bluuebunny/crossref_metadata_2025 huggingface dataset:
Summer Temperature and All-cause Mortality from 2006 to 2015 for Smart City Jaipur, India
Authors: Rathi Suresh K. , Sodani P. R. , Joshi Suresh
Published: May 2021

A considerable association between temperature and all-cause mortality has been documented in various studies. Further insights can be obtained from studying the impact of temperature and heat index (HI) for Jaipur city’s all-cause mortality. The objective of this work was to assess the association between the extreme heat (daily maximum temperature, daily minimum temperature, daily mean temperature, relative humidity and HI) and all-cause mortality for summer months (March to June) from 2006 to 2015 for urban population of Jaipur. For summer months, we collected the data on various temperature and all-cause mortality parameters for at least 10 years. The student’s t-test and ANOVA were used to analyse variations in mean temperature, maximum temperature and HI. The Pearson correlation coefficient was used to study the relationship between ambient heat and lag time effect all-cause mortality. A total of 75,571 deaths (all-cause mortality) for 1,203 summer days (2006–2015) were analysed in relation to temperature and relative humidity. The mean daily all-cause mortality has been estimated at 62.8 ± 15.2 for the study period. There is a significant increase of 39% per day all-cause mortality at the maximum temperature of 45 °C and above. However only 10% rise per day all-cause mortality for extreme danger days (HI > 54 °C). The mean daily all-cause mortality shows a significant association with daily maximum temperature ( F = 34.6, P < .0001) and HI (discomfort index) from caution to extreme danger risk days ( F = 5.0, P < .0019). The lag effect of extreme heat on all-cause mortality for the study period (2006 to 2015) was at a peak period on the same day of the maximum temperature ( r = 0.245 at P < .01) but continues up to four days. The study concludes that the effect of ambient heat on all-cause mortality increase is clearly evident (rise of 39% deaths/day). Accordingly, focus should be put on developing adaptation measures against ambient heat. This analysis may satisfy policy makers’ needs. Extreme heat-related mortality needs further study to reduce adverse effects on health among Jaipur’s urban population.
The Influence of Adverse Childhood Experiences (ACEs) on the Functional Impairment of Justice-Involved Adolescents: A Comparison of Baseline to Follow-Up Reports of Adversity
Authors: Duron Jacquelynn F. , Williams-Butler Abigail , Liu Feng-Yi Y. , Nesi Danielle , Fay Kathleen Pirozzolo , Kim Bo-Kyung Elizabeth
Published: May 2021

Adverse childhood experiences (ACEs) have long been recognized for negatively influencing individual outcomes such that each additional ACE exposure increases the risk for negative health and behavioral outcomes. Little is known, however, about how the more recent accumulation of ACEs occurring in follow-up periods influence global functioning considering the past accumulation of ACEs reported at baseline by justice-involved adolescents. Participants were 851 adolescents who completed the Northwestern Juvenile Project (NJP), a longitudinal survey. OLS regression models were used to examine the influence of follow-up and baseline ACEs on the functional impairment of youth. Results indicate that both follow-up and baseline ACEs were associated with worse functioning over time with baseline ACEs demonstrating a greater effect. This study highlights the importance of assessing accumulations of ACEs over time for adolescents in the juvenile justice system and considering how youth of different characteristics and experiences may differently encounter functional impairment. Implications for offering trauma-informed services to disrupt the effects of adversity on adolescents’ functioning are discussed.
Engaging target users to appraise and refine clinical practice guidelines in pediatric concussion: An integrated knowledge translation approach
Authors: Paniccia Melissa , Provvidenza Christine , Kingsnorth Shauna , Ippolito Christina , Zemek Roger , Reed Nick
Published: May 2021

Background

Clinical practice guidelines are systematically developed statements that assist clinicians in making evidence informed decisions regarding patient care. Within pediatric concussion, the Ontario Neurotrauma Foundation released the Guidelines for Diagnosing and Managing Pediatric Concussion in 2014. The purpose of this study was to evaluate the 2014 guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) evaluation tool, in addition to a brief knowledge translation survey, and to utilize the collected feedback from end users to inform improvements to support an updated version. An integrated knowledge translation approach was employed using clinical experts as guideline appraisers.

Methods

A purposive sample of researchers, physicians, allied health professionals, policy makers, educators and knowledge translation experts involved in updating the guidelines (N = 31) completed the AGREE II Likert scale survey regarding the 2014 guideline, and provided written justifications for their ratings. Domain and item AGREE II scaled scores were reported stratified by demographic factors, and written justifications were synthesized using content analysis to determine areas of improvement for the 2014 guideline.

