bluuebunny/crossref_metadata_2025 huggingface dataset:
THIS IS NOT A DRILL: Mobile Telephony, Information Verification, and Expressive Communication During Hawaii’s False Missile Alert
Authors: Ling Rich , Oppegaard Brett
Published: March 2021

On Saturday, 13 January 2018, residents of Hawaii received a chilling message through their smartphones. It read, in all caps, BALLISTIC MISSILE THREAT INBOUND TO HAWAII. SEEK IMMEDIATE SHELTER. THIS IS NOT A DRILL. The message was mistakenly sent, but many residents lived in a threatened state of mind for the 38 minutes it took before a retraction was made. This study is based on a survey of 418 people who experienced the alert, recollecting their immediate responses, including how they attempted to verify the alert and how they used their mobile devices and social media for expressive interactions during the alert period. With the ongoing testing in the United States of nationwide Wireless Emergency Alerts, along with similar expansions of these systems in other countries, the event in Hawaii serves to illuminate how people understand and respond to mobile-based alerts. It shows the extreme speed that information—including misinformation—can flow in an emergency, and, for many, expressive communication affects people’s reactions.
Novel predictor markers for early differentiation between transient tachypnea of newborn and respiratory distress syndrome in neonates
Authors: Elfarargy Mohamed Shawky , Al-Ashmawy Ghada M , Abu-Risha Sally , Khattab Haidy
Published: March 2021

Neonatal Respiratory Distress Syndrome (RDS) and Transient Tachypnea of newborn (TTN) are common similar neonatal respiratory diseases. Study the early predictor markers in differentiation between TTN and RDS in neonates. A prospective case control study which was done in Neonatal Intensive Care Unit (NICU) of Tanta University Hospital (TUH) from September 2016 to March 2018. Three groups of neonates were included in the study: RDS group (45 neonates), TTN group (45 neonates), and control group (45 healthy neonates). There were statistically significant difference (SSD) between our studied three groups as regard serum Malondialdehyde (MDA), Superoxide dismutase SOD, Lactate dehydrogenase (LDH), and blood PH and P-values were 0.001* for these comparative parameters. The ROC curve of RDS cases revealed that the serum MDA Cut off, sensitivity and specificity were 1.87 mmol/L, 98%, 96%, respectively which had the highest sensitivity and specificity followed by the serum SOD then the serum LDH and lastly the blood PH while in TTN cases, the serum MDA Cut off, sensitivity and specificity were 0.74 mmol/L, 96%, 93%, respectively then the serum SOD then the serum LDH and lastly the blood PH. Serum MDA, SOD, LDH, and PH had a beneficial role as early predictors in differentiation between TTN and RDS in neonates.
Acute moderate-intensity exercise increases total antioxidant capacity and anti-inflammatory responses in competitive cyclists: The role of adiponectin
Authors: Jakus Tadeja , Jurdana Mihaela , Žiberna Lovro , Pražnikar Zala J
Published: March 2021

High-intensity exercise can elicit acute changes in the biochemical and physiological processes in the body of an athlete, including increased oxidative stress and inflammation. The purpose of this study was to explore the effect of acute moderate-intensity exercise on total antioxidant capacity (TAC) and serum levels of anti-inflammatory adiponectin (APN), and inflammatory markers in competitive cyclists. Ten male cyclists (age 15–26 years, body mass index 19.4–24.7 kg/m2) participated in this study. Each subject performed the maximal oxygen uptake test (VO2peak) and completed a 10-min cycling exercise at a workload of 50% of the peak of VO2peak. Blood samples were collected on three different occasions: after an overnight fasting and at the exercise workloads of 50% and 100% VO2peak. We measured APN, TAC, inflammatory markers as well as assessed nutrient and energy intake for each participant. Baseline concentration of serum APN (10.92 µg/mL) significantly increased at 50% and at 100% VO2peak. In addition, TAC also increased after acute exercise (0.079 vs 0.093 nmol/µL). The concentration of APN at 50% VO2peak positively correlated with the CRP ( r = 0.640, p = 0.046) and negatively correlated with TNF-α ( r = −0.696, p = 0.025). This test showed that short (10 min) and medium-intensity (50% VO2peak) exercise activity in trained athletes evoked beneficial antioxidant and anti-inflammatory responses. Importantly, this response correlates with the increase in APN levels thereby showing that highly trained individuals have beneficial responses originating from adipose tissue. Our observations show that a short training at moderate activity can be an important preservative strategy during the recovery training period.
Becoming E-Petition: An Assemblage-Based Framework for Analysis and Research
Authors: Briassoulis Helen
Published: March 2021

