bluuebunny/crossref_metadata_2025 huggingface dataset:
Cartilage Matrix Degeneration Occurs within the First Year after ACLR and Is Associated with Impaired Clinical Outcome
Authors: Williams Ashley A. , Deadwiler Brittney C. , Dragoo Jason L. , Chu Constance R.
Published: December 2021

Objective

Anterior cruciate ligament reconstruction (ACLR) has not been shown to decrease the risk for development of post-traumatic osteoarthritis. Magnetic resonance imaging (MRI) T2 mapping can be used to assess cartilage compositional changes. This study tests whether (1) worse cartilage arthroscopic status at ACLR is reflected by higher cartilage T2 values in matched study regions 6 weeks and 1 year after ACLR, and (2) increasing cartilage T2 values between 6 weeks and 1 year after ACLR are associated with worsening patient-reported outcomes.

Design

Twenty-two participants with ACLR and 26 controls underwent 3T MRI. T2 values in medial and lateral femoral and tibial cartilage were measured at 6 weeks and 1 year after ACLR and compared with arthroscopic grades, Knee injury and Osteoarthritis Outcome Scores (KOOS), and control T2 values.

Results

Most (59%-86%) cartilage study regions examined by arthroscopy demonstrated intact articular surfaces. Average T2 value increased in 3 of 4 study regions between 6 weeks and 1 year after ACLR ( P = .001-.011). T2 value increased ( P < .013) even for participants whose cartilage had intact articular surfaces at ACLR. Participants with ACLR who showed greater increases in cartilage T2 values had less improvement to KOOS Quality of Life ( P = .009, ρ = −0.62).

Discussion

Cartilage status assessed arthroscopically at ACLR and by MRI T2 maps 6 weeks later was healthier than cartilage status assessed by MRI T2 maps at 1-year follow-up. Progressive T2 elevations were observed over the first year after ACLR even in patients with arthroscopically intact cartilage at the time of surgery and were associated with reduced improvement in knee quality of life suggesting preosteoarthritis.
Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis
Authors: Kan Shiyi , Duan Mengmeng , Liu Yang , Wang Chunli , Xie Jing
Published: December 2021

Purpose of Review

Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes.

Designs

To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied.

Results

In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive.

Conclusion

This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.
Inequality trends in the distribution of healthcare human resources in eastern Iran
Authors: Sotodeh Manesh Sam , Hedayati Zafarghandi Mahsa , Merati Zahra , Ebrahimzadeh Javad , Delpasand Mansoor
Published: December 2021

Background

Inequitable distribution of human resources in healthcare is one of the main obstacles to improve any health system. This study aimed to evaluate inequalities in the distribution of human resources in healthcare in South Khorasan Province, Iran.

Methods

We have investigated three types of health staff (i.e. nurses, general practitioners, and specialists) from 2013 to 2018. Data were collected from the annual reports of the Statistical Centre of Iran. The Gini coefficient and time trend regression were applied to measure the inequality.

Results

The distribution of specialists and general practitioners were the highest and lowest inequality, respectively. Inequalities in the distribution of nurses and specialists have decreased from 2013 to 2018, while the Gini coefficients of the general practitioners have increased from 0.31 to 0.38. According to the regression analysis, inequality in the distribution of nurses and specialists was decreasing over the time; however, the decline was only significant for specialists. While the coefficient B for general practitioners is positive, this indicates raised inequality, but the observed increase was not significant.

Conclusions

This study revealed that Iran, similar to several other low- and middle-income countries, is with faced the challenge of inequitable distribution of human resources in healthcare, which in turn indicates the necessity of reforms at national and regional levels to address inequalities in the distribution of healthcare human resources, particularly in South Khorasan Province. Hence, the main policy recommendation is to focus on continuous monitoring and evaluation of resource allocation in South Khorasan Province to reduce inequalities.
Features associated with SARS-COV-2 positivity among people presenting with acute respiratory tract infections to public Hospitals in Harari region, Ethiopia
Authors: Birhanu Abdi , Ayana Galana Mamo , Bayu Miesso , Mohammed Ahmed , Dessie Yadeta
Published: December 2021

Background:

Despite investigating coronavirus among respiratory tract infected cases is a top priority to prevent further transmission, severe acute respiratory syndrome coronavirus 2 positivity among this group of patients remains unexplored in resource-limited settings. Therefore, this study intended to assess the severe acute respiratory syndrome coronavirus 2 positivity among patients presenting with acute respiratory tract infection from 1 July to 31 December 2020 in Harar Region, Ethiopia, from 15 February to 10 March 2021.

