bluuebunny/crossref_metadata_2025 huggingface dataset:
Vulnerability identified in clinical practice: a qualitative analysis
Authors: Sossauer Laura , Schindler Mélinée , Hurst Samia
Published: November 2019

Background

Although it is the moral duty of physicians to protect vulnerable patients, there are no data on how vulnerability is perceived in clinical practice. This study explores how physicians classify someone as “vulnerable”.

Method

Thirty-three physicians were initially questioned about resource allocation problems in their work. The results of these interviews were examined with qualitative study software to identify characteristics associated with vulnerability in patients. Data were conceptualized, classified and cross-linked to highlight the major determinants of vulnerability.

The findings revealed the principal factors that make patients vulnerable in clinical practice, according to our definition of vulnerability: the likelihood of having one’s interests unjustly considered.

Results

Vulnerability can arise as a result of a mismatch between the characteristics of patients and physicians, the healthcare system, the treatment, or the communication between physicians and patients. Vulnerability appears as a gap between a patient’s needs and the means intended to meet them. Vulnerability can further be the result of doing too little or too much for patients. This result suggests that structures provided by healthcare systems are not as differentiated as they should be to cover all situations. Our initial definition of vulnerability was illustrated and supported by our results, showing that it encompasses all factors involved, not solely personal characteristics, indicating the need for a more pragmatic approach for use in clinical practice.

Conclusion

Vulnerability is not due to a single factor but appears under certain circumstances when there is a discrepancy between a patient’s interests and the care provided, despite existing compensation systems.
Mapping, framing, shaping: a framework for empirical bioethics research projects
Authors: Huxtable Richard , Ives Jonathan
Published: November 2019

Background

There is growing interest in the use and incorporation of empirical data in bioethics research. Much of the recent focus has been on specific “empirical bioethics” methodologies, which attempt to integrate the empirical and the normative. Researchers in the field are, however, beginning to explore broader questions, including around acceptable standards of practice for undertaking such research.

The framework:

In this article, we further widen the focus to consider the overall shape of an empirical bioethics research project. We outline a framework that identifies three key phases of such research, which are conveyed via a landscaping metaphor of Mapping-Framing-Shaping. First, the researcher maps the field of study, typically by undertaking literature reviews. Second, the researcher frames particular areas of the field of study, exploring these in depth, usually via qualitative research. Finally, the researcher seeks to (re-)shape the terrain by issuing recommendations that draw on the findings from the preceding phases. To qualify as empirical bioethics research, the researcher will utilise a methodology that seeks to bridge these different elements in order to arrive at normative recommendations. We illustrate the framework by citing examples of diverse projects which broadly adopt the three-phase framework. Amongst the strengths of the framework are its flexibility, since (as the examples indicate) it does not prescribe any specific methods or particular bridging methodology. However, the framework might also have its limitations, not least because it appears particularly to capture projects that involve qualitative – as opposed to quantitative – research.

Conclusions

Despite its possible limitations, we offer the Mapping-Framing-Shaping framework in the hope that this will prove useful to those who are seeking to plan and undertake empirical bioethics research projects.
Fetal Down syndrome screening models for developing countries; Part II: Cost-benefit analysis
Authors: Wanapirak Chanane , Buddhawongsa Piyaluk , Himakalasa Woraluck , Sarnwong Auttapan , Tongsong Theera
Published: November 2019

Background

To identify the most cost-beneficial model as a national policy of screening and diagnosis of fetal Down syndrome (DS) in developing countries.

Methods

Cost-benefit analysis (CBA) was performed based on the effectiveness and probabilities derived from a large prospective study on MSS (maternal serum screening) among Thai population. Various models including maternal age alone, STS (second trimester screen), I-S (independent screen: first or second trimester screen depending on the time of first visit), C-S (contingent serum screen) plus STS, maternal age with NIPS (non-invasive prenatal test), STS alone with NIPS, I-S with NIPS, C-S plus STS with NIPS, and Universal NIPS were compared.

Results

I-S with NIPS as a secondary screening was most cost-beneficial (Benefit/Cost ratio 4.28). Cost-benefit is directly related to the costs of NIPS.

Conclusion

In addition to simplicity and feasibility, I-S with expensive NIPS as a secondary screening is the most cost-beneficial method for low resource settings and should be included in universal healthcare coverage as a national policy. This study could be a model for developing countries or a guideline for international health organizations to help low resource countries, probably leading to a paradigm shift in prenatal diagnosis of fetal DS in the developing world.
Meeting unmet needs following minor stroke: the SUN randomised controlled trial protocol
Authors: Finch Emma , Foster Michele , Cruwys Tegan , Fleming Jennifer , Aitken Philip , Jaques Katherine , Williams Ian , Shah Darshan
Published: November 2019

Background

Whilst there are comprehensive guidelines for the rehabilitation of people with severe impairments from stroke, there has been less attention on the health and rehabilitation needs of people with minor stroke. Our study will assess whether a new multi-component service pathway using an integrated model based around primary care will reduce unmet need following minor stroke compared with usual care 1 and 3 months post-hospital discharge.

Methods

One hundred ten patients with minor stroke will be recruited within a parallel, randomised controlled trial design comparing a new service pathway and usual care.

