bluuebunny/crossref_metadata_2025 huggingface dataset:
Covering #MeToo across the News Spectrum: Political Accusation and Public Events as Drivers of Press Attention
Authors: Ghosh Shreenita , Su Min-Hsin , Abhishek Aman , Suk Jiyoun , Tong Chau , Kamath Kruthika , Hills Ornella , Correa Teresa , Garlough Christine , Borah Porismita , Shah Dhavan
Published: October 2020

Garnering coverage across the political spectrum is a major challenge for burgeoning social movements. The #MeToo movement stands out due to the volume of attention it generated. Yet, it is unclear how news media across the partisan spectrum covered the movement using different sexual violence language markers, latent topic, and word choices and which accusations and events drove media attention. To examine this, we used Media Cloud to extract 17,877 news articles from nine media outlets across the political spectrum, containing specific n-grams or co-occurrences of (1) “metoo,” (2) “sexual misconduct,” (3) “sexual harassment,” and (4) “sexual assault” from October 2017 through February 2018. The analyses first examined whether language and attention differed across the ideological news ecology and then turned to time-series modeling of these discourses to examine what drove press coverage and structural topic modeling (STM) and term frequency-inverse document frequency (TF-IDF) analysis to understand latent topics and language usage. Findings reveal that (1) left-leaning media dedicated more relative attention across all topics—#MeToo, sexual misconduct, sexual harassment, and sexual assault—relative to centrist and right-leaning media. Moreover, across the right, left, and centrist media, the language markers “misconduct,” “harassment,” and “assault” decreased over the study period, while the mentions of #MeToo movement increased during the same period; (2) stories relating to entertainment and those accusing politicians, especially those belonging to the party in power at the Federal level, seemed to be by far the strongest driver of news media attention; and (3) we further observed partisan differences in topics of news coverage and language usage.
The state of wearable health technologies: a transdisciplinary literature review
Authors: Li Caining , Lin Sapphire H. , Chib Arul
Published: October 2020

This review evaluated transdisciplinary empirical research on wearable health technologies using the input-mechanism-output model and addressed a major concern relating to the invasiveness of wearables. The dataset consisted of 250 published papers that investigated wearables for health-related purposes. Papers focused on technological inputs and health output factors, de-emphasizing theoretical mechanisms that could effectively translate the former into the latter. The lack of transdisciplinary research in the field is limiting both identification of effectiveness and evidence of beneficial health outcomes, with a considerable divide between technologists and public health researchers. Privacy concerns relate to increasing trends in collecting data for mental health and physical health, with the latter escalating exponentially. Invasiveness of wearables has increased over time in terms of collected signals and the derived health information, monitoring both users and their social and physical environments. We conclude with reflections for conceptual development, commercial application and policy regulation.
Development and Validation of Nine Deprescribing Algorithms for Patients on Hemodialysis to Decrease Polypharmacy
Authors: Lefebvre Melissa J. , Ng Patrick C. K. , Desjarlais Arlene , McCann Dennis , Waldvogel Blair , Tonelli Marcello , Garg Amit X. , Wilson Jo-Anne , Beaulieu Monica , Marin Judith , Orsulak Cali , Lloyd Anita , McIntyre Caitlin , Feldberg Jordanne , Bohm Clara , Battistella Marisa
Published: October 2020

Background:

Polypharmacy is ubiquitous in patients on hemodialysis (HD), and increases risk of adverse events, medication interactions, nonadherence, and mortality. Appropriately applied deprescribing can potentially minimize polypharmacy risks. Existing guidelines are unsuitable for nephrology clinicians as they lack specific instructions on how to deprescribe and which safety parameters to monitor.

Objective:

To develop and validate deprescribing algorithms for nine medication classes to decrease polypharmacy in patients on HD.

Design:

Questionnaires and materials sent electronically.

Participants:

Nephrology practitioners across Canada (nephrologists, nurse practitioners, renal pharmacists).

Methods:

A literature search was performed to develop the initial algorithms via Lynn’s method for development of content-valid clinical tools. Content and face validity of the algorithms was evaluated over three interview rounds using Lynn’s method for determining content validity. Canadian nephrology clinicians each evaluated three algorithms (15 clinicians per round, 45 clinicians in total) by rating each algorithm component on a four-point Likert scale for relevance; face validity was rated on a five-point scale. After each round, content validity index of each component was calculated and revisions made based on feedback. If content validity was not achieved after three rounds, additional rounds were completed until content validity was achieved.

Results:

After three rounds of validation, six algorithms achieved content validity. After an additional round, the remaining three algorithms achieved content validity. The proportion of clinicians rating each face validity statement as “Agree” or “Strongly Agree” ranged from 84% to 95% (average of all five questions, across three rounds).

