bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in the effectiveness of first-line tumour necrosis factor inhibitors in axial spondyloarthritis: results from the EuroSpA Research Collaboration Network
Authors: Hellamand Pasoon , van de Sande Marleen , Ørnbjerg Lykke MIdtbøll , Klausch Thomas , Nurmohamed Michael T , van Vollenhoven Ronald F , Nordström Dan , Hokkanen Anna Mari , Santos Maria Jose , Vieira-Sousa Elsa , Loft Anne G , Glintborg Bente , Hetland Merete Lund , Lindström Ulf , Wallman Johan K , Michelsen Brigitte , Klami Kristianslund Eirik , Ciurea Adrian , Nissen Michael S , Codreanu Catalin , Mogosan Corina , Macfarlane Gary J , Rotariu Ovidiu , Rotar Ziga , Tomšič Matija , Castrejon Isabel , Otero-Varela Lucia , Gudbjornsson Bjorn , Geirsson Arni Jon , Vencovský Jiří , Pavelka Karel , Gulle Semih , Zengin Berrin , Iannone Florenzo , Foti Rosario , Ostergaard Mikkel , van der Horst-Bruinsma Irene 
Published: December 2023

ObjectiveEvidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi.MethodsData from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were pooled. We investigated the association of sex with treatment response using logistic regression. The primary outcome was clinically important improvement (CII) at 6 months according to Ankylosing Spondylitis Disease Activity Score with C-reactive protein (CRP) (≥1.1 decrease). We adjusted for age, country and TNFi start year. A secondary outcome was retention rates over 24 months of follow-up assessed by Kaplan-Meier estimator.ResultsIn total, 6451 axSpA patients with data on CII were assessed for treatment response; 2538 (39%) were women and 3913 (61%) were men. Women presented at baseline with lower CRP levels but had higher scores on patient-reported outcome measures. At 6 months, 53% of the women and 66% of the men had CII. Women had a lower relative risk of CII compared with men (0.81; 95% CI 0.77 to 0.84). This sex difference was similar in adjusted analysis (0.85; 95% CI 0.82 to 0.88). Retention rates were evaluated in 27 702 patients. The TNFi 6/12/24 months retention rates were significantly lower among women (79%/66%/53%) than men (88%/79%/69%).ConclusionTreatment response and retention rates are lower among women with axSpA initiating their first TNFi. Sex differences in treatment effectiveness were present regardless of the outcome measure used for treatment response, and differences in retention rates transpired early and increased as time progressed.
Diagnostic utility of serum IgG4 level in IgG4-related diseases: a comprehensive systematic review and meta-analysis
Authors: Chang Che-Tzu , Chan Tien-Ming , Yu Han-Hua , Yu Kuang-Hui 
Published: December 2023

BackgroundDespite many studies suggesting an association between serum IgG4 and IgG4-related diseases (IgG4-RD), the evidence of the utility of serum IgG4 titres in differentiating between IgG4-RD and non-IgG4-RD remains uncertain.MethodsThe primary analysis was based on published studies. Data were pooled by means of a random-effect model, and sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR–), diagnostic ORs (DOR) and summary receiver operating characteristic curve (SROC) were calculated. Subgroup analyses were performed based on the racial/ethnic distribution of these studies.ResultsA total of 27 studies with 1691 (8.6%) IgG4-RD cases and 17 944 non-IgG4-RD subjects were included. Moreover, 1462 (86.5%) of the 1691 IgG4-RD patients had elevated serum IgG4 levels whereas 10.5% (1,882 of 17,944) of the non-IgG4-RD subjects had elevated serum IgG4 levels. The pooled sensitivity of serum IgG4 was 86% (85%–88%), specificity was 90% (89%–90%), LR+ was 9.19 (7.16–11.78), LR– was 0.17 (0.12–0.24), and the DOR was 60.8 (40.9–90.4), respectively. The area under the SROC curve for the differential diagnosis between IgG4-RD and non-IgG4-RD was 0.95 (0.94–0.97). Ethnic subgroup analyses revealed different findings with respect to DOR for Asian (103.8; 95% CI 63.3 to 170.2), and Caucasian (25.7; 95% CI 17.6 to 37.5) populations.ConclusionsOverall, elevated serum IgG4 levels were associated with IgG4-RD. The results revealed a moderate-to-high sensitivity (86%, 85%–88%) and high specificity (90%, 89%–90%). Subgroup analyses in serum IgG4 diagnostic performance revealed differences among Asian and Caucasian populations.
IDH1-Mutant Preleukemic Hematopoietic Stem Cells Can Be Eliminated by Inhibition of Oxidative Phosphorylation
Authors: Landberg Niklas , Köhnke Thomas , Feng Yang , Nakauchi Yusuke , Fan Amy C. , Linde Miles H. , Karigane Daiki , Lim Kelly , Sinha Rahul , Malcovati Luca , Thomas Daniel , Majeti Ravindra 
Published: December 2023