The new service pathway will comprise a self-management kit, customised General Practitioner checklist, and a series of minor stroke educational topics. Participants will complete assessments pre-hospital discharge and 1 and 3 months later. The primary outcome measure will be the Survey of Unmet Needs and Service Usage. Secondary outcome measures will include assessments of ability, adjustment and participation; social group connectedness; return to work; health-related quality of life; and perceptions of the new service pathway (intervention group only). Mixed model repeated measures will be used to analyse within and between group differences at each time point. Return to work will be analysed using Chi square tests. Perceptions of the new service pathway will be analysed qualitatively.

Dissemination of results

The project will produce an evidence-based, multicomponent service pathway for minor stroke patients, applicable to other health services nationally and internationally. Dissemination will include publications and presentations.

Trial registration

Prospectively registered - Australian New Zealand Clinical Trials Registry (ACTRN12619000133134p) 30 January 2019.
Correction to: Does specialist physician supply affect pediatric asthma health outcomes?
Authors:   The Paediatric Chairs of Canada, Filler Guido , Kovesi Tom , Bourdon Erik , Jones Sarah Ann , Givelichian Laurentiu , Rockman-Greenberg Cheryl , Gilliland Jason , Williams Marion , Orrbine Elaine , Piedboeuf Bruno
Published: November 2019

In the original publication of this article [1], the institutional author’s name needs to be revised from The Paediatric Chairs of Canada Mark Bernstein to The Paediatric Chairs of Canada.
Can public health policies on alcohol and tobacco reduce a cancer epidemic? Australia's experience
Authors: Jiang Heng , Livingston Michael , Room Robin , Gan Yong , English Dallas , Chenhall Richard
Published: November 2019

Background

Although long-term alcohol and tobacco use have widely been recognised as important risk factors for cancer, the impacts of alcohol and tobacco health policies on cancer mortality have not been examined in previous studies. This study aims to estimate the association of key alcohol and tobacco policy or events in Australia with changes in overall and five specific types of cancer mortality between the 1950s and 2013.

Methods

Annual population-based time-series data between 1911 and 2013 on per capita alcohol and tobacco consumption and head and neck (lip, oral cavity, pharynx, larynx and oesophagus), lung, breast, colorectum and anus, liver and total cancer mortality data from the 1950s to 2013 were collected from the Australian Bureau of Statistics and Cancer Council Victoria, the WHO Cancer Mortality Database and the Australian Institute of Health and Welfare. The policies with significant relations to changes in alcohol and tobacco consumption were identified in an initial model. Intervention dummies with estimated lags were then developed based on these key alcohol and tobacco policies and events and inserted into time-series models to estimate the relation of the particular policy changes with cancer mortality.

Results

Liquor licence liberalisation in the 1960s was significantly associated with increases in the level of population drinking and thereafter of male cancer mortality. The introduction of random breath testing programs in Australia after 1976 was associated with a reduction in population drinking and thereafter in cancer mortality for both men and women. Meanwhile, the release of UK and US public health reports on tobacco in 1962 and 1964 and the ban on cigarette ads on TV and radio in 1976 were found to have been associated with a reduction in Australian tobacco consumption and thereafter a reduction in mortality from all cancer types except liver cancer. Policy changes on alcohol and tobacco during the 1960s–1980s were associated with greater changes for men than for women, particularly for head and neck, lung and colorectum cancer sites.

Conclusion

This study provides evidence that some changes to public health policies in Australia in the twentieth century were related to the changes in the population consumption of alcohol and tobacco, and in subsequent mortality from various cancers over the following 20 years.
Bioinformatics analysis of capsid protein of different subtypes rabbit hemorrhagic disease virus
Authors: Qi Ruibin , Zhu Jie , Miao Qiuhong , Tang Aoxing , Dong Dandan , Wang Xiaoxue , Liu Guangqing
Published: November 2019

Background

Rabbit Hemorrhagic Disease Virus (RHDV) belongs to the Caliciviridae family, is a highly lethal pathogen to rabbits. Increasing numbers of studies have demonstrated the existence of antigenic variation in RHDV, leading to the emergence of a new RHDV isolate (RHDVb). However, the underlying factors determining the emergence of the new RHDV and its unpredictable epidemiology remain unclear. To investigate these issues, we selected more than 184 partial and/or complete genome sequences of RHDV from GenBank and analyzed their phylogenetic relationships, divergence, and predicted protein modification sites.

Results

Phylogenetic analysis showed that classic RHDV isolates, RHDVa, and RHDVb formed different clades. It’s interesting to note that RHDVa being more closely related to classic RHDV than RHDVb, while RHDVb had a closer genetic relationship to Rabbit Calicivirus (RCV) than to classic RHDV isolates. Moreover, divergence analysis suggested that the accumulation of amino acid (aa) changes might be a consequence of adaptive diversification of capsid protein (VP60) during the division between classical RHDV, RHDVa, RHDVb, and RCV. Notably, the prediction of N-glycosylation sites suggested that RHDVb subtypes had two unique N-glycosylation sites (aa 301, 362) but lacked three other N-glycosylation sites (aa 45, 308, 474) displayed in classic RHDV and RHDVa VP60 implying this divergence of N-glycosylation sites in RHDV might affect viral virulence. Analysis of phosphorylation sites also indicated that some phosphorylation sites in RHDVa and RHDVb differed from those in classic RHDV, potentially related to antigenic variation in RHDV.

