bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between social jetlag trajectories and body mass index among young adults
Authors: Chang Chia-Shuan , Chang Ling-Yin , Wu Chi-Chen , Chang Hsing-Yi
Published: October 2023

Study Objectives

This study employed longitudinal data collected repeatedly from individuals over the course of several years to examine the trajectories of social jetlag from ages 11 to 22 years and their associations with subsequent body mass index (BMI). Potential sex differences were also investigated.

Methods

Data were obtained from two longitudinal studies conducted in Taiwan (N = 4287). Social jetlag was defined as ≥ 2 hours of absolute difference in sleep midpoint between weekdays and weekends. BMI was calculated using weight (kg)/height(m)2 and categorized as underweight (<18 kg/m2), normal weight (18 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese (≥27 kg/m2). Group-based trajectory modeling and multinomial logistic regression were applied to investigate study objectives.

Results

Four distinct trajectories of social jetlag throughout the adolescent years were identified, with corresponding proportions as follows: low-stable (42%), moderate-decreasing (19%), low-increasing (22%), and chronic (17%) trajectories. Among males, the risk of being underweight (aOR, 1.96; 95% CI: 1.35 to 2.84) or obese (aOR, 1.40; 95% CI: 1.02 to 1.92) was higher in individuals with a low-increasing trajectory than in those with a low-stable trajectory. Among females, those with a low-increasing (aOR, 1.61; 95% CI: 1.02 to 2.54) or chronic (aOR, 2.04; 95% CI: 1.27 to 3.25) trajectory were at a higher risk of being obese relative to those with a low-stable trajectory.

Conclusions

Addressing the development of increasing or chronic social jetlag during adolescence can help prevent abnormal BMI in young adulthood. Practitioners should consider sex differences in treatment or consultation.
Does Local Political Representation Affect the Childcare Coverage Rate in Austrian Municipalities?
Authors: Walenta-Bergmann Carmen
Published: October 2023

Historically, the provision of childcare has been a forgotten area of Austrian family policy. During the last decade, much effort was made to catch up with other European countries, but notable differences persist between Austrian regions and municipalities. This article engages the following question: does local political representation affect the public childcare coverage rate in Austrian municipalities? Based on a unique longitudinal data set (2003–2018) containing yearly measures for 1,789 Austrian municipalities, several hierarchical regression models are calculated. The results reveal a positive effect of women and left-party share in the local councils as well as an interaction effect between the two. The findings suggest that women have an impact on the share of children in public childcare only in a right-wing-dominated political sphere.
Megasphaera elsdenii and Saccharomyces cerevisiae as direct fed microbials and their impact on ruminal microbiome during an acute acidosis challenge in continuous culture
Authors: Arce-Cordero Jose A , Liu Ting , Monteiro Hugo F , Jeong Kwang C , Faciola Antonio P
Published: October 2023

Our objective was to evaluate the effects of combinations of Saccharomyces cerevisiae and Megasphaera elsdenii as direct-fed microbials (DFM) on ruminal microbiome during an acute acidosis challenge in a continuous culture system. Treatments provided a DFM dose of 1 × 108 colony-forming unit (CFU)/mL, as follows: control (no DFM), YM1 (S. cerevisiae and M. elsdenii strain 1), YM2 (S. cerevisiae and M. elsdenii strain 2), and YMM (S. cerevisiae and half of the doses of M. elsdenii strains 1 and 2). We conducted four experimental periods of 11 d, which consisted of non-acidotic days (1 to 8) and acidotic challenge days (9 to 11) to establish acute ruminal acidosis conditions with a common basal diet containing 12% neutral detergent fiber and 58% starch. Treatments were applied from days 8 to 11, and samples of liquid and solid-associated bacteria were collected on days 9 to 11. Overall, 128 samples were analyzed by amplification of the V4 region of bacterial 16S rRNA, and data were analyzed with R and SAS for alpha and beta diversity, taxa relative abundance, and correlation of taxa abundance with propionate molar proportion. We observed a lower bacterial diversity (Shannon index, P = 0.02) when YM1 was added to the diet in comparison to the three other treatments. Moreover, compared to control, addition of YM1 to the diet increased relative abundance of phylum Proteobacteria (P = 0.05) and family Succinivibrioceae (P = 0.05) in the solid fraction and tended to increase abundance of family Succinivibrioceae (P = 0.10) and genus Succinivibrio (P = 0.09) in the liquid fraction. Correlation analysis indicated a positive association between propionate molar proportion and relative abundance of Proteobacteria (r = 0.36, P = 0.04) and Succinivibrioceae (r = 0.36, P = 0.05) in the solid fraction. The inclusion of YM1 in high-grain diets with a high starch content resulted in greater abundance of bacteria involved in succinate synthesis which may have provided the substrate for the greater propionate synthesis observed.
Macrophage RAGE deficiency prevents myocardial fibrosis by repressing autophagy‐mediated macrophage alternative activation
Authors: He Jiaqi , Wei Lan , Tan Shengan , Liang Birong , Liu Jing , Lu Lu , Wang Ting , Wang Junyan , Huang Yusheng , Chen Zixin , Li Huan , Zhang Lu , Zhou Zheng , Cao Yanhong , Ye Xiaohan , Yang Zhongqi , Xian Shaoxiang , Wang Lingjun
Published: October 2023

