bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of omega-3 polyunsaturated fatty acids in the intensive care unit
Authors: Singer Pierre , Calder Philip C.
Published: March 2023

Purpose of review

This review provides an update on the actions of omega-3 polyunsaturated fatty acids (PUFAs) and presents the most recent findings from trials in patients in the intensive care unit (ICU) setting including relevant meta-analyses. Many specialized pro-resolving mediators (SPMs) are produced from bioactive omega-3 PUFAs and may explain many of the beneficial effects of omega-3 PUFAs, although other mechanisms of action of omega-3 PUFAs are being uncovered.

Recent findings

SPMs resolve inflammation, promote healing and support antiinfection activities of the immune system. Since publication of the ESPEN guidelines, numerous studies further support the use of omega-3 PUFAs. Recent meta-analyses favor the inclusion of omega-3 PUFAs in nutrition support of patients with acute respiratory distress syndrome or sepsis. Recent trials indicate that omega-3 PUFAs may protect against delirium and liver dysfunction in patients in the ICU, although effects on muscle loss are unclear and require further investigation. Critical illness may alter omega-3 PUFA turnover. There has been significant discussion about the potential for omega-3 PUFAs and SPMs in treatment of coronavirus disease 2019.

Evidence for benefits of omega-3 PUFAs in the ICU setting has strengthened through new trials and meta-analyses. Nevertheless, better quality trials are still needed. SPMs may explain many of the benefits of omega-3 PUFAs.
Do omega-3 fatty acids increase risk of atrial fibrillation?
Authors: Bork Christian S. , Myhre Peder L. , Schmidt Erik B.
Published: March 2023

Purpose of the review

To summarize the findings from recent observational follow-up studies and randomized trials of plant- and marine omega-3 fatty acids on the risk of atrial fibrillation (AF).

Recent findings

Recent randomized cardiovascular outcome trials have indicated that supplements with marine omega-3 fatty acids may be associated with a higher risk of AF, and a meta-analysis has suggested that marine omega-3 fatty acid supplements were associated with a 25% higher relative risk of AF. Also, a recent large observational study reported a modest higher risk of AF in habitual users of marine omega-3 fatty acid supplements. However, recent observational biomarker studies of circulating and adipose tissue content of marine omega-3 fatty acids have in contrast reported a lower risk of AF. Very limited knowledge exists on the role of plant-derived omega-3 fatty acids and AF.

Marine omega-3 fatty acid supplements may increase the risk of AF, whereas biomarkers reflecting consumption of marine omega-3 fatty acids have been linked to a lower risk of AF. Clinicians should inform patients that marine omega-3 fatty acid supplement may increase AF risk, and this should be taking into account when discussing pros and cons of taking supplements with marine omega-3 fatty acids.
Nutritional regulation of hepatic de novo lipogenesis in humans
Authors: Cross Eloise , Dearlove David J. , Hodson Leanne
Published: March 2023

Purpose of review

De novolipogenesis (DNL) is a metabolic process occurring mainly within the liver, in humans. Insulin is a primary signal for promoting DNL; thus, nutritional state is a key determinant for upregulation of the pathway. However, the effects of dietary macronutrient composition on hepatic DNL remain unclear. Nor is it clear if a nutrition-induced increase in DNL results in accumulation of intra-hepatic triglyceride (IHTG); a mechanism often proposed for pathological IHTG. Here, we review the latest evidence surrounding the nutritional regulation of hepatic DNL.

Recent findings

The role of carbohydrate intake on hepatic DNL regulation has been well studied, with only limited data on the effects of fats and proteins. Overall, increasing carbohydrate intake typically results in an upregulation of DNL, with fructose being more lipogenic than glucose. For fat, it appears that an increased intake of n-3 polyunsaturated fatty acids downregulates DNL, whilst, in contrast, an increased dietary protein intake may upregulate DNL.

Although DNL is upregulated with high-carbohydrate or mixed-macronutrient meal consumption, the effects of fat and protein remain unclear. Additionally, the effects of different phenotypes (including sex, age, ethnicity, and menopause status) in combination with different diets (enriched in different macronutrients) on hepatic DNL requires elucidation.
Health-care–Related Practices in Virtual Behavioral Health Treatment for Major Depression Before and During the COVID-19 Pandemic
Authors: Weinfield Nancy S. , Tavel Heather M. , Goodrich Glenn , McCracken Courtney E. , Basra Sundeep , Gander Jennifer C. , Davis Teaniese L. , Ritzwoller Debra P. , Roblin Douglas W.
Published: March 2023

Background:

The abrupt shift to virtual care at the onset of the COVID-19 pandemic had the potential to disrupt care practices in virtual behavioral health encounters. We examined changes over time in virtual behavioral health-care-related practices for patient encounters with diagnoses of major depression.

Methods:

This retrospective cohort study utilized electronic health record data from 3 integrated health care systems. Inverse probability of treatment weighting was used to adjust for covariates across 3 time periods, prepandemic (January 2019–March 2020), peak-pandemic shift to virtual care (April 2020–June 2020), and recovery of health care operations (July 2020–June 2021). First virtual follow-up behavioral health department encounters after an incident diagnostic encounter were examined for differences across the time periods in rates of antidepressant medication orders and fulfillments, and completion of patient-reported symptoms screeners in service of measurement-based care.

