bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical strategies to enhance resident engagement in clinical quality improvement
Authors: Koller James P. , Cochran Kelly A. , Headrick Linda A.
Published: February 2022

Background

Engaging residents in meaningful quality improvement (QI) is difficult. Challenges include competing demands, didactics which lack connection to meaningful work, suboptimal experiential learning, unclear accountability, absence of timely and relevant data, and lack of faculty coaches and role models. Various strategies to address these challenges for engagement have been described, but not as a unified approach. This paper describes a bundle of practical strategies to address common challenges to resident engagement in QI, illustrated through the experience of one residency education program.

Methods

62 categorical residents in the University of Missouri Internal Medicine residency participated in a longitudinal QI curriculum integrated into residency clinic assignments with dedicated QI work sessions and brief just-in-time didactics with mentorship from faculty coaches. Residents completed at least two PDSA (Plan-Do-Study-Act) cycles for their projects. The experience included clear expectations and tools for accountability. Project criteria included importance to patients, residents, and the institution. Residents had access to data related to their own practice. A pre-post survey asked residents to self-assess their level of interest and engagement in QI on a 5-point Likert scale, with 1 = least desired and 5 = most desired result. Data were analyzed by paired t-test.

Results

All 62 residents participated in the program as members of ten QI teams. 40/62 residents completed both pre- and post-surveys. Items related to self-assessment of QI in clinical work all changed in the desired direction: likelihood of participation (3.7 to 4.1, p = 0.03), frequency of QI use (3.3 to 3.9, p = 0.001), and opinion about using QI in clinical work (3.9 to 4.0, p = 0.21). Resident assessment of QI priority in clinical work did not change.

Conclusions

We implemented a practical strategies bundle to overcome common challenges to successfully engaging residents in clinical quality improvement. These strategies included QI work integrated into routine clinical assignments, just-in-time didactics, experiential learning with clear expectations and strategic project selection, timely and pertinent data from the residents’ own practice, and real-time faculty coaching.
Satisfaction can co-exist with hesitation: qualitative analysis of acceptability of telemedicine among multi-lingual patients in a safety-net healthcare system during the COVID-19 pandemic
Authors: Nguyen Michelle-Linh T. , Garcia Faviola , Juarez Jennifer , Zeng Billy , Khoong Elaine C. , Nijagal Malini A. , Sarkar Urmimala , Su George , Lyles Courtney R.
Published: February 2022

Background

The COVID-19 pandemic triggered unprecedented expansion of outpatient telemedicine in the United States in all types of health systems, including safety-net health systems. These systems generally serve low-income, racially/ethnically/linguistically diverse patients, many of whom face barriers to digital health access. These patients’ perspectives are vital to inform ongoing, equitable implementation efforts.

Methods

Twenty-five semi-structured interviews exploring a theoretical framework of technology acceptability were conducted from March through July 2020. Participants had preferred languages of English, Spanish, or Cantonese and were recruited from three clinics (general medicine, obstetrics, and pulmonary) within the San Francisco Health Network. Both deductive and inductive coding were performed. In a secondary analysis, qualitative data were merged with survey data to relate perspectives to demographic factors and technology access/use.

Results

Participants were diverse with respect to language (52% non-English-speaking), age (range 23-71), race/ethnicity (24% Asian, 20% Black, 44% Hispanic/Latinx, 12% White), & smartphone use (80% daily, 20% weekly or less). All but 2 had a recent telemedicine visit (83% telephone). Qualitative results revealed that most participants felt telemedicine visits fulfilled their medical needs, were convenient, and were satisfied with their telemedicine care. However, most still preferred in-person visits, expressing concern that tele-visits relied on patients’ abilities to access telemedicine, as well as monitor and manage their own health without in-person physical evaluation.

Conclusions

High satisfaction with telemedicine can co-exist with patient-expressed hesitations surrounding the perceived effectiveness, self-efficacy, and digital access barriers associated with a new model of care. More research is needed to guide how healthcare systems and clinicians make decisions and communicate about visit modalities to support high-quality care that responds to patients’ needs and circumstances.
Applying the WHO-ICRC BEC course to train emergency and inpatient healthcare workers in Sierra Leone early in the COVID-19 outbreak
Authors: Sonenthal Paul D , Kachimanga Chiyembekezo , Komba Doris , Bangura Moses , Ludmer Nicholas , Lado Marta , Patino Marta , Gerrard Rachel B , Vandy Matthew J , Marsh Regan H , Mukherjee Joia , Rouhani Shada A
Published: February 2022

Background

Treating critical illness in resource-limited settings during disease outbreaks is feasible and can save lives. Lack of trained healthcare workers is a major barrier to COVID-19 response. There is an urgent need to train healthcare workers to manage COVID-19. The World Health Organization and International Committee of the Red Cross’s Basic Emergency Care course could provide a framework to cross-train personnel for COVID-19 care while strengthening essential health services.

