bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung regeneration: implications of the diseased niche and ageing
Authors: Melo-Narváez M. Camila , Stegmayr John , Wagner Darcy E. , Lehmann Mareike
Published: October 2020

Most chronic and acute lung diseases have no cure, leaving lung transplantation as the only option. Recent work has improved our understanding of the endogenous regenerative capacity of the lung and has helped identification of different progenitor cell populations, as well as exploration into inducing endogenous regeneration through pharmaceutical or biological therapies. Additionally, alternative approaches that aim at replacing lung progenitor cells and their progeny through cell therapy, or whole lung tissue through bioengineering approaches, have gained increasing attention. Although impressive progress has been made, efforts at regenerating functional lung tissue are still ineffective. Chronic and acute lung diseases are most prevalent in the elderly and alterations in progenitor cells with ageing, along with an increased inflammatory milieu, present major roadblocks for regeneration. Multiple cellular mechanisms, such as cellular senescence and mitochondrial dysfunction, are aberrantly regulated in the aged and diseased lung, which impairs regeneration. Existing as well as new humanin vitromodels are being developed, improved and adapted in order to study potential mechanisms of lung regeneration in different contexts. This review summarises recent advances in understanding endogenous as well as exogenous regeneration and the development ofin vitromodels for studying regenerative mechanisms.
The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent
Authors: Lechasseur Ariane , Morissette Mathieu C.
Published: October 2020

Vaping has become increasingly popular over the past decade. This pragmatic review presents the published biological effects of electronic cigarette vapour inhalation with a focus on the pulmonary effects. Special attention has been devoted to providing the documented effects specific to each major ingredient, namely propylene glycol/glycerol, nicotine and flavouring agents. For each ingredient, findings are divided according to the methodology used, being in vitro studies, animal studies and clinical studies. Finally, we provide thoughts and insights on the current state of understanding of the pulmonary effects of vaping, as well as novel research avenues and methodologies.
Azithromycin for sarcoidosis cough: an open-label exploratory clinical trial
Authors: Fraser Simon D. , Thackray-Nocera Susannah , Shepherd Marica , Flockton Rachel , Wright Caroline , Sheedy Wayne , Brindle Kayleigh , Morice Alyn H. , Kaye Paul M. , Crooks Michael G. , Hart Simon P.
Published: October 2020

Background

Chronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis and self-reported cough.

Methods

We conducted a noncontrolled, open-label clinical trial of azithromycin 250 mg once daily for 3 months in patients with pulmonary sarcoidosis who reported a chronic cough. The primary outcome was number of coughs in 24 h. Secondary outcomes were cough visual analogue scales and quality of life measured using the Leicester Cough Questionnaire and King's Sarcoidosis Questionnaire. Safety outcomes included QTc interval on ECG. Measurements were made at baseline and after 1 and 3 months of treatment.

Results

All 21 patients were white, median age 57 years, 9 males, 12 females, median 3 years since diagnosis. Four were taking oral corticosteroids and none were taking other immunosuppressants. Twenty patients completed the trial. The median (range) number of coughs in 24 h was 228 (43–1950) at baseline, 122 (20–704) at 1 month, and 81 (16–414) at 3 months (p=0.002, Friedman's test). The median reduction in cough count at 3 months was 49.6%. There were improvements in all patient-reported outcomes. Azithromycin was well tolerated.

Conclusion

In a noncontrolled open-label trial in people with sarcoidosis who reported a chronic cough, 3 months of treatment with azithromycin led to improvements in a range of cough metrics. Azithromycin should be tested as a treatment for sarcoidosis cough in a randomised placebo-controlled trial.
Diagnosing COVID-19 pneumonia in a pandemic setting: Lung UltrasoundversusCT (LUVCT) – a multicentre, prospective, observational study
Authors: Lieveld Arthur W.E. , Kok Bram , Schuit Frederik H. , Azijli Kaoutar , Heijmans Jarom , van Laarhoven Arjan , Assman Natascha L. , Kootte Ruud S. , Olgers Tycho J. , Nanayakkara Prabath W.B. , Bosch Frank H.
Published: October 2020

Background

In this coronavirus disease 2019 (COVID-19) pandemic, fast and accurate testing is needed to profile patients at the emergency department (ED) and efficiently allocate resources. Chest imaging has been considered in COVID-19 workup, but evidence on lung ultrasound (LUS) is sparse. We therefore aimed to assess and compare the diagnostic accuracy of LUS and computed tomography (CT) in suspected COVID-19 patients.

Methods

This multicentre, prospective, observational study included adult patients with suspected COVID-19 referred to internal medicine at the ED. We calculated diagnostic accuracy measures for LUS and CT using both PCR and multidisciplinary team (MDT) diagnosis as reference. We also assessed agreement between LUS and CT, and between sonographers.

