bluuebunny/crossref_metadata_2025 huggingface dataset:
Should colorectal cancer screening start at different ages for men and women? Cost‐effectiveness analysis for a resource‐constrained service
Authors: Thomas Chloe , Mandrik Olena , Whyte Sophie , Saunders Catherine L. , Griffin Simon J. , Usher‐Smith Juliet A.
Published: February 2021

Background

Men have a greater risk of colorectal cancer (CRC) than women, but population screening currently starts at the same age for both sexes.

Aim

This analysis investigates whether, in a resource‐constrained setting, it would be more effective and cost‐effective for men and women to start screening for CRC at different ages.

Methods and results

An economic modeling analysis was carried out using the Microsimulation Model in Cancer of the Bowel to compare sex‐stratification against screening everyone from the same age, taking an English National Health Service perspective. Screening men from age 56 and women from age 60, rather than screening everyone from age 58 using a Fecal Immunochemical Test (FIT) threshold of 120 μg/g is expected to produce an additional 0.0004 QALYs for a cost of £0.55 per person at model start (Incremental Cost‐effectiveness Ratio = £1392), and to reduce CRC cases and mortality by 25 and 19 per 100 000 people respectively, while using a similar amount of screening resources. Probabilistic sensitivity analysis indicates a 61% probability that sex‐stratification is more cost‐effective than screening everyone at age 58. Similar benefits of sex‐stratification are found at other FIT thresholds, but become negligible if mean screening start age is reduced to 50.

Conclusion

Where resources are constrained and it is not feasible to screen everyone from the age of 50, starting screening earlier in men than women is likely to be more cost‐effective and gain more health benefits overall than strategies where men and women start screening at the same age.
Dense short connection network for efficient image classification
Authors: Yang Zhenkun , Ma Xianghua , Wang Kefan , An Jing
Published: February 2021

With the continuous development of convolutional neural networks (CNNs), image classification technology has entered a new stage in solving visual cognition tasks. Recent advances have shown that if containing short connections, convolutional networks can be more accurate and efficient to train. However, these short connections almost only exist between convolutional layers, which potentially make the feature information flow insufficiently. In addition, the multi‐scale representation ability of CNNs using short connections can be further explored. Thus, the dense short connection network (DSCNet) for efficient image classification is designed in this paper. In DSCNet, we propose a simple yet effective architectural unit, namely dense short connection (DSC) module, which allows hierarchical dense short connections for multi‐scale context information across different feature channels within a single convolutional layer. DSCNets have several noteworthy advantages: they improve the multi‐scale representation ability, enhance feature propagation, and reduce the number of parameters. To validate our DSC, we conduct comprehensive experiments on CIFAR‐100 and Tiny ImageNet datasets. Experimental results show that DSCNets achieve very competitive results with previous baseline models, whilst requiring less computation to achieve higher recognition accuracy. Further ablation studies show that our proposed method can achieve consistent performance gains in image classification tasks.
Understanding the Chloride Affinity of Barbiturates for Anion Receptor Design
Authors: Petelski Andre Nicolai , Marquez Josefina , Pamies Silvana Carina , Sosa Gladis Laura , Peruchena Nélida María
Published: February 2021

Due to their potential binding sites, barbituric acid (BA) and its derivatives have been used in metal coordination chemistry. Yet their abilities to recognize anions remain unexplored. In this work, we were able to identify four structural features of barbiturates that are responsible for a certain anion affinity. The set of coordination interactions can be finely tuned with covalent decorations at the methylene group. DFT‐D computations at the BLYP‐D3(BJ)/aug‐cc‐pVDZ level of theory show that the C−H bond is as effective as the N−H bond to coordinate chloride. An analysis of the electron charge density at the C−H⋅⋅⋅Cl−and N−H⋅⋅⋅Cl−bond critical points elucidates their similarities in covalent character. Our results reveal that the special acidity of the C−H bond shows up when the methylene group moves out of the ring plane and it is mainly governed by the orbital interaction energy. The amide and carboxyl groups are the best choices to coordinate the ion when they act together with the C−H bond. We finally show how can we use this information to rationally improve the recognition capability of a small cage‐like complex that is able to coordinate NaCl.
Antigen Mass May Influence Trastuzumab Concentrations in Cerebrospinal Fluid After Intrathecal Administration
Authors: Le Tilly Olivier , Azzopardi Nicolas , Bonneau Claire , Desvignes Céline , Oberkampf Florence , Ezzalfani Monia , Ternant David , Turbiez Isabelle , Gutierrez Maya , Paintaud Gilles
Published: February 2021