Results:

Antidepressant medication orders declined modestly but significantly in 2 of the 3 systems during the peak-pandemic period but rebounded during the recovery period. There were no significant changes in patient fulfillment of ordered antidepressant medications. Completion of symptom screeners increased significantly in all 3 systems during the peak-pandemic period and continued to increase significantly in the subsequent period.

Conclusions:

A rapid shift to virtual behavioral health care was possible without compromising health-care-related practices. The transition and subsequent adjustment period have instead been marked by improved adherence to measurement-based care practices in virtual visits, signaling a potential new capacity for virtual health care delivery.
The Predictive Value of a Modified Frailty Index on Perioperative Morbidity and Mortality Following Otologic Surgery
Authors: Quinn Kevin J. , Ma Yuchi , Carli Matthew , Coelho Daniel H.
Published: March 2023

Objectives:

Recently, determinants of frailty have become an increasingly recognized perioperative risk stratification tool. This study examines the predictive value of a 5-factor modified frailty index (mFI-5) on perioperative morbidity and mortality in patients undergoing otologic surgery, with a subgroup analysis based on surgery site.

Study Design:

Cross-sectional analysis.

Setting:

National surgical quality improvement program dataset 2005–2019.

Patients:

Current procedural terminology (CPT) codes were used to identify patients undergoing all otologic surgeries.

Interventions:

Otologic surgeries as indicated by CPT codes, including external ear, middle ear/mastoid, implants, and inner ear/facial nerve subgroups.

Main Outcome Measures:

Primary outcomes examined in this study included rates of overall complications and life-threatening complications within 30 days after surgery. Overall complications included superficial surgical site infections (SSI), deep incisional SSI, readmission, deep vein thrombosis, life-threatening complications, and mortality. Life-threatening complications included those classified as Clavien-Dindo grade IV: cerebrovascular accident, mechanical ventilation for more than 48 hours, reintubation, pulmonary embolism, acute renal failure, cardiac arrest, and myocardial infarction.

Results:

A total of 16,859 patients who underwent otologic surgery were identified, resulting in a cohort that was 47.5% male with an average age of 47.6 years (17.1 SD). Multivariable regression analysis of the entire cohort demonstrated a score of 3 or more on the mFI-5 was independently predictive of all postoperative complications (odds ratio (OR): 2.02, P < 0.0001). However, subgroup analysis showed that only “external ear” surgery correlated with mFi-5 (OR 8.03, P = 0.013).

Conclusions:

Higher frailty scores as measured by the mFI-5 correlate with postoperative morbidity and mortality after otologic surgery, though subgroup analysis reveals an association only with cases performed on the external ear. These findings suggest that for most otologic surgery, the mFI-5 frailty score is not predictive of postoperative complications.
The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device
Authors: Lambert Heather , Hiu Shaun , Coulthard Malcolm G. , Matthews John N. S. , Holstein Eva-Maria , Crosier Jean , Agbeko Rachel , Brick Thomas , Duncan Heather , Grant David , Mok Quen , Nyman Andrew Gustaf , Pappachan John , Boucher Chris , Bulmer Joe , Chisholm Denise , Cromie Kirsten , Emmet Victoria , Feltbower Richard G. , Ghose Arunoday , Grayling Michael , Harrison Rebecca , Kennedy Ciara A. , McColl Elaine , Morris Kevin , Norman Lee , Office Julie , Parslow Roger , Pattinson Christine , Sharma Shriya , Smith Jonathan , Steel Alison , Steel Rachel , Straker Jayne , Vrana Lamprini , Walker Jenn , Wellman Paul , Whitaker Mike , Wightman Jim , Wilson Nina , Wirz Lucy , Wood Ruth
Published: March 2023

Objectives:

Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH).

Design:

Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence.

Setting:

Clusters were six U.K. PICUs.

Patients:

Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance.

Interventions:

In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances.

Measurements and Main Results:

At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03–0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between.

Conclusions:

NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.
Mission Disimpaction: Endoscopic Management of Stercoral Colitis in an Adolescent
Authors: Thomas Michael J. , Nanagiri Apoorva , Duvidovich Svetlana , Levy Lior , Bamji Natasha
Published: March 2023

Stercoral colitis is a rare entity of inflammatory colitis with high morbidity and mortality attributable to colonic fecaloma impaction, often a result of chronic constipation. Despite demographic imbalance favoring elders, children hold comparative risk factors for chronic constipation. Suspicion for stercoral colitis is warranted in nearly every stage of life. Computerized tomography (CT) is diagnostic for stercoral colitis, where radiological findings correlate to high sensitivity and specificity. Difficulty exists discerning from other acute and chronic intestinal etiologies with overlapping nonspecific symptoms and laboratory markers. Management involves prompt risk assessment for perforation and immediate disimpaction to avoid ischemic injury, with endoscopic directed disimpaction standard of care for nonoperative measures. Our case describes stercoral colitis in an adolescent with contributive risk factors for fecaloma impaction and is one of the first adolescent case reports involving successful endoscopic management.
The Utility of Quantitative Parameters of Shear-Wave Elastography to Predict Prognostic Histologic Features of Breast Cancer
Authors: Avdan Aslan Aydan , Gültekin Serap , İnan Mehmet Arda
Published: March 2023

