bluuebunny/crossref_metadata_2025 huggingface dataset:
Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes
Authors: Coluzzi Charles , Guillemet Martin , Mazzamurro Fanny , Touchon Marie , Godfroid Maxime , Achaz Guillaume , Glaser Philippe , Rocha Eduardo P C
Published: October 2023

Bacterial lineages acquire novel traits at diverse rates in part because the genetic background impacts the successful acquisition of novel genes by horizontal transfer. Yet, how horizontal transfer affects the subsequent evolution of core genes remains poorly understood. Here, we studied the evolution of resistance to quinolones in Escherichia coli accounting for population structure. We found 60 groups of genes whose gain or loss induced an increase in the probability of subsequently becoming resistant to quinolones by point mutations in the gyrase and topoisomerase genes. These groups include functions known to be associated with direct mitigation of the effect of quinolones, with metal uptake, cell growth inhibition, biofilm formation, and sugar metabolism. Many of them are encoded in phages or plasmids. Although some of the chronologies may reflect epidemiological trends, many of these groups encoded functions providing latent phenotypes of antibiotic low-level resistance, tolerance, or persistence under quinolone treatment. The mutations providing resistance were frequent and accumulated very quickly. Their emergence was found to increase the rate of acquisition of other antibiotic resistances setting the path for multidrug resistance. Hence, our findings show that horizontal gene transfer shapes the subsequent emergence of adaptive mutations in core genes. In turn, these mutations further affect the subsequent evolution of resistance by horizontal gene transfer. Given the substantial gene flow within bacterial genomes, interactions between horizontal transfer and point mutations in core genes may be a key to the success of adaptation processes.
Investigating the magnetic field of the quiet Sun internetwork
Authors: Sedik Mohamed , Shaltout Abdelrazek M K , Deng Yuanyong , Ichimoto Kiyoshi
Published: October 2023

We analyze the magnetism of the quiet Sun internetwork (IN) using high-spatial-resolution data obtained by the spectropolarimeter (SP) of the Solar Optical Telescope aboard the Hinode satellite near the disk center of the Sun. The SP data were inverted using the Stokes Inversion based on Response functions (SIR) inversion code with a single-component atmosphere with depth dependent in the solar photosphere, assuming gradients in physical parameters along the line of sight (LOS). To avoid the effect of noise, only pixels with Stokes U and/or Q signals above 4.5 times the noise level are considered. The inversion results show that the magnetic field of the IN has mainly hG field strength and the inclination distribution is quasi-isotropic at the solar surface. The field strength decreases with height and becomes predominantly horizontal at the upper layers. At the mid photosphere, the distributions of field strength and inclination are consistent with those derived by Milne–Eddington inversion. The mean transverse and longitudinal flux densities are 66 Mx cm−2 and 13 Mx cm−2 at log τ = −1.0; we also study the ratio between the transverse and longitudinal components in the IN region as a function of depth in the photosphere, finding that the ratio is almost 2.7 in the deep layer, increasing to 5.1 in the upper layer. The mean field strength is greater than 100 G in the upper photosphere, which is consistent with the results based on the Hanle effect. We present the LOS velocity probability distribution function for IN at different optical depths, where its distribution is mainly associated with upflow velocities of VLOS = 1.2 and 0.6 km s−1 in the deeper and upper layers, respectively. In addition, there exists a reliable inversion analysis, which is obvious from the comparison between the observed and calculated area asymmetries in both Fe i lines of Hinode SP data.
Impact of informal care on the mental health of caregivers during the COVID-19 pandemic
Authors: Fleitas Alfonzo Ludmila , Taouk Yamna , Emerson Eric , King Tania
Published: October 2023

Background

Informal care can affect the mental health of caregivers. The COVID-19 pandemic precipitated many people into informal care. Little is known about the longitudinal effect of informal care throughout the pandemic. We investigate changes in mental health in relation to changes in informal care between July 2020 and September 2021.

Methods

Using data from Understanding Society, we applied fixed-effects modelling to assess mental health variations associated with changes in caregiving among 13 557 participants (50 430 observations). Hours of weekly care were categorized as 0, 1–19, ≥20. Mental health was measured using the General Health Questionnaire (GHQ-12) as a continuous score and a binary indicator. Main analyses were stratified by gender.

Results

Compared to when delivering 0 hours care/week, the GHQ-12 scores of women providing care for 1–19 hours/week were 0.46 points higher (95%CI: −0.11, 1.09), while their mental health scores were 0.99 higher (95%: 0.08, 1.90) when caring for ≥20 hours/week. Changes on the binary GHQ-12 measure were only evident for women when providing ≥20 hours of weekly care. These changes were not substantial among men.

Conclusion

Informal care adversely impacted the mental health of women carers during the COVID-19 pandemic. Support programmes for informal carers should focus on alleviating caregiving loads in women.
Monitoring of Argatroban in Critically Ill Patients: A Prospective Study Comparing Activated Partial Thromboplastin Time, Point-of-Care Viscoelastic Testing with Ecarin Clotting Time and Diluted Thrombin Time to Mass Spectrometry
Authors: Heubner Lars , Oertel Reinhard , Tiebel Oliver , Mehlig-Warnecke Nicole , Beyer-Westendorf Jan , Mirus Martin , Roessler Martin , Renner Bertold , Spieth Peter Markus
Published: October 2023

Background

The direct thrombin inhibitor argatroban is indicated for the treatment of heparin-induced thrombocytopenia II, but it is also used off-label to treat critically ill patients presenting with heparin resistance, severe antithrombin deficiency, or hypercoagulability. Direct drug monitoring is not routinely available, and argatroban dosing is mainly based on global coagulation assays such as activated partial thromboplastin time (PTT) or diluted thrombin time (TT), both of which have limitations in patients with hypercoagulability.

