bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sessions of acupuncture and nutritional therapy evaluation for atrial fibrillation (Santé-AF): a randomised feasibility study
Authors: Charlesworth Karen , Torgerson David J. , Watson Judith M. 
Published: February 2025

Abstract

Background
Atrial fibrillation is a common cardiac arrhythmia, associated with debilitating symptoms and a decrease in health-related quality of life. Current treatments for atrial fibrillation may not provide symptomatic relief and are associated with risks and adverse responses. Large-scale trials are justified to investigate whether complementary therapies may improve symptoms and/or health-related quality of life in atrial fibrillation. To reduce the uncertainty of a future trial, a feasibility study was carried out.

Design and methods
A three-arm, parallel-group, pragmatic randomised controlled feasibility study recruited 30 participants with paroxysmal AF aged 45–70 from NHS primary care, randomising to Group A (acupuncture + usual care), Group B (nutritional therapy + usual care) or Group C (usual care alone) using a 2:2:1 allocation ratio in favour of the interventions. Interventions were delivered by private practitioners. Seven feasibility objectives were investigated, including participants’ willingness to take part, appropriateness of eligibility criteria, participant retention and acceptability of interventions and study assessments. Additional exploratory feasibility objectives were investigated, including the effect of the COVID-19 pandemic and the safety of interventions. Data was analysed using descriptive statistics and reflexive thematic analysis, and the study used a sequential convergent mixed methods design to understand whether, and why, objectives were feasible and to make recommendations for a future trial.

Results
Five feasibility objectives’ progression criteria were met, one did not meet its progression threshold and one was abandoned as infeasible to analyse but did not affect feasibility. Recommendations for a future trial include changes in eligibility criteria to reflect real-world populations and changes to assessment methods to reduce participant burden. Uncertainty remains around the effect on the feasibility of reversion to pre-COVID therapy and study assessment delivery, including a recommended longer follow-up.

Conclusion
A future large-scale trial was found to be feasible with adjustments, but some uncertainty remains.

Trial registration
ISRCTN13671984. Registered on June 04, 2020.
Health needs assessment tool for identifying the health issues among community residents with unmet needs
Authors: Kobashi Yurie 
Published: February 2025

Abstract

Background
This study aimed to discuss the method for designing a community project, especially in a resource-limited setting, using a health needs assessment tool, the Community Health Issues Interview Sheet, for the design of a project in the initial phase.

Methods
The Community Health Issues Interview Sheet was developed; this tool applied more than four field and modified based on feedback from researchers and stakeholders.

Results
When researchers from outside a target community design a community project, there are three factors to consider: resource size, target population, and focused health issues. The interview sheet was aimed at identifying priority health issues among the target population.

Conclusions
All community projects should be well-designed, and priority health issues should be assessed using a health needs assessment tool, such as the interview sheet in the initial project stage. Further education for researchers about project design in communities with resource-limited settings should be provided, and research on the experience of using the health needs assessment tool should be accumulated.
Application of the quality by design (QbD) approach to the development and validation of analytical methods for the quantification of Lumateperone Tosylate as the bulk drug and capsule dosage form by HPLC
Authors: Bavadekar Vasudha S. , Joshi Angha M. , Desai Ujwala S. 
Published: February 2025

Abstract

Background
The current studies involve the development of a liquid chromatographic method that is highly effective (HPLC) for the Lumateperone Tosylate method that is simple, rapid, accurate, precise, and economical, all made possible by analytical quality by design (AQbD). The HPLC method’s experimental settings were multivariately optimised by using the design of experiments to determine critical method parameters, and the Ishikawa diagram was used for risk assessment. A two-factor, three-level design was used for the factor screening investigations. Mathematical models were created using two independent factors: the buffer’s pH and the composition of the mobile phase. The response surface methodology and the impacts of these independent aspects were thoroughly examined using central composite design, which allowed for the evaluation of the critical method attributes (CMAs). The parameters of method robustness include retention time, peak area, and symmetry factor. Utilising the desirability function, the optimisation of the CMAs took place at the same time.