Results

One hundred and eighty-seven patients were recruited between March 19 and May 4, 2020. Area under the receiver operating characteristic (AUROC) was 0.81 (95% CI 0.75–0.88) for LUS and 0.89 (95% CI 0.84–0.94) for CT. Sensitivity and specificity for LUS were 91.9% (95% CI 84.0–96.7) and 71.0% (95% CI 61.1–79.6), respectively,versus88.4% (95% CI 79.7–94.3) and 82.0% (95% CI 73.1–89.0) for CT. Negative likelihood ratio was 0.1 (95% CI 0.06–0.24) for LUS and 0.14 (95% CI 0.08–0.3) for CT. No patient with a false negative LUS required supplemental oxygen or admission. LUS specificity increased to 80% (95% CI 69.9–87.9) compared to MDT diagnosis, with an AUROC of 0.85 (95% CI 0.79–0.91). Agreement between LUS and CT was 0.65. Interobserver agreement for LUS was good: 0.89 (95% CI 0.83–0.93).

Conclusion

LUS and CT have comparable diagnostic accuracy for COVID-19 pneumonia. LUS can safely exclude clinically relevant COVID-19 pneumonia and may aid COVID-19 diagnosis in high prevalence situations.
A foundation for reference models for drug combinations with an application to Loewe’s reference model
Authors: De Mulder Wim , Kuiper Martin
Published: October 2020

Background

Treating patients with combinations of drugs that have synergistic effects has become widespread practice in the clinic. Drugs work synergistically when the observed effect of a drug combination is larger than the effect predicted by the reference model. The reference model is a theoretical null model that returns the combined effect of given doses of drugs under the assumption that these drugs do not interact. There is ongoing debate on what it means for drugs to not interact. The controversy transcends mathematical punctuality, as different non-interaction principles result in different reference models. A famous reference model that has been in existence for already a long time is Loewe’s reference model. Loewe’s vision on non-interaction was purely intuitive: two drugs do not interact if all combinations of doses that result in a certain given effect lie on a straight line.

Results

We show that Loewe’s reference model can be obtained from much more fundamental principles. First, we introduce the new notion of complementary dose. Secondly, we reformulate the existing concept of equivalent dose, whereby our formulation is more general than existing ones. Finally, a very general non-interaction principle is put forward. The proposed non-interaction principle represents a certain interplay between complementary and equivalent doses: drugs are non-interacting if complementarity is preserved under equivalence. It is then shown that Loewe’s reference model naturally follows from these principles by an appropriate choice of complementarity.

Conclusions

The presented work increases insight into Loewe’s reference model for drug combinations, which is realized by the introduction of a very general non-interaction principle that does not refer to any specific dose-response curve, nor to any property of applicable dose-response curves.
Identification of fruit size associated quantitative trait loci featuring SLAF based high-density linkage map of goji berry (Lycium spp.)
Authors: Rehman Fazal , Gong Haiguang , Li Zhong , Zeng Shaohua , Yang Tianshun , Ai Peiyan , Pan Lizhu , Huang Hongwen , Wang Ying
Published: October 2020

Background

Goji (Lycium spp., 2n = 24) is a fruit bearing woody plant popular as a superfood for extensive medicinal and nutritional advantages. Fruit size associated attributes are important for evaluating small-fruited goji berry and plant architecture. The domestication traits are regulated quantitatively in crop plants but few studies have attempted on genomic regions corresponding to fruit traits.

Results

In this study, we established high-resolution map using specific locus amplified fragment (SLAF) sequencing for de novo SNPs detection based on 305 F1 individuals derived from L. chinense and L. barbarum and performed quantitative trait loci (QTL) analysis of fruit size related traits in goji berry. The genetic map contained 3495 SLAF markers on 12 LGs, spanning 1649.03 cM with 0.47 cM average interval. Female and male parents and F1 individuals` sequencing depth was 111.85-fold and 168.72-fold and 35.80-fold, respectively. The phenotype data were collected for 2 successive years (2018–2019); however, two-year mean data were combined in an extra year (1819). Total 117 QTLs were detected corresponding to multiple traits, of which 78 QTLs in 2 individual years and 36 QTLs in extra year. Six Promising QTLs (qFW10–6.1, qFL10–2.1, qLL10–2.1, qLD10–2.1, qLD12–4.1, qLA10–2.1) were discovered influencing fruit weight, fruit length and leaf related attributes covering an interval ranged from 27.32–71.59 cM on LG10 with peak LOD of 10.48 and 14.6% PVE. Three QTLs targeting fruit sweetness (qFS3–1, qFS5–2) and fruit firmness (qFF10–1) were also identified. Strikingly, various traits QTLs were overlapped on LG10, in particular, qFL10–2.1 was co-located with qLL10–2.1, qLD10–2.1 and qLA10–2.1 among stable QTLs, harbored tightly linked markers, while qLL10–1 was one major QTL with 14.21 highest LOD and 19.3% variance. As LG10 harbored important traits QTLs, we might speculate that it could be hotspot region regulating fruit size and plant architectures.

