bluuebunny/crossref_metadata_2025 huggingface dataset:
“Histological and Immunohistochemical Evaluation of Human Breast Capsules Formed Around Five Different Expander Surfaces”
Authors: Cagli Barbara , Carotti Simone , Segreto Francesco , Francesconi Maria , Marangi Giovanni F. , Tenna Stefania , Diomedi Michele , Perrone Giuseppe , Morini Sergio , Persichetti Paolo
Published: February 2023

Background:

Polyurethane (PU) coating and implant texturization were designed to reduce the incidence of capsular contracture (CC), even if the link between surface type and CC remains unclear. To date the etiopathogenetic aspects have not been fully clarified. The aim of this study was to evaluate capsules formed around 5 different breast expanders.

Methods:

Thirty patients were divided into randomized groups implanted with 5 different expanders: Smooth, coated with PU foam (Poly), with a low-microtextured, high-microtextured, and macrotextured surface (L-Micro, H-Micro, Macro). Specimens of the capsules were removed at implant reconstruction and evaluated for morphology and immunohistochemistry expression of α-smooth muscle actin (α-SMA), collagen type I and III, CD68, CD34, and CD3. Remodeling combined index was also evaluated.

Results:

Expression of α-SMA was significantly increased in Smooth capsules versus Poly, L-Micro, and H-Micro groups (p=0.007; p=0.010; p=0.028), while the prevalence of collagen type I in Smooth capsules and collagen type III in Poly capsules identified a stable versus an unstable tissue. Remodeling combined index and α-SMA showed an inverted correlation. CD68 and CD34 cellular expression increased significantly in Poly capsules with respect to Smooth (p<0.001; p<0.001) and Macro groups (p<0.001; p<0.001). CD3 showed no significant difference among the groups.

Conclusions:

In this human study we observed that an increased tissue remodeling and a reduced myofibroblasts activation, along with the inflammatory infiltration and the neo-angiogenesis, especially in Poly and L-Micro groups, might promote the formation of an unstable and less fibrotic capsule, lowering the risk of CC.
Impact of Vasodilation on Oxygen-Enhanced Functional Lung MRI at 0.55 T
Authors: Wieslander Björn , Seemann Felicia , Javed Ahsan , Bruce Christopher G. , Ramasawmy Rajiv , Jaimes Andrea , Lucas Katherine , Frasier Victoria , O'Brien Kendall J. , Potersnak Amanda , Khan Jaffar M. , Schenke William H. , Chen Marcus Y. , Lederman Robert J. , Campbell-Washburn Adrienne E.
Published: February 2023

Background

Oxygen-enhanced magnetic resonance imaging (OE-MRI) can be used to assess regional lung function without ionizing radiation. Inhaled oxygen acts as a T1-shortening contrast agent to increase signal in T1-weighted (T1w) images. However, increase in proton density from pulmonary hyperoxic vasodilation may also contribute to the measured signal enhancement. Our aim was to quantify the relative contributions of the T1-shortening and vasodilatory effects of oxygen to signal enhancement in OE-MRI in both swine and healthy volunteers.

Methods

We imaged 14 anesthetized female swine (47 ± 8 kg) using a prototype 0.55 T high-performance MRI system while experimentally manipulating oxygenation and blood volume independently through oxygen titration, partial occlusion of the vena cava for volume reduction, and infusion of colloid fluid (6% hydroxyethyl starch) for volume increase. Ten healthy volunteers were imaged before, during, and after hyperoxia. Two proton density–weighted (PDw) and 2 T1w ultrashort echo time images were acquired per experimental state. The median PDw and T1w percent signal enhancement (PSE), compared with baseline room air, was calculated after image registration and correction for lung volume changes. Differences in median PSE were compared using Wilcoxon signed rank test.

Results

The PSE in PDw images after 100% oxygen was similar in swine (1.66% ± 1.41%, P = 0.01) and in healthy volunteers (1.99% ± 1.79%, P = 0.02), indicating that oxygen-induced pulmonary vasodilation causes ~2% lung proton density increase. The PSE in T1w images after 100% oxygen was also similar (swine, 9.20% ± 1.68%, P < 0.001; healthy volunteers, 10.10% ± 3.05%, P < 0.001). The PSE in T1w enhancement was oxygen dose-dependent in anesthetized swine, and we measured a dose-dependent PDw image signal increase from infused fluids.

Conclusions

The contribution of oxygen-induced vasodilation to T1w OE-MRI signal was measurable using PDw imaging and was found to be ~2% in both anesthetized swine and in healthy volunteers. This finding may have implications for patients with regional or global hypoxia or vascular dysfunction undergoing OE-MRI and suggest that PDw imaging may be useful to account for oxygen-induced vasodilation in OE-MRI.
Personalized and privacy-preserving federated heterogeneous medical image analysis with PPPML-HMI
Authors: Zhou Juexiao , Zhou Longxi , Wang Di , Xu Xiaopeng , Li Haoyang , Chu Yuetan , Han Wenkai , Gao Xin
Published: February 2023

