bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral phenotyping of embryonic development reveals integrative thermodynamic responses
Authors: Tills Oliver , Spicer John I. , Ibbini Ziad , Rundle Simon D.
Published: May 2021

Background

Energy proxy traits (EPTs) are a novel approach to high dimensional organismal phenotyping that quantify the spectrum of energy levels within different temporal frequencies associated with mean pixel value fluctuations from video. They offer significant potential in addressing the phenotyping bottleneck in biology and are effective at identifying lethal endpoints and measuring specific functional traits, but the extent to which they might contribute additional understanding of the phenotype remains unknown. Consequently, here we test the biological significance of EPTs and their responses relative to fundamental thermodynamic principles. We achieve this using the entire embryonic development ofRadix balthica, a freshwater pond snail, at different temperatures (20, 25 & 30 °C) and comparing responses against predictions from Arrhenius’ equation (Q10 = 2).

Results

We find that EPTs are thermally sensitive and their spectra of frequency response enable effective high-dimensional treatment clustering throughout organismal development. Temperature-specific deviation in EPTs from thermodynamic predictions were evident and indicative of physiological mitigation, although they differed markedly in their responses from manual measures. The EPT spectrum was effective in capturing aspects of the phenotype predictive of biological outcomes, and suggest that EPTs themselves may reflect levels of energy turnover.

Conclusions

Whole-organismal biology is incredibly complex, and this contributes to the challenge of developing universal phenotyping approaches. Here, we demonstrate the biological relevance of a new holistic approach to phenotyping that is not constrained by preconceived notions of biological importance. Furthermore, we find that EPTs are an effective approach to measuring even the most dynamic life history stages.
Long-read metagenomics retrieves complete single-contig bacterial genomes from canine feces
Authors: Cuscó Anna , Pérez Daniel , Viñes Joaquim , Fàbregas Norma , Francino Olga
Published: May 2021

Background

Long-read sequencing in metagenomics facilitates the assembly of complete genomes out of complex microbial communities. These genomes include essential biologic information such as the ribosomal genes or the mobile genetic elements, which are usually missed with short-reads. We applied long-read metagenomics with Nanopore sequencing to retrieve high-quality metagenome-assembled genomes (HQ MAGs) from a dog fecal sample.

Results

We used nanopore long-read metagenomics and frameshift aware correction on a canine fecal sample and retrieved eight single-contig HQ MAGs, which were > 90% complete with < 5% contamination, and contained most ribosomal genes and tRNAs. At the technical level, we demonstrated that a high-molecular-weight DNA extraction improved the metagenomics assembly contiguity, the recovery of the rRNA operons, and the retrieval of longer and circular contigs that are potential HQ MAGs. These HQ MAGs corresponded toSuccinivibrio,Sutterella,Prevotellamassilia,Phascolarctobacterium,Catenibacterium, Blautia, andEnterococcusgenera. Linking our results to previous gastrointestinal microbiome reports (metagenome or 16S rRNA-based), we found that some bacterial species on the gastrointestinal tract seem to be more canid-specific –Succinivibrio,Prevotellamassilia,Phascolarctobacterium,Blautia_Asp900541345–, whereas others are more broadly distributed among animal and human microbiomes –Sutterella,Catenibacterium,Enterococcus,andBlautia sp003287895.SutterellaHQ MAG is potentially the first reported genome assembly forSutterella stercoricanis, as assigned by 16S rRNA gene similarity. Moreover, we show that long reads are essential to detect mobilome functions, usually missed in short-read MAGs.

Conclusions

We recovered eight single-contig HQ MAGs from canine feces of a healthy dog with nanopore long-reads. We also retrieved relevant biological insights from these specific bacterial species previously missed in public databases, such as complete ribosomal operons and mobilome functions. The high-molecular-weight DNA extraction improved the assembly’s contiguity, whereas the high-accuracy basecalling, the raw read error correction, the assembly polishing, and the frameshift correction reduced the insertion and deletion errors. Both experimental and analytical steps ensured the retrieval of complete bacterial genomes.
Whole-genome resequencing using next-generation and Nanopore sequencing for molecular characterization of T-DNA integration in transgenic poplar 741
Authors: Chen Xinghao , Dong Yan , Huang Yali , Fan Jianmin , Yang Minsheng , Zhang Jun
Published: May 2021

Background

The molecular characterization information of T-DNA integration is not only required by public risk assessors and regulators, but is also closely related to the expression of exogenous and endogenous genes. At present, with the development of sequencing technology, whole-genome resequencing has become an attractive approach to identify unknown genetically modified events and characterise T-DNA integration events.

