMB composition and diversity with lymphoma biology and treatment outcome. Patients with diffuse large B-cell lymphoma (DLBCL), marginal zone (MZL), and follicular lymphoma (FL) were recruited at Mayo Clinic, Minnesota, and Perlmutter Cancer Center, NYU Langone Health. The pretreatment GMB was analyzed using 16S ribosomal RNA gene sequencing. We examined GMB compositions in 3 contexts: lymphoma patients (51) compared with healthy controls (58), aggressive (DLBCL) (8) compared with indolent (FL, MZL) (18), and the association of GMB with immunochemotherapy treatment outcomes (8 responders, 6 nonresponders). Respectively, we found that the pretreatment GMB in lymphoma patients had a distinct composition compared with healthy controls (P < .001); GMB compositions in DLBCL patients were significantly different than indolent patients (P = .01) with a trend toward reduced microbial diversity in DLBCL patients (P = .08); and pretreatment GMB diversity and composition were significant predictors of treatment responses (P = .01). The impact of these pilot results is limited by our small sample size, and should be considered a proof of principle. If validated, our results could lead toward improved treatment outcomes by improving medication stewardship and informing which GMB-targeted therapies should be tested to improve patient outcomes.
Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol
Authors: Rajendra Akhil , Jain Hasmukh , Bonda V. N. Avinash , Nayak Lingaraj , Tembhare Prashant , Shetty Dhanlaxmi , Thorat Jayashree , Jain Hemani , Subramanian Papagudi Ganesan , Patkar Nikhil , Chatterjee Gaurav , Khattry Navin , Gokarn Anant , Punatar Sachin , Mokal Smruti , Bagal Bhausaheb , Sengar Manju
Published: February 2021

The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.
A longitudinal study monitoring the quality of life in a national cohort of older adults in Chile before and during the COVID-19 outbreak
Authors: Herrera M. Soledad , Elgueta Raúl , Fernández M. Beatriz , Giacoman Claudia , Leal Daniella , Marshall Pío , Rubio Miriam , Bustamante Felipe
Published: February 2021

Background

Confinement during the COVID-19 pandemic has placed great stress on older adults, which may be affecting their quality of life. Thus, this study aims to describe the changes in mental and physical health, isolation and loneliness, residence and socioeconomic resources in a national cohort of Chilean older adults before and during the COVID-19 outbreak. It also analyzes the changes in depressive symptoms by changes in the other quality of life indicators before and during the COVID-19 outbreak. Possible methodological biases of telephone surveys in older adults living in non-developed countries are also discussed.

Methods

Between June and September 2020, a random subsample of 720 people who had participated in the face-to-face V National Survey on Quality of Life in Older Adults in Chile conducted at the end of 2019 was followed up by telephone. Descriptive bivariate analyses were performed using t-test and non-parametric tests for independent variables, comparing the baseline sample with the current 2020 follow-up sample during the peak of the pandemic outbreak in Latin America. Furthermore, descriptive bivariate analysis through t-test and non-parametric test for paired samples compared the follow-up subsample at baseline with the not-included sample, examining possible biases of the telephone interview compared with the face-to-face interview.

Results

In the panel, there was no variation in self-rated health. The health symptoms that worsened were memory, stomach, and mood problems. Depressive symptoms and anxiety increased; similarly, smartphone users, social contacts, intergenerational co-residence and resilience increased. The telephone follow-up sample had a higher educational level and greater smartphone use than those not included in the subsample.

Conclusions

Although some physical and mental health indicators have worsened during the pandemic, older adults mobilized resources that could allow them to maintain their quality of life, such as improved resilience. Thus, these findings can guide future research and the development of efficient strategies to improve these resources among older adults to ensure wellbeing.
Clinical impact of estradiol/testosterone ratio in patients with acute ischemic stroke
Authors: Choi Jung-Won , Ryoo In Woo , Hong Jun Yeong , Lee Kyung-Yul , Nam Hyo Suk , Kim Won Chan , Oh Seung-Hun , Kang Jaeku , Lee Hoi Young , Na Sang-Jun , Heo Ji Hoe , Lee Kee Ook
Published: February 2021

Background

Sex hormones may be associated with a higher incidence of ischemic stroke or stroke-related events. In observational studies, lower testosterone concentrations are associated with infirmity, vascular disease, and adverse cardiovascular risk factors. Currently, female sexual hormones are considered neuroprotective agents. The purpose of this study was to assess the role of sex hormones and the ratio of estradiol/testosterone (E/T) in patients with acute ischemic stroke (AIS).

