bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical practice guideline recommendations on tapering and discontinuing antidepressants for depression: a systematic review
Authors: Sørensen Anders , Juhl Jørgensen Karsten , Munkholm Klaus 
Published: February 2022

Background: Tapering and discontinuing antidepressants are important aspects of the management of patients with depression and should therefore be considered in clinical practice guidelines. Objectives: We aimed to assess the extent and content, and appraise the quality, of guidance on tapering and discontinuing antidepressants in major clinical practice guidelines on depression. Methods: Systematic review of clinical practice guidelines on depression issued by national health authorities and major national or international professional organisations in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland and New Zealand (PROSPERO CRD42020220682). We searched PubMed, 14 guideline registries and the websites of relevant organisations (last search 25 May 2021). The clinical practice guidelines were assessed for recommendations and information relevant to tapering and discontinuing antidepressants. The quality of the clinical practice guidelines as they pertained to tapering and discontinuation was assessed using the AGREE II tool. Results: Of the 21 included clinical practice guidelines, 15 (71%) recommended that antidepressants are tapered gradually or slowly, but none provided guidance on dose reductions, how to distinguish withdrawal symptoms from relapse or how to manage withdrawal symptoms. Psychological challenges were not addressed in any clinical practice guideline, and the treatment algorithms and flow charts did not include discontinuation. The quality of the clinical practice guidelines was overall low. Conclusion: Current major clinical practice guidelines provide little support for clinicians wishing to help patients discontinue or taper antidepressants in terms of mitigating and managing withdrawal symptoms. Patients who have deteriorated upon following current guidance on tapering and discontinuing antidepressants thus cannot be concluded to have experienced a relapse. Better guidance requires better randomised trials investigating interventions for discontinuing or tapering antidepressants.
Electrochemotherapy as a treatment option for feline nasal melanoma
Authors: Little Annika , Macfarlane Michael 
Published: February 2022

Case summary A 4-year-old domestic shorthair cat presented to North Downs Specialist Referrals for treatment of a 7 mm melanoma of the nasal planum. Two treatments of electrochemotherapy using intravenous bleomycin as a chemotherapeutic agent were administered. The tumour was no longer visible after treatment. At the 292-day follow-up there was no recurrence at the site and the patient was clinically well. Relevance and novel information There are few data concerning the outcomes of cats with non-ocular feline melanomas and there are currently minimal descriptions in the literature of electrochemotherapy as a treatment option. The available data suggest that nasal melanoma may have a worse prognosis, and that melanomas are locally invasive and have a high propensity for metastasis. The current most effective means for local control is surgery with wide margins. Given the location in this case, this would have required nasal planectomy, while electrochemotherapy provided an effective and possibly more attractive alternative.
Inflation-Adjusted Medicare Reimbursement Has Decreased for Orthopaedic Sports Medicine Procedures: Analysis From 2000 to 2020
Authors: Pollock Jordan R. , Richman Evan H. , Estipona Benzi I. , Moore M. Lane , Brinkman Joseph C. , Hinckley Nathaniel B. , Haglin Jack M. , Chhabra Anikar 
Published: February 2022

Background: Decreases in Medicare reimbursement have been noted among many medical specialties. An in-depth analysis of the subspecialty of orthopaedic sports medicine is needed to determine changes in Medicare reimbursement in this field. Purpose/Hypothesis: The purpose was to elucidate the trends in inflation-adjusted Medicare reimbursement for orthopaedic sports medicine procedures between 2000 and 2020. It was hypothesized that Medicare reimbursement decreased substantially during the study period. Study Design: Economic decision and analysis; Level of evidence, 4. Methods: The Physician Fee Schedule Look-up Tool was used to extract Medicare reimbursement information between 2000 and 2020 for 67 procedures related to orthopaedic sports medicine. These values were adjusted for inflation using the Consumer Price Index. The compound annual growth rate (CAGR) was calculated to measure the annual rate of change, and descriptive analyses were performed using the Student t test. Results: Between 2000 and 2020, inflation-adjusted Medicare reimbursement for the 67 included procedures decreased by an average of 33% (CAGR = –2.2%; R 2 = 0.78). Reimbursement decreased for procedures related to the shoulder and elbow by 34% (CAGR = –2.3%; R 2 = 0.80), for hip-related procedures by 23% (CAGR = –1.4%; R 2 = 0.77), for knee-related procedures by 31% (CAGR = –2.0%; R 2 = 0.81), and for procedures relating to the foot and ankle by 38% (CAGR = –2.5%; R 2 = 0.79). Conclusion: Study findings indicated that inflation-adjusted Medicare reimbursement decreased substantially between 2000 and 2020 for orthopaedic sports medicine procedures, ranging from a 23% decrease for hip-related procedures to a 38% decrease for foot and ankle–related procedures. The results of this study could be used to provide further context for health care policy decisions and help ensure sustainable financial environments for orthopaedic sports medicine surgeon.
Genotoxic aldehydes in the hematopoietic system
Authors: Wang Meng , Dingler Felix A. , Patel K. J. 
Published: February 2022

