bluuebunny/crossref_metadata_2025_split huggingface dataset:
10 Years of belimumab experience: What have we learnt?
Authors: Levy Roger A , Gonzalez-Rivera Tania , Khamashta Munther , Fox Norma Lynn , Jones-Leone Angela , Rubin Bernie , Burriss Susan W , Gairy Kerry , Maurik Andre van , Roth David A 
Published: July 2021

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE. Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab’s effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.
Metformin Antagonizes Ovarian Cancer Cells Malignancy Through MSLN Mediated IL-6/STAT3 Signaling
Authors: Yang Xu , Huang Mei , Zhang Qin , Chen Jiao , Li Juan , Han Qian , Zhang Lu , Li JiaQi , Liu Shuai , Ma YuLan , Li Lan , Yang Lei , Zou SiYing , Han Bin 
Published: July 2021

Background: Ovarian cancer is the most lethal gynecological malignancy, and chemotherapy remains the cornerstone for ovarian cancer management. Due to the unsatisfactory prognosis, a better understanding of the underlying molecular carcinogenesis is urgently required. Methods: Assays for determining cell growth, cell motility, and apoptosis were employed to evaluate the potential antitumor effects of metformin against ovarian cancer cells. Molecular biological methods were employed to explore the underlying mechanism. Human ovarian cancer samples and Gene Expression Profiling Interactive Analysis (GEPIA) dataset were used for uncovering the clinical significances of mesothelin (MSLN) on ovarian cancer. Results: In the present work, we found that metformin treatment led to cell growth and cell migration inhibition, and induced cell apoptosis. Metformin administration also impaired cancer cell stemness and the capillary-like structure formation capacity of SKOV3 cells. On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFβ1 expression. We also observed an oncogenic function of MSLN on ovarian cancer. Conclusions: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFβ1 downregulation.
Calling nurses to care for burn victims after color-dust explosion
Authors: Tsai Yu-Lun , Yi Tin , Chiang Hsien-Hsien , Lan Hsiang-Yun , Chiang Hui-Hsun , Liaw Jen-Jiuan 
Published: July 2021

Background: Healthcare professionals follow codes of ethics, making them responsible for providing holistic care to all disaster victims. However, this often results in ethical dilemmas due to the need to provide rapid critical care while simultaneously attending to a complex spectrum of patient needs. These dilemmas can cause negative emotions to accumulate over time and impact physiological and psychological health, which can also threaten nurse–patient relationships. Aim: This study aimed to understand the experience of nurses who cared for burn victims of the color-dust explosion and the meaning of ethical relationships between nurse and patient. Research design: A qualitative descriptive study using a phenomenological approach. Participants and research context: Clinical nurses who provided care to the patients of the Formosa color-dust explosion of 2015 were selected by purposive sampling (N = 12) from a medical center in Taiwan. Data were collected using individual in-depth semi-structured interviews. Audiotaped interviews were transcribed and analyzed using Colaizzi’s method. Ethical considerations: This study was approved by the institutional review board of the study hospital. All participants provided written informed consent. Findings Three main themes described the essence of the ethical dilemmas experienced by nurses who cared for the burn-injured patients: (1) the calling must be answered, (2) the calling provoked my feelings, and (3) the calling called out my strengths. Conclusions: Healthcare providers should recognize that nurses believed they had an ethical responsibility to care for color-dust explosion burn victims. Understanding the feelings of nurses during the care of patients and encouraging them to differentiate between the self and the other by fostering patient–nurse relationships based on intersubjectivity could help nurses increase self-care and improve patient caregiving.
Clinical outcomes of the piggyback secondary implantation of a novel multifocal lens in the ciliary sulcus: A case series
Authors: Valvecchia Gerardo , Cervantes-Coste Guadalupe , Asis Oscar , Pereyra Federico , Garza-León Manuel , Gomez Caride Gastón , Ferlini Leonardo , Gonzalez-Salinas Roberto 
Published: July 2021