Conclusions

This report highlights the extremely saturated linkage map using SLAF-seq and novel loci contributing fruit size-related attributes in goji berry. Our results will shed light on domestication traits and further strengthen molecular and genetic underpinnings of goji berry; moreover, these findings would better facilitate to assemble the reference genome, determining potential candidate genes and marker-assisted breeding.
The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study
Authors: Chung Goh Eun , Shin Eunsoon , Kwak Min-Sun , In Yang Jong , Lee Jong-Eun , Choe Eun Kyung , Yim Jeong Yoon
Published: October 2020

Background

Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD.

Methods

We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes.

Results

The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531).

Conclusions

This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.
Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa
Authors: Sloot Rosa , Shanaube Kwame , Claassens Mareli , Telisinghe Lily , Schaap Ab , Godfrey-Faussett Peter , Ayles Helen , Floyd Sian
Published: October 2020

Background

A more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study.

Methods

We used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006–2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers’ definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, ‘def1’) were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, ‘def2’; IFN-g < 0.2 to ≥1.05 IU/ml, ‘def3’; IFN-g < 0.2 to ≥1.4 IU/ml, ‘def4’). Poisson regression was used for analysis.

Results

One thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9–32.6) using def1, 19.0 using def2 (CI:15.2–23.7), 14.7 using def3 (CI:11.5–18.8), and 12.0 using def4 (CI:9.2–15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4–0.9), in analysis including both countries. The same direction of associations were found using def 2–4.

Conclusion

High conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity.
Dimensions of women’s empowerment on access to skilled delivery services in Nepal
Authors: Khatiwada Januka , Muzembo Basilua Andre , Wada Koji , Ikeda Shunya
Published: October 2020

Background

Each day, approximately 810 women die during pregnancy and childbirth and 94% of the deaths take place in low and middle income countries. Only 45% of the births in South Asia are attended by skilled professionals, which is lower than that in other Asian regions. Antenatal and postnatal care received from skilled providers can help prevent maternal and neonatal mortality by identifying pregnancy-related complications. Women’s empowerment is considered to be a significant determinant of maternal health care outcomes; however, studies on the contextual influences of different dimensions of empowerment in Nepal are relatively limited. Therefore, this study analyzed nationwide survey data to examine the influence of women’s economic empowerment, sociocultural empowerment, familial/interpersonal empowerment and media and information technology empowerment on accessing skilled delivery services among the married women in Nepal.

Methods

This study examined the influence of women’s empowerment on skilled delivery services among married women (n = 4400) aged 15–49 years using data from the 2016 Nepal Demographic and Health Survey. Descriptive analysis and binary logistic regression analysis were employed to analyze the data.

Results

Significant associations were found between women’s media and information technology empowerment, economic empowerment and sociocultural empowerment and access to skilled birth attendants. Specifically, the education of women, their occupation, owning a bank account, media exposure, and internet use were significantly associated with the use of skilled birth attendants.

Conclusion

Focusing on women’s access to media and information technology, economic enhancement and education may increase the use of skilled birth attendants in Nepal.
CircRNAs as potential biomarkers for the clinicopathology and prognosis of glioma patients: a meta-analysis
Authors: Ding Xiangqian , Yang Luyao , Geng Xin , Zou Yanghong , Wang Zhigang , Li Yao , Qi Renli , Wang Wei , Li Jinghui , Yu Hualin
Published: October 2020

Background

An increasing number of studies have reported circular RNAs (circRNAs) as new potential biomarkers for the prognosis of gliomas. However, the overall prognostic value of circRNAs for glioma remains unclear. Therefore, this study is the first comprehensive evaluation of the clinicopathological and prognostic value of dysregulated circRNAs in the treatment of glioma patients.

Methods

We systematically reviewed the online databases of PubMed, Web of Science, EMBASE, and Cochrane Library to identify studies that explored the relationship between circRNA expression and clinicopathological and prognostic factors in glioma through April 11, 2020. The quality of the included studies was evaluated by the Newcastle-Ottawa Scale (NOS) checklists. Clinicopathological features were assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs), and overall survival (OS) was assessed by hazard ratios (HRs) and 95% CIs.

