bluuebunny/crossref_metadata_2025 huggingface dataset:
Short- to Midterm Clinical and Radiological Outcomes After Matrix-Associated Autologous Chondrocyte Implantation for Chondral Defects in Knees
Authors: Dai Xuesong , Fang Jinghua , Wang Siheng , Luo Jianyang , Xiong Yan , Zhang Miaofeng , Zhu Sunan , Yu Xinning
Published: February 2021

Background:

Matrix-associated autologous chondrocyte implantation (MACI) has been proven to provide favorable short-term results for chondral defects in knees. However, it remains unclear whether the clinical benefits of MACI persist in the longer term.

Purpose:

The purpose of this prospective study was to evaluate the clinical and radiological outcomes, at short- and midterm follow-up, for patients undergoing MACI for focal chondral defects of the knee.

Study Design:

Case series; Level of evidence, 4.

Methods:

A total of 30 consecutive patients (31 knees) were treated using MACI between October 2010 and March 2018. There were 24 male patients and 6 female patients with an average age of 26 years (range, 12-48 years). The areas of the cartilage defect were consistently >2 cm2. All patients underwent MACI for a focal chondral defect of the femoral condyles or trochlea in the knee. These patients had been evaluated for up to 5 years, with an average follow-up of 44 months (range, 6-60 months) postoperatively. The International Knee Documentation Committee (IKDC) score, Lysholm score, and magnetic resonance imaging (MRI) with T2 mapping were used to assess the outcomes.

Results:

No patients were lost to follow-up. Mean IKDC scores improved from 58.6 (range, 40.2-80.5) to 79.1 (range, 39.1-94.3) at 12 months and up to 88.4 (range, 83.9-100) at 5 years; mean Lysholm scores improved from 67.3 (range, 46-95) to 90.6 (range, 71-100) at 12 months and up to 95.9 (range, 85-100) at 5 years. The MRI with T2 mapping value of the transplanted area was evaluated for 21 knees, which revealed no differences compared with the normal area at 12 months postoperatively.

Conclusion:

From the first year onward, the clinical outcome scores and MRI with T2 mapping values showed continuous and marked improvement, suggesting that MACI is a valid option for localized cartilage defects in the knee.
A Personal Perspective on Patient Involvement in Educating Health Care Providers: From Two Lenses
Authors: Adam Holly L
Published: February 2021

This article provides my perspective on the importance of hearing and integrating patients’ voices in the education of health care providers from 2 lenses, as a patient and as a nurse. It highlights why and how patients should be actively involved in health professions education. It is important that health care professions be reminded that patients want to be involved in health professions education; this will enable them to establish meaningful partnerships with patients along the continuum of their education, as well as improve upon their delivery of patient-centred care.
Double-edged effects of work-related technology use after hours on employee well-being and recovery: The role of appraisal and its determinants
Authors: Reinke Kathrin , Ohly Sandra
Published: February 2021

Research suggests that work-related use of information and communication technologies (ICTs) after hours involves both harms and benefits for employee well-being. Yet, these findings are mainly based on examining the extent of ICT use as the focal construct of interest. Based on cognitive appraisal theories of stress, we argue that research needs to include individuals’ evaluation of their work-related ICT use after hours as well as the conditions shaping this appraisal to explain double-edged effects of ICT use on well-being. Thus, we investigate (1) how situational and personal factors influence whether work-related ICT use after hours is evaluated as positive or negative, and (2) how these factors and ICT use appraisal relate to employee well-being and recovery, beyond the extent of ICT use. We collected data in a daily diary study over five consecutive days. Multilevel path analyses with data from 51 employees and 151 daily observations indicated that goal progress and autonomous motivation for ICT use were positively related to positive ICT use appraisal. Besides, goal progress predicted less and overload predicted more negative ICT use appraisal. In turn, ICT use appraisal was associated with employees’ affective states and psychological detachment in the evening, beyond the extent of ICT use. Additionally, we found several indirect effects of goal progress and overload on employee well-being and recovery via ICT use appraisal. Our findings emphasize the need to investigate ICT usage experiences to explain the double-edged consequences of work-related ICT use after hours on employee well-being.
Financing resilience efforts to confront future urban and sea-level rise flooding: Are coastal megacities in Association of Southeast Asian Nations doing enough?
Authors: Causevic Amar , LoCastro Matthew , David Dharish , Selvakkumaran Sujeetha , Gren Åsa
Published: February 2021