Results

In this study, we performed genome resequencing of Pb29, a transgenic high-resistance poplar 741 line that has been commercialized, using next-generation and Nanopore sequencing. The results revealed that there are two T-DNA insertion sites, located at 9,283,905–9,283,937 bp on chromosome 3 (Chr03) and 10,868,777–10,868,803 bp on Chr10. The accuracy of the T-DNA insertion locations and directions was verified using polymerase chain reaction amplification. Through sequence alignment, different degrees of base deletions were detected on the T-DNA left and right border sequences, and in the flanking sequences of the insertion sites. An unknown fragment was inserted between the Chr03 insertion site and the right flanking sequence, but the Pb29 genome did not undergo chromosomal rearrangement. It is worth noting that we did not detect the API gene in the Pb29 genome, indicating that Pb29 is a transgenic line containing only the BtCry1AC gene. On Chr03, the insertion of T-DNA disrupted a gene encoding TAF12 protein, but the transcriptional abundance of this gene did not change significantly in the leaves of Pb29. Additionally, except for the gene located closest to the T-DNA integration site, the expression levels of four other neighboring genes did not change significantly in the leaves of Pb29.

Conclusions

This study provides molecular characterization information of T-DNA integration in transgenic poplar 741 line Pb29, which contribute to safety supervision and further extensive commercial planting of transgenic poplar 741.
Using the geometric average hazard ratio in sample size calculation for time-to-event data with composite endpoints
Authors: Cortés Martínez Jordi , Geskus Ronald B. , Kim KyungMann , Melis Guadalupe Gómez
Published: May 2021

Background

Sample size calculation is a key point in the design of a randomized controlled trial. With time-to-event outcomes, it’s often based on the logrank test. We provide a sample size calculation method for a composite endpoint (CE) based on the geometric average hazard ratio (gAHR) in case the proportional hazards assumption can be assumed to hold for the components, but not for the CE.

Methods

The required number of events, sample size and power formulae are based on the non-centrality parameter of the logrank test under the alternative hypothesis which is a function of the gAHR. We use the web platform, CompARE, for the sample size computations. A simulation study evaluates the empirical power of the logrank test for the CE based on the sample size in terms of the gAHR. We consider different values of the component hazard ratios, the probabilities of observing the events in the control group and the degrees of association between the components. We illustrate the sample size computations using two published randomized controlled trials. Their primary CEs are, respectively, progression-free survival (time to progression of disease or death) and the composite of bacteriologically confirmed treatment failure or Staphylococcus aureus related death by 12 weeks.

Results

For a target power of 0.80, the simulation study provided mean (± SE) empirical powers equal to 0.799 (±0.004) and 0.798 (±0.004) in the exponential and non-exponential settings, respectively. The power was attained in more than 95% of the simulated scenarios and was always above 0.78, regardless of compliance with the proportional-hazard assumption.

Conclusions

The geometric average hazard ratio as an effect measure for a composite endpoint has a meaningful interpretation in the case of non-proportional hazards. Furthermore it is the natural effect measure when using the logrank test to compare the hazard rates of two groups and should be used instead of the standard hazard ratio.
Evaluation by simulation of clinical trial designs for evaluation of treatment during a viral haemorrhagic fever outbreak
Authors: Manchon Pauline , Belhadi Drifa , Mentré France , Laouénan Cédric
Published: May 2021

Background

Viral haemorrhagic fevers are characterized by irregular outbreaks with high mortality rate. Difficulties arise when implementing therapeutic trials in this context. The outbreak duration is hard to predict and can be short compared to delays of trial launch and number of subject needed (NSN) recruitment. Our objectives were to compare, using clinical trial simulation, different trial designs for experimental treatment evaluation in various outbreak scenarios.

Methods

Four type of designs were compared: fixed or group-sequential, each being single- or two-arm. The primary outcome was 14-day survival rate. For single-arm designs, results were compared to a pre-trial historical survival rate pH. Treatments efficacy was evaluated by one-sided tests of proportion (fixed designs) and Whitehead triangular tests (group-sequential designs) with type-I-error = 0.025. Both survival rates in the control arm pC and survival rate differences Δ (including 0) varied. Three specific cases were considered: “standard” (fixed pC, reaching NSN for fixed designs and maximum sample size NMax for group-sequential designs); “changing with time” (increased pC over time); “stopping of recruitment” (epidemic ends). We calculated the proportion of simulated trials showing treatment efficacy, with K = 93,639 simulated trials to get a type-I-error PI95% of [0.024;0.026].

Results

Under H0 (Δ = 0), for the “standard” case, the type-I-error was maintained regardless of trial designs. For “changing with time” case, when pC > pH, type-I-error was inflated, and when pC < pH it decreased. Wrong conclusions were more often observed for single-arm designs due to an increase of Δ over time. Under H1 (Δ = + 0.2), for the “standard” case, the power was similar between single- and two-arm designs when pC = pH. For “stopping of recruitment” case, single-arm performed better than two-arm designs, and fixed designs reported higher power than group-sequential designs. A web R-Shiny application was developed.