Methods:

A facility-based cross-sectional study design was used. Severe acute respiratory syndrome coronavirus 2 was tested by assaying oropharyngeal swabs using reverse transcriptase–polymerase chain reaction among patients presenting with acute respiratory tract infection in Harari Public Hospitals. A binary logistic regression was used to identify factors associated with severe acute respiratory syndrome coronavirus 2 positivity with an adjusted odds ratio at a 95% confidence interval.

Results:

Out of a total of 1692 study participants, 388 (22.9%) of them tested positive for severe acute respiratory syndrome coronavirus 2. Of these severe acute respiratory syndrome coronavirus 2 positive patients, 364 (21.6%) patients presented with lower respiratory tract infection, while the rest only 24 (1.4%) presented with upper respiratory tract infection. Independent variables included separated/divorced in marital status (AOR = 0.53, 95% CI: 0.29–0.95), presenting with cough, fever, and difficulty of breathing (AOR = 2.5, 95% CI: 1.22–4.7), age group of 30–39 years (AOR = 0.35, 95% CI: 0.15–0.79), 40–49 years (AOR = 0.37, 95% CI: 0.14–0.94), and 50–59 years (AOR = 0.31, 95% CI: 0.13–0.76) compared to patients with the age of ⩾ 60 years, had statistically significant association with severe acute respiratory syndrome coronavirus 2 positivity.

Conclusion:

Severe acute respiratory syndrome coronavirus 2 was positive among 388 (22.9%) acute respiratory tract infected people. Elder age, particular symptoms, such as cough, fever, and difficulty of breathing, and married marital status were associated with a severe acute respiratory syndrome coronavirus 2 positive test. In resource-limited setups, where a shortage of testing equipment is common, these findings could contribute to boosting targeted symptom-oriented screening schemes. Moreover, this study could have paramount clinical importance for further studies in the country.
Clinical characteristics of patients with undergoing unplanned excisions of malignant soft tissue tumors
Authors: Morinaga Sei , Miwa Shinji , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Igarashi Kentaro , Tada Kaoru , Langit Mickhael B , Yonezawa Hirotaka , Araki Yoshihiro , Asano Yohei , Tsuchiya Hiroyuki
Published: December 2021

Introduction

Malignant soft tissue tumors are rare tumors representing <1% of all malignancies. As these tumors are rare, it is not uncommon that malignant soft tissue tumor excision is performed without the required preoperative imaging, staging, or wide resection margins for sarcomas. The purpose of this study was to investigate the characteristics of patients with undergoing unplanned excisions. Risk factors for tumor recurrence and mortality in patients treated with unplanned excisions were also analyzed.

Methods

Forty-nine patients who underwent unplanned excision at other hospitals and additional wide excision at our hospital between January 2002 and December 2018 were identified. Among them, 42 patients with follow-up for more than 1 year were included in this retrospective study. The relationships between sex, age, tumor depth, histological grade, location, size, surgical margin at additional wide excision, residual tumor, reconstruction, kind of hospital where the primary excision was done (sarcoma vs non-sarcoma center), preoperative examination, chemotherapy, radiation therapy, and oncological outcomes were statistically analyzed.

Results

Mean patient age was 57.3 years (15–85 years) and the mean observation period was 72.5 months (14–181 months). This analysis showed 53.8% tumors that underwent unplanned excisions were small (<5 cm) and 70.7% tumors were superficial. Multivariate analysis revealed that a positive margin during additional wide excision was significantly associated with a lower 5-year LRFS ( p < 0.01).

Conclusion

Most of the tumors underwent unplanned excisions were small (<5 cm) and superficial. Surgeons should be aware that a positive margin during additional wide excision is an independent risk factor for local recurrence.
Dimensions of Psychological Well-being and Subjective Happiness in the New Normal: An Exploration
Authors: Warrier Uma , Dilip D.  , Jain Heena , Agha Kakul
Published: December 2021

The pandemic has brought in unprecedented changes in societies across the globe. It has altered the equilibrium and forced individuals to move out of their comfort zone, leading to disturbance in psychological well-being in the new normal (Kuster, 2021). This empirical study examines the effect of psychological well-being (PWB) on subjective happiness (SH) of students of higher educational institutions (HEIs) during the global pandemic. Total of 290 students of HEIs were administered with the PWB questionnaire and SH questionnaire. The relationship between the variables was examined using multiple regression. The results indicated that the SH levels of the sample were above average (M = 19.76). SH was found to be more in women. No gender difference was found in PWB levels. The findings also revealed that improving PWB will positively influence the SH (r = 0.581) of the students. PWB can explain 32% variation of SH. Self-acceptance (p = .01), autonomy (p = .01), positive relationships with others (p = .03), and personal growth (p = .002) increases the feeling of SH. The findings validate the set point theory that while recent life events influence SH, individuals tend to return to natural set point over a period in time. The findings add to the repertoire of research on PWB and SH in the context of Set point theory. Study findings can help in strategizing the student counselling process as well as curriculum design of HEIs to ensure greater SH of its stakeholders.
Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer
Authors: Bourguillon Richard O. , Stokes William A. , Dorth Jennifer , Schmitt Nicole C.
Published: December 2021

