bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive End-Expiratory Pressure and Respiratory Rate Modify the Association of Mechanical Power and Driving Pressure With Mortality Among Patients With Acute Respiratory Distress Syndrome
Authors: Tonna Joseph E. , Peltan Ithan D. , Brown Samuel M. , Grissom Colin K. , Presson Angela P. , Herrick Jennifer S. , Vasques Francesco , Keenan Heather T.
Published: December 2021

IMPORTANCE:

Mechanical power and driving pressure have known associations with survival for patients with acute respiratory distress syndrome.

OBJECTIVES:

To further understand the relative importance of mechanical power and driving pressure as clinical targets for ventilator management.

DESIGN:

Secondary observational analysis of randomized clinical trial data.

SETTING AND PARTICIPANTS:

Patients with the acute respiratory distress syndrome from three Acute Respiratory Distress Syndrome Network trials.

MAIN OUTCOMES AND MEASURES:

After adjusting for patient severity in a multivariate Cox proportional hazards model, we examined the relative association of driving pressure and mechanical power with hospital mortality. Among 2,410 patients, the relationship between driving pressure and mechanical power with mortality was modified by respiratory rate, positive end-expiratory pressure, and flow.

RESULTS:

Among patients with low respiratory rate (< 26), only power was significantly associated with mortality (power [hazard ratio, 1.82; 95% CI, 1.41–2.35; p < 0.001] vs driving pressure [hazard ratio, 1.01; 95% CI, 0.84–1.21; p = 0.95]), while among patients with high respiratory rate, neither was associated with mortality. Both power and driving pressure were associated with mortality at high airway flow (power [hazard ratio, 1.28; 95% CI, 1.15–1.43; p < 0.001] vs driving pressure [hazard ratio, 1.15; 95% CI, 1.01–1.30; p = 0.041]) and neither at low flow. At low positive end-expiratory pressure, neither was associated with mortality, whereas at high positive end-expiratory pressure (≥ 10 cm H2O), only power was significantly associated with mortality (power [hazard ratio, 1.22; 95% CI, 1.09–1.37; p < 0.001] vs driving pressure [hazard ratio, 1.16; 95% CI, 0.99–1.35; p = 0.059]).

CONCLUSIONS AND RELEVANCE:

The relationship between mechanical power and driving pressure with mortality differed within severity subgroups defined by positive end-expiratory pressure, respiratory rate, and airway flow.
Plasma Soluble CD14 Subtype Levels Are Associated With Clinical Outcomes in Critically Ill Subjects With Coronavirus Disease 2019
Authors: Mabrey F. Linzee , Morrell Eric D. , Bhatraju Pavan K. , Sathe Neha A. , Sakr Sana S. , Sahi Sharon K. , West T. Eoin , Mikacenic Carmen , Wurfel Mark M.
Published: December 2021

IMPORTANCE:

In bacterial sepsis, CD14 and its N-terminal fragment (soluble CD14 subtype, “Presepsin”) have been characterized as markers of innate immune responses and emerging evidence has linked both to coronavirus disease 2019 pathophysiology.

OBJECTIVES:

Our aim was to determine the relationship between the soluble form of CD14 and soluble CD14 subtype plasma levels, coronavirus disease 2019 status, and coronavirus disease 2019-related outcomes.

DESIGN:

A prospective cohort study.

SETTING:

ICUs in three tertiary hospitals in Seattle, WA.

PARTICIPANTS:

Two-hundred four critically ill patients under investigation for coronavirus disease 2019.

MAIN OUTCOMES AND MEASURES:

We measured plasma soluble CD14 and soluble CD14 subtype levels in samples collected upon admission. We tested for associations between biomarker levels and coronavirus disease 2019 status. We stratified by coronavirus disease 2019 status and tested for associations between biomarker levels and outcomes.

RESULTS:

Among 204 patients, 102 patients had coronavirus disease 2019 and 102 patients did not. In both groups, the most common ICU admission diagnosis was respiratory failure or pneumonia and proportions receiving respiratory support at admission were similar. In regression analyses adjusting for age, sex, race/ethnicity, steroid therapy, comorbidities, and severity of illness, soluble CD14 subtype was 54% lower in coronavirus disease 2019 than noncoronavirus disease 2019 patients (fold difference, 0.46; 95% CI, 0.28–0.77; p = 0.003). In contrast to soluble CD14 subtype, soluble CD14 levels did not differ between coronavirus disease 2019 and noncoronavirus disease 2019 patients. In both coronavirus disease 2019 and noncoronavirus disease 2019, in analyses adjusting for age, sex, race/ethnicity, steroid therapy, and comorbidities, higher soluble CD14 subtype levels were associated with death (coronavirus disease 2019: adjusted relative risk, 1.21; 95% CI, 1.06–1.39; p = 0.006 and noncoronavirus disease 2019: adjusted relative risk, 1.19; 95% CI, 1.03–1.38; p = 0.017), shock, and fewer ventilator-free days. In coronavirus disease 2019 only, an increase in soluble CD14 subtype was associated with severe acute kidney injury (adjusted relative risk, 1.23; 95% CI, 1.05–1.44; p = 0.013).

