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Abstract Smart molecules have attracted increasing attention due to their transformative role in creating the next generation of smart structures and devices. Smart bistable coordination complexes are a class of functional complexes which have two stable states that can be reversibly switched in response to external stimuli. Such bistable molecules play a vital role in various applications, such as sensors, data storage, spintronics, smart windows, optical switches, information encryption and decryption, displays, actuators, etc. Herein, the recent research studies into the development of these smart bistable metal coordination complexes are reviewed. According to the different external stimuli, these smart bistable coordination systems have been classified and summarized, including light‐responsive systems, thermally‐responsive systems, electrically‐responsive systems, mechanically‐responsive systems, and some other cases. These systems are further subdivided according to the changes in signals (e.g., color, fluorescence, spin state, crystalline phase) under external stimuli. The design principles of each type of smart bistable metal complexes as well as their broad and innovative applications are comprehensively described. Finally, the challenges and opportunities in this field are briefly analyzed and discussed.

Abstract ALPN‐101 (ICOSL vIgD‐Fc) is an Fc fusion protein of a human inducible T cell costimulatory ligand (ICOSL) variant immunoglobulin domain (vIgD) designed to inhibit the cluster of differentiation 28 (CD28) and inducible T cell costimulator (ICOS) pathways simultaneously. A first‐in‐human study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ALPN‐101 in healthy adult subjects. ALPN‐101 was generally well‐tolerated with no evidence of cytokine release, clinically significant immunogenicity, or severe adverse events following single subcutaneous (SC) doses up to 3 mg/kg or single intravenous (IV) doses up to 10 mg/kg or up to 4 weekly IV doses of up to 1 mg/kg. ALPN‐101 exhibited a dose‐dependent increase in exposure with an estimated terminal half‐life of 4.3–8.6 days and SC bioavailability of 60.6% at 3 mg/kg. Minimal to modest accumulation in exposure was observed with repeated IV dosing. ALPN‐101 resulted in a dose‐dependent increase in maximum target saturation and duration of high‐level target saturation. Consistent with its mechanism of action, ALPN‐101 inhibited cytokine production in whole blood stimulated by Staphylococcus aureus enterotoxin B ex vivo, as well as antibody responses to keyhole limpet hemocyanin immunization, reflecting immunomodulatory effects upon T cell and T‐dependent B cell responses, respectively. In conclusion, ALPN‐101 was well‐tolerated in healthy subjects with dose‐dependent PK and PD consistent with the known biology of the CD28 and ICOS costimulatory pathways. Further clinical development of ALPN‐101 in inflammatory and/or autoimmune diseases is therefore warranted.

Abstract It has often been suggested that the productivity of an ecosystem affects the number of species that it can support. Despite decades of study, the nature, extent, and underlying mechanisms of this relationship are unclear. One suggested mechanism is the “more individuals” hypothesis (MIH). This proposes that productivity controls the number of individuals in the ecosystem, and that more individuals can be divided into a greater number of species before their population size is sufficiently small for each to be at substantial risk of extinction. Here, we test this hypothesis using REvoSim: an individual‐based eco‐evolutionary system that simulates the evolution and speciation of populations over geological time, allowing phenomena occurring over timescales that cannot be easily observed in the real world to be evaluated. The individual‐based nature of this system allows us to remove assumptions about the nature of speciation and extinction that previous models have had to make. Many of the predictions of the MIH are supported in our simulations: Rare species are more likely to undergo extinction than common species, and species richness scales with productivity. However, we also find support for relationships that contradict the predictions of the strict MIH: species population size scales with productivity, and species extinction risk is better predicted by relative than absolute species population size, apparently due to increased competition when total community abundance is higher. Furthermore, we show that the scaling of species richness with productivity depends upon the ability of species to partition niche space. Consequently, we suggest that the MIH is applicable only to ecosystems in which niche partitioning has not been halted by species saturation. Some hypotheses regarding patterns of biodiversity implicitly or explicitly overlook niche theory in favor of neutral explanations, as has historically been the case with the MIH. Our simulations demonstrate that niche theory exerts a control on the applicability of the MIH and thus needs to be accounted for in macroecology.