Objective

The rising incidence of head and neck squamous cell carcinoma (HNSCC) calls for the assessment and improvement of currently available therapies that may enhance the therapeutic ratio in these patients. Statin drugs are one of the most widely used drug classes in the world for their lipid‐lowering properties. As such, statins have been widely studied and found to possess pleiotropic effects that may make them effective in cancer treatment and toxicity mitigation. The aim of this review is to examine the potential use of statin drugs as adjunctive therapy in patients with HNSCC.

Data Sources

PubMed.

Review Methods

Any preclinical or clinical articles pertaining to the effects of statin drugs on treatment‐related toxicity or survival outcomes in patients with head and neck cancer were included in this narrative review.

Conclusions

Emerging data suggest that statins may improve survival and reduce toxicities associated with chemotherapy and radiotherapy in patients with head and neck cancer, by mechanisms that are poorly understood at present.

Implications for Practice

Given their affordability and safety, statins deserve further study as a tool to improve oncologic outcomes and enhance survivorship in patients with HNSCC.
Ergodic site response model for subduction zone regions
Authors: Parker Grace A , Stewart Jonathan P
Published: December 2021

We present an ergodic site response model with regional adjustments for use with subduction zone ground-motion models. The model predicts site amplification of peak ground acceleration, peak ground velocity, and 5% damped pseudo-spectral accelerations of the orientation-independent horizonal component for oscillator periods from 0.01 to 10 s. The model depends on the time-averaged shear-wave velocity in the upper 30 m ( VS30), basin depth, and region and is independent of subduction earthquake type. It has three components: a linear site-amplification term in the form of VS30-scaling, a nonlinear term that depends on VS30 and shaking intensity parameterized by peak ground acceleration at the reference-rock velocity condition of 760 m/s, and a basin sediment-depth term for Japan and Cascadia conditioned on the depth to the 2.5 km/s shear-wave velocity isosurface ( Z2.5). A global VS30-scaling model is provided along with regional adjustments for Japan, Taiwan, South America, Alaska, and Cascadia. The nonlinear model is global, with a functional form that has often been used to fit nonlinear responses inferred from simulations, but here we calibrate it empirically. Relative to a prior model for shallow earthquakes in active tectonic regions, our subduction zone global VS30-scaling is comparable at short periods (<1.0 s) but weaker at long periods, while the nonlinear site response is generally less pronounced but extends to lower levels of shaking. Basin depth models are conditioned on the difference of the actual Z2.5 and a VS30-conditioned mean Z2.5. Sites with positive differential depths have increased long-period site responses and decreased short-period responses, with the opposite occurring for negative differential depths.
Altered brain functional network dynamics in classic trigeminal neuralgia: a resting-state functional magnetic resonance imaging study
Authors: Zhang Pengfei , Jiang Yanli , Liu Guangyao , Han Jiao , Wang Jun , Ma Laiyang , Hu Wanjun , Zhang Jing
Published: December 2021

Background

Accumulating studies have indicated a wide range of brain alterations with respect to the structure and function of classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain processes in the brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN.

Methods

Resting-state functional magnetic resonance imaging and three-dimensional T1-weighted images were obtained from 41 CTN patients and 43 matched healthy controls (HCs). After group independent component analysis, sliding window based dynamic functional network connectivity (dFNC) analysis was applied to investigate specific FC states and related temporal properties. Then, the dynamics of the whole brain topological organization were estimated by calculating the coefficient of variation of graph-theoretical properties. Further correlation analyses were performed between all these measurements and clinical data.

Results

Two distinct states were identified. Of these, the state 2, characterized by complicated coupling between default mode network (DMN) and cognitive control network (CC) and tight connections within DMN, was expressed more in CTN patients and presented as increased fractional windows and dwell time. Moreover, patients switched less frequently between states than HCs. Regarding the dynamic topological analysis, disruptions in global graph-theoretical properties (including network efficiency and small-worldness) were observed in patients, coupled with decreased variability in nodal efficiency of anterior cingulate cortex (ACC) in the salience network (SN) and the thalamus and caudate nucleus in the subcortical network (SC). The variation of topological properties showed negative correlation with disease duration and attack frequency.