Conclusion

The genetic relationship between RHDVb and RCV was closer than classic RHDV isolates. Moreover, compared to RHDV and RHDVa, RHDVb had two unique N-glycosylation sites but lacked three sites, which might affect the virulence of RHDV. These results may provide new clues for further investigations of the origin of new types of RHDV and the mechanisms of genetic variation in RHDV.
Dietary intervention reduces left atrial enlargement in dogs with early preclinical myxomatous mitral valve disease: a blinded randomized controlled study in 36 dogs
Authors: Li Qinghong , Heaney Allison , Langenfeld-McCoy Natalie , Boler Brittany Vester , Laflamme Dorothy P.
Published: November 2019

Background

Myxomatous mitral valve disease (MMVD), the most common naturally-occurring heart disease in dogs, is associated with alterations in energy metabolism, oxidative stress and inflammation. Energy deprivation plays a causal role in the development of heart failure. This study was designed to determine if a cardiac protection blend (CPB) of nutrients containing medium-chain triglycerides as an alternative energy source, fish oil to reduce inflammation, antioxidants, and other key nutrients important to cardiac health and function could slow or prevent MMVD progression. Nineteen dogs with early stage MMVD and 17 breed-, age-, and sex-matched healthy dogs were enrolled for a 6-month blinded, placebo-controlled study. Dogs in each cardiac health group were randomly assigned to either control diet (CON) or CPB-supplemented diet. Echocardiography was performed at baseline, 3 months and 6 months.

Results

No changes were found in healthy dogs. While MMVD-CON dogs had an average 10% increase over baseline in left atrial diameter (LAD) and left atrial to aortic root ratio (LA/Ao) at 6 months, MMVD-CPB dogs showed 3% decreases, resulting significant diet by time interactions (P = 0.037,P = 0.005, respectively). More MMVD-CON dogs progressed from stage B1 to B2 during the study. A positive correlation was found between 6-month changes in LAD and blood pressures in MMVD-CPB dogs (systolic:P = 0.050, diastolic:P = 0.035) but not MMVD-CON dogs.

Conclusions

Our results demonstrated efficacy of CPB-based dietary intervention in reducing LA size and mitral regurgitation, and in slowing or preventing the progression of early MMVD in dogs.
Development and comparison of enzyme-linked immunosorbent assays based on recombinant trimeric full-length and truncated spike proteins for detecting antibodies against porcine epidemic diarrhea virus
Authors: Chang Chia-Yu , Peng Ju-Yi , Cheng Yun-Han , Chang Yen-Chen , Wu Yen-Tse , Tsai Pei-Shiue , Chiou Hue-Ying , Jeng Chian-Ren , Chang Hui-Wen
Published: November 2019

Background

Since 2010, outbreaks of genotype 2 (G2) porcine epidemic diarrhea virus (PEDV) have caused high mortality in neonatal piglets and have had devastating impacts on the swine industry in many countries. A reliable serological assay for evaluating the PEDV-specific humoral and mucosal immune response is important for disease survey, monitoring the efficacy of immunization, and designing strategies for the prevention and control of PED. Two PEDV spike (S) glycoprotein-based indirect enzyme-linked immunosorbent assays (ELISAs) were developed using G2b PEDV-Pintung 52 (PEDV-PT) trimeric full-length S and truncated S1–501proteins derived from the human embryonic kidney (HEK)-293 cell expression system. The truncated S1–501protein was selected from a superior expressed stable cell line. The sensitivity and specificity of these two ELISAs were compared to immunostaining of G2b PEDV-PT infected cells and to a commercial nucleocapsid (N)-based indirect ELISA kit using a panel of PEDV negative and hyperimmune sera.

Results

The commercial N-based ELISA exhibited a sensitivity of 37%, a specificity of 100%, and a fair agreement (kappa = 0.37) with the immunostaining result. In comparison, the full-length S-based ELISA showed a sensitivity of 97.8%, a specificity of 94%, and an almost perfect agreement (kappa = 0.90) with the immunostaining result. Interestingly, the S1–501-based ELISA had even higher sensitivity of 98.9% and specificity of 99.1%, and an almost perfect agreement (kappa = 0.97) with the immunostaining result. A fair agreement (kappa< 0.4) was seen between the commercial N-based ELISA and either of our S-based ELISAs. However, the results of the full-length S-based ELISA shared an almost perfect agreement (kappa = 0.92) with that of S1–501-based ELISA.

Conclusions

Both full-length S-based and S1–501-based ELISAs exhibit high sensitivity and high specificity for detecting antibodies against PEDVs. Considering the high protein yield and cost-effectiveness, the S1–501-based ELISA could be used as a reliable, sensitive, specific, and economic serological test for PEDV.
Multiplex malaria antigen detection by bead-based assay and molecular confirmation by PCR shows no evidence of Pfhrp2 and Pfhrp3 deletion in Haiti
Authors: Herman Camelia , Huber Curtis S. , Jones Sophie , Steinhardt Laura , Plucinski Mateusz M. , Lemoine Jean F. , Chang Michelle , Barnwell John W. , Udhayakumar Venkatachalam , Rogier Eric
Published: November 2019

Background

The Plasmodium falciparum parasite is the only human malaria that produces the histidine-rich protein 2 and 3 (HRP2/3) antigens. Currently, HRP2/3 are widely used in malaria rapid diagnostic tests (RDTs), but several global reports have recently emerged showing genetic deletion of one or both of these antigens in parasites. Deletion of these antigens could pose a major concern for P. falciparum diagnosis in Haiti which currently uses RDTs based solely on the detection of the HRP2/3 antigens.

