bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti–PD-1 Antibody, in Advanced Solid Tumors
Authors: Curigliano Giuseppe , Gelderblom Hans , Mach Nicolas , Doi Toshihiko , Tai David , Forde Patrick M. , Sarantopoulos John , Bedard Philippe L. , Lin Chia-Chi , Hodi F. Stephen , Wilgenhof Sofie , Santoro Armando , Sabatos-Peyton Catherine A. , Longmire Tyler A. , Xyrafas Alexandros , Sun Haiying , Gutzwiller Sabine , Manenti Luigi , Naing Aung 
Published: April 2021

Abstract

Purpose:
Sabatolimab (MBG453) and spartalizumab are mAbs that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programmed death-1 (PD-1), respectively. This phase I/II study evaluated the safety and efficacy of sabatolimab, with or without spartalizumab, in patients with advanced solid tumors.

Patients and Methods:
Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended phase II dose (RP2D) for future studies. Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20 to 1,200 mg, every 2 or 4 weeks (Q2W or Q4W). Spartalizumab was administered intravenously, 80 to 400 mg, Q2W or Q4W.

Results:
Enrolled patients (n = 219) had a range of cancers, most commonly ovarian (17%) and colorectal cancer (7%); patients received sabatolimab (n = 133) or sabatolimab plus spartalizumab (n = 86). The MTD was not reached. The most common adverse event suspected to be treatment-related was fatigue (9%, sabatolimab; 15%, combination). No responses were seen with sabatolimab. Five patients receiving combination treatment had partial responses (6%; lasting 12–27 months) in colorectal cancer (n = 2), non–small cell lung cancer (NSCLC), malignant perianal melanoma, and SCLC. Of the five, two patients had elevated expression of immune markers in baseline biopsies; another three had &gt;10% TIM-3–positive staining, including one patient with NSCLC who received prior PD-1 therapy.

Conclusions:
Sabatolimab plus spartalizumab was well tolerated and showed preliminary signs of antitumor activity. The RP2D for sabatolimab was selected as 800 mg Q4W (alternatively Q3W or Q2W schedules, based on modeling), with or without 400 mg spartalizumab Q4W.
Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer
Authors: Malone Clare F. , Dharia Neekesh V. , Kugener Guillaume , Forman Alexandra B. , Rothberg Michael V. , Abdusamad Mai , Gonzalez Alfredo , Kuljanin Miljan , Robichaud Amanda L. , Conway Amy Saur , Dempster Joshua M. , Paolella Brenton R. , Dumont Nancy , Hovestadt Volker , Mancias Joseph D. , Younger Scott T. , Root David E. , Golub Todd R. , Vazquez Francisca , Stegmaier Kimberly 
Published: April 2021

Abstract

Cancer dependency maps, which use CRISPR/Cas9 depletion screens to profile the landscape of genetic dependencies in hundreds of cancer cell lines, have identified context-specific dependencies that could be therapeutically exploited. An ideal therapy is both lethal and precise, but these depletion screens cannot readily distinguish between gene effects that are cytostatic or cytotoxic. Here, we use a diverse panel of functional genomic screening assays to identify NXT1 as a selective and rapidly lethal in vivo relevant genetic dependency in MYCN-amplified neuroblastoma. NXT1 heterodimerizes with NXF1, and together they form the principal mRNA nuclear export machinery. We describe a previously unrecognized mechanism of synthetic lethality between NXT1 and its paralog NXT2: their common essential binding partner NXF1 is lost only in the absence of both. We propose a potential therapeutic strategy for tumor-selective elimination of a protein that, if targeted directly, is expected to cause widespread toxicity.