Methods

Blood samples were obtained from critically ill patients treated with argatroban. Activated PTT and diluted TT were measured with a STA R Max3 analyzer (STAGO Deutschland GmbH, Germany) using an argatroban-calibrated kit. Ecarin clotting time was measured using a point-of-care viscoelastic test device. Liquid chromatography with tandem mass spectrometry was performed using a reversed-phase column, a solvent gradient, and an API4000 mass spectrometer with electrospray. Correlation was described using Pearson correlation coefficient r and Bayesian multilevel regression to estimate relationships between outcomes and covariates.

Results

From June 2021 to March 2022, 205 blood samples from 22 patients were analyzed, allowing for 195 activated PTT–liquid chromatography with tandem mass spectrometry comparisons, 153 ecarin clotting time–liquid chromatography with tandem mass spectrometry comparison, and 105 diluted TT–liquid chromatography with tandem mass spectrometry comparisons. Compared to liquid chromatography with tandem mass spectrometry, performance of argatroban quantification was best for diluted TT (r = 0.91), followed by ecarin clotting time (r = 0.58) and activated PTT (r = 0.48). Regression analysis revealed that patients with sepsis were more prone to argatroban overdosing (coefficient, 4.194; 95% credible interval, 2.220 to 6.792).

Conclusions

Although activated PTT monitoring of argatroban is the most commonly used test, in critically ill patients, diluted TT provides more precise measurements. Alternately, point-of-care viscoelastic ecarin clotting time also provides guidance for argatroban dosing to identify overdosing if available. The data also suggested that patients with sepsis are at greater risk for argatroban overdosing.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
A Novel Fluorescence-Based Leak Test Method for Rectal Anastomoses Using Aerosolized Indocyanine Green
Authors: Kondo Akihiro , Yokota Naoya , Kobayashi Nobuya , Feng Dongping , Asano Eisuke , Kumamoto Kensuke , Kobara Hideki , Okano Keiichi
Published: October 2023

BACKGROUND:

The intraoperative air leak test is commonly performed during rectal surgery to evaluate anastomotic integrity. However, its drawbacks include occasional difficulties in visualizing the exact point of the leak while maintaining the pelvis under saline, the need for repeat testing to identify the leak point, and a lack of continuous visualization of the leak point.

OBJECTIVE:

We aimed to evaluate the feasibility and clinical applicability of using aerosolized indocyanine green, a fluorescent tracer, for detecting rectal anastomotic leakage.

DESIGN:

Animal pre-clinical study.

SETTING:

Animal laboratory at Kagawa University.

PATIENTS:

Six healthy adult female beagles were included.

INTERVENTIONS:

An anastomotic leakage model with a single air leak point was created in each dog. Indocyanine green was aerosolized using a nebulizer kit with a stream of carbon dioxide flowing at 1.5–2.0 L/min. The aerosol was administered into the rectum transanally, and laparoscopic observations were performed.

MAIN OUTCOME MEASURES:

Air leak points were observed using a near-infrared fluorescence laparoscope, following which the presence of corresponding indocyanine green fluorescence was verified.

RESULTS:

Aerosolized indocyanine green was visualized laparoscopically at all anastomosis sites but not elsewhere. The median time from the administration of the aerosol to its visualization was 4.5 s. Pathological examinations were performed 4 weeks post-surgery in all dogs, and no histological abnormalities related to aerosolized indocyanine green administration were observed at the anastomosis sites.

LIMITATIONS:

The leak points were surgically created and did not occur naturally.

CONCLUSIONS:

Visualization of air leaks at the sites of rectal anastomosis was laparoscopically achievable by administering aerosolized indocyanine green transanally into the rectum in our canine model. This novel fluorescent leak test could be a valid alternative to established methods.
Clinical Experience of a Smart Articulating Digital Device for Transanal Minimally Invasive Surgery
Authors: Khan Mohammad Faraz , Kearns Emma , Cahill Ronan A.
Published: October 2023

BACKGROUND:

The constrained access associated with transanal minimally invasive surgery has led surgeons to deploy robotic-assisted platforms to offset inherent maneuverability limitations and, perhaps, skills deficits.

IMPACT OF INNOVATION:

A handheld, powered 5-mm lightweighted laparoendoscopic electromechanical digital device (HandX, HumanXtensions, Israel) with hardware and software components that convert surgical hand movements precisely to the instrument’s articulating tip and enable robotic transanal minimally invasive surgery with full tip roticulation for hook diathermy and suturing.

