bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Starting to think that way from the start": Approaching deprescribing decision-making for people accessing palliative care - a qualitative exploration of healthcare professionals views.
Authors: Robinson-Barella Anna , Richardson Charlotte Lucy , Bayley Zana , Husband Andy , Bojke Andy , Bojke Rona , Exley Catherine , Hanratty Barbara , Elverson Joanna , Jansen Jesse , Todd Adam 
Published: March 2024

Abstract

Background:
Deprescribing has been defined as the planned process of reducing or stopping medications that may no longer be beneficial or are causing harm, with the goal of reducing medication burden while improving patient quality of life. At present, little is known about the specific challenges of decision-making to support deprescribing for patients who are accessing palliative care. By exploring the perspectives of healthcare professionals, this qualitative study aimed to address this gap, and explore the challenges of, and potential solutions to, making decisions about deprescribing in a palliative care context.
Methods:
Semi-structured interviews were conducted with healthcare professionals in-person or via video call, between August – January 2023. Perspectives on approaches to deprescribing in palliative care; when and how they might deprescribe; and the role of carers and family members within this were discussed. Interviews were audio-recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the NHS Health Research Authority (ref 305394).
Results:
Twenty healthcare professionals were interviewed, including: medical consultants, nurses, specialist pharmacists, and general practitioners (GPs). Participants described the importance of deprescribing decision-making, and that it should be a considered, proactive, and planned process. Three themes were developed from the data, which centred on: (1) professional attitudes, competency and responsibility towards deprescribing; (2) changing the culture of deprescribing; and (3) involving the patient and family/caregivers in deprescribing decision-making.
Conclusions:
This study sought to explore the perspectives of healthcare professionals with responsibility for making deprescribing decisions with people accessing palliative care services. A range of healthcare professionals identified the importance of supporting decision-making in deprescribing, so it becomes a proactive process within a patient’s care journey, rather than a reactive consequence. Future work should explore how healthcare professionals, patients and their family can best be supported in the shared decision-making processes of deprescribing.
Trial registration:
Ethical approval was obtained from the NHS Health Research Authority (ref 305394).
Natural History Study of Recessive Dystrophic Epidermolysis Bullosa Wounds and Patient Reported Outcomes Using Mobile Application Home Photography
Authors: Fulchand Shivali , Nazaroff Jaron , Harris Nicki , So Jodi , Eid Edward , Li Shufeng , Lu Ying , Tang Jean 
Published: March 2024

Abstract

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, blistering genetic disease where wounding and wound pain are the most commonly reported problems by patients. The natural history of RDEB wounds has not been prospectively studied, thus limiting the design of clinical trial endpoints.
Objective: To determine differences in spontaneous wound closure between chronic open vs recurrent RDEB wounds.
Methods: We conducted a prospective observational study in which participants used a mobile application to upload weekly photographs of multiple target wounds for up to 6 months and reported associated wound pain and itch (Photo Cohort). We also utilized a separate dataset of placebo-treated wounds from a previously completed trial (Validation Cohort) to validate the differences in characteristics and spontaneous closure rates between chronic open vs recurrent wounds. 13 RDEB participants from a single academic center were enrolled in the prospective Photo Cohort while data from 57 trial participants was leveraged in the Validation Cohort .
Results: For the Photo Cohort, 734 photos were collected from 69 wounds, of which 42 (73.7%) were chronic open wounds. Chronic open wounds were larger, more painful, and much less likely to experience spontaneous wound closure (17% vs 100% P<0.001) with much higher time-to-closure (25.7 weeks vs. 5.7 weeks, P<0.0001) than recurrent wounds during follow-up. Baseline wound size was the sole predictor of spontaneous wound closure in the Photo Cohort (12.8, 95% CI: 3.3-48, P<0.01., Findings in the Validation Cohort recapitulated those in the Photo Cohort (26% chronic open wounds had spontaneous closure vs 86% recurrent wounds, P<0.001, and time-to-closure of 14.6 weeks vs. 8 weeks for recurrent wounds). In multivariable models, wounds of the recurrent type had a 29-fold greater likelihood to close spontaneously compared with chronic open wound type (P=0.0045).
Conclusions: Chronic open wounds tend to be larger, more painful, have a much lower probability of spontaneous closure, and longer time-to-closure than recurrent wounds. The distinction between wound types can be leveraged to predict spontaneous wound closure and guide wound selection and observation in RDEB clinical trials.
Retinal Detachment in Type IX collagen recessive Stickler syndrome
Authors: Snead Martin , Maghsoudi Daniel , Nixon Thomas , Martin Howard , Richards Allan , McNinch Annie , Alexander Philip , Poulson Arabella 
Published: March 2024