Results
According to the contour diagram’s optimised data, 10 mM ammonium acetate buffer (pH = 3.2): acetonitrile (80:20 v/v) was selected as a mobile phase with a 1 mL/min flow rate. A Zorbax SB C18 250 × 4.6 mm, 5 μ chromatographic column with a UV detector at 230 nm was used and oven temperature was maintained at 25 °C. Lumateperone Tosylate showed linearity in the concentration range of 25–250 µg/mL (r2 = 0.9921). % RSD for interday and intraday precision was found to be 0.25–0.52 and 0.12–0.32, respectively. The % assay of drug content was found to be 100.01 ± 0.06, and accuracy was found to be 100.30–100.65%. In compliance with ICH recommendations, the optimised assay conditions were validated.

Conclusion
Therefore, it was clearly shown from the results that the AQbD methodology could be effectively used to optimise the HPLC method for Lumateperone Tosylate analysis. The technique was used to assess the Lumateperone Tosylate content in capsules as well.
The Risk of Adrenal Insufficiency after Treatment with Relatlimab in Combination with Nivolumab is Higher than Expected
Authors: Chamorro-Pareja Natalia , Faje Alexander T , Miller Karen K 
Published: February 2025

Abstract

Context
Adrenal insufficiency from hypophysitis is a complication of immune checkpoint inhibitor (ICI) therapy. However, the risk associated with relatlimab, a lymphocyte activation gene 3 inhibitor, is unknown. Relatlimab was approved in 2022 in combination with nivolumab for the treatment of unresectable or metastatic melanoma.

Objective
To determine the prevalence, identify risk factors, and characterize the clinical presentation of central adrenal insufficiency in patients receiving relatlimab-nivolumab compared to nivolumab alone.

Methods
Retrospective analysis of Mass General Brigham healthcare system patients who received relatlimab-nivolumab from 2015 to 2023 matched by age, sex and race to individuals receiving monotherapy with nivolumab, an ICI with a risk of hypophysitis of &lt;1%.

Results
Adrenal insufficiency was diagnosed in 10 patients (7.6%) after relatlimab-nivolumab administration and in 1 patient (0.8%) after nivolumab monotherapy (p=0.00056). Within the relatlimab-nivolumab group, median age and sex were comparable in patients who developed adrenal insufficiency compared to those who did not. The median number of doses received by subjects who developed adrenal insufficiency was 7 (4-10) compared to 3 (2-6) in those who did not (p=0.03). The most common presenting symptoms were fatigue, anorexia, nausea, and vomiting. No patients were diagnosed with additional anterior pituitary hormone deficiencies or AVP deficiency, though not all patients were evaluated for these diagnoses.

Conclusions
This study is the first cohort analysis of hypophysitis in patients treated with relatlimab-nivolumab compared to nivolumab monotherapy. Combination treatment with relatlimab-nivolumab confers a significantly higher risk of developing adrenal insufficiency, likely secondary to hypophysitis, compared to nivolumab alone.
Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance
Authors: Apostolopoulou Maria , Lambadiari Vaia , Roden Michael , Dimitriadis George D 
Published: February 2025

Abstract
People with type 1 diabetes (T1D) are usually considered to exclusively exhibit β-cell failure, but they frequently also feature insulin resistance. This review discusses the mechanisms, clinical features, and therapeutic relevance of insulin resistance by focusing mainly on human studies using gold-standard techniques (euglycemic–hyperinsulinemic clamp). In T1D, tissue-specific insulin resistance can develop early and sustain throughout disease progression. The underlying pathophysiology is complex, involving both metabolic- and autoimmune-related factors operating synergistically. Insulin treatment may play an important pathogenic role in predisposing individuals with T1D to insulin resistance. However, the established lifestyle-related risk factors and peripheral insulin administration inducing glucolipotoxicity, hyperinsulinemia, hyperglucagonemia, inflammation, mitochondrial abnormalities, and oxidative stress cannot always fully explain insulin resistance in T1D, suggesting a phenotype distinct from type 2 diabetes. The mutual interaction between insulin resistance and impaired endothelial function further contributes to diabetes-related complications. Insulin resistance should therefore be considered a treatment target in T1D. Aside from lifestyle modifications, continuous subcutaneous insulin infusion can ameliorate insulin resistance and hyperinsulinemia, thereby improving glucose toxicity compared with multiple injection insulin treatment. Among other concepts, metformin, pioglitazone, incretin-based drugs such as GLP-1 receptor agonists, sodium-glucose cotransporter inhibitors, and pramlintide can improve insulin resistance, either directly or indirectly. However, considering the current issues of high cost, side effects, limited efficacy, and their off-label status, these agents in people with T1D are not widely used in routine clinical care at present.
Perceptions and support of the Muslim community towards the development of marine halal tourism
Authors: Chairani Nur , Hidayaturrahman Mohammad 
Published: February 2025