Myocardial fibrosis (MF) is the characteristic pathological feature of various cardiovascular diseases that lead to heart failure (HF) or even fatal outcomes. Alternatively, activated macrophages are involved in the development of fibrosis and tissue remodeling. Although the receptor for advanced glycation end products (RAGE) is involved in MF, its potential role in regulating macrophage function in cardiac fibrosis has not been fully investigated. We aimed to determine the role of macrophage RAGE in transverse aortic constriction (TAC)‐induced MF. In this study, we found that RAGE expression was markedly increased in the infiltrated alternatively activated macrophages within mice hearts after TAC. RAGE knockout mice showed less infiltration of alternatively activated macrophages and attenuated cardiac hypertrophy and fibrosis compared to the wild‐type mice. Our data suggest that mice with macrophage‐specific genetic deletion of RAGE were protected from interstitial fibrosis and cardiac dysfunction when subjected to pressure overload, which led to a decreased proportion of alternatively activated macrophages in heart tissues. Our in vitro experiments demonstrated that RAGE deficiency inhibited the differentiation into alternatively activated macrophages by suppressing autophagy activation. In the co‐culture system, in vitro polarization of RAW264.7 macrophages toward an alternatively activated phenotype stimulated the expression of α‐smooth muscle actin and collagen in cardiac fibroblasts. However, the knockdown of RAGE and inhibition of autophagy in macrophages showed reduced fibroblast‐to‐myofibroblast transition (FMT). Collectively, our results suggest that RAGE plays an important role in the recruitment and activation of alternatively activated macrophages by regulating autophagy, which contributes to MF. Thus, blockage of RAGE signaling may be an attractive therapeutic target for the treatment of hypertensive heart disease.
Spirituality and health outcomes within the context of social determinants of health
Authors: Wedgeworth Monika , Cody Shameka L.
Published: October 2023

Spirituality has a significant impact on patients' overall quality of life, however, it is often overlooked in the context of social determinants of health (SDOH). Nurses are well positioned to lead the expansion of SDOH models to include spirituality; however, routine nursing care does not emphasize spiritual assessment knowledge and skills. This article discusses spirituality and how it fits into the SDOH model, nursing education, and interdisciplinary healthcare. Spiritual care training may improve the confidence of nurses to integrate routine mental and spiritual assessments in clinical practice and serve as leaders in promoting spiritual care within interdisciplinary healthcare teams.
Patient Motivation to Reduce or Discontinue Opioids for Chronic Pain
Authors: Crouch Taylor B. , Donovan Emily , Smith Wally R. , Barth Kelly , Becker William C. , Svikis Dace
Published: October 2023

Objectives:

This study aimed to assess levels and predictors of self-efficacy and motivation to change opioid use among a community sample of patients using opioids for CP, as well as patient-reported barriers to pursuing opioid discontinuation.

Methods:

Participants with a variety of chronic pain conditions, recruited from ResearchMatch.org, completed a battery of electronic, self-report questionnaires assessing demographic and medical characteristics, pain treatment history, and levels of readiness, self-efficacy, and other attitudes toward reducing or discontinuing opioid use. Multiple regression analyses and analyses of variance were conducted to examine predictors of readiness and self-efficacy to change opioid use. A modified version of rapid qualitative analysis was utilized to analyze themes in participant responses to an open-ended item about “what it would take” to consider opioid discontinuation.

Results:

The final sample included N=119 participants, the majority of whom were female (78.2%), Caucasian (77.3%), and well-educated. Readiness and self-efficacy to decrease or stop opioid use were fairly low on a 0-10 Visual Analog Scale (2.6-3.8) and significantly higher to decrease than stop (P<0.01). Higher readiness to change was predicted by lower pain severity and higher concern about opioids, whereas higher self-efficacy was predicted by shorter pain duration. Results from the qualitative analyses revealed that availability of an alternative treatment option was the most commonly cited requirement to consider opioid discontinuation.

Discussion:

Patients with lower pain severity, shorter duration of pain, and higher concerns about opioids may be a prime target from a motivation standpoint for interventions addressing opioid tapering and discontinuation.
Anterior Cervical Discectomy and Fusion Versus Cervical Disc Replacement for a Workers’ Compensation Population in an Ambulatory Surgical Center
Authors: Patel Madhav R. , Jacob Kevin C. , Prabhu Michael C. , Shah Vivek P. , Vanjani Nisheka N. , Pawlowski Hanna , Singh Kern
Published: October 2023

Study Design:

Retrospective Cohort.

Objective:

To evaluate patient-reported outcome measures (PROM) and minimal clinically important difference (MCID) achievement outcomes between anterior cervical discectomy and fusion (ACDF) and cervical disk replacement (CDR) in the Workers’ Compensation (WC) population.

Summary of Background Data:

No studies to our knowledge have compared PROMs and MCID attainment between ACDF and CDR among patients with WC insurance undergoing surgery in an outpatient ambulatory surgical center (ASC).

Methods:

WC insurance patients undergoing primary, single/double-level ACDF/CDR in an ASC were identified. Patients were divided into ACDF versus CDR. PROMs were collected at preoperative/6-week/12-week/6-month/1-year timepoints, including PROMIS-PF, SF-12 PCS/MCS, VAS neck/arm, and NDI.

