bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical anatomy of the atrioventricular conduction axis
Authors: Sánchez-Quintana Damián , Cabrera Jose-Angel , Anderson Robert H 
Published: February 2024

Abstract
It is axiomatic that the chances of achieving accurate capture of the conduction axis and its fascicles will be optimized by equally accurate knowledge of the relationship of the components to the recognizable cardiac landmarks, and we find it surprising that acknowledged experts should continue to use drawings that fall short in terms of anatomical accuracy. The accuracy achieved by Sunao Tawara (1906) in showing the location of the atrioventricular conduction axis is little short of astounding. Our purpose in bringing this to current attention is to question the need of the experts to have produced such inaccurate representations, since the findings of Tawara have been extensively endorsed in very recent years. The recent studies do no more than point to the amazing accuracy of the initial account of Tawara. At the same time, we draw attention to the findings described in the middle of the 20th century by Ivan Mahaim (1947). These observations have tended to be ignored in recent accounts. They are, perhaps, of equal significance to those seeking specifically to pace the left fascicles of the branching atrioventricular bundle.
Adequacy of health message tailoring for ethnic minorities: Pasifika communities in Sydney, Australia, during COVID-19
Authors: Palu Elizabeth , McBride Kate A , Simmons David , Thompson Ronda , Cavallaro Cassandra , Cooper Ellen , Felila Makeleta , MacMillan Freya 
Published: February 2024

Abstract
Ethnic minorities, such as Pasifika, residing in high-income countries were at higher risk of COVID-19 infection during the pandemic. To understand the experiences of Pasifika, including message dissemination and barriers to tailored public health messaging during the pandemic, a qualitative study was undertaken, underpinned by Laswell’s Model of Communication and Bandura’s social cognitive theory with data collected using Pasifika methods. Pasifika adults (n = 65) were recruited across Sydney from July 2020 to March 2022. Health care professionals (HCP) (n = 17) employed by four local health districts (LHDs) and Pasifika community-based organizations delivering multicultural COVID-19-related work within the study catchment, were also recruited. Five themes were constructed from the data of: (i) prevailing fear and uncertainty over COVID-19 infection and losing employment; (ii) limited knowledge of government perpetuating distrust in Government as a benevolent source of information; (iii) faith and trust as priorities for health decision-making; (iv) ‘Coconut wireless’—the role of family, friends and community in disseminating public health messages through word of mouth; and (v) limited health literacy affecting compliance with public health orders. Community members identified important messages and resources had not been sufficiently distributed. Most HCPs understood the necessity of grassroots-level engagement but reported existing approaches were inadequate to navigate challenges. These findings highlight the need for public health promotion and communication strategies that consider both the social and cultural determinants of health. We propose a 7-point checklist as a cultural appropriateness lens to assist the development and rating of existing or new health promotion messaging and resources.
Exploring settings as social complex adaptive systems in setting-based health research: a scoping review
Authors: Keshavarz Mohammadi Nastaran , Rezaei Zahed , Burggraf Larissa , Pype Peter 
Published: February 2024

Abstract
Since launching health health-promoting settings approach to health by WHO, valuable progress has happened in implementing its holistic concepts in settings such as cities, schools, workplaces, hospitals and healthcare services. However, significant knowledge–intention–success gaps still exist in creating sustainable health-promoting changes in settings. The complexity of the task of bridging this gap has contributed to the call for a complexity-informed paradigm shift to health as well as settings, followed by increasing consultation of relevant complexity theories, frameworks and tools in health research. This paper provides a critical scoping review of the application of complex adaptive system (CAS) theory in settings-based health promotion research. We included 14 papers, mostly qualitative studies, reporting on planning or implementation of change initiatives, less on its evaluation. CAS theory application was often incomplete thereby reducing the potential benefit of using this lens to understand change management. We suggest some recommendations how to comprehensively apply the CAS theory in setting-based health research and to report on all CAS characteristics to enhance the understanding of settings as adaptive health-promoting settings.
A76 COMBINING TOFACITINIB AND USTEKINUMAB FOR REFRACTORY ULCERATIVE COLITIS: A CASE REPORT
Authors: Bucheeri M A , Alabdulkarim B , Wolman S 
Published: February 2024

