bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision information extraction for rare disease epidemiology at scale
Authors: Kariampuzha William Z. , Alyea Gioconda , Qu Sue , Sanjak Jaleal , Mathé Ewy , Sid Eric , Chatelaine Haley , Yadaw Arjun , Xu Yanji , Zhu Qian 
Published: March 2023

Abstract
Background
The United Nations recently made a call to address the challenges of an estimated 300 million persons worldwide living with a rare disease through the collection, analysis, and dissemination of disaggregated data. Epidemiologic Information (EI) regarding prevalence and incidence data of rare diseases is sparse and current paradigms of identifying, extracting, and curating EI rely upon time-intensive, error-prone manual processes. With these limitations, a clear understanding of the variation in epidemiology and outcomes for rare disease patients is hampered. This challenges the public health of rare diseases patients through a lack of information necessary to prioritize research, policy decisions, therapeutic development, and health system allocations.

Methods
In this study, we developed a newly curated epidemiology corpus for Named Entity Recognition (NER), a deep learning framework, and a novel rare disease epidemiologic information pipeline named EpiPipeline4RD consisting of a web interface and Restful API. For the corpus creation, we programmatically gathered a representative sample of rare disease epidemiologic abstracts, utilized weakly-supervised machine learning techniques to label the dataset, and manually validated the labeled dataset. For the deep learning framework development, we fine-tuned our dataset and adapted the BioBERT model for NER. We measured the performance of our BioBERT model for epidemiology entity recognition quantitatively with precision, recall, and F1 and qualitatively through a comparison with Orphanet. We demonstrated the ability for our pipeline to gather, identify, and extract epidemiology information from rare disease abstracts through three case studies.

Results
We developed a deep learning model to extract EI with overall F1 scores of 0.817 and 0.878, evaluated at the entity-level and token-level respectively, and which achieved comparable qualitative results to Orphanet’s collection paradigm. Additionally, case studies of the rare diseases Classic homocystinuria, GRACILE syndrome, Phenylketonuria demonstrated the adequate recall of abstracts with epidemiology information, high precision of epidemiology information extraction through our deep learning model, and the increased efficiency of EpiPipeline4RD compared to a manual curation paradigm.

Conclusions
EpiPipeline4RD demonstrated high performance of EI extraction from rare disease literature to augment manual curation processes. This automated information curation paradigm will not only effectively empower development of the NIH Genetic and Rare Diseases Information Center (GARD), but also support the public health of the rare disease community.
Epigenetics as a versatile regulator of fibrosis
Authors: Liu Yangdan , Wen Dongsheng , Ho Chiakang , Yu Li , Zheng Danning , O’Reilly Steven , Gao Ya , Li Qingfeng , Zhang Yifan 
Published: March 2023

AbstractFibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made many efforts to understand the mechanism of fibrogenesis and to develop therapeutic strategies; yet, the outcome remains unsatisfactory. In recent years, advances in epigenetics, including chromatin remodeling, histone modification, DNA methylation, and noncoding RNA (ncRNA), have provided more insights into the fibrotic process and have suggested the possibility of novel therapy for organ fibrosis. In this review, we summarize the current research on the epigenetic mechanisms involved in organ fibrosis and their possible clinical applications.
Graphical Abstract
Risk, lifestyle and non-communicable diseases of poverty
Authors: Manderson Lenore , Jewett Sara 
Published: March 2023

AbstractCommon discourse in public health and preventive medicine frames non-communicable diseases, including cardiovascular and metabolic diseases, as diseases of ‘lifestyle’; the choice of terminology implies that their prevention, control and management are amenable to individual action. In drawing attention to global increases in the incidence and prevalence of non-communicable disease, however, we increasingly observe that these are non-communicable diseases of poverty. In this article, we call for the reframing of discourse to emphasize the underlying social and commercial determinants of health, including poverty and the manipulation of food markets. We demonstrate this by analysing trends in disease, which indicate that diabetes- and cardiovascular-related DALYS and deaths are increasing particularly in countries categorized as low-middle to middle levels of development. In contrast, countries with very low levels of development contribute least to diabetes and document low levels of CVDs. Although this might suggest that NCDs track increased national wealth, the metrics obscure the ways in which the populations most affected by these diseases are among the poorest in many countries, and hence, disease incidence is a marker of poverty not wealth. We also illustrate variations in five countries — Mexico, Brazil, South Africa, India and Nigeria — by gender, and argue that these differences are associated with gender norms that vary by context rather than sex-specific biological pathways.We tie these trends to shifts in food consumption from whole foods to ultra-processed foods, under colonialism and with continued globalization. Industrialization and the manipulation of global food markets influence food choice in the context of limited household income, time, and household and community resources. Other factors that constitute risk factors for NCDs are likewise constrained by low household income and the poverty of the environment for people with low income, including the capacity of individuals in sedentary occupations to engage in physical activity. These contextual factors highlight extremely limited personal power over diet and exercise. In acknowledging the importance of poverty in shaping diet and activity, we argue the merit in using the term non-communicable diseases of poverty and the acronym NCDP. In doing so, we call for greater attention and interventions to address structural determinants of NCDs.
Antiviral activities of Artemisia vulgaris L. extract against herpes simplex virus
Authors: Xiao Ji , Liu Ping , Hu Yuze , Liu Tao , Guo Yuying , Sun Pinghua , Zheng Junxia , Ren Zhe , Wang Yifei 
Published: March 2023