CONCLUSIONS:

Higher plasma soluble CD14 subtype is associated with worse clinical outcomes in critically ill patients irrespective of coronavirus disease 2019 status though soluble CD14 subtype levels were lower in coronavirus disease 2019 patients than noncoronavirus disease 2019 patients. Soluble CD14 subtype levels may have prognostic utility in coronavirus disease 2019.
Extracorporeal Membrane Oxygenation Support for Influenza A: Retrospective Review of the Extracorporeal Life Support Organization Registry Comparing H1N1 With Other Subtypes
Authors: O’Neil Erika R. , Lin Huiming , Li Meng , Shekerdemian Lara , Tonna Joseph E. , Barbaro Ryan P. , Abella Jayvee R. , Rycus Peter , MacLaren Graeme , Anders Marc M. , Alexander Peta M. A.
Published: December 2021

OBJECTIVES:

Although there is a substantial published experience of extracorporeal membrane oxygenation during the H1N1 pandemic, less is known about the use of extracorporeal membrane oxygenation in patients with other subtypes of the influenza A virus. We hypothesized that the severity of illness and survival of patients supported with extracorporeal membrane oxygenation would differ for those with H1N1 influenza A compared with other subtypes of influenza A.

DESIGN, SETTING, PATIENTS:

Retrospective study of extracorporeal membrane oxygenation–supported adults (> 18 yr) with influenza A viral infection reported to the Extracorporeal Life Support Organization Registry between 2009 and 2019. We describe the frequency and compare characteristics and factors associated with in-hospital survival using a least absolute shrinkage and selection operator regression analysis.

MAIN OUTCOMES AND MEASURES:

Of 2,461 patients supported with extracorporeal membrane oxygenation for influenza A, 445 had H1N1, and 2,004 had other subtypes of influenza A. H1N1 was the predominant subtype between 2009 and 2011. H1N1 patients were younger, with more severe illness at extracorporeal membrane oxygenation cannulation and higher reported extracorporeal membrane oxygenation complications than those with other influenza A subtypes. Patient characteristics including younger age and higher weight and patient management characteristics including longer ventilation duration before extracorporeal membrane oxygenation were associated with worse survival. Extracorporeal membrane oxygenation complications were associated with reduced survival. There was no difference in survival to hospital discharge according to influenza subtype after adjusting for other characteristics.

CONCLUSIONS:

Patients supported with extracorporeal membrane oxygenation for H1N1 were younger, with more severe illness than those supported for other influenza A subtypes. Survival to hospital discharge was associated with patient characteristics, management characteristics, and extracorporeal membrane oxygenation complications but was not impacted by the specific influenza A subtype.
Using Mnemonic in Management of Multiple Sclerosis
Authors: Toufic El Hussein Mohamed , Wong Ashley
Published: December 2021

BACKGROUND: Multiple sclerosis (MS) is a disease involving demyelination of the central nervous system. Medication management in MS is a vital step in preventing further disease progression. OBJECTIVE: This article presents healthcare providers with an aide-mémoire in the form of a mnemonic to assist in the medication management of MS. METHODS: We explored recent guidelines, systematic reviews, and randomized controlled trials using PubMed, MEDLINE, and CINAHL to analyze the role and efficacy of pharmacotherapy in relapse prevention of MS. CONCLUSION: It is crucial to consider the classifications of MS and its pathophysiology to determine which medication produces the best results. Our proposed mnemonic can support a clinician's recall ability and assist in identifying the respective MS medication.
Pediatric Extracorporeal Life Support Transport in Western Canada: Experience over 14 years
Authors: Leung Karen Ka Yan , Garcia Guerra Gonzalo , Decaen Allan , Granoski Donald , Leroux Lisa , Ryerson Lindsay , Blackwood Jaime , Spence Tanya , Lequier Laurance
Published: December 2021

This retrospective cohort study describes all children transported on extracorporeal life support (ECLS) by the Stollery Children’s Hospital Pediatric Transport team (SCH-PTT) between 2004 and 2018. We compared outcomes and complications between primary (SCH-PTT performed ECLS cannulation) vs. secondary (cannulation performed by referring facility) transports, as well as secondary transports from referring centers with and without an established ECLS cannulation program. SCH-PTT performed 68 ECLS transports during the study period. Median (IQR) transport distance was 298 (298–1,068) kilometers. Mean (SD) times from referral call to ECLS-initiation were: primary transports 7.8 (2.9) vs. 2.5(3.5) hours for secondary transports, p value < 0.001. Complications were common (n = 65, 95%) but solved without leading to adverse outcomes. There were no significant differences in the number of complications between primary and secondary transports. There was no significant difference in survival to ECLS decannulation between primary 9 (90%) and secondary transports 43 (74%), p value = 0.275. ECLS survival was higher for children cannulated by the SCH-PTT or a center with an ECLS cannulation program: 42 (82%) vs. 10 (59%), p value = 0.048. Critically ill children on ECLS can be safely transported by a specialized pediatric ECLS transport team. Secondary transports from a center with an ECLS cannulation program are also safe and have similar results as primary transports.
Risk factors of vesicoureteral reflux and urinary tract infections in children with imperforate anus
Authors: Wu Chung-Wei , Wei Chang-Ching , Lin Cheng-Li , Chao Hsiao-Huei , Wei Tse-Chun , Hsieh Tsung-Hsueh , Lin Ching-Yuang
Published: December 2021

Imperforate anus (IA) is associated with several urological anomalies, including vesicoureteral reflux (VUR), a major contributor to high morbidity in patients with anorectal malformations. This retrospective study was performed to elucidate the risk factors of vesicoureteral reflux (VUR) and UTI in children with IA.