In this study, we aimed to investigate the correlation of stiffness values of shear-wave elastography (SWE) and histopathological prognostic factors in patients with breast cancer. Between January 2021 and June 2022, SWE images of 138 core-biopsy proven breast cancer lesions from 132 patients were retrospectively reviewed. Histopathogic prognostic factors, including tumor size, histologic grade, histologic type, hormone receptor positivity, human epidermal growth factor receptor (HER2) status, immunohistochemical subtype and Ki-67 index were documented. Elasticity values including mean and maximum elasticity (E
mean and E
max) and lesion-to-fat ratio (E
ratio) were recorded. The association between histopathological prognostic factors and elasticity values were assessed using Mann-Whitney U and Kruskal-Wallis test, and multiple linear regression analysis. Tumor size, histological grade, and Ki-67 index were significantly associated with the E
ratio (P < 0.05). Larger tumor size and higher Ki-67 index also showed significantly higher E
mean and E
max values (P < 0.05). However, hormone receptor positivity, HER2 status, and immunohistochemical subtype were not significantly associated with elasticity values (P > 0.05). Multivariate logistic regression analysis revealed that tumor size was significantly associated with E
mean, E
max, and E
ratio values (P < 0.05). A high Ki-67 index was also significantly associated with high E
ratio values. Larger tumor size and higher Ki-67 index are independently associated with high E
ratio values. Preoperative SWE may improve the performance of conventional ultrasound in predicting prognosis and treatment planning.
Differentiation Between Compressive Cervical and Thoracic Myelopathy Using the Central Motor Conduction Time Ratio
Authors: Kamei Naosuke , Nakamae Toshio , Nakanishi Kazuyoshi , Maruyama Toshiaki , Nakao Kazuto , Farid Fadlyansyah , Adachi Nobuo
Published: March 2023

Purpose:

Thoracic myelopathy is a rare condition whose diagnosis is often missed or delayed. This study aimed to differentiate between cervical and thoracic myelopathy using motor-evoked potential testing.

Methods:

The authors included 835 patients with compressive cervical myelopathy and 94 patients with compressive thoracic myelopathy. Myelopathy using motor-evoked potentials were recorded from the bilateral abductor digiti minimi and abductor hallucis muscles through transcranial magnetic stimulation. The peripheral conduction time was measured through electrical stimulation of the ulnar and tibial nerves; moreover, the central motor conduction time (CMCT) was calculated by subtracting the peripheral conduction time from the myelopathy using motor-evoked potential latency.

Results:

The most accurate differentiation between compressive cervical myelopathy and compressive thoracic myelopathy was achieved by the CMCT ratios (CMCT-ADM:CMCT-AH; cutoff value of 0.490, sensitivity of 83.0%, and specificity of 80.5%). After excluding patients with compressive cervical myelopathy who had spinal cord compression at C6-7, the cutoff value was 0.490, with a sensitivity of 83.0% and specificity of 87.3%.

Conclusions:

Determining the CMCT ratio (cutoff value of 0.490) through motor-evoked potential testing could facilitate differentiation between compressive cervical myelopathy and compressive thoracic myelopathy.
Continuous Electroencephalogram Use and Hospital Outcomes in Critically Ill Children
Authors: Oh Ahyuda , Wusthoff Courtney J. , Kim Hyunmi
Published: March 2023

Purpose:

To examine the association between CEEG use and discharge status, length of hospitalization, and health care cost in a critically ill pediatric population.

Methods:

Four thousand three hundred forty-eight critically ill children were identified from a US nationwide administrative health claims database; 212 (4.9%) of whom underwent CEEG during admissions (January 1, 2015–june 30, 2020). Discharge status, length of hospitalization, and health care cost were compared between patients with and without CEEG use. Multiple logistic regression analyzed the association between CEEG use and these outcomes, controlling for age and underlying neurologic diagnosis. Prespecified subgroups analysis was performed for children with seizures/status epilepticus, with altered mental status and with cardiac arrest.

Results:

Compared with critically ill children without CEEG, those who underwent CEEG were likely to have shorter hospital stays than the median (OR = 0.66; 95% CI = 0.49–0.88; P = 0.004), and also total hospitalization costs were less likely to exceed the median (OR = 0.59; 95% CI = 0.45–0.79; P < 0.001). There was no difference in odds of favorable discharge status between those with and without CEEG (OR = 0.69; 95% CI = 0.41–1.08; P = 0.125). In the subgroup of children with seizures/status epilepticus, those with CEEG were less likely to have unfavorable discharge status, compared with those without CEEG (OR = 0.51; 95% CI = 0.27–0.89; P = 0.026).

Conclusions:

Among critically ill children, CEEG was associated with shorter stay and lower costs of hospitalization but was not associated with change of favorable discharge status except the subgroup with seizures/status epilepticus.
Interhemispheric Asymmetries in Intracortical Facilitation Correlate With Fatigue Severity in Individuals With Poststroke Fatigue
Authors: Kindred John H. , Gregory Chris M. , Kautz Steven A. , Bowden Mark G.
Published: March 2023

Purpose:

Poststroke fatigue (PSF) contributes to increased mortality and reduces participation in rehabilitative therapy. Although PSF's negative influences are well known, there are currently no effective evidence-based treatments for PSF. The lack of treatments is in part because of a dearth of PSF pathophysiological knowledge. Increasing our understanding of PSF's causes may facilitate and aid the development of effective therapies.

