bluuebunny/crossref_metadata_2025 huggingface dataset:
“The Facebook is a state of Roma”: Negotiating identities, building communities, and belongingness online among Roma in the Czech Republic
Authors: Hatef Azeta
Published: February 2022

This article examines social media as a site for identity negotiation and community building among Roma in the Czech Republic. As Roma are continually denied authority over the construction of their identities, their Czech-ness, claim to physical spaces, and generally made to feel that they do not belong—both in the material and symbolic sense—this article examines how individual activists and community organizers utilize media as a resource to combat spatial alienation. This ethnographic study pays close attention to the cultivation of community through Facebook groups, the utilization of groups and event pages to organize, and the affordances and challenges of moving online efforts offline. At the same time, this article explores tensions and contradictions of these digital spaces that may involve issues like the lack of resources and the fragmentation of community—and of communal space—by such variables as age, language, and technological access and literacy. Ultimately, this article suggests that social media may embody both emotional and material places manifesting as additional/alternative places to negotiate identities and belonging for Roma in the Czech Republic. The findings of this research carry important implications for those with complicated relationships to home(lands), including geographically displaced people.
The digital divide in the US criminal justice system
Authors: Ramirez Fanny
Published: February 2022

The growing use of digital evidence from smartphones and social media has led to a digital divide in the US criminal justice system that advantages law enforcement and prosecutors while further increasing the vulnerability of poor people and people of color who rely on public legal assistance. Drawing on a year-long ethnographic study of one of the first digital forensics laboratories in a public defender office, I argue that digital inclusion in the form of better resources for public defenders is necessary for equitable and fair representation in today’s criminal justice system. Findings show that access to digital forensic technologies is an important equalizing tool that allows public defenders to (1) mount strong, data-driven cases; (2) create counter narratives that challenge depictions of marginalized defendants as dangerous; and (3) engage in nuanced storytelling to highlight the complexities of human relationships and life circumstances that shape cases.
Gendered violence and sexualized representations in video games: (Lack of) effect on gender-related attitudes
Authors: Cross Liam , Kaye Linda K , Savostijanovs Juris , McLatchie Neil , Johnston Matthew , Whiteman Liam , Mooney Robyn , Atherton Gray
Published: February 2022

This research explored how gender portrayals in video games affect gender-related attitudes. Two hundred participants from the United Kingdom and Malaysia participated across three experiments, where the appearance and behaviour of video game characters were manipulated with regard to target (enemy) gender (Study 1), sexually explicit attire (Study 2) and level of character agency (Study 3). We found minimal evidence that exposure to gender-stereotyped content resulted in differential gender-related attitudes (implicit associations, hostile and benevolent sexism, or rape myth acceptance). However, Study 1 findings showed that individuals who played a first-person shooter with male enemies showed lower endorsement of some (benevolent) sexist attitudes (cf. control) and showed difference in game behaviour (cf. female enemies). Together, our results suggest that short-term exposure to video games containing female characters (sexualised, passive, or otherwise) does not consistently lead to the endorsement of negative gender attitudes.
A Systematic Review of Gender-Based Violence Prevention and Response Interventions for HIV Key Populations: Female Sex Workers, Men Who Have Sex With Men, and People Who Inject Drugs
Authors: Decker Michele R. , Lyons Carrie , Guan Kathleen , Mosenge Vanessa , Fouda Ghislane , Levitt Daniel , Abelson Anna , Nunez Gnilane Turpin , Njindam Iliassou Mfochive , Kurani Shaheen , Baral Stefan
Published: February 2022