Limitations:

Algorithm development was guided by existing deprescribing protocols intended for the general population and the expert opinions of our study team, due to a lack of background literature on HD-specific deprescribing protocols. There is no universally accepted method for the validation of clinical decision-making tools.

Conclusions:

Nine medication-specific deprescribing algorithms for patients on HD were developed and validated by clinician review. Our algorithms are the first medication-specific, patient-centric deprescribing guidelines developed and validated for patients on HD.
Communal Violence in Twenty-first Century India: Moving Beyond the Hindi Heartland
Authors: Shastri Sanjal
Published: October 2020

Using communal violence data between 2006 and 2017, this study challenges the idea that communal violence is primarily an issue in the Hindi Heartland. The data demonstrates how Karnataka and West Bengal are also witnessing rising levels of communal violence. The study goes on to take a closer look at the rise of the Bharatiya Janata Party (BJP) in Karnataka and West Bengal. It demonstrates how a combination of factors ranging from localized narratives of Hindu nationalism, caste coalitions, alliances with regional parties and the decline of the Communist Party of India (Marxist) (CPI[M]) in West Bengal and the Janata Party (JP)/Dal in Karnataka have been crucial factors for BJP’s rise in these two states.
Return to Play and Performance After Primary ACL Reconstruction in American Football Players: A Systematic Review
Authors: Ross Bailey J. , Savage-Elliott Ian , Brown Symone M. , Mulcahey Mary K.
Published: October 2020

Background:

Anterior cruciate ligament (ACL) injuries are among the most common sports-related injuries, and they can have a negative impact on players’ ability to return to play (RTP). There is a paucity of literature focused on RTP after ACL reconstruction (ACLR) in collision sports.

Purpose:

To characterize the impact that an ACL injury has on the ability to RTP and the post-ACLR performance level in American football players.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

An electronic search was performed using the following databases: the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature. Included studies were written in English; were published since the year 2000; examined only American football players; and reported on RTP, performance, and/or career length after primary ACLR.

Results:

The initial search yielded 442 unique studies. Of these, 427 were removed after screening, leaving 15 studies that met inclusion criteria. An additional 2 studies were identified in these studies’ references, yielding a total of 17. The rate of RTP after ACLR for football players was 67.2% (1249/1859), and the mean time to return was 11.6 months (range, 35.8-55.8 weeks). Although considerable heterogeneity existed in the study design and outcomes measured, in general, a majority of football players experienced greater declines from their preinjury performance level than controls over the same time period.

Conclusion:

An ACL injury negatively affected football players’ ability to RTP and their post-ACLR performance. The degree of effect varied by several factors, including playing position, preinjury performance level, and National Football League Draft round. These results may be used by physicians and football players to develop reasonable expectations for returning to play and performance after an ACL injury.
Role of greater occipital nerve block for preventive treatment of chronic migraine: A critical review
Authors: Chowdhury Debashish , Mundra Ankit
Published: October 2020

Objective:

The aim of this study is to critically analyze the evidence of the efficacy and safety of greater occipital nerve (GON) block for the preventive treatment of chronic migraine (CM).

Background:

A rigorous scientific assessment of efficacy and safety of the GON block for preventive treatment in CM is not available. This critical review was undertaken for this purpose.

Methods:

References for this review were identified by searches of articles published in the English language in PubMed between 1969 and April 15, 2020 using “greater occipital nerve block,” “chronic migraine,” “migraine,” “headache,” and “treatment” as keywords.

Results:

Out of potential 532 articles, 9 open-label and 4 placebo-controlled trials that studied the role of GON block for prevention of CM were identified and reviewed. Open-label trials reported a reduction of headache severity and frequency in 35–68% of patients. The beneficial effect of a single block lasted up to 4 weeks. Randomized controlled trials (RCTs) used varied methodology and techniques of GON block and the outcomes were reported at different time points. A single RCT showed a beneficial effect of the GON block at 1 week. However, the GON block was found to be safe and well tolerated.

Conclusion:

Long-term efficacy of GON block in CM shall need further well-designed RCTs using standardized methodology. This study, in addition, reviewed the limitations and uncertainties regarding the technique and methods of use of GON block in CM.
Awareness of Stroke Warning Symptoms, Risk Factors, and Response to Acute Stroke in Biswanath District, Assam, India
Authors: Kurmi Sima , Mathews Elezebeth , Kodali Prakash Babu , Thankappan K. R.
Published: October 2020

Introduction:

This study was undertaken with the following objectives: (a) to find out the awareness of warning symptoms and risk factors of stroke, (b) response to acute stroke, and (c) factors associated with awareness, risk factors, and response to acute stroke among community-dwelling adults in Biswanath district of Assam.