Conclusions

At an outbreak beginning, group-sequential two-arm trials should be preferred, as the infected cases number increases allowing to conduct a strong randomized control trial. Group-sequential designs allow early termination of trials in cases of harmful experimental treatment. After the epidemic peak, fixed single-arm design should be preferred, as the cases number decreases but this assumes a high level of confidence on the pre-trial historical survival rate.
Tai Chi exercise improves age‐associated decline in cerebrovascular function: a cross‐sectional study
Authors: Li Lili , Wang Jingjing , Guo Shaoying , Xing Yangqi , Ke Xiongwen , Chen Yinghao , He Yuan , Wang Shun , Wang Jiayu , Cui Xinwu , Wang Zhihua , Tang Lixu
Published: May 2021

Background

Tai Chi exercise has been reported to enhance physical and mental health in the older adults; however, the mechanism remains elusive.

Trial design

We recruited 289 older adults practicing Tai Chi for over 3 years, together with 277 age-matched older and 102 young adults as controls. 168 Tai Chi practitioners were successfully matched to 168 older controls aged 60–69 based on a propensity score for statistics.

Methods

Cerebrovascular function was evaluated by measuring the hemodynamics of the carotid artery. Spearman correlation was performed to validate the age-associated physiological parameters.

Results

Cerebrovascular function in older adults significantly degenerated compared with the young, and was substantially correlated with age. Compared with the older control group, Tai Chi practitioners showed significant improvements in CVHI (cerebral vascular hemodynamics indices) Score (P = 0.002), mean blood flow velocity (P = 0.014), maximal blood flow velocity (P = 0.04) and minimum blood flow velocity (P < 0.001), whereas the age-related increases in pulse wave velocity (P = 0.022), characteristic impedance (P = 0.021) and peripheral resistance (P = 0.044) were lowered.

Conclusions

These data demonstrate a rejuvenation role of Tai Chi in improving the age-related decline of the cerebrovascular function.

Trial registration

Chinese Clinical Trial Registry (ChiCTR1900025187)
Rotavirus gastroenteritis in Pakistan, 2018: updated disease burden
Authors: Basharat Nosheen , Sadiq Asma , Dawood Muhammad , Ali Shahid , Khan Alam , Ullah Rooh , Khan Hayat , Aziz Aamir , Ali Hamid , Shah Aamer Ali , Ali Ijaz , Khan Jadoon
Published: May 2021

Objective

Rotavirus A (RVA) is a significant cause of severe diarrheal illness and one of the common causes of death in children under the age of five. This study was aimed at detecting the prevalence of RVA in Pakistan after rotavirus vaccines were introduced. Fecal samples were obtained from 813 children from different hospitals in Rawalpindi and Islamabad, Pakistan, from January 2018 to December 2018. To obtain additional information from the parents / guardians of the children, a standard questionnaire was used.

Results

Using an enzyme-linked immunosorbent assay kit (ELISA), rotavirus antigen was detected and ELISA positive samples were subjected to reverse transcription PCR (RT-PCR). The findings showed 22% prevalence of RVA in children with acute gastroenteritis (AGE) via ELISA and 21% prevalence via RT-PCR in children with AGE. There was no statistically significant difference between gender, age and RVA infections. The winter, spring and fall/autumn seasons were statistically significant for RVA prevalence.

Conclusion

The present study will provide post vaccine prevalence data for the health policy makers. The implementation of rotavirus vaccines, along with adequate nutrition for babies, clean water supply and maternal hygienic activities during infant feeding, is recommended. Furthermore, continuous surveillance is mandatory in the whole country to calculate the disease burden caused by RVA.
Artificial pneumothorax improves radiofrequency ablation of pulmonary metastases of hepatocellular carcinoma close to mediastinum
Authors: Zuo Taiyang , Lin Wenli , Liu Fengyong , Xu Jinshun
Published: May 2021

Background

To investigate the feasibility, safety and efficacy of percutaneous radiofrequency ablation (RFA) of pulmonary metastases from hepatocellular carcinoma (HCC) contiguous with the mediastinum using the artificial pneumothorax technique.

Method

A total of 40 lesions in 32 patients with pulmonary metastases from HCC contiguous with the mediastinum accepted RFA treatment from August 2014 to May 2018 via the artificial pneumothorax technique. After ablation, clinical outcomes were followed up by contrast enhanced CT. Technical success, local tumor progression (LTP), intrapulmonary distant recurrence (IDR), and adverse events were evaluated. Overall survival (OS) and local tumor progression free survival (LTPFS) were recorded for each patient.

