bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: a systematic literature review
Authors: Ugarte-Gil Manuel Francisco , Mendoza-Pinto Claudia , Reátegui-Sokolova Cristina , Pons-Estel Guillermo J. , van Vollenhoven Ronald F , Bertsias George , Alarcon Graciela S. , Pons-Estel Bernardo A 
Published: September 2021

BackgroundRemission and low disease activity (LDA) have been proposed as the treatment goals for patients with systemic lupus erythematosus (SLE). Several definitions for each have been proposed in the literature.ObjectiveTo assess the impact of remission/LDA according to various definitions on relevant outcomes in patients with SLE.MethodsThis systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using PubMed (1946–week 2, April 2021), Cochrane library (1985–week 2, week 2, April 2021) and EMBASE (1974–week 2, April 2021). We included longitudinal and cross-sectional studies in patients with SLE reporting the impact of remission and LDA (regardless their definition) on mortality, damage accrual, flares, health-related quality of life and other outcomes (cardiovascular risk, hospitalisation and direct costs). The quality of evidence was evaluated using the Newcastle-Ottawa Scale.ResultsWe identified 7497 articles; of them, 31 studies met the inclusion criteria and were evaluated. Some articles reported a positive association with survival, although this was not confirmed in all of them. Organ damage accrual was the most frequently reported outcome, and remission and LDA were reported as protective of this outcome (risk measures varying from 0.04 to 0.95 depending on the definition). Similarly, both states were associated with a lower probability of SLE flares, hospitalisations and a better health-related quality of life, in particular the physical domain.ConclusionRemission and LDA are associated with improvement in multiple outcomes in patients with SLE, thus reinforcing their relevance in clinical practice.PROSPERO registration numberCRD42020162724.
Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension
Authors: Briot Karine , Portale Anthony A , Brandi Maria Luisa , Carpenter Thomas O , Cheong Hae Ii , Cohen-Solal Martine , Crowley Rachel K , Eastell Richard , Imanishi Yasuo , Ing Steven , Insogna Karl , Ito Nobuaki , Jan de Beur Suzanne , Javaid Muhammad K , Kamenicky Peter , Keen Richard , Kubota Takuo , Lachmann Robin H , Perwad Farzana , Pitukcheewanont Pisit , Ralston Stuart H , Takeuchi Yasuhiro , Tanaka Hiroyuki , Weber Thomas J , Yoo Han-Wook , Nixon Annabel , Nixon Mark , Sun Wei , Williams Angela , Imel Erik A 
Published: September 2021

ObjectivesTo report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks.MethodsAdults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT).ResultsSubjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks.ConclusionsAdults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function.Trial registration numberNCT02526160.
EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody–Drug Conjugate HER3–DXd
Authors: Haikala Heidi M. , Lopez Timothy , Köhler Jens , Eser Pinar O. , Xu Man , Zeng Qing , Teceno Tyler J. , Ngo Kenneth , Zhao Yutong , Ivanova Elena V. , Bertram Arrien A. , Leeper Brittaney A. , Chambers Emily S. , Adeni Anika E. , Taus Luke J. , Kuraguchi Mari , Kirschmeier Paul T. , Yu Channing , Shiose Yoshinobu , Kamai Yasuki , Qiu Yang , Paweletz Cloud P. , Gokhale Prafulla C. , Jänne Pasi A. 
Published: September 2021

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are the standard-of-care treatment for EGFR-mutant non–small cell lung cancers (NSCLC). However, most patients develop acquired drug resistance to EGFR TKIs. HER3 is a unique pseudokinase member of the ERBB family that functions by dimerizing with other ERBB family members (EGFR and HER2) and is frequently overexpressed in EGFR-mutant NSCLC. Although EGFR TKI resistance mechanisms do not lead to alterations in HER3, we hypothesized that targeting HER3 might improve efficacy of EGFR TKI. HER3–DXd is an antibody–drug conjugate (ADC) comprised of HER3-targeting antibody linked to a topoisomerase I inhibitor currently in clinical development. In this study, we evaluated the efficacy of HER3–DXd across a series of EGFR inhibitor–resistant, patient-derived xenografts and observed it to be broadly effective in HER3-expressing cancers. We further developed a preclinical strategy to enhance the efficacy of HER3–DXd through osimertinib pretreatment, which increased membrane expression of HER3 and led to enhanced internalization and efficacy of HER3–DXd. The combination of osimertinib and HER3–DXd may be an effective treatment approach and should be evaluated in future clinical trials in EGFR-mutant NSCLC patients.

Significance:
EGFR inhibition leads to increased HER3 membrane expression and promotes HER3–DXd ADC internalization and efficacy, supporting the clinical development of the EGFR inhibitor/HER3–DXd combination in EGFR-mutant lung cancer.
See related commentary by Lim et al., p. 18
Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy
Authors: Zhang Mingming , Zhou Linghui , Zhao Houli , Zhang Yanlei , Wei Guoqing , Hong Ruimin , Wu Wenjun , Xu Huijun , Wang Linqin , Ni Fang , Cui Jiazhen , Peng Shuixiu , Huang Chih-Hua , Chang Alex H. , Hu Yongxian , Huang He 
Published: September 2021

Abstract

Purpose:
B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown.

