bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down’s syndrome mouse model
Authors: Urbano-Gámez Jesús David , Casañas Juan José , Benito Itziar , Montesinos María Luz
Published: May 2021

Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.
CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Cui Qingya , Qian Chongsheng , Xu Nan , Kang Liqing , Dai Haiping , Cui Wei , Song Baoquan , Yin Jia , Li Zheng , Zhu Xiaming , Qu Changju , Liu Tianhui , Shen Wenhong , Zhu Mingqing , Yu Lei , Wu Depei , Tang Xiaowen
Published: May 2021

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.
Increased expression of KPNA2 predicts unfavorable prognosis in ovarian cancer patients, possibly by targeting KIF4A signaling
Authors: Cui Xiangrong , Wang Honghong , Wu Xueqing , Huo Kai , Jing Xuan
Published: May 2021

Background

Karyopherin α-2 (KPNA2) is a member of karyopherin family, which is proved to be responsible for the import or export of cargo proteins. Studies have determined that KPNA2 is associated with the development and prognosis of various cancers, yet the role of KPNA2 in ovarian carcinoma and its potential molecular mechanisms remains unclear.

Materials and methods

The expression and prognosis of KPNA2 in ovarian cancer was investigated using GEPIA and Oncomine analyses. Mutations of KPNA2 in ovarian cancer were analyzed by cBioPortal database. The prognostic value of KPNA2 expression was evaluated by our own ovarian carcinoma samples using RT-qPCR. Subsequently, the cell growth, migration and invasion of ovarian cancer cells were investigated by CCK-8 and transwell assay, respectively. The protein levels of KPNA2 and KIF4A were determined by western blot.

Results

We obtained the following important results. (1) KPNA2 and KIF4A wereoverexpressed in ovairan cancer tissues and cells. (2) Among patients with ovarian cancer, overexpressed KPNA2 was associated with lower survival rate. (3) Mutations (R197* and S140F) in KPNA2 will have some influences on protein structure, and then may cause protein function abnormal. (4) KPNA2 konckdown inhibited proliferation, migration, invasion, as well as the expression of KIF4A.

Conclusion

KPNA2, as a tumorigenic gene in ovarian cancer, accelerated tumor progression by up-regulating KIF4A, suggesting that KPNA2 might be a hopeful indicator of treatment and poor prognosis.
Clinical outcomes and safety of passive leg raising in out-of-hospital cardiac arrest: a randomized controlled trial
Authors: Azeli Youcef , Bardají Alfredo , Barbería Eneko , Lopez-Madrid Vanesa , Bladé-Creixenti Jordi , Fernández-Sender Laura , Bonet Gil , Rica Elena , Álvarez Susana , Fernández Alberto , Axelsson Christer , Jiménez-Herrera Maria F.
Published: May 2021

Background

There are data suggesting that passive leg raising (PLR) improves hemodynamics during cardiopulmonary resuscitation (CPR). This trial aimed to determine the effectiveness and safety of PLR during CPR in out-of-hospital cardiac arrest (OHCA).

Methods

We conducted a randomized controlled trial with blinded assessment of the outcomes that assigned adults OHCA to be treated with PLR or in the flat position. The trial was conducted in the Camp de Tarragona region. The main end point was survival to hospital discharge with good neurological outcome defined as cerebral performance category (CPC 1–2). To study possible adverse effects, we assessed the presence of pulmonary complications on the first chest X-rays, brain edema on the computerized tomography (CT) in survivors and brain and lungs weights from autopsies in non-survivors.

Results

In total, 588 randomized cases were included, 301 were treated with PLR and 287 were controls. Overall, 67.8% were men and the median age was 72 (IQR 60–82) years. At hospital discharge, 3.3% in the PLR group and 3.5% in the control group were alive with CPC 1–2 (OR 0.9; 95% CI 0.4–2.3, p = 0.91). No significant differences in survival at hospital admission were found in all patients (OR 1.0; 95% CI 0.7–1.6, p = 0.95) and among patients with an initial shockable rhythm (OR 1.7; 95% CI 0.8–3.4, p = 0.15). There were no differences in pulmonary complication rates in chest X-rays [7 (25.9%) vs 5 (17.9%), p = 0.47] and brain edema on CT [5 (29.4%) vs 10 (32.6%), p = 0.84]. There were no differences in lung weight [1223 mg (IQR 909–1500) vs 1239 mg (IQR 900–1507), p = 0.82] or brain weight [1352 mg (IQR 1227–1457) vs 1380 mg (IQR 1255–1470), p = 0.43] among the 106 autopsies performed.