Ε-petitions, the digital version of printed petitions, are increasingly being used as complimentary means of nonconfrontational, online citizen mobilization/protest. They attract considerable research interest because they provide (big) data to study e-petitioning and the political and other aspects of socio-spatial issues. E-petition studies lack discussion of ontology, of “what is an e-petition,” implicitly treating e-petitions as “systems-as-a-whole” or, seldom, as relational formations. Acknowledging the foundational role of ontology, Assemblage Thinking (AT) is argued to beget a more judicious approach when e-petitions are employed as research instruments to study the “who-what-when-where-and-how” of a socio-spatial issue and, concurrently, their situated contribution to issue-related decision-making. After presenting the reductionist/essentialist and the nonreductionist/relational approaches to the study of e-petitions and introducing ΑΤ, an assemblage-based framework is proposed that conceptualizes e-petitions as multiplicities comprising assemblages, dynamic compositions emerging from processes of heterogeneous components coming together to serve a purpose. A concomitant methodology is outlined and an illustrative example is offered. The advantages of assemblage-based over reductionist/essentialist approaches for the situated co-analysis of socio-spatial issues and e-petitions are discussed, indicating how they address prominent concerns of the literature, and future research directions are suggested.
Tobacco Smoking and the Association With First Incidence of Mood, Anxiety, and Substance Use Disorders: A 3-Year Prospective Population-Based Study
Authors: Monshouwer Karin , ten Have Margreet , de Graaf Ron , Blankers Matthijs , van Laar Margriet
Published: March 2021

There is consistent evidence from cross-sectional studies that smoking is positively associated with mental disorders. The research on the prospective association, however, is inconsistent. In the present study, we aimed to further increase the knowledge of this association by addressing several issues in the body of research. Data used were from a nationally representative, population-based cohort study among 18- to 64-year-olds at baseline. Compared with nonsmokers, smokers at baseline were significantly more likely to experience first incidence of any mood, anxiety, or substance use disorder at 3-year follow-up while controlling for a wide range of confounding factors. The association with incident mood and anxiety disorders was particularly high among heavy smokers. The dose-effect analyses on later substance use disorders showed unclear results, warranting further research. Additional analyses showed that results at 6-year follow-up were very similar, except for a weaker relationship between smoking and substance use disorders.
Increase in Suicidal Thinking During COVID-19
Authors: Fortgang Rebecca G. , Wang Shirley B. , Millner Alexander J. , Reid-Russell Azure , Beukenhorst Anna L. , Kleiman Evan M. , Bentley Kate H. , Zuromski Kelly L. , Al-Suwaidi Maha , Bird Suzanne A. , Buonopane Ralph , DeMarco Dylan , Haim Adam , Joyce Victoria W. , Kastman Erik K. , Kilbury Erin , Lee Hye-In S. , Mair Patrick , Nash Carol C. , Onnela Jukka-Pekka , Smoller Jordan W. , Nock Matthew K.
Published: March 2021

There is concern that the COVID-19 pandemic may cause increased risk of suicide. In the current study, we tested whether suicidal thinking has increased during the COVID-19 pandemic and whether such thinking was predicted by increased feelings of social isolation. In a sample of 55 individuals recently hospitalized for suicidal thinking or behaviors and participating in a 6-month intensive longitudinal smartphone monitoring study, we examined suicidal thinking and isolation before and after the COVID-19 pandemic was declared a national emergency in the United States. We found that suicidal thinking increased significantly among adults (odds ratio [ OR] = 4.01, 95% confidence interval [CI] = [3.28, 4.90], p < .001) but not adolescents ( OR = 0.84, 95% CI = [0.69, 1.01], p = .07) during the onset of the COVID-19 pandemic. Increased feelings of isolation predicted suicidal thinking during the pandemic phase. Given the importance of social distancing policies, these findings support the need for digital outreach and treatment.
Multimodality Intraoperative Neuromonitoring in Lateral Lumbar Interbody Fusion: A Review of Alerts in 628 Patients
Authors: Alluri Ram K. , Vaishnav Avani S. , Sivaganesan Ahilan , Ricci Luke , Sheha Evan , Qureshi Sheeraz A.
Published: March 2021

Study Design:

Retrospective review of private neuromonitoring databases.

Objectives:

To review neuromonitoring alerts in a large series of patients undergoing lateral lumbar interbody fusion (LLIF) and determine whether alerts occurred more frequently when more lumbar levels were accessed or more frequently at particular lumbar levels.

Methods:

Intraoperative neuromonitoring (IONM) databases were reviewed and patients were identified undergoing LLIF between L1 and L5. All cases in which at least one IONM modality was used (motor evoked potentials (MEP), somatosensory evoked potentials (SSEP), evoked electromyography (EMG)) were included in this study. The type of IONM used and incidence of alerts were collected from each IONM report and analyzed. The incidence of alerts for each IONM modality based on number of levels at which at LLIF was performed and the specific level an LLIF was performed were compared.

