bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avoiding Patient Abandonment: A Pathway to Ethical Resolution in Situations of Untenable Patient–Surgeon Relationships
Authors: Prescher Hannes , Gudex Leah M. , Mauch Jaclyn T. , Vercler Christian J. 
Published: September 2024

Background:
A trusting partnership between patient and surgeon lies at the core of a successful therapeutic relationship. However, there are conditions that can jeopardize this partnership and create an ethical dilemma for the surgeon, who is guided by a moral obligation to care for the patient without causing unnecessary harm. The authors present a discussion of several pathways to achieve ethical resolution to therapeutic relationships that have grown untenable, with a focus on patients with comorbid psychiatric illness. The principal objective of these pathways is to prevent further delivery of futile interventions while avoiding patient abandonment.

Methods:
A review of the literature was performed, and principles of clinical ethics were applied to provide guidelines for care in situations of untenable patient–surgeon relationships.

Results:
There are no published ethical guidelines for resolving a therapeutic impasse in surgical patients with psychiatric illness. The authors applied ethical principles of treatment futility, nonmaleficence, beneficence, and patient abandonment to develop a framework for navigating difficult postoperative patient relationships.

Conclusions:
Managing postoperative surgical patients with comorbid psychiatric conditions presents a unique challenge. In severe cases, therapeutic discharge may be ethically permissible and necessary to disrupt a maladaptive treatment cycle to prevent future patient harm. Specific precautions must be taken to avoid patient abandonment.
Unraveling the Long-term Natural History of Branch Duct Intraductal Papillary Mucinous Neoplasm
Authors: Assawasirisin Charnwit , Fagenholz Peter , Qadan Motaz , Hernandez-Barco Yasmin , Aimprasittichai Satita , Kambadakone Avinash , Mino-Kenudson Mari , Ike Amarachi , Chen Sheng-Yin , Sheng Chen , Brugge William , Warshaw Andrew L. , Lillemoe Keith D. , Fernández-del Castillo Carlos 
Published: September 2024

Objective:
To describe the long-term natural history of branch duct intraductal papillary mucinous neoplasm (BD-IPMN).

Background:
The BD-IPMN is a known precursor of pancreatic cancer, yet its long-term natural history is largely unknown.

Methods:
We retrospectively reviewed patients with BD-IPMN who were followed at the Massachusetts General Hospital for at least 10 years without surgical intervention. Patient and cyst characteristics, development of worrisome features (WF), need for surgery, and malignancy were recorded. The risk of pancreatic cancer in this cohort was compared with the general population by determining the standardized incidence ratio.

Results:
Three hundred sixteen patients with BD-IPMN who were followed for at least 10 years without intervention were identified. The median age was 63 years, and the median follow-up was 13.5 years (range: 10–28.8 years). Median cyst size at diagnosis was 1.2 cm (IQR: 0.8–1.7), was 1.8 cm (IQR: 1.2–2.6) at 10 years, and increased to 2.0 cm (IQR: 1.3–3.0) by the end of surveillance. At the 10-year mark, 24% of patients had WF, and by the end of surveillance, an additional 20% had developed WF or high-risk stigmata. 8.2% of patients developed pancreatic malignancy (high-grade dysplasia or invasive cancer). The standardized incidence ratio for pancreatic cancer was 9.28 (95% CI: 5.82–14.06), with almost two-thirds of invasive cancers occurring within the pancreatic cyst.

Conclusions:
After 10 years of surveillance for BD-IPMN without intervention, the disease continues to progress, and 1 of every 12 patients will develop malignancy. The risk of pancreatic cancer appears to be 9 times higher than in the comparable age-matched population.
Service specification for senior care workers with traditional Chinese medicine specialty
Authors: Zou Qi , Tang Qin , Wang Lei , Geng Jiawei , Deng Baofeng , Yu Zhen , An Ayue , Wei Lixin , Tong Xiaoying , Rong Peijing 
Published: September 2024