Methods:

Twenty individuals, >6 months post stroke, participated in this cross-sectional study. Fourteen participants had clinically relevant pathological PSF, based on fatigue severity scale (FSS) scores (total score ≥36). Single-pulse and paired-pulse transcranial magnetic stimulation were used to measure hemispheric asymmetries in resting motor threshold, motor evoked potential amplitude, and intracortical facilitation (ICF). Asymmetry scores were calculated as the ratios between lesioned and nonlesioned hemispheres. The asymmetries were then correlated (Spearman rho) to FSS scores.

Results:

In individuals with pathological PSF (N = 14, range of total FSS scores 39–63), a strong positive correlation (r
s = 0.77, P = 0.001) between FSS scores and ICF asymmetries was calculated.

Conclusions:

As the ratio of ICF between the lesioned and nonlesioned hemispheres increased so did self-reported fatigue severity in individuals with clinically relevant pathological PSF. This finding may implicate adaptive/maladaptive plasticity of the glutamatergic system/tone as a contributor to PSF. This finding also suggests that future PSF studies should incorporate measuring facilitatory activity and behavior in addition to the more commonly studied inhibitory mechanisms. Further investigations are required to replicate this finding and identify the causes of ICF asymmetries.
EEG Monitoring in Critically Ill Children: Establishing High-Yield Subgroups
Authors: Fung France W. , Parikh Darshana S. , Donnelly Maureen , Jacobwitz Marin , Topjian Alexis A. , Xiao Rui , Abend Nicholas S.
Published: March 2023

Purpose:

Continuous EEG monitoring (CEEG) is increasingly used to identify electrographic seizures (ES) in critically ill children, but it is resource intense. We aimed to assess how patient stratification by known ES risk factors would impact CEEG utilization.

Methods:

This was a prospective observational study of critically ill children with encephalopathy who underwent CEEG. We calculated the average CEEG duration required to identify a patient with ES for the full cohort and subgroups stratified by known ES risk factors.

Results:

ES occurred in 345 of 1,399 patients (25%). For the full cohort, an average of 90 hours of CEEG would be required to identify 90% of patients with ES. If subgroups of patients were stratified by age, clinically evident seizures before CEEG initiation, and early EEG risk factors, then 20 to 1,046 hours of CEEG would be required to identify a patient with ES. Patients with clinically evident seizures before CEEG initiation and EEG risk factors present in the initial hour of CEEG required only 20 (<1 year) or 22 (≥1 year) hours of CEEG to identify a patient with ES. Conversely, patients with no clinically evident seizures before CEEG initiation and no EEG risk factors in the initial hour of CEEG required 405 (<1 year) or 1,046 (≥1 year) hours of CEEG to identify a patient with ES. Patients with clinically evident seizures before CEEG initiation or EEG risk factors in the initial hour of CEEG required 29 to 120 hours of CEEG to identify a patient with ES.

Conclusions:

Stratifying patients by clinical and EEG risk factors could identify high- and low-yield subgroups for CEEG by considering ES incidence, the duration of CEEG required to identify ES, and subgroup size. This approach may be critical for optimizing CEEG resource allocation.
Impact of family support on the cognitive functions of Egyptian elderly
Authors: Moustafa Sara A. , Gaballah Nada , Heikal Shimaa , Salama Mohamed
Published: March 2023

Background

Social support is essential in the daily activities of the elderly, which can impact their cognitive functions over time.

Aim of the study

This study investigates the hypothesis that there is a link between social support and cognitive function in the elderly living in the Egyptian community using the Arabic translation of the Survey of Health, Ageing, Retirement in Europe (SHARE) questionnaire.

Subjects and methods

Cross-sectional analytic study was conducted as a part of the pilot study for A Longitudinal Study of Egyptian Healthy Ageing (AL-SEHA) project. It included 299 participants (50+ years of age). Investigators collected data using the Arabic translation of the SHARE questionnaire in five Egyptian Universities. Data were then uploaded to the Social Research Centre (SRC) at the American University in Cairo (AUC).

Results

The prevalence of declined cognitive functions was 39.467% (95% CI: 33.89-45.04). Cognitive impairment was significantly less among university and postgraduate degree holders (p<0.001), married (p=0.0378) or contacted by their kids on a daily or weekly basis (p=0.0364).

Conclusion

Being married, with a university degree or higher, and increased contact frequency with children, all showed positive correlation with cognitive function in our sample. In conclusion, this research contributes to our understanding of the impact of family network and support and cognitive function in the older Egyptian population. Our findings can be a base to add on to the literature.
Typological distinction of remotely sensed metrics of neighborhood vegetation for environmental health intervention design
Authors: Fleischer Daniel , Turner Jay , Heitmann Ivan , Bucknum Brent , Bhatnagar Aruni , Yeager Ray
Published: March 2023

The extent to which urban vegetation improves environmental quality and affects the health of nearby residents is dependent on typological attributes of “greenness”, such as canopy area to alleviate urban heat, grass to facilitate exercise and social interaction, leaf area to disperse and capture air pollution, and biomass to absorb noise pollution. The spatial proximity of these typologies to individuals further modifies the extent to which they impart benefits and influence health. However, most evaluations of associations between greenness and health utilize a single metric of greenness and few measures of proximity, which may disproportionately represent the effect of a subset of mediators on health outcomes.