Results:

A total of 628 patients undergoing LLIF across 934 levels were reviewed. EMG was used in 611 (97%) cases, SSEP in 561 (89%), MEP in 144 (23%). The frequency of IONM alerts for EMG, SSEP and MEPs did not significantly increase as the number of LLIF levels accessed increased. No EMG, SSEP, or MEP alerts occurred at L1-L2. EMG alerts occurred in 2-5% of patients at L2-L3, L3-L4, and L4-L5 and did not significantly vary by level ( P = .34). SSEP and MEP alerts occurred more frequently at L4-L5 versus L2-L3 and L3-L4 ( P < .03).

Conclusions:

IONM may provide the greatest utility at L4-L5, particularly MEPs, and may not be necessary for more cephalad LLIF procedures such as at L1-L2.
Nitrofurantoin-Associated Acute Granulomatous Interstitial Nephritis
Authors: Anupama B. K. , Sampat Parth , Gambhir Harvir S.
Published: March 2021

We report the case of a 71-year-old female who was incidentally found to have nonoliguric acute kidney injury on a routine workup for new-onset visual hallucination. Further history revealed inadvertent usage of nitrofurantoin for 3 months for an anticipated urological procedure. Renal biopsy demonstrated acute granulomatous interstitial nephritis. The renal function significantly improved following discontinuation of nitrofurantoin and corticosteroid administration. We highlight a rare association of nitrofurantoin with acute granulomatous interstitial nephritis through this case report.
Rates of Concomitant Meniscal Tears in Pediatric Patients With Anterior Cruciate Ligament Injuries Increase With Age and Body Mass Index
Authors: Perkins Crystal A. , Christino Melissa A. , Busch Michael T. , Egger Anthony , Murata Asahi , Kelleman Michael , Willimon S. Clifton
Published: March 2021

Background:

Anterior cruciate ligament (ACL) tears are frequently associated with meniscal injury. Risk factors for concomitant meniscal injuries have been studied in the adult population but less so in pediatric patients.

Purpose:

To evaluate the relationship between age and body mass index (BMI) and the presence of a concomitant meniscal tear at the time of ACL reconstruction (ACLR) in pediatric patients.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

A single-institution retrospective review was performed of patients aged <19 years who underwent primary ACLR over a 3.5-year period. Revision ACLR and multiligament knee reconstructions were excluded. Logistic regression was used to identify risk factors associated with having a meniscal tear at the time of surgery. Subgroup analysis was performed for medial and lateral meniscal tears.

Results:

Included in this study were 453 patients (230 males, 223 females; median age, 15 years). Of these, 265 patients (58%) had a meniscal tear, including 150 isolated lateral meniscal tears, 53 isolated medial meniscal tears, and 62 patients with both lateral and medial meniscal tears. Median time from injury to surgery was 48 days. For every 1-year increase in age, there was a 16% increase in the adjusted odds of having any meniscal tear (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.05-1.27; P = .002), with a 20% increase in the odds of having a medial meniscal tear (OR, 1.20; 95% CI, 1.07-1.35; P = .002) and a 16% increase in the odds of having a lateral meniscal tear (OR, 1.16; 95% CI, 1.05-1.27; P = .003). For every 2-point increase in BMI, there was a 12% increase in the odds of having any meniscal tear (OR, 1.12; 95% CI, 1.02-1.22; P = .016) and a 10% increase in the odds of having a lateral meniscal tear (OR, 1.10; 95% CI, 1.01-1.19; P = .028).

Conclusion:

Pediatric patients undergoing ACLR had a 58% incidence of concomitant meniscal pathology. Increasing age and BMI were independent risk factors for these injuries, while no association was found between time to surgery and meniscal pathology.
Downbeat Nystagmus in a 7-Year-Old Girl With Epstein-Barr Virus-Associated Meningitis and Cerebellitis
Authors: Wade Cameron Alexander , Toupin David Neil , Darpel Kyle , Jones Kimberly , Lightner Donita
Published: March 2021

Downbeat nystagmus is a type of jerk nystagmus that may be seen in patients with lesions affecting the vestibulocerebellum. This is a case of a 7-year-old girl presenting with a history of fever, headache, and episodic vertigo with downbeat nystagmus. The diagnosis of Epstein-Barr virus meningitis with acute cerebellitis was made by contrast magnetic resonance imaging, cerebrospinal fluid analysis, and serum Epstein-Barr virus titers. Contrast magnetic resonance imaging demonstrated enhancement of the meninges and inferior cerebellar folia, correlating with the neuroophthalmological symptom of downbeat nystagmus.
Who’s Taking What? “Applied STEM” Coursetaking for High School Students With Learning Disabilities
Authors: Gottfried Michael A. , Plasman Jay , Freeman Jennifer A. , Dougherty Shaun
Published: March 2021

