bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining the Effect of Intraoperative TXA on Postoperative Blood Loss in ACDF
Authors: Steinle Anthony M. , Fogel Jessa D. , Chen Jeffrey W. , Chanbour Hani , Vaughan Wilson E. , Karwandyar Ayub , Croft Andrew J. , McDonough Judy , Chandler Philip J. , Gardocki Raymond , Zuckerman Scott L. , Abtahi Amir M. , Stephens Byron F.
Published: August 2023

Study Design:

Retrospective cohort study using prospectively collected data.

Objective:

To determine the effectiveness of intraoperative tranexamic acid (TXA) in anterior cervical discectomy and fusion (ACDF) on postoperative blood loss.

Summary of Background Data:

TXA has been proven to be a safe and effective agent in reducing blood loss after cervical surgery; however, its efficacy when used intraoperatively for ACDF surgeries had yet to be researched. Currently, there are few studies examining the effects of intraoperative TXA in cervical spinal fusion, and none specifically examining TXA use in ACDF.

Methods:

A tertiary medical center’s prospectively collected spine registry was queried between 1/1/18 and 12/1/21 for all patients who underwent elective ACDF surgery and received a drain postoperatively. Patients were separated into 2 groups; those who had received intraoperative TXA and those who did not. Baseline demographic and operative variables were collected from the registry. The primary outcome was postoperative blood loss over a 24-hour period. Secondary outcomes included total drain output, intraoperative estimated blood loss, operative duration, drain duration, changes in preoperative to postoperative hemoglobin and hematocrit levels, and rate of transfusions, complications, revisions, and reoperations. Univariate and multivariate regression analyses were performed.

Results:

Two hundred eighty-six patients were included. One hundred ninety patients underwent ACDF and did not receive intraoperative TXA, whereas 96 patients underwent ACDF and did receive TXA. There were no differences in any demographic or baseline variables. Multivariate analysis showed intraoperative TXA was associated with shorter drain duration (β=−5.74, 95% CI: −10.9 to −0.53, P=0.031) and reduction in 24-hour drain output (β=−12.2, 95% CI: −19.4 to −4.89, P=0.001) and total drain output (β=−14.0, 95% CI: −22.9 to −5.05, P=0.002).

Conclusions:

TXA use during ACDF procedures leads to a decrease in perioperative blood loss and faster drain removal. TXA is an effective and safe agent for reducing perioperative blood loss in ACDF surgery.

Level of Evidence:

III
ATP Stress Myocardial Contrast Echocardiography Assessment of Coronary Microvascular Disease with Spasmodic Characteristics: A Case Report
Authors: Liu Xuebing , Li Chunmei
Published: August 2023

Here, a patient with chest pain and <50% stenosis on coronary angiography, where ATP stress myocardial contrast echocardiography (MCE) revealed that coronary flow reserve was reduced to 1.71 was presented. Perfusion delay occurred in the left ventricular wall of the apex of the heart before ATP stress, and the perfusion delay area was significantly reduced at peak stress. Similar to the characteristics of “reverse redistribution” of radionuclide myocardium perfusion in coronary vasospasm, the delayed perfusion area in the recovery period was larger than that detected before stress. Together with increased spectral resistance of the distal segment of left anterior descending coronary artery and chest pain, these findings indicated coronary microvascular disease with spasmodic characteristics in this patient. The perfusion characteristics on ATP stress determined by MCE and changes in coronary spectrum have value for the diagnosis and treatment of coronary microvascular disease with spasmodic characteristics.
Postpartum maternal tachycardia – diagnostic pitfalls!
Authors: Mathur Charlotte , Tohani Arun , Patil Vinod , Khan Ayub , Otigbah Chineze
Published: August 2023

Purpose of review

Maternal tachycardia is a common sign with a multitude of causes. We attempt to look at the most common sinister ones in the postpartum period.

Recent findings

Current guidelines differ in the definition of maternal tachycardia. It has been associated with adverse outcomes such as increased length of stay as well as higher mortality if there is underlying peripartum cardiomyopathy. Some recent studies look at common investigations and how these apply to peripartum women, such as ECG markers of arrhythmogenesis, reference ranges for PCT and echocardiogram findings during pregnancy prior to diagnosis of peripartum cardiomyopathy.

Physiological changes make it difficult to interpret maternal tachycardia and thus how best to manage it. We propose the idea of a three-step approach for the assessment of patients, aiming to identify causes including tachyarrhythmias, obstetric haemorrhage, sepsis, venous thromboembolism and peripartum cardiomyopathy.

The first step ‘BEDSIDE’ applies to all patients looking at observations, history and examination. The second step ‘BASIC’, applies to most patients and covers ECG and basic blood tests. The final step ‘EXTRA’ assesses the need for further investigations including additional blood tests and imaging. By using this model, clinicians and healthcare professionals should be able to rationalise the need for more invasive investigations whilst maintain good high-quality care.
Update on gestational diabetes and adverse pregnancy outcomes
Authors: Ugwudike Bryan , Kwok ManHo
Published: August 2023

Purpose of review

To explore the recent literature concerning the effect of gestational diabetes (GDM) on adverse pregnancy outcomes (APO).