TECHNOLOGY, MATERIALS, AND METHODS:

After bench and biomedical model training, HandX was used in 3 transanal minimally invasive surgery procedures (2 male patients and 1 female patient, mean age 66.3 years). The rectal lesions averaged 30 mm in maximum dimension and were located posteriorly (n = 2) and laterally (n = 1) a mean of 3 cm from the anal verge. Standard transanal minimally invasive surgery setup and instrumentation (Gelport Path, Applied Medical with Airseal, and Conmed) were used, adding the HandX device for circumferential lesion marking and hemostatic full-thickness excision as well as defect suturing where appropriate.

PRELIMINARY RESULTS:

All procedures were completed without undue prolongation (operating times <1 hour) despite nuisance hemorrhoidal bleeding in 1 patient. All lesions were fully excised, with 2 being T1 cancers and 1 tubulovillous adenoma with high-grade dysplasia. All patients were discharged within 48 hours postoperatively (1 experienced secondary hemorrhage on postoperative day 5).

CONCLUSIONS AND FUTURE DIRECTIONS:

HandX capably facilitated endoscopic robot-like instrument movement for transanal minimally invasive surgery without disrupting workflows. With time dedicated to instrument understanding and training, HandX increased dexterity with a small operating room footprint and may offer greater cost-effectiveness than other platforms.
Combined Robotic Ventral Mesh Rectopexy and Sacrocolpopexy for Multicompartmental Pelvic Organ Prolapse
Authors: Devane Liam , Ranson Stacy , Bustamante-Lopez Leonardo Alfonso , Uwah Martin , Kudish Bela , Kow Natha , Hoff John , Monson John R.T. , deBeche-Adams Teresa
Published: October 2023

BACKGROUND:

Multispecialty management should be the preferred approach for the treatment of pelvic floor dysfunction, as there is often multicompartmental prolapse.

OBJECTIVE:

To assess the safety of combined robotic ventral-mesh rectopexy and either uterine or vaginal fixation for treatment of multicompartmental pelvic organ prolapse at our institution.

DESIGN:

Retrospective analysis.

SETTINGS:

Tertiary referral academic center.

PATIENTS:

All patients who underwent a robotic approach and combined procedure and discussed at a biweekly pelvic floor multidisciplinary team meeting.

MAIN OUTCOME MEASURES:

Operative time, intraoperative blood loss and complications. Postoperative pelvic organ prolapse quantification score, length of stay, 30-day morbidity, and readmission.

RESULTS:

From 2018 to 2021, there were 321 operations for patients with multicompartmental prolapse. Mean age was 63.4 years. The predominant pelvic floor dysfunction was rectal prolapse in 170 cases (60%). Pelvic organ prolapse quantification scores were II in 146 patients (53%), III in 121 (44%), and IV in 9 (3%); 315 of the 323 cases included robotic ventral mesh rectopexy (98%). Sacrocolpopexy or sacrohysteropexy was performed in 281 patients (89%). Other procedures included 175 hysterectomies (54%), 104 oophorectomies (32%), 151 sling procedures (47%), 149 posterior repairs (46%), and 138 cystocele repairs (43%). The operative time for ventral mesh rectopexy was 211 minutes and combined pelvic floor reconstruction 266 minutes. Average length of stay was 1.6 days. Eight patients were readmitted within 30 days, 1 with a severe headache and 7 patients with postoperative complications (2.5%): pelvic collection, perirectal collection both requiring radiologic drainage. Four complications required reoperation: epidural abscess, small-bowel obstruction, missed enterotomy requiring resection, and urinary retention requiring sling revision. There were no mortalities.

LIMITATIONS:

Retrospective single-center study.

CONCLUSIONS:

A combined robotic approach for multicompartmental pelvic organ prolapse is a safe and viable procedure with a relatively low rate of morbidity and no mortality. This is the highest volume series of combined robotic pelvic floor reconstruction in the literature and demonstrates a low complication rate and short length of stay.
Efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache with concomitant nonalcoholic fatty liver disease in climacteric women
Authors: Pei Feng , Hu Wei-Jia , Zhao Yu-Liang
Published: October 2023

Objective

This study aimed to assess the efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache (CTTH) with concomitant nonalcoholic fatty liver disease (NAFLD) in climacteric women.

Methods

In this study, we enrolled 150 climacteric women with CTTH and concomitant NAFLD. The participants were divided into three groups based on the random number table: medication group, acupuncture group, and acupuncture-medication group. Treatment continued for 2 months. The efficacy of CTTH was assessed based on the visual analog scale/score (VAS). The influence on NAFLD was assessed based on body mass index (BMI), controlled attenuation parameter (CAP), and the ratio of hepatic-splenic computed tomography (CT) value. The Participant Health Questionnaire-9 (PHQ-9) score was compared among the three groups.

Results

A total of 123 participants completed the trial, including 37 participants in the medication group, 41 participants in the acupuncture group, and 45 participants in the acupuncture-medication group. Results are summarized hereinafter. (1) The total clinical efficiency rates of the medication group, acupuncture group, and acupuncture-medication group were 89.19% (33 of 37), 90.24% (37 of 41), and 95.65% (44 of 46), respectively. (2) Except for the BMI of the medication group (P = 0.063), a significant difference in VAS, BMI, CAP, the ratio of hepatic-splenic CT value, and PHQ-9 score was found in the three groups (P < 0.01). (3) There was a significant difference in VAS, BMI, CAP, and PHQ-9 among the three groups (P < 0.01), with those in the acupuncture-medication group being superior. No difference in the ratio of hepatic-splenic CT value was found (P = 0.440). (4) The efficacy differed significantly among the three groups (χ
2 = 8.130, P = 0.017), and it was significantly superior in the acupuncture-medication group (P = 0.008, P = 0.013).

