bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D-printed microplate inserts for long term high-resolution imaging of live brain organoids
Authors: Oksdath Mansilla Mariana , Salazar-Hernandez Camilo , Perrin Sally L. , Scheer Kaitlin G. , Cildir Gökhan , Toubia John , Sedivakova Kristyna , Tea Melinda N. , Lenin Sakthi , Ponthier Elise , Yeo Erica C. F. , Tergaonkar Vinay , Poonnoose Santosh , Ormsby Rebecca J. , Pitson Stuart M. , Brown Michael P. , Ebert Lisa M. , Gomez Guillermo A. 
Published: March 2021

AbstractBackgroundOrganoids are a reliable model used in the study of human brain development and under pathological conditions. However, current methods for brain organoid culture generate tissues that range from 0.5 to 2 mm of size, which need to be constantly agitated to allow proper oxygenation. The culture conditions are, therefore, not suitable for whole-brain organoid live imaging, required to study developmental processes and disease progression within physiologically relevant time frames (i.e. days, weeks, months).ResultsHere we designed 3D-printed microplate inserts adaptable to standard 24 multi-well plates, which allow the growth of multiple organoids in pre-defined and fixed XYZ coordinates. This innovation facilitates high-resolution imaging of whole-cerebral organoids, allowing precise assessment of organoid growth and morphology, as well as cell tracking within the organoids, over long periods. We applied this technology to track neocortex development through neuronal progenitors in brain organoids, as well as the movement of patient-derived glioblastoma stem cells within healthy brain organoids.ConclusionsThis new bioengineering platform constitutes a significant advance that permits long term detailed analysis of whole-brain organoids using multimodal inverted fluorescence microscopy.
Quorum sensing-mediated inter-specific conidial anastomosis tube fusion between Colletotrichum gloeosporioides and C. siamense
Authors: Mehta Nikita , Baghela Abhishek 
Published: March 2021

AbstractMany plant pathogenic filamentous fungi undergo fusion of conidia through conidial anastomosis tubes (CATs), which is believed to facilitate horizontal gene transfer between species. We discovered a remarkable inter-specific CAT fusion between two important plant fungal pathogensColletotrichum gloeosporioidesandC. siamense. In an invitro assay, under no selection pressure, the inter-specific CAT fusion was preferred with higher frequency (25% ± 5%) than intra-specific CAT fusion (11% ± 3.6%). Different stages of CAT fusion viz. CAT induction, homing, and fusion were observed during this inter-specific CAT fusion. The CAT fusion was found to be higher in absence of nutrients and under physiological stresses. This CAT fusion involved a quorum sensing phenomenon, wherein the CAT induction was dependent on conidial density and the putative quorum sensing molecule was extractable in chloroform. Movement of nuclei, mitochondria, and lipid droplets were observed during the CAT fusion. Post CAT fusion, the resulting conidia gave rise to putative heterokaryotic progenies with variable colony characteristics as compared to their parental strains. Few heterokaryons showed variable AFLP banding pattern compared to their parental strains, thereby suggesting a possible genetic exchange between the two species through CAT fusion. The heterokaryotic progenies exhibited varied fitness under different stress conditions. Our study illustrated a possible role of inter-specific CAT fusion in generation of genetic and phenotypic diversity in these fungal pathogens.
Mutational analysis of p53 gene in cervical cancer and useful polymorphic variants in exons 3 and 4
Authors: Gbadegesin Michael A. , Omotoso Olabode E. , Oluwasola Timothy A. O. , Okolo Clement A. , Soremekun Opeyemi , Ogun Gabriel O. , Oluwasola Abideen O. , Odunola Oyeronke A. 
Published: March 2021

Abstract
Background
Factors contributing to the pathogenesis and progression of cervical cancer include poor attitude to screening and health intervention, late presentation, among others. Mutations in p53 gene have been attributed to several cancer cases. The present study was designed to find relationships between the mutation patterns in p53 gene and cervical carcinoma staging. Such knowledge could contribute to early diagnosis of cervical cancer.

