bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of azvudine in reducing mortality of COVID-19 patients: a systematic review and meta-analysis
Authors: Wang Yaqi , Xie Huaiya , Wang Luo , Fan Junping , Zhang Ying , Pan Siqi , Zhou Wangji , Chen Qiaoling , Liu Xueqi , Wu Aohua , Zhang Hong , Wang Jinglan , Tian Xinlun 
Published: February 2024

Abstract
Background
Azvudine has been approved for the treatment of coronavirus disease 2019 (COVID-19) patients in China, and this meta-analysis aims to illustrate the safety of azvudine and its effectiveness in reducing mortality.

Methods
PubMed, Embase, Web of science, Cochrane Library and the Epistemonikos COVID-19 Living Overview of Evidence database (L.OVE) were searched to aggregate currently published studies. Cochrane risk of bias tool and ROBINS-I tool were used to assess the risk of bias of randomized controlled study and cohort study respectively. Odds radios (ORs) with 95% confidence interval (CIs) were combined for dichotomous variables. Publication bias was assessed by Egger’s test and funnel plots.

Results
A total of 184 articles were retrieved from the included databases and 17 studies were included into the final analysis. Pooled analysis showed that azvudine significantly reduced mortality risk in COVID-19 patients compared with controls (OR: 0.41, 95%CI 0.31–0.54, p < 0.001). Besides, either mild to moderate or severe COVID-19 patients could benefit from azvudine administration. There was no significant difference in the incidence of ICU admission (OR: 0.90, 95%CI 0.47–1.72, p = 0.74) and invasive ventilation (OR: 0.94, 95%CI 0.54–1.62, p = 0.82) between azvudine and control group. The incidence of adverse events was similar between azvudine and control (OR: 1.26, 95%CI 0.59–2.70, p = 0.56).

Conclusions
This meta-analysis suggests that azvudine could reduce the mortality risk of COVID-19 patients, and the safety of administration is acceptable.

Trial registration
PROSPERO; No.: CRD42023462988; URL: https://www.crd.york.ac.uk/prospero/.
Quantitative assessment of H&E staining for pathology: development and clinical evaluation of a novel system
Authors: Dunn Catriona , Brettle David , Cockroft Martin , Keating Elizabeth , Revie Craig , Treanor Darren 
Published: February 2024

Abstract
Background
Staining tissue samples to visualise cellular detail and tissue structure is at the core of pathology diagnosis, but variations in staining can result in significantly different appearances of the tissue sample. While the human visual system is adept at compensating for stain variation, with the growth of digital imaging in pathology, the impact of this variation can be more profound. Despite the ubiquity of haematoxylin and eosin staining in clinical practice worldwide, objective quantification is not yet available. We propose a method for quantitative haematoxylin and eosin stain assessment to facilitate quality assurance of histopathology staining, enabling truly quantitative quality control and improved standardisation.

Methods
The stain quantification method comprises conventional microscope slides with a stain-responsive biopolymer film affixed to one side, called stain assessment slides. The stain assessment slides were characterised with haematoxylin and eosin, and implemented in one clinical laboratory to quantify variation levels.

Results
Stain assessment slide stain uptake increased linearly with duration of haematoxylin and eosin staining (r = 0.99), and demonstrated linearly comparable staining to samples of human liver tissue (r values 0.98–0.99). Laboratory implementation of this technique quantified intra- and inter-instrument variation of staining instruments at one point in time and across a five-day period.

Conclusion
The proposed method has been shown to reliably quantify stain uptake, providing an effective laboratory quality control method for stain variation. This is especially important for whole slide imaging and the future development of artificial intelligence in digital pathology.
Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario
Authors: Shuldiner Jennifer , Lam Emily , Shah Nida , Grimshaw Jeremy , Desveaux Laura , Heisey Ruth , Taccone Michael S. , Taljaard Monica , Thavorn Kednapa , Hodgson David , Gupta Sumit , Lofters Aisha , Ivers Noah , Nathan Paul C. 
Published: February 2024

Abstract
Background
Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time.

Methods
This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP’s impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants’ consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later.
The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed.

Discussion
The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population.

Trial registration
ClinicalTrials.gov NCT05832138.
Challenges in diagnosing canine spindle cell tumours using immunohistochemistry, illustrated by three nonpigmented malignant cases from the nictitating membrane
Authors: Bundgaard Kjellingbro Kristine , Naranjo Freixa Carolina , Hjorth Mikkelsen Lauge , Heegaard Steffen 
Published: February 2024

Abstract
Background
Nonpigmented malignant spindle cell tumours of the membrana nictitans are rare in dogs. In twenty-three years only three cases have been diagnosed in Scandinavia. This study describes the three cases of malignant tumours of the membrana nictitans recorded by the Eye Pathology Section, University of Copenhagen, Denmark, with reference to the clinical appearance and work-up, the treatment and prognosis, and the histopathological description including immunohistochemistry. The three cases are compared to previous publications on canine tumours of the nictitating membrane. We emphasize the importance of using protocols that are adapted to the specific species such as dogs. Opposite the human tissue responses, we even need more than one marker when diagnosing melanomas in dogs.