Increasing and improving the science, technology, engineering, and mathematics (STEM) educational pipeline has been a point of emphasis for decades, and federal policy in the United States has urged high schools to embed new types of STEM courses into the curriculum. As one example, applied STEM courses—one growing branch within career and technical education (CTE)—are designed to reinforce traditional academic STEM content and to motivate students’ interests and long-term pursuits in STEM areas. That said, little is known about who takes these courses, and applied-STEM-CTE enrollment in these courses has not been explored in the research for students with learning disabilities. Using the High School Longitudinal Study (a nationally representative data set of high school students), we asked whether CTE coursetaking differed for students with learning disabilities compared with those without disabilities, and whether there were specific coursetaking differences in applied-STEM-CTE. We found that students with learning disabilities were more likely to earn more units in CTE courses compared with students without disabilities. Yet, when looking at applied-STEM-CTE courses, we see that although students with learning disabilities earn more CTE units than students without disabilities, students with learning disabilities do not take different amounts of applied-STEM-CTE courses. Implications are discussed.
Book review: Sreeram Chaulia, Trumped: Emerging Powers in a Post-American World
Authors: Westcott Stephen P.
Published: March 2021

Sreeram Chaulia, Trumped: Emerging Powers in a Post-American World. New Delhi: Bloomsbury India, 2019, 237 pp. ISBN: 978-9-3891-6594-4.
Book review: Shanthie Mariet D’Souza (Ed.), Countering Insurgencies and Violent Extremism in South and Southeast Asia
Authors: Ramakrishna Kumar
Published: March 2021

Shanthie Mariet D’Souza (Ed.), Countering Insurgencies and Violent Extremism in South and Southeast Asia. London and New York: Routledge, 2019. 376 pp., ISBN 9781138615557.
Response to Telemedicine Visits From Patients With Parkinsonism During the COVID-19 Pandemic on Postvisit Surveys
Authors: Deeb Wissam , Hess Christopher W , Gamez Noheli , Patel Bhavana , Moore Kathryn , Armstrong Melissa J
Published: March 2021

Parkinson’s disease and parkinsonism are common chronic neurodegenerative disorders that tend to affect older adults and cause physical and sometimes cognitive limitations. Given that these limitations could impact successful telemedicine use, we aimed to investigate the experiences of patients with parkinsonism using telemedicine during the COVID-19 pandemic. A 19-item survey was emailed to patients with parkinsonism following telemedicine visits at a single US tertiary care parkinsonism specialty clinic. Seventy-four individuals responded, out of 270 invitations sent. Almost two-thirds (61.6%) of the respondents were comfortable with using technology in general, and almost all were very satisfied with their telemedicine experience. The most commonly reported benefits included cost and travel savings, ease of access to a specialist, and time savings. Issues with technology and previsit instructions were the most commonly identified challenges (28%). Urgent implementation, due to the pandemic, of telemedicine care for patients with parkinsonism was feasible and well received. The challenges most commonly reported by patients could be potentially alleviated by better education and support.
A Communication Audit Exercise to Enhance Virtual Team and Individual Communication Skills
Authors: Bailey-Hughes Brenda
Published: March 2021

This article outlines a unique student activity designed to close the gap between students’ perceived and actual communication and team behavior during virtual group meetings. The Communication Audit exercise requires that students record an online small group meeting and then review the recording while categorizing each verbal remark into observable behaviors aligned to the instructor’s learning objectives. The audit delivers objective data to students concerning their team habits and leads to excellent discussions of opportunities to improve team dynamics and individual contributions to a team process.
Supportive care for animals on toxicology studies: An industrial best practices survey conducted by the IQ 3Rs TPS CRO Outreach Working Group
Authors: Salian-Mehta Smita , Wilson Jolaine M , Burr Holly N , Greenstein Abigail Wolf , Murray Kathleen , West Wanda , Poy Nancy
Published: March 2021

Contract Research Organizations (CROs) conducting toxicology studies on behalf of biopharmaceutical sponsors and others routinely provide supportive care for animals to minimize pain and distress on studies. A large number of guidance documents govern the care of experimental animals, however there is currently no uniform approach on the communication between sponsor and their CRO partners in providing a standard definition of and strategies for administering supportive care in toxicity studies. This survey was conducted by the CRO Outreach Working Group (WG), a part of the 3Rs Translational and Predictive Sciences (TPS) Leadership Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium), to better understand the provision of supportive care on nonclinical studies. The survey aimed to define supportive care strategies, identify alternatives to supportive care, and understand regulatory feedback and implications about supportive care decisions. The survey was distributed to members of the 3Rs Leadership Group of the IQ Consortium and several CRO partners, representing 35 organizations as potential respondents. The results of the survey from 13 respondents provided positive feedback that helped in highlighting the existing best practices for supportive care. Areas of enhancements identified included greater consistency in the inclusion of sponsor veterinarians on project teams for externalized studies, the timing of initiation of supportive care, and increased sharing of regulatory outcomes. Suggested best practices include creating a plan of action for veterinary care prior to study start, and enhancing information sharing regarding expected toxicities from previous study findings. Improved communication regarding supportive care will pave the way for enhanced 3Rs initiatives, refining the existing animal care paradigm and helping to ensure the most ethical toxicology study designs.
Re-writing punishment? Songs and narrative problem-solving
Authors: Crockett Thomas Phil , McNeill Fergus , Cathcart Frödén Lucy , Collinson Scott Jo , Escobar Oliver , Urie Alison
Published: March 2021