Abstract

Rare preleukemic hematopoietic stem cells (pHSC) harboring only the initiating mutations can be detected at the time of acute myeloid leukemia (AML) diagnosis. pHSCs are the origin of leukemia and a potential reservoir for relapse. Using primary human samples and gene editing to model isocitrate dehydrogenase 1 (IDH1) mutant pHSCs, we show epigenetic, transcriptional, and metabolic differences between pHSCs and healthy hematopoietic stem cells (HSC). We confirm that IDH1-driven clonal hematopoiesis is associated with cytopenia, suggesting an inherent defect to fully reconstitute hematopoiesis. Despite giving rise to multilineage engraftment, IDH1-mutant pHSCs exhibited reduced proliferation, blocked differentiation, downregulation of MHC class II genes, and reprogramming of oxidative phosphorylation metabolism. Critically, inhibition of oxidative phosphorylation resulted in the complete eradication of IDH1-mutant pHSCs but not IDH2-mutant pHSCs or wild-type HSCs. Our results indicate that IDH1-mutant preleukemic clones can be targeted with complex I inhibitors, offering a potential strategy to prevent the development and relapse of leukemia.

Significance:
A high burden of pHSCs is associated with worse overall survival in AML. Using single-cell sequencing, metabolic assessment, and gene-edited human models, we find human pHSCs with IDH1 mutations to be metabolically vulnerable and sensitive to eradication by complex I inhibition.
See related commentary by Steensma, p. 83.
This article is featured in Selected Articles from This Issue, p. 80
Developing Offshore Wind Farms – A Comparison and Analysis of the Legal and Governance Frameworks of the North Sea Coastal States
Authors: Nieuwenhout Ceciel 
Published: December 2023

Abstract
With high offshore wind ambitions, the North Sea coastal states have each followed a different path in the development of the legal framework for offshore wind development. This article compares the legal frameworks of the coastal states on three main issues: the location choice, including selection of developers; the permitting procedures, and the connection of the owf s. The analysis shows legislative and governance convergence across the North Sea, but also a few instances where different choices are made. The consequences of the choices are discussed and analysed, with recommendations for other coastal states wishing to develop an offshore wind regulatory framework.
Comparison of Fixed Dosing vs Train of Four Titration of Cisatracurium in COVID-19 ARDS Patients
Authors: Banerjee Oyshik , Elefritz Jessica L. , Doepker Bruce A. , Atyia Sara A. , Brummel Nathan E. , Smith Rachel M. , Handley Demond , Cape Kari M. 
Published: December 2023

Background: Early neuromuscular blockade with cisatracurium has been associated with improved outcomes in moderate-severe acute respiratory distress syndrome (ARDS). Previous studies have demonstrated increased drug utilization without benefits in oxygenation using fixed dose cisatracurium compared to train-of-four (TOF) titration. Objective: We sought to compare a novel, lower fixed dose cisatracurium protocol to TOF titration evaluating the impact on PaO2:FiO2 ratio (P/F). Methods: We conducted a single-center retrospective cohort study comparing fixed dose cisatracurium to TOF titration. We included patients aged 18-89 treated for COVID-19 ARDS with a baseline P/F≤200 who received a cisatracurium infusion for ≥12 h. The primary outcome was change in P/F at 48 h from baseline. Secondary outcomes included change in P/F at 24 h and 7 days, need for mechanical ventilation at day 28, and cisatracurium utilization. Results: Analyses included 125 patients (fixed dose = 65, TOF = 60). Severe ARDS was common with a baseline median P/F of 73.7 vs 79.5, P = .133. The change in P/F at 48 h was larger in the TOF cohort in the adjusted analysis (24.9 vs 70.8, P < .005). The rate and total cumulative dose of cisatracurium were higher in the fixed dose cohort (5 vs 3 mcg/kg/min, P < .001; 1034 vs 612 mg, P < .001) despite similar infusion durations (44.1 h vs 48.5 h, P = .642). Conclusions: Patients in the TOF cisatracurium cohort had improved P/F at 48 h compared to the fixed dose cohort, while also using only 60% of the cumulative dose. Future directions should include analysis of the implications of increased cisatracurium exposure on patient outcomes.
Anti-rheumatic and Memory-enhancing Effect of Memantine on Complete Freund’s Adjuvant-induced Rheumatoid Arthritis Compared to Methotrexate in Wistar Rats
Authors: Jalgaonkar Sharmila V. , Ourasang Sumith , Tripathi Raakhi K. , Vaideeswar Pradeep , Badhe Padma 
Published: December 2023

