bluuebunny/crossref_metadata_2025_split huggingface dataset:
Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters
Authors: Lau Estee P. M. , Ing Matthew , Vekaria Sona , Tan Ai Ling , Charlesworth Chloe , Fysh Edward , Shrestha Ranjan , Yap Elaine L. C. , Smith Nicola A. , Kwan Benjamin C. H. , Saghaie Tajalli , Roy Bapti , Goddard John , Muruganandan Sanjeevan , Badiei Arash , Nguyen Phan , Hamid Mohamed Faisal Abdul , George Vineeth , Fitzgerald Deirdre , Maskell Nick , Feller-Kopman David , Murray Kevin , Chakera Aron , Lee Y C Gary 
Published: April 2024

Abstract
Background
Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC.

Methods
A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants.

Discussion
Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections.

Ethics and dissemination
Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration
Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.
Safety and efficacy of ketorolac in improving the prognosis of acute type A aortic dissection patients: a protocol of a randomized, double-blinded, and placebo-controlled study
Authors: Lv Zhikang , Pan Tuo , Zhang Haitao , Wang Yapeng , Matniyaz Yusanjian , Tang Yuxian , Lu Lichong , Wang Dongjin 
Published: April 2024

Abstract
Background
Acute type A aortic dissection (aTAAD) is a critical and life-threatening condition. Previous research has demonstrated that the use of ketorolac not only reduces the progression, incidence, and severity of aortic aneurysms in animal models, but also decreases postoperative mortality and complications in patients undergoing open abdominal aortic aneurysm replacement. However, there is a lack of studies investigating the efficacy of ketorolac in treating aTAAD in humans. Therefore, we conducted a study to evaluate the safety and efficacy of ketorolac in patients with aTAAD. Our hypothesis was that ketorolac treatment for aTAAD patients would meet safety indicators and effectively improve patient prognosis.

Methods/design
This study is a single-center, randomized, double-blinded, and placebo-controlled study. A total of 120 patients with aTAAD will be recruited and will be randomized into the ketorolac group and placebo group with a ratio of 1:1. Ketorolac tromethamine 60 mg per 2 ml will be intramuscularly injected within 2 h before surgery, followed by intramuscular injections of 30 mg per 1 ml BID. on the first and second postoperative days in the Ketorolac group, while 0.9% saline will be administered at the same dose, dosage form, and time in the placebo group. This study aims to evaluate the safety and efficacy of ketorolac in improving the prognosis of aTAAD. The primary endpoint is the composite endpoint event concerning drug-related adverse events. Secondary endpoints include drug-related adverse events, laboratory examination of blood, diagnostic imaging tests, clinical biomarkers, etc.

Discussion
This study has been approved by the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number: 2023–197-02). This study is designed to evaluate the safety and efficacy of ketorolac in patients with aTAAD. All participating patients will sign an informed consent form, and the trial results will be published in international peer-reviewed journals.

Trial registration
The Chinese Clinical Trial Registry (http://www.chictr.org.cn) ChiCTR2300074394. Registered on 4 October 2023.
Advances in the study of the interaction between schistosome infections and the host's intestinal microorganisms
Authors: Hong Ao , Umar Abdulrahim , Chen Hao , Yu Zheng , Huang Jing 
Published: April 2024

AbstractSchistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut–liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite–host–microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut–liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis.
Graphical Abstract
Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review
Authors: Kim Justin J. Y. , Dennett Liz , Ospina Maria B. , Hicks Anne , Vliagoftis Harissios , Adatia Adil 
Published: April 2024

Abstract
Purpose
Immunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations.

Methods
Literature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies.

Results
A total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review.

Conclusion
It is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.
Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window
Authors: Çam Sefa Burak , Çiftci Eda , Gürbüz Nazlıhan , Altun Bülent , Korkusuz Petek 
Published: April 2024

Abstract
Background
Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform.

Methods
hBMMSC-Exos were isolated and characterized. Real-time impedance-based cell proliferation analysis (RTCA) determined the effective dose and treatment window for acute hypoxic PT injury. A 2-lane 3D gravity-driven microfluidic platform was set to mimic PT in vitro. ZO-1, acetylated α-tubulin immunolabelling, and permeability index assessed structural; cell proliferation by WST-1 measured functional integrity of PT.

Results
hBMMSC-Exos induced PT proliferation with ED50 of 172,582 µg/ml at the 26th hour. Hypoxia significantly decreased ZO-1, increased permeability index, and decreased cell proliferation rate on 24–48 h in the microfluidic platform. hBMMSC-Exos reinforced polarity by a 1.72-fold increase in ZO-1, restored permeability by 20/45-fold against 20/155 kDa dextran and increased epithelial proliferation 3-fold compared to control.