Conclusions

Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in treating CTTH in climacteric women compared with either acupuncture or medication. Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in subsiding the negative moods in participants with CTTH and concomitant NAFLD.
Exploration of the association between menopausal symptoms, gastrointestinal symptoms, and perceived stress: survey-based analysis
Authors: Brimienė Ieva , Šiaudinytė Monika , Burokas Aurelijus , Grikšienė Ramunė
Published: October 2023

Objective

The study aimed to evaluate the relationship between menopausal symptoms, gastrointestinal symptoms, and experienced stress in women from premenopause to postmenopause.

Methods

We conducted a cross-sectional study using an anonymous survey that included questions on demographics, health (gynecological, gastrointestinal), and lifestyle (physical activity, sleep, etc) factors, the Perceived Stress Scale (PSS), and the Menopause-Specific Quality of Life Questionnaire (MENQOL).

Results

Data of 693 participants aged 50.1 ± 3.2 years were analyzed. We found that the MENQOL total score increased depending on the stages of reproductive aging (P < 0.001) and positively correlated with PSS scores (r = 0.47, P < 0.001). Age, reproductive stage, body mass index (BMI), PSS score, diagnosis of depression or anxiety disorder, physical activity, and frequency of defecation appeared to have significant association with the total MENQOL score (P < 0.05). The analysis within separate MENQOL domains revealed that PSS score and diagnosis of depression or anxiety disorder were associated with higher scores in all MENQOL domains (P < 0.05) except sexual. Physical activity and the values of the Bristol stool form scale were related to the vasomotor items (P < 0.05). The frequency of defecation was an independent contributor to the psychosocial and sexual domains (P < 0.05). BMI, physical activity, and frequency of defecation were associated with physical symptoms (P < 0.05).

Conclusions

Perceived stress and some gastrointestinal symptoms in women were associated with menopausal symptoms. Reproductive stages, physical activity, BMI, and previously diagnosed depression or anxiety disorder were related to the intensity of menopausal symptoms. However, further research is needed to confirm the relationship between stress, gastrointestinal, and menopausal symptoms.
Implementing a Discharge Follow-up Phone Call Program Reduces Readmission Rates in an Integrated Health System
Authors: Lukanski Amy , Watters Shelley , Bilderback Andrew L. , Buchanan Dan , Hodges Jacob C. , Burwell David , Triola Amy , Marroquin Oscar C. , Martin Susan C. , Zapf Rachel L. , Kip Paula L. , Minnier Tami E.
Published: October 2023

In this study, we sought to determine the effect of implementing a large-scale discharge follow-up phone call program on hospital readmission rates. Previous work has shown that patients with unaddressed concerns during discharge have significantly higher rates of care complications and hospital readmissions. This study is an observational quality improvement project completed from April 17, 2020 to January 31, 2022 at 22 hospitals in a large, integrated academic health system. A nurse-led scripted discharge follow-up phone call program was implemented to contact all patients discharged from inpatient care within 72 hours of discharge. Readmission rates were tracked before and after project implementation. Over a 21-month span, 137,515 phone calls were placed, and 57.92% of patients were successfully contacted within 7 days of discharge. The 7-day readmission rate for contacted patients was 2.91% compared with 4.73% for noncontacted patients. The 30-day readmission rate for contacted patients was 11.00% compared with 12.17% for noncontacted patients. We have found that discharge follow-up phone calls targeting patients decreases risk of readmission, which improves overall patient outcomes.
Hospital Adaptions to Mitigate the COVID-19 Pandemic Effects on MARQUIS Toolkit Implementation and Sustainability
Authors: Rhoten Bethany , Jones Abigail C. , Maxwell Cathy , Stolldorf Deonni P.
Published: October 2023

Objective:

To explore the perceived effects of COVID-19 on MARQUIS toolkit implementation and sustainability, challenges faced by hospitals in sustaining medication reconciliation efforts, and the strategies used to mitigate the negative effects of the pandemic.

Data Sources and Study Settings:

Primary qualitative data were extracted from a Web-based survey. Data were collected from hospitals that participated in MARQUIS2 (n = 18) and the MARQUIS Collaborative (n = 5).

Study Design:

A qualitative, cross-sectional study was conducted.

Data Collection/Data Extraction:

Qualitative data were extracted from a Research Electronic Data Capture survey databased and uploaded into an Excel data analysis template. Two coders independently coded the data with a third coder resolving discrepancies.

Principal Findings:

Thirty-one team members participated, including pharmacists (n = 20; 65%), physicians (n = 9; 29%), or quality-improvement (QI) specialists (n = 2; 6%) with expertise in medication reconciliation (MedRec) (14; 45%) or QI (10; 32%). Organizational resources were limited, including funding, staffing, and access to pharmacy students. To support program continuation, hospitals reallocated staff and used new MedRec order sets. Telemedicine, workflow adaptations, leadership support, QI team involvement, and ongoing audits and feedback promoted toolkit sustainability.

