bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing cultural competency among Canadian chiropractors: a cross-sectional survey of Canadian Chiropractic Association members
Authors: Bakaa Nora , Southerst Danielle , Côté Pierre , Macedo Luciana , Carlesso Lisa C. , MacDermid Joy , Mior Silvano
Published: January 2023

Background

There is a paucity of research assessing cultural competency among Canadian chiropractors. Therefore, the aims of this study were to (1) measure cultural competency among Canadian chiropractors, (2) understand chiropractors’ perspectives of challenges and attitudes regarding the delivery of chiropractic services to equity-seeking communities, and (3) assess contextual factors associated with cultural competency.

Methods

We conducted a cross-sectional survey of members of the Canadian Chiropractic Association (CCA) (May–July 2021). The survey instrument consisted of 57 questions related to demographics, cultural competency, perceptions about health disparities, and challenges in delivery of rehabilitation. Cultural competency was measured using the Cultural Awareness and Sensitivity and Cultural Competence Behaviours subscales of the Cultural Competence Assessment Instrument. We conducted a multivariate linear regression to assess factors that may be associated with cultural competency.

Results

A total of 3143 CCA members responded (response rate of 41%). Mean scores for the Cultural Awareness and Sensitivity subscale were 5.8/7 (95% CI 5.7; 5.8) and 4.2/7 (95% CI 4.1; 4.2) for the Cultural Competence Behaviour subscale. Most chiropractors (72–78%) reported observing important cultural health disparities across various care-related outcomes. Cost of services and language were identified as barriers to providing care to equity-seeking communities. Cultural Awareness and Sensitivity scores were weakly associated with gender (men), years of clinical practice, cultural health disparities, the statement “I think some people have an agenda to look for discrimination even where it does not exist (DEI attitudes),” race (Caucasian), and prior DEI training, (R2 = 0.15,p < 0.0001). Cultural Competence Behaviour scores were weakly associated with race (Caucasian), cultural health disparities, prior DEI training, increased years of clinical experience, and higher Cultural Awareness and Sensitivity scores (R2 = 0.19,p < 0.0001).

Conclusion

This study provides the first description of cultural competency within the chiropractic profession in Canada. Findings suggest a gap between knowledge and behaviour and uncover several barriers and challenges that may inform the development of profession-specific training in cultural competence.
COVID-19: critical case of a patient with an atypical manifestation of the disease
Authors: Barrón-Palma Eira Valeria , Ríos-Zaragoza Siddhartha , Sanchez-Sandoval Ana Laura
Published: January 2023

Background

COVID-19 was initially described as a severe acute respiratory disease that could drive to pneumonia, compromising the life of the patients in the worst scenario. However, even though in most of the cases the respiratory symptoms are still the most common manifestations of the disease, nowadays it is considered as a complex multisystem illness, affecting a variety of organs and tissues. Asymptomatic and atypic cases have also been described, where symptoms are not related to those first described, as is the case of this report.

Case presentation

On November 23, 2020, a 53-year-old woman goes to the emergency room due to gastrointestinal symptoms. The admission diagnosis was inflammatory bowel disease and a mild event of idiopathic chronic ulcerative colitis, and the initial treatment was focused on the metabolic acidosis, and the reestablishment the hydroelectrolytic and hemodynamic balance. Then, she was transferred to the Gastroenterology Unit where she was treated for one week. During her hospitalization, she showed a refractory shock caused by progressive organ deterioration (renal and neurological), requiring a double-vasopressor support, oxygenation, and ventilation. Considering the laboratory tests results and computed tomography scans, a COVID-19 test was carried out, obtaining a positive result with a high viral load. The S gene of the virus was amplified and sequenced, finding an uncommon mutation rarely reported worldwide. After considerable systemic deterioration, the patient presented cardiorespiratory arrest, with no response and died on December 1, after 8 days of hospitalization.

Conclusions

In this report we describe the pathogenesis, clinical manifestations, and outcome of a patient with atypical COVID-19 symptoms (mainly gastrointestinal), rapidly evolving and with lethal consequences. Therefore, it is important to emphasize the need to strengthen patient surveillance in health centers, including those who do not present typical symptoms of COVID-19.In addition, it will be important to track the identified mutation (H1058Y) in the S viral gene and assess whether it could be associated with a different clinical manifestation of the disease or if it was just an isolated event.
On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates
Authors: Kim Chang Gon , Kim Min Hwan , Kim Jee Hung , Kim Seul-Gi , Kim Gun Min , Kim Tae Yeong , Ryu Won-Ji , Kim Jee Ye , Park Hyung Seok , Park Seho , Cho Young Up , Park Byeong Woo , Kim Seung Il , Jeong Joon , Sohn Joohyuk
Published: January 2023

Background

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated.

Methods

Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics.

Results

In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency.