Patients and Methods:
Between July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis–associated risk factors.

Results:
Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and 4 cases of CRS grades 1 to 2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete remission (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the 1-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 50.2%, respectively. The median PFS was 12.7 months. Cox modeling revealed that poor PFS was associated with extramedullary disease [HR = 2.59, 95% confidence interval (95% CI) = 1.29–5.21, P = 0.008], light chain multiple myeloma (HR = 2.53, 95% CI = 1.03–5.97, P = 0.035), high-risk cytogenetics (HR = 2.80, 95% CI = 1.27–6.14, P = 0.01), and prior treatment with more than 3 therapeutic lines (HR = 3.14, 95% CI = 1.34–7.34, P = 0.008). Among the 41 CR cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR = 4.51, 95% CI = 1.86–10.9, P = 0.001), light chain multiple myeloma (HR = 4.89, 95% CI = 1.52 – 15.7, P = 0.008), or high-risk cytogenetics (HR = 5.09, 95% CI = 1.63–15.9, P = 0.005).

Conclusions:
Anti-BCMA CAR T-cell therapy is safe and effective for R/R multiple myeloma. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.
Making Industrial Policy Work for Decarbonization
Authors: Meckling Jonas 
Published: September 2021

AbstractIndustrial policy has begun to move into the center of debates on climate policy. This represents a shift away from climate policy as we know it—as classic environmental policy. Industrial policy and environmental policy differ in their policy goals, policy instruments, and distributional effects, one primarily concerned with economic development, the other with cutting greenhouse gas emissions. This raises questions about policy interactions between industrial and environmental policy in broader climate policy mixes and how these affect global decarbonization. This article identifies complementary and conflictual dynamics between industrial policy and environmental policy in both domestic and international climate politics. It shows how green industrial policy can advance climate goals and cooperation but can also present challenges to deepening climate cooperation and reducing greenhouse gas emissions. Developing an understanding of policy interactions is central to leveraging the potential of industrial policy to accelerate global decarbonization.
Dynamic Transitions between Neural States Are Associated with Flexible Task Switching during a Memory Task
Authors: Liu Wei , Kohn Nils , Fernández Guillén 
Published: September 2021

Abstract
Flexible behavior requires switching between different task conditions. It is known that such task switching is associated with costs in terms of slowed RT, reduced accuracy, or both. The neural correlates of task switching have usually been studied by requiring participants to switch between distinct task conditions that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e., memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a think/no-think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a no-think was preceded by a think trial instead of another no-think trial. Neurally, we demonstrate that think–no-think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task condition, assessed by decoding accuracy, were lower immediately after task switching compared with the nonswitch transitions, suggesting a switch-induced delay in the neural transition toward the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carryover of the previous task set activation is associated with the switching cost, leading to less successful memory suppression.
The Reading Signatures of Agreement Attraction
Authors: Lago Sol , Acuña Fariña Carlos , Meseguer Enrique 
Published: September 2021

Abstract
The comprehension of subject-verb agreement shows “attraction effects,” which reveal that number computations can be derailed by nouns that are grammatically unlicensed to control agreement with a verb. However, previous results are mixed regarding whether attraction affects the processing of grammatical and ungrammatical sentences alike. In a large-sample eye-tracking replication of Lago et al. (2015), we support this “grammaticality asymmetry” by showing that the reading profiles associated with attraction depend on sentence grammaticality. In ungrammatical sentences, attraction affected both fixation durations and regressive eye-movements at the critical disagreeing verb. Meanwhile, both grammatical and ungrammatical sentences showed effects of the attractor noun number prior to the verb, in the first- and second-pass reading of the subject phrase. This contrast suggests that attraction effects in comprehension have at least two different sources: the first reflects verb-triggered processes that operate mainly in ungrammatical sentences. The second source reflects difficulties in the encoding of the subject phrase, which disturb comprehension in both grammatical and ungrammatical sentences.
Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review
Authors: Cho Jiacai , Lee Joanne , Sia Ching-Hui , Koo Chieh Sian , Tan Benjamin YQ , Hong Weizhen , Choi Ellie , Goh Xueying , Chai Louis , Chandran Nisha Suyien , Chua Horng Ruey , Chan Bernard PL , Muthiah Mark , Low Ting Ting , Yap Eng Soo , Lahiri Manjari 
Published: September 2021

Introduction:
We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.

Methods:
We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.

Results:
169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.

Conclusion:
Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
Clinical audit of current Helicobacter pylori treatment outcomes in Singapore
Authors: Ang Tiing Leong , Lim Kim Wei , Ang Daphne , Wong Yu Jun , Tan Malcolm , Wong Andrew Siang Yih 
Published: September 2021

Introduction:

H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore.

Methods:
Clinical data of H. pylori-positive patientswho underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by 13C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI.

Results:
A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first-and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; P = 0.028). PAC was superior to PMC (P < 0.001) but similar to PBMT (P = 0.518) and PBAC (P = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; P = 0.674).