This article analyses findings from the Economic and Social Research Council/Arts and Humanities Research Council (ESRC/AHRC)-funded ‘Distant Voices – Coming Home’ project (ES/POO2536/1), which uses creative methods to explore crime, punishment and reintegration. Focusing on songs co-written in Scottish prisons, we argue that the songs serve to complicate and substantiate our grasp of what state punishment does to people, as well as perhaps affording their prison-based co-writers both moments and modalities of resistance to dominant narratives within criminal justice. In doing so, they creatively express and explore affective and perhaps even unconscious aspects of the self. We argue that our work contributes to a more expansive and considered treatment of narrative in criminology; one that admits and engages with a more diverse and creative range of expressions of experience and selfhood, all of them partial and some of them contradictory. By attending to diverse kinds of narratives embodied in these songs, we learn more about what criminalisation, penalisation and incarceration do to people and to their stories.
RETRACTED ARTICLE: Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells
Authors: Chen Hao , Luo Min , Wang Xiangping , Liang Ting , Huang Chaoyuan , Huang Changjie , Wei Lining
Published: March 2021

Background

Nasopharyngeal carcinoma (NPC) is a tumor deriving from nasopharyngeal epithelium. Peptidyl-arginine deiminase 4 (PAD4) is a vital mediator of histone citrullination and plays an essential role in regulating disease process. Radiotherapy is an essential method to treat NPC. In this research, we explored the effect of PAD4 on NPC radiosensitivity.

Methods

We enrolled 50 NPC patients, established mice xenograft model, and purchased cell lines for this study. Statistical analysis and a series of experiments including RT-qPCR, clonogenic survival, EdU, Transwell, and wound healing assays were done.

Results

Our data manifested that PAD4 (mRNA and protein) presented a high expression in NPC tissues and cells. GSK484, an inhibitor of PAD4, could inhibit activity of PAD4 in NPC cell lines. PAD4 overexpression promoted the radioresistance, survival, migration, and invasion of NPC cells, whereas treatment of GSK484 exerted inhibitory effects on radioresistance and aggressive phenotype of NPC cells. Additionally, GSK484 could attenuate the effect of PAD4 of NPC cell progression. More importantly, we found that GSK484 significantly inhibited tumor size, tumor weight and tumor volume in mice following irradiation.

Conclusions

PAD4 inhibitor GSK484 attenuated the radioresistance and cellular progression in NPC.
Bayesian approach for predicting responses to therapy from high-dimensional time-course gene expression profiles
Authors: Fukushima Arika , Sugimoto Masahiro , Hiwa Satoru , Hiroyasu Tomoyuki
Published: March 2021

Background

Historical and updated information provided by time-course data collected during an entire treatment period proves to be more useful than information provided by single-point data. Accurate predictions made using time-course data on multiple biomarkers that indicate a patient’s response to therapy contribute positively to the decision-making process associated with designing effective treatment programs for various diseases. Therefore, the development of prediction methods incorporating time-course data on multiple markers is necessary.

Results

We proposed new methods that may be used for prediction and gene selection via time-course gene expression profiles. Our prediction method consolidated multiple probabilities calculated using gene expression profiles collected over a series of time points to predict therapy response. Using two data sets collected from patients with hepatitis C virus (HCV) infection and multiple sclerosis (MS), we performed numerical experiments that predicted response to therapy and evaluated their accuracies. Our methods were more accurate than conventional methods and successfully selected genes, the functions of which were associated with the pathology of HCV infection and MS.

Conclusions

The proposed method accurately predicted response to therapy using data at multiple time points. It showed higher accuracies at early time points compared to those of conventional methods. Furthermore, this method successfully selected genes that were directly associated with diseases.
Transcriptomic and volatile signatures associated with maize defense against corn leaf aphid
Authors: Pingault Lise , Varsani Suresh , Palmer Nathan , Ray Swayamjit , Williams W. Paul , Luthe Dawn S. , Ali Jared G. , Sarath Gautam , Louis Joe
Published: March 2021

Background

Maize (Zea mays L.) is a major cereal crop, with the United States accounting for over 40% of the worldwide production. Corn leaf aphid [CLA; Rhopalosiphum maidis (Fitch)] is an economically important pest of maize and several other monocot crops. In addition to feeding damage, CLA acts as a vector for viruses that cause devastating diseases in maize. We have shown previously that the maize inbred line Mp708, which was developed by classical plant breeding, provides heightened resistance to CLA. However, the transcriptomic variation conferring CLA resistance to Mp708 has not been investigated.

