bluuebunny/crossref_metadata_2025 huggingface dataset:
Age estimation in three distinct east Asian population groups using southern Han Chinese dental reference dataset
Authors: Jayaraman Jayakumar , Wong Hai Ming , Roberts Graham J. , King Nigel M. , Cardoso Hugo F. V. , Velusamy Pavethynath , Vergara Ronaldo G. , Yanagita Keni-ichi , Jorns Teekayu P.
Published: November 2019

Background

Dental age estimation can assist in the identification of victims following natural disasters and it can also help to solve birth date disputes in individuals involved in criminal activities. A reference dataset (RDS) has been developed from the dental development of 2306 subjects of southern Han Chinese origin and subsequently validated. This study aimed to test the applicability of the southern Han Chinese dental maturation RDS on three distinct East Asian population groups.

Methods

A total of 953 dental panoramic radiographs of subjects aged 2 to 24 years were obtained from Philippines, Thailand and Japan. The staging of dental development was conducted according to Anglo-Canadian classification system. The dental age (DA) was calculated using six methods; one un-weighted average and five weighted average (n-tds, sd-tds, se-tds, 1/sd-tds, 1/se-tds) methods based on the scores of the southern Han Chinese RDS. Statistical significance was set at p < 0.05 and the variation between chronological age (CA) and DA was evaluated using paired t-test and Bland & Altman scatter plots.

Results

From six dental age calculations, all methods of DA accurately estimated the age of Japanese and few methods in Filipino subjects (n-tds, 1/sd-tds, 1/se-tds). There was consistent overestimation of age for all the methods for Thai females (p < 0.05).

Conclusions

The southern Han Chinese dental reference dataset was shown to be most accurate for Japanese, followed by Thai males and it was particularly ineffective for Filipinos and Thai females.
The exploration of the knowledge, attitudes and practice behaviors of advanced care planning and its related predictors among Taiwanese nurses
Authors: Hsieh Chiu-Chu , Huang Hsiang-Ping , Tung Tao-Hsin , Chen I-Chien , Beaton Randal D. , Jane Sui-Whi
Published: November 2019

Background

Despite the documented and well known patient benefits of ACP, the completion of ACP, only a minority of patients, during the advanced or EOL stage of their illnesses, receive such care. The misconceptions about ACP for healthcare providers, such as nurses, might become potential barriers to the effective implication of ACP. Also, from the transcultural perspective, it is evident essential to explore Taiwanese nurses’ attitudes, knowledge, and actions of ACP. The purposes of this study were to explore the implication of ACP or hospice care for nurses caring for non-cancer chronic illness patients at a regional teaching hospital in Taiwan; and, to identify predictors of those nurses’ knowledge, attitudes, and actions toward ACP.

Methods

This cross-sectional study with a purposive sample of 218 nurses was conducted at a teaching hospital in southern Taiwan. Structured questionnaires were employed and data were analyzed with descriptive statistics, t-test, one-way ANOVAs, Pearson’s correlation and multiple regressions.

Results

16.1% of Taiwanese physicians actively initiated ACP issues or conversations with patients or their family members. Nurses’ attitudes toward ACP were fairly positive but their knowledge about ACP was insufficient and actions of ACP were not positively executed. The predictors of ACP-Knowledge (ACP-K) included position title, education hours and lacking of educational training. The predictors of ACP-Attitude (ACP-A) included ACP-K and “fear of patient or family member not accepting”, whereas ACP-A, position title, “patients do not feel necessary” and “not sure physician’s concern” were the predictors of ACP-Act.

Conclusion

Continuous education and training for nurses regarding ACP needs to be improved by taking those predictors found in this current study into account, and more studies on the nurse’s role in ACP also should be further examined.

Trial registration

KAFGH 106–012. Date of registration 1 May 2017.
Development and internal validation of a Nomogram for preoperative prediction of surgical treatment effect on cesarean section diverticulum
Authors: Wang Yizhi , Zhu Qinyi , Lin Feikai , Xie Li , Li Jiarui , Wang Xipeng
Published: November 2019

Background

The aim of this study was to develop and validate an individualized score based on preoperative parameters to predict patient outcomes after vaginal repair of cesarean section diverticulum.

Methods

This is a retrospective cohort study (Canadian Task Force classification II-2). Patients were enrolled between Jun 11, 2012, to May 27, 2016. Multivariable logistic regression analyses were used to construct the predictive model. Then, we generated a nomogram to assess the individualized risk of poor prognosis after operation. This prediction model included information from 167 eligible patients diagnosed with cesarean section diverticulum who underwent vaginal repair. Class-A healing group was defined as CSD patients who had menstruation duration of no more than 7 days and a thickness of the remaining muscular layer of no less than 5.8 mm after vaginal repair according to conferences. Others were included in the non-class-A healing group. A final nomogram was computed using a multivariable logistic regression model.