Results

Twenty-four eligible studies, including 22 studies of clinicopathological features, 1 diagnostic study, and 18 studies of prognosis, that included a total of 1390 patients were ultimately included in this study. Meta-analysis showed that highly expressed oncogenic circRNAs were significantly related to poor clinicopathological features (age: P = 0.026; tumor size: P ≤ 0.001; tumor grade: P ≤ 0.001; KPS: P = 0.012) and worse overall survival (OS) (HR = 2.01, 95% CI: 1.61–2.50, P ≤ 0.001). Moreover, we found that highly expressed tumor-suppressor circRNAs were related to better clinicopathological features (gender: P = 0.042; age: P = 0.014; tumor size: P = 0.022; tumor grade: P ≤ 0.001) and longer OS (HR = 2.70, 95% CI: 1.82–3.99, P ≤ 0.001).

Conclusions

In conclusion, there is a significant correlation between the dysregulated expression of circRNAs and the clinicopathology and prognosis of glioma patients.
Internet non-use among Canadian Indigenous older adults: Aboriginal Peoples Survey (APS)
Authors: Ali-Hassan Hossam , Eloulabi Rama , Keethakumar Asvini
Published: October 2020

Background

Older adults benefit considerably from Internet use, as it can improve their overall health and quality of life, for example through accessing healthcare services and reducing social isolation. The aim of this study is to assess the prevalence and characteristics of Indigenous older adults in Canada who do not use the Internet.

Methods

The Aboriginal Peoples Survey (APS) 2017 was used and analysis was restricted to those above 65 years of age. The main outcome variable was non-use of the internet in a typical month. Multivariable logistic regression was conducted to assess the relationship between each of the sociodemographic, socioeconomic, lifestyle and health factors and internet non-use.

Results

The prevalence of Indigenous older adults who reported never using the Internet in a typical month was 33.6% with the highest prevalence reported by residents of the Canadian territories while the lowest prevalence was reported in British Columbia. After adjustment, results indicated that older age (OR = 4.02, 95% CI 3.54–4.57 comparing 80+ to 65–69 years of age), being a male (OR = 1.52, 95% CI 1.41–1.63), married (OR = 1.34, 95% CI 1.25–1.44), and living in rural areas (OR = 1.95, 95% CI 1.79–2.13) increased the odds of not using the Internet. First Nation individuals and those who have a strong sense of belonging to the Indigenous identity were more likely to not use the Internet compared to their counterparts. In addition, those who were less educated (OR = 8.74, 95% CI 7.03–1 0.87 comparing less than secondary education to Bachelor’s Degree and above), unemployed (OR = 1.41, 95% CI 1.26–1.57), smoked cigarettes, used marijuana and those with lower self-perceived mental health and unmet health needs were at increased odds of Internet non-use compared to their counterparts.

Conclusions

Findings from this study show that a large proportion of the Indigenous older adults in Canada do not use the internet. It is necessary to address Indigenous communities’ lack of internet access and to create interventions that are consistent with Indigenous values, traditions, and goals.
Operative invasiveness does not affect the prognosis of patients with non-small cell lung cancer
Authors: Motono Nozomu , Iwai Shun , Iijima Yoshihito , Usuda Katsuo , Uramoto Hidetaka
Published: October 2020

Background

The relationship between operative invasiveness and the prognosis in non-small cell lung cancer (NSCLC) patients who have undergone surgery has been controversial.

Methods

Clinical data were analyzed for 463 NSCLC patients. Operative invasiveness was defined by wound length, operation time, and the postoperative C-reactive protein (postCRP) level. The operative approach was divided into video-assisted thoracic surgery (VATS) and thoracotomy.

Results

The wound length and operation time were significantly correlated with the postCRP level (correlation coefficient (CC) = 0.39, p <  0.01; CC = 0.54, p <  0.01, respectively). The postCRP level in the VATS group was significantly lower than that in the thoracotomy group (12.2 mg/dl vs 20.58 mg/dl, p <  0.01). The relapse-free survival differed significantly based on wound length (p <  0.01), operation time (p = 0.01), CRP level (p <  0.01), and operative approach (p <  0.01). The carcinoembryonic antigen level (hazard ratio [HR], 1.58; p = 0.02), pathological stage (pStage) (HR, 2.57; p <  0.01), vascular invasion (HR, 1.95; p = 0.01), and preoperative CRP level (preCRP) (HR, 1.91; p <  0.01) were identified as significant prognostic factors for relapse-free survival in a multivariate analysis. Furthermore, the multivariate analysis showed that smoking history (HR, 2.36; p = 0.03), pStage (HR, 3.26; p <  0.01), and preCRP level were significant prognostic factors for overall survival.

