Miracle-dz/UniFAR-FTUs huggingface dataset:
Layer 5 Corticofugal Projections from Diverse Cortical Areas: Variations on a Pattern of Thalamic and Extrathalamic Targets

The cerebral cortex, with all its computational power, can only influence behavior via corticofugal connections originating from layer 5 (L5) cells (Sherman and Guillery, 2013). To begin to establish the global pattern of these outputs, we examined L5 efferents originating from four cortical areas: somatosensory, visual, motor, and prefrontal (i.e., ventromedial orbitofrontal) cortex. We injected Cre-dependent adeno-associated virus in an Rbp4-Cre transgenic mouse line (both sexes) to label these L5 efferents selectively. Our study reveals that, across this diverse series of cortical regions, L5 commonly projects to multiple thalamic and extrathalamic sites. We also identified several novel corticofugal targets (i.e., the lateral dorsal nucleus, submedial nucleus) previously unidentified as L5 targets. We identified common patterns for these projections: all areas innervated both thalamus and the midbrain, and all areas innervated multiple thalamic targets, including those with core and matrix cell types (Jones, 1998). An examination of the terminal size within each of these targets suggests that terminal populations of L5 efferents are not consistently large but vary with cortical area and target; and in some cases, these include small terminals only. Overall, our data reveal more widespread and diverse L5 efferents than previously appreciated, suggesting a generalizable role for this cortical layer in influencing motor commands and cognitive processes. SIGNIFICANCE STATEMENT While the neocortex is responsible for coordination of complex behavior, it requires communication with subcortical regions to do so. It is specifically cortical layer 5 (L5) that is thought to underlie these behaviors, although it is unknown whether this holds true across functionally different cortical areas. Using a selective viral tracing method and transgenic mice, we examined the connectivity of four cortical regions (somatosensory, visual, motor and prefrontal cortex) to assess the generalizability of these L5 projections. All areas of cortex projected to overlapping as well as distinct thalamic and brainstem structures. Terminals within these regions varied in size, implicating that L5 has a broad and diverse impact on behavior.
Optimal target localisation and eight-year outcome for subthalamic stimulation in patients with Parkinson’s disease

Abstract Objective Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a useful therapy to improve motor functions and reduce dependence on medication in patients with Parkinson’s disease (PD). The purpose of the study is to assess the long-term clinical outcomes of STN-DBS and to determine the optimal placement of electrodes that for the most positive outcomes. Methods A consecutive series of 42 PD patients were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after STN-DBS lead implantation. Postoperatively, patients were evaluated during both the medication ‘ON’ period (medication suppressed symptoms) and the medication ‘OFF’ period (when medication failed to suppress symptoms), and the results were compared to the baseline values prior to surgery. Follow-up assessments, focusing on motor functions, were performed 1, 3, 5, and 8 years after the initial implantation surgery. The locations of electrodes were measured and compared against the clinical outcomes. Results STN-DBS remarkably improved the UPDRS-II, -III, and -IV dyskinesia and motor fluctuation scores in the OFF-medication condition when compared to baseline values. In addition, the dose of levodopa needed to elicit an effect declined sharply in the OFF-medication condition. Over time, the axial signs progressively worsened even with continuous stimulation and a levodopa response. The location of electrodes correlated with the most beneficial outcomes was the dorsal STN margin. Conclusions Our results confirm that overall, stimulation-induced motor improvement is still evident after 8 years. However, the primary best outcome declines with the progressive loss of favourable axial signs.
Detection of silent reflux events by nuclear scintigraphy in healthy dogs