Conclusion

In this trial, PLR during CPR did not improve survival to hospital discharge with CPC 1–2. No evidence of adverse effects has been found.

Clinical trial registration

ClinicalTrials.gov: NCT01952197, registration date: September 27, 2013, https://clinicaltrials.gov/ct2/show/NCT01952197.
Genome-wide DNA mutations in Arabidopsis plants after multigenerational exposure to high temperatures
Authors: Lu Zhaogeng , Cui Jiawen , Wang Li , Teng Nianjun , Zhang Shoudong , Lam Hon-Ming , Zhu Yingfang , Xiao Siwei , Ke Wensi , Lin Jinxing , Xu Chenwu , Jin Biao
Published: May 2021

Background

Elevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological evolution. However, how long-term elevations in temperature influence the accumulation of mutations in plants remains unknown.

Results

Multigenerational exposure of Arabidopsis MA (mutation accumulation) lines and MA populations to extreme heat and moderate warming results in significantly increased mutation rates in single-nucleotide variants (SNVs) and small indels. We observe distinctive mutational spectra under extreme and moderately elevated temperatures, with significant increases in transition and transversion frequencies. Mutation occurs more frequently in intergenic regions, coding regions, and transposable elements in plants grown under elevated temperatures. At elevated temperatures, more mutations accumulate in genes associated with defense responses, DNA repair, and signaling. Notably, the distribution patterns of mutations among all progeny differ between MA populations and MA lines, suggesting that stronger selection effects occurred in populations. Methylation is observed more frequently at mutation sites, indicating its contribution to the mutation process at elevated temperatures. Mutations occurring within the same genome under elevated temperatures are significantly biased toward low gene density regions, special trinucleotides, tandem repeats, and adjacent simple repeats. Additionally, mutations found in all progeny overlap significantly with genetic variations reported in 1001 Genomes, suggesting non-uniform distribution of de novo mutations through the genome.

Conclusion

Collectively, our results suggest that elevated temperatures can accelerate the accumulation, and alter the molecular profiles, of DNA mutations in plants, thus providing significant insight into how environmental temperatures fuel plant evolution.
Demonstrating trustworthiness when collecting and sharing genomic data: public views across 22 countries
Authors: Milne Richard , Morley Katherine I. , Almarri Mohamed A. , Anwer Shamim , Atutornu Jerome , Baranova Elena E. , Bevan Paul , Cerezo Maria , Cong Yali , Costa Alessia , Critchley Christine , Fernow Josepine , Goodhand Peter , Hasan Qurratulain , Hibino Aiko , Houeland Gry , Howard Heidi C. , Hussain S. Zakir , Malmgren Charlotta Ingvoldstad , Izhevskaya Vera L. , Jędrzejak Aleksandra , Jinhong Cao , Kimura Megumi , Kleiderman Erika , Leach Brandi , Liu Keying , Mascalzoni Deborah , Mendes Álvaro , Minari Jusaku , Nicol Dianne , Niemiec Emilia , Patch Christine , Pollard Jack , Prainsack Barbara , Rivière Marie , Robarts Lauren , Roberts Jonathan , Romano Virginia , Sheerah Haytham A. , Smith James , Soulier Alexandra , Steed Claire , Stefànsdóttir Vigdis , Tandre Cornelia , Thorogood Adrian , Voigt Torsten H. , Wang Nan , West Anne V. , Yoshizawa Go , Middleton Anna
Published: May 2021

Background

Public trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.

Methods

We analyse the ‘Your DNA, Your Say’ online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.

Results

Providing transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data—endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.

Conclusions

Our findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
Hard wiring of normal tissue-specific chromosome-wide gene expression levels is an additional factor driving cancer type-specific aneuploidies
Authors: Patkar Sushant , Heselmeyer-Haddad Kerstin , Auslander Noam , Hirsch Daniela , Camps Jordi , Bronder Daniel , Brown Markus , Chen Wei-Dong , Lokanga Rachel , Wangsa Darawalee , Wangsa Danny , Hu Yue , Lischka Annette , Braun Rüdiger , Emons Georg , Ghadimi B. Michael , Gaedcke Jochen , Grade Marian , Montagna Cristina , Lazebnik Yuri , Difilippantonio Michael J. , Habermann Jens K. , Auer Gert , Ruppin Eytan , Ried Thomas
Published: May 2021

Background

Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood.

Methods

In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms.

Results

This analysis revealed a complex picture of factors driving tumor karyotype evolution in which some recurrent chromosomal copy number reflect the chromosome arm-wide gene expression levels of the their normal tissue of tumor origin.