Halal Tourism is a culture-based tourism that prioritizes Islamic Principles and Sharia and hopes to build a superior moral personality as its foundation. The research used a qualitative descriptive method to develop marine halal tourism in Indonesia, especially on the island of Madura. Problem-solving methods used interviews, observations, documentation, and literature studies that refer to the Muslim community's perception of marine halal tourism in Indonesia. The results of this evaluation show that by cooperating with the Government of the Tourism Office, the community and other parties in the perception and support of the Muslim community to develop Marine Halal Tourism on the island of Madura and explore the potential of local areas to increase tourist visitor satisfaction to enjoy facility services by Islamic Sharia. In this case, Halal Maritime Tourism can provide positive things for the Muslim community, especially on Madura Island, so that they can maintain their culture and customs to maintain honor, and foreign tourists can also appreciate the local culture on Madura Island.

Keywords: Halal tourism, Maritime tourism, Muslim tourism.
Identification of halal labels on primary and secondary drug packaging at RSUD Dr. Soegiri Lamongan
Authors: Khoiro Niswatin , Kusumanegara Sri Bintang Sahara Mahaputra , Handayani Riana Prastiwi 
Published: February 2025

The majority of religions practiced by residents in the Lamongan area are Islam. In Islam, it is commanded to seek treatment with what is halal and is prohibited from seeking treatment with what is haram. Consumers cannot meet the manufacturer directly, but they must pay attention to the halal label on the drug packaging to consider their choices. This study aims to determine the percentage of drugs with the halal logo at Dr Soegiri Lamongan. This research used an observational design with samples of oral medication packaging at Dr. RSUD. Soegiri Lamongan and use a purposive sampling technique. The instrument used is an observation sheet. The research results showed that from 395 items of oral drugs at RSUD Dr Soegiri Lamongan had a halal label 97 (25%) consisting of capsule preparations of 12 (22%) medicinal items, caplets 6 (12%) medicinal items, tablets 65 (27%) medicinal items, dry syrup 1 (10%) items of medicine, suspension 4 (40%) items of medicine, elixir 1 (100%) items of medicine, drops 2 (25%) items of medicine, and syrup 6 (35%) items of medicine. In contrast, those that do not have a halal label are 298 (75%) oral drugs. The McNemar Test results showed a value of p = 0.000 with a significance value of p < 0.05 for all drugs and oral solid drugs. Meanwhile, the results of the McNemar test on oral liquid drugs show a value of p = 1.000 with a significance value of p > 0.05. Thus, many oral drugs still do not have a halal label on their packaging. Thus, many oral drugs still do not have a halal label on their packaging. However, these drugs are not necessarily haram. The certification process takes quite a long time, and the critical points for halal medicine, which lie in the ingredients, processing, packaging, and storage, are important things in the halal certification process to obtain a halal medicine label.

Keywords: Critical points, Drug, Halal label, Packaging.
Production and characterization of halal-based gelatin derived from Red Nile Tilapia (Oreochromis niloticus) fishbone
Authors: Rahmayanti Mayu , Irsyadulibad Mohamad , Dewi Tanaya Jati Dharma , Firdausi Amalia Salsa Billah , Megawati Dewi Sinta 
Published: February 2025