Conclusions

The present study indicated disrupted flexibility of brain topological organization under persistent noxious stimulation and further highlighted the important role of “dynamic pain connectome” regions (including DMN/CC/SN) in the pathophysiology of CTN from the temporal fluctuation aspect. Additionally, the findings provided supplementary evidence for current knowledge about the aberrant cortical-subcortical interaction in pain development.
Age- and frequency-dependent changes in dynamic contrast perception in visual snow syndrome
Authors: Eren Ozan E. , Straube Andreas , Schöberl Florian , Ruscheweyh Ruth , Eggert Thomas , Schankin Christoph J.
Published: December 2021

Objective

Patients with visual snow syndrome (VSS) suffer from a debilitating continuous (“TV noise-like”) visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient’s history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds.

Methods

Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases.

Results

The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20).

Conclusions

This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS.
Sources, spatial distribution, and abundance of marine debris on Thondi coast, Palk Bay, Southeast coast of India
Authors: Perumal Karthikeyan , Boopathi Vishwanath , Chellaiyan Stella , Muthuramalingam Subagunasekar , Raja Prakash
Published: December 2021

Background

The Thondi coast is rich in valuable natural marine resources and socio-economically significant activities like agriculture, aquaculture, and fishing. The area receives an excess of untreated solid and liquid waste as a result of these activities. The study focuses on the abundance, distribution, and status of the Clean-Coast Index (CCI) of marine debris from the Thondi coast, Palk Bay, Southeast coast of India. This is the first research work focused on assessing the type and quantity of marine debris on the Thondi coast.

Results

A total of 1636 marine debris items/m2 and their 4.09 concentration of the items/m2 were determined in the marine debris: plastics (77.49%), cotton swabs (8.62%), cigarette butts (10.15%), and food containers (3.73%). From the result, the CCI had ranged between 4.25 (clean) and 20.4 (extremely dirty) with a mean of 8.92 (moderate) in the Thondi coast assessed.

Conclusion

This study was conducted for the first time in this region. Finally, the high CCI value of 20.4 on the coast indicated that the marine debris pollution levels were high at the time of sampling in the middle part of the Thondi coast (most of the beaches are covered with plastic) due to land-based marine debris (62.45%), sea-originated marine debris (21.14%), and unknown sources (16.41%) of the items. Our findings served as a baseline for potential evaluations of the marine environment. Input prevention should be the goal of management efforts, including proper waste management, plastic recycling, and stringent penalties for illegal waste dumping.
MCKAT: a multi-dimensional copy number variant kernel association test
Authors: Maus Esfahani Nastaran , Catchpoole Daniel , Khan Javed , Kennedy Paul J.
Published: December 2021

Background

Copy number variants (CNVs) are the gain or loss of DNA segments in the genome. Studies have shown that CNVs are linked to various disorders, including autism, intellectual disability, and schizophrenia. Consequently, the interest in studying a possible association of CNVs to specific disease traits is growing. However, due to the specific multi-dimensional characteristics of the CNVs, methods for testing the association between CNVs and the disease-related traits are still underdeveloped. We propose a novel multi-dimensional CNV kernel association test (MCKAT) in this paper. We aim to find significant associations between CNVs and disease-related traits using kernel-based methods.

Results

We address the multi-dimensionality in CNV characteristics. We first design a single pair CNV kernel, which contains three sub-kernels to summarize the similarity between two CNVs considering all CNV characteristics. Then, aggregate single pair CNV kernel to the whole chromosome CNV kernel, which summarizes the similarity between CNVs in two or more chromosomes. Finally, the association between the CNVs and disease-related traits is evaluated by comparing the similarity in the trait with kernel-based similarity using a score test in a random effect model. We apply MCKAT on genome-wide CNV datasets to examine the association between CNVs and disease-related traits, which demonstrates the potential usefulness the proposed method has for the CNV association tests. We compare the performance of MCKAT with CKAT, a uni-dimensional kernel method. Based on the results, MCKAT indicates stronger evidence, smallerp-value, in detecting significant associations between CNVs and disease-related traits in both rare and common CNV datasets.

