bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Trainee Evaluations of Faculty by Rater and Ratee Gender
Authors: Cullen Michael J. , Zhou You , Sackett Paul R. , Mustapha Taj , Hane Jessica , Culican Susan M.
Published: April 2023

Purpose

To examine whether gender differences exist in medical trainees’ (residents’ and fellows’) evaluations of faculty at a number of clinical departments.

Method

The authors conducted a single-institution (University of Minnesota Medical School) retrospective cohort analysis of 5,071 trainee evaluations of 447 faculty (for which trainee and faculty gender information was available) completed between July 1, 2019, and June 30, 2022. The authors developed and employed a 17-item measure of clinical teaching effectiveness, with 4 dimensions: overall teaching effectiveness, role modeling, facilitating knowledge acquisition, and teaching procedures. Using both between- and within-subject samples, they conducted analyses to examine gender differences among the trainees making ratings (rater effects), the faculty receiving ratings (ratee effects), and whether faculty ratings differed by trainee gender (interaction effects).

Results

There was a statistically significant rater effect for the overall teaching effectiveness and facilitating knowledge acquisition dimensions (B = −0.28 and −0.14, 95% CI: [−0.35, −0.21] and [−0.20, −0.09], respectively, P < .001, medium corrected effect sizes between −0.34 and −0.54); female trainees rated male and female faculty lower than male trainees on both dimensions. There also was a statistically significant ratee effect for the overall teaching effectiveness and role modeling dimensions (B = −0.09 and −0.08, 95% CI: [−0.16, −0.02] and [−0.13, −0.04], P = .01 and < .001, respectively, small to medium corrected effect sizes between −0.16 and −0.44); female faculty were rated lower than male faculty on both dimensions. There was not a statistically significant interaction effect.

Conclusions

Female trainees rated faculty lower than male trainees and female faculty were rated lower than male faculty on 2 teaching dimensions each. The authors encourage researchers to continue to examine the reasons for the evaluation differences observed and how implicit bias interventions might help to address them.
Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005–2016
Authors: Li Wei , Wu Hong , Xu Xuewen , Zhang Yange
Published: April 2023

Background:

Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States.

Methods:

This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes.

Results:

After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: −0.07 to −0.02; P = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose–response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses.

Conclusions:

Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.
Pilot Trial of a Peer-to-Peer Psychoeducational Intervention for Parents of Black Children Awaiting a Developmental Evaluation
Authors: Dababnah Sarah , Reyes Charina , Kim Irang , Badawi Deborah G. , Chung Yoonzie , Shaia Wendy E.
Published: April 2023

Objective:

This study examined the short-term impact on child, family, and parent outcomes of a peer-to-peer psychoeducational intervention, Parents Taking Action (PTA) for Black families of children awaiting developmental-behavioral pediatric evaluations.

Methods:

We targeted parents and other primary caregivers of Black children aged 8 years or younger awaiting a developmental or autism evaluation at an academic tertiary care hospital. Using a single-arm design, we recruited participants directly from the appointment waitlist and used flyers in local pediatric and subspecialty clinics. Eligible participants received a version of PTA adapted for Black children in two 6-week modules delivered synchronously online. In addition to initial baseline demographic data, we collected 4 standardized measures of parent stress and depression, family outcomes (e.g., advocacy), and child behavior at preintervention, midintervention, and postintervention. We calculated effect sizes and used linear mixed models to examine changes over time.

Results:

Fifteen participants completed PTA, the majority of whom were Black mothers with annual household incomes <$50,000. All children were Black and mostly boys, with an average age of 4.6 years. Parent depression, the family outcome total score, and 3 family outcomes (understanding child's strengths, needs, and abilities; knowing rights and advocating for child; and helping child develop and learn) significantly improved pre-post intervention, with medium to large effect sizes. Furthermore, the family outcome total score and “knowing rights and advocating for child” outcome significantly increased by midintervention (d = 0.62–0.80).

Conclusion:

Peer-delivered interventions can result in positive outcomes for families awaiting diagnostic evaluations. Further research is needed to confirm findings.
Executive Functioning, Language, and Behavioral Abilities Related to Obstructive Sleep Apnea in Down Syndrome
Authors: Soltani Amanallah , Schworer Emily K. , Amin Raouf , Hoffman Emily K. , Esbensen Anna J.
Published: April 2023

Objectives:

Obstructive sleep apnea (OSA) is highly prevalent among individuals with Down syndrome (DS), and the nonphysiological consequences of OSA require examination to inform treatment planning. This study aimed to investigate the association between OSA and aspects of language, executive functioning, behavioral, social abilities, and sleep problems in youth with DS aged 6 to 17 years.

Methods:

Multivariate analysis of covariance was used to compare 3 groups adjusted for age, participants with DS with untreated OSA (n = 28), participants with DS without OSA (n = 38), and participants with DS with treated OSA (n = 34). To be eligible for the study, participants had to have an estimated mental age of 3 years. No children were excluded based on estimated mental age.