Continued greenhouse gas emissions will lead to a rise in temperatures, accompanied by rising sea levels threatening low-lying coastal cities. This vulnerability is especially acute in developing countries’ cities. This study reviews whether Bangkok, Manila, and Jakarta, less prepared emerging urban centers of developing countries, are investing in adaptation projects for resilience against sea-level rise and urban flooding. Sea-level rise and urban flooding resilience projects were identified in the selected cities through secondary research methods, data on multilateral climate funds, and other aggregated funding databases such as Aid Atlas, Cities Adaptation Action, and City Risk Index. Our findings show that even though these cities do have some adaptation projects to address coastal flooding and rising sea-level threats, the funding has been disparate and dispersed due to a lack of continuous, sizeable, and diverse financing options and does not come close to the requirement, given the risks, of covering potential disaster-related losses. Our findings further highlight the need to expand financing beyond multilateral funds and bilateral funding agreements and to include financial mechanisms that incentivize potential stakeholders to invest in projects that ordinarily are considered nonrevenue generating.
Hearing Impaired Participants Improve More Under Envelope-Transcranial Alternating Current Stimulation When Signal to Noise Ratio Is High
Authors: Erkens Jules , Schulte Michael , Vormann Matthias , Wilsch Anna , Herrmann Christoph S
Published: February 2021

An issue commonly expressed by hearing aid users is a difficulty to understand speech in complex hearing scenarios, that is, when speech is presented together with background noise or in situations with multiple speakers. Conventional hearing aids are already designed with these issues in mind, using beamforming to only enhance sound from a specific direction, but these are limited in solving these issues as they can only modulate incoming sound at the cochlear level. However, evidence exists that age-related hearing loss might partially be caused later in the hearing processes due to brain processes slowing down and becoming less efficient. In this study, we tested whether it would be possible to improve the hearing process at the cortical level by improving neural tracking of speech. The speech envelopes of target sentences were transformed into an electrical signal and stimulated onto elderly participants’ cortices using transcranial alternating current stimulation (tACS). We compared 2 different signal to noise ratios (SNRs) with 5 different delays between sound presentation and stimulation ranging from 50 ms to 150 ms, and the differences in effects between elderly normal hearing and elderly hearing impaired participants. When the task was performed at a high SNR, hearing impaired participants appeared to gain more from envelope-tACS compared to when the task was performed at a lower SNR. This was not the case for normal hearing participants. Furthermore, a post-hoc analysis of the different time-lags suggest that elderly were significantly better at a stimulation time-lag of 150 ms when the task was presented at a high SNR. In this paper, we outline why these effects are worth exploring further, and what they tell us about the optimal tACS time-lag.
Enhanced homology-directed repair for highly efficient gene editing in hematopoietic stem/progenitor cells
Authors: De Ravin Suk See , Brault Julie , Meis Ronald J. , Liu Siyuan , Li Linhong , Pavel-Dinu Mara , Lazzarotto Cicera R. , Liu Taylor , Koontz Sherry M. , Choi Uimook , Sweeney Colin L. , Theobald Narda , Lee GaHyun , Clark Aaron B. , Burkett Sandra S. , Kleinstiver Benjamin P. , Porteus Matthew H. , Tsai Shengdar , Kuhns Douglas B. , Dahl Gary A. , Headey Stephen , Wu Xiaolin , Malech Harry L.
Published: February 2021