Abstract
Background
Artemisia vulgaris L. is often used as a traditional Chinese medicine with the same origin of medicine and food. Its active ingredient in leaves have multiple biological functions such as anti-inflammatory, antibacterial and insecticidal, anti-tumor, antioxidant and immune regulation, etc. It is confirmed that folium Artemisiae argyi has obvious anti-HBV activity, however, its antiviral activity and mechanism against herpesvirus or other viruses are not clear. Hence, we aimed to screen the crude extracts (Fr.8.3) isolated and extracted from folium A. argyi to explore the anti-herpesvirus activity and mechanism.

Methods
The antiherpes virus activity of Fr.8.3 was mainly characterized by cytopathic effects, real-time PCR detection of viral gene replication and expression levels, western blotting, viral titer determination and plaque reduction experiments. The main components of Fr.8.3 were identified by using LC–MS, and selected protein targets of these components were investigated through molecular docking.

Results
We collected and isolated a variety of A. vulgaris L. samples from Tangyin County, Henan Province and then screened the A. vulgaris L. leaf extracts for anti-HSV-1 activity. The results of the plaque reduction test showed that the crude extract of A. vulgaris L.-Fr.8.3 had anti-HSV-1 activity, and we further verified the anti-HSV-1 activity of Fr.8.3 at the DNA, RNA and protein levels. Moreover, we found that Fr.8.3 also had a broad spectrum of antiviral activity. Finally, we explored its anti-HSV-1 mechanism, and the results showed that Fr.8.3 exerted an anti-HSV-1 effect by acting directly on the virus itself. Then, the extracts were screened on HSV-1 surface glycoproteins and host cell surface receptors for potential binding ability by molecular docking, which further verified the phenotypic results. LC–MS analysis showed that 1 and 2 were the two main components of the extracts. Docking analysis suggested that compounds from extract 1 might similarly cover the binding domain between the virus and the host cells, thus interfering with virus adhesion to cell receptors, which provides new ideas and insights for clinical drug development for herpes simplex virus type 1.

Conclusion
We found that Fr.8.3 has anti-herpesvirus and anti-rotavirus effects. The main 12 components in Fr.8.3 were analyzed by LC–MS, and the protein targets were finally predicted through molecular docking, which showed that alkaloids may play a major role in antiviral activity.
A comprehensive review on traditional uses, phytochemistry and pharmacological properties of Paeonia emodi Wall. ex Royle: current landscape and future perspectives
Authors: Zahra Nida , Iqbal Javed , Arif Muhammad , Abbasi Banzeer Ahsan , Sher Hassan , Nawaz Ayesha Fazal , Yaseen Tabassum , Ydyrys Alibek , Sharifi-Rad Javad , Calina Daniela 
Published: March 2023