Results:

After adjusting for age, participants with untreated OSA showed a common pattern of lower estimated marginal mean scores than those with treated OSA and those with no OSA in expressive and receptive vocabulary and higher estimated marginal mean scores with executive functions, everyday memory, attention, internalizing and externalizing behavior, social behavior, and sleep problems. However, only the group differences for executive function (emotional regulation) and internalizing behavior were statistically significant.

Conclusion:

Study findings corroborate and extend prior findings related to OSA and clinical outcomes for youth with DS. The study highlights the importance of OSA treatment in youth with DS and provides clinical recommendations for this population. Additional studies are necessary to control the effects of health and demographic variables.
Improving Access to Diagnostic Evaluations for Developmental Disabilities Through an Initial Assessment Model
Authors: DeVries Lindsey , Dempsey Jack , Wilson Rebecca
Published: April 2023

Objective:

This study aimed to evaluate a novel model of care to improve access to diagnostic evaluations for autism spectrum disorder and/or developmental delays for school-age children.

Methods:

An “initial assessment” (IA) model for children aged 7 to 9 years was implemented at a large regional pediatric hospital. Referral patterns and the number of patients evaluated with the IA model were obtained through the electronic health record (EHR). Referral patterns from the EHR were checked against clinician surveys.

Results:

Total IA volume had a strong negative association with school-age WL volume (r(22) = −0.92, p < 0.001), indicating that as IA volume increased, the WL volume declined. Evaluation of referral patterns after IAs revealed that approximately 1 in 3 children seen for IA did not require further evaluation and could be immediately removed from the WL.

Conclusion:

Results indicate that implementation of a novel IA model was strongly associated with a decrease in WL volume for neurodevelopmental evaluations of school-age children. These findings support a “right-fit” approach to optimize clinical resources and improve access to neurodevelopmental evaluations.
Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Authors: Cindi Zinhle , Kawuma Aida N. , Maartens Gary , Bradford Yuki , Sokhela Simiso , Chandiwana Nomathemba , Venter Willem D. Francois , Wasmann Roeland E. , Denti Paolo , Wiesner Lubbe , Ritchie Marylyn D. , Haas David W. , Sinxadi Phumla
Published: April 2023

Background

Tenofovir is a component of preferred combination antiretroviral therapy (ART) regimens in Africa. Few pharmacogenetic studies have been conducted on tenofovir exposure in Africa, where genetic diversity is greatest.

Objective

We characterized the pharmacogenetics of plasma tenofovir clearance in Southern Africans receiving tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF).

Methods

Adults randomized to TAF or TDF in dolutegravir-containing arms of the ADVANCE trial (NCT03122262) were studied. Linear regression models stratified by study arm examined associations with unexplained variability in tenofovir clearance. We investigated genetic associations with polymorphisms selected a priori followed by genome-wide associations.

Results

A total of 268 participants (138 and 130 in the TAF and TDF arm, respectively) were evaluable for associations. Among polymorphisms previously associated with any drug-related phenotype, IFNL4 rs12979860 was associated with more rapid tenofovir clearance in both arms (TAF: P = 0.003; TDF: P = 0.003). Genome-wide, the lowest P values for tenofovir clearance in TAF and TDF arms were LINC01684 rs9305223 (P = 3.0 × 10−8) and intergenic rs142693425 (P = 1.4 × 10−8), respectively.

Conclusion

Among Southern Africans randomized to TAF or TDF in ADVANCE, unexplained variability in tenofovir clearance was associated with a polymorphism in IFNL4, an immune-response gene. It is unclear how this gene would affect tenofovir disposition.
Comparison Between Patient and Plastic Surgeon Aesthetic Analysis in Rhinoplasty Consultation
Authors: Alosfoor Mariam , Alkhalifah Ahmad Ali , Algadiem Emran Ali , Alarfaj Abdullah A. , Alsalman Abdullah
Published: April 2023

Background:

The surgeon’s aesthetic analysis of the nose is based on scientific measures of its proportions and dimensions. Because the primary aim of rhinoplasty is targeted at the patient’s satisfaction with self-image, patients’ perception and satisfaction are of paramount importance. The aim of this study was to evaluate surgeon versus patient nasal aesthetic analysis.

Method:

A cross-sectional study was conducted on 57 primary rhinoplasty consultations during the period June and September 2017 at the Plastic Surgery Clinic in King Fahad Hospital-Hofuf. The surgeon and the patients were handed identical questionnaires before the consultations. The questionnaire has 27 components regarding the nasal appearance.

Results:

The surgeon’s and the patients’ perceptions regarding reliability was assessed by Cohen’s Kappa and Pearson’s correlation coefficient. There was moderate agreement with the overall appearance of the nose (κ = 0.2–0.39). The most agreed-upon components were “dorsal hump” (κ = 0.6, P = 0.001) and “tip drops down” (κ = 0.41, P = 0.002). The columella and the suitability of the front part of the nose had the largest disagreement (κ = -0.06 and κ = −0.09, respectively). The level of agreement among most of the questionnaires’ components was slight or nonexistent (κ = 0.004–0.39).