We used the National Health Insurance Research Database (NHIRD) to estimate the frequency of congenital anomalies of the kidney and urinary tract (CAKUT) in children with IA. We also investigated the frequencies of VUR, UTI, and CAKUT in children with IA along with the risk factors of VUR.

We enrolled 613 children between 2000 and 2008 (367 males and 246 females; 489 low-position IA and 124 high-position IA). High-position IA was associated with a significantly increased risk of VUR compared with low-position IA (OR: 2.68, 95% CI: 1.61, 4.45). In addition, children with IA along with CAKUT, hydronephrosis, or UTI had a higher risk of VUR (OR: 8.57, 95% CI: 3.75, 19.6; OR: 7.65, 95% CI: 4.48, 13.1; and OR: 31.8, 95% CI: 11.5, 88.3, respectively). UTI, as well as chromosomal anomalies, were more frequent in children with high-position IA.

Patients with a high-position IA had a greater risk of VUR, particularly those with CAKUT, hydronephrosis, or UTI. Such patients must periodically undergo urinalysis to screen for UTI and early voiding cystourethrogram to rule out VUR and prevent consequent renal damage. Chromosomal analysis is suggested to rule out Down syndrome.
Preoperative patients’ quality of life and outcomes after colorectal surgery
Authors: Martin David , Romain Benoît , Demartines Nicolas , Hübner Martin
Published: December 2021

The aim of this prospective study was to assess the influence of preoperative life satisfaction on objective and subjective outcomes after elective colorectal surgery. Preoperative life satisfaction was assessed using a validated questionnaire (Échelle de Mesure des Manifestations du Bien-Être Psychologique). Postoperative quality of life was assessed by the Cleveland Global Quality of Life and QLQ-C30. Number of footsteps was recorded from preoperative day 5 to postoperative day 3. Physical activity, length of stay, and complications were compared between patients with low and high preoperative life satisfaction. Fifty patients were included. There was no difference between the 2 groups concerning postoperative objective (length of stay, complications, and number of footsteps) and subjective (Cleveland Global Quality of Life and QLQ-C30) recovery. In conclusion, preoperative life satisfaction of colorectal surgery patients had no influence on outcomes and physical activity in colorectal surgery.
Comparison of the efficacy and safety of tenofovir and telbivudine in interrupting mother-to-child transmission of hepatitis B virus
Authors: Zhu Bo , Lv Xiaojing , Zhao Zhiying , Chen Liwen , Chen Xiuli , Li Congjie , Li Suwen , Dai Erhei
Published: December 2021

The present study is aimed to evaluate and compare the efficacy and safety of tenofovir (TDF) and telbivudine (TBV) in interrupting hepatitis B virus (HBV) mother-to-child transmission (MTCT), and to provide evidence-based treatment options to clinicians and patients.

Hepatitis B e-antigen (HBeAg)-positive pregnant women (644 in total) with high HBV DNA load (≥2 × 105 IU/mL) and who received TDF (n = 214) or TBV (n = 380) in the second or third trimester, or received no treatment (n = 50) were included in this retrospective analysis.

HBV DNA levels in mothers at delivery were significantly lower than baseline in the 2 treatment groups. HBV DNA levels in the TDF group were significantly different between the mothers receiving treatment in the second trimester and those receiving treatment in the third trimester; however, significant difference was not observed in the TBV group. The proportion of hepatitis B surface antigen (HBsAg)-positive infants at the age of 7 to 12 months in the TDF, TBV, and control groups were 0.00% (0/174), 0.30% (1/331), and 5.0% (2/40) with a significant difference between the treatment groups and the control group, but no difference between the TDF and TBV group (P > .05). However, no serious adverse events were observed in infants and mothers of all groups.

TBV and TDF can effectively reduce the HBV DNA level and MTCT rate in pregnant women with high HBV DNA load (≥2 × 105 IU/mL); both antiviral drugs are safe for infants and mothers. Since TDF was more effective in reducing HBV DNA levels during the second trimester, its use during the period is recommended to prevent HBV MTCT.
Real-world effectiveness and sensitivity of palbociclib plus endocrine therapy in HR+/HER2– patients with metastatic breast cancer
Authors: Li Jingping , Zhang Xiangmei , Yang Chao , Lv Yalei , Yang Hua , Kong Xiangshun , Han Meng , Wang Zunyi , Ma Jie , Han Jianjun , Liu Yunjiang
Published: December 2021

