bluuebunny/crossref_metadata_2025 huggingface dataset:
TRIM study protocol - a prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma
Authors: Naeser Ylva , Helgadottir Hildur , Brandberg Yvonne , Hansson Johan , Bagge Roger Olofsson , Elander Nils O. , Ingvar Christian , Isaksson Karolin , Flygare Petra , Nilsson Cecilia , Jakobsson Frida , del Val Munoz Olga , Valachis Antonis , Jansson Malin , Sparring Charlotte , Ohlsson Lars , Dyrke Ulf , Papantoniou Dimitrios , Sundin Anders , Ullenhag Gustav J.
Published: December 2020

Background

The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only.

Methods

The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/− whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group.

Discussion

This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM.

Results

The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden.

Trial registration

ClinicalTrials.gov, NCT 03116412. Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412
Survival impact of extended cycles of second-line chemotherapy in platinum-sensitive relapsed ovarian cancer patients with residual tumor after six cycles
Authors: Kim Se Ik , Hwang Woo Yeon , Lee Maria , Kim Hee Seung , Kim Kidong , Chung Hyun Hoon , No Jae Hong , Kim Jae-Weon , Kim Yong Beom , Park Noh Hyun , Song Yong-Sang , Suh Dong Hoon
Published: December 2020

Background

To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy.

Methods

In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups.

Results

The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84–1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72–2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery.

Conclusions

More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy.
Emergence of spatio-temporal variations in chemotherapeutic drug efficacy: in-vitro and in-Silico 3D tumour spheroid studies
Authors: Sheraton M. V. , Chiew G. G. Y. , Melnikov V. , Tan E. Y. , Luo K. Q. , Verma N. , Sloot P. M. A.
Published: December 2020

Background

The mechanisms of action and efficacy of cisplatin and paclitaxel at cell population level are well studied and documented, however the localized spatio-temporal effects of the drugs are less well understood. We explore the emergence of spatially preferential drug efficacy resulting from variations in mechanisms of cell-drug interactions.

Methods

3D spheroids of HeLa-C3 cells were treated with drugs, cisplatin and paclitaxel. This was followed by sectioning and staining of the spheroids to track the spatio-temporal apoptotic effects of the drugs. A mechanistic drug-cell interaction model was developed and simulated to analyse the localized efficacy of these drugs.

Results

The outcomes of drug actions on a local cell population was dependant on the interactions between cell repair probability, intracellular drug concentration and cell’s mitosis phase. In spheroids treated with cisplatin, drug induced apoptosis is found to be scattered throughout the volume of the spheroids. In contrast, effect of paclitaxel is found to be preferentially localized along the periphery of the spheroids. Combinatorial treatments of cisplatin and paclitaxel result in varying levels of cell apoptosis based on the scheduling strategy.

Conclusions

The preferential action of paclitaxel can be attributed to the cell characteristics of the peripheral population. The model simulations and experimental data show that treatments initiated with paclitaxel are more efficacious due to the cascading of spatial effects of the drugs.
Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma
Authors: Liu Xiangye , Li Tingting , Kong Delong , You Hongjuan , Kong Fanyun , Tang Renxian
Published: December 2020

Background

Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown.

Methods

The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package.

Results

We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC.

Conclusion

In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.
Comprehensive analysis of prognostic gene signatures based on immune infiltration of ovarian cancer
Authors: Yan Shibai , Fang Juntao , Chen Yongcai , Xie Yong , Zhang Siyou , Zhu Xiaohui , Fang Feng
Published: December 2020

Background

Ovarian cancer (OV) is one of the most common malignant tumors of gynecology oncology. The lack of effective early diagnosis methods and treatment strategies result in a low five-year survival rate. Also, immunotherapy plays an important auxiliary role in the treatment of advanced OV patient, so it is of great significance to find out effective immune-related tumor markers for the diagnosis and treatment of OV.

Methods

Based on the consensus clustering analysis of single-sample gene set enrichment analysis (ssGSEA) score transformed via The Cancer Genome Atlas (TCGA) mRNA profile, we obtained two groups with high and low levels of immune infiltration. Multiple machine learning methods were conducted to explore prognostic genes associated with immune infiltration. Simultaneously, the correlation between the expression of mark genes and immune cells components was explored.