Abstract Resolution of relationships at lower taxonomic levels is crucial for answering many evolutionary questions, and as such, sufficiently varied species representation is vital. This latter goal is not always achievable with relatively fresh samples. To alleviate the difficulties in procuring rarer taxa, we have seen increasing utilization of historical specimens in building molecular phylogenies using high throughput sequencing. This effort, however, has mainly focused on large‐bodied or well‐studied groups, with small‐bodied and under‐studied taxa under‐prioritized. Here, we utilize both historical and contemporary specimens, to increase the resolution of phylogenetic relationships among a group of under‐studied and small‐bodied metazoans, namely, cheilostome bryozoans. In this study, we pioneer the sequencing of air‐dried cheilostomes, utilizing a recently developed library preparation method for low DNA input. We evaluate a de novo mitogenome assembly and two iterative methods, using the sequenced target specimen as a reference for mapping, for our sequences. In doing so, we present mitochondrial and ribosomal RNA sequences of 43 cheilostomes representing 37 species, including 14 from historical samples ranging from 50 to 149 years old. The inferred phylogenetic relationships of these samples, analyzed together with publicly available sequence data, are shown in a statistically well‐supported 65 taxa and 17 genes cheilostome tree, which is also the most broadly sampled and largest to date. The robust phylogenetic placement of historical samples whose contemporary conspecifics and/or congenerics have been sequenced verifies the appropriateness of our workflow and gives confidence in the phylogenetic placement of those historical samples for which there are no close relatives sequenced. The success of our workflow is highlighted by the circularization of a total of 27 mitogenomes, seven from historical cheilostome samples. Our study highlights the potential of utilizing DNA from micro‐invertebrate specimens stored in natural history collections for resolving phylogenetic relationships among species.

Abstract The period of disrupted human activity caused by the COVID‐19 pandemic, coined the “anthropause,” altered the nature of interactions between humans and ecosystems. It is uncertain how the anthropause has changed ecosystem states, functions, and feedback to human systems through shifts in ecosystem services. Here, we used an existing disturbance framework to propose new investigation pathways for coordinated studies of distributed, long‐term social‐ecological research to capture effects of the anthropause. Although it is still too early to comprehensively evaluate effects due to pandemic‐related delays in data availability and ecological response lags, we detail three case studies that show how long‐term data can be used to document and interpret changes in air and water quality and wildlife populations and behavior coinciding with the anthropause. These early findings may guide interpretations of effects of the anthropause as it interacts with other ongoing environmental changes in the future, particularly highlighting the importance of long‐term data in separating disturbance impacts from natural variation and long‐term trends. Effects of this global disturbance have local to global effects on ecosystems with feedback to social systems that may be detectable at spatial scales captured by nationally to globally distributed research networks.

Abstract Background There is a need to develop a multipurpose obsessive–compulsive disorder (OCD) measure that is useful for cross disorder research and as a reliable clinical rating scale. The current study examined the psychometric properties and established clinical cutoffs for the parent‐report version of the Toronto Obsessive–Compulsive Scale (TOCS), a 21‐item rating scale of obsessive–compulsive traits. Method Participants ranged in age from 6 to 21 years old and had a primary diagnosis of OCD (n = 350, 50% female), attention‐deficit/hyperactivity disorder (ADHD) (n = 820, 25% female), autism spectrum disorder (ASD) (n = 794, 22% female), or were typically developing controls (n = 391, 51% female). Confirmatory factor analyses, internal consistency reliability, and convergent and divergent validity of the TOCS were examined in the OCD group. Using various scoring approaches, receiver operating characteristic (ROC) analyses were used to establish a clinical cut‐off by splitting the OCD group into a discovery sample (166 OCD cases, 164 controls) and a validation sample (184 OCD cases, 227 controls). Classification accuracy and TOCS scores were compared across OCD, ADHD, and ASD groups. Results The psychometric properties of the TOCS were confirmed. ROC analyses across TOCS scoring approaches in the discovery sample indicated excellent diagnostic discrimination (AUC ≥0.95, sensitivity 77%–92%, specificity 92%–98%). Established cutoffs, when applied in the independent validation sample of OCD cases and controls, showed an overall classification accuracy of 85%–90%. The TOCS total score and symptom count showed good discrimination of OCD from ADHD (AUC ≥0.86) and ASD (AUC ≥0.81). The OCD group scored significantly higher on all TOCS dimensions (except Hoarding) than the ADHD and ASD groups. Conclusion The TOCS is a reliable and valid rating scale with strong sensitivity and specificity in discriminating OCD cases from controls, as well as from ASD and ADHD. It is a quantitative OCD measure with important clinical and research applications, with particular relevance for cross disorder phenotyping and population‐based studies.