Gender-based violence (GBV) is that perpetrated based on sex, gender identity, or perceived adherence to socially defined gender norms. This human rights violation is disproportionately experienced by HIV key populations including female sex workers (FSW), people who inject drugs (PWID), and men who have sex with men (MSM). Consequently, addressing GBV is a global priority in HIV response. There is limited consensus about optimal interventions and little known about effectiveness. Our systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in International Prospective Register of Systematic Reviews. Peer-reviewed and non-peer-reviewed literature were searched for articles that described a GBV prevention or response intervention specifically for key populations including FSW, PWID, and MSM. Results were organized by level(s) of implementation and pillars of a comprehensive GBV response: prevention, survivor support, and accountability/justice. Of 4,287 articles following removal of duplicates, 32 unique interventions (21 FSW, seven PWID, and nine MSM, not mutually exclusive) met inclusion criteria, representing 13 countries. Multisectoral interventions blended empowerment, advocacy, and crisis response with reductions in violence. Individual-level interventions included violence screening and response services. Violence-related safety promotion and risk reduction counseling within HIV risk reduction programming reduced violence. Quantitative evaluations were limited. Violence prevention and response interventions for FSW, PWID, and MSM span individual, community, and multisectoral levels with evidence of promising practices at each level. The strongest evidence supported addressing violence in the context of sexually transmitted infection/HIV risk reduction. As interventions continue to emerge, the rigor of accompanying evaluations must simultaneously advance to enable clarity on the health and safety impact of GBV prevention and response programming.
Design and control of underwater robot system for sea cucumber fishing
Authors: Shi Xinxin , Zhu Chenyang , Lu Pengcheng
Published: February 2022

Sea cucumber fishing is an important application of underwater robots. In order to realize the function of sea cucumber fishing, an underwater robot system for sea cucumber fishing is designed, which can reduce operation requirements and costs while realizing sea cucumber fishing. The overall system plan includes the design of subsystems such as power supply system, fishing system, transmission system, propulsion system, balance and positioning system, and anti-collision airbag. According to the actual needs of sea cucumber fishing, the mechanical structure and size of each subsystem are designed, and SolidWorks is used to complete the three-dimensional modeling of the overall system. The sliding mode control and adaptive sliding mode control algorithms are used to compare the positioning control effects of the underwater vehicle to verify the effectiveness of the system design.
Oral health status and quality of life of the parental caregivers of children with Down syndrome: A case-control study
Authors: Schwertner Carolina , Silva Caroline Dias da , Grando Débora , Hilgert Juliana Balbinot , Hashizume Lina Naomi
Published: February 2022

The aim of this study was to investigate the oral health status and quality of life (QOL) of the parental caregivers of individuals with Down syndrome (DS), and to evaluate whether there is an association between these variables. The sample of this cross-sectional study was composed by parental caregivers of children with DS (CCDS) and parental caregivers of children without DS (CNDSC). Oral examination was undertaken and a questionnaire was given to participants. QOL was evaluated by WHOQOL-Bref. CCDS presented a higher number of dental prosthesis users and higher gingival bleeding index compared to CNDSC. When oral health was associated with QOL, the use of dental prosthesis was associated with physical domain and the variables having chronic disease and family income were associated with the social domain for both caregivers. The results suggest that caregivers of children with DS have similar oral health and QOL compared to caregivers of children without DS. In both caregivers, oral health status is associated with QOL.
The experience of under-screened and never-screened participants using clinician-supported self-collection cervical screening within the Australian National Cervical Screening Program
Authors: Creagh Nicola S , Zammit Claire , Brotherton Julia ML , Saville Marion , McDermott Tracey , Nightingale Claire , Kelaher Margaret
Published: February 2022

Background:

Australia has had significant successes in the prevention of cervical cancer. However, there is considerable scope for improving screening participation. In December 2017, Australia shifted from cytology to a human papillomavirus–based screening program as part of the renewed National Cervical Screening Program. This provided the opportunity to introduce a clinician-supported self-collection cervical screening pathway, which allows screening participants aged 30 years or more and who are under-screened or never-screened to screen via a self-collected human papillomavirus test.

Objective:

This study aimed to explore screening participant experiences of a clinician-supported self-collection cervical screening pathway.