Results

A prognostic classifier including 5 genes (CXCL11, S1PR4, TNFRSF17, FPR1 and DHRS95) was established and its robust efficacy for predicting overall survival was validated via 1129 OV samples. Some significant variations of copy number on gene loci were found between two risk groups and it showed that patients with fine chemosensitivity has lower risk score than patient with poor chemosensitivity (P = 0.013). The high and low-risk groups showed significantly different distribution (P < 0.001) of five immune cells (Monocytes, Macrophages M1, Macrophages M2, T cells CD4 menory and T cells CD8).

Conclusion

The present study identified five prognostic genes associated with immune infiltration of OV, which may provide some potential clinical implications for OV treatment.
Efficacy and safety of atropine to control myopia progression: a systematic review and meta-analysis
Authors: Zhao Congling , Cai Chunyan , Ding Qiang , Dai Hongbin
Published: December 2020

Background

The effect and safety of atropine on delaying the progression of myopia has been extensively studied, but its optimal dose is still unclear. Therefore, the purpose of this meta-analysis is to systematically evaluate the safety and effectiveness of atropine in controlling the progression of myopia, and to explore the relationship between the dose of atropine and the effectiveness of controlling the progression of myopia.

Methods

This work was done through the data searched from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, a meta-analysis was performed using Revman5.3 software.

Results

A total of 10 randomized controlled trials (RCTs) were included. Myopia progression was mitigated greater in the atropine treatment group than that in the control group, with MD = − 0.80, 95% CI (− 0.94, − 0.66) during the whole observation period. There was a statistical difference among 0.05, 0.5, and 1.0% atropine (P = 0.004). In addition, less axial elongation was shown, with MD = − 0.26, 95% CI (− 0.33, − 0.18) during the whole observation period.

Conclusion

The effectiveness of atropine in controlling the progression of myopia was dose related. A 0.05% atropine was likely to be the optimal dose.
Citalopram intoxication in four week old infant
Authors: Janson Jo-Anne , Wasylewicz Arthur T. M. , Eijkemans Marianne , Kerskes Marieke
Published: December 2020

Background

In contrast to intoxications in toddlers which can be due to accidental ingestions, many intoxications in infants are due to medication errors. To our knowledge, this is the first case report of a citalopram intoxication in an infant, and may offer new insight on possible screening methods for intoxication as well as pharmacokinetics of citalopram in small infants.

Case presentation

This case report describes an unintentional citalopram intoxication in a 4 week old infant due to a vitamin D drops ‘look alike’ error. The infant showed extreme jitteriness and opisthotonus at presentation, as well as prolonged signs of gastro-oesophageal reflux. No cardiac rhythm disturbances or convulsions were seen. The clinical course combined with Finnegan scores was correlated to and supported by pharmacokinetic and pharmacokinetic data of citalopram in the patient.

Conclusions

Using Finnegan scores in general pediatric practice could help objectify follow-up of acute intoxications in young infants with neurological symptoms.
Coverage outcomes (effects), costs, cost-effectiveness, and equity of two combinations of long-lasting insecticidal net (LLIN) distribution channels in Kenya: a two-arm study under operational conditions
Authors: Worrall Eve , Were Vincent , Matope Agnes , Gama Elvis , Olewe Joseph , Mwambi Dennis , Desai Meghna , Kariuki Simon , Buff Ann M. , Niessen Louis W.
Published: December 2020

Background

Malaria-endemic countries distribute long-lasting insecticidal nets (LLINs) through combined channels with ambitious, universal coverage (UC) targets. Kenya has used eight channels with variable results. To inform national decision-makers, this two-arm study compares coverage (effects), costs, cost-effectiveness, and equity of two combinations of LLIN distribution channels in Kenya.

Methods

Two combinations of five delivery channels were compared as ‘intervention’ and ‘control’ arms. The intervention arm comprised four channels: community health volunteer (CHV), antenatal and child health clinics (ANCC), social marketing (SM) and commercial outlets (CO). The control arm consisted of the intervention arm channels except mass campaign (MC) replaced CHV. Primary analysis used random sample household survey data, service-provider costs, and voucher or LLIN distribution data to compare between-arm effects, costs, cost-effectiveness, and equity. Secondary analyses compared costs and equity by channel.

