bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anakinra and canakinumab for patients with R92Q-associated autoinflammatory syndrome: a multicenter observational study from the AIDA Network
Authors: Gaggiano Carla , Rigante Donato , Hernández-Rodríguez José , Vitale Antonio , Tarsia Maria , Soriano Alessandra , Lopalco Giuseppe , Iannone Florenzo , Abdel Jaber Masen , Giacomelli Roberto , Wiȩsik-Szewczyk Ewa , Cattalini Marco , Frassi Micol , Piga Matteo , Ragab Gaafar , Sota Jurgen , Zunica Fiammetta , Floris Alberto , Sabato Vito , Hegazy Mohamed Tharwat , Araújo Olga , Pelegrín Laura , Fabbiani Alessandra , Renieri Alessandra , Grosso Salvatore , Fabiani Claudia , Frediani Bruno , Cantarini Luca 
Published: September 2021

Background: This study aims at describing the therapeutic outcome of patients carrying the R92Q variant in the TNFRSF1A gene treated with anakinra (ANA) or canakinumab (CAN) and identifying any factors predictive of complete response to IL-1 inhibition. Methods: Clinical data of patients treated with ANA or CAN for recurrent inflammatory attacks due to the presence of the R92Q variant were retrospectively collected and analysed. Results: Data about 20 treatment courses with IL-1 inhibitors (16 with ANA and 4 with CAN) from 19 patients were collected. Mean age at disease onset was 20.2 ± 14.8 years. In 5 cases (26%) the R92Q variant was found in a family member affected by recurrent fever. The therapeutic response was complete in 13(68%) and partial in 2 patients (11%); treatment failure was observed in 4 cases (21%). Median AIDAI decreased from 10 (interquartile range [IQR] = 28) to 0 (IQR = 1) at the 12-month follow-up visit ( p < 0.001). Mean ESR and median CRP dropped respectively from 40.8 ± 24.8 to 9.1 ± 4.5 mm/h ( p < 0.001) and from 3.0 (IQR = 1.9) to 0.3 (IQR = 0.3) mg/dl ( p < 0.001) after 12 months of treatment. A steroid-sparing effect was observed from the third month of treatment ( p < 0.01). Thirteen patients (65%) were still on treatment at the last follow-up visit (median duration of treatment 17 (IQR = 38) months). The presence of R92Q mutation in a symptomatic relative ( p = 0.022), the relapsing remitting disease course ( p < 0.001) and the presence of migratory erythematous skin rashes during fever attacks ( p = 0.005) were associated with complete efficacy of IL-1 inhibitors. Conclusions: R92Q patients showed a favourable response to ANA and CAN, particularly when the mutation segregated in a family member and when a relapsing-remitting disease course or TNF-α receptor-associated periodic syndrome (TRAPS) typical skin rash were observed. In the subgroup of patients not taking advantage of IL-1 blockage different molecular mechanisms underlying the autoinflammatory picture are likely to exist.
Effect of Silver Nitrate Application on the Success of Endoscopic Dacryocystorhinostomy
Authors: Çetin Yaser S. , Akın Ramazan , Düzenli Ufuk , Turan Mahfuz , Bozan Nazım 
Published: September 2021

