bluuebunny/crossref_metadata_2025 huggingface dataset:
The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual “window of treatment success” in RA patients
Authors: Marklein Bianka , Jenning Madeleine , Konthur Zoltán , Häupl Thomas , Welzel Franziska , Nonhoff Ute , Krobitsch Sylvia , Mulder Debbie M. , Koenders Marije I. , Joshua Vijay , Cope Andrew P. , Shlomchik Mark J. , Anders Hans-Joachim , Burmester Gerd R. , Hensvold Aase , Catrina Anca I. , Rönnelid Johan , Steiner Günter , Skriner Karl
Published: September 2021

Background

There is a need for biomarker to identify patients “at risk” for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers.

Methods

Using protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry.

Results

HnRNP-DL was highly expressed in stress granules, citrullinated in the rheumatoid joint and targeted by autoantibodies either as native or citrullinated proteins in patient subsets with different developed RA disease. Structural citrullination dependent epitopes (SCEs) of hnRNP-DL were detected in 58% of the SLE patients although 98% of these sera were α-CCP-2-negative. To obtain a specific citrullinated signal value, we subtracted the native antibody value from the citrullinated signal. The citrullinated/native index of autoantibodies against hnRNP-DL (CNDL-Index) was identified as a new value for an “individual window of treatment success” in early RA and for the detection of RF IgM/α-CCP-2 seronegative RA patients (24–46%). Negative CNDL-index was found in SLE patients, risk-RA and early RA cohorts such as EIRA where the majority of these patients are DAS28-responders to methotrexate (MTX) treatment (87%). High positive CNDL-values were associated with more severe RA, shared epitope and parenchymal changes in the lung. Specifically, native α-hnRNP-DL is TLR7/9-dependent, associated with pain and ROC analysis revealed an association to initial MTX or etanercept treatment response, especially in seronegative RA patients.

Conclusion

CNDL-index defines people at risk to develop RA and the “window of treatment success” thereby closing the sensitivity gap in RA.
Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice
Authors: Wang Mingzhu , Zhu Zhengyang , Lin Xiaoying , Li Haichang , Wen Chengping , Bao Jie , He Zhixing
Published: September 2021

Background

Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.

Methods

Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone.

Results

The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella.

Conclusions

These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.
Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase I clinical trial
Authors: Kim Hee Jin , Cho Kyung Rae , Jang Hyemin , Lee Na Kyung , Jung Young Hee , Kim Jun Pyo , Lee Jung Il , Chang Jong Wook , Park Seongbeom , Kim Sung Tae , Moon Seung Whan , Seo Sang Won , Choi Soo Jin , Na Duk L.
Published: September 2021

Backgrounds

Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies.

Objectives

We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer’s disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood–derived MSCs (hUCB-MSCs).

Methods

We recruited nine mild-to-moderate Alzheimer’s disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study.

Results

After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed.

Conclusions

Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy.

Trial registration

ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017
Chronic inflammation-induced senescence impairs immunomodulatory properties of synovial fluid mesenchymal stem cells in rheumatoid arthritis
Authors: Lee Hyeon-Jeong , Lee Won-Jae , Hwang Sun-Chul , Choe Yongho , Kim Saetbyul , Bok Eunyeong , Lee Sangyeob , Kim Seung-Joon , Kim Hyun-Ok , Ock Sun-A , Noh Hae-Sook , Rho Gyu-Jin , Lee Sang-Il , Lee Sung-Lim
Published: September 2021

Background

Although the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood.

Methods

We established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties.

Results

The presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA.

Conclusion

We conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.

Graphical abstract
High-flow nasal oxygen cannula vs. noninvasive mechanical ventilation to prevent reintubation in sepsis: a randomized controlled trial
Authors: Tongyoo Surat , Tantibundit Porntipa , Daorattanachai Kiattichai , Viarasilpa Tanuwong , Permpikul Chairat , Udompanturak Suthipol
Published: September 2021

Background

High-flow nasal oxygen cannula (HFNC) and noninvasive mechanical ventilation (NIV) can prevent reintubation in critically ill patients. However, their efficacy in post-extubated sepsis patients remains unclear. The objective of this study was to compare the efficacy of HFNC vs. NIV to prevent reintubation in post-extubated sepsis patients.

Methods

We conducted a single-centre, prospective, open-labelled, randomised controlled trial at the medical intensive care unit of Siriraj Hospital, Mahidol University, Bangkok, Thailand. Sepsis patients who had been intubated, recovered, and passed the spontaneous breathing trial were enrolled and randomly assigned in a 1:1 ratio to receive either HFNC or NIV support immediately after extubation. The primary outcome was rate of reintubation at 72 h after extubation.