Conclusions

On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.
Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control
Authors: Gunasekara Chathura J. , MacKay Harry , Scott C. Anthony , Li Shaobo , Laritsky Eleonora , Baker Maria S. , Grimm Sandra L. , Jun Goo , Li Yumei , Chen Rui , Wiemels Joseph L. , Coarfa Cristian , Waterland Robert A.
Published: January 2023

Background

Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition.

Results

We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with methylation and gene expression in internal organs. We also discover unprecedented mQTL at these regions. Genetic influences on CoRSIV methylation are extremely strong (median R2=0.76), cumulatively comprising over 70-fold more human mQTL than detected in the most powerful previous study. Moreover, mQTL beta coefficients at CoRSIVs are highly skewed (i.e., the major allele predicts higher methylation). Both surprising findings are independently validated in a cohort of 47 non-GTEx individuals. Genomic regions flanking CoRSIVs show long-range enrichments for LINE-1 and LTR transposable elements; the skewed beta coefficients may therefore reflect evolutionary selection of genetic variants that promote their methylation and silencing. Analyses of GWAS summary statistics show that mQTL polymorphisms at CoRSIVs are associated with metabolic and other classes of disease.

Conclusions

A focus on systemic interindividual epigenetic variants, clearly enhanced in mQTL content, should likewise benefit studies attempting to link human epigenetic variation to the risk of disease.
The effects of imaging markers on clinical trajectory in cerebral amyloid angiopathy: a longitudinal study in a memory clinic
Authors: Jang Hyemin , Chun Min Young , Kim Hee Jin , Na Duk L. , Seo Sang Won
Published: January 2023

Background

We investigated the relevance of various imaging markers for the clinical trajectory of cerebral amyloid angiopathy (CAA) patients in a memory clinic.

Methods

A total of 226 patients with probable CAA were included in this study with a mean follow-up period of 3.5 ± 2.7 years. Although all had more than one follow-up visit, 173 underwent follow-up Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SB) ranging from 2 to 15 time points. Among 226, 122 patients underwent amyloid-β (Aβ) PET imaging. The prevalence of intracerebral hemorrhage (ICH) and its imaging predictors was investigated. The effects of CAA imaging markers and Aβ PET positivity on longitudinal cognition based on the MMSE and CDR-SB were evaluated using mixed effects models.

Results

During the follow-up, 10 (4.4%) patients developed ICH: cortical superficial siderosis (cSS; hazard ratio [HR], 6.45) and previous lobar ICH (HR, 4.9), but lobar cerebral microbleeds (CMBs) were not predictors of ICH development. The presence of CMIs (p = 0.045) and Aβ positivity (p = 0.002) were associated with worse MMSE trajectory in CAA patients. Regarding CDR-SB trajectory, only Aβ positivity was marginally associated with worse longitudinal change (p = 0.050).

Conclusion

The results of the present study indicated that various imaging markers in CAA patients have different clinical relevance and predictive values for further clinical courses.
Trends in clinical characteristics and outcomes of all critically ill COVID-19 adult patients hospitalized in France between March 2020 and June 2021: a national database study
Authors: Naouri Diane , Vuagnat Albert , Beduneau Gaëtan , Dres Martin , Pham Tai , Mercat Alain , Combes Alain , Demoule Alexandre , Kimmoun Antoine , Schmidt Matthieu , Jamme Matthieu
Published: January 2023

Introduction

Studies regarding coronavirus disease 2019 (COVID-19) were mainly performed in the initial wave, but some small-scale data points to prognostic differences for patients in successive waves. We therefore aimed to study the impact of time on prognosis of ICU-admitted COVID-19 patients.

Method

We performed a national retrospective cohort study, including all adult patients hospitalized in French ICUs from March 1, 2020 to June 30, 2021, and identified three surge periods. Primary and secondary outcomes were in-hospital mortality and need for invasive mechanical ventilation, respectively.

Results

105,979 critically ill ICU-admitted COVID-19 patients were allocated to the relevant three surge periods. In-hospital mortality for surges 1, 2, and 3 was, respectively, 24%, 27%, and 24%. Invasive mechanical ventilation was the highest level of respiratory support for 42%, 32%, and 31% (p < 0.001) over the whole period, with a decline in the use of vasopressors over time. Adjusted for age, sex, comorbidities, and modified Simplified Acute Physiology Score II at ICU admission, time period was associated with less invasive mechanical ventilation and a high risk of in-hospital death. Vaccination against COVID-19 was associated with a lower likelihood of invasive mechanical ventilation (adjusted sub-hazard ratio [aSHR] = 0.64 [0.53–0.76]) and intra-hospital death (aSHR = 0.80, [0.68–0.95]).