Conclusions:

The surgeon and patients have a minimum agreement regarding the view of nasal appearance, mostly with the suitability of the front part and the columella. The parts of the nose agreed upon the most were “dorsal hump” and “tip drops down”. Exploring the differences between patient and surgeon aesthetic analysis of the nose will aid in addressing the discrepancies and improving surgical outcome and satisfaction.
30 Years of Experience in Musculocutaneous Latissimus Dorsi Flap Phalloplasty with Reinnervation: Optimal Principles
Authors: Adamyan Ruben T. , Startseva Olesya I. , Gabriyanchik Mark A.
Published: April 2023

Background:

The technique of urogenital plastic surgery continues to pose difficulties for surgeons due to physical features of the anatomical region, which complicates the correction of various severe male urogenital pathologies. The goal of the surgeon is to create a neophallus that allows for urination and intercourse with minimal damage to the donor site. This special topic provides a historical overview and principles for optimal phalloplasty. To improve results in latissimus dorsi free-flap phalloplasty, we share our approach, its benefits, and the lessons we have learned.

Methods:

We performed a retrospective review of patients who underwent shaft-only, two-stage or one-stage latissimus dorsi flap phalloplasty with or without reinnervation at a single institution from 1991 through 2020. Patients with a minimum of 1 year of follow-up were included. Data on the patient’s demographics, the procedure, and the results of the operation were maintained.

Results:

In total, 592 latissimus dorsi flap phalloplasties were performed during the entire study period. Of the phalloplasties, 494 (83.5%) were performed for gender-affirming surgery, of which 470 were performed for transgender patients and 24 for intersex patients. Twenty-five patients (4.2%) had congenital malformations, 17 (2.9%) had oncologic resections, and 56 had posttraumatic loss (9.5%).

Conclusion:

Latissimus dorsi flap total phalloplasty with reinnervation is currently one of the few methods that can solve not only an aesthetic problem, but also a functional one without the use of an endoprosthesis if the level of reinnervation and muscle contraction is sufficient.
Soluble ORF2 protein enhances HEV replication and induces long-lasting antibody response and protective immunity in vivo
Authors: Ralfs Philipp , Holland Brantley , Salinas Eduardo , Bremer Bill , Wang Minghang , Zhu Jingting , Ambardekar Charuta , Blasczyk Heather , Walker Christopher M. , Feng Zongdi , Grakoui Arash
Published: April 2023

Background and Aims:

The HEV is a small positive–sense RNA virus that encodes a cytoplasmic form of the capsid protein (ORF2c), essential for virion structure, and a secreted glycosylated form (ORF2s) that accumulates at high titer in serum and can mask neutralizing epitopes. We explored the contribution of ORF2s to HEV replication and its role in generating antibodies against ORF2 in a nonhuman primate model.

Approach and Results:

We used a recombinant HEV genotype 3 variant that does not express ORF2s due to the introduction of stop codons (ORF2smut). Rhesus macaques (RMs) were given intrahepatic injections of infectious wildtype HEV (ORF2swt) RNA or a variant lacking ORF2s expression (ORF2smut). The replication of the ORF2smut virus was delayed by ~2 weeks compared with ORF2swt, and peak titers were nearly tenfold lower. Reversions of the 3 mutations that blocked ORF2s expression were not detected in the ORF2smut genomes, indicating genetic stability. However, serum antibodies against ORF2 were transiently detected in RMs infected with ORF2smut, whereas they were long-lasting in RMs infected with ORF2swt. Moreover, RMs infected with ORF2smut were more susceptible to reinfection, as evidenced by the viral RNA detected in fecal samples and the expansion of HEV-specific CD8+ T cells.

Conclusions:

These findings indicate that ORF2s may be dispensable for viral replication in vivo but is required for long-lived antibody-mediated responses that protect against HEV re-exposure.
Long-term Outcomes After Lamellar Endothelial Keratoplasty Compared With Penetrating Keratoplasty for Corneal Endothelial Dysfunction: A Systematic Review
Authors: Lemaitre Daniel , Tourabaly Moise , Borderie Vincent , Dechartres Agnes
Published: April 2023

Purpose:

The purpose of this study is to evaluate long-term outcomes of endothelial keratoplasty (EK) compared with penetrating keratoplasty (PK) for corneal endothelial dysfunction [Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK)].

Methods:

In this systematic review, we searched PubMed, the Cochrane Library, and Embase up to May 2022 and considered all types of studies addressing our objective. Graft survival at 5, 10, and 15 years was the main outcome.