Objectives To compare the clinical outcomes of patients undergoing additional procedures in endoscopic endonasal dacryocystorhinostomy (End-DCR) surgery and discuss the factors affecting the success of End-DCR surgery in light of relevant literature. Methods The study included 155 patients who underwent End-DCR surgery in our clinic due to epiphora. This was a prospective randomized, single-blind, controlled trial. Group I (control) included 54 patients who did not undergo silicone stent insertion or silver nitrate application, group II included 51 patients who underwent silicone stent insertion only, and group III included 50 patients who underwent silver nitrate application only. Statistical analysis was performed on follow-up data regarding anatomic and functional success rates. Results Revision surgery was performed in 16 patients who developed persistent epiphora in the postoperative period, including 6 in group I, 7 in group II, and 3 in group III ( P = .4). The most common reason for revision surgery was stenosis of the neo-ostium ( n = 8), followed by granulation tissue formation ( n = 5) and synechia formation ( n = 3). Granuloma formation was the most common postoperative complication, and a significant difference was found among the groups with regard to granuloma formation ( P = .04). At postoperative month 12, the functional success rate was estimated to be 88%, 86%, and 94%, and the anatomic success rate was estimated to be 94%, 92%, and 96% in groups I, II, and III, respectively, with no significant difference, found among the 3 groups with regard to both rates ( P = .79 and P = .76, respectively). Conclusion The results indicated that stenting and silver nitrate application did not affect surgical success. Our preliminary results on silver nitrate cauterization showed that it is an effective, inexpensive, and practical method to reduce granulation formation in the postoperative period.
Risk Factors for Injuries in Runners: A Systematic Review of Foot Strike Technique and Its Classification at Impact
Authors: Burke Aoife , Dillon Sarah , O’Connor Siobhán , Whyte Enda F. , Gore Shane , Moran Kieran A. 
Published: September 2021

Background: It has been suggested that foot strike technique (FST) at initial contact is related to running-related injuries (RRIs). Purpose: To explore the relationship between FST and RRIs. Study Design: Systematic review; Level of evidence, 3. Methods: A systematic electronic search was performed using MEDLINE, PubMed, SPORTDiscus, Scopus, and Web of Science databases. Included were studies published in the English language that explored the relationship between FST and RRIs between January 1960 and November 2020. Results were extracted and collated. The Grading of Recommendations, Assessment, Development and Evaluation approach was applied to synthesize the quality of evidence. Results: We reviewed 13 studies exploring the relationship between FST and RRIs. Of these, 6 studies reported FST categorically (foot strike pattern [FSP]), and 7 reported continuous measures (foot contact angle, ankle flexion angle, and strike index). Three of the 6 studies looking at categorical FSP found rearfoot strikers have a significantly greater retrospective injury rate than do non– rearfoot strikers, with 1 other study noting a greater risk associated with midfoot and forefoot strike. Regarding the continuous measures of FST, only 1 of the 7 studies reported a significant relationship with RRIs. Conclusion: There was low evidence to suggest a relationship between FST (or its subcategories of categorical FSP and continuous measures) and RRIs. While two-thirds of the categorical studies found a relationship between FSP and RRIs, these studies were very low quality, with limitations such as retrospective study design, low participant numbers, and poor FSP assessment methods. More large-scale prospective studies are required.
Endoscopically Assisted Reconstruction of the Achilles Tendon Using Semitendinosus Graft
Authors: Carmont Michael R. , Saha Arunansu , Rhind John-Henry , Nilsson Niklas , Karlsson Jón , Nilsson-Helander Katarina 
Published: September 2021

Background: Chronic ruptures of the Achilles tendon may lead to symptomatic weakness, despite rehabilitation. Open reconstruction yields good outcome but has a high complication rate, notably wound problems. Endoscopically assisted free semitendinosus transfer restores ankle and preserves first metatarsophalangeal joint (MTPJ) function. Indications: The main indication for the procedure is symptomatic chronic rupture of the Achilles tendon with a palpable tendon gap. Technique Description: The procedure can be split into 4 stages: graft harvest, calcaneum and tunnel preparation, proximal graft attachment, and finally graft passage and screw insertion. Discussion/Conclusion: Following reconstruction, patients use a cast in full plantar flexion for 2 weeks, then a graduated walker for full weight-bearing.
HLFexpression defines the human hematopoietic stem cell state
Authors: Lehnertz Bernhard , Chagraoui Jalila , MacRae Tara , Tomellini Elisa , Corneau Sophie , Mayotte Nadine , Boivin Isabel , Durand Aurélie , Gracias Deanne , Sauvageau Guy 
Published: September 2021