Methods

We conducted a prospective cohort study evaluating the Basic Emergency Care course for healthcare workers from emergency and inpatient units at two hospitals in Sierra Leone, a low-income country in West Africa. Baseline, post-course, and six month assessments of knowledge and confidence were completed. Questions on COVID-19 were added at six months. We compared change from baseline in knowledge scores and proportions of participants “very comfortable” with course skills using paired Student’s t-tests and McNemar’s exact tests, respectively.

Results

We enrolled 32 participants of whom 31 completed pre- and post-course assessments. Six month knowledge and confidence assessments were completed by 15 and 20 participants, respectively. Mean knowledge score post-course was 85% (95% CI: 82% to 88%), which was increased from baseline (53%, 48% to 57%, p-value < 0.001). There was sustained improvement from baseline at six months (73%, 67% to 80%, p-value 0.001). The percentage of participants who were “very comfortable” performing skills increased from baseline for 27 of 34 skills post-training and 13 skills at six months. Half of respondents strongly agreed the course improved ability to manage COVID-19.

Conclusions

This study demonstrates the feasibility of the Basic Emergency Care course to train emergency and inpatient healthcare workers with lasting impact. The timing of the study, at the beginning of the COVID-19 pandemic, provided an opportunity to illustrate the strategic overlap between building human resource capacity for long-term health systems strengthening and COVID-19. Future efforts should focus on integration with national training curricula and training of the trainers for broader dissemination and implementation at scale.
Scientific achievements and reflections after 20 years of vector biology and control research at the Pu Teuy mosquito field research station, Thailand
Authors: Sirisopa Patcharawan , Sukkanon Chutipong , Bangs Michael J. , Nakasathien Sutkhet , Hii Jeffrey , Grieco John P. , Achee Nicole L. , Manguin Sylvie , Chareonviriyaphap Theeraphap
Published: February 2022

Additional vector control tools are needed to supplement current strategies to achieve malaria elimination and control of Aedes-borne diseases in many settings in Thailand and the Greater Mekong Sub-region. Within the next decade, the vector control community, Kasetsart University (KU), and the Ministry of Higher Education, Science, Research and Innovation must take full advantage of these tools that combine different active ingredients with different modes of action. Pu Teuy Mosquito Field Research Station (MFRS), Department of Entomology, Faculty of Agriculture, Kasetsart University (KU), Thailand was established in 2001 and has grown into a leading facility for performing high-quality vector biology and control studies and evaluation of public health insecticides that are operationally relevant. Several onsite mosquito research platforms have been established including experimental huts, a 40-m long semi-field screening enclosure, mosquito insectary, field-laboratory, and living quarters for students and researchers. Field research and assessments ranged from ‘basic’ investigations on mosquito biology, taxonomy and genetics to more ‘applied’ studies on responses of mosquitoes to insecticides including repellency, behavioural avoidance and toxicity. In the course of two decades, 51 peer-reviewed articles have been published, and 7 masters and 16 doctoral degrees in Entomology have been awarded to national and international students. Continued support of key national stakeholders will sustain MFRS as a Greater Mekong Subregion centre of excellence and a resource for both insecticide trials and entomological research.
Community engagement for malaria elimination in the Greater Mekong Sub-region: a qualitative study among malaria researchers and policymakers
Authors: Kaehler Nils , Adhikari Bipin , Cheah Phaik Yeong , von Seidlein Lorenz , Day Nicholas P. J. , Dondorp Arjen M. , Pell Christopher
Published: February 2022

Background

Community engagement has increasingly received attention in malaria research and programme interventions, particularly as countries aim for malaria elimination. Although community engagement strategies and activities are constantly developing, little is known about how those who implement research or programmes view community engagement. This article explores the perspectives of researchers and policy makers in the Greater Mekong Sub-region (GMS) on community engagement for malaria control and elimination.

Methods

Semi-structured interviews were conducted among 17 policymakers and 15 senior researchers working in the field of malaria. All interviews were audio-recorded and transcribed in English. Transcribed data were analysed using deductive and inductive approaches in QSR NVivo. Themes and sub-themes were generated.

Results

Researchers and policymakers emphasized the importance of community engagement in promoting participation in malaria research and interventions. Building trust with the community was seen as crucial. Respondents emphasized involving authority/leadership structures and highlighted the need for intense and participatory engagement. Geographic remoteness, social, cultural, and linguistic diversity were identified as barriers to meaningful engagement. Local staff were described as an essential ‘connect’ between researchers or policymakers and prospective participants. Sharing information with community members, using various strategies including creative and participatory methods were highlighted.