Methods:

Interviews (n = 45) were conducted with participants who had used the clinician-supported self-collection cervical screening pathway in the Australian National Cervical Screening Program between December 2017 and April 2019. Interviews were analyzed using template analysis.

Results:

Under-screened and never-screened participants reported a variety of interrelated barriers to cervical screening due to the nature of the test. For these participants, self-collection was a preferable way to perform screening as it overcame various barriers, was easy to use and promoted a sense of empowerment. Participants reported that the role of their practitioner was influential in their decision to undertake cervical screening, and that the support and information provided was a key factor in their experiences of the self-collection pathway.

Conclusion:

Findings support the use of a clinician-supported model of care, as an alternative screening modality in Australia’s National Cervical Screening Program. As more countries consider the move from a cytology to human papillomavirus–based cervical screening program, this model may assist in greater engagement of under-screened participants.
Intraperitoneal Insulin Delivery: Evidence of a Physiological Route for Artificial Pancreas From Compartmental Modeling
Authors: Lo Presti Jorge , Galderisi Alfonso , Doyle Francis J. , Zisser Howard C. , Dassau Eyal , Renard Eric , Toffanin Chiara , Cobelli Claudio
Published: February 2022

Background

Intraperitoneal insulin delivery has proven to safely overcome a major limit of subcutaneous delivery—meal announcement—and has been able to optimize glycemic control in adults under controlled experimental conditions. In addition, intraperitoneal delivery avoids peripheral hyperinsulinemia resulting from the subcutaneous route and restores a physiological liver gradient.

Methods

Relying on a unique data set of intraperitoneal closed-loop insulin delivery obtained with a Model Predictive Controller (MPC), we develop a compartmental model of intraperitoneal insulin kinetics, which, once included in the UVa/Padova T1D simulator, will facilitate the investigation of various control strategies, for example, the simpler Proportional Integral Derivative controller versus MPC.

Results

Intraperitoneal insulin kinetics can be described with a 2-compartment model including liver and plasma.

Conclusion

Intraperitoneal insulin transit is fast enough to render irrelevant the addition of a peritoneal compartment, proving the peritoneum being a virtual—not actual—transit space for insulin delivery.
Neurology Morbidity and Mortality Conferences and Quality Improvement: Single-Center Experience and National Survey
Authors: Ryan Sophia L. , McKee Kathleen E. , Londono-Sanchez Lizbeth , Dougherty Sarah , Singhal Aneesh B.
Published: February 2022

Background

Morbidity and Mortality (M&M) conferences are widespread but vary in goals and methodology. Some focus on clinical enigmas while an increasing number utilize quality improvement (QI) tools to effect systems change. Little is known about the current state of US Neurology M&Ms.

Methods

We surveyed 56 US academic neurology departments regarding their M&Ms to understand the use of QI tools and assess variability. Additionally, we reviewed the evolution of M&Ms in our department.

Results

The survey was completed by 44 (80%) departments; 68% reported quarterly frequency with 61% discussing 1–2 safety events per conference. The number of written guidelines or protocols resulting from M&Ms in 2 years varied from 0 (14% of departments), 1–2 (45%), to >5 (5%). Institutional culture regarding quality and safety and conference timing were cited by 71% as important in improving participation. In our own department, the M&M format changed in 2014 based on a sentinel patient event combined with improving safety culture across the hospital: neurology M&Ms transformed into thematic quarterly conferences utilizing QI tools. Attendance increased 3-fold, and in 7 years, we have generated 26 guidelines or pathways with corresponding decision-support tools, among other improvement efforts, resulting in specific systems changes. Based on survey results and our experience, suggested M&M “best practices” include the use of just culture, peer review protection, safety event analysis with QI methodology, trainee involvement, and logistical optimization.