Results
From the sequence analysis of p53 gene fragment isolated by polymerase chain reactions (PCR), nineteen (19) polymorphic variants were identified. Missense mutations occurred in 47% of the samples, 32% were silent mutations, 16% were frameshift mutations and 5% nonsense mutations. Socio-biological characteristics of the study participants revealed that 60% have husbands with multiple sexual partners and that only 23.3% of the participants have ever had the Papanicolaou (Pap) smear test prior to diagnosis, whilst 20% were unaware of the screening test.

Conclusions
Increased severity of cervical carcinoma staging as revealed from the histopathological analysis was found to be associated with accumulation of higher levels of mutations in the p53 gene. Molecular analysis of p53 gene mutations may prove useful as a screening biomarker for cervical cancer.
SOX10Mutation Screening for 117 Patients with Kallmann Syndrome
Authors: Shima Hirohito , Tokuhiro Etsuro , Okamoto Shingo , Nagamori Mariko , Ogata Tsutomu , Narumi Satoshi , Nakamura Akie , Izumi Yoko , Jinno Tomoko , Suzuki Erina , Fukami Maki 
Published: March 2021

AbstractIntroductionKallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism (HH) and olfactory dysfunction. Although SOX10, a causative gene for Waardenburg syndrome (WS) and peripheral demyelinating neuropathy, central demyelination, WS, and Hirschsprung disease (PCWH) has previously been implicated in KS, the clinical significance of SOX10 variants as the cause of KS remains uncertain.Patients and MethodsA total of 117 patients with KS underwent mutation screening of SOX10 and 14 other causative genes for KS/HH. Rare SOX10 variants were subjected to in silico and in vitro analyses. We also examined clinical data of the patients and their parents with SOX10 variants.ResultsSequence analysis identified 2 heterozygous variants of SOX10 (c.1225G &gt; T, p.Gly409* and c.475C &gt; T, p.Arg159Trp) in patients 1–3, as well as in the parents of patients 1 and 3. The variants were assessed as pathogenic/likely pathogenic, according to the American College of Medical Genomics guidelines. Both variants lacked in vitro transactivating activity for the MITF promoter and exerted no dominant-negative effects. Patients 1–3 carried no pathogenic variants in other genes examined. The patients presented with typical KS, while such features were absent in the parents of patients 1 and 3. None of the 5 variant-positive individuals exhibited hypopigmentation, while 1 and 2 individuals exhibited complete and partial hearing loss, respectively.ConclusionThese results provide evidence that SOX10 haploinsufficiency accounts for a small percentage of KS cases. SOX10 haploinsufficiency is likely to be associated with a broad phenotypic spectrum, which includes KS without other clinical features of WS/PCWH.
Prepubertal gonad investment modulates thymus function: evidence in a teleost fish
Authors: Paiola Matthieu , Moreira Catarina , Hétru Julie , Duflot Aurélie , Pinto Patricia I. S. , Scapigliati Giuseppe , Knigge Thomas , Monsinjon Tiphaine 
Published: March 2021

ABSTRACT
Thymus plasticity following gonadectomy or sex hormone replacement has long since exemplified sex hormone effects on the immune system in mammals and, to a lesser extent, in ‘lower vertebrates’, including amphibians and fish. Nevertheless, the underlying physiological significances as well as the ontogenetic establishment of this crosstalk remain largely unknown. Here, we used a teleost fish, the European sea bass, Dicentrarchus labrax, to investigate: (1) whether the regulation of thymus plasticity relies on resource trade-off with somatic growth and reproductive investment and (2) if the gonad–thymus interaction takes place during gonadal differentiation and development. Because gonadal development and, supposedly, thymus function in sea bass depend on environmental changes associated with the winter season, we evaluated thymus changes (foxn1 expression, and thymocyte and T cell content) in juvenile D. labrax raised for 1 year under either constant or fluctuating photoperiod and temperature. Importantly, in both conditions, intensive gonadal development following sex differentiation coincided with a halt of thymus growth, while somatic growth continued. To the best of our knowledge, this is the first study showing that gonadal development during prepuberty regulates thymus plasticity. This finding may provide an explanation for the initiation of the thymus involution related to ageing in mammals. Comparing fixed and variable environmental conditions, our work also demonstrates that the extent of the effects on the thymus, which are related to reproduction, depend on ecophysiological conditions, rather than being directly related to sexual maturity and sex hormone levels.
The Impact of Lower Limb Immobilization and Rehabilitation on Angiogenic Proteins and Capillarization in Skeletal Muscle
Authors: GLIEMANN LASSE , RYTTER NICOLAI , JØRGENSEN TUE SMITH , PIIL PETER , CARTER HOWARD , NYBERG MICHAEL , GRASSI MARCELLO , DAUMER MARTIN , HELLSTEN YLVA 
Published: March 2021