Palbociclib has shown satisfactory outcomes when combined with endocrine therapy (ET) in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC). However, data in Asia are currently scarce.This retrospective study aimed to evaluate the real-world effectiveness, sensitivity, and toxicity of palbociclib plus ET in HR+/HER2– MBC in North China. We recruited patients with HR+/HER2– MBC from August 2018 to July 2020 across 7 hospitals in North China. The primary endpoint was to evaluate progression-free survival (PFS) after initial progress on palbociclib therapy. The secondary endpoints included determining predictive biomarkers of palbociclib sensitivity and toxicity of palbociclib.A total of 54 patients were analyzed in this cohort with an estimated median follow-up time of 14.3 months. Patients who received palbociclib as a first-line treatment showed significantly prolonged PFS compared with those who received palbociclib as a second-line or beyond treatment (21.8 months vs 15.9 months vs 6.8 months) (P < .001). Besides, patients with Ki67 <30% (P = .024) and PR ≥20% (P = .041) in metastatic tumors had significantly longer PFS. The Cox proportional-hazards regression analyses proved that different lines (P = .001 in multivariate analysis), Ki67 <30% (P = .035 in multivariate analysis), and PR ≥20% (P = .045 in univariate analysis) in metastatic tumors affected PFS significantly. The most common adverse events were hematologic, with 31.48% of patients having neutropenia.Palbociclib plus ET significantly prolonged PFS for patients with HR+/HER2– MBC who received first-line therapy, with manageable toxicity. The values of Ki67 and PR in metastatic tumors may be potential predictive biomarkers of palbociclib sensitivity.
Veterans with Traumatic Brain Injury–related Ocular Injury and Vision Dysfunction: Vision Rehabilitation Utilization
Authors: Winkler Sandra L. , Marszalek Jacob , Wang Xinping , Finch Dezon , Rakoczy Chrystyna , Delikat Jemy , Kelleher Valerie , Williams Michael , Zuniga Esteban , Rice Candice , Pollard Kendra , Cockerham Glenn
Published: December 2021

SIGNIFICANCE

Visual dysfunction is frequently associated with traumatic brain injury (TBI). Although evidence regarding the prevalence of symptoms of this population has been published, little is known about health care utilization. A retrospective review of the data derived from the Department of Veterans Affairs (VA)–mandated “Traumatic Brain Injury Specific Ocular Health and Visual Functioning Examination for Polytrauma Rehabilitation Center Patients” provided a unique opportunity to investigate vision rehabilitation utilization.

PURPOSE

The purpose of this study was to understand (a) the frequency of vision rehabilitation follow-up visits at 6, 12, and 24 months; (b) the association between follow-up and demographic, comorbidity, and severity of TBI covariates as well as ocular and visual symptoms, geographic access, and evaluating facility; and (c) why some veterans did not follow up with recommendations.

METHODS

Retrospective and survey designs were used. The sample included 2458 veterans who served in the Operation Enduring Freedom/Operation Iraqi Freedom conflicts and received care at one of the five VA Polytrauma Rehabilitation Centers between January 1, 2008, and December 31, 2017. Quantitative and qualitative descriptive analyses and stepwise logistic regression were performed.

RESULTS

About 60% of veterans followed up with recommended vision rehabilitation with visits equally split between VA Polytrauma Rehabilitation Centers and community VA facilities. For each 10-year increase in age, there was a corresponding reduction of 12% in the odds of follow-up. Veterans with decreased visual field had 50% greater odds of follow-up than those who did not. Veterans with difficulty reading had 59% greater odds of follow-up than those who did not. Those who had a double vision had 45% greater odds of follow-up than those who did not.

CONCLUSIONS

Our findings suggest that the need for vision rehabilitation may extend as long as 2 years after TBI. Access to vision rehabilitation is complicated by the paucity of available neuro-optometric services.
Opioid Prescribing Patterns of Optometrists in the Medicare Part D Database
Authors: Dryden Stephen C. , O'Malley Holly A. , Adams Lindsey R. , Nix Garrett C. , Rho Jonathan E. , Vacheron Albert B. , Fleming James C. , Fowler Brian T.
Published: December 2021

SIGNIFICANCE

This study aimed to determine the prescription rates and prescribing trends of opioids by optometrists in the Centers for Medicare & Medicaid Services (CMS) part D database from 2013 to 2017 and to assess opioid prescribing patterns of U.S. optometrists in the CMS part D database.

METHODS

With internal review board approval, a retrospective observational cohort study was conducted on optometrists listed in the CMS part D database who prescribed opioids from 2013 to 2017.

RESULTS

There was an average of 26,477 optometrists in the CMS database from 2013 to 2017, of which 5.9% prescribed opioids. Of those prescribing opioids, optometrists wrote an average of 5.9 opioid prescriptions per year. Those writing greater than 10 opioid prescriptions averaged 24.2 annually. Overall, of opioid prescribing optometrists, opioid prescriptions comprised 7% of prescriptions written per year.

CONCLUSIONS

Most optometrists do not prescribe opioids, and the vast majority of those who do write few opioid prescriptions. The total number of optometrists prescribing opioids and the total number of opioid prescriptions declined from 2013 to 2017. Further investigation into the opioid prescribing practices by optometrists will help better understand specific pain needs, as opioid prescribing patterns may differ depending on patient population.
Stereothresholds during Voluntary Head Movement and Disconjugate Image Motion
Authors: Bedell Harold E. , Tsang Dorcas K. , Ukwade Michael T.
Published: December 2021

SIGNIFICANCE

Stereothresholds increase in the presence of disconjugate image motion, whether this motion results from vergence errors that occur during active head movements or is imposed externally.

PURPOSE

During rapid voluntary oscillations of the head, vergence eye position has been reported to vary with a peak-to-peak amplitude of about 0.5°—a considerably greater amplitude than when the head is still. Concurrently, stereopsis was reported to be unaffected by voluntary head motion. In the present study, we measured stereothresholds during voluntary side-to-side head movements and during imposed disconjugate image motion with the head stationary, to simulate that produced during active head movement.