Methods

Between January 2011 and December 2016, 146 male patients with AIS and 152 age- and sex-matched control subjects were included in this study. Sex hormones, including estradiol, progesterone, and testosterone, were evaluated in the AIS patient and control groups. We analyzed the clinical and physiological levels of sex hormones and hormone ratios in these patients.

Results

The E/T ratio was significantly elevated among patients in the stroke group compared to those in the control group (P = 0.001). Categorization of data into tertiles revealed that patients with the highest E/T ratio were more likely to have AIS [odds ratio (OR) 3.084; 95% Confidence interval (CI): 1.616-5.886; P < 0.001) compared with those in the first tertile. The E/T ratio was also an independent unfavorable outcome predictor with an adjusted OR of 1.167 (95% CI: 1.053-1.294; P = 0.003).

Conclusions

These findings support the hypothesis that increased estradiol and reduced testosterone levels are associated with AIS in men.
Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells
Authors: Matsuzawa Fumihiko , Kamachi Hirofumi , Mizukami Tatsuzo , Einama Takahiro , Kawamata Futoshi , Fujii Yuki , Fukai Moto , Kobayashi Nozomi , Hatanaka Yutaka , Taketomi Akinobu
Published: February 2021

Background

Mesothelin is a 40-kDa glycoprotein that is highly overexpressed in various types of cancers, however molecular mechanism of mesothelin has not been well-known. Amatuximab is a chimeric monoclonal IgG1/k antibody targeting mesothelin. We recently demonstrated that the combine therapy of Amatuximab and gemcitabine was effective for peritonitis of pancreatic cancer in mouse model.

Methods

We discover the role and potential mechanism of mesothelin blockage by Amatuximab in human pancreatic cells both expressing high or low level of mesothelin in vitro experiment and peritonitis mouse model of pancreatic cancer.

Results

Mesothelin blockage by Amatuximab lead to suppression of invasiveness and migration capacity in AsPC-1 and Capan-2 (high mesothelin expression) and reduce levels of pMET expression. The combination of Amatuximab and gemcitabine suppressed proliferation of AsPC-1 and Capan-2 more strongly than gemcitabine alone. These phenomena were not observed in Panc-1 and MIA Paca-2 (Mesothelin low expression). We previously demonstrated that Amatuximab reduced the peritoneal mass in mouse AsPC-1 peritonitis model and induced sherbet-like cancer cell aggregates, which were vanished by gemcitabine. In this study, we showed that the cancer stem cell related molecule such as ALDH1, CD44, c-MET, as well as proliferation related molecules, were suppressed in sherbet-like aggregates, but once sherbet-like aggregates attached to peritoneum, they expressed these molecules strongly without the morphological changes.

Conclusions

Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.
Gliosarcoma in patients under 20 years of age. A clinicopathologic study of 11 cases and detailed review of the literature
Authors: Din Nasir Ud , Ishtiaq Hira , Rahim Shabina , Abdul-Ghafar Jamshid , Ahmad Zubair
Published: February 2021

Background

Gliosarcoma is a rare variant of IDH- wild type glioblastoma with both glial and mesenchymal differentiation. It accounts for approximately 2% of glioblastomas and has a poor prognosis similar to that of classic glioblastoma. It is seen mostly between 40 and 60 years of age with a mean age over 50 years. Pediatric gliosarcoma is even rarer than gliosarcoma in adults. We describe the clinicopathological features of gliosarcoma in patients under 20 years of age and determine whether there are significant differences from gliosarcoma in adults. We also present detailed review of published literature on pediatric gliosarcoma.

Methods

Slides of gliosarcomas in patients under 20 years of age were reviewed. Clinicopathological features were noted in detail and follow up was obtained.