ABSTRACT

Purpose
Skeletal muscle vascularization is important for tissue regeneration after injury and immobilization. We examined whether complete immobilization influences capillarization and oxygen delivery to the muscle and assessed the efficacy of rehabilitation by aerobic exercise training.

Methods
Young healthy males had one leg immobilized for 14 d and subsequently completed 4 wk of intense aerobic exercise training. Biopsies were obtained from musculus vastus lateralis, and arteriovenous blood sampling for assessment of oxygen extraction and leg blood flow during exercise was done before and after immobilization and training. Muscle capillarization, muscle and platelet content of vascular endothelial growth factor (VEGF), and muscle thrombospondin-1 were determined.

Results
Immobilization did not have a significant impact on capillary per fiber ratio or capillary density. The content of VEGF protein in muscle samples was reduced by 36% (P = 0.024), and VEGF to thrombospondin-1 ratio was 94% lower (P = 0.046). The subsequent 4-wk training period increased the muscle VEGF content and normalized the muscle VEGF to thrombospondin-1 ratio but did not influence capillarization. Platelet VEGF content followed the trend of muscle VEGF. At the functional level, oxygen extraction, blood flow, and oxygen delivery at rest and during submaximal exercise were not affected by immobilization or training.

Conclusions
The results demonstrate that just 2 wk of leg immobilization leads to a strongly reduced angiogenic potential as evidenced by reduced muscle and platelet VEGF content and a reduced muscle VEGF to thrombospondin-1 ratio. Moreover, a subsequent period of intensive aerobic exercise training fails to increase capillarization in the previously immobilized leg, possibly because of the angiostatic condition caused by immobilization.
Microstructural Plasticity in the Hippocampus of Healthy Older Adults after Acute Exercise
Authors: CALLOW DANIEL D. , WON JUNYEON , ALFINI ALFONSO J. , PURCELL JEREMY J. , WEISS LAUREN R. , ZHAN WANG , SMITH J. CARSON 
Published: March 2021

ABSTRACT

Introduction
The hippocampus experiences structural and functional decline with age and is a critical region for memory and many cognitive processes. Exercise is beneficial for the aging brain and shows preferential benefits for hippocampal volume, activation, and memory-related cognitive processes. However, research thus far has primarily focused on the effects of exercise on long-term volumetric changes in the hippocampus using structural magnetic resonance imaging. Critically, microstructural alterations within the hippocampus over short time intervals are associated with neuroplasticity and cognitive changes that do not alter its volume but are still functionally relevant. However, it is not yet known if microstructural neuroplasticity occurs in the hippocampus in response to a single session of exercise.

Methods
We used a within-subject design to determine if a 30-min bout of moderate-intensity aerobic exercise altered bilateral hippocampal diffusion tensor imaging measures in healthy older adults (n = 30) compared with a seated rest control condition.

Results
Significantly lower fractional anisotropy and higher mean diffusivity were found after exercise relative to seated rest within the bilateral hippocampus, and this effect was driven by higher radial diffusivity. No significant differences in axial diffusivity were observed.