METHODS

Stereothresholds were measured for a pair of 30-arcmin bright vertical lines presented on an oscilloscope and viewed through a custom mirror haploscope. Data were obtained from four normal observers during voluntary side-to-side head movements at temporal frequencies up to 1.5 Hz and also while the head remained still. In addition, stereothresholds were measured with the head stationary when opposite rotations of the galvanometer-driven mirrors in each channel of the haploscope created disconjugate image motion to simulate vergence variability during active head movement.

RESULTS

During head motion, average stereothresholds increased from about 10 to about 14 arcsec. With imposed disconjugate image motion, stereothresholds rose systematically to about 35 arcsec when the peak-to-peak motion amplitude was 0.5°. Stereothresholds depend primarily on the amplitude of imposed motion and only marginally on variations of the disjunctive-motion wave form.

CONCLUSIONS

Stereothresholds are elevated modestly during active head movements. The results obtained with imposed disjunctive image motion are consistent with a previously proposal that stereothresholds vary according to the unsigned, time-averaged deviation of the stereotarget from the plane of the horopter.
Rheinheimera lutimaris sp. nov., a marine bacterium isolated from coastal sediment
Authors: Yu Qunfang , Qi Yanxiang , Pu Jinji
Published: December 2021

A Gram-stain-negative, aerobic, rod-shaped bacterium, designated strain YQF-2T, was isolated from coastal sediment sampled in Jiangsu Province and characterized phylogenetically and phenotypically. Optimal bacterial growth occurred at 28 °C (range 4–38 °C) and pH 7 (pH 6–10). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YQF-2T was related to members of the genus

Rheinheimera

and shared the highest sequence identities with

Rheinheimera pacifica

KMM 1406T (98.6%), followed by

Rheinheimera aestuarii

H29T (98.4%),

Rheinheimera japonica

KMM 9513T (98.3%),

Rheinheimera aquimaris

SW-353T (98.3%),

Rheinheimera hassiensis

E48T (97.8%) and

Rheinheimera muenzenbergensis

E49T (97.7%). The 16S rRNA gene sequence identities between strain YQF-2T and other members of the genus

Rheinheimera

were below 97.2%. The digital DNA–DNA hybridization value between strain YQF-2T and

R. pacifica

KMM 1406T was 23.3±2.3%. The average nucleotide identity value between strain YQF-2T and

R. pacifica

KMM 1406T was 79.7%. The unique respiratory quinone was ubiquinone-8. Phosphatidylethanolamine and phosphatidylglycerol were identified as the major polar lipids. The strain had summed feature 3 (C16:1
ω7c and/or C16:1
ω6c), summed feature 8 (C18:1
ω7c and/or C18:1
ω6c), C16:0, C12:0 3-OH and iso-C17:0 3-OH as major fatty acids. The G+C content of the genomic DNA was 50.0 mol%. On the basis of phenotypic, genotypic and phylogenetic evidence, strain YQF-2T represents a novel species of the genus

Rheinheimera

, for which the name Rheinheimera lutimaris sp. nov. is proposed, with the type strain YQF-2T (=KCTC 72184T=MCCC 1K03663T).
Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication
Authors: Falci Finardi Nicole , Kim HyeongJun , Hernandez Lee Z. , Russell Matthew R. G. , Ho Catherine M-K , Sreenu Vattipally B. , Wenham Hannah A. , Merritt Andy , Strang Blair L.
Published: December 2021

The shortcomings of current anti-human cytomegalovirus (HCMV) drugs has stimulated a search for anti-HCMV compounds with novel targets. We screened collections of bioactive compounds and identified a range of compounds with the potential to inhibit HCMV replication. Of these compounds, we selected bisbenzimide compound RO-90-7501 for further study. We generated analogues of RO-90-7501 and found that one compound, MRT00210423, had increased anti-HCMV activity compared to RO-90-7501. Using a combination of compound analogues, microscopy and biochemical assays we found RO-90-7501 and MRT00210423 interacted with DNA. In single molecule microscopy experiments we found RO-90-7501, but not MRT00210423, was able to compact DNA, suggesting that compaction of DNA was non-obligatory for anti-HCMV effects. Using bioinformatics analysis, we found that there were many putative bisbenzimide binding sites in the HCMV DNA genome. However, using western blotting, quantitative PCR and electron microscopy, we found that at a concentration able to inhibit HCMV replication our compounds had little or no effect on production of certain HCMV proteins or DNA synthesis, but did have a notable inhibitory effect on HCMV capsid production. We reasoned that these effects may have involved binding of our compounds to the HCMV genome and/or host cell chromatin. Therefore, our data expand our understanding of compounds with anti-HCMV activity and suggest targeting of DNA with bisbenzimide compounds may be a useful anti-HCMV strategy.
Comparative genomics of Chinese and international isolates of Escherichia albertii: population structure and evolution of virulence and antimicrobial resistance
Authors: Luo Lijuan , Wang Hong , Payne Michael J. , Liang Chelsea , Bai Li , Zheng Han , Zhang Zhengdong , Zhang Ling , Zhang Xiaomei , Yan Guodong , Zou Nianli , Chen Xi , Wan Ziting , Xiong Yanwen , Lan Ruiting , Li Qun
Published: December 2021

Escherichia albertii

is a recently recognized species in the genus

Escherichia

that causes diarrhoea. The population structure, genetic diversity and genomic features have not been fully examined. Here, 169