Results:

Seventy-nine patients were included, 51 ACDF/28 CDR. While operative time (56.4 vs. 54.4 min), estimated blood loss (29.2 vs. 25.9 mL), POD0 pain (4.9 vs. 3.8), and POD0 narcotic consumption (21.2 vs. 14.5 oral morphine equivalents) were higher in ACDF patients, none reached statistical significance (P>0.050, all). One-year arthrodesis rate was 100.0% among ACDF recipients with available imaging (n=36). ACDF cohort improved from preoperative for PROMIS-PF from 12 weeks to 1 year, SF-12 PCS at 6 months, all timepoints for VAS neck/arm, and 12 weeks/6 months for NDI (P≤0.044, all). CDR cohort improved from preoperative for PROMIS-PF at 6 months, VAS neck/arm from 12 weeks to 1 year, and NDI at 12 weeks/6 months (P≤0.049, all). CDR cohort reported significantly lower VAS neck at 12 weeks/1 year and VAS arm at 12 weeks (P≤0.039, all). MCID achievement rates did not differ.

Conclusion:

While operative duration/estimated blood loss/acute postoperative pain/narcotic consumption were, on average, higher among ACDF recipients, these were not statistically significant, possibly due to the limited sample size. ACDF and CDR ASC patients generally demonstrated comparable arm pain/disability/physical function/mental health, though neck pain was significantly lower at multiple timepoints among CDR patients. Clinically meaningful PROM improvements were comparable. Larger, multicentered studies are required to confirm our results.
Bioenergetic Crisis in ICU-Acquired Weakness Gene Signatures Was Associated With Sepsis-Related Mortality: A Brief Report
Authors: Kobara Seibi , Rad Milad G. , Grunwell Jocelyn R. , Coopersmith Craig M. , Kamaleswaran Rishikesan
Published: October 2023

OBJECTIVES:

To investigate the relationship between ICU-acquired weakness (ICUAW) signatures and sepsis-related mortality using gene expression from the blood within 24 hours of sepsis onset.

DESIGN:

Observational study using differential gene expression analysis.

SETTING:

Publicly available gene expression profile GSE54514, single-center medical and surgical ICU.

PATIENTS:

Patients with primary bacteremia- and respiratory-triggered sepsis including 8 nonsurvivors and 13 survivors who were 18 years old and older and admitted to ICU.

MEASUREMENTS AND MAIN RESULTS:

Among validated 526 ICUAW gene signatures, differential gene expression analysis controlling for age identified 38 significantly expressed genes between nonsurvivors and survivors. Functional enrichment analysis of differentially expressed ICUAW genes identified impaired cadherin binding, sarcomere formation, and energy metabolism among nonsurvivors.

CONCLUSIONS:

Our findings demonstrated a biological association between sepsis-related mortality and ICUAW signatures in the early phase of sepsis. Defects in energy metabolism and muscle fiber formation were associated with sepsis-related mortality.
Patient’s Perspective of Awake Proning: A Cross-Sectional Interview-Based Survey From COVID-19–Recovered Patients
Authors: Sethi Sher M. , Hirani Sana , Iqbal Rodaba , Ahmed Amber S.
Published: October 2023

IMPORTANCE AND OBJECTIVES:

To assess the knowledge, attitude, and practice of the patients who underwent prone positioning during their COVID-19 illness in the hospital.

DESIGN:

Cross-sectional study.

SETTING:

Aga Khan University Hospital, Karachi, Pakistan.

PARTICIPANTS:

COVID-19–recovered patients.

INTERVENTIONS:

None.

MAIN OUTCOMES AND MEASURES:

Knowledge was assessed by five questions with a dichotomous response (yes/no). An yes response was awarded 1 score. Since there were five questions, five would be the highest score. Patients’ perceptions of the therapy were assessed by four questions, each scored on a Likert scale of 5 (5 = strongly agree, 4 = agree, 3 = neither agree nor disagree, 2 = disagree, and 1 = strongly disagree). As it had four questions, the maximum score achieved could therefore be 20. Proning practices were assessed using seven questions: four were used to calculate practice scores, whereas three were open-ended regarding the patient’s experience. Each question carries a different score, and the maximum score was 8.

RESULTS:

The study included 98 patients. The mean age of the patients was 57 years (sd, 12.2 yr). Majority of the patients were males (70.4%). 69.1% of males and 76.6% of females fell in the poor knowledge group. The poor knowledge cohort had an educational level of 48% in high school, 45.5% in graduates, and 6% in postgraduates. Compared with 56.5% of males, 73% of females preferred prone positioning. Sixty percent of those with a high school education viewed prone positioning favorably, whereas 46% of those with graduate and postgraduate did. Seventy-nine percent of males and 63% of females scored positively on the practice questionnaire. Eighty percent of graduates and postgraduates preferred proning practices to 67% of participants with high school education levels.