Conclusions:

COVID-19 affected the capacity of hospitals to sustain the MARQUIS toolkit. However, hospitals adapted various strategies to sustain the toolkit.
Impact of an STI Diagnosis on People Living With HIV in La Romana, Dominican Republic: A Cross-Sectional, Qualitative, Descriptive Study
Authors: Sanabria Gabriella , Stonbraker Samantha , Bateman Mark , Halpern Mina , Amesty Silvia
Published: October 2023

The objective of this study was to explore how receiving a sexually transmitted infection (STI) diagnosis affects subsequent STI knowledge and sexual risk behavior among key populations in La Romana, Dominican Republic (DR) who participated in a parent study 12 to 24 months before the current study. Nine participants, with a mean age of 37 years (range 20-54 years) and a female majority (89%), who were recruited from the parent study completed in-depth interviews, questionnaires assessing STI knowledge, and received STI testing. Interviews were analyzed using qualitative descriptive methodology and questionnaire data, comparing individual's responses between the parent and current studies. Participants reported safer sexual behaviors after original STI diagnosis, such as more frequent condom use. Questionnaires showed improvement in STI knowledge between the parent and current studies. Three participants had an STI reinfection. Findings warrant further exploration into more comprehensive and targeted STI treatment methods for key populations in the DR.
Weight bias reduction intervention among nurse practitioner students using simulation-based experiences
Authors: Oliver Tracy L. , Burrell Sherry A. , Furman Gail E. , Diewald Lisa K. , Mariani Bette , Starck Megan R. , Shenkman Rebecca
Published: October 2023

Few nurse practitioner (NP) programs include obesity and weight bias education in their curriculum. However, NPs will likely provide care for people living with obesity, many of whom have been discriminated against based on their weight by previous providers, and many NP students may feel unprepared to navigate weight management competently. This pilot study included a weight bias reduction (WBR) intervention, which included a simulation-based experience (SBE) with a standardized participant (SP) and educational activities embedded within the NP curriculum. Nineteen NP students participated in this pilot study, but only seven students had matching data for preintervention to postintervention scores. There were no statistically significant differences in preintervention and postintervention Attitudes Toward Obese Persons (ATOP) or Beliefs About Obese Persons (BAOP) scores. Despite this small sample size and not achieving statistical significance, SBE-SP holds promise to depict realistic patient encounters to improve NPs' attitudes and beliefs toward persons with obesity and to reduce weight bias. Therefore, incorporating SBE-SP may be a feasible component of the NP curriculum.
Follow-Up After PICU Discharge for Patients With Acquired Brain Injury: The Role of an Abbreviated Neuropsychological Evaluation and a Return-to-School Program*
Authors: Williams Cydni N. , Hall Trevor A. , Baker Victoria A. , Chertow Daniel J. , Vanderlind W. Michael , Bosworth Christopher C. , Hartman Mary E.
Published: October 2023

OBJECTIVES:

To present the results of an abbreviated testing protocol used to screen for neurocognitive and psychological sequelae of critical illness among PICU survivors with acquired brain injury in our post-discharge follow-up programs and describe our process for facilitating this population’s return to academic life.

DESIGN:

Retrospective cohort study.

SETTING:

Neurocritical care follow-up programs at two U.S. academic, tertiary medical/surgical PICUs.

PATIENTS:

Children greater than 4 years old enrolled in the neurocritical care follow-up programs (n = 289) at these institutions who underwent neurocognitive and psychological testing between 2017 and 2021.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

One month after discharge from the hospital, nearly half of the children and/or their parents (48%) in our neurocritical care follow-up programs identified some type of emotional or behavioral concern compared to their premorbid state, and 15% reported some type of cognitive concern. On evaluation, 35% of the children were given a new neurocognitive diagnosis. Neurocognitive domains regulated by the executive functioning system were the most commonly affected, including attention (54%), memory (31%), and processing speed (27%). One-quarter of the children were given a new psychological diagnosis, most commonly post-traumatic stress disorder or stress-related symptoms (12%). Over 80% of patients in the programs were given new recommendations for school, for both new academic services and new classroom accommodations. Over half of children (57%) were referred for comprehensive follow-up neuropsychological evaluation.

CONCLUSIONS:

Abbreviated neurocognitive and psychological evaluation successfully identifies the same deficits commonly found among PICU survivors who undergo longer, more complete testing protocols. When combined with services aimed at successfully reintegrating PICU survivors back to school, this focused evaluation can provide an effective and efficient means of screening for cognitive and emotional deficits among PICU survivors and establish a rationale for early academic support upon the child’s return to school.
Cues to care: Chronic disease diagnosis in young adult trauma patients
Authors: Adams Ursula , Portelli Tremont Jaclyn , Yohann Avital , Aldridge Joshua , Riggins Stephanie , Brownstein Michelle , Charles Anthony ,   Prevention in Young Adult Trauma Patients Multicenter Study Group, Udekwu Pascal Osita
Published: October 2023

BACKGROUND

Prevention of chronic disease necessitates early diagnosis and intervention. In young adults, a trauma admission may be an early contact with the health care system, representing an opportunity for screening and intervention. This study estimates the prevalence of previously diagnosed disease and undiagnosed disease (UD)—diabetes mellitus, hypertension, obesity, and alcohol and substance use—in a young adult trauma population. We determine factors associated with UD and examine outcomes in patients with UD.

