bluuebunny/crossref_metadata_2025_split huggingface dataset:
3GOLD: optimized Levenshtein distance for clustering third-generation sequencing data
Authors: Logan Robert , Fleischmann Zoe , Annis Sofia , Wehe Amy Wangsness , Tilly Jonathan L. , Woods Dori C. , Khrapko Konstantin 
Published: March 2022

Abstract
Background
Third-generation sequencing offers some advantages over next-generation sequencing predecessors, but with the caveat of harboring a much higher error rate. Clustering-related sequences is an essential task in modern biology. To accurately cluster sequences rich in errors, error type and frequency need to be accounted for. Levenshtein distance is a well-established mathematical algorithm for measuring the edit distance between words and can specifically weight insertions, deletions and substitutions. However, there are drawbacks to using Levenshtein distance in a biological context and hence has rarely been used for this purpose. We present novel modifications to the Levenshtein distance algorithm to optimize it for clustering error-rich biological sequencing data.

Results
We successfully introduced a bidirectional frameshift allowance with end-user determined accommodation caps combined with weighted error discrimination. Furthermore, our modifications dramatically improved the computational speed of Levenstein distance. For simulated ONT MinION and PacBio Sequel datasets, the average clustering sensitivity for 3GOLD was 41.45% (S.D. 10.39) higher than Sequence-Levenstein distance, 52.14% (S.D. 9.43) higher than Levenshtein distance, 55.93% (S.D. 8.67) higher than Starcode, 42.68% (S.D. 8.09) higher than CD-HIT-EST and 61.49% (S.D. 7.81) higher than DNACLUST. For biological ONT MinION data, 3GOLD clustering sensitivity was 27.99% higher than Sequence-Levenstein distance, 52.76% higher than Levenshtein distance, 56.39% higher than Starcode, 48% higher than CD-HIT-EST and 70.4% higher than DNACLUST.

Conclusion
Our modifications to Levenshtein distance have improved its speed and accuracy compared to the classic Levenshtein distance, Sequence-Levenshtein distance and other commonly used clustering approaches on simulated and biological third-generation sequenced datasets. Our clustering approach is appropriate for datasets of unknown cluster centroids, such as those generated with unique molecular identifiers as well as known centroids such as barcoded datasets. A strength of our approach is high accuracy in resolving small clusters and mitigating the number of singletons.
Implications of analysing time-to-event outcomes as binary in meta-analysis: empirical evidence from the Cochrane Database of Systematic Reviews
Authors: Salika Theodosia , Turner Rebecca M. , Fisher David , Tierney Jayne F. , White Ian R. 
Published: March 2022

Abstract
Background
Systematic reviews and meta-analysis of time-to-event outcomes are frequently published within the Cochrane Database of Systematic Reviews (CDSR). However, these outcomes are handled differently across meta-analyses. They can be analysed on the hazard ratio (HR) scale or can be dichotomized and analysed as binary outcomes using effect measures such as odds ratios (OR) or risk ratios (RR). We investigated the impact of reanalysing meta-analyses from the CDSR that used these different effect measures.

Methods
We extracted two types of meta-analysis data from the CDSR: either recorded in a binary form only (“binary”), or in binary form together with observed minus expected and variance statistics (“OEV”). We explored how results for time-to-event outcomes originally analysed as “binary” change when analysed using the complementary log–log (clog-log) link on a HR scale. For the data originally analysed as HRs (“OEV”), we compared these results to analysing them as binary on a HR scale using the clog-log link or using a logit link on an OR scale.

Results
The pooled HR estimates were closer to 1 than the OR estimates in the majority of meta-analyses. Important differences in between-study heterogeneity between the HR and OR analyses were also observed. These changes led to discrepant conclusions between the OR and HR scales in some meta-analyses. Situations under which the clog-log link performed better than logit link and vice versa were apparent, indicating that the correct choice of the method does matter. Differences between scales arise mainly when event probability is high and may occur via differences in between-study heterogeneity or via increased within-study standard error in the OR relative to the HR analyses.

