Miracle-dz/UniFAR-FTUs huggingface dataset:
Hedgehog signaling plays a crucial role in hyperalgesia associated with neuropathic pain in mice

Neuropathic pain is a debilitating chronic syndrome of the nervous system caused by nerve injury. In Drosophila, the Hedgehog (Hh) signaling pathway is related to increased pain sensitivity (hyperalgesia) but does not affect the baseline nociceptive threshold. In general, the contribution of the Hh signaling pathway to neuropathic pain in vertebrates is a highly debated issue. Alternatively, we investigated the potential role of Hh signaling in mechanical allodynia using a mouse model of neuropathic pain. Seven days after spinal nerve‐transection (SNT) surgery, microglial activation increased in the ipsilateral spinal dorsal horn compared with that in the sham group; however, 21 days after surgery, microglial activation decreased. Contrastingly, astrocyte activation in the spinal cord did not differ between the groups. On day 21 of postsurgery, the SNT group showed marked upregulation of sonic hedgehog expression in peripheral glial cells but not in dorsal root ganglion (DRG) neurons. Intrathecal administration of the Hh signaling inhibitor vismodegib attenuated the mechanical allodynia observed on day 21 postsurgery. Conversely, intrathecal treatment with the Hh signaling activator smoothened agonist in naive mice induced mechanical allodynia, which was abolished by the ATP transporter inhibitor clodronate. Moreover, inhibition of Hh signaling by pretreatment with vismodegib significantly reduced ATP secretion and the frequency/number of spontaneous elevations of intracellular calcium ion levels in cultured DRG cells. Thus, the Hh signaling pathway appears to modulate the neural activity of DRG neurons via ATP release, and it plays an important role in sustaining mechanical allodynia and hypersensitivity in a mouse model of neuropathic pain.
Characterization of Hypothalamic MCH Neuron Development in a 3D Differentiation System of Mouse Embryonic Stem Cells

Abstract Hypothalamic melanin-concentrating hormone (MCH) neurons are important regulators of multiple physiological processes, such as sleep, feeding, and memory. Despite the increasing interest in their neuronal functions, the molecular mechanism underlying MCH neuron development remains poorly understood. We report that a three-dimensional culture of mouse embryonic stem cells (mESCs) can generate hypothalamic-like tissues containing MCH-positive neurons, which reproduce morphologic maturation, neuronal connectivity, and neuropeptide/neurotransmitter phenotype of native MCH neurons. Using this in vitro system, we demonstrate that Hedgehog (Hh) signaling serves to produce major neurochemical subtypes of MCH neurons characterized by the presence or absence of cocaine- and amphetamine-regulated transcript (CART). Without exogenous Hh signals, mESCs initially differentiated into dorsal hypothalamic/prethalamic progenitors and finally into MCH+CART+ neurons through a specific intermediate progenitor state. Conversely, activation of the Hh pathway specified ventral hypothalamic progenitors that generate both MCH+CART− and MCH+CART+ neurons. These results suggest that in vivo MCH neurons may originate from multiple cell lineages that arise through early dorsoventral patterning of the hypothalamus. Additionally, we found that Hh signaling supports the differentiation of mESCs into orexin/hypocretin neurons, a well-defined cell group intermingled with MCH neurons in the lateral hypothalamic area (LHA). The present study highlights and improves the utility of mESC culture in the analysis of the developmental programs of specific hypothalamic cell types.
Movement therapy in lung transplantation candidates assisted by a lightweight wearable robot