Results

The tumor size was 1.4 ± 0.6 cm in diameter. RFA procedures were all successfully performed without intra-ablative complications. Technical success was noted in 100% of the patients. Five cases of LTP and 8 cases of IDR occurred following the secondary RFA for treatment. Slight pain was reported in all patients. No major complications were observed. The 1, 2, and 3-year LTPFS rates were 90.6, 81.2, and 71.8%, and the 1, 2, and 3-year OS rates were 100, 100 and 87.5%, respectively.

Conclusion

Artificial pneumothorax adjuvant RFA is a feasible, safe, and efficient method for treatment of pulmonary metastases from HCC contiguous with the mediastinum.
Short‐term changes in and preoperative factors affecting vaulting after posterior chamber phakic Implantable Collamer Lens implantation
Authors: Zhu Qiu-Jian , Chen Wen-Jing , Zhu Wei-Jian , Xiao Hai-Xiang , Zhu Man-Hui , Ma Lie , Yuan You , Song E.
Published: May 2021

Background

To describe the very early vault changes in the first month after Implantable Collamer Lens (ICL) implantation and to evaluate the effect of preoperative biometric factors on vault.

Methods

Eighty-three eyes from eighty-three subjects with complete data who met follow-up requirements were recruited in this retrospective study between May 2019 and March 2020. We quantitatively assessed the postoperative vault at 2 h, 1 day, 1 week, and 1 month following implantation. Associations between the postoperative vault and age, ICL size, spherical equivalent (SE), axial length (AL), central corneal thickness (CCT), flat keratometry (K), steep K, mean K, anterior chamber depth (ACD), crystalline lens thickness (LT), white-to-white (WTW) diameter obtained by three devices, horizontal and vertical sulcus-to-sulcus (STS) diameter, bright and dark pupil sizes (BPS and DPS) and DPS-BPS were investigated using Spearman’s correlation analysis and stepwise multiple regression analysis.

Results

The mean vault values at 2 h, 1 day, 1 week, and 1 month after ICL implantation were 672.05 ± 30.72, 389.15 ± 28.33, 517.23 ± 30.76 and 530.12 ± 30.22 μm, respectively. Significant differences were found in the vault values at 2 h, 1 day and 1 week after the operation. The ICL size (β = 0.942; p < 0.001), followed by horizontal STS (β = -0.517; p < 0.001), crystalline LT (β = -0.376; p < 0.001) and vertical STS (β = -0.257; p = 0.017), significantly influenced the vault at 1 month after the operation. The multiple regression equation was expressed as follows: central vault (µm) = -1369.05 + 657.121 × ICL size- 287.408 × horizontal STS − 432.497 × crystalline LT − 137.33 × vertical STS (adjusted R2 = 0.643).

Conclusions

After ICL implantation, the vault decreased and then increased, but it did not return to the vault value 2 h after surgery. The ICL size, horizontal and vertical STS and crystalline LT are key factors for predicting postoperative vaulting.
Intraocular pressure changes after phacoemulsification in pseudoexfoliation versus healthy eyes
Authors: Ramezani Farshid , Nazarian Mohammad , Rezaei Leila
Published: May 2021

Background

Pseudoexfoliation (PXF) syndrome is the most common cause of secondary glaucoma worldwide. This systemic disorder causes further damage to the optic nerve and ultimately increases the need for surgical interventions. Therefore, intraocular pressure (IOP) control is very important in these patients. The aim of this study was to compare IOP changes after phacoemulsification in subjects with PXF syndrome compared to those without this syndrome.

Methods

61 patients were enrolled in this prospective clinical study. Subjects were assigned into two groups based on presence or absence of PXF syndrome. IOP and anterior chamber angle parameters including: angle opening distance (AOD) and trabecular-iris surface area (TISA) measured one day preoperatively and 3 months postoperatively. Intraoperative metrics factors including: infusion fluid usage (IFU), cumulative dissipated energy (CDE) and aspiration time (AT) were obtained from the phacoemulsification machine at the end of each surgery. IOP changes, anterior chamber angle parameters and intraoperative metrics factors were compared between groups.

Results

Mean IOP before surgery was significantly higher in the PXF group (14.70 mm Hg) compared to controls (12.87 mm Hg) (P-value < 0.01). Phacoemulsification decreased IOP in both, but to greater extent in the PXF group (p-value < 0.01). AOD and TISA also increased significantly following surgery in both groups. The results showed that postoperative IOP was negatively correlated with preoperative IOP in both groups (p-value < 0.01). Also, IOP after phacoemulsification was negatively correlated with IFU in the PXF group (p-value = 0.03).

