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Triple-negative breast cancer (TNBC) has the highest rate of distant metastasis and poorest overall survival among breast cancer subtypes. In a phase II study, adagloxad simolenin (AdaSim), a synthetic Globo H conjugate vaccine administered with adjuvant OBI-821, was shown to induce IgM and IgG anti-Globo H humoral responses in patients with metastatic breast cancer overexpressing the glycosphingolipid Globo H. GLORIA is an ongoing phase III, randomized, open-label clinical trial to evaluate the safety and efficacy of AdaSim and the quality of life (QoL) of patients receiving AdaSim plus standard of care (SOC) versus SOC alone in high-risk, early-stage TNBC. The primary end point is invasive progression-free survival; secondary end points include overall survival, QoL, breast cancer-free interval, distant disease-free survival, safety, and tolerability.

High-mountain plant communities are strongly determined by abiotic conditions, especially low temperature, and are therefore susceptible to effects of climate warming. Rising temperatures, however, also lead to increased evapotranspiration, which, together with projected shifts in seasonal precipitation patterns, could lead to prolonged, detrimental water deficiencies. The current study aims at comparing alpine plant communities along elevation and water availability gradients from humid conditions (north-eastern Alps) to a moderate (Central Apennines) and a pronounced dry period during summer (Lefka Ori, Crete) in the Mediterranean area. We do this in order to (1) detect relationships between community-based indices (plant functional leaf and growth traits, thermic vegetation indicator, plant life forms, vegetation cover and diversity) and soil temperature and snow duration and (2) assess if climatic changes have already affected the vegetation, by determining directional changes over time (14-year period; 2001-2015) in these indices in the three regions. Plant community indices responded to decreasing temperatures along the elevation gradient in the NE-Alps and the Apennines, but this elevation effect almost disappeared in the summer-dry mountains of Crete. This suggests a shift from low-temperature to drought-dominated ecological filters. Leaf trait (Leaf Dry Matter Content and Specific Leaf Area) responses changed in direction from the Alps to the Apennines, indicating that drought effects already become discernible at the northern margin of the Mediterranean. Over time, a slight increase in vegetation cover was found in all regions, but thermophilisation occurred only in the NE-Alps and Apennines, accompanied by a decline of cold-adapted cushion plants in the Alps. On Crete, xeromorphic shrubs were increasing in abundance. Although critical biodiversity losses have not yet been observed, an intensified monitoring of combined warming-drought impacts will be required in view of threatened alpine plants that are either locally restricted in the south or weakly adapted to drought in the north., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Premise: Examining community turnover across climate gradients at multiple scales is vital to understanding biogeographic response to climate change. This approach is especially important for alpine plants in which the relative roles of topographic complexity and nonclimatic or stochastic factors vary across spatial scales., Methods: We examined the structure of alpine plant communities across elevation gradients in the White Mountains, California. Using community climatic niche means (CCNMs) and measures of community dissimilarity, we explored the relation between community composition and elevation gradients at three scales: the mountain range, individual peaks, and within elevation contours., Results: At the mountain range scale, community turnover and CCNMs showed strongly significant relations with elevation, with an increase in the abundance of cooler and wetter-adapted species at higher elevations. At the scale of single peaks, we found weak and inconsistent relations between CCNMs and elevation, but variation in community composition explained by elevation increased. Within the elevation contours, the range of CCNMs was weakly positively correlated with turnover in species identity, likely driven by microclimate and other site-specific factors., Conclusions: Our results suggest that there is strong environmental sorting of alpine plant communities at broad scales, but microclimatic and site-specific, nonclimatic factors together shape community turnover at finer scales. In the context of climate change, our results imply that community-climate relations are scale-dependent, and predictions of local alpine plant range shifts are limited by a lack of topoclimatic and habitat information., (© 2019 Botanical Society of America.)

While vegetation has intensively been surveyed on mountain summits, limited knowledge exists about the diversity and community structure of soil biota. Here, we study how climatic variables, vegetation, parent material, soil properties, and slope aspect affect the soil microbiome on 10 GLORIA (Global Observation Research Initiative in Alpine environments) mountain summits ranging from the lower alpine to the nival zone in Switzerland. At these summits we sampled soils from all four aspects and examined how the bacterial and fungal communities vary by using Illumina MiSeq sequencing. We found that mountain summit soils contain highly diverse microbial communities with a total of 10,406 bacterial and 6,291 fungal taxa. Bacterial α-diversity increased with increasing soil pH and decreased with increasing elevation, whereas fungal α-diversity did not change significantly. Soil pH was the strongest predictor for microbial β-diversity. Bacterial and fungal community structures exhibited a significant positive relationship with plant communities, indicating that summits with a more distinct plant composition also revealed more distinct microbial communities. The influence of elevation was stronger than aspect on the soil microbiome. Several microbial taxa responded to elevation and soil pH. Chloroflexi and Mucoromycota were significantly more abundant on summits at higher elevations, whereas the relative abundance of Basidiomycota and Agaricomycetes decreased with elevation. Most bacterial OTUs belonging to the phylum Acidobacteria were indicators for siliceous parent material and several OTUs belonging to the phylum Planctomycetes were associated with calcareous soils. The trends for fungi were less clear. Indicator OTUs belonging to the genera Mortierella and Naganishia showed a mixed response to parent material, demonstrating their ubiquitous and opportunistic behaviour in soils. Overall, fungal communities responded weakly to abiotic and biotic factors. In contrast, bacterial communities were strongly influenced by environmental changes suggesting they will be strongly affected by future climate change and associated temperature increase and an upward migration of vegetation. Our results provide the first insights into the soil microbiome of mountain summits in the European Alps that are shaped as a result of highly variable local environmental conditions and may help to predict responses of the soil biota to global climate change.