Intravenous administration of monoclonal antibodies leads to low concentrations in the central nervous system, which is a serious concern in neuro‐oncology, especially in leptomeningeal carcinomatosis of HER2‐overexpressing breast cancer. Case reports of i.t. administrations of trastuzumab have shown promising results in these patients but dosing regimens are empirical in absence of pharmacokinetic (PK) study. With a population PK approach, we described the fate of trastuzumab after i.t. administration in 21 women included in a phase I–II clinical trial. Trastuzumab was administered by i.t. route every week for 8 weeks and both cerebrospinal fluid (CSF) and serum were sampled to measure trough concentrations. Some patients showed noticeable CSF concentration fluctuations predicted using a target‐mediated drug disposition. This target was latent and produced with a delayed feedback. Apparent volumes of distribution were close to physiological volumes (V1 = 3.25 L, V2 = 0.644 L, for serum and CSF, respectively). Estimated (constant) transfer from serum to CSF was very slow (k12 = 0.264 mg/day) whereas estimated half‐life of transfer from CSF to serum was rapid (2.2 days). From the individual parameters of patients, a single i.t. administration of 150 mg of trastuzumab corresponded to median mean residence times of 3.8 days and 15.6 days in CSF and serum, respectively. Survival without neurological relapse was not related to trastuzumab exposure. This study confirms that transfer of trastuzumab from serum to CSF is very limited and that this monoclonal antibody, when administered by i.t. route, is rapidly transferred to the serum.
Population PK‐PD Modeling of Circulating Lymphocyte Dynamics in Chronic Lymphocytic Leukemia Patients Under Ibrutinib Treatment
Authors: Gallais Fanny , Ysebaert Loïc , Despas Fabien , De Barros Sandra , Obéric Lucie , Allal Ben , Chatelut Etienne , White‐Koning Mélanie
Published: February 2021

Ibrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL). Absolute lymphocyte count (ALC) is a clinical criterion used for the monitoring of CLL. Ibrutinib has several effects on lymphocytes, and has highly variable pharmacokinetics (PK). The objective of this work was to build a PK‐pharmacodynamic (PD) model describing ALC dynamics under ibrutinib treatment in patients with CLL. ALC observations before and after ibrutinib treatment initiation in patients with CLL were included in the analysis. A population PK‐PD model was developed based on physio‐pharmacological knowledge. Individual PK concentrations at each hospital visit were included in the model. The association between PD parameters and lymphocytosis, and between PD parameters and response to treatment were assessed. A total of 94 patients, 658 ALC and 1,501 PK observations were included in model development. The final PK‐PD model accurately described ALC dynamics for different patient profiles. It consisted in two compartments (tissues and blood circulation) with ibrutinib plasmatic concentration inducing two drug effects: stimulation of lymphocyte redistribution and death. Patients with hyperlymphocytosis had significantly higher tissues to circulation baseline lymphocyte count ratio, and lower death effect. Patients who progressed under ibrutinib had significantly lower baseline lymphocyte counts in tissues (2‐fold lower) and blood (3‐fold lower). The first PK‐PD model for ALC in patients with CLL under ibrutinib treatment was developed. This model suggests that estimated lymphocyte counts in tissues and blood could be used as an early predictor of response in patients with CLL.
Anti‐Infective Dosing in Special Populations: Pregnancy
Authors: Hazenberg Phoebe , Navaratnam Kate , Busuulwa Paula , Waitt Catriona
Published: February 2021

Substantial anatomical and physiological changes occur during pregnancy and labor, which impact on drug absorption, distribution, metabolism, and elimination. Reduced maternal concentrations may have a clinically important impact on the efficacy of anti‐infectives for mother, fetus, and neonate, with potential dosing implications. However, there is a paucity of pregnancy‐specific data examining this. Existing data on the pharmacokinetics of anti‐infectives in pregnancy are summarized and evaluated, with emphasis on agents that are used in treatment of HIV, tuberculosis, malaria, and common bacterial infections. Limitations and challenges in achieving ideal study designs in pregnant populations are highlighted, and key quality considerations for the generation of the highest quality evidence are outlined. PubMed was searched for each chosen anti‐infective. Pharmacokinetic studies which either compared pharmacokinetics from pregnant women against nonpregnant controls, or which assessed concentrations against a known minimum inhibitory concentration were included. Two independent reviewers extracted data from each study and appraised them using the 24‐point ClinPK Checklist. The main finding was that there is a lack of published data for anti‐infectives in pregnancy, despite their clinical importance. Of the studies identified, only those investigating cobicistat‐boosted antiretroviral regimens firmly concluded that these should not be used in pregnancy. Most studies concluded either that further research was needed, or that there were significant pharmacokinetic differences between pregnant and nonpregnant participants which had uncertain clinical significance. Challenges in applying existing quality grading systems to these studies were noted, suggesting a development of a refined system for appraisal of pharmacokinetic studies in "special populations" may be warranted.
Generation of Neurosphere‐Derived Organoid‐Like‐Aggregates (NEDAS) from Neural Stem Cells
Authors: Watanabe Fumihiro , Schoeffler Austin , Fair Summer R. , Hester Mark E. , Fedorko Josh , Imitola Jaime
Published: February 2021