Conclusions

Policymakers and researchers involved in malaria prevention and control in the GMS viewed community engagement as crucial for promoting participation in research or programmatic interventions. Given the difficulties of the ‘last mile’ to elimination, sustained investment in community engagement is needed in isolated areas of the GMS where malaria transmission continues. Involving community-based malaria workers is ever more critical to ensure the elimination efforts engage hard-to-reach populations in remote areas of GMS.
A social innovation model for equitable access to quality health services for rural populations: a case from Sumapaz, a rural district of Bogota, Colombia
Authors: Bautista-Gómez Martha Milena , van Niekerk Lindi
Published: February 2022

Background

Despite efforts to extend Universal Health Coverage in Colombia, rural and remote populations still face significant challenges in accessing equitable health services. Social innovation has been growing in Colombia as a creative response to the country’s social problems including access to healthcare. This paper presents the findings of a social innovation case study, which was implemented in the rural area of Sumapaz in  Colombia, with the purpose of holistically addressing the health needs of the local population and enhancing health service access.

Methods

A case study methodology was used to investigate and understand the process by which the Model of Integral Health Care for Rural Areas was developed and how the various strategies were defined and implemented. Qualitative methods were used in the data collection and all data was analysed using Farmer et al. staged framework on grassroots social innovation which includes growing the idea; implementing the idea; sustainability and diffusion.

Results

The social innovation model was designed as a co-learning process based on community participation. The model was implemented adopting a holistic health approach and considerate of the conditions of a rural context. As a result of this process, access to quality health services were enhanced for the vulnerable rural community. The model has also provided outcomes that transcend health and contribute to individual and community development in different areas eg. agriculture.

Conclusion

The Model of Integral Health Care for Rural Areas is a social innovation in health that demonstrates how Universal Health Coverage can be achieved for vulnerable populations through a series of creative strategies which fill systemic voids in access and co-ordination of care, as well as in addresings upstream environmental factors responsible for ill-health.
Evidence-informed decision about (de-)implementing return-to-work coordination to reduce sick leave: a case study
Authors: Tikka Christina , Verbeek Jos , Hoving Jan L. , Kunz Regina
Published: February 2022

Background

Coordination of return to work (RtW) is implemented in many countries, but a Cochrane review found no considerable effect on workers’ sick leave compared to usual care. The aim of the study is to analyse how the evidence from this review can be used for decisions about (de-)implementing RtW coordination in a country-specific setting, using Finland as an example.

Methods

We conducted a systematic literature search and online survey with two groups of experts to compare interventions included in the Cochrane review to Finnish RtW practice using content analysis methods. We applied the evidence-to-decision (EtD) framework criteria to draw conclusions about (de-)implementing RtW coordination in Finland, including benefits, harms and costs of the intervention compared to usual care.

Results

We included seven documents from the literature search and received data from 10 of 42 survey participants. RtW coordination included, both in Finland and in the review, at least one face-to-face meeting between the physician and the worker, a workers’ needs assessment, and an individual RtW plan and its implementation. Usual care focuses on medical treatment and may include general RtW advice. RtW coordination would be cost-saving if it decreases sick leave with at least 2 days compared to usual care. The evidence in the Cochrane review was mainly of low certainty, and the effect sizes had relatively wide confidence intervals. Only a new, high-quality and large randomized controlled trial (RCT) can decrease the current uncertainty, but this is unlikely to happen. The EtD framework did not provide arguments for further implementation or for de-implementation of the intervention.

Conclusions

Interventions evaluated in the Cochrane review are similar to RtW coordination and usual care interventions in Finland. Considering all EtD framework criteria, including certainty of the evidence and costs, de-implementation of RtW coordination interventions in Finland seems unnecessary. Better evidence about the costs and stakeholders’ values regarding RtW coordination is needed to improve decision-making.
Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adults
Authors: Fernandes Juliana Ruiz , Pinto Thalyta Nery Carvalho , Arruda Liã Barbara , da Silva Cibele Cristine Berto Marques , de Carvalho Celso Ricardo Fernandes , Pinto Regina Maria Carvalho , da Silva Duarte Alberto José , Benard Gil
Published: February 2022

Background

COPD is associated with an abnormal lung immune response that leads to tissue damage and remodeling of the lung, but also to systemic effects that compromise immune responses. Cigarette smoking also impacts on innate and adaptative immune responses, exerting dual, pro- and anti-inflammatory effects. Previously, we showed that COPD patients presented accelerated telomere shortening and decreased telomerase activity, while, paradoxically, cigarette-smokers exhibited preserved telomerase activity and slower rate of telomere shortening.