Results

In this study, we contrasted the defense responses of the resistant Mp708 genotype to those of the susceptible Tx601 genotype at the transcriptomic (mRNA-seq) and volatile blend levels. Our results suggest that there was a greater transcriptomic remodeling in Mp708 plants in response to CLA infestation compared to the Tx601 plants. These transcriptomic signatures indicated an activation of hormonal pathways, and regulation of sesquiterpenes and terpenoid synthases in a constitutive and inducible manner. Transcriptomic analysis also revealed that the resistant Mp708 genotype possessed distinct regulation of ethylene and jasmonic acid pathways before and after aphid infestation. Finally, our results also highlight the significance of constitutive production of volatile organic compounds (VOCs) in Mp708 and Tx601 plants that may contribute to maize direct and/or indirect defense responses.

Conclusions

This study provided further insights to understand the role of defense signaling networks in Mp708’s resistance to CLA.
Accounting for confounding by time, early intervention adoption, and time-varying effect modification in the design and analysis of stepped-wedge designs: application to a proposed study design to reduce opioid-related mortality
Authors: Rennert Lior , Heo Moonseong , Litwin Alain H. , Gruttola Victor De
Published: March 2021

Background

Beginning in 2019, stepped-wedge designs (SWDs) were being used in the investigation of interventions to reduce opioid-related deaths in communities across the United States. However, these interventions are competing with external factors such as newly initiated public policies limiting opioid prescriptions, media awareness campaigns, and the COVID-19 pandemic. Furthermore, control communities may prematurely adopt components of the intervention as they become available. The presence of time-varying external factors that impact study outcomes is a well-known limitation of SWDs; common approaches to adjusting for them make use of a mixed effects modeling framework. However, these models have several shortcomings when external factors differentially impact intervention and control clusters.

Methods

We discuss limitations of commonly used mixed effects models in the context of proposed SWDs to investigate interventions intended to reduce opioid-related mortality, and propose extensions of these models to address these limitations. We conduct an extensive simulation study of anticipated data from SWD trials targeting the current opioid epidemic in order to examine the performance of these models in the presence of external factors. We consider confounding by time, premature adoption of intervention components, and time-varying effect modification— in which external factors differentially impact intervention and control clusters.

Results

In the presence of confounding by time, commonly used mixed effects models yield unbiased intervention effect estimates, but can have inflated Type 1 error and result in under coverage of confidence intervals. These models yield biased intervention effect estimates when premature intervention adoption or effect modification are present. In such scenarios, models incorporating fixed intervention-by-time interactions with an unstructured covariance for intervention-by-cluster-by-time random effects result in unbiased intervention effect estimates, reach nominal confidence interval coverage, and preserve Type 1 error.

Conclusions

Mixed effects models can adjust for different combinations of external factors through correct specification of fixed and random time effects. Since model choice has considerable impact on validity of results and study power, careful consideration must be given to how these external factors impact study endpoints and what estimands are most appropriate in the presence of such factors.
Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study
Authors: Amanat Man , Rezaei Nima , Roozbeh Mehrdad , Shojaei Maziar , Tafakhori Abbas , Zoghi Anahita , Darazam Ilad Alavi , Salehi Mona , Karimialavijeh Ehsan , Lima Behnam Safarpour , Garakani Amir , Vaccaro Alexander , Ramezani Mahtab
Published: March 2021

Backgrounds

The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death.

Methods

Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements.

Results

We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up.

Conclusion

Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.
Tumor-infiltrating B cells and T cells correlate with postoperative prognosis in triple-negative carcinoma of the breast
Authors: Kuroda Hajime , Jamiyan Tsengelmaa , Yamaguchi Rin , Kakumoto Akinari , Abe Akihito , Harada Oi , Masunaga Atsuko
Published: March 2021

Background

In this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method.

Methods

We investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available.

Results

The strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs (r = 0.177; p < 0.001), CD8+ TILs (r = 0.085; p = 0.002), and FOXP3+ TILs (r = 0.0043; p = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs (r = 0.012; p = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival (p < 0.001) and overall survival (p < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis.

Conclusions

CD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.
Professional perspectives on providing recovery-oriented services in Taiwan: a qualitative study
Authors: Chang Yen-Ching , Chang Ling-Hui , Hsu Su-Ting , Huang Meng-Wen
Published: March 2021

Background

The experiences of professionals in well-established recovery-oriented programs are valuable for professionals in similar practice settings. This study explored professionals’ experiences with providing recovery-oriented services in community psychiatric rehabilitation organizations.

Methods

Semi-structured interviews were conducted with 14 professionals from five recovery-oriented psychiatric rehabilitation organizations in Taiwan. The interviews were recorded and transcribed verbatim. Thematic analysis was used for the qualitative data analysis.