Objectives To evaluate the anti-inflammatory and memory-enhancing effects of memantine (MEM) in complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) in Wistar rats. The effect of MEM on cognition in CFA-induced RA was also evaluated. Materials and Methods The rats were randomly assigned to one of five groups: sham control (SC), disease control (DC)—CFA 0.1 mg, positive control (PC)—methotrexate (MTX) 1 mg/kg, low dose MEM—20 mg/kg, and high dose MEM (HD-M)—50 mg/kg. All groups received a subcutaneous injection of CFA in the left paw on day 0, except for the SC group, which received a distilled water (DW) injection. The study drugs, MEM and MTX, were administered orally from days 15 to 28. The SC group received DW orally from days 15 to 28. Variables for physical (paw volume, paw surface temperature, and ankle joint diameter) and behavior (open field test, grip strength test, and water corn test) were performed on days 1, 0, 7, 14, 21, and 28. On day 28, blood was collected for serum inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Ex vivo radiological changes in the ankle joint were recorded using a digitalized X-ray machine. Histopathology of the ankle joint was performed. Results When compared to the DC group, the HD-M group showed a significant improvement in all physical and behavioral characteristics ( p < 0.001). When compared to the DC group, TNF-α, IL-6 levels, and histopathological scores were significantly lower in the HD-M group ( p < 0.01). Conclusion MEM reduces inflammation and improves memory in Wistar rats with CFA-induced RA. MEM can be used as an anti-inflammatory drug in elderly patients at risk of dementia.
Primary Uterine Alveolar Soft Part Sarcoma in a Postmenopausal Woman: Histopathologic and Immunohistochemical Characteristics of a Rare Case
Authors: Gupta Anjali , Gupta Parikshaa , Kaur Amarjot , Kumari Snigdha , Nalini Gupta , Gainder Shalini 
Published: December 2023

Background Primary uterine alveolar soft part sarcoma (ASPS) is a rare, indolent mesenchymal malignancy with less than 40 patients documented in the literature. Case We report an example of ASPS in a 61-year-old postmenopausal woman. Macroscopically, the uterus showed multiple nodular masses. Microscopic examination revealed tumor arranged in nests and alveolar pattern. The tumor cells were moderately to markedly pleomorphic, epithelioid to polygonal, with eccentrically placed nuclei, vesicular chromatin, prominent macro-nucleoli, and moderate to abundant eosinophilic cytoplasm. PAS-positive and diastase-resistant intracytoplasmic crystals were also seen in some tumor cells. On immunohistochemistry, the tumor cells showed diffuse positivity for vimentin and nuclear positivity for TFE3, a surrogate marker for ASPS. These were negative for SMA, desmin, CD10, h-caldesmon, cyclin D1, EMA, Melan A, and CD34. SMARCB1 expression was retained. Based on the histopathology and IHC, a final diagnosis of uterine ASPS was rendered. Conclusions Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare tumors. Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare sarcoma in an uncommon site with an unusual age.
Ink blot leakage in central retinal artery occlusion
Authors: Venkatesh Ramesh , Joshi Aishwarya , Thadani Atul , Rubble Mangla , Handa Ashit , Chhablani Jay 
Published: December 2023