Conclusion

A multi-dimensional copy number variant kernel association test can detect statistically significant associated CNV regions with any disease-related trait. MCKAT can provide biologists with CNV hot spots at the cytogenetic band level that CNVs on them may have a significant association with disease-related traits. Using MCKAT, biologists can narrow their investigation from the whole genome, including many genes and CNVs, to more specific cytogenetic bands that MCKAT identifies. Furthermore, MCKAT can help biologists detect significantly associated CNVs with disease-related traits across a patient group instead of examining each subject’s CNVs case by case.
Comparative analysis of aneurysm subtypes associated genes based on protein–protein interaction network
Authors: Sun Ruya , Zhou Yuan , Cui Qinghua
Published: December 2021

The arterial aneurysm refers to localized dilation of blood vessel wall and is common in general population. The majority of aneurysm cases remains asymptomatic until a sudden rupture which is usually fatal and of extremely high mortality (~ 50–60%). Therefore, early diagnosis, prevention and management of aneurysm are in urgent need. Unfortunately, current understanding of disease driver genes of various aneurysm subtypes is still limited, and without appropriate biomarkers and drug targets no specialized drug has been developed for aneurysm treatment. In this research, aneurysm subtypes were analyzed based on protein–protein interaction network to better understand aneurysm pathogenesis. By measuring network-based proximity of aneurysm subtypes, we identified a relevant closest relationship between aortic aneurysm and aortic dissection. An improved random walk method was performed to prioritize candidate driver genes of each aneurysm subtype. Thereafter, transcriptomes of 6 human aneurysm subtypes were collected and differential expression genes were identified to further filter potential driver genes. Functional enrichment of above driver genes indicated a general role of ubiquitination and programmed cell death in aneurysm pathogenesis. Especially, we further observed participation of BCL-2-mediated apoptosis pathway and caspase-1 related pyroptosis in the development of cerebral aneurysm and aneurysmal subarachnoid hemorrhage in corresponding transcriptomes.
Regulatory modules of human thermogenic adipocytes: functional genomics of large cohort and Meta-analysis derived marker-genes
Authors: B. Tóth Beáta , Barta Zoltán , Barta Ákos Barnabás , Fésüs László
Published: December 2021

Background

Recently, ProFAT and BATLAS studies identified brown and white adipocytes marker genes based on analysis of large databases. They offered scores to determine the thermogenic status of adipocytes using the gene-expression data of these markers. In this work, we investigated the functional context of these genes.

Results

Gene Set Enrichment Analyses (KEGG, Reactome) of the BATLAS and ProFAT marker-genes identified pathways deterministic in the formation of brown and white adipocytes. The collection of the annotated proteins of the defined pathways resulted in expanded white and brown characteristic protein-sets, which theoretically contain all functional proteins that could be involved in the formation of adipocytes. Based on our previously obtained RNA-seq data, we visualized the expression profile of these proteins coding genes and found patterns consistent with the two adipocyte phenotypes. The trajectory of the regulatory processes could be outlined by the transcriptional profile of progenitor and differentiated adipocytes, highlighting the importance of suppression processes in browning. Protein interaction network-based functional genomics by STRING, Cytoscape and R-Igraph platforms revealed that different biological processes shape the brown and white adipocytes and highlighted key regulatory elements and modules including GAPDH-CS, DECR1, SOD2, IL6, HRAS, MTOR, INS-AKT, ERBB2 and 4-NFKB, and SLIT-ROBO-MAPK. To assess the potential role of a particular protein in shaping adipocytes, we assigned interaction network location-based scores (betweenness centrality, number of bridges) to them and created a freely accessible platform, the AdipoNET (https//adiponet.com), to conveniently use these data. The Eukaryote Promoter Database predicted the response elements in the UCP1 promoter for the identified, potentially important transcription factors (HIF1A, MYC, REL, PPARG, TP53, AR, RUNX, and FoxO1).

Conclusion

Our integrative approach-based results allowed us to investigate potential regulatory elements of thermogenesis in adipose tissue. The analyses revealed that some unique biological processes form the brown and white adipocyte phenotypes, which presumes the existence of the transitional states. The data also suggests that the two phenotypes are not mutually exclusive, and differentiation of thermogenic adipocyte requires induction of browning as well as repressions of whitening. The recognition of these simultaneous actions and the identified regulatory modules can open new direction in obesity research.
Genome-wide association of single nucleotide polymorphism loci and candidate genes for frogeye leaf spot (Cercospora sojina) resistance in soybean
Authors: Gu Xin , Huang Shanshan , Zhu Zhiguo , Ma Yansong , Yang Xiaohe , Yao Liangliang , Gao Xuedong , Zhang Maoming , Liu Wei , Qiu Lei , Zhao Haihong , Wang Qingsheng , Li Zengjie , Li Zhimin , Meng Qingying , Yang Shuai , Wang Chao , Hu Xiping , Ding Junjie
Published: December 2021

Background

Frogeye leaf spot (FLS) is a destructive fungal disease that affects soybean production. The most economical and effective strategy to control FLS is the use of resistant cultivars. However, the use of a limited number of resistant loci in FLS management will be countered by the emergence of new high-virulence Cercospora sojina races. Therefore, we identified quantitative trait loci (QTL) that control resistance to FLS and identified novel resistant genes using a genome-wide association study (GWAS) on 234 Chinese soybean cultivars.