Results

The factors contained in the individualized prediction nomogram included the depth/ the thickness of the remaining muscular layer ratio, number of menstruation days before surgery, White blood cell and fibrinogen. This model demonstrated adequate discrimination and calibration (C-index = 0.718). There was a significant difference in the number of postmenstrual spotting days (12.98 ± 3.86 VS 14.46 ± 2.86, P = 0.022) and depth/ the thickness of the remaining muscular layer ratio (2.81 ± 1.54 VS 4.00 ± 3.09, P = 0.001) between two groups. Decision curve analysis showed that this nomogram was clinically useful.

Conclusions

This cesarean section diverticulum score can predict the outcomes of cesarean section diverticulum and can be useful for counseling patients who are making treatment decisions.
Prevalence, and health- and sociodemographic associations for visits to traditional and complementary medical providers in the seventh survey of the Tromsø study
Authors: Kristoffersen Agnete E. , Broderstad Ann Ragnhild , Musial Frauke , Stub Trine
Published: November 2019

Background

Patient-centered culturally sensitive health care (PC-CSHC) has emerged as a primary approach to health care. This care focuses on the cultural diversity of the patients rather than the views of the health care professionals. PC-CSHC enables the patient to feel comfortable, respected, and trusted in the health care delivery process. As users of traditional and complementary medicine (T&CM) rarely inform their conventional health care providers of such use, the providers need to identify the users of T&CM themselves to avoid negative interaction with conventional medicine and to be able to provide them with PC-CSHC. Since the patterns of traditional medicine (TM) use are different to those of complementary medicine (CM), the aim of this study was to investigate the prevalence, and the health- and sociodemographic associations for visits to TM- and CM providers in an urban population.

Method

The data were collected through two self-administrated questionnaires from the seventh survey of the Tromsø Study, a population-based cohort study conducted in 2015–2016. All inhabitants of Tromsø aged 40 or above were invited (n = 32,591) andn = 21,083 accepted the invitation (response rate 65%). Pearson chi-square tests and one-way ANOVA tests were used to describe differences between the groups whereas binary logistic regressions were used for adjusted values.

Results

The results revealed that 2.5% of the participants had seen a TM provider, 8.5% had seen a CM provider whereas 1% had visited both a TM and a CM provider during a 12-month period. TM users tended to be older, claim that religion was more important to them, have poorer economy and health, and have lower education compared to CM users. We found that more than 90% of the participants visiting T&CM providers also used conventional medicine.

Conclusion

A considerable number of the participants in this study employed parallel health care modalities including visits to conventional, traditional, and complementary medicine providers. To offer patient-centered culturally sensitive health care that is tailored to the patients’ treatment philosophy and spiritual needs, conventional health care providers need knowledge about, and respect for their patients’ use of parallel health care systems.
Sedative and hypnotic effects of compound Anshen essential oil inhalation for insomnia
Authors: Zhong Yu , Zheng Qin , Hu Pengyi , Huang Xiaoying , Yang Ming , Ren Guilin , Du Qing , Luo Jun , Zhang Kenan , Li Jing , Wu Haixia , Guo Yuanyuan , Liu Shanshan
Published: November 2019

Backgrounds

The chemical composition of many essential oils indicates that they have sedative and hypnotic effects, but there is still a lack of systematic studies on the sedative and hypnotic effects of essential oils. In addition, aromatherapy does not seem to have the side effects of many traditional psychotropic substances, which is clearly worthwhile for further clinical and scientific research. The clinical application of essential oils in aromatherapy has received increasing attention, and detailed studies on the pharmacological activities of inhaled essential oils are increasingly needed.

Hypothesis/purpose

As insomniacs are usually accompanied by symptoms of depression and anxiety of varying degrees, based on the theory of aromatherapy of Traditional Chinese Medicine, this experiment is to study a Compound Anshen essential oil that is compatible with Lavender essential oil, Sweet Orange essential oil, Sandalwood essential oil and other aromatic medicine essential oils with sedative and hypnotic effects, anti-anxiety and anti-depression effects. To study the sedative and hypnotic effects of Compound Anshen essential oil inhaled and the main chemical components of Compound Anshen essential oil, and to compare and analyze the pharmacodynamics of diazepam, a commonly used drug for insomnia.

Methods

The Open field test and Pentobarbital-induced sleep latency and sleep time experiments were used to analyze and compare the sedative and hypnotic effects of inhaling Compound Anshen essential oil and the administration of diazepam on mice. The changes of 5-HT and GABA in mouse brain were analyzed by Elisa. The main volatile constituents of Compound Anshen essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS).

Results

Inhalation of Compound Anshen essential oil can significantly reduce the spontaneous activity of mice, reduce latency of sleeping time and prolong duration of sleeping time. The results of enzyme-linked immunosorbent assay showed that Compound Anshen essential oil can increase the content of 5-HT and GABA in mouse brain. The main volatile chemical constituents of the Compound Anshen essential oil are D-limonene (24.07%), Linalool (21.98%), Linalyl acetate (15.37%), α-Pinene (5.39%), and α-Santalol (4.8%).