Conclusion

Preoperative CRP level was associated with poor prognosis. Although the VATS approach might be less invasive procedure for NSCLC patients, operative invasiveness does not affect the prognosis.
Optimal specimen type for accurate diagnosis of infectious peripheral pulmonary lesions by mNGS
Authors: Wang Qing , Wu Bo , Yang Donglin , Yang Chao , Jin Zhixian , Cao Jie , Feng Jing
Published: October 2020

Background

Reports on the application of metagenomic next-generation sequencing (mNGS) to the diagnosis of peripheral pulmonary lesions (PPLs) are scarce. There have been no studies investigating the optimal specimen type for mNGS.

Methods

We used mNGS to detect pathogens in matched transbronchial lung biopsy (TBLB), bronchoalveolar lavage fluid (BALF), and bronchial needle brushing (BB) specimens from 39 patients suspected of having infectious PPLs. We explored differences in microbial composition and diagnostic accuracy of mNGS for the 3 specimen types.

Results

mNGS was more sensitive than conventional culture for detection of bacteria and fungi in TBLB, BALF, and BB specimens, with no difference in the sensitivity of mNGS across the different specimen types. mNGS showed higher sensitivity for fungi or uncategorized pulmonary pathogens in TBLB+BALF+BB compared to TBLB but not BALF or BB specimens. There were no significant differences between the 3 specimen types in the relative abundance of pathogens, or between TBLB and BB specimens in the relative abundance of 6 common lower respiratory tract commensals.

Conclusions

mNGS has a higher sensitivity than the conventional culture method for detecting pathogens in TBLB, BALF, or BB specimens. mNGS of BB samples is a less invasive alternative to TBLB for the diagnosis of infectious PPLs.
Four-corner fusion method using a bioabsorbable plate for scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists: a case series study
Authors: Zenke Yukichi , Oshige Toshihisa , Menuki Kunitaka , Hirasawa Hideyuki , Yamanaka Yoshiaki , Tajima Takafumi , Kosugi Kenji , Sakai Akinori
Published: October 2020

Background

Scaphoid excision and four-corner arthrodesis is an acceptable salvage procedure for the treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) wrists, since first popularized in the 1980s. We investigated the potential application of novel bioabsorbable plates and screws made of un-sintered hydroxyapatite/poly-L-lactide composite for the treatment of metacarpal fractures. We used this material for the fixation of four-corner fusions for SLAC or SNAC wrists commencing from April 2009. The purpose of this study was to clarify the controversy in the literature regarding the use of these plates.

Methods

The surgical procedures and clinical outcomes of four-corner fusions using a bioabsorbable (poly-L-lactic acid and hydroxyapatite) plate were reported. Ten patients (mean age, 59.2 years) with SLAC or SNAC wrists underwent fusions between April 2009 and June 2016. The primary diseases were scapholunate ligament injury, Preiser disease, and scaphoid pseudarthrosis. The mean postoperative follow-up period was 45.9 months (range, 12–86).

Results

In all patients, bone union was achieved without dislocation or pain. The mean wrist flexion and extension arc improved from 78.5 degrees before surgery to 90.5 degrees after surgery. Mean grip strength improved from 51 to 69% after surgery, and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score improved from 53.5 to 14.3. No complications such as infection, avascular swelling, or tendon adhesion were observed. This implant requires no removal of internal fixation devices, produces stable outcomes, and is an effective fusion technique.

Conclusions

We summarized the outcomes of four-corner arthrodesis using bioabsorbable plates. Satisfactory clinical results were shown, with no obvious complications. This novel plate also serves as a good alternative for patients who are allergic to metals. Furthermore, bioabsorbable plates are advantageous as they do not require removal.
Challenges to effective and autonomous genetic testing and counseling for ethno-cultural minorities: a qualitative study
Authors: Cohen-Kfir Nehama , Bentwich Miriam Ethel , Kent Andrew , Dickman Nomy , Tanus Mary , Higazi Basem , Kalfon Limor , Rudolf Mary , Falik-Zaccai Tzipora C.
Published: October 2020

Background

The Arab population in Israel is a minority ethnic group with its own distinct cultural subgroups. Minority populations are known to underutilize genetic tests and counseling services, thereby undermining the effectiveness of these services among such populations. However, the general and culture-specific reasons for this underutilization are not well defined. Moreover, Arab populations and their key cultural-religious subsets (Muslims, Christians, and Druze) do not reside exclusively in Israel, but are rather found as a minority group in many European and North American countries. Therefore, focusing on the Arab population in Israel allows for the examination of attitudes regarding genetic testing and counseling among this globally important ethnic minority population.

Methods

We used a qualitative research method, employing individual interviews with 18 women of childbearing age from three religious subgroups (i.e., Druze, Muslim, and Christian) who reside in the Acre district, along with focus group discussions with healthcare providers (HCPs; 9 nurses and 7 genetic counselors) working in the same geographical district.