Results

The multiple distribution channels used in both arms of the study achieved high LLIN ownership and use. The intervention arm had significantly lower reported LLIN use the night before the survey (84·8% [95% CI 83·0–86·4%] versus 89·2% [95% CI 87·8–90·5%], p < 0·0001), higher unit costs ($10·56 versus $7·17), was less cost-effective ($86·44, 95% range $75·77–$102·77 versus $69·20, 95% range $63·66–$77·23) and more inequitable (Concentration index [C.Ind] = 0·076 [95% CI 0·057 to 0·095 versus C.Ind = 0.049 [95% CI 0·030 to 0·067]) than the control arm. Unit cost per LLIN distributed was lowest for MC ($3·10) followed by CHV ($10·81) with both channels being moderately inequitable in favour of least-poor households.

Conclusion

In line with best practices, the multiple distribution channel model achieved high LLIN ownership and use in this Kenyan study setting. The control-arm combination, which included MC, was the most cost-effective way to increase UC at household level. Mass campaigns, combined with continuous distribution channels, are an effective and cost-effective way to achieve UC in Kenya. The findings are relevant to other countries and donors seeking to optimise LLIN distribution.

Trial registration

The assignment of the intervention was not at the discretion of the investigators; therefore, this study did not require registration.
Meeting Indigenous youth where they are at: knowing and doing with 2SLGBTTQQIA and gender non-conforming Indigenous youth: a qualitative case study
Authors:   Native Youth Sexual Health Network (NYSHN), Hardy Billie-Jo , Lesperance Alexa , Foote Iehente , Firestone Michelle , Smylie Janet
Published: December 2020

Background

Research carried out in partnership with Indigenous youth at The Native Youth Sexual Health Network (NYSHN) demonstrates that Indigenous youth can (and do) develop and implement public health interventions amongst their peers and within their communities, when supported by non-youth allies and mentors.

Methods

Together, NYSHN and Well Living House researchers co-designed a qualitative case study to demonstrate and document how Indigenous youth can and do practice their own form of public health implementation research (PHIR) in the realm of mental health promotion for 2SLGBTTQQIA and Gender Non-Conforming Indigenous youth. Academic and Indigenous youth researchers were: participant observers; conducted a focus group; and designed and implemented an online survey with Indigenous youth project participants. Governance, intellectual property, financial terms and respective academic and NYSHN roles and responsibilities were negotiated using a customized community research agreement. The data were thematically analyzed using a critical decolonizing lens that recognizes the historic and ongoing marginalization of Indigenous peoples while also highlighting the unique and diverse strengths of Indigenous communities’ knowledge and practice in maintaining their health and wellbeing.

Results

Analysis revealed how colonialism and intergenerational trauma have impacted Indigenous youth identity and the value of self-determination as it relates to their identity, their relationships, health and wellbeing. We also learned how knowing and doing about and for Indigenous youth needs to be youth determined – ‘nothing about us, without us’ -- yet also supported by allies. Finally, our analysis shares some promising practices in knowing and doing for and with Indigenous youth.

Conclusions

This study provides a reminder of the need to centre Indigenous youth throughout PHIR in order to realize sustainable benefit from research, services and programming. It emphasizes the need to recognize Indigenous youth as leaders and partners in these initiatives, support their efforts to self-determine, compensate them as partners, and prioritize Indigenous youth-determined frameworks and accountability mechanisms.
Determinants of the utilization of allergy management measures among hay fever sufferers: a theory-based cross-sectional study
Authors: Muzalyova Anna , Brunner Jens O.
Published: December 2020

Background

The quality of life of chronically ill individuals, such as hay fever sufferers, is significantly dependent on their health behavior. This survey aimed to explain the health-related behavior of allergic individuals using the protection motivation theory (PMT) and the transtheoretical model (TTM).

Methods

The influencing variables stated by PMT were operationalized based on data from semistructured pilot interviews and a pretest with 12 individuals from the target population. The final questionnaire inquired perceived seriousness and severity of hay fever, response efficacy, response costs, self-efficacy, and the use of various hay fever management measures in relation to the TTM stages. Multivariate logistic regression was performed to investigate the relationships between the PMT constructs and the examined health behavior.