Methods

From September 2012 through February 2014, dried blood spots (DBS) were collected in Haiti from 9317 febrile patients presenting to 17 health facilities in 5 departments throughout the country as part of a bed net intervention study. All DBS from RDT positive persons and a random sampling of DBS from RDT negative persons were assayed for P. falciparum DNA by nested and PET-PCR (n = 2695 total). All PCR positive samples (n = 331) and a subset of PCR negative samples (n = 95) were assayed for three malaria antigens by a multiplex bead assay: pan-Plasmodium aldolase (pAldo), pan-Plasmodium lactate dehydrogenase (pLDH), and HRP2/3. Any samples positive for P. falciparum DNA, but negative for HRP2/3 antigens were tested by nested PCR for Pfhrp2 and Pfhrp3 gene deletions.

Results

Of 2695 DBS tested for Plasmodium DNA, 345 (12.8%) were originally found to be positive for P. falciparum DNA; 331 of these had DBS available for antigen detection. Of these, 266 (80.4%) were positive for pAldo, 221 (66.8%) positive for pLDH, and 324 (97.9%) were positive for HRP2/3 antigens. Seven samples (2.1%) positive for P. falciparum DNA were not positive for any of the three antigens by the bead assay, and were investigated for potential Pfhrp2/3 gene deletion by PCR. These samples either successfully amplified Pfhrp2/3 genes or were at an estimated parasite density too low for sufficient DNA to perform successful genotyping.

Conclusions

Malaria positive samples in multiple Haitian sites were found to contain the HRP2/3 antigens, and no evidence was found of Pfhrp2/3 deletions. Malaria RDTs based on the detection of the HRP2/3 antigens remain a reliable P. falciparum diagnostic tool as Haiti works towards malaria elimination.
A collective tracking method for preliminary sperm analysis
Authors: Wei Sung-Yang , Chao Hsuan-Hao , Huang Han-Ping , Hsu Chang Francis , Li Sheng-Hsiang , Hsu Long
Published: November 2019

Background

Total motile sperm count (TMSC) and curvilinear velocity (VCL) are two important parameters in preliminary semen analysis for male infertility. Traditionally, both parameters are evaluated manually by embryologists or automatically using an expensive computer-assisted sperm analysis (CASA) instrument. The latter applies a point-tracking method using an image processing technique to detect, recognize and classify each of the target objects, individually, which is complicated. However, as semen is dense, manual counting is exhausting while CASA suffers from severe overlapping and heavy computation.

Methods

We proposed a simple frame-differencing method that tracks motile sperms collectively and treats their overlapping with a statistical occupation probability without heavy computation. The proposed method leads to an overall image of all of the differential footprint trajectories (DFTs) of all motile sperms and thus the overall area of the DFTs in a real-time manner. Accordingly, a theoretical DFT model was also developed to formulate the overall DFT area of a group of moving beads as a function of time as well as the total number and average speed of the beads. Then, using the least square fitting method, we obtained the optimal values of the TMSC and the average VCL that yielded the best fit for the theoretical DFT area to the measured DFT area.

Results

The proposed method was used to evaluate the TMSC and the VCL of 20 semen samples. The maximum TMSC evaluated using the method is more than 980 sperms per video frame. The Pearson correlation coefficient (PCC) between the two series of TMSC obtained using the method and the CASA instrument is 0.946. The PCC between the two series of VCL obtained using the method and CASA is 0.771. As a consequence, the proposed method is as accurate as the CASA method in TMSC and VCL evaluations.

Conclusion

In comparison with the individual point-tracking techniques, the collective DFT tracking method is relatively simple in computation without complicated image processing. Therefore, incorporating the proposed method into a cell phone equipped with a microscopic lens can facilitate the design of a simple sperm analyzer for clinical or household use without advance dilution.
A “Swiss paradox” in the United States? Level of spatial aggregation changes the association between income inequality and morbidity for older Americans
Authors: Cohen Steven A. , Greaney Mary L. , Klassen Ann C.
Published: November 2019

Although a preponderance of research indicates that increased income inequality negatively impacts population health, several international studies found that a greater income inequality was associated with better population health when measured on a fine geographic level of aggregation. This finding is known as a “Swiss paradox”. To date, no studies have examined variability in the associations between income inequality and health outcomes by spatial aggregation level in the US. Therefore, this study examined associations between income inequality (Gini index, GI) and population health by geographic level using a large, nationally representative dataset of older adults. We geographically linked respondents’ county data from the 2012 Behavioral Risk Factor Surveillance System to 2012 American Community Survey data. Using generalized linear models, we estimated the association between GI decile on the state and county levels and five population health outcomes (diabetes, obesity, smoking, sedentary lifestyle and self-rated health), accounting for confounders and complex sampling. Although state-level GI was not significantly associated with obesity rates (b = − 0.245, 95% CI − 0.497, 0.008), there was a significant, negative association between county-level GI and obesity rates (b = − 0.416, 95% CI − 0.629, − 0.202). State-level GI also associated with an increased diabetes rate (b = 0.304, 95% CI 0.063, 0.546), but the association was not significant for county-level GI and diabetes rate (b = − 0.101, 95% CI − 0.305, 0.104). Associations between both county-level GI and state-level GI and current smoking status were also not significant. These findings show the associations between income inequality and health vary by spatial aggregation level and challenge the preponderance of evidence suggesting that income inequality is consistently associated with worse health. Further research is needed to understand the nuances behind these observed associations to design informed policies and programs designed to reduce socioeconomic health inequities among older adults.
Mutational spectrum of tobacco associated oral squamous carcinoma and its therapeutic significance
Authors: Batta Nishant , Pandey Manoj
Published: November 2019

Oral squamous cell cancer (OSCC) is a common malignancy attributed to use of chewing smokeless tobacco and smoking. Most of the targeted strategies are based on EGFR expression and mutation; however, none of them has shown significant improvement in survival and response rates. We carried out this study to evaluate mutational profile of tobacco associated oral carcinoma with special emphasis on EGFR and its downstream events.