E. albertii

isolates from different sources and regions in China were sequenced and combined with 312 publicly available genomes (from additional 14 countries) for genomic analyses. The

E. albertii

population was divided into two clades and eight lineages, with lineage 3 (L3), L5 and L8 more common in China. Clinical isolates were observed in all clades/lineages. Virulence genes were found to be distributed differently among lineages: subtypes of the intimin encoding gene eae and the cytolethal distending toxin gene cdtB were lineage associated, and the second type three secretion system (ETT2) island was truncated in L3 and L6. Seven new eae subtypes and one new cdtB subtype (cdtB-VI) were identified. Alarmingly, 85.9 % of the Chinese

E. albertii

isolates were predicted to be multidrug-resistant (MDR) with 35.9 % harbouring genes capable of conferring resistance to 10 to 14 different drug classes. The majority of the MDR isolates were of poultry source from China and belonged to four sequence types (STs) [ST4638, ST4479, ST4633 and ST4488]. Thirty-four plasmids with some carrying MDR and virulence genes, and 130 prophages were identified from 17 complete

E. albertii

genomes. The 130 intact prophages were clustered into five groups, with group five prophages harbouring more virulence genes. We further identified three

E. albertii

specific genes as markers for the identification of this species. Our findings provided fundamental insights into the population structure, virulence variation and drug resistance of

E. albertii

.
Mobility of β-lactam resistance under ampicillin treatment in gut microbiota suffering from pre-disturbance
Authors: Laskey Alexander , Devenish John , Kang Mingsong , Savic Mirjana , Chmara John , Dan Hanhong , Lin Min , Robertson James , Bessonov Kyrylo , Gurnik Simone , Liu Kira , Nash John H. E. , Topp Edward , Guan Jiewen
Published: December 2021

Ingestion of food- or waterborne antibiotic-resistant bacteria may lead to dissemination of antibiotic resistance genes (ARGs) in the gut microbiota. The gut microbiota often suffers from various disturbances. It is not clear whether and how disturbed microbiota may affect ARG mobility under antibiotic treatments. For proof of concept, in the presence or absence of streptomycin pre-treatment, mice were inoculated orally with a β-lactam-susceptible

Salmonella enterica

serovar Heidelberg clinical isolate (recipient) and a β-lactam resistant

Escherichia coli

O80:H26 isolate (donor) carrying a blaCMY-2
gene on an IncI2 plasmid. Immediately following inoculation, mice were treated with or without ampicillin in drinking water for 7 days. Faeces were sampled, donor, recipient and transconjugant were enumerated, blaCMY-2
abundance was determined by quantitative PCR, faecal microbial community composition was determined by 16S rRNA amplicon sequencing and cecal samples were observed histologically for evidence of inflammation. In faeces of mice that received streptomycin pre-treatment, the donor abundance remained high, and the abundance of S. Heidelberg transconjugant and the relative abundance of

Enterobacteriaceae

increased significantly during the ampicillin treatment. Co-blooming of the donor, transconjugant and commensal

Enterobacteriaceae

in the inflamed intestine promoted significantly (P<0.05) higher and possibly wider dissemination of the blaCMY-2
gene in the gut microbiota of mice that received the combination of streptomycin pre-treatment and ampicillin treatment (Str–Amp) compared to the other mice. Following cessation of the ampicillin treatment, faecal shedding of S. Heidelberg transconjugant persisted much longer from mice in the Str–Amp group compared to the other mice. In addition, only mice in the Str–Amp group shed a commensal

E. coli

O2:H6 transconjugant, which carries three copies of the blaCMY-2
gene, one on the IncI2 plasmid and two on the chromosome. The findings highlight the significance of pre-existing gut microbiota for ARG dissemination and persistence during and following antibiotic treatments of infectious diseases.
Revealing microbial species diversity using sequence capture by hybridization
Authors: Marre Sophie , Gasc Cyrielle , Forest Camille , Lebbaoui Yacine , Mosoni Pascale , Peyret Pierre
Published: December 2021

Targeting small parts of the 16S rDNA phylogenetic marker by metabarcoding reveals microorganisms of interest but cannot achieve a taxonomic resolution at the species level, precluding further precise characterizations. To identify species behind operational taxonomic units (OTUs) of interest, even in the rare biosphere, we developed an innovative strategy using gene capture by hybridization. From three OTU sequences detected upon polyphenol supplementation and belonging to the rare biosphere of the human gut microbiota, we revealed 59 nearly full-length 16S rRNA genes, highlighting high bacterial diversity hidden behind OTUs while evidencing novel taxa. Inside each OTU, revealed 16S rDNA sequences could be highly distant from each other with similarities down to 85 %. We identified one new family belonging to the order

Clostridiales

, 39 new genera and 52 novel species. Related bacteria potentially involved in polyphenol degradation have also been identified through genome mining and our results suggest that the human gut microbiota could be much more diverse than previously thought.
COP1 promotes seed germination by destabilizing RGA-LIKE2 (RGL2) in Arabidopsis
Authors: Lee Byoung-Doo , Yim Yehyun , Cañibano Esther , Kim Suk-Hwan , García-León Marta , Rubio Vicente , Fonseca Sandra , Paek Nam-Chon
Published: December 2021