Conclusions

We conclude that the cancer type-specific distribution of chromosomal arm gains and losses is potentially “hardwiring” gene expression levels characteristic of the normal tissue of tumor origin, in addition to broadly modulating the expression of tissue-specific tumor driver genes.
Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses
Authors: van Deuren Rosanne C. , Arts Peer , Cavalli Giulio , Jaeger Martin , Steehouwer Marloes , van de Vorst Maartje , Gilissen Christian , Joosten Leo A. B. , Dinarello Charles A. , Mhlanga Musa M. , Kumar Vinod , Netea Mihai G. , van de Veerdonk Frank L. , Hoischen Alexander
Published: May 2021

Background

The interleukin (IL)-1 pathway is primarily associated with innate immunological defense and plays a major role in the induction and regulation of inflammation. Both common and rare genetic variation in this pathway underlies various inflammation-mediated diseases, but the role of rare variants relative to common variants in immune response variability in healthy individuals remains unclear.

Methods

We performed molecular inversion probe sequencing on 48 IL-1 pathway-related genes in 463 healthy individuals from the Human Functional Genomics Project. We functionally grouped common and rare variants, over gene, subpathway, and inflammatory levels and performed the Sequence Kernel Association Test to test for association with in vitro stimulation-induced cytokine responses; specifically, IL-1β and IL-6 cytokine measurements upon stimulations that represent an array of microbial infections: lipopolysaccharide (LPS), phytohaemagglutinin (PHA),Candida albicans(C. albicans), andStaphylococcus aureus(S. aureus).

Results

We identified a burden ofNCF4rare variants with PHA-induced IL-6 cytokine and showed that the respective carriers are in the 1% lowest IL-6 producers. Collapsing rare variants in IL-1 subpathway genes produces a bidirectional association with LPS-induced IL-1β cytokine levels, which is reflected by a significant Spearman correlation. On the inflammatory level, we identified a burden of rare variants in genes encoding for proteins with an anti-inflammatory function withS. aureus-induced IL-6 cytokine. In contrast to these rare variant findings which were based on different types of stimuli, common variant associations were exclusively identified withC. albicans-induced cytokine over various levels of grouping, from the gene, to subpathway, to inflammatory level.

Conclusions

In conclusion, this study shows that functionally grouping common and rare genetic variants enables the elucidation IL-1-mediated biological mechanisms, specifically, for IL-1β and IL-6 cytokine responses induced by various stimuli. The framework used in this study may allow for the analysis of rare and common genetic variants in a wider variety of (non-immune) complex phenotypes and therefore has the potential to contribute to better understanding of unresolved, complex traits and diseases.
PhenCards: a data resource linking human phenotype information to biomedical knowledge
Authors: Havrilla James M. , Liu Cong , Dong Xiangchen , Weng Chunhua , Wang Kai
Published: May 2021

We present PhenCards (https://phencards.org), a database and web server intended as a one-stop shop for previously disconnected biomedical knowledge related to human clinical phenotypes. Users can query human phenotype terms or clinical notes. PhenCards obtains relevant disease/phenotype prevalence and co-occurrence, drug, procedural, pathway, literature, grant, and collaborator data. PhenCards recommends the most probable genetic diseases and candidate genes based on phenotype terms from clinical notes. PhenCards facilitates exploration of phenotype, e.g., which drugs cause or are prescribed for patient symptoms, which genes likely cause specific symptoms, and which comorbidities co-occur with phenotypes.
LOAD-intensity and time-under-tension of exercises for men who have Achilles tendinopathy (the LOADIT trial): a randomised feasibility trial
Authors: Hasani Fatmah , Haines Terry , Munteanu Shannon E. , Schoch Peter , Vicenzino Bill , Malliaras Peter
Published: May 2021

Background

One potential reason for disparate outcomes of exercise for Achilles tendinopathy is poor knowledge about whether exercise parameters (i.e. different exercise doses) influence outcome. Whether parameters that are important for tendon adaptation influence clinical outcomes in Achilles tendinopathy has not been investigated. Therefore, this research aimed to assess the feasibility of conducting a fully powered randomised trial to investigate the efficacy of different load-intensity and time-under-tension exercise parameters for Achilles tendinopathy.

Methods

A factorial four-arm, randomised trial. Forty-eight male participants (18–70 years old) with mid-portion Achilles tendinopathy (≥ 3 months) were recruited. Participants were randomly allocated to high (6 repetition maximum) or low intensity (18 repetition maximum) exercise, performed with either high (6 s per cycle) or low (2 s per cycle) time-under-tension. Participants performed 12-weeks of standing and seated calf raise exercises three times per week in a gym setting using a Smith machine. One session per week was supervised (via videoconference). Primary feasibility outcomes (recruitment and retention rate, exercise adherence and fidelity [i.e. time-under-tension, volume, load intensity], incidence of adverse events, health care use and productivity cost) were collected weekly. Means and standard deviations were determined for parametric data, medians and interquartile range for non-parametric continuous data, and frequency counts for discrete data.