Abstract Background Reflux and aspiration in people are associated with respiratory disease, whereas approximately 50% of healthy adults microaspirate without apparent consequence. In dogs, analogous information is lacking. Hypothesis Healthy dogs commonly have gastroesophageal reflux and a proportion of these dogs will have laryngopharyngeal reflux with silent aspiration. Animals Twelve healthy, client‐owned dogs. Methods Prospective study: Dogs were free‐fed a meal containing (111 MBq) colloidal 99m‐technetium phytate. Dynamic‐scans were performed 5 and 30 minutes postingestion. Time‐activity curves, reflux margination, volume, frequency, and duration were evaluated over 7 regions of interest in dorsal ± left‐lateral recumbency. Static scans (dorsal recumbency) were performed 2 and 18 hours postfeeding to detect aspiration. Reflux and aspiration were defined as counts ≥200% background activity ± decreased gastric counts. Between‐group comparisons were performed by Wilcoxon rank‐sum test or one‐way ANOVA on ranks with significance of P < . 05. Results In this study, reflux of variable magnitude was detected in 12/12 dogs. No significant differences in outcome parameters were detected with recumbency (P > .05). Margination to the pharynx and proximal, middle, and distal esophagus was identified in 5/12, 2/12, 3/12, and 2/12 dogs, respectively. Median (IQR) reflux frequency and duration were 2 events/5 minutes (1‐3.3 events/5 minutes) and 6 seconds (4‐9 seconds) respectively. No dog had detectable aspiration. Conclusions and Clinical Importance Nuclear scintigraphy can document reflux in dogs. Reflux, but not aspiration, is common in healthy dogs and must be considered when interpreting results in clinically affected dogs.
A comparison of tractor-trailer units and high-speed forwarders used in Alpine forestry

The introduction of modern forwarders to Alpine forest operations must account for the traditional forwarding units used by local logging contractors. They generally use the same machine for extraction and intermediate off-road transportation on mountain trails, inaccessible to heavy road vehicles. Conventional forwarders are not designed for fast transportation on trail and cannot replace conventional tractor-trailer units. However, new high-speed forwarders could qualify for substitution. CNR set up a long-term follow-up study to determine the use pattern of three conventional tractor-trailer units and three high-speed forwarders. For this purpose, CNR installed commercial Global Positioning System/Global System for Mobile Communications data loggers for continuous real-time collection of the main work data, including position, status, speed and fuel consumption. The study showed that new forwarders could actually travel at a speed higher than 20 km h−1, and they performed both extraction and intermediate transportation. They were capable of independent relocation, which made them suitable for small-scale forestry. Both machine types were used intensively, but the annual usage of forwarders was almost twice as large as that of tractor-trailer units (i.e. 1301 vs. 717 hours per year). Furthermore, forwarders had a 27% higher hourly productivity and a 50% higher fuel consumption per hour, compared with tractor-trailer units.
SOME EFFECTS OF MALEIC HYDRAZIDE ON INTERNODE ELONGATION, CELL ENLARGEMENT, AND STEM ANATOMY

THAT MALEIC HYDRAZIDE (MH) is ani anti-mitotic appears to be well established. Greulach and Atchison (1950) found that MH inhibited mitosis in onion root tips and soon afterward Deysson and Rollen (1951) and Darlington and McLeish (1951) reported the inhibition of mitosis in several species of plants by MH. Subsequent reports on the anltimitotic action of MH have been made by Girolami (1951), Compton (1952), Rao and Wittwer (1952), and Greulach and Atchison (1953).
Dietary flavonoid fisetin binds human SUMO1 and blocks sumoylation of p53

Flavonoids are plant-derived compounds that occur abundantly in fruits and vegetables and have been shown to possess potent anti-cancer, antioxidant, and anti-inflammatory properties. However, their direct targets and molecular mechanism of action are not well characterized, hampering exploitation of the beneficial properties of flavonoids for drug development. Small ubiquitin-related modifier 1 (SUMO1) is attached to target proteins as part of a post-translational modification system implicated in a myriad of cellular processes from nuclear trafficking to transcriptional regulation. Using a combination of surface plasmon resonance, differential scanning fluorimetry and fluorescence quenching studies, we provide evidence for direct binding of the dietary flavonoid fisetin to human SUMO1. Our NMR chemical shift perturbation analyses reveal that binding to fisetin involves four conserved amino acid residues (L65, F66, E67, M82) previously shown to be important for conjugation of SUMO1 to target proteins. In vitro sumoylation experiments indicate that fisetin blocks sumoylation of tumor suppressor p53, consistent with fisetin negatively affecting post-translational modification and thus the biological activity of p53. A series of differential scanning fluorimetry experiments suggest that high concentrations of fisetin result in destabilization and unfolding of SUMO1, presenting a molecular mechanism by which flavonoid binding affects its activity. Overall, our data establish a novel direct interaction between fisetin and SUMO1, providing a mechanistic explanation for the ability of fisetin to modulate multiple key signaling pathways inside cells.
Chemoradiation for cervical cancer treatment portends high risk of pelvic floor dysfunction