Significance:
We provide a framework for identifying new therapeutic targets from functional genomic screens. We nominate NXT1 as a selective lethal target in neuroblastoma and propose a therapeutic approach where the essential protein NXF1 can be selectively eliminated in tumor cells by exploiting the NXT1–NXT2 paralog relationship.
See related commentary by Wang and Abdel-Wahab, p. 2129.
This article is highlighted in the In This Issue feature, p. 2113
Populism and Environmental Performance
Authors: Böhmelt Tobias 
Published: April 2021

AbstractThis article examines the impact of populism on environmental politics, focusing on countries’ outcome-level performance. I develop the argument that populist leadership likely undermines environmental quality. First, populist leaders tend to reject and refrain from implementing “green” policies, as these are usually promoted by “corrupt elites.” Second, populism erodes democratic institutions, thus offsetting a series of mechanisms that are related to better environmental outcomes. Empirically, I combine data from the Global Populism Database covering sixty-six countries and more than two hundred executive leaders with information on environmental performance at the outcome level. The findings suggest that populist leadership is strongly linked to lower environmental performance—also when controlling for a series of alternative influences and distinguishing between left- and right-wing populism. This research greatly adds to our understanding of the determinants of environmental policies, the role of regime type and ideology, and the literature on populism.
WikiAsp: A Dataset for Multi-domain Aspect-based Summarization
Authors: Hayashi Hiroaki , Budania Prashant , Wang Peng , Ackerson Chris , Neervannan Raj , Neubig Graham 
Published: April 2021

AbstractAspect-based summarization is the task of generating focused summaries based on specific points of interest. Such summaries aid efficient analysis of text, such as quickly understanding reviews or opinions from different angles. However, due to large differences in the type of aspects for different domains (e.g., sentiment, product features), the development of previous models has tended to be domain-specific. In this paper, we propose WikiAsp,1 a large-scale dataset for multi-domain aspect- based summarization that attempts to spur research in the direction of open-domain aspect-based summarization. Specifically, we build the dataset using Wikipedia articles from 20 different domains, using the section titles and boundaries of each article as a proxy for aspect annotation. We propose several straightforward baseline models for this task and conduct experiments on the dataset. Results highlight key challenges that existing summarization models face in this setting, such as proper pronoun handling of quoted sources and consistent explanation of time-sensitive events.
Courtship rhythm in Nasonia vitripennis is affected by the clock gene period
Authors: Dalla Benetta Elena , van de Zande Louis , Beukeboom Leo W. 
Published: April 2021

Abstract
The clock gene period (per) is a regulator of circadian rhythms but may also play a role in the regulation of ultradian rhythms, such as insect courtship. Males of the parasitoid wasp Nasonia vitripennis court females by performing series of head movements (‘head-nods’) and wing vibrations within repeated cycles. The pattern of cycle duration and head-nod number is species-specific and has a genetic basis. In this study, the possible involvement of per in regulating Nasonia courtship rhythms was investigated in a southern and northern European strain that differ in number and timing of courtship components. Knockdown of per via RNA interference (RNAi) resulted in a shortening of the circadian free running period (tau) in constant darkness (DD), and increased both the cycle duration and the number of head-nods per cycle in both strains. These results point at a role of per in the regulation of ultradian rhythms and male courtship behaviour of N. vitripennis and may contribute to resolving the controversy about the role of per in insect courtship behaviour.
Effects of Audiovisual Presentations on Visual Localization Errors: One or Several Multisensory Mechanisms?
Authors: Nazaré Cristina Jordão , Oliveira Armando Mónica 
Published: April 2021

Abstract
The present study examines the extent to which temporal and spatial properties of sound modulate visual motion processing in spatial localization tasks. Participants were asked to locate the place at which a moving visual target unexpectedly vanished. Across different tasks, accompanying sounds were factorially varied within subjects as to their onset and offset times and/or positions relative to visual motion. Sound onset had no effect on the localization error. Sound offset was shown to modulate the perceived visual offset location, both for temporal and spatial disparities. This modulation did not conform to attraction toward the timing or location of the sounds but, demonstrably in the case of temporal disparities, to bimodal enhancement instead. Favorable indications to a contextual effect of audiovisual presentations on interspersed visual-only trials were also found. The short sound-leading offset asynchrony had equivalent benefits to audiovisual offset synchrony, suggestive of the involvement of early-level mechanisms, constrained by a temporal window, at these conditions. Yet, we tentatively hypothesize that the whole of the results and how they compare with previous studies requires the contribution of additional mechanisms, including learning-detection of auditory-visual associations and cross-sensory spread of endogenous attention.
‘Our Traditions Will Kill Us!’: Negotiating Marriage Celebrations in the Face of Legal Regulation of Tradition in Tajikistan
Authors: Borisova Elena 
Published: April 2021