Results

Eleven cases of gliosarcoma were reported in patients under 20 years of age. Ages ranged from three to 19 years (mean age 13 years). Frontal, parietal and temporal lobes were the commonest locations. Mean and median tumor size was six and five cm respectively. All 11 cases demonstrated the classic biphasic pattern. In 10 cases, glial component was astrocytic and was highlighted on GFAP. Sarcomatous component in most cases resembled fibrosarcoma and was high grade in 72.7%. Glial areas were reticulin poor while sarcomatous areas were reticulin rich. In over 45% cases, bizarre tumor giant cells were seen in the sarcomatous areas. In 1 case, sarcomatous areas showed extensive bone and cartilage formation. Other histologic features included hyalinized blood vessels, hemorrhage, infarction, gemistocytic cells, rhabdoid cells etc. Follow up was available in nine patients, five received chemoradiation post resection while three received radiotherapy only. Prognosis was dismal and eight patients died within one to 14 months following resection.

Conclusions

Gliosarcomas in patients under 20 comprised 13% of all gliosarcomas reported during the study period. Frequency and mean age were higher compared to other published reports. Pathological features were similar to those described in literature. Clinicopathological features and prognosis of pediatric gliosarcomas were similar to adult gliosarcomas.
Clinical profile and outcome of acute organophosphate poisoning in children of Upper Egypt: a cross-sectional study
Authors: Abdel Baseer Khaled A. , Gad Eman Fathala , Abdel Raheem Yaser F.
Published: February 2021

Background

Organophosphates are one of the most common agents of poisoning in developing countries including Egypt. Due to lack of data about characteristics of organophosphates poisoning in our localities, we aimed to evaluate its clinical pattern and factors affecting outcome.

Methods

It was a cross-sectional study conducted in South valley University hospital between January 2019 and December 2019. It included all children ≤16 years of age presented with organophosphates poisoning. Diagnosis was performed from the history taken from the patient’s relatives and presenting symptoms. Demographic data, mode and route of poisoning, time from exposure to presentation, clinical symptomatology, grading and routine investigations were evaluated in addition to treatment taken and outcome.

Results

During the study period, 108 children; mean age was 7.95 ± 4.11 years (range 1. 5-16 years) presented with organophosphorous poisoning. Sixty five (60%) cases were females and 43 (40%) were males. Unintentional acts (87%) were detected more than suicidal (13%) and inhalation route (63.8%) more than ingestion (36. 2%). Miosis was the most frequent clinical sign (100%) followed by respiratory distress (77.7%). Regarding time of presentation to emergency department, 43 (40%) cases were presented within 6 h while others presented more than 6 h post-exposure. Mechanical ventilation (MV) was needed for 14 (13%) cases and 6 (5.5%) cases died due to respiratory failure. Duration of hospital stay, mean time interval from toxic exposure to hospital presentation, leucocytosis, need for MV and cumulative dose of pralidoxime were significantly higher in non survivors than survivors while Pao2 (partial arterial oxygen) and GCS (Glasgow coma scale) were significantly lower.

Conclusion

This study concluded that time consumed till presentation to hospital, low GCS, need for MV, leucocytosis, decreased PaO2 and increased cumulative dose of pralidoxime were independent risk factors of mortality.
Global and reflective rumination are related to suicide attempts among patients experiencing major depressive episodes
Authors: Tang Hao , Xiong Tingting , Shi Jiabo , Chen Yu , Liu Xiaoxue , Zhang Siqi , Wang Huan , Lu Qing , Yao Zhijian
Published: February 2021

Background

Recent attention has focused on the role of rumination in suicidality, with evidence indicating that rumination may be positively related to suicidal ideation. There remains disagreement on the nature of the relationship between rumination and suicide attempts, especially in major affective disorders. This study was designed to identify whether rumination is a risk factor for attempted suicide.

Methods

A total of 309 patients with major depressive episodes were recruited for this study, including 170 patients with major depression and 139 patients with bipolar disorder. All participants were categorized into two groups based on a series of clinical assessments: suicide attempters (n = 87) and non-suicide attempters (n = 222). Rumination was evaluated with the Ruminative Responses Scale. A binary logistic regression analysis was carried out to evaluate the relationship between rumination and suicide attempts.

