bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors For Prolonged Opioid Use After Spine Surgery
Authors: Kowalski Christopher , Ridenour Ryan , McNutt Sarah , Ba Djibril , Liu Guodong , Bible Jesse , Aynardi Michael , Garner Matthew , Leslie Douglas , Dhawan Aman
Published: April 2021

Study Design:

Retrospective review.

Objective:

Our purpose was to evaluate factors associated with increased risk of prolonged post-operative opioid pain medication usage following spine surgery, as well as identify the risk of various post-operative complications that may be associated with pre-operative opioid usage.

Methods:

The MarketScan commercial claims and encounters database includes approximately 39 million patients per year. Patients undergoing cervical and lumbar spine surgery between the years 2005-2014 were identified using CPT codes. Pre-operative comorbidities including DSM-V mental health disorders, chronic pain, chronic regional pain syndrome (CRPS), obesity, tobacco use, medications, and diabetes were queried and documented. Patients who utilized opioids from 1-3 months prior to surgery were identified. This timeframe was chosen to exclude patients who had been prescribed pre- and post-operative narcotic medications up to 1 month prior to surgery. We utilized odds ratios (OR), 95% Confidence Intervals (CI), and regression analysis to determine factors that are associated with prolonged post-operative opioid use at 3 time intervals.

Results:

553,509 patients who underwent spine surgery during the 10-year period were identified. 34.9% of patients utilized opioids 1-3 months pre-operatively. 25% patients were still utilizing opioids at 6 weeks, 17.3% at 3 months, 12.7% at 6 months, and 9.0% at 1 year after surgery. Pre-operative opioid exposure was associated with increased likelihood of post-operative use at 6-12 weeks (OR 5.45, 95% CI 5.37-5.53), 3-6 months (OR 6.48, 95% CI 6.37-6.59), 6-12 months (OR 6.97, 95% CI 6.84-7.11), and >12 months (OR 7.12, 95% CI 6.96-7.29). Mental health diagnosis, tobacco usage, diagnosis of chronic pain or CRPS, and non-narcotic neuromodulatory medications yielded increased likelihood of prolonged post-op opioid usage.

Conclusions:

Pre-operative narcotic use and several patient comorbidities diagnoses are associated with prolonged post-operative opioid usage following spine surgery. Chronic opioid use, diagnosis of chronic pain, or use of non-narcotic neuromodulatory medications have the highest risk of prolonged post-operative opioid consumption. Patients using opiates pre-operatively did have an increased 30 and 90-day readmission risk, in addition to a number of serious post-operative complications. This data provides spine surgeons a number of variables to consider when determining post-operative analgesia strategies, and provides health systems, providers, and payers with information on complications associated with pre-operative opioid utilization.
Impact of the early COVID-19 era on endometriosis patients: Symptoms, stress, and access to care
Authors: Ramos-Echevarría Paola M , Soto-Soto Denisse M , Torres-Reverón Annelyn , Appleyard Caroline B , Akkawi Tala , Barros-Cartagena Bárbara D , López-Rodríguez Verónica , Castro-Figueroa Eida M , Flores-Caldera Idhaliz
Published: April 2021

Introduction:

Monitoring the impact of natural disasters such as pandemics on health and wellbeing is a public health priority. Stress is proven to affect pain intensity and quality of life of endometriosis patients. A cross-sectional study was conducted to determine whether the measures implemented to mitigate COVID-19 infections had a substantial impact on risk behaviors, endometriosis symptoms, stress, and access to healthcare.

Methods:

Electronic questionnaires that measured COVID-19 impact and peri-traumatic stress were disseminated through social media over June–September 2020 and completed by 82 adult patients with endometriosis living in Puerto Rico. Descriptive data analysis and correlations were done in quantitative data and systematic analysis of free text was done on qualitative responses.

Results:

Participants self-reported worsening of endometriosis symptoms and high levels of peri-traumatic stress, as well as changes in risk behaviors (exercise, nutrition, sedentarism, sleep) during the pandemic in comparison to the previous months. They also reported substantial barriers in access to medical appointments, scheduled procedures, and prescriptions. Electronic health modalities (telemedicine, mobile apps) were considered acceptable alternatives for gynecologic care during natural disasters.

Conclusion:

The COVID-19 pandemic negatively impacts the health and wellbeing of endometriosis patients while imposing substantial restrictions on access to health care. These timely insights will guide the development and implementation of plans to address barriers to health care and minimize long-term detrimental effects of natural disasters on the health of those living with stress-related disorders such as endometriosis.
Osteochondral Lesions of the Distal Tibial Plafond: A Systematic Review of Lesion Locations and Treatment Outcomes
Authors: Allahabadi Sachin , Allahabadi Sameer , Allala Ruthvik , Garg Kartik , Pandya Nirav K. , Lau Brian C.
Published: April 2021

Background:

Osteochondral lesions of the tibial plafond (OLTPs) remain less common than osteochondral lesions of the talus (OLTs), but recognition of the condition has increased.