Abstract
Reactive aldehydes are potent genotoxins that threaten the integrity of hematopoietic stem cells and blood production. To protect against aldehydes, mammals have evolved a family of enzymes to detoxify aldehydes, and the Fanconi anemia DNA repair pathway to process aldehyde-induced DNA damage. Loss of either protection mechanisms in humans results in defective hematopoiesis and predisposition to leukemia. This review will focus on the impact of genotoxic aldehydes on hematopoiesis, the sources of endogenous aldehydes, and potential novel protective pathways.
Structural basis of von Willebrand factor multimerization and tubular storage
Authors: Zeng Jianwei , Shu Zimei , Liang Qian , Zhang Jing , Wu Wenman , Wang Xuefeng , Zhou Aiwu 
Published: February 2022

AbstractThe von Willebrand factor (VWF) propeptide (domains D1D2) is essential for the assembly of VWF multimers and its tubular storage in Weibel-Palade bodies. However, detailed molecular mechanism underlying this propeptide dependence is unclear. Here, we prepared Weibel-Palade body-like tubules using the N-terminal fragment of VWF and solved the cryo-electron microscopy structures of the tubule at atomic resolution. Detailed structural and biochemical analysis indicate that the propeptide forms a homodimer at acidic pH through the D2:D2 binding interface and then recruits 2 D’D3 domains, forming an intertwined D1D2D’D3 homodimer in essence. Stacking of these homodimers by the intermolecular D1:D2 interfaces brings 2 D3 domains face-to-face and facilitates their disulfide linkages and multimerization of VWF. Sequential stacking of these homodimers leads to a right-hand helical tubule for VWF storage. The clinically identified VWF mutations in the propeptide disrupted different steps of the assembling process, leading to diminished VWF multimers in von Willebrand diseases (VWD). Overall, these results indicate that the propeptide serves as a pH-sensing template for VWF multimerization and tubular storage. This sheds light on delivering normal propeptide as a template to rectify the defects in multimerization of VWD mutants.
Novel CFTR modulator combinations maximise rescue of G85E and N1303K in rectal organoids
Authors: Ensinck Marjolein M. , De Keersmaecker Liesbeth , Ramalho Anabela S. , Cuyx Senne , Van Biervliet Stephanie , Dupont Lieven , Christ Frauke , Debyser Zeger , Vermeulen François , Carlon Marianne S. 
Published: February 2022

IntroductionCystic fibrosis (CF) is a severe monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Several types of CFTR modulators (correctors/potentiators) have been developed to overcome protein dysfunction associated with these mutations. CFTR modulator therapy is now available for the major CF-causing mutations; however, 10% of people with CF remain without causal treatments. By combining investigational and market-approved CFTR modulators, we aimed to maximise functional rescue of iva-, luma- and tezacaftor refractory mutants G85E and N1303K.MethodsWe used the well-established forskolin-induced swelling (FIS) in primary rectal organoids to assess responses to different CFTR corrector and potentiator types. The FIS analysis was performed with brightfield microscopy, allowing both 1-h and 24-h follow-up. Corrector and potentiator activity of elexacaftor was investigated.ResultsFor G85E, maximal rescue was observed by a combination of elexacaftor and corr4a. For N1303K, the quadruple combination teza-elexa-ivacaftor with apigenin was required to obtain a rescue similar to that of luma-ivacaftor rescued F508del. Elexacaftor rescued G85E and N1303K by different mechanisms, with chronic corrector effects on G85E and acute potentiation of N1303K only in the presence of ivacaftor. Synergy in N1303K rescue for iva-elexacaftor and apigenin suggests at least three potentiator mechanisms for this mutant. 24-h FIS identified ivacaftor as the main CFTR modulator for N1303K and elexacaftor and apigenin as co-potentiators.ConclusionsNovel combinations of CFTR modulators can further improve functional rescue of G85E and N1303K in rectal organoids, although for N1303K, more effective CFTR modulators are still needed.
MiR-18a-3p improves cartilage matrix remodeling and inhibits inflammation in osteoarthritis by suppressing PDP1
Authors: Feng Xiaoguang , Lu Jiajun , Wu Yixiong , Xu Haiyun 
Published: February 2022