Abstract
Senior care workers specializing in traditional Chinese medicine (TCM) healthcare have become an indispensable force in institutional care, community care, and home care. The first Chinese nursing service team aimed to improve the health of the elderly by providing continuous services for physical and mental well-being, disease prevention, physical amelioration, and overall health enhancement using TCM concepts, methods, and technologies. The primary purpose of formulating this TCM health and elderly care worker service specification was to standardize services within the TCM elderly care industry, ensuring that the elderly receive better health and elderly care services supported by technical expertise. This specification outlined the basic requirements for TCM health and elderly care workers, including standards for service content, service quality control, service evaluation, and improvement. It primarily focused on the content and requirements of TCM health and elderly care services, such as constitution identification, life care, acupoint healthcare, and TCM auxiliary nursing for elderly individuals with chronic diseases. This specification is applicable to TCM health and elderly care personnel at various levels of hospitals and healthcare institutions and is noted for its strong applicability and effectiveness.
A near-complete genome assembly of the bearded dragonPogona vitticepsprovides insights into the origin ofPogonasex chromosomes
Authors: Guo Qunfei , Pan Youliang , Dai Wei , Guo Fei , Zeng Tao , Chen Wanyi , Mi Yaping , Zhang Yanshu , Shi Shuaizhen , Jiang Wei , Cai Huimin , Wu Beiying , Zhou Yang , Wang Ying , Yang Chentao , Shi Xiao , Yan Xu , Chen Junyi , Cai Chongyang , Yang Jingnan , Xu Xun , Gu Ying , Dong Yuliang , Li Qiye 
Published: September 2024

AbstractBackgroundThe agamid dragon lizardPogona vitticepsis one of the most popular domesticated reptiles to be kept as pets worldwide. The capacity of breeding in captivity also makes it emerging as a model species for a range of scientific research, especially for the studies of sex chromosome origin and sex determination mechanisms.ResultsBy leveraging the CycloneSEQ and DNBSEQ sequencing technologies, we conducted whole genome and long-range sequencing for a captive-bred ZZ male to construct a chromosome-scale reference genome forP. vitticeps. The new reference genome is ∼1.8 Gb in length, with a contig N50 of 202.5 Mb and all contigs anchored onto 16 chromosomes. Genome annotation assisted by long-read RNA sequencing greatly expanded theP. vitticepslncRNA catalog. With the chromosome-scale genome, we were able to characterize the whole Z sex chromosome for the first time. We found that over 80% of the Z chromosome remains as pseudo-autosomal region (PAR) where recombination is not suppressed. The sexually differentiated region (SDR) is small and occupied mostly by transposons, yet it aggregates genes involved in male development, such asAMH,AMHR2andBMPR1A. Finally, by tracking the evolutionary origin and developmental expression of the SDR genes, we proposed a model for the origin ofP. vitticepssex chromosomes which considered the Z-linkedAMHas the master sex-determining gene.ConclusionsOur study provides novel insights into the sex chromosome origin and sex determination of this model lizard. The near-completeP. vitticepsreference genome will also benefit future study of amniote evolution and may facilitate genome-assisted breeding.
Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury
Authors: Sung Eun-Ah , Dozmorov Mikhail G. , Song SuJeong , Aung Theingi , Park Min Hee , Sime Patricia J. , Chae Wook-Jin 
Published: September 2024

AbstractLow-density lipoprotein receptor-related protein 6 (LRP6) is a receptor for Wnt ligands. Tissue fibrosis is a progressive pathological process with excessive extracellular matrix proteins (ECM) deposition. Myofibroblasts, identified by alpha-smooth muscle actin (αSMA) expression, play an important role in tissue fibrosis by producing ECM production. Here we found that Wnt antagonist Dickkopf1 (DKK1) induced gene expressions associated with inflammation and fibrosis in lung fibroblasts. We demonstrated that genetic deletion of LRP6 in αSMA-expressing cells usingActa2-creLrp6fl/fl(Lrp6AKO) mice abrogated bleomycin (BLM)-induced lung inflammation and fibrosis phenotype, suggesting an important role of LRP6 in modulating inflammation and fibrotic processes in the lung. Our results highlight the crucial role of LRP6 in fibroblasts in regulating inflammation and fibrosis upon BLM-induced lung injury.
Neural-symbolic hybrid model for myosin complex in cardiac ventriculum decodes structural bases for inheritable heart disease from its genetic encoding
Authors: Burghardt Thomas P. 
Published: September 2024