CONCLUSIONS AND RELEVANCE:

Our study population had a little understanding of awake proning, found it unpleasant, and practiced for a shorter period than advised. Despite the overall negative attitude toward the position, our patients highly recommend this position to future patients.
Exposure to Perfluoroalkyl Substances and Hyperlipidemia Among Adults
Authors: Xing Weilong , Liang Mengyuan , Gu Wen , Wang Zhen , Fan Deling , Zhang Bing , Sun Shuai , Wang Lei , Shi Lili
Published: October 2023

Background

The present study aims to explore the relationship between perfluoroalkyl substances (PFAS) exposure and hyperlipidemia using data from the National Health and Nutrition Examination Survey.

Methods

A total of 1600 subjects were included in the analysis, and nine kinds of PFAS were measured. Multivariate logistic regression analysis was performed to explore the association between serum PFAS and hyperlipidemia.

Results

Compared with the lowest quartile of perfluoromethylheptane sulfonic acid isomers (Sm-PFOS), the percentage change for hyperlipidemia was 57% and 41% in the third and highest quartile of PFOS. The positive association between Sm-PFOS and hyperlipidemia remained significant in population younger than 60 years, and the odds ratio for hyperlipidemia in fourth quartile of Sm-PFOS was 1.81.

Conclusions

These findings indicated that serum Sm-PFOS was independently associated with a higher risk for hyperlipidemia. The epidemiological study warrants further study to elucidate the causal relationship between them.
Excellence in Academic Physical Therapy: Promoting a Culture of Data Sharing
Authors: North Sara E. , Kosior Ken , Altenburger Peter , Binder-Macleod Stuart , Brechter Jacklyn , Deoghare Harsha , Topp Kimberly
Published: October 2023

Background and Purpose.

Data analytics are increasingly important in health professions education to identify trends and inform organizational change in rapidly evolving environments. Unfortunately, limitations exist in data currently available to determine physical therapy (PT) academic excellence. It is imperative that the American Council of Academic Physical Therapy (ACAPT) be able to demonstrate data-informed progress in addressing the common challenges faced by Doctor of Physical Therapy programs.

Position and Rationale.

The Task Force to Explore Data and Technology to Evaluate Program Outcomes was convened by ACAPT to explore current and desired data and the needs, technology, and costs that would be required for ACAPT to assess program outcomes relative to excellence criteria. The Task Force performed a gap analysis of measures of excellence, provided evidence-based recommendations for advancing the use of data and technology systems in academic PT, and generated a comprehensive Assessment Excellence Map that subsequently led to a new streamlined Excellence Framework in the launch of the ACAPT Center for Excellence.

Discussion and Conclusion.

The vision of universal excellence in PT education necessitates clear alignment and centralization of common data to support efficient processes to assess excellence. The transformative nature of data is untapped in PT academic endeavors, and nascent work to establish and sustain a culture of centralized data sharing and assessment will help to drive program-level and profession-level excellence in PT education.
Determinants of Cochlear Implant Satisfaction and Decisional Regret in Adult Cochlear Implant Users
Authors: Shannon Christian M. , Schvartz-Leyzac Kara C. , Dubno Judy R. , McRackan Theodore R.
Published: October 2023

Objective

Determine associations expected and actual cochlear implant (CI) outcomes, decisional regret, and satisfaction in experienced adult CI users.

Study Design

Cross-sectional cohort study.

Setting

Tertiary medical center.

Patients

Thirty-nine adult CI users meeting traditional bilateral hearing loss indications with ≥12 months CI experience.

Interventions/Main Outcome Measures

Patients completed the validated Satisfaction with Amplification in Daily Living and Decisional Regret instruments. Pre- and post-CI outcomes (CI Quality of Life [CIQOL]-Expectations; CIQOL-35 Profile; CNC words, AzBio Sentences) were obtained from a prospectively maintained clinical database.

Results

Using established cutoff scores, 29% of patients reported a substantial degree of post-CI decisional regret. For each CIQOL domain, patients without decisional regret obtained post-CI outcome scores closer to pre-CI expectations compared with patients with decisional regret (d = 0.34 to 0.91); similar results were observed with higher CI user satisfaction (d = 0.17–0.83). Notably, the degree of pre- to post-CI improvement in CNC or AzBio scores did not differ between patients with and without decisional regret or with lower and higher satisfaction. Finally, greater pre-/postimprovement in CIQOL-35 Profile domain scores demonstrated far stronger associations with lower decisional regret and higher satisfaction than changes in speech recognition scores.

Conclusions

Patients with better alignment of their pre-CI expectations and post-CI outcomes and greater pre-/post-CIQOL improvement had lower decisional regret and higher satisfaction. This emphasizes the importance of evidence-based pre-CI counseling regarding real-world CI benefits and caution against assuming that improvements in speech recognition are related to patient satisfaction.
Albumin Infusion Reduces Fluid Loading for Postresuscitation Syndrome in a Pig Model of Refractory Cardiac Arrest Resuscitated With Venoarterial Extra Corporeal Membrane Oxygenation
Authors: Lescroart Mickaël , Pequignot Benjamin , Orlowski Sophie , Reynette Nathan , Martini Bana , Albuisson Eliane , Tran N’Guyen , Grandmougin Daniel , Levy Bruno
Published: October 2023