Results:

Fifty cohort studies were included. At 5 years, in FECD and BK, graft survival seemed higher after EK than PK. Two comparative studies showed either a higher 5-year graft survival after EK than PK or no significant differences. Including noncomparative studies, in FECD, the 5-year graft survival ranged from 0.69 to 0.98 for PK, from 0.93 to 1.00 for DSEK, and from 0.93 to 0.99 for Descemet membrane endothelial keratoplasty (DMEK). In BK, the 5-year graft survival ranged from 0.39 to 0.91 for PK, from 0.65 to 0.89 for DSEK, and from 0.84 to 0.95 for DMEK. The 10-year graft survival ranged from 0.20 to 0.90 for PK and from 0.62 to 0.92 for EK. The mean 5-year best spectacle-corrected visual acuity ranged from 0.73 to 0.43 LogMAR for PK, from 0.61 to 0.09 for DSEK, and from 0.31 to 0.05 for DMEK. The 5-year rejection rate ranged from 11.0% to 28.7% for PK, from 5.0% to 7.9% for DSEK, and from 1.7% to 2.6% for DMEK.

Conclusions:

These results suggest a higher 5-year graft survival and better secondary outcomes after EK. Nevertheless, the level of evidence was low.

Prospero Registration:

CRD42021260614.
Two point four million cataract surgeries: 30 years with the Swedish National Cataract Register, 1992-2021
Authors: Bro Tomas , Behndig Anders , Viberg Andreas , Zetterberg Madeleine , Kugelberg Maria , Nilsson Ingela , Thorburn William , Stenevi Ulf , Lundström Mats
Published: April 2023

The present review summarizes data collected by the Swedish National Cataract Register (NCR), which by the end of 2021 contained data for more than 2.4 million cataract surgeries between 1992 and 2021. During these 30 years, the cataract surgery rate rose from 3700 to 12 800. The coverage of NCR is very high including 93% of all cataract procedures in Sweden between 2010 and 2021. Independently of demographic changes, the proportion of operations of patients age 60 to 79 has increased while the proportion of 80 to 90+ has decreased. The median visual acuity of the first eye planned for surgery was 0.1 decimal in 1992 and has increased to 0.5 decimal in 2021. Patient-reported outcome measures have been registered with the Catquest-9SF questionnaire since 2008, demonstrating intervention at an earlier stage, but consistently favorable outcomes. Surgical complications have decreased; endophthalmitis has decreased from 0.10% to below 0.02%, and posterior capsule rupture from 2.8% to 0.6%.
Coordinating Care for People With HIV Who Have Lower Incomes and Alternative Sources of Health Care Coverage
Authors: Au Melanie , Coombs Ellie , Jones Andrew , Carley Frances , Talwar-Hebert Maya , Addison West , Mills Robert J. , Cohen Stacy M. , Klein Pamela W. , Cheever Laura , Gilman Boyd
Published: April 2023

As people with HIV increasingly access affordable health care coverage—enabling them to obtain medical care from private providers—understanding how they use the Ryan White HIV/AIDS Program (RWHAP), and their unmet health care needs, can enhance their overall care. We analyzed RWHAP client-level data and interviewed staff and clients at 29 provider organizations to identify trends in health care coverage and service use for clients who received medical care from private providers. The RWHAP helps cover the cost of premiums and copays for these clients and provides medical and support services that help them stay engaged in care and virally suppressed. The RWHAP plays an important role in HIV care and treatment for clients with health care coverage. The growing number of people who receive a combination of services from RWHAP providers and private providers offers opportunities for greater care coordination through communication and data sharing between these settings.
Athletes With Attention-Deficit/Hyperactivity Disorder: Position Statement of the American Medical Society for Sports Medicine
Authors: Pujalte George G.A. , Narducci Dusty Marie , Smith Michael Seth , King Rebecca , Logan Kelsey , Callender Shelley Street , Liebman Catherine A. , Kane Shawn F. , Israel Michael P. , Wolf Sigrid F. , Nuti Rathna , Khodaee Morteza
Published: April 2023

Athletes of all ages may be affected by medical and mental health issues. Sports medicine physicians should be familiar with common conditions that may affect the well-being of athletes, such as attention-deficit/hyperactivity disorder (ADHD). ADHD behaviors have the potential to affect a person's ability to concentrate. It is likely that social and cognitive therapies combined with pharmacotherapy will be the most effective way to treat ADHD in athletes. Medications used for ADHD, especially stimulant types, are known to improve alertness, reaction time, anaerobic performance, and endurance, which would potentially improve athletic performance. Furthermore, stimulant medications may enable student athletes with ADHD to focus on academic studies for longer periods of time, beyond usual levels of fatigue, important for those who may be exhausted after practices and games. The purported performance enhancement effects and potential adverse effects of stimulant medications have prompted many sports governing bodies to ban prescription stimulants or establish strict rules for their use. Athletes taking physician-prescribed stimulants to treat ADHD need to provide the appropriate documentation for approval before competition or risk punitive measures. Physicians should strive to provide a high quality of care to athletes with ADHD through early diagnosis, appropriate and careful multidisciplinary treatment, and complete and timely documentation to facilitate continued sports participation.
Academic-Practice Partnership in Research
Authors: Bacon Cynthia Thornton , Jenkins Marjorie
Published: April 2023

Academic-clinical partnerships describe relationships between 2 groups to advance mutual interests, particularly collaboration on research projects. In this column, members of the Association of Leadership Science in Nursing discuss a 10-year partnership between a nurse professor at a southeast university and a nurse scientist at a health system in the southeast United States, reflections on meeting the criterion standard in our research pursuits, and lessons learned.
Evaluating Burnout and Resiliency in New Graduate Nurses
Authors: Catarelli Bryce , Nobles Patrick , Aull Michael , Yi Fan
Published: April 2023

OBJECTIVE

The aim of this study was to evaluate current levels of and factors contributing toward burnout and resiliency among new graduate nurses to identify effective mitigation strategies.