ABSTRACTBackgroundHuman ventriculum myosin (βmys) powers contraction sometimes in complex with myosin binding protein C (MYBPC3). The latter regulates βmys activity and impacts overall cardiac function. Nonsynonymous single nucleotide variants (SNVs) change protein sequence in βmys or MYBPC3 causing inheritable heart diseases by affecting the βmys/MYBPC3 complex. Muscle genetics encode instructions for contraction informing native protein construction, functional integration, and inheritable disease impairment. A digital model decodes these instructions and evolves by continuously processing new information content from diverse data modalities in partnership with the human agent.MethodsA general neural-network contraction model characterizes SNV impacts on human health. It rationalizes phenotype and pathogenicity assignment given the SNVs genetic characteristics and in this sense decodes βmys/MYBPC3 complex genetics and implicitly captures ventricular muscle functionality. When a SNV modified domain locates to an inter-protein contact in βmys/MYBPC3 it affects complex coordination. Domains involved, one in βmys and the other in MYBPC3, form coordinated domains (co-domains). Co-domains are bilateral implying potential for their SNV modification probabilities to respond jointly to a common perturbation to reveal their location. Human genetic diversity from the serial founder effect is the common systemic perturbation coupling co-domains that are mapped by a methodology called 2-dimensional correlation genetics (2D-CG).ResultsInterpreting the general neural-network contraction model output involves 2D-CG co-domain mapping that provides natural language expressed structural insights. It aligns machine-learned intelligence from the neural network model with human provided structural insight from the 2D-CG map, and other data from the literature, to form a neural-symbolic hybrid model integrating genetic and protein interaction data into a nascent digital twin. This process is the template for combining new information content from diverse data modalities into a digital model that can evolve. The nascent digital twin interprets SNV implications to discover disease mechanism, can evaluate potential remedies for efficacy, and does so without animal models.HighlightsNeural-symbolic hybrid model decodes muscle genetics into contraction mechanisms And evolves in virtuous cycleOptimize-Interpret-Revise-Repeataided by human partner Nascent digital twin unravels inheritable disease mechanism without animal models And estimates cardiac phenotype coupling strength to myosin thick-filament structures
A semi-parametric multiple imputation method for high-sparse, high-dimensional, compositional data
Authors: Sohn Michael B. , Scheible Kristin , Gill Steven R. 
Published: September 2024

AbstractHigh sparsity (i.e., excessive zeros) in microbiome data, which are high-dimensional and compositional, is unavoidable and can significantly alter analysis results. However, efforts to address this high sparsity have been very limited because, in part, it is impossible to justify the validity of any such methods, as zeros in microbiome data arise from multiple sources (e.g., true absence, stochastic nature of sampling). The most common approach is to treat all zeros as structural zeros (i.e., true absence) or rounded zeros (i.e., undetected due to detection limit). However, this approach can underestimate the mean abundance while overestimating its variance because many zeros can arise from the stochastic nature of sampling and/or functional redundancy (i.e., different microbes can perform the same functions), thus losing power. In this manuscript, we argue that treating all zeros as missing values would not significantly alter analysis results if the proportion of structural zeros is similar for all taxa, and we propose a semi-parametric multiple imputation method for high-sparse, high-dimensional, compositional data. We demonstrate the merits of the proposed method and its beneficial effects on downstream analyses in extensive simulation studies. We reanalyzed a type II diabetes (T2D) dataset to determine differentially abundant species between T2D patients and non-diabetic controls.
Recruitment of SH3P2–DRP1A by HYCCIN2 Drives Membrane Tubulation in Arabidopsis Embryonic Cell Plate Formation
Authors: Hsu Ya-Wen , Juan Chine-Ta , Guo Cian-Ling , Wang Huei-Jing , Jauh Guang-Yuh 
Published: September 2024