Results

A general lack of knowledge regarding the goals and practice of genetic counseling resulting in negative preconceptions of genetic testing was identified amongst all counselees. Counselors’ objective of respecting patient autonomy in decision-making, together with counselees’ misunderstanding of genetic risk data, caused uncertainty, frustration, and distrust. In addition, certain interesting variations were found between the different religious subgroups regarding their attitudes to genetic counseling.

Conclusions

The study highlights the miscommunications between HCPs, particularly counselors from the majority ethno-cultural group, and counselees from a minority ethno-cultural group. The need for nuanced understanding of the complex perspectives of minority ethno-cultural groups is also emphasized. Such an understanding may enhance the effectiveness of genetic testing and counseling among the Arab minority group while also genuinely empowering the personal autonomy of counselees from this minority group in Israel and other countries.
Do the dynamics of vaccine programs improve the full immunization of children under the age of five in Cameroon?
Authors: Nda’chi Deffo Rodrigue , Fomba Kamga Benjamin
Published: October 2020

Background

Among the eight Millennium Development Goals (MDGs), three were devoted to health. Two amongst which MDG4 in relation to the reduction of infant mortality has not been achieved in Least Developed Countries (LDC). In Africa, a significant part of infant mortality is due to vaccine-preventable diseases administered free of charge by the Extended Program on Immunization (EPI). As such, in the “social equity” pillar of Sustainable Development Goals (SDG), the MDGs related to health have yet been taken into account. The achievement of these objectives requires an understanding of the immunization behavior of children under 5 years of age through an analysis of immunization dynamics between 1991 and 2011.

Methods

We use data from Demographic and Health Surveys (DHS) of 1991, 1998, 2004 and 2011 carried out by the National Institute of Statistics (NIS). The module concerning EPI vaccines was administered to 3350, 2317, 8125 and 25,524 under 5 in 1991, 1998, 2004 and 2011 respectively. The Immunization analysis was made from the logistic model for complete immunization and the Oaxaca’s decomposition to assess the contribution of the unexplained part, which is that of the strategies/programs implemented between 1991 and 2011 by the EPI to improve immunization.

Results

In general, children with vaccination card are more than 7 times likely to be fully immunized than their counterparts who do not have any. This result was higher in 1991 (approximately 57) and lowest in 2011 (5). In addition, the child’s birth order reduces his/her probability of being fully immunized and the impact increases with the latter’s birth order. On the other hand, the mother’s age as well as her level of education increase the child’s likelihood of receiving all basic vaccines. Moreover, the contributions of EPI partners in terms of immunization support as well as strategies to promote immunization through communication for development are of a particular importance in increasing immunization coverage. They significantly explain 67.62% of the 0.105 gain recorded within the 2011–2004 period and 72.46% of the 0.069 gain recorded within the 2004–1998 period.

Conclusion

The contribution of EPI partner organizations is fundamental for the achievement of EPI objectives. Since they contribute to increase the likelihood of fully immunized children. The link with child immunization is done through the specific characteristics to the mother.
“It is always me against the Norwegian system.” barriers and facilitators in accessing and using dementia care by minority ethnic groups in Norway: a qualitative study
Authors: Czapka Elżbieta Anna , Sagbakken Mette
Published: October 2020

Background

Dementia is one of the greatest health challenges in the contemporary world. Due to several barriers to accessing health care services, elderly immigrants constitute a group that poses special challenges in dementia diagnosis and treatment. The aim of this study was to explore the barriers and facilitators in accessing and using dementia care services by minority ethnic groups in Norway.

Methods

The study utilised a qualitative design. The participants included family caregivers of individuals from minority ethnic groups living with dementia, representatives of immigrant communities, and representatives of health and care personnel working with people living with dementia. Individual semi-structured in-depth interviews were carried out in 2018 and 2019 in Oslo and Akershus. Interviews were analysed using thematic analyses.

Results

Several barriers and facilitators in accessing and using dementia care services were identified, the most important of which were related to lack of knowledge of dementia, lack of awareness of dementia care services, lack of language skills, culturally based differences, the organisation of Norwegian dementia care services, and immigrants’ socio-economic status. According to the study participants, having health care personnel in the family and further adaptation of dementia services to the needs of people with different cultural and linguistic backgrounds facilitate access to dementia services.