AbstractPaeoniaemodi Wall. ex Royle is commonly known as Himalayan paeony has great importance as a food and medicine. The practice of Paeoniaemodi Wall. ex Royle is very ancient and it is conventionally used for a wide range of illnesses in the folk system of medicine because of its wide beneficial phytochemical profile. The main purpose of the current review was the synthesis of recent data on botany, ethnopharmacology, phytochemistry and potential pharmacological mechanisms of action of Paeoniaemodi Wall. ex Royle, thus offering new prospects for the development of new adjuvant natural therapies. Using scientific databases such as PubMed/MedLine, Scopus, Web of Science, ScienceDirect, Google Scholar, Springer, and Wiley, a comprehensive literature search was performed for Paeoniaemodi Wall. ex Royle. For searching, we used the next MeSH terms: “Biological Product/isolation and purification”, “Biological Products/pharmacology”, “Drug Discovery/methods”, “Ethnopharmacology, Medicine”, “Traditional/methods”, “Paeonia/chemistry”, “Plant Extracts/pharmacology”, “Phytochemicals/chemistry”, “Phytochemicals/pharmacology”, “Plants, Medicinal”. The results of the most recent studies were analyzed and the most important data were summarized in tables and figures. Phytochemical research of Paeoniaemodi Wall. ex Royle has led to the isolation of triterpenes, monoterpenes, phenolic acids, fatty acids, organic compounds, steroids, free radicals and some other classes of primary metabolites. In addition, diverse pharmacological activities like antibacterial, antifungal, anticoagulant, airway relaxant lipoxygenase and beta-glucuronidase inhibiting activity, radical scavenging activity, phytotoxic and insecticidal activities have been reported for Paeoniaemodi Wall. ex Royle. Different bioactive compounds of Paeoniaemodi Wall. ex Royle has proven their therapeutic potential in modern pharmacological and biomedical research to cure numerous gastrointestinal and nervous disorders. In future, further in vitro and in vivo therapeutic studies are required to identify new mechanisms of action, pharmacokinetics studies, and new pharmaceutical formulations for target transport and possible interaction with allopathic drugs. Also, new research regarding quality evaluation, toxicity and safety data in humans is needed.
The correlation between Trichomonas vaginalis infection and reproductive system cancer: a systematic review and meta-analysis
Authors: Zhang Zhenchao , Li Dongxian , Li Yuhua , Zhang Rui , Xie Xianghuan , Yao Yi , Zhao Linfei , Tian Xiaowei , Yang Zhenke , Wang Shuai , Yue Xuejing , Mei Xuefang 
Published: March 2023

Abstract
Background
Trichomonas vaginalis (T. vaginalis) is a microaerophilic protozoan parasite which is responsible for trichomoniasis, the most common non-viral sexually transmitted infection in the world. The infection greatly damages the reproductive system. However, whether T. vaginalis infection can cause reproductive system cancer remains controversial.

Methods
This study systematically searched PubMed, EMBASE, Ovid and Google scholar, and 144 relevant articles were retrieved and classified into three categories: epidemiological investigations (68), reviews (30) and research articles (46). These three types of articles were verified according to their respective inclusion and exclusion criteria. Stata 16 was used to conduct a meta-analysis on the articles of epidemiological investigations for analysing the correlation between T. vaginalis infection and reproductive system cancer.

Results
The result of meta-analysis indicated that the rate of T. vaginalis infection in the cancer group was significantly higher than that in the non-cancer group (OR = 1.87, 95% CI 1.29–2.71, I2 = 52%). Moreover, the cancer rate of the population infected with T. vaginalis was significantly higher than that of the population without T. vaginalis infection (OR = 2.77, 95% CI 2.37–3.25, I2 = 31%). The review articles and most research articles stated that the infection of T. vaginalis could lead to cancer and the pathogenic mechanisms were as follows: T. vaginalis promoting inflammatory response, T. vaginalis infection changing the internal environment around parasitic sites and signal transduction pathway, the metabolites secreted by T. vaginalis inducing carcinogenesis and T. vaginalis increasing other pathogenic microbial infection to promote the occurrence of cancer.

Conclusions
Our study confirmed that there was a correlation between the infection of T. vaginalis and reproductive system cancer, and provided some possible research directions for clarifying the carcinogenic mechanisms caused by T. vaginalis infection.
A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report
Authors: Oka Takakazu 
Published: March 2023

Abstract
Background
Some patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complain of persistent fatigue, dyspnea, pain, and cognitive dysfunction. These symptoms are often described as “long COVID”. Whether a patient with long COVID might develop myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is of interest, as is the treatment and management of ME/CFS in a post-COVID patient. Here I report a patient, who, after an infection with SARS-CoV-2, developed ME/CFS and recovered after treatment.

Case presentation
The patient was a previously healthy 55-year-old woman who worked as a nurse and became ill with COVID-19 pneumonia. She then presented with severe fatigue, post-exertional malaise, dyspnea, pain, cognitive dysfunction, tachycardia, and exacerbation of fatigue on physical exertion, which persisted for more than 6 months after her recovery from COVID-19 pneumonia. She was bedridden for more than half of each day. The patient was treated from multiple perspectives, which included (1) instructions on eating habits and supplements; (2) cognitive and behavioral modifications for coping with physical, emotional, and cognitive fatigue; (3) instructions on conditioning exercises to improve deconditioning due to fatigue and dyspnea; and (4) pharmacotherapy with amitriptyline and hochuekkito, a Japanese herbal (Kampo) medicine. The patient made a complete recovery after completing the prescribed regimen and was able to return to work as a nurse.

