bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Adult Spinal Deformity Surgical Outcome Prediction Tools in Adult Symptomatic Lumbar Scoliosis
Authors: Wondra James P. , Kelly Michael P. , Greenberg Jacob , Yanik Elizabeth L. , Ames Christopher P. , Pellise Ferran , Vila-Casademunt Alba , Smith Justin S. , Bess Shay , Shaffrey Christopher I. , Lenke Lawrence G. , Serra-Burriel Miquel , Bridwell Keith H.
Published: July 2022

Study Design.

A post hoc analysis.

Objective.

Advances in machine learning (ML) have led to tools offering individualized outcome predictions for adult spinal deformity (ASD). Our objective is to examine the properties of these ASD models in a cohort of adult symptomatic lumbar scoliosis (ASLS) patients.

Summary of Background Data.

ML algorithms produce patient-specific probabilities of outcomes, including major complication (MC), reoperation (RO), and readmission (RA) in ASD. External validation of these models is needed.

Methods.

Thirty-nine predictive factors (12 demographic, 9 radiographic, 4 health-related quality of life, 14 surgical) were retrieved and entered into web-based prediction models for MC, unplanned RO, and hospital RA. Calculated probabilities were compared with actual event rates. Discrimination and calibration were analyzed using receiver operative characteristic area under the curve (where 0.5=chance, 1=perfect) and calibration curves (Brier scores, where 0.25=chance, 0=perfect). Ninety-five percent confidence intervals are reported.

Results.

A total of 169 of 187 (90%) surgical patients completed 2-year follow up. The observed rate of MCs was 41.4% with model predictions ranging from 13% to 68% (mean: 38.7%). RO was 20.7% with model predictions ranging from 9% to 54% (mean: 30.1%). Hospital RA was 17.2% with model predictions ranging from 13% to 50% (mean: 28.5%). Model classification for all three outcome measures was better than chance for all [area under the curve=MC 0.6 (0.5–0.7), RA 0.6 (0.5–0.7), RO 0.6 (0.5–0.7)]. Calibration was better than chance for all, though best for RA and RO (Brier Score=MC 0.22, RA 0.16, RO 0.17).

Conclusions.

ASD prediction models for MC, RA, and RO performed better than chance in a cohort of adult lumbar scoliosis patients, though the homogeneity of ASLS affected calibration and accuracy. Optimization of models require samples with the breadth of outcomes (0%–100%), supporting the need for continued data collection as personalized prediction models may improve decision-making for the patient and surgeon alike.
The Psychometric Properties of Version 2 of the Canadian Nurse Informatics Competency Assessment Scale
Authors: Kleib Manal , Nagle Lynn M.
Published: July 2022

In 2020, we conducted a mixed methods study comprised of a cross-sectional survey in which we applied a modified version of the 21-item Canadian Nurse Informatics Competency Assessment Scale and one-on-one interviews to explore self-perceived nursing informatics competency and readiness for future digital health practice. A total of 221 senior-level students in BScN programs in western Canada participated. This article reports on results related to the factor structure and internal consistency reliability of the 26-item (version 2) of the Canadian Nurse Informatics Competency Assessment Scale. Exploratory principal component analysis with the varimax rotation revealed a four-component structure, explaining 55.10% of the variance. All items on the Canadian Nurse Informatics Competency Assessment Scale 2 had good loadings, except item 7, which did not load to any domain but was retained based on an evaluation of the α value and item relevance to nursing practice. A few items shifted to different domains. The overall reliability of the Canadian Nurse Informatics Competency Assessment Scale 2 was (α = .916) and its subscales: information and knowledge management (α = .814), professional and regulatory accountability (α = .741), and use of information and communication technology (α = .895). This study provided preliminary evidence for the factor structure and reliability of the Canadian Nurse Informatics Competency Assessment Scale 2 among nursing students. Further testing is recommended.
Trajectories of Postpartum Recovery: What is Known and Not Known
Authors: Daly Deirdre , Higgins Agnes , Hannon Susan , O’Malley Deirdre , Wuytack Francesca , Moran Patrick , Cusack Cinny , Begley Cecily
Published: July 2022

Women’s postpartum health is a public health issue that has lifelong consequences. Timely recognition and treatment of physical and mental health issues can have positive health consequences while lack of access to effective treatments or health care services can lead to long-term health problems. To advance knowledge of priority health symptoms and trajectories of postpartum recovery from women’s health perspectives, we share findings from the Maternal health And Maternal Morbidity in Ireland (MAMMI) study. Data from 3047 first-time mothers recruited to a longitudinal maternal health study in Ireland from 2012 to 2017 reveal the trajectories of maternal health and health problems experienced up to 12 months postpartum. Morbidities explored include urinary incontinence, pelvic girdle pain, and sexual and mental health issues. Viewed together, and over time, the scale and persistent nature of many physical and mental health problems become apparent, yet considerable proportions of women were not asked directly about health problems by health care professionals. When women do not know what is and is not normal postpartum, they may suffer in silence and the consequence is that health problems/issues that are preventable, and treatable, are likely to become chronic. To make positive contributions to women’s health, maternity care systems must be truly woman-centered and structured in ways that place emphasis on women’s own health needs. In systems where women’s voices and concerns are acknowledged and central, women are likely to thrive and flourish in motherhood.
SARS-CoV-2 Infections in Icelandic Children: Close Follow-up of All Confirmed Cases in a Nationwide Study
Authors: Thors Valtyr , Bjornsdottir Kristin L. , Love Thorvardur , Haraldsson Asgeir
Published: July 2022

Introduction:

Children are less likely to acquire SARS-CoV-2 infections than adults and when infected, usually have milder disease. True infection and complication rates are, however, difficult to ascertain. In Iceland, a strict test, trace and isolate policy was maintained from the start of the pandemic and offers more accurate information of the number of truly infected children in a nationwide study.