Conclusions

Patients with PXF syndrome exhibited a reduction in IOP and increase in anterior chamber angle parameters after phacoemulsification. We observed a greater IOP reduction in PXF subjects when it was compared to controls. Higher preoperative IOP and intraoperative IFU were associated with more IOP reduction in the PXF group.
Experiences and outcomes of group volunteer befriending with patients with severe mental illness: an exploratory mixed-methods study in Colombia
Authors: Botero-Rodríguez Felipe , Hernandez María Camila , Uribe-Restrepo José Miguel , Cabariqe Camilo , Fung Catherine , Priebe Stefan , Gómez-Restrepo Carlos
Published: May 2021

Background

Improving care for patients with severe mental illness in Latin America requires effective strategies that are low-cost. One such strategy is a volunteering scheme, referred to as befriending, which seeks to support the social integration of patients. Despite positive reports in other world regions, this intervention has not been studied in Latin America. Whilst befriending programmes commonly form patient-volunteer dyads, group arrangements may be an alternative with some benefits. Here, we aim to explore the feasibility, experiences and outcomes of a group volunteer befriending intervention for patients with severe mental illness in Colombia.

Methods

In this exploratory non-controlled study, 10 groups of five individuals were formed, each consisting of three individuals with schizophrenia or bipolar disorder and two volunteers from the community in Bogotá, Colombia. Each group was encouraged to participate together in social activities within their community over a 6-month period. Patients’ quality of life, objective social outcomes, symptom levels and internalised stigma were assessed before and after the intervention. Patients’ and volunteers’ experiences were explored in semi-structured interviews which were analysed using inductive content analysis.

Results

Outcomes were available for 23 patients. Whilst their objective social situation had significantly improved at the end of the intervention, other outcomes did not show statistically significant differences. The interviews with participants revealed positive experiences which fell into five categories: 1) stigma reduction; 2) personal growth; 3) formation of relationships; 4) continuity and sustainability of befriending; 5) acceptability and feasibility of befriending.

Conclusions

A volunteer befriending programme in small groups of two volunteers and three patients is feasible and associated with positive experiences of participants. Such programmes may also improve the objective social situation of patients. This low-cost intervention may be useful for patients with severe mental illnesses in Latin America.

Trial registration

ISRCTN72241383 (Date of Registration: 04/03/2019, retrospectively registered).
Person-centred interventions for problem gaming: a stepped care approach
Authors: Park Jennifer J. , Wilkinson-Meyers Laura , King Daniel L. , Rodda Simone N.
Published: May 2021

Background

Problem gaming is reported by approximately 1–3% of the population and is associated with decreased health and wellbeing. Research on optimal health responses to problem gaming remains limited. This study aimed to identify and describe the key components of a person-centred approach to interventions for problem gaming for individuals who voluntary seek assistance.

Methods

Online interviews were conducted with 20 adults (90% male; Mage = 23y) currently seeking help for problem gaming. The interview protocol was guided by a health care access framework which investigated participants’ experiences and needs related to accessing professional support. Transcripts were analysed in NVivo using qualitative content analysis to systematically classify participant data into the themes informed by this framework.

Results

Participants had mixed views on how the negative consequences of problem gaming could be best addressed. Some indicated problems could be addressed through self-help resources whereas others suggested in-person treatment with a health professional who had expertise in gaming. Participants described the essential components of an effective health service for problem gaming as including: valid and reliable screening tools; practitioners with specialist knowledge of gaming; and access to a multimodal system of intervention, including self-help, internet and in-person options that allow gamers to easily transition between types and intensity of support.

Conclusion

A comprehensive health care approach for interventions for problem gaming is in its infancy, with numerous service access and delivery issues still to be resolved. This study highlights the importance of involving individuals with gaming-related problems in developing solutions that are fit for purpose and address the spectrum of individual preferences and needs. These findings recommend a stepped healthcare system that adheres to evidence-based practice tailored to each individual and the implementation of standard assessment and routine outcome monitoring.
Urban-rural differences in catastrophic health expenditure among households with chronic non-communicable disease patients: evidence from China family panel studies
Authors: Fu Xian-zhi , Sun Qi-wei , Sun Chang-qing , Xu Fei , He Jun-jian
Published: May 2021

Background

The prevalence of chronic non-communicable diseases (NCDs) challenges the Chinese health system reform. Little is known for the differences in catastrophic health expenditure (CHE) between urban and rural households with NCD patients. This study aims to measure the differences above and quantify the contribution of each variable in explaining the urban-rural differences.

Methods

Unbalanced panel data were obtained from the China Family Panel Studies (CFPS) conducted between 2012 and 2018. The techniques of Fairlie nonlinear decomposition and Blinder-Oaxaca decomposition were employed to measure the contribution of each independent variable to the urban-rural differences.

Results

The CHE incidence and intensity of households with NCD patients were significantly higher in rural areas than in urban areas.

The urban-rural differences in CHE incidence increased from 8.07% in 2012 to 8.18% in 2018, while the urban-rural differences in CHE intensity decreased from 2.15% in 2012 to 2.05% in 2018. From 2012 to 2018, the disparity explained by household income and self-assessed health status of household head increased to some extent. During the same period, the contribution of education attainment to the urban-rural differences in CHE incidence decreased, while the contribution of education attainment to the urban-rural differences in CHE intensity increased slightly.