To develop an approach to address this potentially substantial limitation of future studies evaluating associations between greenness and health, we measured and evaluated distinct attributes, correlations, and spatial dependency of 13 different metrics of greenness in a residential study area of Louisville, Kentucky, representative of many urban residential areas across the Eastern United States. We calculated NDVI, other satellite spectral indices, LIDAR derived leaf area index and canopy volume, streetview imagery derived semantic view indices, distance to parks, and graph-theory based ecosystem connectivity metrics. We utilized correlation analysis and principal component analysis across spatial scales to identify distinct groupings and typologies of greenness metrics.

Our analysis of correlation matrices and principal component analysis identified distinct groupings of metrics representing both physical correlates of greenness (trees, grass, their combinations and derivatives) and also perspectives on those features (streetview, aerial, and connectivity / distance). Our assessment of typological greenness categories contributes perspective important to understanding strengths and limitations of metrics evaluated by past work correlating greenness to health. Given our finding of inconsistent correlations between many metrics and scales, it is likely that many past investigations are missing important context and may underrepresent the extent to which greenness may influence health. Future epidemiological investigations may benefit from these findings to inform selection of appropriate greenness metrics and spatial scales that best represent the cumulative influence of the hypothesized effects of mediators and moderators. However, future work is needed to evaluate the effect of each of these metrics on health outcomes and mediators therein to better inform the understanding of metrics and differential influences on environments and health.
Contrast-Enhanced Magnetic Resonance Imaging Based T1-Mapping and Extracellular Volume Fractions are Associated with Peripheral Artery Disease
Authors: Fitian Asem , Shieh Michael C. , Gimnich Olga A. , Belousova Tatiana , Taylor Addison A. , Ballantyne Christie M. , Bismuth Jean , Shah Dipan J. , Brunner Gerd
Published: March 2023

Background

Extracellular volume fraction (ECV), measured with contrast-enhanced magnetic resonance imaging (CE-MRI), has been utilized to study myocardial fibrosis but its role in peripheral artery disease (PAD) remains unknown. We hypothesized that T1-mapping and ECV differ between PAD patients and matched-controls.

Methods and Results

A total of 37 individuals (18 PAD, 19 controls) underwent 3.0T CE-MRI at the mid-calf. T1-mapping was done before and after gadolinium contrast with a motion corrected Modified Look Locker Inversion Recovery (MOLLI) pulse sequence. T1 values were calculated with a 3-parameter Levenberg-Marquardt curve fitting algorithm. T1-maps were quantified in 5 calf muscle compartments (anterior [AM], lateral [LM], and deep posterior [DM] muscle groups; soleus [SM], and gastrocnemius [GM] muscles). Averaged peak blood pool T1 values were obtained from the posterior (PT) and anterior tibialis (AT); and peroneal artery (PE). PAD ECV was calculated for each muscle group. T1 values and ECV are heterogeneous across calf muscle compartments. Native peak T1 values of the AM, LM, and DM were significantly higher in PAD patients compared to controls (all p<0.028). ECV of the AM and SM were significantly higher in PAD patients compared to controls (AM: 26.4% (21.2, 31.6) vs. 17.3% (10.2, 25.1), p=0.046; SM: 22.7% (19.5, 27.8) vs. 13.8% (10.2, 19.1), p=0.020).

Conclusions

Native peak T1 values and ECV fractions of several calf muscle compartments are higher in PAD patients compared with matched-controls. These data suggest a potential utility of ECV to noninvasively determine skeletal muscle fibrosis in PAD.
Convergent Evolution of A-Lineage (Clade 19B) SARS-CoV-2 Spike Sequences with B-Lineage Variants of Concern Affects Virus Replication in a Temperature-Dependent Manner on Human Nasal Epithelial Cell Cultures
Authors: Yoon Steve , Anaya Eddy , Sachithanandham Jaiprasath , Pinsky Benjamin , Sullivan David , Mostafa Heba H. , Pekosz Andrew
Published: March 2023