Results
The dogs presented were an 8-year-old Dachshund, a 12-year-old Akita and a 14-year-old Shetland Sheepdog. All three dogs were entire females. All three nictitating membrane tumours developed on the right nictitating membrane as firm or multilobulated hyperaemic masses. Two of the tumours were macroscopically nonpigmented, the third being partly pigmented on the surface and ulcerated. According to the histopathology and for two of the cases immunohistochemistry with dog-adapted protocols the diagnoses included one hemangiosarcoma and two amelanotic melanomas. Tumour regrowth developed in all three cases and repeated resections were completed 1, 2 and 3 times, respectively, with recurrence experienced within 1.5 months − 3 years.

Conclusions
Nonpigmented malignant spindle cell tumours of the canine membrana nictitans are rare. Treatment of choice should be complete excision with a minimal histologic tumour-free distance and in case of a recurrence a full resection of the nictitating membrane. We strongly recommend a dog-adapted protocol for immunohistochemistry.
PAIN2.0: study protocol for a multicentre randomised controlled trial to evaluate the efficacy of a 10-week outpatient interdisciplinary multimodal pain therapy to manage recurrent pain for patients with risk factors of developing chronic pain in Germany
Authors: Meyer-Moock Sandra , Szczotkowski Daniel , Schouten Leonie , Petzke Frank , Milch Lena , Metz-Oster Beatrice , Zinndorf Louise , Geber Christian , Hoffmann Greta , Preißler Anke , Marschall Ursula , Rottke Felix , Waidner Anja , Möller André , Isenberg Thomas , Lindena Gabriele , Gärtner Anne , Kaiser Ulrike , Kohlmann Thomas 
Published: February 2024

Abstract
Background
Up to 27% of the German population suffers from recurrent or persistent pain (lasting more than three months). Therefore, prevention of chronic pain is one major object of pain management interventions. The aim of this nationwide, multicentre, randomised controlled trial is to evaluate the efficacy of a 10-week ambulatory (outpatient) interdisciplinary multimodal pain therapy (A-IMPT) for patients with recurrent pain and at risk of developing chronic pain. This project was initiated by the German Pain Society (Deutsche Schmerzgesellschaft e.V.) and the public health insurance provider BARMER. It is currently funded by the German Innovation Fund (01NVF20023). The study PAIN2.0 focuses on reducing pain intensity and pain-related disability and investigates whether this intervention can improve physical activity, psychological well-being, and health literacy.

Methods
PAIN2.0 is designed as a multicentre 1:1 randomised controlled trial with two parallel groups (randomisation at the patient level, planned N = 1094, duration of study participation 12 months, implemented by 22 health care facilities nationwide). After 6 months, patients within the control group also receive the intervention. The primary outcomes are pain intensity and pain-related impairment, measured as Characteristic Pain Intensity (PI) and Disability Score (DS) (Von Korff), as well as patient-related satisfaction with the intervention. Secondary outcomes are the number of sick leave days, sickness allowance, treatment costs, psychological distress, health-related quality of life, and catastrophizing. The effects of the intervention will be analysed by a parallel-group comparison between the intervention and control groups. In addition, the long-term effects within the intervention group will be observed and a pre-post comparison of the control group before and after the intervention will be performed.

Discussion
Recurrent or persistent pain is common in the German population and causes high costs for patients and society. The A-IMPT aims to improve pain and pain-related impairments in pain patients at risk of chronification, thereby reducing the risk of developing chronic pain with its high socioeconomic burden. This new therapy could easily be integrated into existing therapy programs if positively evaluated.

Trial registration
The trial PAIN2.0 has been registered in the German Clinical Trials Register (DRKS) since 21/11/2022 with the ID DRKS00030773.
Toxocara canis infection in multiple types of animals: ophthalmological and pathological observations
Authors: Zheng Shuxin , Sun Limei , Huang Li , Xie Yue , Ding Xiaoyan 
Published: February 2024