Results

Appraisers scored the editorial independence (88.9%) and scope and purpose (80.8%) domains the highest, indicating high quality. The guidelines scored the lowest in the applicability domain (69.3%). Participants with less than 10 years of experience in their respective disciplines, as well as physicians and allied health professionals consistently provided higher ratings across domains compared to other professions.

Conclusions

The process of evaluating the 2014 guideline resulted in these important outcomes: (1) identified areas of the guideline that may have affected the lack of previous clinical uptake while abiding by a clinical practice guideline development framework; (2) shared and informed decision making regarding content and format of the revised clinical practice guideline; and (3) targeted content, clinical questions and dissemination strategies, which are key to clinical uptake.
Validation of a QTL for Grain Size and Weight Using an Introgression Line from a Cross between Oryza sativa and Oryza minuta
Authors: Feng Yue , Yuan Xiaoping , Wang Yiping , Yang Yaolong , Zhang Mengchen , Yu Hanyong , Xu Qun , Wang Shan , Niu Xiaojun , Wei Xinghua
Published: May 2021

Background

Grain size and weight are important target traits determining grain yield and quality in rice. Wild rice species possess substantial elite genes that can be served as an important resource for genetic improvement of rice. In this study, we identify and validate a novel QTL on chromosome 7 affecting the grain size and weight using introgression lines from cross ofOryza sativaandOryza minuta.

Results

An introgression line ‘IL188’ has been achieved from a wild speciesOryza minuta(2n = 48, BBCC, W303) intoO. sativa japonicaNipponbare. The F2and F2:3populations derived from a cross between IL188 and Nipponbare were used to map QTLs for five grain size traits, including grain length (GL), grain width (GW), grain length to width ratio (LWR), grain thickness (GT) and thousand grain weight (TGW). A total of 12 QTLs for the five grain traits were identified on chromosomes 1, 2, 3, 6, 7, and 8. The QTL-qGL7controlling GL on chromosome 7 was detected stably in the F2and F2:3populations, and explained 15.09–16.30% of the phenotypic variance. To validate the effect ofqGL7, eight residual heterozygous line (RHL) populations were developed through selfing four F2:3and four F2:4plants with different heterozygous segments for the target region. By further developing SSR and Indel markers in the target interval,qGL7was delimited to a ~ 261 kb region between Indel marker Y7–12 and SSR marker Y7–38, which also showed significant effects on grain width and thousand grain weight. Comparing with the reference genome of Nipponbare, stop or frameshift mutations in the exon of the three putative genesLOC_Os07g36830,LOC_Os07g36900andLOC_Os07g36910encoding F-box domain-containing proteins may be the candidate genes forqGL7. Scanning electron microscopy analysis of the glume’s epidermal cells showed that the cell length and width of NIL-qGL7IL188was higher than NIL-qGL7Nip, indicating thatqGL7increases grain size and weight by regulating cell expansion.

Conclusions

In this study, we detected 12 QTLs regulating grain size and weight using an introgression line from a cross betweenOryza sativaandOryza minuta. Of these loci, we confirmed and delimited theqGL7to a ~ 261 kb region. Three putative genes,LOC_Os07g36830,LOC_Os07g36900andLOC_Os07g36910encoding F-box domain-containing proteins may be the candidate genes forqGL7. These results provide a basis for map-based cloning of theqGL7gene and useful information for marker assisted selection in rice grain quality improvement.
The health-related quality of life in Iranian patients with COVID-19
Authors: Alinia Cyrus , Yaghmaei Safura , Abdullah Farman Zahir , Ahmadi Asad , Samadi Nasrin , Pourteimour Sima , Safari Hossein , Mahmoodi Hassan , Moradi Ghobad , Piroozi Bakhtiar
Published: May 2021

Background

COVID-19 is a public health emergency with a high mortality rate and it reduces the patient’s Health-Related Quality of Life (HRQoL) significantly. This effect is measured in the current study.

Methods

In a cross-sectional study in Iran, 320 randomly selected treated patients from COVID-19 were studied. To collect the required data, we applied a questionnaire that included socio-demographic factors, clinical characteristics, and questions on the patients’ HRQoL. Time trade-off (TTO) approach was used to measure the lost HRQoL attributed to COVID-19. Besides, we applied a two-limit Tobit regression model to determine the effects of the socio-demographic factors on patients’ health utility and the visual analogue scale approach was used to estimate the perceived total current health status.