Goal To assess the impact of chemoradiation on pelvic floor (PF) muscle function after the treatment of cervical cancer (CC). Methods We performed a prospective cohort study of women between the ages of 20 and 70 years old who had a diagnosis of CC. Patients were treated with chemoradiation at the Barretos Cancer Hospital (BCH), between August 2016 and July 2017. We performed three evaluations at different time points after chemoradiation treatment to compare changes in muscle function. Pelvic floor muscle function was assessed through perineometry (PNM) and surface electromyography (EMG) at the following time points: Pretreatment Moment 1 (M1): evaluated before chemoradiation; Moment 2 (M2): at the first follow-up medical visit (usually 3 to 4 months after treatment); and Moment 3 (M3): at the second follow-up medical visit (usually after 6 to 9 months after treatment). Mean vaginal squeeze pressure levels were determined by PNM and muscle electromyographic activity by EMG and the results were evaluated by Generalized Linear Model comparisons. Results Forty-nine patients were evaluated at M1; 35 at M2; and 32 at M3, so that 32 patients had all three muscle evaluations performed. There was a statistically significant increase in the frequency of women with urgency urinary incontinence at the M2 evaluation time (41.9%), compared to pretreatment M1 (18.6%), p<0.001. The means of the vaginal squeeze pressures reduced through M1 to M3 in the phasic (M1: 17.7 mmHg; M3: 11.27mmHg) and tonic contractions (M1: 10.56 mmHg; M3: 7.52mmHg), p = 0.01 and p = 0.03 respectively. There was no difference in pelvic floor function in the three evaluations M1-M3, measured by EMG. The pelvic floor strength assessed by PMN and their interactions with anthropometric, parity and hormonal status variables, showed that a high body mass index (BMI) significantly influenced decreases in pelvic floor muscle function before and after treatment. Conclusion These results show that chemoradiation causes reduction of muscle function of the pelvic floor, especially in the late phase after the end of treatment. Both the high BMI and urgent urinary incontinence symptoms were related to decreased muscle strength.
The Ubiquitin-Proteasome System Does Not Regulate the Degradation of Porcine β-Microseminoprotein during Sperm Capacitation

Sperm capacitation, one of the key events during successful fertilization, is associated with extensive structural and functional sperm remodeling, beginning with the modification of protein composition within the sperm plasma membrane. The ubiquitin-proteasome system (UPS), a multiprotein complex responsible for protein degradation and turnover, participates in capacitation events. Previous studies showed that capacitation-induced shedding of the seminal plasma proteins such as SPINK2, AQN1, and DQH from the sperm surface is regulated by UPS. Alterations in the sperm surface protein composition also relate to the porcine β-microseminoprotein (MSMB/PSP94), seminal plasma protein known as immunoglobulin-binding factor, and motility inhibitor. MSMB was detected in the acrosomal region as well as the flagellum of ejaculated boar spermatozoa, while the signal disappeared from the acrosomal region after in vitro capacitation (IVC). The involvement of UPS in the MSMB degradation during sperm IVC was studied using proteasomal interference and ubiquitin-activating enzyme (E1) inhibiting conditions by image-based flow cytometry and Western blot detection. Our results showed no accumulation of porcine MSMB either under proteasomal inhibition or under E1 inhibiting conditions. In addition, the immunoprecipitation study did not detect any ubiquitination of sperm MSMB nor was MSMB detected in the affinity-purified fraction containing ubiquitinated sperm proteins. Based on our results, we conclude that UPS does not appear to be the regulatory mechanism in the case of MSMB and opening new questions for further studies. Thus, the capacitation-induced processing of seminal plasma proteins on the sperm surface may be more complex than previously thought, employing multiple proteolytic systems in a non-redundant manner.
How long are Canadians waiting to access specialty care? Retrospective study from a primary care perspective.