Conclusions
To the best of my knowledge, this is the first detailed report on a patient infected with SARS-CoV-2 followed by long COVID with the signs/symptoms of ME/CFS who recovered after treatment. I hope this case report will be helpful to health care practitioners by its presentation of some of the therapeutic options for alleviating disabling signs/symptoms in patients with post-COVID ME/CFS.
Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses
Authors: Li Yupei , Chen Yu , Yang Tinghang , Chang Kaixi , Deng Ningyue , Zhao Weifeng , Su Baihai 
Published: March 2023

AbstractBoth high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.
correctKin: an optimized method to infer relatedness up to the 4th degree from low-coverage ancient human genomes
Authors: Nyerki Emil , Kalmár Tibor , Schütz Oszkár , Lima Rui M. , Neparáczki Endre , Török Tibor , Maróti Zoltán 
Published: March 2023

AbstractKinship analysis from very low-coverage ancient sequences has been possible up to the second degree with large uncertainties. We propose a new, accurate, and fast method, correctKin, to estimate the kinship coefficient and the confidence interval using low-coverage ancient data. We perform simulations and also validate correctKin on experimental modern and ancient data with widely different genome coverages (0.12×–11.9×) using samples with known family relations and known/unknown population structure. Based on our results, correctKin allows for the reliable identification of relatedness up to the 4th degree from variable/low-coverage ancient or badly degraded forensic whole genome sequencing data.
Creating a best practice template for participant communication plans in global health clinical studies
Authors: Shelly Colleen E. , Logan Caroline , Skorochod Beth , Wiyeh Alison , Ndwandwe Duduzile , Choko Augustine , Valea Innocent , Titanji Boghuma K. 
Published: March 2023

Abstract
Background
Clinical trial participants have a right to be informed throughout the entire process of human subject research. As part of this pillar of research ethics, participants and other stakeholders should be made aware of research findings after a trial has been completed. Though participants have both a right, and a desire to be informed of research outcomes, studies show that they rarely receive communication about study findings. Our aim was (1) to understand what, if any, role communication plans play in current global health clinical research protocols and (2) to use our findings to develop a communication plan template tailored to clinical research carried out in low-and-middle-income countries (LMIC) while minimizing colonial assumptions. While the template was drafted in the LMIC context, the principles are universally applicable and should be considered best practices for all global health clinical trials.

Methods
We carried out a mixed-method study over a period of 6 months to understand the role of communication with study participants and other stakeholders in clinical trials. The semiquantitative analysis included mining publicly available clinical trial protocols for communication-related language. Qualitative interviews (n = 7) were used to gather knowledge and insight from clinical trial experts to inform the development of a communication plan template.

Results
None of the 48 mined clinical trial protocols included a communication plan. Of the 48, 21% (n = 21) protocols included communication-related language, and 10% (n = 5) described plans to share trial results with participants.

Conclusion
The use of communication plans in global health clinical trials is lacking. To our knowledge, this is the first in-depth analysis of communication plans in clinical trials to date. We recommend that researchers utilize the developed communication plan template throughout the entire research process to ensure a human-centered approach to participant communication. This communication plan should apply to all phases of a research trial, with a particular emphasis on plans to share results in an accessible and engaging manner once the trial has been completed.
Selenite as a dual apoptotic and ferroptotic agent synergizes with EGFR and KRAS inhibitors with epigenetic interference
Authors: Chan Lok Seng , Liu Johnson , Li Molly S. C. , Li Lili , Tao Qian , Mok Tony S. K. 
Published: March 2023

Abstract
Background
Selenium, an essential trace element, has previously been investigated as a pro-apoptotic and DNA demethylation agent. It sensitizes the response to chemotherapy in patients who were refractory to cytotoxic agents. Meanwhile, ferroptosis is a novel approach to cancer treatment by triggering cell death and reversing drug resistance. The role of selenium in treating cancer cells harboring druggable oncogenic alterations and its underlying mechanism are largely unknown.

Results
We treated lung adenocarcinoma cell lines—EGFR-mutant H1975 (H1975 EGFR p.L858R and p.T790M) and KRAS-mutant H358 (H358 KRAS p.G12C), with sodium selenite to examine its effect on cell apoptosis, ferroptosis, and DNA methylation, as well as its interaction with existing targeted therapy, osimertinib, and adagrasib. We observed selenite to be a dual apoptotic and ferroptotic agent on lung cancer cells, associated with the activation of p38-ATF4-DDIT3 axis in the unfolded protein response. Ferroptosis induction was more remarkable in H1975 than H358. Selenite also altered cellular DNA methylation machinery through downregulating DNMT1 and upregulating TET1, though not as a major mechanism of its activity. Low-dose selenite synergized with osimertinib in EGFR-mutant H1975, and with adagrasib in KRAS-mutant H358, with stronger synergism observed in H1975.

Conclusion
These results suggest that selenite is a potential apoptotic and ferroptotic drug candidate for the treatment of especially EGFR- and potentially KRAS-mutant lung cancer.