Conclusions
We identified that dichotomising time-to-event outcomes may be adequate for low event probabilities but not for high event probabilities. In meta-analyses where only binary data are available, the complementary log–log link may be a useful alternative when analysing time-to-event outcomes as binary, however the exact conditions need further exploration. These findings provide guidance on the appropriate methodology that should be used when conducting such meta-analyses.
Asthma and COPD exacerbation in relation to outdoor air pollution in the metropolitan area of Berlin, Germany
Authors: Hoffmann Christina , Maglakelidze Mariam , von Schneidemesser Erika , Witt Christian , Hoffmann Peter , Butler Tim 
Published: March 2022

Abstract
Background
Ambient air pollution poses a major risk for the development and aggravation of respiratory diseases. Evidence suggests that even in low-level air pollution environments there is a risk for an increase in adverse respiratory symptoms. We examined whether variations in daily air pollution levels of nitrogen dioxide, ozone, or particulate matter in Berlin, Germany were associated with hospital admissions of chronic obstructive pulmonary disease (COPD) and asthma patients in a time series analysis.

Methods
We calculated single and multi-pollutant models, investigated possible lags in effect, and analysed the influence of meteorological variables on the results. Data from January 2005 through December 2015 were used to quantify the concentration–response.

Results
The risk ratio for asthma patients to be hospitalised on the same day of NO2 exposure was 1.101 per 10 µg/m3 NO2 increase (95% CI: 1.013 to 1.195), for COPD patients 1.123 (95% CI: 1.081 to 1.168). Neither the exposure to ozone (95% CI: 0.904 to 1.020), PM10 (95% CI: 0.990 to 1.127), nor PM2.5 (95% CI: 0.981 to 1.148) was associated with an increased risk ratio for asthma patients to be hospitalised. Risk ratios for the hospital admission of COPD patients were also not increased due to ozone (95% CI: 0.981 to 1.033), PM10 (95% CI: 0.988 to 1.032), or PM2.5 (95% CI: 0.966 to 1.019) exposure. The presented risk ratios and confidence intervals relate to the day of exposure. We found no increased hospitalisation risks with a delayed occurrence on subsequent days.

Conclusions
A quantifiable, statistically significant increase in risk for asthma and COPD exacerbations owing to NO2 exposure at levels well below European regulatory limit values was observed.
The emerging role of deubiquitylating enzymes as therapeutic targets in cancer metabolism
Authors: Tu Rongfu , Ma Junpeng , Zhang Peng , Kang Ye , Xiong Xiaofan , Zhu Junsheng , Li Miao , Zhang Chengsheng 
Published: March 2022

AbstractCancer cells must rewire cellular metabolism to satisfy the unbridled proliferation, and metabolic reprogramming provides not only the advantage for cancer cell proliferation but also new targets for cancer treatment. However, the plasticity of the metabolic pathways makes them very difficult to target. Deubiquitylating enzymes (DUBs) are proteases that cleave ubiquitin from the substrate proteins and process ubiquitin precursors. While the molecular mechanisms are not fully understood, many DUBs have been shown to be involved in tumorigenesis and progression via controlling the dysregulated cancer metabolism, and consequently recognized as potential drug targets for cancer treatment. In this article, we summarized the significant progress in understanding the key roles of DUBs in cancer cell metabolic rewiring and the opportunities for the application of DUBs inhibitors in cancer treatment, intending to provide potential implications for both research purpose and clinical applications.
Successful treatment with proton beam therapy for a solitary sternal metastasis of breast cancer: a case report
Authors: Ishikawa Yojiro , Suzuki Motohisa , Yamaguchi Hisashi , Seto Ichiro , Machida Masanori , Takagawa Yoshiaki , Jingu Keiichi , Kikuchi Yasuyuki , Murakami Masao 
Published: March 2022

Abstract
Background
Breast cancer infrequently metastasizes to the sternum as solitary metastasis. We experienced successful treatment with proton beam therapy for a case of sternal metastasis of breast cancer. This case demonstrates for the first time the role of proton therapy in the treatment of oligometastatic sternal metastasis with limited tolerance of normal tissue due to previous photon irradiation.