Results

Between 1st October 2017 and 31st October 2019, 222 patients were enrolled and 112 were assigned to the HFNC group and 110 to the NIV group. Both groups were well matched in baseline characteristics. The median [IQR] age of the HFNC group was 66 [50–77] vs. 65.5 [54–77] years in the NIV group. The most common causes of intubation at admission were shock-related respiratory failure (57.1% vs. 55.5%) and acute hypoxic respiratory failure (34.8% vs. 40.9%) in the HFNC and NIV groups, respectively. The duration of mechanical ventilation before extubation was 5 [3–8] days in the HFNC group vs. 5 [3–9] days in the NIV group. There was no statistically significant difference in the primary outcome: 20/112 (17.9%) in the HFNC group required reintubation at 72 h compared to 20/110 (18.2%) in the NIV group [relative risk (RR) 0.99: 95% confidence interval (CI) (0.70–1.39); P = 0.95]. The 28-day mortality was not different: 8/112 (7.1%) with HFNC vs. 10/110 (9.1%) with NIV (RR 0.88: 95% CI (0.57–1.37); P = 0.59).

Conclusions

Among sepsis patients, there was no difference between HFNC and NIV in the prevention of reintubation at 72 h after extubation.

Clinical Trial Registration ClinicalTrials.gov Identifier: NCT03246893; Registered 11 August 2017; https://clinicaltrials.gov/ct2/show/NCT03246893?term=surat+tongyoo&draw=2&rank=3
Robust localization in wireless networks from corrupted signals
Authors: Osama Muhammad , Zachariah Dave , Dwivedi Satyam , Stoica Petre
Published: September 2021

We address the problem of timing-based localization in wireless networks, when an unknown fraction of data is corrupted by non-ideal propagation conditions. While timing-based techniques can enable accurate localization, they are sensitive to corrupted data. We develop a robust method that is applicable to a range of localization techniques, including time-of-arrival, time-difference-of-arrival and time-difference in schedule-based transmissions. The method is distribution-free, is computationally efficient and requires only an upper bound on the fraction of corrupted data, thus obviating distributional assumptions on the corrupting noise. The robustness of the method is demonstrated in numerical experiments.
Cellobiose dehydrogenase from the agaricomycete Coprinellus aureogranulatus and its application for the synergistic conversion of rice straw
Authors: Nghi Do Huu , Kellner Harald , Büttner Enrico , Huong Le Mai , Duy Le Xuan , Giap Vu Dinh , Quynh Dang Thu , Hang Tran Thi Nhu , Verberckmoes An , Diels Ludo , Liers Christiane , Hofrichter Martin
Published: September 2021

From the biotechnological viewpoint, the enzymatic disintegration of plant lignocellulosic biomass is a promising goal since it would deliver fermentable sugars for the chemical sector. Cellobiose dehydrogenase (CDH) is a vital component of the extracellular lignocellulose-degrading enzyme system of fungi and has a great potential to improve catalyst efficiency for biomass processing. In the present study, a CDH from a newly isolated strain of the agaricomycete Coprinellus aureogranulatus (CauCDH) was successfully purified with a specific activity of 28.9 U mg−1. This pure enzyme (MW = 109 kDa, pI = 5.4) displayed the high oxidative activity towards β-1–4-linked oligosaccharides. Not least, CauCDH was used for the enzymatic degradation of rice straw without chemical pretreatment. As main metabolites, glucose (up to 165.18 ± 3.19 mg g−1), xylose (64.21 ± 1.22 mg g−1), and gluconic acid (5.17 ± 0.13 mg g−1) could be identified during the synergistic conversion of this raw material with the fungal hydrolases (e.g., esterase, cellulase, and xylanase) and further optimization by using an RSM statistical approach.
Fashion informatics of the Big 4 Fashion Weeks using topic modeling and sentiment analysis
Authors: Choi Yeong-Hyeon , Yoon Seungjoo , Xuan Bin , Lee Sang-Yong Tom , Lee Kyu-Hye
Published: September 2021

This study used several informatics techniques to analyze consumer-driven social media data from four cities (Paris, Milan, New York, and London) during the 2019 Fall/Winter (F/W) Fashion Week. Analyzing keywords using a semantic network analysis method revealed the main characteristics of the collections, celebrities, influencers, fashion items, fashion brands, and designers connected with the four fashion weeks. Using topic modeling and a sentiment analysis, this study confirmed that brands that embodied similar themes in terms of topics and had positive sentimental reactions were also most frequently mentioned by the consumers. A semantic network analysis of the tweets showed that social media, influencers, fashion brands, designers, and words related to sustainability and ethics were mentioned in all four cities. In our topic modeling, the classification of the keywords into three topics based on the brand collection’s themes provided the most accurate model. To identify the sentimental evaluation of brands participating in the 2019 F/W Fashion Week, we analyzed the consumers’ sentiments through positive, neutral, and negative reactions. This quantitative analysis of consumer-generated social media data through this study provides insight into useful information enabling fashion brands to improve their marketing strategies.
Male prisoners’ experiences of taking part in research about suicide and violence: a mixed methods study
Authors: Hemming Laura , Pratt Daniel , Haddock Gillian , Bhatti Peer , Shaw Jennifer
Published: September 2021

Background

There is an apparent reluctance to engage ‘vulnerable’ participants in conversation about sensitive topics such as suicide and violence and this can often lead to a paucity of research in these areas. This study aimed to explore the experiences of male prisoners taking part in quantitative and qualitative research on suicide and violence.