Neurosphere cultures have been used to propagate and study the intrinsic properties of neural stem cells (NSCs) for more than two decades but this method has many limitations. It is well known that neurospheres fuse in culture, but the long‐term biological consequences of this phenomena are not well characterized. We leveraged the fusion behavior of human neurospheres to improve upon this technique with our Neurosphere‐derived organoid‐like aggregates (NEDAS) culture method, allowing the fusion of human NSCs at high density, which were maintained in orbital shaker conditions for 8‐12 weeks without passing leading to the formation of 3D organoid‐like aggregates without the use of Matrigel. NEDAS organoids proliferate and self‐organize into neural rosettes, expressing PAX6 and SOX2 in ventricular zone (VZ)‐like proliferative areas. Outside these rosettes, we identified corridors of migratory radial glial progenitors expressing Phospo‐vimentin, CRYAB. In addition to DLX2, CXCR4 + progenitors. Further, we found immature neurons within cortical‐like areas highly enriched for DCX and TUJ1, in addition to GABA+ and excitatory VGLUT1+ neurons. Here, we provide a protocol to generate NEDAS, additionally, we present a protocol for immunostaining of NEDAS organoids for confocal imaging. This protocol may be useful to dissect the self‐organization and morphogenetic programs of populations of human NSCs offering an advantageous alternative to the conventional neurospheres method, generating more cell type diversity, within tissue‐like aggregates over extended periods of time without dissociation or passing. NEDAS may be a complementary method to cerebral organoids protocols from IPSCs. © 2021 Wiley Periodicals LLC.

This article was corrected on 19 July 2022. See the end of the full text for details.

Basic Protocol 1: Preparation and expansion of cultures of human neural stem cells in reduced growth factor basement matrix

Basic Protocol 2: Formation and fusion of neurospheres derived matrigel‐free organoid‐like aggregates (NEDAS)

Basic Protocol 3: Harvest, cryosection, and imaging protocol for NEDAS
Realizing the promise of dialogue: Transformative dialogue in divided communities
Authors: Cleven Erik , Saul Judith A.
Published: February 2021

This article introduces an approach to conflict transformation called transformative dialogue. Building on transformative theory, it differs from other approaches in two important ways. First, it sees the ethical relation to conflict parties as of primary importance, taking priority over any analysis or conceptualization of conflict. Second, transformative dialogue posits a different relationship between conflict analysis and practice. Rather than prioritizing a particular mode of analysis, transformative dialogue starts from the primacy of human agency, prioritizing people's own experience and ways of understanding their conflicts. In this way, transformative dialogue addresses many of the weaknesses in current peacebuilding models.
Semidwarf winter wheat roots contain fewer organic acids than wild‐type varieties under phosphorus stress
Authors: McGrail Rebecca K. , Van Sanford David A. , McNear David H.
Published: February 2021

Organic acids are exuded by plant roots into the rhizosphere for a variety of reasons, including nutrient acquisition. The most frequently reported organic acids are those involved in the Krebs cycle and other important biochemical pathways that are responsible for the production of important plant metabolites, including oxalic, malic, and citric acid. Many studies report increased citric and malic acid exudation when plants are P‐deficient. Because plant breeding is typically carried out under heavily fertilized conditions, it is possible that wheat (Triticum aestivum L.) breeders have unintentionally selected for varieties with decreased nutrient acquisition capability from soil organic matter and soil colloids. In this study, we evaluated a diverse panel of 10 winter wheat cultivars, which included wild‐type (tall) and semidwarf varieties, for organic acid content. Plants were grown in solution culture with and without P for 24 d. Thirty 1‐cm root tips were bulked per sample and the extracts were analyzed by high‐performance liquid chromatography for citric, malic, and oxalic acid content. Under P deficiency, total organic acid content differed between wild‐type and semidwarf varieties, with wild‐type cultivars containing more organic acids in the root tips. This difference in total production was driven by oxalic acid, whereas citric and malic acid concentrations were conserved. Unlike citric and malic acid, oxalic acid is not necessary for major metabolic processes and therefore may be expendable. Breeding for semidwarf wheat corresponds with unintentional changes to root system function that could impact nutrient acquisition and other rhizosphere processes.
Benzoic Anhydride as a Bifunctional Electrolyte Additive for Hydrogen Fluoride Capture and Robust Film Construction over High‐Voltage Li‐Ion Batteries
Authors: Jiang Sen , Wu Haihua , Yin Junying , Wei Zhihua , Wu Jiahao , Wei Lai , Gao Dunfeng , Xu Xin , Gao Yunfang
Published: February 2021

High‐voltage LiNi0.8Co0.1Mn0.1O2 (NCM811)‐based Li‐ion batteries (LIBs) with enhanced performance can be achieved by properly tailoring the electrolyte systems. Benzoic anhydride (BA) was proposed here as a promising bifunctional electrolyte additive that can not only construct a robust cathode‐electrolyte interface (CEI) film on the electrode surface but also capture HF/H2O in the electrolyte effectively. Compared to the cell without the BA additive, the capacity of Li/NCM811 half‐cell with 1.0 wt % BA was increased from 128.5 to 149.6 mAh g−1 after 200 cycles at 1 C between 3.0 and 4.3 V. Even at a higher cut‐off voltage of 4.5 V, the BA‐containing Li/NCM811 half‐cell delivered a capacity retention of 69 % after 200 cycles, much higher than that of the half‐cell without the additive (56 %). Both theoretical calculation and experimental results verified that the BA additive could be preferentially oxidized to form a stable interface film with high conductivity that protected the NCM811 cathode and suppressed the decomposition of the electrolyte.
Adaptive optics for structured illumination microscopy based on deep learning
Authors: Zheng Yao , Chen Jiajia , Wu Chenxue , Gong Wei , Si Ke
Published: February 2021