Abstract

Background
The paradigm for Inflammatory Bowel Disease (IBD) management has shifted towards prioritizing remission of inflammation over symptom control, emphasizing sustained, corticosteroid-free remission at the clinical, endoscopic, and histologic levels. The shift is due to the recognition that uncontrolled inflammation often causes morbidity; after one year of biological therapy, 40% of patients still experience persistent disease activity.
Several approaches have been proposed to address this challenge, including drug level monitoring, dosage titration, antibody screening, and, as a last resort, surgical intervention. Emerging limited studies suggest the potential efficacy of combining two biological agents or a biological agent with small molecules in IBD, contrasting the efficacy and safety concerns encountered with their use in rheumatological diseases.

Aims
To describe a case of successful combination therapy with Tofacitinib and Ustekinumab in refractory Ulcerative Colitis with a review of the current literature.

Methods
This case describes a 35-year-old male patient with severe Ulcerative Colitis refractory to 5-ASA, Azathioprine, Infliximab with Methotrexate, Vedolizumab, Ustekinumab and Tofacitinib. His disease persisted with primary treatment failures requiring hospital admissions and rescuing with parenteral steroids. He was switched back to Ustekinumab with minimal symptom improvement but required repeated steroid courses to achieve control. After deliberations, Tofacitinib was added. This combination achieved remission of his symptoms and inflammatory markers, mainly guided by fecal calprotectin (from 3728 µg/g to 46 µg/g), as well as endoscopic and histologic remission. He is being weaned off the oral budesonide he had been on to augment his response.

Results
After 4 years of combination therapy, he remains in remission with no adverse events or infections.
Reassuringly, Janus Kinase inhibitors (i.e., Tofacitinib) have a short half-life, allowing prompt discontinuation if indicated, especially in the event of infection. Furthermore, biologics such as Vedolizumab, Ustekinumab, and Risankizumab offer minimal systemic immunosuppression and do not appear to raise the risk of infection.
Apart from safety concerns and limited data on the use of combination therapy, significant economic implications exist. However, the attainability of cheaper generic forms of small molecules (e.g., Tofacitinib roughly costs a quarter of the brand price in Ontario, Canada) adds another advantage to their combination use.

Conclusions
Combination therapy with biologics and small molecules is a potential consideration for treating severe or refractory Ulcerative Colitis or IBD. To bridge the knowledge gap regarding combination therapies in IBD, further studies are needed on efficacy, safety, long-term effects, and economic impact.

Funding Agencies
None
A295 A CHALLENGING DIAGNOSTIC CASE - SEVERE ACUTE HEPATITIS POTENTIALLY ASSOCIATED WITH COVID-19 IN AN IMMUNOCOMPETENT YOUNG ADULT
Authors: Lawendy B , Hudson D , Abdul-Karim R 
Published: February 2024

Abstract

Background
Severe hepatitis with liver enzymes in the thousands is usually associated with viral etiologies, toxins, vascular aetiologies, acute gall stones, autoimmune hepatitis, and Wilson disease. Acute hepatitis in the moderate range has been associated with COVID19 infection.

Aims
A potential case of severe hepatitis with initial ALT of 6863, who tested positive for COVID19. Acetaminophen ingestion confounded the presentation.