Results

The overall mean (SE) and median (IQR) of the health utility values were 0.863 (0.01) and 0.909 (0.21) respectively. These values for the traders (those who were willing to lose a part of their remaining time of life to avoid the disease) were estimated at 0.793 (0.01) and 0.848 (0.17), respectively. The lowest amount of utility value belonged to the elderly (mean (SE) = 0.742 (0.04); median (IQR) = 0.765 (0.42)) and those living in rural areas (mean (SE)) = 0.804 (0.03); median (IQR) = 0.877 (0.30)). The univariate analysis showed that age, place of residence, and household size had a statistically significant effect on health utility. Moreover, findings of the regression analysis indicated that the participants’ age and hospitalization status were the key determinants of COVID-19 health utility value.

Conclusion

COVID-19 is associated with a substantial and measurable decrease in HRQoL. This decline in HRQoL can be directly compared with that induced by systemic health states.
Inter-hospital and inter-disciplinary variation in planned birth practices and readiness for change: a survey study
Authors: Coates Dominiek , Donnolley Natasha , Foureur Maralyn , Henry Amanda
Published: May 2021

Background

How the application of evidence to planned birth practices, induction of labour (IOL) and prelabour caesarean (CS), differs between Australian maternity units remains poorly understood. Perceptions of readiness for practice change and resources to implement change in individual units are also unclear.

Aim

To identify inter-hospital and inter-professional variations in relation to current planned birth practices and readiness for change, reported by clinicians in 7 maternity units.

Method

Custom-created survey of maternity staff at 7 Sydney hospitals, with questions about women’s engagement with decision making, indications for planned birth, timing of birth and readiness for change. Responses from midwives and medical staff, and from each hospital, were compared.

Findings

Of 245 completed surveys (27% response rate), 78% were midwives and 22% medical staff. Substantial inter-hospital variation was noted for stated planned birth indication, timing, women’s involvement in decision-making practices, as well as in staff perceptions of their unit’s readiness for change. Overall, 48% (range 31–64%) and 64% (range 39–89%) agreed on a need to change their unit’s caesarean and induction practices respectively. The three units where greatest need for change was perceived also had least readiness for change in terms of leadership, culture, and resources. Regarding inter-disciplinary variation, medical staff were more likely than midwifery staff to believe women were appropriately informed and less likely to believe unit practice change was required.

Conclusion

Planned birth practices and change readiness varied between participating hospitals and professional groups. Hospitals with greatest perceived need for change perceived least resources to implement such change.
Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review
Authors: Maghsoomi Zohreh , Emami Zahra , Malboosbaf Ramin , Malek Mojtaba , Khamseh Mohammad E.
Published: May 2021

Background

It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC.

Methods

For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews.

Results

Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively.

Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported.

Conclusion

Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events.

Trial registration

PROSPERO registration number: CRD42019125245.
Socioeconomic inequalities in lifestyle risk factors across low- and middle-income countries
Authors: Dieteren Charlotte , Bonfrer Igna
Published: May 2021

Background

The heavy and ever rising burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) warrants interventions to reduce their underlying risk factors, which are often linked to lifestyles. To effectively supplement nationwide policies with targeted interventions, it is important to know how these risk factors are distributed across socioeconomic segments of populations in LMICs. This study quantifies the prevalence and socioeconomic inequalities in lifestyle risk factors in LMICs, to identify policy priorities conducive to the Sustainable Development Goal of a one third reduction in deaths from NCDs by 2030.

Methods

Data from 1,278,624 adult respondents to Demographic & Health Surveys across 22 LMICs between 2013 and 2018 are used to estimate crude prevalence rates and socioeconomic inequalities in tobacco use, overweight, harmful alcohol use and the clustering of these three in a household. Inequalities are measured by a concentration index and correlated with the percentage of GDP spent on health. We estimate a multilevel model to examine associations of individual characteristics with the different lifestyle risk factors.

Results

The prevalence of tobacco use among men ranges from 59.6% (Armenia) to 6.6% (Nigeria). The highest level of overweight among women is 83.7% (Egypt) while this is less than 12% in Burundi, Chad and Timor-Leste. 82.5% of women in Burundi report that their partner is “often or sometimes drunk” compared to 1.3% in Gambia. Tobacco use is concentrated among the poor, except for the low share of men smoking in Nigeria. Overweight, however, is concentrated among the better off, especially in Tanzania and Zimbabwe (Erreygers Index (EI) 0.227 and 0.232). Harmful alcohol use is more concentrated among the better off in Nigeria (EI 0.127), while Chad, Rwanda and Togo show an unequal pro-poor distribution (EI respectively − 0.147, − 0.210, − 0.266). Cambodia exhibits the largest socioeconomic inequality in unhealthy household behaviour (EI − 0.253). The multilevel analyses confirm that in LMICs, tobacco and alcohol use are largely concentrated among the poor, while overweight is concentrated among the better-off. The associations between the share of GDP spent on health and the socioeconomical distribution of lifestyle factors are multidirectional.