Abstract

Objective
Stickler Syndrome (SS) is associated with eye, joint and orofacial abnormalities. Most cases are dominantly inherited through variants in genes encoding type-II/XI collagen (COL2A1/COL11A1), with patients having up to 78% retinal detachment (RD) risk.1 More recently, rarer cases of recessive SS have been identified, associated with pathogenic variants of genes encoding type-IX collagen (COL9A1-3), but there is limited published data on patients’ phenotype or RD risk. Our study aimed to investigate the RD risk in recessive SS, primarily to determine whether patients would benefit from prophylactic retinopexy. A secondary objective was to explore patient phenotypes, identifying key features which clinicians should identify, leading to genetic testing and early diagnosis.
Methods
We report 13 cases from 11 families with Type-IX collagen recessive SS, identified from the cohort attending the National Stickler Syndrome Service at Addenbrooke’s Hospital, Cambridge, between 1/1/15–31/12/22. Patients underwent multidisciplinary assessment by ophthalmology, rheumatology and audiology.
Results
6/11 families exhibited previously undescribed genetic variants, and 7 had consanguineous parents. Clinical findings included abnormal vitreous architecture and high myopia. 15.4% of patients developed RD secondary to horseshoe retinal tears, with no cases of bilateral RD or Giant Retinal Tears. No patients had cleft palate, 30.8% had midfacial hypoplasia. Hearing loss was more prevalent (91.7%) than that reported for dominant SS. Arthropathy was uncommon but highly variable in manifestation.
Conclusions
There is currently insufficient evidence to suggest that all patients with recessive Stickler Syndrome require prophylactic retinopexy, and it should only be offered case-by-case according to individual risk assessment.
Evaluation of Primary Healthcare Centers’ Service Availability and Readiness for Implementing Diabetes Care in Abuja, Nigeria: A Cross-Sectional, Formative Assessment
Authors: Orji Ikechukwu A. , Baldridge Abigail S. , Ikechukwu-Orji Mercy U. , Banigbe Bolanle , Eze Nelson C. , Chopra Aashima , Omitiran Kasarachi , Iyer Guhan , Odoh Deborah , Alex-Okoh Morenike , Reng Rifkatu , Hirschhorn Lisa R. , Huffman Mark D. , Ojji Dike B. 
Published: March 2024

Abstract
Introduction:
Noncommunicable diseases (NCDs) are associated with a high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of the National Multi-Sectoral Action Plan for the Prevention and Control of NCDs, Nigeria has committed to implementing the World Health Organization (WHO) Package of Essential NCD control interventions. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems, equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the WHO package components and the readiness of PHCs to implement a DM screening, evaluation, and management program.
Methods
This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August 2021 and October 2021. The service availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain.
Results
All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] staff = 5 [4–9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1–4]. At least one staff member was recently trained in DM care in only 11 (36%) of the PHCs. The study also reported high availability (100%) of paper-based health management information systems (HMIS) and DM screening services using a glucometer (87%), but low availability of DM treatment (23%), printed job aids (27%), and national guidelines/protocols (0%).
Conclusion
This systematic assessment of PHCs’ readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs in terms of equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and ensure a reliable supply of essential DM medications.
Disentangling Mnemonic Metacognition from Confidence by Communication between the Precuneus and Hippocampus
Authors: Jiang Hongjie , pan kai , Guo Xinxia , Zheng Zhe , Zhu Zhoule , Wu Hemmings , Zhu Junming , Santos-Pata Diogo , zhang jianmin , Kwok Sze Chai 
Published: March 2024

Abstract
Metacognition, the ability to introspectively monitor confidence prior to decision-making, remains an area with unclear neural mechanisms, particularly concerning the intercommunication among various brain regions. Recently, the precuneus has emerged as a key player in mnemonic metacognitive tasks, while the hippocampus's involvement in memory function is well-established. Our study sought to examine the roles of the precuneus and hippocampus in mnemonic metacognition, employing intracranial electrode recordings from patients with intractable epilepsy to analyze the regulatory and correlational dynamics between these regions. We identified distinct communication patterns between the precuneus and hippocampus during metacognition and confidence generation. Furthermore, we conducted a quantitative assessment of the temporal dynamics involved in metacognition and the generation of confidence. Our observations reveal that introspective judgments typically occur subsequent to the generation of confidence. Our study sheds light on the neural underpinnings of metacognition and the genesis of confidence, focusing on the interplay between the hippocampus and the precuneus. This investigation lays the groundwork for deepening our comprehension of the nuances distinguishing confidence from metacognition.
Retrosynthesis prediction enhanced by in-silico reaction data augmentation
Authors: Yang Yi , Zhang Xu , Mo Yiming , Wang Wenguan 
Published: March 2024