Structured illumination microscopy (SIM) is widely used in biological imaging for its high resolution, fast imaging speed, and simple optical setup. However, when imaging thick samples, the structured illumination patterns in SIM will suffer from optical aberrations, leading to a serious deterioration in resolution. Therefore, it is necessary to reconstruct structured illumination patterns with high quality and efficiency in deep tissue imaging. Here we demonstrate an adaptive optics (AO) correction method based on deep learning in wide‐field SIM imaging system. The mapping between the coefficients of the first 15 Zernike modes and their corresponding distorted patterns is established to train the convolution neural network (CNN). The results show that the optimized CNN can predict the aberration phase within ~10.1 ms with a personal computer. The correlation index between the aberration phases and their corresponding predicted aberration phase is up to 0.9986. This method is highly robust and effective for patterns with various spatial densities and illumination conditions and able to effectively correct the imaging distortion caused by optical aberration in SIM system.
A method for routing and data aggregating in cluster‐based wireless sensor networks
Authors: Sharifi Sedigheh Sadat , Barati Hamid
Published: February 2021

Wireless sensor networks (WSNs) consist of a large number of small nodes, containing sensors; these sensors serve as powerful devices to gather data in different environments. One of the major challenges facing WSNs is their limited energy resources, which affects network lifetime directly. This paper provides a method of hierarchical routing and data aggregating for WSNs. In the proposed method, the network is clustered, and some nodes are selected as cluster heads. On constructing a rendezvous region and selecting backbone nodes, a tree is formed within backbone‐tree nodes. The aggregated data are sent to the sink through backbone‐tree nodes and cluster heads. Here, there are two modes of data transmission. The proposed method is simulated by Network Simulator (NS‐2) software and compared with based data aggregation and rendezvous‐based routing protocol. The results of simulation reveal that our method causes a decrease in end‐to‐end delay and energy consumption as well as an increase in the number of alive nodes and packet delivery rate.
Anatomical distribution and expression of CYP in humans: Neuropharmacological implications
Authors: Fanni Daniela , Pinna Federica , Gerosa Clara , Paribello Pasquale , Carpiniello Bernardo , Faa Gavino , Manchia Mirko
Published: February 2021

The cytochrome P450 (CYP450) superfamily is responsible for the metabolism of most xenobiotics and pharmacological treatments generally used in clinical settings. Genetic factors as well as environmental determinants acting through fine epigenetic mechanisms modulate the expression of CYP over the lifespan (fetal vs. infancy vs. adult phases) and in diverse organs. In addition, pathological processes might alter the expression of CYP. In this selective review, we sought to summarize the evidence on the expression of CYP focusing on three specific aspects: (a) the anatomical distribution of the expression in body districts relevant in terms of drug pharmacokinetics (liver, gut, and kidney) and pharmacodynamics, focusing for the latter on the brain, since this is the target organ of psychopharmacological agents; (b) the patterns of expression during developmental phases; and (c) the expression of CYP450 enzymes during pathological processes such as cancer. We showed that CYP isoforms show distinct patterns of expression depending on the body district and the specific developmental phases. Of particular relevance for neuropsychopharmacology is the complex regulatory mechanisms that significantly modulate the complexity of the pharmacokinetic regulation, including the concentration of specific CYP isoforms in distinct areas of the brain, where they could greatly affect local substrate and metabolite concentrations of drugs.
Intense pulsed light for pigmented and vascular lesions and skin rejuvenation: Two decades of clinical trials
Authors: Rachidi Saleh , Goldberg David J.
Published: February 2021

Background

The wide wavelength spectrum of intense pulsed light (IPL) provides an opportunity for a versatile array of clinical applications in dermatology.

Methods

Key randomized clinical trials which took place in the past 20 years were summarized, focusing on skin rejuvenation, including pigmented and vascular lesions. We searched Pubmed using the key words intense, pulsed, light, and skin, then filtered results for randomized clinical trials.

Results and Conclusions

Studies uniformly showed improvement in pigmented and vascular lesions with IPL. Efficacy in treating rhytides was only observed in some studies. IPL was also effective as a light source in treating actinic keratosis with photodynamic therapy. Rare cases of post‐inflammatory hyperpigmentation were observed.
Nonablative radiofrequency for the treatment of androgenetic alopecia: An open‐label study
Authors: Lim Rachel K. , Verner Ines , Wambier Carlos G. , Kolodchenko Yegor , Goren Andy
Published: February 2021

Introduction

Androgenetic alopecia (AGA) is the most common type of progressive hair loss, and current treatments are limited. Wound healing has been associated with hair regrowth; consequently, its mechanism has been suggested for treatment of hair loss. Nonablative radiofrequency (RF), which induces wound healing mechanisms through thermal damage, has been shown to increase hair growth when applied to the scalp. In this study, we aim to evaluate a specially adapted non‐ablative RF device as a noninvasive, nonsystemic treatment for AGA.