BACKGROUND

New graduate nurses are at a high risk of increased turnover in the 1st year of employment. An evidence-based, graduate-nurse centered approach is essential to improving nurse retention among this cohort.

METHODS

A cross-sectional study involving 43 new graduate nurses was completed in July 2021 (a subset of a larger sample of 390 staff nurses). Nurses were recruited to complete the Brief Resilience Scale, the Copenhagen Burnout Inventory, and a demographic survey.

RESULTS

New graduate nurses scored within “normal resiliency.” This cohort reported moderate levels of burnout overall. Higher levels were reported within personal- and work-related subgroups.

CONCLUSIONS

Strategies to reduce burnout and increase resiliency in new graduate nurses should be focused on improving personal and work-related burnout.
Long-Term Functional Outcomes at 1-Year After Hospital Discharge in Critically Ill Neonates With Congenital Diaphragmatic Hernia
Authors: O’Hara Jill E. , Buchmiller Terry L. , Bechard Lori J. , Akhondi-Asl Alireza , Visner Gary , Sheils Catherine , Becker Ronald , Studley Mollie , Lemire Lindsay , Mullen Mary P. , Vitali Sally , Mehta Nilesh M. , Dickie Belinda , Zalieckas Jill M. , Albert Ben D.
Published: April 2023

OBJECTIVES:

Congenital diaphragmatic hernia (CDH) is a birth defect associated with long-term morbidity. Our objective was to examine longitudinal change in Functional Status Scale (FSS) after hospital discharge in CDH survivors.

DESIGN:

Single-center retrospective cohort study.

SETTING:

Center for comprehensive CDH management at a quaternary, free-standing children’s hospital.

PATIENTS:

Infants with Bochdalek CDH were admitted to the ICU between January 2009 and December 2019 and survived until hospital discharge.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

One hundred forty-two infants (58% male, mean birth weight 3.08 kg, 80% left-sided defects) met inclusion criteria. Relevant clinical data were extracted from the medical record to calculate FSS (primary outcome) at hospital discharge and three subsequent outpatient follow-up time points. The median (interquartile range [IQR]) FSS score at hospital discharge was 8.0 (7.0–9.0); 39 patients (27.5%) had at least moderate impairment (FSS ≥ 9). Median (IQR) FSS at 0- to 6-month (n = 141), 6- to 12-month (n = 141), and over 12-month (n = 140) follow-up visits were 7.0 (7.0–8.0), 7.0 (6.0–8.0), and 6.0 (6.0–7.0), respectively. Twenty-one patients (15%) had at least moderate impairment at over 12-month follow-up; median composite FSS scores in the over 12-month time point decreased by 2.0 points from hospital discharge. Median feeding domain scores improved by 1.0 (1.0–2.0), whereas other domain scores remained without impairment. Multivariable analysis demonstrated right-sided, C- or D-size defects, extracorporeal membrane oxygenation use, cardiopulmonary resuscitation, and chromosomal anomalies were associated with impairment.

CONCLUSIONS:

The majority of CDH survivors at our center had mild functional status impairment (FSS ≤ 8) at discharge and 1-year follow-up; however, nearly 15% of patients had moderate impairment during this time period. The feeding domain had the highest level of functional impairment. We observed unchanged or improving functional status longitudinally over 1-year follow-up after hospital discharge. Longitudinal outcomes will guide interdisciplinary management strategies in CDH survivors.
A Medicolegal Perspective on the Development of Facial Hypertrophic Scars in a Child after Contact with Alkaline Battery Content
Authors: Demir Canser Yilmaz , Asirdizer Mahmut , Hekimoglu Yavuz
Published: April 2023

  

One of the main causes of injuries in children is batteries.

Serious morbidity can result from ingesting batteries or rubbing their contents into the body.