Material and methods:

All children with positive PCR for SARS-CoV-2 infections from February 28, 2020 to August 31, 2021 were followed up through telephone consultations for at least 14 days and their symptoms were registered. Symptom severity and duration were categorized based on age groups and the source of infection was registered.

Results:

A total of 1749 children were infected with SARS-CoV-2 in 3 waves of infections. All waves had similar disease severity whereas the incidence was 5-fold higher in the third wave (3.5 vs. 0.73/1000 children/month). No children had severe symptoms, 81 (4.6%) had moderate symptoms, 1287 (73.9%) had mild and 374 (21.5%) were asymptomatic. Symptoms from upper (n = 839, 48%) and lower respiratory tract (n = 744, 43%) were most common. Median duration of symptoms was 5 days and adolescents had a higher risk of prolonged duration [OR:1.84 (1.39–2.43)]. Nineteen (1.1%) children needed medical attention, but no child was hospitalized. The source of infection was a household member in 65% of cases.

Discussion:

During the first 3 waves of the pandemic, SARS-CoV-2 infections in Icelandic children were mild and none were hospitalized. The most common symptoms were respiratory symptoms followed by fever, headache and tiredness. This study helps shed light on true complication rates of children with confirmed SARS-CoV-2 infection.
Pseudomonas aeruginosa Early-Onset Neonatal Sepsis: Could Maternal Healthcare Occupation Be a Risk Factor?
Authors: Tabarani Christy , Baker Carol J.
Published: July 2022

Pseudomonas aeruginosa is a rare cause of early-onset sepsis in neonates, even among infants with identifiable risk factors. Herein we describe the first case, to our knowledge, of P. aeruginosa early-onset sepsis in a term infant with no identifiable risk factor and propose that maternal healthcare occupation could predispose to gastrointestinal/genital colonization with this potential pathogen.
Pronociceptive autoantibodies in the spinal cord mediate nociceptive sensitization, loss of function, and spontaneous pain in the lumbar disk puncture model of chronic back pain
Authors: Guo Tian-Zhi , Shi Xiaoyou , Li Wen-wu , Wei Tzuping , Sahbaie Peyman , Clark J. David , Kingery Wade S.
Published: July 2022

Previously, we observed that B cells and autoantibodies mediated chronic nociceptive sensitization in the mouse tibia fracture model of complex regional pain syndrome and that complex regional pain syndrome patient antibodies were pronociceptive in fracture mice lacking mature B cells and antibodies (muMT). The current study used a lumbar spinal disk puncture (DP) model of low back pain in wild-type (WT) and muMT mice to evaluate pronociceptive adaptive immune responses. Spinal disks and cords were collected 3 weeks after DP for polymerase chain reaction and immunohistochemistry analyses. Wild-type DP mice developed 24 weeks of hindpaw mechanical allodynia and hyperalgesia, grip weakness, and a conditioned place preference response indicative of spontaneous pain, but pain responses were attenuated or absent in muMT DP mice. Spinal cord expression of inflammatory cytokines, immune cell markers, and complement components were increased in WT DP mice and in muMT DP mice. Dorsal horn immunostaining in WT DP mice demonstrated glial activation and increased complement 5a receptor expressionin spinal neurons. Serum collected from WT DP mice and injected into muMT DP mice caused nociceptive sensitization, as did intrathecal injection of IgM collected from WT DP mice, and IgM immune complexes were observed in lumbar spinal disks and cord of WT DP mice. Serum from WT tibia fracture mice was not pronociceptive in muMT DP mice and vice versa, evidence that each type of tissue trauma chronically generates its own unique antibodies and targeted antigens. These data further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain state.
A Mathematical Model of Artificial Pulse Synchronization for the HeartMate3 Left Ventricular Assist Device
Authors: May-Newman Karen
Published: July 2022

Constant speed control of rotary LVADs attenuates vascular pulsatility, which has been linked to clinical complications such as thrombus formation, bleeding, and valvular dysfunction. Speed modulation can improve pulsatility and washout, but optimization requires coordination with the native heartbeat. A simple mathematical model of the left ventricle-left ventricular assist device (LV-LVAD) flow interaction was developed that sums the individual contributions of the native LV and the HeartMate3 artificial pulse (AP) to predict the total systemic flow. The model flow and pulsatility predictions results were in good agreement with experimental data from a mock circulatory loop measured for full bypass support conditions. The model was used to evaluate three schemes for optimizing the synchronization of the AP with the native heart. The optimized interaction occurred when the AP speed increase occurred during contraction, resulting in a doubling of flow pulsatility, and corresponded to an increase in the area enclosed by the dynamic pressure-flow relation. The model provides a simple tool for exploring the optimization of LVAD speed modulation that can reduce the time and expense of mock loop studies during the development process.
18F-FDG Brain PET Findings in Narcolepsy Type 2
Authors: Varughese Robin T. , Kothare Sanjeev V. , Franceschi Ana Marija
Published: July 2022