Abstract Ecosystems are changing in complex and unpredictable ways, and analysis of these changes is facilitated by coordinated, long‐term research. Meeting diverse societal needs requires an understanding of what populations and communities will be dominant in 20, 50, and 100 yr. This paper is a product of a synthesis effort of the U.S. National Science Foundation funded Long‐Term Ecological Research (LTER) network addressing the LTER core research area of populations and communities. This analysis revealed that each LTER site had at least one compelling story about what their site would look like in 50 or 100 yr. As the stories were prepared, themes emerged, and the stories were grouped into papers along five themes for this special issue: state change, connectivity, resilience, time lags, and cascading effects. This paper addresses the resilience theme and includes stories from the Baltimore (urban), Hubbard Brook (northern hardwood forest), Andrews (temperate rain forest), Moorea (coral reef), Cedar Creek (grassland), and North Temperate Lakes (lakes) sites. The concept of resilience (the capacity of a system to maintain structure and processes in the face of disturbance) is an old topic that has seen a resurgence of interest as the nature and extent of global environmental change have intensified. The stories we present here show the power of long‐term manipulation experiments (Cedar Creek), the value of long‐term monitoring of forests in both natural (Andrews, Hubbard Brook) and urban settings (Baltimore), and insights that can be gained from modeling and/or experimental approaches paired with long‐term observations (North Temperate Lakes, Moorea). Three main conclusions emerge from the analysis: (1) Resilience research has matured over the past 40 yr of the LTER program; (2) there are many examples of high resilience among the ecosystems in the LTER network; (3) there are also many warning signs of declining resilience of the ecosystems we study. These stories highlight the need for long‐term studies to address this complex topic and show how the diversity of sites within the LTER network facilitates the emergence of overarching concepts about this important driver of ecosystem structure, function, services, and futures.

Abstract Background Myotonic dystrophy type 1 (DM1) is caused by CTG repeat expansions in the DMPK gene and is the most common form of muscular dystrophy. Patients can have long delays from onset to diagnosis, since clinical signs and symptoms are often nonspecific and overlapping with other disorders. Clinical genetic testing by Southern blot or triplet‐primed PCR (TP‐PCR) is technically challenging and cost prohibitive for population surveys. Methods Here, we present a high throughput, low‐cost screening tool for CTG repeat expansions using TP‐PCR followed by high resolution melt curve analysis with saturating concentrations of SYBR GreenER dye. Results We determined that multimodal melt profiles from the TP‐PCR assay are a proxy for amplicon length stoichiometry. In a screen of 10,097 newborn blood spots, melt profile analysis accurately reflected the tri‐modal distribution of common alleles from 5 to 35 CTG repeats, and identified the premutation and full expansion alleles. Conclusion We demonstrate that robust detection of expanded CTG repeats in a single tube can be achieved from samples derived from specimens with minimal template DNA such as dried blood spots (DBS). This technique is readily adaptable to large‐scale testing programs such as population studies and newborn screening programs.

Abstract The development of antimicrobial drug resistance among pathogenic bacteria and fungi is one of the most significant health issues of the 21st century. Recently, advances in nanotechnology have led to the development of nanomaterials, particularly metals that exhibit antimicrobial properties. These metal nanomaterials have emerged as promising alternatives to traditional antimicrobial therapies. In this review, a broad overview of metal nanomaterials, their synthesis, properties, and interactions with pathogenic micro‐organisms is first provided. Secondly, the range of nanomaterials that demonstrate passive antimicrobial properties are outlined and in‐depth analysis and comparison of stimuli‐responsive antimicrobial nanomaterials are provided, which represent the next generation of microbiocidal nanomaterials. The stimulus applied to activate such nanomaterials includes light (including photocatalytic and photothermal) and magnetic fields, which can induce magnetic hyperthermia and kinetically driven magnetic activation. Broadly, this review aims to summarize the currently available research and provide future scope for the development of metal nanomaterial‐based antimicrobial technologies, particularly those that can be activated through externally applied stimuli.