Results

Here, we evaluated the naive, CM, EM and TEMRAsubsets of TCD4 and TCD8 cells according to the expression of CCR7/CD45RA. We compared age-matched COPD patients, cigarette-smokers without clinical-laboratory evidence of pulmonary compromise, and healthy individuals. They were additionally compared with a group of young adults. For each subset we analysed the expression of markers associated with late differentiation, senescence and exhaustion (CD27/CD28/CD57/KLRG1/PD1). We show that COPD patients presented a drastically reduced naive cells pool, and, paradoxically, increased fractions of naive cells expressing late differentiation, senescence or exhaustion markers, likely impacting on their immunocompetence. Pronounced phenotypic alterations were also evidenced in their three memory T-cell subsets compared with the other aged and young groups, suggesting an also dysfunctional memory pool. Surprisingly, our smokers showed a profile closer to the Healthy aged than COPD patients. They exhibited the usual age-associated shift of naive to EM TCD4 and TCD8 cells, but not to CM or TEMRAT-cells. Nonetheless, their naive T-cells phenotypes were in general similar to those of the Youngs and Healthy aged, suggesting a rather phenotypically preserved subset, while the memory T-cells exhibited increased proportions of cells with the late-differentiation or senescence/exhaustion markers as in the Healthy aged.

Conclusion

Our study extends previous findings by showing that COPD patients have cells expressing a full range of late differentiated, senescent or exhausted phenotypes encompassing all TCD4 and TCD8 subsets, consistent with a premature immunosenescence phenotype. Surprisingly, the smokers group’s results suggest that moderate to heavy chronic cigarette smoking did not accelerate the pace of immunosenescence as compared with the Healthy aged.
Microtubule disruption reduces metastasis more effectively than primary tumor growth
Authors: Thompson Keyata N. , Ju Julia A. , Ory Eleanor C. , Pratt Stephen J. P. , Lee Rachel M. , Mathias Trevor J. , Chang Katarina T. , Lee Cornell J. , Goloubeva Olga G. , Bailey Patrick C. , Chakrabarti Kristi R. , Jewell Christopher M. , Vitolo Michele I. , Martin Stuart S.
Published: February 2022

Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth.
Pericardiocentesis: ultrasound guidance is essential
Authors: Blanco Pablo , Figueroa Liliana , Menéndez María Fernanda , Berrueta Belén
Published: February 2022

Background

Pericardial effusion is a common entity which may have important implications in patient’s prognosis. In several cases, pericardiocentesis is indicated for diagnostic and/or therapeutic purposes.

Case presentation

A blind pericardiocentesis failed in a 95-year-old woman admitted to the emergency department with a large pericardial effusion incidentally diagnosed in the ambulatory setting. Ultrasound-guided pericardiocentesis aided in easily accessing to the pericardial cavity, without periprocedural complications.

Conclusions

Ultrasound-guided pericardiocentesis is simple, safe and effective, and should replace the blind technique. This procedure should be part of the armamentarium of ultrasound-guided practices of emergency or critical care physicians.
Association between hypoglycemia and dementia in patients with diabetes: a systematic review and meta-analysis of 1.4 million patients
Authors: Huang Lifen , Zhu Manlian , Ji Jie
Published: February 2022

Background

Diabetes mellitus (DM) is known to be a risk factor for dementia. However, it is unclear if hypoglycemic events play a role in the risk of dementia. We aimed to systematically review evidence on the risk of dementia in DM patients based on prior hypoglycemic events.

Methods

PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched till 15th November 2021 for cohort studies assessing the risk of dementia based on prior hypoglycemic events in DM patients. Adjusted data were pooled in a random-effects model.

Results

Ten studies with a total of 1,407,643 patients were included. Pooled analysis of all ten studies indicated that hypoglycemic episodes were associated with a statistically significant increase in the risk of dementia in DM patients as compared to those not experiencing hypoglycemic episodes (HR: 1.44 95% CI: 1.26, 1.65 I2 = 89% p < 0.00001). The results did not change on the exclusion of any study. Sub-group analysis based on the study population, type of study, adjustment for glycated hemoglobin, gender, and the number of hypoglycemic episodes also presented similar results.

Conclusions

Evidence from observational studies with a large sample size indicates that DM patients with hypoglycemic episodes are at increased risk of dementia. Anti-hyperglycemic drugs should be adequately tailored in these patients to avoid the risk of dementia.
A cancer graph: a lung cancer property graph database in Neo4j
Authors: Tuck David
Published: February 2022

Objectives

A novel graph data model of non-small cell lung cancer clinical and genomic data has been constructed with two aims: (1) provide a suitable model for facilitating graph analytics within the Neo4j framework or through tools which can interact through existing Neo4j APIs; and (2) provide a base model extensible to other cancer types and additional datasets such as those derived from electronic health records and other real world sources.

Data description

Clinical and genomic data integrated with a novel property graph database schema from publicly available datasets and analyses based on The Cancer Genome Atlas lung cancer datasets augmented by with subgraphs patient-patient social network from similarity and correlation as well as individual based biological networks.
A simple adaptive difference algorithm with CO2 measurements for evaluating plant growth under environmental fluctuations
Authors: Gonome Hiroki , Yamada Jun , Nishimura Norito , Arai Yuta , Hirai Minoru , Kumagai Naoki , Rajagopalan Uma Maheswari , Kono Takahiro
Published: February 2022

Objective

The aim of this study is to demonstrate an adaptive method that is robust toward environmental fluctuations and provides a real-time measure of plant growth by measuring CO2 consumption. To verify the validity of the proposed method, the relation between the plant growth and variation in light conditions with a closed experimental system was investigated.