Methods

Participants at four male prisons completed a visual analogue scale of mood before and after data collection for both a cross-sectional study and also a qualitative interview. Participants were also asked to give three words to describe their experience of participation. A paired samples T-test was conducted to explore the difference in pre- and post-mood ratings, and content analysis was conducted to explore the positive and negative comments on participants’ experiences.

Results

Overall, participants’ mood significantly improved after participating in a cross-sectional study about suicide and violence (from 4.8 out of 10 to 5.3, p = 0.016), and there was no significant change in mood following participation in a related qualitative study (5.1 to 5.0, p = 0.793). Participants primarily described their experiences as positive, stating that the process had been satisfying, calming, interesting, enlightening and beneficial. A smaller number of participants described their experiences as stressful, challenging, saddening, uncomfortable and bizarre.

Conclusions

This study has found that researching sensitive topics such as suicide and violence with male prisoners did not have a negative impact on mood, rather that participants largely enjoyed the experience. These findings dispel the myth that research about sensitive topics with prisoners is too risky and could inform how future researchers assess levels of risk to participants.
Application of a composite measure of product adherence, protocol compliance, and semen exposure to a phase III microbicide HIV prevention trial
Authors: Jacot Terry A. , Clark Meredith R. , Adedipe Oluwatosin E. , Godbout Susan , Cunningham Tina , Ju Susan , Schwartz Jill L. , Delany-Moretlwe Sinead , Thurman Andrea R. , Doncel Gustavo F.
Published: September 2021

Background

Strict adherence to antiretroviral-based microbicide use is important for effective HIV prevention. We previously developed a composite measure of product adherence, protocol compliance, and semen exposure for determining vaginal use of tenofovir (TFV) 1% gel applicators through biomarkers and residual drug analyses. In this study, we tested the ability of the composite measure in vaginally used TFV gel applicators from a Phase III HIV prevention clinical trial.

Methods

Used vaginal gel applicators from the FACTS 001 study were swabbed for detection of vaginal bacterial markers (vaginal insertion), semen DNA markers (semen exposure), and residual TFV gel (product use).

Results

Of 1,098 evaluable TFV and placebo applicators, 80% had detectable vaginal insertion biomarkers and 52% had semen biomarkers. Ninety-nine percent of vaginally inserted applicators TFV applicators had detectable residual TFV as measured by liquid chromatography with tandem mass spectroscopy (LC–MS/MS). Residual TFV levels were also successfully detected using Fourier Transform Infrared (FTIR)-based spectroscopy.

Conclusions

Vaginal insertion and semen exposure biomarkers were detectable on used TFV 1% gel applicators. Residual TFV on these gel applicators was detectable by LC–MS/MS and FTIR-based spectroscopy, which has potential to be a more convenient and quicker method for detecting drug use. With continual improvements, this composite measure of product adherence, protocol compliance, and semen exposure has potential to assess use of not only TFV gel but also other topical microbicides or products.
Digital subtraction of temporally sequential mammograms for improved detection and classification of microcalcifications
Authors: Loizidou Kosmia , Skouroumouni Galateia , Pitris Costas , Nikolaou Christos
Published: September 2021

Background

Our aim was to demonstrate that automated detection and classification of breast microcalcifications, according to Breast Imaging Reporting and Data System (BI-RADS) categorisation, can be improved with the subtraction of sequential mammograms as opposed to using the most recent image only.

Methods

One hundred pairs of mammograms were retrospectively collected from two temporally sequential rounds. Fifty percent of the images included no (BI-RADS 1) or benign (BI-RADS 2) microcalcifications. The remaining exhibited suspicious findings (BI-RADS 4-5) in the recent image. Mammograms cannot be directly subtracted, due to tissue changes over time and breast deformation during mammography. To overcome this challenge, optimised preprocessing, image registration, and postprocessing procedures were developed. Machine learning techniques were employed to eliminate false positives (normal tissue misclassified as microcalcifications) and to classify the true microcalcifications as BI-RADS benign or suspicious. Ninety-six features were extracted and nine classifiers were evaluated with and without temporal subtraction. The performance was assessed by measuring sensitivity, specificity, accuracy, and area under the curve (AUC) at receiver operator characteristics analysis.