Methods:

Using a cross-sectional design, a community-based study was done among 340 adults (mean age 38 years, men 55%) selected using multistage cluster sampling. Information on sociodemographic variables, stroke warning symptoms, risk factors, and response to acute stroke was collected using an adapted World Health Organization (WHO) STEPs stroke surveillance tool. Bivariate and logistic regression analysis were done to find out the factors associated with stroke warning symptoms, risk factors, and response to acute stroke. A “ P” value < .05 was considered for statistical significance.

Results:

Awareness of stroke was significantly higher among males ( P < .01), better educated ( P < .01), government employees ( P < .05), high-income group ( P < .01), and those who reported receiving information from a professional source ( P < .01) compared to their counterparts. Knowledge of at least one stroke risk factor and providing at least one correct response to acute stroke was higher among males, better educated, government employees, higher income groups, and those who received information from professional source compared to their counterparts ( P < .05).

Conclusion:

Awareness of stroke warning symptoms, risk factors, and response to acute stroke needs to be improved focusing on women, low education groups, those working in the nongovernment sector, and low-income groups by health professionals.
Ultrasonography-Guided Core Needle Biopsy Diagnostic Value in Breast Lump Assessment: An Experience From the Middle East
Authors: Al-Ismaeel Ahmed Hussein , Nugud Ahmed , Nugud Assmaa , Nugud Shomous
Published: October 2020

Objective:

Breast cancer is a leading cause of mortality in industrialized and developing countries. Mammography and a core needle biopsy are among the detection methods that are used to diagnose and confirm tumor subtypes.

Methods:

A retrospective, noninterventional observational study was conducted in a tertiary center between January 2009 and December 2014. A total of 265 patients underwent ultrasonography (US)–guided core needle biopsy (CNB). A cohort of 147 patients met the inclusion criteria and data were subsequently extracted from their medical records.

Results:

From this cohort, US-CNB detected malignant lesions in 109 patients, with a total sensitivity and specificity for malignancy at 96.33% and 75.10%, respectively. The most frequent malignant tumor diagnosed with US-CNB was invasive ductal carcinoma. The most common benign masses detected were 38 (32.1%) fibroadenomas and fat necrosis. The positive and negative predictive values for US-CNB were 92.4% and 87.5%, respectively.

Conclusion:

The findings would suggest that the use of US-CNB could play a major role in the identification and management of the breast lesions. It could also redeem any biopsy errors or operator inexperience. Sensitivity and specificity in detecting tumors, malignant or benign, using US-CNB could aid in efforts to provide an appropriate medical management plan.
Collateral effects of the coronavirus disease 2019 pandemic on lung cancer diagnosis in Korea
Authors: Park Ji Young , Lee Ye Jin , Kim Taehee , Lee Chang Youl , Kim Hwan Il , Kim Joo-Hee , Park Sunghoon , Hwang Yong Il , Jung Ki-Suck , Jang Seung Hun
Published: October 2020

Background

The COVID-19 pandemic is predicted to significantly affect patients with lung cancer, owing to its rapid progression and high mortality. Studies on lung cancer diagnosis and treatment during an epidemic are lacking. We analyzed the impact of COVID-19 on lung cancer diagnosis in Korea, where lung cancer incidence continues to rise.

Methods

The number of newly diagnosed lung cancer cases in three university-affiliated hospitals during the pandemic and their clinical features were compared with lung cancer cases diagnosed during the same period in the past 3 years. The effectiveness of measures taken by the study hospitals to prevent nosocomial transmission was reviewed.

Results

A total of 612 patients were diagnosed with lung cancer from February through June, 2017–2020. During the pandemic, the number of patients who sought consultation at the division of pulmonology of study hospitals dropped by 16% from the previous year. Responding to the pandemic, the involved hospitals created physically isolated triage areas for patients with acute respiratory infection symptoms. Wide-range screening and preventive measures were implemented, thus minimizing the delay in lung cancer diagnosis. No patient acquired COVID-19 due to hospital exposure. The proportion of patients with stage III–IV non-small-cell lung cancer (NSCLC) significantly increased (2020: 74.7% vs. 2017: 57.9%, 2018: 66.7%, 2019: 62.7%, p = 0.011). The number of lung cancers diagnosed during this period and the previous year remained the same.