Results

A total of 569 allergic individuals completed the online questionnaire. Only 33.26% of allergic individuals were in the maintenance stage for treatment under medical supervision, and almost 60% preferred hay fever self-management. A total of 67.56% had a well-established habit of taking anti-allergic medication, but only 25.31% had undergone specific immunotherapy. The likelihood of seeking medical supervision was positively influenced by perceived severity (OR = 1.35, 95% CI: 1.02–1.81), perceived seriousness (OR = 2.12, 95% CI: 1.56–2.89), and self-efficacy (OR = 4.52, 95% CI: 3.11–6.65). The perceived severity of symptoms predicted the practice of hay fever self-management (OR = 1.60, 95% CI: 1.21–2.11), as well as anti-allergic medication intake (OR = 1.65, 95% CI: 1.16–2.35). The latter measure was also positively influenced by self-efficacy (OR = 1.52, 95% CI: 1.01–2.28) and hay fever self-management (OR = 4.76, 95% CI: 2.67–7.49). Undergoing specific immunotherapy was significantly predicted only by medical supervision (OR = 9.80, 95% CI: 8.16–13.80). Allergen avoidance was a strategy used by allergic individuals who preferred hay fever self-management (OR = 2.56, 95% CI: 1.87–3.52) and experienced notable symptom severity (OR = 2.12, 95% CI: 1.60–2.81).

Conclusion

Educational interventions that increase the awareness of health risks associated with inadequate hay fever management and measures to increase self-efficacy might be beneficial for the promotion of appropriate hay fever management among allergic individuals.
Parental drinking according to parental composition and adolescent binge drinking: findings from a nationwide high school survey in Japan
Authors: Inoura Satoshi , Shimane Takuya , Kitagaki Kunihiko , Wada Kiyoshi , Matsumoto Toshihiko
Published: December 2020

Background

Alcohol problems in parents have been revealed to affect adolescent alcohol misuse. However, few studies examine the effects of parental drinking on adolescent risky drinking (including binge drinking) in the general population. In particular, previous study findings are inconsistent regarding the influence of parental drinking according to parental composition. In this study, we aimed to examine the relationship between parental drinking, according to parental composition, and binge drinking among high school students in Japan.

Methods

We performed a secondary analysis of the Nationwide High School Survey on Drug Use and Lifestyle 2018, Japan. A total of 46,848 valid surveys from high school students of 78 schools were included for analysis. Logistic regression analysis with a generalized linear mixed model was conducted with binge drinking as the dependent variable and “parental drinking according to parental composition” (e.g., father’s drinking, mother’s drinking, father’s absence, mother’s absence, both parents drinking, and neither parent at home) as the independent variable, after adjusting with covariates. Binge drinking was defined as five or more alcoholic drinks for male adolescents or four or more alcoholic drinks for females on the same occasion within two hours.

Results

In the fully adjusted models, adolescents whose mothers drink (adjusted odds ratio (AOR): 1.50, 95% confidence interval (CI): 1.06–2.12) were significantly associated with adolescent binge drinking. This risk was significantly higher among students with neither parent living at home (AOR: 4.35, 95% CI: 2.10–9.02).

Conclusion

Parental drinking and absence do affect adolescent binge drinking; our findings show that adolescents are more likely to engage in binge drinking if their mothers drink or if they are not living with either parent. Therefore, it is important to engage parents and non-parental family members in future programs and interventions to prevent adolescent binge drinking.
Racial discrimination and allostatic load among First Nations Australians: a nationally representative cross-sectional study
Authors: Cave Leah , Cooper Matthew N. , Zubrick Stephen R. , Shepherd Carrington C. J.
Published: December 2020

Background

Increased allostatic load is linked with racial discrimination exposure, providing a mechanism for the biological embedding of racism as a psychosocial stressor. We undertook an examination of how racial discrimination interacts with socioecological, environmental, and health conditions to affect multisystem dysregulation in a First Nations population.

Methods

We conducted latent class analysis (LCA) using indicators of life stress, socioeconomic background, and physical and mental health from a nationally representative sample of Australian Aboriginal adults (N = 2056). We used LCA with distal outcomes to estimate the effect of the latent class variable on our derived allostatic load index and conducted a stratified analysis to test whether allostatic load varied based on exposure to racial discrimination across latent classes.

Results

Our psychosocial, environmental, and health measures informed a four-class structure; ‘Low risk’, ‘Challenged but healthy’, ‘Mental health risk’ and ‘Multiple challenges’. Mean allostatic load was highest in ‘Multiple challenges’ compared to all other classes, both in those exposed (4.5; 95% CI: 3.9, 5.0) and not exposed (3.9; 95% CI: 3.7, 4.2) to racial discrimination. Allostatic load was significantly higher for those with exposure to racial discrimination in the ‘Multiple challenges’ class (t = 1.74, p = .04) and significantly lower in the ‘Mental health risk’ class (t = − 1.67, p = .05).