Heterogeneous data is endemic due to the use of diverse models and settings of devices by hospitals in the field of medical imaging. However, there are few open-source frameworks for federated heterogeneous medical image analysis with personalization and privacy protection simultaneously without the demand to modify the existing model structures or to share any private data. In this paper, we proposed PPPML-HMI, an open-source learning paradigm for personalized and privacy-preserving federated heterogeneous medical image analysis. To our best knowledge, personalization and privacy protection were achieved simultaneously for the first time under the federated scenario by integrating the PerFedAvg algorithm and designing our novel cyclic secure aggregation with the homomorphic encryption algorithm. To show the utility of PPPML-HMI, we applied it to a simulated classification task namely the classification of healthy people and patients from the RAD-ChestCT Dataset, and one real-world segmentation task namely the segmentation of lung infections from COVID-19 CT scans. For the real-world task, PPPML-HMI achieved ∼5% higher Dice score on average compared to conventional FL under the heterogeneous scenario. Meanwhile, we applied the improved deep leakage from gradients to simulate adversarial attacks and showed the solid privacy-preserving capability of PPPML-HMI. By applying PPPML-HMI to both tasks with different neural networks, a varied number of users, and sample sizes, we further demonstrated the strong robustness of PPPML-HMI.
Association of Cancer History with Structural Brain Aging Markers of Alzheimer’s Disease and Dementia Risk
Authors: Wang Jingxuan , Sims Kendra D. , Ackley Sarah F. , Chen Ruijia , Kobayashi Lindsay C. , Hayes-Larson Eleanor , Mayeda Elizabeth Rose , Buto Peter , Zimmerman Scott C. , Graff Rebecca E. , Glymour M. Maria
Published: February 2023

Background and Objectives

Cancer survivors are less likely than comparably-aged individuals without a cancer history to develop Alzheimer’s disease and related dementias (ADRD). We investigated the association between cancer history and structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences at the mean values of MRI markers and quantile regression to examine whether the association varies across the distribution of MRI markers of brain aging.

Methods

Among UK Biobank participants with ≥1 brain MRI, we considered total gray matter volume, total brain volume, hippocampal volume, white matter hyperintensity volume, and mean cortical thickness in the Alzheimer’s disease (AD) signature region. Cancer history was ascertained from national registry and self-report. We first specified linear mixed models with random intercepts to assess mean differences in MRI markers according to cancer history. Next, to examine whether effects of cancer history on these markers varies across the ADRD risk distribution, we specified quantile regression models to assess differences in quantile cut-points of the distribution of MRI markers according to cancer history. Models adjusted for demographics, APOE-ε4 status, and health behaviors.

Results

The sample included 42,242 MRIs on 37,588 participants with no cancer history (mean age 64.1 years), and 6,073 MRIs on 5,514 participants with a cancer diagnosis prior to MRI (mean age 66.7 years). Cancer history was associated with smaller mean hippocampal volume (b=-19 mm3, 95% confidence interval [CI]=-36, -1) and lower mean cortical thickness in the AD signature region (b=-0.004 mm, 95% CI=-0.007, -0.000). Quantile regressions indicated cancer history had larger effects on high quantiles of white matter hyperintensities (10thpercentile b=-49 mm3, 95% CI=-112, 19; 90thpercentile b=552 mm3, 95% CI= 250, 1002) and low quantiles of cortical thickness (10thpercentile b=-0.006 mm, 95% CI=-0.011, -0.000; 90thpercentile b=0.003 mm3, 95% CI=-0.003, 0.007), indicating individuals most vulnerable to ADRD were more affected by cancer history.

Discussion

We found no evidence that cancer history was associated with less ADRD-related neurodegeneration. To the contrary, adults with cancer history had worse MRI indicators of dementia risk. Adverse associations were largest in the highest-risk quantiles of neuroimaging markers.
Structural and functional pathology in cocaine use disorder with polysubstance use: a multimodal fusion approach
Authors: Rasgado-Toledo Jalil , Duvvada Sai Siddharth , Shah Apurva , Ingalhalikar Madhura , Alluri Vinoo , Garza-Villarreal Eduardo A.
Published: February 2023

Cocaine use disorder (CUD) is described as a compulsive urge to seek and consume cocaine despite the inimical consequences. MRI studies from different modalities have shown that CUD patients exhibit structural and/or functional connectivity pathology among several brain regions. Nevertheless, both connectivities are commonly studied and analyzed separately, which may potentially obscure its relationship between them, and with the clinical pathology. Here, we compare and contrast structural and functional brain networks in CUD patients and healthy controls (HC) using multimodal fusion. The sample consisted of 63 (8 females) CUD patients and 42 (9 females) healthy controls (HC), recruited as part of the SUDMEX CONN database. For this, we computed a battery of graph-based measures from multi-shell diffusion-weighted imaging and resting state fc-fMRI to quantify local and global connectivity. Then we used multimodal canonical component analysis plus joint independent component analysis (mCCA+jICA) to compare between techniques, and evaluate group differences and its association with clinical alteration. Unimodal results showed a striatal decrease in the participation coefficient, but applied supervised data fusion revealed other regions with cocaine-related alterations in joint functional communication. When performing multimodal fusion analysis, we observed a higher centrality of the interrelationship and a lower participation coefficient in patients with CUD. In contrast to the unimodal approach, the multimodal fusion method was able to reveal latent information about brain regions involved in impairment due to cocaine abuse. The present results could help in understanding the pathology of CUD in order to develop better pre-treatment/post-treatment intervention designs.
Deciphering causal proteins in Alzheimer’s disease: A novel Mendelian randomization method integrated with AlphaFold3 for 3D structure prediction
Authors: Yao Minhao , Miller Gary W. , Vardarajan Badri N. , Baccarelli Andrea A. , Guo Zijian , Liu Zhonghua
Published: February 2023