A 16-year-old adolescent boy with extensive travel throughout West Africa presented with a 6-year history of social withdrawal, anhedonia, and daytime sleepiness. The patient’s electroencephalography was normal. Initial MRI revealed small pituitary gland and left temporal developmental venous anomaly. Subsequently obtained 18F-FDG brain PET was notable for markedly severe hypometabolism in the brainstem. Further workup revealed a normal orexin, autoimmune encephalitis panel, and negative titers for Trypanosoma brucei and cruzi in the CSF. Outpatient sleep study showed mild obstructive sleep apnea, and multiple sleep latency test revealed reduced mean sleep latency at 7 minutes with sleep-onset REM in 3/5 naps, findings consistent with narcolepsy type 2.
Necessity of Routine Chest Radiograph Following Chest Tube Removal in Pediatric Patients After Cardiovascular Surgery
Authors: Slak Peter , Winant Abbey J. , Lee Edward Y. , Plut Domen
Published: July 2022

Purpose:

Chest tube placement and subsequent removal is a routine step in patient management after cardiovascular surgery. The purpose of this retrospective study is to determine the necessity of routine chest radiography following chest tube removal in order to detect potential complications in pediatric patients after cardiovascular surgery.

Materials and Methods:

We retrospectively reviewed the hospital records of all consecutive children up to 5 years of age who had cardiovascular surgery at our hospital between January 2015 and December 2020. Two radiologists independently evaluated routine chest radiographs performed 4 hours following chest tube removal for the presence of potential complications. In all post chest tube removal chest radiographs that demonstrated a complication, the patient’s medical record was investigated in order to determine if there was an associated clinical or laboratory test abnormality, and if the radiographically detected complication led to a change in patient management. Inter-rater agreement between the 2 reviewers was evaluated with κ statistics.

Results:

We identified 147 children (73 [49.7%] male and 74 [50.3%] female; mean age=13.8 mo old; range 0 to 60 mo) who met the inclusion criteria. Complications were detected on routine chest radiograph after chest tube removal in 10 patients (6.8%) including pneumothorax (n=5, 3.4%), pleural effusion (n=3, 2%), pneumomediastinum (n=1, 0.7%), and pneumopericardium (n=1, 0.7%). No clinical or laboratory abnormalities were present in all children affected with radiographically detected complications on routine chest radiograph 4 hours after chest tube removal, and there was no need for intervention in any affected patients. There was high inter-rater κ agreement between the 2 independent reviewers for detecting complications on chest radiographs after chest tube removal (κ=0.94).

Conclusion:

Our study shows that routine chest radiograph performed shortly after chest tube removal may not be necessary for the safe management of asymptomatic children after cardiovascular surgery because complications are rare and do not require intervention. In addition, obviating performance of this routine chest radiograph following chest tube removal will lead to a substantial decrease in exposure to unnecessary ionizing radiation in children who undergo frequent radiographs and lower medical costs.
A Randomized Controlled Clinical Trial of Transanal Irrigation Versus Conservative Treatment in Patients With Low Anterior Resection Syndrome After Rectal Cancer Surgery
Authors: Pieniowski Emil H.A. , Bergström Charlotta M. , Nordenvall Caroline A.M. , Westberg Karin S. , Johar Asif M. , Tumlin Ekelund Susanne F. , Larsson Kristina R. , Pekkari Klas J. , Jansson Palmer Gabriella C. , Lagergren Pernilla , Abraham-Nordling Mirna
Published: July 2022

Objective:

The aim of the study was to evaluate transanal irrigation (TAI) as a treatment for low anterior resection syndrome (LARS).

Background:

LARS is a bowel disorder that is common after sphincter preserving rectal cancer surgery. Despite symptomatic medical treatment of LARS many patients still experience bowel symptoms that may have a negative impact on quality of life (QoL). TAI is a treatment strategy, of which the clinical experience is promising but scientific evidence is limited.

Materials and Methods:

A multicenter randomized trial comparing TAI (intervention) with conservative treatment (control) was performed. Inclusion criteria were major LARS, age above 18 years, low anterior resection with anastomosis and a defunctioning stoma as primary surgery, >6 months since stoma reversal, anastomosis without signs of leakage or stricture, and no signs of recurrence at 1-year follow-up. The primary endpoint was differences in bowel function at 12-month follow-up measured by LARS score, Cleveland Clinic Florida Fecal Incontinence Score, and 4 study-specific questions. The secondary outcome was QoL.