Batteries must be labeled with child-friendly warnings.
Evolution of stridulatory mechanisms: vibroacoustic communication may be common in leaf-footed bugs and allies (Heteroptera: Coreoidea)
Authors: Forthman Michael , Downie Chandler , Miller Christine W. , Kimball Rebecca T.
Published: April 2023

Intra- and interspecific communication is crucial to fitness via its role in facilitating mating, territoriality and defence. Yet, the evolution of animal communication systems is puzzling—how do they originate and change over time? Studying stridulatory morphology provides a tractable opportunity to deduce the origin and diversification of a communication mechanism. Stridulation occurs when two sclerotized structures rub together to produce vibratory and acoustic (vibroacoustic) signals, such as a cricket ‘chirp’. We investigated the evolution of stridulatory mechanisms in the superfamily Coreoidea (Hemiptera: Heteroptera), a group of insects known for elaborate male fighting behaviours and enlarged hindlegs. We surveyed a large sampling of taxa and used a phylogenomic dataset to investigate the evolution of stridulatory mechanisms. We identified four mechanisms, with at least five evolutionary gains. One mechanism, occurring only in male Harmostini (Rhopalidae), is described for the first time. Some stridulatory mechanisms appear to be non-homoplastic apomorphies within Rhopalidae, while others are homoplastic or potentially homoplastic within Coreidae and Alydidae, respectively. We detected no losses of these mechanisms once evolved, suggesting they are adaptive. Our work sets the stage for further behavioural, evolutionary and ecological studies to better understand the context in which these traits evolve and change.
Scaling of erythrocyte shape and nucleus size among squamate reptiles: reanalysis points to constrained, proportional rather than adaptive changes
Authors: Bury Stanisław , Kratochvíl Lukáš , Starostová Zuzana
Published: April 2023

Small erythrocytes might be beneficial for blood rheology, as they contribute less to blood viscosity than large erythrocytes. We predicted that rheological disadvantages of larger erythrocytes could be alleviated by relatively smaller nucleus size in larger cells allowing higher flexibility and by more elongated shape. Across squamate reptiles, we found that species with larger erythrocytes tend to have smaller ratio of nucleus size to cell size (N : C ratio), but that larger erythrocytes tend to be rounder, not more elongated. Nevertheless, we document that in fact nucleus area changes with erythrocyte area more or less linearly, which is also true for the relationship between cell length and cell width. These linear relationships suggest that nucleus size and cell size, and cell width and cell length, might be constrained to largely proportional mutual changes. The shifts in widely used N : C ratio and elongation ratio (cell length/cell width) with cell size might be misleading, as they do not reflect adaptive or maladaptive changes of erythrocytes, but rather mathematically trivial scaling of the ratios of two variables with a linear relationship with non-zero intercepts. We warn that ratio scaling without analyses of underlying patterns of evolutionary changes can lead to misinterpretation of evolutionary processes.
Short-time diffusive fluxes over membrane receptors yields the direction of a signalling source
Authors: Lindsay Alan E. , Bernoff Andrew J. , Navarro Hernández Adrián
Published: April 2023

An essential ability of many cell types is to detect stimuli in the form of shallow chemical gradients. Such cues may indicate the direction that new growth should occur, or the location of a mate. Amplification of these faint signals is due to intra-cellular mechanisms, while the cue itself is generated by the noisy arrival of signalling molecules to surface bound membrane receptors. We employ a new hybrid numerical-asymptotic technique coupling matched asymptotic analysis and numerical inverse Laplace transform to rapidly and accurately solve the parabolic exterior problem describing the dynamic diffusive fluxes to receptors. We observe that equilibration occurs on long timescales, potentially limiting the usefulness of steady-state quantities for localization at practical biological timescales. We demonstrate that directional information is encoded primarily in early arrivals to the receptors, while equilibrium quantities inform on source distance. We develop a new homogenization result showing that complex receptor configurations can be replaced by a uniform effective condition. In the extreme scenario where the cell adopts the angular direction of the first impact, we show this estimate to be surprisingly accurate.
Genetic Evidence Causally Linking Pancreas Fat to Pancreatic Cancer: A Mendelian Randomization Study
Authors: Yamazaki Hajime , Streicher Samantha A. , Wu Lang , Fukuhara Shunichi , Wagner Róbert , Heni Martin , Grossman Steven R. , Lenz Heinz-Josef , Setiawan Veronica Wendy , Marchand Loic Le , Huang Brian Z.
Published: April 2023

Background & Aims

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and any clues to understanding its elusive etiology could lead to breakthroughs in prevention, early detection, or treatment. Observational studies have shown a relationship between pancreas fat accumulation and PDAC, but the causality of this link is unclear. We therefore investigated whether pancreas fat is causally associated with PDAC using two-sample Mendelian randomization.

Methods

We leveraged eight genetic variants associated with pancreas fat (P<5×10-8) from a genome-wide association study (GWAS) in the UK Biobank (25,617 individuals), and assessed their association with PDAC in the Pancreatic Cancer Cohort Consortium I-III and the Pancreatic Cancer Case-Control Consortium dataset (8,275 PDAC cases and 6,723 non-cases). Causality was assessed using the inverse-variance weighted method. Although none of these genetic variants were associated with body mass index (BMI) at genome-wide significance, we further conducted a sensitivity analysis excluding genetic variants with a nominal BMI association in GWAS summary statistics from the UK Biobank and the Genetic Investigation of Anthropometric Traits consortium dataset (806,834 individuals).