Methods
Case Report

Results
A 48-year-old woman, with history of Insomnia on Zopiclone, presented to Hospital with a 6-day history of fatigue, malaise, muscle aches and subjective fevers. She had a ten pack-years smoking history, consumed 8 alcoholic beverages weekly, used marijuana infrequently, and denied any herbal or naturopathic supplement usage. She was double vaccinated against COVID19 over a year ago.
On the 2nd day of symptoms, she ingested 5 grams of Acetaminophen over a 24-hour period. Subsequently, she continued to use Acetaminophen, but did not exceed a daily dosage of 4 grams. On the 5th day, she presented to clinic and was found to have elevated liver enzymes: ALT 6863, AST 5785, ALP 62, GGT 60, and INR 1.1 with Bilirubin 8. She had nausea and emesis, prompting her to present to the hospital on the 6th day. The patient was alert and oriented, with mild tenderness in the right upper quadrant with no jaundice, ascites, peripheral edema, or encephalopathy.
She had reactive lymphocytosis consistent with a potential viral infection. Testing for acute hepatitis A, B, and C, HIV, EBV, CMV, herpes simplex virus, and varicella-zoster was negative. COVID19 was detected by rapid antigen testing and confirmed via PCR. Blood and urine toxicology screens were unremarkable. Acetaminophen was detected at a low level of 67 μg/mL at presentation and given the diagnostic dilemma & concern for concomitant acetaminophen-associated liver injury she was started on N-acetylcysteine (NAC) infusion. Acetaminophen level was trended until undetectable. Ceruloplasmin and alpha-1 antitrypsin were unremarkable. Iron studies showed an elevated Ferritin 1032. Autoimmune workup was negative except for anti-dense fine speckled autoantibodies with 1:80 (low) titre. Abdominal ultrasound with doppler was normal.
Her liver enzymes improved (Figure1) without signs of acute fulminant liver failure. She was discharged after 48 hours (day 7). In follow-up, her labs were: ALT 11, AST 16, INR 1.1, Bilirubin 6, and Ferritin 61.

Conclusions
To our knowledge, this is one of the first case reports of severe hepatitis, possibly due to COVID-19 in an immunocompetent adult, however, concerns for concomitant unintentional acetaminophen toxicity complicate the diagnosis. NAC was given to mitigate diagnostic error given the risk of anchoring bias. If patient condition had deteriorated liver biopsy would have been considered.

Funding Agencies
None
A299 ACUTE TUMOUR RUPTURE POST-TRANSARTERIAL CHEMOEMBOLIZATION IN A PATIENT WITH HEPATOCELLULAR CARCINOMA
Authors: Parthasarathy P , Khan M 
Published: February 2024

Abstract

Background
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing worldwide incidence. Transarterial chemoembolization (TACE) is an interventional radiological (IR) therapy used largely in intermediate stage HCC, which can provide successful bridge or downstaging to liver transplantation and increased survival rates. Tumour rupture is a very rare complication of TACE, with an estimated incidence of 0.68%. Potential risk factors include tumour size ampersand:003E 10 cm, and location of lesions in the right lobe or near the liver capsule. However, the pathophysiology of post-TACE tumour rupture is still not fully understood.

Aims
We aim to describe a case of HCC tumour rupture that occurred in the first 30 hours post-TACE. We also aim to highlight the extent of multiorgan ischemia associated with this tumour-related arterial bleed.

Methods
A PubMed literature review was done to ensure that post-TACE tumour rupture was a rare and sparsely reported event. Subsequently, inpatient notes, laboratory and imaging data were obtained from the patient's medical record in an anonymized manner.

Results
A 66-year-old male with alcohol-related liver cirrhosis (MELDNa 7; Child-Pugh Class A) was diagnosed with a 3.3 cm HCC, spanning segments 5 and 8. Six months later, after multidisciplinary discussion, he underwent successful elective TACE of a segment 8 artery that was supplying the HCC, as a bridge to liver transplantation. The next day, he developed diffuse abdominal pain, emesis, tachycardia, and abdominal firmness and tenderness. Labs showed a 45 g/L drop in hemoglobin (121 g/L to 76 g/L), leukocytosis (27.0 x109/L), and an elevated lactate (4.4 mmol/L). Computed tomography (CT) scan confirmed tumour rupture, with moderate-to-large hemoperitoneum with active bleeding from the embolized region of the HCC, and associated gas. Emergent IR-guided embolization was performed to the bleeding segment 8 artery.
CT scan two days later revealed interval ischemic infarction of the spleen, pancreatic tail, and stomach. This widespread ischemia was suspected to be due to hypovolemic hypoperfusion vs. post-TACE embolic phenomena. Aggressive supportive measures, antibiotics, and anticoagulation were implemented.
Due to tumour rupture, the patient was deemed no longer a suitable candidate for liver transplantation. Futility of definitive management was discussed, and the patient opted for medical care without resuscitation. After optimization of nutritional and physical functioning parameters, he was discharged home with medical management for pain and ascites.