Purpose:

To systematically evaluate the literature on lesion locations and treatment outcomes of OLTPs, whether in isolation or in combination with OLTs.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A search was performed using the PubMed, Embase, and CINAHL databases for studies on lesion locations or with imaging or treatment outcomes of OLTPs. Case reports and reports based on expert opinion were excluded. Lesion locations as well as outcome measure results were aggregated. The Methodological Index for Non-randomized Studies score was used to assess methodological quality when applicable.

Results:

Included in this review were 10 articles, all published in 2000 or later. Most studies were evidence level 4, and the mean Methodological Index for Non-randomized Studies score was 8.6 (range, 8-10). Overall, 174 confirmed OLTP cases were identified, and the mean patient age was 38.8 years. Of the 157 lesions with confirmed locations, the most common was central-medial (32/157; 20.4%). Of 6 studies on treatment outcomes, all but 1 evaluated bone marrow stimulation techniques. Microfracture of small lesions (<150 mm2) was the most common treatment utilized. Imaging and functional outcomes appeared favorable after treatment. The data did not support differences in outcomes between isolated OLTPs and OLTPs with coexisting OLTs.

Conclusion:

Osteochondral lesions of the distal tibia most commonly occurred at the central-medial tibial plafond. Microfracture of small lesions was the most common treatment utilized, and clinical and magnetic resonance imaging results were favorable, although data were heterogeneous. Areas for future research include the following: the effect of patient factors and additional pathologies on outcomes; larger or deeper lesion treatment; more direct comparisons of outcomes between kissing or coexisting lesions and isolated lesions; and head-to-head comparison of treatments, such as microfracture, bone marrow–derived cell transplantation, and osteochondral autografts/allografts.
Improving Patient\Population Health: Using ‘Why’ to Develop a Transformative Research Center
Authors: Aebersold Michelle , McCullagh Marjorie , Titler Marita , Jiang Yun , Zhang Xingyu , Tschannen Dana , Friese Christopher
Published: April 2021

Introduction

Novel approaches to address the most vexing problems facing patients and vulnerable populations are needed. The purpose of this project was to establish an innovative research Center based on the principles of transformational organizations.

Methods

A new Center formed included faculty members with expertise in cancer, serious illness, and population health. Applying Sinek’s “why, how, and what” framework, members developed and refined a purpose statement and strategic objectives. The Center now includes members representing diverse disciplines. Year 1 accomplishments included a refined mission and vision statement, two funded research proposals, one submitted training grant, one administrative hire, and active recruitment of two-research faculty to support Center activities.

Conclusions

The newly-formed Center for Improving Patient and Population Health has enabled scholars within a research-intensive school of nursing to forge new partnerships to compete successfully for larger, complicated grant proposals on shorter deadlines. Opportunities exist to integrate students and research staff more fully into Center operations.
People as infrastructure politics in global north cities: Chicago’s South Side
Authors: Wilson David
Published: April 2021

People as infrastructure politics, a fruitful new analytic in urban political studies, has mysteriously been minimally studied in global north cities and their most punished places, America’s rust belt environments. I chronicle a flourishing people as infrastructure politics in one American rust belt city setting, Chicago’s neglected South Side. Here hundreds of subalterns participate in this resistance politics to reverse what I focus on: a commodifying blues club. Subalterns extract life-giving stuff from this space as they toil in Chicago’s and the South Side’s low-wage economies and marginalized communities. I show that this group’s political acts and practices, guided by their ordinary space’s interwovenness with taut political alliances and alternative ways to see, prove more sly and proactive than we have recognized. This slyness, first, entails an active use of a “back-path politics” as actions confront less club practices than the discursive content of practices. This slyness, second, leads with what I term resistive fragments: momentary, political charged interventions that powerfully resound across the club. The results suggest that this distinctive resistance politics is alive in America’s rust belt cities, closely mirrors realities in global south cities, and is far more complex that we had previously known.
Irreducible Fractures and Dislocations of the Ankle Associated With Entrapment of the Posterior Tibial Tendon Within the Tibiofibular Interosseous Space: A Case Series and Literature Review
Authors: Colomb Eric , Muscatelli Stefano , Morash Joel G. , Crawford Eileen A. , Holmes James R. , Walton David M.
Published: April 2021

Level of Evidence: Level IV, case series.
Geographic Distribution of Foot and Ankle Orthopedic Surgeons Throughout the United States
Authors: Fanelli Matthew , Cush Coleman , Zhang Hui , Wagner Benjamin , Young Amanda J. , Grandizio Louis Christopher , Cush Gerard
Published: April 2021

Background:

At present, the geographic distribution of orthopedic foot and ankle (OFA) surgeons in the United States is poorly defined. The purpose of this investigation is to determine the geographic distribution of OFA surgeons in the United States. We hypothesize that there will be differences in OFA surgeon density throughout the United States and that economic factors may play a role in access to subspecialty OFA care.

Methods:

A current membership list was obtained from the American Orthopaedic Foot & Ankle Society (AOFAS). Active members were categorized relative to states and US congressional districts, using publicly available census data. The relationship between income and surgeon density was determined using a Pearson correlation.