Lentivector gene therapy for X-linked chronic granulomatous disease (X-CGD) has proven to be a viable approach, but random vector integration and subnormal protein production from exogenous promoters in transduced cells remain concerning for long-term safety and efficacy. A previous genome editing–based approach using Streptococcus pyogenes Cas9 mRNA and an oligodeoxynucleotide donor to repair genetic mutations showed the capability to restore physiological protein expression but lacked sufficient efficiency in quiescent CD34+ hematopoietic cells for clinical translation. Here, we report that transient inhibition of p53-binding protein 1 (53BP1) significantly increased (2.3-fold) long-term homology-directed repair to achieve highly efficient (80% gp91phox+ cells compared with healthy donor control subjects) long-term correction of X-CGD CD34+ cells.
Effectiveness of community and school-based sanitation interventions in improving latrine coverage: a systematic review and meta-analysis of randomized controlled interventions
Authors: Igaki Satoshi , Duc Nguyen Tran Minh , Nam Nguyen Hai , Nga Tran Thi Tuyet , Bhandari Parshal , Elhamamsy Amr , Lotify Caroline Ibrahim , Hewalla Mostafa Elsayed , Tawfik Gehad Mohamed , Mathenge Peterson Gitonga , Hashizume Masahiro , Huy Nguyen Tien
Published: February 2021

Introduction

Approximately 1000 children die each year due to preventable water and sanitation-related diarrheal diseases. Six in 10 people lacked access to safely managed sanitation facilities in 2015. Numerous community- and school-based approaches have been implemented to eradicate open defecation practices, promote latrine ownership, improve situation sanitation, and reduce waterborne disease.

Objective

Given that current evidence for sanitation interventions seem promising, the aim of this study was to systematically summarize existing research on the effectiveness of community- and school-based randomized controlled sanitation intervention in improving (1) free open defecation (safe feces disposal), (2) latrine usage, (3) latrine coverage or access, and (4) improved latrine coverage or access.

Methods

Eight electronic databases were searched: PubMed, Scopus, WHO Global Health Library (GHL), Virtual Health Library (VHL), POPLINE, Web of Science, Cochrane, and Google Scholar up to 26 April 2019. Original randomized clinical trials addressing community-based or school-based intervention that reported feces disposal and latrine coverage were deemed eligible. More than two researchers independently contributed to screening of papers, data extraction, and bias assessment. We conducted a meta-analysis by random-effects model. The risk of bias was assessed by the Cochrane risk of bias tool.

Results

Eighteen papers that matched all criteria and 16 studies were included in the final meta-analysis. Compared to the control, the sanitation intervention significantly increased safe feces disposal (OR 2.19, 95% CI 1.51–3.19,p< 0.05,I2= 97.28), latrine usage (OR 3.72, 95% CI 1.71–8.11,p< 0.05,I2= 91.52), latrine coverage or access (OR 3.95, 95% CI 2.08–7.50,p< 0.05,I2= 99.07), and improved latrine coverage or access (OR 3.68, 95% CI 1.52–8.91,p< 0.05,I2= 99.11). A combination of education and latrine construction was more effective compared to educational intervention alone.

Conclusion

Our study showed strong evidence for both community- and school-based sanitation interventions as effective for the safe disposal of human excreta. The finding suggests major implications for health policy and design of future intervention in developing countries.
Benchmarking workflows to assess performance and suitability of germline variant calling pipelines in clinical diagnostic assays
Authors: Krishnan Vandhana , Utiramerur Sowmithri , Ng Zena , Datta Somalee , Snyder Michael P. , Ashley Euan A.
Published: February 2021

Background

Benchmarking the performance of complex analytical pipelines is an essential part of developing Lab Developed Tests (LDT). Reference samples and benchmark calls published by Genome in a Bottle (GIAB) consortium have enabled the evaluation of analytical methods. The performance of such methods is not uniform across the different genomic regions of interest and variant types. Several benchmarking methods such as hap.py, vcfeval, and vcflib are available to assess the analytical performance characteristics of variant calling algorithms. However, assessing the performance characteristics of an overall LDT assay still requires stringing together several such methods and experienced bioinformaticians to interpret the results. In addition, these methods are dependent on the hardware, operating system and other software libraries, making it impossible to reliably repeat the analytical assessment, when any of the underlying dependencies change in the assay. Here we present a scalable and reproducible, cloud-based benchmarking workflow that is independent of the laboratory and the technician executing the workflow, or the underlying compute hardware used to rapidly and continually assess the performance of LDT assays, across their regions of interest and reportable range, using a broad set of benchmarking samples.