Results

The proposed method was used to measure the photosynthetic rate induced by photosynthetic photon flux density (PPFD) and to evaluate plant growth under continuous and pulsed light in arugula plants. The PPFD-dependent change in photosynthetic rate was measured. And in the condition range of 200–10,000 μs pulse period and 50% duty ratio of pulsed light, there was no change in the growth rate of plants assuming the same PPFD as continuous light. These experiments showed the validity of the adaptive method in removing environmental fluctuations without precise control of temperature and humidity.
Systemic problems require systemic solutions: the need for coordination and cooperation to improve research quality
Authors: Ganley Emma , Coriat Anne-Marie , Shenow Sarah , Prosser David
Published: February 2022

Various factors contribute to low reproducibility and replicability of scientific findings. Whilst not all of these are necessarily problematic, there is growing acceptance that there is room for improvement. Many sectoral organisations have a role to play in this, by refining incentives and rewards, promoting specific behaviours such as open research practices, and exploring innovations in grant funding and scientific publishing. However, given the systems nature of the challenge, real change will require the coordination of these efforts, and partnerships that ensure alignment of activity and interoperability of training. Efforts to improve research quality will require investment, in infrastructure, training, and research on research to ensure that innovative solutions are evidence-based, and potential unintended consequences are explored (and avoided). National structures (e.g., the planned UK Committee on Research Integrity) should focus on understanding the research system, identifying areas for improvement, and promoting research to understand the impact of novel approaches and innovations, in order to advise on how to maximise benefit and avoid harm.
The type of anticoagulant used for plasma collection affects in vitro Rhodococcus equi assays
Authors: Rivolta Alejandra A. , Pittman Dana C. , Kappes Amanda J. , Stancil Robert K. , Kogan Clark , Sanz Macarena G.
Published: February 2022

Objective

The efficacy of Rhodococcus equi-specific hyperimmune plasma (HIP) is usually evaluated in vitro. Anticoagulants (AC) used for plasma collection can negatively impact bacterial replication but their effect on R. equi growth has not been evaluated. The aim of this study was to establish the effect that AC routinely used in veterinary medicine (ACD, K2EDTA, Li Heparin, and Na Citrate) have on in vitro R. equi growth. To assess this, in vitro assays commonly used to test HIP efficacy (direct effect on microorganism and macrophage infection), were performed using each AC and non-treated bacteria.

Results

There was no direct effect of ACD, Li Heparin or Na Citrate on R. equi growth. These AC significantly (p < 0.05) delayed growth for 12 h following opsonization. The number of R. equi colonies after macrophage infection was significantly (p < 0.05) lower 72 h post-opsonization with Na Citrate. K2EDTA inhibited the formation of R. equi colonies by 12 h in all the assays. In conclusion, AC should be taken into consideration when interpreting in vitro results as their negative effect on bacterial growth may be mistakenly interpreted as HIP efficacy. ACD and Li Heparin appear more appropriate for the selected assays.
Primary hypothyroidism and chronotypes in adult women
Authors: Arosemena Marilyn A. , Ramos Alberto R. , Marcus Erin N. , Slota Katarzyna A. , Cheung Joseph , Castillo Pablo R.
Published: February 2022

Objective

Abnormal thyroid function may disrupt sleep architecture. We aimed to determine the frequency of various chronotypes in women with hypothyroidism. We performed a single-center retrospective study at an ambulatory clinic from January 2013-December 2015. Participants were women with hypothyroidism. Chronotype was determined from the Munich ChronoType Questionnaire. The χ2 test was used to compare differences in clinical characteristics and sleep patterns in early and intermediate/late chronotypes. The t test was used to compare differences between means.

Results

We evaluated 99 patients (mean [SD], 56 [7] years): calculated chronotype revealed: 56% early, 38% intermediate and 6% late. Analysis with the χ2 test showed significant differences between early and intermediate/late calculated chronotypes for sleep latency (P = 0.01), light exposure (P = 0.009), and no alcohol intake (P = 0.001). t test showed the following differences in mean (SD) between chronotypes: sleep duration, 7.30 (1.39) hours (early chronotype) and 7.04 (2.06) hours (intermediate/late); body mass index (BMI), 29.4 (7.3) (early) and 31.1 (6.8) (intermediate/late); and TSH level, 2.89 (3.69) mIU/L (early) and 1.69 (1.41) mIU/L (intermediate/late). Early chronotypes were frequent in women with hypothyroidism. Light exposure and BMI may influence chronotypes in patients with hypothyroidism; findings are consistent with healthier behaviors in patients who tend toward morningness.
Novel epigenetic network biomarkers for early detection of esophageal cancer
Authors: Maity Alok K. , Stone Timothy C. , Ward Vanessa , Webster Amy P. , Yang Zhen , Hogan Aine , McBain Hazel , Duku Margaraet , Ho Kai Man Alexander , Wolfson Paul , Graham David G. ,   SPIT Study Group, Beck Stephan , Teschendorff Andrew E. , Lovat Laurence B.
Published: February 2022

Background

Early detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity.