Conclusion

In this large database of ICU patients admitted for COVID-19, we observed a decline in invasive mechanical ventilation, vasopressors, and RRT use over time but a high risk of in-hospital death. Vaccination was identified as protective against the risk of invasive mechanical ventilation and in-hospital death.
Hand pose estimation based on improved NSRM network
Authors: Yang Shiqiang , He Duo , Li Qi , Wang Jinhua , Li Dexin
Published: January 2023

Hand pose estimation is the basis of dynamic gesture recognition. In vision-based hand pose estimation, the performance of hand pose estimation is affected due to the high flexibility of hand joints, local similarity and severe occlusion among hand joints. In this paper, the structural relations between hand joints are established, and the improved nonparametric structure regularization machine (NSRM) is used to achieve more accurate estimation of hand pose. Based on the NSRM network, the backbone network is replaced by the new high-resolution net proposed in this paper to improve the network performance, and then the number of parameters is decreased by reducing the input and output channels of some convolutional layers. The experiment of hand pose estimation is carried out by using public dataset, the experimental results show that the improved NSRM network has higher accuracy and faster inference speed for hand pose estimation.
Caspase-8 contributes to an immuno-hot microenvironment by promoting phagocytosis via an ecto-calreticulin-dependent mechanism
Authors: Gong Zhihua , Jia Qingzhu , Guo Jinming , Li Chongyi , Xu Shouxia , Jin Zheng , Chu Han , Wan Yisong Y. , Zhu Bo , Zhou Yi
Published: January 2023

Background

Caspase-8 (Casp8) acts as an initiator in cell apoptosis signaling. However, the role of Casp8 in tuning the tumor immune microenvironment remains controversial due to the complicated crosstalk between immune-tolerogenic apoptotic cell death and immunogenic cell death cascades.

Methods

The Cancer Genome Atlas (TCGA) and publicly accessible immune checkpoint blockade (ICB)-treated cohorts were used to investigate the clinical relevance of Casp8. A tumor-bearing mouse model was used to characterize changes in the tumor microenvironment and to explore the efficacy of ICB treatment under Casp8 knockout conditions.

Results

By exploring TCGA datasets, we showed that the expression level of Casp8 was associated with an immuno-hot microenvironment across various solid tumor types. Casp8 deficiency leads to decreased CD8+ T cell infiltration and resistance to anti-PD-L1 therapy in a mouse model. Mechanistically, Casp8 deficiency or pharmacological disruption results in impaired ecto-calreticulin transition in tumor cells, which in turn hampers antigen presentation in draining lymph nodes. Furthermore, radiotherapy restored sensitivity to anti-PD-L1 treatment via elevated calreticulin surface expression.

Conclusions

Our data revealed a causative role of Casp8 in modulating the immunogenicity of tumor cells and responsiveness to ICB immunotherapies and proposed radiotherapy as a salvage approach to overcome Casp8 deficiency-mediated ICB resistance.
Spatial ecology of translocated American Eel (Anguilla rostrata) in a large freshwater lake
Authors: Stahl Aliénor , Larocque Sarah M. , Gardner-Costa Jesse , Mathers Alastair , Pratt Thomas C. , Schlueter Scott , Midwood Jonathan D.
Published: January 2023

American Eel (Anguilla rostrata) undertake extensive migrations from their rearing grounds to spawn in the Sargasso Sea, and historically the upper St. Lawrence River and Lake Ontario provided an important source for large, fecund female eel. Following declines in the Lake Ontario population, glass eel were translocated from eastern Canada from 2006 to 2010. From 2016 to 2018, large, presumably translocated yellow eel (N = 230) with the potential to begin maturing and out-migrating within their year of capture were collected in spring and fall and tagged with acoustic transmitters. Eel were released into eastern Lake Ontario and tracked to better understand their movement patterns prior to and during migration, and the timing of migration. Most eels successfully migrated out of Lake Ontario (64%). Timing of migration was consistent regardless of year or tagging season and primarily occurred in late summer or fall, with cooling water temperatures and decreasing sky illumination associated with initiation for fall tagged eel. Eels were mostly detected in eastern Lake Ontario and those in western Lake Ontario were mostly detected in shallow waters (< 20 m) close to shore. Eels were detected on fewer receivers in the winter, suggesting reduced movements during this season. Finally, larger individuals spent less time in the system, particularly when tagged in the fall. These findings confirm that translocated eels can migrate out of Lake Ontario; however, the weeks when migration occurred were more aligned with timing in their natal range (i.e., eastern Canada) than with naturally recruited eels from Lake Ontario. This temporal mismatch requires further consideration, since it may influence arrival times of translocated eel to the spawning grounds and their recruitment potential. These results can be used to inform future assessments of eel translocation efficacy and can also aid in the design of future tracking studies to more completely explore the downstream migration success of eel translocated into the highly productive waters of Lake Ontario.
Feasibility of a meditation intervention for stroke survivors and informal caregivers: a randomized controlled trial
Authors: Beauchamp Jennifer E. S. , Sharrief Anjail , Chaoul Alejandro , Casameni Montiel Tahani , Love Mary F. , Cron Stanley , Prossin Alan , Selvaraj Sudhakar , Dishman Deniz , Savitz Sean I.
Published: January 2023

Background

Depressive symptoms are a significant psychological complication of stroke, impacting both survivors and informal caregivers of survivors. Randomized controlled trials are needed to determine optimal non-pharmacological strategies to prevent or ameliorate depressive symptoms in stroke survivors and their informal caregivers.