Gelatin is one of the chemical products derived from protein hydrolysis. The demand for gelatin in Indonesia increases yearly, but domestic production still needs to meet the demand, leading to imports. International gelatin production statistics indicate that 58% is derived from pig skin, which is prohibited for Muslims. Therefore, this research aims to produce halal-based gelatin that meets quality standards. Red Nile Tilapia (Oreochromis niloticus) fishbones are used as the raw material for this study, as their halal status is clear in the Quran and Hadith. The fishbones are soaked in different concentrations of phosphoric acid, namely F1 (4%), F2 (6%), and F3 (8%), for 48 hours, then extracted using distilled water solvent in a water bath for 6 hours. The extracted solution is filtered, and the filtrate is dried in an oven at 50°C for 48 hours. The gelatin yield is statistically analyzed using correlation methods, and its functional groups are identified using FTIR spectroscopy. Compared to existing standards, gelatin characteristics are evaluated through organoleptic tests, such as pH, gel strength, viscosity, moisture content, and ash content. The gelatin yield for F1 is 8.15 ± 0.18%; F2 is 12.08 ± 0.12%, and F3 is 15.66 ± 0.26%. The research demonstrates that phosphoric acid concentration significantly influences gelatin yield, with higher concentrations resulting in higher yields. The FTIR spectra also indicate that the synthesized gelatin resembles commercial gelatin in spectra and absorption peaks. All gelatin variations meet the requirements for organoleptic properties, gel strength, moisture content, and ash content, while only F1 and F2 meet the pH requirements.

Keywords: FTIR, halal gelatin, Red Nile Tilapia (Oreochromis niloticus) fishbone.
Swelling capacity analysis and oversize deviation of nata de coco processed by CV ABC Yogyakarta
Authors: Yahya Mirza Auly , Khairi Amalya Nurul , Uddin A. B. M. Helal 
Published: February 2025

Nata de coco is a food product derived from fermented coconut water with the help of the bacterium Acetobacter xylinum. CV ABC is the company that always produces nata de coco and notices the quality of the product. The problem in this study lies in the product standard testing, which often results in deviations from the swelling capacity test and the oversized test, which do not comply with company standards, thereby reducing the quality of Nata de Coco products. This research activity aims to analyze and formulate solutions related to the factors that cause deviations in production results. The method used is quantitative, with a graphical control chart to determine the magnitude of deviations that occur in the swelling capacity test and oversize test. Fishbone diagrams are used to determine the factors causing nata de coco to deviations from company standards. The data is in the form of documentation of the results of the swelling capacity test and the oversized test of 15 data. Data collection used a random sampling technique, which involved taking 400-gram samples of nata de coco from each batch. The results of the 15-day analysis showed that the swelling capacity test did not meet company standards by 7 days, or 47%, and the oversized test did not meet the maximum limit by 4 days, or 27%. Factors that dominate the causes of irregularities are equipment and people. There is a need for machine standardization and employee discipline to maintain the quality of nata de coco.

Keywords: Nata de coco, Oversize, Swelling capacity.
Volatile profile and its application on species authentication of meat-based food
Authors: Indrasti Dias , Ramadhina Siti Hanifah Rifan 
Published: February 2025

Meat and meat-based food produces a certain composition of volatile compounds, which can be used to identify its origin and, consequently, for food authentication. Numerous studies have explored the application of volatile compounds in identifying meat-based food using volatilomics, an emerging analytical technique. This review focuses on the volatile compound profiles, the factors influencing their production, method of extraction and detection, and their application in meat and meat-based products, with a brief discussion on their potential use for Halal authentication. The major volatile compounds associated with meat aromas include aldehydes, ketones, and alcohols, with variation in composition among different types of meat, though no definite pattern has been identified. Most of these volatile compounds are byproducts of the Maillard reaction, Strecker degradation, or interaction of both, as well as thiamine degradation. Head space-solid phase microextraction (HS-SPME) is meat's standard volatile compounds extraction method due to its convenience, solvent-free process, high sensitivity, and practicality. Gas chromatography-mass spectrometry (GC-MS) is the primary analytical technique for detecting volatile metabolites and is considered the most effective among available methods The volatilomics approach has also been applied in Halal authentication to distinguish among different animal species. The volatile compound profiles can differentiate meat-based products derived from chicken, beef, and pork. While the volatilomics approach shows great potential for use in Halal authentication, additional complementary methods are still required to obtain more comprehensive data.