Results

Total recruitment (76%) and retention (90%) rates were high. Exercise adherence ranged from 45 to 63% and fidelity ranged from 8 to 83% across the groups. Thirty-one participants reported 64 adverse events over the 3 months. Twenty-one participants (70%) reported mild events. Participants reported reduced presenteeism more than absenteeism.

Conclusions

A fully powered trial is feasible. The proposed trial design and interventions demonstrated acceptable recruitment and retention rates and safety profile. However, exercise fidelity and adherence to the gym-based intervention was not acceptable. Strategies to improve intervention adherence and fidelity should be considered in future trials.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12618001315202. Registered retrospectively on August 6th, 2018.
Blood DNA methylation and COVID-19 outcomes
Authors: Balnis Joseph , Madrid Andy , Hogan Kirk J. , Drake Lisa A. , Chieng Hau C. , Tiwari Anupama , Vincent Catherine E. , Chopra Amit , Vincent Peter A. , Robek Michael D. , Singer Harold A. , Alisch Reid S. , Jaitovich Ariel
Published: May 2021

Background

There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data.

Results

Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score.

Conclusion

Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.
Aortic dissection diagnosed on stroke computed tomography protocol: a case report
Authors: Usui Takami , Suzuki Kazufumi , Niinami Hiroshi , Sakai Shuji
Published: May 2021

Background

Aortic dissection is one of the causes of stroke. Because cerebral infarction with aortic dissection is a contraindication to intravenous recombinant tissue plasminogen activator (rt-PA) therapy, exclusion of aortic dissection is necessary prior to its administration. However, imaging takes time to provide a diagnosis, possibly causing delays in surgical treatment.

Case presentation

A 65-year-old Japanese female patient was transported to the hospital for a suspected stroke, with back pain and left upper and lower extremity palsy which occurred while eating. Upon arrival at the hospital, the left lower limb paralysis had improved, but the left upper limb paralysis remained. Right back pain had also developed. A plain head computed tomography (CT) scan performed 110 minutes after onset showed no acute bleeding or infarction. Subsequent CT perfusion (CTP) showed acute perfusion disturbance in the right hemisphere without infarction, known as ischemic penumbra. The four-dimensional maximum-intensity projection image reconstructed from CTP showed a delayed enhancement at the right internal carotid and right middle cerebral arteries compared to the contralateral side, suggesting a proximal vascular lesion. Contrast helical CT from the neck to abdomen revealed an acute aortic dissection of Stanford type A with false lumen patency. The dissection extended to the proximal right common carotid artery. The patient underwent an emergency total arch replacement and open stent graft. After recovering well, the patient was ambulatory upon discharge from the hospital. The combination of plain head CT, CTP, and helical CT scan from the neck to abdomen enabled us to evaluate for stroke and aortic dissection within a short amount of time, allowing for early therapeutic intervention.

Conclusions

When acute stroke is suspected due to neurological deficits, plain head CT is the first choice for imaging diagnosis. The addition of cervical CT angiography can reliably exclude stroke due to aortic dissection. CTP can identify ischemic penumbra, which cannot be diagnosed by plain head CT or diffusion-weighted magnetic resonance imaging. These combined stroke CT protocols helped us avoid missing an aortic dissection.
Hemolytic uremic syndrome related to Shiga-like toxin-producing Escherichia coli with encephalitis hiding a human herpesvirus-6 infection: a case report
Authors: Mounier Sophie , Gavotto Arthur , Tenenbaum Julie , Meyer Pierre , Fila Marc , Baleine Julien
Published: May 2021

Background

Cardiac and neurological involvement in hemolytic uremic syndrome are life-threatening complications. The most frequent complications of cardiac involvement in hemolytic uremic syndrome are myocarditis and cardiac dysfunction due to fluid overload. Pericarditis remains very rare in hemolytic uremic syndrome. To our knowledge, only five cases of cardiac tamponade associated with hemolytic uremic syndrome have been described in literature.