Conclusion

Structured M&Ms incorporating suggested QI-informed “best practices” can be highly effective in driving system change within neurology.
Glioblastoma with Gliomatosis Cerebri Growth Pattern Presenting as Rapidly Progressive Dementia
Authors: Rhee John Y. , Gonzalez Castro Luis Nicolas
Published: February 2022

The differential diagnosis of rapidly progressive dementia includes neurodegenerative, toxic/metabolic, infectious, inflammatory, vascular, and malignant etiologies. This case highlights a patient with rapidly progressive cognitive decline that remained a diagnostic dilemma due to nonspecific symptoms of disorientation that progressed to persistent alteration in mental status over the span of three months. Routine laboratory testing did not help clarify the diagnosis and initial brain imaging showed only subtle abnormalities that were not commensurate with the patient’s neurologic examination. As imaging findings evolved over time to reveal a multifocal process, a biopsy was pursued, with histology consistent with infiltrating glioma and molecular testing consistent with glioblastoma. Glioblastoma with gliomatosis cerebri growth pattern should be considered on the differential diagnosis of rapidly progressive dementia in patients with multifocal imaging findings.
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.
Where horizontal and vertical surveillances meet: Sense-making of US COVID-19 contact-tracing apps during a health crisis
Authors: Baik Jeeyun (Sophia) , Jang Eugene
Published: February 2022

Analyzing user reviews of seven US digital contact-tracing apps for COVID-19, this article unpacks how the new form of surveillance technology is understood and experienced by individuals during a global health crisis. The findings suggest that the app users felt empowered via self-tracking capacity and expressed community-level care and concerns, including those regarding the marginalized. At the same time, the users were raising doubts over technical effectiveness, navigating varying levels of voluntary choice available, and negotiating privacy concerns depending on the (dis)trust they held of institutional entities behind the governance of the apps. We argue that it is critical to investigate how surveillance technologies are situated across horizontal and vertical relationships in people's everyday lives to fully understand the individual and societal acceptance and/or refusal of the very systems during crises.
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.
Focus and Interaction in Writing Conferences for EFL Writers
Authors: Yang Luxin
Published: February 2022

It is widely recognized that writing conferences benefit second or foreign language writers for the immediacy and the potential to address their needs and provide tailored and individualized support. However, limited attention has been given to the foci and interaction between teacher and student in writing conferences longitudinally. To address this need, this study examined writing conferences between five university English-as-a-foreign-language (EFL) students and their instructor in an argumentative writing course over one semester in a key Chinese university. Multiple sources of data were collected, including conferences, students’ essay drafts and written reflections, and interviews with the students and the instructor. Data analyses show that the conferences covered a large variety of topics such as varied aspects about argumentative writing, learning habits, and expectations about the course, which were related to English proficiency and English writing ability of each student. Second, the instructor took different approaches to communicate with each student in writing conferences considering their difficulties and needs. Finally, the conferences contribute to a deliberative process critical to the process of learning to write argumentation. The students found conversations with the instructor helpful in their subsequent revisions whereas the instructor gained a better understanding of students’ difficulties in writing. This study suggests that more research is needed to examine the role of conferences in EFL writing instruction. This study supports that conferences, as an important aid, will facilitate EFL students in the process of learning to write in English in addition to teacher written feedback and peer review.
College, Career, Commitment, Oh My: How Emerging Adult Women Balance Romantic Relationships, Career Plans, and Financial Stability
Authors: Youmans Amanda R. , Canby Nicholas K. , Córdova James V.
Published: February 2022

In a highly gendered society where both relational expectations and career aspirations are socialized goals, emerging adult women are uniquely positioned when considering their futures. Choices regarding education, career, and romantic relationships are linked to social pressures, leading young women to be conflicted about what goals to prioritize. This study analyzes interviews exploring how women in committed relationships currently in college, or recently graduated, are balancing these life domains at the intersection of gender in the United States. Findings indicate that emerging adult women struggle with their own desires for romantic commitment in the face of societal presumptions, logistical battles, and feelings of instability anxiety. Yet, commitment, communication, and faith in serendipity emerged as protective relationship factors. Although continuing a romantic relationship is not impossible during such instability, relationships for young women today may not exist without notable individual compromise and hold more significance concerning young women’s perceived autonomy.
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.
A Case Study of Pain Management at End-of-Life for a Patient on High-Dose Buprenorphine
Authors: Katz Naomi T , Lloyd-Jones Martyn , Demediuk Lucy , McLaughlin Kerry , McKechnie Megan , Gold Michelle
Published: February 2022