OBJECTIVE To calculate patient wait times for specialist care using data from primary care clinics across Canada. DESIGN Retrospective chart audit. SETTING Primary care clinics. PARTICIPANTS A total of 22 primary care clinics across 7 provinces and 1 territory. MAIN OUTCOME MEASURES Wait time 1, defined as the period between a patient's referral by a family physician to a specialist and the visit with said specialist. RESULTS Overall, 2060 referrals initiated between January 2014 and December 2016 were included in the analysis. The median national wait time 1 was 78 days (interquartile range [IQR] of 34 to 175 days). The shortest waits were observed in Saskatchewan (51 days; IQR = 23 to 101 days) and British Columbia (59 days; IQR = 29 to 131 days), whereas the longest were in New Brunswick (105 days; IQR = 43 to 242 days) and Quebec (104 days; IQR = 36 to 239 days). Median wait time 1 varied substantially among different specialty groups, with the longest wait time for plastic surgery (159 days; IQR = 59 to 365 days) and the shortest for infectious diseases (14 days; IQR = 6 to 271 days). CONCLUSION This is the first national examination of wait time 1 from the primary care perspective. It provides a picture of patient access to specialists across provinces and specialty groups. This research provides decision makers with important context for developing programs and policies aimed at addressing the largely ignored stage of the wait time continuum from the time of referral to eventual appointment time with the specialist.
Sensitivity Analysis of Sensors in a Hydraulic Condition Monitoring System Using CNN Models

Condition monitoring (CM) is a useful application in industry 4.0, where the machine’s health is controlled by computational intelligence methods. Data-driven models, especially from the field of deep learning, are efficient solutions for the analysis of time series sensor data due to their ability to recognize patterns in high dimensional data and to track the temporal evolution of the signal. Despite the excellent performance of deep learning models in many applications, additional requirements regarding the interpretability of machine learning models are getting relevant. In this work, we present a study on the sensitivity of sensors in a deep learning based CM system providing high-level information about the relevance of the sensors. Several convolutional neural networks (CNN) have been constructed from a multisensory dataset for the prediction of different degradation states in a hydraulic system. An attribution analysis of the input features provided insights about the contribution of each sensor in the prediction of the classifier. Relevant sensors were identified, and CNN models built on the selected sensors resulted equal in prediction quality to the original models. The information about the relevance of sensors is useful for the system’s design to decide timely on the required sensors.
Emergency department: A sociological perspective

As a complex space that can be interpreted on individual, societal and systemic levels, there is a need for analysis of emergency medicine that transcends the biomedical paradigm to explore its sociological influences. The ED is a social structure of different roles, responsibilities and relationships that can be analysed through observation of the different institutionalised activities which highlight the hierarchies and culturally influenced interactions taking place between actors. Institutionalised activities that provide insight into the social structure of the ED include deference to doctors by patients in the context of environmental chaos, segregated handover of information and discharge‐oriented patient care that de‐emphasises the impact of social background.
Pathophysiology of Bone Loss in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy and Lifestyle Modifications for the Management of Bone Health: A Comprehensive Review

Androgen-deprivation therapy (ADT) is a systemic therapy administered for the management of advanced prostate cancer (PCa). Although ADT may improve survival, long-term use reduces bone mass density (BMD), posing an increased risk of fracture. Considering the long natural history of PCa, it is essential to preserve bone health and quality-of-life in patients on long-term ADT. As an alternative to pharmacological interventions targeted at preserving BMD, current evidence recommends lifestyle modifications, including individualized exercise and nutritional interventions. Exercise interventions include resistance training, aerobic exercise, and weight-bearing impact exercise, and have shown efficacy in preserving BMD. At the same time, it is important to take into account that PCa is a progressive and debilitating disease in which a substantial proportion of patients on long-term ADT are older individuals who harbor axial bone metastases. Smoking cessation and limited alcohol consumption are commonly recommended lifestyle measures in patients receiving ADT. Contemporary guidelines regarding lifestyle modifications vary by country, organization, and expert opinion. This comprehensive review will provide an evidence-based, updated summary of lifestyle interventions that could be implemented to preserve bone health and maintain quality-of-life throughout the disease course of PCa.
Process Evaluation of a Clustered Randomized Control Trial of a Comprehensive Intervention to Reduce the Risk of Cardiovascular Events in Primary Health Care in Rural China