Results:

A total of 45 patients were included, 22 in the TAI group and 23 in the control group. Follow-up was available for 16 and 22 patients, respectively. At 12 months, patients in the TAI group reported significantly lower LARS scores (22.9 vs 32.4; P=0.002) and Cleveland Clinic Florida Fecal Incontinence Score (6.4 vs 9.2; P=0.050). In addition, patients in the TAI group also scored significantly higher QoL [8 of 16 European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) QoL aspects] compared with the control group.

Conclusions:

The results confirm our clinical experience that TAI reduces symptoms included in LARS and improves QoL.
Assessing the use of Extended Venous Thromboembolism Prophylaxis on the Rates of Venous Thromboembolism and Postpancreatectomy Hemorrhage Following Pancreatectomy for Malignancy
Authors: Stitzel Henry J. , Hue Jonathan J. , Elshami Mohamedraed , McCaulley Lauren , Hoehn Richard S. , Rothermel Luke D. , Ammori John B. , Hardacre Jeffrey M. , Winter Jordan M. , Ocuin Lee M.
Published: July 2022

Objective:

To compare rates of venous thromboembolism (VTE) and postpancreatectomy hemorrhage (PPH) in patients with pancreatic or periampullary malignancy preimplementation and postimplementation of routine extended VTE prophylaxis.

Background:

Guidelines recommend up to 28 days of VTE prophylaxis following major abdominal cancer operations. There is a paucity of data examining rates of VTE and PPH in patients who receive extended VTE prophylaxis following pancreatectomy.

Methods:

Single-institution analysis of patients who underwent pancreatectomy for malignancy (2004–2021). VTE and PPH rates within 90 days of discharge were compared based on receipt of extended VTE prophylaxis with enoxaparin.

Results:

A total of 478 patients were included. Twenty-two (4.6%) patients developed a postoperative VTE, 12 (2.5%) of which occurred postdischarge. Twenty-five (5.2%) patients experienced PPH, 13 (2.7%) of which occurred postdischarge. There was no associated difference in the development of postdischarge VTE between patients who received extended VTE prophylaxis and those who did not (2.3% vs 2.8%, P=0.99). There was no associated difference in the rate of postdischarge PPH between patients who received extended VTE prophylaxis and those who did not (3.4% vs 1.9%, P=0.43). In the subset of patients on antiplatelet agents, the addition of enoxaparin did not appear to be associated with higher VTE (3.9 vs. 0%, P=0.31) or PPH (3.0 vs. 4.5%, P=0.64) rates.

Conclusions:

Extended VTE prophylaxis following pancreatectomy for malignancy was not associated with differences in postdischarge VTE and PPH rates. These data suggest extended VTE prophylaxis is safe but may not be necessary for all patients following pancreatectomy.
Reduced Morbidity and Mortality Associated With Minimally Invasive Single-vessel Coronary Artery Bypass Compared With Conventional Sternotomy
Authors: Cain Michael T. , Joyce David L. , Szabo Aniko , Wu Ruizhe , Kohmoto Takushi , Joyce Lyle D. , Pearson Paul J.
Published: July 2022

Objective:

We aimed to describe the safety and clinical benefits of minimally invasive, nonsternotomy coronary artery bypass grafting (MICABG) using data from The Society of Thoracic Surgeons (STS) National Database.

Background:

MICABG has gained popularity, owing to expected lower perioperative morbidity and shorter recovery. Despite this, concerns remain regarding anastomotic quality and the validity of proposed perioperative benefits.

Methods:

We queried the STS National Database for all patients who underwent single-vessel coronary artery bypass grafting (CABG) from January 2014 to December 2016 to compare outcomes of MICABG with conventional CABG. Patients who underwent concomitant or emergent procedures were excluded. Propensity-weighted cohorts were compared by operative approach with adjustment for variability across institutions.

Results:

Of 12,406 eligible patients, 2688 (21.7%) underwent MICABG, and 9818 (78.3%) underwent conventional CABG. Propensity weighting produced excellent balance in patient characteristics, including completeness of revascularization, body mass index, and STS predictive risk scores. MICABG was associated with significant reduction of in-hospital mortality [odds ratio (OR)=0.32, absolute reduction (AR)=0.91%, P<0.0001]; 30-day mortality (OR=0.51, AR=0.88%, P=0.001), duration of ventilation (8.62 vs 12.6 hours, P<0.0001), prolonged hospitalization (OR=0.77, AR=1.6, P=0.043), deep wound infection (OR=0.33, AR=0.68, P<0.004), postoperative transfusions (OR=0.52, AR=7.7%, P<0.0001), and STS composite morbidity (OR=0.72, AR=1.19%, P=0.008). Subgroup analysis of only off-pump left internal mammary artery-left anterior descending CABG showed similar findings. Major adverse cardiac events and graft occlusion did not differ between groups.

Conclusions:

MICABG is associated with lower mortality and perioperative morbidity compared with conventional sternotomy CABG. MICABG may have a role in treating single-vessel disease.
The Effect of Bariatric Surgery on Long-term Depression Treatment in Patients With Obesity
Authors: Smith Valerie A. , Maciejewski Matthew L. , Berkowitz Theodore S.Z. , Mitchell James E. , Liu Chuan-Fen , Bradley Katharine A. , Olsen Maren K. , Livingston Edward L. , Arterburn David E.
Published: July 2022

Objective:

In a large multisite cohort of Veterans who underwent Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (LSG), initiation of (ie, incident) and persistence of (ie, continuation of preoperative) depression treatment are compared with matched nonsurgical controls.