In Australia, high-dose sublingual buprenorphine and long-acting injectable buprenorphine are available. High-dose buprenorphine is used predominantly in the setting of opioid use disorder and has a role in chronic pain. Palliative care specialists are increasingly involved in pain management and end-of-life care for patients on these medications, yet there is a lack of education and training about high-dose buprenorphine for palliative care specialists. We describe our experience caring for John (fictional name), a gentleman with chronic pain and a new high-grade post-transplant lymphoproliferative disorder prescribed high-dose buprenorphine. We share the challenges and experience in caring for John as he deteriorated into the terminal phase and died of his illness. We include potential management options and the rationale for our decision to rotate John from high-dose sublingual buprenorphine to subcutaneous oxycodone. We conclude with practice implications and suggestions for improved patient care and clinician experience, including increased collaboration between palliative medicine, acute pain, and addiction medicine services, increased education and training for palliative care specialists about high-dose buprenorphine, and ultimately the development of consensus high-dose buprenorphine to oral morphine equivalence guidelines.
Genotoxic aldehydes in the hematopoietic system
Authors: Wang Meng , Dingler Felix A. , Patel K. J.
Published: February 2022

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

The 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

Introduction

Cystic 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.

Methods

We 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.

Results

For 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.

Conclusions

Novel 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

Osteoarthritis (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

Background

For 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.

Results

In 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.

Conclusions

To 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

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

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

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

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

Background

Elderly 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.

Methods

Clinical 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.

Results

A 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.

Conclusions

We 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.
Barriers to and motives for engagement in an exercise-based cardiac rehabilitation programme in Ireland: a qualitative study
Authors: Bourke Alison , Niranjan Vikram , O’Connor Raymond , Woods Catherine
Published: February 2022

Background

Insufficient physical activity (PA) is a leading risk factor for premature death worldwide. Ireland’s public healthcare system, the Health Service Executive (HSE), has supported the development of the National Exercise Referral Framework (NERF) to tackle low levels of PA amongst those with non-communicable diseases (NCDs). ‘NERF centres’ are medically supervised PA programmes across Ireland that have established referral pathways with local hospitals and general practitioners. ULMedX is one such NERF centre offering exercise-based cardiac rehabilitation (EBCR) with the aim of intervention development to reduce early drop-out and maximise adherence for optimal health benefits.

Aim

The purpose of this research was to identify the major factors influencing participants’ adherence and early drop-out at ULMedX. Exploring areas for future development were also prioritised.

Design & setting

Qualitative interviews were conducted with long-term attenders and people who have dropped out (PWDO) from ULMedX.

Methods

Guided by the Theory of Planned Behaviour the 1–1 semi-structured interviews were performed, transcribed, and evaluated through thematic analysis.

Results

Analysis was performed on 14 participants (50% female; mean age 67.3 years), comprising long-term attenders (n = 7; 13-month duration, 64% of classes) and PWDO (n = 7; 2.8-month duration, 22% of classes). Three major factors affecting adherence and drop-out were identified: social support, perceived outcomes from participation and practical barriers to attendance. Areas for future development included the provision of evening and advanced classes, psychological support, more exercise variety, more educational seminars and new members start as their own group.

Conclusion

The findings suggest participants at ULMedX are more likely to have had a better experience and commit to the programme if they believed involvement would benefit their physical and mental health, increase their exercise motivation by engendering a positive attitude to exercise, and that the ability to attend was within their control. Future interventions at ULMedX should have their structures centred around these motives for engagement. ULMedX should also test the participant recommendations to overcome the common barriers to adherence.