Conclusions

Compared with urban households with NCD patients, rural households with NCD patients had higher risk of incurring CHE and heavier economic burden of diseases. There was no substantial change in urban-rural inequality in the incidence and intensity of CHE in 2018 compared to 2012. Policy interventions should give priority to improving the household income, education attainment and health awareness of rural patients with NCDs.
Exploring the impact of number and type of comorbidities on the risk of severe COPD exacerbations in Korean Population: a Nationwide Cohort Study
Authors: Kim Youngmee , Kim Ye-Jee , Kang Yu Mi , Cho Won-Kyung
Published: May 2021

Background

It is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort. This study focused on severe exacerbations that required hospitalisation or emergency room visits.

Methods

The National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed. Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort). Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort). Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined. A logistic regression model was used to analyse association with exacerbations.

Results

Asthma (1.57 [1.39–1.76] and 1.24 [1.06–1.44]), lung cancer (1.84 [1.30–2.59] and 2.28 [1.54–3.37]), and heart failure (1.39 [1.16–1.67] and 1.52 [1.18–1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively). The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors. High cholesterol levels and body mass index exerted protective effects against exacerbation.

Conclusions

The number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients.
Prolonged antibiotic prophylaxis use in elective orthopaedic surgery – a cross-sectional analysis
Authors: Rohrer Felix , Maurer Anita , Noetzli Hubert , Gahl Brigitta , Limacher Andreas , Hermann Tanja , Bruegger Jan
Published: May 2021

Purpose

Surgical antibiotic prophylaxis (SAP) prevents surgical site infections (SSI). In orthopaedic surgery, the use of prolonged SAP (PSAP) has been reported in daily routine, despite guidelines advising against it. Therefore, we asked: What is the proportion of PSAP use, defined as administration of SAP ≥24 h after elective orthopaedic surgery? Are there patient- and surgery-related predictors of PSAP use?

Methods

This cross-sectional analysis investigated 1292 patients who underwent elective orthopaedic surgery including total joint arthroplasties at one Swiss centre between 2015 and 2017. Patient comorbidities, surgical characteristics and occurrence of SSI at 90 days in PSAP group were compared to the SAP group (< 24 h post-operative).

Results

PSAP use was 12% (155 of 1292). Patient-related factors associated with PSAP compared to the SAP group included older age (63 vs. 58y;p < 0.001), higher BMI (29 vs. 27 kg/m2;p < 0.001), ASA classification ≥3 (31% vs. 17%;p < 0.001) and lung disease (17% vs. 9%;p = 0.002). Surgery-related factors associated with PSAP were use of prosthetics (62% vs. 45%;p < 0.001), surgery of the knee (65% vs. 25%;p < 0.001), longer surgery duration (87 vs. 68 min;p < 0.001) and presence of drains (90% vs. 65%;p < 0.001). All four SSI occurred in the SAP group (0 vs. 4;p = 1.0). Surgeons administered PSAP with varying frequencies; proportions ranged from 0 to 33%.

Conclusion

PSAP use and SSI proportions were lower than reported in the literature. Several patient- and surgery-related factors associated with PSAP use were identified and some were potentially modifiable. Also, experienced surgeons seemed to implement differing approaches regarding the duration of SAP administration.
The evolution of medical students’ preparedness for clinical practice during the transition of graduation: a longitudinal study from the undergraduate to postgraduate periods
Authors: Chaou Chung-Hsien , Yu Shiuan-Ruey , Chang Yu-Che , Ma Shou-De , Tseng Hsu-Min , Hsieh Ming-Ju , Fang Ji-Tseng
Published: May 2021

Background

Graduating from medical school and beginning independent practice appears to be a major transition for medical students across the world. It is often reported that medical graduates are underprepared for independent practice. Most previous studies on undergraduates’ preparedness are cross-sectional. This study aimed to characterize the development and trend of medical students’ preparedness and its association with other objective and subjective indicators from the undergraduate to postgraduate periods.

Methods

This was a prospective cohort study. The participants were recruited and followed from two years before graduation to the postgraduate period. The preparedness for independent practice, professional identity, and teamwork experience were biannually measured using previously validated questionnaires. The participants’ basic demographic information, clinical learning marks from the last two years, and national board exam scores were also collected.

Results

A total of 85 participants completed 403 measurements in the 5 sequential surveys. The mean age at recruitment was 23.6, and 58 % of participants were male. The overall total preparedness score gradually increased from 157.3 (SD=21.2) at the first measurement to 175.5 (SD=25.6) at the fifth measurement. The serial individual preparedness scores revealed both temporal differences within the same learner and individual differences across learners. Despite the variations, a clear, steady increase in the overall average score was observed. Participants were least prepared in the domain of patient management at first, but the score increased in the subsequent measurements. The participants with better final preparedness had better professional identity (p<0.01), better teamwork experience (p < 0.01), and higher average clinical rotation marks (p<0.05).