Conclusion

The study found that the inhalation of Compound Anshen essential oil has sedative and hypnotic effect. This study provides a theoretical basis for further research and development of the sedative and hypnotic effects of Compound Anshen essential oil based on the theory of aromatherapy.
Studies on antidiarrheal and laxative activities of aqueous-ethanol extract of Asphodelus tenuifolius and underlying mechanisms
Authors: Aslam Naveed , Janbaz Khalid Hussain
Published: November 2019

Background

Asphodelus tenuifolius Cav. (Asphodelaceae) has traditional reputability in treatment of diarrhea and constipation but no scientific study has been reported for its gastrointestinal effects. Present study was conducted to evaluate antidiarrheal and laxative activities of the plant.

Methods

Aqueous-ethanol crude extract of Asphodelus tenuifolius (At.Cr) was subjected to phytochemical screening and liquid-liquid fractionation. In vivo studies of charcoal meal intestinal transit test, antidiarrheal activity against castor oil induced diarrhea and laxative activity were performed in mice. In vitro experiments were conducted upon rabbit jejunum preparations using standard tissue bath techniques.

Results

Phytochemical screening indicated presence of alkaloids, anthraquinones, flavonoids, saponins, steroids, tannins and phenols in At.Cr. In charcoal meal intestinal transit test, At.Cr increased (p < 0.001) intestinal motility at 100 mg/kg dose, but decreased (p < 0.001) it at 500 mg/kg dose, when compared to the control group. At.Cr (300–700 mg/kg) provided protection from castor oil induced diarrhea in mice, which was significant (p < 0.001) at 500 and 700 mg/kg doses, as compared to the saline treated control group. At.Cr (50 and 100 mg/kg) enhanced total and wet feces counts in normal mice, as compared to saline treated control. In jejunum preparations, At.Cr inhibited spontaneous, K+ (80 mM) and K+ (25 mM) mediated contractions, similar to verapamil. Pre-incubation of jejunum preparations with At.Cr resulted in rightward nonparallel shift in Ca+ 2 concentration response curves, similar to verapamil. The spasmolytic activity was concentrated in ethylacetate fraction. Aqueous fraction exhibited spasmogenicity upon spontaneous contractions, which was blocked in presence of verapamil, but remained unaffected by other tested antagonists.

Conclusion

The Asphodelus tenuifolius crude extract possesses gut modulatory activity, which may normalize gut functions in diarrhea and constipation. The spasmolytic activity of the extract was found to be mediated through Ca+ 2 channel blocking action. The spasmogenic activity, found partitioned in aqueous fraction, possibly involves Ca+ 2 influx through voltage gated Ca+ 2 channels. The study supports ethnic uses of the plant in diarrhea and constipation.
Alignment of roles of near-peer mentors for medical students underrepresented in medicine with medical education competencies: a qualitative study
Authors: Prunuske Amy , Houss BreAnna , Wirta Kosobuski Anna
Published: November 2019

Background

Medical student learning experiences should facilitate progressive development of competencies required for practice. Medical school training opportunities have traditionally focused on acquiring medical knowledge and patient care competencies while affording less opportunity to receive feedback on practice-based improvement and system-based practice competencies. The Prematriculation program at the University of Minnesota Medical School Duluth Campus (UM MSD) utilized near-peer mentors to support the transition of students underrepresented in medicine, including American Indian/ Alaska Natives (AI/AN) and those from rural backgrounds, into medical school. The purpose of this study is to better define the role of near-peer mentors and explore the alignment of near-peer mentorship with the ACGME core competencies.

Methods

An important component of the Prematriculation program, designed to prepare incoming under-represented students for medical school, was the inclusion of near-peer mentors. The six near-peer mentors participated in semi-structured interviews or focus groups within 1 year of serving as a near-peer mentor. Themes emerged from open-coding of the transcripts.

Results

The near-peer mentors drew on their own experiences to transmit information that supported the socialization of the matriculating students into medical school. Direct benefits to the mentors included solidifying their own understanding of medical knowledge and execution of procedural skills. Mentors provided examples of benefits related to their own development of interpersonal communication and professionalism skills. Operating in the context of the program provided opportunities to engage mentors in practice-based improvement and system-based practice.

Conclusions

Serving as a near-peer mentor offers significant benefits to medical students from backgrounds underrepresented in medicine. By taking on the peer mentoring leadership role, students progressed toward the competencies required of an effective physician. Given the importance of acquiring these competencies, it is worth considering how near-peer mentoring can be applied more broadly across the medical school curriculum.
Validating surgical procedure codes for inflammatory bowel disease in the Swedish National Patient Register
Authors: Forss Anders , Myrelid Pär , Olén Ola , Everhov Åsa H. , Nordenvall Caroline , Halfvarson Jonas , Ludvigsson Jonas F.
Published: November 2019

Background

About 50% of patients with Crohn’s disease (CD) and about 20% of those with ulcerative colitis (UC) undergo surgery at some point during the course of the disease. The diagnostic validity of the Swedish National Patient Register (NPR) has previously been shown to be high for inflammatory bowel disease (IBD), but there are little data on the validity of IBD-related surgical procedure codes.