Patients and methods

A total of 46 histologically proven cases were recruited between January 2017 and January 2019. Apart from detailed clinical and histological studies, the paraffin-embedded tissue was submitted for expression of 50 genes using Next Generation Sequencing using Ion Ampliseq Cancer Hotspot Panel v2.

Results

The mean age of patients was 47.8 ± 10.9 years. Majority had tumors on buccal mucosa (24) and tongue (13). Nineteen of these tumors were larger than 4 cm, and 5 had adjacent site involvement. Thirty one were node positive. TP53 mutations were commonest seen in 19 followed by CDKN2A in 11, HRAS in 8, PIK3CA in 3, SMARCB1 in 2, and KIT, EGFR, BRAF, STK11, ABL1, RB1 in one case each. Concomitant TP53 mutation was identified with other mutations like CDKN2A, HRAS, KIT, PIK3CA, STK11, SMARCB1, ABL1, and RB1 making tobacco-associated OSCC as a heterogeneous mutational tumor with multiple events. A patient with TP53 mutations has poor disease free survival (47.4 vs 63% p = 0.17); however, this was not statistically significant.

Conclusion

The study shows a heterogeneous mutational spectrum with multiple mutational events in OSCC. The low EGFR mutation rates and higher mutations in EGFR downstream pathways including that in TP53 and HRAS suggest that anti EGFR strategies may not succeed in these tumors and newer agents and therapeutic combinations need to be tried.
Medicinal plants of the Bible—revisited
Authors: Dafni Amots , Böck Barbara
Published: November 2019

Background

Previous lists number from 55 to 176 plant species as “Biblical Medicinal Plants.” Modern studies attest that many names on these lists are no longer valid. This situation arose due to old mistranslations and/or mistakes in botanical identification. Many previously recognized Biblical plants are in no way related to the flora of the Bible lands. Accordingly, the list needs revision.

Methods

We re-examine the list of possible medicinal plants in the Bible based on new studies in Hebrew Biblical philology and etymology, new studies on the Egyptian and Mesopotamian medicinal use of plants, on ethnobotany and on archaeobotany.

Results

In our survey, we suggest reducing this list to 45 plant species. Our contribution comprises 20 “newly” suggested Biblical Medicinal Plants. Only five species are mentioned directly as medicinal plants in the Bible: Fig (Ficus carica), Nard (Nardostachys jatamansi), Hyssop (Origanum syriacum), balm of Gilead (Commiphora gileadensis) and Mandrake (Mandragora officinarum). No fewer than 18 medicinal plants are mentioned in old Jewish post-Biblical sources, in addition to those in the Bible. Most of these plants (15) are known also in Egypt and Mesopotamia while three are from Egypt only. Seven of our suggested species are not mentioned in the Bible or in the Jewish post-Biblical literature but were recorded as medicinal plants from Egypt, as well as from Mesopotamia. It is quite logical to assume that they can be included as Biblical Medicinal Plants.

Conclusions

All our suggested Biblical Medicinal Plants are known as such in Ancient Egypt and/or Mesopotamia also. Examination of our list shows that all these plants have been in continuous medicinal use in the Middle East down the generations, as well as being used in the Holy Land today. Precisely in King Solomon’s words, “That which has been is what will be, that which is done is what will be done. And there is nothing new under the sun” (Ecclesiastes 1:9).
Early clinical outcomes of simple pannus removal for mechanical aortic valve stenosis
Authors: Cui Huimin , Zhang Lin , Wei Shixiong , Jiang Shengli
Published: November 2019

Background

This study aimed to confirm the safety and feasibility of simple pannus removal in patients with mechanical aortic valve dysfunction for pannus overgrowth by evaluating its early clinical outcomes.

Methods

From March 2015 to April 2019, 24 consecutive patients with mechanical aortic valve dysfunction due to subaortic pannus underwent reoperation. In 12 patients the repeat aortic valve replacement (AVR) was performed, and 12 received the simple pannus removal to preserve the previously implanted prosthesis.

Results

There was only 1 in-hospital death in simple pannus removal group. Significant differences were obtained between procedures in cardiopulmonary bypass (CPB) and aortic cross-clamp time (128.7 vs 179.7 and 74.2 vs 132.7 mins, respectively, P < 0.05). The C-reactive protein (CRP) in simple pannus removal group was lower on the first day (0.13 ± 0.09 vs 0.31 ± 0.22 mg/dl, P < 0.05) and continued to be lower within 1 week after operation. There was no significant difference between procedures in aortic transvalvular peak velocity and transvalvular mean pressure gradient (TMPG) (2.6 ± 0.4 vs 2.5 ± 0.4 m/s and 13.2 ± 3.6 vs 11.6 ± 2.6 mmHg, respectively, P > 0.05) in echocardiography 1 week after operation. In addition, the aortic transvalvular peak velocity and TMPG in echocardiography 1 week after operation in pannus removal group between the repeat and initial surgery were not statistically significant (2.6 ± 0.4 vs. 2.5 ± 0.3 m/s, 13.2 ± 3.6 vs. 13.0 ± 3.5 mmHg, P > 0.05).