Results

A total of 30,890 single nucleotide polymorphism (SNP) markers were used to estimate linkage disequilibrium (LD) and population structure. The GWAS results showed four loci (p < 0.0001) distributed over chromosomes (Chr.) 5 and 20, that are significantly associated with FLS resistance. No previous studies have reported resistance loci in these regions. Subsequently, 45 genes in the two resistance-related haplotype blocks were annotated. Among them, Glyma20g31630 encoding pyruvate dehydrogenase (PDH), Glyma05g28980, which encodes mitogen-activated protein kinase 7 (MPK7), and Glyma20g31510, Glyma20g31520 encoding calcium-dependent protein kinase 4 (CDPK4) in the haplotype blocks deserves special attention.

Conclusions

This study showed that GWAS can be employed as an effective strategy for identifying disease resistance traits in soybean and narrowing SNPs and candidate genes. The prediction of candidate genes in the haplotype blocks identified by disease resistance loci can provide a useful reference to study systemic disease resistance.
Non-conveyance of older adult patients and association with subsequent clinical and adverse events after initial assessment by ambulance clinicians: a cohort analysis
Authors: Lederman Jakob , Lindström Veronica , Elmqvist Carina , Löfvenmark Caroline , Ljunggren Gunnar , Djärv Therese
Published: December 2021

Background

Older adults (age ≥ 65 years) represent a significant proportion of all patients who are not transported to hospital after assessment by ambulance clinicians (non-conveyed patients). This study aimed to fill the knowledge gap in the understanding of the prevalence of older adult non-conveyed patients and investigate their characteristics and risk factors for subsequent and adverse events with those of younger non-conveyed patients comparatively.

Methods

This population-based retrospective cohort study included all adult non-conveyed patients who availed the ambulance service of Region Stockholm, Sweden in 2015; they were age-stratified into two groups: 18–64 and ≥ 65 years. Inter-group differences in short-term outcomes (i.e. emergency department visits, hospitalisations, and mortality within 7 days following non-conveyance) were assessed using multivariate regression analyses.

Results

Older adult patients comprised 48% of the 17,809 non-conveyed patients. Dispatch priority levels were generally lower among older non-conveyed patients than among younger patients. Non-conveyance among older patients occurred more often during daytime, and they were more frequently assessed by ambulance clinicians with nonspecific presenting symptoms. Approximately one in five older adults was hospitalised within 7 days following non-conveyance. Patients presenting with infectious symptoms had the highest mortality risk following non-conveyance. Oxygen saturation level < 95% or systolic blood pressure > 160 mmHg had significantly higher associations with hospitalisation within 7 days following non-conveyance in older adult patients.

Conclusions

Older adult patients have an increased risk for adverse events following non-conveyance. In combination with a complex and variating presentation of symptoms and vital signs proved difficult for dispatch operators and ambulance clinicians to identify and assess, the identified risks raise questions on the patient safety of older adult non-conveyed patients. The results indicate a system failure that need to be managed within the ambulance service organisation to achieve higher levels of patient safety for older non-conveyed patients.
COPD – do the right thing
Authors: Sandelowsky Hanna , Weinreich Ulla Møller , Aarli Bernt B. , Sundh Josefin , Høines Kristian , Stratelis Georgios , Løkke Anders , Janson Christer , Jensen Christian , Larsson Kjell
Published: December 2021

A gap exists between guidelines and real-world clinical practice for the management and treatment of chronic obstructive pulmonary disease (COPD). Although this has narrowed in the last decade, there is room for improvement in detection rates, treatment choices and disease monitoring. In practical terms, primary care practitioners need to become aware of the huge impact of COPD on patients, have non-judgemental views of smoking and of COPD as a chronic disease, use a holistic consultation approach and actively motivate patients to adhere to treatment.

This article is based on discussions at a virtual meeting of leading Nordic experts in COPD (the authors) who were developing an educational programme for COPD primary care in the Nordic region. The article aims to describe the diagnosis and lifelong management cycle of COPD, with a strong focus on providing a hands-on, practical approach for medical professionals to optimise patient outcomes in COPD primary care.
Printed educational materials directed at Ontario family physicians do not improve adherence to guideline recommendations for diabetes management: a pragmatic, factorial, cluster randomized controlled trial [ISRCTN72772651]
Authors: Howie Alison H. , Klar Neil , Nash Danielle M. , Reid Jennifer N. , Zwarenstein Merrick
Published: December 2021

Background

Printed educational materials (PEMs) have long been used to inform clinicians on evidence-based practices. However, the evidence for their effects on patient care and outcomes is unclear. In Ontario, despite widely available clinical practice guidelines recommending antihypertensives and cholesterol-lowering agents for patients with diabetes, prescriptions remain low. We aimed to determine whether PEMs can influence physicians to intensify prescribing of these medications.