Results

Using temporal subtraction, the contrast ratio improved ~ 57 times compared to the most recent mammograms, enhancing the detection of the radiologic changes. Classifying as BI-RADS benign versus suspicious microcalcifications, resulted in 90.3% accuracy and 0.87 AUC, compared to 82.7% and 0.81 using just the most recent mammogram (p = 0.003).

Conclusion

Compared to using the most recent mammogram alone, temporal subtraction is more effective in the microcalcifications detection and classification and may play a role in automated diagnosis systems.
Achieving sustainable development goals from the perspective of solid waste management plans
Authors: Elsheekh K. M. , Kamel R. R. , Elsherif D. M. , Shalaby A. M.
Published: September 2021

Achieving the Sustainable Development Goals (SDGs) by 2030 ad is one of the challenges and among the cross-cutting issues that countries around the world strive to achieve, despite it is not mandatory, to take control of the various negative environmental, economic, social, and urban impacts that threatened cities, in addition to benefits that are realized from achieving it. The research aims to promote the achievement of Sustainable Development Goals from the perspective of solid waste management (SWM) plans and programs, through analyzing and finding the interrelationship between SWM plans and programs and the related specific targets for each goal, in addition to using experts’ questionnaires to conclude the varying degrees of impact of SWM plans and programs at the level of 17 SDGs, which have been classified into groups, according to the most and the least affected by the SWM plans and programs. Where the goals of “sustainable cities and communities” and “good health and well-being” came in the lead of the goals; however, the goals of “quality education” and “peace, justice, and institutions” came in the tail of the goals that are affected by SWM plans and programs, according to the experts’ opinion.
Magical thinking and moral injury: exclusion culture in psychiatry
Authors: Beale Chloe
Published: September 2021

This is an article about exclusion. We might not like to admit it – even fail to realise it – but National Health Service (NHS) mental health service structures have become increasingly focused on how to deny people care instead of help them to access it. Clinicians learn the art of self-delusion, convincing ourselves we are not letting patients down but, instead, doing the clinically appropriate thing. Well-meant initiatives become misappropriated to justify neglect. Are we trying to protect ourselves against the knowledge that we're failing our patients, or is collusion simply the easiest option? Problematic language endemic in psychiatry reveals a deeper issue: a culture of fear and falsehood, leading to iatrogenic harm. An excessively risk-averse and under-resourced system may drain its clinicians of compassion, losing sight of the human being behind each ‘protected’ bed and rejected referral.
Art as Information Ecology
Authors: Hoelscher Jason A.
Published: September 2021

In Art as Information Ecology, Jason A. Hoelscher offers not only an information theory of art but an aesthetic theory of information. Applying close readings of the information theories of Claude Shannon and Gilbert Simondon to 1960s American art, Hoelscher proposes that art is information in its aesthetic or indeterminate mode—information oriented less toward answers and resolvability than toward questions, irresolvability, and sustained difference. These irresolvable differences, Hoelscher demonstrates, fuel the richness of aesthetic experience by which viewers glean new information and insight from each encounter with an artwork. In this way, art constitutes information that remains in formation---a difference that makes a difference that keeps on differencing. Considering the works of Frank Stella, Robert Morris, Adrian Piper, the Drop City commune, Eva Hesse, and others, Hoelscher finds that art exists within an information ecology of complex feedback between artwork and artworld that is driven by the unfolding of difference. By charting how information in its aesthetic mode can exist beyond today's strictly quantifiable and monetizable forms, Hoelscher reconceives our understanding of how artworks work and how information operates.
Evaluation of local, regional and abscopal effects of Boron Neutron Capture Therapy (BNCT) combined with immunotherapy in an ectopic colon cancer model
Authors: Trivillin Verónica A. , Langle Yanina V. , Palmieri Mónica A. , Pozzi Emiliano C.C. , Thorp Silvia I. , Benitez Frydryk Debora N. , Garabalino Marcela A. , Monti Hughes Andrea , Curotto Paula M. , Colombo Lucas L. , Santa Cruz Iara S. , Ramos Paula S. , Itoiz María E. , Argüelles Claudia , Eiján Ana M. , Schwint Amanda E.
Published: September 2021

We previously demonstrated, for the first time, the abscopal effect of Boron Neutron Capture Therapy (BNCT) in an ectopic model of syngeneic colon cancer in BDIX rats.

Objective:

The aim of the present study was to evaluate the local and regional therapeutic efficacy and abscopal effect of BNCT mediated by boronophenyl-alanine, combined with Bacillus Calmette-Guerin (BCG) as an immunotherapy agent in this model.

Methods:

The local effect of treatment was evaluated in terms of tumor response in the irradiated tumor-bearing right hind flank. Metastatic spread to tumor-draining lymph nodes was analyzed as an indicator of regional effect. The abscopal effect of treatment was assessed as tumor growth inhibition in the contralateral (non-irradiated) left hind flank inoculated with tumor cells 2 weeks post-irradiation. The experimental groups BNCT, BNCT + BCG, BCG, Beam only (BO), BO +BCG, SHAM (tumor-bearing, no treatment, same manipulation) were studied.