Results

Here we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett’s Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status.

Conclusions

Given our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacteriumF. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation.
Combination of gut microbiota and plasma amyloid-β as a potential index for identifying preclinical Alzheimer’s disease: a cross-sectional analysis from the SILCODE study
Authors: Sheng Can , Yang Kun , He Beiqi , Du Wenying , Cai Yanning , Han Ying
Published: February 2022

Background

Plasma amyloid-β (Aβ) may facilitate identification of individuals with brain amyloidosis. Gut microbial dysbiosis in Alzheimer’s disease (AD) is increasingly being recognized. However, knowledge about alterations of gut microbiota in preclinical AD, as well as whether the combination of plasma Aβ and gut microbiota could identify preclinical AD, remains largely unknown.

Methods

This study recruited 34 Aβ-negative cognitively normal (CN−) participants, 32 Aβ-positive cognitively normal (CN+) participants, and 22 patients with cognitive impairment (CI), including 11 patients with mild cognitive impairment (MCI) and 11 AD dementia patients. All participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Meso Scale Discovery (MSD) kits were used to quantify the plasma Aβ40, Aβ42, and Aβ42/Aβ40 in CN− and CN+ participants. Using Spearman’s correlation analysis, the associations of global standard uptake value rate (SUVR) with altered gut microbiota and plasma Aβ markers were separately evaluated. Furthermore, the discriminative power of the combination of gut microbiota and plasma Aβ markers for identifying CN+ individuals was investigated.

Results

Compared with the CN− group, the CN+ group showed significantly reduced plasma Aβ42 (p = 0.011) and Aβ42/Aβ40 (p = 0.003). The relative abundance of phylum Bacteroidetes was significantly enriched, whereas phylum Firmicutes and class Deltaproteobacteria were significantly decreased in CN+ individuals in comparison with that in CN− individuals. Particularly, the relative abundance of phylum Firmicutes and its corresponding SCFA-producing bacteria exhibited a progressive decline tendency from CN− to CN+ and CI. Besides, the global brain Aβ burden was negatively associated with the plasma Aβ42/Aβ40 (r = −0.298, p = 0.015), family Desulfovibrionaceae (r = −0.331, p = 0.007), genus Bilophila (r = −0.247, p = 0.046), and genus Faecalibacterium (r = −0.291, p = 0.018) for all CN participants. Finally, the combination of plasma Aβ markers, altered gut microbiota, and cognitive performance reached a relatively good discriminative power in identifying individuals with CN+ from CN− (AUC = 0.869, 95% CI 0.782 ~ 0.955).

Conclusions

This study provided the evidence that the gut microbial composition was altered in preclinical AD. The combination of plasma Aβ and gut microbiota may serve as a non-invasive, cost-effective diagnostic tool for early AD screening. Targeting the gut microbiota may be a novel therapeutic strategy for AD.

Trial registration

This study has been registered in ClinicalTrials.gov (NCT03370744, https://www.clinicaltrials.gov) in November 15, 2017.
The economic cost of implementing antigen-based rapid diagnostic tests for COVID-19 screening in high-risk transmission settings: evidence from Germany
Authors: Hurtado Alfonso Valenzuela , Nguyen Hoa Thi , Schenkel Viktoria , Wachinger Jonas , Seybold Joachim , Denkinger Claudia M. , De Allegri Manuela
Published: February 2022

Background

Antigen-based rapid diagnostic tests (Ag-RDT) have been implemented in hospitals and nursing homes to screen for infectious individuals without symptoms suggestive of SARS-CoV-2 infections and to prevent entry into these high-risk settings. Despite their benefits for screening, the cost of large-scale implementation is largely understudied. Our study presents evidence on their implementation costs in high-risk settings.

This study aimed to estimate the economic costs of implementing Ag-RDT-based screening for SARS-CoV-2 in two tertiary care hospitals (University Hospital Heidelberg - UKHD, and Charité – Universitätsmedizin Berlin) and one nursing home in Germany.

Methods

We adopted a health system perspective and followed the three sequential steps to costing: identification of resources, measurement of resource consumption, and valuation of costs. Data on resource consumption were collected between October 2020 and April 2021 through various techniques and data sources. The cost estimation considered all costs along the screening algorithm including PCR confirmation tests for positive cases. We estimated the costs for the two implementation modalities observed: staff dedicated exclusively to screening and staff not dedicated exclusively to screening. Furthermore, cost estimations were performed under both observed capacity use and hypothetical capacity use assumptions (60, 80 and 100%).