Results:

We identified a list of 1103 active AOFAS members. There was an average of 0.38 and 0.40 OFA surgeons per 100 000 people in each state and congressional district, respectively. We found a weak negative relationship demonstrating that regions with higher levels of poverty had fewer OFA surgeons, with a Pearson correlation coefficient of –0.14 (95% CI: –0.24, –0.04), P = .008.

Conclusion:

There is wide geographic variation of OFA surgeon density throughout the United States. Regions with higher levels of poverty were weakly associated with decreased population density of OFA surgeons compared to regions with lower poverty levels. Understanding these trends may aid in developing both recruitment and referral strategies for complex foot and ankle care in underserved regions.

Level of Evidence:

Level V.
Photography as Business: The Wild Ride of a Young Entrepreneur in His New Venture
Authors: Ford-Eickhoff Karen , Cress Aaron
Published: April 2021

Aaron, a young entrepreneur, was striving to establish a self-funded business that combined his love of photography with the ability to earn a living while doing what he enjoyed. Aaron’s journey was filled with many high points, low points, and major detours as he simultaneously navigated starting a business, earning an undergraduate degree, and marrying a Chinese woman whose visa was about to expire. Aaron’s experience illustrated the many challenges young entrepreneurs may encounter and must then conquer. Covering a decade of Aaron’s life, from age 19 to 29, his story particularly focused on the opportunities as well as the challenges that arose along the way. Aaron’s experiences exemplified the need for entrepreneurial risk-taking, creativity, and ability to bounce back when adversity struck. Concluding with several possible paths along which his journey may take him in the future, the case sets the stage for readers to evaluate the options and decide what they think Aaron should do.
Diagnostic Performance of Ultrasonography in Patients With Pneumonia: An Updated Comparative Systematic Review and Meta-analysis
Authors: Sistani Sharareh Sanei , Parooie Fateme
Published: April 2021

Objectives:

A chest radiograph (CXR) is still the preferred diagnostic method when pneumonia is suspected, although the sensitivity is relatively low. The aim of this study was to compare the diagnostic sensitivity, specificity, and accuracy of ultrasonography (US) for the diagnosis of community-acquired pneumonia (CAP), compared with CXR.

Materials and Methods:

A principled search was conducted to identify original English articles using PubMed, EMBASE, Web of Science, Scopus, and the Cochrane library, with the end date of October 2020. A combination of keywords, such as “ultrasound” or “ultrasonography,” “pneumonia,” “sensitivity,” and “specificity,” was used. Methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Statistical analysis was completed on the resulting study data.

Results:

The search produced 16 eligible articles that reported on 2040 patients. The overall pooled sensitivity for US and CXR, to diagnose pneumonia, was 0.96 and 0.65, respectively. The overall pooled specificity for US and CXR was 0.85 and 0.81, respectively. The overall pooled positive likelihood ratio for US and CXR was 9.74 and 3.67, respectively. The negative likelihood ratio for US and CXR was 0.05 and 0.42, respectively. In addition, summary receiver operative characteristics areas under the curve were 0.98 for US and 0.77 for CXR.

Conclusion:

This review demonstrated that lung US is a useful technique for the diagnosis of pneumonia. This diagnostic method can be used by emergency physicians with high accuracy, sensitivity, and specificity. Among an elderly population, this diagnostic method may be a better choice than CXR. The rapid performance of lung US may facilitate a quick, cost-effective, and safe diagnosis of this potentially fatal disease.
Type 2 diabetes risk in sarcoidosis patients untreated and treated with corticosteroids
Authors: Entrop Joshua P. , Kullberg Susanna , Grunewald Johan , Eklund Anders , Brismar Kerstin , Arkema Elizabeth V.
Published: April 2021

Background

The rate of type 2 diabetes mellitus (T2D) is increased in sarcoidosis patients but it is unknown if corticosteroid treatment plays a role. We investigated whether the T2D risk is higher in untreated and corticosteroid-treated sarcoidosis patients compared with the general population.

Methods

In this cohort study, individuals with two or more International Statistical Classification of Diseases and Related Health Problems (ICD) codes for sarcoidosis were identified from the Swedish National Patient Register (NPR) (n=5754). Corticosteroid dispensations within 3 months before or after the first sarcoidosis diagnosis were identified from the Swedish Prescribed Drug Register (PDR). General population comparators without sarcoidosis were matched to cases 10:1 on age, sex and region of residence (n=61 297). Incident T2D was identified using ICD codes (NPR) and antidiabetic drug dispensations (PDR). Follow-up was from the second sarcoidosis diagnosis/matching date until T2D, emigration, death or study end (December 2013). Cox regression models adjusted for age, sex, education, country of birth, healthcare regions and family history of diabetes were used to estimate hazard ratios (HRs). We used flexible parametric models to examine the T2D risk over time.