Methods

An open‐label study was conducted to evaluate the efficacy of a nonablative RF device for treatment of AGA. Patients diagnosed with Hamilton–Norwood Stage 3 or above were recruited and received 10 weekly RF treatment sessions. Hair counts were performed before and after treatment manually by a medical resident.

Results

Ten male and 10 female subjects were recruited. Hair count, hair density (per cm2), vellus hair density (per cm2), terminal hair density (per cm2), cumulative thickness (mm/cm2), number of follicular units, density of follicular units (per cm2), and average hair per unit increased from before to after treatment. Only the increases in hair count, overall hair density, terminal hair density, cumulative thickness, and average hair count/unit were statistically significant (p < .05).

Discussion

We observed significant improvement in hair growth in 19 out of 20 patients. Overall, significant improvement was observed in total hair counts, terminal hair counts, hair shaft thickness, and in the number of follicular units. Further clinical research is warranted to further explore nonablative RF for treatment of AGA.
The influence of social motivation on neural correlates of cognitive control in girls
Authors: Barker Tyson V. , Buzzell George A. , Troller‐Renfree Sonya V. , Bowman Lindsay C. , Pine Daniel S. , Fox Nathan A.
Published: February 2021

Motivation influences cognitive control, particularly in childhood and adolescence. Previous work finds that the error‐related negativity (ERN), an event‐related potential (ERP) linked to cognitive control following errors, is influenced by social motivation. However, it is unclear whether the influences of social motivation on the ERN extend to stimulus‐locked neural correlates of cognitive control. This study reexamines how social motivation influences cognitive control in adolescence by exploring motivational influences on two stimulus‐locked ERPs; the N2 and P3. Adolescent girls (8–17 years of age) completed a flanker task under two different conditions. In the social condition, girls were led to believe that they were evaluated by a peer during a flanker task. In the nonsocial condition, girls completed a flanker task while evaluated by a computer. Results revealed that all girls exhibited a larger P3 in social as compared to nonsocial contexts, whereas the N2 was not different between contexts. In addition, the largest P3 enhancements were observed among younger girls. These findings suggest that social motivation influences some ERP components related to cognitive control, and such influences change across development. Additionally, findings suggest the importance of including multiple ERPs when interpreting the functional significance of motivation on cognitive control.
Metabolic profiling of deschloro‐N‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry
Authors: Larabi Islam Amine , Zerizer Fanny , Ameline Alice , Etting Isabelle , Joseph Delphine , Kintz Pascal , Alvarez Jean Claude
Published: February 2021

The aim of this study was to identify new markers of deschloro‐N‐ethyl‐ketamine (O‐PCE), a ketamine analogue that has been involved in acute intoxications with severe outcomes including death and whose metabolism has never been studied before. In vitro study after 2‐h incubation with pooled human liver microsomes (HLMs) cross‐checked by the analysis of urine and hair from a 43‐year‐old O‐PCE user (male) were performed by liquid chromatography–high resolution mass spectrometry (LC‐HRMS). Acquired data were processed by the Compound Discoverer® software, and a full metabolic profile of O‐PCE was proposed. In total, 15 metabolites were identified, 10 were detected in vitro (HLMs) and confirmed in vivo (urine and/or hair), two were present only in HLMs, and the remaining three metabolites were identified only in biological specimens. While O‐PCE was no longer detected in urine, nine metabolites were identified allowing to increase its detection window. In descending order of metabolites abundance, we suggest using 2‐en‐PCA‐N‐Glu (34%, first), M3 (16%, second), O‐PCA‐N‐Glu (15.4%, third), OH‐O‐PCE (15%, fourth) and OH‐PCE (11.9%, fifth) as target metabolites to increase the detection window of O‐PCE in urine.

In hair, nine metabolites were identified. OH‐PCA was the major compound (78%) with a relevant metabolite to parent drug ratio (=6) showing its good integration into hair and making it the best marker for long‐term monitoring of O‐PCE exposure.
Nonframeshifting indel variations in polyalanine repeat of HOXD13 gene underlies hereditary limb malformation for two Chinese families
Authors: Zu Bailing , Wang Zhigang , Xu Yunlan , You Guoling , Fu Qihua
Published: February 2021

Background

Polydactyly and syndactyly are the most common hereditary limb malformations. Molecular genetic testing is of great significance for hereditary limb malformations, which can establish prognosis and recurrence risk of surgical intervention.

Methods

The present study aimed to identify the genetic etiologies of a three‐generation family with postaxial polydactyly and a four‐generation family with postaxial syndactyly. Whole exome sequencing was used, followed by standard mutation screening procedure, Sanger sequencing and bioinformatics analysis.