Hemodynamic instability in postresuscitation syndrome worsens survival and neurological outcomes. Venoarterial extracorporeal membrane oxygenation (VA ECMO) for refractory cardiac arrest might improve outcomes. Hemodynamical support under VA ECMO relies on norepinephrine and crystalloids. The present work aims to assess the effects of albumin (ALB) infusion in a swine model of ischemic refractory cardiac arrest implanted by VA ECMO. Cardiac arrest was performed in 18 pigs and VA ECMO was initiated after 30 minutes cardiopulmonary resuscitation (CPR). Pigs were randomly assigned to standard care (norepinephrine + crystalloids) versus ALB group (ALB + standard care). Hemodynamical assessments were performed over 6 hours. Severe hypoalbuminemia was observed in the control group and could be reversed with ALB infusion. Total crystalloid load was significantly reduced with ALB infusion (1,000 [1,000–2,278] ml vs. 17,000 [10,000–19,000] ml, ALB versus control group, respectively, p < 0.001). There was no significant impact with regard to lactate clearance (29.16% [12.5–39.32] and 10.09% [6.78–29.36] for control versus ALB groups, respectively, p = 0.185), sublingual capillary microvascular parameters, or cerebral near-infrared spectrometer (NIRS) values. Compared to standard care, ALB infusion was highly effective in reducing fluid loading in a porcine model of postresuscitation syndrome after refractory cardiac arrest treated with VA ECMO.
Depigmentation of Melanin-containing Tissues Using Hypochlorous Acid to Enhance Hematoxylin-eosin and Immunohistochemical Staining
Authors: Wang Lu , Wang Gangping
Published: October 2023

Pathologists diagnose diseases by observing the histologic and cellular morphology microscopically. However, the high pigmentation in melanin-containing tumors can hide the tumor cell structures, making diagnosing challenging. Previously, hydrogen peroxide and potassium permanganate were utilized for melanin bleaching with several limitations. For instance, hydrogen peroxide has a weak bleaching ability, and the process is time-consuming (12 h). Meanwhile, potassium permanganate affects the antigenicity of antigens and is unsuitable for immunohistochemical (IHC) staining. In this study, the hypochlorous acid (HClO) solution was applied to hematoxylin-eosin and IHC staining of melanin tissue sections. The study discovered that 1% HClO could completely bleach melanin particles in tumor tissues in a short period (19.95 ± 2.53 min) without compromising the hematoxylin-eosin staining. In addition, 2% HClO was utilized for bleaching at room temperature for 61.17 ± 4.32 minutes after the tissue was incubated with 3,3’-diaminobenzidine in IHC staining. This treatment effectively removed melanin without negatively impacting 3,3’-diaminobenzidine signal expression, thus ensuring that the sections met the necessary diagnostic requirements. Therefore, this method could facilitate pathologists in disease diagnosis of melanin-containing tissues.
Anatomic Location of Tissue Expander Placement Is Not Associated With Delay in Adjuvant Therapy in Women With Breast Cancer
Authors: Elder Erin , Fasola Carolina , Clavin Nicholas , Hecksher Anna , Trufan Sally , Schepel Courtney , Donahue Erin , Warren Yancey , White Richard L. , Hadzikadic-Gusic Lejla
Published: October 2023

Background

Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown.

Methods

A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy.

Results

Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% (P< 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction (P <0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival.

Conclusions

Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment.
Lower Extremity Pediatric Tissue Expansion
Authors: Yusuf Cynthia T. , Lopez Christopher D. , Girard Alisa O. , Khoo Kimberly H. , Yang Robin , Redett Richard J.
Published: October 2023

Background

Tissue expansion is a well-established approach to soft tissue reconstruction in the pediatric population for lower extremity pathologies. Unfortunately, complication rates range from 19% to 40% in literature, including infection and implant extrusion, leading to delays in reconstruction. These challenges have prompted investigation toward categorizing risk factors for lower extremity tissue expander placement.

Methods

A retrospective study of pediatric patients who underwent lower extremity tissue expander placement by the senior author (R.J.R.) was performed over a 16-year period. Patient charts were reviewed to categorize baseline and operative characteristics. Primary outcome variables were surgical-site infection, expander extrusion, and expander deflation. Univariate and multivariate logistic regressions were performed (α < 0.05).

Results

There were 59 tissue expanders in our cohort. The overall complication rate was 27.1% with a 77.2% successful reconstruction rate. Greater number of expanders placed during 1 operation is associated with 2.5 increased odds of having any complication and is associated with 0.4 decreased odds of having a successful reconstruction. Incisions made in scar tissue for expander placement appear to be associated with a greater than 7 times increased odds of readmission.