Conclusions

Racial discrimination may not always modify physiological vulnerability to disease. Social and economic contexts must be considered when addressing the impact of racism, with a focus on individuals and sub-populations experiencing co-occurring life challenges.
Community acceptability of dolutegravir-based HIV treatment in women: a qualitative study in South Africa and Uganda
Authors: Alhassan Yussif , Twimukye Adelline , Malaba Thoko , Orrell Catherine , Myer Landon , Waitt Catriona , Lamorde Mohammed , Kambugu Andrew , Reynolds Helen , Khoo Saye , Taegtmeyer Miriam
Published: December 2020

Background

Despite concerns about dolutegravir use in pregnancy, most low- and middle-income countries are accelerating the introduction of dolutegravir-based regimens into national antiretroviral treatment programmes. Questions remain about the acceptability of dolutegravir use in women due to the potential risks in pregnancy. This study from South Africa and Uganda explored community values, preferences and attitudes towards the use of dolutegravir-based regimens in women.

Methods

This study employed a qualitative design involving in-depth interviews and focus group discussion conducted between August 2018 to March 2019. The study was conducted in the months following an announcement of a potential risk for neural tube defects with dolutegravir use among women during conception and the first trimester. Participants included HIV positive pregnant and lactating women and their partners. They were selected purposively from urban poor communities in South Africa and Uganda. Data was analysed thematically in NVivo.

Results

Forty-four in-depth interviews and 15 focus group discussions were conducted. Most participants had positive views of dolutegravir-based regimens and perceived it to be more desirable compared with efavirenz-containing regimens. There was widespread concern about use of dolutegravir during pregnancy and among women of childbearing age due to publicity around the possible association with neural tube defects. Acceptability was gendered, with nearly all male participants preferring their female spouses of childbearing potential not to use dolutegravir, while most women not planning pregnancy wanted access to contraception alongside dolutegravir. Community awareness and knowledge of dolutegravir was low and characterised by negative information. Women were concerned about HIV-related stigma and wanted the privacy features of dolutegravir to be strengthened with modification of the pill appearance and disguised packaging.

Conclusions

Dolutegravir-based regimens were found to be generally acceptable for use in women except during pregnancy. Interest in a dolutegravir-based regimen was linked with its perceived potential to enhance health, privacy and reduce stigma while concerns about neural tube defects were the main potential barrier to dolutegravir uptake in women. In order to optimise the community acceptability and uptake of acceptability-based regimen among women it is critical to strengthen community awareness and understanding of dolutegravir treatment, improve contraception services alongside the introduction of dolutegravir, and engage with male partners.
Effect of arthroscopic acromioplasty on reducing critical shoulder angle: a protocol for a prospective randomized clinical trial
Authors: Long Yi , Hou Jingyi , Tang Yiyong , Li Fangqi , Yu Menglei , Zhang Congda , Yang Rui
Published: December 2020

Background

The critical shoulder angle (CSA), which helps to predict patients who are at risk of rotator cuff tears (RCTs) with large degree and who are susceptible to osteoarthritis with low angle, has been identified as one of the most vital acromial parameters; anterolateral and lateral acromioplasties have been proven to be valid ways to reduce CSA. However, no study has compared the effect of different acromioplasties on the reduction of the large CSA (≥33°) clinically. Additionally, either anterolateral or lateral acromioplasty could not precisely correct large CSAs to a favorable range (30–33°) in each patient. Thus, we will propose a novel precise acromioplasty technique for the purpose of reducing CSA accurately and effectively, and compare the effectiveness of different acromioplasties on the reduction of the CSA.

Methods

A total of 60 RCT patients who have indications for arthroscopic rotator cuff repair and with pre-operative CSA ≥33° will be recruited in outpatient center of Sun Yat-sen Memorial Hospital. Eligible participants will be randomly allocated to Group A (anterolateral acromioplasty), Group B (lateral acromioplasty) or Group C (precise acromioplasty) via a random, computer-generated number system. Three surgical plans will be made for each participant respectively by one professional surgeon according to the results of randomization allocation. The post-operative CSA will be measured 2 days post-operation. Follow-up will be maintained at 3, 6, and 12 months after surgery including the visual analog scale score, the University of California at Los Angeles score, the Constant Shoulder Score and the American Shoulder and Elbow Surgeon Shoulder Assessment Form. Finally, all outcomes will be assessed by two researchers who are blinded to the recruitment and allocation.

