bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men
Authors: Comninos Alexander N , Hansen Morten S , Courtney Alan , Choudhury Sirazum , Yang Lisa , Mills Edouard G , Phylactou Maria , Busbridge Mark , Khir Muaza , Thaventhiran Thilipan , Bech Paul , Tan Tricia , Abbara Ali , Frost Morten , Dhillo Waljit S 
Published: March 2022

Abstract

Context
Osteoporosis results from disturbances in bone formation and resorption. Recent nonhuman data suggest that the reproductive hormone kisspeptin directly stimulates osteoblast differentiation in vitro and thus could have clinical therapeutic potential. However, the effects of kisspeptin on human bone metabolism are currently unknown.

Objective
To assess the effects of kisspeptin on human bone metabolism in vitro and in vivo.

Methods
In vitro study: of Mono- and cocultures of human osteoblasts and osteoclasts treated with kisspeptin. Clinical study: Randomized, placebo-controlled, double-blind, 2-way crossover clinical study in 26 men investigating the effects of acute kisspeptin administration (90 minutes) on human bone metabolism, with blood sampling every 30 minutes to +90 minutes. Cells for the in vitro study were from 12 male blood donors and 8 patients undergoing hip replacement surgery. Twenty-six healthy eugonadal men (age 26.8 ± 5.8 years) were included in the clinical study. The intervention was Kisspeptin (vs placebo) administration. The main outcome measures were changes in bone parameters and turnover markers.

Results
Incubation with kisspeptin in vitro increased alkaline phosphatase levels in human bone marrow mesenchymal stem cells by 41.1% (P = .0022), and robustly inhibited osteoclastic resorptive activity by up to 53.4% (P &lt; .0001), in a dose-dependent manner. Kisspeptin administration to healthy men increased osteoblast activity, as evidenced by a 20.3% maximal increase in total osteocalcin (P = .021) and 24.3% maximal increase in carboxylated osteocalcin levels (P = .014).

Conclusion
Collectively, these data provide the first human evidence that kisspeptin promotes osteogenic differentiation of osteoblast progenitors and inhibits bone resorption in vitro. Furthermore, kisspeptin acutely increases the bone formation marker osteocalcin but not resorption markers in healthy men, independent of downstream sex steroid levels. Kisspeptin could therefore have clinical therapeutic application in the treatment of osteoporosis.
Childhood Height Growth Rate Association With the Risk of Islet Autoimmunity and Development of Type 1 Diabetes
Authors: Li Zhiguo , Veijola Riitta , Koski Eileen , Anand Vibha , Martin Frank , Waugh Kathleen , Hyöty Heikki , Winkler Christiane , Killian Michael B , Lundgren Markus , Ng Kenney , Maziarz Marlena , Toppari Jorma 
Published: March 2022

Abstract

Context
Rapid growth has been suggested to promote islet autoimmunity and progression to type 1 diabetes (T1D). Childhood growth has not been analyzed separately from the infant growth period in most previous studies, but it may have distinct features due to differences between the stages of development.

Objective
We aimed to analyze the association of childhood growth with development of islet autoimmunity and progression to T1D diagnosis in children 1 to 8 years of age.

Methods
Longitudinal data of childhood growth and development of islet autoimmunity and T1D were analyzed in a prospective cohort study including 10 145 children from Finland, Germany, Sweden, and the United States, 1-8 years of age with at least 3 height and weight measurements and at least 1 measurement of islet autoantibodies. The primary outcome was the appearance of islet autoimmunity and progression from islet autoimmunity to T1D.

Results
Rapid increase in height (cm/year) was associated with increased risk of seroconversion to glutamic acid decarboxylase autoantibody, insulin autoantibody, or insulinoma-like antigen-2 autoantibody (hazard ratio [HR] = 1.26 [95% CI = 1.05, 1.51] for 1-3 years of age and HR = 1.48 [95% CI = 1.28, 1.73] for &gt;3 years of age). Furthermore, height rate was positively associated with development of T1D (HR = 1.80 [95% CI = 1.15, 2.81]) in the analyses from seroconversion with insulin autoantibody to diabetes.

Conclusion
Rapid height growth rate in childhood is associated with increased risk of islet autoimmunity and progression to T1D. Further work is needed to investigate the biological mechanism that may explain this association.
Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Nonalcoholic Fatty Liver Disease in Middle Age
Authors: Zhou Haobin , Zeng Xianghui , Xue Yuting , Wang Xiao , Liu Shenrong , Zhu Zongyuan , Luo Zichao , Ma Zhuang , Zhang Hao , Zhan Qiong , Bai Yujia , Huang Xingfu , Zeng Qingchun , Ren Hao , Xu Dingli 
Published: March 2022

Abstract

Context
Diabetes has a bidirectional association with nonalcoholic fatty liver disease (NAFLD) and increases the risk of cirrhosis and related complications.