Methods

A prospective, randomized, parallel-group, single-center, feasibility study. Participants were assigned to a 4-week meditation intervention or expressive writing control group. The intervention comprised four facilitator-led group meditation sessions, one session per week and building upon prior session(s). Descriptive statistics were used to examine the proportion of eligible individuals who enrolled, retention and adherence rates, and the proportion of questionnaires completed. Data were collected at baseline, immediately after the 4-week intervention period, and 4 and 8 weeks after the intervention period. Secondary analysis tested for changes in symptoms of depression (Center for Epidemiologic Studies-Depression [CES-D]), anxiety [State-Trait Anxiety Inventory for Adults (STAI)], and pain (Brief Pain Inventory-Short Form) in the intervention group via paired t tests. Linear mixed models were used to compare longitudinal changes in the measures between the groups. Intervention and trial design acceptability were preliminary explored.

Results

Seventy-one (77%) individuals enrolled and 26 (37%) completed the study (baseline and 8-week post-intervention visits completed). Forty-two (66%) participants completed baseline and immediate post-intervention visits. Mean questionnaire completion rate was 95%. The median meditation group session attendance rate for the intervention group was 75.0%, and the mean attendance rate was 55%. Non-significant reductions in CES-D scores were found. Paired t tests for stroke survivors indicated a significant reduction from baseline through week 8 in BPI-sf severity scores (p = 0.0270). Repeated measures analysis with linear mixed models for informal caregivers indicated a significant reduction in in STAI-Trait scores (F [3,16.2] = 3.28, p = 0.0479) and paired t test showed a significant reduction from baseline to week 4 in STAI-Trait scores (mean = − 9.1250, 95% CI [− 16.8060 to 1.4440], p = 0.0262). No between-group differences were found.

Conclusions

Future trials will require strategies to optimize retention and adherence before definitive efficacy testing of the meditation intervention.

Trial registration: ClinicalTrials.gov Identifier: NCT03239132. Registration date: 03/08/2017
Emotional processing in patients with single brain damage in the right hemisphere
Authors: Álvarez-Fernández Sonia , Andrade-González Nelson , Simal Patricia , Matias-Guiu Jordi A. , Gómez-Escalonilla Carlos , Rodriguez-Jimenez Roberto , Stiles Bryan J. , Lahera Guillermo
Published: January 2023

Background

The interest in the relationship between brain damage and social cognition has increased in recent years. The objectives of the present study were the following: (1) to evaluate and compare emotional facial recognition and subjective emotional experience in patients who have suffered a single ischemic stroke in the right hemisphere (RH) and in healthy people, (2) to analyze the relationship between both variables in both groups of subjects, and (3) to analyze the association between the cerebral location of the stroke and these two variables.

Methods

Emotional facial recognition and the subjective emotional experience of 41 patients who had suffered a single ischemic stroke in the RH and 45 volunteers without previous cerebrovascular pathology were evaluated.

Results

Brain damaged patients performed lower in facial emotional recognition and had a less intense subjective emotional response to social content stimuli compared to healthy subjects. Likewise, among patients with RH ischemic stroke, we observed negative associations between facial recognition of surprise and reactivity to unpleasant images, and positive associations between recognition of disgust and reactivity to pleasant images. Finally, patients with damage in the caudate nucleus of the RH presented a deficit in the recognition of happiness and sadness, and those with damage in the frontal lobe exhibited a deficit in the recognition of surprise, compared to those injured in other brain areas.

Conclusions

Emotional facial recognition and subjective emotional experience are affected in patients who have suffered a single ischemic stroke in the RH. Professionals caring for stroke patients should improve their understanding of the general condition of affected persons and their environment, assess for risk of depression, and facilitate their adaptation to work, family, and social environments.
Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses
Authors: Okonechnikov Konstantin , Federico Aniello , Schrimpf Daniel , Sievers Philipp , Sahm Felix , Koster Jan , Jones David T. W. , von Deimling Andreas , Pfister Stefan M. , Kool Marcel , Korshunov Andrey
Published: January 2023

Nowadays medulloblastoma (MB) tumors can be treated with risk-stratified approaches with up to 80% success rate. However, disease relapses occur in approximately 30% of patients and successful salvage treatment strategies at relapse remain scarce. Acquired copy number changes or TP53 mutations are known to occur frequently in relapses, while methylation profiles usually remain highly similar to those of the matching primary tumors, indicating that in general molecular subgrouping does not change during the course of the disease. In the current study, we have used RNA sequencing data to analyze the transcriptome profiles of 43 primary-relapse MB pairs in order to identify specific molecular features of relapses within various tumor groups. Gene variance analysis between primary and relapse samples demonstrated the impact of age in SHH-MB: the changes in gene expression relapse profiles were more pronounced in the younger patients (< 10 years old), which were also associated with increased DNA aberrations and somatic mutations at relapse probably driving this effect. For Group 3/4 MB transcriptome data analysis uncovered clear sets of genes either active or decreased at relapse that are significantly associated with survival, thus could be potential predictive markers. In addition, deconvolution analysis of bulk transcriptome data identified progression-associated differences in cell type enrichment. The proportion of undifferentiated progenitors increased in SHH-MB relapses with a concomitant decrease of differentiated neuron-like cells, while in Group 3/4 MB relapses cell cycle activity increases and differentiated neuron-like cells proportion decreases as well. Thus, our findings uncovered significant transcriptome changes in the molecular signatures of relapsed MB and could be potentially useful for further clinical purposes.
Application of hyperspectral imaging technology to digitally protect murals in the Qutan temple
Authors: Gao Zhenhua , Du Mingyi , Cao Ning , Hou Miaole , Wang Wanfu , Lyu Shuqiang
Published: January 2023