Discussion

This is the first clinical trial to evaluate the impact of different acromioplasties on the reduction of the CSA. Additionally, this study will provide a new precise acromioplasty technique, which is a novel precision and individualized treatment to prevent degenerative RCTs by reducing the CSA.

Trial registration

ChiCTR2000032343. Registered on April 26th, 2020.
Advising special population emergency medicine residency applicants: a survey of emergency medicine advisors and residency program leadership
Authors: Pelletier-Bui Alexis E. , Schrepel Caitlin , Smith Liza , Zhang Xiao Chi , Kellogg Adam , Edens Mary Ann , Jones Christopher W. , Hillman Emily
Published: December 2020

Background

The objective of this study was to determine the advising and emergency medicine (EM) residency selection practices for special population applicant groups for whom traditional advice may not apply.

Methods

A survey was distributed on the Council of Residency Directors in EM and Clerkship Directors in EM Academy listservs. Multiple choice, Likert-type scale, and fill-in-the-blank questions addressed the average EM applicant and special population groups (osteopathic; international medical graduate (IMG); couples; at-risk; re-applicant; dual-accreditation applicant; and military). Percentages and 95% confidence intervals [CI] were calculated.

Results

One hundred four surveys were completed. Of respondents involved in the interview process, 2 or more standardized letters of evaluation (SLOEs) were recommended for osteopathic (90.1% [95% CI 84–96]), IMG (82.5% [73–92]), dual-accreditation (46% [19–73]), and average applicants (48.5% [39–58]). Recommendations for numbers of residency applications to submit were 21–30 (50.5% [40.7–60.3]) for the average applicant, 31–40 (41.6% [31.3–51.8]) for osteopathic, and > 50 (50.9% [37.5–64.4]) for IMG. For below-average Step 1 performance, 56.0% [46.3–65.7] were more likely to interview with an average Step 2 score. 88.1% [81.8–94.4] will consider matching an EM-EM couple. The majority were more likely to interview a military applicant with similar competitiveness to a traditional applicant. Respondents felt the best option for re-applicants was to pursue the Supplemental Offer and Acceptance Program (SOAP) for a preliminary residency position.

Conclusion

Advising and residency selection practices for special population applicants differ from those of traditional EM applicants. These data serve as an important foundation for advising these distinct applicant groups in ways that were previously only speculative. While respondents agree on many advising recommendations, outliers exist.
Preparedness of non-hospital health centers to manage patients with life-threatening emergency conditions: findings from a qualitative study
Authors: Sadeghi-Bazargani Homayoun , Amir-Behghadami Mehrdad , Gholizadeh Masoumeh , Janati Ali , Rahmani Farzad
Published: December 2020

Background

Management of Life-threatening Emergency (LTE) patients in urban and rural areas is an important challenge, which can affect pre-hospital mortality rate. Therefore, Non-hospital Health Center (NHHC) must be prepared to manage such emergency cases that may occur in the geographic area where these centers act. The aim of this study was to explore domains related to the preparedness of NHHCs to manage LTE patients through resorting to healthcare providers’ and experts’ perspectives.

Methods

A qualitative exploratory study was applied using Semi-Structured Interviews (SSIs) and Focus Group Discussions (FGDs). Prior to beginning data collection, the study and its objectives were explained to the participants and their informed consents were obtained. Then, SSIs and FGDs were conducted by two trained researchers using an interview guide, which was developed through literature review and consulting experts. In total, 12 SSIs were done with the providers at different NHHCs in Tabriz. In addition, 2 FGDs were conducted with the specialists in Emergency Medicine (EM) and Primary Health Care (PHC), and the executives of health centers, with over 5 years of work experience, and Emergency Medical Services (EMS) experts. Purposive sampling method was used in this study. All SSIs and FGDs were audio recorded and subsequently transcribed. Framework Analysis was employed to manually analyze the interview transcripts from all the SSIs and FGDs.

Results

The interview transcripts analysis resulted in the emergence of 3 themes and 11 sub-themes, categorized according to Donabedian’s triple model. 5 sub-themes were related to input, including medical equipment and supplies, environmental infrastructures of the centers, emergency medicines, human resource, and protocols, guidelines and policies. 4 sub-themes were related to process, including providing clinical services, medicine storage capacity, maintenance of equipment, and management process. Finally, 2 sub-themes were related to outcome, which were patients’ satisfaction with the quality of care and improved survival of LTE patients.