Conclusions
Post-TACE tumour rupture is a rare occurrence for which the pathophysiology is not fully understood. This case provides an important reminder of this potential adverse event. Early detection and management are imperative to facilitating a favourable outcome in this life-threatening condition.

Funding Agencies
None
Non-gravid uterine torsion associated with small bowel obstruction
Authors: Barnabas Goh , Mathew Samuel , Shamassi Maryam , Rafique Mohammad 
Published: February 2024

Abstract
Uterine torsion is a rare condition. Even more so in cases of non-gravid torsion. We present the case of a post-menopausal woman in her 70s who arrived to our emergency department acutely unwell with abdominal pain and vomiting on a background of a large leiomyomatous uterus, complicated by aspiration pneumonia, acute anaemia, and acute kidney injury. Computed tomography demonstrated a small bowel obstruction secondary to a large heterogeneous calcified pelvic mass. Laparotomy performed demonstrated a large leimyomatous uterus that had torted on the cervical pedicle associated with perforation of the lower anterior segment. A short segment of healthy jejunum was adhered to the uterine fundus, which was easily mobilized. Total hysterectomy and bilateral oophorectomy was performed. The patient made a full recovery. Histopathology demonstrated a calcified leiomyomatous uterus with adjacent haemorrhagic infarction of the uterine wall.
Endosperm cell death: roles and regulation in angiosperms
Authors: Doll Nicolas M , Nowack Moritz K 
Published: February 2024

Abstract
Double fertilization in angiosperms results in the formation of a second zygote, the fertilized endosperm. Unlike its embryo sibling, the endosperm is a transient structure that eventually undergoes developmentally controlled programmed cell death (PCD) at specific time points of seed development or germination. The nature of endosperm PCD exhibits a considerable diversity, both across different angiosperm taxa and within distinct endosperm tissues. In endosperm-less species, PCD might cause central cell degeneration as a mechanism preventing the formation of a fertilized endosperm. In most other angiosperms, embryo growth necessitates the elimination of surrounding endosperm cells. Nevertheless, complete elimination of the endosperm is rare and, in most cases, specific endosperm tissues persist. In mature seeds, these persisting cells may be dead, such as the starchy endosperm in cereals, or remain alive to die only during germination, like the cereal aleurone or the endosperm of castor beans. In this review, we explore current knowledge surrounding the cellular, molecular, and genetic aspects of endosperm PCD, and the influence environmental stresses have on PCD processes. Overall, this review provides an exhaustive overview of endosperm PCD processes in angiosperms, shedding light on its diverse mechanisms and its significance in seed development and seedling establishment.
Confined chaos and the chaotic angular motion of Atlas, a Saturn’s inner satellite
Authors: Pereira Lucas S , Mourão Daniela C , Winter Othon C 
Published: February 2024