Background:

Bariatric surgery has been associated with short-term improvements in depression but less is known about longer term outcomes.

Methods:

In a retrospective cohort study, we matched 1713 Veterans with depression treatment who underwent bariatric surgery in Veterans Administration bariatric centers from fiscal year 2001 to 2016 to 15,056 nonsurgical controls using sequential stratification and examined the persistence of depression treatment via generalized estimating equations. Incidence of depression treatment was compared using Cox regression models between 2227 surgical patients and 20,939 matched nonsurgical controls without depression treatment at baseline.

Results:

In surgical patients with depression treatment at baseline, the use of postsurgical depression treatment declined over time for both surgical procedures, but postsurgical patients had greater use of depression treatment at 5 years [RYGB: odds ratio=1.24, 95% confidence interval (CI): 1.04–1.49; LSG: odds ratio=1.27, 95% CI: 1.04–1.56] compared with controls. Among those without depression treatment at baseline, bariatric surgery was associated with a higher incidence of depression treatment compared with matched controls (RYGB: hazard ratio=1.34, 95% CI: 1.17–1.53; LSG: hazard ratio at 1–5 years=1.27, 95% CI: 1.10–1.47).

Conclusions:

Bariatric surgery was associated with a greater risk of postoperative incident depression treatment and greater persistence of postoperative depression treatment. Depression may worsen for some patients after bariatric surgery, so clinicians should carefully monitor their patients for depression postoperatively.
Host lysolipid differentially modulates virulence factor expression and antimicrobial susceptibility in Pseudomonas aeruginosa
Authors: McSorley James C. , MacFadyen Alison C. , Kerr Leena , Tucker Nicholas Peter
Published: July 2022

Lysophosphatidic acid (LPA) occurs naturally in inflammatory exudates and has previously been shown to increase the susceptibility of

Pseudomonas aeruginosa

to β-lactam antibiotics whilst concomitantly reducing accumulation of the virulence factors pyoverdine and elastase. Here it is demonstrated that LPA can also exert inhibitory effects upon pyocyanin production in

P. aeruginosa

, as well as influencing susceptibility to a wide range of chemically diverse non β-lactam antimicrobials. Most strikingly, LPA markedly antagonizes the effect of the polycationic antibiotics colistin and tobramycin at a concentration of 250 µg ml−1 whilst conversely enhancing their efficacy at the lower concentration of 8.65 µg ml−1, approximating the maximal physiological concentrations found in inflammatory exudates. Transcriptomic responses of the virulent strain UCBPP-PA14 to LPA were analysed using RNA-sequencing along with BioLog phenoarrays and whole cell assays in attempts to delineate possible mechanisms underlying these effects. The results strongly suggest involvement of LPA-induced carbon catabolite repression together with outer-membrane (OM) stress responses whilst raising questions about the effect of LPA upon other

P. aeruginosa

virulence factors including type III secretion. This could have clinical relevance as it suggests that endogenous LPA may, at concentrations found in vivo, differentially modulate antibiotic susceptibility of

P. aeruginosa

whilst simultaneously regulating expression of virulence factors, thereby influencing host–pathogen interactions during infection. The possibility of applying exogenous LPA locally as an enhancer of select antibiotics merits further investigation.
Ancient DNA from Protohistoric Period Cambodia indicates that South Asians admixed with local populations as early as 1st-3rd centuries CE
Authors: Changmai Piya , Pinhasi Ron , Pietrusewsky Michael , Stark Miriam T. , Ikehara-Quebral Rona Michi , Reich David , Flegontov Pavel
Published: July 2022

Indian cultural influence is remarkable in present-day Mainland Southeast Asia (MSEA), and it may have stimulated early state formation in the region. Various present-day populations in MSEA harbor a low level of South Asian ancestry, but previous studies failed to detect such ancestry in any ancient individual from MSEA. In this study, we discovered a substantial level of South Asian admixture (ca. 40% – 50%) in a Protohistoric individual from the Vat Komnou cemetery at the Angkor Borei site in Cambodia. The location and direct radiocarbon dating result on the human bone (95% confidence interval is 78 – 234 calCE) indicate that this individual lived during the early period of Funan, one of the earliest states in MSEA, which shows that the South Asian gene flow to Cambodia started about a millennium earlier than indicated by previous published results of genetic dating relying on present-day populations. Plausible proxies for the South Asian ancestry source in this individual are present-day populations in Southern India, and the individual shares more genetic drift with present-day Cambodians than with most present-day East and Southeast Asian populations.
Cerebral perfusion in post-stroke aphasia and its relation to residual language abilities
Authors: Ivanova Maria V. , Pappas Ioannis , Inglis Benjamin , Pracar Alexis , Herron Timothy J. , Baldo Juliana V. , Kayser Andrew S. , D’Esposito Mark , Dronkers Nina F.
Published: July 2022