Conclusions

Reconstruction of soft tissue pathologies using lower extremity tissue expanders in the pediatric population is an effective yet challenging technique. This study identified that the number of expanders inserted during 1 operation, incisions made over scar tissue, and expanders placed in the anterior thigh were correlated with having a negative impact on reconstructive outcomes. Extra care should be taken with patients who require multiple expanders during 1 operation and with choosing the location and incision of expander placement.
Critical systolic blood pressure threshold for endovascular aortic occlusion – A multinational analysis to determine when to place a REBOA
Authors: Ordoñez Carlos A. , Parra Michael W. , Caicedo Yaset , Rodríguez-Holguín Fernando , García Alberto F. , Serna José J. , Serna Carlos , Franco María Josefa , Salcedo Alexander , Padilla-Londoño Natalia , Herrera-Escobar Juan P. , Zogg Cheryl , Orlas Claudia P. , Palacios Helmer , Saldarriaga Luis , Granados Marcela , Scalea Thomas , McGreevy David T. , Kessel Boris , Hörer Tal M. , Dubose Joseph , Brenner Megan ,   AAST-AORTA Investigators*; ABO Trauma Registry Group*
Published: October 2023

Background

Systolic blood pressure (SBP) is a potential indicator that could guide when to use a resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma patients with life-threatening injuries. This study aims to determine the optimal SBP threshold for REBOA placement by analyzing the association between SBP pre-REBOA and 24-hour mortality in severely injured hemodynamically unstable trauma patients.

Methods

We performed a pooled analysis of the Aortic Balloon Occlusion (ABO) trauma and AORTA registries. These databases record the details related to the use of REBOA and include data from 14 countries worldwide. We included patients who had suffered penetrating and/or blunt trauma. Patients who arrived at the hospital with a SBP pre-REBOA of 0 mm Hg and remained at 0 mm Hg after balloon inflation were excluded. We evaluated the impact that SBP pre-REBOA had on the probability of death in the first 24 hours.

Results

A total of 1107 patients underwent endovascular aortic occlusion, of these, 848 met inclusion criteria. The median age was 44 years [IQR, 27-59 years] and 643(76%) were male. The median injury severity score was 34 [IQR, 25-45]. The median SBP pre-REBOA was 65 mm Hg [IQR: 49-88 mm Hg]. Mortality at 24-hours was reported in 279 (32%) patients. Math modelling shows that predicted probabilities of the primary outcome increased steadily in SBP pre-REBOA below 100 mm Hg. Multivariable mixed-effects analysis shows that when SBP pre-REBOA was lower than 60 mm Hg, the risk of death was more than 50% (relative risk, 1.5; 95%CI, 1.17-1.92; P = .001)

Discussion

In patients who do not respond to initial resuscitation, the use of REBOA in SBP’s between 60- and 80-mm Hg may be a useful tool in resuscitation efforts before further decompensation or complete cardiovascular collapse. The findings from our study are clinically important as a first step in identifying candidates for REBOA.

Study Type

Observational Study

Level of Evidence

Level IV
Explore intersection genes of oxymatrine and COVID-19 with lung cancer as potential therapeutic targets based on network pharmacology
Authors: Wu Wei , Cheng Chuan , Yuan Dongdong , Peng Li , Li Le
Published: October 2023

Introduction. Oxymatrine is a natural quinazine alkaloid extracted from Sophora flavescens and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer.

Hypothesis/Gap Statement. Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients.

Aim. The objective of this study was to assess the pharmacological mechanisms and targets of oxymatrine in relation to COVID-19 lung cancer.

Methodology. Utilizing network pharmacology analysis, a selection of 2628 genes were identified as co-targets for both COVID-19 and lung cancer. Subsequently, a clinicopathological analysis was conducted by integrating RNA-Seq and clinical data obtained from the TCGA-LUAD lung cancer dataset, which was acquired from the official TCGA website. The identification of pharmacological targets for oxymatrine was accomplished through the utilization of various databases including Pharm mapper, SWISS Target prediction, and STITCH. These identified targets were further investigated for protein-protein interaction (PPI) using STRING, as well as for gene ontology (GO) and KEGG pathways.

Results. The effects of oxymatrine on COVID-19-induced lung cancer were mediated by immune regulation, cytoprotection, antiviral, and anti-inflammatory activities, immune regulation, and control of related signalling pathways, including the formation of the neutrophil extracellular trap, phagosome, Toll-like receptor signalling pathway, apoptosis, proteoglycans in cancer, extracellular matrix disassembly, and proteolysis involved in cellular protein catabolism. Furthermore, important substances and genes like ALB, MMP3, MMP1, and TLR4 may affect how oxymatrine suppresses lung cancer/COVID-19 development.

Conclusion. To treat COVID-19 or lung cancer paired with COVID-19, oxymatrine may improve the therapeutic efficacy of current clinical antiviral medicines and immunotherapy.
Marker effect p-values for single-step GWAS with the algorithm for proven and young in large genotyped populations
Authors: Leite Natália Galoro , Bermann Matias , Tsuruta Shogo , Misztal Ignacy , Lourenco Daniela
Published: October 2023

Background

Although single-step GBLUP (ssGBLUP) is a breeding value method, single-nucleotide polymorphism (SNP) effects can be backsolved from ssGBLUP genomic estimated breeding values (GEBV), and p-values can be obtained as a measure of estimation certainty. This enables single-step genome-wide association studies (ssGWAS). However, obtaining p-values for ssGWAS relies on the inversion of dense matrices, which poses computational limitations in large genotyped populations. In this study, we present an algorithm to approximate p-values for SNP in ssGWAS with many genotyped animals. The approximation relies on the algorithm for proven and young (APY) and submatrices for core animals. To test that, we first compared SNP p-values obtained with an exact inversion using the genomic relationship matrix (G−1) for 50K genotyped animals to those estimated with an exact inversion usingand those obtained with the proposed approximation based on. Then, we compared these results with those obtained with the proposed approximation using 450K genotyped animals.