Results

Our study indicates that the average cost per Ag-RDT is highly dependent on the capacity use and implementation mode. Staff time and test kits are the two main cost drivers of implementing the large-scale screening programs for SARS-CoV-2 using Ag-RDTs. For hospitals, the average cost per test in UKHD was €30.12 (capacity observed); €14.56 (non-dedicated mode); €19.47, €16.37, €14.53 at 60, 80, 100% capacity respectively (dedicated mode); and at Charité €13.10 (non-dedicated mode). For the nursing home the estimated average cost per test was €15.03 (non-dedicated mode).

Conclusions

The information on the estimated costs by mode of implementation and capacity use may support the planning of Ag-RDT-based covid-19 screening programs suitable for each institution. Further research is needed to cost this screening strategy for COVID-19 in other high-risk, high-income settings to reach generalizability.
Autophagy-mediated degradation of NOTCH1 intracellular domain controls the epithelial to mesenchymal transition and cancer metastasis
Authors: Zada Sahib , Hwang Jin Seok , Lai Trang Huyen , Pham Trang Minh , Ahmed Mahmoud , Elashkar Omar , Kim Wanil , Kim Deok Ryong
Published: February 2022

Backgound

Autophagy controls levels of cellular components during normal and stress conditions; thus, it is a pivotal process for the maintenance of cell homeostasis. In cancer, autophagy protects cells from cancerous transformations that can result from genomic instability induced by reactive oxygen species or other damaged components, but it can also promote cancer survival by providing essential nutrients during the metabolic stress condition of cancer progression. However, the molecular mechanism underlying autophagy-dependent regulation of the epithelial to mesenchymal transition (EMT) and metastasis is still elusive.

Methods

The intracellular level of NOTCH1 intracellular domain (NICD) in several cancer cells was studied under starvation, treatment with chloroquine or ATG7-knockdown. The autophagy activity in these cells was assessed by immunocytochemistry and molecular analyses. Cancer cell migration and invasion under modulation of autophagy were determined by in vitro scratch and Matrigel assays.

Results

In the study, autophagy activation stimulated degradation of NICD, a key transcriptional regulator of the EMT and cancer metastasis. We also found that NICD binds directly to LC3 and that the NICD/LC3 complex associates with SNAI1 and sequestosome 1 (SQSTM1)/p62 proteins. Furthermore, theATG7knockdown significantly inhibited degradation of NICD under starvation independent of SQSTM1-associated proteasomal degradation. In addition, NICD degradation by autophagy associated with the cellular level of SNAI1. Indeed, autophagy inhibited nuclear translocation of NICD protein and consequently decreased the transcriptional activity of its target genes. Autophagy activation substantially suppressed in vitro cancer cell migration and invasion. We also observed that NICD and SNAI1 levels in tissues from human cervical and lung cancer patients correlated inversely with expression of autophagy-related proteins.

Conclusions

These findings suggest that the cellular level of NICD is regulated by autophagy during cancer progression and that targeting autophagy-dependent NICD/SNAI1 degradation could be a strategy for the development of cancer therapeutics.
History-dependent operators and prox-regular sweeping processes
Authors: Nacry Florent , Sofonea Mircea
Published: February 2022

We consider an abstract inclusion in a real Hilbert space, governed by an almost history-dependent operator and a time-dependent multimapping with prox-regular values. We establish the unique solvability of the inclusion under appropriate assumptions on the data. The proof is based on the arguments of monotonicity, fixed point, and prox-regularity. We then use our result in order to deduce some direct consequences, including an existence and uniqueness result for a class of sweeping processes associated with prox-regular sets. Finally, we provide an example in a finite dimensional case inspired by a rheological model in solid mechanics.
LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
Authors: Chang Eunice Eun Seo , Ho Philip Wing-Lok , Liu Hui-Fang , Pang Shirley Yin-Yu , Leung Chi-Ting , Malki Yasine , Choi Zoe Yuen-Kiu , Ramsden David Boyer , Ho Shu-Leong
Published: February 2022

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities betweenLRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a therapeutic target in PD.LRRK2mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies. This review provides a rationale for the use ofLRRK2KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from differentLRRK2KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.
Analysis and appraisal of fascine in Shahe ancient bridge ruins, Xi’an, Shaanxi, China
Authors: Mai Bingjie , Liu Naiming , Liu JiaoJiao , Liu Dan , Li Jin , Wang Juanli , Chen Aidong , Cao Jing , Li Yuhu
Published: February 2022

