Miracle-dz/UniFAR-FTUs huggingface dataset:
FLOWERING LOCUS T2 Promotes Shoot Apex Development and Restricts Internode Elongation via the 13-Hydroxylation Gibberellin Biosynthesis Pathway in Poplar

The adaptation and survival of boreal and temperate perennials relies on the precise demarcation of the growing season. Seasonal growth and development are defined by day length and temperature signals. Under long-day conditions in spring, poplar FLOWERING LOCUS T2 (FT2) systemically induces shoot growth. In contrast, FT2 downregulation induced by autumnal short days triggers growth cessation and bud set. However, the molecular role of FT2 in local and long-range signaling is not entirely understood. In this study, the CRISPR/Cas9 editing tool was used to generate FT2 loss of function lines of hybrid poplar. Results indicate that FT2 is essential to promote shoot apex development and restrict internode elongation under conditions of long days. The application of bioactive gibberellins (GAs) to apical buds in FT2 loss of function lines was able to rescue bud set. Expression analysis of GA sensing and metabolic genes and hormone quantification revealed that FT2 boosts the 13-hydroxylation branch of the GA biosynthesis pathway in the shoot apex. Paclobutrazol treatment of WT leaves led to limited internode growth in the stem elongation zone. In mature leaves, FT2 was found to control the GA 13-hydroxylation pathway by increasing GA2ox1 and reducing GA3ox2 expression, causing reduced GA1 levels. We here show that in poplar, the FT2 signal promotes shoot apex development and restricts internode elongation through the GA 13-hydroxylation pathway.
Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Objective To conduct a meta-analysis of the efficacy and safety of 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer based on existing clinical evidence. Methods Search for retrospective studies about 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer from establishment to July 2021 in PubMed and EMBASE. The primary endpoint was 225Ac-PSMA-617 biochemical response evaluation criteria after treatment [any prostate specific antigen (PSA) decrease and PSA decrease >50% from baseline] to evaluate the treatment effect. Secondary endpoints included assessment of overall survival (OS), progression-free survival (PFS), molecular response, and toxicity for all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Use stata16.0 software for analysis, fixed-effects model for data merging and forest plots for display. Results A total of 6 retrospective studies, namely, 201 patients, were included in the final analysis. The pooled proportions of patients with decreased PSA and PSA decreased by more than 50% were 87.0% (95% confidence interval, 0.820 to 0.920) and 66.1% (95% confidence interval, 0.596 to 0.726), respectively. The pooled proportions of OS and PFS were 12.5 months (95%CI: 6.2–18.8 months) and 9.1 months (95%CI: 2.6–15.7 months). The patients showing molecular responses were 54% (95% confidence interval: 25–84%). In all studies, the most common side effect of 225Ac-PSMA-617 TAT was xerostomia, with any degree of xerostomia occurring in 77.1% (155 out of 201), and grade III only accounted for 3.0%. The second was 30.3% (61 out of 201) anemia of any degree, and grade III accounts for 7.5% (15 out of 201). Grade III leukopenia and thrombocytopenia were 4.5% (9 out of 201) and 5.5% (11 out of 201), respectively. Only 6 (3.0%) of 201 patients had Grade III nephrotoxicity. Conclusion 225Ac-PSMA-617 is an effective and safe treatment option for mCRPC patients, and the toxicity caused by it is relatively low. However, future randomized controlled trials and prospective trials are required in the future to judge the therapeutic effects and survival benefits compared with existing clinical treatments. Systematic Review Registration PROSPERO: CRD42021281967.
Classifications and Characteristics of Marine Heatwaves in the Northern South China Sea