Conclusions

The proportion of patients with advanced NSCLC increased during the COVID-19 pandemic.
An atypical presentation of a mesenteric Meckel’s diverticulum in a 7-year-old warmblood mare: case report
Authors: Stas E. , Kranenburg L. , Witt P. , de Grauw J. , van den Brand J. , Ensink J. , Brommer H.
Published: October 2020

Background

Meckel’s diverticula are a rare cause of small intestinal strangulation, diagnosed at laparotomy or necropsy. This congenital anomaly of the gastrointestinal tract originates from a remnant of the vitelline duct. In reported equine cases, they present as a full-thickness diverticulum on the antimesenteric border of the distal jejunum or proximal ileum.

Case presentation

On laparotomy a Meckel’s diverticulum positioned at the mesenteric side was found to be the cause of small intestinal strangulation. This position is very uncommon and to the best knowledge of the authors there is no unambiguous description of another case.

Conclusions

Meckel’s diverticula should be on the list of differential diagnoses in cases of small intestinal strangulation. As in humans, equine Meckel’s diverticula can have the standard antimesenteric as well as a more exceptional mesenteric location. This case adds to the series of anecdotal reports of anomalies with regard to Meckel’s diverticula in the horse.
Effects of dietary supplementation with different concentration of molasses on growth performance, blood metabolites and rumen fermentation indices of Nubian goats
Authors: Osman Osman A. , Elkhair Nawal M. , Abdoun Khalid A.
Published: October 2020

Background

Molasses is a potential energy supplement; extensively used to improve growth performance, milk and meat characteristics in goats at relatively low concentrations of 5–40% of the diet. Few data are available concerning feeding molasses to goat kids; therefore, the current study aimed to investigate the effects of dietary supplementation with higher concentrations of molasses on growth performance, blood metabolites and rumen fermentation indices. Twenty male Nubian goat kids (4–6 months old; 9–10 kg BW) were randomly assigned to 4 groups receiving different concentration of molasses: 0% (M-0), 30% (M-30), 40% (M-40) and 45% (M-45) for 5 weeks. Feed (DFI) and water intake (DWI) were measured daily, while the blood and rumen liquor samples were collected weekly.

Results

The DFI increased and feed conversion ratio (FCR) decreased in all molasses-supplemented groups (P ≤ 0.05), whereas DWI increased in M-30 and decreased in M-45 (P ≤ 0.05). The final BW and average daily gain (ADG) increased (P < 0.0001) in groups M-30 and M-40 compared to the control and M-45. Blood pH was significantly influenced by dietary molasses concentration (MC) and the duration of molasses supplementation (MD), where it decreased in groups M-30 and M-45 compared to the control and M-40 (P < 0.05). The MC had no significant effect on blood Hb, HCT, TLC, albumin, [K+], AST, ALT and total protozoa count (TPC), as well as ruminal-[Na+], [K+], strong ion difference concentration ([SID3]) and [NH3]; however, only [NH3] was significantly affected by MD and the interaction between MC and MD (MC × MD). Serum TP, globulins, [Na+] and [Cl−] increased (P ≤ 0.05) in all supplemented groups, while A/G ratio and [SID3] decreased (P ≤ 0.05). Ruminal pH decreased (P < 0.0001) in M-40 and M-45 compared to the control and M-30. However, [VFAs] increased (P < 0.04) in M-30 and M-40 compared to the control and M-45, while osmolality increased (P ≤ 0.05) in M-30 compared to the other groups.

Conclusions

Dietary supplementation with molasses at a concentration of 30% for 3 weeks improved growth performance, protein metabolism and rumen fermentation without compromising animal health, immunity, and electrolytes and acid-base homeostasis.
Laparoscopic resection of hepatic epithelioid hemangioendothelioma: report of eleven rare cases and literature review
Authors: Xu Jianjun , Hu Shaobo , Li Suzhen , Wang Weimin , Zhou Xing , Wu Yuzhe , Su Zhe , Cheng Xiang , Gao Yang , Zheng Qichang
Published: October 2020

Background

Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare borderline tumor of vascular endothelial origin. Laparoscopic resection of HEHE has never been reported.

Methods

The clinical data of eleven patients with HEHE (4 women and 7 men) who were diagnosed and treated at the Union Hospital (Wuhan, China), and Wuhan Asia General Hospital (Wuhan, China), between March 2012 and July 2020 were analyzed retrospectively.

Results

The mean age of HEHE patients was 42.4 ± 13.9 years (range 22–67 years). All patients underwent laparoscopic surgery alone or in combination with radiofrequency ablation. Most tumors showed aggressive growth or metastasis. By immunohistochemistry, tumor cells were positive for CD31, CD34, ERG, PCK, FLi-1, TFE-3, and Ki-67 (labeling index range, 5–15%). In one of the patients, the tumor was accompanied by partial necrosis with a local appearance of epithelioid angiosarcoma. Postoperative adjuvant treatment included chemotherapy, sorafenib, and Huaier granule. As of July 2020, the median follow-up duration was 36 months (range, 9–60 months), with 2 (18.2%) patients experiencing tumor recurrence.