Objective
To investigate the association between visit-to-visit fasting glucose (FG) variability in early adulthood and NAFLD in middle age.

Methods
This prospective cohort study included 2467 Black and White adults aged 18 to 30 years at baseline (1985-1986) who were followed over 25 years in the Coronary Artery Risk Development in Young Adults Study. FG variability measures included coefficient of variation about the mean FG (CV-FG), the SD of FG (SD-FG), and the average real variability of FG (ARV-FG) across 25 years (year 0, 7, 10, 15, 20, and 25 examinations). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units on computed tomography scan at year 25 examination after excluding other causes of hepatic steatosis.

Results
Of the 2467 participants, 241 (9.8%) had NAFLD at year 25. In multivariate analysis, the odds ratio for NAFLD was 2.80 (95% CI, 1.69-4.64; P trend &lt; 0.001) for the fourth quartile vs first quartile of CV-FG after adjusting for confounding variables, including mean FG. Similar results were observed for SD-FG and ARV-FG.

Conclusion
Greater visit-to-visit FG variability in early adulthood was associated with higher risk of NAFLD in middle age independent of mean FG level. FG variability may help identify individuals at high risk for NAFLD.
Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management
Authors: Hophan Shelby Lynn , Odnokoz Olena , Liu Huiping , Luo Yuan , Khan Seema , Gradishar William , Zhou Zhuan , Badve Sunil , Torres Mylin A , Wan Yong 
Published: March 2022

AbstractDuctal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.
Selective requirement for polycomb repressor complex 2 in the generation of specific hypothalamic neuronal subtypes
Authors: Yaghmaeian Salmani Behzad , Balderson Brad , Bauer Susanne , Ekman Helen , Starkenberg Annika , Perlmann Thomas , Piper Michael , Bodén Mikael , Thor Stefan 
Published: March 2022

ABSTRACT
The hypothalamus displays staggering cellular diversity, chiefly established during embryogenesis by the interplay of several signalling pathways and a battery of transcription factors. However, the contribution of epigenetic cues to hypothalamus development remains unclear. We mutated the polycomb repressor complex 2 gene Eed in the developing mouse hypothalamus, which resulted in the loss of H3K27me3, a fundamental epigenetic repressor mark. This triggered ectopic expression of posteriorly expressed regulators (e.g. Hox homeotic genes), upregulation of cell cycle inhibitors and reduced proliferation. Surprisingly, despite these effects, single cell transcriptomic analysis revealed that most neuronal subtypes were still generated in Eed mutants. However, we observed an increase in glutamatergic/GABAergic double-positive cells, as well as loss/reduction of dopamine, hypocretin and Tac2-Pax6 neurons. These findings indicate that many aspects of the hypothalamic gene regulatory flow can proceed without the key H3K27me3 epigenetic repressor mark, but points to a unique sensitivity of particular neuronal subtypes to a disrupted epigenomic landscape.
How octopus arm muscle contractile properties and anatomical organization contribute to arm functional specialization
Authors: Zullo Letizia , Di Clemente Alessio , Maiole Federica 
Published: March 2022

ABSTRACT
Octopus arms are highly flexible structures capable of complex motions and are used in a wide repertoire of behaviors. Movements are generated by the coordinated summation of innervation signals to packed arrays of muscles oriented in different directions and moving based on their anatomical relationships. In this study, we investigated the interplay between muscle biomechanics and anatomical organization in the Octopus vulgaris arm to elucidate their role in different arm movements. We performed isometric and isotonic force measurements on isolated longitudinal and transverse arm muscles and showed that longitudinal muscles have a higher rate of activation and relaxation, lower twitch-to-tetanus ratio and lower passive tension than transverse muscles, thus prompting their use as faster and slower muscles, respectively. This points to the use of longitudinal muscles in more graded responses, such as those involved in precise actions, and transverse muscles in intense and sustained actions, such as motion stabilization and posture maintenance. Once activated, the arm muscles exert forces that cause deformations of the entire arm, which are determined by the amount, location, properties and orientation of their fibers. Here, we show that, although continuous, the arm manifests a certain degree of morphological specialization, where the arm muscles have a different aspect ratio along the arm. This possibly supports the functional specialization of arm portions observed in various motions, such as fetching and crawling. Hence, the octopus arm as a whole can be seen as a ‘reservoir’ of possibilities where different types of motion may emerge at the limb level through the co-option of the muscle contractile properties and structural arrangement.
Seeing Picasso: an investigation into the visual system of the triggerfish Rhinecanthus aculeatus
Authors: Cheney Karen L. , Hudson Jemma , de Busserolles Fanny , Luehrmann Martin , Shaughnessy Abigail , van den Berg Cedric , Green Naomi F. , Marshall N. Justin , Cortesi Fabio 
Published: March 2022