Results

The same genomic regions in chromosomes 7 and 20 were identified with p-values obtained withG−1,, and the approximation based onwhen using 50k genotyped animals and 1.5M in the pedigree. In terms of computational requirements, obtaining p-values with the approximation based onrepresented a reduction of 38 times in wall-clock time and ten times in memory requirement compared to using the exact inversion with. When the approximation was applied to a population of 450K genotyped animals and 1.8 in the pedigree, apart from the two genomic regions in chromosomes 7 and 20 previously identified with the smaller genotyped population, two new significant regions on chromosomes 6 and 14 were uncovered, indicating an increase in GWAS detection power when including more genotypes in the analyses. The process of obtaining p-value with the approximation and 450K genotyped individuals took 24.5 wall-clock hours and 87.66 GB of memory, which is expected to increase linearly with the addition of noncore genotyped individuals.

Conclusions

With an algorithm that approximates the prediction error variance of SNP effects based on APY, ssGWAS with p-values for SNP is possible in large genotyped populations. The computational cost of obtaining p-values in ssGWAS is no longer a limitation in extensive populations with many genotyped animals.
A gene with a thousand alleles: the HYPer-variable effectors of plant-parasitic nematodes
Authors: Sonawala Unnati , Beasley Helen , Thorpe Peter , Varypatakis Kyriakos , Senatori Beatrice , Jones John T. , Derevnina Lida , den Akker Sebastian Eves-van
Published: October 2023

Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms, including effectors and immune receptors, are part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the HYPer-variable (HYP) effectors of plant-parasitic nematodes.

We discovered single effector gene loci that can harbour potentially thousands of allelic variants. These alleles vary in the number, but principally in the organisation, of motifs within a central Hyper Variable Domain (HVD). Using targeted long-read sequencing, we dramatically expand the HYP repertoire of two plant-parasitic nematodes,Globodera pallidaandG. rostochiensis,such that we can define distinct sets of species-specific “rules” underlying the apparently flawless genetic rearrangements. Finally, by analysing the HYP complement of 68 individual nematodes we made the unexpected finding that despite the huge number of alleles, most individuals are homozygous. Taken together, these data point to a novel mechanism of programmed genetic variation, termed HVD-editing, where alterations are locus-specific, strictly governed by rules, and can theoretically produce thousands of variants without errors.
Predicting functional consequences of recent natural selection in Britain
Authors: Poyraz Lin , Colbran Laura L. , Mathieson Iain
Published: October 2023

Ancient DNA can directly reveal the contribution of natural selection to human genomic variation. However, while the analysis of ancient DNA has been successful at identifying genomic signals of selection, inferring the phenotypic consequences of that selection has been more difficult. Most trait-associated variants are non-coding, so we expect that a large proportion of the phenotypic effects of selection will also act through non-coding variation. Since we cannot measure gene expression directly in ancient individuals, we used an approach (Joint-Tissue Imputation; JTI) developed to predict gene expression from genotype data. We tested for changes in the predicted expression of 17,384 protein coding genes over a time transect of 4500 years using 91 present-day and 616 ancient individuals from Britain. We identified 28 genes at seven genomic loci with significant (FDR < 0.05) changes in predicted expression levels in this time period. We compared the results from our transcriptome-wide scan to a genome-wide scan based on estimating per-SNP selection coefficients from time series data. At five previously identified loci, our approach allowed us to highlight small numbers of genes with evidence for significant shifts in expression from peaks that in some cases span tens of genes. At two novel loci (SLC44A5andNUP85), we identify selection on gene expression not captured by scans based on genomic signatures of selection. Finally we show how classical selection statistics (iHS and SDS) can be combined with JTI models to incorporate functional information into scans that use present-day data alone. These results demonstrate the potential of this type of information to explore both the causes and consequences of natural selection.
Membrane Mimetic-Dependence of GPCR Energy Landscapes
Authors: Thakur Naveen , Ray Arka Prabha , Lyman Edward , Gao Zhan-Guo , Jacobson Kenneth A. , Eddy Matthew T.
Published: October 2023

Protein function strongly depends on temperature, which is related to temperature-dependent changes in the equilibria of protein conformational states. We leveraged variable-temperature19F-NMR spectroscopy to interrogate the temperature dependence of the conformational landscape of the human A2Aadenosine receptor (A2AAR), a class A GPCR. Temperature-induced changes in the conformational equilibria of A2AAR in lipid nanodiscs were markedly dependent on the efficacy of bound drugs. While antagonist complexes displayed only modest changes as the temperature rose, both full and partial agonist complexes exhibited substantial increases in the active state population. Importantly, the temperature-dependent response of complexes with both full and partial agonists exhibited a pronounced sensitivity to the specific membrane mimetic employed. In striking contrast to observations within lipid nanodiscs, in detergent micelles the active state population exhibited different behavior for A2AAR complexes with both full and partial agonists. This underscores the importance of the protein environment in understanding the thermodynamics of GPCR activation.