Results

40% of sarcoidosis patients were treated with corticosteroid at diagnosis. The T2D rate was 7.7 per 1000 person-years in untreated sarcoidosis, 12.7 per 1000 person-years in corticosteroid-treated sarcoidosis and 5.5 per 1000 person-years in comparators. The HR for T2D was 1.4 (95% CI 1.2–1.8) associated with untreated sarcoidosis and 2.3 (95% CI 2.0–3.0) associated with corticosteroid-treated sarcoidosis. The T2D risk was highest for corticosteroid-treated sarcoidosis in the first 2 years after diagnosis.

Conclusions

Sarcoidosis is associated with an increased risk of T2D especially in older, male, corticosteroid-treated patients at diagnosis. Screening for T2D for these patients is advisable.
High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis
Authors: Chakrabarti Arindam , Mar Jordan S. , Choy David F. , Cao Yi , Rathore Nisha , Yang Xiaoying , Tew Gaik W. , Li Olga , Woodruff Prescott G. , Brightling Christopher E. , Grimbaldeston Michele , Christenson Stephanie A. , Bafadhel Mona , Rosenberger Carrie M.
Published: April 2021

Introduction

COPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral biomarker of COPD exacerbations characterised by bacterial/neutrophilic inflammation is lacking. Granulocyte-colony stimulating factor (G-CSF) is a key cytokine elevated during bacterial infection and mediates survival, proliferation, differentiation and function of neutrophils.

Objective

We hypothesised that high peripheral G-CSF would be indicative of COPD exacerbations with a neutrophilic and bacterial phenotype associated with microbial dysbiosis.

Methods

Serum G-CSF was measured during hospitalised exacerbation (day 0 or D0) and after 30 days of recovery (Day30 or D30) in 37 subjects. In a second cohort, serum and sputum cytokines were measured in 59 COPD patients during stable disease, at exacerbation, and at 2-weeks and 6-weeks following exacerbation.

Results

Serum G-CSF was increased during exacerbation in a subset of patients. These exacerbations were enriched for bacterial but not viral or type-2 biologies. The median serum G-CSF level was 1.6-fold higher in bacterial exacerbation compared to nonbacterial exacerbation (22 pg·mL−1versus13 pg·mL−1, p=0.0007). Serum G-CSF classified bacterial exacerbations with an area under the curve (AUC) for the receiver operating characteristic (ROC) curve equal to 0.76. Exacerbations with a two-fold or greater increase in serum G-CSF were characterised by neutrophilic inflammation, with increased sputum and blood neutrophils, and high sputum interleukin (IL)-1β, IL-6 and serum amyloid A1 (SAA1) levels. These exacerbations were preceded by dysbiosis, with decreased microbiome diversity and enrichment of respiratory pathogens such asHaemophilusandMoraxella. Furthermore, serum G-CSF at exacerbation classified neutrophilic-dysbiotic exacerbations (AUC for the ROC curve equal to 0.75).

Conclusions

High serum G-CSF enriches for COPD exacerbations characterised by neutrophilic inflammation with underlying bacterial dysbiosis.
Endothelial dysfunction in COPD: a systematic review and meta-analysis of studies using different functional assessment methods
Authors: Theodorakopoulou Marieta P. , Alexandrou Maria Eleni , Bakaloudi Dimitra Rafailia , Pitsiou Georgia , Stanopoulos Ioannis , Kontakiotis Theodoros , Boutou Afroditi K.
Published: April 2021

Background

Cardiovascular disease is a major cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be one of the pathogenetic mechanisms involved. This is a systematic review and meta-analysis of studies using any available functional method to examine differences in endothelial function between patients with COPD and individuals without COPD (controls).

Methods

Literature search involved PubMed and Scopus databases. Eligible studies included adult patients and evaluated endothelial damageviafunctional methods. The Newcastle–Ottawa scale was applied to evaluate the quality of retrieved studies. Subgroup analyses were performed to explore heterogeneity across the studies. Funnel plots were constructed to evaluate publication bias.

Results

Of the 21 reports initially identified, 19 studies with a total of 968 participants were included in the final meta-analysis. A significantly impaired response in endothelium-dependent (weighted mean between-group difference (WMD) −2.59, 95% CI −3.75 to −1.42) and -independent vasodilation (WMD −3.13, 95% CI −5.18 to −1.09) was observed in patients with COPD compared to controls. When pooling all studies together, regardless of the technique used for assessment of vascular reactivity, pronounced endothelial dysfunction was observed in COPD compared to controls (standardised mean difference (SMD) −1.19, 95% CI −1.69 to −0.68). Subgroup analysis showed that the difference was larger when patients with COPD were compared with nonsmoking controls (SMD −1.75, 95% CI −2.58 to −0.92). Sensitivity analyses confirmed the results.