METHODS

This is a multicenter, retrospective cohort study of adult trauma patients 18 to 40 years old admitted to participating Level I trauma centers between January 2018 and December 2020. Three Level 1 trauma centers in a single state participated in the study. Trauma registry data and chart review were examined for evidence of previously diagnosed disease or UD. Patient demographics and outcomes were compared between cohorts. Multivariable regression modeling was performed to assess risk factors associated with any UD.

RESULTS

The analysis included 6,307 admitted patients. Of these, 4,843 (76.8%) had evidence of at least 1 UD, most commonly hypertension and obesity. In multivariable models, factors most associated with risk of UD were age (adjusted odds ratio [aOR], 0.98; 95% confidence interval [CI], 0.98–0.99), male sex (aOR, 1.43; 95% CI, 1.25–1.63), and uninsured status (aOR, 1.57; 95% CI, 1.38–1.80). Only 24.5% of patients had evidence of a primary care provider (PCP), which was not associated with decreased odds of UD. Clinical outcomes were significantly associated with the presence of chronic disease. Of those with UD and no PCP, only 11.2% were given a referral at discharge.

CONCLUSION

In the young adult trauma population, the UD burden is high, especially among patients with traditional sociodemographic risk factors and even in patients with a PCP. Because of short hospital stays in this population, the full impact of UD may not be visible during a trauma admission. Early chronic disease diagnosis in this population will require rigorous, standard screening measures initiated within trauma centers.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Parental early life environments drive transgenerational plasticity of offspring metabolism in a freshwater fish (Danio rerio)
Authors: Massey Melanie D. , Dalziel Anne C.
Published: October 2023

Parental experiences can lead to changes in offspring phenotypes through transgenerational plasticity (TGP). TGP is expected to play a role in improving the responses of offspring to changes in climate, but little is known about how the early lives of parents influence offspring TGP. Here, we use a model organism, zebrafish (Danio rerio), to contrast the effects of early and later life parental thermal environments on offspring routine metabolism. To accomplish this, we exposed both parents to either constant optimal (27°C) or environmentally realistic diel fluctuating (22–32°C) temperatures during early (embryonic and larval) and later (juvenile and adult) life in a factorial design. We found significant reduction of routine metabolic rates (greater than 20%) at stressful temperatures (22°C and 32°C) after biparental early life exposure to fluctuating temperatures, but little effect of later life parental temperatures on offspring metabolism. This reduction reflects metabolic compensation and is expected to enhance offspring body sizes under stressful temperatures. These changes occur over and above the effects of parental environments on egg size, suggesting alternate non-genetic mechanisms influenced offspring metabolic rates.
Hummingbirds use wing inertial effects to improve manoeuvrability
Authors: Haque Mohammad Nasirul , Cheng Bo , Tobalske Bret W. , Luo Haoxiang
Published: October 2023

Hummingbirds outperform other birds in terms of aerial agility at low flight speeds. To reveal the key mechanisms that enable such unparalleled agility, we reconstructed body and wing motion of hummingbird escape manoeuvres from high-speed videos; then, we performed computational fluid dynamics modelling and flight mechanics analysis, in which the time-dependent forces within each wingbeat were resolved. We found that the birds may use the inertia of their wings to achieve peak body rotational acceleration around wing reversal when the aerodynamic forces were small. The aerodynamic forces instead counteracted the reversed inertial forces at a different wingbeat phase, thereby stabilizing the body from inertial oscillations, or they could become dominant and provide additional rotational acceleration. Our results suggest such an inertial steering mechanism was present for all four hummingbird species considered, and it was used by the birds for both pitch-up and roll accelerations. The combined inertial steering and aerodynamic mechanisms made it possible for the hummingbirds to generate instantaneous body acceleration at any phase of a wingbeat, and this feature is probably the key to understanding the unique dexterity distinguishing hummingbirds from other small-size flyers that solely rely on aerodynamics for manoeuvering.
Cooperative motility, force generation and mechanosensing in a foraging non-photosynthetic diatom
Authors: Zheng Peng , Kumadaki Kayo , Quek Christopher , Lim Zeng Hao , Ashenafi Yonatan , Yip Zhi Ting , Newby Jay , Alverson Andrew J. , Jie Yan , Jedd Gregory
Published: October 2023

Diatoms are ancestrally photosynthetic microalgae. However, some underwent a major evolutionary transition, losing photosynthesis to become obligate heterotrophs. The molecular and physiological basis for this transition is unclear. Here, we isolate and characterize new strains of non-photosynthetic diatoms from the coastal waters of Singapore. These diatoms occupy diverse ecological niches and display glucose-mediated catabolite repression, a classical feature of bacterial and fungal heterotrophs. Live-cell imaging reveals deposition of secreted extracellular polymeric substance (EPS). Diatoms moving on pre-existing EPS trails (runners) move faster than those laying new trails (blazers). This leads to cell-to-cell coupling where runners can push blazers to make them move faster. Calibrated micropipettes measure substantial single-cell pushing forces, which are consistent with high-order myosin motor cooperativity. Collisions that impede forward motion induce reversal, revealing navigation-related force sensing. Together, these data identify aspects of metabolism and motility that are likely to promote and underpin diatom heterotrophy.
The economy of pollen dispersal in flowering plants
Authors: Johnson Steven D. , Harder Lawrence D.
Published: October 2023