Methods

Using patient chart data as the gold standard, surgical procedure codes registered between 1966 and 2014 in the NPR were abstracted and validated in 262 randomly selected patients with a medical diagnosis of IBD. Of these, 53 patients had reliable data about IBD-related surgery. The positive predictive value (PPV), sensitivity and specificity of the surgical procedure codes were calculated.

Results

In total, 158 surgical procedure codes were registered in the NPR. One hundred fifty-five of these, representing 60 different procedure codes, were also present in the patient charts and validated using a standardized form. Of the validated codes 153/155 were concordant with the patient charts, corresponding to a PPV of 96.8% (95%CI = 93.9–99.1). Stratified in abdominal, perianal and other surgery, the corresponding PPVs were 94.1% (95%CI = 88.7–98.6), 100% (95%CI = 100–100) and 98.1% (95%CI = 93.1–100), respectively. Of 164 surgical procedure codes in the validated patient charts, 155 were registered in the NPR, corresponding to a sensitivity of the surgical procedure codes of 94.5% (95%CI = 89.6–99.3). The specificity of the NPR was 98.5% (95%CI = 97.6–100).

Conclusions

Data on IBD-related surgical procedure codes are reliable, with the Swedish National Patient Register showing a high sensitivity and specificity for such surgery.
Do choosing wisely recommendations about low-value care target income-generating treatments provided by members? A content analysis of 1293 recommendations
Authors: Zadro Joshua R. , Farey John , Harris Ian A. , Maher Christopher G.
Published: November 2019

Background

It is unknown to what extent Choosing Wisely recommendations about income-generating treatments apply to members of the society generating the recommendations.

The primary aim of this study is to determine the proportion of Choosing Wisely recommendations targeting income-generating treatments, and whether recommendations from professional societies on income-generating treatments are more likely to target members or non-members. The secondary aim is to determine the prevalence of qualified statements, and whether qualified statements are more likely to appear in recommendations targeting income-generating or non-income-generating treatments that apply to members.

Methods

We performed a content analysis of all Choosing Wisely recommendations, with data extracted from Choosing Wisely websites. Two researchers coded recommendations as test or treatment-based, for or against a procedure, containing qualified statements, income-generating and applying to members. Disagreements were resolved by discussion or consultation with a third researcher. A Chi-squared test evaluated whether society recommendations on income-generating treatments were more likely to target members or non-members; and whether qualified statements were more likely to appear in recommendations targeting income-generating or non-income-generating treatments that apply to members.

Results

We found 1293 Choosing Wisely recommendations (48.3% tests and 48.6% treatments). Ninety-eight treatment recommendations targeted income-generating treatments (17.8%), and recommendations on income-generating treatments were less likely to target members compared to non-members (15.6% vs. 40.4%,p < 0.001). Nearly half of all recommendations were qualified (41.9%), with a similar proportion of recommendations targeting income-generating and non-income-generating treatments that apply to members containing qualified statements (49.4% vs. 42.0%,p = 0.23).

Conclusions

Many societies provide Choosing Wisely recommendations that minimise impact on their own members. Only 20% of treatment recommendations target income-generating treatments, and of these recommendations mostly target non-members. Many recommendations are also qualified. Increasing the number of recommendations from societies that are unqualified and target member clinicians responsible for de-implementation of low-value and costly treatments should be a priority.
The Discharge Communication Study: research protocol for a mixed methods study to investigate and triangulate discharge communication experiences of patients, GPs, and hospital professionals, alongside a corresponding discharge letter sample
Authors: Weetman Katharine , Dale Jeremy , Scott Emma , Schnurr Stephanie
Published: November 2019

Background

Discharge letters are crucial during care transitions from hospital to home. Research indicates a need for improvement to increase quality of care and decrease adverse outcomes. These letters are often sent from the hospital discharging physician to the referring clinician, typically the patient’s General Practitioner (GP) in the UK, and patients may or may not be copied into them. Relatively little is known about the barriers and enablers to sending patients discharge letters. Hence, the aim of this study was to investigate from GP, hospital professional (HP) and patient perspectives how to improve processes of patients receiving letters and increase quality of discharge letters. The study has a particular focus on the impacts of receiving or not receiving letters on patient experiences and quality of care.

Methods

The setting was a region in the West Midlands of England, UK. The research aimed to recruit a minimum of 30 GPs, 30 patients and 30 HPs in order to capture 90 experiences of discharge communication. Participating GPs initially screened and selected a range of recent discharge letters which they assessed to be successful and unsuccessful exemplars. These letters identified potential participants who were invited to take part: the HP letter writer, GP recipient and patient. Participant viewpoints are collected through interviews, focus groups and surveys and will be “matched” to the discharge letter sample, so forming multiple-perspective “quartet” cases. These “quartets” allow direct comparisons between different discharge experiences within the same communicative event. The methods for analysis draw on techniques from the fields of Applied Linguistics and Health Sciences, including: corpus linguistics; inferential statistics; content analysis.