Recent findings

Literature search on PubMed, Medline and British Journal of Obstetrics and Gynaecology was conducted using keywords. Search fields were filtered down to include articles from 2019 onwards. GDM is common during pregnancy and is on the rise because of increasing in obesity rates. GDM tended to show an increased risk of APO compared with non-GDM. Treatment of these pregnancies tended to improve these outcomes, particularly for LGA and macrosomia. Additional factors such as prepregnancy BMI and gestational weight gain (GWG) were shown to influence risk. More studies are needed to determine the true effect on postpartum haemorrhage (PPH) and induction of labour (IOL).

The review agrees with the findings from previous studies and adds to the current literature. Early intervention to manage glycaemic control and GWG may help improve these outcomes. Public health strategies that tackle obesity rates will help to reduce prepregnancy BMI and, therefore, rates of GDM.
Oral gonadotrophin-releasing hormone (GnRH) antagonists: the continuing search for the ideal nonsurgical therapy of uterine fibroids with a cautionary tale
Authors: Sim-Ifere Ogagaoghene , Aref-Adib Mehrnoosh , Odejinmi Funlayo
Published: August 2023

Purpose of review

Uterine fibroids are very common with a prevalence of over 70%. They present a significant economic and psychological burden. A variety of nonsurgical treatments exist for its management encompassing hormonal and nonhormonal methods. Gonadotrophin-releasing hormone (GnRH) antagonists are a novel treatment for uterine fibroids. They cause a rapid reduction in endogenous GnRH, leading to a dose-dependent reduction in levels of oestradiol and progesterone, thus reduction in bleeding. The addition of hormones, estrogen, and progesterone, known as add-back therapy, helps curb the menopausal side effects. As such, they pose a potential long-term nonsurgical therapy for management of symptomatic fibroids.

Recent findings

There are various uses of GnRH antagonists and the results from the clinical trials are promising. Caution needs to be taken when new treatment options are introduced with audit and data collection tools in place to assess effectiveness as well as any side effects.

This article highlights the uses of GnRH antagonists in practice and reflects on previous novel treatments for fibroids with a focus on Ulipristal acetate. It states the importance of using audit tools and multiinstitutional databases to prevent and allow early discovery of issues such as those that encumbered Ulipristal.
A comparative analysis of ambulatory blood pressure characteristics in acute stroke and non-stroke Indian patients
Authors: Hegde Subhaschandra B. , Aroor Shivaramakrishna , Anupama Yedabettu Janardana , Hegde Shrikanth N. , Prajapati Hiren , Verberk Willem J.
Published: August 2023

Objective:

The objective of this study is to identify 24-h blood pressure (BP) characteristics after acute stroke in Indian hospitalized patients.

Methods:

In total, 769 patients [284 women (36.9%)] admitted at a hospital in South India were analyzed. Of these, 364 patients (47.3%) had recently experienced stroke. All patients underwent ambulatory blood pressure measurement (ABPM) so that ABPM patterns and ABPM risk parameters of stroke and non-stroke patients could be compared. Additionally, to investigate the relationship between ABPM parameters and stroke, a stepwise logistic regression analysis was employed.

Results:

Stroke patients had significantly higher BP than non-stroke patients (24-h ABP: 145.0 ± 22.1 vs. 133.7 ± 20.5 mmHg, P < 0.001), with similar dipping status. ABPM parameters mostly associated with stroke (all P < 0.001) were: nighttime [odds ratios (OR): 1.587, 95% confidence interval (95% CI): 1.341–1.885], 24-h (1.584, 1.34–1.881), minimum nighttime (1.582, 1.339–1.879), daytime (1.540, 1.304–1.827), and morning SBP (1.517, 1.287–1.797). Non-dipping status was relatively more common in stroke patients (79% vs. 71%, P < 0.05) but dipping percentage did not show a significant linear relationship with stroke.

Conclusion:

Several ABPM characteristics were strongly associated with stroke in Indian hospitalized patients. Specifically, minimum nighttime and average morning SBP may be considered as important and practical parameters for its relationship with stroke.
Defining optimal blood pressure control for pre-transplant end-stage renal disease patients: scoping review
Authors: Nishimura Yoshito , Khan Mohammad , Lee Benjamin , Arayangkool Chinnawat , Zhang James , Palanisamy Amudha , Banerjee Dipanjan , Izutsu Christie
Published: August 2023

Background

Strict blood pressure control is essential to prevent cardiovascular disease and is associated with decreased mortality. However, in patients with end-stage renal disease awaiting renal transplantation, the level of optimal blood pressure control is not yet defined.

Methods

Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including ‘end-stage renal disease’, ‘blood pressure’, and ‘pre-transplant’ from their inception to 7 August 2022.

Results

Seven observational studies, including one population-based study, were included in the review. Most studies investigated factors associated with post-transplant graft failure or mortality. There was considerable heterogeneity in defining optimal pre-transplant blood pressure measurement frequency among studies (average of three measurements vs. single measurement). One study suggested that low pre-transplant diastolic blood pressure (<50 mmHg) was associated with lower odds of delayed graft failure and mortality. Two studies noted that pre-transplant hypertension, or clinical criteria of hypertension that were present prior to transplant, was associated with post-transplant adverse outcomes. In contrast, one study noted that pre-transplant sustained hypotension with mean blood pressure <80 mmHg, was associated with a higher frequency of delayed graft failure.