Hyperspectral imaging technology is a research hotspot in the field of cultural heritage protection. It can be used to quickly and noninvasively obtain detailed spectral information from the surfaces of cultural relics of different categories. We can intuitively analyse pigment compositions, line characteristics, painting skills and patterns using spectral information. Hyperspectral imaging has high scientific significance and application value for the protection, restoration and research of ancient murals and other cultural relics. In this study, a mural from Daheitian hall in the Qutan temple, Qinghai Province, China, was used as a sample. The hyperspectral data were acquired and analysed for several purposes. Pigment spectral matching and abundance inversion were carried out to obtain the pigment distribution. These data were enhanced by continuum removal and histogram stretching to obtain hidden information. The dark channel prior, Criminisi and Retinex methods were used to virtually restore the image of the mural. The results indicated that by using hyperspectral imaging data, the constructed pure pigment spectrum library and suitable approaches, the types and distributions of mural pigments can be quantitatively analysed, and the lines in murals can be extracted. Hyperspectral images are helpful for identifying information hidden by pigments or surface materials. Mural images can be enhanced, and hidden information can be highlighted using enhancement methods, such as continuum removal and histogram linear stretching. In addition, hyperspectral imaging data have unique advantages in the restoration of mural images, and the combination of defogging methods and image inpainting algorithms can realize the virtual restoration of mural images. In brief, hyperspectral imaging technology was found to have a highly favourable effect on pigment analysis, line extraction, information enhancement, hidden information extraction and the virtual restoration of ancient murals.
Understanding the microbial fibre degrading communities & processes in the equine gut
Authors: Wunderlich Georgia , Bull Michelle , Ross Tom , Rose Michael , Chapman Belinda
Published: January 2023

The equine gastrointestinal tract is a self-sufficient fermentation system, housing a complex microbial consortium that acts synergistically and independently to break down complex lignocellulolytic material that enters the equine gut. Despite being strict herbivores, equids such as horses and zebras lack the diversity of enzymes needed to completely break down plant tissue, instead relying on their resident microbes to carry out fibrolysis to yield vital energy sources such as short chain fatty acids. The bulk of equine digestion occurs in the large intestine, where digesta is fermented for 36–48 h through the synergistic activities of bacteria, fungi, and methanogenic archaea. Anaerobic gut dwelling bacteria and fungi break down complex plant polysaccharides through combined mechanical and enzymatic strategies, and notably possess some of the greatest diversity and repertoire of carbohydrate active enzymes among characterized microbes. In addition to the production of enzymes, some equid-isolated anaerobic fungi and bacteria have been shown to possess cellulosomes, powerful multi-enzyme complexes that further enhance break down. The activities of both anaerobic fungi and bacteria are further facilitated by facultatively aerobic yeasts and methanogenic archaea, who maintain an optimal environment for fibrolytic organisms, ultimately leading to increased fibrolytic microbial counts and heightened enzymatic activity. The unique interactions within the equine gut as well as the novel species and powerful mechanisms employed by these microbes makes the equine gut a valuable ecosystem to study fibrolytic functions within complex communities. This review outlines the primary taxa involved in fibre break down within the equine gut and further illuminates the enzymatic strategies and metabolic pathways used by these microbes. We discuss current methods used in analysing fibrolytic functions in complex microbial communities and propose a shift towards the development of functional assays to deepen our understanding of this unique ecosystem.
In silico identification of prospective virulence factors associated with candidiasis in Meyerozyma guilliermondii strain SO from genome dataset
Authors: Zainudin Robiatul Azilah , Sabri Suriana , Salleh Abu Bakar , Abu Arpah , Khairuddin Raja Farhana Raja , Oslan Siti Nurbaya
Published: January 2023

Background

Meyerozyma guilliermondii is a prospective yeast that has extensively contributed to the biotechnology sector. In 2015, M. guilliermondii strain SO which was isolated from spoiled orange has successfully been developed as an inducer-free expression system and attained a significant impact in producing industrially important recombinant proteins. The species possesses high similarity to Candida albicans which may cause candidiasis. The industrial-benefiting M. guilliermondii strain SO has been underexplored for its virulence status. Thus, this study aimed to document the potential virulence factors through the comprehensive in silico analysis of M. guilliermondii strain SO genome. This analysis demonstrated the molecular characterization which could distinguish the pathogenicity status of M. guilliermondii.