Hidden confounding biases hinder identifying causal protein biomarkers for Alzheimer’s disease in non-randomized studies. While Mendelian randomization (MR) can mitigate these biases using protein quantitative trait loci (pQTLs) as instrumental variables, some pQTLs violate core assumptions, leading to biased conclusions. To address this, we propose MR-SPI, a novel MR method that selects valid pQTL instruments using the Anna Karenina Principle and performs robust post-selection inference. Integrating MR-SPI with AlphaFold3, we developed a computational pipeline to identify causal protein biomarkers and predict 3D structural changes. Applied to genome-wide proteomics data from 54,306 UK Biobank participants and 455,258 subjects (71,880 cases and 383,378 controls) for a genome-wide association study of Alzheimer’s disease, we identified seven proteins (TREM2, PILRB, PILRA, EPHA1, CD33, RET, and CD55) with structural alterations due to missense mutations. These findings offer insights into the etiology and potential drug targets for Alzheimer’s disease.
The association between multidimensional sleep health and gestational weight gain: nuMoM2b Sleep Duration and Continuity Study
Authors: Hawkins Marquis S. , Pokutnaya Darya Y. , Bodnar Lisa M. , Levine Michele D. , Buysse Daniel J. , Davis Esa M. , Wallace Meredith L. , Zee Phyllis C. , Grobman William A. , Reid Kathryn J. , Facco Francesca L.
Published: February 2023

Background

Although poor sleep health is associated with weight gain and obesity in the non-pregnant population, research on the impact of sleep health on weight change among pregnant people using a multidimensional sleep-health framework is needed. This study examined associations among mid-pregnancy sleep health indicators, multidimensional sleep health, and gestational weight gain (GWG).

Methods

We conducted a secondary data analysis of the Nulliparous Pregnancy Outcome Study: Monitoring Mothers-to-be Sleep Duration and Continuity Study (n=745). Indicators of individual sleep domains (i.e., regularity, nap duration, timing, efficiency, and duration) were assessed via actigraphy between 16 and 21 weeks of gestation. We defined “healthy” sleep in each domain based on empirical thresholds. Multidimensional sleep health was based on sleep profiles derived from latent class analysis. Total GWG, the difference between self-reported pre-pregnancy weight and the last measured weight before delivery, was converted to z-scores using gestational age- and BMI-specific charts. GWG was defined as low (<−1 SD), moderate (−1 or +1 SD), and high (>+1 SD).

Results

Nearly 50% of the participants had a healthy sleep profile (i.e., healthy sleep in most domains), whereas others had a sleep profile defined as having varying degrees of poor health in each domain. While indicators of individual sleep domains were not associated with GWG, multidimensional sleep health was related to low and high GWG. Participants with a sleep profile characterized as having low efficiency, late timing, and long sleep duration (vs. healthy sleep profile) had a higher risk (RR 1.7; 95% CI 1.0, 3.1) of low GWG a lower risk of high GWG (RR 0.5 95% CI 0.2, 1.1) (vs. moderate GWG).

Conclusions

Multidimensional sleep health was more strongly associated with GWG than individual sleep domains. Future research should determine whether sleep health is a valuable intervention target for optimizing GWG.

Synopsis

Study question

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What is the association between mid-pregnancy multidimensional sleep health and gestational weight gain?

What’s already known?

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Sleep is associated with weight and weight gain outside of pregnancy

What does this study add?

-

We identified patterns of sleep behaviors associated with an increased risk of low gestational weight gain
The Q-IMPROvE (Queensland-IMplementation of PRecision Oncology in brEast cancer) pilot study
Authors: McCart Reed Amy E , McCurry Therese , Hollway Georgina , Al-Saig Haidar , Andelkovic Vladimir , Cuff Katharine , Cummings Margaret , Fairbairn David , Inglis Po-ling , Jagger Gillian , Johanson Helene , Kalinowski Lauren , Kondrashova Olga , Koufariotis Lambros T. , Kuchel Anna , Ladwa Rahul , Lau Chiyan , Lundie Ben , Fan Helen Mar , McCarthy Nicole , Middleton Kathryn , Murugappan Kowsalya , Nalder Mark , Niland Colleen , Nottage Michelle K , O’Byrne Kenneth J , Pearson John V , Roberts Kate , Hormaechea Gorane Santamaria , Snell Cameron , Steinke Karin , Suder Aneta , Tam Diana , Walpole Euan , Woodward Natasha , Wong Clement , Wong Ho Yi , Xu Wen , Simpson Peter T , Waddell Nicola , Lakhani Sunil R
Published: February 2023

Background

The cancer genomics field has embraced the advent of precision oncology, and vast volumes of data have been mined for biomarkers of drug actionability. While some cancers, such as lung cancer, have detailed panels of actionable genomic biomarkers, sequencing panels have been less useful in breast cancer given its large number of cancer driver genes mutated at a relatively low frequency. Furthermore, mutation signatures have potential to assist in identifying homologous recombination deficient tumours for targeting with PARP inhibitor therapy.