Case summary

A 27-month-old Caucasian girl presented with symptoms of nonbloody diarrhea and tonic-clonic seizures. The diagnosis of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome with central nervous system involvement was made, and stool examination revealed infection with a Shiga-like toxin-producing Escherichia coli. She did not need renal replacement therapy but had severe neurological impairment. The patient’s course was complicated by pericardial effusion. A pericardiocentesis was performed via an apical approach because the pericardial effusion was predominantly surrounding the left ventricle. Effusion analysis showed an exudate and positivity for human herpesvirus-6B on polymerase chain reaction with viremia. This finding was consistent with primary human herpesvirus-6 infection with encephalitis.

Conclusion

We report this uncommon case of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome associated with a severe human herpesvirus-6 infection. Secondary isolated pericardial effusion and atypical neurological involvement are uncommon in Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome and should lead the physician to perform additional investigations.
Physician blame and vulnerability: novel predictors of physician willingness to work with patients who misuse opioids
Authors: Franz Berkeley , Dhanani Lindsay Y. , Brook Daniel L.
Published: May 2021

Background

Successfully combating the opioid crisis requires patients who misuse opioids to have access to affirming and effective health care. However, there is a shortage of physicians who are willing to work with these patients. We investigated novel predictors of what might be contributing to physicians’ unwillingness to engage with this patient population to better identify and direct interventions to improve physician attitudes.

Methods

333 physicians who were board certified in the state of Ohio completed a survey about their willingness to work with patients who misuse opioids. The hypothesized relationships between the proposed predictors and willingness to work with this patient population were tested using multivariate regression, supplemented with qualitative analysis of open-text responses to questions about the causes of addiction.

Results

Perceptions of personal invulnerability to opioid misuse and addiction, opioid misuse and addiction controllability, and health care provider blame for the opioid crisis were negatively associated with physician willingness to work with patients who misuse opioids after controlling for known predictors of physician bias toward patients with substance use disorders. Physicians working in family and internal medicine, addiction medicine, and emergency medicine were also more willing to work with this patient population.

Conclusions

Distancing oneself and health care professionals from opioid misuse and placing blame on those who misuse are negatively associated with treatment willingness. Interventions to improve physician willingness to work with patients who misuse opioids can target these beliefs as a way to improve physician attitudes and provide patients with needed health care resources.
Evaluation of the effect of the capitation compensation mechanism among pulmonary tuberculosis patients with a full period of treatment
Authors: Hu Xing-Yu , Gao Guang-Ying
Published: May 2021

Background

PTB is an infectious disease, which not only seriously affects people’s health, but also causes a heavier disease economic burden on patients. At present, reform of the medical insurance payment can be an effective method to control medical expenses. Therefore, our study is to explore the compensation mechanism for pulmonary tuberculosis (PTB) patients with a full period of treatment, to alleviate the financial burden of PTB patients and provide a reference and basis for the reform of PTB payment methods in other regions and countries.

Methods

The quantitative data of PTB patients was collected from the first half of 2015 to the first half of 2018 in Dehui Tuberculosis Hospital in Jilin Province, and medical records of PTB patients registered in the first half of 2018 (n = 100) from the hospital was randomly selected. Descriptive analysis of these quantitative data summarized the number, cost, medication and compliance. Semi-structured in depth interviews with policymakers and physicians were conducted to understand the impact of interventions and its causes.

Results

After implementation of the compensation mechanism, the number of PTB patient visits in 2018 was increased by 14.2%, average medical costs for outpatients and inpatients were significantly reduced by 31.8% and 47.0%, respectively, and the auxiliary medication costs was reduced by 36.5%. Moreover, the hospital carried out standardized management of tuberculosis, and the patient compliance was very high, reaching almost 90%.

Conclusions

The capitation compensation mechanism with a full period of treatment was a suitable payment method for PTB, and it is worthy of promotion and experimentation. In addition, the model improved patient compliance and reduced the possibility of drug-resistant PTB. However, due to the short implementation time of the model in the pilot areas, the effect remains to be further observed and demonstrated.
Machine learning-based mathematical modelling for prediction of social media consumer behavior using big data analytics
Authors: Chaudhary Kiran , Alam Mansaf , Al-Rakhami Mabrook S. , Gumaei Abdu
Published: May 2021

Social media is popular in our society right now. People are using social media platforms to purchase various products. We collected the data from various social media platforms. We analyzed the data for prediction of the consumer behavior on the social media platform. We considered the consumer data from Facebook, Twitter, Linked In and YouTube, Instagram, and Pinterest, etc. There are diverse and high-speed, high volume data which are coming from social media platform, so we used predictive big data analytics. In this paper, we have used the concept of big data technology to process data and analyze it to predict consumer behavior on social media. We have analyzed consumer behavior on social media platforms based on some parameters and criteria. We analyzed the consumer perception, attitude towards the social media platform. To get good quality of result, we pre-process data using various data pre-processing to detect outlier, noises, error, and duplicate record. We developed mathematical modeling using machine learning to predict consumer behavior on the social media platform. This model is a predictive model for predicting consumer behavior on the social media platform. 80% of data are used for training purposes and 20% for testing.
National drug utilization trend of analgesics in China: an analysis of procurement data at 793 public hospitals from 2013 to 2018
Authors: Shi Honghao , Chen Xianwen , Liu Xueli , Zhu He , Yu Fei , Ung Carolina Oi Lam , Chan Wai Sin , Hu Hao , Han Sheng
Published: May 2021