Conclusions
The real-time potency assay and 3D gravity-driven microfluidic acute hypoxic PT injury platform precisely demonstrated the therapeutic performance window of allogeneic hBMMSC-Exos on ischemic AKI based on structural and functional cellular data. The novel standardized, non-invasive two-step system validates the cell-based personalized theragnostic tool in a real-time physiological microenvironment prior to safe and efficient clinical usage in nephrology.
Automatic classification of spread‐F types in ionogram images using support vector machine and convolutional neural network
Authors: Benchawattananon Phongsachot , Siritaratiwat Apirat , Supnithi Pornchai , Nishioka Michi , Perwitasari Septi , Suthisopapan Puripong , Kruesubthaworn Anan 
Published: April 2024

AbstractAn ionogram image serves as a valuable data for examining the ionospheric bottom side characteristics and variabilities. Spread-F is indicated or identified by plasma irregularity in the ionospheric region. Diffused echo in the ionogram images particularly pose challenges for efficient interpretation required in further applications. An automatic classification of spread-F is presented in this study. Ionogram images are automatically classified using preprocessing techniques to improve the classification performance. In this study, the classification is designed by two machine learning algorithms, including support vector machine (SVM) and convolutional neural network (CNN). The CNN model with preprocessing technique outperforms the SVM alternative based on 4,692 labelled ionogram images from the FMCW-type ionosonde at Chumphon station, Thailand. The model successfully classified clear, frequency spread-F (FSF), range spread-F (RSF), strong spread-F (SSF), and unidentified class with an accuracy of 98.0%, 85.1%, 90.7%, 66.7%, and 99.2%, respectively. The proposed automatic classification models achieved to classify classes of ionogram images. In addition, the image filtering and data preprocessing are useful with ionogram images for improving the model classification performance.
Graphical Abstract
Braille glove design toward interdisciplinary approach for visually impaired people: developing independent sensing design with MXene and embroidery
Authors: Kim Miha , Shin Hwansoo , Jekal Mee 
Published: April 2024

AbstractThis study developed a wearable device designed to aid visually impaired people (VIP) who are unfamiliar with Braille and/or struggle to learn and use Braille employing the design thinking process. VIP often face challenges in learning and using Braille, and even with existing equipment, including smart technologies, they frequently experience aesthetic and emotional discomfort beyond usability and accessibility. The interdisciplinary research team conducted mixed-method research following the double diamond module of the design thinking process. Initially, qualitative interviews to analyze VIP’s Braille utilization were conducted to derive design factors. Subsequently, identified design factors were applied to conduct experiments with appropriate embroidery methods and connection structures using MXene-coated yarn. The strategies effectively enhanced pressure sensing performance by two times and realized highly localized and independent sensing to enable Braille recognition. Finally, a specific design for the wearable Braille recognition glove was proposed that incorporated these findings. The proposed wearable glove, equipped with a high-performance Braille recognition sensor, is designed to enhance the psychological and aesthetic satisfaction of VIP. The glove’s universal design and accompanying technical support allow VIP to maintain their existing Braille reading methods while enjoying enhanced performance and avoiding social stigmas.
CA19-9 producing locally advanced papillary thyroid carcinoma: a case report
Authors: Morikawa Hiroki , Oba Takaaki , Kitazawa Ayaka , Iji Ryoko , Kiyosawa Nami , Amitani Masatsugu , Shimizu Tadafumi , Kanai Toshiharu , Uehara Takeshi , Ito Ken-ichi 
Published: April 2024

Abstract
Background
CA19-9 is a tumor marker for gastrointestinal and biliary-pancreatic adenocarcinomas; however, its association with thyroid cancer is unknown. Here, we report a case of CA19-9 producing locally advanced papillary thyroid carcinoma (PTC).

Case presentation
A 66-year-old woman who was identified with a thyroid tumor after a close examination of an elevated serum CA19-9 level, which was detected at health screening, was referred to our hospital. Ultrasonography revealed a 34 × 31 mm hypoechoic lesion in the lower pole of the left thyroid lobe. Computed tomography revealed a solid thyroid tumor with tracheal invasion without any distant metastases. Bronchoscopy revealed tumor exposure into the tracheal lumen on the left side of the trachea. Fine-needle aspiration cytology led to a diagnosis of papillary thyroid carcinoma (PTC). The patient underwent a total thyroidectomy, tracheal sleeve resection with end-to-end anastomosis, and lymph node dissection in the left cervical and superior mediastinal regions (D3c) with a reversed T-shaped upper sternotomy down to the third intercostal level. Histopathological analysis confirmed the diagnosis of PTC with tracheal invasion and no lymph node metastases (pT4a Ex2 N0). Immunohistochemical staining showed the expression of CA19-9 in cancer cells. Postoperatively, the serum CA19-9 level of the patient decreased to within the normal range.