Methods

A pragmatic, 2 × 2 factorial, cluster randomized controlled trial was designed to ascertain the effect of two PEM formats on physician prescribing: a postcard-sized message (“outsert”) or a longer narrative article (“insert”). Ontario family physician practices (clusters) were randomly allocated to receive the insert, outsert, both or neither. Physicians were eligible if they were in active practice and their patients were included if they were over 65 years with a diabetes diagnosis; both were unaware of the trial. Administrative databases at ICES (formerly the Institute for Clinical Evaluative Sciences) were used to link patients to their physician and to analyse prescribing patterns at baseline and 1 year following PEM mailout. The primary outcome was intensification defined as the addition of a new antihypertensive or cholesterol-lowering agent, or dose increase of a current drug, measured at the patient level. Analyses were by intention-to-treat and accounted for the clustering of patients to physicians.

Results

We randomly assigned 4231 practices (39% of Ontario family physicians) with a total population of 185,526 patients (20% of patients with diabetes in Ontario primary care) to receive the insert, outsert, both, and neither; among these, 4118 practices were analysed (n = 1025, n = 1037, n = 1031, n = 1025, respectively). No significant treatment effect was found for the outsert (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.98 to 1.04) or the insert (OR 0.99, 95% CI 0.96 to 1.02). Percent of intensification in the four arms was similar (approximately 46%). Adjustment for physician characteristics (e.g., age, sex, practice location) had no impact on these findings.

Conclusions

PEMs have no effect on physician’s adherence to recommendations for the management of diabetes-related complications in Ontario. Further research should investigate the effect of other strategies to narrow this evidence-to-practice gap.

Trial registration

ISRCTN72772651. Retrospectively registered 21 July 2005.
A case of primary intestinal lymphangiectasia with non-Hodgkin lymphoma
Authors: Hu Doudou , Cui Xianghua , Ren Wanlei , Zhang Jian , Guan Xin , Jiang Xiangjun
Published: December 2021

Background

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma.

Case presentation

A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory.

Conclusion

Our report supports the hypothesis that PIL is associated with lymphoma development.
Changing socio-economic and ethnic disparities in influenza/A/H1N1 infection early in the 2009 UK epidemic: a descriptive analysis
Authors: Munday James D. , Pebody Richard , Atkins Katherine E. , van Hoek Albert Jan
Published: December 2021

Background

Higher incidence of and risk of hospitalisation and death from Influenza A(H1N1)pdm09 during the 2009 pandemic was reported in ethnic minority groups in many high-income settings including in the United Kingdom (UK). Many of these studies rely on geographical and temporal aggregation of cases and can be difficult to interpret due to the spatial and temporal factors in outbreak spread. Further, it can be challenging to distinguish between disparities in health outcomes caused by variation in transmission risk or disease severity.

Methods

We used anonymised laboratory confirmed and suspected case data, classified by ethnicity and deprivation status, to evaluate how disparities in risk between socio-economic and ethnic groups vary over the early stages of the 2009 Influenza A(H1N1)pdm09 epidemic in Birmingham and London, two key cities in the emergence of the UK epidemic. We evaluated the relative risk of infection in key ethnic minority groups and by national and city level deprivation rank.

Results

We calculated higher incidence in more deprived areas and in people of South Asian ethnicity in both Birmingham and London, although the magnitude of these disparities reduced with time. The clearest disparities existed in school-aged children in Birmingham, where the most deprived fifth of the population was 2.8 times more likely to be infected than the most affluent fifth of the population.

Conclusions

Our analysis shows that although disparities in reported cases were present in the early phase of the Influenza A(H1N1)pdm09 outbreak in both Birmingham and London, they vary substantially depending on the period over which they are measured. Further, the development of disparities suggest that clustering of social groups play a key part as the outbreak appears to move from one ethnic and socio-demographic group to another. Finally, high incidence and large disparities between children indicate that they may hold an important role in driving inequalities.
Quantitative contrast enhanced dual energy CT to predict avascular necrosis: a feasibility study of proximal humerus fractures
Authors: Hoover Kevin B. , Starks Alexandria O. , Robila Valentina , Riddle Daniel L.
Published: December 2021

Background

Avascular necrosis is a delayed complication of proximal humerus fractures that increases the likelihood of poor clinical outcomes. CT scans are routinely performed to guide proximal humerus fracture management. We hypothesized iodine concentration on post-contrast dual energy CT scans identifies subjects who develop avascular necrosis and ischemia due to compromised blood flow.