Conclusions

This study emphasizes the importance of lifestyle risk factors in LMICs and the socioeconomic variation therein. Given the different socioeconomic patterns in lifestyle risk factors - overweight patters in LMICs differ considerably from those in high income countries- tailored interventions towards specific high-risk populations are warranted to supplement nationwide policies.
Maternal tobacco exposure and health-related quality of life during pregnancy: a national-based study of pregnant women in China
Authors: Sun Weiwei , Huang Xinyu , Wu Huailiang , Zhang Casper J. P. , Yin Zongzhi , Fan Qianqian , Wang Huiyun , Jayavanth Pallavi , Akinwunmi Babatunde , Wu Yanxin , Wang Zilian , Ming Wai-kit
Published: May 2021

Background

With the increase of the number of smokers, tobacco exposure among pregnant women is becoming more and more common. Pregnant women exposed to first-hand smoke and second-hand smoke are susceptible to physiological and psychological health issues has been proved in previous studies. Nevertheless, there are no enough studies focus on the impact of third-hand smoke during pregnancy. This study aimed to assess and compare health-related quality of life for pregnant women with exposure to first-hand smoke, second-hand smoke, third-hand smoke and non-exposure to tobacco in mainland China.

Methods

National-based cross-sectional study is based on a questionnaire survey which collects information including demographics, smoking behaviors and self-evaluation. All questionnaires were delivered and collected from August to September 2019. EuroQol group’s visual analog scale and EuroQoL Five-dimension Questionnaire were used to collect data in mainland China.

Results

Totally, 15,682 pregnant women were included in this study, among which non-exposure to smoke were 7564 (48.2%), exposed to first-hand smoke, second-hand smoke and third-hand smoke were 89 (0.6%), 2349 (15.0%), and 5680 (36.2%) respectively. Pregnant women without tobacco exposure had the highest EuroQol group’s visual analog scale score (mean value = 85.4[SD = 14.0]), while those with first-hand smoke had the lowest score (mean value = 77.4[SD = 22.2]). Among all five dimensions of EuroQoL Five-dimension Questionnaire, there were significant differences of EQ-index among groups with different tobacco exposure in usual activity and anxiety or depression dimensions (p < 0.001).

Conclusions

Third-hand smoke exposure had close relationship with low health-related quality of life in pregnant women. Moreover, second-hand smoke exposure significantly led more problems on mental dimension of pregnant women.
Interactions among mTORC, AMPK and SIRT: a computational model for cell energy balance and metabolism
Authors: Sadria Mehrshad , Layton Anita T.
Published: May 2021

Background

Cells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of perturbations. In tissues a deficit of these mechanisms is commonly associated with cellular aging and diseases, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as being able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell. In particular, mTOR, AMPK, and sirtuins are known to play an essential role in the management of metabolic stress and energy balance in mammals.

Methods

To understand the complex interactions of these signalling pathways and environmental signals, and how those interactions may impact lifespan and health-span, we have developed a computational model of metabolic signalling pathways. Specifically, the model includes (i) the insulin/IGF-1 pathway, which couples energy and nutrient abundance to the execution of cell growth and division, (ii) mTORC1 and the amino acid sensors such as sestrin, (iii) the Preiss-Handler and salvage pathways, which regulate the metabolism of NAD+ and the NAD+ -consuming factor SIRT1, (iv) the energy sensor AMPK, and (v) transcription factors FOXO and PGC-1α.

Results

The model simulates the interactions among key regulators such as AKT, mTORC1, AMPK, NAD+ , and SIRT, and predicts their dynamics. Key findings include the clinically important role of PRAS40 and diet in mTORC1 inhibition, and a potential link between SIRT1-activating compounds and premature autophagy. Moreover, the model captures the exquisite interactions of leucine, sestrin2, and arginine, and the resulting signal to the mTORC1 pathway. These results can be leveraged in the development of novel treatment of cancers and other diseases.