Mating success of flowering plants depends strongly on the efficiencies of pollen removal from flowers and its subsequent dispersal to conspecific stigmas. We characterized the economy of pollen dispersal in flowering plants by analysing pollen fates and their correlates for 228 species. The mean percentage of pollen removed from flowers (removal efficiency) varied almost twofold according to the type of pollen-dispersal unit, from less than 45% for orchids and milkweeds with solid pollinia, to greater than 80% for species with granular monads or sectile (segmented) pollinia. The mean percentage of removed pollen reaching stigmas (pollen transfer efficiency, PTE) varied from 2.4% for species with separate monads to 27.0% for orchids with solid pollinia. These values tended to be higher in plants with single pollinator species and in those with non-grooming pollinators. Nectar production increased removal efficiency, but did not influence PTE. Among types of pollen-dispersal units, the net percentage of produced pollen that was dispersed to stigmas varied negatively with removal efficiency and positively with PTE, indicating the relative importance of the latter for overall pollen economy. These findings confirm the key importance of floral traits, particularly pollen packaging, for pollen dispersal outcomes and highlight the under-appreciated pollination efficiency of non-grooming pollinators.
Does word flickering improve reading? Negative evidence from four experiments using low and high frequencies
Authors: Lubineau Marie , Watkins Cassandra Potier , Glasel Hervé , Dehaene Stanislas
Published: October 2023

Does word flickering facilitate reading? Despite a lack of scientific evidence, flickering glasses and lamps for dyslexia are being marketed in various countries. We conducted four experiments to assess their efficacy. Two experiments involved a computerized lexical decision task with constant display or low-frequency flickering (10 or 15 Hz). Among 375 regular adult readers, flicker noticeably slowed down word recognition, while slightly biasing the decision towards pseudowords. No significant effect was observed in 20 dyslexic children. In 22 dyslexic children, we also evaluated the impact of the Lexilight lamp and Lexilens glasses, which operate at higher frequencies, on reading fluency, letter identification and mirror letter processing. No detectable impact was observed. Lastly, in two participants who claimed to benefit from flickering glasses, we orthogonally manipulated whether the glasses were actually on, and whether the participant thought they were on. Only a small placebo effect was noted in one participant. Our findings starkly contrast with marketing claims that these tools can help 90% of dyslexics, and emphasize the role of rigorous scientific research in empowering dyslexic individuals to make informed decisions.
Characterizing citrullination by mass spectrometry-based proteomics
Authors: Rebak A. S. , Hendriks I. A. , Nielsen M. L.
Published: October 2023

Citrullination is an important post-translational modification (PTM) of arginine, known to play a role in autoimmune disorders, innate immunity response and maintenance of stem cell potency. However, citrullination remains poorly characterized and not as comprehensively understood compared to other PTMs, such as phosphorylation and ubiquitylation. High-resolution mass spectrometry (MS)-based proteomics offers a valuable approach for studying citrullination in an unbiased manner, allowing confident identification of citrullination modification sites and distinction from deamidation events on asparagine and glutamine. MS efforts have already provided valuable insights into peptidyl arginine deaminase targeting along with site-specific information of citrullination in for example synovial fluids derived from rheumatoid arthritis patients. Still, there is unrealized potential for the wider citrullination field by applying MS-based mass spectrometry approaches for proteome-wide investigations. Here we will outline contemporary methods and current challenges for studying citrullination by MS, and discuss how the development of neoteric citrullination-specific proteomics approaches still may improve our understanding of citrullination networks.

This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Citrullination and the protein code: crosstalk between post-translational modifications in cancer
Authors: Harada Koyo , Carr Simon M. , Shrestha Amit , La Thangue Nicholas B.
Published: October 2023

Post-translational modifications (PTMs) of proteins are central to epigenetic regulation and cellular signalling, playing an important role in the pathogenesis and progression of numerous diseases. Growing evidence indicates that protein arginine citrullination, catalysed by peptidylarginine deiminases (PADs), is involved in many aspects of molecular and cell biology and is emerging as a potential druggable target in multiple diseases including cancer. However, we are only just beginning to understand the molecular activities of PADs, and their underlying mechanistic details
in vivo
under both physiological and pathological conditions. Many questions still remain regarding the dynamic cellular functions of citrullination and its interplay with other types of PTMs. This review, therefore, discusses the known functions of PADs with a focus on cancer biology, highlighting the cross-talk between citrullination and other types of PTMs, and how this interplay regulates downstream biological events.

This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Citrullination of matrisomal proteins in health and diseases
Authors: Saifi Mohammad Aslam , Ho I-Cheng
Published: October 2023

Proteins once translated are subjected to post-translational modifications (PTMs) that can critically modify their characteristics. Citrullination is a unique type of PTM that is catalysed by peptidylarginine deiminase (PAD) enzymes, which regulate a multitude of physiological functions such as apoptosis, gene expression and immune response by altering the structure and function of cellular proteins. However, emerging data have unravelled compelling evidence to support that PAD-mediated citrullination is not exclusive to cellular proteins; rather citrullination of extracellular matrix (ECM) proteins also plays a major contributing role in various physiological/pathological conditions. Here, we discuss putative mechanisms for citrullination-induced alterations in the function of ECM proteins. Further, we put emphasis on influential roles of ECM citrullination in various pathological scenarios to underscore the clinical potential of its manipulation in human diseases.