ABSTRACT The aim of this pilot-study was to investigate the safety, feasibility and tolerability of an assisted mobilization of patients with advanced pulmonary diseases, using a lightweight, exoskeleton-type robot (Myosuit, MyoSwiss AG, Zurich, Switzerland). Ten patients performed activities of daily life (ADL) both with and without the device. The mean age was 53.6 (±5.6) years; 70% were male. The assessment of outcome included the evaluation of vital signs, adverse events, rates of perceived exertion and dyspnea (PRE, PRD), the ability to perform ADL and the individual acceptability. Robotic-assisted mobilization was feasible in all patients. No adverse events occurred. RPE and RPD showed no significant difference with or without the Myosuit (mean difference in RPE -1.7, 95%-confidence interval (CI) -1.16, 4.49; p = 0.211; mean difference in RPD 0.00, 95%-CI -1.88, 1.88; p = 0.475). 80% of patients were interested to participate in a robotic-assisted training on a regular basis. A robotic exoskeleton-assisted mobilization is safe, feasible, well-tolerated and well-accepted. The results are highly encouraging to further pursue this highly innovative approach.
Beyond the snapshot: optimizing prognostication and prediction by moving from fixed to functional multidimensional cancer pathology

The role of pathology in patient management has evolved over time from the retrospective review of cells, tissue, and disease (‘what happened’) to a prospective outlook (‘what will happen’). Examination of a static, two‐dimensional hematoxylin and eosin (H&E)‐stained tissue slide has traditionally been the pathologist's primary task, but novel ancillary techniques enabled by technological breakthroughs have supported pathologists in their increasing ability to predict disease status and behaviour. Nevertheless, the informational limits of 2D, fixed tissue are now being reached and technological innovation is urgently needed to ensure that our understanding of disease entities continues to support improved individualized treatment options. Here we review pioneering work currently underway in the field of cancer pathology that has the potential to capture information beyond the current basic snapshot. A selection of exciting new technologies is discussed that promise to facilitate integration of the functional and multidimensional (space and time) information needed to optimize the prognostic and predictive value of cancer pathology. Learning how to analyse, interpret, and apply the wealth of data acquired by these new approaches will challenge the knowledge and skills of the pathology community. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Discrepancies between prokaryotes and eukaryotes need to be considered in soil DNA‐based studies

Summary Metabarcoding approaches are exponentially increasing our understanding of soil biodiversity, with a major focus on the bacterial part of the microbiome. Part of the soil diversity are also eukaryotes that include fungi, algae, protists and Metazoa. Nowadays, soil eukaryotes are targeted with the same approaches developed for bacteria and archaea (prokaryotes). However, fundamental differences exist between domains. After providing a short historical overview of the developments of metabarcoding applied to environmental microbiology, we compile the most important differences between domains that prevent direct method transfers between prokaryotic and eukaryotic soil metabarcoding approaches, currently dominated by short‐read sequencing. These include the existence of divergent diversity concepts and the variations in eukaryotic morphology that affect sampling and DNA extraction. Furthermore, eukaryotes experienced much more variable evolutionary rates than prokaryotes, which prevent capturing the entire eukaryotic diversity in a soil with a single amplification protocol fit for short‐read sequencing. In the final part we focus on future potentials for optimization of eukaryotic metabarcoding that include superior possibility of functionally characterizing eukaryotes and to extend the current information obtained, such as by adding a real quantitative component. This review should optimize future metabarcoding approaches targeting soil eukaryotes and kickstart this promising research direction.
Needs assessment for career development programs in the Taiwan Power Company (TPC)

Needs Assessment for Career Development Programs in the Taiwan Power Company (TPC). (May 2005) Yi-Hsuan Lee, B.A., Fu Jen Catholic University, Taiwan Chair of Advisory Committee: Dr. Kenneth E. Paprock The harmonious meshing of employee career development needs and corporate missions, goals, and objectives is a necessity for the growth and maintenance of both the individual and the organization. This study was designed to investigate Taiwan Power Company (TPC) white-collar employees’ perceptions of career development program needs. The purposes of the study were (a) to identify the perceptions of career development program needs; (b) to explore the underlying constructs among current and future positions in regard to the employee’s perceptions of career development program needs; (c) to investigate the differences among perceptions of career development needs; (d) to determine whether or not differences among perceptions of career development program needs exist among respondents who differ in terms of gender, age, and education; and (e) to discover if individuals who differ in terms of job functions and job roles have different opinions on whether the selected career development programs were already provided or should be provided by the company.
To be or not be (in the LAD): emerging roles of lamin proteins in transcriptional regulation