Conclusions

The preparedness for practice of medical students from the undergraduate to postgraduate periods is associated with their professional identity, teamwork experience, and objective clinical rotation endpoint. Although preparedness generally increases over time, educators must understand that there are temporal fluctuations and individual differences in learners’ preparedness.
Early procedural training increases anesthesiology residents’ clinical production: a comparative pre-post study of the payoff in clinical training
Authors: Bisgaard Claus Hedebo , Rodt Svein Aage , Musaeus Peter , Petersen Jens Aage Kølsen , Rubak Sune Leisgaard Mørck
Published: May 2021

Background

Competency-based education has been shown to enhance clinical skills, improve patient care, and reduce number of complications resulting in a better return on investments. Residents constitute an important workforce at many hospitals. Yet, the effect of training on residents’ contribution to production in patient care is scarcely studied. This study evaluated the effects of early competency-based procedural training on residents’ contribution to patient care in central venous catheterization and spinal and epidural anesthesia.

Methods

The design was a non-randomized cohort study of first-year anesthesiology residents. The intervention group received additional early focused skills training while three control groups received traditional competency-based education. The residents’ contributions to patient care were compared between the intervention group (n = 20), a historical control group (n = 19), and between a contemporary control group (n = 7) and a historical control group (n = 7) from different departments. The residents’ vs specialists’ procedural production share was compared between years within each study group. We calculated specialist time saved compared to the time spent providing additional skills training in the intervention group.

Results

We found statistically significant increases in residents’ vs specialists’ share of total production after the intervention for epidural anesthesia: 2015: 0.51 (0.23, 0.70) to 2017: 0.94 (0.78, 1.05),p = 0.011 and central venous catheterization: 2015: 0.30 (0.23, 0.36) to 2016: 0.46 (0.35, 0.55),p = .008; and to 2017: 0.64 (0.50, 0.79),p = 0.008.

Comparison between residents and specialists on production of the three procedures before and after the intervention showed a surplus of 21 h of freed specialist time per year.

Conclusions

Early procedural training results in more productive residents and freed specialist time for additional supervision, other clinical tasks or research. This provides empirical support for a positive correlation between early focused training and increased independent production among residents.
Sales and pricing decisions for HIV self-test kits among local drug shops in Tanzania: a prospective cohort study
Authors: Chiu Calvin , Hunter Lauren A. , McCoy Sandra I. , Mfaume Rashid , Njau Prosper , Liu Jenny X.
Published: May 2021

Background

Public health initiatives must look for ways to cost-effectively scale critical interventions to achieve high coverage. Private sector distribution channels, can potentially distribute preventive healthcare products to hard-to-reach populations, decongest public healthcare systems, and increase the sustainability of programs by getting customers to share costs. However, little is known about how sellers set prices for new products. By introducing a new product, HIV self-test kits, to local drug shops, we observed whether shops experimented with pricing, charged different buyers different prices, and whether prices converged within the local market over our study period.

Methods

From August to December 2019, we provided free HIV self-test kits, a new product, to 26 drug shops in Shinyanga, Tanzania to sell to the local community. We measured sales volume, price, customer age and sex using shop records. Using a multiple linear regression model, we conducted F-tests to determine whether shop, age, sex, and time (week) respectively were associated with price. We measured willingness-to-pay to restock test kits at the end of the study.

Results

514 test kits were sold over 18 weeks; 69% of buyers were male, 40% were aged 25–34 and 32% aged 35–44. Purchase prices ranged from 1000 to 6000 Tsh (median 3000 Tsh; ~$1.30 USD). Within shops, prices were 11.3% higher for 25–34 and 12.7% higher for 45+ year olds relative to 15–19-year olds (p = 0.029) and 13.5% lower for men (p = 0.023) on average. Although prices varied between shops, prices varied little within shops over time, and did not converge over the study period or cluster geospatially. Mean maximum willingness-to-pay to restock was 2000 Tsh per kit.

Conclusions

Shopkeepers charged buyers different prices depending on buyers’ age and sex. There was limited variation in prices within shops over time and low demand among shopkeepers to restock at the end of the study. Given the subsidized global wholesale price ($2 USD or ~ 4600 Tsh), further demand creation and/or cost-reduction is required before HIV self-test kits can become commercially viable in drug shops in this setting. Careful consideration is needed to align the motivations of retailers with public health priorities while meeting their private for-profit needs.
The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials
Authors: O’Driscoll C. , Buckman J. E. J. , Fried E. I. , Saunders R. , Cohen Z. D. , Ambler G. , DeRubeis R. J. , Gilbody S. , Hollon S. D. , Kendrick T. , Kessler D. , Lewis G. , Watkins E. , Wiles N. , Pilling S.
Published: May 2021

Background

Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes.