Conclusions

This is the first report of laparoscopic hepatectomy of HEHE. Curative laparoscopic hepatectomy might be an acceptable treatment for appropriate HEHE patients.
Using data to support evidence-informed decisions about skilled birth attendants in fragile contexts: a situational analysis from Democratic Republic of the Congo
Authors: Baba Amuda , Martineau Tim , Theobald Sally , Sabuni Paluku , Raven Joanna
Published: October 2020

Background

Most low- and middle-income countries are experiencing challenges in maternal health in relation to accessing skilled birth attendants (SBA). The first step in addressing this problem is understanding the current situation. We aimed to understand SBA’s availability and distribution in Ituri Province, North Eastern Democratic Republic of the Congo (DRC) from 2013 to 2017.

Methods

We used available data on SBAs (doctors, nurses and midwives) from the Ituri Provincial Human Resource for Health Management Unit’s database from 2013 to 2017. The current distribution across and within three categories of district (rural, peri-urban and urban) and characteristics of SBAs as well as 5-year trends and vacancy trends were identified. Data on training outputs for SBA cadres was collected from training schools in the province. Descriptive analysis, disaggregating by district, cadre and gender where possible, was conducted using Excel.

Results

The national ratio of SBAs per 1000 population is four times less than the Sustainable Development Goals threshold (4.45) while the Ituri Province ratio is one of the lowest in DRC. There are more doctors and nurses in urban and peri-urban districts compared to posts, and shortages of midwives in all district categories, particularly in rural districts. From 2013 to 2017, occupied posts for doctors and nurses in all three categories of districts increase while midwives decrease in peri-urban and rural districts. There is clear gender and occupational segregation: doctors and nurses are more likely to be male, whereas midwives are more likely to be female. The projections of training outputs show a surplus against authorised posts of doctors and nursing increasing, while the shortfall for midwives remains above 75%.

Conclusion

This is the first study to use existing human resource data to analyse availability and distribution of SBAs in a DRC province. This has provided insight into the mismatch of supply and demand of SBAs, highlighting the extreme shortage of midwives throughout the province. Further investigations are needed to better understand the situation and develop strategies to ensure a more equitable distribution of SBAs throughout this province and beyond. Without this, DRC will continue to struggle to reduce maternal mortality.
The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis
Authors: Rüger Marvin , Kipp Eugenia , Schubert Nadine , Schröder Nicole , Pufe Thomas , Stope Matthias B. , Kipp Markus , Blume Christian , Tauber Simone C. , Brandenburg Lars-Ove
Published: October 2020

Background

Bacterial meningitis is still a cause of severe neurological disability. The brain is protected from penetrating pathogens by the blood-brain barrier and the innate immune system. The invading pathogens are recognized by pattern recognition receptors including the G-protein-coupled formyl peptide receptors (FPRs), which are expressed by immune cells of the central nervous system. FPRs show a broad spectrum of ligands, including pro- and anti-inflammatory ones. Here, we investigated the effects of the annexin A1 mimetic peptide Ac2-26 in a mouse model of pneumococcal meningitis.

Methods

Wildtype (WT) and Fpr1- and Fpr2-deficient mice were intrathecally infected with Streptococcus pneumoniae D39 (type 2). Subsequently, the different mice groups were treated by intraperitoneal injections of Ac2-26 (1 mg/kg body weight) 2, 8, and 24 h post-infection. The extent of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR) 30 h post-infection.

Results

Ac2-26-treated WT mice showed less severe neutrophil infiltration, paralleled by a reduced induction of pro-inflammatory glial cell responses in the hippocampal formation and cortex. While meningitis was ameliorated in Ac2-26-treated Fpr1-deficient mice, this protective effect was not observed in Fpr2-deficient mice. Irrespective of Ac2-26 treatment, inflammation was more severe in Fpr2-deficient compared to Fpr1-deficient mice.