Results

Genetically determined higher levels of pancreas fat using the eight genetic variants was associated with increased risk of PDAC. For one standard deviation increase in pancreas fat levels (i.e., 7.9% increase in pancreas fat fraction), the odds ratio of PDAC was 2.46 (95%CI:1.38-4.40, P=0.002). Similar results were obtained after excluding genetic variants nominally linked to BMI (odds ratio:3.79, 95%CI:1.66-8.65, P=0.002).

Conclusions

This study provides genetic evidence for a causal role of pancreas fat in the pathogenesis of PDAC. Thus, reducing pancreas fat could lower the risk of PDAC.
Curation and description of a blood glucose management and nutritional support cohort using the eICU collaborative research database
Authors: Fitzgerald Oisin , Perez-Concha Oscar , Gallego-Luxan Blanca , Rudd Lachlan , Jorm Louisa
Published: April 2023

Freely available electronic medical record (EMR) data collections have transformed data science and observational research in critical care medicine. Descriptive characterisation of these data collections can aid in highlighting variation in clinical practice and patient outcomes across Intensive Care Units (ICUs). Glycaemic control and nutritional management are important aspects of patient management in the ICU. Blood glucose on admission has a well-known U-shaped relationship with mortality and morbidity, with both hypo- and hyper-glycemia being associated with poor patient outcomes. The importance of nutritional support has been highlighted in critical care guidelines. However, both areas have open research questions and highly variable clinical practices that observational data may help highlight and inform. To aid in this research, we curated a database of patients using the eICU collaborative research data (eICU-CRD), which we describe in the current paper, focusing on patient blood glucose, insulin therapy and enteral nutrition. The eICU-CRD is derived from a telehealth EMR covering 208 United States hospitals from 2014-2015. In addition to descriptive statistics and graphical analysis, we highlight any limitations in data quality. Our results are in line with previous research suggesting the eICU-CRD cohort is of lower illness severity than the average ICU patient cohort and so receive less invasive interventions. Examinations of data missingness revealed issues with medication orders and non-reporting of nutrition by several hospitals. Overall, with care around missingness we believe the eICU-CRD to be a valuable resource in evidence generation for critical care research.
Polyethylene Glycol-Mediated Directional Conjugation of Biological Molecules for Enhanced Immunoassays at the Point-of-Care
Authors: Battalapalli Dheerendranath , Chakraborty Purbali , Jain Disha , Obaro Stephen K. , Gurkan Umut , Bonomo Robert A. , Draz Mohamed
Published: April 2023

Rapid and reliable point-of-care (POC) diagnostic tests can make a significant impact on global health. One of the most common approaches for developing POC systems is the use of target-specific biomolecules. However, the conjugation of biomolecules can result in decreased activity, which may compromise the analytical performance and accuracy of the developed systems. Here, we present a polymer-based cross-linking protocol for controlled and directed conjugation of biological molecules. Our protocol utilizes a bifunctional thiol-polyethylene glycol (PEG)-hydrazide polymer to enable site-directed conjugation of IgG antibodies to the surface of screen-printed metal electrodes. The metal surface of the electrodes is first modified with thiolated PEG molecules, leaving the hydrazide groups available to react with the aldehyde group in Fc fragments of the oxidized IgG antibodies. UsingKlebsiella pneumoniaecarbapenemase-2 (KPC2) antibody as a model antibody used for antimicrobial resistance (AMR) testing, our results demonstrate a ∼10-fold increase in antibody coupling, compared with the standardN-hydroxysuccinimide (NHS)-based conjugation chemistry, and effective capture (> 94%) of the target KPC2 enzyme antigen on the surface of modified electrodes. This straightforward and easy-to-perform strategy of site-directed antibody conjugation can be engineered for coupling other protein and non-protein-based biological molecules commonly used in POC testing and development, thus enhancing the potential for improved diagnostic accuracy and performance.
An information-theoretic analysis of agrammatism in Broca’s aphasia
Authors: Rezaii Neguine
Published: April 2023

Recently we proposed and tested a novel framework based on information theory about the features of agrammatism in patients with the nonfluent variant of primary progressive aphasia (nfvPPA). These features include short sentences, simplified structures, the omission of function words, reduced use of verbs, and increased use of heavy verbs. After distinguishing the syntactic and lexical features of agrammatism, we proposed that the lexical features are not defects but rather a compensatory response to structural deficits. We showed that although patients with nfvPPA have difficulty using complex structures, they use more informative words to facilitate the transfer of their intended message. In this work, we demonstrated the generalizability of our findings to patients with Broca’s aphasia who share similar neuroanatomical involvements with patients with nfvPPA. We found that patients with Broca’s aphasia use simpler syntactic structures as measured by higher syntax frequency. We also found that the use of simpler syntax predicts the use of lower-frequency words. Furthermore, our study showed that producing sentences of lower word frequency is likely achieved through the canonical features of agrammatism, i.e., higher proportions of content words over function words, nouns over verbs, and heavy verbs over light verbs.
Effect of cell isolation magnetic particles on DNA quantification by UV absorbance spectrophotometry
Authors: Bajwa Izza Usman , Sigaud Samuel
Published: April 2023

