bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicted coronavirus Nsp5 protease cleavage sites in the human proteome
Authors: Scott Benjamin M. , Lacasse Vincent , Blom Ditte G. , Tonner Peter D. , Blom Nikolaj S. 
Published: April 2022

AbstractBackgroundThe coronavirus nonstructural protein 5 (Nsp5) is a cysteine protease required for processing the viral polyprotein and is therefore crucial for viral replication. Nsp5 from several coronaviruses have also been found to cleave host proteins, disrupting molecular pathways involved in innate immunity. Nsp5 from the recently emerged SARS-CoV-2 virus interacts with and can cleave human proteins, which may be relevant to the pathogenesis of COVID-19. Based on the continuing global pandemic, and emerging understanding of coronavirus Nsp5-human protein interactions, we set out to predict what human proteins are cleaved by the coronavirus Nsp5 protease using a bioinformatics approach.ResultsUsing a previously developed neural network trained on coronavirus Nsp5 cleavage sites (NetCorona), we made predictions of Nsp5 cleavage sites in all human proteins. Structures of human proteins in the Protein Data Bank containing a predicted Nsp5 cleavage site were then examined, generating a list of 92 human proteins with a highly predicted and accessible cleavage site. Of those, 48 are expected to be found in the same cellular compartment as Nsp5. Analysis of this targeted list of proteins revealed molecular pathways susceptible to Nsp5 cleavage and therefore relevant to coronavirus infection, including pathways involved in mRNA processing, cytokine response, cytoskeleton organization, and apoptosis.ConclusionsThis study combines predictions of Nsp5 cleavage sites in human proteins with protein structure information and protein network analysis. We predicted cleavage sites in proteins recently shown to be cleaved in vitro by SARS-CoV-2 Nsp5, and we discuss how other potentially cleaved proteins may be relevant to coronavirus mediated immune dysregulation. The data presented here will assist in the design of more targeted experiments, to determine the role of coronavirus Nsp5 cleavage of host proteins, which is relevant to understanding the molecular pathology of coronavirus infection.
Physiological adjustment of pomegranate pericarp responding to sunburn and its underlying molecular mechanisms
Authors: Liu Chunyan , Su Ying , Li Jiyu , Jia Botao , Cao Zhen , Qin Gaihua 
Published: April 2022

Abstract
Background
Sunburn is common in pomegranate, and sunburned fruits have poor appearance and low marketability. However, the physiological and metabolic responses to sunburn and their underlying molecular mechanisms in pomegranate fruit are little understood. Fruit of sunburn-sensitive cultivar ‘Hongyushizi’ was used to carry out physiological parameter detection and widely-targeted metabolomics and transcriptome study.

Results
Malondialdehyde and relative conductivity increased with the severity of sunburn, which indicated increased membrane injury. Meanwhile, the content of antioxidants (total phenols and flavonoids), which reduce and repair membrane damage, increased and were accompanied by increases in total antioxidant capacity. In sunburned fruits compared with controls, 129 metabolites changed (including naringenin, pelargonidin and kaempferol) and 447 differentially expressed genes including CHI (Pgr25966.1), F3′5′H (Pgr26644.1), and CHS (Pgr005566.1) may have contributed to these changes. Transcription factors, such as NAC 5 (Pgr008725.1), MYB 93 (Pgr001791.1), and MYB 111 (Pgr027973.1) may be involved in phenylpropanoid and flavonoid biosynthesis by regulating the CHI, F3′5′H, and CHS etc.

Conclusions
These findings provide insight into the sunburn mechanisms of pomegranate, and also into the genetic improvement of fruit sunburn.
The impact of COVID-19 on the number of active small primary care businesses by severity of the pandemic: evidence from South Korea
Authors: Son Kyung-Bok 
Published: April 2022

Abstract
Background
Health systems have become financially fragile owing to the economic recession caused by the COVID-19 pandemic. However, small primary care businesses have received less policy attention than public health and secondary care. We aimed to estimate the impact of COVID-19 on the number of active small primary care businesses in South Korea.