AbstractOsteoarthritis (OA) is a degenerative disease characterized by synovial inflammation. MiR-18a-3p was reported to be downregulated in knee anterior cruciate ligament of OA patients. In the present study, the specific functions and mechanism of miR-18a-3p in OA were explored. An in vitro model of OA was established using 10 ng/ml IL-1β to treat ATDC5 cells, and medial meniscus instability surgery was performed on Wistar rats to establish in vivo rat model of OA. RT-qPCR revealed that miR-18a-3p was downregulated in IL-1β-stimulated ATDC5 cells. MiR-18a-3p overexpression inhibited secretion of inflammatory cytokines and concentration of matrix metalloproteinases, as shown by ELISA and western blotting. The binding relation between miR-18a-3p and pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1) was detected by luciferase reporter assays. MiR-18a-3p targeted PDP1 and negatively regulated PDP1 expression. Results of rescue assays revealed that PDP1 upregulation reserved the suppressive effect of miR-18a-3p overexpression on levels of inflammatory cytokines and matrix metalloproteinases in IL-1β-stimulated ATDC5 cells. H&E staining was used to observe pathological changes of synovial tissues in the knee joint of Wistar rats. Safranin O-fast green/hematoxylin was used to stain cartilage samples of knee joints. MiR-18a-3p overexpression suppressed OA progression in vivo. Overall, miR-18a-3p improves cartilage matrix remodeling and suppresses inflammation in OA by targeting PDP1.
ProtPlat: an efficient pre-training platform for protein classification based on FastText
Authors: Jin Yuan , Yang Yang 
Published: February 2022

AbstractBackgroundFor the past decades, benefitting from the rapid growth of protein sequence data in public databases, a lot of machine learning methods have been developed to predict physicochemical properties or functions of proteins using amino acid sequence features. However, the prediction performance often suffers from the lack of labeled data. In recent years, pre-training methods have been widely studied to address the small-sample issue in computer vision and natural language processing fields, while specific pre-training techniques for protein sequences are few.ResultsIn this paper, we propose a pre-training platform for representing protein sequences, called ProtPlat, which uses the Pfam database to train a three-layer neural network, and then uses specific training data from downstream tasks to fine-tune the model. ProtPlat can learn good representations for amino acids, and at the same time achieve efficient classification. We conduct experiments on three protein classification tasks, including the identification of type III secreted effectors, the prediction of subcellular localization, and the recognition of signal peptides. The experimental results show that the pre-training can enhance model performance effectively and ProtPlat is competitive to the state-of-the-art predictors, especially for small datasets. We implement the ProtPlat platform as a web service (https://compbio.sjtu.edu.cn/protplat) that is accessible to the public.ConclusionsTo enhance the feature representation of protein amino acid sequences and improve the performance of sequence-based classification tasks, we develop ProtPlat, a general platform for the pre-training of protein sequences, which is featured by a large-scale supervised training based on Pfam database and an efficient learning model, FastText. The experimental results of three downstream classification tasks demonstrate the efficacy of ProtPlat.
Pango lineage designation and assignment using SARS-CoV-2 spike gene nucleotide sequences
Authors: O’Toole Áine , Pybus Oliver G. , Abram Michael E. , Kelly Elizabeth J. , Rambaut Andrew 
Published: February 2022