Method

Individual patient data from six RCTs of depressed patients (totaln = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators.

Results

Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms.

Conclusion

The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.
circ_NRIP1 is oncogenic in malignant development of esophageal squamous cell carcinoma (ESCC) via miR-595/SEMA4D axis and PI3K/AKT pathway
Authors: Zhou Shifan , Guo Zhizhong , Zhou Chaofeng , Zhang Yu , Wang Sai
Published: May 2021

Background

The hsa_circ_0004771 derived from NRIP1 (called circ_NRIP1) is a recently identified oncogenic circRNA. Here, we intended to investigate the role and mechanism of circ_NRIP1 in esophageal squamous cell carcinoma (ESCC), a prevalent and aggressive type of esophageal cancer.

Methods

Expression of circ_NRIP1, miRNA-595-5p (miR-595) and semaphorin 4D (SEMA4D) was detected by RT-qPCR and western blotting. Cell growth was assessed by colony formation assay, MTS assay, flow cytometry, and xenograft experiment; migration and invasion were evaluated by transwell assay and western blotting. Dual-luciferase reporter assay identified the relationship among circ_NRIP1, miR-595 and SEMA4D. Western blotting measured phosphatidylinositol-3-hydroxykinase (PI3K)/AKT pathway-related proteins.

Results

Expression of circ_NRIP1 was upregulated in ESCC tissues and cells. Knockdown of circ_NRIP1 could enhance apoptosis rate and E-cadherin expression, but suppress colony formation, cell viability, migration, invasion, and snail expression in KYSE30 and KYSE450 cells, as well as retarded tumor growth in mice. The suppressive role of circ_NRIP1 knockdown in cell growth, migration and invasion in vitro was abated by blocking miR-595; meanwhile, miR-595 overexpression elicited similar anti-tumor role in KYSE30 and KYSE450 cells, which was abrogated by restoring SEMA4D. Notably, circ_NRIP1 was a sponge for miR-595, and SEMA4D was a target of miR-595. Besides, PI3K/AKT signal was inhibited by circ_NRIP1 knockdown and/or miR-595 overexpression via indirectly or directly regulating SEMA4D.

Conclusion

circ_NRIP1 functioned as an oncogene in ESCC, and modulated ESCC cell growth, migration and invasion both in vitro and in vivo via targeting miR-595/SEMA4D axis and inhibiting PI3K/AKT signaling pathway.
Emulating causal dose-response relations between air pollutants and mortality in the Medicare population
Authors: Wei Yaguang , Yazdi Mahdieh Danesh , Di Qian , Requia Weeberb J. , Dominici Francesca , Zanobetti Antonella , Schwartz Joel
Published: May 2021

Background

Fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) are major air pollutants that pose considerable threats to human health. However, what has been mostly missing in air pollution epidemiology is causal dose-response (D-R) relations between those exposures and mortality. Such causal D-R relations can provide profound implications in predicting health impact at a target level of air pollution concentration.

Methods

Using national Medicare cohort during 2000–2016, we simultaneously emulated causal D-R relations between chronic exposures to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) and all-cause mortality. To relax the contentious assumptions of inverse probability weighting for continuous exposures, including distributional form of the exposure and heteroscedasticity, we proposed a decile binning approach which divided each exposure into ten equal-sized groups by deciles, treated the lowest decile group as reference, and estimated the effects for the other groups. Binning continuous exposures also makes the inverse probability weights robust against outliers.

Results

Assuming the causal framework was valid, we found that higher levels of PM2.5, O3, and NO2 were causally associated with greater risk of mortality and that PM2.5 posed the greatest risk. For PM2.5, the relative risk (RR) of mortality monotonically increased from the 2nd (RR, 1.022; 95% confidence interval [CI], 1.018–1.025) to the 10th decile group (RR, 1.207; 95% CI, 1.203–1.210); for O3, the RR increased from the 2nd (RR, 1.050; 95% CI, 1.047–1.053) to the 9th decile group (RR, 1.107; 95% CI, 1.104–1.110); for NO2, the DR curve wiggled at low levels and started rising from the 6th (RR, 1.005; 95% CI, 1.002–1.018) till the highest decile group (RR, 1.024; 95% CI, 1.021–1.027).

Conclusions

This study provided more robust evidence of the causal relations between air pollution exposures and mortality. The emulated causal D-R relations provided significant implications for reviewing the national air quality standards, as they inferred the number of potential early deaths prevented if air pollutants were reduced to specific levels; for example, lowering each air pollutant concentration from the 70th to 60th percentiles would prevent 65,935 early deaths per year.