Patients and Methods

To investigate whether whole genome sequencing could benefit breast cancer patients we initiated the Q-IMPROvE (Queensland-IMplementation of PRecision Oncology in brEast cancer) prospective pilot study. We report the analysis of matched tumour and normal genomes of 28 high-risk breast cancer patients undergoing treatment in the neo-adjuvant setting.

Results

Using whole genome sequencing, we detected actionable events that would otherwise not have been identified. A quarter of patients demonstrated a defect in homologous recombination DNA repair using the HRDetect and HRD scores. Germline variants of importance (BRCA1, CHEK2) were identified in two patients that did not meet clinical guidelines for germline genetic testing. Somatically,TP53andPIK3CAwere the most commonly mutated breast cancer driver genes.

Conclusions

We have demonstrated the benefit of whole genome sequencing of both the tumour and germline for breast cancer patients otherwise not meeting clinical criteria for genetic health referrals.
Baseline TyG index, myoglobin, and cerebral infarction history predict the onset of pulmonary hypertension in coronary artery disease patients after PCI treatment within a median of 4.5 years: a prospective cohort study
Authors: Xie Li , Fu Shilin , Xu Yuzheng , Ran Litong , Luo Jing , Rao Rongsheng , Chen Jianfei , Bian Shi-Zhu , Qian Dehui
Published: February 2023

Aim

To identify the predictive role of the TyG index for the onset of pulmonary hypertension in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) treatment.

Methods

We performed this prospective cohort study among CAD patients who received PCI treatment in our center from July 2016 to October 2022. The baselines of echocardiography at both cross-sections and blood biomarkers. A coronary angiography operation was also performed. Within a median of 4.5 years of follow-up, the patients underwent echocardiography to measure their pulmonary hypertension (PH).

Results

Baseline BNP was statistically higher in the PH patients (p = 0.007). The baseline myoglobin (MYO), was significantly higher among PH patients (p < 0.001). Though the glucose level showed no difference between PH and non-PH groups, the HDL-C was in a lower level in the PH group (p = 0.033). However, TyG index showed no differences between PH and non-PH groups [6.95 (6.47-7.36) vs. 7.15 (6.49-7.96), p = 0.202]. In the univariate regression, cerebral infarction history, right atria end-diastolic internal diameter, MYO, triglyceride, HDL-C and TyG index (p < 0.05) were potential predictors for PH. Finally, the adjusted logistic regression indicated that cerebral infarction history (p = 0.39), MYO (p = 0.044) and TyG index (p = 0.048) were independent predictors of the onset of PH.

Conclusion

PH is prevalent in CAD patients after PCI treatment. The baseline TyG index, cerebral infarction history, and MYO level were independent predictors for PH in CAD patients after PCI treatment.
Effects of an innovative daily physical activity intervention on the health and fitness status of primary school children: a cluster randomized controlled trial
Authors: Jarnig Gerald , Kerbl Reinhold , van Poppel Mireille N.M.
Published: February 2023

Aims

An important barrier for a nationwide implementation of a daily physical activity (PA) intervention at primary schools is the lack of spatial and human resources. Therefore, the aim was to develop an innovative PA intervention that can be implemented, without additional spatial and human resource requirements. The effects of this intervention on anthropometrics and health-related fitness of primary school children were investigated.

Methods

In twelve primary schools, 24 classes were randomly allocated to an intervention and control group. In the intervention group, children received mix physical education lessons, cognitive content using movement, and additional opportunities for extracurricular physical activities (home exercises) over a 9-month period. In the control group, children received the usual physical education classes. At baseline (Sept 2021) and at follow-up immediately after the intervention (June 2022), body weight, height, waist circumference and fitness parameters (cardiorespiratory fitness, muscle strength, flexibility) were measured. Intervention effects were assessed using multilevel regression models, adjusted for gender, urban/rural school, sports club membership, and for baseline values of the outcome parameter. Interactions between intervention and being a member of a sports club were assessed.

Results

Of 485 invited children, 412 (85%) were included in the analyses; 228 in the intervention and 184 in the control group. Children were 9.7 (SD 0.5) years old at baseline. In the total intervention group, a reduction in waist-to-height ratio and increase in all fitness parameters were found compared to the control group. Interactions with being a member of a sports club were found, and intervention effects were more pronounced in the group of children who were not a member of a sports club.

Conclusions

Our daily physical activity intervention for primary schools showed positive effects on important health related parameters, especially for children who were not in a sports club and had most of their PA at school. Wider implementation of this intervention in primary schools is warranted, which should be feasible, since we made sure that no extra resources are needed.

Trial registration

DRKS00025515.
Assessing the accuracy of a digital symptom checker tool for suggestion of reproductive health conditions: a clinical vignettes study
Authors: Peven Kimberly , Wickham Aidan , Wilks Octavia , Kaplan Yusuf C. , Marhol Andrei , Ahmed Saddif , Bamford Ryan , Prentice Carley , Meczner Andras , Fenech Matthew , Gilbert Stephen , Klepchukova Anna , Ponzo Sonia
Published: February 2023

Background

Reproductive health conditions such as endometriosis, uterine fibroids and polycystic ovary syndrome affect a large proportion of women and people who menstruate worldwide. Prevalence estimates for these conditions range from 5-40% of women of reproductive age. Long diagnostic delays, up to 12 years, are common and contribute to health complications and increased healthcare costs. Symptom checker apps provide users with information and tools to better understand their symptoms and thus have the potential to reduce the time to diagnosis for reproductive health conditions.