ABSTRACTCytokinesis marks the culmination of cell division when the cytoplasm undergoes division to yield two daughter cells. This intricate process encompasses various biological phenomena, including the organization of the cytoskeleton and the dynamics of vesicles. The development of the cell plate aligns with alterations in the cytoskeleton structure and vesicles derived from thetrans-Golgi, ultimately resulting in the formation of the planar cell plate. Nevertheless, the coordination of these processes in plants remains to be determined. Here, we introduce HYCCIN-CONTAINING2 (HYC2) as a pivotal cytoskeleton cross-linking protein that accumulates at phragmoplasts and plays a crucial role in cell plate formation. A genetic study involving the depletion of HYC2 post-anaphase in Arabidopsis revealed HYC2’s function in cell plate formation. HYC2 interacted with dynamin-related protein 1A (DRP1A) and SH3 domain-containing protein 2 (SH3P2), essential for membrane tubulation during cell plate formation. The recruitment of SH3P2 and DRP1A to the cell plate and phragmoplast organization was compromised in homozygoushyc2-2mutant globular embryos. Our results shed light on the cytoskeletal function of HYC2 in assembling the cell plate, potentially by guiding vesicles containing SH3P2–DRP1A to the planar cell plate.Significance statementDuring plant cell division, a new membrane is constructed at the division plane, and vesicles fuse to form a transient compartment known as the cell plate. This structure undergoes stabilization via membrane remodeling events, including tubulation, to generate robust membrane intermediates. Apart from DRP1A and SH3P2, our understanding of other protein components involved in membrane remodeling still needs to be completed. HYC2 is a plant counterpart to the human Hyccin protein involved in neuronal myelination and displaying bundling capabilities for microtubules and microfilaments. Our study demonstrates that HYC2 is crucial in recruiting proteins during membrane tubulation in the cell plate formation in developing Arabidopsis embryos. These findings underscore the molecular function and vital role of the Hyccin protein in cell plate formation.One Sentence SummaryPlant HYC2 displays bundling capabilities for microtubules and microfilaments to recruit DRP1A and SH3P2 during membrane tubulation in the cell plate formation in developing Arabidopsis embryos.
Autoantigen TRIM21 (Ro52) assembles pro-inflammatory immune complexes following lytic cell death
Authors: Jones Esther L. , Demarco Benjamin , de Jong Madelon M.E , Cai Han , Hill Sarah , Glass Ryan E. , Harris Gemma , Nayar Saba , Fisher Benjamin A. , Gérard Audrey , Bezbradica Jelena S. , Dustin Lynn B. 
Published: September 2024

AbstractSjögren’s disease (SjD) causes localised and systemic inflammation due to autoantibody production against intracellular proteins, such as TRIM21/Ro52. TRIM21 is an E3 ubiquitin ligase which binds antibody Fc domains on opsonised pathogens, which have escaped extracellular immunity and entered cytosols; TRIM21 ubiquitinates these, driving their proteasomal degradation. How and why TRIM21 becomes an autoantigen remains unclear. We show that TRIM21 is released upon lytic cell death (pyroptosis/necroptosis) but not apoptosis. Released TRIM21 binds circulating antibody Fc domains, and forms large immune complexes (ICs). These are further enhanced with TRIM21/Ro52 seropositive SjD plasma antibodies, where interactions are mediated via both Fc and F(ab’)2domains. TRIM21-ICs are taken up by macrophages, which in high interferon environments drive pro-inflammatory responses, antigen presentation, and inflammatory and metabolic transcriptional changes. Whilst many cytosolic proteins are released by dead cells, due to its high affinity for antibodies, TRIM21 can generate large ICs. This may perpetuate inflammation and antigen presentation, causing TRIM21 to be highly autoimmunogenic.One Sentence SummaryHow the intracellular protein TRIM21 becomes an autoantigen.
The FAIR Data Point Populator: collaborative FAIRification and population of FAIR Data Points
Authors: Wijnbergen Daphne , Kaliyaperumal Rajaram , Burger Kees , Bonino da Silva Santos Luiz Olavo , Mons Barend , Roos Marco , Mina Eleni 
Published: September 2024

AbstractBackgroundUse of the FAIR principles (Findable, Accessible, Interoperable and Reusable) allows the rapidly growing number of biomedical datasets to be optimally (re)used. An important aspect of the FAIR principles is metadata. The FAIR Data Point specifications and reference implementation have been designed as an example on how to publish metadata according to the FAIR principles. Various tools to create metadata have been created, but many of these have limitations, such as interfaces that are not intuitive, metadata that does not adhere to a common metadata schema, limited scalability, and inefficient collaboration. We aim to address these limitations in the FAIR Data Point Populator.ResultsThe FAIR Data Point Populator consists of a GitHub workflow together with Excel templates that have tooltips, validation and documentation. The Excel templates are targeted towards non-technical users, and can be used collaboratively in online spreadsheet software. A more technical user then uses the GitHub workflow to read multiple entries in the Excel sheets, and transform it into machine readable metadata. This metadata is then automatically uploaded to a connected FAIR Data Point. We applied the FAIR Data Point Populator on the metadata of two datasets, and a patient registry. We were then able to run a query on the FAIR Data Point Index, in order to retrieve one of the datasets.ConclusionThe FAIR Data Point Populator addresses several limitations of other tools. It makes creating metadata easier, ensures adherence to a common metadata schema, allows bulk creation of metadata entries and increases collaboration. As a result of this, the barrier of entry for FAIRification is lower, which enables the creation of FAIR data by more people.
Biomanufacturing of a functional microbial phytase in an insect host
Authors: Retief C. , Kumar S. , Tepper K. , Maselko M. 
Published: September 2024