Premise of the Study: With biodiversity and rates of climate change among the highest, the eastern Himalaya are critical for understanding the interaction of these two variables. However, there is a dearth of longitudinal data sets that address the effects of climate change on the exceptional alpine biodiversity of the Himalaya., Methods: We established permanent alpine vegetation monitoring plots in three mountain chains of the Hengduan Mountains, the easternmost Himalaya, which have warmed 0.03-0.05°C yr -1 since 1985. Recently, we resampled plots (176 1-m 2 quadrat plots and 88 sections of 11 summits in three Hengduan mountain chains) to measure changes in vegetation after 7 years., Key Results: Over 7 years, Tibetan alpine vegetation increased in number of species (+8 species/summit; +2.3 species/m 2 ), in frequency (+47.8 plants/m 2 ), and in diversity (+1.6 effective species/m 2 ). Stepwise regressions indicated that warmer temperatures, southerly aspects, and higher elevations were associated with greater increases in these vegetation metrics. Unexpectedly, Himalayan endemic species increased (+1.4 species/m 2 ; +8.5 plants/m 2 ), especially on higher-elevation summits. In contrast, the increase in relative abundance of non-alpine species was greater at lower-elevation summits. Plants used by local Tibetans also increased (+1.3 species/m 2 ; +32 plants/m 2 )., Conclusions: As in other alpine areas, biodiversity is increasing with climate change in the Himalaya. Unlike other areas, endemic species are proliferating at the highest summits and are indicators of change., (© 2019 Botanical Society of America.)

Background: Continuous delivery of levodopa-carbidopa intestinal gel (LCIG) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease (PD) patients., Objective: To compare the effectiveness and safety of LCIG monotherapy vs polytherapy in patients in the GLORIA registry., Methods: This was a post hoc analysis of a 24-month, multinational observational registry where advanced PD patients with persistent motor complications received LCIG (with adjunctive PD treatment, as necessary). Patients were categorized retrospectively into three stable treatment groups: LCIG monotherapy, LCIG in combination with oral levodopa only ("levodopa monotherapy" [including nighttime oral levodopa]), or LCIG in combination with any other antiparkinsonian medication ("LCIG polytherapy")., Results: Of 356 patients, 208 were on stable regimens (LCIG monotherapy n = 80; levodopa monotherapy n = 47; LCIG polytherapy n = 81). Baseline characteristics were similar across groups. LCIG monotherapy showed significant improvements until month 18 in activities of daily living and quality of life, and until month 24 for Unified Parkinson's Disease Rating Scale (UPDRS) motor examination (p < 0.05), "Off" time (p < 0.001), "On" time with dyskinesia (p < 0.01), and non-motor symptoms (p < 0.01). More patients in the levodopa monotherapy and LCIG polytherapy groups experienced treatment-related adverse drug reactions (ADRs) including dyskinesias and serious ADRs than did patients in the LCIG monotherapy group. There were few polyneuropathy-related ADRs, of which one case of polyneuropathy led to discontinuation from the Levodopa monotherapy group., Conclusions: These data demonstrate that LCIG monotherapy is an effective treatment option in appropriate advanced PD patients; however, definitive baseline clinical predictors identifying patients who can discontinue concomitant oral therapy have not yet been defined.

High mountain ecosystems and their biota are governed by low-temperature conditions and thus can be used as indicators for climate warming impacts on natural ecosystems, provided that long-term data exist. We used data from the largest alpine to nival permanent plot site in the Alps, established in the frame of the Global Observation Research Initiative in Alpine Environments (GLORIA) on Schrankogel in the Tyrolean Alps, Austria, in 1994, and resurveyed in 2004 and 2014. Vascular plant species richness per plot increased over the entire period, albeit to a lesser extent in the second decade, because disappearance events increased markedly in the latter period. Although presence/absence data could only marginally explain range shift dynamics, changes in species cover and plant community composition indicate an accelerating transformation towards a more warmth-demanding and more drought-adapted vegetation, which is strongest at the lowest, least rugged subsite. Divergent responses of vertical distribution groups of species suggest that direct warming effects, rather than competitive displacement, are the primary causes of the observed patterns. The continued decrease in cryophilic species could imply that trailing edge dynamics proceed more rapidly than successful colonisation, which would favour a period of accelerated species declines., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)

Classical approaches to investigating temporal and spatial changes in community composition offer only partial insight into the ecology that drives species distribution, community patterns and processes, whereas a functional approach can help to determine many of the underlying mechanisms that drive such patterns. Here, we aim to bring these two approaches together to understand such drivers, using an elevation gradient of sites, a repeat species survey and species functional traits. We used data from a repeat vegetation survey on five alpine summits and measured plant height, leaf area, leaf dry matter content and specific leaf area (SLA) for every species recorded in the surveys. We combined species abundances with trait values to produce a community trait-weighted mean (CTWM) for each trait, and then combined survey results with the CTWMs. Across the gradient of summits, more favourable conditions for plant growth (warmer, longer growing season) occurred at the lower elevations. Vegetation composition changes between 2004 and 2011 (according to non-metric multi-dimensional scaling ordination) were strongly affected by the high and increasing abundance of species with high SLA at high elevations. Species life-form categories strongly affected compositional changes and functional composition, with increasing dominance of tall shrubs and graminoids at the lower-elevation summits, and an overall increase in graminoids across the gradient. The CTWM for plant height and leaf dry matter content significantly decreased with elevation, whereas for leaf area and SLA it significantly increased. The significant relationships between CTWM and elevation may suggest specific ecological processes, namely plant competition and local productivity, influencing vegetation preferentially across the elevation gradient, with the dominance of shrubs and graminoids driving the patterns in the CTWMs.