Methods
We selected clinics, dental clinics, oriental clinics, and pharmacies as primary care businesses. Our estimation took advantage of regional variations in COVID-19 cases in South Korea. We determined the number of active primary care businesses from 2019 1Q to 2021 1Q on a quarterly basis, and conducted interrupted time series analysis to estimate the effects of COVID-19 on this sector.

Results
This study found no significant increase or decrease in the number of clinics, dental clinics, and oriental clinics immediately after the pandemic began or in the time trends after the pandemic. However, there was a significant increase in the number of pharmacies immediately after the pandemic. The most affected area presented different trends in the number of pharmacies, dental clinics, and oriental clinics.

Conclusions
Impact of the pandemic on the number of active small primary care business were low in South Korea. However, the impact varied according to the type of primary care setting and severity of the pandemic. The additional public health role of primary care could be associated with the sustenance of primary care businesses.
The effectiveness of governmental nonpharmaceutical interventions against COVID-19 at controlling seasonal influenza transmission: an ecological study
Authors: Qiu Zekai , Cao Zicheng , Zou Min , Tang Kang , Zhang Chi , Tang Jing , Zeng Jinfeng , Wang Yaqi , Sun Qianru , Wang Daoze , Du Xiangjun 
Published: April 2022

Abstract
Background
A range of strict nonpharmaceutical interventions (NPIs) were implemented in many countries to combat the coronavirus 2019 (COVID-19) pandemic. These NPIs may also be effective at controlling seasonal influenza virus infections, as influenza viruses have the same transmission path as severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate the effects of different NPIs on the control of seasonal influenza.

Methods
Data for 14 NPIs implemented in 33 countries and the corresponding influenza virological surveillance data were collected. The influenza suppression index was calculated as the difference between the influenza positivity rate during its period of decline from 2019 to 2020 and during the influenza epidemic seasons in the previous 9 years. A machine learning model was developed using an extreme gradient boosting tree regressor to fit the NPI and influenza suppression index data. The SHapley Additive exPlanations tool was used to characterize the NPIs that suppressed the transmission of influenza.

Results
Of all NPIs tested, gathering limitations had the greatest contribution (37.60%) to suppressing influenza transmission during the 2019–2020 influenza season. The three most effective NPIs were gathering limitations, international travel restrictions, and school closures. For these three NPIs, their intensity threshold required to generate an effect were restrictions on the size of gatherings less than 1000 people, ban of travel to all regions or total border closures, and closing only some categories of schools, respectively. There was a strong positive interaction effect between mask-wearing requirements and gathering limitations, whereas merely implementing a mask-wearing requirement, and not other NPIs, diluted the effectiveness of mask-wearing requirements at suppressing influenza transmission.

Conclusions
Gathering limitations, ban of travel to all regions or total border closures, and closing some levels of schools were found to be the most effective NPIs at suppressing influenza transmission. It is recommended that the mask-wearing requirement be combined with gathering limitations and other NPIs. Our findings could facilitate the precise control of future influenza epidemics and other potential pandemics.
18F-FDG-PET/CT in relapsed multiple myeloma: Are prognostic thresholds different from first-line therapy?
Authors: Zukovs Romans , Antke Christina , Mamlins Eduards , Sawicki Lino Morris , Mohring Annemarie , Lopez y Niedenhoff David , Boquoi Amelie , Kondakci Mustafa , Antoch Gerald , Müller Hans-Wilhelm , Fenk Roland , Haas Rainer 
Published: April 2022

Abstract
Purpose
While 18F-FDG PET/CT yields valuable prognostic information for patients in first-line therapy of multiple myeloma (MM), its prognostic relevance in relapse is not established. Available studies of relapsed MM describe prognostic thresholds for frequently used PET/CT parameters that are significantly higher than those identified in the first-line setting. The purpose of this study was to evaluate the prognostic role of PET/CT in relapsed MM, based on parameters used in the first-line setting.