Conclusion

This systematic review summarizes the current evidence regarding the relationship between pre-transplant blood pressure control and post-transplant outcomes in end-stage renal disease patients. While the results from the included studies are mixed, more stringent blood pressure control than currently practiced may be beneficial to decrease graft failure and mortality in this patient population.
Rural-Urban Differences in Health Care Unaffordability During the Postpartum Period
Authors: MacDougall Hannah , Hanson Stephanie , Interrante Julia D. , Eliason Erica
Published: August 2023

Objective:

The objective of this study was to examine health care unaffordability for rural and urban residents and by postpartum status.

Methods:

We used cross-sectional survey data on female-identifying respondents ages 18–44 (n=17,800) from the 2019 to 2021 National Health Interview Study. Outcomes of interest were 3 measures of health care unaffordability. We conducted bivariate and multivariable regression models to assess the association between health care unaffordability, rurality, and postpartum status.

Results:

Bivariate analyses showed postpartum people reported statistically significantly higher rates of being unable to pay medical bills and having problems medical paying bills, as compared with nonpostpartum people. Rural residents also reported statistically significantly higher rates of being unable to pay their medical bills and having problems paying medical bills as compared with urban residents. In adjusted models, the predicted probability of being unable to pay medical bills among postpartum respondents was 12.8% (CI, 10.1–15.5), which was statistically significantly higher than among nonpostpartum respondents. Similarly, postpartum respondents had statistically significantly higher predicted probabilities of reporting problems paying medical bills (18.4%, CI, 15.4–21.4) as compared with nonpostpartum respondents. The rural residency was not significantly associated with the health care unaffordability outcome measures in adjusted models.

Conclusions:

Both postpartum and rural respondents reported higher rates of being unable to pay medical bills and having problems paying medical bills; however, after adjusting for covariates, only postpartum respondents reported statistically significantly higher rates of these outcomes. These results suggest that postpartum status may present challenges to health care affordability that span the urban/rural context.
Established and potential cardiovascular risk factors in metabolic syndrome: Effect of bariatric surgery
Authors: Bashir Bilal , Adam Safwaan , Ho Jan H. , Linn Zara , Durrington Paul N. , Soran Handrean
Published: August 2023

Purpose of review

The aim of this review was to provide an overview of the role of novel biomarkers in metabolic syndrome, their association with cardiovascular risk and the impact of bariatric surgery on these biomarkers.

Recent findings

Metabolic syndrome encompasses an intricate network of health problems, and its constituents extend beyond the components of its operational definition. Obesity-related dyslipidaemia not only leads to quantitative changes in lipoprotein concentration but also alteration in qualitative composition of various lipoprotein subfractions, including HDL particles, rendering them proatherogenic. This is compounded by the concurrent existence of obstructive sleep apnoea (OSA) and nonalcoholic fatty liver disease (NAFLD), which pave the common pathway to inflammation and oxidative stress culminating in heightened atherosclerotic cardiovascular disease (ASCVD) risk. Bariatric surgery is an exceptional modality to reverse both conventional and less recognised aspects of metabolic syndrome. It reduces the burden of atherosclerosis by ameliorating the impact of obesity and its related complications (OSA, NAFLD) on quantitative and qualitative composition of lipoproteins, ultimately improving endothelial function and cardiovascular morbidity and mortality.

Several novel biomarkers, which are not traditionally considered as components of metabolic syndrome play a crucial role in determining ASCVD risk in metabolic syndrome. Due to their independent association with ASCVD, it is imperative that these are addressed. Bariatric surgery is a widely recognized intervention to improve the conventional risk factors associated with metabolic syndrome; however, it also serves as an effective treatment to optimize novel biomarkers.
Management of the sensitized heart transplant candidate
Authors: Kittleson Michelle M.
Published: August 2023

Purpose of review

For sensitized heart transplant candidates who have antibodies to human leukocyte antigens (HLA), finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting heart transplantation has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease.

Recent findings

Advances in the assessment of HLA antibodies allow for identification of heart transplant candidates who may benefit from desensitization strategies to widen the donor pool and mitigate the risk of adverse posttransplant outcomes.

Antibody sensitization is a barrier to successful heart transplantation and strategies to identify sensitized patients, stratify their risk, and mitigate this risk through desensitization is crucial to optimize the quality of life and survival of HT recipients.
Association of aortic dissection and lipoprotein (a): a meta-analysis
Authors: Motawea Karam R. , Elhalag Rowan H. , Rouzan Samah S. , Talat Nesreen E. , Reyad Sarraa M. , Chébl Pensée , Mohamed Mai S. , Shah Jaffer
Published: August 2023

Background and Aim:

Some studies reported a positive relation between aortic dissection (AD) and increased lipoprotein (a) (LP(a)), while other studies reported no association, so the authors aimed to do a meta-analysis to establish the relation between AD and high levels of LP(a).

Methods:

PubMed, Scopus, Web of Science, SAGE, EMBASE, Science Direct, and Cochrane Library were searched. The inclusion criteria were any randomized control trials or observational studies that measured the levels of LP(a) in AD patients and healthy controls. The authors excluded case reports, case series, noncontrolled studies, reviews, editorials, and animal studies.