The first three months of the COVID-19 pandemic was dominated by two SARS-CoV-2 lineages: A-lineages (Clade 19B) and B-lineages (Clade 19A). However, with the emergence of the Spike D614G substitution in B.1 lineages (Clade 20A), both early lineages were outcompeted and remained near-extinction from mid-2020 onwards. In early-2021, there was a re-emergence and persistence of novel A-lineage variants with substitutions in the Spike gene resembling those found in Variants of Concern (VOCs). An early A.3 variant (MD-HP00076/2020) and three A.2.5 variants (MD-HP02153/2021, MD-HP05922/2021 and CA-VRLC091/2021) were isolated and characterized for their genomic sequences, antibody neutralization, andin vitroreplication. All A.2.5 isolates had five Spike mutations relative to the A.3 variant sequence: D614G, L452R, Δ141-143, D215A, and ins215AGY. Plaque reduction neutralization assays demonstrated that A.2.5 isolates had a 2.5 to 5-fold reduction in neutralization using contemporaneous COVID-19 convalescent plasma when compared to A.3.In vitroviral characterization in VeroE6 cell lines revealed that the A.3 isolate grew faster and spread more than A.2.5. On VeroE6-TMPRSS2 cells, significant syncytia formation was also observed with the A.2.5 isolates, however Spike cleavage efficiency did not explain these differences. In human nasal epithelial cell (hNEC) cultures, the A.2.5 isolates grew significantly faster and to higher total infectious virus titers than A.3. All A.2.5 lineage isolates grew significantly faster at 37°C than at 33°C irrespective of cell type, and to higher peak titers except compared to A.3. This suggests A.2.5’s adapted to improve replication using similar mutations found in the B-lineage SARS-CoV-2 variants.

Importance

While both A- and B-lineage SARS-CoV-2 variants emerged and circulated together during the early months of the pandemic, the B-lineages that acquired Spike D614G eventually outcompeted all other variants. We show that the A-lineage variants eventually evolved mutations including Spike D614G and Spike L452R that improved their in vitro replication in human nasal epithelial cells in a temperature dependent manner, suggesting there are some highly selectable mutation landscapes that SARS-CoV-2 can acquire to adapt to replication and transmission in humans.
Individual, organisational and system capacities, and the functioning of a multi-country implementation-focused network for maternal, newborn and child health: Bangladesh, Ethiopia, Malawi, and Uganda
Authors: Tesfa Anene , Nakidde Catherine , Akter Kohenour , Khatun Fatama , Mwandira Kondwani , Lemma Seblewengel , Seruwagi Gloria , Mwaba Kasonde , English Mike , Daniels-Howell Callie ,   QCN Evaluation Group, Djellouli Nehla , Colbourn Tim , Marchant Tanya
Published: March 2023

Better policies, investments, and programs are needed to improve the integration and quality of maternal, newborn, and child health services. Previously, partnerships and collaborations that involved multiple countries with a unified aim have been observed to yield positive results. Since 2017, the WHO and partners have hosted the Quality of Care Network [QCN], a multi-country implementation network focused on improving maternal, neonatal, and child health care. In this paper we examine the functionality of QCN in different contexts. We focus on implementation capacities and contexts in four network countries: Bangladesh, Ethiopia, Malawi, and Uganda. In each country, the study was conducted over several consecutive rounds between 2019-2022, employing 227 key informant interviews with major stakeholders and members of the network countries, and 42 facility observations. The collected data were coded using Nvivo-12 software and categorized thematically. The study showed that individual, organizational and system-level capacities, and circumstances all played an important role in shaping implementation success in network countries, but that these levels were inter-linked. Across all levels, systems that enabled leadership, motivated and trained staff, and created a positive culture of data use were critical – from the policy making arena including addressing financing issues - to the day-to-day practice improvement at the front line. Some characteristics of QCN actively supported these levels, for example shared learning forums for continuous learning, a focus on data and tracking progress, and emphasising the importance of coordinated efforts towards a common goal. However, inadequate system financing and capacity also hampered network functioning, especially in the face of external shocks.
Genome-wide screen identifies host loci that modulateM. tuberculosisfitness in immunodivergent mice
Authors: Meade Rachel K. , Long Jarukit E. , Jinich Adrian , Rhee Kyu Y. , Ashbrook David G. , Williams Robert W. , Sassetti Christopher M. , Smith Clare M.
Published: March 2023

Genetic differences among mammalian hosts andMycobacterium tuberculosis(Mtb) strains determine diverse tuberculosis (TB) patient outcomes. The advent of recombinant inbred mouse panels and next-generation transposon mutagenesis and sequencing approaches has enabled dissection of complex host- pathogen interactions. To identify host and pathogen genetic determinants ofMtbpathogenesis, we infected members of the BXD family of mouse strains with a comprehensive library ofMtbtransposon mutants (TnSeq). Members of the BXD family segregate forMtb-resistant C57BL/6J (B6 orB) andMtb-susceptible DBA/2J (D2 orD) haplotypes. The survival of each bacterial mutant was quantified within each BXD host, and we identified those bacterial genes that were differentially required forMtbfitness across BXD genotypes. Mutants that varied in survival among the host family of strains were leveraged as reporters for “endophenotypes”, each bacterial fitness profile directly probing specific components of the infection microenvironment. We conducted QTL mapping of these bacterial fitness endophenotypes and identified 140host-pathogenquantitative trait loci (hpQTL). We identified a QTL hotspot on chromosome 6 (75.97–88.58 Mb) associated with the genetic requirement of multipleMtbgenes;Rv0127(mak),Rv0359(rip2),Rv0955(perM), andRv3849(espR). Together, this screen reinforces the utility of bacterial mutant libraries as precise reporters of the host immunological microenvironment during infection and highlights specific host-pathogen genetic interactions for further investigation. To enable downstream follow-up for both bacterial and mammalian genetic research communities, all bacterial fitness profiles have been deposited into GeneNetwork.org and added into the comprehensive collection of TnSeq libraries in MtbTnDB.
LSTrAP-denovo: Automated Generation of Transcriptome Atlases for Eukaryotic Species Without Genomes
Authors: Lim Peng Ken , Mutwil Marek
Published: March 2023

Structured Abstract

Motivation

Despite the abundance of species with transcriptomic data, a significant number of the species still lack genomes, making it difficult to study gene function and expression in these organisms. Whilede novotranscriptome assembly can be used to assemble protein-coding transcripts from RNA-sequencing (RNA-seq) data, the datasets used often only feature samples of arbitrarily-selected or similar experimental conditions which might fail to capture condition-specific transcripts.

