Miracle-dz/UniFAR-FTUs huggingface dataset:
Inferring Homologous Recombination Deficiency of Ovarian Cancer From the Landscape of Copy Number Variation at Subchromosomal and Genetic Resolutions

Background Homologous recombination deficiency (HRD) is characterized by overall genomic instability and has emerged as an indispensable therapeutic target across various tumor types, particularly in ovarian cancer (OV). Unfortunately, current detection assays are far from perfect for identifying every HRD patient. The purpose of this study was to infer HRD from the landscape of copy number variation (CNV). Methods Genome-wide CNV landscape was measured in OV patients from the Australian Ovarian Cancer Study (AOCS) clinical cohort and >10,000 patients across 33 tumor types from The Cancer Genome Atlas (TCGA). HRD-predictive CNVs at subchromosomal resolution were identified through exploratory analysis depicting the CNV landscape of HRD versus non-HRD OV patients and independently validated using TCGA and AOCS cohorts. Gene-level CNVs were further analyzed to explore their potential predictive significance for HRD across tumor types at genetic resolution. Results At subchromosomal resolution, 8q24.2 amplification and 5q13.2 deletion were predominantly witnessed in HRD patients (both p < 0.0001), whereas 19q12 amplification occurred mainly in non-HRD patients (p < 0.0001), compared with their corresponding counterparts within TCGA-OV. The predictive significance of 8q24.2 amplification (p < 0.0001), 5q13.2 deletion (p = 0.0056), and 19q12 amplification (p = 0.0034) was externally validated within AOCS. Remarkably, pan-cancer analysis confirmed a cross-tumor predictive role of 8q24.2 amplification for HRD (p < 0.0001). Further analysis of CNV in 8q24.2 at genetic resolution revealed that amplifications of the oncogenes, MYC (p = 0.0001) and NDRG1 (p = 0.0004), located on this fragment were also associated with HRD in a pan-cancer manner. Conclusions The CNV landscape serves as a generalized predictor of HRD in cancer patients not limited to OV. The detection of CNV at subchromosomal or genetic resolution could aid in the personalized treatment of HRD patients.
Safety and Efficacy of Endovascular Treatment for Progressive Stroke in Patients With Acute Basilar Artery Occlusion

Background and Purpose: It is unknown the benefit of endovascular therapy (EVT) for progressive stroke in patients with basilar artery occlusion (BAO). The aim of this study was to compare the efficacy and safety of EVT with standard medical therapy (SMT) in a population of BAO patients with progressive stroke. Methods: The EVT for Acute Basilar Artery Occlusion Study (BASILAR) is a national prospective registry of consecutive patients with acute BAO within 24 h of symptom onset. According to the applied therapy, all patients were divided into SMT and EVT groups. Subsequently, the EVT group was divided into early (≤6 h) and late groups (>6 h) according to the time window. The efficacy outcome was favorable functional outcomes (modified Rankin Scale score ≤ 3) at 90 days. The safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage (sICH) after EVT. Results: The EVT cohort presented more frequently with a favorable functional outcome (adjusted odds ratio, 5.49; 95% confidence interval, 2.06–14.61, p = 0.01) and with a decreased mortality (adjusted odds ratio, 0.3; 95% confidence interval, 0.17–0.54, p < 0.001). What's more, EVT still safe (P = 0.584, P = 0.492, respectively) and effective (P = 0.05) in patients with progressive stroke when the treatment time window exceeds 6 h. Conclusions: EVT was more effective and safer than SMT for progressive stroke in patients with BAO. Besides, EVT remains safe and effective in patients with progressive stroke when the treatment time window exceeds 6 h. Predictors of desirable outcome in progressive stroke patients undergoing EVT included lower baseline NIHSS score, higher baseline pc-ASPECTs, successful recanalization and shorter puncture to recanalization time.
Evidences for Red Pigment Concentrating Hormone (RPCH) and Beta-Pigment Dispersing Hormone (β-PDH) Inducing Oocyte Meiotic Maturation in the Chinese Mitten Crab, Eriocheir sinensis