Discussion

This mixed-methods study is novel in attempting to triangulate views of patients, GPs and HPs in relation to specific discharge letters. Patient and practitioner involvement will inform design decisions and interpretation of findings. Recommendations for improving discharge letters and the process of patients receiving letters will be made, with the intention of informing guidelines on discharge communication. Ethics approval was granted in July 2017 by the UK Health Research Authority. Findings will be disseminated in peer-reviewed journals, reports and newsletters, and presentations.
Synthetic high-density lipoprotein nanoparticles for the treatment of Niemann–Pick diseases
Authors: Schultz Mark L. , Fawaz Maria V. , Azaria Ruth D. , Hollon Todd C. , Liu Elaine A. , Kunkel Thaddeus J. , Halseth Troy A. , Krus Kelsey L. , Ming Ran , Morin Emily E. , McLoughlin Hayley S. , Bushart David D. , Paulson Henry L. , Shakkottai Vikram G. , Orringer Daniel A. , Schwendeman Anna S. , Lieberman Andrew P.
Published: November 2019

Background

Niemann–Pick disease type C is a fatal and progressive neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in late endosomes and lysosomes. We sought to develop new therapeutics for this disorder by harnessing the body’s endogenous cholesterol scavenging particle, high-density lipoprotein (HDL).

Methods

Here we design, optimize, and define the mechanism of action of synthetic HDL (sHDL) nanoparticles.

Results

We demonstrate a dose-dependent rescue of cholesterol storage that is sensitive to sHDL lipid and peptide composition, enabling the identification of compounds with a range of therapeutic potency. Peripheral administration of sHDL toNpc1 I1061Thomozygous mice mobilizes cholesterol, reduces serum bilirubin, reduces liver macrophage size, and corrects body weight deficits. Additionally, a single intraventricular injection into adultNpc1 I1061Tbrains significantly reduces cholesterol storage in Purkinje neurons. Since endogenous HDL is also a carrier of sphingomyelin, we tested the same sHDL formulation in the sphingomyelin storage disease Niemann–Pick type A. Utilizing stimulated Raman scattering microscopy to detect endogenous unlabeled lipids, we show significant rescue of Niemann–Pick type A lipid storage.

Conclusions

Together, our data establish that sHDL nanoparticles are a potential new therapeutic avenue for Niemann–Pick diseases.
Comparative evaluation of two commercial ELISA kits for detection of antibodies against Akabane virus in cattle serum
Authors: Li Xiaolin , Jing Hongli , Liu Xiaofei , Wang Qin , Qiu Songyin , Liu Dandan , Wu Shaoqiang , Lin Xiangmei
Published: November 2019

Background

Akabane disease (AD), a barrier to international trade for endemic areas with far economic impact on the countries, is caused by Akabane virus (AKAV). Commercial enzyme-linked immunosorbent assay (ELISA) is a commonly used diagnostic technique for AKAV infection, including the IDEXX and IDVET ELISA kits. However, the comparative evaluation of the IDEXX and IDVET ELISA kits has not been published. The object of this study was to evaluate the test performance of the two commercial ELISA kits in detecting serum anti-AKAV antibodies in cattle.

Results

With virus neutralization test (VNT) as the “relative gold standard”, the diagnostic sensitivity (DSe) was 80.39% (123/153) and 93.46% (143/153) for the IDEXX and IDVET ELISA kit, when suspect samples were included. The diagnostic specificity (DSp) for the IDEXX and IDVET ELISA kit was 93.48% (502/537) and 82.31% (442/537), respectively.

Conclusion

Both of the tested ELISA kits could be applied to detect antibodies against AKAV in cattle serum. The IDVET ELISA kit had a higher DSe. The IDEXX ELISA kit possessed the higher DSp. These results have important implications if the kits are used to screen herds or individual cattle in surveillance programs, or at border crossings for import-export inspection and quarantine.
Accurate detection of KRAS, NRAS and BRAF mutations in metastatic colorectal cancers by bridged nucleic acid-clamp real-time PCR
Authors: Nagakubo Yuki , Hirotsu Yosuke , Amemiya Kenji , Oyama Toshio , Mochizuki Hitoshi , Omata Masao
Published: November 2019

Background

Patients with metastatic colorectal cancer can benefit from anti-EGFR therapy, such as cetuximab and panitumumab. However, colorectal cancers harboring constitutive activating mutations in KRAS, NRAS and BRAF genes are not responsive to anti-EGFR therapy. To select patients for appropriate treatment, genetic testing of these three genes is routinely performed.

Methods

We applied bridged nucleic acid-clamp real-time PCR (BNA-clamp PCR) to detect somatic hotspot mutations in KRAS, NRAS and BRAF. PCR products from BNA-clamp PCR were subsequently analyzed Sanger sequencing. We then compared results with those from the PCR–reverse sequence-specific oligonucleotide probe (PCR-rSSO) method, which has been used as in vitro diagnostic test in Japan. To validate the mutation status, we also performed next generation sequencing using all samples.