Conclusions

Simple pannus removal was a safe and effective procedure with satisfied early clinical outcomes for pannus overgrowth in mechanical aortic valve. However, further randomized and long-term follow-up studies were warranted to determine the clinical effects of the simple aortic pannus removal.
Clinical application and observation of modified Ivor-Lewis surgery in Siewert type II adenocarcinoma of the Esophagogastric junction
Authors: Yin Qifan , Wang Wenhao , Liu Huining , Yang Guang , Zhou Shaohui , Liu Lijun
Published: November 2019

Background

The surgical approach (transthoracic or transabdominal) for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) still remains controversial. We made a bold attempt to adopt the modified Ivor-Lewis surgery, No turning over, thoraco-laparoscopic esophagogastrectomy, two-field lymphadenectomy and intrathoracic anastomosis, to observe the clinical application and effect.

Method

Data of patients with Siewert type II AEG were collected in the Hebei General Hospital from June 2017 to February 2019. The operation time, surgical blood loss, the number of dissected lymph nodes, duration of drainage tube, postoperative complications, the length of postoperative hospital stay were collected to assess the safety and feasibility of modified Ivor-Lewis surgery.

Results

A total of 20 patients with Siewert type II AEG were analyzed in our research, there was no case of turning to thoracotomy, laparotomy or death during the operation.The average operation time, surgical blood loss, amount of dissected lymph nodes, duration of drainage tube, postoperative hospital stay of all enrolled patients was 4.67, 0.57 h, 156, 56.80 ml, 22.55, 3.91, 8.6, 2.21 days, 12.85, 2.5 days respectively. Among all the enrolled patients, one patient(5%) developed anastomotic fistula and one patient(5%) developed hematemesis after operation, eventually, these two patients were discharged successfully.

Conclusion

For patients with Siewert type II AEG, The modified Ivor-Lewis surgery, No turning over, thoraco-laparoscopic esophagogastrectomy, two-field lymphadenectomy and intrathoracic anastomosis, is safe and feasible. The feasibility and safety could be further and better investigated with a RCT to achieve more conclusive results.
Qualitative assessment of EOB-GD-DTPA and Gd-BT-DO3A MR contrast studies in HCC patients and colorectal liver metastases
Authors: Granata Vincenza , Fusco Roberta , Maio Francesca , Avallone Antonio , Nasti Guglielmo , Palaia Raffaele , Albino Vittorio , Grassi Roberto , Izzo Francesco , Petrillo Antonella
Published: November 2019

Aim

To compare liver-specific EOB-GD-DTPA and liver-non-specific Gd-BT-DO3A MR, in hepatocellular carcinoma (HCC) and liver colorectal metastases.

Material and methods

Seventy HCC patients with 158 nodules and 90 colorectal liver metastases (mCRC) with 370 lesions were included in the retrospective analysis. HCC patients underwent MR at 0 time (MR0), after 3 (MR3) and 6 months (MR6) using two different CM; 69 mCRC patients underwent MR with Gd-EOB-BTPA and 21 mCRC patients with Gd-BT-DO3A. We evaluated arterial phase hyperenhancement, lesion-to-liver contrast during portal phase, hepatobiliary phase parenchymal hyperenhancement.

Results

In HCC patients arterial phase hyperenhancement degree was statistically higher (p = 0.03) with Gd-BT-DO3A (mean 4) than GD-EOB-DTPA (mean 2.6), while we found no significant statistical differences among mean (2.6) values at MR0 and MR6 using GD-EOB-DTPA. For all 209 patients underwent Gd-EOB-DTPA, we found that lesion-to-liver contrast during portal phase mean value was 4 while for patients underwent MR with Gd-BT-DO3A was 3 (p = 0.04). For HCC hepatobiliary phase parenchymal hyperenhancement mean value was 2.4. For mCRC patients: among 63 patients underwent previous chemotherapy hepatobiliary phase parenchymal hyperenhancement mean value was 3.1 while for 6 patients no underwent previous chemotherapy was 4 (p = 0.05).

Conclusions

Gd-EOB-DTPA should be chosen in pre surgical setting in patients with colorectal liver metastases.
Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer
Authors: Pan Yu , Lu Fengchun , Fei Qinglin , Yu Xingxing , Xiong Ping , Yu Xunbin , Dang Yuan , Hou Zelin , Lin Wenji , Lin Xianchao , Zhang Zheyang , Pan Minggui , Huang Heguang
Published: November 2019

Background

Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME.

Methods

Using immunohistochemistry, we examined tumor-infiltrating CD68+ pan-macrophages (CD68+ M) and CD163+ M2 macrophages (CD163+ M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45+ immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline.