Methods
Our retrospective study included 36 patients with MM who had received autologous or allogeneic stem cell transplantation, suffered at least one relapse, and underwent FDG-PET/CT at relapse. Number of focal bone lesions (FL), maximal standardised uptake value (SUVmax), and presence of PET-positive extramedullary lesions (EMD) were analysed.

Results
For the number of FLs, the prognostic value was demonstrated with a cut-off of > 3 (median OS 3.8 months vs. not reached, p = 0.003). Median OS of patients with SUVmax ≤ 4 was not reached, while it was 3.9 months in patients with SUVmax > 4 (p = 0.014). Presence of EMD was a significant prognostic parameter too, with median OS of 3.6 months versus not reached (p = 0.004). The above-mentioned parameters showed prognostic significance for PFS as well. Combination of higher ISS stage and PET/CT parameters identified patients with particularly short OS (3.7 months vs. not reached, p < 0.001) and PFS (3.6 vs. 11.7 months p < 0.001).

Conclusion
The PET/CT parameters SUVmax > 4, nFL > 3, and presence of EMD identify patients with poor prognosis not only in the first-line setting but also in relapsed MM.
Downregulation of KRAB zinc finger proteins in 5-fluorouracil resistant colorectal cancer cells
Authors: Chauvin Anaïs , Bergeron Danny , Vencic Jean , Lévesque Dominique , Paquette Benoit , Scott Michelle S. , Boisvert François-Michel 
Published: April 2022

AbstractRadio-chemotherapy with 5-flu orouracil (5-FU) is the standard of care treatment for patients with colorectal cancer, but it is only effective for a third of them. Despite our understanding of the mechanism of action of 5-FU, drug resistance remains a significant limitation to the clinical use of 5-FU, as both intrinsic and acquired chemoresistance represents the major obstacles for the success of 5-FU-based chemotherapy. In order to identify the mechanism of acquired resistance, 5-FU chemoresistance was induced in CRC cell lines by passaging cells with increasing concentrations of 5-FU. To study global molecular changes, quantitative proteomics and transcriptomics analyses were performed on these cell lines, comparing the resistant cells as well as the effect of chemo and radiotherapy. Interestingly, a very high proportion of downregulated genes were annotated as transcription factors coding for Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter were downregulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. To confirm the observations of the proteomic and transcriptomic approaches, the abundance of 20 different KZFPs and control mRNAs was validated by RT-qPCR. In fact, several KZFPs were no longer detectable using qPCR in cell lines resistant to 5-FU, and the KZFPs that were downregulated only in one or two cell lines showed similar pattern of expression as measured by the omics approaches. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights a possible new mechanism involved in the cellular adaptation to 5-FU and therefore identifies potential new therapeutic targets to overcome this resistance.
Diagnostic value of mid-regional pro-Adrenomedullin as a biomarker of invasive bacterial infection in children: a systematic review
Authors: Corr Michael Paul , Fairley Derek , McKenna James P. , Shields Michael D. , Waterfield Thomas 
Published: April 2022

Abstract
Background
Invasive bacterial infections (IBI) in children present a difficult clinical challenge. They are often life-threatening, however in the early stages they can be hard to differentiate from benign viral infections. This leaves clinicians with the risk of missing a serious IBI diagnosis or inappropriately using antimicrobials in a child with a viral infection- contributing to the ongoing development of increased antimicrobial resistance. Hence, biomarkers which could aid in early detection of IBI and differentiation from viral infections are desirable. Mid-Regional pro-Adrenomedullin (MR-proADM) is a biomarker which has been associated with IBI. The aim of this systematic review was to determine its diagnostic accuracy in identifying children with IBI.

Methods
A strategy was devised to search online databases MEDLINE, Embase, Web of Science and Scopus for human clinical trials reporting the accuracy of MR-proADM in children. Against predesigned inclusion and exclusion criteria full texts were selected for inclusion and data extraction. True positives, false positives, true negatives and false negatives were extracted from each included study to fill 2 × 2 tables. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool methodological quality of each study was assessed.

Results
A total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed and four texts (totaling 1404 patients) were included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible.

Conclusion
There is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI.