The classifications and associated characteristics of marine heatwaves (MHWs) in the northern South China Sea (SCS) have been investigated. Based on the ratio of the area with MHWs to the total area of the northern SCS, the MHWs are divided into three categories, i.e., narrow coverage, moderate coverage, and wide coverage. Different kinds of MHWs (i.e., narrow coverage, moderate coverage, and wide coverage) contribute around 64, 28, and 8% to the total days with MHWs, respectively. Narrow coverage MHW scatters over the northern SCS continental shelf, and moderate (wide) coverage MHWs are concentrated east of Hainan Island (mid of northern SCS continental shelf). Wide coverage MHWs contribute more than 50% to the total MHW cumulative sea surface temperature (SST) anomalies. The cumulative days and temperature anomalies of all kinds of MHWs exhibit significant long-term trends and decadal variability.
Aquaglyceroporin Modulators as Emergent Pharmacological Molecules for Human Diseases

Aquaglyceroporins, a sub-class of aquaporins that facilitate the diffusion of water, glycerol and other small uncharged solutes across cell membranes, have been recognized for their important role in human physiology and their involvement in multiple disorders, mostly related to disturbed energy homeostasis. Aquaglyceroporins dysfunction in a variety of pathological conditions highlighted their targeting as novel therapeutic strategies, boosting the search for potent and selective modulators with pharmacological properties. The identification of selective inhibitors with potential clinical applications has been challenging, relying on accurate assays to measure membrane glycerol permeability and validate effective functional blockers. Additionally, biologicals such as hormones and natural compounds have been revealed as alternative strategies to modulate aquaglyceroporins via their gene and protein expression. This review summarizes the current knowledge of aquaglyceroporins’ involvement in several pathologies and the experimental approaches used to evaluate glycerol permeability and aquaglyceroporin modulation. In addition, we provide an update on aquaglyceroporins modulators reported to impact disease, unveiling aquaglyceroporin pharmacological targeting as a promising approach for innovative therapeutics.
Follicle-Stimulating Hormone Induces Lipid Droplets via Gαi/o and β-Arrestin in an Endometrial Cancer Cell Line

Follicle-stimulating hormone (FSH) and its G protein-coupled receptor, FSHR, represents a paradigm for receptor signaling systems that activate multiple and complex pathways. Classically, FSHR activates Gαs to increase intracellular levels of cAMP, but its ability to activate other G proteins, and β-arrestin-mediated signaling is well documented in many different cell systems. The pleiotropic signal capacity of FSHR offers a mechanism for how FSH drives multiple and dynamic downstream functions in both gonadal and non-gonadal cell types, including distinct diseases, and how signal bias may be achieved at a pharmacological and cell system-specific manner. In this study, we identify an additional mechanism of FSH-mediated signaling and downstream function in the endometrial adenocarcinoma Ishikawa cell line. While FSH did not induce increases in cAMP levels, this hormone potently activated pertussis toxin sensitive Gαi/o signaling. A selective allosteric FSHR ligand, B3, also activated Gαi/o signaling in these cells, supporting a role for receptor-mediated activation despite the low levels of FSHR mRNA. The low expression levels may attribute to the lack of Gαs/cAMP signaling as increasing FSHR expression resulted in FSH-mediated activation of the Gαs pathway. Unlike prior reports for FSH-mediated Gαs/cAMP signaling, FSH-mediated Gαi/o signaling was not affected by inhibition of dynamin-dependent receptor internalization. While chronic FSH did not alter cell viability, FSH was able to increase lipid droplet size. The β-arrestins are key adaptor proteins known to regulate FSHR signaling. Indeed, a rapid, FSH-dependent increase in interactions between β-arrestin1 and Gαi1 was observed via NanoBiT complementation in Ishikawa cells. Furthermore, both inhibition of Gαi/o signaling and siRNA knockdown of β-arrestin 1/2 significantly reduced FSH-induced lipid droplet accumulation, implying a role for a Gαi/o/β-arrestin complex in FSH functions in this cell type. As FSH/FSHR has been implicated in distinct hormone-dependent cancers, including endometrial cancer, analysis of the cancer genome database from 575 human endometrial adenocarcinoma tumors revealed that a subpopulation of samples expressed FSHR. Overall, this study highlights a novel mechanism for FSHR signal pleiotropy that may be exploited for future personalized therapeutic approaches.
Comparison of Various Vagal Maneuvers for Supraventricular Tachycardia by Network Meta-Analysis