Results

We found that CD47 expression correlated with the level of CD68+ M but not CD163+ M2. High levels of tumor-infiltrating CD68+ M, CD163+ M2, and CD47 expression were significantly associated with worse survival. CD47high/CD68+ Mhigh and CD47high/CD163+ M2high correlated significantly with shorter survival, whereas CD47low/CD68+ Mlow and CD47low/CD163+ M2low correlated with longer survival. Intriguingly, CD47 blockade decreased the tumor burden in the Panc02 but not in the MPC-83 syngeneic mouse model. Using scRNA-seq, we showed that anti-CD47 treatment significantly remodeled the intratumoral lymphocyte and macrophage compartments in Panc02 tumor-bearing mice by increasing the pro-inflammatory macrophages that exhibit anti-tumor function, while reducing the anti-inflammatory macrophages. Moreover, CD47 blockade not only increased the number of intratumoral CD8+ T cells, but also remodeled the T cell cluster toward a more activated one. Further, combination therapy targeting both CD47 and PD-L1 resulted in synergistic inhibition of PDAC growth in the MPC-83 but not in Panc02 model. MPC-83 but not Panc02 mice treated with both anti-CD47 and anti-PD-L1 showed increased number of PD-1+CD8+ T cells and enhanced expression of key immune activating genes.

Conclusion

Our data indicate that CD47 targeting induces compartmental remodeling of tumor-infiltrating immune cells of the TME in PDAC. Different PDAC mouse models exhibited differential response to the anti-CD47 and anti-PD-L1 blockade due to the differential effect of this combination treatment on the infiltrating immune cells and key immune activating genes in the TME established by the different PDAC cell lines.
Loss of SIM2s inhibits RAD51 binding and leads to unresolved replication stress
Authors: Pearson Scott J. , Elswood Jessica , Barhoumi Rola , Ming-Whitfield Brittini , Rijnkels Monique , Porter Weston W.
Published: November 2019

Background

Mutations in genes associated with homologous recombination (HR) increase an individual’s risk of developing triple-negative breast cancer (TNBC). Although known for their role in repairing dsDNA breaks, HR repair elements also stabilize and restart stalled replication forks. Essential to these functions are RAD51 and its paralogs, each of which has a unique role in preventing replication fork collapse and restart. However, progress toward understanding the regulation of these factors has been slow. With such a pivotal role in the maintenance of genomic integrity, furthering our understanding of this pathway through the discovery of new factors involved in HR is important. Recently, we showed that singleminded-2s (SIM2s) is stabilized in response to dsDNA breaks and is required for effective HR.

Methods

Initial analysis of the effect loss of SIM2s has on replication stress resolution was conducted using DNA combing assays in established breast cancer cell lines. Further analysis was conducted via immunostaining to determine the effect loss of SIM2s has on factor recruitment. In vivo confirmation was achieved through the use of a mammary epithelial cell conditional knockout mouse model before SIM2s’ role in RAD51 recruitment was determined by immunoblotting.

Results

Here, we show loss of SIM2s decreases replication fork stability, leading to fork collapse in response to genotoxic stress. Furthermore, loss of SIM2s results in aberrant separation of sister chromatids during mitosis, which has been previously shown to result in chromosomal fragmentation and aneuploidy. Interestingly, loss of SIM2s was shown to result in failure of RAD51 to localize to sites of replication stress in both breast cancer cell lines and primary mammary epithelial cells. Finally, we observed SIM2 is stabilized in response to genotoxic stress and interacts with RAD51, which is necessary for RAD51-DNA binding.

Conclusions

Together, these results show a role for SIM2s in the resolution of replication stress and further characterize the necessity of SIM2s for effective RAD51 loading in response to DNA damage or stress, ultimately promoting genomic integrity and thus preventing the accumulation of cancer-promoting mutations.
Microtubule destabilization caused by silicate via HDAC6 activation contributes to autophagic dysfunction in bone mesenchymal stem cells
Authors: Li Zheng , Liu Shuhao , Fu Tengfei , Peng Yi , Zhang Jian
Published: November 2019

Background

Silicon-modified biomaterials have been extensively studied in bone tissue engineering. In recent years, the toxicity of silicon-doped biomaterials has gradually attracted attention but requires further elucidation. This study was designed to explore whether high-dose silicate can induce a cytotoxicity effect in bone mesenchymal stem cells (BMSCs) and the role of autophagy in its cytotoxicity and mechanism.

Methods

Morphologic changes and cell viability of BMSCs were detected after different doses of silicate exposure. Autophagic proteins (LC3, p62), LC3 turnover assay, and RFP-GFP-LC3 assay were applied to detect the changes of autophagic flux following silicate treatment. Furthermore, to identify the potential mechanism of autophagic dysfunction, we tested the acetyl-α-tubulin protein level and histone deacetylase 6 (HDAC6) activity after high-dose silicate exposure as well as the changes in microtubule and autophagic activity after HDAC6 siRNA was applied.

Results

It was found that a high dose of silicate could induce a decrease in cell viability; LC3-II and p62 simultaneously increased after high-dose silicate exposure. A high concentration of silicate could induce autophagic dysfunction and cause autophagosomes to accumulate via microtubule destabilization. Results showed that acetyl-α-tubulin decreased significantly with high-dose silicate treatment, and inhibition of HDAC6 activity can restore microtubule structure and autophagic flux.

Conclusions

Microtubule destabilization caused by a high concentration of silicate via HDAC6 activation contributed to autophagic dysfunction in BMSCs, and inhibition of HDAC6 exerted a cytoprotection effect through restoration of the microtubule structure and autophagic flux.
Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients
Authors: Mousseaux Cyril , Dupont Axelle , Rafat Cédric , Ekpe Kenneth , Ghrenassia Etienne , Kerhuel Lionel , Ardisson Fanny , Mariotte Eric , Lemiale Virginie , Schlemmer Benoît , Azoulay Elie , Zafrani Lara
Published: November 2019

Background

Severe hypercalcemia (HCM) is a common reason for admission in intensive-care unit (ICU). This case series aims to describe the clinical and biological features, etiologies, treatments, and outcome associated with severe HCM. This study included all patients with a total calcemia above 12 mg/dL (3 mmol/L) admitted in two ICUs from January 2007 to February 2017.