Trial registration
PROSPERO CRD42018096295.
Perspectives on barriers to treatment engagement of people with eating disorder symptoms who have not undergone treatment: a qualitative study
Authors: Liu Livia , Hay Phillipa , Conti Janet 
Published: April 2022

Abstract
Background
Many people with an eating disorder (ED) never engage with an evidence-based ED treatment. Of the few studies that have qualitatively explored barriers to receiving treatment, some do so in relation to mental health conditions in general, and others focus on participants who have already undergone treatment.
This study aims to address this gap in the literature by exploring the barriers to ED treatment engagement from the perspectives of individuals in the community with an ED (either self-identified or professionally diagnosed) and had not received ED treatment/s.

Method
Fifty-six of 772 participants in an online Eating Disorders Treatment Experience survey had self-identified as having symptoms consistent with an ED, or had received a diagnosis of an ED and indicated that they had never undergone treatment for an ED. They were asked to share the reasons for which they did not receive treatment with an open-ended question. Qualitative analysis of survey responses was completed using the Framework Method to generate overarching themes that encapsulated the diverse participant accounts.

Results
The thematic analysis generated two main themes, each with two subthemes. The first theme was the negotiation of the need for treatment within oneself (intrapersonal factors; theme 1). The second theme explored interpersonal contexts that shaped the participant’s decision not to seek treatment (interpersonal/external factors; theme 2). Two cross-cutting subthemes of fear and health literacy were also generated that demonstrated a high degree of overlap with the aforementioned main themes.

Conclusions
The process by which individuals decide whether or not to engage with ED treatment services is complex and involves intra- and interpersonal negotiations intertwined with health literacy and fear. A factor not prominent in previous research was negative self-perceptions and the belief of being undeserving of treatment. These factors have implications for ongoing community and clinical interventions to further address barriers to ED treatment engagement.
The effect of BMI on long-term outcomes after operatively treated ankle fractures: a study with up to 16 years of follow-up
Authors: Cardoso Diogo Vieira , Paccaud Joris , Dubois-Ferrière Victor , Barea Christophe , Hannouche Didier , Veljkovic Andrea , Lübbeke Anne 
Published: April 2022

Abstract
Background
Ankle fractures are a common injury and the main cause of post-traumatic ankle arthritis. The prevalence of obesity is increasing worldwide, and this population is known to have poorer short and midterm outcomes after ankle fractures. Our objective is to assess long-term patient-reported outcomes in patients with operatively treated ankle fractures, and the effect of BMI on these results using the new and validated patient-reported outcome questionnaire, the Manchester Oxford foot and ankle questionnaire (MOXFQ).

Methods
We performed a retrospective review of all ankle fractures treated operatively in a ten-year period from 2002–2012. The MOXFQ and SF-12 were sent to all patients and were obtained, on average, 11.1 years after surgery (range 5.3–16.2 years).

Results
Two thousand fifty-five ankle fractures were reviewed, of which 478 (34%) patients completed the questionnaires. The mean age was 48.1 ± 15.5 years, 52% were men and the mean BMI was 26.1 ± 4.5 kg/m2. Of the 478, 47% were of normal weight, 36% were overweight, and 17% were obese. Overall, 2.1% were type A, 69.9% B, and 24.9% type C fractures. There were no significant differences in the type of fracture between the BMI groups. Comparing obese and non-obese patients, there were large differences in MOXFQ pain (33 ± 29 vs. 18.7 ± 22.1, effect size 0.55), and function scores (27.3 ± 29 vs. 12.5 ± 21.1, effect size 0.58). No differences in complications and reoperations rates were observed. The BMI value at surgery correlated more strongly with the MOXFQ pain score than the BMI at follow-up (Spearman’s Rho 0.283 vs. 0.185, respectively).

Conclusion
These findings reveal that obese patients have significant worse long-term outcomes, namely increased pain, poorer function, and greater impairment in everyday life after an operatively treated ankle fracture. Moreover, pain and function linearly declined with increasing BMI. Our findings appear to indicate that increased BMI at surgery is an important contributor to adverse outcome in the operative management of rotational ankle fractures.