Materials and methods

55 patients with proximal humerus fractures enrolled between 2014 and 2017 underwent clinical, radiographic and contrast enhanced dual energy CT assessment. Iodine densities of the humeral head and the glenoid (control) were measured on CT. Subjects managed with open reduction internal fixation or conservatively (non-surgical) were followed for up to two years for radiographic evidence of avascular necrosis. Arthroplasty subjects underwent histopathologic evaluation for ischemia of the resected humeral head.

Results

17 of 55 subjects (30.9%) were treated conservatively, 21 (38.2%) underwent open reduction internal fixation and 17 of 55 (30.9%) underwent arthroplasty. Of the 38 subjects treated conservatively or with ORIF, 20 (52.6%) completed 12 months of follow up and 14 (36.8%) 24 months of follow up. At 12 months follow up, two of 20 subjects (10%) and at 24 months 3 of 14 subjects (21.4%) developed avascular necrosis. At 12 months, the mean humerus/glenoid iodine ratio was 1.05 (standard deviation 0.24) in subjects with AVN compared to 0.91 (0.24) in those who did not. At 24 months, subjects with avascular necrosis had a mean humerus/glenoid iodine concentration ratio of 1.06 (0.17) compared to 0.924 (0.21) in those who did not. Of 17 arthroplasty subjects, 2 had severe ischemia and an iodine ratio of 1.08 (0.30); 5 had focal ischemia and a ratio of 1.00 (0.36); and 8 no ischemia and a ratio of 0.83 (0.08).

Conclusions

Quantifying iodine using dual energy CT in subjects with proximal humerus fractures is technically feasible. Preliminary data suggest higher humeral head iodine concentration may increase risk of avascular necrosis; however, future studies must enroll and follow enough subjects managed with open reduction internal fixation or conservatively for two or more years to provide statistically significant results.

Trial Registrations NCT02170545 registered June 23, 2014, ClinicalTrials.gov.
First diagnosis of thrombotic thrombocytopenic purpura after SARS-CoV-2 vaccine – case report
Authors: Osmanodja Bilgin , Schreiber Adrian , Schrezenmeier Eva , Seelow Evelyn
Published: December 2021

Background

We report a case of a 25-year-old male patient, who developed acquired thrombotic thrombocytopenic purpura (aTTP) after receiving a first dose of mRNA-based SARS-CoV-2 vaccine Spikevax (mRNA-1273, Moderna Biotech, USA). While this is the first case in literature describing a case of aTTP after receiving the Spikevax vaccine, there are two other cases after mRNA-based Covid-19 vaccine and two after adenoviral SARS-CoV-2 vaccine.

Case presentation

The patient presented with persisting malaise, fever, headache, word-finding difficulties, nausea, vomiting, petechial bleeding, and hematuria 13 days after receiving a first dose of vaccination. Laboratory testing showed low platelet count, Coombs-negative hemolytic anemia, and mild acute kidney injury. We excluded vaccine induced immune thrombotic thrombocytopenia (VITT) as another important differential diagnosis and the final diagnosis was established after ADAMTS-13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) activity was found to be < 1% (reference range > 40%) and ADAMTS-13 antibodies being 72.2 IU/L (reference range < 12 IU/L).

We initiated empiric therapy of plasmapheresis and corticosteroids on admission and started caplacizumab the day after. The patient’s thrombocyte count normalized 3 days after admission, hemolysis and acute kidney injury resolved after 2 weeks. The patient received 2 doses of rituximab (1 g each) after the diagnosis of immune TTP was established. One month after the initial presentation, the patient is in good overall condition, but still receives daily caplacizumab due to ADAMTS-13 activity of < 1%.

Conclusions

Low platelet count after vaccination against SARS-CoV-2 has gained attraction after vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a rare but severe complication of adenoviral-based vaccines. Thrombotic thrombocytopenic purpura (TTP) is an important differential diagnosis, but there are only few reports of TTP following SARS-CoV-2 vaccination. Despite pathophysiological and clinical differences of both entities, diagnostic uncertainty can result in the acute setting, since they share main symptoms such as headache and neurological alterations in addition to thrombocytopenia. In difference to other cases reported, this patient developed first symptoms of TTP as early as 4 days after vaccination, which suggests that vaccination merely acted as trigger for occult TTP, instead of truly inducing an autoimmunological process.