Results

Both global ruminative levels and the two subtypes of rumination, brooding and reflection, were significantly higher in the suicide attempters than the non-suicide attempters. After controlling for age, current depression and anxiety symptoms, and episode frequency, it was found that global rumination and reflection (but not brooding) were positively associated with suicide attempts.

Conclusion

These results suggest that rumination may be a risk factor for suicide attempts and highlight the maladaptive nature of reflection in patients with major depressive episodes.
Clinical features and prognostic analysis of patients with Aspergillus isolation during acute exacerbation of chronic obstructive pulmonary disease
Authors: Gu Yu , Ye Xianping , Wang Yu , Shen Kunlu , Zhong Jinjin , Chen Bilin , Su Xin
Published: February 2021

Background

Lower respiratory tract (LRT) specimen culture is widely performed for the identification of Aspergillus. We investigated the clinical features and prognosis of patients with Aspergillus isolation from LRT specimens during acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

This is a 6-year single-center, real-world study. 75 cases out of 1131 hospitalized AECOPD patients were positive for Aspergillus. These patients were carefully evaluated and finally diagnosed of pulmonary aspergillosis (PA, 60 cases, 80%) or colonization (15 cases, 20%). Comparisons of clinical data were performed between these two groups. A cox regression model was used to confirm prognostic factors of Aspergillus infection.

Results

The PA group had worse lung function and higher rates of systemic corticosteroid use and broad-spectrum antibiotic use before admission than the colonization group. The PA group had significantly higher in-hospital mortality and 180-day mortality than the colonization group (45% (27/60) vs. 0% (0/15), p = 0.001, and 52.5% (31/59) vs. 6.7% (1/15), p < 0.001, respectively). By multivariable analysis among Aspergillus infection patients, antifungal therapy (HR 0.383, 95% CI 0.163–0.899, p = 0.027) was associated with improved survival, whereas accumulated dose of systemic steroids > 700 mg (HR 2.452, 95% CI 1.134–5.300, p = 0.023) and respiratory failure at admission (HR 5.983, 95% CI 2.487–14.397, p < 0.001) were independently associated with increased mortality. Significant survival differential was observed among PA patients without antifungals and antifungals initiated before and after Aspergillus positive culture (p = 0.001).

Conclusions

Aspergillus isolation in hospitalized AECOPD patients largely indicated PA. AECOPD patients with PA had worse prognosis than those with Aspergillus colonization. Empirical antifungal therapy is warranted to improve the prognosis for Aspergillus infection.
A comparative analysis of NLRP3-related inflammatory mediators in synovial fluid in temporomandibular joint osteoarthritis and internal derangement
Authors: Jia Mengying , Lv Yaoguang , Xu Yingjie , Gong Zhongcheng
Published: February 2021

Background

The nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathway is a highlighted topic in the field of inflammation. However, there is little research on the relationship between the NLRP3 inflammasome pathway and temporomandibular joint osteoarthritis (TMJOA). The aim of this study was to examine the expression of inflammatory mediators related to the NLRP3 inflammasome in the synovial fluid of patients with condylar cartilage degeneration and verify the clinical effects of sodium hyaluronic acid (HA) treatment on TMJOA.

Methods

Patients diagnosed with temporomandibular joint internal derangement (TMJID) without condylar defects and TMJOA with condylar defects were divided into two groups. There were thirty patients in each group, and inflammatory mediators related to the NLRP3 inflammasome, including interleukin-1 beta (IL-1β), IL-18, NLRP3, and cysteinyl aspartate specific proteinase 1 (CASP1), in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Eighteen patients in the TMJOA group were retested after two HA treatments to evaluate the therapeutic effects of HA.

Results

IL-1β, IL-18, NLRP3 and CASP1 were all positive in the two groups, and TMJOA patients with condylar defects had higher expression of these molecules than TMJID patients (P < 0.05). IL-1β, IL-18, and NLRP3 were decreased after two HA treatments (P<0.05), but there was no significant difference in CASP1 after two HA injections (P = 0.549).