Results

The genome data were generated from Illumina HiSeq 4000 sequencing platform and assembled into 51 scaffolds successfully accumulating a genome size of 10.63 Mbp. These enclosed 5,335 CDS genes and 5,349 protein sequences with 43.72% GC content. About 99.29% of them were annotated to public databases. Komagataella phaffii, Saccharomyces cerevisiae and the reference strain of M. guilliermondii (ATCC 6260) were used as the controls. They were compared with our in-house strain SO to identify the consensus domain or subdomain which could putatively be considered as virulence factors. Candida albicans was used as the pathogenic model. Hence, hidden Markov model against strain SO proteome had identified secreted aspartic proteases (SAP), phospholipase C (PLC) and phospholipase D (PLD) with an E-value of 2.4e−107, 9.5e−200 and 0.0e+00, respectively, in resemblance of C. albicans. The topology of the phylogenetic analysis indicated that these virulence factors in M. guilliermondii strain SO and C. albicans branched from the same node and clustered together as a clade, signifying their molecular relatedness and congeneric among these species, subsequently proposing the virulence status of M. guilliermondii.

Conclusion

The SAP, PLC and PLD genes’ features that were significant in expressing determinants of pathogenicity were successfully identified in M. guilliermondii strain SO genome dataset, thus concluding the virulency of this species. On account of this finding, the strategy of gene knockout through CRISPR-Cas9 or homologous recombination strategies is needed to engineer the feasible novel expression host system. Over and above, the genetically modified strain of M. guilliermondii allegedly may eradicate the risk of candidiasis infection.
The adult and pediatric palliative care: differences and shared issues
Authors: Chelazzi Cosimo , Villa Gianluca , Lanini Iacopo , Romagnoli Stefano , Latronico Nicola
Published: January 2023

Adult and pediatric palliative care (PC) share common aims and ethical principles but differ in many organizational and practical aspects. The aim of this narrative review is to analyze these differences and focus on which key aspects of pediatric palliative care could integrate adult services for a better care of suffering patients.

Interventions which are peculiar of pediatric PC respect to adult PC include: an earlier referral to the PC service to identify the needs and plan the interventions at an earlier stage of the disease; consequently, a more systematic cooperation with the disease-specific physicians to reduce the burden of treatments; a better integration with the community and the social surroundings of the patients, to prevent social isolation and preserve their social role; a more dynamic organization of the PC services, to give patients the chance of being stabilized at in-hospital or residential settings and subsequently discharged and cared at home whenever possible and desired; the implementation of respite care for adults, to help the families coping with the burden of the disease of their beloved and promote the home-based PC.

This review underlines the relevance of some key-aspects of pediatric PC that can be beneficial also within PC of adults. Its findings give the chance for a more dynamic and modern organization of adult PC services and may serve as a basis of future research for new interventions.
Noncoding Mutations in a Thyroid Hormone Receptor Gene That Impair Cone Photoreceptor Function
Authors: Liu Hong , Lu Ailing , Kelley Kevin A , Forrest Douglas
Published: January 2023

The function of a hormone receptor requires mechanisms to control precisely where, when, and at what level the receptor gene is expressed. An intriguing case concerns the selective induction of thyroid hormone receptor β2 (TRβ2), encoded by Thrb, in the pituitary and also in cone photoreceptors, in which it critically regulates expression of the opsin photopigments that mediate color vision. Here, we investigate the physiological significance of a candidate enhancer for induction of TRβ2 by mutagenesis of a conserved intron region in its natural context in the endogenous Thrb gene in mice. Mutation of e-box sites for bHLH (basic-helix-loop-helix) transcription factors preferentially impairs TRβ2 expression in cones whereas mutation of nearby sequences preferentially impairs expression in pituitary. A deletion encompassing all sites impairs expression in both tissues, indicating bifunctional activity. In cones, the e-box mutations disrupt chromatin acetylation, blunt the developmental induction of TRβ2, and ultimately impair cone opsin expression and sensitivity to longer wavelengths of light. These results demonstrate the necessity of studying an enhancer in its natural chromosomal context for defining biological relevance and reveal surprisingly critical nuances of level and timing of enhancer function. Our findings illustrate the influence of noncoding sequences over thyroid hormone functions.
Patient and Operative Factors Predict Risk of Discretionary Prolonged Postoperative Mechanical Ventilation in a Broad Surgical Cohort
Authors: Clark Michael G. , Mueller Dorothee A. , Dudaryk Roman , Li Gen , Freundlich Robert E.
Published: January 2023

BACKGROUND:

Patients undergoing surgery with general anesthesia and endotracheal intubation are ideally extubated upon case completion, as prolonged postoperative mechanical ventilation (PPMV) has been associated with poor outcomes. However, some patients require PPMV for surgical reasons, such as airway compromise, while others remain intubated at the discretion of the anesthesia provider. Incidence and risk factors for discretionary PPMV (DPPMV) have been described in individual surgical subspecialties and intensive care unit (ICU) populations, but are relatively understudied in a broad surgical cohort. The present study seeks to fill this gap and identify the perioperative risk factors that predict DPPMV.