Results

Two nonframeshifting insertion/deletion (indel) mutations in HOXD13 (c.206_207ins AGCGGCGGCTGCGGCGGCGGCGGC:p.A68insAAAAAAAA or c.171_182delGGCGGCGGCGGC: p.56_60delAAAA) were successfully identified as the pathogenic mutation. The two nonframeshifting indel mutations led to truncation or expansion of homopolymeric alanine (Poly‐Ala) repeats of HOXD13 proteins. Sequence alignment of HOXD13 protein among many different species for Poly‐Ala position is highly conserved. Hypothetical three‐dimensional (3‐D) structural analysis further showed mutant HOXD13 proteins (p.A68insAAAAAAAA and p.56_60delAAAA) converted the disordered fragment into a short β‐strand (residues 63‐68 or residues 64‐68), thereby forming a conformational change.

Conclusions

The present study identified two nonframeshifting mutations of HOXD13 polyalanine repeat location in two Chinese families with postaxial polydactyly or postaxial syndactyly. Our results also provide new insights into genetic counseling and clinical management.
The long and the short of tails
Authors: Rashid Dana J. , Chapman Susan C.
Published: February 2021

Amniote tails display a wide variety of features for adaptation to diverse environments. Each feature originates from its own distinct developmental processes, and these processes in turn attest to an organism's evolutionary history. In this perspective, we discuss the ontogeny of tails from embryonic to adult stages, amniote tail regeneration, the mechanisms underlying tail length and neural systems, and the benefits of studying tails across vertebrates, in mammals, birds, and non‐avian reptiles.
Gastrointestinal symptoms following treatment for anorexia nervosa: A systematic literature review
Authors: West Madeline , McMaster Caitlin M. , Staudacher Heidi M. , Hart Susan , Jacka Felice N. , Stewart Tim , Loughman Amy , Rocks Tetyana , Ruusunen Anu
Published: February 2021

Objective

Gastrointestinal (GI) disturbances are a frequent and burdensome experience for patients with anorexia nervosa (AN). How GI symptoms respond to current interventions is not well characterized, yet is critical to facilitate treatment success, and to inform the development of new treatments for AN. Therefore, the aim of this systematic review was to identify which treatments are effective in improving GI symptoms in patients with AN.

Method

A systematic search for studies of AN treatments measuring GI symptoms pre‐ and post‐treatment was conducted in May 2020 (PROSPERO ID: CRD42020181328). After removal of duplicates, title and abstracts of 3,370 studies were screened. Methodological quality was assessed using National Institute of Health Quality Assessment Tool.

Results

Following full‐text screening, 13 studies (12 observational studies and 1 randomized double‐blind placebo‐controlled trial) with 401 participants met eligibility criteria and were included. All observational studies included a component of nutritional rehabilitation, with half (n = 6) involving concurrent psychological treatment. The randomized controlled trial reported a drug therapy. Eleven studies reported an improvement in all (n = 6) or at least one (n = 5) patient‐reported GI symptom following treatment. Two studies reported no change. Methodological quality was fair or poor across all studies.

Discussion

This is the first systematic review to synthesize available evidence on the trajectory of patient‐reported GI symptoms from commencement to end of treatment for AN. The results suggest that most studies showed improvement in one or more GI symptom in response to current treatments. Future therapeutic approaches should consider GI symptoms within their design for optimal treatment adherence and outcomes.
Smartphone apps for eating disorders: A systematic review of evidence‐based content and application of user‐adjusted analyses
Authors: Wasil Akash R. , Patel Raveena , Cho Jin Young , Shingleton Rebecca M. , Weisz John R. , DeRubeis Robert J.
Published: February 2021

Objective

To examine the frequency of evidence‐based treatment elements in popular smartphone apps for eating disorders (EDs), and to characterize the extent to which real‐world users encounter different elements.

Method

We searched the Apple App Store and Google Play Store for apps offering treatment or support to individuals with EDs. Then, we created a codebook of 47 elements found in evidence‐based treatments for EDs. We examined the presence or absence of each element within each ED app. We also acquired estimates of the monthly active users (MAU) of each app.

Results

The ED apps (n = 28) included a median of nine elements of empirically supported treatments (mean = 9.46, SD = 6.28). Four apps accounted for 96% of all MAU. MAU‐adjusted analyses revealed that several elements are reaching more users than raw frequency tallies would suggest. For example, assessments were included in 32% of apps, but 84% of users used an app with assessments. Similar trends were found for cognitive restructuring (21% of apps, 56% of MAU), activity scheduling (39%, 57%), and self‐monitoring (14%, 46%). Problem solving, exposure, and relapse prevention strategies, elements that are prominent in face‐to‐face empirically supported treatments, were rarely included in the apps.