Background Vagal maneuvers (VagMs) are recommended as the first-line treatment of supraventricular tachycardia (SVT). However, the optimal type of VagMs remains unproven. Aim This study aims to compare the effectiveness and adverse events amongst VagMs on SVT via network meta-analyses (NMAs). Methods We systematically searched randomized controlled trials (RCTs) that involved adults with SVT and compared VagMs without language restrictions. We determined the initial and final responses of conversion rate to sinus rhythm and adverse events. Risk of bias (RoB) was appraised by Cochrane revised tool, and contribution matrix was calculated. NMAs were synthesized using frequentist random-effects model and presented as relative risk (RR) with 95% CI. The order of probability was presented as surface under the cumulative ranking curve analysis (SUCRA). Sensitivity analysis was performed using both Bayesian and frequentist approach with fixed- or random-effects models. Certainty of evidence (CoE) was rated by using the Grading of Recommendations, Assessment, Development, and Evaluations methodology. Results Fourteen RCTs with 2,180 patients were enrolled. Small portion of mixed estimates was contributed from high overall RoB studies. Compared with carotid sinus massage (CSM), the modified Valsalva maneuver (MVM) was the most effective VagM after initial performance [SUCRA: 0.9992, RR: 5.47 (1.77–16.93)] and at the end of study [SUCRA: 1.0000, RR: 3.62 (2.04–6.39), CoE: high]. The standard VM did not elicit better conversion rate to the sinus rhythm than CSM at the initial response [SUCRA: 0.4395, RR: 1.97 (0.63–6.15)] and at the end of the study [SUCRA: 0.4795, RR: 1.64 (0.94–2.87), CoE: moderate]. The SUCRA value of CSM at the initial and final responses was the least one amongst three VagMs (0.0613 and 0.0205, respectively). Adverse events amongst three VagMs were similar (CoE: low). Sensitivity analyses yielded consistent results. Conclusion We recommended MVM as the first choice of VagM for rhythm conversion before the pharmacological management of SVT.
Clinical Application of Circulating Tumor Cells and Circulating Endothelial Cells in Predicting Bladder Cancer Prognosis and Neoadjuvant Chemosensitivity

Purpose To investigate the role of circulating rare cells (CRCs), namely, circulating tumor cells (CTCs) and circulating endothelial cells (CECs), in aiding early intervention, treatment decision, and prognostication in bladder cancer. Methods A total of 196 patients with pathologically confirmed bladder cancer, namely, 141 non-muscle invasive bladder cancer (NMIBC) and 55 muscle invasive bladder cancer (MIBC) patients. There were 32 patients who received cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Subtraction enrichment combined with immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy was used for CTC/CEC detection. Kaplan–Meier analysis and Cox regression were used to evaluate the overall survival (OS) and recurrence-free survival (RFS). Receiver operator characteristic analysis was used to discriminate NAC sensitivity. Results CTCs and CECs were related to clinicopathological characteristics. Triploid CTCs, tetraploid CTCs, and total CECs were found to be higher in incipient patients than in relapse patients (P = 0.036, P = 0.019, and P = 0.025, respectively). The number of total CECs and large cell CECs was also associated with advanced tumor stage (P = 0.028 and P = 0.033) and grade (P = 0.028 and P = 0.041). Remarkably, tumor-biomarker-positive CTCs were associated with worse OS and RFS (P = 0.026 and P = 0.038) in NMIBC patients underwent TURBT. CECs cluster was an independent predictor of recurrence in non-high-risk NMIBC patients underwent TURBT (HR = 9.21, P = 0.040). For NAC analysis, pre-NAC tetraploid CTCs and small cell CTCs demonstrated the capability in discriminating NAC-sensitive from insensitive patients. Additionally, tetraploid CTCs and single CTCs elevated post-NAC would indicate chemoresistance. Conclusion CTCs and CECs may putatively guide in diagnosis, prognosis prediction, and therapeutic decision-making for bladder cancer.
Performance Evaluation of In Vitro Screening and Diagnostic Kits for Hepatitis C Virus Infection