Level of evidence
III.
Robot-assisted radical prostatectomy in the treatment of patients with clinically high-risk localized and locally advanced prostate cancer: single surgeons functional and oncologic outcomes
Authors: Shin Tae Young , Lee Yong Seong 
Published: April 2022

Abstract
Background
Optimal treatment approaches for high-risk localized and locally advanced prostate cancer remain controversial and there are currently no standard treatments. These patients with high-risk localized and locally advanced prostate cancer are usually offered radiotherapy in combination with hormonal therapy. We report functional and oncologic outcomes of patients who underwent primary robot-assisted radical prostatectomy (RARP) and assess the role of RARP in patients with high-risk localized and locally advanced prostate cancer.

Methods
This study included 188 patients with high-risk localized (clinical stage T2c or a pretreatment prostate-specific antigen level > 20 ng/mL or a biopsy Gleason score ≥ 8) and/or locally advanced (any PSA, cT3-4 or cN+) prostate cancer who underwent RARP between July 2013 and May 2020. Functional outcomes including postoperative continence and potency were assessed at 1, 3, 6, and 12 months after RARP. Oncologic outcomes comprised positive surgical margins (PSMs), biochemical recurrence (BCR), BCR-free survival, and clinical recurrence (CR)-free survival rates at 1 and 3 years.

Results
The median operative time was 185 (interquartile range [IQR] 130–260) minutes. Based on postoperative pathology, the rates of PSMs in the entire cohort and in those with stage pT2 disease were 26.6% and 8.5%, respectively. The continence and potency rates at 12 months were 88.3% and 56.4%, respectively. The BCR rate was 22.3%, and the median time to BCR was 10.5 (IQR 3.5–26.9) months. The 1- and 3-year BCR-free survival rates were 87.6% and 78.7%, respectively, and the 1- and 3-year CR-free survival rates were 97.5% and 90.8%, respectively.

Conclusions
Most patients with clinically high-risk localized and locally advanced prostate cancer treated with primary RARP remained BCR-free and CR-free during the 1- and 3-year follow-up, demonstrating the good functional outcomes with RARP. RARP was a safe and feasible minimally invasive surgical alternative to radiotherapy or hormonal therapy in select patients with high-risk localized and locally advanced prostate cancer. These results should be validated to assure the reproducibility of measurements in prospective randomized-controlled studies on primary RARP.
Pigmentary complications after non-medical male circumcision
Authors: Tirana Radwa , Othman Doa , Gad Dalia , Elsadek Menan , Fahmy Mohamed A. Baky 
Published: April 2022

Abstract
Background
A wide spectrum of complications are reported after male circumcision (MC), the non-aesthetic complications are well known, but the pigmentary complications scale are not reported precisely.

Methods
This is a prospective cohort study of 550 circumcised boys; aged from 6 months to 14 years (62% aged 5 years) who were examined and appropriately investigated for the incidence of pigmentary complications after circumcision. Most diagnoses were clinically, but dermoscopy was done for 17 case and a skin biopsy for 14 cases. Patients with personal or family history of vitiligo, or congenital nevi were excluded. Available hospital records details and parents' statements were revised. The main outcome measures are the incidence of different pigmentary complications and circumcision details; data were analyzed by a non-parametric tests including the Mann–Whitney U test.

Results
69 cases had 72 confirmed pigmentary complications discovered at 2–36 months after commencement of circumcision (mean 18). 48 cases had pigmentary complications directly related to MC, 11 cases were probably related and 10 unrelated to MC. The most common lesion is the circular hyperpigmented scar (29 cases); liner hyperpigmented scar in 13, spotted exogenous melanosis in 18 cases, melanocytic nevi (7), hypopigmentation diagnosed in 3 cases, but kissing nevus is the rarest finding (2). Topical corticosteroid was tried in 15 cases, surgical excision of pigmented scar were done for 19 cases, local laser used for 4 resistant cases and reassurance with follow up for the rest.

Conclusion
Pigmentary complications after male circumcision are not rare and its management is challenging.