Discussion

Evidence‐based content is commonly included in ED apps, with certain elements reaching more users than others. Additionally, the top four apps are responsible for nearly all active users. We recommend that ED clinicians and researchers familiarize themselves with these apps—those that patients are most likely to encounter.
Reproductive interference hampers species coexistence despite conspecific sperm precedence
Authors: Iritani Ryosuke , Noriyuki Suzuki
Published: February 2021

Negative interspecific mating interactions, known as reproductive interference, can hamper species coexistence in a local patch and promote niche partitioning or geographical segregation of closely related species. Conspecific sperm precedence (CSP), which occurs when females that have mated with both conspecific and heterospecific males preferentially use conspecific sperm for fertilization, might contribute to species coexistence by mitigating the costs of interspecific mating and hybridization. We discussed whether two species exhibiting CSP can coexist in a local environment in the presence of reproductive interference. First, using a behaviorally explicit mathematical model, we demonstrated that two species characterized by negative mating interactions are unlikely to coexist because the costs of reproductive interference, such as loss of mating opportunity with conspecific partners, are inevitably incurred when individuals of both species are present. Second, we experimentally examined differences in mating activity and preference in twoHarmonialadybird species known to exhibit CSP. These behavioral differences may lead to local extinction ofH. yedoensisbecause of reproductive interference byH. axyridis. This prediction is consistent with field observations thatH. axyridisuses various food sources and habitats whereasH. yedoensisis confined to a less preferred prey item and a pine tree habitat. Finally, by a comparative approach, we observed that niche partitioning or parapatric distribution, but not sympatric coexistence in the same habitat, is maintained between species with CSP belonging to a wide range of taxa, including vertebrates and invertebrates living in aquatic or terrestrial environments. Taken together, it is possible that reproductive interference may destabilize local coexistence even in closely related species that exhibit CSP.
Butterfly species diversity and their floral preferences in the Rupa Wetland of Nepal
Authors: Subedi Bandana , Stewart Alyssa B. , Neupane Bijaya , Ghimire Sudha , Adhikari Hari
Published: February 2021

Floral attributes often influence the foraging choices of nectar‐feeding butterflies, given the close association between plants and these butterfly pollinators. The diversity of butterflies is known to a large extent in Nepal, but little information is available on the feeding habits of butterflies. This study was conducted along the periphery of Rupa Wetland from January to December 2019 to assess butterfly species diversity and to identify the factors influencing their foraging choices. In total, we recorded 1535 individuals of 138 species representing all six families. For our examination of butterfly–nectar plant interactions, we recorded a total of 298 individuals belonging to 31 species of butterfly visiting a total of 28 nectar plant species. Overall, total butterfly visitation was found to be significantly influenced by plant category (herbaceous preferred over woody), floral color (yellow white and purple preferred over pink), and corolla type (tubular preferred over nontubular). Moreover, there was a significant positive correlation between the proboscis length of butterflies and the corolla tube length of flowers. Examining each butterfly family separately revealed that, for four of the families (Lycaenidae, Nymphalidae, Papilionidae, and Pieridae), none of the tested factors (flower color, plant category, and corolla type) were shown to significantly influence butterfly abundance at flowers. However, Hesperidae abundance was found to be significantly influenced by both flower color (with more butterflies observed at yellow flowers than purple) and flower type (with more butterflies observed at tubular flowers than nontubular flowers). Our results reveal that Rupa Lake is a suitable habitat for butterflies, providing valuable floral resources. Hence, further detailed studies encompassing all seasons, a greater variety of plants, and other influential factors in different ecological regions are fundamental for creating favorable environments to sustain important butterfly pollinators and help create balanced wetland ecosystems.
Effects of forest disturbance on the fitness of an endemic rodent in a biodiversity hotspot
Authors: Ademola Olaoluwa John , Vanden Broecke Bram , Leirs Herwig , Mulungu Loth S. , Massawe Apia W. , Makundi Rhodes H.
Published: February 2021

Praomys delectorumoccurs abundantly in both disturbed and intact forests in the Ukaguru Mountains within the Eastern Arc Mountains (EAM), Morogoro, Tanzania. While previous studies have reported that anthropogenic disturbances such as grazing, wood cutting, and harvesting have a positive effect on the population density ofP. delectorum, the impact of habitat disturbance on its demographic traits is still unknown. We performed a capture–mark–recapture study in both disturbed and intact forests from June 2018 to February 2020 in order to investigate the effects of habitat disturbance on abundance and two demographic traits: survival and maturation ofP. delectorumin the Ukaguru Mountains. We found no variation in abundance or maturation between intact and disturbed forests, but habitat type did affect survival. However, this effect was sex‐dependent since female survival was higher in disturbed forests, while male survival remained similar across the two forest types potentially due to differences in predation pressure or food availability between the two habitats. Continuous demographic monitoring ofP. delectorumin EAM is necessary given that the increasing human population surrounding the landscape is leading to higher deforestation rates and expansion of the pine plantation in the forest reserve.
Traits explain sorting of C4 grasses along a global precipitation gradient
Authors: Jardine Emma C. , Thomas Gavin H. , Osborne Colin P.
Published: February 2021

Species distributions are closely associated with moisture availability, but the underlying mechanisms remain unresolved. Drought relations are especially important for plants such as C4 grasses that dominate seasonally dry ecosystems. Here, we test the hypothesis that C4 grass species sampled across global precipitation gradients show variation in survival under drought that can be explained by their traits.

Our experiment subjected 18 C4 grass species to a lethal drought under controlled environmental conditions. The number of days until death was measured, along with root traits, senescence, and aspects of hydraulic function.

We identified two strategies: Drought‐avoiding species that stayed green as the water potential declined and drought‐tolerating species that senesced more quickly but could extend survival via drought‐tolerant meristems.