Abstract
Background
More than 2 million SARS-CoV-2 genome sequences have been generated and shared since the start of the COVID-19 pandemic and constitute a vital information source that informs outbreak control, disease surveillance, and public health policy. The Pango dynamic nomenclature is a popular system for classifying and naming genetically-distinct lineages of SARS-CoV-2, including variants of concern, and is based on the analysis of complete or near-complete virus genomes. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. It is therefore important to understand how much information about Pango lineage status is contained in spike-only nucleotide sequences. Here we explore how Pango lineages might be reliably designated and assigned to spike-only nucleotide sequences. We survey the genetic diversity of such sequences, and investigate the information they contain about Pango lineage status.

Results
Although many lineages, including the main variants of concern, can be identified clearly using spike-only sequences, some spike-only sequences are shared among tens or hundreds of Pango lineages. To facilitate the classification of SARS-CoV-2 lineages using subgenomic sequences we introduce the notion of designating such sequences to a “lineage set”, which represents the range of Pango lineages that are consistent with the observed mutations in a given spike sequence.

Conclusions
We find that many lineages, including the main variants-of-concern, can be reliably identified by spike alone and we define lineage-sets to represent the lineage precision that can be achieved using spike-only nucleotide sequences. These data provide a foundation for the development of software tools that can assign newly-generated spike nucleotide sequences to Pango lineage sets.
Single-molecule long-read sequencing reveals the potential impact of posttranscriptional regulation on gene dosage effects on the avian Z chromosome
Authors: Wang Jianmei , Xi Yang , Ma Shengchao , Qi Jingjing , Li Junpeng , Zhang Rongping , Han Chunchun , Li Liang , Wang Jiwen , Liu Hehe 
Published: February 2022

Abstract
Background
Mammalian sex chromosomes provide dosage compensation, but avian lack a global mechanism of dose compensation. Herein, we employed nanopore sequencing to investigate the genetic basis of gene expression and gene dosage effects in avian Z chromosomes at the posttranscriptional level.

Results
In this study, the gonad and head skin of female and male duck samples (n = 4) were collected at 16 weeks of age for Oxford nanopore sequencing. Our results revealed a dosage effect and local regulation of duck Z chromosome gene expression. Additionally, AS and APA achieve tissue-specific gene expression, and male-biased lncRNA regulates its Z-linked target genes, with a positive regulatory role for gene dosage effects on the duck Z chromosome. In addition, GO enrichment and KEGG pathway analysis showed that the dosage effects of Z-linked genes were mainly associated with the cellular response to hormone stimulus, melanin biosynthetic, metabolic pathways, and melanogenesis, resulting in sex differences.

Conclusions
Our data suggested that post transcriptional regulation (AS, APA and lncRNA) has a potential impact on the gene expression effects of avian Z chromosomes. Our study provides a new view of gene regulation underlying the dose effects in avian Z chromosomes at the RNA post transcriptional level.
Clopidogrel-induced neutropenia in an 80-year-old patient with chronic kidney disease who underwent percutaneous coronary intervention: a case report and literature review
Authors: Pan Yannan , Liu Bing , Liu Junmeng , Zhuang Wei , He Qing , Lan Ming 
Published: February 2022

Abstract
Background
Clopidogrel is a widely-used antiplatelet and acts as an adenosine diphosphate receptor inhibitor. Neutropenia is a rare but serious adverse effect of clopidogrel. It is unknown whether this adverse effect has any association with impaired kidney function.

Case presentation
An 80-year-old male with chronic kidney disease was diagnosed with non-ST elevation myocardial infarction and underwent percutaneous coronary intervention. During hospitalization, the patient was diagnosed with contrast-induced nephropathy, treated symptomatically, and discharged with a back-to-baseline creatinine level. Two weeks later, the patient presented to the emergency department with fever and chills. Complete blood count showed leukopenia (0.84 × 103/mm3) and severe neutropenia (0.13 × 103/mm3). Blood cultures were positive for Pseudomonas aeruginosa. Clopidogrel was stopped immediately and switched into ticagrelor. Imipenem and granulocyte colony-stimulating factor were administered to the patient. The patient’s white blood cell and absolute neutrophil count were within the normal range after four days of treatment. The patient was discharged after a 10-day hospitalization, and his complete blood counts were normal during further follow-ups.