Results

In 50 formalin-fixed paraffin-embedded tissues, KRAS mutations were detected at frequencies of 50% (25/50) and 52% (26/50) by PCR-rSSO and BNA-clamp PCR with Sanger sequencing, respectively, and NRAS mutations were detected at 12% (6/50) and 12% (6/50) by PCR-rSSO and BNA-clamp PCR with Sanger sequencing, respectively. The concordance rate for detection of KRAS and NRAS mutations between the two was 94% (47/50). However, there were three discordant results. We validated these three discordant and 47 concordant results by next generation sequencing. All mutations identified by BNA-clamp PCR with Sanger sequencing were also identified by next generation sequencing. BNA-clamp PCR detected BRAF mutations in 6% (3/50) of tumor samples.

Conclusions

Our results indicate that BNA-clamp PCR with Sanger sequencing detects somatic mutations in KRAS, NRAS and BRAF with high accuracy.
The economic burden of malaria on households and the health system in a high transmission district of Mozambique
Authors: Alonso Sergi , Chaccour Carlos J. , Elobolobo Eldo , Nacima Amilcar , Candrinho Baltazar , Saifodine Abuchahama , Saute Francisco , Robertson Molly , Zulliger Rose
Published: November 2019

Background

Malaria remains a leading cause of morbidity and mortality in Mozambique. Increased investments in malaria control have reduced the burden, but few studies have estimated the costs of malaria in the country. This paper estimates the economic costs associated with malaria care to households and to the health system in the high burden district of Mopeia in central Mozambique.

Methods

Malaria care-seeking and morbidity costs were routinely collected among 1373 households with at least one child enrolled in an active case detection (ACD) cohort in Mopeia, and through cross-sectional surveys with 824 families in 2017 and 805 families in 2018. Household costs included direct medical expenses, transportation and opportunity costs of the time lost due to illness. Structured questionnaires were used to estimate the health system costs associated with malaria care in all 13 district health facilities. Cost estimations followed an ingredient-based approach with a top-down allocation approach for health system expenses.

Results

Among participants in cross-sectional studies, households sought care for nine severe malaria cases requiring hospital admission and for 679 uncomplicated malaria cases. Median household costs associated with uncomplicated malaria among individuals of all ages were US$ 3.46 (IQR US$ 0.07–22.41) and US$ 81.08 (IQR US$ 39.34–88.38) per severe case. Median household costs were lower among children under five (ACD cohort): US$ 1.63 (IQR US$ 0.00–7.79) per uncomplicated case and US$ 64.90 (IQR US$ 49.76–80.96) per severe case. Opportunity costs were the main source of household costs. Median health system costs associated with malaria among patients of all ages were US$ 4.34 (IQR US$ 4.32–4.35) per uncomplicated case and US$ 26.56 (IQR US$ 18.03–44.09) per severe case. Considering household and health system costs, the overall cost of malaria care to society was US$ 7.80 per uncomplicated case and US$ 107.64 per severe case, representing an economic malaria burden of US$ 332,286.24 (IQR US$ 186,355.84–1,091,212.90) per year only in Mopeia.

Conclusions

Despite the provision of free malaria services, households in Mopeia incur significant direct and indirect costs associated with the disease. Furthermore, the high malaria cost on the Mozambican health system underscores the need to strengthen malaria prevention to reduce the high burden and improve productivity in the region.
Adherence to the pro-inflammatory diet in relation to prevalence of irritable bowel syndrome
Authors: Salari-Moghaddam Asma , Keshteli Ammar Hassanzadeh , Esmaillzadeh Ahmad , Adibi Peyman
Published: November 2019

Objective

There is no prior study that examined the association between nutrient-based dietary inflammatory index (DII) and odds of Irritable Bowel Syndrome (IBS). We examined the association between DII score and odds of IBS and its severity among Iranian adults.

Methods

In this cross-sectional study, dietary intakes of 3363 Iranian adults were examined using a validated Dish-based 106-item Semi-quantitative Food Frequency Questionnaire (DS-FFQ). DII was calculated based on dietary intakes derived from DS-FFQ. IBS was assessed using a modified Persian version of Rome III questionnaire.

Results

After adjustment for potential confounders, we found that participants in the highest quintile of DII score had greater chance for IBS compared with those in the lowest quintile (OR: 1.36; 95% CI: 1.03–1.80). By gender, we found a significant association between DII score and IBS among women (OR: 1.41; 95% CI: 1.00–2.00). By BMI status, overweight or obese (BMI ≥ 25 kg/m2) individuals in top quintile of DII score had greater odds for IBS than those in the bottom quintile (OR: 1.64; 95% CI: 1.07–2.53). No significant association was observed between a pro-inflammatory diet and severity of IBS symptoms.

Conclusions

Consumption of a pro-inflammatory diet was associated with increased odds of IBS, in particular among women and those with BMI ≥ 25 kg/m2.
Evaluating adherence to recommended diets in adults 1991–2015: revised China dietary guidelines index
Authors: Huang Feifei , Wang Zhihong , Wang Liusen , Wang Huijun , Zhang Jiguo , Du Wenwen , Su Chang , Jia Xiaofang , Ouyang Yifei , Wang Yun , Li Li , Jiang Hongru , Zhang Bing
Published: November 2019

Background

The China Dietary Guidelines Index (CDGI) is a diet quality evaluation index that can present the overall diet quality and is comparable between individuals. The aim of this study was to revise CDGI for Chinese adults according to the Chinese Dietary Guidelines 2016 (CDG-2016), evaluate adherence to recommended diets between 1991 and 2015, and analyze the trend, variation, and determinants of diet quality.