Abstract
Based on extensive ethnographic research in northern Tajikistan, this article examines the implications of the law ordering traditions and rituals (tanzim), including marriage celebrations, in Tajikistan. At the centre of my analysis is the figure of a state employed ‘worker of culture’, Farkhod, whose family was affected by recent, rather militant, attempts by the state to regulate tradition. By following the story of his daughter’s wedding, I analyse how Farkhod tries to reconcile his roles of a caring father, a respectful community member, and a law-abiding citizen. I argue that the tanzim exacerbates the mismatch between the government’s attempts to impose a rigid notion of tradition and promote the idea of a certain kind of modern citizen, and people’s own understandings of being a modern and moral person having a good wedding.
With or Without You: Qing, Li, Fa, and Legal Pluralism in China
Authors: Liu Qian 
Published: April 2021

Abstract
The concept of legal pluralism was introduced to China in the mid-1990s to address the conflict between state law and local norms and customs. More than two decades after its introduction, the scope of legal pluralism in China has shifted to the coexistence and interaction between state law and nonstate orders. In this article, I review theoretical discussions and empirical studies on legal pluralism in China. The existing studies on legal pluralism focus mostly on rural villages, which marginalizes the lived experience of urban residents who are also caught in China’s rapid legal transplantation in recent decades. At the same time, law and society scholars who study labor dispute resolution in urban China tend to frame the questions as legal mobilization, rather than legal pluralism. The term qingli 情理[commonsense feelings of justice] is a common theme underlying the scholarship of legal pluralism and legal mobilization in China, and thus it has the potential to bring them together and bridge the findings of the two bodies of scholarship. This article contributes to the literature on Chinese law and society by demonstrating the role that qingli plays in bridging different areas of sociolegal studies.
Prognostic Factors for the Outcome of Salivary Gland Holmium: YAG Laser Intraductal Lithotripsy
Authors: Wang Shuo-Jen , Chen Lung-Che , Lin Yi-Chih , Chen Yen-Chun , Dang Luong Huu , Chen Po-Yueh , Su Chin-Hui , Hung Shih-Han 
Published: April 2021

Objectives: Holmium: YAG laser has gained its popularity throughout the years and is used to treat sialolithiasis, which helps to overcome the limitations of traditional sialendoscopic lithotripsy for larger-sized salivary stones. However, little information is available regarding factors predicting the success rate of Holmium: YAG laser intraductal lithotripsy. The purpose of this study is to investigate the factors affecting the success rates of Holmium: YAG laser lithotripsy for salivary stones treatment in a tertiary care hospital. Methods: A retrospective study conducted in patients receiving sialolithiasis surgery under sialendoscopy from May 2013 to March 2015 at Mackay Memorial Hospital, Taiwan. Data on various factors, including patients’ age, gender, glands, size of largest stone, multiple stones (≥2 stones), location of the stone (distal duct, middle duct, proximal duct, and hilum), and operative time. The success of the surgery defined as patients without any complaints such as swelling or tenderness. Logistic regression and Fisher exact tests were employed to examine these factors on the success rate. Results: Fifty-four patients who received sialendoscopy surgery with a mean age of 35.74 years old recruited. Logistic regression identified the operation time exceeding 210 minutes showed 23.497 folds higher odd ratio of having a result of operation failure ( P < .05). Conclusion: The prolonged operation time is the sole independent factor affecting the successful outcome for salivary gland intraductal laser lithotripsy. We recommend operative time be no more than 210 minutes to increase the success rate in salivary gland Holmium: YAG laser intraductal lithotripsy.
Determinants of Anthropometric Failure Among Tribal Children Younger than 5 Years of Age in Palghar, Maharashtra, India
Authors: Jeyakumar Angeline , Godbharle Swapnil , Giri Bibek Raj 
Published: April 2021