Background

This research aimed to evaluate analgesic utilization in public hospitals from 2013 to 2018 by analyzing the procurement data of 793 hospitals in China.

Methods

This study applied a retrospective observational study by using a database of the Chinese Pharmaceutical Association. The final dataset covers 30 provinces and municipalities in China, with a total of 793 public hospitals with complete procurement records of analgesics from January 2013 to December 2018. Procurement cost and dosage utilization were analyzed through descriptive trend statistics.

Results

From the procurement cost data, analgesics mainly consisted of opioids and non-steroidal anti-inflammatory drugs (NSAIDs), and the annual cost of both types of drugs increased yearly. The 6-year total cost of opioids accounts for 57% (17,800 million CNY), followed by the cost of NSAIDs accounts for 37% (11,400 million CNY). From 2013 to 2018, the annual cost of opioids nearly doubled, while the annual cost of NSAIDs doubled. The total 6-year clinical drug dosage of opioids accounts for 45% (675 million total defined daily dose (DDD)), and the NSAIDs account for 50% (747 million total DDD). From 2013 to 2018, the annual clinical drug dosage of NSAIDs increased by about 0.6 times. The annual clinical drug dosage of opioids has more than doubled. The top three opioid drugs were dezocine injection, remifentanil injection, and sufentanil injection solution. the top three NSAIDs were flurbiprofen injection, parecoxib injection, and celecoxib oral solution.

Conclusion

In China, analgesics utilization increased rapidly at public hospitals from 2013 to 2018. The utilization of analgesics was highly concentrated in NSAIDs and opioids. Within the two types of analgesics, the main analgesics utilization is also highly concentrated, with some highly risky analgesics. The rational guideline for the utilization of analgesics needs to be established with the support of real-world evidence.
Exchange rates and immigration policy
Authors: Shin Adrian J.
Published: May 2021

What explains cross-national and temporal variations in migrant rights? This article argues that policymakers implement more exclusionary or inclusive policies toward migrants in response to exchange-rate fluctuations. Since exchange rates affect the real value of remittances, exchange-rate depreciation of the host state’s currency makes migration less valuable for existing and potential migrants, while exchange-rate appreciation increases the degree of migrant pressure on the host state by doing the opposite. This well-documented relationship between exchange rate valuation and migration movements affects how host country governments craft immigration policy. Under exchange-rate depreciation, policymakers will implement more inclusive policies to deter the “exit” of migrants and maintain a stable supply of labor. Under exchange-rate appreciation, increased migration pressures heighten public anxiety over immigration in the host country, in turn causing policymakers to restrict further immigration by implementing more exclusionary policies. Consistent with the argument, the empirical results show that the purchasing-power-parity (PPP) currency values of migrants’ home countries are positively correlated with more pro-migrant policies in host countries.
A rare case of Polyarteritis Nodosa associated with autoimmune hepatitis: a case report
Authors: Kennedy Freda , Kapelow Rachel , Kalyon Bilge D. , Roth Nitzan C. , Rishi Arvind , Barilla-LaBarca Maria-Louise
Published: May 2021

Background

Polyarteritis nodosa is a type of vasculitis affecting medium- and small-sized arteries that has been associated with hepatitis B but does not have an established relationship with autoimmune hepatitis. Here we report the case of an adult patient with autoimmune hepatitis who, shortly after diagnosis, developed life-threatening polyarteritis nodosa.

Case presentation

A 45-year-old woman was diagnosed with autoimmune hepatitis after initially presenting with a two-month history of fatigue, nausea, and anorexia and a three-week history of scleral icterus. Her liver biopsy showed mild portal fibrosis and her liver chemistries improved with prednisone and azathioprine. Three months later, she presented to the emergency department with fever, bilateral ankle pain, rash, oral ulcers, and poor vision. Physical examination was notable for erythema nodosum, anterior uveitis, retinal vasculitis, and frosted branch angiitis (frosted branch angiitis (a widespread florid translucent perivascular exudate). She subsequently developed repeated episodes of ischemic acute bowel necrosis that required multiple surgeries and extensive small bowel resections. Surgical pathology of the small bowel resection revealed ischemic necrosis, medium and small vessel vasculitis with microvascular thrombi consistent with polyarteritis nodosa. Azathioprine was discontinued and she was treated with pulse steroids followed by a prednisone taper, cyclophosphamide, and intravenous immune globulin with overall improvement in her symptomatology. Since her hospitalization, she has been maintained on low-dose prednisone and mycophenolate mofetil.