Abstract

Recent advances in machine learning (ML) have expedited retrosynthesis research by assisting chemists to design experiments more efficiently. However, all ML-based methods consume substantial amounts of paired training data (i.e., chemical reaction: product-reactant(s) pair), which is costly to obtain. Moreover, companies view reaction data as a valuable asset and restrict the accessibility to researchers. These issues prevent the creation of more powerful retrosynthesis models due to their data-driven nature. As a response, we exploit easy-to-access unpaired data (i.e., one component of product-reactant(s) pair) for generating in-silico paired data to facilitate model training. Specifically, we present RetroWISE, a self-boosting framework that employs a base model inferred from real paired data to perform in-silico reaction generation and augmentation using unpaired data, ultimately leading to a superior model. On three benchmark datasets, RetroWISE achieves the best overall performance against state-of-the-art models (e.g., +8.6% top-1 accuracy on the USPTO-50K test dataset). Moreover, it consistently improves the prediction accuracy of rare transformations. These results show that RetroWISE overcomes the training bottleneck by in-silico reactions, thereby paving the way toward more effective ML-based retrosynthesis models.
Interformer: An Interaction-Aware Model for Protein-Ligand Docking and Affinity Prediction
Authors: Lai Houtim , Wang Longyue , Qian Ruiyuan , Ye Geyan , Huang Juhong , Wu Fandi , Wu Fang , Zeng Xiangxiang , Liu Wei 
Published: March 2024

Abstract

In recent years, there has been a growing interest in using deep learning models for protein-ligand docking and affinity prediction, both vital for structure based drug design. However, many of these models overlook the intricate modeling of interactions between ligand and protein atoms, thereby constraining their capabilities in generalization and interpretability. In this paper, we introduce \textsc{Interformer}, a unified model built upon the Graph-Transformer architecture, which specially crafted to capture non-covalent interactions through the interaction-aware mixture density network. Besides, we incorporated a new strategy that utilizes negative samples, effective interaction distribution correction for affinity prediction. Experimental results on widely-used and our in-house datasets demonstrate the effectiveness and universality of the proposed approach. Extensive analyses confirm our claim that our approach improves performance by modelling protein-ligand specific interactions. Encouragingly, our approach propels the SOTA performance docking tasks forward. We intend to make our code publicly available, hoping to facilitate future research in this field.
Characteristics of adult retroperitoneal lymphangioma: a single center Chinese cohort study of 15 cases
Authors: Liu Jie , Zhong Zhi-Han , Zheng Shu-Sen 
Published: March 2024

Abstract
Background
Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease.
Methods
We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022.
Results
The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via Computed Tomography(CT)(n = 10, 66.67%) or magnetic resonance imaging༈MRI༉ (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients.
Conclusions
Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions.
Correction of batch effects in high throughput proximity extension assays for proteomic studies using bridging controls: the BAMBOO method.
Authors: Smits H.M. , Delemarre E.M. , Pandit A. , Schoneveld A.H. , Oldenburg B. , Wijk F. van , Nierkens S. , Drylewicz J. 
Published: March 2024