Under favorable moisture, temperature and light conditions, gibberellin (GA) biosynthesis is induced and triggers seed germination. A major mechanism by which GA promotes seed germination is by promoting the degradation of the DELLA protein RGL2, a major repressor of germination in Arabidopsis seeds. Analysis of seed germination phenotypes of constitutively photomorphogenic 1 (cop1) mutants and complemented COP1-OX/cop1-4 lines in response to GA and paclobutrazol (PAC) suggested a positive role for COP1 in seed germination and a relation with GA signaling. cop1-4 mutant seeds showed PAC hypersensitivity, but transformation with a COP1 overexpression construct rendered them PAC insensitive, with a phenotype similar to that of rgl2 mutant (rgl2-SK54) seeds. Furthermore, cop1-4 rgl2-SK54 double mutants showed a PAC-insensitive germination phenotype like that of rgl2-SK54, identifying COP1 as an upstream negative regulator of RGL2. COP1 interacts directly with RGL2 and in vivo this interaction is strongly enhanced by SPA1. COP1 directly ubiquitinates RGL2 to promote its degradation. Moreover, GA stabilizes COP1 with consequent RGL2 destabilization. By uncovering this COP1-RGL2 regulatory module, we reveal a novel mechanism whereby COP1 positively regulates seed germination and controls the expression of germination-promoting genes.
Obesity affects mitochondrial metabolism and proliferative potential of equine endometrial progenitor cells
Authors: Smieszek Agnieszka , Marcinkowska Klaudia , Pielok Ariadna , Sikora Mateusz , Valihrach Lukas , Carnevale Elaine , Marycz Krzysztof
Published: December 2021

The study aimed to investigate the influence of obesity on cellular features of equine endometrial progenitor cells (Eca EPCs), including viability, proliferation capacity, mitochondrial metabolism, and oxidative homeostasis. Eca EPCs derived from non-obese (Non-OB) and obese (OB) mares were characterized by cellular phenotype and multipotency. Obesity-induced changes in the activity of Eca EPCs include the decline of their proliferative activity, clonogenic potential, mitochondrial metabolism and enhanced oxidative stress. Eca EPCs isolated from obese mares were characterized by an increased occurrence of early apoptosis, loss of mitochondrial dynamics, and senescence-associated phenotype. Attenuated metabolism of Eca EPCs OB was related to increased expression of pro-apoptotic markers (CASP9, BAX, P53, P21), enhanced expression of OPN, PI3K and AKT, simultaneously with decreased signaling stabilizing cellular homeostasis (including mitofusin, SIRT1, FOXP3). Obesity alters functional features and the self-renewal potential of endometrial progenitor cells. The impaired cytophysiology of progenitor cells from obese endometrium predict lower regenerative capacity if used as autologous transplants.
Brain-wide neural co-activations in resting human
Authors: Ding Lei , Shou Guofa , Cha Yoon-Hee , Sweeney John A. , Yuan Han
Published: December 2021

Spontaneous neural activity in human as assessed with resting-state functional magnetic resonance imaging (fMRI) exhibits brain-wide coordinated patterns in the frequency of <0.1Hz. However, fast brain-wide networks at the timescales of neuronal events (milliseconds to sub-seconds) and their spatial, spectral, and propagational characteristics remain unclear due to the temporal constraints of hemodynamic signals. With milli-second resolution and whole-head coverage, scalp-based electroencephalography (EEG) provides a unique window into brain-wide networks with neuronal-timescale dynamics, shedding light on the organizing principles of brain function. Using state-of-the-art signal processing techniques, we reconstructed cortical neural tomography from resting-state EEG and extracted component-based co-activation patterns (cCAPs). These cCAPs revealed brain-wide intrinsic networks and their dynamics, indicating the configuration/reconfiguration of resting human brains into recurring and propagating functional states, which are featured with the prominent spatial phenomena of global patterns and anti-state pairs of co-(de)activations. Rich oscillational structures across a wide frequency band (i.e., 0.6Hz, 5Hz, and 10Hz) were embedded in the dynamics of these functional states. We further identified a superstructure that regulated between-state propagations and governed a significant aspect of brain-wide network dynamics. These findings demonstrated how resting-state EEG data can be functionally decomposed using cCAPs to reveal rich structures of brain-wide human neural activations.
Molecular Graph Contrastive Learning with Parameterized Explainable Augmentations
Authors: Wang Yingheng , Min Yaosen , Shao Erzhuo , Wu Ji
Published: December 2021

Learning generalizable, transferable, and robust representations for molecule data has always been a challenge. The recent success of contrastive learning (CL) for self-supervised graph representation learning provides a novel perspective to learn molecule representations. The most prevailing graph CL framework is to maximize the agreement of representations in different augmented graph views. However, existing graph CL frameworks usually adopt stochastic augmentations or schemes according to pre-defined rules on the input graph to obtain different graph views in various scales (e.g. node, edge, and subgraph), which may destroy topological semantemes and domain prior in molecule data, leading to suboptimal performance. Therefore, designing parameterized, learnable, and explainable augmentation is quite necessary for molecular graph contrastive learning. A well-designed parameterized augmentation scheme can preserve chemically meaningful structural information and intrinsically essential attributes for molecule graphs, which helps to learn representations that are insensitive to perturbation on unimportant atoms and bonds. In this paper, we propose a novel Molecular Graph Contrastive Learning with Parameterized Explainable Augmentations, MolCLE for brevity, that self-adaptively incorporates chemically significative information from both topological and semantic aspects of molecular graphs. Specifically, we apply deep neural networks to parameterize the augmentation process for both the molecular graph topology and atom attributes, to highlight contributive molecular substructures and recognize underlying chemical semantemes. Comprehensive experiments on a variety of real-world datasets demonstrate that our proposed method consistently outperforms compared baselines, which verifies the effectiveness of the proposed framework. Detailedly, our self-supervised MolCLE model surpasses many supervised counterparts, and meanwhile only uses hundreds of thousands of parameters to achieve comparative results against the state-of-the-art baseline, which has tens of millions of parameters. We also provide detailed case studies to validate the explainability of augmented graph views.