Conclusions

The study shows the need to develop inclusive policies that promote a patient-centred approach to ensure that individuals from minority ethnic groups receive appropriate dementia care.
Clinicians’ experience of providing care: a rapid review
Authors: Pervaz Iqbal Maha , Manias Elizabeth , Mimmo Laurel , Mears Stephen , Jack Briony , Hay Liz , Harrison Reema
Published: October 2020

Background

Health care services internationally are refocussing care delivery towards patient centred, integrated care that utilises effective, efficient and innovative models of care to optimise patient outcomes and system sustainability. Whilst significant efforts have been made to examine and enhance patient experience, to date little has progressed in relation to provider experience. This review aims to explore this knowledge gap by capturing evidence of clinician experience, and how this experience is defined and measured in the context of health system change and innovation.

Methods

A rapid review of published and grey literature review was conducted utilising a rapid evidence assessment methodology. Seventy-nine studies retrieved from the literature were included in the review. Fourteen articles were identified from the grey literature search and one article obtained via hand searching. In total, 94 articles were included in the review. This study was commissioned by and co-designed with the New South Wales, Ministry of Health.

Results

Clinician experience of delivering health care is inconsistently defined in the literature, with identified articles lacking clarity regarding distinctions between experience, engagement and work-related outcomes such as job satisfaction. Clinician experience was commonly explored using qualitative research that focused on experiences of discrete health care activities or events in which a change was occurring. Such research enabled exploration of complex experiences. In these contexts, clinician experience was captured in terms of self-reported information that clinicians provided about the health care activity or event, their perceptions of its value, the lived impacts they experienced, and the specific behaviours they displayed in relation to the activity or event. Moreover, clinician’s experience has been identified to have a paucity of measurement tools.

Conclusion

Literature to date has not examined clinician experience in a holistic sense. In order to achieve the goals identified in relation to value-based care, further work is needed to conceptualise clinician experience and understand the nature of measurement tools required to assess this. In health system application, a broader ‘clinician pulse’ style assessment may be valuable to understand the experience of clinical work on a continuum rather than in the context of episodes of change/care.
Accuracy and reproducibility of somatic point mutation calling in clinical-type targeted sequencing data
Authors: Karimnezhad Ali , Palidwor Gareth A. , Thavorn Kednapa , Stewart David J. , Campbell Pearl A. , Lo Bryan , Perkins Theodore J.
Published: October 2020

Background

Treating cancer depends in part on identifying the mutations driving each patient’s disease. Many clinical laboratories are adopting high-throughput sequencing for assaying patients’ tumours, applying targeted panels to formalin-fixed paraffin-embedded tumour tissues to detect clinically-relevant mutations. While there have been some benchmarking and best practices studies of this scenario, much variant calling work focuses on whole-genome or whole-exome studies, with fresh or fresh-frozen tissue. Thus, definitive guidance on best choices for sequencing platforms, sequencing strategies, and variant calling for clinical variant detection is still being developed.

Methods

Because ground truth for clinical specimens is rarely known, we used the well-characterized Coriell cell lines GM12878 and GM12877 to generate data. We prepared samples to mimic as closely as possible clinical biopsies, including formalin fixation and paraffin embedding. We evaluated two well-known targeted sequencing panels, Illumina’s TruSight 170 hybrid-capture panel and the amplification-based Oncomine Focus panel. Sequencing was performed on an Illumina NextSeq500 and an Ion Torrent PGM respectively. We performed multiple replicates of each assay, to test reproducibility. Finally, we applied four different freely-available somatic single-nucleotide variant (SNV) callers to the data, along with the vendor-recommended callers for each sequencing platform.

Results

We did not observe major differences in variant calling success within the regions that each panel covers, but there were substantial differences between callers. All had high sensitivity for true SNVs, but numerous and non-overlapping false positives. Overriding certain default parameters to make them consistent between callers substantially reduced discrepancies, but still resulted in high false positive rates. Intersecting results from multiple replicates or from different variant callers eliminated most false positives, while maintaining sensitivity.

Conclusions

Reproducibility and accuracy of targeted clinical sequencing results depend less on sequencing platform and panel than on variability between replicates and downstream bioinformatics. Differences in variant callers’ default parameters are a greater influence on algorithm disagreement than other differences between the algorithms. Contrary to typical clinical practice, we recommend employing multiple variant calling pipelines and/or analyzing replicate samples, as this greatly decreases false positive calls.
Dyspnea, effort and muscle pain during exercise in lung transplant recipients: an analysis of their association with cardiopulmonary function parameters using machine learning
Authors: Braccioni Fausto , Bottigliengo Daniele , Ermolao Andrea , Schiavon Marco , Loy Monica , Marchi Maria Rita , Gregori Dario , Rea Federico , Vianello Andrea
Published: October 2020

Background

Despite improvement in lung function, most lung transplant (LTx) recipients show an unexpectedly reduced exercise capacity that could be explained by persisting peripheral muscle dysfunction of multifactorial origin. We analyzed the course of symptoms, including dyspnea, muscle effort and muscle pain and its relation with cardiac and pulmonary function parameters during an incremental exercise testing.