Case presentation
A 40-year-old Japanese female presented with lumpiness in her left breast. The patient was diagnosed with breast cancer (cT1N0M0, cStage IA) and underwent partial mastectomy with axillary lymph node dissection. After the mastectomy, the patient received radiation therapy with 50 Gy in 25 fractions for initial irradiation of the left breast. After the initial irradiation of 50 Gy, the patient received 10 Gy in five fractions of a sequential boost for the tumor bed to a total dose of 60 Gy. Although the patient was administered tamoxifen after radiation therapy, solitary sternal metastasis occurred 6 months after radiation therapy. She refused chemotherapy and requested proton beam therapy for her sternal metastasis. The daily proton beam therapy fractions were 2.5 relative biological effectiveness, receiving a total dose of 70 Gy relative biological effectiveness. An acute side effect of grade 2 dermatitis according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. occurred during proton beam therapy, but there was no acute or late complication of more than grade 3. At 3 years after proton beam therapy, the patient remains in complete remission without surgery or chemotherapy.

Discussion and conclusion
Proton beam therapy for solitary sternal metastasis of breast cancer is considered to be a therapeutic option.
Lonely, harassed and abandoned in society: the lived experiences of Iranian homeless youth
Authors: Johari Fatemeh , Iranpour Abedin , Dehghan Mahlagha , Alizadeh Somayeh , Safizadeh Mansoure , Sharifi Hamid 
Published: March 2022

Abstract
Introduction
Homelessness is increasing among young adults in large cities. According to the United Nations, there are more than one billion absolute or relative homeless people in the world. This study was conducted to explain the lived experiences of homeless youth in southeastern Iran.

Materials and methods
In this qualitative study, we recruited 13 participants in a big city, southeast Iran, in 2020. The participant was young homeless adults aged 18–29 years who were using homeless shelters provided by the municipality, sleeping in parks or on streets. Data were collected through in-depth and semi-structured interviews and three focus group discussions. Data were analyzed by conventional qualitative content analysis.

Results
The main category of “lonely, annoyed, and abandoned in society” and three subcategories of avoidance of/by society, comprehensive harassment, and lack of comprehensive support were extracted. The experiences of young homeless adults showed that they escaped from the community due to addiction, feeling like a burden to others, and social isolation, and not only have they been left without support in society, but they have also suffered from all kinds of physical and psychological harassments.

Conclusion
The lived experiences of homeless people show that in addition to appropriate facilities and living conditions, they require respect, reduced social stigma, discrimination, and favorable conditions for a return to life. Therefore, authorities should identify and settle their problems and needs.
Stress detection using natural language processing and machine learning over social interactions
Authors: Nijhawan Tanya , Attigeri Girija , Ananthakrishna T. 
Published: March 2022

AbstractCyberspace is a vast soapbox for people to post anything that they witness in their day-to-day lives. Social media content is mostly used for review, opinion, influence, or sentiment analysis. In this paper, we aim to extend sentiment and emotion analysis for detecting the stress of an individual based on the posts and comments shared by him/her on social networking platforms. We leverage large-scale datasets with tweets to accomplish sentiment analysis with the aid of machine learning algorithms and a deep learning model, BERT for sentiment classification. We also adopted Latent Dirichlet Allocation which is an unsupervised machine learning method for scanning a group of documents, recognizing the word and phrase patterns within them, and gathering word groups and alike expressions that most precisely illustrate a set of documents. This helps us to predict which topic is linked to the textual data. With the aid of these models, we will be able to detect the emotion of users online. Further, these emotions can be used to analyze stress or depression. In conclusion, the ML models and a BERT model have a very good detection rate. This research is useful for the well-being of one's mental health. The results are evaluated using various metrics at the macro and micro levels and indicate that the trained model detects the status of emotions based on social interactions.
Bridging the gap between academia and practice: novel organogram at the Pharmacy Council of India
Authors: Doshi Mansi , Parbat Minesh , Paudyal Vibhu , Marriott John 
Published: March 2022