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but sub-optimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate 1) how stroke affects perfusion outside of lesioned areas in chronic aphasia, and 2) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analyzed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n=43) and age-matched healthy controls (n=25). We used anatomically-defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioral outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.
Revisiting biological sex as a risk factor for COVID-19: a fact or mirage of numbers?
Authors: Singh Samer
Published: July 2022

Biological sex is considered a risk factor for COVID-19. The prevailing view supposes males are about two-fold more impacted than females based on early-stage studies. The observed higher male deaths in COVID-19 are purportedly a result of biological differences that make males more vulnerable to adverse outcomes in infectious diseases. Research and policy paradigms seem to follow a similar line of thought to mitigate COVID-19 impact on populations. The analysis of sex-disaggregated data could help us evaluate the veracity of assertions for a preferred evidence-guided response. The analysis of the sex-disaggregated data available for the top 70 countries contributing about 80% of total deaths (as of 15 September 2021; on average two waves of infections experienced) indicates average Case Sex (Male: Female) ratio (CSR) of 1.09±0.35 (marginally more male cases) and Death Sex ratio (DSR) of 1.48± 0.47. Consideration of only laboratory-confirmed cases indicates the mortality sex ratio (MSR) in COVID-19 (MSR-COVID) to be 1.37±0.30. The prevailing MSR for the same countries was 1.758±0.409. The relative change in the mortality rate for males as compared to females in COVID-19 (ratio: MSR-COVID/prevailing MSR-PP) was 0.818±0.261 much lower than anticipated (2 or higher). Overall, over three-fold more countries (51/70) experienced a higher rate of female mortality than male mortality (15/70). Together, it suggests a more disproportionately severe impact of COVID-19 on females than on males, contrary to the prevailing view. Identification and analysis of country-specific factors contributing to differential impact on sexes, whether biological or environmental, seem warranted.
Validation and Implementation of Real Time PCR for Rapid Identification of Candida auris from Clinical Surveillance Samples in a Local Public Health Laboratory Setting
Authors: Mikhail Lydia , Crumpler Megan , Bourgeois Marie , Roberts Jill
Published: July 2022

Background

Candida auris is a worldwide emerging pathogen known for causing infections and outbreaks in health care settings. In Orange County, CA, C. auris has been circulating and causing outbreaks in long term care facilities since 2019, with a total of 1,017 cases detected from February 2019 to December 2021.

Objective

To evaluate an rt-PCR assay for rapid identification and assessment of colonization of C. auris from patient surveillance samples at the OC Public Health Laboratory.

Method

An extraction protocol using the MasterPure kit and automated EZ1 Advanced XL followed by rt-PCR using PerfeCTa Multiplex qPCR TaqMan, and the 7500 Fast Dx was conducted. The assay was evaluated using 131 previously confirmed patient samples and 123 prospective fresh samples from different body sites.

Results

The assay was highly reproducible at an LOD of 230 CFU/ml. The sensitivity and specificity of the 131 samples was 90 % and 86 % respectively and for the 123 samples it was 93% and 90% respectively. ROC analysis was calculated using all samples (n = 254) to determine the most ideal diagnostic value. The AUC was 0.922 and optimal cutoff was a cycle threshold 36.78. A CT ≤37.00 is the ideal diagnostic value for patient surveillance samples.

Conclusion

The successful implementation of the rt-PCR assay for C. auris in a local public health laboratory allows for accurate and rapid screening and identification of C. auris which can contribute to enhanced surveillance and control of C. auris spread in local health care facilities.
Perception is Rich and Probabilistic
Authors: Jabar Syaheed B. , Fougnie Daryl
Published: July 2022

When we see a stimulus, e.g. a star-shaped object, our intuition is that we should perceive a single, coherent percept (even if it is inaccurate). But the neural processes that support perception are complex and probabilistic. Simple lines cause orientation-selective neurons across a population to fire in a probabilistic-like manner. Does probabilistic neural firing lead to non-probabilistic perception, or are the representations behind perception richer and more complex than intuition would suggest? To test this, we briefly presented a complex shape and had participants report the correct shape from a set of options. Rather than reporting a single value, we used a paradigm designed to encourage to directly report a representation over shape space—participants placed a series of Gaussian bets. We found that participants could report more than point-estimates of shape. The spread of responses was correlated with accuracy, suggesting that participants can convey a notion of relative imprecision. Critically, as participants placed more bets, the mean of responses show increased precision. The later bets were systematically biased towards the target rather than haphazardly placed around bet 1. These findings strongly indicate that participants were aware of more than just a point-estimate; Perceptual representations are rich and likely probabilistic.
Salient sounds distort time perception and production
Authors: Symons Ashley , Dick Fred , Tierney Adam
Published: July 2022

The auditory world is often cacophonous, with some sounds capturing attention and distracting us from our goals. Despite the universality of this experience, many questions remain about how and why sound captures attention, how rapidly behavior is disrupted, and how long this interference lasts. Here we use a novel measure of behavioral disruption to test two predictions made by models of auditory salience. First, models predict that goal-directed behavior is disrupted at points in time that feature a high degree of spectrotemporal change. We find that behavioral disruption is precisely time-locked to the onset of distracting sound events: participants tapping to a metronome speed up immediately after the onset of distractors. Moreover, this response is greater for more salient sounds (larger amplitude) and sound changes (greater pitch shift). Second, models predict that different auditory features are combined into an overarching salience map. We find that the time course of behavioral disruption is highly similar after acoustically disparate sound events, suggesting overlapping mechanisms of attentional capture: both sound onsets and pitch shifts of continuous background sounds speed responses at 750 ms, with these effects dying out by 1750 ms. These temporal distortions can be observed using only data from the first trial across participants. A potential mechanism underlying these results is that arousal increases after distracting sound events, leading to an expansion of time perception, and causing participants to misjudge when their next movement should begin.