Background Sugar‐sweetened beverages are associated with hypertension. We assessed the relation of important food sources of fructose‐containing sugars with incident hypertension using a systematic review and meta‐analysis of prospective cohort studies. Methods and Results We searched MEDLINE, EMBASE, and Cochrane (through December week 2, 2018) for eligible studies. For each food source, natural log‐transformed risk ratios (RRs) for incident hypertension were pooled using pair‐wise meta‐analysis and linear and nonlinear dose‐response meta‐analyses. Certainty in our evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. We identified 26 reports, including 15 prospective cohorts (930 677 participants; 363 459 cases). Sugar‐sweetened beverages showed harmful (RRper‐355‐mL, 1.10 [95% CI, 1.08, 1.12]) whereas fruit (RRper‐240‐g, 0.94 [95% CI, 0.96, 0.99]) and yogurt showed protective associations (RRper‐125‐g, 0.95 [95% CI, 0.94, 0.97]) with incident hypertension throughout the dose range. One hundred percent fruit juice showed a protective association only at moderate doses (RRat‐100‐mL, 0.97 [95% CI, 0.94, 0.99]). The pair‐wise protective association of dairy desserts was not supported by linear dose‐response analysis. Fruit drinks or sweet snacks were not associated with hypertension. Certainty of the evidence was “low” for sugar‐sweetened beverages, 100% fruit juice, fruit, and yogurt and “very low” for fruit drinks, sweet snacks, and dairy desserts. Conclusions The harmful association between sugar‐sweetened beverages and hypertension does not extend to other important food sources of fructose‐containing sugars. Further research is needed to improve our estimates and better understand the dose‐response relationship between food sources of fructose‐containing sugars and hypertension. Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02702375.

York Platelet Syndrome (YPS) is a calcium channelopathy caused by gain of function in STIM1, a gene which acts as a calcium sensor. It is characterized by platelet abnormalities and muscle weakness. Medical literature emphasizes the hematologic aspects of the cases with few data of the neuromuscular and neuropathologic evaluation. We present a patient with YPS whose myopathy was the most prominent aspect. She presented around 2 years of age with proximal weakness and easy bruisability. YPS was diagnosed in the infant at 16 months of age at the National Institutes of Health. Muscle biopsy demonstrated a severe chronic myopathy. Rimmed vacuoles and tubular aggregates were noted. Although YPS is rare, the combination of a congenital myopathy with thrombocytopenia may facilitate the diagnosis and enable further insights into the disease.

BackgroundThere is a heightened interest in plant‐based diets for cardiovascular disease prevention. Although plant protein is thought to mediate such prevention through modifying blood lipids, the effect of plant protein in specific substitution for animal protein on blood lipids remains unclear. To assess the effect of this substitution on established lipid targets for cardiovascular risk reduction, we conducted a systematic review and meta‐analysis of randomized controlled trials using the Grading of Recommendations Assessment, Development, and Evaluation system. Methods and ResultsMEDLINE, EMBASE, and the Cochrane Registry were searched through September 9, 2017. We included randomized controlled trials of ≥3 weeks comparing the effect of plant protein in substitution for animal protein on low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, and apolipoprotein B. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences with 95% confidence intervals. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality (certainty) of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. One‐hundred twelve randomized controlled trials met the eligibility criteria. Plant protein in substitution for animal protein decreased low‐density lipoprotein cholesterol by 0.16 mmol/L (95% confidence interval, −0.20 to −0.12 mmol/L; P

Background: The association between influenza vaccination and implantable cardiac defibrillator (ICD) therapies during influenza season is not known and is described in this study. Understanding this association is important since reduction in ICD therapies during influenza season via use of influenza vaccination would benefit patients physically and psychologically. Methods: Patients presenting to the Sunnybrook Health Sciences Center ICD clinic between September 1st, 2011 and November 31st, 2011 were asked to complete a survey evaluating their use of the influenza vaccine. The number of patients with any ICD therapy and the total number of ICD therapies in the six months before and the three months during the 2010–2011 influenza season were determined. Poisson regression analysis was employed to assess differences in the average number of ICD therapies received during the influenza season based on vaccine status (vaccinated vs. unvaccinated). The analysis was repeated after limiting the cohort to patients with a left ventricular ejection fraction ≤35%. Results: A total of 229 patients completed the survey, 78% of whom received the influenza vaccine. Four patients had more than one ICD shock during the study period. Electrical storm was rare (n=2). A trend toward more ICD therapies (unadjusted incident rate ratio (IRR)=3.2; P=0.07) and appropriate ICD shocks (unadjusted IRR=9.0; P=0.17) was noted for unvaccinated compared to vaccinated patients. This association persisted when analysis was limited to patients with a left ventricular ejection fraction ≤35% (all ICD therapies: unadjusted IRR=5.8; P=0.045; adjusted IRR=2.6; P=0.33). No patient who received the influenza vaccine, and had a reduced ejection fraction, received an approprite ICD shock during influenza season (unadjusted P