Conclusions

The NLRP3 inflammasome signaling pathway may be involved in condylar degeneration. HA could reduce some inflammatory molecules to alleviate inflammation.
The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China
Authors: Weerasuriya Chathika K , Harris Rebecca C , McQuaid C Finn , Bozzani Fiammetta , Ruan Yunzhou , Li Renzhong , Li Tao , Rade Kirankumar , Rao Raghuram , Ginsberg Ann M , Gomez Gabriela B , White Richard G
Published: February 2021

Background

Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India.

Methods

We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses.

Results

By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 73% (UI:66–76) and 72% (UI:65–77), and the PSI vaccine by 29% (UI: 27–31) and 47% (UI: 37–58) in China and India, respectively.

In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 1.0 million (UI: 0.6–1.3) and 0.8 million (UI: 0.5–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively.

Conclusions

Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.
A hemizygous mutation in the FOXP3 gene (IPEX syndrome) resulting in recurrent X-linked fetal hydrops: a case report
Authors: Shangaris Panicos , Ho Alison , Marnerides Andreas , George Simi , AlAdnani Mudher , Yau Shu , Jansson Mattias , Hoyle Jacqueline , Ahn Joo Wook , Ellard Sian , Irving Melita , Wellesley Diana , Pasupathy Dharmintra , Holder-Espinasse Muriel
Published: February 2021

Background

Fetal hydrops is excessive extravasation of fluid into the third space in a fetus, which could be due to a wide differential of underlying pathology. IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome primarily affects males. It is a monogenic primary immunodeficiency syndrome of X-linked recessive inheritance due to FOXP3 gene variants. It is characterised by the development of multiple autoimmune disorders in affected individuals.

Case presentation

We present a rare cause of male fetal hydrops in the context of IPEX syndrome and discuss FOXP3 gene variants as a differential for ‘unexplained’ fetal hydrops that may present after the first trimester.

Discussion and conclusions

In all similar cases, the pathological process begins during intrauterine life. Furthermore, there are no survivors described. Consequently, this variant should be considered as a severe one, associated with intrauterine life onset and fatal course, i.e., the most severe IPEX phenotype.
Optimization of whole-genome sequencing of Plasmodium falciparum from low-density dried blood spot samples
Authors: Teyssier Noam B. , Chen Anna , Duarte Elias M. , Sit Rene , Greenhouse Bryan , Tessema Sofonias K.
Published: February 2021

Background

Whole-genome sequencing (WGS) is becoming increasingly useful to study the biology, epidemiology, and ecology of malaria parasites. Despite ease of sampling, DNA extracted from dried blood spots (DBS) has a high ratio of human DNA compared to parasite DNA, which poses a challenge for downstream genetic analyses. The effects of multiple methods for DNA extraction, digestion of methylated DNA, and amplification were evaluated on the quality and fidelity of WGS data recovered from DBS.

Methods

Low parasite density mock DBS samples were created, extracted either with Tween-Chelex or QIAamp, treated with or without McrBC, and amplified with one of three different amplification techniques (two sWGA primer sets and one rWGA). Extraction conditions were evaluated on performance of sequencing depth, percentiles of coverage, and expected SNP concordance.

Results

At 100 parasites/μL, Chelex-Tween-McrBC samples had higher coverage (5 × depth = 93% genome) than QIAamp extracted samples (5 × depth = 76% genome). The two evaluated sWGA primer sets showed minor differences in overall genome coverage and SNP concordance, with a newly proposed combination of 20 primers showing a modest improvement in coverage over those previously published.

Conclusions

Overall, Tween-Chelex extracted samples that were treated with McrBC digestion and are amplified using 6A10AD sWGA conditions had minimal dropout rate, higher percentages of coverage at higher depth, and more accurate SNP concordance than QiaAMP extracted samples. These findings extend the results of previously reported methods, making whole genome sequencing accessible to a larger number of low density samples that are commonly encountered in cross-sectional surveys.
Recombinant human endostatin combined with chemotherapy for advanced squamous cell lung cancer: a meta-analysis
Authors: Feng Li , Wang Zhicong , Jing Li , Zhou Zhiguo , Shi Shuai , Deng Ruoying , Liu Yibing , Meng Qingju
Published: February 2021

Background

This paper aims to compare the efficacy and safety of recombinant human endostatin combined with chemotherapy in patients with squamous cell lung cancer (SqCLC).