Results:

BNCT and BNCT + BCG induced a highly significant local anti-tumor response, whereas BCG alone induced a weak local effect. BCG and BNCT + BCG induced a significant abscopal effect in the contralateral non-irradiated leg. The BNCT + BCG group showed significantly less metastatic spread to tumor-draining lymph nodes vs SHAM and vs BO.

Conclusion:

This study suggests that BNCT + BCG-immunotherapy would induce local, regional and abscopal effects in tumor-bearing animals. BNCT would be the main effector of the local anti-tumor effect whereas BCG would be the main effector of the abscopal effect.

Advances in knowledge:

Although the local effect of BNCT has been widely evidenced, this is the first study to show the local, regional and abscopal effects of BNCT combined with immunotherapy, contributing to comprehensive cancer treatment with combined therapies.
Progress and pitfalls with the use of image-guided personalised approaches in lymphoma
Authors: Illidge Tim M , Phillips Elizabeth H
Published: September 2021

The use of 18F-FDG PET CT has become an essential part of the management of patients with lymphoma. The last decade has seen unrivalled progress in research efforts to personalise treatment approaches using PET as a predictive imaging biomarker. Critical to this success has been the standardisation of PET methods and reporting, including the 5-point Deauville scale, which has enabled the delivery of robust clinical trial data to develop response-adapted treatment approaches.(1, 2) The utility of PET as a predictive imaging biomarker in assessing treatment success or failure has been investigated extensively in malignant lymphomas. Considerable progress has been made over the last decade, in using PET to direct more personalised “risk-adapted” approaches, as well as an increased understanding of some of the limitations. Arguably the greatest success has been in Hodgkin Lymphoma (HL) where PET was initially demonstrated to be a powerful predictive biomarker (3) and is now routinely used in both early-stage and advanced HL to reduce or escalate the use of chemotherapy as well as guiding the delivery of more selective radiotherapy to patients.
Comparison of CBCT and panoramic radiography for the assessment of bone loss and root resorption on the second molar associated with third molar impaction: a systematic review
Authors: Moreira-Souza Larissa , Butini Oliveira Luciana , Gaêta-Araujo Hugo , Almeida-Marques Marcia , Asprino Luciana , Oenning Anne Caroline
Published: September 2021

Objective:

To investigate whether the use of cone beam CT (CBCT) changes the diagnosis of external root resorption (ERR) or marginal bone loss (MBL) involving a second molar adjacent to an impacted third molar.

Methods:

A systematic search was applied in PubMed, EMBASE, Scopus, Web of Science, LILACS, Google Scholar, OpenGrey, and ProQuest. Studies assessing the detection of ERR or MBL in a second molar adjacent to an impacted third molar through CBCT and panoramic radiography (PAN) were included. Prevalence and agreement between PAN and CBCT on the detection of ERR and MBL were collected. The risk of bias was assessed using the MAStARI.

Results:

A total of 593 papers were identified, and after a 2-phase selection, 5 studies were included in the narrative synthesis. Regarding ERR, its prevalence in PAN was reported from 5.31 to 19.5% and from 22.8 to 62.0% in CBCT. The percentage of agreement varied from 28.5 to 74.0%. The prevalence of MBL varied from 21.9 to 62.9% in PAN, while those values varied from 21.6 to 80% in CBCT images. The percentage of agreement between PAN and CBCT for the detection of MBL ranged from 66.0 to 85.0%. Four studies presented low risk of bias and one had moderate risk.

Conclusions:

More ERR and MBL are assessed in CBCT compared to PAN. There is a considerable agreement between PAN and CBCT assessment of ERR and MBL, however, mostly related to the absence of the pathology rather its presence.
Protein Supplementation Does Not Improve Aerobic and Anaerobic Fitness in Collegiate Dancers Performing Cycling Based High Intensity Interval Training
Authors: Alfiero Christopher J. , Brooks Samantha J. , Bideganeta Hannah M. , Contreras Coby , Brown Ann F.
Published: September 2021