Objective

This study aims to evaluate the accuracy of three symptom checkers developed by Flo Health assessing symptoms of endometriosis, uterine fibroids and polycystic ovary syndrome (PCOS) against current medical guidelines.

Methods

Independent general practitioners were recruited to create clinical case vignettes of simulated users with and without the conditions of interest. Vignettes were reviewed, modified and approved by separate general practitioners. A further independent panel of general practitioners reviewed the cases and designated a final classification. Vignettes were entered into the symptom checkers and the outcomes were compared with the final classification from the panel using accuracy metrics including percent agreement, sensitivity and specificity.

Results

A total of 24 cases were created per condition. Overall, exact matches between the vignette classification and the symptom checker outcome was 83.3% for endometriosis and uterine fibroids, and 87.5% for PCOS. While sensitivity was high for all conditions (>81%) and very high (100%) for PCOS, specificity was >81% for endometriosis and uterine fibroids and 75% for PCOS.

Conclusion

The single condition symptom checkers have high levels of accuracy for endometriosis, uterine fibroids and PCOS. Given long delays in diagnosis for many reproductive health conditions, which lead to increased medical costs and potential health complications for individuals and healthcare providers, innovative health apps and symptom checkers hold the potential to improve care pathways.
DNA damage, nucleolar stress and dysregulated energy metabolism as mechanisms of multimorbidity in cardiovascular disease
Authors: Tomkova Kristina , Roman Marius , Adebayo Adewale S , Sheikh Sophia , Yusoff Syabira , Gulston Melanie , Joel-David Lathishia , Lai Florence Y , Murgia Antonio , Eagle-Hemming Bryony , Aujla Hardeep , Chad Tom , Richardson Gavin D , Griffin Julian L , Murphy Gavin J , Woźniak Marcin J
Published: February 2023

Background

People with two or more underlying chronic conditions (multimorbidity) are more susceptible to adverse events following surgery. This study used -omics methods to compare samples from people with or without multimorbidity in a cardiac surgery cohort.

Methods and Results

Measurements of the myocardial transcriptome and metabolites involved in energy production were performed in 53 and 57 sequential participants, respectively. Untargeted analysis of the metabolome in blood and myocardium was performed in 30 sequential participants. Mitochondrial respiration in circulating monocytes was measured in 63 participants. Ninety-eight of 144 participants (68%) had multimorbidity. Three major processes were affected by multimorbidity: innate immune response, DNA damage and associated epigenetic changes, and mitochondrial energy production. The innate immune response was upregulated in multimorbidity and most of the included comorbidities. The DNA damage, epigenetic changes, and aspects of mitochondrial function were specific for multimorbidity. Histone 2B, its ubiquitination enzymes and AKT3 were upregulated in the multimorbid group, supporting our hypothesis of senescence-like changes in multimorbidity. In addition, senescence-associated secretory phenotype analytes, IL-1β, its receptor, GM-CSF and fractalkine increased with the number of accumulating comorbidities. DNA damage was confirmed by independent immunohistochemistry experiments, which also identified nucleolar instability as more prominent in the multimorbid myocardium.

Conclusions

Multimorbidity in people with cardiovascular disease is characterized by biological aging processes that are known to increase susceptibility to metabolic stress. These present novel therapeutic targets for organ protection interventions.
Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens
Authors: Wang Wei , Goguet Emilie , Paz Padilla Stephanie , Vassell Russell , Pollett Simon , Mitre Edward , Weiss Carol D.
Published: February 2023

We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron SARS-CoV-2 variants after a bivalent or ancestral COVID-19 mRNA booster vaccine or post-vaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately two-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed.
PREVALENCE OF DEPRESSION AND ANXIETY IN COLOMBIA: WHAT HAPPENED DURING COVID-19 PANDEMIC?
Authors: Martínez-Cabezas Sandra , Pinilla-Roncancio Mónica , Carrasquilla Gabriel , Casas Germán , González-Uribe Catalina
Published: February 2023

The COVID-19 pandemic has impacted the well-being of millions of people around the globe. During the COVID-19 pandemic, the mental health of the population was affected, which means that governments would need to implement different actions to mitigate and treat mental health disorders result of the pandemic.

This study aims to estimate the prevalence of anxiety and depression for female and male adolescents and adults in Colombia before the COVID-19 pandemic. It also aimed to estimate the potential increase of the prevalence in each group as a result of the COVID-19 pandemic in 2020. We used the Individual Registry of Health Services Delivery data from 2015 - 2021 to estimate the observed prevalence of anxiety and depression. Using the National Mental Health Survey 2015, we simulated the expected prevalence of anxiety and depression for adolescents (12 to 17 years) and adults (18 or older) from 2016 to 2020. We used an arithmetic static Monte Carlo simulation process to estimate the expected prevalence. The results of the analysis using revealed an important increase in the observed prevalence of these disorders for adults and adolescents and men and women between 2015 and February 2020. When we simulated different scenarios using the National Mental Health Survey and estimated the prevalence of both depression and anxiety for adults and adolescents, we found that the prevalence of depression and anxiety has had an important increase in the last five years for all groups and had an important increase during the 2020. This increase has been greater for women than for men, and for adolescents than adults. Our results show the number of people who need potential attention from the health system in Colombia and highlight the importance to think about how to avoid and detect potential cases of anxiety and depression especially in female adolescents.
Real-world data validation of the PurIST pancreatic ductal adenocarcinoma gene expression classifier and its prognostic implications
Authors: Wenric Stephane , Davison James M. , Guittar John , Mayhew Gregory M. , Beebe Kirk D. , Wang Yun E. , Iyer Amrita A. , Kang Hyunseok P. , Milburn Michael V. , Chung Vincent , Bekaii-Saab Tanios , Perou Charles M.
Published: February 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is amongst the deadliest cancers, with few modern tools to inform patient prognosis and help guide treatment options. Transcriptome-based molecular subtyping is one emerging technology that has been employed to help patients optimize available therapeutic approaches. Here we retrospectively demonstrate the clinical validity of PurIST (Purity Independent Subtyping of Tumors), an RNA-based classifier that divides PDAC patients into two subtypes with differential prognoses, as a validated laboratory-developed test (LDT) on the Tempus Labs sequencing platform.

