bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Walk me through the final day”: A thematic analysis study on the family caregiver experience of the Medical Assistance in Dying procedure day
Authors: Nissim Rinat , Chu Paige , Stere Alison , Tong Eryn , An Ekaterina , Selby Debbie , Bean Sally , Isenberg-Grzeda Elie , Rodin Gary , Li Madeline , Hales Sarah 
Published: May 2024

Background: Legalization of assisted dying is progressively expanding worldwide. In Canada, the Medical Assistance in Dying Act became law in 2016. As assisted dying regulations evolve worldwide, comprehending its subjective impact and broader consequences, especially on family members, becomes pivotal for shaping practice, policy, and training. Aim: The goal of this study is to understand the experience of family caregivers on the assisted dying procedure day. Design: Qualitative, thematic analysis, research using semi-structured interviews. Setting/participants: Family caregivers of patients who received assisted dying in two hospitals in Canada were recruited. Interviews were conducted at least 6 months after patient death. Conceptual saturation was achieved after analyzing 18 interviews. Results: While caregivers expressed gratitude for the availability of Medical Assistance in Dying, they also described the procedure day as potentially jarring and unsettling. We identified five aspects that shaped their experience: attuned support from the clinical team; preparation for clinical details; congruence between the setting and the importance of the event; active participation and ceremony; and pacing and timing of the procedure. Together, these aspects impacted the level of uneasiness felt by caregivers on the procedure day. Conclusions: This study emphasized the importance of a family-centered approach to delivering Medical Assistance in Dying. It underscored recognizing the needs of family caregivers during the procedure day and offering strategies to ease their experience. Healthcare providers in jurisdictions where assisted dying is legal or deliberated should consider the applicability of these findings to their unique context.
Causes, risks and care circumstances associated with death in older adults diagnosed with HIV in a tertiary centre in Malaysia
Authors: Wong Hoi Yee , Pui Li Wong , Abdul Kahar Maria Kahar Bador , Chong Meng Li , Shenoi Sheela , Rozanova Julia , Syed Omar Sharifah Faridah , Neelamegam Malinee , Lee Yew Kong , Rajasuriar Reena 
Published: May 2024

Background A substantial number of older adults succumb soon after HIV diagnosis despite ART. We explored the causes, risk factors and circumstances before death among older adults acquring HIV. Methods We recruited individuals newly diagnosed at our centre from 2016-2020 and analysed data of those who died. Patients were stratified to older (≥50 years) or younger (<50 years) based on their age at diagnosis and attributes were compared. The Cox proportional multivariable model was used to identify factors associated with all-cause mortality. Results Among 75 deaths reported, the majority of deaths were AIDS-related and late presentation was common in both age groups. The majority of deaths occurred in the first 12 months after care presentation and over two-thirds in both groups disengaged from care prior to death. Older age remained an independent factor associated with death after adjusting for confounders including opportunistic infections, late presentation to care, ART initiation and chronic comorbidities at presentation. Conclusion Most causes of death in our setting were AIDS-related and associated with late care presentation both in young and older individuals, although older age at diagnosis remained an independent risk factor. Our findings highlight the urgent need to encourage prompt ART initiation following diagnosis, especially in older adults.
Real-world analysis of afatinib as a first-line treatment for patients with advanced stage non-small-cell lung cancer with uncommon EGFR mutations: a multicenter study in Vietnam
Authors: Pham Van Luan , Le Tuan Anh , Pham Cam Phuong , Hoa Nguyen Thi Thai , Do Anh Tu , Nguyen Tuan Khoi , Nguyen Minh Hai , Thu Hoang Thi Anh , Hao Vuong Dinh Thy , Tam Nguyen Dac Nhan , Khiem Dang Van , Nguyen Thi Oanh , Trang Vo Thi Huyen , Do Hung Kien , Vu Ha Thanh , Nguyen Thi Thuy Hang , Pham Van Thai , Trinh Le Huy , Dung Nguyen Khac , Nguyen Hoang Gia , Truong Cong Minh , Chau Pham Tran Minh , Nguyen Thi Bich Phuong 
Published: May 2024

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X–S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X–S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.
The efficacy of botulinum toxin in neuropathic pain: a systematic review
Authors: Oliveira Kaísa Menezes , Barreto Eduardo Silva Reis , Alencar Vinicius Borges , Lins-Kusterer Liliane Elze Falcão , Azi Liana Maria Torres de Araujo , Kraychete Durval Campos 
Published: May 2024