This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Inhibiting MEK1 R189 citrullination enhances the chemosensitivity of docetaxel to multiple tumour cells
Authors: Xue Teng , Fei Shujia , Gu Jian , Li Nan , Zhang Pengxue , Liu Xiaoqiu , Thompson Paul R , Zhang Xuesen
Published: October 2023

Drug resistance is still a big challenge for cancer patients. We previously demonstrated that inhibiting peptidylarginine deiminase 2 (PADI2) enzyme activity with Cl-amine increases the efficacy of docetaxel (Doc) on tamoxifen-resistant breast cancer cells with PADI2 expression. However, it is not clear whether this effect applies to other tumour cells. Here, we collected four types of tumour cells with different PADIs expression and fully evaluated the inhibitory effect of the combination of PADIs inhibitor (BB-Cla) and Doc
in vitro
and
in vivo
on tumour cell growth. Results show that inhibiting PADIs combined with Doc additively inhibits tumour cell growth across the four tumour cells. PADI2-catalysed citrullination of MEK1 Arg 189 exists in the four tumour cells, and blocking the function of MEK1 Cit189 promotes the anti-tumour effect of Doc in these tumour cells. Further analysis shows that inhibiting MEK1 Cit189 decreases the expression of cancer cell stemness factors and helps prevent cancer cell stemness maintenance. Importantly, this combined treatment can partially restore the sensitivity of chemotherapy-resistant cells to docetaxel or cisplatin in tumour cells. Thus, our study provides an experimental basis for the combined therapeutic approaches using docetaxel- and PADIs inhibitors-based strategies in tumour treatment.

This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Citrulline is not a major determinant of autoantibody reactivity to neutrophil extracellular traps
Authors: de Bont Cynthia , Pruijn Ger J. M.
Published: October 2023

One of the main strategies of neutrophils in responding to microbial infections is the formation of neutrophil extracellular traps (NETs). NETs are web-like structures of decondensed chromatin associated with antimicrobial proteins. Citrullination plays an important role during NET formation and a substantial fraction of NET-associated proteins appeared to be citrullinated. The release of citrullinated intracellular proteins from netting neutrophils led to the hypothesis that the production of anti-citrullinated protein autoantibodies by autoimmune patients, in particular patients with rheumatoid arthritis, might be initiated when citrullinated NET components are not properly cleared and are exposed to the immune system. Here, we discuss the processes that lead to NET formation, including the role of peptidylarginine deiminase activation and our current knowledge on citrullinated NET-associated proteins. Citrulline-dependent epitopes do not appear to play a major role in the recognition of NETs by autoantibodies from rheumatoid arthritis and systemic lupus erythematosus patients, even though anti-NET autoantibodies are frequently observed in sera from these patients. The neutrophil proteases associated with NETs have a major impact on the integrity of NET-associated proteins when NET formation is induced by activating isolated human neutrophils. Cleavage/degradation of these proteins also resulted in a strong reduction of the reactivity with autoantibodies.

This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.
Cancer associated fibroblasts mitigate the efficacy of the combination of chemotherapy and BCL-xL targeting in triple negative breast cancer cells
Authors: Nocquet Lisa , Roul Julie , Duarte Laurine , Campone Mario , Juin Philippe P. , Souazé Frédérique
Published: October 2023

Triple negative breast cancers (TNBC) present a poor prognosis primarily due to their resistance to chemotherapy. This resistance is understood to associate with elevated expression of certain antiapoptotic members within the proteins of the BCL-2 family (namely BCL-xL, MCL-1 and BCL-2). These regulate cell death by inhibiting pro-apoptotic protein activation through binding and sequestration and they can be selectively antagonized by BH3 mimetics. Yet the individual influences of BCL-xL, MCL-1, and BCL-2 on the sensitivity of TNBC cells to chemotherapy, and their regulation by cancer-associated fibroblasts (CAFs), major components of the tumor stroma and key contributors to therapy resistance remain to be delineated. By utilizing engineered TNBC cell line MDA-MB-231 deficient in BCL-2 family proteins and BH3 mimetics, we show that BCL-xL and MCL-1 promote cancer cell survival by compensatory mechanisms. This cell line shows limited sensitivity to chemotherapy, in line with the clinical resistance observed in TNBC patients. We elucidate that BCL-xL plays a pivotal role in therapy response, as its depletion or pharmacological inhibition heightened chemotherapy effectiveness. Moreover, BCL-xL expression is associated to chemotherapy resistance in patient-derived tumoroids where its pharmacological inhibition enhances ex vivo response to chemotherapy. In a co-culture model of cancer cells and CAFs, we observe that even in a context where BCL-xL inhibition renders cancer cells more susceptible to chemotherapy, those in contact with CAFs display reduced sensitivity to chemotherapy. Thus CAFs exert a profound pro-survival effect in breast cancer cells, even in a setting highly favoring cell death through combined chemotherapy and inhibition of the main actor of chemoresistance, BCL-xL.