CCS CONCEPTS

• Mathematics of computing → Graph algorithms; • Applied computing → Bioinformatics; • Computing methodologies → Neural networks; Unsupervised learning.
Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors
Authors: Senger Gökçe , Santaguida Stefano , Schaefer Martin H.
Published: December 2021

Aneuploidy, a state of chromosome imbalance, is a hallmark of human tumors, but its role in cancer still remains to be fully elucidated. To understand the consequences of whole chromosome-level aneuploidies on the proteome, we integrated aneuploidy, transcriptomic and proteomic data from hundreds of TCGA/CPTAC tumor samples. We found a surprisingly large number of expression changes happened on other, non-aneuploid chromosomes. Moreover, we identified an association between those changes and co-complex members of proteins from aneuploid chromosomes. This co-abundance association is tightly regulated for aggregation-prone aneuploid proteins and those involved in a smaller number of complexes. On the other hand, we observe that complexes of the cellular core machinery are under functional selection to maintain their stoichiometric balance in aneuploid tumors. Ultimately, we provide evidence that those compensatory and functional maintenance mechanisms are established through post-transcriptional control and that the degree of success of a tumor to deal with aneuploidy-induced stoichiometric imbalance impacts the activation of cellular protein degradation programs and patient survival.
A descriptive analysis of 2020 California Occupational Safety and Health Administration COVID-19-related complaints
Authors: Thomas Marilyn D , Matthay Ellicott C. , Duchowny Kate A. , Riley Alicia R. , Khela Harmon , Chen Yea-Hung , Bibbins-Domingo Kirsten , Glymour M. Maria
Published: December 2021

COVID-19 mortality disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7,820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.
Data and code availability statements in systematic reviews of interventions were often missing or inaccurate: a content analysis
Authors: Page Matthew J , Nguyen Phi-Yen , Hamilton Daniel G , Haddaway Neal R , Kanukula Raju , Moher David , McKenzie Joanne E
Published: December 2021

Objectives: To estimate the frequency of data and code availability statements in a random sample of systematic reviews with meta-analysis of aggregate data, summarise the content of the statements and investigate how often data and code files were shared.
Methods: We searched for systematic reviews with meta-analysis of aggregate data on the effects of a health, social, behavioural or educational intervention that were indexed in PubMed, Education Collection via ProQuest, Scopus via Elsevier, and Social Sciences Citation Index and Science Citation Index Expanded via Web of Science during a four-week period (between November 2nd and December 2nd, 2020). Records were randomly sorted and screened independently by two authors until our target sample of 300 systematic reviews was reached. Two authors independently recorded whether a data or code availability statement (or both) appeared in each review and coded the content of the statements using an inductive approach.
Results: Of the 300 included systematic reviews with meta-analysis, 86 (29%) had a data availability statement and seven (2%) had both a data and code availability statement. In 12/93 (13%) data availability statements, authors stated that data files were available for download from the journal website or a data repository, which we verified as being true. While 39/93 (42%) authors stated data were available upon request, 37/93 (40%) implied that sharing of data files was not necessary or applicable to them, most often because "all data appear in the article" or "no datasets were generated or analysed".
Discussion: Data and code availability statements appear infrequently in systematic review manuscripts. Authors who do provide a data availability statement often incorrectly imply that data sharing is not applicable to systematic reviews. Our results suggest the need for various interventions to increase data and code sharing by systematic reviewers.
Production of novel Spike truncations in Chinese hamster ovary cells
Authors: Minami Shiaki A. , Jung Seongwon , Huang Yihan , Harris Bradley S. , Kenaston Matthew W. , Faller Roland , Nandi Somen , McDonald Karen A. , Shah Priya S.
Published: December 2021

SARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to improve yields. Alternatively, Spike receptor binding domain (RBD) is commonly expressed with higher titers, though it has lower sensitivity in serological assays. Here, we improve transient Spike expression in Chinese hamster ovary (CHO) cells. We demonstrate that Spike titers increase significantly over the expression period, maximizing at 14 mg/L at day 7. In comparison, RBD titers peak at 54 mg/L at day 3. Next, we develop 8 Spike truncations (T1-T8) in pursuit of a truncation with high expression and antibody binding. The truncations T1 and T4 express at 130 mg/L and 73 mg/L, respectively, which are higher than our RBD titers. Purified proteins were evaluated for binding to antibodies raised against full-length Spike. T1 has similar sensitivity as Spike against a monoclonal antibody and even outperforms Spike for a polyclonal antibody. These results suggest T1 is a promising Spike alternative for use in various applications.