Results

The analyses documented three main themes with 13 subthemes. Recovery-oriented service implementation included seven subthemes: Enabling clients to set their own goals and make decisions, using a strengths-based approach, establishing partnerships with clients, improving individuals’ self-acceptance, encouraging community participation, seeking family, peer, and organizational support, and building team collaboration. Problems with implementing recovery-oriented services included limited policy and organizational support, a lack of understanding of recovery among professionals, stigma, clients’ lack of motivation or self-confidence in their own ability to achieve recovery, and passive or overprotective family members. Strategies to resolve implementation problems included policy changes and organizational support, improving the recovery competence and confidence of professionals, and family and public education.

Conclusions

To date, this is the first known study examining the perspectives of mental health professionals who have experience implementing recovery-oriented services in Asia. The participants identified family collaboration, anti-stigma efforts, and changes in policy and attitudes as critical to successful implementation and delivery of recovery-oriented services.
Post-traumatic stress disorder following childbirth
Authors: Ertan Deniz , Hingray Coraline , Burlacu Elena , Sterlé Aude , El-Hage Wissam
Published: March 2021

Background

Childbirth experience could be complicated and even traumatic. This study explored the possible risk factors for post-traumatic stress disorder following childbirth (PTSD-FC) in mothers and partners.

Methods

Through a cross-sectional online survey biographical, medical, psychological, obstetrical and trauma history data were collected. The PTSD-FC, postnatal depression, social support, and perceived mother-infant bond in 916 mothers and 64 partners were measured through self-reported psychometric assessments.

Results

Our findings highlight the possible impact of several risk factors such as emergency childbirth, past traumatic experiences and distressing events during childbirth on PTSD-FC. The difficulties in mother-infant bond and the postpartum depression were highly associated with the total score of PTSD-FC symptoms for mothers. While for partners, post-partum depression was highly associated with the total score of PTSD-FC.

Conclusions

Our study demonstrated significant links between psychological, traumatic and birth-related risk factors as well as the perceived social support and the possible PTSD following childbirth in mothers and partners. Given that, a specific attention to PTSD-FC and psychological distress following childbirth should be given to mothers and their partners following childbirth.
The giant resectable carcinoma of gall bladder—a case report
Authors: Bains Lovenish , Maranna Haraesh , Lal Pawan , Kori Ronal , Kaur Daljit , Mallya Varuna , Singh Veerpal
Published: March 2021

Background

Gall bladder cancer (GBC) is the fifth most common malignancy in the gastrointestinal system and the most common malignancy of the biliary system. GBC is a very aggressive malignancy having a 5 year survival rate of 19%. Giant Gall Bladder (GGB) is an uncommon condition that can result from cholelithiasis or chronic cholecystitis and rarely with malignancy.

Case report

A 65 year old lady presented with vague abdominal pain for 12 years and right abdominal lump of size 20 × 8 cms was found on examination. CT scan showed a circumferentially irregularly thickened wall (2.5 cm) of gall bladder indicative of malignancy. Per-operatively a GB of size 24 × 9 cm was noted and patient underwent radical cholecystectomy. It was surprise to find such a giant malignant GB with preserved planes. Histopathology, it was well differentiated adenocarcinoma of gall bladder of Stage II (T2a N0 M0).

Discussion

It is known that mucocoele of GB can attain large size, however chronic cholecystitis will lead to a shrunken gall bladder rather than an enlarged one. A malignant GB of such size and resectable is rare without any lymph node involvement or liver infiltration. Few cases of giant benign gall bladder have been reported in literature, however this appears to be the largest resectable gall bladder carcinoma reported till date as per indexed literature.

Conclusion

Giant GB is an uncommon finding. They are mostly benign, however malignant cases can occur. Radiological findings may suggest features of malignancy and define extent of disease. Prognosis depends on stage of disease and resectability, irrespective of size.
Using the Delphi technique to determine objectives and topical outline for a pharmaceutical care course: an experience from the Cuban higher education system
Authors: Martínez-Sánchez Alina M.
Published: March 2021

Background

Being pharmaceutical care one of the four areas defined by the International Pharmaceutical Federation’s Global Competence Framework, the curriculum redesigned scheme is a priority task to perform a pharmaceutical workforce capable to contribute significantly to the appropriate use of medicines. Therefore, the pharmacy curriculum should be adapted, in order to provide pharmacists with new knowledge and skills to provide pharmaceutical care services. This study used a modified Delphi technique to define objectives and topical outlines for a pharmaceutical care course on a pharmacy curriculum.

Methods

A modified Delphi process was used to determine a consensus among proposed course objectives and topical outlines. The preliminary phase of the study included a compilation of prospective objectives and outline topics on which to structure informational flow through the Delphi. A two-round modified Delphi process were completed by the participants in the study. The Delphi questionnaire was organized using six domains: the theoretical program foundation; recommended for teaching literature; instructional and educational objectives of the program (course structure); teaching methods; knowledge, skills and professional values considered; and students’ performance assessments. Nineteen items for evaluation within the referred domains were considered.