Conclusions

In patients with recent diagnosis of autoimmune hepatitis, there should be a modest suspicion for concomitant polyarteritis nodosa if symptoms and signs of multisystem vasculitis develop.
Role of chest radiograph in MERS-Cov pneumonia: a single tertiary referral center experience in the United Arab Emirates
Authors: Das Karuna M. , Alkoteesh Jamal Aldeen , Sheek-Hussein Mohamud , Alzadjali Samira Ali , Alafeefi Mariam Tareq , Singh Rajvir , Statsenko Yauhen , Soteriades Elpidoforos S. , Singh Vishwajeet , Van Gorkom Klaus
Published: May 2021

Background

The Middle East respiratory syndrome coronavirus (MERS-Cov) continues to be a source of concern due to intermittent outbreaks. Serial chest radiographic changes in MERS-Cov patients were analyzed for various variables that could be compared to the patients’ final outcomes in a cluster of MERS-Cov patients and to identify a predictor of mortality in the United Arab Emirates.

Results

A total of 44 MERS-Cov cases were reviewed. The mean age of the patients was 43.7 ± 14.7 years. The chest radiograph was abnormal in 14/44 (31.8%). The commonest radiology features include ground-glass opacities (seven of 14, 50%), ground-glass and consolidation (seven of 14, 50%), pleural effusion (eight of 14, 57.1%), and air bronchogram (three of 14, 21.4%). The mortality rate was 13.6% (six of 44); the deceased group (6 of 44, 13.6%) was associated with significantly higher incidence of mechanical ventilation (p < 0.001), pleural effusion (p < 0.001), chest radiographic score (8.90 ± 6.31, p < 0.001), and type 4 radiographic progression of disease (p < 0.001). A chest radiographic score at presentation was seen to be an independent and strong predictor of mortality (OR [95% confidence interval] 3.20 [1.35, 7.61]). The Cohen κ coefficient for the interobserver agreement was k = 0.89 (p = 0.001).

Conclusion

The chest radiographic score, associated with a higher degree of disease progression (type 4), particularly in patients with old age or with comorbidity, may indicate a poorer prognosis in MERS-Cov infection, necessitating intensive care unit management or predicting impending death.
Numerical analysis on the time-varying temperature field distribution patterns of ballastless track steel-concrete composite box girders at ambient temperature based on field measurements
Authors: Wen Wangqing , Li Shiwei , Yan Aiguo , Zeng Jiahua
Published: May 2021

To analyze the time-varying temperature field distribution pattern of ballastless track steel-concrete composite box girders for a high-speed railway at ambient temperature, a numerical model for analyzing the time-varying temperature field of steel-concrete composite box girders was established based on the long-term monitoring data for the internal and external environments of the main girder of the Ganjiang Bridge on the Nanchang-Ganzhou high-speed railway. The influence of factors such as the deck pavement and the ambient wind speed on the time-varying temperature field of the steel-concrete composite box girders were considered. The results showed that there was a significant difference in the vertical temperature gradient patterns on sections at the side web and at the middle web at the same moment in time due to the hindering effect of the track board on the heat exchange between the ambient temperature and the main girder. Increasing the wind speed accelerated the rate of heat exchange between the main girder surface and the environment. In particular, when the internal temperature of the girder was higher than the ambient temperature, the higher the wind speed was, the larger the temperature gradient was. This study lays a foundation for accurate analysis of the structural response of ballastless track steel-concrete composite girder bridges at ambient temperature.
Models of care in forensic psychiatry
Authors: Kennedy Harry G.
Published: May 2021

Forensic psychiatry services have grown and become more complex in structures, processes and pathways. Legacy customs, practices and changing policy are now organised into formal models of care. These are written accounts of how a health service is delivered, outlining best practice and services for patients progressing through the stages of their condition and the care and treatment available. This article explores the four key elements of a model of care: goals; pathways and processes; treatment programmes; and systematic evaluation. It describes the most common model of care in forensic services, which builds on structures of stratified therapeutic security. It also considers variations on this basic or standard model matched to needs arising from the complex interrelationship with other parts of the mental health service for the population served and with criminal justice, primary care and physical health, housing and welfare agencies.
Mother–infant interaction in women with depression in pregnancy and in women with a history of depression: the Psychiatry Research and Motherhood – Depression (PRAM-D) study
Authors: Bind Rebecca H. , Biaggi Alessandra , Bairead Aoife , Du Preez Andrea , Hazelgrove Katie , Waites Freddie , Conroy Susan , Dazzan Paola , Osborne Sarah , Pawlby Susan , Sethna Vaheshta , Pariante Carmine M.
Published: May 2021

Background

Little is known about the effects of depression before birth on the quality of the mother–infant interaction.