Background: Measuring undernutrition using composite index of anthropometric failure (CIAF) and identifying its determinants in tribal regions is essential to recognize the true burden of undernutrition in these settings. Objective: To determine anthropometric failure and its determinants among tribal children younger than 5 years in Palghar, Maharashtra, India. Methods: A cross-sectional survey employing CIAF was performed in children <5 years to estimate undernutrition in the tribal district of Palghar in Maharashtra, India. Anthropometric measurements, maternal and child characteristics were recorded from 577 mother–child pairs in 9 villages. Results: As per Z score, prevalence of stunting, wasting, and underweight were 48%, 13%, and 43%, respectively. According to CIAF, 66% of children had at least one manifestation of undernutrition and 40% had more than one manifestation of undernutrition. Odds of anthropometric failure were 1.5 times higher among children of mothers who were illiterate (adjusted odds ratio [AOR] =1.57, 95% CI: 1.0-2.3), children who had birth weight >2.5 kg had lesser odds (AOR: 0.63, 95% CI: 0.4-0.9) of anthropometric failure, and children who had initiated early breastfeeding had 1.5 times higher odds of anthropometric failure (crude odds ratio: 1.5, 95% CI: 1.0-2.1). However, when adjusted for other independent variables, the results were not significant. Conclusion: The alarming proportion of anthropometric failure among tribal children calls for urgent short-term interventions to correct undernutrition and long-term interventions to improve maternal literacy and awareness to prevent and manage child undernutrition.
When Communities Pull Their Weight: The Economic Costs of an Integrated Agriculture and Nutrition Home-Grown Preschool Meal Intervention in Malawi
Authors: Margolies Amy , Gelli Aulo , Daryanani Roshan , Twalibu Aisha , Levin Carol 
Published: April 2021

Background: Community-based preschool meals can provide an effective platform for implementing integrated agriculture and nutrition programs. However, there is little evidence on the costs and cost-efficiency of implementing these types of multisectoral interventions. Objectives: Assess the economic costs and cost-efficiency of implementing an effective integrated nutrition-sensitive intervention through a preschool platform in Malawi, including community-level contributions. Methods: The Strengthening Economic Evaluation for Multisectoral Strategies for Nutrition (SEEMS-Nutrition) framework and methods were applied to assess financial and economic costs of the intervention. A mixed-methods approach was used to measure and allocate costs for program activities and inputs using financial expenditure data combined with micro-costing. All costs were allocated to input and expenditure categories using the SEEMS-Nutrition framework. To facilitate comparisons with existing school meals programs, activities were also mapped against a standardized school feeding supply chain framework. Results: The total annualized cost of the program was US$197 377, inclusive of both financial and economic costs. The annual economic cost of the program ranged from US$160 per preschool child to US$41 per beneficiary. The principal drivers of cost by program activity were training (46%), school meals provision (19%), monitoring and evaluation (12%), and establishing and running community groups (6.5%). Notably, community contributions accounted for 25% and were driven by food donations and volunteer labor. Conclusions: Cost per beneficiary estimates of implementing an integrated agriculture–nutrition intervention through an early childhood development platform compare favorably with similar interventions. Further research is needed that applies a standardized economic evaluation framework to such multisectoral interventions.
Correlation between adolescent orthodontic quality of life and ABO Discrepancy Index in an orthodontic treatment-seeking population: A cross-sectional study
Authors: Swan Matthew , Tabbaa Sawsan , Buschang Peter , Toubouti Youssef , Bashir Rehana 
Published: April 2021