Results

Consensus was achieved among 15 participants regarding 10 objectives, and eleven topical outlines related to pharmaceutical care teaching in an undergraduate pharmacy course. Despite this favorable valuation and considering the qualitative evaluations provided by the participants, it was believed appropriate to analyze the recommendation for the inclusion of literature for the teaching of the course in Spanish language (73%). It resulted in a project proposal for the elaboration of a book by a group of authors from all the faculties of pharmacy in the country.

Conclusion

A Delphi expert panel achieved consensus on topical outline and objectives for a pharmaceutical care course. The results of this study can be used to underline the didactic guidance for pharmaceutical care teaching and learning useful for future pharmacy curriculum upgrades.
Cholinergic manipulations affect sensory responses but not attentional enhancement in macaque MT
Authors: Veith Vera Katharina , Quigley Cliodhna , Treue Stefan
Published: March 2021

Background

Attentional modulation in the visual cortex of primates is characterized by multiplicative changes of sensory responses with changes in the attentional state of the animal. The cholinergic system has been linked to such gain changes in V1. Here, we aim to determine if a similar link exists in macaque area MT. While rhesus monkeys performed a top-down spatial attention task, we locally injected a cholinergic agonist or antagonist and recorded single-cell activity.

Results

Although we confirmed cholinergic influences on sensory responses, there was no additional cholinergic effect on the attentional gain changes. Neither a muscarinic blockage nor a local increase in acetylcholine led to a significant change in the magnitude of spatial attention effects on firing rates.

Conclusions

This suggests that the cellular mechanisms of attentional modulation in the extrastriate cortex cannot be directly inferred from those in the primary visual cortex.
Precision-cut bovine udder slices (PCBUS) as an in-vitro-model of an early phase of infection of bovine mastitis
Authors: Filor Viviane , Petry Monique , Meißner Jessica , Kietzmann Manfred
Published: March 2021

Background

The aim of this study was to establish precision-cut bovine udder slices (PCBUS) as an in-vitro-model to investigate pathophysiological processes in the early phase of mastitis in order to have the possibility to investigate new therapeutic approaches for the treatment of such udder inflammation in later studies. Furthermore, this model should contribute to substitute in-vivo-experiments. Bovine mastitis is one of the most common and costly infectious diseases in the dairy industry, which is largely associated with the use of antimicrobial agents. Given this problem of antimicrobial resistance, it is essential to step up research into bacterial infectious diseases. Thus, the transfer of the in-vitro-model of precision-cut tissue slices to the bovine udder enables broad research into new therapeutic approaches in this area and can also be used to address issues in basic research or the characterisation of complex pathophysiological processes.

Results

A stimulation with LPS, PGN or the combination of both substances (LPS:PGN) demonstrates the ability of the PCBUS to react with a significant secretion of IL-1ß, TNF-α and PGE2.

Conclusion

The slices represent an instrument for investigating pharmacological interactions with udder tissue, which can be useful for studies on pharmacological questions and the understanding of complex pathophysiological processes of infection and inflammation.
Fetal heart rate development during labour
Authors: Urdal Jarle , Engan Kjersti , Eftestøl Trygve , Haaland Solveig H. , Kamala Benjamin , Mdoe Paschal , Kidanto Hussein , Ersdal Hege
Published: March 2021

Background

Fresh stillbirths (FSB) and very early neonatal deaths (VEND) are important global challenges with 2.6 million deaths annually. The vast majority of these deaths occur in low- and low-middle income countries. Assessment of the fetal well-being during pregnancy, labour, and birth is normally conducted by monitoring the fetal heart rate (FHR). The heart rate of newborns is reported to increase shortly after birth, but a corresponding trend in how FHR changes just before birth for normal and adverse outcomes has not been studied. In this work, we utilise FHR measurements collected from 3711 labours from a low and low-middle income country to study how the FHR changes towards the end of the labour. The FHR development is also studied in groups defined by the neonatal well-being 24 h after birth.

Methods

A signal pre-processing method was applied to identify and remove time periods in the FHR signal where the signal is less trustworthy. We suggest an analysis framework to study the FHR development using the median FHR of all measured heart rates within a 10-min window. The FHR trend is found for labours with a normal outcome, neonates still admitted for observation and perinatal mortality, i.e. FSB and VEND. Finally, we study how the spread of the FHR changes over time during labour.

Results

When studying all labours, there is a drop in median FHR from 134 beats per minute (bpm) to 119 bpm the last 150 min before birth. The change in FHR was significant ($$p<0.05$$

p
<
0.05

) using Wilcoxon signed-rank test. A drop in median FHR as well as an increased spread in FHR is observed for all defined outcome groups in the same interval.

Conclusion

A significant drop in FHR the last 150 min before birth is seen for all neonates with a normal outcome or still admitted to the NCU at 24 h after birth. The observed earlier and larger drop in the perinatal mortality group may indicate that they struggle to endure the physical strain of labour, and that an earlier intervention could potentially save lives. Due to the low amount of data in the perinatal mortality group, a larger dataset is required to validate the drop for this group.