Introduction Neuropathic pain (NP) is characterised as a lesion or disease directly affecting the somatosensory system. This study aims to analyse the efficacy of botulinum toxin type A (BT-A) in the treatment of neuropathic pain. Methods This systematic literature review, guided by PRISMA, applied the PICO strategy with the following criteria: (P = patients with neuropathic pain, I = botulinum toxin, C = placebo or active drug, and O = pain relief). Results Fourteen articles, all randomised controlled trials with a placebo control, were included in the review. A total of 645 patients were randomised, with 353 patients receiving treatment with botulinum toxin type A in doses ranging from 25U to 400U. The evaluated studies addressed trigeminal neuralgia, diabetic polyneuropathy, post-herpetic neuralgia, spinal cord injury, phantom limb pain, and peripheral neuropathic pain after trauma or surgery. Conclusion BT-A has emerged as a promising treatment for various origins of neuropathic pain. Therefore, future studies should adopt stricter criteria regarding dosage and routes of administration to ensure effective and consistent BT-A application.
Gonadotropin-releasing hormone antagonist (relugolix) for treatment of uterine adenomyosis with symptomatic endometriosis
Authors: Matsushima Takashi , Nagashima Asako , Harigane Eika , Watanabe Asako , Shinmura Hiroki , Ouchi Nozomi , Kurashina Ryuhei , Suzuki Shunji , Iida Shinya 
Published: May 2024

Objective: To determine the effects of relugolix administration for uterine adenomyosis on uterine volume and subjective symptoms. Methods: This retrospective observational study included 30 patients with clinical symptoms of endometriosis complicated with uterine adenomyosis who were treated with 40 mg/day of relugolix orally for >16 weeks. The uterine volume was calculated pre- and post-administration, and the volume percentage post-administration. Furthermore, the presence or absence of subjective post-administration symptoms and adverse effects were also examined. Results: The median (interquartile range) long diameter, short diameter, width, and volume of the patients’ uteri pre- and post-administration of relugolix significantly decreased from 9.63 (9.02–11.00) to 8.00 (6.84–9.12) cm, 6.47 (5.58–8.02) to 5.00 (4.26–5.63) cm, 6.91 (5.68–8.46) to 5.49 (4.58–6.00) cm, and 221.04 (146.52–390.26) to 111.90 (71.59–165.84) cm3, respectively ( p < 0.001 for all four items). Additionally, the uterus volume post-administration was 48.30% (33.88–62.54%) of that pre-administration. Heavy menstrual bleeding, dysmenorrhea, and chronic pelvic pain occurred in 23 (76.7%), 21 (70.0%), and 13 (43.3%) of the 30 patients, respectively; however, all patients experienced resolution of all symptoms. Nine, three, and one patients had hot flashes, mild arthralgia, and a mild headache, respectively. No cases of persistent irregular or heavy bleeding were observed during treatment. Conclusions: Relugolix contributes to volume reduction and eliminates subjective symptoms of uterine adenomyosis, suggesting that it is an effective treatment for uterine adenomyosis.
N-terminal pro-brain natriuretic peptide is associated with pulmonary hypertension or diastolic dysfunction in patients with systemic sclerosis: An Australian prospective cross-sectional study
Authors: Ha Francis J , Brown Zoe , Stevens Wendy , Prior David , Ross Laura , Ferdowsi Nava , Nikpour Mandana , Burns Andrew T 
Published: May 2024

Introduction: Pulmonary arterial hypertension and left ventricular diastolic dysfunction are associated with significant morbidity and mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide has been proposed as part of composite screening algorithms for pulmonary arterial hypertension. Our aim was to assess the prevalence of pulmonary hypertension and diastolic dysfunction, and evaluate their association with serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients. Methods: Patients with systemic sclerosis were prospectively enrolled to undergo N-terminal pro-brain natriuretic peptide testing and transthoracic echocardiography at a tertiary Australian centre from January to October 2022. We collected demographic and transthoracic echocardiography variables including pulmonary hypertension estimated by tricuspid regurgitant velocity and diastolic dysfunction assessed by the ASE/EACVI 2016 guidelines. Pearson’s correlation coefficient was used to evaluate association between N-terminal pro-brain natriuretic peptide and echocardiographic parameters. Results: Sixty-one patients were enrolled (median age = 62 years (interquartile range = 55–69 years); 84% female). Two-thirds of patients had limited systemic sclerosis (40/61). Five patients (8%) had high likelihood of pulmonary hypertension by transthoracic echocardiography. Seven patients (11%) had diastolic dysfunction; however, seven patients (11%) had indeterminate diastology. Six patients underwent right heart catheterisation, with five patients diagnosed with pulmonary hypertension. N-terminal pro-brain natriuretic peptide in patients with pulmonary hypertension or diastolic dysfunction was significantly higher (median = 207 and 226 pg/mL, respectively) compared to patients without either condition (median = 69 pg/mL, p = 0.01). N-terminal pro-brain natriuretic peptide showed a statistically significant although limited correlation with estimated pulmonary pressures measured by tricuspid regurgitant velocity (r = 0.44, p = 0.002) and left ventricular filling pressures (r = 0.27, p = 0.04). Conclusion: Pulmonary hypertension and diastolic dysfunction are both observed in systemic sclerosis. N-terminal pro-brain natriuretic peptide is associated with both conditions; however, it cannot distinguish between the two disease processes. Right heart catheterisation may be required to make this distinction.
Cross-sectional associations between patterns and composition of upright and stepping events with physical function: insights from The Maastricht Study
Authors: Culverhouse Joshua , Hillsdon Melvyn , Koster Annemarie , Bosma Hans , de Galan Bastiaan E. , Savelberg Hans H.C.M. , Pulsford Richard 
Published: May 2024