Conclusions

The results of this study can provide a new perspective for health managers and policy makers on how to evaluate the preparedness of NHHCs in managing LTE patients. In addition, it will be used to develop instruments to measure the preparedness of these centers.
Engineering of a genome-reduced strain Bacillus amyloliquefaciens for enhancing surfactin production
Authors: Zhang Fang , Huo Kaiyue , Song Xingyi , Quan Yufen , Wang Shufang , Zhang Zhiling , Gao Weixia , Yang Chao
Published: December 2020

Background

Genome reduction and metabolic engineering have emerged as intensive research hotspots for constructing the promising functional chassis and various microbial cell factories. Surfactin, a lipopeptide-type biosurfactant with broad spectrum antibiotic activity, has wide application prospects in anticancer therapy, biocontrol and bioremediation. Bacillus amyloliquefaciens LL3, previously isolated by our lab, contains an intact srfA operon in the genome for surfactin biosynthesis.

Results

In this study, a genome-reduced strain GR167 lacking ~ 4.18% of the B. amyloliquefaciens LL3 genome was constructed by deleting some unnecessary genomic regions. Compared with the strain NK-1 (LL3 derivative, ΔuppΔpMC1), GR167 exhibited faster growth rate, higher transformation efficiency, increased intracellular reducing power level and higher heterologous protein expression capacity. Furthermore, the chassis strain GR167 was engineered for enhanced surfactin production. Firstly, the iturin and fengycin biosynthetic gene clusters were deleted from GR167 to generate GR167ID. Subsequently, two promoters PRsuc and PRtpxi from LL3 were obtained by RNA-seq and promoter strength characterization, and then they were individually substituted for the native srfA promoter in GR167ID to generate GR167IDS and GR167IDT. The best mutant GR167IDS showed a 678-fold improvement in the transcriptional level of the srfA operon relative to GR167ID, and it produced 311.35 mg/L surfactin, with a 10.4-fold increase relative to GR167.

Conclusions

The genome-reduced strain GR167 was advantageous over the parental strain in several industrially relevant physiological traits assessed and it was highlighted as a chassis strain for further genetic modification. In future studies, further reduction of the LL3 genome can be expected to create high-performance chassis for synthetic biology applications.
Point-of-care cerebrospinal fluid Gram stain for the management of acute meningitis in adults: a retrospective observational study
Authors: Taniguchi Tomohiro , Tsuha Sanefumi , Shiiki Soichi , Narita Masashi
Published: December 2020

Background

Gram stain of cerebrospinal fluid (CSF) is widely used in the diagnosis of acute meningitis, however, it is often conducted in the laboratory, as only some hospitals have access to point-of-care Gram stain (PCGS). The purpose of this study was to demonstrate the clinical impact and utility of PCGS in diagnosing and treating both bacterial and aseptic meningitis in adults.

Methods

This was a hospital-based, retrospective observational study at a referral center in Okinawa, Japan. We reviewed the records of all patients aged 15 years or older who were admitted to the Division of Infectious Diseases between 1995 and 2015 and finally diagnosed with bacterial (n = 34) or aseptic meningitis (n = 97). For bacterial meningitis, we compared the treatments that were actually selected based on PCGS with simulated treatments that would have been based on the Japanese guidelines. For aseptic meningitis, we compared the rates of antibiotic use between real cases where PCGS was available and real cases where it was not.

Results

PCGS was the most precise predictor for differentiating between bacterial and aseptic meningitis (sensitivity 91.2%, specificity 98.9%), being superior in this regard to medical histories, vital signs and physical examinations, and laboratory data available in the emergency room (ER). In bacterial meningitis, PCGS reduced the frequency of meropenem use (1/34 = 3.0%) compared with simulated cases in which PCGS was not available (19/34 = 55.9%) (p< 0.001). In aseptic meningitis cases, the rate of antibiotic administration was lower when PCGS was used (38/97 = 39.2%) than when it was not (45/74 = 60.8%) (p = 0.006).

Conclusions

PCGS of CSF distinguishes between bacterial and aseptic meningitis more accurately than other predictors available in the ER. Patients with bacterial meningitis are more likely to receive narrower-spectrum antimicrobials when PCGS is used than when it is not. PCGS of CSF thus can potentially suppress the empiric use of antimicrobials for aseptic meningitis.
Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles
Authors: Park Dong Jun , Yun Wan Su , Kim Woo Cheol , Park Jeong-Eun , Lee Su Hoon , Ha Sunmok , Choi Jin Sil , Key Jaehong , Seo Young Joon
Published: December 2020

Background

Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules.