Conclusions

Patients with COPD have significantly impaired endothelial function compared to controls without COPD. Future studies should delineate the importance of endothelial dysfunction towards development of cardiovascular disease in COPD.
LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma
Authors: Wang Jiancheng , Yin Gang , Bian Hu , Yang Jiangli , Zhou Pengcheng , Yan Kai , Liu Cheng , Chen Pei , Zhu Jun , Li Zhi , Xue Tongqing
Published: April 2021

Background

Long non-coding RNA (lncRNA) XIST has been implicated in the progression of a variety of tumor diseases. The purpose of this study was to explore the molecular role of lncRNA XIST in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods

The expression levels of lncRNA XIST, miR-192 and TRIM25 in HBV-related HCC tissues and HepG2.2.15 cells were detected by qRT-PCR. Biological information and luciferin gene reporter assay were performed to detect the interaction among lncRNA XIST, miR-192 and TRIM25. CCk-8 assay, wound healing assay and colony formation assay were conducted to detect the proliferation and migration ability of HepG2.2.15 cells.

Results

qRT-PCR results showed that the expression levels of lncRNA XIST were remarkably increased in HBV-related HCC tissues and HepG2.2.15 cells. In addition, miR-192 was a direct target gene of lncRNA XIST, and the expression of miR-192 and lncRNA XIST were negatively correlated. Moreover, overexpression of miR-192 observably inhibited the proliferation and migration of HCC cells, while overexpression of lncRNA XIST showed an opposite effect. Furthermore, TRIM25 was a direct target of miR-192, and lncRNA XIST could up-regulate the expression of TRIM25 by targeting miR-192.

Conclusion

LncRNA XIST could up-regulate the expression of TRIM25 by targeting and binding to miR-192, thus accelerating the occurrence and development of HCC.
Localized environmental heterogeneity drives the population differentiation of two endangered and endemic Opisthopappus Shih species
Authors: Ye Hang , Wang Zhi , Hou Huimin , Wu Jiahui , Gao Yue , Han Wei , Ru Wenming , Sun Genlou , Wang Yiling
Published: April 2021

Background

Climate heterogeneity not only indirectly shapes the genetic structures of plant populations, but also drives adaptive divergence by impacting demographic dynamics. The variable localized climates and topographic complexity of the Taihang Mountains make them a major natural boundary in Northern China that influences the divergence of organisms distributed across this region. Opisthopappus is an endemic genus of the Taihang Mountains that includes only two spatially partitioned species Opisthopappus longilobus and Opisthopappus taihangensis. For this study, the mechanisms behind the genetic variations in Opisthopappus populations were investigated.

Results

Using SNP and InDel data coupled with geographic and climatic information, significant genetic differentiation was found to exist either between Opisthopappus populations or two species. All studied populations were divided into two genetic groups with the differentiation of haplotypes between the groups. At approximately 17.44 Ma of the early Miocene, O. taihangensis differentiated from O. longilobus under differing precipitation regimes due to the intensification of the Asian monsoon. Subsequently, intraspecific divergence might be induced by the dramatic climatic transformation from the mid- to late Miocene. During the Pleistocene period, the rapid uplift of the Taihang Mountains coupled with violent climatic oscillations would further promote the diversity of the two species. Following the development of the Taihang Mountains, its complex topography created geographical and ecological heterogeneity, which could lead to spatiotemporal isolation between the Opisthopappus populations. Thus the adaptive divergence might occur within these intraspecific populations in the localized heterogeneous environment of the Taihang Mountains.

Conclusions

The localized environmental events through the integration of small-scale spatial effects impacted the demographic history and differentiation mechanism of Opisthopappus species in the Taihang Mountains. The results provide useful information for us to understand the ecology and evolution of organisms in the mountainous environment from population and species perspective.
Temporal transcriptome profiling of developing seeds reveals candidate genes involved in oil accumulation in safflower (Carthamus tinctorius L.)
Authors: Li Dandan , Wang Qing , Xu Xin , Yu Jingsheng , Chen Zhiyu , Wei Bo , Wu Wei
Published: April 2021

Background

The investigation of molecular mechanisms involved in lipid metabolism plays a critical role for the genetic engineering of safflower (Carthamus tinctorius L.) to increase the oil accumulation level or to change the oil composition. Although transcript sequences are currently available for the leaves and flowers of safflower, a wide range scan of temporal transcripts at different stages of seed development has not been conducted for safflower.

Results

In this study, temporal transcriptome sequencing was executed at 10, 14, 18, and 22 days after flowering (DAF) to uncover the molecular networks concerned in the biosynthesis of unsaturated fatty acids (USFAs). The results revealed that the biosynthesis of fatty acids is a dominant cellular process from 10 to 14 DAF, while degradation mainly happens after 18 DAF. Significant expression changes of two genes, stearoyl-[acyl-carrier-protein] 9-desaturase gene (SAD) from 10 to 14 DAF and oleate desaturase (FAD2–1) from 14 to 18 DAF, were detected at the transcriptomic levels, and the temporal expression patterns revealed by the transcriptomic analysis were confirmed using quantitative real-time PCR experiments. In addition, 13 candidate transcription factors (TFs) involved in regulating the expression level of the FAD2–1 gene were identified.