The effects of a 6-week cycling high-intensity interval training (HIIT) concurrently with protein supplementation on aerobic and anaerobic fitness and body composition in collegiate dancers was investigated. Eighteen participants enrolled in a collegiate dance program were matched into
three groups: high-protein (HP; 90 g˙d−1), moderate-protein (MP; 40 g˙d−1), and control (C; 0 g˙d−1). All participants performed a 6-week HIIT intervention. Participants completed a graded exercise test, Wingate anaerobic test
(Wingate), and dual energy x-ray absorptiometry scan before and after the intervention. Peak heart rate (HRpeak), peak oxygen uptake (VOpeak), peak power output (PPO), lactate threshold (LT), and ventilatory thresholds 1 (VT1 ) and 2 (VT2) were assessed
during the graded exercise test. Peak power output, mean power output (MPO), and fatigue index (FI) were assessed during the Wingate. Lean mass (LM), fat mass (FM), visceral adipose tissue, appendicular skeletal muscle mass, and appendicular skeletal muscle mass index were assessed during
dual energy x-ray absorptiometry. Body composition index (BCI) was calculated from pre and post LM and FM. Habitual diet was recorded weekly. Significance was set at p ≤ 0.05. No significant differences in VO2peak and percent fat mass (%FM) were observed between groups prior
to the intervention. Significant main effects for time were observed for HRpeak (p = 0.02), VO2peak (p < 0.001), PPO (p < 0.01), LT (p < 0.001), VT1 (p < 0.001), and VT2 (p < 0.001) during the graded exercise test, and PPO (p <
0.01) and FI (p < 0.01) during the Wingate. Significant main effects for time were observed for LM (kg; p = 0.01) and FM (kg; p < 0.01). Body composition index was improved for all groups, however, no significant differences by group were observed. No significant differences were observed
between groups for the measured outcomes (p > 0.05). Therefore, there was no effect of protein supplementation in the short 6-week intervention. This cycling based HIIT routine increased physical fitness, optimized aesthetics, and was a simple addition to an existing collegiate dance curriculum.
H3K36me3 and PSIP1/LEDGF associate with several DNA repair proteins, suggesting their role in efficient DNA repair at actively transcribing loci
Authors: Sundarraj Jayakumar , Taylor Gillian C.A. , von Kriegsheim Alex , Pradeepa Madapura M
Published: September 2021

Background: Trimethylation at histone H3 at lysine 36 (H3K36me3) is associated with expressed gene bodies and recruit proteins implicated in transcription, splicing and DNA repair. PC4 and SF2 interacting protein (PSIP1/LEDGF) is a transcriptional coactivator, possesses an H3K36me3 reader PWWP domain. Alternatively spliced isoforms of PSIP1 binds to H3K36me3 and suggested to function as adaptor proteins to recruit transcriptional modulators, splicing factors and proteins that promote homology-directed repair (HDR), to H3K36me3 chromatin.

Methods: We performed chromatin immunoprecipitation of H3K36me3 followed by quantitative mass spectrometry (qMS) to identify proteins associated with H3K36 trimethylated chromatin in mouse embryonic stem cells (mESCs). We also performed stable isotope labelling with amino acids in cell culture (SILAC) followed by qMS for a longer isoform of PSIP1 (PSIP/p75) and MOF/KAT8 in mESCs and mouse embryonic fibroblasts ( MEFs). Furthermore, immunoprecipitation followed by western blotting was performed to validate the qMS data. DNA damage in PSIP1 knockout MEFs was assayed by a comet assay.

Results: Proteomic analysis shows the association of proteins involved in transcriptional elongation, RNA processing and DNA repair with H3K36me3 chromatin. Furthermore, we show DNA repair proteins like PARP1, gamma H2A.X, XRCC1, DNA ligase 3, SPT16, Topoisomerases and BAZ1B are predominant interacting partners of PSIP /p75. We further validated the association of PSIP/p75 with PARP1, hnRNPU and gamma H2A.X  and also demonstrated accumulation of damaged DNA in PSIP1 knockout MEFs.

Conclusions: In contrast to the previously demonstrated role of H3K36me3 and PSIP/p75 in promoting homology-directed repair (HDR), our data support a wider role of H3K36me3 and PSIP1 in maintaining the genome integrity by recruiting proteins involved in DNA damage response pathways to the actively transcribed loci.
Engagement of ethics and regulatory authorities on human infection studies: Proceedings of an engagement workshop in Zambia
Authors: Kunda-Ng'andu Evelyn Muleba , Simuyandi Michelo , Kapulu Melissa , Chirwa-Chobe Masuzyo , Mwanyungwi-Chinganya Hope , Mwale Stanley , Chilengi Roma , Sharma Anjali
Published: September 2021