Conclusions
Some PTCs produce CA19-9, although less frequently. When elevated serum CA19-9 levels are observed, PTC should be included in the differential diagnosis for further investigation.
Ambiguous citizenship policies: Examining implementation gaps across levels of legislation in Jordan
Authors: Frost Lillian 
Published: April 2024

AbstractDespite the prevalence of ambiguous citizenship policies that say one thing in law and another in implementing regulations, few studies have focused on systematically studying this type of implementation gap, particularly in contexts beyond North America and Europe. This largely has remained the case despite research on discursive policy gaps, which occur between a policy’s stated objectives and its laws, efficacy gaps, which describe when a policy’s outcomes fail to meet its goals, and compliance gaps, which reflect disparities between a state’s commitments to international law and its corresponding domestic policies. How can we advance conceptualizations of law-regulation implementation gaps? This paper proposes one approach by focusing on the content of domestic laws, on the one hand, and the content of related implementing regulations, on the other. When law-regulation discrepancies occur, they illustrate the agency of senior officials in writing this intentional ambiguity into different levels of legislation, challenging assumptions about institutional weakness and lower-level bureaucratic discretion as chief drivers of implementation gaps. The paper illustrates this concept by analyzing discrepancies between Jordan’s nationality and passports laws and their related implementing regulations, particularly regarding Gaza refugees’ access to passports, investors’ access to nationality, and Palestinian-Jordanians’ subjection to nationality withdrawals. These diverse cases of intentional ambiguity demonstrate that such gaps can serve to partially exclude or include a group and can occur with noncitizen and citizen as well as more or less vulnerable groups.
Association of serum sodium minus chloride level at initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and hyperkalemia in patients with CKD: a case control study
Authors: Mae Haruki , Fujimaru Takuya , Shimoyama Koutarou , Kadota Nozomi , Konishi Kasumi , Itou Yugo , Nagahama Masahiko , Taki Fumika , Nakayama Masaaki 
Published: April 2024

Abstract
Background
Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) exert a renoprotective effect on patients with chronic kidney disease (CKD). Despite their benefit, one of their side effects is hyperkalemia, and it is one of the most common reasons for discontinuation of these drugs. Hyperchloremic metabolic acidosis is a known risk factor for hyperkalemia in patients with CKD. However, whether it is a risk factor for hyperkalemia after initiating ACE-I or ARB remains unclear.

Methods
In a previous study, serum sodium minus chloride level ([Na+) − (Cl−]) was identified as useful for diagnosing metabolic acidosis. To estimate the baseline acid–base status, we determined for the cutoff value of [Na+] − [Cl−] that correlates with [HCO3−] below 24 mEq/L in patients with CKD. We then investigated whether this cutoff value was associated with hyperkalemia (serum potassium level ≥ 5.0 mEq/L) after initiating ACE-I or ARB in patients with CKD.

Results
In the investigation of the cutoff value of [Na+] − [Cl−], 612 patients were examined, and [Na+] − [Cl−] showed a good correlation with [HCO3−] (r = 0.67, p < 0.001). Based on receiver operating curve analysis, we derived a cut-off value of [Na+] − [Cl−] below 33.5 mEq/L. Using this cut off value, the sensitivity and specificity of [Na+] − [Cl−] for metabolic acidosis were 75.2% and 75.0%, respectively. To explore whether metabolic acidosis is associated with hyperkalemia after initiating ACE-I or ARB, we examined 1143 patients with CKD. Among this cohort, 403 (35.3%) patients had [Na+] − [Cl−] < 33.5 mEq/L at baseline, and the incidence of hyperkalemia was significantly higher in univariate analysis (9.2% versus 4.2%, p = 0.03). However, in multivariate analysis, [Na+] − [Cl−] < 33.5 mEq/L was not associated with hyperkalemia (odds ratio 1.13; 95% confidence interval 0.65–1.95).

Conclusions
Hyperchloremic metabolic acidosis was not associated with hyperkalemia after initiation of ACE-I or ARB in patients with CKD.
Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer
Authors: Lin Gigin , Hsieh Ching-Yi , Lai Ying-Chieh , Wang Chun-Chieh , Lin Yenpo , Lu Kuan-Ying , Chai Wen-Yen , Chen Albert P. , Yen Tzu-Chen , Ng Shu-Hang , Lai Chyong-Huey 
Published: April 2024

Abstract
Background
Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer.

Methods
This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39–60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups.

Results
The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different.

Conclusions
This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy.

Trial registration
ClinicalTrials.gov NCT04951921, registered 7 July 2021.

Relevance statement
This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients’ immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer.

Key points
• Effective radiotherapy induces abscopal effect via altering immune metabolism.
• Hyperpolarized 13C MRS evaluates patients’ immune potential non-invasively.
• Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.

Graphical Abstract