ABSTRACT
Vision is used by animals to find food and mates, avoid predators, defend resources and navigate through complex habitats. Behavioural experiments are essential for understanding animals' perception but are often challenging and time-consuming; therefore, using species that can be trained easily for complex tasks is advantageous. Picasso triggerfish, Rhinecanthus aculeatus, have been used in many behavioural studies investigating vision and navigation. However, little is known about the molecular and anatomical basis of their visual system. We addressed this knowledge gap here and behaviourally tested achromatic and chromatic acuity. In terms of visual opsins, R. aculeatus possessed one rod opsin gene (RH1) and at least nine cone opsins: one violet-sensitive SWS2B gene, seven duplicates of the blue–green-sensitive RH2 gene (RH2A, RH2B, RH2C1-5) and one red-sensitive LWS gene. However, only five cone opsins were expressed: SWS2B expression was consistent, while RH2A, RH2C-1 and RH2C-2 expression varied depending on whether fish were sampled from the field or aquaria. Levels of LWS expression were very low. Using fluorescence in situ hybridisation, we found SWS2B was expressed exclusively in single cones, whereas RH2A and RH2Cs were expressed in opposite double cone members. Anatomical resolution estimated from ganglion cell densities was 6.8 cycles per degree (cpd), which was significantly higher than values obtained from behavioural testing for black-and-white achromatic stimuli (3.9 cpd) and chromatic stimuli (1.7–1.8 cpd). These measures were twice as high as previously reported. This detailed information on their visual system will help inform future studies with this emerging focal species.
Shoulder Injury Related to Vaccine Administration and a Growing Challenge: A Focused Review
Authors: Pettyjohn Eric W. , Clugston James R. , Zaremski Jason L. 
Published: March 2022

Abstract
Shoulder injury related to vaccine administration (SIRVA), an entity that causes acute shoulder pain and may limit range of motion (ROM) after vaccination, is a condition where a small but significant percentage of patients are experiencing in light of the current push for mass immunizations against SARS-CoV-2 worldwide. A search of literature related to SIRVA was performed across multiple electronic databases. Women, patients reporting vaccine injection location to be too high, and patients without prior history of shoulder pain were the most common historical factors in those experiencing SIRVA. Tenderness to palpation and limited shoulder ROM were the most associated physical examination findings. When using magnetic resonance imaging, tendinopathy, subacromial-subdeltoid bursitis, and rotator cuff tears (partial or complete) were the most common findings. Radiographic imaging rarely aided the diagnosis. SIRVA is an entity that health care providers should be aware of to improve the care of patients that may experience these symptoms after vaccine administration.
First report of Serratia marcescens associated with black rot of Citrus sinensis fruit, and evaluation of its biological control measures in Bangladesh
Authors: Hasan Mohammed Faruk , Islam Mohammed Asadul , Sikdar Biswanath 
Published: March 2022

Background: The present study was designed to isolate and identify the phyto-pathogen responsible for black rot of Citrus sinensis, and to determine its biological control measures. Methods: The pathogen was isolated from infected oranges and cultured on Luria-Bertani medium. Gram staining method was used to identify the morphological characteristics of the causal agents of the black rot. Advanced molecular technique was applied to facilitate proper detection of the isolated bacteria. Phylogenetic trees were analyzed using the Neighbor-Joining method. Antimicrobial screening was conducted by disc diffusion method. Antagonistic activity was evaluated by well diffusion method. Results: Gram staining of the causal agent showed rod shaped, small and pink bacteria. Polymerase chain reaction of the 16S ribosomal RNA gene amplified an approximately 1465 bp product. The nucleotide sequences of the isolated bacterial sample 1 (BS1) and bacterial sample 2 (BS2) had 99.34% and 99.45% similarities with the reference of Serratia marcescens sequence in NCBI GenBank. The obtained sequences were deposited in GenBank. Two isolates showed virulence capability on some fresh fruits, which confirmed the stain detection and Koch’s postulates. Allium sativum extract showed the largest (27.33±1.5 mm) diameter of zone of inhibition against BS1, at 30µg/disc concentration. In the antagonistic assay, Rhizobium leguminosarum showed largest (19±1 mm) zone of inhibition against BS1. Conclusions: Findings of the current investigations are constructive for identification of causative pathogens in Citrus sinensis black rot disease and their biological control measures.
Economic burden of out-of-pocket expenditure, productivity cost during pregnancy and COVID-19 impact on household economy in a cohort of pregnant women in Anuradhapura District, Sri Lanka; A study protocol
Authors: Gunarathne Sajaan Praveena , Wickramasinghe Nuwan Darshana , Agampodi Thilini Chanchala , Prasanna Indika Ruwan , Agampodi Suneth Buddhika 
Published: March 2022