Results:

After a search of the literature, four studies were included in the meta-analysis with 678 patients included in the analysis. The pooled analysis showed a statistically significant association between the AD group and increased levels of LP(a), decreased levels of TG, low-density lipoprotein cholesterol, and TC compared with the control group (MD=11.71, 95% CI=4.11–19.32, P-value=0.003), (MD=−0,32, 95% CI=−0.48 to −0.16, P-value<0.0001 ), (MD=−0,21, 95% CI=−0.42 to −0.1, P-value=0.04), (MD=−0,58, 95% CI=−0.62 to −0.54, P-value<0.00001), respectively.

Conclusion:

Our study showed that AD is significantly associated with increased levels of LP(a). The significant increase in LP(a) in AD was associated with decreased levels of TG, low-density lipoprotein cholesterol, and TC. Future clinical trials testing Lp (a) targeting medications could be useful in the primary, or secondary prevention of AD in high risk patients.
Prevalence of hypercholesterolaemia in outpatient children aged 9–11 years
Authors: Ibrahim Nour , Chreitah Ahmad , Zreik Youssef
Published: August 2023

Background:

Hypercholesterolaemia is a silent disease that is considered to be one of the main risk factors for cardiovascular disease, often beginning in childhood, and early diagnosis and management may reduce the risk of developing atherosclerosis and early cardiovascular disease in early adulthood.

Objectives:

The purpose of this study was to evaluate the importance of universal screening for dyslipidemia in children aged 9–11 years.

Methods:

An observational, descriptive, cross-sectional study was conducted from July 2021 to June 2022. A total of 532 children (279 girls and 253 boys) aged 9–11 years were enroled, and non-fasting blood samples were obtained to measure total cholesterol (TC) levels in the blood.

Results:

The mean serum TC was 136.4±28.1 mg/dl. Thirty-two children (6%) of the screened participants had abnormal TC levels; those were tested subsequently by fasting serum TC, and 19 children were confirmed as dyslipidemic (3.5%). The prevalence of borderline blood cholesterol levels (TC between 170 and 199 mg/dl) was 2.6% CI 95% (2.2–3.2), and the prevalence of hypercholesterolaemia (TC ≥200 mg/dl) was 0.9% CI 95% (0.5–1.4). A positive correlation was found between body mass index and blood cholesterol level. (r = 0.55, P =0.002).

Conclusions:

Universal non-fasting TC screening in children aged 9–11 years old is effective in detecting hypercholesterolaemia. Since the authors found that the positive family history as the sole basis for selective examination in children is insufficient.
Ventilator associated pneumonia in intensive care unit patients: a systematic review
Authors: Mumtaz Hassan , Saqib Muhammad , Khan Wajiha , Ismail Syed M. , Sohail Hassan , Muneeb Muhammad , Sheikh Shazia S.
Published: August 2023

Ventilator-associated pneumonia (VAP) is the most common ICU acquired pneumonia among patients who are invasively intubated for mechanical ventilation. Patients with VAP suffer an increased mortality risk, financial burden, and length of stay in the hospital. The authors aimed to review the literature to describe the incidence, mortality, and microbiological evidence of VAP. We selected 13 peer-reviewed articles published from 1 January 2010 to 15 September 2022 from electronic databases for studies among adult or pediatric patients diagnosed with VAP expressed per thousand days admitted in the ICU. The VAP rates ranged from 7 to 43 per thousand days, varying among different countries of the world. A significant rate of mortality was observed in 13 studies ranging from 6.3 to 66.9%. Gram-negative organisms like Acinetobacter spp., Pseudomonas aeruginosa Gram-positive organisms like Staphylococcus aureus were frequently found. Our findings suggest an alarming situation of VAP among patients admitted to the intensive care units with increasing incidence and mortality. The review also found that VAP is more common in males and that there is a significant variation in the incidence and mortality rates of VAP among different countries. The findings of this review can inform the development of infection control and prevention strategies to reduce the burden of VAP. Thus, there is a crucial need for control and preventive measures like interventional studies and educational programs on staff training, hand-hygiene, and the appropriate use of ventilator bundle approach to curb this preventable threat that is increasing at an alarming rate.
Immunoglobulin A nephropathy in remission: a case report
Authors: Mahat Asim , Lageju Nimesh , Neupane Durga , Mishra Upama , Koirala Sefali
Published: August 2023

Introduction:

Immunoglobulin A nephropathy is the most prevalent form of primary glomerulonephritis.

Case presentation:

A 33-year-old military male presented with complaints of fever, headache, myalgia, chills, and haematuria for 10 years. His lab results showed elevated serum creatinine levels and proteinuria. A renal biopsy was done which was consistent with a diagnosis of immunoglobulin A nephropathy. He was managed with antihypertensive, including angiotensin-converting enzyme inhibitors, steroids and immunosuppressants, and Omega-3 fatty acids. There was remission of the symptoms and the patient’s serum creatinine and sonogram findings returned to baseline.

Conclusion:

Routine follow-up along with the appropriate use of medications can limit disease complications and progression.
The effect of multidisciplinary team on survival rates of women with breast cancer: a systematic review and meta-analysis
Authors: Pangarsa Eko A. , Rizky Daniel , Tandarto Kevin , Setiawan Budi , Santosa Damai , Hadiyanto Jessica N. , Kyana Salma , Suharti Catharina
Published: August 2023

Background:

Breast cancer is quite frequent all around the world. This disease was responsible for an estimated 2.1 million malignancies in 2022, making it the seventh-highest cause of cancer deaths globally. A multidisciplinary team (MDT) care policy was developed in the United Kingdom (UK) in 1995 to enhance the quality of care for cancer patients. The purpose of this systematic review and meta-analysis study is to assess the effects of MDT on breast cancer survival rates.