Aim A reliable kit with high sensitivity and specificity is indispensable for diagnosing hepatitis C virus (HCV) infection. Detection kits for anti-HCV antibodies (anti-HCV) are used for screening, and quantification kits for HCV RNA and HCV antigen (Ag) are used for the definite diagnosis of HCV infection or the evaluation of the pathological condition of and therapeutic effects in patients with chronic hepatitis C. Several kits are currently available for these purposes and are provided for clinical use in Japan. In this study, we aimed to evaluate the performance of these kits. Methods We used International Standards for HCV RNA and HCV Ag and a regional reference panel to evaluate the performance of thirteen anti-HCV, five HCV RNA, and two HCV Ag kits. Results All specimens in the regional reference panel were diagnosed correctly by all anti-HCV kits, although the distributions of the quantified values varied, and the ratios of titer classification were not identical across kits. All HCV RNA kits quantified the International Standard with minimum deviation and diagnosed the specimens of the reference panel correctly. The quantified values of the International Standard by two HCV Ag kits were inconsistent. HCV Ag titers of some specimens were underestimated owing to the amino acid polymorphisms in comparison with HCV RNA titers. Conclusions The evaluation with International Standards and the regional reference panel was useful for assessing the quality of screening and diagnostic kits for HCV infection, and such quality control is essential for the clinical usage of these kits.
Site-Specific Sequence Exchange Between Homologous and Non-homologous Chromosomes

Transgene integration typically takes place in an easy-to-transform laboratory variety before the transformation event is introgressed through backcrosses to elite cultivars. As new traits are added to existing transgenic lines, site-specific integration can stack new transgenes into a previously created transgenic locus. In planta site-specific integration minimizes the number of segregating loci to assemble into a breeding line, but cannot break genetic linkage between the transgenic locus and nearby undesirable traits. In this study, we describe an additional feature of an in planta gene-stacking scheme, in which the Cre (control of recombination) recombinase not only deletes transgenic DNA no longer needed after transformation but also mediates recombination between homologous or non-homologous chromosomes. Although the target site must first be introgressed through conventional breeding, subsequent transgenes inserted into the same locus would be able to use Cre-mediated translocation to expedite a linkage drag-free introgression to field cultivars.
The role of cues in expert project manager sensemaking

Sensemaking forms the foundation of expertise as it comprises the initial stage of information processing that influences judgement and decision-making. Two related studies were undertaken to investigate the role of cues in the context of expert project management. First, a qualitative study was conducted using the critical incident technique and involving nine project managers who had successfully delivered projects. The data were analysed by identifying the critical incidents and the associated cues that were used as the basis of sensemaking in project-related situations. These cues converged into three categories: feedback, context cues and tacit knowledge. The second study examined the construct validity of the cues that emerged in Study 1 using a cue utilization scale that was administered through an online survey. There were 23 experienced project managers and 78 naïve participants who participated in the study. Differences in patterns of cue utilization were evident between the two cohorts based on the perceived levels of project complexity and project phases. The research outcomes offer empirical support for the relationship between cues and sensemaking in project management, and provide a basis for further research into the acquisition of sensemaking skills and the development of cue-based training initiatives to facilitate the progression towards expert project management.
Regional Associations of Cortical Superficial Siderosis and β-Amyloid-Positron-Emission-Tomography Positivity in Patients With Cerebral Amyloid Angiopathy