Abstract
Introduction
Age-related declines in physical functioning have significant implications for health in later life. Physical activity (PA) volume is associated with physical function, but the importance of the pattern in which PA is accumulated is unclear. This study investigates associations between accelerometer-determined daily PA patterns, including composition and temporal distribution (burstiness) of upright and stepping events, with physical function.

Methods
Data was from participants who wore an activPAL3 accelerometer as part of The Maastricht Study. Exposures included a suite of metrics describing the composition and the temporal distribution (burstiness) of upright and sedentary behaviour. Physical function outcomes included the six-minute walk test (6MWT), timed chair-stand test (TCST), grip strength (GS), and SF-36 physical functioning sub-scale (SF-36pf). Multivariable linear regression models were used to assess associations, adjusting for covariates including overall PA volume (daily step count).

Results
Participants(n = 6085) had 6 or 7 days of valid data. Upright and stepping event metrics were associated with physical function outcomes, even after adjusting PA volume. Higher sedentary burstiness was associated with better function (6MWT, TCST, and SF-36pf), as was duration and step volume of stepping events (6MWT, TCST, GS, and SF-36pf), step-weighted cadence (6MWT, TCST, and SF-36pf). Number of stepping events was associated with poorer function (6MWT, GS, and SF-36pf), as was upright event burstiness (SF-36pf). Associations varied according to sex.

Conclusion
Our study reveals that diverse patterns of physical activity accumulation exhibit distinct associations with various measures of physical function, irrespective of the overall volume. Subsequent investigations should employ longitudinal and experimental studies to examine how changing patterns of physical activity may affect physical function, and other health outcomes.
Determinants of shared e-scooter usage and their policy implications. findings from a survey in Braga, Portugal
Authors: Dias Gabriel , Ribeiro Paulo , Arsenio Elisabete 
Published: May 2024

AbstractShared e-scooter systems have become an alternative for micromobility users in cities since 2017. The success of the shared e-scooter service can be related to the provision of more last-mile flexibility and convenience to users. They can also be seen as a replacement for private cars and on-demand ridesharing, especially in highly crowded urban environments. Therefore, the main objective of this research is to disclose the main characteristics that determine shared e-scooter usage and their policy implication in a medium-sized city in the North of Portugal. To meet this purpose, a survey was conducted, and statistical analyses were performed to correlate the sociodemographic characteristics of respondents with the willingness to use shared e-scooters. Results show that gender, origin of the trip, and the main mode of transport affect the usage of e-scooters, thus specific policies should be developed to decrease these inequalities. Special attention needs to be given to the creation and expansion of dedicated areas for e-scooter ridership, zoning, and some traffic calming measures to promote a safe, user-centric, and more pleasant environment for shared e-scooter riders.
New reports of pathogen spectrum associated with bulb rot and their interactions during the development of rot in tulip
Authors: Nisa Qadrul , Gulzar Gazala , Dar Mohammad Saleem , Shahnaz Efath , Banday Saba , Bhat Zahoor A. , El-Sheikh Mohamed A. , Nabi Sajad Un , Arya Vivak M. , Anwar Ali , Mansoor Sheikh 
Published: May 2024