Conclusions
These findings suggest that a single exercise session can lead to microstructural alterations in the hippocampus of healthy older adults. These differences may be associated with changes in the extracellular space and glial, synaptic, and dendritic processes within the hippocampus. Repeated microstructural alterations resulting from acute bouts of exercise may accumulate and precede larger volumetric and functional improvements in the hippocampus.
Altered Triceps Surae Muscle–Tendon Unit Properties after 6 Months of Static Stretching
Authors: MOLTUBAKK MARIE M. , VILLARS FABIENNE O. , MAGULAS MELINA M. , MAGNUSSON STIG P. , SEYNNES OLIVIER R. , BOJSEN-MØLLER JENS 
Published: March 2021

ABSTRACT

Introduction
This study examined the effects of 24 wk of daily static stretching of the plantarflexors (unilateral 4 × 60-s stretching, whereas the contralateral leg served as a control; n = 26) on joint range of motion (ROM), muscle–tendon unit morphological and mechanical properties, neural activation, and contractile function.

Methods
Torque–angle/velocity was obtained in passive and active conditions using isokinetic dynamometry, whereas muscle–tendon morphology and mechanical properties were examined using ultrasonography.

Results
After the intervention, ROM increased (stretching, +11° ± 7°; control, 4° ± 8°), and passive torque (stretching, −10 ± 11 N·m; control, −7 ± 10 N·m) and normalized EMG amplitude (stretching, −3% ± 6%; control, −3% ± 4%) at a standardized dorsiflexion angle decreased. Increases were seen in passive tendon elongation at a standardized force (stretching, +1.3 ± 1.6 mm; control, +1.4 ± 2.1 mm) and in maximal passive muscle and tendon elongation. Angle of peak torque shifted toward dorsiflexion. No changes were seen in tendon stiffness, resting tendon length, or gastrocnemius medialis fascicle length. Conformable changes in ROM, passive dorsiflexion variables, tendon elongation, and angle of peak torque were observed in the nonstretched leg.

Conclusions
The present findings indicate that habitual stretching increases ROM and decreases passive torque, altering muscle–tendon behavior with the potential to modify contractile function.
Interpretable Machine Learning Model for Early Prediction of Mortality in ICU Patients with Rhabdomyolysis
Authors: LIU CHAO , LIU XIAOLI , MAO ZHI , HU PAN , LI XIAOMING , HU JIE , HONG QUAN , GENG XIAODONG , CHI KUN , ZHOU FEIHU , CAI GUANGYAN , CHEN XIANGMEI , SUN XUEFENG 
Published: March 2021

ABSTRACT

Purpose
Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from RM is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients.

Method
Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III database. We extracted data from the first 24 h after patient ICU admission. Data from the two data sets were merged for further analysis. The merged data sets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model.

Results
In total, 938 patients with RM were eligible for this analysis. The area under the receiver operating characteristic curve (AUC) of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915, and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression, AUC = 0.862; support vector machine, AUC = 0.843; random forest, AUC = 0.825; and naive Bayesian, AUC = 0.805) and clinical scores (Sequential Organ Failure Assessment, AUC = 0.747; Acute Physiology Score III, AUC = 0.721).

Conclusions
Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24 h of admission to the ICU.
The Robot Revolution: Managerial and Employment Consequences for Firms
Authors: Dixon Jay , Hong Bryan , Wu Lynn 
Published: March 2021