AbstractHuman ocular toxocariasis (OT), caused by pet roundwormToxocara canis(Nematoda Ascaridoidea), is a worldwide ocular parasitic infection that poses a severe threat to eyesight, especially in school-aged children. However, the infection process and pathological mechanism ofToxocaraare difficult to study in the human body. This study was designed to explore long-term ocular manifestations in different rodents infected withToxocara canis, uncovering the specific pathological mechanism and migration pathway of larvae after infection. The three types of experimental animals we selected were C57BL/6 mice, Mongolian gerbils and Brown Norway rats. Mice were randomly divided into five groups and infected orally with 1000, 2000, 4000, 8000 and 10,000T. caniseggs; gerbils were randomly divided into four groups and infected orally with 1000, 2000, 4000 and 10,000T. caniseggs; rats were randomly divided into three groups and infected orally with 2000, 6000 and 10,000T. caniseggs. Their ocular changes were closely observed and recorded for at least 2 months. We also enucleated the eyeballs of some animals to perform pathological sectioning and hematoxylin-eosin staining. After 3 dpi (days post-infection), hemorrhagic lesions, mechanical injury of the retina and larval migration could be observed in some infected animals. The ocular infection and mortality rates tended to be stable at 7 dpi. Larval tissue, structure disorder and inflammation could be observed in the pathological sections. In conclusion, the mice infected with 2000 T. caniseggs and gerbils infected with 1000, 2000 and 4000 T. caniseggs showing obvious ocular lesions and lower mortality rates could provide a basis for long-term observation.Graphical Abstract
Medico-legal risks of point-of-care ultrasound: a closed-case analysis of Canadian Medical Protective Association medico-legal cases
Authors: Prager Ross , Wu Derek , Garber Gary , Finestone P. J. , Zang Cathy , Aslanova Rana , Arntfield Robert 
Published: February 2024

Abstract
Background
Point-of-care ultrasound (POCUS) has become a core diagnostic tool for many physicians due to its portability, excellent safety profile, and diagnostic utility. Despite its growing use, the potential risks of POCUS use should be considered by providers. We analyzed the Canadian Medical Protective Association (CMPA) repository to identify medico-legal cases arising from the use of POCUS.

Methods
We retrospectively searched the CMPA closed-case repository for cases involving diagnostic POCUS between January 1st, 2012 and December 31st, 2021. Cases included civil-legal actions, medical regulatory authority (College) cases, and hospital complaints. Patient and physician demographics, outcomes, reason for complaint, and expert-identified contributing factors were analyzed.

Results
From 2012 to 2021, there were 58,626 closed medico-legal cases in the CMPA repository with POCUS determined to be a contributing factor for medico-legal action in 15 cases; in all cases the medico-legal outcome was decided against the physicians. The most common reasons for patient complaints were diagnostic error, deficient assessment, and failure to perform a test or intervention. Expert analysis of these cases determined the most common contributing factors for medico-legal action was failure to perform POCUS when indicated (7 cases, 47%); however, medico-legal action also resulted from diagnostic error, incorrect sonographic approach, deficient assessment, inadequate skill, inadequate documentation, or inadequate reporting.

Conclusions
Although the most common reason associated with the medico-legal action in these cases is failure to perform POCUS when indicated, inappropriate use of POCUS may lead to medico-legal action. Due to limitations in granularity of data, the exact number of civil-legal, College cases, and hospital complaints for each contributing factor is unavailable. To enhance patient care and mitigate risk for providers, POCUS should be carefully integrated with other clinical information, performed by providers with adequate skill, and carefully documented.
Nintedanib in systemic sclerosis treatment: a case report
Authors: Kudsi Maysoun , Tarcha Raghad , Khalayli Naram 
Published: February 2024

Abstract
Background
Nintedanib was approved for the treatment of scleroderma and scleroderma-related interstitial lung disease, as it decrease the forced expiratory volume.

Case presentation
A 48-year-old Asian female patient with systemic scleroderma 6 years ago developed breathlessness, nausea, heart palpation, and sudden severe occipital headache over the preceding week. She was receiving aspirin 81 mg/day and amlodipine 5 mg/day. Her diagnosis was diffuse scleroderma with pulmonary hypertension, interstitial lung involvement, and renal crisis. The modified Rodnan score was 18. We begin captopril at a dose of 12.5 mg, progressively escalating to 200 mg/day, and oral nintedanib was started at 150 mg. A total of 12 months after initiation of treatment, the patient’s kidney function was normal. The pulmonary function tests improved. The modified Rodnan score was reduced to 10. We did not encounter any side effects in our case due to nintedanib treatment.

Conclusion
Treatment with nintedanib is crucial for slowing lung function decline. Diarrhea was the most common adverse event. Scleroderma renal crisis occurs in 10% of patients and typically presents with an abrupt onset of hypertension and kidney failure. The optimal antihypertensive agent for scleroderma renal crisis is an ACE inhibitor. The mainstay of therapy in scleroderma renal crisis has been shown to improve or stabilize renal function in approximately 70% of patients and improve survival in nearly 80% at 1 year. Nintedanib may be effective, and fairly safe to use. Further exploration is anticipated to advance a new period of systemic sclerosis treatment.
Comparison of clinical and radiological outcomes for the anterior and medial approaches to open reduction in the treatment of bilateral developmental dysplasia of the hip: a systematic review protocol
Authors: Jenner Edward Alan , Chauhan Govind Singh , Burahee Abdus , Choudri Junaid , Gardner Adrian , Bache Christopher Edward 
Published: February 2024

Abstract
Background
Developmental dysplasia of the hip (DDH) affects 1–3% of newborns and 20% of cases are bilateral. The optimal surgical management strategy for patients with bilateral DDH who fail bracing, closed reduction or present too late for these methods to be used is unclear. There are proponents of both medial approach open reduction (MAOR) and anterior approach open reduction (AOR); however, there is little evidence to inform this debate.