Results

The benchmarking workflow was used to evaluate the performance characteristics for secondary analysis pipelines commonly used by Clinical Genomics laboratories in their LDT assays such as the GATK HaplotypeCaller v3.7 and the SpeedSeq workflow based on FreeBayes v0.9.10. Five reference sample truth sets generated by Genome in a Bottle (GIAB) consortium, six samples from the Personal Genome Project (PGP) and several samples with validated clinically relevant variants from the Centers for Disease Control were used in this work. The performance characteristics were evaluated and compared for multiple reportable ranges, such as whole exome and the clinical exome.

Conclusions

We have implemented a benchmarking workflow for clinical diagnostic laboratories that generates metrics such as specificity, precision and sensitivity for germline SNPs and InDels within a reportable range using whole exome or genome sequencing data. Combining these benchmarking results with validation using known variants of clinical significance in publicly available cell lines, we were able to establish the performance of variant calling pipelines in a clinical setting.
Elucidation of molecular and hormonal background of early growth cessation and endodormancy induction in two contrasting Populus hybrid cultivars
Authors: Boldizsár Ákos , Soltész Alexandra , Tanino Karen , Kalapos Balázs , Marozsán-Tóth Zsuzsa , Monostori István , Dobrev Petre , Vankova Radomira , Galiba Gábor
Published: February 2021

Background

Over the life cycle of perennial trees, the dormant state enables the avoidance of abiotic stress conditions. The growth cycle can be partitioned into induction, maintenance and release and is controlled by complex interactions between many endogenous and environmental factors. While phytohormones have long been linked with dormancy, there is increasing evidence of regulation by DAM and CBF genes. To reveal whether the expression kinetics of CBFs and their target PtDAM1 is related to growth cessation and endodormancy induction in Populus, two hybrid poplar cultivars were studied which had known differential responses to dormancy inducing conditions.

Results

Growth cessation, dormancy status and expression of six PtCBFs and PtDAM1 were analyzed. The ‘Okanese’ hybrid cultivar ceased growth rapidly, was able to reach endodormancy, and exhibited a significant increase of several PtCBF transcripts in the buds on the 10th day. The ‘Walker’ cultivar had delayed growth cessation, was unable to enter endodormancy, and showed much lower CBF expression in buds. Expression of PtDAM1 peaked on the 10th day only in the buds of ‘Okanese’. In addition, PtDAM1 was not expressed in the leaves of either cultivar while leaf CBFs expression pattern was several fold higher in ‘Walker’, peaking at day 1. Leaf phytohormones in both cultivars followed similar profiles during growth cessation but differentiated based on cytokinins which were largely reduced, while the Ox-IAA and iP7G increased in ‘Okanese’ compared to ‘Walker’. Surprisingly, ABA concentration was reduced in leaves of both cultivars. However, the metabolic deactivation product of ABA, phaseic acid, exhibited an early peak on the first day in ‘Okanese’.

Conclusions

Our results indicate that PtCBFs and PtDAM1 have differential kinetics and spatial localization which may be related to early growth cessation and endodormancy induction under the regime of low night temperature and short photoperiod in poplar. Unlike buds, PtCBFs and PtDAM1 expression levels in leaves were not associated with early growth cessation and dormancy induction under these conditions. Our study provides new evidence that the degradation of auxin and cytokinins in leaves may be an important regulatory point in a CBF-DAM induced endodormancy. Further investigation of other PtDAMs in bud tissue and a study of both growth-inhibiting and the degradation of growth-promoting phytohormones is warranted.
Genome-wide search and structural and functional analyses for late embryogenesis-abundant (LEA) gene family in poplar
Authors: Cheng Zihan , Zhang Xuemei , Yao Wenjing , Zhao Kai , Liu Lin , Fan Gaofeng , Zhou Boru , Jiang Tingbo
Published: February 2021

Background

The Late Embryogenesis-Abundant (LEA) gene families, which play significant roles in regulation of tolerance to abiotic stresses, widely exist in higher plants. Poplar is a tree species that has important ecological and economic values. But systematic studies on the gene family have not been reported yet in poplar.