METHODS:

After obtaining institutional review board (IRB) exemption, existing electronic health record databases at our large referral center were retrospectively queried for adult surgeries performed between January 2018 and December 2020 with general anesthesia, endotracheal intubation, and by surgical services that do not routinely leave patients intubated for surgical reasons. Patients who arrived to the ICU intubated after surgery were identified as experiencing DPPMV. Selection of candidate risk factors was performed with LASSO-regularized logistic regression, and surviving variables were used to generate a multivariable logistic regression model of DPPMV risk.

RESULTS:

A total of 32,915 cases met inclusion criteria, of which 415 (1.26%) experienced DPPMV. Compared to extubated patients, those with DPPMV were more likely to have undergone emergency surgery (42.9% versus 3.4%; P < .001), surgery during an existing ICU stay (30.8% versus 2.8%; P < 0.001), and have 20 of the 31 elixhauser comorbidities (P < .05 for each comparison), among other differences. A risk model with 12 variables, including American Society of Anesthesiologists (ASA) physical classification status, emergency surgery designation, four Elixhauser comorbidities, surgery during an existing ICU stay, surgery duration, estimated number of intraoperative handoffs, and vasopressor, sodium bicarbonate, and albuterol administration, yielded an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.96–0.97) for prediction of DPPMV.

CONCLUSIONS:

DPPMV was uncommon in this broad surgical cohort but could be accurately predicted using readily available patient-specific and operative factors. These results may be useful for preoperative risk stratification, postoperative resource allocation, and clinical trial planning.
IGF2 interacts with the imprinted gene Cdkn1c to promote terminal differentiation of neural stem cells
Authors: Lozano-Ureña Anna , Lázaro-Carot Laura , Jiménez-Villalba Esteban , Montalbán-Loro Raquel , Mateos-White Isabel , Duart-Abadía Pere , Martínez-Gurrea Irene , Nakayama Keiichi I. , Fariñas Isabel , Kirstein Martina , Gil-Sanz Cristina , Ferrón Sacri R.
Published: January 2023

Adult neurogenesis is supported by multipotent neural stem cells (NSCs) with unique properties and growth requirements. Adult NSCs constitute a reversibly quiescent cell population that can be activated by extracellular signals from the microenvironment in which they reside in vivo. Although genomic imprinting plays a role in adult neurogenesis through dose regulation of some relevant signals, the roles of many imprinted genes in the process remain elusive. Insulin-like growth factor 2 (IGF2) is encoded by an imprinted gene that contributes to NSC maintenance in the adult subventricular zone through a biallelic expression in only the vascular compartment. We show here that IGF2 additionally promotes terminal differentiation of NSCs into astrocytes, neurons and oligodendrocytes by inducing the expression of the maternally expressed gene cyclin-dependent kinase inhibitor 1c (Cdkn1c), encoding the cell cycle inhibitor p57. Using intraventricular infusion of recombinant IGF2 in a conditional mutant strain with Cdkn1c-deficient NSCs, we confirm that p57 partially mediates the differentiation effects of IGF2 in NSCs and that this occurs independently of its role in cell-cycle progression, balancing the relationship between astrogliogenesis, neurogenesis and oligodendrogenesis.
Nucleophagy contributes to genome stability through degradation of type II topoisomerases A and B and nucleolar components
Authors: Muciño-Hernández Gabriel , Acevo-Rodríguez Pilar Sarah , Cabrera-Benitez Sandra , Guerrero Adán Oswaldo , Merchant-Larios Horacio , Castro-Obregón Susana
Published: January 2023

The nuclear architecture of mammalian cells can be altered as a consequence of anomalous accumulation of nuclear proteins or genomic alterations. Most of the knowledge about nuclear dynamics comes from studies on cancerous cells. How normal healthy cells maintain genome stability, avoiding accumulation of nuclear damaged material, is less understood. Here, we describe that primary mouse embryonic fibroblasts develop a basal level of nuclear buds and micronuclei, which increase after etoposide-induced DNA double-stranded breaks. Both basal and induced nuclear buds and micronuclei colocalize with the autophagic proteins BECN1 and LC3B (also known as MAP1LC3B) and with acidic vesicles, suggesting their clearance by nucleophagy. Some of the nuclear alterations also contain autophagic proteins and type II DNA topoisomerases (TOP2A and TOP2B), or the nucleolar protein fibrillarin, implying they are also targets of nucleophagy. We propose that basal nucleophagy contributes to genome and nuclear stability, as well as in response to DNA damage.
Critical Power and Respiratory Compensation Point Are Not Equivalent in Patients with COPD
Authors: TILLER NICHOLAS B. , PORSZASZ JANOS , CASABURI RICHARD , ROSSITER HARRY B. , FERGUSON CARRIE
Published: January 2023

Introduction

Several studies report that pulmonary oxygen uptake (V̇O2) at the respiratory compensation point (RCP) is equivalent to the V̇O2 at critical power (CP), suggesting that the variables can be used interchangeably to demarcate the threshold between heavy and severe intensity domains. However, if RCP is a valid surrogate for CP, their values should correspond even when assessed in patients with chronic obstructive pulmonary disease (COPD) in whom the “normal” mechanisms linking CP and RCP are impeded. The aim of this study was to compare V̇O2 at CP with V̇O2 at RCP in patients with COPD.