AbstractHematopoietic stem cells (HSCs) sustain blood cell homeostasis throughout life and can regenerate all blood lineages after transplantation. Despite this clear functional definition, highly enriched isolation of human HSCs can currently only be achieved through combinatorial assessment of multiple surface antigens. Although several transgenic HSC reporter mouse strains have been described, no analogous approach to prospectively isolate human HSCs has been reported. To identify genes with the most selective expression in human HSCs, we profiled population and single-cell transcriptomes of unexpanded and ex vivo cultured cord blood–derived hematopoietic stem and progenitor cells as well as peripheral blood, adult bone marrow, and fetal liver. On the basis of these analyses, we propose the master transcription factor HLF (hepatic leukemia factor) as one of the most specific HSC marker genes. To directly track its expression in human hematopoietic cells, we developed a genomic HLF reporter strategy, capable of selectively labeling the most immature blood cells on the basis of a single engineered parameter. Most importantly, HLF-expressing cells comprise all stem cell activity in culture and in vivo during serial transplantation. Taken together, these results experimentally establish HLF as a defining gene of the human HSC state and outline a new approach to continuously mark these cells with high fidelity.
Abnormal B-cell development in TIMP-deficient bone marrow
Authors: Weiss Ashley , Saw Sanjay , Aiken Alison , Aliar Kazeera , Shao Yang W. , Fang Hui , Narala Swami , Shetty Ronak , Waterhouse Paul D. , Khokha Rama 
Published: September 2021

Abstract
Bone marrow (BM) is the primary site of hematopoiesis and is responsible for a lifelong supply of all blood cell lineages. The process of hematopoiesis follows key intrinsic programs that also integrate instructive signals from the BM niche. First identified as an erythropoietin-potentiating factor, the tissue inhibitor of metalloproteinase (TIMP) protein family has expanded to 4 members and has widely come to be viewed as a classical regulator of tissue homeostasis. By virtue of metalloprotease inhibition, TIMPs not only regulate extracellular matrix turnover but also control growth factor bioavailability. The 4 mammalian TIMPs possess overlapping enzyme-inhibition profiles and have never been studied for their cumulative role in hematopoiesis. Here, we show that TIMPs are critical for postnatal B lymphopoiesis in the BM. TIMP-deficient mice have defective B-cell development arising at the pro-B-cell stage. Expression analysis of TIMPless hematopoietic cell subsets pointed to an altered B-cell program in the Lineage−Sca-1+c-Kit+ (LSK) cell fraction. Serial and competitive BM transplants identified a defect in TIMP-deficient hematopoietic stem and progenitor cells for B lymphopoiesis. In parallel, reverse BM transplants uncovered the extrinsic role of stromal TIMPs in pro- and pre-B-cell development. TIMP deficiency disrupted CXCL12 localization to LepR+ cells, and increased soluble CXCL12 within the BM niche. It also compromised the number and morphology of LepR+ cells. These data provide new evidence that TIMPs control the cellular and biochemical makeup of the BM niche and influence the LSK transcriptional program required for optimal B lymphopoiesis.
Systemic bevacizumab for refractory bleeding and transfusion-dependent anemia in Heyde syndrome
Authors: Song Andrew B. , Sakhuja Rahul , Gracin Nancy M. , Weinger Ronald , Kasthuri Raj S. , Al-Samkari Hanny 
Published: September 2021