Results

131 patients with HCM were included. HCM was related to hematologic malignancy in 58 (44.3%), solid tumors in 29 (22.1%), endocrinopathies in 16 (12.2%), and other causes in 28 (21.3%) patients. 108 (82.4%) patients fulfilled acute kidney injury (AKI) criteria. Among them, 25 (19%) patients required renal replacement therapy (RRT). 51 (38.9%) patients presented with neurological symptoms, 73 (55.7%) patients had cardiovascular manifestations, and 50 (38.1%) patients had digestive manifestations. The use of bisphosphonates (HR, 0.42; 95% CI, 0.27–0.67;P < 0.001) was the only treatment significantly associated with a decrease of total calcemia below 12 mg/dL (3 mmol/L) at day 5. ICU and Hospital mortality rates were, respectively, 9.9% and 21.3%. Simplified Acute Physiologic Score (SAPS II) (OR, 1.05; 95% CI 1.01–1.1;P = 0.03) and an underlying solid tumor (OR, 13.83; 95% CI 2.24–141.25;P = 0.01) were two independent factors associated with hospital mortality in multivariate analysis.

Conclusions

HCM is associated with high mortality rates, mainly due to underlying malignancies. The course of HCM may be complicated by organ failures which are most of the time reversible with early ICU management. Early ICU admission and prompt HCM management are crucial, especially in patients with an underlying solid tumor presenting with neurological symptoms.
Error bounds of block sparse signal recovery based on q-ratio block constrained minimal singular values
Authors: Wang Jianfeng , Zhou Zhiyong , Yu Jun
Published: November 2019

In this paper, we introduce the q-ratio block constrained minimal singular values (BCMSV) as a new measure of measurement matrix in compressive sensing of block sparse/compressive signals and present an algorithm for computing this new measure. Both the mixed ℓ2/ℓq and the mixed ℓ2/ℓ1 norms of the reconstruction errors for stable and robust recovery using block basis pursuit (BBP), the block Dantzig selector (BDS), and the group lasso in terms of the q-ratio BCMSV are investigated. We establish a sufficient condition based on the q-ratio block sparsity for the exact recovery from the noise-free BBP and developed a convex-concave procedure to solve the corresponding non-convex problem in the condition. Furthermore, we prove that for sub-Gaussian random matrices, the q-ratio BCMSV is bounded away from zero with high probability when the number of measurements is reasonably large. Numerical experiments are implemented to illustrate the theoretical results. In addition, we demonstrate that the q-ratio BCMSV-based error bounds are tighter than the block-restricted isotropic constant-based bounds.
A new mixed discontinuous Galerkin method for the electrostatic field
Authors: Zaghdani Abdelhamid , Ezzat Mohamed
Published: November 2019

We introduce and analyze a new mixed discontinuous Galerkin method for approximation of an electric field. We carry out its error analysis and prove an error estimate that is optimal in the mesh size. Some numerical results are given to confirm the theoretical convergence.
Multiple periodic orbits of high-dimensional differential delay systems
Authors: Sun Zhongmin , Ge Weigao , Li Lin
Published: November 2019

In this paper, we consider differential delay systems of the form
$$x'(t)=-\sum_{s=1}^{2k-1}(-1)^{s+1} \nabla F \bigl(x(t-s) \bigr), $$x′(t)=−∑s=12k−1(−1)s+1∇F(x(t−s)), in which the coefficients of the nonlinear terms with different hysteresis have different signs. Such systems have not been studied before. The multiplicity of the periodic orbits is related to the eigenvalues of the limit matrix. The results provide a theoretical basis for the study of differential delay systems.
Environmental variables vis-a-vis distribution of herbaceous tracheophytes on northern sub-slopes in Western Himalayan ecotone
Authors: Pandita Shevita , Kumar Vinod , Dutt Harish Chander
Published: November 2019

Background

In the northern hemisphere, the north face of the mountains has a high diversity of species which is attributed to the moist and shady conditions at the north face. Other environmental variables may also influence the species diversity on the northern faces of the mountain and therefore needs to be studied in detail. The northern slopes represent three different sub-slopes—north, north east, and north west. During the current investigation of Pir-Panjal and Dauladhar ranges in Bhadarwah valley, fine-scale studies on the relationship between vegetation and four variables (soil pH, moisture content, electrical conductivity, and steepness) were conducted. The study determined the role of these variables on the vegetation of three different sub-slopes. The sampling was done at the confluence of two communities (forest and grassland) at three sites on the northern sub-slopes of the lesser stratum in western Himalayan.

Results

The result revealed that rich herbaceous diversity prevails on the lesser Himalayan stratum (Bhadarwah valley). As many as 65.8% species differ from site to site, whereas species commonality among the sites is minimum. The role of environmental variables on the species composition at different sub-slopes of the north mountain face is deduced through canonical correspondence analysis (CCA).

Conclusions

The availability of solar light increases air and soil temperature on the north east–facing slope. All the environmental variables (soil pH, moisture, electrical conductivity, and mountain steepness) are insignificant at pure north face for the species composition. Therefore, it can be concluded that some other environmental variables may influence the species composition which are needed to be further investigated.