Results

On the basis of genome-wide search, we identified 88 LEA genes from Populus trichocarpa and renamed them as PtrLEA. The PtrLEA genes have fewer introns, and their promoters contain more cis-regulatory elements related to abiotic stress tolerance. Our results from comparative genomics indicated that the PtrLEA genes are conserved and homologous to related genes in other species, such as Eucalyptus robusta, Solanum lycopersicum and Arabidopsis. Using RNA-Seq data collected from poplar under two conditions (with and without salt treatment), we detected 24, 22 and 19 differentially expressed genes (DEGs) in roots, stems and leaves, respectively. Then we performed spatiotemporal expression analysis of the four up-regulated DEGs shared by the tissues, constructed gene co-expression-based networks, and investigated gene function annotations.

Conclusion

Lines of evidence indicated that the PtrLEA genes play significant roles in poplar growth and development, as well as in responses to salt stress.
Effect of implantation site of the His bundle pacing leads on pacing parameters: a single-center experience
Authors: Tang Oushan , Zhou Haoliang , Yuan Caidi , Cheng Yinhong , Lv Jin
Published: February 2021

Background

HB pacing is a promising approach to achieve physiological pacing, but its efficacy and long-term effects require further validation. In current study, we deemed to investigate the effect of the His bundle pacing (HBP) lead location on pacing parameters.

Methods

2D echocardiography imaging was performed after successful implantation, according to which the patients were divided into groups A (whose His lead tips were at the atrial side) and B (whose His lead tips were at the ventricular side). The capture thresholds, sensing values, and H-V intervals between the two groups were compared.

Results

Thirteen patients were in group A and 16 patients were in group B. The average capture thresholds during, 1 month, and 1 year after operation were 1.20 ± 0.34, 0.69 ± 0.29, and 0.92 ± 0.80 V/0.5 ms for group A and 1.14 ± 0.43, 0.81 ± 0.39, and 0.98 ± 0.59 V/0.5 ms for group B, respectively. The difference between the two groups was not significant. The threshold values in both groups decreased significantly in 1 month and slightly increased in 1 year. The sensing values of group A were 1.87 ± 0.82, 1.95 ± 0.76, and 1.88 ± 0.75 mV, while those of group B were 4.53 ± 1.37, 4.69 ± 1.38, and 4.59 ± 1.42 mV. The difference among the three time points was not significant. However, the sensing values in group A were consistently significantly lower than those in group B. The HV interval in group A was significantly longer than that in group B.

Conclusions

The implantation site of HBP leads has a significant effect on sensing values for that His leads crossing the tricuspid annulus toward the ventricle are associated with higher sensing values, compared to a more proximal location. Meanwhile, lead location has no evident effect on capture thresholds that is improved significantly shortly after operation.
Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis
Authors:   on behalf of the Sichuan & Wuhan Collaboration Research Group, and Sichuan Treatment Expert Group for COVID-19, China, Wang Gang , Luo Feng Ming , Liu Dan , Liu Jia Sheng , Wang Ye , Chen Hong , Tian Pan Wen , Fan Tao , Tang Li , Yu He , Wang Lan , Feng Mei , Ni Zhong , Wang Bo , Song Zhi Fang , Wu Xiao Ling , Wang Hong Jun , Tong Xiang , Xue Miao , Lei Xian Ying , Long Bo , Jia Chao , Xiao Jun , Shang Juan , Xiong Nian , Luo Jian Fei , Liang Zong An , Li Wei Min
Published: February 2021

Background

There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic.

Methods

The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes.

Results

The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64).

Conclusions

The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.
Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial
Authors:   for the ACTG A5300/IMPAACT I2003 PHOENIx Feasibility study team, Demers Anne-Marie , Kim Soyeon , McCallum Sara , Eisenach Kathleen , Hughes Michael , Naini Linda , Mendoza-Ticona Alberto , Pradhan Neeta , Narunsky Kim , Poongulali Selvamuthu , Badal-Faesen Sharlaa , Upton Caryn , Smith Elizabeth , Shah N. Sarita , Churchyard Gavin , Gupta Amita , Hesseling Anneke , Swindells Susan
Published: February 2021

Background

Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

Methods

As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability.