Conclusions

In summary, this study demonstrates anti-inflammatory properties of Ac2-26 in a model of bacterial meningitis, which are mediated via FPR2, but not FPR1. Ac2-26 and other FPR2 modulators might be promising targets for the development of novel therapies for Streptococcus pneumoniae-induced meningitis.
Urban gardening and neglected and underutilized species in Salvador, Bahia, Brazil
Authors: da Cunha Manuela Alves , Paraguassú Lidice Almeida Arlego , Assis José Geraldo de Aquino , Silva Arthur Benjamin de Paula Carvalho , Cardoso Ryzia de Cassia Vieira
Published: October 2020

Background

Urban agriculture has been evidenced as a food production and environmental sustainability strategy, although it faces many obstacles in Latin American countries. Additionally, in urban areas, low consumption of fruit and greenery is noticeable, along with loss in food diversity, including the neglected and underutilized species (NUS), which involve potential to strengthen local food systems. For this reason, this work has sought to map urban gardens in the city of Salvador, Bahia, Brazil, characterizing their gardeners, and to systematize information regarding food produced and the use of NUS.

Methods

The municipality’s urban gardens were mapped and data was collected from the gardeners. The study included two steps: (i) garden localization; (ii) on-site visits for interviews with gardeners and verification of cultivated food, destination of production, availability, and use of NUS.

Results

Eighteen active food gardens were located, seventeen of which participated in the study: eight (8) communal (UCG) and nine (9) private (UPG). Respondents were on average 55.76 years old, mostly (52.9%) male, working at UPG (88.9%). Women predominated in the UCG (87.5%), with higher levels of education. For 52.9% of the interviewees, the garden was their main source of income. Food produced at the urban gardens was consumed by 82.4% of the gardeners and their families. In 70.6% of the gardens, production was also sold, while 47.1% donated. During the survey, 59 NUS were found and 76.5% of respondents reported consuming 19 of the species. NUS leaves, fruits, and seeds were found to be eaten raw, boiled, or sautéed in various preparations, especially Coleus amboinicus Lour. (76.5%), Eryngium foetidum L. (35.3%), Talinum fruticosum (L.) Juss., and Pereskia aculeata Mill (both 29.4%). Occurrence and utilization of NUS did not present significant associations with the gardens or gardeners (p > 0.05).

Conclusions

Salvador urban gardens, even in small numbers and without government support, have produced affordable food for the local population, preserved food diversity, and the tradition of NUS cultivation and use. Thus, urban gardens are reaffirmed as relevant spaces that should be included in public policies in order to promote food and nutritional security, biodiversity, and urban environmental sustainability.
Implementing a multilevel intervention to accelerate colorectal cancer screening and follow-up in federally qualified health centers using a stepped wedge design: a study protocol
Authors: Kim Karen , Polite Blasé , Hedeker Donald , Liebovitz David , Randal Fornessa , Jayaprakash Manasi , Quinn Michael , Lee Sang Mee , Lam Helen
Published: October 2020

Background

Screening for colorectal cancer (CRC) not only detects disease early when treatment is more effective but also prevents cancer by finding and removing precancerous polyps. Because many of our nation’s most disadvantaged and vulnerable individuals obtain health care at federally qualified health centers, these centers play a significant role in increasing CRC screening among the most vulnerable populations. Furthermore, the full benefits of cancer screenings must include timely and appropriate follow-up of abnormal results. Thus, the purpose of this study is to implement a multilevel intervention to increase rates of CRC screening, follow-up, and referral-to-care in federally qualified health centers, as well as simultaneously to observe and to gather information on the implementation process to improve the adoption, implementation, and sustainment of the intervention. The multilevel intervention will target three different levels of influences: organization, provider, and individual. It will have multiple components, including provider and staff education, provider reminder, provider assessment and feedback, patient reminder, and patient navigation.

Methods

This study is a multilevel, three-phase, stepped wedge cluster randomized trial with four clusters of clinics from four different FQHC systems. In the first phase, there will be a 3-month waiting period during which no intervention components will be implemented. After the 3-month waiting period, we will randomize two clusters to cross from the control to the intervention and the remaining two clusters to follow 3 months later. All clusters will stay at the same phase for 9 months, followed by a 3-month transition period, and then cross over to the next phase.

Discussion

There is a pressing need to reduce disparities in CRC outcomes, especially among racial/ethnic minority populations and among populations who live in poverty. Single-level interventions are often insufficient to lead to sustainable changes. Multilevel interventions, which target two or more levels of changes, are needed to address multilevel contextual influences simultaneously. Multilevel interventions with multiple components will affect not only the desired outcomes but also each other. How to take advantage of multilevel interventions and how to implement such interventions and evaluate their effectiveness are the ultimate goals of this study.