Conclusions

This study presents a state-of-the-art computational model for investigating the interactions among signaling pathways and environmental stimuli in growth, ageing, metabolism, and diseases. The model can be used as an essential component to simulate gene manipulation, therapies (e.g., rapamycin and wortmannin), calorie restrictions, and chronic stress, and assess their functional implications on longevity and ageing‐related diseases.
Mitochondrial DNA leakage induces odontoblast inflammation via the cGAS-STING pathway
Authors: Zhou Lu , Zhang Yi-Fei , Yang Fu-Hua , Mao Han-Qing , Chen Zhi , Zhang Lu
Published: May 2021

Background

Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts.

Methods

The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured.

Results

The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown.

Conclusion

Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis.

Graphic abstract
Comparison of short-term outcomes between direct anterior approach (DAA) and SuperPATH in total hip replacement: a systematic review and network meta-analysis of randomized controlled trials
Authors: Ramadanov Nikolai , Bueschges Simon , Liu Kuiliang , Lazaru Philip , Marintschev Ivan
Published: May 2021

Background

Two minimally invasive approaches showed some advantages in outcomes compared to conventional approaches (CAs)—the direct anterior approach (DAA) and the supercapsular percutaneously assisted approach in THA (SuperPATH). To the best of our knowledge, DAA and SuperPATH have never been compared, neither in clinical studies, nor in a meta-analysis. To conduct a systematic review and network meta-analysis of randomized controlled trials comparing short-term outcomes of DAA and SuperPATH in total hip joint arthroplasty (THA).

Methods

A systematic literature search up to May 2020 was performed to identify randomized controlled trials (RCTs) comparing SuperPATH with CAs and DAA with CAs in THA. We measured surgical, functional, and radiological outcomes. A network meta-analysis, using frequentist methods, was performed to assess treatment effects between DAA and SuperPATH. Information was borrowed from the above-mentioned RCTs, using the CA group as a common comparator.

Results

A total of 16 RCTs involving 1392 patients met the inclusion criteria, three trials with a level I evidence, 13 trials with a level II evidence. The overall network meta-analysis showed that SuperPATH reduced operation time (fixed effect model: MD = 12.8, 95% CI 9.9 to 15.7), incision length (fixed effect model: MD = 4.3, 95% CI 4.0 to 4.5; random effect model: MD = 4.3, 95% CI 0.2 to 8.4), intraoperative blood loss (fixed effect model: MD = 58.6, 95% CI 40.4 to 76.8), and early pain intensity (VAS 1 day postoperatively with a fixed effect model: MD = 0.8, 95% CI 0.4 to 1.2). The two approaches did not differ in acetabular cup positioning angles and in functional outcome.

Conclusions

Our overall findings suggested that the short-term outcomes of THA through SuperPATH were superior to DAA. SuperPATH showed better results in decreasing operation time, incision length, intraoperative blood loss, and early pain intensity. DAA and SuperPATH were equal in functional outcome and acetabular cup positioning.
Attenuated serum vasoactive intestinal peptide concentrations are correlated with disease severity of non-traumatic osteonecrosis of femoral head
Authors: Liu Ming , Zhao Gan , Wei Biao-Fang
Published: May 2021

Background and objective

The neuropeptide vasoactive intestinal peptide is a 28-amino acid neuropeptide that has been shown to stimulate bone repair and angiogenesis. The purpose of this study was to explore the potential role of serum VIP concentration in osteonecrosis of femoral trauma (ONFH).

Methods

One hundred five patients diagnosed with non-traumatic ONFH and 103 healthy individuals were enrolled in our study. Serum VIP, tumor necrosis factor-α (TNF-α), interluekin-1 beta (IL-1β), and macrophage colony-stimulating factor (M-CSF) levels also were detected using the commercial ELISA kit. Radiographic progression was evaluated using FICAT classification. The clinical severity of ONFH was assessed by visual analog score (VAS) and Harris Hip Score (HHS). Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of VIP in radiographic progression.

Results

The serum VIP level of patients with non-traumatic ONFH was significantly lower than that of healthy controls. There was no significant difference between the alcohol group, the steroid-induction group, and the idiopathic group. Serum VIP levels were significantly higher in ONFH patients with femoral head pre-collapse stage than collapse stage. Serum VIP levels were significantly lower. FICAT 4 non-traumatic ONFH patients had significantly lower serum concentrations of VIP when compared with FICAT 3 and FICAT 2. Moreover, serum VIP levels were significantly lower in ONFH patients with FICAT 3 than FICAT 2. Serum VIP levels were negatively related to FICAT stage. In addition, serum VIP levels were negatively associated with VAS score and positively associated with HHS score. Last, we found serum VIP levels were negatively associated with serum TNF-α and IL-1β levels. ROC curve analysis indicated that decreased serum VIP could serve as a decent biomarker with regard to the diagnosis of radiographic progression.