Results

We developed the Large-Scale Transcriptome Assembly Pipeline forde novoassembled transcripts (LSTrAP-denovo) to automatically generate transcriptome atlases of eukaryotic species. Specifically, given an NCBI TaxID, LSTrAP-denovocan (1) filter undesirable RNA-seq accessions based on read data, (2) select RNA-seq accessions via unsupervised machine learning to construct a sample-balanced dataset for download, (3) assemble transcripts via over-assembly, (4) functionally annotate coding sequences (CDS) from assembled transcripts and (5) generate transcriptome atlases in the form of expression matrices for downstream transcriptomic analyses.

Availability and Implementation

LSTrAP-denovois easy to implement, written in python, and is freely available athttps://github.com/pengkenlim/LSTrAP-denovo/.

Supplementary Information

Supplementary data are available in the forms of supplementary figures, supplementary tables, and supplementary methods.
Calcium buffering tunes intrinsic excitability of spinal dorsal horn parvalbumin-expressing interneurons: A computational model
Authors: Ma Xinyue , Miraucourt Loïs , Qiu Haoyi , Sharif-Naeini Reza , Khadra Anmar
Published: March 2023

Parvalbumin-expressing interneurons (PVINs) play a crucial role within the dorsal horn of the spinal cord by preventing touch inputs from activating pain circuits. After nerve injury, their output is decreased via mechanisms that are not fully understood. In this study, we show that PVINs from nerve-injured mice change their firing pattern from tonic to adaptive. To examine the ionic mechanisms responsible for this decreased output, we employed a reparametrized Hodgkin-Huxley (HH) type model of PVINs, which predicted (1) the firing pattern transition is due to an increased contribution of small conductance calcium-activated potassium (SK) channels, enabled by (2) impairment in intracellular calcium buffering systems. Analyzing the dynamics of the HH-type model further demonstrated that a generalized Hopf bifurcation differentiates the two types of state transitions observed in the transient firing of PVINs. Importantly, this predicted mechanism holds true when we embed the PVINs model within the neuronal circuit model of the spinal dorsal horn. To experimentally validate this hypothesized mechanism, we used pharmacological modulators of SK channels and demonstrated that (1) tonic firing PVINs from naïve mice become adaptive when exposed to an SK channel activator, and (2) adapting PVINs from nerve-injured mice return to tonic firing upon SK channel blockade. Our work provides important insights into the cellular mechanism underlying the decreased output of PVINs in the spinal dorsal horn after nerve injury and highlights potential pharmacological targets for new and effective treatment approaches to neuropathic pain.

Significant Statement

Parvalbumin-expressing interneurons (PVINs) exert crucial inhibitory control over Aβfiber- mediated nociceptive pathways at the spinal dorsal horn. The loss of their inhibitory tone leads to neuropathic symptoms, like mechanical allodynia, via mechanisms that are not fully understood. This study identifies the reduced intrinsic excitability of PVINs as a potential cause for their decreased inhibitory output in nerve-injured condition. Combining computational and experimental approaches, we predict a calcium-dependent mechanism that modulates PVINs’ electrical activity following nerve injury: a depletion of cytosolic calcium buffer allows for the rapid accumulation of intracellular calcium through the active membranes, which in turn potentiates SK channels and impedes spike generation. Our results therefore pinpoint SK channels as interesting therapeutic targets for treating neuropathic symptoms.
Drought and recovery in barley: key gene networks and retrotransposon response
Authors: Paul Maitry , Tanskanen Jaakko , Jääskeläinen Marko , Chang Wei , Dalal Ahan , Moshelion Menachem , Schulman Alan H.
Published: March 2023

During drought, plants close their stomata at a critical soil water content (SWC), together with diverse physiological, developmental, and biochemical responses.

Using precision-phenotyping lysimeters, we imposed pre-flowering drought on four barley varieties (Arvo, Golden Promise, Hankkija 673 and Morex) and followed their physiological responses. For Golden Promise, we carried out RNA-seq on leaf transcripts before and during drought, and during recovery, also examining retrotransposonBARE1expression. Transcriptional data were subjected to network analysis.

The varieties differed by their critical SWC, Hankkija 673 responding at the highest and Golden Promise at the lowest. Pathways connected to drought and salinity response were strongly upregulated during drought; pathways connected to growth and development were strongly downregulated. During recovery, growth and development pathways were upregulated; altogether 117 networked genes involved in ubiquitin-mediated autophagy were downregulated. The differential response to SWC suggests adaptation to distinct rainfall patterns.