Abstract

Background: The proximity extension assay (PEA) facilitates large-scale proteomic studies involving a large number of proteins and samples. However, inevitable discrepancies in day-to-day measurements may introduce the inherent risk of undesirable variation, known as batch effects, which may impact down-stream statistical analyses and increase the chances of false discoveries. The implementation of bridging controls on each plate has been suggested to mitigate this complication, but a clear method on how to use this strategy is still lacking. In this study, we characterized potential batch effects in proteomics using PEAs and generated guidelines to mitigate batch effects using bridging controls.
Results: This study characterized three distinct types of batch effects (protein-specific, sample-specific, and plate-wide) in PEA proteomic studies. We developed a new method, BAMBOO (Batch AdjustMents using Bridging cOntrOls), based on a robust regression model. In a simulation study, we compared BAMBOO with established batch correction techniques; median centering, median of the difference (MOD), and ComBat. We observed that median centering and ComBat were significantly impacted by outliers within the bridging controls, whereas BAMBOO and MOD were more robust when no plate-wide batch effects were introduced. Moreover, upon introduction of plate-wide batch effects, BAMBOO was performing better than MOD in terms of accuracy, true negative rate and true positive rate. Inclusion of 10-12 bridging controls was found to optimally correct for batch effects. Applying the different methods to experimental data showed that BAMBOO and MOD result in a reduced incidence of false discoveries compared to the alternative methods.
Conclusion: Our study underscores the prevalent existence of batch effects in PEA proteomic studies, which can be corrected using bridging controls using an innovative, robust and effective tool, BAMBOO. The use of BAMBOO may enhance the reliability of large-scale analyses in the proteomic field using PEA.
Causation Between the Gut Microbiota and Inguinal Hernia: A Two-Sample Double-Sided Mendelian Randomization Study
Authors: Wu Changyuan , Zhu Yujin , Xi Hongwei 
Published: March 2024

Abstract

Background
Inguinal hernias are the most common type of enterocele and are frequently caused by defects in the abdominal wall muscles in the groin area. Numerous animal models and human studies have shown that the gut microbiota is associated with skeletal muscle aging and loss. However, the causation between the gut microbiota and inguinal hernia remains unclear. To reveal the causal association between the gut microbiota and inguinal hernia, we conducted a two-sample double-sided Mendelian randomization analysis.
Methods
We used genome-wide association analysis (GWAS) summary statistics of the gut microbiota from the MiBioGen consortium and GWAS statistics of inguinal hernia from the FinnGen R10 database. The causation between the gut microbiota and inguinal hernia was explored through the inverse variance weighted (IVW) method, MR Egger regression method, weighted median method, weighted model method, and simple model method. Sensitivity analysis was used to test whether the Mendelian randomization analysis results were reliable. Reverse Mendelian randomization was used to conduct effect analysis and sensitivity analysis using the entire gut microbiota as the outcome.
Results
The IVW results indicated that Verrucomicrobia, Lactobacilliales, Clostridiaceae1, Butyricococcus, Categorybacter, Hungatella, Odoribacter, and Olsenella had a direct negative causation with the gut microbiota. The reverse Mendelian Randomization results showed that Eubacterium brachygroup, Eubacterium eligensgroup, Eubacterium xylanophilumgroup, Coprococcus3, Ruminococcus1, and Senegalimassilia were directly related to inguinal hernia. The bilateral sensitivity analysis revealed no heterogeneity or horizontal pleiotropy.
Conclusions
The results confirmed that 8 bacterial traits had a negative causation with inguinal hernia. Reverse MR analysis revealed a positive correlation between inguinal hernia and 6 bacterial traits. Modulating the diversity and components of the gut microbiota is envisaged to contribute to improving the incidence and prognosis of inguinal hernia.
Hidden RIP mutation – a ‘back-seat driver’ of effector diversity revealed by pan-genome analysis of the necrotroph Parastagonospora nodorum across the Western Australian wheat-belt region.
Authors: Hane James , Jones Darcy , Rybak Kasia , Hossain Mohitul , Bertazzoni Stefania , Williams Angela , Tan Kar-Chun , Phan Huyen 
Published: March 2024

Abstract

The fungal species Parastagonospora nodorum is an important pathogen of wheat and model necrotroph with significant genomic resources. In this study, population-level pan-genome data for 173 P. nodorum isolates - 156 from the Western Australian (WA) wheat-belt, and 17 internationally-sourced isolates – were examined for genomic diversity and pathogenicity effector gene content. A heterothallic core population was observed across all regions of WA, with asexually-reproducing clonal clusters in dryer northern regions. An abundant potential for SNP diversity –the majority in the form of repeat-induced point (RIP)-like C-T transitions - was evenly spread across the genome, however increases in non-synonymous mutations were concentrated around repeat-rich regions. Known effector genes and effector-like candidates were typically located around these and sub-telomeric regions. Protein isoform profiles of known effector loci (SnToxA, SnTox1, SnTox3, SnTox267, and SnTox5) indicated similarly low-level non-synonymous and high-level silent RIP-like mutations, and showed distinctive profiles across WA relative to international isolates. Prediction of novel effector genes across resulted in 186 candidate secreted predicted effector proteins (CSEPs), 69 with functional annotations that included 6 confirmed effectors. These new P. nodorum pan-genomic resources and diagnostic methods will support new approaches to region-specific surveillance and management of host-pathogen interactions in commercial crops.