Conclusion

Attenuated serum VIP concentrations are correlated with disease severity of non-traumatic ONFH. Decreased serum VIP may serve as a potential indicator of non-traumatic ONFH.
Cyclin-dependent kinase 9 (CDK9) predicts recurrence in Middle Eastern epithelial ovarian cancer
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Masoodi Tariq , Annaiyappanaidu Padmanaban , Al-Badawi Ismail A. , Al-Dayel Fouad , Al-Kuraya Khawla S.
Published: May 2021

Background

Cyclin-dependent kinase 9 (CDK9) has been shown to play an important role in tumorigenesis of several malignancies. However, the expression of CDK9 in ovarian cancer from Middle Eastern ethnicity remains unknown.

Methods

A tissue microarray of 441 epithelial ovarian cancer (EOC) samples was used to study the expression of CDK9 immunohistochemically and their clinico-pathological associations were determined. Cox proportional hazards regression model was used for univariate and multivariate analysis of recurrence-free survival.

Results

CDK9 over-expression was noted in 56.2 % (248/441) of EOCs and was associated with adverse clinico-pathological parameters such as distant metastasis (p < 0.0001), stage IV tumors (p < 0.0001), tumor recurrence (p = 0.0105) and high Ki-67 index (p < 0.0001). Importantly, CDK9 over-expression was an independent predictor of poor recurrence-free survival (Hazard ratio = 1.51; 95 % confidence interval = 1.15–1.98;p = 0.0030). We also found that CDK9 outperforms Ki-67 as a predictor of tumor recurrence in EOC.

Conclusions

Our results show that CDK9 expression correlates with markers of advanced disease in Middle Eastern EOC and is also a prognostic marker. CDK9 overexpression also identifies a subset of patients with highest likelihood of recurrence across the patient cohort. These patients may benefit from additional alternative therapies targeting CKD9.
Outcomes of vitrectomy for retinal detachment in a patient with Ehlers–Danlos syndrome type IV: a case report
Authors: Lumi Xhevat , Bergant Gaber , Lumi Anila , Mahnic Mina
Published: May 2021

Background

The Ehlers–Danlos syndrome (EDS) is a group of connective tissue disorders characterized by fragile blood vessels and an increased tendency for bleeding and scarring. Here, we report the outcome of a pars plana vitrectomy for the treatment of rhegmatogenous retinal detachment in a patient with EDS type IV (vascular type).

Case presentation

A 40-year-old Slovenian man with high myopia, unilateral bullous retinal detachment, and vitreous hemorrhage was referred for surgery. The patient had a history of colon perforation, muscle and arterial rupture in both lower limbs, and recurrent shoulder joint luxations. Genetic testing revealed a pathogenic mutation in the COL3A1 gene. The patient underwent a 25-gauge three-port pars plana vitrectomy. The tendency for bleeding during surgery was prevented by endodiathermy applied to the edges of the retinal breaks. Endolaser photocoagulation was performed under air. The surgical procedure was completed with the injection of gas tamponade, followed by the patient remaining for a few days in a face-down position. Mild postoperative vitreous hemorrhage was resorbed in first week after the surgery. Postoperative extensive pigment dispersion on the posterior lens face persisted for several weeks. After the gas tamponade had resorbed, the retina was flat and remained attached during the follow-up period. Eight months after the surgery, visual acuity continued to improve from a preoperative 6/38 to 6/6.6 (Snellen chart) at the last checkup.

Conclusion

A small-gauge pars plana vitrectomy with gas tamponade and laser photocoagulation under air may successfully achieve reattachment of the retina in patients with high myopia with EDS type IV and restore visual acuity.
Lipid and lipoprotein predictors of functional outcomes and long-term mortality after surgical sepsis
Authors: Guirgis Faheem W. , Leeuwenburgh Christiaan , Moldawer Lyle , Ghita Gabriela , Black Lauren Page , Henson Morgan , DeVos Elizabeth , Holden David , Efron Phil , Reddy Srinivasa T. , Moore Frederick A.
Published: May 2021

Rationale

Sepsis is a life-threatening, dysregulated response to infection. Lipid biomarkers including cholesterol are dynamically regulated during sepsis and predict short-term outcomes. In this study, we investigated the predictive ability of lipid biomarkers for physical function and long-term mortality after sepsis.

Methods

Prospective cohort study of sepsis patients admitted to a surgical intensive-care unit (ICU) within 24 h of sepsis bundle initiation. Samples were obtained at enrollment for lipid biomarkers. Multivariate regression models determined independent risk factors predictive of poor performance status (Zubrod score of 3/4/5) or survival at 1-year follow-up.