AbstractHeyde syndrome, the co-occurrence of aortic stenosis and bleeding gastrointestinal (GI) angiodysplasia, is managed with aortic valve replacement. However, severe bleeding and anemia can preclude safe use of the antiplatelet or anticoagulant therapy required for this intervention. We present a case of the novel and successful treatment of severe, refractory bleeding and transfusion dependence with antiangiogenic therapy in a patient with Heyde syndrome. After systemic bevacizumab was initiated, the patient achieved durable hemostasis with normalization of hemoglobin and liberation from red cell transfusion and dependence on iron infusion; aspirin therapy was successfully initiated where it had previously failed. This durable hemostasis facilitated her subsequent successful transcatheter aortic valve replacement. Plasma vascular endothelial growth factor levels, which were monitored during therapy, paradoxically rose after bevacizumab was initiated but normalized after it was discontinued. Given the angiogenic dysregulation of Heyde syndrome, systemic bevacizumab may be an effective and safe targeted therapy for managing refractory GI bleeding, which thereby facilitates antiplatelet therapy and aortic valve replacement in these challenging cases. Additional investigation into the therapeutic role of inhibiting angiogenesis as a hemostatic modality in Heyde syndrome is warranted.
Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis
Authors: Hadchouel Alice , Drummond David , Pontoizeau Clément , Aoust Laura , Hurtado Nedelec Maria-Margarita , El Benna Jamel , Gachelin Elsa , Perisson Caroline , Vigier Clémentine , Schiff Manuel , Lacaille Florence , Molina Thierry Jo , Berteloot Laureline , Renolleau Sylvain , Ottolenghi Chris , Tréluyer Jean-Marc , de Blic Jacques , Delacourt Christophe 
Published: September 2021

IntroductionPulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase (MARS1) gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease.MethodsFour patients received methionine supplementation and were followed for respiratory, hepatic, growth and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species production by patient monocytes before and after methionine supplementation was also studied.ResultsMethionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or noninvasive ventilation could be weaned off within 60 days. In addition, liver dysfunction, inflammation and growth delay improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes.ConclusionMethionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in theMARS1gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.
A randomised trial of prednisoloneversusprednisolone and itraconazole in acute-stage allergic bronchopulmonary aspergillosis complicating asthma
Authors: Agarwal Ritesh , Muthu Valliappan , Sehgal Inderpaul Singh , Dhooria Sahajal , Prasad Kuruswamy Thurai , Garg Mandeep , Aggarwal Ashutosh Nath , Chakrabarti Arunaloke 
Published: September 2021

BackgroundWhether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone in reducing exacerbations in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone–itraconazole combinationversusprednisolone monotherapy in ABPA.MethodsWe randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (4 months) or a combination of prednisolone and itraconazole (4 and 6 months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates, percentage decline in serum total IgE at 6 weeks, time to first ABPA exacerbation and treatment-emergent adverse events (TEAEs).ResultsWe randomised 191 subjects to receive either prednisolone (n=94) or prednisolone–itraconazole combination (n=97). The 1-year exacerbation rate was 33% and 20.6% in the prednisolone monotherapy and prednisolone–itraconazole combination arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All of the subjects experienced a composite response at 6 weeks, along with a decline in serum total IgE (mean decline 47.6%versus45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to TEAEs.ConclusionsThere was a trend towards a decline in ABPA exacerbations at 1 year with the prednisolone–itraconazole combinationversusprednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA.
Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data-driven approach and a lung organoid model of SARS-CoV-2 entry
Authors: Duarte Rodrigo R. R. , Copertino Dennis C. , Iñiguez Luis P. , Marston Jez L. , Bram Yaron , Han Yuling , Schwartz Robert E. , Chen Shuibing , Nixon Douglas F. , Powell Timothy R. 
Published: September 2021

Abstract
Background
Vaccination programs have been launched worldwide to halt the spread of COVID-19. However, the identification of existing, safe compounds with combined treatment and prophylactic properties would be beneficial to individuals who are waiting to be vaccinated, particularly in less economically developed countries, where vaccine availability may be initially limited.

Methods
We used a data-driven approach, combining results from the screening of a large transcriptomic database (L1000) and molecular docking analyses, with in vitro tests using a lung organoid model of SARS-CoV-2 entry, to identify drugs with putative multimodal properties against COVID-19.

Results
Out of thousands of FDA-approved drugs considered, we observed that atorvastatin was the most promising candidate, as its effects negatively correlated with the transcriptional changes associated with infection. Atorvastatin was further predicted to bind to SARS-CoV-2’s main protease and RNA-dependent RNA polymerase, and was shown to inhibit viral entry in our lung organoid model.