We identified several strongly differentially expressed genes not earlier associated with drought response in barley.BARE1transcription is strongly transcriptionally upregulated by drought and downregulated during recovery unequally between the investigated cultivars. The downregulation of networked autophagy genes suggests a role for autophagy in drought response; its importance to resilience should be further investigated.
Exploration of Speech Induced Suppression using Functional Near-Infrared Spectroscopy (fNIRS)
Authors: Walczak Eryk Jan
Published: March 2023

Speech-Induced Suppression (SIS) is a suppression of brain activity by speech. It is believed to be caused by the internal predictions of the consequences of speech movements which lead to attenuation of related neural activity (1, 2). Previous research (3) showed that SIS of the EEG signal can be observed in some speaking tasks but the results were not consistent. This study found that fNIRS can be used to test neural activity related to speech production. Grand averaged signals showed that conditions involving vocalisation actually elicited higher activity than those without vocalisation. When statistical models were fitted to the obtained data, and controlled for participant-related variation, these results did not hold. No statistically significant differences between conditions were found. Even though haemoglobin concentration changes are slower than ERPs, they capture the neural activity underlying speech-production processes. The current results suggest that fNIRS can be used to study speech production.
Targeted Phasing of 2-200 Kilobase DNA Fragments with a Short-Read Sequencer and a Single-Tube Linked-Read Library Method
Authors: Mikhaylova Veronika , Rzepka Madison , Kawamura Tetsuya , Xia Yu , Chang Peter L. , Zhou Shiguo , Pham Long , Modi Naisarg , Yao Likun , Perez-Agustin Adrian , Pagans Sara , Boles T. Christian , Lei Ming , Wang Yong , Garcia-Bassets Ivan , Chen Zhoutao
Published: March 2023

In the human genome, heterozygous sites are genomic positions with different alleles inherited from each parent. On average, there is a heterozygous site every 1-2 kilobases (kb). Resolving whether two alleles in neighboring heterozygous positions are physically linked—that is, phased—is possible with a short-read sequencer if the sequencing library captures long-range information. TELL-Seq is a library preparation method based on millions of barcoded micro-sized beads that enables instrument-free phasing of a whole human genome in a single PCR tube. TELL-Seq incorporates a unique molecular identifier (barcode) to the short reads generated from the same high-molecular-weight (HMW) DNA fragment (known as ‘linked-reads’). However, genome-scale TELL-Seq is not cost-effective for applications focusing on a single locus or a few loci. Here, we present an optimized TELL-Seq protocol that enables the cost-effective phasing of enriched loci (targets) of varying sizes, purity levels, and heterozygosity. Targeted TELL-Seq maximizes linked-read efficiency and library yield while minimizing input requirements, fragment collisions on microbeads, and sequencing burden. To validate the targeted protocol, we phased seven 180-200 kb loci enriched by CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis, four 20 kb loci enriched by CRISPR/Cas9-mediated protection from exonuclease digestion, and six 2-13 kb loci amplified by PCR. The selected targets have clinical and research relevance (BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, andPKI3CA). These analyses reveal that targeted TELL-Seq provides a reliable way of phasing allelic variants within targets (2-200 kb in length) with the low cost and high accuracy of short-read sequencing.
Cyclic di-GMP interact with putrescine via a PilZ domain receptor YcgR
Authors: Gu Weihan , Chen Yufan , Chen Zhongqiao , Gao Huagui , Xie Congcong , Zhang Lian-hui , Liao Lisheng
Published: March 2023

The cell motility is one of the key pathogenic factors that contribute to the virulence ofDickeya oryzea,which is a prevalent bacterial pathogen capable of infecting a range of crops and plants. We showed recently that the bacterial second messenger c-di-GMP, and the putrescine-mediated quorum sensing (QS) system, are both involved in the regulation of the bacterial motility inD. oryzeaEC1. In this study, we set to determine whether and how there two signaling mechanisms work together to modulate the bacterial motility. The results showed that the second messenger signaling system interacts with the putrescine QS system via the c-di-GMP receptor YcgR, which could promote the activity of SpeA, the rate-limiting enzyme in the putrescine biosynthesis pathway, thereby increasing the intracellular putrescine levels. However, it was shown that this facilitative effect could be inhibited by c-di-GMP molecules. In addition, we demonstrated the dominance of c-di-GMP over putrescine in the regulation of bacterial motility. The findings from this study provide the first insight into the interaction between c-di-GMP and putrescine in bacteria and provide a valuable reference for the study of intracellular second messenger system and polyamine-mediated quorum sensing system in other bacteria.

Importance

Dickea oryzeais a major bacterial pathogen capable of infesting many plants and crops, causing significant economic damage to rice and banana production especially. Bacterial motility is a key pathogenic factor ofD. oryzeato compete for food resources and infect their host species, which is negatively regulated by c-di-GMP and positively regulated by putrescine, respectively. However, the connection between c-di-GMP and putrscine in regulating the motility ofD.oryzeais not understood. Here we revealed the link and the mechanism of interaction between them, showing that c-di-GMP interact with putrescine via a receptor of c-di-GMP. The significance of our research is in providing the first insight into the interaction between c-di-GMP and putrescine and the methods and experimental designs in our study will provide a valuable reference for subsequent studies on the link between c-di-GMP and putrescine in other bacteria and even the regulatory mechanisms of complex bacterial motility networks, respectively.