Results

The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation.

Conclusions

It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.
Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice
Authors: Zhu Wei Zhong , Olson Aaron , Portman Michael , Ledee Dolena
Published: December 2020

Background

Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice.

Methods

Aged (18–20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting.

Results

Serial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference andp < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways.

Conclusion

We identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction.
Predicting 30-days mortality for MIMIC-III patients with sepsis-3: a machine learning approach using XGboost
Authors: Hou Nianzong , Li Mingzhe , He Lu , Xie Bing , Wang Lin , Zhang Rumin , Yu Yong , Sun Xiaodong , Pan Zhengsheng , Wang Kai
Published: December 2020

Background

Sepsis is a significant cause of mortality in-hospital, especially in ICU patients. Early prediction of sepsis is essential, as prompt and appropriate treatment can improve survival outcomes. Machine learning methods are flexible prediction algorithms with potential advantages over conventional regression and scoring system. The aims of this study were to develop a machine learning approach using XGboost to predict the 30-days mortality for MIMIC-III Patients with sepsis-3 and to determine whether such model performs better than traditional prediction models.

Methods

Using the MIMIC-III v1.4, we identified patients with sepsis-3. The data was split into two groups based on death or survival within 30 days and variables, selected based on clinical significance and availability by stepwise analysis, were displayed and compared between groups. Three predictive models including conventional logistic regression model, SAPS-II score prediction model and XGBoost algorithm model were constructed by R software. Then, the performances of the three models were tested and compared by AUCs of the receiver operating characteristic curves and decision curve analysis. At last, nomogram and clinical impact curve were used to validate the model.

Results

A total of 4559 sepsis-3 patients are included in the study, in which, 889 patients were death and 3670 survival within 30 days, respectively. According to the results of AUCs (0.819 [95% CI 0.800–0.838], 0.797 [95% CI 0.781–0.813] and 0.857 [95% CI 0.839–0.876]) and decision curve analysis for the three models, the XGboost model performs best. The risk nomogram and clinical impact curve verify that the XGboost model possesses significant predictive value.

Conclusions

Using machine learning technique by XGboost, more significant prediction model can be built. This XGboost model may prove clinically useful and assist clinicians in tailoring precise management and therapy for the patients with sepsis-3.
Exploration of predictive and prognostic alternative splicing signatures in lung adenocarcinoma using machine learning methods
Authors: Cai Qidong , He Boxue , Zhang Pengfei , Zhao Zhenyu , Peng Xiong , Zhang Yuqian , Xie Hui , Wang Xiang
Published: December 2020

Background

Alternative splicing (AS) plays critical roles in generating protein diversity and complexity. Dysregulation of AS underlies the initiation and progression of tumors. Machine learning approaches have emerged as efficient tools to identify promising biomarkers. It is meaningful to explore pivotal AS events (ASEs) to deepen understanding and improve prognostic assessments of lung adenocarcinoma (LUAD) via machine learning algorithms.

Method

RNA sequencing data and AS data were extracted from The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database. Using several machine learning methods, we identified 24 pairs of LUAD-related ASEs implicated in splicing switches and a random forest-based classifiers for identifying lymph node metastasis (LNM) consisting of 12 ASEs. Furthermore, we identified key prognosis-related ASEs and established a 16-ASE-based prognostic model to predict overall survival for LUAD patients using Cox regression model, random survival forest analysis, and forward selection model. Bioinformatics analyses were also applied to identify underlying mechanisms and associated upstream splicing factors (SFs).

Results

Each pair of ASEs was spliced from the same parent gene, and exhibited perfect inverse intrapair correlation (correlation coefficient = − 1). The 12-ASE-based classifier showed robust ability to evaluate LNM status of LUAD patients with the area under the receiver operating characteristic (ROC) curve (AUC) more than 0.7 in fivefold cross-validation. The prognostic model performed well at 1, 3, 5, and 10 years in both the training cohort and internal test cohort. Univariate and multivariate Cox regression indicated the prognostic model could be used as an independent prognostic factor for patients with LUAD. Further analysis revealed correlations between the prognostic model and American Joint Committee on Cancer stage, T stage, N stage, and living status. The splicing network constructed of survival-related SFs and ASEs depicts regulatory relationships between them.

Conclusion

In summary, our study provides insight into LUAD researches and managements based on these AS biomarkers.