Purpose: Evaluate the clinical outcomes of the secondary piggyback add-on IOL implantation in the ciliary sulcus for pseudophakic patients previously implanted with a monofocal IOL, who pursue a spectacle-free option after IOL surgery. Methods: A prospective case series including seven pseudophakic patients who underwent an in-the-bag monofocal IOL implantation. All eyes underwent a piggyback IOL implantation of the new sulcus designed A4 AddOn IOL in the ciliary sulcus as a secondary procedure for pseudophakic patients pursuing a spectacle-free option for near and intermediate distance after IOL surgery. Results: Seven eyes from six patients were included in this study, from which 4 (71.43%) were female, with a mean age of 58.33 ± 3.5 years (range 54–63; 95% CI 54.66, 62.01). The postoperative spherical equivalent at the 3-month visit was −0.10 m ± 0.82. Also, the UDVA was 0.11 ± 0.08 logMAR, the UIVA 0.01 ± 0.03, and the UNVA 0.01 ± 0.03 3 months after their surgical procedure. Conclusions: The A4 AddOn multifocal IOL’s secondary piggyback implant is an efficient alternative for monofocal pseudophakic patients seeking presbyopia solutions. This sulcus-designed IOL provides an optimal visual outcome for near and distance vision.
Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study
Authors: Hartung Hans-Peter , Derfuss Tobias , Cree Bruce AC , Sormani Maria Pia , Selmaj Krzysztof , Stutters Jonathan , Prados Ferran , MacManus David , Schneble Hans-Martin , Lambert Estelle , Porchet Hervé , Glanzman Robert , Warne David , Curtin Francois , Kornmann Gabrielle , Buffet Bénédicte , Kremer David , Küry Patrick , Leppert David , Rückle Thomas , Barkhof Frederik 
Published: July 2021

Background: The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions. Objective and Methods: This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24. Additional endpoints included numbers of T2 and T1-hypointense lesions, magnetization transfer ratio, and brain atrophy. In total, 270 participants were randomized to receive monthly intravenous temelimab (6, 12, or 18 mg/kg) or placebo for 24 weeks; at week 24 placebo-treated participants were re-randomized to treatment groups. Results: The primary endpoint was not met. At week 48, participants treated with 18 mg/kg temelimab had fewer new T1-hypointense lesions ( p = 0.014) and showed consistent, however statistically non-significant, reductions in brain atrophy and magnetization transfer ratio decrease, as compared with the placebo/comparator group. These latter two trends were sustained over 96 weeks. No safety issues emerged. Conclusion: Temelimab failed to show an effect on features of acute inflammation but demonstrated preliminary radiological signs of possible anti-neurodegenerative effects. Current data support the development of temelimab for progressive MS. Trial registration: CHANGE-MS: ClinicalTrials.gov: NCT02782858, EudraCT: 2015-004059-29; ANGEL-MS: ClinicalTrials.gov: NCT03239860, EudraCT: 2016-004935-18
Magnitude and factors associated with anemia among diabetic patients in Ethiopia: A systematic review and meta-analysis
Authors: Atlaw Daniel , Tariku Zerihun 
Published: July 2021