Purpose To describe a typical case of acute central retinal artery occlusion (CRAO) with an ink-blot pattern of hyperfluorescent leak on fundus fluorescein angiography (FFA). Case description A 21-year-old woman came to the clinic with one day of painless right eye vision loss. Her right eye had finger counting at ½ meter. Her right eye had a relative afferent pupillary defect, but her anterior segment and intraocular pressure of both eyes were normal. Results The right eye fundus showed signs of acute CRAO with severe grade on optical coherence tomography (OCT). FFA imaging showed a mid-phase hyperfluorescent leak that persisted until the late stage. OCT scan through the hyperfluorescent spot showed absence of neurosensory detachment with normal retinal pigment epithelium, ruling out a central serous chorioretinopathy (CSCR). Ocular massage and anterior chamber paracentesis were performed. At the 10-day follow-up, the patient's visual acuity was counting fingers at ½ meter, and the OCT scan showed findings of CRAO chronicity. The hyperfluorescent spot disappeared on the subsequent FFA. Conclusion We report a case of ink-blot leakage on FFA, similar to that observed in CSCR in an eye with acute CRAO. We propose that the hyperfluorescent spot in our acute CRAO was likely caused by red blood cell aggregation or rouleaux formation.
Development of an educational program for ultrasound-based tip location during placement of PICC-port to improve the competence of specialized nurse
Authors: Shen Yan , Zhou Xingmei , Yu Jiaqi , Chang Jian , Li Xin , Li Xianrui , Zhang Huiyan 
Published: December 2023

Objectives: To create an educational program and provide a valid, evidence-based course for ultrasound-based tip location during placement of PICC-port for specialized nurses. Materials and methods: We designed three phases for program development. Phase 1: summarizing the evidences as a knowledge foundation; Phase 2: developing an educational program for ultrasound-based tip location during placement of PICC-port; Phase 3: expert panel to validate the developed program. Results: The educational program was composed of five parts and 12 lessons, with three lessons each devoted to basic knowledge, practice, and testing, respectively. First, the criteria for defining an expert trainer is determined. Second, some basic conditions are confirmed. Third, the image acquisition windows of transthoracic echocardiographic are recommended. Fourth, the knowledge about ultrasound-based tip location is categorized. Fifth, the procedures for ultrasound-based tip location combined with “bubble test” were listed. The program’s content was verified by experts and found to have a validity coefficient of 0.95. Conclusion: The program, encompassing theoretical and practical components, as well as assessment items, can be applied in specialized nursing education and skills training, and it enhances nurses’ competence in accurately identifying the tip location during the placement of PICC-ports and other central venous access implants.
Upper Hemisternotomy Versus Full Sternotomy for Replacement of the Supracoronary Ascending Aorta and Aortic Valve
Authors: Shah Vishal N. , Binongo Jose , Wei Jane , Till Brian M. , King Colin , McGee Jacqueline , Plestis Konstadinos A. 
Published: December 2023

Objective: Upper hemisternotomy (UHS) for supracoronary ascending aorta replacement (scAAR) with concomitant aortic valve replacement (AVR) results in less trauma and potentially faster convalescence compared with full sternotomy (FS). Direct head-to-head studies are lacking. We compared a group of UHS patients with a matched group of FS patients undergoing scAAR and AVR. Methods: There were 198 patients who underwent scAAR and AVR procedures by a single surgeon between 1999 and 2020. After matching 6 preoperative characteristics, there were 50 UHS and 50 FS patients. Patients who required acute type A aortic dissection repair, reoperations, concomitant procedures, or hypothermic circulatory arrest were excluded. Results: In the matched sample, the hospital mortality rate was 1% (1 of 100). The median cardiopulmonary bypass time was 150 (interquartile range [IQR], 131 to 172) min and 164.5 (IQR, 138 to 190) min, respectively, for the UHS and FS groups ( P = 0.08). The median aortic cross-clamp time was 121 (IQR, 107 to 139) min during UHS and 131 (IQR, 115 to 159) min during FS ( P = 0.05). The median ventilation time was 7 (IQR, 3 to 14) h versus 17 (IQR, 10 to 24) h, respectively, after UHS and FS ( P = 0.005). The median hospital length of stay was 7 (IQR, 6 to 9) days after UHS and 8 (IQR, 7 to 11) days after FS ( P = 0.05). Conclusions: The low morbidity and mortality support the wider use of UHS for scAAR and AVR in appropriately selected patients. Larger studies are needed to confirm these initial findings.
Experience in early diagnosis of pyoderma gangrenosum: A case report
Authors: Shen Cong mo , Li Feng 
Published: December 2023

The early clinical manifestations of pyoderma gangrenosum are not characteristic, it resembles other infectious skin lesions and is difficult to identify in the early stages. The exploratory surgery for direct observation of the superficial fascia of the suspected infection site for signs of infection, together with the collection of tissue samples for bacterial culture, combined with histopathological biopsy and clinical manifestations, was of significant value in the differential diagnosis of this disease and infectious skin lesions with similar manifestations. We introduce a patient who was admitted to hospital with redness and swelling of the left calf and foot for 7 days. The local appearance of the lesion resembled a carbuncle or early-stage necrotizing fasciitis. We performed surgical exploration for a definitive diagnosis but found no signs of infection, therefore, infection could be preliminarily ruled out. The disease was finally diagnosed as pyoderma gangrenosum, which was treated with hormone therapy and recovered after dressing change.
Changes in Quality of Life Among Collegiate Athletes During COVID-19
Authors: Harris Thomas , Sanfilippo Jennifer , Haraldsdottir Kristin , Anderson Scott , Watson Andrew 
Published: December 2023