Results

Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens.

Conclusions

RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.
Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes
Authors: Beddhu Srinivasan , Boucher Robert E. , Sun Jie , Balu Niranjan , Chonchol Michel , Navaneethan Sankar , Chertow Glenn M. , Townsend Raymond , Haley William , Cheung Alfred K. , Conroy Molly B. , Raj Dominic S. , Xu Dongxiang , George Thomas , Yunis Reem , Wei Guo , Canton Gador , Bates Jeffrey , Chen Jing , Papademetriou Vasilios , Punzi Henry , Wiggers Alan , Wright Jackson T. , Greene Tom , Yuan Chun
Published: February 2021

Background

It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events.

Methods

In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial.

(SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint.

Results

One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events.

Conclusions

Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening.

Trial Registration

NCT01475747, registered on November 21, 2011.
Correction to: High fascin-1 expression in colorectal cancer identifies patients at high risk for early disease recurrence and associated mortality
Authors: Tampakis Athanasios , Tampaki Ekaterini-Christina , Nonni Afrodite , Kostakis Ioannis D. , Posabella Alberto , Kontzoglou Konstantinos , von Flüe Markus , Felekouras Evangelos , Kouraklis Gregory , Nikiteas Nikolaos
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Elevated glucose level leads to rapid COVID-19 progression and high fatality
Authors: Wang Wenjun , Shen Mingwang , Tao Yusha , Fairley Christopher K. , Zhong Qin , Li Zongren , Chen Hui , Ong Jason J. , Zhang Dawei , Zhang Kai , Xing Ning , Guo Huayuan , Qin Enqiang , Guan Xizhou , Yang Feifei , Zhang Sibing , Zhang Lei , He Kunlun
Published: February 2021

Objectives

We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients.

Methods

We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality.

Results

The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8–5.5), 3.0 (1.0–7.0), 3.0 (1.0–8.0), and 6.5 (4.0–16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19.

Conclusions

Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.
Consumption of antidiabetic medicines in Portugal: results of a temporal data analysis of a thirteen‐year study (2005–2017)
Authors: Moura Artur Mendes , Martins Sofia Oliveira , Raposo João Filipe
Published: February 2021

Background

Studies of drug utilization in patients with diabetes, a chronic disease that can be treated with a wide range of available medicines, have attracted substantial social and clinical interest.

Objective

To characterize antidiabetic medicine consumption between 2005 and 2017, to evaluate the trends of these medicines in mainland Portugal, and to compare district consumption. An additional objective was to perform a statistical analysis on drug consumption in different regions of Portugal.

Methods

A descriptive, longitudinal observational study; the setting was mainland Portugal ( excluding Azores and Madeira).

Each medicine has a respective defined daily dose (DDD). The sum of the DDD, provides the annual consumption in terms of the DDD for each district each year. When calculating the annual average for the resident district population and the number of days in a year, the denominator is expressed as 1000 inhabitants per day (TID).

Main outcome measure: The DDD/TID for mainland Portugal (for all districts) between 2005 and 2017 for antidiabetic medicines.

Information was obtained from the official database of prescription medicine invoices with reimbursement in mainland Portugal.

Results

In mainland Portugal, the antidiabetic medicine consumption was 49.3 DDD/TID in 2005 and 88.2 DDD/TID in 2017. The consumption of insulins and their analogs increased from 10.8% to 17.4% compared to the total consumption of antidiabetic medicines.

In 2017, the level of biguanide consumption was 23.1 DDD/TID, that of sulphonylurea consumption was 15.8 DDD/TID, that of DPP-4 inhibitor consumption was 6.8 DDD/TID, and that of SGLT2 inhibitor consumption was 3.0 DDD/TID. The oral consumption of fixed-dose combinations reached 21.4 DDD/TID.