Background: In Ethiopia, diabetes is estimated to affect about half a million people. About 35% of individuals with diabetes are complicated by microvascular diseases like retinopathy, nephropathy, cardiovascular, and anemia. Even though there are some studies conducted on prevalence and associated factors of anemia in diabetic patients, their findings were variable. Therefore, this meta-analysis is aimed to determine the pooled prevalence and factors associated with anemia among diabetic patients. Methods: PubMed, CINAHL, POPLINE, ScienceDirect, African Journals Online, and Google Scholar were systematically searched to identify related studies. The heterogeneity of studies was assessed using Cochran’s Q test and I2 tests. A random-effects model was used to estimate the pooled prevalence of anemia among diabetic patients in Ethiopia. Publication bias was evaluated by employing Egger’s tests. Results: After reviewing 503 articles, 6 articles fulfilled inclusion criteria and remained for the final meta-analysis. The pooled prevalence of anemia among diabetic patients was 24.81% (95% confidence interval: 19.38–30.25). Age greater than 60 years old (pooled odds ratio, 95% confidence interval: 3.73 (2.23–6.77)), glomerular filtration rate less than 60 mL/min/1.73 m2 (pooled odds ratio, 95% confidence interval: 12.65 (8.71–18.37)), and being diabetic for more than 10 years (pooled odds ratio, 95% confidence interval: 10.21 (7.00–15.04)) were found to be determinants of anemia among diabetic patients in Ethiopia. Conclusion: Overall, one in four diabetic patients develops anemia in Ethiopia. Age, glomerular filtration rate, and duration of being diabetic are factors significantly associated with the occurrence of anemia in diabetic patients.
The Effectiveness of Telenursing for Self-Management Education on Cardiometabolic Conditions: A Pilot Project on a Remote Island of Ōsakikamijima, Japan
Authors: Moriyama Michiko , Kazawa Kana , Jahan Yasmin , Ikeda Mika , Mizukawa Mariko , Fukuoka Yasuko , Harada Koji , Rahman Md Moshiur 
Published: July 2021

Introduction: Providing self-management education for residents with cardiometabolic conditions in remote islands is a challenge due to the shortage of primary care practitioners (PCPs), specialist physicians, and nurses. Therefore, we applied telenursing with lifestyle-related chronic diseases in remote island residents in Japan. This project aimed to improve the self-management behavior, cardiometabolic indicators, self-efficacy, and quality of life (QoL) of residents with cardiometabolic risks. Methods: We chose Ōsakikamijima Island, Hiroshima Prefecture, Japan, which is designated under the Remote Islands Development Act. The project was conducted from 2013 to 2014. The residents aged over 40 and under 75 years old, selected from the annual specific health check-up examination and from PCPs for screening cardiometabolic risks (urinary protein, glycohemoglobin A1c, systolic and diastolic blood pressure (BP), Low-density lipoprotein cholesterol, High-density lipoprotein cholesterol, and triglyceride) were included. The effectiveness of telenursing for self-management education was 6-month-long with a 6-month follow-up and evaluated by a single-group pre-and post-test design. Face-to-face health education was applied at the initial interview followed by telenursing (biweekly telephone calls till third-month, and a monthly telephone call during the fourth and fifth-month) by the trained nurses outside the island. To enhance participants’ self-monitoring health behavior changes, the nurses used motivational interviewing and behavior change techniques based on the transtheoretical model. Results: A total of 130 residents, 42 agreed to participate, 41 finished the 6-month program, and 33 completed the 12-month follow-up. Most of their behavior changes like self-management behaviors, cardiometabolic indicators, and self-efficacy at 6-month were improved significantly except QoL. Among the 12-month study periods, self-management behaviors, body mass index, systolic BP, diastolic BP, and self-efficacy (sense of control), (all P < .05) showed significant improvement. Conclusion: This study results indicated that telenursing might be effective to improve the lifestyles-related behaviors in chronic diseases on the remote island of Ōsakikamijima, Japan.
Outcomes for older people with long-term conditions attending day care services delivered by paid staff or volunteers: a comparative study
Authors: Lunt Catherine , Shiels Chris , Dowrick Christopher , Lloyd-Williams Mari 
Published: July 2021