Significance Statement

The noisy world constantly challenges our pursuit of goals. When driving, for example, a cacophony of mechanical, musical, and conversational sounds surrounds us and can wrench our focus away from the road. While the physiological signatures of auditory attentional capture are well researched, we know surprisingly little about how sound affects moment-to-moment behavior: How quickly do sounds affect our actions, how transient is the effect, and how is action affected by changes in sound properties? Here we use a synchronized tapping paradigm to show that loud sounds and large acoustic changes cause rapid distortions in time perception. However, these distortions were corrected within 2 seconds, showing that goal-directed behavior is transiently vulnerable yet ultimately resilient in the face of distraction.
Obox4promotes zygotic genome activation upon loss ofDux
Authors: Guo Youjia , Kitano Tomohiro , Inoue Kimiko , Murano Kensaku , Hirose Michiko , Li Ten D. , Sakashita Akihiko , Ishizu Hirotsugu , Ogonuki Narumi , Matoba Shogo , Sato Masayuki , Ogura Atsuo , Siomi Haruhiko
Published: July 2022

Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However,Dux-knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by an unknown factor(s). Here we present multiple lines of evidence that the multicopy homeobox gene,Obox4, encodes a transcription factor that is highly expressed in mouse 2-cell embryos and redundantly drives ZGA. Genome-wide profiling revealed that OBOX4 specifically binds and activates MERVL LTRs as well as a subset of murine endogenous retroviruses with lysine tRNA primer (MERVK) LTRs. Depletion ofObox4is tolerated by embryogenesis, whereas concomitantObox4/Duxdepletion markedly compromises embryonic development. Our study identified OBOX4 as a transcription factor that provides genetic redundancy to pre-implantation development.
Tank Fouling Community Enhances Coral Microfragment Growth
Authors: Page Chris , Perry Riley , Lager Claire , Daly Jonathan , Bouwmeester Jessica , Henley E. Michael , Hagedorn Mary
Published: July 2022

Anthropogenic stressors threaten reefs worldwide and natural in situ coral reproduction may be inadequate to meet this challenge. Land-based culture can provide increased coral growth, especially with microfragments. We tested whether culture methods using different algal fouling communities could improve the growth and health metrics of microfragments of the Hawaiian coral, Porites compressa. Culture method fouling communities were: 1) similar to a reef environment (Mini Reef); 2) clean tanks managed to promote crustose coralline algae (Clean Start); and, 3) tanks curated beforehand with poorly-competing algae (Green Film) assessed in winter and summer months. The Green Film method during the winter produced the fastest microfragment mean growth at 28 days until the first row of new polyps developed and the highest tank metric scores. Time efficient, standardized methods for land-based culture designed to maximize growth and production of coral fragments will contribute considerably to the success of large scale restoration efforts.
Mesophyll specific expression of a bacterial mercury transporter-based vacuolar sequestration machinery sufficiently enhances mercury tolerance of Arabidopsis
Authors: Uraguchi Shimpei , Ohshiro Yuka , Okuda Mayuu , Kawakami Shiho , Yoneyama Nene , Tsuchiya Yuta , Nakamura Ryosuke , Takanezawa Yasukazu , Kiyono Masako
Published: July 2022

We aimed to efficiently enhance plant Hg(II) tolerance by the transgenic approach utilizing a bacterial mercury transporter MerC, an Arabidopsis mesophyll specific promoter pRBCS1A, and a vacuolar membrane targeting syntaxin AtVAM3/SYP22. We generated two independent homozygous Arabidopsis pRBCS1A-TCV lines expressing mT-Sapphire-MerC-AtVAM3 under the control of pRBCS1A. Quantitative RT-PCR showed that the transgene was expressed specifically in shoots of pRBCS1A-TCV lines. Confocal analyses further demonstrated the leaf mesophyll specific expression of mT-Sapphire-MerC-AtVAM3. Confocal observation of the protoplast derived from the F1 plants of the pRBCS1A-TCV line and the tonoplast marker line p35S-GFP-δTIP showed the tonoplast colocalization of mT-Sapphire-MerC-AtVAM3 and GFP-δTIP. These results clearly demonstrated that mT-Sapphire-MerC-AtVAM3 expression in Arabidopsis is spatially regulated as designed at the transcript and the membrane trafficking levels. We then examined the Hg(II) tolerance of the pRBCS1A-TCV lines as well as the p35S-driven MerC-AtVAM3 expressing line p35S-CV under the various Hg(II) stress conditions. Short-term (12 d) Hg(II) treatment indicated the enhanced Hg(II) tolerance of both pRBCS1A-TCV and p35S-CV lines. The longer (3 weeks) Hg(II) treatment highlighted the better shoot growth of the transgenic plants compared to the wild-type Col-0 and the pRBCS1A-TCV lines were more tolerant to Hg(II) stress than the p35S-CV line. These results suggest that mesophyll-specific expression of MerC-AtVAM3 is sufficient or even better to enhance the Arabidopsis Hg(II) tolerance. The Hg accumulation in roots and shoots did not differ between the wild-type Col-0 and the MerC-AtVAM3 expressing plants, suggesting that the boosted Hg(II) tolerance of the transgenic lines would be attributed to vacuolar Hg-sequestration by the tonoplast-localized MerC. Further perspectives of the MerC-based plant engineering are also discussed.
Neural response to repeated auditory stimuli and its association with early language development in children with Fragile X syndrome
Authors: An Winko W. , Nelson Charles A. , Wilkinson Carol L.
Published: July 2022