After employing a geographical division between north and south and between coastal and inland regions, the consumption of several different drugs showed statistically significant differences.

Conclusions

When comparing 2017 with 2005, the panorama was quite different, with higher levels of consumption of antidiabetic medicines, insulins and their analogs, noninsulin medicines, long-acting and fast-acting insulins and their analogs, metformin, DPP-4 inhibitors and, mainly, metformin combined with a DPP-4 inhibitor. The SGLT2 inhibitors achieved a representative consumption.

Different consumption patterns may be related to sociodemographic factors or to clinical practices.
Guideline-based quality assurance: a conceptual framework for the definition of key elements
Authors: Parmelli Elena , Langendam Miranda , Piggott Thomas , Adolfsson Jan , Akl Elie A. , Armstrong David , Braithwaite Jeffrey , Brignardello-Petersen Romina , Follmann Markus , Leś Zbigniew , Meerpohl Joerg J. , Neamtiu Luciana , Qaseem Amir , Rossi Paolo Giorgi , Saz-Parkinson Zuleika , van der Wees Philip J. , Schünemann Holger J.
Published: February 2021

Background

In 2017, the European Commission’s Joint Research Centre (JRC) started developing a methodological framework for a guideline-based quality assurance (QA) scheme to improve cancer quality of care. During the first phase of the work, inconsistency emerged about the use of terminology for the definition, the conceptual underpinnings and the way QA relates to health questions that are answered in guidelines.

The objective of this final of three articles is to propose a conceptual framework for an integrated approach to guideline and QA development and clarify terms and definitions for key elements. This work will inform the upcoming European Commission Initiative on Colorectal Cancer (ECICC).

Methods

A multidisciplinary group of 23 experts from key organizations in the fields of guideline development, performance measurement and quality assurance participated in a mixed method approach including face-to-face dialogue and several rounds of virtual meetings. Informed by results of a systematic literature review that indicated absence of an existing framework and practical examples, we first identified the relations of key elements in guideline-based QA and then developed appropriate concepts and terminology to provide guidance.

Results

Our framework connects the three key concepts of quality indicators, performance measures and performance indicators integrated with guideline development. Quality indicators are constructs used as a guide to monitor, evaluate, and improve the quality of the structure, process and outcomes of healthcare services; performance measures are tools that quantify or describe measurable elements of practice performance; and performance indicators are quantifiable and measurable units or scores of practice, which should be guided by guideline recommendations.

Conclusions

The inconsistency in the way key terms of QA are used and defined has confused the field. Our conceptual framework defines the role, meaning and interactions of the key elements for improving quality in healthcare. It directly builds on the questions asked in guidelines and answered through recommendations. These findings will be applied in the forthcoming ECICC and for the future updates of ECIBC. These are large-scale integrated projects aimed at improving healthcare quality across Europe through the development of guideline-based QA schemes; this will help in implementing and improving our approach.
Impact of COVID-19 on health services utilization in Province-2 of Nepal: a qualitative study among community members and stakeholders
Authors: Singh Devendra Raj , Sunuwar Dev Ram , Shah Sunil Kumar , Karki Kshitij , Sah Lalita Kumari , Adhikari Bipin , Sah Rajeeb Kumar
Published: February 2021

Background

The COVID-19 pandemic has posed unprecedented challenges and threats to the health care system, particularly affecting the effective delivery of essential health services in resource-poor countries such as Nepal. This study aimed to explore community perceptions of COVID-19 and their experiences towards health services utilization during the pandemic in Province-2 of Nepal.

Methods

The semi-structured qualitative interviews were conducted among purposively selected participants (n = 41) from a mix of rural and urban settings in all districts (n = 8) of the Province 2 of Nepal. Virtual interviews were conducted between July and August 2020 in local languages. The data were analyzed using thematic network analysis in NVivo 12 Pro.