AbstractBackgroundInsects, such as Black Soldier Flies (Hermetia illucens), are increasingly used as sustainable animal feed ingredients that can be reared on plentiful organic substrates such as agricultural residues and pre-consumer food waste. Genetically engineering insects to heterologously express feed additive enzymes has the potential to generate more value from organic waste, while improving livestock health and productivity.Phytases are widely used feed additive enzymes that hydrolyse the phosphate groups from the myo-inositol backbone of phytic acid, a phosphate rich antinutrient compound that monogastric animals cannot efficiently digest. Dietary phytase supplementation improves absorption of phosphorous, proteins, and cationic nutrients, while mitigating the negative environmental effects of phytic acid rich excreta.ResultsWe evaluated the potential of using insects to biomanufacture microbial feed additive enzymes by engineering the model insect,Drosophila melanogaster, to express phytases. One histidine acid phytase, three beta propellor phytases, three purple acid phosphatases, and one PTP-like phytase were selected for screening inD. melanogaster. Transgenic flies expressing the AppA histidine acid phytase fromE. colihad 27.82 FTU/g of phytase activity, which exceeds the 0.5-1.0 FTU/g required in animal feed. Maximum activity from AppA phytase expressed byD. melanogasterwas observed at pH 5 and 55 °C, however, more than 50% of phytase activity was present at 25 °C and pH 2.Here we demonstrate that insects may be suitable hosts for the heterologous expression of a microbial phytase enzyme with applications for improving animal feed nutrition and organic waste valorisation.
Quantitative site-specific glycoproteomics by ZenoTOF reveals glyco-signatures for breast cancer diagnosis
Authors: Yang Yi , Zhao Dan , Luo Ji , Lin Ling , Lin Yuxiang , Shan Baozhen , Chen Hongxu , Qiao Liang 
Published: September 2024

ABSTRACTIntact glycopeptide characterization by mass spectrometry has proven a versatile tool for site-specific glycoproteomics analysis and biomarker screening. Here, we present a method using the ZenoTOF instrument with optimized fragmentation for intact glycopeptide identification and demonstrate its ability to analyze large-cohort glycoproteomes. From 124 clinical serum samples of breast cancer, non-cancerous diseases, and non-disease controls, a total of 6901 unique site-specific glycans on 807 gly-cosites of proteins were detected. Much more differences of glycoproteome were observed in breast diseases than the proteome. By employing machine learning, 15 site-specific glycans were determined as potential glyco-signatures in detecting breast cancer. The results demonstrate that our method provides a powerful tool in glycoproteomic analyses for biomarker discovery studies.
Force variability is a potential biomarker of motor impairment in hemispheric stroke survivors
Authors: Shi Fandi , Rymer William Zev , Son Jongsang 
Published: September 2024

AbstractDuring voluntary isometric contractions of upper extremity muscles in individuals with chronic stroke, the magnitude of force variability appears to increase consistently as force increases. However, research on how such force variability changes with increasing motor impairment remains limited. This study aims to determine whether force variability is increased on the paretic side during either index finger abduction or elbow flexion in the same group of stroke survivors, and whether these changes are consistent across different muscles. Force variability was assessed using the standard deviation of force during sustained isometric contractions. Linear mixed-effects models were implemented to test whether force variability is changed on the paretic side post stroke, and whether such alterations show dependence on force level and on the degree of impairment. The results demonstrated a significant increase in force variability on the paretic side across force levels during finger abduction, while force variability for elbow flexion was increased only at high force levels. In addition, the force variability appears to increase as isometric elbow flexion force increases, whereas no clear trend was found during index finger abduction. The increase in force variability demonstrated moderate-strong dependence on the reduction in maximum muscle strength on the paretic side during elbow flexion, suggesting that monitoring force variability could potentially serve as a quantitative diagnostic tool for assessing severity of impairment in motor control and for raising potential mechanisms at the motor unit level.