Methods

A cohort comprising 258 late-stage PDAC patients with available transcriptomic and outcomes data was drawn from the Tempus clinicogenomic database and classified using PurIST into one of two subtypes (“Basal” or “Classical”). Differences in patient survival from the date of diagnosis were compared between subtypes, and between two common first-line treatment regimens, FOLFIRINOX, and gemcitabine + nab-paclitaxel.

Results

Of the 258 PDAC patients in the validation cohort, PurIST classified 173 as classical subtype, 59 as basal subtype, and 26 as no-calls. Reinforcing previous findings, patients of the basal subtype had significantly lower overall survival than those of the classical subtype. Notably, differential survival by subtype was significant among the subset of patients on FOLFIRINOX, but not those on gemcitabine + nab-paclitaxel.

Conclusions

The implementation of PurIST on a high-throughput clinical laboratory RNA-Seq platform and the demonstration of the model’s clinical utility in a real-world cohort together show that PurIST can be used at scale to refine PDAC prognosis and thereby inform treatment selection to improve outcomes for advanced-stage PDAC patients.
A Distinct Nasal Microbiota Signature in Peritoneal Dialysis Patients
Authors: Khan Iman , Wu Sylvia , Hudson Anika , Hughes Clayton , Stryjniak Gabriel , Westblade Lars F. , Satlin Michael J. , Tedrow Nicholas , Uhlemann Anne-Catrin , Kraft Colleen , Dadhania Darshana M. , Silberzweig Jeffrey , De Vlaminck Iwijn , Li Carol , Srivatana Vesh , Lee John Richard
Published: February 2023

Rationale & Objective

The nasal passages harbor both commensal and pathogenic bacteria. In this study, we sought to characterize the anterior nasal microbiota in PD patients using 16S rRNA gene sequencing.

Study Design

Cross-sectional.

Setting & Participants

We recruited 32 PD patients, 37 kidney transplant (KTx) recipients, 22 living donor/healthy control (HC) participants and collected anterior nasal swabs at a single point in time.

Predictors

We performed 16S rRNA gene sequencing of the V4-V5 hypervariable region to determine the nasal microbiota.

Outcomes

Nasal microbiota profiles were determined at the genus level as well as the amplicon sequencing variant level.

Analytical Approach

We compared nasal abundance of common genera among the 3 groups using Wilcoxon rank sum testing with Benjamini-Hochberg adjustment. DESeq2 was also utilized to compare the groups at the ASV levels.

Results

In the entire cohort, the most abundant genera in the nasal microbiota included:Staphylococcus, Corynebacterium, Streptococcus, andAnaerococcus. Correlational analyses revealed a significant inverse relationship between the nasal abundance ofStaphylococcusand that ofCorynebacterium. PD patients have a higher nasal abundance ofStreptococcusthan KTx recipients and HC participants. PD patients have a more diverse representation ofStaphylococcusandStreptococcusthan KTx recipients and HC participants. PD patients who concurrently have or who developed futureStaphylococcusperitonitis had a numerically higher nasal abundance ofStaphylococcusthan PD patients who did not developStaphylococcusperitonitis.

Limitations

16S RNA gene sequencing provides taxonomic information to the genus level.

Conclusions

We find a distinct nasal microbiota signature in PD patients compared to KTx recipients and HC participants. Given the potential relationship between the nasal pathogenic bacteria and infectious complications, further studies are needed to define the nasal microbiota associated with these infectious complications and to conduct studies on the manipulation of the nasal microbiota to prevent such complications.
Geometric versus hemodynamic indexes for rupture-destined aneurysms: a retrospective cohort and a repeated-measures study
Authors: Lee Chan-Hyuk , Kwak Hyo-Sung , Kang Hyun-Seung , Jung Keun-Hwa , Jeong Seul-Ki
Published: February 2023

Background and purpose

A proper stratification of intracranial aneurysms (IA) is critical in identifying rupture-destined aneurysms (RDA) and unruptured intracranial aneurysms (UIA). We aimed to determine the utility of geometric and hemodynamic indexes in differentiating RDA and UIA, and to examine the characteristics of natural evolutionary changes of UIA.

Methods

RDA was defined as having subsequent subarachnoid hemorrhage (SAH), and UIA was examined using follow-up time-of-flight magnetic resonance angiography (TOF-MRA). In addition to geometric indexes such as aspect or size ratio, aneurysmal signal intensity gradient (SIG), anin-vivoapproximated wall shear stress (WSS) from TOF-MRA, was measured. The difference (delta) between the maximum and minimum values of SIG in an aneurysm compared to parent arterial values was designated as the delta-SIG ratio.