Abstract

Background

Fragile X syndrome (FXS) is the most prevalent form of inherited intellectual disability and is the most common monogenetic cause of autism. Previous studies have linked the structural and functional alterations in FXS with impaired sensory processing and sensory hypersensitivity, which may hinder the early development of cognitive functions such as language comprehension. In this study, we compared the P1 response in event-related potential (ERP) and its habituation to repeated auditory stimuli in male children (2-7 years old) with and without FXS, and examined their association with clinical measures in these two groups.

Methods

We collected high-density electroencephalography (EEG) data in an auditory oddball paradigm from 12 children with FXS and 11 age- and sex-matched typically developing (TD) children. After standardized EEG pre-processing, we conducted a spatial principal component (PC) analysis and identified two major PCs — a frontal PC and a temporal PC. Within each PC, we compared the P1 amplitude and inter-trial phase coherence (ITPC) between the two groups, and performed a series of linear regression analysis to study the association between these EEG measures and several clinical measures, including assessment scores for language development, non-verbal skills, and sensory hypersensitivity.

Results

At the temporal PC, both early and late standard stimuli evoked a larger P1 response (p = 0.0037, p<0.0001, respectively) and higher ITPC (p = 0.0402, p = 0.0027) in FXS than in TD. We observed habituation of ITPC in both groups at the frontal PC (p = 0.0149 for FXS; p = 0.0244 for TD). Linear regression analysis showed that within the FXS group reduced frontal P1 response to late standard stimuli and increased habituation were associated with better languages scores. No associations were observed with non-verbal skills or sensory hypersensitivity.

Conclusion

We identified P1 amplitude and ITPC in the temporal region as a contrasting EEG phenotype between the FXS and the TD groups. P1 response and habituation in the frontal region may be reflective of the language outcome in male children with FXS. These EEG measures are potential biomarkers for early diagnosis and future language development in patients with FXS.
A Quantitative Characterization of the Spatial Distribution of Brain Metastases from Breast Cancer and Respective Molecular Subtypes
Authors: Mahmoodifar Saeedeh , Pangal Dhiraj J. , Cardinal Tyler , Craig David , Simon Thomas , Tew Ben Yi , Yang Wensha , Chang Eric , Yu Min , Neman Josh , Mason Jeremy , Toga Arthur , Salhia Bodour , Zada Gabriel , Newton Paul K.
Published: July 2022

1.

Brain metastases (BM) remain a significant cause of morbidity and mortality in breast cancer (BC) patients. Specific factors promoting the process of BM and predilection for selected neuro-anatomical regions remain unknown, yet may have major implications for prevention or treatment. Anatomical spatial distributions of BM from BC suggest a predominance of metastases in the hindbrain and cerebellum. Systematic approaches to quantifying BM location or location-based analyses based on molecular subtypes, however, remain largely unavailable. We analyzed stereotactic Cartesian coordinates derived from 134 patients undergoing gamma-knife radiosurgery (GKRS) for treatment of 407 breast cancer BMs to quantitatively study BM spatial distribution along principal component axes and by intrinsic molecular subtype (ER,PR,Herceptin). We corroborated that BC BMs show a consistent propensity to arise posteriorly and caudally, and that Her2+ tumors are relatively more likely to arise medially rather than laterally. To compare the distributions among varying BC molecular subtypes, we used the notion of mutual information, which revealed that the ER-PR-Her2+ and ER-PR-Her2-subtypes showed the smallest amount of mutual information and were most molecularly distinct. Using kernel density estimators, we found a propensity for triple negative BC to arise in more superiorly or cranially situated BMs. BM location maps according to vascular and anatomical distributions using cartesian coordinates to aid in systematic classification of tumor locations were additionally developed. Further characterization of these patterns may have major impacts on treatment or management of cancer patients.

Significance

The quantitative spatial distribution of breast cancer metastases to the brain, and the effects of breast cancer molecular subtype on distribution frequencies remain poorly understood. We present a novel and shareable workflow for characterizing and comparing spatial distributions of BM which may aid in identifying therapeutic or diagnostic targets and interactions with the tumor microenvironment.