Measurements and main results

The study included 104 patients with surgical sepsis. Enrollment total cholesterol and high-density lipoprotein (HDL-C) levels were lower, and myeloperoxidase (MPO) levels were higher for patients with poor performance status at 1 year. A similar trend was seen in comparisons based on 1-year mortality, with HDL-C and ApoA-I levels being lower and MPO levels being higher in non-survivors. However, multivariable logistic regression only identified baseline Zubrod and initial SOFA score as significant independent predictors of poor performance status at 1 year. Multivariable Cox regression modeling for 1-year survival identified high Charlson comorbidity score, low ApoA-I levels, and longer vasopressor duration as predictors of mortality over 1-year post-sepsis.

Conclusions

In this surgical sepsis study, lipoproteins were not found to predict poor performance status at 1 year. ApoA-I levels, Charlson comorbidity scores, and duration of vasopressor use predicted 1 year survival. These data implicate cholesterol and lipoproteins as contributors to the underlying pathobiology of sepsis.
“Real-world” radiomics from multi-vendor MRI: an original retrospective study on the prediction of nodal status and disease survival in breast cancer, as an exemplar to promote discussion of the wider issues
Authors: Doran Simon J. , Kumar Santosh , Orton Matthew , d’Arcy James , Kwaks Fenna , O’Flynn Elizabeth , Ahmed Zaki , Downey Kate , Dowsett Mitch , Turner Nicholas , Messiou Christina , Koh Dow-Mu
Published: May 2021

Background

Most MRI radiomics studies to date, even multi-centre ones, have used “pure” datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in “real-world” scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice.

Methods

One hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests.

Results

Prediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9–51.8% (radiomic features from different combinations of image contrasts), and 26.7–35.6% (clinical plus radiomics features).

Conclusions

Radiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results.
Parameterization of physical properties of layered body structure into equivalent circuit model
Authors: Lee Jiho , Park Sung-Min
Published: May 2021

Background

This study presents a novel technique to develop an equivalent circuit model (ECM) for analyzing the responses of the layered body structure to transcutaneous electrical nerve stimulation (TENS) by parameterizing electrical and geometrical properties.Many classical ECMs are non-parametric because of the difficulty in projecting intrapersonal variability in the physical properties into ECM. However, not considering the intrapersonal variability hampers patient-specifically analyzing the body response to TENS and personal optimization of TENS parameter design. To overcome this limitation, we propose a tissue property-based (TPB) approach for the direct parameterization of the physical properties in the layered body structure and thus enable to quantify the effects of intrapersonal variability.

Results

The proposed method was first validated through in vitro phantom studies and then was applied in-vivo to analyze the TENS on the forearm. The TPB-ECM calculated the impedance network in the forearm and corresponding responses to TENS. In addition, the modelled impedance was in good agreement with well-known impedance properties that have been achieved empirically.

Conclusions

The TPB approach uses the parameterized circuit components compared to non-parametric conventional ECMs, thus overcoming the intrapersonal variability problem of the conventional ECMs. Therefore, the TPB-ECM has a potential for widely-applicable TENS analysis and could provide impactful guidance in the TENS parameter design.
Nasal airflow of patient with septal deviation and allergy rhinitis
Authors: Lim Zi Fen , Rajendran Parvathy , Musa Muhamad Yusri , Lee Chih Fang
Published: May 2021

A numerical simulation of a patient’s nasal airflow was developed via computational fluid dynamics. Accordingly, computerized tomography scans of a patient with septal deviation and allergic rhinitis were obtained. The three-dimensional (3D) nasal model was designed using InVesalius 3.0, which was then imported to (computer aided 3D interactive application) CATIA V5 for modification, and finally to analysis system (ANSYS) flow oriented logistics upgrade for enterprise networks (FLUENT) to obtain the numerical solution. The velocity contours of the cross-sectional area were analyzed on four main surfaces: the vestibule, nasal valve, middle turbinate, and nasopharynx. The pressure and velocity characteristics were assessed at both laminar and turbulent mass flow rates for both the standardized and the patient’s model nasal cavity. The developed model of the patient is approximately half the size of the standardized model; hence, its velocity was approximately two times more than that of the standardized model.
Cervical and ocular vestibular evoked myogenic potentials in epileptic patients
Authors: Kabel Abd El Mageed Hassan , Afifi Khaled Hatem , ElFakhrany Samar Mohammed , Moaty Asmaa Salah
Published: May 2021

Background

Vertigo and dizziness are very common complaints that may be related to epilepsy. The purpose of this study was to assess vestibulo-spinal and linear vestibulo-ocular function in epileptic patients in the inter ictal period. The current observational study was carried out in audio-vestibular unit Menoufia University. Subjects in the current study were divided into two groups: The control group included 30 normal individuals not complaining from any dizzy symptoms and the epileptic cases group included 30 epileptic patients. All subjects in the study were submitted to cervical and ocular vestibular evoked myogenic potential.