AbstractHarm with inappropriate and irrational use of medications is a global challenge. The need for and patient access to medicines optimisation services is apparent globally and amplified in India due to multiple reasons. Clinical pharmacists are ideally placed to promote patient safety with medicines use optimisation and other pharmaceutical care services through appropriate legislative, policy, and compensation mechanisms to achieve optimal patient outcomes. The need is for a move at a global level, an enabling organisational structure at Pharmacy Councils and in practice regulations, particularly in countries where clinical roles are still in infancy. This narrative describes the current status and future needs for development of medicines optimisation services across sectors through regulatory and organisational reforms at the Pharmacy Council of India with additional registration, continuing professional development, renewal and licensing requirements for clinical pharmacists to respond to patient and societal needs in India.
Cross-sectional survey of SARS-CoV-2 testing at US airports and one health department’s proactive management of travelers
Authors: Shaum Anna , Figueroa Argelia , Lee Danica , Ertl Allison , Rothney Erin , Borntrager Denise , Davenport Emily , Gulati Reena K. , Brown Clive M. 
Published: March 2022

Abstract
Background
Many health departments and private enterprises began offering SARS-CoV-2 testing to travelers at US airports in 2020. Persons with positive SARS-CoV-2 test results who have planned upcoming travel may be subject to US federal public health travel restrictions.
We assessed availability of testing for SARS-CoV-2 at major US airports. We then describe the management of cases and close contacts at Denver International Airport’s testing site.

Methods
We selected 100 US airports. Online surveys were conducted during November–December 2020 and assessed availability of testing for air travelers, flight crew, and airport employees. Respondents included health department (HD) staff or airport directors.
We analyzed testing data and management practices for persons who tested positive and their close contacts at one airport (Denver International) from 12/21/2020 to 3/31/2021.

Results
Among the 100 selected airports, we received information on 77 airports; 38 (49%) had a testing site and several more planned to offer one (N = 7; 9%). Most sites began testing in the fall of 2020. The most frequently offered tests were RT-PCR or other NAAT tests (N = 28).
Denver International Airport offered voluntary SARS-CoV-2 testing. Fifty-four people had positive results among 5724 tests conducted from 12/21/2020 to 3/31/2021 for a total positivity of < 1%. Of these, 15 were travelers with imminent flights. The Denver HD issued an order requiring the testing site to immediately report cases and notify airlines to cancel upcoming flight itineraries for infected travelers and their traveling close contacts, minimizing the use of federal travel restrictions.

Conclusions
As of December 2020, nearly half of surveyed US airports had SARS-CoV-2 testing sites. Such large-scale adoption of airport testing for a communicable disease is unprecedented and presents new challenges for travelers, airlines, airports, and public health authorities. This assessment was completed before the US and other countries began enforcing entry testing requirements; testing at airports will likely increase as travel demand returns and test requirements for travel evolve.
Lessons from Denver demonstrate how HDs can play a key role in engaging airport testing sites to ensure people who test positive for SARS-CoV-2 immediately before travel do not travel on commercial aircraft.
The mycotoxin deoxynivalenol (DON) can deteriorate vaccination efficacy against porcine reproductive and respiratory syndrome virus (PRRSV) at subtoxic levels
Authors: Rückner Antje , Plagge Lisa , Heenemann Kristin , Harzer Maxi , Thaa Bastian , Winkler Janine , Dänicke Sven , Kauffold Johannes , Vahlenkamp Thomas W. 
Published: March 2022