Conclusions

These results create a link between fatty acid biosynthesis and gene expression at different developmental stages of the seeds, provide insight into the underlying lipid metabolism, and meanwhile lay an important foundation for the genetic engineering of safflower varieties. We have identified novel candidate genes, including TFs, that are worthy of further exploration.
Differentiation of brain metastases from small and non-small lung cancers using apparent diffusion coefficient (ADC) maps
Authors: Müller Sebastian Johannes , Khadhraoui Eya , Neef Nicole E. , Riedel Christian Heiner , Ernst Marielle
Published: April 2021

Background

Brain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a less  aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.

Methods

We enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.

Results

Out of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988.

Conclusions

In patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.

Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).
Development and validation of multiparametric MRI-based nomogram for predicting occult metastasis risk in early tongue squamous cell carcinoma
Authors: Saenthaveesuk Pensiri , Yang Le , Zeng Bin , Xu Meng , Young Simon , Liao Guiqing , Liang Yujie
Published: April 2021

Background

Nomograms are currently used in predicting individualized outcomes in clinical oncology of several cancers. However, nomograms for evaluating occult nodal metastasis of patients with squamous cell carcinoma of lateral tongue (SCCLT) have not been widely investigated for their functionality. This retrospective cohort study was designed to address this question.

Methods

This study was divided into primary and validation cohorts. The primary cohort comprised 120 patients diagnosed between 2012 and 2017, whereas the validation cohort included 41 patients diagnosed thereafter. The diagnostic value of multiparametric MRI, including radiologic tumor thickness threshold (rTTT) in three-dimensions, paralingual distance, and sublingual distance were investigated. A nomogram was developed based on stepwise logistic regression of potential predictors associated with nodal metastasis in the primary cohort and then tested for predictive accuracy in the validation cohort using area under the curve (AUC) and goodness-of-fit tests.

Results

Multivariate analysis, tumor size (odd ratio [OR] 15.175, 95% confidence interval [CI] 1.436–160.329,P = 0.024), rTTT (OR 11.528, 95% CI 2.483–53.530,P = 0.002), paralingual distance (OR 11.976, 95% CI 1.981–72.413,P = 0.005), and tumor location (OR 6.311, 95% CI 1.514–26.304,P = 0.011) were included in the nomogram to predict the likelihood of having cervical metastasis. A nomogram cutoff value of 210 points (sensitivity 93.8%, specificity 87.5%) was significantly different to classify the patients metastasis risk group (P < 0.001). Nomogram showed predictive accuracy with AUC 0.881 (95% CI 0.779–0.983,P < 0.001) and good calibration after the validation.

Conclusions

A preoperative nomogram incorporating multiparametric MRI demonstrated good prediction and performed adequately in our study. Three-dimensional assessment of occult metastasis risk value obtained from this nomogram can assist in preoperative decision making for individual patients with early-stage SCCLT. The probability of nodal metastasis tended to be greater than 20% in patients with high metastasis risk or nomogram total score > 210 points.
The Regeneración Urbana, Calidad de Vida y Salud - RUCAS project: a Chilean multi-methods study to evaluate the impact of urban regeneration on resident health and wellbeing
Authors: Baeza Fernando , Vives Vergara Alejandra , González Francisca , Orlando Laura , Valdebenito Roxana , Cortinez-O’Ryan Andrea , Slesinski Claire , Diez Roux Ana V.
Published: April 2021

Background

The available evidence of the health effects of urban regeneration is scarce In Latin America, and there are no studies focused on formal housing that longitudinally evaluate the impact of housing and neighborhood interventions on health. The “Regeneración Urbana, Calidad de Vida y Salud” (Urban Regeneration, Quality of Life, and Health) or RUCAS project is a longitudinal, multi-method study that will evaluate the impact of an intervention focused on dwellings, built environment and community on the health and wellbeing of the population in two social housing neighborhoods in Chile.

Methods

RUCAS consists of a longitudinal study where inhabitants exposed and unexposed to the intervention will be compared over time within the study neighborhoods (cohorts), capitalizing on interventions as a natural experiment. Researchers have developed a specific conceptual framework and identified potential causal mechanisms. Proximal and more distal intervention effects will be measured with five instruments, implemented pre- and post-interventions between 2018 and 2021: a household survey, an observation tool to evaluate dwelling conditions, hygrochrons for measuring temperature and humidity inside dwellings, systematic observation of recreational areas, and qualitative interviews. Survey baseline data (956 households, 3130 individuals) is presented to describe sociodemographics, housing and health characteristics of both cohorts, noting that neighborhoods studied show worse conditions than the Chilean population.

Discussion

RUCAS’ design allows for a comprehensive evaluation of the effects that the intervention could have on various dimensions of health and health determinants. RUCAS will face some challenges, like changes in the intervention process due to adjustments of the master plan, exogenous factors –including COVID-19 pandemic and associated lockdowns– and lost to follow-up. Given the stepped wedge design, that the study capitalizes on within household changes over time, the possibility of adjusting data collection process and complementarity of methods, RUCAS has the flexibility to adapt to these circumstances. Also, RUCAS’ outreach and retention strategy has led to high retention rates. RUCAS will provide evidence to inform regeneration processes, highlighting the need to consider potential health effects of regeneration in designing such interventions and, more broadly, health as a key priority in urban and housing policies.
Are people aware of the link between alcohol and different types of Cancer?
Authors: Calvert Collin M. , Toomey Traci , Jones-Webb Rhonda
Published: April 2021

Background

Alcohol consumption is causally linked to several different types of cancer, including breast, liver, and colorectal cancer. While prior studies have found low awareness of the overall alcohol-cancer link, few have examined how awareness differs for each type of cancer. Greater awareness of risks associated with alcohol use may be a key factor in reducing alcohol-related cancer incidence.