Plants that stay‐green for longer occupied drier habitats and had the longest survival under drought, facilitated by narrow root diameter and isohydric stomatal behavior. Plants that senesced quickly had thicker roots, an anisohydric strategy, and occupied wetter habitats.

Global distributions of C4 grasses can be predicted by variation in rates of senescence, meristem survival, root traits, and stomatal strategy, showing the value of these traits for understanding plant distributions in relation to climate.
Integrated effects of rainfall regime and canopy structure on interception loss: A comparative modelling analysis for an artificial larch forest
Authors: Tu Lihui , Xiong Wei , Wang Yanhui , Yu Pengtao , Liu Zebin , Han Xinsheng , Yu Yipeng , Shi Zhongjie , Guo Hao , Li Zhenhua , Wang Xiao , Xu Lihong
Published: February 2021

Model optimization is essential for accurately simulating rainfall interception loss (I) in artificial forests and for quantifying the influence of canopy structure, rainfall regime, and meteorological variables on I. Herein, the revised Gash (addressing physical mechanisms) and Wang (addressing canopy structural impacts) models were used for comparative I simulations using a larch plantation in NW China. We used throughfall (Tf) and stemflow (Sf) measurements from the growing seasons of three consecutive years and found that from the total rainfall measured (1371.6 mm) in 59 selected rain events, Tf, Sf, and I accounted for 80.8%, 1.6%, and 17.6%, respectively. Surprisingly, the two tested models showed similar behaviours in their I simulations, with their performances classified as “very good,” exhibiting 5% and 2.3% cumulative I relative errors for the revised Gash and Wang models, respectively. We noted that, although I was well simulated for light–moderate rain events (<25 mm), absolute errors increased significantly as rainfall amount and duration increased, owing to the constant evaporation rate applied in the models. Leaf area index (LAI) explained 40% of the water detention variation in the canopy, rather than I, which only reflected canopy storage capacity dynamics during the growing season. Collectively, our results revealed that models only addressing the independent impact of wet evaporation or structural dynamics are inadequate for accurately simulating I during heavy rain events (>25 mm). Therefore, future models should account for the potential errors arising from evaporation estimation and consider the effects of LAI.
Understanding community assembly rules in managed floodplain food webs
Authors: Corline Nicholas J. , Peek Ryan A. , Montgomery Jacob , Katz Jacob V. E. , Jeffres Carson A.
Published: February 2021

Community assembly has been an important topic in ecological research and theory for over a century. Recently, restoration ecologists have emphasized the use of community assembly rules, such as environmental filtering, to better inform management actions. Although there has been a strong call for the use of community assembly rules in terrestrial restoration ecology, few studies have examined their potential use in providing habitat benefits such as food resources to native species in large‐scale managed aquatic ecosystems. In this study, we found evidence of deterministic community assembly mechanisms in zooplankton communities in floodplain and seasonally inundated off‐channel habitats in California’s Central Valley. Additionally, we found that all sampled off‐channel floodplain habitat types had similar zooplankton communities and that assembly in floodplain habitats was governed by variables associated with increased water residence time. This study is the first to determine community assembly rules in floodplain‐river ecosystems in order to assist managers in providing floodplain food‐web benefits to native fish and wildlife species at the landscape scale.
Tolerability of eptinezumab in overweight, obese or type 1 diabetes patients
Authors: Baker Brian , Schaeffler Barbara , Hirman Joe , Hompesch Marcus , Pederson Susan , Smith Jeff
Published: February 2021

Introduction

In addition to its role in the pathogenesis of migraine, calcitonin gene‐related peptide (CGRP) is implicated in the regulation of insulin secretion. However, there are limited data on the use of CGRP inhibitor monoclonal antibodies in individuals who are overweight/obese and those with diabetes.

Methods

Two randomized, double‐blind, placebo‐controlled trials were conducted to assess the safety and metabolic effects of eptinezumab in non‐migraine overweight/obese patients (study 1) and patients with type 1 diabetes (T1D; study 2). The primary end‐point in overweight/obese patients was safety and changes in basal metabolic rate (BMR), defined as the energy expenditure during the fasting and resting states. In patients with T1D, the primary end‐points were safety and insulin sensitivity as assessed by the bodyweight and insulin concentration corrected glucose infusion rate (M/I).

Results

A total of 24 patients were enrolled in study 1, and 21 patients were enrolled in study 2. In overweight/obese patients, there was no significant difference in the least squares (LS) mean change in BMR between the eptinezumab‐ and placebo‐treated patients from baseline to day 7 (6.4 vs −25.2 Kcal/day; LS mean difference 31.6 [95% confidence interval −90.6, 153.8]). In patients with T1D, there was no significant difference in insulin sensitivity between the eptinezumab and placebo groups. Eptinezumab was well tolerated in both studies with a similar rate of adverse events between treatment groups, and no new safety signals were identified.

Conclusion

Eptinezumab was well tolerated and not associated with adverse metabolic effects in patients who were overweight/obese or had T1D, providing ongoing support for the use of eptinezumab in these subgroups of patients with migraine.