Methods

Food, cooking oil, and condiment intakes were estimated based on twenty-four-hour dietary recalls over three consecutive days and the household weighing method. Based on the food and nutrients recommendations for people with different energy requirements in CDG-2016, CDGI was revised as China Dietary Guidelines Index (2019)-Adults (CDGI(2019)-A) by equal weight continuity scoring. Three-level random intercept-slope growth models were applied to analyze the trend, variation, and determinants at both the community and individual levels.

Results

CDGI(2019)-A, the sum of fourteen component scores with a range of 0–110 points, increased significantly from 38.2 in 1991 to 47.3 in 2015. Components with a score of less than half were milk (91.6%), fruits (72.0%), nuts (82.5%), other cereals and beans (82.6%), and seafood (77.7%). Between-individual accounted for 25.6% of the total score variation, of which 87.4% derived from the community level. CDGI(2019)-A score displayed a positive association with being female, having higher education, having higher income, living in an urban area, and knowing the CDG-2016 recommendations. The impact of income and awareness of CDG-2016 varied significantly across communities.

Conclusions

Although quality of diet has been improving in China, overall quality remains poor, primarily because of inadequate intake of milk and dairy products, nuts, fruits, other cereals and miscellaneous beans, and seafood. Intervention at the community level may improve diet quality more efficiently than at the individual level, and the most effective intervention should be selected in different communities according to local conditions.
Role of hypoxia in cancer therapy by regulating the tumor microenvironment
Authors: Jing Xinming , Yang Fengming , Shao Chuchu , Wei Ke , Xie Mengyan , Shen Hua , Shu Yongqian
Published: November 2019

Aim

Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy.

Methods

Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms.

Results

Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux.

Conclusion

Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.
Multilayered stable 2D nano-sheets of Ti2NTx MXene: synthesis, characterization, and anticancer activity
Authors: Szuplewska A. , Rozmysłowska-Wojciechowska A. , Poźniak S. , Wojciechowski T. , Birowska M. , Popielski M. , Chudy M. , Ziemkowska W. , Chlubny L. , Moszczyńska D. , Olszyna A. , Majewski J. A. , Jastrzębska A. M.
Published: November 2019

Background

The biological activity of MXenes has been studied for several years because of their potential biomedical applications; however, investigations have so far been limited to 2D titanium carbides. Although monolayered Ti2NTx MXene has been expected to have biological activity, experimental studies revealed significant difficulties due to obstacles to its synthesis, its low stability and its susceptibility to oxidation and decomposition.

Results

In this paper, we report our theoretical calculations showing the higher likelihood of forming multilayered Ti2NTx structures during the preparation process in comparison to single-layered structures. As a result of our experimental work, we successfully synthesized multilayered Ti2NTx MXene that was suitable for biological studies by the etching of the Ti2AlN MAX phase and further delamination. The biocompatibility of Ti2NTx MXene was evaluated in vitro towards human skin malignant melanoma cells, human immortalized keratinocytes, human breast cancer cells, and normal human mammary epithelial cells. Additionally, the potential mode of action of 2D Ti2NTx was investigated using reactive oxygen tests as well as SEM observations. Our results indicated that multilayered 2D sheets of Ti2NTx showed higher toxicity towards cancerous cell lines in comparison to normal ones. The decrease in cell viabilities was dose-dependent. The generation of reactive oxygen species as well as the internalization of the 2D sheets play a decisive role in the mechanisms of toxicity.

Conclusions

We have shown that 2D Ti2NTx in the form of multilayered nanoflakes exhibits fair stability and can be used for in vitro studies. These results show promise for its future applications in biotechnology and nanomedicine.
Non-doctoral factors influencing the surgical choice of Chinese patients with breast cancer who were eligible for breast-conserving surgery
Authors: Chen Rui , You Sainan , Yin Zinan , Zhu Qiannan , Jiang Chaojun , Li Shuo , Li Yan , Zha Xiaoming , Wang Jue
Published: November 2019

Background

The rate of breast-conserving surgery (BCS) is low in China. Many patients choose mastectomy even when informed that there is no difference in the overall survival rate compared with that of BCS plus radiotherapy. This study aimed to investigate the factors that influenced the surgical choice in patients eligible for BCS.

Methods

Female patients with breast carcinoma were enrolled in a single center from March 2016 to January 2017. They made their own decision regarding the surgical approach. Univariate analysis was employed to determine the factors associated with the different breast surgical approaches. Significant factors (defined as P < 0.05) were then incorporated into multivariate logistic regression models to determine the factors that independently influenced patients’ decision.