Flood control initiated Chinese civilization. Chinese civilization has a long history, and Chinese ancestors invented “aquatic engineering technology” for flood control and water management, including the Fascine body, as early as two thousand years ago. The Fascine body is a structure used to protect the bank and prevent breaching of an ancient Chinese flood control project. Excavation of the Shahe ancient bridge ruins in Xi’an City, Shaanxi Province, China led to discovery of a Fascine body structure. Through 14C dating, fibre, slice observations, infrared spectroscopy, X-ray diffraction, thermogravimetric analyses and SEM energy spectrum analyses of the fascine material, microbes in the structure and the surrounding soil were identified, the dominant microbial community was analyzed, and microbial diseases were controlled in a targeted manner. Research on the fascine bank ruins identified the width and length boundaries of the Shahe ancient bridge, determined the exact age of the Shahe ancient bridge, provided important materials for research on ancient bridges, river embankments and other ruins, and provided important clues for the traffic and layout around Chang’an during the Qin and Han Dynasties of Chinese history.
Association between the presence of delirium during intensive care unit admission and cognitive impairment or psychiatric problems: the Korean ICU National Data Study
Authors: Ko Ryoung-Eun , Kang Danbee , Park Hyejung , Cho Juhee , Suh Gee Young , Chung Chi Ryang
Published: February 2022

Objective

Delirium in the intensive care unit (ICU) may be a preventable risk factor for cognitive impairment or psychiatric problems. We aimed to evaluate the association between the presence of delirium during hospitalization involving ICU care and post-discharge cognitive impairment or psychiatric problems.

Design

A retrospective cohort study.

Setting

A database of nationwide insurance claims data.

Patients

All adult patients aged 18 years or older who were admitted to an ICU between January 1, 2008, and May 31, 2015, and had no history of previous cognitive impairment or psychiatric problems were included in the study.

Interventions

None.

Measurements and main results

Of 306,011 patients who met the inclusion criteria, the proportion of those who experienced delirium during hospitalization was 55.0% (n = 168,190). The patients with delirium during hospitalization had significantly increased odds for cognitive impairment (adjusted hazard ratio [HR] 1.17; 95% confidence interval [CI] 1.05–1.29) and psychiatric problems (adjusted HR 1.78; 95% CI 1.67–1.90) after discharge compared with patients without delirium. In patients who had delirium, the incidence of cognitive impairment was 210.8 per 1000 person-years. In 19,496 patients who were diagnosed with cognitive impairment, depression (n = 3233, 16.5%), sleep disorder (n = 1791, 9.2%), and anxiety (n = 1683, 8.6%) were commonly co-diagnosed. The most common psychiatric problem was sleep disorder (148.7 per 1000 person-years), followed by depression (133.3 per 1000 person-years).

Conclusions

Among patients received ICU care, those who experienced delirium during hospitalization had an increased risk of developing cognitive impairment or psychiatric problems post-discharge. Many patients showed multiple cognitive impairment and psychiatric problems during the follow-up period. Efforts to decrease these problems should be made to increase the quality of life of these ICU survivors.
Insulins for the long term management of diabetes mellitus in dogs: a review
Authors: Shiel Robert E. , Mooney Carmel T.
Published: February 2022

The year 2021 marked the centenary of the isolation of a therapeutic form of insulin and its successful use in dogs. This was a landmark moment that subsequently and rapidly led to the commercial manufacture of insulin for use in humans. The impact of insulin was almost miraculous as those destined to die from their diabetes mellitus returned to life. Over the past 100 years, insulin formulations have been modified to attempt to provide a predictable and prolonged duration of action while avoiding the development of hypoglycaemia. This has led to an ever-growing variety of insulin types in human medicine, many of which have subsequently been used in dogs. The purpose of this review article is to provide an overview of available insulin types and their application to the chronic management of canine diabetes mellitus.
The impacts of learning analytics and A/B testing research: a case study in differential scientometrics
Authors: Baker Ryan S. , Nasiar Nidhi , Gong Weiyi , Porter Chelsea
Published: February 2022

Background

In recent years, research on online learning platforms has exploded in quantity. More and more researchers are using these platforms to conduct A/B tests on the impact of different designs, and multiple scientific communities have emerged around studying the big data becoming available from these platforms. However, it is not yet fully understood how each type of research influences future scientific discourse within the broader field. To address this gap, this paper presents the first scientometric study on how researchers build on the contributions of these two types of online learning platform research (particularly in STEM education). We selected a pair of papers (one using A/B testing, the other conducting learning analytics (LA), on platform data of an online STEM education platform), published in the same year, by the same research group, at the same conference. We then analyzed each of the papers that cited these two papers, coding from the paper text (with inter-rater reliability checks) the reason for each citation made.

Results

After statistically comparing the frequency of each category of citation between papers, we found that the A/B test paper was self-cited more and that citing papers built on its work directly more frequently, whereas the LA paper was more often cited without discussion.

Conclusions

Hence, the A/B test paper appeared to have had a larger impact on future work than the learning analytics (LA) paper, even though the LA paper had a higher count of total citations with a lower degree of self-citation. This paper also established a novel method for understanding how different types of research make different contributions in learning analytics, and the broader online learning research space of STEM education.