Results

This study analyzed 20 RDA in 20 patients and 45 UIA in 41 patients with follow-up TOF-MRA. While geometric indexes did not show significant differences between the RDA and UIA, the delta-SIG ratio was significantly higher in the RDA than in the UIA (1.5±0.6 vs. 1.1±0.3, P=0.032). The delta-SIG ratio showed a significantly higher area under the receiver operating characteristics curve for SAH than the size ratio (0.72 [95% confidence interval (CI), 0.58–0.87] vs. 0.56 [95% CI, 0.41–0.72], P=0.033). The longitudinal re-examination of TOF-MRA in the UIA group showed evidence of aneurysmal growth with hemodynamic stability.

Conclusions

The delta-SIG ratio showed significantly higher discriminatory results between RDA and UIA compared to geometric indexes. Aneurysmal rupture risk should be assessed by considering both geometric and hemodynamic information.

This study was registered onClinicalTrials.gov(NCT05450939).
Was access and quality of healthcare affected during COVID-19 pandemic? A qualitative enquiry into healthcare access for non-communicable diseases in Central India
Authors: Nagi Raunaq Singh , Chatterjee Anirban , Singhal Kritika , Kokane Arun M
Published: February 2023

Objective

COVID-19 pandemic has had significant impacts on healthcare systems across the world. However, its impact on healthcare systems in Low- and Middle-Income Countries (LMICs) has been especially devastating, resulting in restricted access to healthcare. The present study was conducted to assess healthcare access for non-communicable diseases (NCDs) in Central India.

Design

Inductive and deductive thematic analysis of in-depth semi-structured interviews.

Setting

Study was conducted in communities of two urban and rural districts of central India.

Participants

Interviewed participants included PLNCDs, their caregivers, community dwellers, CHWs such as, Accredited Social Health Activists (ASHAs) and Anganwadi Workers (AWWs), Medical Officers, and Community Leaders. Recruitment of the participants was done via purposive and convenience sampling.

Result

A total of fifty Key Informant Interviews were (KIIs) conducted. All participants reported facing considerable difficulties while trying to access care from both public as well as private healthcare facilities. Absence of staff, equipment and medicines, restricted commute, misconceptions regarding the spread of COVID-19, and the stigma attached to COVID-19 infection acted as major barriers to accessing care, while door-to-door visits by community health workers, community support, and presence of privately owned healthcare facilities in the vicinity acted as facilitators.

Conclusion

In our study, we found that continued functioning of primary healthcare centres, ensuring uninterrupted supply of medicine and effective dissemination of information regarding COVID-19 could have acted to ease access to healthcare. Going ahead, capacity building to offset the impact of future emergencies and pandemics should be a crucial consideration while developing resilient healthcare systems.

Strengths and limitations of this study

Our study is the first study to explore the barriers faced by PLNCDs of low socio-economic status during the pandemic.

We explored the perspectives of both patients and healthcare workers before triangulating the data findings.

The study was conducted in the PLNCDs of lower socio-economic group and hence the perspectives and experiences of other socio-economic groups are yet to be explored.
Shark and ray genome size estimation: methodological optimization for inclusive and controllable biodiversity genomics
Authors: Kadota Mitsutaka , Tatsumi Kaori , Yamaguchi Kazuaki , Uno Yoshinobu , Kuraku Shigehiro
Published: February 2023

Estimate of nuclear DNA content serves as an independent tool for validating the completeness of whole genome sequences and investigating the among-species variation of genome sizes, but for some species, the requirement of fresh cells makes this tool highly inaccessible. Here we focused on elasmobranch species (sharks and rays), and using flow cytometry or quantitative PCR (qPCR), estimated the nuclear DNA contents of brownbanded bamboo shark, white spotted bamboo shark, zebra shark, small-spotted catshark, sandbar shark, slendertail lanternshark, megamouth shark, red stingray, and ocellate spot skate. Our results revealed their genome sizes spanning from 3.40 pg (for ocellate spot skate) to 13.34 pg (for slendertail lanternshark), in accordance with the huge variation of genome sizes already documented for elasmobranchs. Our improved qPCR-based method enabled accurate genome size estimation without using live cells, which has been a severe limitation with elasmobranchs. These findings and our methodology are expected to contribute to better understanding of the diversity of genome sizes in elasmobranchs even including species with limited availability of fresh tissue materials. It will also help validate the completeness of already obtained or anticipated whole genome sequences.
Multiplex Base Editing to Protect from CD33-Directed Therapy: Implications for Immune and Gene Therapy
Authors: Borot Florence , Humbert Olivier , Newby Gregory A , Fields Emily , Kohli Sajeev , Radtke Stefan , Laszlo George S. , Mayuranathan Thiyagaraj , Ali Abdullah Mahmood , Weiss Mitchell J. , Yen Jonathan S. , Walter Roland B. , Liu David R. , Mukherjee Siddhartha , Kiem Hans-Peter
Published: February 2023

On-target toxicity to normal cells is a major safety concern with targeted immune and gene therapies. Here, we developed a base editing (BE) approach exploiting a naturally occurring CD33 single nucleotide polymorphism leading to removal of full-length CD33 surface expression on edited cells. CD33 editing in human and nonhuman primate (NHP) hematopoietic stem and progenitor cells (HSPCs) protects from CD33-targeted therapeutics without affecting normal hematopoiesisin vivo, thus demonstrating potential for novel immunotherapies with reduced off-leukemia toxicity. For broader applications to gene therapies, we demonstrated highly efficient (>70%) multiplexed adenine base editing of the CD33 and gamma globin genes, resulting in long-term persistence of dual gene-edited cells with HbF reactivation in NHPs.In vitro, dual gene-edited cells could be enriched via treatment with the CD33 antibody-drug conjugate, gemtuzumab ozogamicin (GO). Together, our results highlight the potential of adenine base editors for improved immune and gene therapies.