Background: The COVID-19 pandemic has had a significant effect on the mental health of athletes. How this has affected quality of life (QoL), specifically in the college population, is poorly defined. Hypothesis: During the COVID-19 pandemic, the mental and physical QoL will have decreased in collegiate athletes as compared with before the pandemic. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Division I athletes from a total of 23 varsity teams at a single institution completed surveys between 2018 and 2022. QoL was assessed using the Veterans RAND 12-Item Health Survey (VR-12). VR-12 scores were separated into mental component scores (MCS) and physical component scores (PCS). Separate linear mixed effects models evaluated changes in MCS and PCS from pre-COVID to during COVID overall, as well as differences in changes by sex and sport type (individual, team). Results: For all athletes, the PCS increased (54.6 [95% CI 54.4-54.7] vs 55.1 [54.9-55.3]; P < 0.01) and the MCS decreased (55.2 [54.9-55.5] vs 53.5 [53.1-53.8]; P < 0.01) from pre-COVID to during COVID. When evaluating for sex, women demonstrated a greater increase in PCS (0.57 ± 0.22; P = 0.01) and greater decrease in MCS (1.06 ± 0.38; P < 0.01). With respect to sport type, individual sports demonstrated a greater decrease in MCS (1.46 ± 0.39; P < 0.01), but no interaction was identified for PCS (0.42 ± 0.23; P = 0.07). Conclusion: Collegiate athletes demonstrated a decrease in their self-reported mental QoL during the COVID-19 pandemic, as compared with before the pandemic. This effect was most evident in women and in individual sports. Athletes also reported an increase in physical QoL during COVID that was also larger in women, but not related to sport. Clinical Relevance: This study demonstrates the impact of the COVID-19 pandemic on collegiate athletes’ QoL, including negative effects on mental health. It also identifies cohorts of athletes (women, individual) who may be more significantly affected.
The efficacy, acceptability and safety of acceptance and commitment therapy for fibromyalgia – a systematic review and meta-analysis
Authors: Eastwood Florence , Godfrey Emma 
Published: December 2023

Background Fibromyalgia (FM) is a chronic pain disorder characterised by widespread pain, fatigue and cognitive symptoms. Acceptance and commitment therapy (ACT) aims to improve psychological flexibility and has been found to be beneficial in treating chronic pain; however, there are few studies evaluating its efficacy in treating FM. Aim This systematic review and meta-analysis evaluated the efficacy of acceptance and commitment therapy in patients with fibromyalgia. Methods PubMed, Embase and PsychInfo databases were searched. Randomised Controlled Trials (RCTs) were eligible for inclusion if participants had FM, and the intervention was based on the ACT framework/model, and not combined with any other active therapy; any non-ACT control was accepted. A meta-analysis was performed, with the primary outcomes pain acceptance (chronic pain acceptance questionnaire, CPAQ), health-related quality of life (fibromyalgia impact questionnaire, FIQ), attrition rate and frequency of adverse events, and the secondary outcomes pain intensity, disability, depression, anxiety, and fatigue. Results Six RCTs, with a total of 384, mostly-female, participants were included, with ACT being delivered online, in a group setting, or one-to-one. ACT was superior to controls in improving FIQ score at post-intervention (SMD −1.05, 95% CI −2.02, −0.09) and follow-up (SMD −1.43, 95% CI −2.17, −0.69) and CPAQ post-intervention (SMD 1.05, 95% CI 0.61, 1.49) and at follow-up (SMD 0.95, 95% CI 0.40, 1.49). Attrition was below 20% in 4/6 studies and no adverse events were reported as attributable to ACT. All secondary outcomes showed large-to-moderate pooled effect estimates post-intervention, indicating improvement in anxiety, depression, pain and disability. Fatigue also improved, with a large negative effect. Conclusions The results suggest ACT improved outcomes in patients with FM: there was an overall improvement in all outcomes post-intervention, with most maintained at follow-up. This review was, however, limited by the small body of evidence and differing methodologies of included studies.