Aims

To understand whether depression, either in pregnancy or in lifetime before pregnancy, disrupts postnatal mother–infant interactions.

Method

We recruited 131 pregnant women (51 healthy, 52 with major depressive disorder (MDD) in pregnancy, 28 with a history of MDD but healthy pregnancy), at 25 weeks’ gestation. MDD was confirmed with the Structured Clinical Interview for DSM-IV Disorders. Neonatal behaviour was assessed at 6 days with the Neonatal Behavioural Assessment Scale, and mother–infant interaction was assessed at 8 weeks and 12 months with the Crittenden CARE-Index.

Results

At 8 weeks and 12 months, dyads in the depression and history-only groups displayed a reduced quality of interaction compared with healthy dyads. Specifically, at 8 weeks, 62% in the depression group and 56% in the history-only group scored in the lowest category of dyadic synchrony (suggesting therapeutic interventions are needed), compared with 37% in the healthy group (P= 0.041); 48% and 32%, respectively, scored the same at 12 months, compared with 14% in the healthy group (P= 0.003). At 6 days, neonates in the depression and history-only groups exhibited decreased social-interactive behaviour, which, together with maternal socioeconomic difficulties, was also predictive of interaction quality, whereas postnatal depression was not.

Conclusions

Both antenatal depression and a lifetime history of depression are associated with a decreased quality of mother–infant interaction, irrespective of postnatal depression. Clinicians should be aware of this, as pregnancy provides an opportunity for identification and intervention to support the developing relationship.
Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular Block in Patients Having Catheter-Based Neurointerventional Procedures: A Randomized Trial
Authors: Farag Ehab , Rivas Eva , Bravo Mauro , Hussain Shazam , Argalious Maged , Khanna Sandeep , Seif John , Pu Xuan , Mao Guangmei , Bain Mark , Elgabaly Mohamed , Esa Wael Ali Sakr , Sessler Daniel I.
Published: May 2021

BACKGROUND:

Catheter-based endovascular neurointerventions require deep neuromuscular blocks during the procedure and rapid subsequent recovery of strength to facilitate neurological evaluation. We tested the primary hypothesis that sugammadex reverses deep neuromuscular blocks faster than neostigmine reverses moderate neuromuscular blocks.

METHODS:

Patients having catheter-based cerebral neurointerventional procedures were randomized to: (1) deep rocuronium neuromuscular block with posttetanic count 1 to 2 and 4-mg/kg sugammadex as the reversal agent or (2) moderate rocuronium neuromuscular block with train-of-four (TOF) count 1 during the procedure and neuromuscular reversal with 0.07-mg/kg neostigmine to a maximum of 5 mg. Recovery of diaphragmatic function was assessed by ultrasound at baseline before the procedure and 90 minutes thereafter. The primary outcome—time to reach a TOF ratio ≥0.9 after administration of the designated reversal agent—was analyzed with a log-rank test. Secondary outcomes included time to successful tracheal extubation and the difference between postoperative and preoperative diaphragmatic contraction speed and distance.

RESULTS:

Thirty-five patients were randomized to sugammadex and 33 to neostigmine. Baseline characteristics and surgical factors were well balanced. The median time to reach TOF ratio ≥0.9 was 3 minutes (95% confidence interval [CI], 2-3 minutes) in patients given sugammadex versus 8 minutes (95% CI, 6-10 minutes) in patients given neostigmine. Sugammadex was significantly faster by a median of 5 minutes (95% CI, 3-6 minutes; P < .001). However, times to tracheal extubation and diaphragmatic function at 90 minutes did not differ significantly.

CONCLUSIONS:

Sugammadex reversed deep rocuronium neuromuscular blocks considerably faster than neostigmine reversed moderate neuromuscular blocks. However, times to extubation did not differ significantly, apparently because extubation was largely determined by the time required for awaking from general anesthesia and because clinicians were willing to extubate before full neuromuscular recovery. Sugammadex may nonetheless be preferable to procedures that require a deep neuromuscular block and rapid recovery.