Magnetic particles are commonly used to isolate specific cell types from blood samples. Residual particles present in the genomic DNA extracted from these cells can interfere with concentration measurements by UV absorbance spectrophotometry. In this study, we determined the degree of inaccuracy of DNA quantification by UV spectrophotometry, in the context of the lineage-specific chimerism analysis workflow. We showed that the presence of residual magnetic particles and RNA leads to an overestimation of the DNA concentration.
Acute dorsal genital nerve stimulation increases subjective arousal in women with and without spinal cord injury: a preliminary investigation
Authors: Bottorff Elizabeth C. , Gupta Priyanka , Ippolito Giulia M. , Moore Mackenzie B. , Rodriguez Gianna M. , Bruns Tim M.
Published: April 2023

Introduction

Female sexual dysfunction (FSD) impacts an estimated 40% of women. Unfortunately, female sexual function is understudied, leading to limited treatment options for FSD. Neuromodulation has demonstrated some success in improving FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD.

Methods

This study consists of a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations.

Results

We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations.

Discussion

This is the first study to measure sexual arousal in response to acute neuromodulation in women. This study demonstrates that acute DGNS, but not TNS, can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for female sexual dysfunction.
Can an online battery match in-person cognitive testing in predicting age-related cortical changes?
Authors: Thienel R. , Borne L. , Faucher C. , Robinson G.A. , Fripp J. , Giorgio J. , Ceslis A. , McAloney K. , Adsett J. , Galligan D. , Martin N.G. , Breakspear M. , Lupton M. K.
Published: April 2023

Understanding how cognition and brain structure change across the lifespan is crucial for gaining insight into the healthy ageing process, as well as identifying early signs of neurodegenerative changes. In our recent prospective study of healthy ageing in midlife and older adults1, we compared the association of two cognitive batteries with age-related variability in brain morphology. Our findings revealed that online cognitive testing, which is more cost-effective, demonstrated comparable association to sulcal width as comprehensive in person assessment. Both cognitive assays show similarly strong correlations with sulcal width. In addition, it was found that both cognitive assessment assays showed a more pronounced age-related decline in individuals with Aβ burden. These findings suggest that online assessment is able to detect accelerated cognitive ageing comparably to the in-person assay in our preclinical sample, even in the early stages of Aβ accumulation before significant structural brain changes occur. Taken together with their greater cost effectiveness, online cognitive testing could lead to more equitable early detection and intervention for neurodegenerative diseases.
What would other emergency stroke teams do? Using explainable machine learning to understand variation in thrombolysis practice
Authors: Pearn Kerry , Allen Michael , Laws Anna , Monks Thomas , Everson Richard , James Martin
Published: April 2023

Objectives

To understand between-hospital variation in thrombolysis use among patients in England and Wales who arrive at hospital within 4 hours of stroke onset.

Design

Machine learning was applied to the Sentinel Stroke National Audit Programme (SSNAP) data set, to learn which patients in each hospital would likely receive thrombolysis.

Setting

All hospitals (n=132) providing emergency stroke care in England and Wales. Thrombolysis use in patients arriving within 4 hours of known or estimated stroke onset ranged from 7% to 49% between hospitals.

Participants

88,928 stroke patients recorded in the national stroke audit who arrived at hospital within 4 hours of stroke onset, from 2016 to 2018.

Intervention

Extreme Gradient Boosting (XGBoost) machine learning models, coupled with a SHAP model for explainability.

Main Outcome Measures

Shapley (SHAP) values, providing estimates of how patient features, and hospital identity, influence the odds of receiving thrombolysis.

Results

The XGBoost/SHAP model revealed that the odds of receiving thrombolysis reduced 9 fold over the first 120 minutes of arrival-to-scan time, varied 30 fold depending on stroke severity, reduced 3 fold with estimated rather than precise stroke onset time, fell 6 fold with increasing pre-stroke disability, fell 4 fold with onset during sleep, fell 5 fold with use of anticoagulants, fell 2 fold between 80 and 110 years of age, reduced 3 fold between 120 and 240 minutes of onset-to-arrival time, and varied 13 fold between hospitals. The hospital attended explained 56% of the variance in between-hospital thrombolysis use, adding in other hospital processes explained 74%, the patient population alone explained 36%, and the combined information from both patient population and hospital processes explained 95% of the variance in between-hospital thrombolysis use. Patient SHAP values expose how suitable a patient is considered for thrombolysis. Hospital SHAP values expose the threshold at which patients are likely to receive thrombolysis.

Conclusions

Using explainable machine learning, we have identified that the majority of the between-hospital variation in thrombolysis use in England and Wales, for patients arriving with time to thrombolyse, may be explained by differences in in-hospital processes and differences in attitudes to judging suitability for thrombolysis.