AbstractBulb rot, a highly damaging disease of tulip plants, has hindered their profitable cultivation worldwide. This rot occurs in both field and storage conditions posing significant challenges. While this disease has been attributed to a range of pathogens, previous investigations have solely examined it within the framework of a single-pathogen disease model. Our study took a different approach and identified four pathogens associated with the disease: Fusarium solani, Penicillium chrysogenum, Botrytis tulipae, and Aspergillus niger. The primary objective of our research was to examine the impact of co-infections on the overall virulence dynamics of these pathogens. Through co-inoculation experiments on potato dextrose agar, we delineated three primary interaction patterns: antibiosis, deadlock, and merging. In vitro trials involving individual pathogen inoculations on tulip bulbs revealed that B. tulipae,was the most virulent and induced complete bulb decay. Nonetheless, when these pathogens were simultaneously introduced in various combinations, outcomes ranged from partial bulb decay to elongated rotting periods. This indicated a notable degree of antagonistic behaviour among the pathogens. While synergistic interactions were evident in a few combinations, antagonism overwhelmingly prevailed. The complex interplay of these pathogens during co-infection led to a noticeable change in the overall severity of the disease. This underscores the significance of pathogen-pathogen interactions in the realm of plant pathology, opening new insights for understanding and managing tulip bulb rot.
DCGAN-DTA: Predicting drug-target binding affinity with deep convolutional generative adversarial networks
Authors: Kalemati Mahmood , Zamani Emani Mojtaba , Koohi Somayyeh 
Published: May 2024

Abstract
Background
In recent years, there has been a growing interest in utilizing computational approaches to predict drug-target binding affinity, aiming to expedite the early drug discovery process. To address the limitations of experimental methods, such as cost and time, several machine learning-based techniques have been developed. However, these methods encounter certain challenges, including the limited availability of training data, reliance on human intervention for feature selection and engineering, and a lack of validation approaches for robust evaluation in real-life applications.

Results
To mitigate these limitations, in this study, we propose a method for drug-target binding affinity prediction based on deep convolutional generative adversarial networks. Additionally, we conducted a series of validation experiments and implemented adversarial control experiments using straw models. These experiments serve to demonstrate the robustness and efficacy of our predictive models. We conducted a comprehensive evaluation of our method by comparing it to baselines and state-of-the-art methods. Two recently updated datasets, namely the BindingDB and PDBBind, were used for this purpose. Our findings indicate that our method outperforms the alternative methods in terms of three performance measures when using warm-start data splitting settings. Moreover, when considering physiochemical-based cold-start data splitting settings, our method demonstrates superior predictive performance, particularly in terms of the concordance index.

Conclusion
The results of our study affirm the practical value of our method and its superiority over alternative approaches in predicting drug-target binding affinity across multiple validation sets. This highlights the potential of our approach in accelerating drug repurposing efforts, facilitating novel drug discovery, and ultimately enhancing disease treatment. The data and source code for this study were deposited in the GitHub repository, https://github.com/mojtabaze7/DCGAN-DTA. Furthermore, the web server for our method is accessible at https://dcgan.shinyapps.io/bindingaffinity/.
Metabolomics analysis of different diameter classes of Taxus chinensis reveals that the resource allocation is related to carbon and nitrogen metabolism
Authors: Pan Liben , Li Yi , Zhao Wen , Sui Yushu , Yang Nan , Liu Longjie , Liu Yang , Tang Zhonghua , Mu Liqiang 
Published: May 2024

AbstractTaxus chinensis (Taxus cuspidata Sieb. et Zucc.) is a traditional medicinal plant known for its anticancer substance paclitaxel, and its growth age is also an important factor affecting its medicinal value. However, how age affects the physiological and metabolic characteristics and active substances of T. chinensis is still unclear. In this study, carbon and nitrogen accumulation, contents of active substances and changes in primary metabolites in barks and annual leaves of T. chinensis of different diameter classes were investigated by using diameter classes instead of age. The results showed that leaves and barks of small diameter class (D1) had higher content of non-structural carbohydrates and C, which were effective in enhancing defense capacity, while N content was higher in medium (D2) and large diameter classes (D3). Active substances such as paclitaxel, baccatin III and cephalomannine also accumulated significantly in barks of large diameter classes. Moreover, 21 and 25 differential metabolites were identified in leaves and barks of different diameter classes, respectively. The differential metabolites were enhanced the TCA cycle and amino acid biosynthesis, accumulate metabolites such as organic acids, and promote the synthesis and accumulation of active substances such as paclitaxel in the medium and large diameter classes. These results revealed the carbon and nitrogen allocation mechanism of different diameter classes of T. chinensis, and its relationship with medicinal components, providing a guidance for the harvesting and utilization of wild T. chinensis.