Results

There was no significant difference between the control and epileptic group regarding the age and sex distribution. Sixty-seven percent of epileptic cases had dizzy symptoms. There was statistically significant difference in the latency and amplitude of c and o VEMP between the control and the epileptic group, 39/60 ears (65%) in the study group had cVEMP abnormalities, 32/60 ears (53%) had oVEMP abnormalities. Abnormal c and o VEMP were reported in 28/60 ears (46.7%). There was statistically significant relationship between VEMP abnormalities and duration of seizures, frequency of epileptic attacks, and type of therapy.

Conclusion

Vestibular abnormalities were frequently reported in epileptic patients in the current study which may be related to the severity and control of epilepsy.
Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples
Authors: Pin Carmen , Collins Teresa , Gibbs Megan , Kimko Holly
Published: May 2021

Quantitative Systems Toxicology (QST) models, recapitulating pharmacokinetics and mechanism of action together with the organic response at multiple levels of biological organization, can provide predictions on the magnitude of injury and recovery dynamics to support study design and decision-making during drug development. Here, we highlight the application of QST models to predict toxicities of cancer treatments, such as cytopenia(s) and gastrointestinal adverse effects, where narrow therapeutic indexes need to be actively managed. The importance of bifurcation analysis is demonstrated in QST models of hematologic toxicity to understand how different regions of the parameter space generate different behaviors following cancer treatment, which results in asymptotically stable predictions, yet highly irregular for specific schedules, or oscillating predictions of blood cell levels. In addition, an agent-based model of the intestinal crypt was used to simulate how the spatial location of the injury within the crypt affects the villus disruption severity. We discuss the value of QST modeling approaches to support drug development and how they align with technological advances impacting trial design including patient selection, dose/regimen selection, and ultimately patient safety.
Blast waves in a paraxial fluid of light
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Authors: Abuzarli M. , Bienaimé T. , Giacobino E. , Bramati A. , Glorieux Q.
Published: May 2021

We study experimentally blast wave dynamics on a weakly interacting fluid of light. The fluid density and velocity are measured in 1D and 2D geometries. Using a state equation arising from the analogy between optical propagation in the paraxial approximation and the hydrodynamic Euler's equation, we access the fluid hydrostatic and dynamic pressure. In the 2D configuration, we observe a negative differential hydrostatic pressure after the fast expansion of a localized over-density, which is a typical signature of a blast wave for compressible gases. Our experimental results are compared to the Friedlander waveform hydrodynamical model (Friedlander F. G., Proc. R. Soc. A: Math. Phys. Sci., 186 (1946) 322). Velocity measurements are presented in 1D and 2D configurations and compared to the local speed of sound, to identify the supersonic region of the fluid. Our findings show an unprecedented control over hydrodynamic quantities in a paraxial fluid of light.
Observation of Dirac-like surface state bands on the top surface of BiSe
Authors: Lohani H. , Majhi K. , Ganesan R. , Gonzalez S. , Di Santo G. , Petaccia L. , Anil Kumar P. S. , Sekhar B. R.
Published: May 2021

Weak topological insulators (TIs) host non-trivial topological surface state bands (SSBs) at the side surface of the crystal while the top (001) surface can be topologically either dark or light. In our detailed angle-resolved photoelectron spectroscopy (ARPES) study we found Dirac-like linearly dispersive SSBs on the (001) surface of BiSe and Sb-doped (8%) BiSe. The lower part of the SSBs buries deep in the bulk valence band (BVB) and the overlap region between the SSBs and BVB increases significantly with Sb doping. These results highlight the role of the interlayer coupling between the Bi bilayer and the Bi2Se3 quintuple layer (QL). Furthermore, in the overlap region the SSBs deviate from the Dirac-like linear dispersion. Interestingly, we observed a large intensity imbalance

) in the SSBs located at the positive and negative

directions. This asymmetry pattern

) gradually reverses to

) as the excitation energy scans from low (14 eV) to high (34 eV) values. The observed photon energy-dependent intensity variation could be a signature of the mixing between the spin and the orbit texture of the SSBs.