Results

Of the 271 patients included, 149 were eligible for BCS; 65 chose BCS and 84 chose mastectomy. On the basis of univariate analysis, patients with younger age, higher income and education, shorter admission to surgery interval, and shorter confirmed diagnosis to surgery interval were more likely to choose BCS than mastectomy (P < 0.05). Meanwhile, patients who resided in rural regions, did not have general medicare insurance, and were diagnosed with breast cancer preoperatively were more inclined to choose mastectomy than BCS (P < 0.05). The multivariate model revealed three independent influencing factors: age at diagnosis (P = 0.009), insurance status (P = 0.035), and confirmed diagnosis to surgery interval (P = 0.037). In addition, patients receiving neoadjuvant chemotherapy (NCT) were more inclined to choose mastectomy.

Conclusion

Surgical choice of patients eligible for BCS was affected by several factors, and age at diagnosis, confirmed diagnosis to surgery interval, and insurance status were independent factors.
Laparoscopic surgery for colorectal cancer with persistent descending mesocolon
Authors: Hiyoshi Yukiharu , Miyamoto Yuji , Eto Kojiro , Nagai Yohei , Iwatsuki Masaaki , Iwagami Shiro , Baba Yoshifumi , Yoshida Naoya , Baba Hideo
Published: November 2019

Background

Persistent descending mesocolon (PDM) is caused by the absence of fusion of the descending colon to the retroperitoneum. We herein report two colorectal cancer cases with PDM that were treated with laparoscopic surgery.

Case presentation

Case 1: a 50-year-old man with sigmoid colon cancer and synchronous liver metastasis. After neoadjuvant chemotherapy, he underwent laparoscopic sigmoidectomy with lymph node dissection cutting the root of the inferior mesenteric artery (IMA) and synchronous liver resection. He experienced postoperative stenosis of the reconstructed colon possibly due to an impaired arterial blood flow in the reconstructed colon.

Case 2: a 77-year-old man with rectal cancer. Laparoscopic low anterior resection preserving the left colic artery (LCA) was performed. Intraoperative infrared ray (IR) imaging using indocyanine green (ICG) showed good blood flow of the reconstructed colon. He had no postoperative complications. In cases of PDM, the mesentery of the descending and sigmoid colon containing the LCA is often shortened, and the marginal artery of the reconstructed colon is located close to the root of the LCA. Lymph node dissection accompanied by cutting the LCA carries a risk of marginal artery injury. Therefore, we recommend lymph node dissection preserving the LCA in colorectal cancer patients with PDM in order to maintain the blood flow of the reconstructed colon. If the IMA and LCA absolutely need to be cut for complete lymph node dissection, the marginal artery should be clearly identified and preserved. In addition, intraoperative IR imaging is extremely useful for evaluating colonic perfusion and reducing the risk of anastomotic complications.

Conclusion

In colorectal cancer surgery in patients with PDM, surgeons should be aware of these tips for maintaining the blood flow of the reconstructed colon and thereby avoid postoperative complications caused by an impaired blood flow.
Circulating PCSK9 and cardiovascular events in FH patients with standard lipid-lowering therapy
Authors: Cao Ye-Xuan , Jin Jing-Lu , Sun Di , Liu Hui-Hui , Guo Yuan-Lin , Wu Na-Qiong , Xu Rui-Xia , Zhu Cheng-Gang , Dong Qian , Sun Jing , Li Jian-Jun
Published: November 2019

Background

Proprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy.

Methods

A total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score ≥ 6) was enrolled and followed up for the occurrence of MACEs. Multidetector CT and coronary angiography were performed to determine coronary artery calcification score (CACS) and Gensini score (GS). Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma PCSK9 concentrations were determined by enzyme immunoassay.

Results

PCSK9 was independently and positively associated CACS and GS at baseline. During a mean follow-up of 3 years, 33 (9.8%) events occurred. Patients with MACEs had higher median PCSK9 compared with those without (332.47 vs. 311.89 ng/mL, p = 0.038). Kaplan–Meier analysis revealed that patients with higher PCSK9 presented lower event-free survival (p = 0.0017). PCSK9 was statistically correlated with MACEs after adjusting for confounding factors, with the HR per SD being 1.86 (1.31–2.65) and 3.70 (1.16–11.82) for the highest tertile compared with the lowest tertile. Adding PCSK9 to Cox prediction model led to a statistical improvement in net reclassification and integrated discrimination.

Conclusion

Elevated levels of PCSK9 were positively associated with the development of CAD and future cardiovascular events, suggesting that measurement of PCSK9 concentration might be useful for cardiovascular risk stratification. Further studies are needed to confirm our results.
Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage
Authors: Ahn Sung-Ho , Savarraj Jude P. J. , Parsha Kaushik , Hergenroeder Georgene W. , Chang Tiffany R. , Kim Dong H. , Kitagawa Ryan S. , Blackburn Spiros L. , Choi H. Alex
Published: November 2019

Background

Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions.

Methods

Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (< 24 h, 24–48 h, 3–5 days, and 6–8 days after SAH) and concentration levels of 41 cytokines were measured by multiplex immunoassay. Logistic regression analysis was used to identify cytokines associated with DCI and poor functional outcomes. Correlation networks were constructed to identify cytokine clusters.

Results

Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes.

Conclusions

Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.