Lamins are components of the nuclear lamina, a protein meshwork that underlies the nuclear membrane. Lamins interact with chromatin in transcriptionally silent regions defined as lamina-associated-domains (LADs). However, recent studies have shown that lamins regulate active transcription inside LADs. In addition, ChIP-seq analysis has shown that lamins interact with lamin-dependent promoters and enhancers located in the interior of the nucleus. Moreover, functional studies suggest that lamins regulate transcription at associated-promoters and long-range chromatin interactions of key developmental gene programs. This review will discuss emerging, non-canonical functions of lamins in controlling non-silent genes located both inside and outside of LADs, focusing on transcriptional regulation and chromatin organization in Drosophila and mammals as metazoan model organisms.
Histomorphological and functional contralateral symmetry in the gastrocnemius muscles of the laboratory rat

It is usual in anatomical and physiological research to assess the effects of some intervention on extremities (e.g., training programmes or injury recovery protocols) using one muscle for the intervention and its contralateral as control. However, the existence of laterality (left‐handedness or right‐handedness) in athletes of different specialities is widely recognized. In rats, gastrocnemius is one of the muscles most widely used because of its importance in locomotion and high relative limb mass. Since we have not found studies reporting laterality assessment on the morphology and function in rat gastrocnemius, our study aimed to evaluate the fibre histochemical, morphometrical and muscle force contractile properties between right and left gastrocnemius of the laboratory rat. Fibre‐type proportion, fibre morphometrical measurements, muscle capillarization and muscle force properties were analysed in the right and left gastrocnemius of six male rats. No statistically significant differences (p = 0.265) were found in gastrocnemius to body weight ratio (‰) between right (6.55 ± 0.40) and left (6.49 ± 0.40) muscles. The muscles analysed showed a great degree of heterogeneity in fibre type distribution, having three clearly distinguished regions named red, mixed and white. In the three regions, there were no statistical differences in fibre type proportions between right and left gastrocnemius, as is indicated by the p‐values (from 0.203 to 0.941) obtained after running t‐Student paired tests for each fibre type. When analysing fibre cross‐sectional area, individual fibre capillarization and fibre circularity, no significant differences between right and left gastrocnemius in any of these morphometrical parameters were found in any muscle region or fibre type. Most of the p‐values (70%) resulting from running t‐Student paired tests were higher than 0.400, and the lowest p‐value was 0.115. Seemingly, global capillary and fibre densities were not statistically different between right and left sides in all muscle regions with p‐values ranging from 0.337 to 0.812. Force parameters normalized to gastrocnemius mass (mN g−1) did not show any significant difference between right (PF = 74.0 ± 13.4, TF = 219.4 ± 13.0) and left (PF = 70.9 ± 10.7, TF = 213.0 ± 18.0) muscles with p = 0.623 (PF) and p = 0.514 (TF). Twitch time parameters (ms) also lacked significant differences between the two sides (CT: 43.4 ± 8.6 vs. 45.0 ± 14.3, p = 0.639; HRT: 77.6 ± 15.0 vs. 82.3 ± 25.3, p = 0.475). Finally, both muscles also showed similar (p = 0.718) fatigue properties. We did find an absence of laterality at the morphological and functional levels, which raises the possibility of using right and left gastrocnemius muscles interchangeably for experimental designs where one muscle is used to analyse data after a physiological intervention and its contralateral muscle plays the control role, thus allowing unbiased paired comparisons to derive accurate conclusions.
Caffeine Combined With Sodium Bicarbonate Improves Pacing and Overall Performance During a High-Intensity Time Trial