Objective: To evaluate the association between adolescents’ orthodontic quality of life before initiating orthodontic treatment and their objective case complexity as measured by the American Board of Orthodontics’ Discrepancy Index (DI). Design and setting: A single-centre, cross-sectional survey study. Methods: The Orthodontic Quality of Life Assessment Survey (OQoLAS) was administered to 240 adolescents (aged 11–14 years) during their record-gathering appointment. After completion of the survey, a DI score was calculated for each patient based on pretreatment measurements. Pearson correlation coefficients, r, were used to assess the association of DI scores with OQoLAS total and subdomain scores. A multiple linear regression of OQoLAS total scores adjusting for age, gender and DI scores was conducted. Results: The study did not find a strong correlation between OQoLAS and DI scores (r = 0.10; P = 0.6497). On average, the OQoLAS scores (functional, emotional and social subdomains of OQoLAS) were slightly higher among girls than among boys but there was no statistical difference for total OQoLAS score between boys and girls (42.4 vs. 45.4, P = 0.2005). However, there was a significant difference in oral health perception rating between boys and girls, with girls being more likely to rate their oral health positively (adjusted P = 0.0226). The total DI scores of boys with respect to girls were not statistically different ( P = 0.4256). The components of the DI that showed highest score were for cephalometric measures, followed by overjet; and the lowest scores were for lateral open bite and buccal posterior crossbite. The measure of association analysis did not show any strong correlation between the OQoLAS (total score and subdomain scores), and DI score or any of its components. Conclusion: Malocclusion severity was not found to be correlated with orthodontic quality of life in adolescents aged 11–14 years seeking orthodontic treatment.
The case for skin camouflage in the management of upper limb scarring – A case series
Authors: Adamson Laura , Selby Anna 
Published: April 2021

Introduction For some people the appearance of their hands is as important as function. Upper limb scarring can cause some patients distress. Skin camouflage is an intervention that can be used to reduce the visual impact of a scar but there is limited published evidence for its use for hand scarring. Methods This is a case series study with a primary objective to determine whether skin camouflage reduces distress in patients with an upper limb scar and to evaluate this new service. Patients experiencing distress from an upper limb scar were recruited from a hand therapy outpatient clinic. The intervention delivered was a one hour skin camouflage session. Photographs of the upper limb pre and post skin camouflage intervention were taken. The patient-rated Michigan Hand Questionnaire (MHQ) and Derriford Appearance Scale (DAS24) were completed before treatment, at 1 week and 1 month after treatment. Results Six participants reporting distress from an upper limb scar received skin camouflage intervention. Only three out of six participants completed all follow-up. All three showed improvement in at least two domains of the MHQ (function and aesthetics) at one month post treatment. Increased confidence during functional and work-based activities was also reported on the DAS24. Participants reported increased engagement in daily activities as a result of being able to camouflage their scars. Conclusions This small case series shows that skin camouflage intervention may be beneficial for some patients who are experiencing distress related to an upper limb scar by increasing function and self-confidence.
IGVL gene region usage correlates with distinct clinical presentation in IgM vs non-IgM light chain amyloidosis
Authors: Sidana Surbhi , Dasari Surendra , Kourelis Taxiarchis V. , Dispenzieri Angela , Murray David L. , King Rebecca L. , McPhail Ellen D. , Ramirez-Alvarado Marina , Kumar Shaji K. , Gertz Morie A. 
Published: April 2021

Abstract
Patients with immunoglobulin M (IgM) light chain (AL) amyloidosis have a distinct clinical presentation compared with those with non-IgM amyloidosis. We hypothesized that differential immunoglobulin light-chain variable region (IGVL) gene usage may explain the differences in organ involvement, because IGVL usage correlates with organ tropism. IGVL usage was evaluated by mass spectrometry of amyloid deposits (IgM, n = 45; non-IgM, n = 391) and differed across the 2 groups. In the λ family, LV2-08 (13% vs 2%; P &lt; .001) and LV2-14 (36% vs 10%; P &lt; .001) usage was more common in IgM vs non-IgM amyloidosis, whereas LV1-44 (0% vs 10%; P = .02) and LV6-57 (2% vs 18%; P = .004) usage was less common. In the κ family, there was a trend toward higher KV4-01 (11% vs 4%; P = .06) usage in IgM amyloidosis. IGVL usage correlated with disease characteristics/organ tropism. LV2-14 (more common in IgM amyloidosis) has historically been associated with peripheral nerve involvement and lower light chain burden, which were more frequent in IgM amyloidosis. LV1-44 (less common in IgM), associated with cardiac involvement, was less frequent in IgM patients. LV6-57 (less common in IgM) is associated with t(11;14), which was less frequent in IgM patients. In conclusion, IGVL gene usage differs in patients with IgM vs non-IgM amyloidosis and may explain the distinct clinical presentation.