As a new general-purpose technology, robots have the potential to radically transform employment and organizations. In contrast to prior studies that predict dramatic employment declines, we find that investments in robotics are associated with increases in total firm employment but decreases in the total number of managers. Similarly, we find that robots are associated with an increase in the span of control for supervisors remaining within the organization. We also provide evidence that robot adoption is not motivated by the desire to reduce labor costs but is instead related to improving product and service quality. Our findings are consistent with the notion that robots reduce variance in production processes, diminishing the need for managers to monitor worker activities to ensure production quality. As additional evidence, we also find that robot investments predict improved performance measurement and increased adoption of incentive pay based on individual employee performance. With respect to changes in skill composition within the organization, robots predict decreases in employment for middle-skilled workers but increases in employment for low- and high-skilled workers. We also find that robots predict not only changes in employment but also corresponding adaptations in organizational structure. Robot investments are associated with both centralization and decentralization of decision-making authority depending on the task, but decision rights in either case are reassigned away from the managerial level of the hierarchy. Overall, our results suggest that robots have distinct and profound effects on employment and organizations that require fundamental changes in firm practices and organizational design.This paper was accepted by Lamar Pierce, organizations.
Why is lived experience important for market stewardship? A proposed framework for why and how lived experience should be included in stewarding disability markets
Authors: Meltzer Ariella , Dickinson Helen , Malbon Eleanor , Carey Gemma 
Published: March 2021

Background: Many countries use market forces to drive reform across disability supports and services. Over the last few decades, many countries have individualised budgets and devolved these to people with disability, so that they can purchase their own choice of supports from an available market of services.
Key points for discussion: Such individualised, market-based schemes aim to extend choice and control to people with disability, but this is only achievable if the market operates effectively. Market stewardship has therefore become an important function of government in guiding markets and ensuring they operate effectively.
The type of evidence that governments tend to draw on in market stewardship is typically limited to inputs and outputs and has less insight into the outcomes services do or do not achieve. While this is a typical approach to market stewardship, we argue it is problematic and that a greater focus on outcomes is necessary.
Conclusions and implications: To include a focus on outcomes, we argue that market stewards need to take account of the lived experience of people with disability. We present a framework for doing this, drawing on precedents where people with disability have contributed lived experience evidence within other policy, research, knowledge production and advocacy contexts.
With the lived experience evidence of people with disability included, market stewardship will be better able to take account of outcomes as they play out in the lives of those using the market and, ultimately, achieve greater choice and control for people with disability.
Factors that influence performance in Olympic air-rifle and small-bore shooting: A systematic review
Authors: Spancken Sina , Steingrebe Hannah , Stein Thorsten 
Published: March 2021

BackgroundAir-rifle and small-bore shooting are fascinating Olympic sports due to their unique performance requirements for accuracy and precision.ObjectiveThe purpose of our study was to systematically research the literature to determine and summarize performance determinants in both air-rifle and small-bore shooting. Since some athletes participate internationally in both disciplines in competition, the disciplines must have some similarity in the performance structure. Therefore, we further investigated whether performance in air-rifle and small-bore shooting can be explained by the same performance determinants.MethodsWe systematically searched in four databases using combined keywords relevant to performance in air-rifle and small-bore shooting. The articles included had undergone peer-review and had a) a direct relation to shooting performance, b) an indirect relation by comparing the performance of shooters of different skill levels, and c) a practical relevance (directly controllable through training). After the quality of each article was assessed, the key data were extracted and summarized.ResultsThe fourteen articles included achieved an average of 60 ± 14% (range 30–80%) in quality assessment. Altogether, articles covered 268 subjects (32% female), of which 19% were elite- and 28% were national-level athletes. Sixteen performance determinants were investigated, which were divided into anthropometric, technical-coordinative, physiological and psychological categories. Both in air-rifle and small-bore shooting, rifle stability and body sway were found to differ between elite- and national-level athletes. In both disciplines, body sway seemed to have no influence on shot score in elite- and national-level athletes. Similarly, heart rate did not correlate with shot score at nearly all performance levels in both disciplines. In national-level air-rifle athletes, horizontal rifle stability, aiming accuracy and aiming time were found to affect shot score.ConclusionsTo be competitive at a national-level in air-rifle shooting, a highly developed aiming process is needed to achieve a high shot score. Lack of data prevented us from drawing evidence-based conclusions in elite-level air-rifle athletes and in small-bore shooting. Future research should investigate possible performance determinants both in air-rifle and in small-bore shooting, especially with elite-level athletes, to confirm or disprove existing findings. Further research should use more complex analyses to investigate the multifaceted processes associated with different performance determinants.