Human infection studies (HIS) have generally been used as a tool in the pathway for vaccine development in high income settings. Over the last decade, this model has been implemented in LMICs with the aim of accelerating development of next generation vaccines that would perform better in these settings. However, in most LMICs, the ethics and regulatory framework for the conduct of these studies are not in place. In Zambia, these studies are yet to be conducted and thus we conducted a stakeholder engagement workshop in October 2019. We engaged with bioethicists, regulatory authority officials, and scientists from within Zambia and other African countries to anticipate and address foreseeable ethical and regulatory issues when conducting HIS in Zambia for the first time. The workshop largely focused on sensitizing the stakeholders on the benefits of these studies with the following main points for consideration on the implementation of these studies in Zambia: need for in-country legal framework and guidelines; need for adequate informed consent based on comprehensive understanding of the concept of HIS and study requirements; and requirements for heightened vigilance to assure participant safety including good ethical and clinical practice with regulatory, ethical, data safety, and community oversight. Additionally, the workshop emphasized the need for rigorous health screening prior to enrolment; suitable infrastructure for containment; and personnel to provide appropriate treatment including emergency resuscitation and evacuation if indicated. Specific recommendations included compensation for burden of participation; access to care and provision for study related injury (e.g. no-fault insurance); and withdrawal and exit procedures to preserve individual and community safety. Finally, the meeting concluded that researchers should actively engage key gate keepers including civic leaders such as parliamentarians, universities, researchers, potential participants and laypersons to avoid circulation of misinformation.
Evaluating Registered Reports Funding Partnerships: a feasibility study
Authors: Clark Robbie , Drax Katie , Chambers Christopher D. , Munafò Marcus , Thompson Jacqueline
Published: September 2021

Background: We studied a novel initiative – Registered Reports Funding Partnerships (RRFPs) – whereby research funders and journals partner in order to integrate their procedures for funding applications and Registered Reports submissions into one process. We investigated the feasibility of conducting a randomised controlled trial (RCT) of the impact of RRFPs on (1) research quality and (2) the efficiency of the research process, from funding to publication.

Methods: We conducted 32 semi-structured interviews and follow-up questionnaires with stakeholders (funders, editors, authors, and reviewers) across six different RRFPs.

Results: A RCT of RRFPs appears to be feasible in principle. The partnership concept seems worthwhile to pursue further and is adaptable to the needs of various funders and publishers, and across disciplines. Three primary outcomes of interest should be measurable, and participant randomisation could conceivably be done in a number of ways. In practice, however, the current volume of submissions going through existing partnerships is too low to support a full trial.  

Conclusions: Although a RCT of RRFPs is conceptually feasible, it will only be possible if organisations are willing to form new partnerships, scale up existing ones, and incorporate a trial (i.e., randomisation) into these partnerships.
The genome sequence of the common wasp, Vespula vulgaris (Linnaeus, 1758)
Authors: Crowley Liam ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: September 2021

We present a genome assembly from an individual female Vespula vulgaris (the common wasp; Arthropoda; Insecta; Hymenoptera; Vespidae). The genome sequence is 188 megabases in span. The majority of the assembly is scaffolded into 25 chromosomal pseudomolecules.
EL AGUA Y EL ETERNO FEMENINO: ESTUDIO DE CIRCE Y EL POETA MANUEL CIGES APARICIO SEGÚN LAS TEORÍAS DE GASTON BACHELARD.
Authors: Barraza María Ignacia
Published: September 2021

La novela Circe y el poeta, escrita por el español Manuel Ciges Aparicio y publicada en 1926, es, como sugiere el título, una reinterpretación del mito de la hechicera griega. Efectivamente, Sara –el personaje femenino con mayor relieve en el relato–, es una moderna seductora a la manera de la Circe (1927) del pintor alemán George Grosz. Este ensayo pretende demostrar –apoyándose en las teorías de Gaston Bachelard acerca de la imaginación material del agua– cómo Ciges Aparicio utiliza dicho elemento como símbolo de lo femenino, del dolor y de la muerte.
LA ESCRITURA AUTOBIOGRÁFICA DE LYGIA TELLES Y CAROLINA DE JESÚS.
Authors: Ribeiro Lilian
Published: September 2021

Este artículo muestra la escritura autobiográfica femenina de las escritoras brasileñas: Carolina María de Jesús, en “Quarto de despejo” (1960) y “Diario de Bitita” (1982), y de Lygia Fagundes Telles, en “As meninas” (1973). Junto al análisis, llevo a cabo también una investigación bibliográfica sobre el tema de la escritura autobiográfica de estas escritoras brasileñas.
EURIPIDE: MISOGINIA O GINOFOBIA?.
Authors: Domenighini Sara
Published: September 2021

Ripercorrendo le origini della civiltà, è If we go back to the origins of civilization, possibile identificare un momento storico in we find an historic moment characterized by cui la società era matriarcale. Analizzando matriarchal society. Through the analysis of le figure femminili presenti nelle tragedie di the feminine figures of Euripides’ tragedies, Euripide, possiamo comprendere il timore we can understand he fears a hypothetic che prova l’autore di un ipotetico ritorno return to woman’s predominance on man al predominio della donna sull’uomo e and we can interpret his reasons. Moreover, interpretarne le ragioni. Euripide, poi, si serve Euripides makes use of catharsis to prevent della catarsi per scongiurare tale eventualità. this possibility.
A Rare Case of Guillain-Barré Syndrome following COVID-19 Vaccination
Authors: Kripalani Yash , Lakkappan Vidyadhara , Parulekar Lipeeka , Shaikh Anjum , Singh Rakesh , Vyas Pradeep
Published: September 2021