Highlights

Active A2AAR population increases with increasing temperature in lipid nanodiscs

Active A2AAR population exhibits different temperature dependence in detergents

Partial agonist complexes present a unique conformational state in nanodiscs

Temperature dependence of partial agonist equilibria depends on membrane mimetic
Early syphilis in Guangzhou, China: presentation, molecular detection ofTreponema pallidum, and genomic sequences in clinical specimens and isolates obtained by rabbit infectivity testing
Authors: Yang Ligang , Zhang Xiaohui , Chen Wentao , Seña Arlene C. , Zheng Heping , Jiang Yinbo , Zhao Peizhen , Chen Rongyi , Wang Liuyuan , ke Wujian , Salazar Juan C. , Parr Jonathan B. , Tucker Joseph D. , Hawley Kelly L. , Caimano Melissa J. , Hennelly Christopher M. , Aghakanian Farhang , Zhang Feifei , Chen Jane S. , Moody M. Anthony , Radolf Justin D. , Yang Bin
Published: October 2023

Background

The global resurgence of syphilis requires novel prevention strategies. Whole genome sequencing (WGS) ofTreponema pallidum(TPA) using different specimen types is essential for vaccine development.

Methods

Patients with primary (PS) and secondary (SS) syphilis were recruited in Guangzhou, China. We collected ulcer exudates and blood from PS participants, and skin biopsies and blood from SS participants forTPA polApolymerase chain reaction (PCR); ulcer exudates and blood were also used to isolateTPAstrains by rabbit infectivity testing (RIT).TPAWGS was performed on 52 ulcer exudates and biopsy specimens and 25 matched rabbit isolates.

Results

We enrolled 18 PS and 51 SS participants from December 2019 to March 2022. Among PS participants,TPADNA was detected in 16 (89%) ulcer exudates and three (17%) blood specimens. Among SS participants,TPADNA was detected in 50 (98%) skin biopsies and 27 (53%) blood specimens.TPA was isolated from 48 rabbits, with a 71% (12/17) success rate from ulcer exudates and 69% (36/52) from SS bloods. Twenty-three matched SS14 clade genomes were virtually identical, while two Nichols clade pairs had discordanttprKsequences. Forty-two of 52 uniqueTPAgenomes clustered in an SS14 East Asia subgroup, while ten fell into two East Asian Nichols subgroups.

Conclusions

OurTPAdetection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS whole blood, with RIT isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

We performedTreponema pallidummolecular detection and genome sequencing from multiple specimens collected from early syphilis patients and isolates obtained by rabbit inoculation. Our results support the use of whole genome sequencing from rabbit isolates to inform syphilis vaccine development.
Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced ECG analysis
Authors: Hughes Rebecca K. , Thornton George D. , Malcolmson James W. , Pierce Iain , Khoury Shafik , Hornell Amanda , Knott Kristopher , Captur Gabriella , Moon James C. , Schlegel Todd T. , Ugander Martin
Published: October 2023

Background

Typical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM.

Methods

A-ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM (n=75 overt, n=32 relative [<15mm hypertrophy]), a subgroup of which underwent cardiovascular magnetic resonance, n=92), and comparator subjects (n=2449), including healthy volunteers (n=1672), patients with coronary artery disease (n=372), left ventricular electrical remodelling (n=108), ischemic (n=114) or non-ischemic cardiomyopathy (n=57), and asymmetrical septal hypertrophy (ASH) HCM (n=126).

Results

Multivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy (area under the receiver operating characteristics curve (AUC) [bootstrapped 95% confidence interval] 0.982 [0.965– 0.993]. Linear discriminant analysis also diagnosed ApHCM with high accuracy (AUC 0.989 [0.986–0.991]).

Conclusion

Explainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting future diagnostic and management strategies may incorporate both features.
Microtubule reorganization during mitotic cell division in the dinoflagellateOstreospiscf.ovata
Authors: Velasquez-Carvajal David , Garampon Flavie , Lemée Rodolphe , Schaub Sebastian , Castagnetti Stefania
Published: October 2023

Dinoflagellates are marine organisms that undergo seasonal explosive proliferation events known as algal blooms. Vegetative cell proliferation is a main contributing factor in these events. However, mechanistical understanding of mitosis and cytokinesis in dinoflagellate remains rudimentary. Using an optimized immunofluorescence protocol, we analysed changes in microtubule organization occurring during the mitotic cycle of the toxic dinoflagellateOstreopsiscf.ovata.This study revealed important features of dinoflagellate cell division. We find that the two flagella and the cortical microtubule array persist throughout the mitotic cycle. Two microtubule bundles are present in the cytoplasm originating from the ventral area, where the basal bodies are located: a cortical bundle and a cytoplasmic ventral bundle. The latter associates with the nucleus in the cell centre in preparation for mitosis and with the acentrosomal extranuclear spindle during mitosis. Analysis of tubulin post-translational modifications identifies two populations of spindle microtubules: polar acetylated microtubules whose length is stable throughout mitosis and central tyrosinated microtubules which elongate during chromosome segregation. During cell division a microtubule rich structure forms along the dorsal-ventral axis, associated with the site of cytokinesis, consistent with a cytokinetic mechanism independent of the actomyosin ring typical of animal and yeast cells.

Summary statement

Our study describes special features of mitosis and cytokinesis in dinoflagellates and uncovers a new alternative mechanism for cell division, highlighting the plasticity of cell biological process in eukaryotic cells.