Methods

Twenty-two COPD patients (14 male/8 female; forced expiratory volume in 1 s, 46% ± 17% pred) performed ramp-incremental cycle ergometry to intolerance (5–10 W·min−1) for the determination of gas exchange threshold (GET) and RCP. CP was calculated from the asymptote of the hyperbolic power–duration relationship from 3–5 constant-power exercise tests to intolerance. CP was validated with a 20-min constant-power ride.

Results

GET was identified in 20 of 22 patients at a V̇O2 of 0.93 ± 0.18 L·min−1 (75% ± 13% V̇O2peak), whereas RCP was identified in just 3 of 22 patients at a V̇O2 of 1.40 ± 0.39 L·min−1 (85% ± 2% V̇O2peak). All patients completed constant-power trials with no difference in peak physiological responses relative to ramp-incremental exercise (P > 0.05). CP was 46 ± 22 W, which elicited a V̇O2 of 1.04 ± 0.29 L·min−1 (90% ± 9% V̇O2peak) during the validation ride. The difference in V̇O2 at 15 and 20 min of the validation ride was 0.00 ± 0.04 L, which was not different from a hypothesized mean of 0 (P = 0.856), thereby indicating a V̇O2 steady state.

Conclusions

In COPD patients, who present with cardiopulmonary and/or respiratory-mechanical dysfunction, CP can be determined in the absence of RCP. Accordingly, CP and RCP are not equivalent in this group.
Bilateral lymphadenopathies on mammograms: a case of mixed connective tissue disease and psoriatic arthropathy
Authors: Giambersio Emilia , Magni Veronica , Sardanelli Francesco
Published: January 2023

Axillary lymphadenopathy is defined as abnormality (e.g., increase in size or density) of lymph nodes in the armpit, caused by malignant diseases such as metastases (mainly from primary breast cancer), lymphoma, or leukaemia as well as benign conditions such as infectious or autoimmune systemic diseases. Appropriate imaging and pathological examinations on needle samples, together with accurate clinical correlation are needed for a correct diagnosis and management.

Herein, we report a case of a 47-year-old female presented at our department of radiology for her annual mammographic screening. Mammography demonstrated multiple bilateral, enlarged, although benign-appearing axillary lymph nodes. While both breasts showed no sign of malignancy on mammograms, the lymphadenopathies suggested a potential underlying inflammatory process. Previous mammography performed five years before did not present any lymphadenopathy. The patient, recalled for additional breast and axillary ultrasound and for clinical correlation, reported that she had been suffering for at least four years from an autoimmune systemic disease, mixed connective tissue disease, recently overlapping with psoriatic arthropathy, thus explaining the aetiology of reactive lymph nodes enlargement.
MRI features of perifibrinous deposits in the placenta due to COVID-19
Authors: Alessa Hiba , Peres Luiz Cesar , Ferriman Emma , Fry Andrew , Whitby Elspeth
Published: January 2023

COVID-19 has been linked to pregnancy complications and loss (1). Infection during pregnancy is usually mild (2). The risk is highest in the third trimester with increased hospital admission rates and maternal and fetal compromise (3). Post-COVID placentitis is uncommon but the effect on the placenta and the fetus is extensive (4). We present a case correlating clinical, imaging, and pathological findings. Case Report: A 29-year-old para 2 gravida 1, with a normal fetal anomaly scan at 22 weeks gestational age (GA) contracted COVID at 24 weeks gestation. Fully recovered but reported reduced fetal movements at 27 weeks and 1 day. Imaging: US scan showed bright echoes within the brain, small lungs, and oligohydramnios. MRI showed abnormal brain signals, small lungs, and oligohydramnios but also a very abnormal placenta. Reduced and heterogeneous T2 signal and a marked reduction in the DWI signal intensity. The placental size was markedly reduced (volume 785.6 cm3 expected for GA is 5604.8–5952.4 cm3. The surface area of attachment was 3220 mm2, expected 22180.4–29293.2 mm2). Pathology: The placenta was small (fifth centile) with massive perivillous fibrin deposition and multifocal chronic deciduitis. Histology revealed placental chorionic villi showing diffuse sclerotic changes surrounded by perivillous fibrin deposition in the intervillous space. The basal plate revealed multifocal chronic deciduitis. When imaging the fetus, it is important to examine the placenta and correlate any abnormalities. The placenta is a forgotten organ and should be routinely included and assessed to allow the detection of important abnormalities.