Objective This is a cross-sectional study to evaluate whether β-amyloid-(Aβ)-PET positivity and cortical superficial siderosis (cSS) in patients with cerebral amyloid angiopathy (CAA) are regionally colocalized. Methods Ten patients with probable or possible CAA (73.3 ± 10.9 years, 40% women) underwent MRI examination with a gradient-echo-T2*-weighted-imaging sequence to detect cSS and 18F-florbetaben PET examination to detect fibrillar Aβ. In all cortical regions of the Hammers Atlas, cSS positivity (MRI: ITK-SNAP segmentation) and Aβ-PET positivity (PET: ≥ mean value + 2 standard deviations of 14 healthy controls) were defined. Regional agreement of cSS- and Aβ-PET positivity was evaluated. Aβ-PET quantification was compared between cSS-positive and corresponding contralateral cSS-negative atlas regions. Furthermore, the Aβ-PET quantification of cSS-positive regions was evaluated in voxels close to cSS and in direct cSS voxels. Results cSS- and Aβ-PET positivity did not indicate similarity of their regional patterns, despite a minor association between the frequency of Aβ-positive patients and the frequency of cSS-positive patients within individual regions (rs = 0.277, p = 0.032). However, this association was driven by temporal regions lacking cSS- and Aβ-PET positivity. When analyzing all composite brain regions, Aβ-PET values in regions close to cSS were significantly higher than in regions directly affected with cSS (p < 0.0001). However, Aβ-PET values in regions close to cSS were not different when compared to corresponding contralateral cSS-negative regions (p = 0.603). Conclusion In this cross-sectional study, cSS and Aβ-PET positivity did not show regional association in patients with CAA and deserve further exploitation in longitudinal designs. In clinical routine, a specific cross-sectional evaluation of Aβ-PET in cSS-positive regions is probably not useful for visual reading of Aβ-PETs in patients with CAA.
Technology as a Double-Edged Sword: Understanding Life Experiences and Coping With COVID-19 in India

The two waves of COVID-19 in India have had severe consequences for the lives of people. The Indian State-imposed various regulatory mechanisms like lockdowns, encouraged remote work, online teaching in academic institutions, and enforced adherence to the COVID protocols. The use of various technologies especially digital/online technologies not only helped to adapt to the “new normal” and cope with the disruptions in pursuing everyday activities but also to manage one’s well-being. However, the availability and accessibility of digital technologies to various sections of the population were not uniform. This paper reports a series of three studies examining the nature of pandemic stress, the impact of technology use on people’s emotional well-being during turbulent times, and the effects of technology use on psychological resources like resilience, self-efficacy, motivation to work, and emotional well-being. The differences in the residential background (Urban/Rural) and SES (Low/High) in the extent of the use of technology and strength of psychological resources were assessed. The findings indicated that the most common causes of concern included worrying about family, friends, partners, fears of getting and giving the viral infection to someone; frustration and or boredom; and changes in normal sleep patterns. It was noted that technology was a double-edged sword and created barriers as well as opportunities for the people. Also, self-efficacy mediated the relationship between the use of technology and emotional wellbeing. The results have policy implications for building resilient communities in the post COVID period.
An efficient K-SVD based Algorithm for detection of Oscillatory mode from ambient data for synchrophasor application

In this paper, an efficient implementation of K-SVD based technique over a learned dictionary to extract the critical modes from the ambient data is presented. The technique creates an appropriate dictionary iteratively and selects the optimal set of sparse coefficients to extract the clean signal for better estimation of the mode. To prove the effectiveness of the proposed technique, a comparative study of simulation results of the proposed approach with other technique such as sparsity technique and RDT-TLS-ESPRIT is carried out for simulated test signal, the real-time phasor measurement unit (PMU) data of indian power system, and the real-time probing data of Western Electricity Coordinating Council (WECC) network through Matlab simulation.
Over-the-Air Statistical Estimation of Sparse Models

We propose schemes for minimax statistical estimation of sparse parameter or observation vectors over a Gaussian multiple-access channel (MAC) under squared error loss, using techniques from statistics, compressed sensing and wireless communication. These “analog” schemes exploit the superposition inherent in the Gaussian MAC, using compressed sensing to reduce the number of channel uses needed. For the sparse Gaussian location and sparse product Bernoulli models, we derive expressions for risk in terms of the numbers of nodes, parameters, channel uses and nonzero entries (sparsity). We show that they offer exponential improvements over existing lower bounds for risk in “digital” schemes that assume nodes to transmit bits errorlessly at the Shannon capacity. This shows that analog schemes that design estimation and communication jointly can efficiently exploit the inherent sparsity in high-dimensional models and observations, and provide drastic improvements over digital schemes that separate source and channel coding in this context.