Methods:

This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Systematic search was conducted in several international databases including Google Scholar, PubMed, EBSCOhost, and Proquest from 2012 to 2022. The authors used RevMan 5.4 to do the meta-analysis of the pooled hazard ratio. Newcastle–Ottawa Scale to measure the risk of bias. Newcastle–Ottawa Scale evaluated participant selection, comparability, and reporting of results using eight subscale items. Egger’s test funnel plot was used to assess the potential publication bias for this study.

Results:

A total of 1187 studies were identified from research database. The authors found a total of six studies from six different countries (China, the UK, Taiwan, Australia, Africa, and France) included for this study. Based on the meta-analysis of the pooled hazard ratio of the included studies, the authors found that the overall effect size of the study was 0.80 (CI 95%: 0.73–0.88).

Conclusions:

Breast cancer patients who participated in well-organized MDT discussions had a greater survival rate than those who did not.
Defining the Nature and Clinicopathologic Significance of Mallory-Denk-like Inclusions in Ovarian Fibromas: A Potential Degenerative Phenomenon Associated With Torsion
Authors: Krishnamurthy Kritika , Stillman Isaac E. , Hecht Jonathan L. , Vyas Monika
Published: August 2023

Mallory-Denk bodies (MBD), described in alcoholic hepatitis, are composed of intermediate filaments admixed with other proteins. These cytoplasmic inclusions are irregularly shaped and eosinophilic as seen under the light microscope. MBD-like inclusions have rarely been described outside the hepatobiliary tree. Though rare, intracytoplasmic inclusions have been reported in ovarian fibromas. This study evaluates a series of torsed ovarian fibromas with intracytoplasmic inclusions resembling MDBs. Forty-three ovarian fibromas were retrieved from the pathology archives. The H&E slides were evaluated for the presence of MBD-like inclusions and histologic evidence of torsion. The cases with histologic features of torsion were included in the study group while the nontorsed fibromas formed the control group. Among the 15 cases of fibromas with torsion, MBD-like intracytoplasmic inclusions were seen in 5 cases, predominantly in the interface between necrotic areas and viable stroma. None of the cases from the control group showed any inclusions. There was no significant difference in the size of the fibroma or patient demographics between cases with and without inclusions. The inclusions were positive for cytokeratin and ubiquitin while being negative for per acidic Schiff and periodic acid-Schiff with diastase reaction, in the 3 cases selected for immunohistochemistry and special stains. Electron microscopy of the index case revealed a predominance of type 3 Mallory hyaline. This is the first report describing MDB-like inclusions in ovarian fibromas. These MDB-like inclusions appear to be limited to a fraction of ovarian fibromas that underwent torsion, suggesting that these inclusions likely result from subacute hypoxic damage to the cells.
Efficacy of Arthroscopic Diskopexy on Condylar Growth in Temporomandibular Joint Anterior Disk Displacement: A Randomized Clinical Trial
Authors: Shen Pei , Bai Guo , Xie Qianyang , Fang Yiming , Pan Lulu , Geng Yang , Wu Shanshan , Li Yan , Lu Haixia , Yang Chi
Published: August 2023

Background:

Adolescents with temporomandibular joint (TMJ) anterior disk displacement (ADD) frequently develop dentofacial deformities. It is unknown whether adjunctive arthroscopic diskopexy compared with orthodontic treatment alone increases condylar growth and then improves dentofacial deformity. This study aimed to determine whether arthroscopic diskopexy before functional appliance (joint-occlusal treatment) or single functional appliance (occlusal treatment) increases condylar growth and improves dentofacial deformity among adolescents with TMJ ADD.

Methods:

A multicenter, randomized, parallel, controlled trial was conducted in 3 centers in China. Adolescents diagnosed with TMJ ADD and dentofacial deformity were enrolled. Eligible participants were randomly assigned to a joint-occlusal group or occlusal group at a ratio of 2:1. Magnetic resonance imaging scans and cephalometric radiographs were evaluated at baseline, at 8 months, and at 14 months. The primary outcome was changes in condylar height from 14 months to baseline. Secondary outcomes were changes in skeletal position.

Results:

A total of 240 patients (14.65 ± 1.88 years of age) were randomized (joint-occlusal group, 160; occlusal group, 80). The overall difference in condylar height between groups was 3.65 mm (95% CI, 3.10 to 4.19 mm; P < 0.001). The between-group differences in condylar height on the left and right sides were 3.60 mm (95% CI, 2.92 to 4.28 mm; P < 0.001) and 3.69 mm (95% CI, 3.06 to 4.32 mm; P < 0.001), respectively. Significant between-group differences were noted in skeletal position (all P < 0.001).

Conclusion:

Joint-occlusal treatment can promote condylar growth and improve dentofacial deformity in adolescents after 14 months when compared with single occlusal treatment.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Myth-Busting the Zone-of-Injury Concept: A Prospective Study on the Vascular Response to High-Energy Lower Extremity Trauma
Authors: Cepas Adas , Kiiski Juha , Majava Marja , Kholová Ivana , Kaartinen Ilkka
Published: August 2023

Background:

Although the zone-of-injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomenon have been reported. In this prospective study, the vascular response to high-energy lower extremity trauma was investigated to evaluate the validity of the zone-of-injury concept.