Methods

Twenty-four bilateral LTx recipients were evaluated in an observational cross-sectional study. Recruited patients underwent incremental cardio-pulmonary exercise testing (CPET). Arterial blood gases at rest and peak exercise were measured. Dyspnea, muscle effort and muscle pain were scored according to the Borg modified scale. Potential associations between the severity of symptoms and exercise testing parameters were analyzed using a Forest-Tree Machine Learning approach, which accomplishes for a ratio between number of observations and number of screened variables less than unit.

Results

Dyspnea score was significantly associated with maximum power output (WR, watts), and minute ventilation (VE, L/min) at peak exercise. In a controlled subgroup analysis, dyspnea score was a limiting symptom only in LTx recipients who reached the higher levels of WR (≥ 101 watts) and VE(≥ 53 L/min). Muscle effort score was significantly associated with breathing reserve as percent of maximal voluntary ventilation (BR%MVV). The lower the BR%MVV at peak exercise (< 32) the higher the muscle effort perception. Muscle pain score was significantly associated with VO2peak, arterial [HCO3−] at rest, and VE/VCO2slope. In a subgroup analysis, muscle pain was the limiting symptom in LTx recipients with a lower VO2peak (< 15 mL/Kg/min) and a higher VE/VCO2slope (≥ 32).

Conclusions

The majority of our LTx recipients reported peripheral limitation as the prevalent reason for exercise termination. Muscle pain at peak exercise was strictly associated with basal and exercise-induced metabolic altered pathways. The onset of dyspnea (breathing effort) was associated with the intensity of ventilatory response to meet metabolic demands for increasing WR. Our study suggests that only an accurate assessment of symptoms combined with cardio-pulmonary parameters allows a correct interpretation of exercise limitation and a tailored exercise prescription. The role and mechanisms of muscle pain during exercise in LTx recipients requires further investigations.
RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells
Authors: Yan Xiaodong , Han Dali , Chen Zhiqiang , Han Chao , Dong Wei , Han Li , Zou Lei , Zhang Jianbo , Liu Yan , Chai Jie
Published: October 2020

Background

Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial–mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation.

Methods

We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues.

Results

We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter.

Conclusions

Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.
Plug for the parasitophorous duct: a solution of two conundra
Authors: Wilairat Prapon , Auparakkitanon Saranya
Published: October 2020

Background

We present two conundra in the biology of intraerythrocytic malaria parasite: how an apparent open parasitophorous duct provide direct access of only a select set of serum proteins to the parasitophorous vacuole, and how proteases mediate membrane lysis to allow merozoite egress.

Solution

We posit the existence of a parasitophorous vacuolar duct plug that is originally formed from a tight junction (or parts thereof) between merozoite apical surface and red blood cell plasma membrane, which by moving over the parasite surface towards the posterior end draws the parasite into the host cell interior, and by remaining at the passage orifice provides a location of transporter(s) for import of serum proteins into parasitophorous vacuole and an opening for merozoite egress upon its dissolution/dismantling through protease(s) action.

Conclusion

This notion obviates the need of a distinct intact parasitophorous vacuolar membrane, which in the proposed model is an extension of the red blood cell membrane but still forms an intracellular compartment for parasite growth and development. The model is testable using existing high-resolution electron and X-ray tomography tools.
Adaptation and validation of social accountability measures in the context of contraceptive services in Ghana and Tanzania
Authors: Boydell Victoria , Steyn Petrus S. , Cordero Joanna Paula , Habib Ndema , Nguyen My Huong , Nai Dela , Shamba Donat
Published: October 2020

Background

Changes in the values, attitudes, and interactions of both service users and health care providers are central to social accountability processes in reproductive health. However, there is little consensus on how best to measure these latent changes. This paper reports on the adaptation and validation of measures that capture these changes in Tanzania and Ghana.

Methods

The CaPSAI theory of change determined the dimensions of the measure, and we adapted existing items for the survey items. Trained data collectors used a survey to collect data from 752 women in Tanzania and 750 women in Ghana attending contraceptive services. We used reliability analysis, exploratory, and confirmatory factor analysis to assess the validity and reliability of these measures in each country.

Results

The measure has high construct validity and reliability in both countries. We identified several subscales in both countries, 10 subscales in Tanzania, and 11 subscales in Ghana. Many of the domains and items were shared across both settings.

Conclusion

The study suggests that the multi-dimensional scales have high construct validity and reliability in both countries. Though there were differences in the two country contexts and in items and scales, there was convergence in the analysis that suggests that this measure may be relevant in different settings and should be validated in new settings.

Trial registration

ACTRN12619000378123.