Methods

We searched the Cochrane Library, PubMed, Embase, CNKI, Wanfang database, Metstr, VIP, and others and manually searched books and magazines until 2019 for articles about the efficacy and safety of recombinant human endostatin combined with chemotherapy in patients with SqCLC. A second search was conducted on the review literature. According to the criteria of the literature screen, the relevant randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) of recombinant human endostatin combined with chemotherapy and chemotherapy alone in the treatment of SqCLC were included. After the data were extracted and analyzed, RevMan 5.3 software was used for meta-analysis for the outcome indicators. Then, heterogeneity tests and sensitivity analyses were carried out, and the publication bias of this study was tested in Stata 13.0 software. Six RCTs and eight non-RCTs were included. In total, 821 patients with SqCLC were included.

Results

The response rate (RR) was 2.12 (95% CI: 1.57–2.85, p < 0.00001). The disease control rate (DCR) was 2.38 (95% CI: 1.70–3.32, p < 0.00001). The difference between the two groups was statistically significant. Regarding safety, the incidence rates of the adverse reactions cardiotoxicity, leukopenia, thrombocytopenia, and gastrointestinal reactions were not significantly different between the two groups (OR = 1.70, 95% CI: 0.79–3.68; OR = 0.93, 95% CI: 0.61–1.42; OR = 1.08, 95% CI: 0.71–1.64; OR = 0.86, 95% CI: 0.56–1.30, respectively).

Conclusion

The combined treatment had a better therapeutic effect than chemotherapy alone. It did not increase the incidence of adverse reactions in the course of treatment.
RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent
Authors: Wang Xin , Tian Linli , Li Yushan , Wang Jingting , Yan Bingrui , Yang Like , Li Qiuying , Zhao Rui , Liu Ming , Wang Peng , Sun Yanan
Published: February 2021

Background

Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood.

Methods

The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability.

Results

The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a “writer” of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the proliferation, invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent.

Conclusion

Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.
Safety and family satisfaction of a home-delivered chemotherapy program for children with cancer
Authors: De Zen Lucia , Del Rizzo Irene , Ronfani Luca , Barbieri Francesca , Rabusin Marco , Dall’Amico Roberto , Barbi Egidio , Robazza Margherita
Published: February 2021

Background

Home chemotherapy programs for children with cancer are safe and feasible, and their impact on the quality of life has been reported in different countries. A home chemotherapy program was implemented between 2011 and 2019 in an Italian region. This pilot study investigates its safety and feasibility, along with parental satisfaction.

Methods

Patients between 0 and 18 years diagnosed with malignancy were included. Deceased patients and patients whose families moved abroad or interrupted contact with the service were excluded. Adverse events comprised immediate deterioration of the patient’s condition, equipment failure, errors in drug storage, dose or patient identification and personnel safety issues. Parental satisfaction was explored through an email survey of 32 Likert-type and short open questions.

Results

Thirty-five patients received 419 doses of intravenous chemotherapy at home (cytarabine, vincristine, vinblastine). No adverse events were reported. Twenty-three families out of 25 eligible completed the survey. Most reported being “very satisfied” with the possibility of maintaining a work/domestic routine and reducing time and financial burden of hospital access. Most were “very satisfied” with the opportunity for their child of being less troubled by the treatment. Besides, most reported being “very satisfied” with the chance for healthy siblings of maintaining their routine and coping with their brother/sister’s disease. Most perceived the program as safe. All families recommended extending the program to all children in the region.

Conclusions

This first Italian study supports home chemotherapy as safe and effective, positively influencing the quality of life for children and their families.
Descriptive analysis of a comparison between lung ultrasound and chest radiography in patients suspected of COVID-19
Authors: Volpicelli Giovanni , Cardinale Luciano , Fraccalini Thomas , Calandri Marco , Piatti Clara , Geninatti Carlotta , Stranieri Giuseppe
Published: February 2021

Background

Lung ultrasound (LUS) and chest radiography (CXR) are the most used chest imaging tools in the early diagnosis of COVID-19 associated pneumonia. However, the relationship between LUS and CXR is not clearly defined. The aim of our study was to describe the comparison between LUS interpretation and CXR readings in the first approach to patients suspected of COVID-19.