Background: Day care services support older people living with long-term conditions (LTC’s). Aims: The aims of the study were to determine outcomes in terms of loneliness and health-related quality of life for older people with LTCs attending day care services in the United Kingdom. Methods: Newly referred older people with LTCs to day care services in North West of England and Wales were invited to participate. The EQ-5D-3L and De Jong Loneliness questionnaires were completed at recruitment, 6 and 12 weeks. Results: Ninty-four older people (64% female), age range 65–99 years; mean number of LTCs 4.3 (range: 2–9) were recruited. About 52% lived alone and 36% lived in one of the 20% most deprived local authorities in England and Wales. Outcomes over 12 weeks were comparable for paid, blended, and for volunteer-led services. Conclusion: Following the Covid-19 pandemic, it is increasingly urgent to support older people with LTCs who may have lost physical and cognitive function during lockdown and to support their recovery. Our study suggests that volunteers can provide services and complement the care provided by paid staff, freeing up resources and enabling increasing numbers of older people to be supported.
The effects of shoulder arthroscopy on ultrasound image quality of the interscalene brachial plexus: a pre-procedure vs post-procedure comparative study
Authors: Panchamia Jason K. , Jagannathan Ram , Pulos Bridget P. , Amundson Adam W. , Sanchez-Sotelo Joaquin , Martin David P. , Smith Hugh M. 
Published: July 2021

Abstract
Background
Fluid extravasation from the shoulder compartment and subsequent absorption into adjacent soft tissue is a well-documented phenomenon in arthroscopic shoulder surgery. We aimed to determine if a qualitative difference in ultrasound imaging of the interscalene brachial plexus exists in relation to the timing of performing an interscalene nerve block (preoperative or postoperative).

Methods
This single-center, prospective observational study compared pre- and postoperative interscalene brachial plexus ultrasound images of 29 patients undergoing shoulder arthroscopy using a pretest-posttest methodology where individual patients served as their own controls. Three fellowship-trained regional anesthesiologists evaluated image quality and confidence in performing a block for each ultrasound scan using a five-point Likert scale. The association of image quality with age, gender, BMI, duration of surgery, obstructive sleep apnea, and volume of arthroscopic irrigation fluid were analyzed as secondary outcomes.

Results
Aggregate preoperative mean scores in quality of ultrasound visualization were higher than postoperative scores (preoperative 4.5 vs postoperative 3.8; p < .001), as was confidence in performing blockade based upon the imaging (preoperative 4.8 vs postoperative 4.2; p < .001). Larger BMI negatively affected visualization of the brachial plexus in the preoperative period (p < 0.05 for both weight categories). Patients with intermediate-high risk or confirmed obstructive sleep apnea had lower aggregate postoperative mean scores compared to the low-risk group for both ultrasound visualization (3.4 vs 4.0; p < .05) and confidence in block performance (3.8 vs 4.4; p < .05).

Conclusion
Due to the potential reduction of ultrasound visualization of the interscalene brachial plexus after shoulder arthroscopy, we advocate for a preoperative interscalene nerve block when feasible.

Trial registration
ClinicalTrials.gov (NCT03657173; September 4, 2018).
Simultaneous heart-kidney transplantation results in respectable long-term outcome but a high rate of early kidney graft loss in high-risk recipients – a European single center analysis
Authors: Beetz Oliver , Thies Juliane , Weigle Clara A. , Ius Fabio , Winkler Michael , Bara Christoph , Richter Nicolas , Klempnauer Jürgen , Warnecke Gregor , Haverich Axel , Avsar Murat , Grannas Gerrit 
Published: July 2021

Abstract
Background
In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization.

Methods
This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe’s largest transplant centers.

Results
Median follow-up was 100.33 (0.46–362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%).

Conclusions
Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a “kidney-after-heart” program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.
Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case
Authors: Sugiyama Atsuhiko , Takeda Takahiro , Koide Mizuho , Yokota Hajime , Mukai Hiroki , Kitayama Yoshihisa , Shibuya Kazumoto , Araki Nobuyuki , Ishikawa Ai , Isose Sagiri , Ito Kimiko , Honda Kazuhiro , Yamanaka Yoshitaka , Sano Terunori , Saito Yuko , Arai Kimihito , Kuwabara Satoshi 
Published: July 2021

Abstract
Background
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS.

Case presentation
A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient.

Conclusions
We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.