ABSTRACT Background: No study has demonstrated the effects of sodium bicarbonate plus caffeine (NaHCO3 + CAF) on power output (PO) distribution (e.g., pacing), physiological parameters and energy system contribution during a 4-km cycling time trial (TT). Thus, we aimed to investigate the effects of NaHCO3 + CAF on pacing, physiological parameters, and energy system contribution during a 4-km cycling TT. Methods: Using a double-blind and counterbalanced design, 10 cyclists performed three ingestion protocols (NaHCO3 + CAF, NaHCO3 and placebo) followed by a 4-km cycling TT. Results: 100 min after substance ingestion, the magnitude of change in blood pH and bicarbonate concentration [HCO3 –] for NaHCO3 + CAF (+0.04 ± 0.03 and +5.9 ± 1.6 mmol·L−1, respectively, P < .05) and NaHCO3 (+0.02 ± 0.03 and +4.1 ± 2.0 mmol·L−1, respectively, P < .05) was more pronounced than in placebo (−0.01 ± 0.02 and 0.4 ± 0.9 mmol·L−1, respectively). The increase in plasma lactate concentration was more pronounced in NaHCO3 + CAF than in NaHCO3 and placebo (P < .05). Mean ventilation and carbon dioxide production were higher in NaHCO3 + CAF compared to NaHCO3 and placebo (P < .05). The PO and anaerobic power output were increased at the beginning of the 4-km TT (P < .05) in NaHCO3 + CAF compared to the other two conditions, resulting in an improved overall performance (P < .05). Conclusion: NaHCO3 + CAF results in a higher PO and increased anaerobic contribution and respiratory parameters during a 4-km cycling TT.
Menopausal hormone therapy: what are the problems in the perception of Chinese physicians?

Abstract Objective This study aimed to investigate Chinese physicians’ perception and attitudes toward menopausal hormone therapy (MHT). Methods This nationwide online survey was conducted in China. Physicians registered in the WeChat groups of the Gynecological Endocrinology Committee of China’s Maternal and Child Health Care Association received a message invitation to complete this anonymous online survey from April 2020 to July 2020. Physicians’ knowledge of and attitudes toward MHT were surveyed. Results In total, 4672 questionnaires were submitted; only completed questionnaires could be submitted. The message was sent to 6021 doctors, so the response rate was 77.6%. Overall, 77.9–92.9% of physicians knew the common indications and contraindications to MHT. Additionally, 90.6%, 85.4%, 80.7% and 37.5% of physicians thought that MHT would increase the risk of venous thrombosis, breast cancer, endometrial cancer and weight gain, respectively. In total, 58.1% of the physicians mistakenly believed that a sex hormone test was one of the necessary examinations to reassess MHT prescription during follow-up visits. We found that 68.5% of physicians would consider using MHT themselves or recommend MHT to their partners in the future, and 11.4% were currently using MHT. Conclusions Most Chinese physicians have basic knowledge of MHT. Their misunderstandings about MHT mainly centered on the risks of endometrial cancer, weight gain and the necessary examinations during follow-up visits. These misunderstandings need to be clarified in future professional training programs.
Moving our care home: A qualitative study of the views and experiences of residents, relatives and staff

Abstract Introduction Involuntary relocation when care homes close can be detrimental to residents’ health and well‐being and is associated with increased mortality. There is little formal evidence to support whether planning can mitigate the impact of such moves. This study aimed to understand the experiences of a whole care home relocation where staff and residents relocated together using existing published guidance. Methods A longitudinal qualitative research study using individual face‐to‐face semi‐structured interviews was conducted between August 2018 and August 2019. Baseline interviews were conducted 6–8 weeks after relocation with follow‐up interviews 10–12 months later. Interviews were recorded, transcribed and analysed using framework analysis. Results 27 interviews were conducted; 19 baseline interviews (4 residents, 7 family members, 8 staff) and 8 follow‐up interviews (2 residents, 2 family members, 4 staff). Participants’ feelings about the relocation were mixed: some reported apprehension before the move but others excitement. Residents and families felt variably involved in planning the move, whereas staff expressed lack of involvement. Time, family support and continuity of care helped participants settle in. The new environment shaped participants’ experiences and abilities to adjust, especially the lack of a homely feeling with the new home, the larger size and changes in staff organisation and management. Conclusions Despite implementation of existing guidance, relocation was still challenging for residents, staff and family members. Future relocations should increase involvement of staff in the planning and design of the home; offer continuous support to those involved; and ensure continuity of care and management style.
Prior Knowledge-Aware Fusion Network for Prediction of Macrovascular Invasion in Hepatocellular Carcinoma