Trial registration

This protocol is registered at clinicaltrials.gov (NCT04514341) on 14 August 2020.
The clonogenic assay: robustness of plating efficiency-based analysis is strongly compromised by cellular cooperation
Authors: Brix Nikko , Samaga Daniel , Hennel Roman , Gehr Katharina , Zitzelsberger Horst , Lauber Kirsten
Published: October 2020

Background

The clonogenic assay is a versatile and frequently used tool to quantify reproductive cell survival in vitro. Current state-of-the-art analysis relies on plating efficiency-based calculations which assume a linear correlation between the number of cells seeded and the number of colonies counted. The present study was designed to test the validity of this assumption and to evaluate the robustness of clonogenic survival results obtained.

Methods

A panel of 50 established cancer cell lines was used for comprehensive evaluation of the clonogenic assay procedure and data analysis. We assessed the performance of plating efficiency-based calculations and examined the influence of critical experimental parameters, such as cell density seeded, assay volume, incubation time, as well as the cell line-intrinsic factor of cellular cooperation by auto-/paracrine stimulation. Our findings were integrated into a novel mathematical approach for the analysis of clonogenic survival data.

Results

For various cell lines, clonogenic growth behavior failed to be adequately described by a constant plating efficiency, since the density of cells seeded severely influenced the extent and the dynamics of clonogenic growth. This strongly impaired the robustness of survival calculations obtained by the current state-of-the-art method using plating efficiency-based normalization. A novel mathematical approach utilizing power regression and interpolation of matched colony numbers at different irradiation doses applied to the same dataset substantially reduced the impact of cell density on survival results. Cellular cooperation was observed to be responsible for the non-linear clonogenic growth behavior of a relevant number of cell lines and the impairment of survival calculations. With 28/50 cell lines of different tumor entities showing moderate to high degrees of cellular cooperation, this phenomenon was found to be unexpectedly common.

Conclusions

Our study reveals that plating efficiency-based analysis of clonogenic survival data is profoundly compromised by cellular cooperation resulting in strongly underestimated assay-intrinsic errors in a relevant proportion of established cancer cell lines. This severely questions the use of plating efficiency-based calculations in studies aiming to achieve more than semiquantitative results. The novel approach presented here accounts for the phenomenon of cellular cooperation and allows the extraction of clonogenic survival results with clearly improved robustness.
Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2
Authors: Zhang Dong-Yan , Sun Qing-Can , Zou Xue-Jing , Song Yang , Li Wen-Wen , Guo Ze-Qin , Liu Shan-Shan , Liu Li , Wu De-Hua
Published: October 2020

Background

Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear.

Methods

Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets.

Results

We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC.

Conclusions

Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.
Practicing outcome-based medical care using pragmatic care trials
Authors: Darsaut Tim E. , Raymond Jean
Published: October 2020

The current separation between medical research and care is an obstacle to essential aspects of good medical practice: the verification that care interventions actually deliver the good outcomes they promise, and the use of scientific methods to optimize care under uncertainty. Pragmatic care trials have been designed to address these problems. Care trials are all-inclusive randomized trials integrated into care. Every item of trial design is selected in the best medical interest of participating patients. Care trials can eventually show what constitutes good medical practice based on patient outcomes. In the meantime, care trials give clinicians and patients the scientific methods necessary for optimization of medical care when no one really knows what to do.

We report the progress of 9 randomized care trials that were used to guide the endovascular or surgical management of 1212 patients with acute stroke, intracranial aneurysms, and arteriovenous malformations in a single center in an elective or acute care context. Care trials were used to address long-standing dilemmas regarding rival medical, surgical, or endovascular management options or to offer innovative instead of standard treatments. The trial methodology, by replacing unrepeatable treatment decisions by 1:1 randomized allocation whenever reliable knowledge was not available, had an immediate impact, transforming unverifiable dogmatic medical practice into verifiable outcome-based medical care. We believe the approach is applicable to all medical or surgical domains, but widespread adoption may require the revision of many currently prevalent views regarding the role of research in clinical practice.
Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials
Authors: Goldman Jennifer G. , Forsberg Leah K. , Boeve Bradley F. , Armstrong Melissa J. , Irwin David J. , Ferman Tanis J. , Galasko Doug , Galvin James E. , Kaufer Daniel , Leverenz James , Lippa Carol F. , Marder Karen , Abler Victor , Biglan Kevin , Irizarry Michael , Keller Bill , Munsie Leanne , Nakagawa Masaki , Taylor Angela , Graham Todd
Published: October 2020

Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson’s disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.
Degos disease: a case report and review of the literature
Authors: Tummidi Santosh , Nagendran Prabhakaran , Gedela Swaroopa , Ramani Jami Rupa , Shankaralingappa Arundhathi
Published: October 2020

Background

Degos disease is a very rare syndrome with multisystem vasculopathy of unknown cause. It can affect the skin, gastrointestinal tract, and central nervous system. However, other organs such as the kidney, lungs, pleura, and liver can also be involved.