Methods

We surveyed 1759 people of legal drinking age at the 2019 Minnesota State Fair. We used multivariable generalized linear models and linear regression models with robust standard errors to investigate factors associated with alcohol-cancer risk awareness. Models were fit examining predictors of overall awareness of alcohol as a risk factor for cancer, and prevalence of awareness of alcohol as a risk factor for specific types of cancer.

Results

Prevalence of awareness varied by cancer type, with awareness of alcohol causing liver cancer having the highest prevalence (92%) and awareness of alcohol causing breast cancer having the lowest prevalence (38%). Factors associated with awareness of alcohol-cancer risk differed by type of cancer.

Conclusions

In general, awareness of the risk of alcohol for certain types of cancer was low to moderate, reflecting a need to inform people not only that alcohol increases risk of cancer, but which types of cancer are most highly associated alcohol.
A novel variant in the PDE4D gene is the cause of Acrodysostosis type 2 in a Lithuanian patient: a case report
Authors: Petraitytė Gunda , Šiaurytė Kamilė , Mikštienė Violeta , Cimbalistienė Loreta , Kriaučiūnienė Dovilė , Matulevičienė Aušra , Utkus Algirdas , Preikšaitienė Eglė
Published: April 2021

Background

Acrodysostosis is a rare hereditary disorder described as a primary bone dysplasia with or without hormonal resistance. Pathogenic variants in the PRKAR1A and PDE4D genes are known genetic causes of this condition. The latter gene variants are more frequently identified in patients with midfacial and nasal hypoplasia and neurological involvement. The aim of our study was to analyse and confirm a genetic cause of acrodysostosis in a male patient.

Case presentation

We report on a 29-year-old Lithuanian man diagnosed with acrodysostosis type 2. The characteristic phenotype includes specific skeletal abnormalities, facial dysostosis, mild intellectual disability and metabolic syndrome. Using patient’s DNA extracted from peripheral blood sample, the novel, likely pathogenic, heterozygous de novo variant NM_001104631.2:c.581G > C was identified in the gene PDE4D via Sanger sequencing. This variant causes amino acid change (NP_001098101.1:p.(Arg194Pro)) in the functionally relevant upstream conserved region 1 domain of PDE4D.

Conclusions

This report further expands the knowledge of the consequences of missense variants in PDE4D that affect the upstream conserved region 1 regulatory domain and indicates that pathogenic variants of the gene PDE4D play an important role in the pathogenesis mechanism of acrodysostosis type 2 without significant hormonal resistance.
Chronic temperature stress inhibits reproduction and disrupts endocytosis via chaperone titration in Caenorhabditis elegans
Authors: Plagens Rosemary N. , Mossiah Isiah , Kim Guisbert Karen S. , Guisbert Eric
Published: April 2021

Background

Temperature influences biology at all levels, from altering rates of biochemical reactions to determining sustainability of entire ecosystems. Although extended exposure to elevated temperatures influences organismal phenotypes important for human health, agriculture, and ecology, the molecular mechanisms that drive these responses remain largely unexplored. Prolonged, mild temperature stress (48 h at 28 °C) has been shown to inhibit reproduction inCaenorhabditis eleganswithout significantly impacting motility or viability.

Results

Analysis of molecular responses to chronic stress using RNA-seq uncovers dramatic effects on the transcriptome that are fundamentally distinct from the well-characterized, acute heat shock response (HSR). While a large portion of the genome is differentially expressed ≥ 4-fold after 48 h at 28 °C, the only major class of oogenesis-associated genes affected is the vitellogenin gene family that encodes for yolk proteins (YPs). Whereas YP mRNAs decrease, the proteins accumulate and mislocalize in the pseudocoelomic space as early as 6 h, well before reproduction declines. A trafficking defect in a second, unrelated fluorescent reporter and a decrease in pre-synaptic neuronal signaling indicate that the YP mislocalization is caused by a generalized defect in endocytosis. Molecular chaperones are involved in both endocytosis and refolding damaged proteins. Decreasing levels of the major HSP70 chaperone, HSP-1, causes similar YP trafficking defects in the absence of stress. Conversely, increasing chaperone levels through overexpression of the transcription factor HSF-1 rescues YP trafficking and restores neuronal signaling.