Methods:

The histologic appearance of arterial and venous walls in the zone of injury was studied in 19 patients (median age, 46 years; interquartile range, 29.5 to 62.5 years) who underwent osteosynthesis and free flap reconstruction after high-energy lower extremity open fracture. Vascular samples were harvested from the injured extremity, and control samples were harvested from the free flap donor site. Histologic and morphometric characteristics of the vessels were analyzed microscopically and using digital pathology QuPath software.

Results:

Vascular samples were harvested on postinjury days 1 through 11. Intimal thickness was more than 3 times greater in arteries harvested from the zone of injury than in control samples (P < 0.01), and the intima/media ratio was 2-fold that in control samples (P = 0.01). Arterial intimal fibrosis was more evident in vessels harvested from the zone of injury (P < 0.01), but medial fibrosis and medial thickness did not differ significantly between groups. Venous intimal thickening (P < 0.01) and the intima/media ratio (P = 0.02) were greater in samples from the zone of injury. Fibrosis-related changes did not differ between groups (P = 0.45).

Conclusions:

These findings support the validity of the zone-of-injury concept by providing a novel histologic basis for this phenomenon. Intimal thickening and arterial intimal fibrosis are prominent histologic features of vessels affected by major lower extremity trauma.
ESA/ASA Jubilee Symposium Surgical Education
Authors: Farmer Diana L , O’Connell P. Ronan , Pugh Carla M. , Lang Hauke , Greenberg Caprice C. , Borel-Rinkes Inne HM , Mellinger John D. , Pinto-Marques Hugo
Published: August 2023

This paper summarizes the proceedings of the joint ESA/ASA symposium on Surgical Education that took place in Bordeaux France as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on use of quantitative metrics to understand technical decisions, coaching during training and beyond and entrustable professional activities were presented by ASA members and discussed by ESA members in a symposium attended by members of both associations
Can Depressive Symptomatology at Diagnosis Predict Cognitive and Functional Decline Over 1 Year in Rural Canadian Patients With Dementia?
Authors: Cai Shuang , Kirk Andrew , Karunanayake Chandima , O’Connell Megan E. , Morgan Debra
Published: August 2023

Introduction:

Depressive symptomatology is often associated with the onset of dementia, although the exact form and directionality of this association is still unclear. The aim of this study is to investigate whether depressive symptomatology at the time of dementia diagnosis was predictive of cognitive, functional, and behavioral decline over 1 year.

Methods:

In a Rural and Remote Memory Clinic, 375 patients consecutively diagnosed with mild cognitive impairment, Alzheimer disease, or non-Alzheimer disease dementia completed the Center for Epidemiological Studies Depression Scale at first visit and 1-year follow-up to assess depressive symptomatology. The same cohort was evaluated for cognitive, functional, and behavioral decline through the completion of 5 clinical tests performed at the first visit and at 1-year follow-up.

Results:

Depressive symptomatology at time of dementia diagnosis did not predict cognitive or functional decline over 1 year, although increases in depressive symptomatology over 1 year significantly correlated with higher caregiver ratings of neuropsychiatric symptom severity and related distress over that time.

Conclusion:

Increasingly severe depressive symptomatology over 1 year correlated with greater caregiver distress. This study points the way for future studies delineating the relationship between depression, dementia progression, and caregiver distress.
Epidermal growth factor receptor promotes infectious spleen and kidney necrosis virus invasion via PI3K-Akt signaling pathway
Authors: Niu Yinjie , Fu Xiaozhe , Lin Qiang , Liang Hongru , Luo Xia , Zuo Shaozhi , Liu Lihui , Li Ningqiu
Published: August 2023

Infectious spleen and kidney necrosis virus disease (ISKNVD) caused significant economic losses to the fishery industry. Epidermal growth factor receptor (EGFR), phosphatidylinositide 3-kinase (PI3K) played an important role in ISKNV invasion. However, the molecular regulatory mechanisms among EGFR, PI3K-Akt, and ISKNV invasion are not clear. In this study, ISKNV infection rapidly induced EGFR activation. While, EGFR activation promoted virus entry, but EGFR inhibitors and specific RNA (siRNA) decreased virus invasion. The PI3K-Akt as downstream signalling of EGFR was activated upon ISKNV infection. Consistent with the trends of EGFR, Akt activation increased ISKNV entry into cells, Akt inhibition by specific inhibitor or siRNA decreased ISKNV invasion. Akt silencing combination with EGFR activation showed that EGFR activation regulation ISKNV invasion is required for activation of the Akt signalling pathway. Those data demonstrated that ISKNV-induced EGFR activation positively regulated virus invasion by PI3K-Akt pathway and provided a better understanding of the mechanism of EGFR-PI3K-Akt involved in ISKNV invasion.
A definition schema for life level and some associated models
Authors: Losonczi Attila
Published: August 2023

We present a mathematical definition schema for measuring life level that is to give options to describe how much a (generalized) organism is alive. It is just a definition schema, not a definition. To make it a real definition configuration is required by applications.

We devote a long section to various examples where we demonstrate how a ready made definition can work and what ways it can provide reasonable values for life levels.