Case presentation

A 35-year-old Hindu woman presented to our dermatology outpatient department with complaints of depigmented painful lesions. A skin punch biopsy taken from the porcelain white atrophic papules which revealed features of Degos disease.

Conclusion

The diagnosis of Degos disease is usually based on the presence of the pathognomonic skin lesions and a tissue biopsy demonstrating a wedge-shaped area of necrosis with thrombotic occlusion of the small arterioles. No specific treatment is currently available for this disease.
Detection of CMY-type beta-lactamases in Escherichia coli isolates from paediatric patients in a tertiary care hospital in Mexico
Authors: Merida-Vieyra Jocelin , De Colsa-Ranero Agustín , Calderón-Castañeda Yair , Aquino-Andrade Alejandra
Published: October 2020

Background

The aim of this study was to detect CMY-type beta-lactamases in E. coli isolates obtained from paediatric patients.

Methods

In total, 404 infection-causing E. coli isolates resistant to third and fourth generation cephalosporins (3GC, 4GC) were collected from paediatric patients over a 2 years period. The identification and susceptibility profiles were determined with an automated microbiology system. Typing of blaCMY and other beta-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaVIM, blaIMP, blaKPC, blaNDM, blaOXA and blaGES) was realized by PCR and sequencing. Phenotypic detection of AmpC-type enzymes was performed using boronic acid (20 mg/mL) and cloxacillin (20 mg/mL) as inhibitors, and the production of extended-spectrum beta-lactamases was determined with the double-disk diffusion test with cefotaxime (CTX) and ceftazidime (CAZ) discs alone and in combination with clavulanic acid. The CarbaNP test and modified carbapenem inhibition method (mCIM) were used for isolates with decreased susceptibility to carbapenems. The clonal origin of the isolates was established by pulsed-field gel electrophoresis (PFGE), phylotyping method and multilocus sequence typing.

Results

CMY-type beta-lactamases were detected in 18 isolates (4.5%). The allelic variants found were CMY-2 (n = 14) and CMY-42 (n = 4). Of the E. coli strains with CMY, the AmpC phenotypic production test was positive in 11 isolates with cloxacillin and in 15 with boronic acid. ESBL production was detected in 13 isolates. Coexistence with other beta-lactamases was observed such as CTX-M-15 ESBL and original spectrum beta-lactamases TEM-1 and TEM-190. In one isolate, the CarbaNP test was negative, the mCIM was positive, and OXA-48 carbapenemase was detected. Phylogroup A was the most frequent (n = 9) followed by B2, E and F (n = 2, respectively), and through PFGE, no clonal relationship was observed. Eleven different sequence types (ST) were found, with ST10 high-risk clone being the most frequent (n = 4). Seventy-two percent of the isolates were from health care-associated infections; the mortality rate was 11.1%.

Conclusions

This is the first report in Mexico of E. coli producing CMY isolated from paediatric patients, demonstrating a frequency of 4.5%. In addition, this is the first finding of E. coli ST10 with CMY-2 and OXA-48.
Parallel and non-parallel changes of the gut microbiota during trophic diversification in repeated young adaptive radiations of sympatric cichlid fish
Authors: Härer Andreas , Torres-Dowdall Julián , Rometsch Sina J. , Yohannes Elizabeth , Machado-Schiaffino Gonzalo , Meyer Axel
Published: October 2020

Background

Recent increases in understanding the ecological and evolutionary roles of microbial communities have underscored the importance of their hosts’ biology. Yet, little is known about gut microbiota dynamics during the early stages of ecological diversification and speciation. We sequenced the V4 region of the 16s rRNA gene to study the gut microbiota of Nicaraguan Midas cichlid fish (Amphilophus cf. citrinellus). Specifically, we tested the hypothesis that parallel divergence in trophic ecology in extremely young adaptive radiations from two crater lakes is associated with parallel changes of their gut microbiota.

Results

Bacterial communities of fish guts and lake water were highly distinct, indicating that the gut microbiota is shaped by host-specific factors. Among individuals of the same crater lake, differentiation in trophic ecology was weakly associated with gut microbiota differentiation, suggesting that diet, to some extent, affects the gut microbiota. However, differences in trophic ecology were much more pronounced across than within species whereas similar patterns were not observed for taxonomic and functional differences of the gut microbiota. Across the two crater lakes, we could not detect conclusive evidence for parallel changes of the gut microbiota associated with trophic ecology.

Conclusions

A lack of clearly differentiated niches during the early stages of ecological diversification might result in non-parallel changes of gut microbial communities, as observed in our study system as well as in other recently diverged fish species.