Background: Cardiovascular disease (CVD) is a major public health challenge in China. This study aims to understand the processes of implementing a comprehensive intervention to reduce CVD events in areas of drug therapy, lifestyle changes, and adherence support in a clustered randomized controlled trial (cRCT). This trial consisted of 67 clusters spanning over 3 years in Zhejiang Province, China. Method: A qualitative process evaluation was nested within the cRCT conducted in 9 township hospitals with 27 healthcare providers, 18 semi-structured interviews, and 23 observational studies of clinical practices within the intervention arm. Results: Effective and repeated trainings using an interactive approach were crucial to improve the prescribing behaviour of family doctors and their patient communication skills. However, the awareness of patients remained limited, thus compromising their use of CVD preventive drugs and adoption of healthy lifestyles. Health system factors further constrained providers’ and patients’ responses to the intervention. Financial barrier was a major concern because of the low coverage of health insurance. Other barriers included limited doctor–patient trust and suboptimal staff motivation. Conclusion: Our study suggests the feasibility of implementing a comprehensive CVD risk reduction strategy in China’s rural primary care facilities. However, health system barriers need to be addressed to ensure the success and sustainability of the intervention.
Transcriptome Profiling of Haloxylon persicum (Bunge ex Boiss and Buhse) an Endangered Plant Species under PEG-Induced Drought Stress

Haloxylon persicum is an endangered western Asiatic desert plant species, which survives under extreme environmental conditions. In this study, we focused on transcriptome analysis of H. persicum to understand the molecular mechanisms associated with drought tolerance. Two different periods of polyethylene glycol (PEG)-induced drought stress (48 h and 72 h) were imposed on H. persicum under in vitro conditions, which resulted in 18 million reads, subsequently assembled by de novo method with more than 8000 transcripts in each treatment. The N50 values were 1437, 1467, and 1524 for the control sample, 48 h samples, and 72 h samples, respectively. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis resulted in enrichment of mitogen-activated protein kinase (MAPK) and plant hormone signal transduction pathways under PEG-induced drought conditions. The differential gene expression analysis (DGEs) revealed significant changes in the expression pattern between the control and the treated samples. The KEGG analysis resulted in mapping transcripts with 138 different pathways reported in plants. The differential expression of drought-responsive transcription factors depicts the possible signaling cascades involved in drought tolerance. The present study provides greater insight into the fundamental transcriptome reprogramming of desert plants under drought.
Organic and Inorganic PCL-Based Electrospun Fibers

In this work, different nanocomposite electrospun fiber mats were obtained based on poly(e-caprolactone) (PCL) and reinforced with both organic and inorganic nanoparticles. In particular, on one side, cellulose nanocrystals (CNC) were synthesized and functionalized by “grafting from” reaction, using their superficial OH– group to graft PCL chains. On the other side, commercial chitosan, graphene as organic, while silver, hydroxyapatite, and fumed silica nanoparticles were used as inorganic reinforcements. All the nanoparticles were added at 1 wt% with respect to the PCL polymeric matrix in order to compare the different behavior of the woven no-woven nanocomposite electrospun fibers with a fixed amount of both organic and inorganic nanoparticles. From the thermal point of view, no difference was found between the effect of the addition of organic or inorganic nanoparticles, with no significant variation in the Tg (glass transition temperature), Tm (melting temperature), and the degree of crystallinity, leading in all cases to high crystallinity electrospun mats. From the mechanical point of view, the highest values of Young modulus were obtained when graphene, CNC, and silver nanoparticles were added to the PCL electrospun fibers. Moreover, all the nanoparticles used, both organic and inorganic, increased the flexibility of the electrospun mats, increasing their elongation at break.