Background: Investigating the out-of-pocket expenditure (OOPE) associated with maternal health is important since OOPE directly affects the affordability of health services. Global evidence suggests the importance of capturing the productivity cost during pregnancy in terms of absenteeism and presenteeism. Furthermore, the impact of the ongoing COVID-19 pandemic on the household economy needs to be further evaluated as pregnant women are one of the most vulnerable groups. This study aims at determining the economic burden of OOPE, productivity cost, and COVID-19 impact on pregnant women's household economy in a cohort of pregnant women in Anuradhapura District, Sri Lanka. Methods: The study setting is all 22 Medical Officer of Health (MOH) areas in Anuradhapura district, Sri Lanka. The study has three components; a follow-up study of a cohort of pregnant women to assess the magnitude and associated factors of OOPE and to assess the productivity cost (Component 1), a qualitative case study to explore the impact and causes of the OOPE under free health services (Component 2) and a cross-sectional study to describe the effects of COVID-19 outbreak on household economy (Component 3). The study samples consist of 1,573 and 1,460 participants for components one and three, respectively, and 25 pregnant women will be recruited for component two. The data will be analyzed using descriptive, parametric, and non-parametric statistics for the first and third components and thematic analysis for the second component. Discussion: With the lack of evidence on OOPE, productivity loss/cost in terms of maternal health, and COVID-19 impact on household economy in Sri Lanka, the evidence generated from this study would be valuable for policymakers, health care administrators, and health care practitioners globally, regionally, and locally to plan for future measures for reducing the OOPE, productivity loss/cost, and minimizing the economic hardship of the COVID-19 outbreak during pregnancy.
Assessment of the feasibility of Juntos: A support programme for families of children affected by Congenital Zika Syndrome
Authors: Duttine Antony , Smythe Tracey , Calheiros de Sá Miriam Ribeiro , Ferrite Silvia , Moreira Maria Elizabeth , Kuper Hannah 
Published: March 2022

Background: The 2015-16 Zika epidemic resulted in thousands of children born with congenital Zika syndrome (CZS). In Brazil, gaps in the health system often caused parents to be left with insufficient information and support. Consequently, we developed and piloted Juntos - a participatory support programme which aims to improve knowledge, capacities and build support networks for caregivers of children with CZS. Methods: Six caregiver groups received the programme between August 2017 and June 2018: three in Rio de Janeiro and three in Bahia. We assessed the feasibility of Juntos against six of the eight areas of a feasibility framework described by Bowen et al. to consider whether Juntos ‘could work’. These areas were: acceptability, demand, implementation, practicality, adaptation and limited efficacy. We used mixed methods including: 1) baseline and end-line questionnaires completed by all group participants; 2) in-depth interviews with 18 participants, seven facilitators and three key stakeholders; 3) participant focus group discussions after each session; 4) researchers session observation; and 5) recording programme costs. Results: 37/48 (77%) enrolled families completed both questionnaires. Acceptability and demand were noted as high, based on participant responses to interview questions, focus group feedback and satisfaction scores. Potential for implementation and practicality were also demonstrated through interviews with facilitators and key stakeholders and analysis of project documents. Two groups included caregivers of children with non-Zika related developmental disabilities, showing potential for adaptability. Self-reported quality of life scores increased in caregivers between baseline and end-line, as did the dimensions of family relationships and daily activities in the Pediatric Quality of Life Inventory (PEDS QL) Family Impact Module, showing limited efficacy. Conclusions: The programme showed feasibility according to Bowen’s framework. However, further research of scale up, particularly in the areas of integration, expansion and limited efficacy are needed to ascertain if the programme is effective.
Identification of Causal Mechanisms from Randomized Experiments: A Framework for Endogenous Mediation Analysis
Authors: Peng Jing 
Published: March 2022

Practice- and Policy-Oriented AbstractExperimental research often focuses on the overall treatment effect and the heterogeneity therein. Whereas this type of research allows us to understand the strength and direction of the treatment effect under different conditions, it does not directly speak to the generative mechanisms, namely, why and how the effect arises. A standard procedure to identify the mechanisms underlying a treatment effect is mediation analysis, but extant mediation analysis frameworks either have no causal interpretation or require the mediators to be unconfounded. Because mediators typically cannot be preassigned beforehand, their endogeneity remains a serious concern even in randomized experiments. This paper presents a flexible endogenous mediation analysis framework that still has causal interpretation when the mediator is endogenous. We discuss the identification conditions for different types of endogenous mediators, including unobserved or partially observed ones, under this framework. We show that endogenous mediation models can be parametrically identified without an instrumental variable when the generating process of the mediator is nonlinear. We further examine how the identification strengths of these models vary with a series of factors. Finally, we provide guidelines on when and how to use endogenous mediation analysis. We offer an R package that implements the proposed models.