Various vaccines against COVID-19 have been developed since SARS-CoV-2 emerged at the end of 2019. Their emergency administration in healthcare settings has been accompanied by numerous adverse effects. A case of Guillain-Barré syndrome following vaccination with Covishield is presented here to highlight this possible adverse condition.
A projective approach to nonnegative matrix factorization
Authors: Groetzner Patrick
Published: September 2021

In data science and machine learning, the method of nonnegative matrix factorization (NMF) is a powerful tool that enjoys great popularity. Depending on the concrete application, there exist several subclasses each of which performs a NMF under certain constraints. Consider a given square matrix $A$. The symmetric NMF aims for a nonnegative low-rank approximation $A\approx XX^T$ to $A$, where $X$ is entrywise nonnegative and of given order. Considering a rectangular input matrix $A$, the general NMF again aims for a nonnegative low-rank approximation to $A$ which is now of the type $A\approx XY$ for entrywise nonnegative matrices $X,Y$ of given order. In this paper, we introduce a new heuristic method to tackle the exact nonnegative matrix factorization problem (of type $A=XY$), based on projection approaches to solve a certain feasibility problem.
Vitamin E highly cross-linked polyethylene reduces mid-term wear in primary total hip replacement: a meta-analysis and systematic review of randomized clinical trials using radiostereometric analysis
Authors: Li Zeng , Xiang Shuai , Wu Cuijiao , Wang Yingzhen , Weng Xisheng
Published: September 2021

Vitamin E incorporation into highly cross-linked polyethylene (HXLPE) has been introduced to improve wear resistance, and vitamin E incorporated HXLPE (VEPE) has been used in total hip arthroplasty. The aim of this meta-analysis was to investigate the wear properties of VEPE in clinical practice by synthesizing the data provided in randomized clinical trials. The effects on implant stability, functional outcomes and revision rate of VEPE were also compared with those of HXPLE or ultra-high molecular weight polyethylene (UHMWPE). Literature searches were conducted on 1 January 2020 using MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases. Randomized controlled trials (RCTs) comparing the aforementioned parameters between VEPE and standard HXPLE/UHMWPE liners were included. Methodological quality and the bias of the included studies were analysed. Meta-analyses were performed using the Review Manager software. Nine RCTs met the eligibility criteria and were included. At early and mid-term follow-up, the vertical penetration and the total penetration of the femoral head were both significantly reduced in the VEPE group. The steady state wear rate of the VEPE group was also remarkably lower. However, at two-year follow-up, significantly increased cup migration was observed in the VEPE group. Moreover, the mid-term clinical outcomes of the VEPE group were worse, while the total revision rates between the two groups were not significantly different. The limited number of included studies may compromise our conclusion regarding clinical outcomes of the VEPE bearing surface. More RCTs with longer follow-up periods are needed to further investigate the effects of VEPE in total hip arthroplasty.

Cite this article: EFORT Open Rev 2021;6:759-770. DOI: 10.1302/2058-5241.6.200072
Management of chronic osteomyelitis of the femur and tibia: a scoping review
Authors: Arshad Zaki , Lau Edward Jun-Shing , Aslam Aiman , Thahir Azeem , Krkovic Matija
Published: September 2021

Osteomyelitis refers to an inflammatory process causing bone destruction and necrosis. Managing such a persistent disease is complex, with a number of authors reporting different techniques. This scoping review aims to map and summarize the literature on treatment of chronic femoral and tibial osteomyelitis, in order to improve the reader’s understanding of potential treatments and identify areas of further research. The methodological framework of the Joanna Briggs Institute was followed. A computer-based search was conducted in PubMed, EMBASE, MEDLINE, EMCARE and CINAHL, for articles reporting treatment of chronic tibial/femoral osteomyelitis. Two reviewers independently performed title/abstract and full-text screening according to pre-defined criteria. A total of 1230 articles were identified, with 40 finally included. A range of treatments are reported, with the core principles being removal of infected tissue, dead-space management and antibiotic therapy. The majority (84.5%) of patients presented with stage III or IV disease according to the Cierny–Mader classification, and Staphylococcus aureus was the most commonly isolated organism. The proportion of patients achieving remission with no recurrence during follow-up varies from 67.7–100.0%. The majority of studies report excellent outcomes in terms of infection remission and lack of recurrence. However, identifying specific patient or treatment-related factors which may affect outcomes is currently challenging due to the nature of the included studies and unclear reporting of treatment outcomes. It is now important to address this issue and identify such factors using further high-level research methods such as randomized controlled trials and comparative cohort studies.

Cite this article: EFORT Open Rev 2021;6:704-715. DOI: 10.1302/2058-5241.6.200136