Conclusions
Small clinical studies reported that general statin use, and specifically, atorvastatin use, are associated with protective effects against COVID-19. Our study corroborrates these findings and supports the investigation of atorvastatin in larger clinical studies. Ultimately, our framework demonstrates one promising way to fast-track the identification of compounds for COVID-19, which could similarly be applied when tackling future pandemics.
Association of physical fitness with quality of life in community-dwelling older adults aged 80 and over in Poland: a cross-sectional study
Authors: Lepsy Ewelina , Radwańska Ewa , Żurek Grzegorz , Żurek Alina , Kaczorowska Antonina , Radajewska Alina , Kołcz Anna 
Published: September 2021

Abstract
Background
Aging is a progressive and irreversible process that negatively affects the quality of life (QOL). Older adults face difficulties related to worsening health, lowering the level of physical and mental efficiency. We aimed to analyze the associations between physical fitness and QOL in Polish older adults considering sex differences.

Methods
This cross-sectional study was performed from March to August 2015. The sample consisted of 100 community-dwelling adults (67 women, 33 men) with a mean age of 82.94 ± 2.67 years. The World Health Organization QOL, Short Form questionnaire (WHOQOL-BREF), and the Fullerton Functional Fitness Test (FFFT) were used. Biometric data, social and environmental situation, nutritional and lifestyle behaviors have been also collected using a questionnaire designed by the authors.

Results
The results obtained in individual domains of WHOWOL-BREF indicate a good level of QOL in all the examined domains. Statistically significant sex differences were obtained in physical (p = 0.01), psychological (p = 0.04) and environmental (p = 0.02) domains in WHOQOL-BREF. It was noted that men perform better in terms of the upper (arm curl, p < 0.001) and lower body strength (chair stand, p = 0.01), aerobic endurance (two-minute step test, p < 0.001), agility and dynamic balance (up and go test, p < 0.001) in FFFT.

Conclusions
Community-dwelling older adults aged 80–93 years in Poland present a good level of QOL, and the higher score was obtained in men. Also, men presented better physical fitness, showed a higher level of independence in daily activities, and assessed better their own QOL than women.
Fewer losses in the cascade of care for latent tuberculosis with solo interferon-gamma release assay screening compared to sequential screening
Authors: Lim R. K. , Talavlikar R. , Chiazor O. , Bietz J. , Gardiner H. , Fisher D. 
Published: September 2021

Abstract
Background
Refugees are at increased risk of developing tuberculosis (TB) soon after resettlement. Targeting high-risk populations for latent tuberculosis infection (LTBI) screening and treatment is an important measure towards eliminating TB in low incidence countries, however, there are low rates of screening and treatment completion in the LTBI cascade of care. The authors hypothesized that an interferon-gamma release assay (IGRA) screening strategy would lead to a higher proportion of refugees completing LTBI screening and treatment, compared to sequential screening with tuberculin skin test (TST) and confirmatory IGRA.

Methods
This retrospective cohort study included eligible refugees screened with a sequential strategy versus a solo-IGRA strategy at different time periods from a centralized refugee clinic. The primary outcome was the proportion completing LTBI screening in each cohort.

Results
A total of 471 subjects were included (240 in sequential screening, 231 in solo-IGRA screening). 54% of refugees completed LTBI screening with sequential testing, compared to 85% of those screened with a solo-IGRA. Time to completing screening was also shorter in the solo-QFT group (difference 16.5 days, p < 0.01, 95% confidence interval 9.3, 23.7). There was a higher incidence of LTBI diagnosis in the solo-IGRA group (41 versus 20, p = 0.002). Screening completion was predicted by solo-IGRA screening (aOR 3.74, 95% confidence interval 2.30, 6.09; p < 0.001) and if refugees were privately-sponsored (aOR 2.81, 95% confidence interval 1.53, 5.15; p = 0.001). Treatment completion rates did not differ between groups.

Conclusion
This study has identified fewer dropouts in the LTBI cascade of care if a solo-IGRA strategy is used for screening. An IGRA should be strongly considered as the screening method for refugees arriving in low-incidence settings if resources are available.