In the second part of the paper we outline many possible ways how one can partially derive life-level values from some simpler principles using probabilistic approach and various other methods. All of those models are still going to stay on a general level however they will suggest some more specific methods.

From technical point of view, we also present various kinds of operations which produce new life level functions, life level systems from already existing ones, and also highlight connections among systems / functions. Some operations also extend the usability of the original life level function, others add nice (expectable) features. We also examine the properties of such operations and the relations among them. Then we apply those techniques for some biologically meaningful extensions / restrictions of life level functions and systems.

We also deal with various averages on already defined life level functions and see how they can be applied, and we also investigate metrics (biological distance functions) that are synchronized with a life level function.

We also build a basic theory about measuring the vitality of sub-organisms regarding a containing (generalized) organism, and we identify some links between this notion and the life level concept.
Enhancing Fairness in Disease Prediction by Optimizing Multiple Domain Adversarial Networks
Authors: Li Bin , Shi Xinghua , Gao Hongchang , Jiang Xiaoqian , Zhang Kai , Harmanci Arif O , Malin Bradley
Published: August 2023

Predictive models in biomedicine need to ensure equitable and reliable outcomes for the populations they are applied to. Unfortunately, biases in medical predictions can lead to unfair treatment and widening disparities, underscoring the need for effective techniques to address these issues. To enhance fairness, we introduce a framework based on a Multiple Domain Adversarial Neural Network (MDANN), which incorporates multiple adversarial components. In an MDANN, an adversarial module is applied to learn a fair pattern by negative gradients back-propagating across multiple sensitive features (i.e., characteristics of individuals that should not be used to discriminate unfairly between individuals when making predictions or decisions.) We leverage loss functions based on the Area Under the Receiver Operating Characteristic Curve (AUC) to address the class imbalance, promoting equitable classification performance for minority groups (e.g., a subset of the population that is underrepresented or disadvantaged.) Moreover, we utilize pre-trained convolutional autoencoders (CAEs) to extract deep representations of data, aiming to enhance prediction accuracy and fairness. Combining these mechanisms, we alleviate biases and disparities to provide reliable and equitable disease prediction. We empirically demonstrate that the MDANN approach leads to better accuracy and fairness in predicting disease progression using brain imaging data for Alzheimer’s Disease and Autism populations than state-of-the-art techniques.
Machine-guided design of synthetic cell type-specificcis-regulatory elements
Authors: Gosai SJ , Castro RI , Fuentes N , Butts JC , Kales S , Noche RR , Mouri K , Sabeti PC , Reilly SK , Tewhey R
Published: August 2023

Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing, and stimulus responses, which collectively define the thousands of unique cell types in the body. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for an intended purpose has arisen naturally through evolution. Here, we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell type specificity. We leverage innovations in deep neural network modeling of CRE activity across three cell types, efficientin silicooptimization, and massively parallel reporter assays (MPRAs) to design and empirically test thousands of CREs. Throughin vitroandin vivovalidation, we show that synthetic sequences outperform natural sequences from the human genome in driving cell type-specific expression. Synthetic sequences leverage unique sequence syntax to promote activity in the on-target cell type and simultaneously reduce activity in off-target cells. Together, we provide a generalizable framework to prospectively engineer CREs and demonstrate the required literacy to write regulatory code that is fit-for-purposein vivoacross vertebrates.
Folded alpha helical putative new proteins fromApilactobacillus kunkeei
Authors: Ye Weihua , Behra Phani Rama Krishna , Dyrhage Karl , Seeger Christian , Joiner Joe D. , Karlsson Elin , Andersson Eva , Chi Celestine N. , Andersson Siv G. E. , Jemth Per
Published: August 2023

The emergence of new proteins is a central question in biology. Most tertiary protein folds known to date appear to have an ancient origin, but it is clear from bioinformatic analyses that new proteins continuously emerge in all organismal groups. However, there is a paucity of experimental data on new proteins regarding their structure and biophysical properties. We performed a detailed phylogenetic analysis and identified 48 putative open reading frames in the honeybee-associated bacteriumApilactobacillus kunkeeifor which no homologs could be identified in closely-related species, suggesting that they could be relatively new on an evolutionary time scale and represent recently evolved proteins. Using circular dichroism-, fluorescence- and nuclear magnetic resonance spectroscopy we investigated five of these proteins and show that they are not intrinsically disordered, but populate alpha-helical dominated folded states with relatively low thermodynamic stability (0-3 kcal/mol). The data demonstrate that small new proteins readily adopt simple folded conformations suggesting that more complex tertiary structures can be continuously re-invented during evolution by fusion of such simple secondary structure elements. These findings have implications for the general view on protein evolution, wherede novoemergence of folded proteins may be a common event.
SUMOylation of the m6A reader YTHDF2 by PIAS1 promotes viral RNA decay to restrict EBV replication
Authors: Sugiokto Febri Gunawan , Saiada Farjana , Zhang Kun , Li Renfeng
Published: August 2023

YTHDF2 is a member of the YTH protein family that binds to N6-methyladenosine (m6A)-modified RNA, regulating RNA stability and restricting viral replication, including Epstein-Barr virus (EBV). PIAS1 is an E3 SUMO ligase known as an EBV restriction factor, but its role in YTHDF2 SUMOylation remains unclear. In this study, we investigated the functional regulation of YTHDF2 by PIAS1. We found that PIAS1 promotes the SUMOylation of YTHDF2 at three specific lysine residues (K281, K571, and K572). Importantly, PIAS1 enhances the antiviral activity of YTHDF2, and SUMOylation-deficient YTHDF2 shows reduced anti-EBV activity. Mechanistically, YTHDF2 lacking SUMOylation exhibits reduced binding to EBV transcripts, leading to increased viral mRNA stability. Furthermore, PIAS1 mediates SUMOylation of YTHDF2’s paralogs, YTHDF1 and YTHDF3. These results collectively uncover a unique mechanism whereby YTHDF2 controls EBV replication through PIAS1-mediated SUMOylation, highlighting the significance of SUMOylation in regulating viral mRNA stability and EBV replication.