Conclusions

These data implicate chaperone titration during chronic stress as a molecular mechanism contributing to endocytic defects that influence multiple aspects of organismal physiology. Notably, HSF-1 overexpression improves recovery of viable offspring after exposure to stress. These findings provide important molecular insights into understanding organismal responses to temperature stress as well as phenotypes associated with chronic protein misfolding.
Do clinicians in areas of declining malaria transmission adhere to malaria diagnosis guidelines? A cross-sectional study from Kampala, Uganda
Authors: Atukunda Angella , Deogratius Mwaka Amos , Arinaitwe Emmanuel , Orishaba Philip , Kamya Moses R. , Nankabirwa Joaniter I.
Published: April 2021

Background

Uganda's clinical management guidelines recommend a malaria laboratory test in all patients presenting with fever (history of fever or an axillary temperature ≥ 37.5 °C), and only those with a positive test receive anti-malarial treatment. However, the current practice in areas with declining malaria transmission remains unknown. This study assessed the clinicians’ diagnostic practices, the factors associated with recommending a test, and the risk of missing a malaria case when a test is not recommended in patients presenting with fever in Kampala, an area of declining malaria transmission in Uganda.

Methods

Between January and March 2020, 383 participants aged ≥ 12 years and presenting to Kisenyi Health Centre IV in Kampala district with fever were enrolled in the study. A questionnaire was administered during exit interviews, routine diagnostic practices were recorded from participant clinical notes, and a research blood slide was obtained for later reading.

Results

Of the enrolled participants, 356 (93%) had a malaria diagnostic test recommended by the clinician. Factors associated with increasing prevalence of having a test recommended included; history of overnight travel (adjusted prevalence ratio [aPR] 1.07, 95% confidence interval [CI] 1.02–1.13, p = 0.011), being married (aPR = 1.07, 95% CI 1.01–1.13, p = 0.022), and having tertiary education (aPR = 1.09 95% CI 1.01–1.17, p = 0.031). Among the 27 participants where a malaria diagnostic test was not recommended, 4 (14.8%) had a positive study smear.

Conclusion

Despite having significant declines in malaria transmission in Kampala in the last decade, clinicians at the study health facility highly adhered to the clinical management guidelines, recommending a malaria test in almost all patients presenting with fever. However, a significant proportion of malaria cases was missed when a test was not recommended. These results highlight the importance of laboratory testing for malaria in all patients who present with fevers and live in endemic settings even when the transmission has significantly declined.
Nanotechnology based solutions for anti-leishmanial impediments: a detailed insight
Authors: Jamshaid Humzah , Din Fakhar ud , Khan Gul Majid
Published: April 2021

As a neglected tropical disease, Leishmaniasis is significantly instigating morbidity and mortality across the globe. Its clinical spectrum varies from ulcerative cutaneous lesions to systemic immersion causing hyperthermic hepato-splenomegaly. Curbing leishmanial parasite is toughly attributable to the myriad obstacles in existing chemotherapy and immunization. Since the 1990s, extensive research has been conducted for ameliorating disease prognosis, by resolving certain obstacles of conventional therapeutics viz. poor efficacy, systemic toxicity, inadequate drug accumulation inside the macrophage, scarce antigenic presentation to body’s immune cells, protracted length and cost of the treatment. Mentioned hurdles can be restricted by designing nano-drug delivery system (nano-DDS) of extant anti-leishmanials, phyto-nano-DDS, surface modified—mannosylated and thiolated nano-DDS. Likewise, antigen delivery with co-transportation of suitable adjuvants would be achievable through nano-vaccines. In the past decade, researchers have engineered nano-DDS to improve the safety profile of existing drugs by restricting their release parameters. Polymerically-derived nano-DDS were found as a suitable option for oral delivery as well as SLNs due to pharmacokinetic re-modeling of drugs. Mannosylated nano-DDS have upgraded macrophage internalizing of nanosystem and the entrapped drug, provided with minimal toxicity. Cutaneous Leishmaniasis (CL) was tackling by the utilization of nano-DDS designed for topical delivery including niosomes, liposomes, and transfersomes. Transfersomes, however, appears to be superior for this purpose. The nanotechnology-based solution to prevent parasitic resistance is the use of Thiolated drug-loaded and multiple drugs loaded nano-DDS. These surfaces amended nano-DDS possess augmented IC50 values in comparison to conventional drugs and un-modified nano-DDS. Phyto-nano-DDS, another obscure horizon, have also been evaluated for their anti-leishmanial response, however, more intense assessment is a prerequisite. Impoverished Cytotoxic T-cells response followed by Leishmanial antigen proteins delivery have also been vanquished using nano-adjuvants. The eminence of nano-DDS for curtailment of anti-leishmanial chemotherapy and immunization associated challenges are extensively summed up in this review. This expedited approach is ameliorating the Leishmaniasis management successfully. Alongside, total to partial eradication of this disease can be sought along with associated co-morbidities.
Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair
Authors: Zhang Xiaobing , Hu Jiajia , Becker Kaelyn V. , Engle Jonathan W. , Ni Dalong , Cai Weibo , Wu Dong , Qu Shuping
Published: April 2021

Background

Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair.

Results

To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited.

Conclusions

The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases.

Graphic abstract