Methods

In the time of the first COVID-19 pandemic surge, we prospectively evaluated adult patients presenting to an emergency department complaining of symptoms raising suspicion of COVID-19. Patients were studied by LUS and only those performing also CXR were analyzed. All the patients performed viral reverse transcriptase-polymerase chain reaction (RT-PCR). LUS studies were classified in 4 categories of probabilities, based on the presence of typical or alternative signs of COVID-19-associated interstitial pneumonia. Accordingly, the CXR readings were retrospectively adapted by 2 experts in 4 categories following the standard language that describes the computed tomography (CT) findings. Patients were divided in two groups, based on the agreement of the LUS and CXR categories. Results were also compared to RT-PCR and, when available, to CT studies.

Results

We analyzed 139 cases (55 women, mean age 59.1 ± 15.5 years old). The LUS vs CXR results disagreed in 60 (43.2%) cases. RT-PCR was positive in 88 (63.3%) cases. In 45 cases, a CT scan was also performed and only 4 disagreed with LUS interpretation versus 24 in the comparison between CT and CXR. In 18 cases, LUS detected signs of COVID-19 pneumonia (high and intermediate probabilities) while CXR reading was negative; in 14 of these cases, a CT scan or a RT-PCR-positive result confirmed the LUS interpretation. In 6 cases, LUS detected signs of alternative diagnoses to COVID-19 pneumonia while CXR was negative; in 4 of these cases, CT scan confirmed atypical findings.

Conclusion

Our study demonstrated a strong disagreement between LUS interpretation and CXR reading in the early approach to patients suspected of COVID-19. Comparison with CT studies and RT-PCR results seems to confirm the superiority of LUS over a second retrospective reading of CXR.
Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results
Authors: van de Beek M. , van Steenoven I. , van der Zande J. J. , Porcelijn I. , Barkhof F. , Stam C. J. , Raijmakers P. G. H. M. , Scheltens P. , Teunissen C. E. , van der Flier W. M. , Lemstra A. W.
Published: February 2021

Background

The DEmEntia with LEwy bOdies Project (DEvELOP) aims to phenotype patients with dementia with Lewy bodies (DLB) and study the symptoms and biomarkers over time. Here, we describe the design and baseline results of DEvELOP. We investigated the associations between core and suggestive DLB symptoms and different aspects of disease burden, i.e., instrumental activities of daily living (IADL) functioning, quality of life (QoL), and caregiver burden.

Methods

We included 100 DLB patients (69 ± 6 years, 10%F, MMSE 25 ± 3) in the prospective DEvELOP cohort. Patients underwent extensive assessment including MRI, EEG/MEG, 123FP-CIT SPECT, and CSF and blood collection, with annual follow-up. Core (hallucinations, parkinsonism, fluctuations, RBD) and suggestive (autonomous dysfunction, neuropsychiatric symptoms) symptoms were assessed using standardized questionnaires. We used multivariate regression analyses, adjusted for age, sex, and MMSE, to evaluate how symptoms related to the Functional Activities Questionnaire, QoL-AD questionnaire, and Zarit Caregiver Burden Interview.

Results

In our cohort, RBD was the most frequently reported core feature (75%), while visual hallucinations were least frequently reported (39%) and caused minimal distress. Suggestive clinical features were commonly present, of which orthostatic hypotension was most frequently reported (64%). Ninety-five percent of patients showed EEG/MEG abnormalities, 88% of 123FP-CIT SPECT scans were abnormal, and 53% had a CSF Alzheimer’s disease profile. Presence of fluctuations, lower MMSE, parkinsonism, and apathy were associated with higher IADL dependency. Depression, constipation, and lower IADL were associated with lower QoL-AD. Apathy and higher IADL dependency predisposed for higher caregiver burden.

Conclusion

Baseline data of our prospective DLB cohort show clinically relevant associations between symptomatology and disease burden. Cognitive and motor symptoms are related to IADL functioning, while negative neuropsychiatric symptoms and functional dependency are important determinants of QoL and caregiver burden. Follow-up is currently ongoing to address specific gaps in DLB research.