Methods
We will perform a systematic review designed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search the medical and scientific databases including the grey and difficult to locate literature. The Medical Subject Headings “developmental dysplasia of the hip”, “congenital dysplasia of the hip”, “congenital hip dislocation”, “developmental hip dislocation”, and their abbreviations, “DDH” and “CDH” will be used, along with the qualifier “bilateral”. Reviewers will independently screen records for inclusion and then independently extract data on study design, population characteristics, details of operative intervention and outcomes from the selected records. Data will be synthesised and a meta-analysis performed if possible. If not possible we will analyse data according to Systematic Review without Meta-Analysis guidance. All studies will be assessed for risk of bias. For each outcome measure a summary of findings will be presented in a table with the overall quality of the recommendation assessed using the Grading of Recommendations Assessment Development and Evaluation approach.

Discussion
The decision to perform MAOR or AOR in patients with bilateral DDH who have failed conservative management is not well informed by the current literature. High-quality, comparative studies are exceptionally challenging to perform for this patient population and likely to be extremely uncommon. A systematic review provides the best opportunity to deliver the highest possible quality of evidence for bilateral DDH surgical management.

Systematic review registration
The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42022362325).
A Pexider system of additive functional equations in Banach algebras
Authors: Dehghanian Mehdi , Sayyari Yamin , Donganont Siriluk , Park Choonkil 
Published: February 2024

AbstractIn this paper, we solve the system of functional equations $$\begin{aligned} \textstyle\begin{cases} f(x+y)+g(y-x)=2f(x), \\ g(x+y)-f(y-x)=2g(y) \end{cases}\displaystyle \end{aligned}$$

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Antioxidant and anti-inflammatory activities of the methanol extract from the bran of the colored wheat, 'Ariheuk'
Authors: Kim Seung-Gyeom , Park So-Hyeon , Auh Joong-Hyuck 
Published: February 2024

AbstractIn vitro antioxidant and anti-inflammatory activities were investigated using a 70% acidic methanol extract of the colored wheat bran, 'Ariheuk.' Active metabolites were identified via metabolomic analysis using multivariate statistical comparisons. The 'Ariheuk' bran extract (ABE) contained a higher total anthocyanin content (0.19 mg C3G/g) than the general wheat bran extract (GBE) (0.01 mg C3G/g). ABE exhibited stronger antioxidant and anti-inflammatory activities than GBE. The mechanism underlying the anti-inflammatory effects of ABE was explored by assessing the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). The crude ABE extract was also partially fractionated into three subfractions (ABE-F1, ABE-F2, and ABE-F3) using preparative liquid chromatography (Prep-LC) to identify the active metabolites. The total anthocyanin content was highest in ABE-F3 (1.91 ± 0.06 mg C3G/g). Among the subfractions, ABE-F2 exhibited the highest antioxidant and anti-inflammatory activities. Several distinct metabolites contributing to the activities of ABE-F2 were identified, including various cyanidin and peonidin derivatives and apigenin derivatives, such as corymboside and schaftoside.
Targeting natural killer cells: from basic biology to clinical application in hematologic malignancies
Authors: Shang Juanjuan , Hu Shunfeng , Wang Xin 
Published: February 2024

AbstractNatural killer (NK) cell belongs to innate lymphoid cell family that contributes to host immunosurveillance and defense without pre-immunization. Emerging studies have sought to understand the underlying mechanism behind NK cell dysfunction in tumor environments, and provide numerous novel therapeutic targets for tumor treatment. Strategies to enhance functional activities of NK cell have exhibited promising efficacy and favorable tolerance in clinical treatment of tumor patients, such as immune checkpoint blockade (ICB), chimeric antigen receptor NK (CAR-NK) cell, and bi/trispecific killer cell engager (BiKE/TriKE). Immunotherapy targeting NK cell provides remarkable advantages compared to T cell therapy, including a decreased rate of graft versus-host disease (GvHD) and neurotoxicity. Nevertheless, advanced details on how to support the maintenance and function of NK cell to obtain better response rate and longer duration still remain to be elucidated. This review systematically summarizes the profound role of NK cells in tumor development, highlights up-to-date advances and current challenges of therapy targeting NK cell in the clinical treatment of hematologic malignancies.