Importance

N6-methyladenosine (m6A) RNA modification pathway plays important roles in diverse cellular processes and viral life cycle. Here, we investigated the relationship between PIAS1 and the m6A reader protein YTHDF2, which is involved in regulating RNA stability by binding to m6A-modified RNA. We found that both the N-terminal and C-terminal regions of YTHDF2 interact with PIAS1. We showed that PIAS1 promotes the SUMOylation of YTHDF2 at three specific lysine residues. We also demonstrated that PIAS1 enhances the anti-Epstein-Barr virus (EBV) activity of YTHDF2. We further revealed that PIAS1 mediates the SUMOylation of other YTHDF family members, namely YTHDF1 and YTHDF3, due to their similarities with YTHDF2. These findings together illuminate an important regulatory mechanism of YTHDF2 in controlling viral RNA decay and EBV replication through PIAS1-mediated SUMOylation.
Integration of Osteoclastogenesis through addition of PBMCs in Human Osteochondral Explants culturedEx vivo
Authors: Cramer Esther E.A. , de Wildt Bregje W.M. , Hendriks Johannes G.E. , Ito Keita , Hofmann Sandra
Published: August 2023

The preservation of tissue specific cells in their native 3D extracellular matrix in bone explants provides a unique platform to study remodeling. Thus far, studies involving bone explant cultures showed a clear focus on achieving bone formation and neglected osteoclast activity and resorption. To simulate the homeostatic bone environmentex vivo, both key elements of bone remodeling need to be represented. This study aimed to assess and include osteoclastogenesis in human osteochondral explants through medium supplementation with RANKL and M-CSF and addition of peripheral blood mononuclear cells (PBMCs), providing osteoclast precursors.

Osteochondral explants were freshly harvested from human femoral heads obtained from hip surgeries and cultured for 20 days in a two-compartment culture system. Osteochondral explants preserved viability and cellular abundance over the culture period, but histology demonstrated that resident osteoclasts were no longer present after 4 days of culture. Quantitative extracellular tartrate resistant acid phosphatase (TRAP) analysis confirmed depletion of osteoclast activity on day 4 even when stimulated with RANKL and M-CSF. Upon addition of PBMCs, a significant upregulation of TRAP activity was measured from day 10 onwards. Evaluation of bone loss trough µCT registration and measurement of extracellular cathepsin K activity revealed indications of enhanced resorption upon addition of PBMCs. Based on the results we suggest that an external source of osteoclast precursors, such as PBMCs, needs to be added in long-term bone explant cultures to maintain osteoclastic activity, and bone remodeling.

Graphical abstract
MET functions in tumour progression and therapy resistance are repressed by intronic polyadenylation
Authors: Boldina Galina , Vallejos Maricarmen , Allard Delphine , Cadix Mandy , Labbé Céline , Vacher Sophie , Hemmingsson Oskar , Gestraud Pierre , Teissandier Aurélie , Martineau Sylvain , Auboeuf Didier , André Fabrice , Kamal Maud , Servant Nicolas , Bièche Ivan , Dutertre Martin , Robert Caroline , Vagner Stéphan
Published: August 2023

Intronic polyadenylation (IPA) leads to the production of transcript isoforms with alternative last exons in thousands of mammalian genes. Widespread regulation of IPA isoforms was observed during oncogenic transformation and in tumoursversushealthy tissues, and several IPA isoforms were involved in oncogenesis. However, little is known about the potential involvement of IPA in tumour progression, such as cancer cell invasiveness and metastasis, and in resistance to anticancer therapies. Here, we show that an IPA isoform ofMET(short MET) whose production is inhibited by U1 snRNP (U1), an essential ribonucleoprotein complex that recognizes the 5’ exon-intron junction of pre-mRNA, is associated with better prognosis in breast cancer. Induction of the short MET isoform, using a steric-blocking antisense oligonucleotide targeting the U1 binding site in the vicinity of the short MET alternative polyadenylation site, antagonizes cell invasiveness. U1 blockade with an antisense oligonucleotide targeting the U1 snRNA also decreases breast cancer cell invasiveness, in both human and mouse cancer cell models, and this effect involves IPA induction inMETand several genes belonging to the RAS/RAF/MAPK signalling pathway. Finally, short MET relieves melanoma cell resistance to MAPK cascade-targeted therapyin vitroandin vivo. IPA isoform levels ofMETand a few other genes (mTOR,EGFRandCTNNA1) help predict such resistance in patients. Altogether, our findings provide evidence for a role of IPA in both cancer cell invasiveness and resistance to therapy. This suggests that IPA isoforms can be exploited as biomarkers and therapeutic targets to combat tumour progression.