Conclusions
Clopidogrel was the most likely primary cause of neutropenia in our case. The incidence of clopidogrel-induced neutropenia is low and the exact mechanism is not fully explained. We provide suggestions on the management of clopidogrel-associated neutropenia, and summarize all five cases of clopidogrel-induced neutropenia in patients with impaired kidney function.
National survey of do not attempt resuscitation decisions on out-of-hospital cardiac arrest in China
Authors: Tian Sijia , Niu Shengmei , Zhang Luxi , Lian Huixin , Zhou Ming , Zhang Xuejiao , Kang Xuqin , Zhang JinJun 
Published: February 2022

Abstract
Background
To investigate and understand the determinants of decisions not to attempt resuscitation following out-of-hospital cardiac arrest, to contribute to establishing rules that are appropriate to China.

Methods
We recruited participants through directors of emergency medical services across China. A 28-question web survey was available between February 5 and March 6, 2021 that targeted demographic information and views on emergency work and cardiopulmonary resuscitation. Each question was assigned a value between 1 and 7 based on the level of importance from low to high. T-tests, one-way analysis of variance, and Kruskal–Wallis H-tests were used to compare continuous variables. Binary logistic regression analysis was used to identify factors influencing when people considered it suitable to initiate cardiopulmonary resuscitation.

Results
The study involved 4289 participants from 31 provinces, autonomous regions and municipalities in mainland China, of whom 52.8% were male. The top three reasons for not attempting cardiopulmonary resuscitation were decomposition/hypostasis/rigor mortis (6.39 ± 1.44 points), massive injury (4.57 ± 2.08 points) and family members’ preference (4.35 ± 1.98 points). In total, 2761 (64.4%) thought emergency services should not attempt cardiopulmonary resuscitation when cardiac arrest had happened more than 30 min before, and there had been no bystander cardiopulmonary resuscitation. Gender (OR 1.233, p = 0.002), religion (OR 1.147, p = 0.046), level (OR 0.903, p = 0.028) or classification of city (OR 0.920, p = 0.049), years of work experience (OR 0.884, p = 0.004), and major (OR 1.032, p = 0.044) all influenced how long after cardiac arrest was considered suitable for initiating cardiopulmonary resuscitation.

Conclusions
Chinese emergency physicians have different perceptions of when not to attempt resuscitation to those practicing elsewhere. The existing guidelines for resuscitation are not suitable for China, and China-specific guidelines need to be established.
Prediction of prognosis in elderly patients with sepsis based on machine learning (random survival forest)
Authors: Zhang Luming , Huang Tao , Xu Fengshuo , Li Shaojin , Zheng Shuai , Lyu Jun , Yin Haiyan 
Published: February 2022

AbstractBackgroundElderly patients with sepsis have many comorbidities, and the clinical reaction is not obvious. Thus, clinical treatment is difficult. We planned to use the laboratory test results and comorbidities of elderly patients with sepsis from a large-scale public database Medical Information Mart for Intensive Care (MIMIC) IV to build a random survival forest (RSF) model and to evaluate the model’s predictive value for these patients.MethodsClinical information of elderly patients with sepsis in MIMIC IV database was collected retrospectively. Machine learning (RSF) was used to select the top 30 variables in the training cohort to build the final RSF model. The model was compared with the traditional scoring systems SOFA, SAPSII, and APSIII. The performance of the model was evaluated by C index and calibration curve.ResultsA total of 6,503 patients were enrolled in the study. The top 30 important variables screened by RSF were used to construct the final RSF model. The new model provided a better C-index (0.731 in the validation cohort). The calibration curve described the agreement between the predicted probability of RSF model and the observed 30-day survival.ConclusionsWe constructed a prognostic model to predict a 30-day mortality risk in elderly patients with sepsis based on machine learning (RSF algorithm), and it proved superior to the traditional scoring systems. The risk factors affecting the patients were also ranked. In addition to the common risk factors of vasopressors, ventilator use, and urine output. Newly added factors such as RDW, type of ICU unit, malignant cancer, and metastatic solid tumor also significantly influence prognosis.