ABSTRACT
The dynamics of the Solar system exhibit inherent chaos and instability. Mathematical tools, such as the maximum Lyapunov characteristic exponent (LCE) and Lyapunov time (TL), play a crucial role in providing a qualitative understanding of chaos within celestial objects, such as asteroids and moonlets. Celestial bodies with relatively small Lyapunov times have garnered significant research interest due to their stable orbits, a phenomenon referred to as stable or confined chaos. Notable examples include Saturn’s satellites: Atlas, with a Lyapunov time on the order of 10 yr, Prometheus, and Pandora. This work aims to study the chaotic behaviour of the Atlas satellite and its relatively small TL. We present a three-dimensional model approach designed to isolate the radial contribution from the LCE and assess its influence within the LCE. Our investigation focuses on the Saturn system, comprising Saturn itself, along with its satellites Atlas, Prometheus, Pandora, and Mimas. To estimate the radial contribution of the LCE, we find the projection of the radial vector of a ghost Atlas (a slightly displaced Atlas) onto the Atlas radial vector, which allows us to calculate the difference between the radial vectors. This methodology enables us to estimate the radial contribution of the LCE and calculate the Lyapunov time. Remarkably, our results demonstrate that orbits remain confined even for integration times exceeding TL. Furthermore, we investigate the temporal behaviour of Atlas’ angular position in its orbit, potentially shedding light on chaotic angular dynamics.
Single‐cell RNA‐Seq reveals the earliest lineage specification and X chromosome dosage compensation in bovine preimplantation embryos
Authors: Hu Bingjie , Jin Hao , Shi Yan , Yu Haotian , Wu Xiaotong , Wang Shaohua , Zhang Kun 
Published: February 2024

AbstractLineage specification and X chromosome dosage compensation are two crucial biological processes that occur during preimplantation embryonic development. Although extensively studied in mice, the timing and regulation of these processes remain elusive in other species, including humans. Previous studies have suggested conserved principles of human and bovine early development. This study aims to provide fundamental insights into these programs and the regulation using a bovine embryo model by employing single‐cell transcriptomics and genome editing approaches. The study analyzes the transcriptomes of 286 individual cells and reveals that bovine trophectoderm/inner cell mass transcriptomes diverge at the early blastocyst stage, after cavitation but before blastocyst expansion. The study also identifies transcriptomic markers and provides the timing of lineage specification events in the bovine embryo. Importantly, we find that SOX2 is required for the first cell decision program in bovine embryos. Moreover, the study shows the occurrence of X chromosome dosage compensation from morula to late blastocyst and reveals that this compensation results from downregulation of X‐linked genes in female embryonic cells. The transcriptional atlas generated by this study is expected to be widely useful in improving our understanding of mammalian early embryo development.
Re-do transoral robotic thyroidectomy is feasible: preliminary results of the surgical feasibility and efficacy of completion transoral robotic thyroidectomy - cohort study
Authors: Oh Moon Young , Park Dawon , Chai Young Jun , Kim Kwangsoon , Kim Hoon Yub 
Published: February 2024

Background:
Transoral robotic thyroidectomy (TORT) has proven to be a safe and effective procedure with favorable surgical and cosmetic outcomes, but its application in completion thyroidectomy procedures remains to be established. In this study, we present our experience with completion TORT, assessing its surgical feasibility and efficacy. between February 2017 and August 2023.

Methods:
We conducted a retrospective analysis of consecutive patients who underwent completion TORT after an initial TORT procedure between February 2017 and August 2023.

Results:
A total of 10 patients (three males and seven females) were included in the study, with a mean age of 42.2±13.5 years. The indications for completion thyroidectomy included five cases of aggressive initial lesions and five cases of metachronous papillary thyroid carcinoma detected in the remnant lobe. The median interval between the initial and completion TORT procedures was 6.5 months. Flap dissection time showed no significant difference between the initial TORT and completion TORT operations (43.3±7.5 vs. 36.2±11.2, P=0.125). However, the mean console time (127.9±42.6 vs. 86.4±26.3 min, P=0.019) and mean total operation time (206.7±65.9 vs. 146.0±34.9 min, P=0.021) were significantly longer during the initial TORT procedure than during the completion TORT procedure. Two patients experienced transient hypoparathyroidism, which resolved within four weeks postoperatively. No other complications, such as vocal cord palsy, mental nerve injury, or bleeding, were observed. The median follow-up period was 21.5 months, and no recurrences were detected in any of the patients.

Conclusions:
Our study demonstrates that re-do TORT is feasible, showing excellent cosmetic results and minimal adverse effects. Completion TORT may be considered a viable option for selected patients who require completion thyroidectomy after an initial TORT procedure.