Macrovascular invasion (MaVI) is a major threat to survival in hepatocellular carcinoma (HCC), which should be treated as early as possible to ensure safety and efficacy. In this aspect, MaVI prediction can be helpful. However, MaVI prediction is difficult because of the inter-class similarity and intra-class variation of HCC in computed tomography (CT) images. Moreover, existing methods fail to include clinical priori knowledge associated with HCC, leading to incomprehensive information extraction. In this paper, we proposed a prior knowledge-aware fusion network (PKAFnet) to accurately achieve MaVI prediction in CT images. First, a perception module was presented to extract features related to tumor marginal heterogeneity in the graph domain, which contributed to rotation invariance and captured intensity variations of tumor margin. Second, a tumor segmentation network was built to obtain global information of a 3D tumor image and information associated with tumor internal heterogeneity in the image domain. Finally, multi-domain features associated with the tumor margin and tumor region were combined by using a multi-domain attentional feature fusion module. Thus, by incorporating MaVI-related prior knowledge, our PKAFnet can alleviate overfitting, which can improve the discriminative ability. The proposed PKAFnet was validated on a multi-center dataset, and remarkable performance was achieved in an independent testing set. Moreover, the interpretability of perception module and segmentation network were presented in our paper, which illustrated the effectiveness and credibility of PKAFnet. Therefore, the proposed method showed great application potential for MaVI prediction.
Modeling of active magnetic regenerators and experimental investigation of passive regenerators with oscillating flow

This thesis presents numerical modeling of active magnetic regenerator (AMR) and passive regenerator tests with oscillating flow. The work serves to investigate and improve the understanding of emerging concepts and technologies in the area of magnetic refrigeration. The discretization scheme of a one dimensional (1D) AMR model is improved for decreasing spurious temperature oscillations in the numerical solution. This transient AMR model is further modified for simulating tapered regenerators, heat loss through the housing wall and regenerators using mixed materials. Magnetocaloric materials (MCM) with a first or second order phase transition (FOPT or SOPT) exhibit different characteristics in isothermal entropy change ∆Siso, adiabatic temperature change ∆Tad and temperature dependence of the magnetocaloric effect (MCE). A theoretical study quantifies the impact of these parameters, showing that all of them are equally important. Based on measured magnetocaloric properties of La(Fe,Mn,Si)13Hy and Gd, a thorough investigation on how to layer typical FOPT or SOPT materials is implemented. For those regenerators, the sensitivity to the working temperature and the Curie temperature variation is evaluated. A concept of mixing FOPT and SOPT materials is also investigated. Furthermore, the entropy production rates due to insufficient heat transfer, viscous dissipation and axial conduction, as well as the total entropy production rate, are calculated and compared for analyzing different loss mechanisms and optimizing AMRs. The impacts of the heat loss through the regenerator housing and the dead volume are also quantified. A multi-parameter optimization reveals the optimal dimensions and operating parameters for different regenerator geometries. In order to evaluate different regenerator geometries, including the emerging epoxy bonded bed and different heat transfer fluids, a passive regenerator test apparatus is constructed and an experimental investigation is presented. The flow and heat transfer characteristics of different regenerators are estimated by presenting the measured and deduced indicators, including the pressure drop, friction factor, effectiveness, heating power and overall Nusselt number. Finally, based on the research in this thesis, the perspectives and some suggestions for the future work are given.