Results

The findings of this research are categorized into four global themes: i) Community and stakeholders’ perceptions towards COVID-19; ii) Impact of COVID-19 and lockdown on health services delivery; iii) Community perceptions and experiences of health services during COVID-19; and iv) COVID-19: testing, isolation, and quarantine services. Most participants shared their experience of being worried and anxious about COVID-19 and reported a lack of awareness, misinformation, and stigma as major factors contributing to the spread of COVID-19. Maternity services, immunization, and supply of essential medicine were found to be the most affected areas of health care delivery during the lockdown. Participants reported that the interruptions in health services were mostly due to the closure of health services at local health care facilities, limited affordability, and involvement of private health sectors during the pandemic, fears of COVID-19 transmission among health care workers and within health centers, and disruption of transportation services. In addition, the participants expressed frustrations on poor testing, isolation, and quarantine services related to COVID-19, and poor accountability from the government at all levels towards health services continuation/management during the COVID-19 pandemic.

Conclusions

This study found that essential health services were severely affected during the COVID-19 pandemic in all districts of Province-2. It is critical to expand and continue the service coverage, and its quality (even more during pandemics), as well as increase public-private sector engagement to ensure the essential health services are available for the population.
Clinical course of IPF in Italian patients during 12 months of observation: results from the FIBRONET observational study
Authors:   the FIBRONET study group, Poletti V. , Vancheri C. , Albera C. , Harari S. , Pesci A. , Metella R. R. , Campolo B. , Crespi G. , Rizzoli S.
Published: February 2021

Background

FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF).

Methods

Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted).

Results

209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study.

Conclusions

FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF.

Trial registration: NCT02803580
Correction to: A novel method of grading gastric intestinal metaplasia based on the combination of subtype and distribution
Authors: Wei Ning , Zhong Zhiheng , Shi Ruihua
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis
Authors: Sun Tong , Xu Yujia , Xu Zhuan , Cao Biyin , Zhang Zubin , Wang Qi , Kong Yan , Mao Xinliang
Published: February 2021

Background

The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis.

Methods

A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT.

Results

Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity.

Conclusions

The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment.
Spinal manipulation and modulation of pain sensitivity in persistent low back pain: a secondary cluster analysis of a randomized trial
Authors: Nim Casper Glissmann , Weber Kenneth Arnold , Kawchuk Gregory Neill , O’Neill Søren
Published: February 2021

Background

Pain hypersensitivity can be assessed using Quantitative Sensory Testing (QST) and is associated with persistent low back pain. Spinal manipulation appears to modify pain hypersensitivity, and this could function as one mechanism leading to clinical improvements. In the current study, we applied a comprehensive QST battery to assess pain sensitivity in a cohort of low back pain patients before and after spinal manipulation to improve our understanding of the association between QST and clinical improvements. This study addresses two questions: Are clinical improvements following spinal manipulation in low back pain patients contingent on pain hypersensitivity, and does pain sensitivity change following spinal manipulation?

Methods

We performed a secondary analysis of data from a randomized clinical trial. One hundred and thirty-two participants with persistent LBP were treated with spinal manipulation four times over two weeks. Patient-reported outcomes and QST were assessed at baseline, after the fourth spinal manipulation session, and 14-days later. The clinical outcomes were changes in low back pain intensity and disability. Using latent profile analysis, we categorized the participants into clusters depending on their baseline QST scores. We used linear mixed models to examine the association between clusters and changes in patient-reported outcomes and QST.

Results

Two clusters emerged: a Sensitized and a Not sensitized. The former had significantly lower regional pressure and thermal pain thresholds, remote pressure pain tolerance, and lower inhibitory conditioned pain modulation than the Not sensitized group. However, we only found between-cluster differences for regional pressure pain threshold following spinal manipulation. Thus, the clusters were not associated with patient-reported pain and disability changes or the remaining QST outcomes.

Conclusions

We report that the baseline QST profile was not associated with clinical improvements following spinal manipulation. We did observe a substantial change for regional pressure pain threshold, which suggests that any effect of spinal manipulation on pain sensitivity is most likely to be observed as changes in regional, mechanical pain threshold. However, the mechanism that invokes clinical improvement and pain sensitivity changes appear distinct. Due to methodological caveats, we advise caution when interpreting the results.

Trial registration

Clinical.Trial.gov identifier: NCT04086667, registered 11 September 2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04086667