Graphical abstract
Prior College Biology Coursework Increases Student Outcomes for Underrepresented Minority Students studying Anatomy and Physiology
Authors: Stephens Brian R.
Published: February 2023

Student performance and achievement in anatomy and physiology (AP) are determining factors in admissions into medical and other health-allied programs. Madison College has had historically poor course retention and pass rates for underrepresented minorities in A&P. Course and enrollment data from 2013 – 2020 were examined to determine whether students who optionally took lab-based biology coursework had improved student outcomes. Underrepresented minority students who completed ≥ 1 lab-based college biology course before entering AP had improved student outcomes evidenced by an increased pass rate and a reduced failure rate. Statistical analysis uncovered a statistically significant association (p≤ 0.10) with prior lab-based college biology coursework and student outcomes in AP for underrepresented minority students.
High resolution cryo-EM and crystallographic snapshots of the large actinobacterial 2-oxoglutarate dehydrogenase: an all-in-one fusion with unique properties
Authors: Yang Lu , Wagner Tristan , Mechaly Ariel , Boyko Alexandra , Bruch Eduardo M. , Megrian Daniela , Gubellini Francesca , Alzari Pedro M. , Bellinzoni Marco
Published: February 2023

Actinobacteria possess unique ways to regulate the oxoglutarate node located in the central position of the tricarboxylic acid cycle, a crossroad between energy conservation and nitrogen metabolism. Here, we studied the decarboxylative oxidation route that leads, through the 2-oxoglutarate dehydrogenase (ODH) complex, to the generation of succinyl-CoA and reduced equivalents to feed the respiratory chain. Compared to most organisms in which the oxidative decarboxylation and reductive acylation steps are carried out by different enzymes within the ODH complex, actinobacteria rely on an all-in-one protein (OdhA) in which both activities are carried out by the same polypeptide. We describe high-resolution cryo-EM and X-ray crystallography snapshots of representative enzymes fromMycobacterium smegmatisandCorynebacterium glutamicum, showing that OdhA is an 800-kDa homohexamer that folds into a three-blade propeller shape. The obligate trimeric and dimeric states of the acyltransferase and dehydrogenase domains, respectively, are critical for maintaining the overall assembly, where both domains interact via subtle readjustments of their interfaces. Complexes obtained with substrate analogues, reaction products and allosteric regulators illustrate how these domains operate. Furthermore, we provide additional insights into the phosphorylation-dependent regulation of this enzymatic machinery by the FHA (Fork-Head Associated) signalling protein OdhI, delivering new molecular details on how this actinobacterial-specific switching mechanism operates. Overall, the quaternary organization of OdhA represents a new piece of the fascinating puzzle of the synergistic, mixed pyruvate dehydrogenase/2-oxoglutarate dehydrogenase actinobacterial supercomplex.
Multi-view learning to unravel the different levels underlying hepatitis B vaccine response
Authors: Affaticati Fabio , Bartholomeus Esther , Mullan Kerry , Van Damme Pierre , Beutels Philippe , Ogunjimi Benson , Laukens Kris , Meysman Pieter
Published: February 2023

The immune system acts as the intricate apparatus dedicated to mounting a defence that ensures host survival from microbial threats. To engage this faceted immune response and provide protection against infectious diseases, vaccinations are the critical tool developed. However, vaccine responses are governed by levels that when interrogated separately only explain a fraction of the immune reaction. To address this knowledge gap, we conducted a feasibility study to determine if multi-view modelling can aid in gaining actionable insights on response markers shared across populations, capture the immune system diversity, and disentangle confounders. We thus sought to assess this multi-view modelling capacity on the responsiveness to Hepatitis B virus (HBV) vaccination.

Seroconversion to vaccine induced antibodies against HBV surface antigen (anti-HBs) in early-converters (n=21; <2 month) and late-converters (n=9; <6 months), was defined based on the anti-HBs titres (>10IU/L). The multi-view data encompassed bulk RNA-seq, CD4+ T cell parameters (including T-cell receptor data), flow cytometry data, and clinical metadata (including age and gender). The modelling included testing single-view and multi-view joint dimensionality reductions. Multi-view joint dimensionality reduction out-performed single-view methods in terms of area under curve and balanced accuracy, confirming an increase in predictive power to be gained. The interpretation of the findings showed that age, gender, inflammation-related gene sets and pre-existing vaccine specific T-cells were associated with vaccination responsiveness.

This multi-view dimensionality reduction approach complements the clinical seroconversion and all single modalities. Importantly, this modelling could identify what features predict HBV vaccine response. This methodology could be extended to other vaccination trials to identify key features regulating responsiveness.