Conclusion:
First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.
Multiscale interactions between monsoon intra-seasonal oscillations and low pressure systems that produce heavy rainfall events of different spatial extents
Authors: Nikumbh Akshaya C , Chakraborty Arindam , Bhat G.S. , Frierson Dargan M. W. 
Published: September 2021

AbstractThe sub-seasonal and synoptic-scale variability of the Indian summer monsoon rainfall are controlled primarily by monsoon intra-seasonal oscillations (MISO) and low pressure systems (LPS), respectively. The positive and negative phases of MISO lead to alternate epochs of above-normal (active) and below-normal (break) spells of rainfall. LPSs are embedded within the different phases of MISO and are known to produce heavy precipitation events over central India. Whether the interaction with the MISO phases modulates the precipitation response of LPSs, and thereby the characteristics of extreme rainfall events (EREs) remains unaddressed in the available literature. In this study, we analyze the LPSs that produce EREs of various spatial extents viz., Small, Medium, and Large over central India from 1979 to 2012. We also compare them with the LPSs that pass through central India and do not give any ERE (LPS-noex). We find that thermodynamic characteristics of LPSs that trigger different spatial extents of EREs are similar. However, they show differences in their dynamic characteristics. The ERE producing LPSs are slower, moister and more intense than LPS-noex. The LPSs that lead to Medium and Large EREs tend to occur during the positive phase of MISO when an active monsoon trough is present over central India. On the other hand, LPS-noex and the LPSs that trigger Small EREs occur mainly during the neutral or negative phases of the MISO. The large-scale dynamic forcing, intensification of LPSs, and diabatic generation of low-level potential vorticity due to the presence of active monsoon trough help in the organization of convection and lead to Medium and Large EREs. On the other hand, the LPSs that form during the negative or neutral phases of MISO do not intensify much during their lifetime and trigger scattered convection, leading to EREs of small size.
Need for and Receipt of Substance Use Disorder Treatment Among Adults, by Gender, in the United States
Authors: Martin Caitlin E. , Parlier-Ahmad Anna Beth , Beck Lori , Scialli Anna , Terplan Mishka 
Published: September 2021

Objectives Disparities in substance use disorder (SUD) treatment use persist across groups, including gender. Using a gender-informed approach to expand treatment capacity and reduce barriers to treatment engagement is vital. We examined SUD treatment need and receipt among people with SUD in the United States, by gender, and assessed gender-specific sociodemographic factors associated with unmet need for SUD treatment and reported treatment barriers. Methods We conducted an analysis of data among adults aged ≥18 with a past-year SUD from the National Survey on Drug Use and Health (2015-2018). We computed population-adjusted frequencies and proportions for SUD treatment need and receipt and assessed gender differences. Multivariate logistic regression assessed gender-specific sociodemographic variables associated with SUD treatment receipt. Results Among adults with a past-year SUD, 63.4% were men and 36.6% were women ( P < .001), only 10.6% received SUD treatment, and a greater percentage of women than men needed treatment for opioid use disorder (11.9% vs 9.9%; P = .002). Receipt of SUD treatment was lowest among women with alcohol use disorder followed by men with alcohol use disorder (7.5% vs 8.9%; P = .052). Non-Latinx Black men had fewer than half the adjusted odds of receiving SUD treatment than non-Latinx White men (adjusted odds ratio [aOR] = 0.44; 95% CI, 0.27-0.71). Latinx women (aOR = 0.37; 95% CI, 0.18-0.73) and non-Latinx Black women (aOR = 0.51; 95% CI, 0.27-0.94) had significantly lower odds of receiving SUD treatment than non-Latinx White women. Conclusions As public health efforts target expanding SUD treatment capacity and addressing disparities in use of SUD treatment, interventions informed by gender and culture should be prioritized.
Outcomes of an Ear Camp Conducted in Bhutan by Thai Rural ENT Foundation—A Descriptive Study
Authors: Pradhan Umesh , Chindavijak Somjin , Tanamai Napas 
Published: September 2021

Background: The Thai Rural ENT foundation has been conducting ear camps in Bhutan for many years to address the shortage of ENT specialists in the kingdom where patients are examined and treated for various ear illnesses. However, there has been no study conducted to assess the outcomes of such camps. This is the first study of its kind to be carried out in Bhutan. Objective: To study the spectrum of ear cases seen during the mobile ear camp, the intervention done and treatment outcomes. Materials and Methods: The study enrolled patients with ear disorders who presented to the mobile ear camp at Monggar Regional Referral Hospital, Bhutan, from January 6, 2020, to January 8, 2020. The following data were recorded: demographic details, preoperative clinical symptoms and otoscopic findings, preoperative audiogram, treatment or surgery done, postoperative middle ear and mastoid infection, wound infection, graft condition, any complications, and postoperative audiogram of operated cases. Patients who underwent surgery were followed up at 1 day, 6 weeks, and 2 months postoperatively. Results: Two hundred ten patients presented with otologic conditions and 43 underwent surgeries. Otitis media was the commonest disease detected, and tympanoplasty was the commonest surgery performed. The tympanic membrane closure rate was 92.1%, and the rate of hearing improvement was 63.2%. Conclusion: The ear camp had beneficial effect and showed good results.