Keywords: Aroma, Chromatography, Halal, Identification, Vapor, Volatilomics.
Psychological care provided by midwives in residential postpartum care facilities in Japan
Authors: Kuwahara Sayaka , Wachi Shigemi , Arai Yoko 
Published: February 2025

Background/Aims In Japan, residential postpartum care facilities admit mothers after discharge from the facility where they gave birth. The psychological elements of postpartum care provided at these facilities is unknown. This study aimed to explore the psychological care (especially care intended to prevent postpartum depression) usually provided by midwives in residential postpartum care facilities. Methods Qualitative induction was used to analyse questionnaires and semi-structured interviews conducted with seven midwives at different facilities providing residential postpartum care in Japan. Results Care was generally focused on acceptance and listening, promoting rest and allowing for reflection on childbirth. Care specifically intended to prevent postpartum depression was focused on initial assessments and prioritised relationships with husbands and family members, while avoiding providing excessive advice or altering mothers' established childcare practices. Conclusions Midwives practices were founded on respect for mothers and providing health guidance and family interactions that matched mothers' needs. Initial assessments were key to preventing postpartum depression, and midwives involved mothers' husbands and other family members in this care. These practices build trusting relationships and help mothers gain confidence in childrearing. Implications for practice Midwives providing psychological care to prevent postpartum depression should focus on initial assessments, and involve the woman's husband and family members.
Clinical safety and pharmacokinetics of a novel oral niclosamide formulation compared with marketed niclosamide chewing tablets in healthy volunteers: A three-part randomized, double-blind, placebo-controlled trial
Authors: Walther Niklas , Schultz-Heienbrok Robert , Staß Heino , Corman Victor M. , Gassen Nils C. , Müller Marcel A. , Drosten Christian , Witzenrath Martin , Lee Hweeling , Posch Maximilian G. 
Published: February 2025

Aim
Niclosamide is an established anthelmintic substance and a promising candidate for treating cancer, viral infections, and other diseases. However, its solubility in aqueous media is low, and the systemic bioavailability of the commercially available chewing tablet is poor, limiting the use of niclosamide for systemic treatment. A liquid oral formulation using polyethylene glycol 400 was developed and investigated in healthy volunteers to assess safety, tolerability, and pharmacokinetics in comparison to the marketed tablet. (ClinicalTrials.gov: NCT04644705).

Methods
The study consisted of three parts: Part A was a double-blind placebo-controlled single ascending dose trial in three dose groups (200, 600, and 1600 mg) with four participants receiving either the investigational niclosamide formulation or placebo (3:1) under fasted and/or fed conditions. Part B was a crossover study comparing 1600 mg investigational niclosamide solution with the marketed 2000 mg chewing tablet in four healthy volunteers. Part C was a double-blind placebo-controlled multiple-dose trial comparing 1200 mg and 1600 mg (verum: placebo 4:2) in two dose groups with six subjects each, who received daily doses for seven days.

Results
No serious or severe adverse events occurred. The most frequent adverse events were mild to moderate gastrointestinal reactions. There was also no apparent dependence between drug exposure levels (AUC, Cmax) and the severity and incidence of adverse events detectable. A relevant food effect was observed with a mean AUClast about 2-fold higher in fed condition compared to fasted condition. In Part B, dose-normalized Cmax and AUClast were similar for niclosamide solution and tablet. Absorption of niclosamide solution was highly variable. Some individuals showed high absorption (Cmax > 2µg/ml) whereas others did absorb only marginally. Importantly, there was no dose linearity in the range of 200 mg – 1600 mg. No signs of relevant systemic drug accumulation after multiple administrations were observed.

Conclusion
Overall safety and tolerability observed in healthy subjects were benign. This is also true for individuals with high absorption (Cmax > 2µg/ml), encouraging further research into niclosamide as a potential therapeutic agent. Galenic optimization, however, will remain challenging as evident from the observed exposure variability and non-linear PK. Non-linearity, if confirmed by additional data, might make niclosamide more suitable for multi-dose rather than high single dose regimens. The observed food effect should also be considered when further investigating systemic niclosamide exposures.

Trial registration
ClinicalTrials.gov NCT04644705