AbstractBackgroundFeedgrain contamination with mycotoxins, including deoxynivalenol (DON, “vomitoxin”) is relatively frequently encountered. Pigs are particularly sensitive to the toxicity of DON. To assess the interplay between DON and porcine reproductive and respiratory syndrome virus (PRRSV), we performed an experimental DON exposure–PRRSV vaccination–challenge infection trial. Three-week-old piglets were divided into four groups. Groups I, II and III (10 animals/group) were vaccinated with a PRRSV modified live vaccine and 2 weeks later challenged with a heterologous field strain. While group I was not supplemented with DON, animals in groups II and III received DON for 4 weeks prior to challenge infection at levels that can be encountered in pig feed, employing a low-dose or high-dose regime (group II: 40 µg DON/kg body weight per day; group III: 80 µg DON/kg body weight per day, corresponding to approx. 1 or 2 mg DON/kg feed, respectively). Eight animals (group IV; unvaccinated, not DON exposed) served as control animals for the challenge infection.ResultsWe assessed clinical signs, virus load in serum and various organs as well as antibody titres in the animals. All vaccinated animals mounted an efficient PRRSV-specific antibody response within 2 weeks, except for 20% of the animals receiving the higher DON dose. Upon virus challenge, the vaccinated animals in group I were protected from clinical signs. Vaccinated DON-exposed animals in group II and III were protected from clinical signs to a lesser extent. Clinical signs in group III receiving the higher dose of DON were as severe as in the (unvaccinated, not DON exposed) control group IV. The animals of group III also displayed lower antibody titres compared with the animals in group I and II.ConclusionsThe experimental vaccination/challenge study therefore revealed that exposure of pigs to DON for a period of 4 weeks deteriorates the efficacy of vaccination against clinical signs of PRRS.
Development and content validation of a self-completed, electronic Pediatric Asthma Symptom Diary
Authors: Clark Marci , Romano Carla , Olayinka-Amao Oyebimpe , Whalley Diane , Crawford Rebecca , Pathak Purnima , Brindicci Caterina , Garg Kristin , Kordy Kattayoun , Everhard Francois , Patalano Francesco , Roesler Zach , Sutton Thomas , Göransson Oskar , Landles Ross , Naujoks Christel , Marvel Jessica , Keininger Dorothy L. 
Published: March 2022

Abstract
Background
Childhood asthma is an important unmet need. To date, patient-reported outcome measures (PROMs) for children with asthma have used a combination of caregiver or proxy-reported and self-reported measures. No comprehensive measure is available to assess the severity and impact of daytime and nighttime asthma symptoms and rescue medication use for self-completion by children aged 6–11 years. This study aimed to develop a novel, interactive, electronic Pediatric Asthma Symptom Diary (ePASD) measuring self-reported key symptom severity and proximal impacts of asthma in young children with varying reading ability and disease severity, consistent with US Food and Drug Administration (FDA) PRO guidance and the International Society for Health Economics and Outcomes Research (ISPOR) good research practices.

Methods
A targeted literature review and clinician interviews were undertaken to characterize symptoms and impacts experienced by children with mild-to-severe asthma. Concept elicitation interviews (CEIs) were conducted with 44 children and their caregivers (30 US; 14 UK). Following item and digital application development, the ePASD was assessed for relevance, understanding, and interpretability through cognitive debriefing interviews (CDIs) with 21 US children. Face validity/translatability assessments were also performed.

Results
Key measurement concepts included cough, wheeze, difficulty breathing, chest tightness/discomfort, nighttime awakening, and daytime activity limitations. Concept saturation was reached during CEIs for primary asthma-related daytime and nighttime symptoms and core impacts. Most CDI participants found the ePASD items clear, understandable, and comprehensive. Standardized training is anticipated to facilitate reliable child self-report.

Conclusion
The ePASD, a novel PROM for children aged 6–11 years with asthma, uses an innovative multimedia approach and has been developed in accordance with FDA PRO guidance and ISPOR good research practices, directly capturing the child’s self-reported asthma symptoms, impacts on daily activities and nighttime awakening, and rescue medication use.
Small cell-like change in prostatic adenocarcinoma and intraductallesions – neuroendocrine or not?
Authors: Athanazio Daniel Abensur , de Souza Maiara Ferreira 
Published: March 2022

Abstract
Background
Small cell-like change in prostatic neoplasia (both invasive adenocarcinoma and intraepithelial lesions) is described in three previous reports. None of them to date proved to be associated with overt prostate neuroendocrine carcinoma.

Case presentation
We report findings from a radical prostatectomy of 80-year-old patient (adenocarcinoma GG5 pT3b with 10% involvement of the gland) with small cell-like change in intraductal carcinoma and in the invasive component. An additional 3.5-mm focus of poorly differentiated carcinoma was observed (PSA, TTF1, chromogranin and CD56 negative; synaptophysin positive in scattered cells; and a Ki67 label index of 50%).

Conclusion
Our case expands the data accumulated on small cell-like change in prostate neoplasia. As most of other reported cases, there was no expression of neuroendocrine markers or high proliferative index in small-cell like areas. On the other hand, for the first time, a transition morphology between acinar adenocarcinoma and neuroendocrine carcinoma was observed in a prostate with small cell-like change.