Red pigment concentrating hormone (RPCH) and pigment dispersing hormone (PDH) are crustacean neuropeptides involved in broad physiological processes including body color changes, circadian rhythm, and ovarian growth. In this study, the full-length cDNA of RPCH and PDH were identified from the brain of the Chinese mitten crab Eriocheir sinensis. The deduced RPCH and PDH mature peptides shared identical sequence to the adipokinetic hormone/RPCH peptides family and the β-PDH isoforms and were designated as Es-RPCH and Es-β-PDH, respectively. Es-RPCH and Es-β-PDH transcripts were distributed in the brain and eyestalks. The positive signals of Es-RPCH and Es-β-PDH were localized in the neuronal clusters 6, 8, 9, 10, and 17 of the brain as revealed by in situ hybridization. The expression level of Es-RPCH and Es-β-PDH mRNA in nervous tissues were all significantly increased at vitellogenic stage, and then decreased at the final meiotic maturation stage. The administrated with synthesized Es-RPCH peptide results in germinal vesicles shift toward the plasma membrane in vitellogenic oocyte, and significant decrease of the gonad-somatic index (GSI) and mean oocyte diameter as well as the expression of vitellogenin mRNA at 30 days post injection in vivo. Similar results were also found when injection of the Es-β-PDH peptide. In vitro culture demonstrated that Es-RPCH and Es-β-PDH induced germinal vesicle breakdown of the late vitellogenic oocytes. Comparative ovarian transcriptome analysis indicated that some reproduction/meiosis-related genes such as cdc2 kinase, cyclin B, 5-HT-R and retinoid-X receptor were significantly upregulated in response to Es-RPCH and Es-β-PDH treatments. Taken together, these results provided the evidence for the inductive effect of Es-RPCH and Es-β-PDH on the oocyte meiotic maturation in E. sinensis.
The Tongue Squamous Carcinoma Cell Line Cal27 Primarily Employs Integrin α6β4-Containing Type II Hemidesmosomes for Adhesion Which Contribute to Anticancer Drug Sensitivity

Integrins are heterodimeric cell surface glycoproteins used by cells to bind to the extracellular matrix (ECM) and regulate tumor cell proliferation, migration and survival. A causative relationship between integrin expression and resistance to anticancer drugs has been demonstrated in different tumors, including head and neck squamous cell carcinoma. Using a Cal27 tongue squamous cell carcinoma model, we have previously demonstrated that de novo expression of integrin αVβ3 confers resistance to several anticancer drugs (cisplatin, mitomycin C and doxorubicin) through a mechanism involving downregulation of active Src, increased cell migration and invasion. In the integrin αVβ3 expressing Cal27-derived cell clone 2B1, αVβ5 expression was also increased, but unrelated to drug resistance. To identify the integrin adhesion complex (IAC) components that contribute to the changes in Cal27 and 2B1 cell adhesion and anticancer drug resistance, we isolated IACs from both cell lines. Mass spectrometry (MS)-based proteomics analysis indicated that both cell lines preferentially, but not exclusively, use integrin α6β4, which is classically found in hemidesmosomes. The anticancer drug resistant cell clone 2B1 demonstrated an increased level of α6β4 accompanied with increased deposition of a laminin-332-containing ECM. Immunofluorescence and electron microscopy demonstrated the formation of type II hemidesmosomes by both cell types. Furthermore, suppression of α6β4 expression in both lines conferred resistance to anticancer drugs through a mechanism independent of αVβ3, which implies that the cell clone 2B1 would have been even more resistant had the upregulation of α6β4 not occurred. Taken together, our results identify a key role for α6β4-containing type II hemidesmosomes in regulating anticancer drug sensitivity.
Modeling of Driver Steering Behavior in Lateral Wind toward Driver Assistance System

Disturbances decrease vehicle stability and increase driver’s mental and physical workload. Especially, lateral wind increases driver’s workload greatly, because driver cannot expect it. Various driver assistance systems by steering assist have been developed to improve vehicle stability in such disturbance. Gap between vehicle motion and driver’s motion recognition characteristics, however, often leads to uncomfortable feeling in driver assistance system with steering assist. Thus, this study aims to develop more comfortable driver assistance system in lateral wind disturbance by studying relationship between driver’s motion recognition characteristics and driving behavior against disturbance. First, the driver’s posture change, the head movement and the corrective steering behavior were measured under various lateral wind conditions utilizing a driving simulator with one dof motion in lateral direction. As the results, strong correlation was found between driver’s head lateral jerk by lateral disturbance and angular acceleration of steering wheel. Then, we build a driver’s steering model against lateral disturbance based on the experimental results. Finally, validity of the proposed model is shown by comparing the steering angle of experimental results and that of simulation results.
Efficient Ways to Combat Doping in a Sports Education Context!? A Systematic Review on Doping Prevention Measures Focusing on Young Age Groups

Youth is characterized by testing and crossing natural boundaries, sometimes with the help of performance-enhancing substances. In this context, doping prevention measures play a crucial role to protect individuals both within and outside the context of elite sport. Based on the PRISMA guidelines, a systematic literature search was conducted in the databases ProQuest (ERIC), Scopus, PSYNDEX/PsychInfo, PubMed, and Web of Science Core Collection to provide an overview of the impact of doping prevention measures, with particular attention to the underlying understanding of learning. As a result of the screening process, 30 of the initial 5,591 articles met the previously defined and recorded eligibility criteria. The analysis led to heterogeneous results regarding content, implementation, target group, or outcome variables considered relevant. Two-thirds of the studies related to the competitive sports context. Nevertheless, there has been a growing interest in studying doping prevention and its effects on non-elite athlete target groups in recent years. In terms of effectiveness, many measures did not achieve long-term changes or did not collect any follow-up data. This contrasts with understanding learning as sustained change and reduces the intended long-term protection of prevention measures, especially for adolescent target groups. Even young age groups from 10 years upwards benefited from doping prevention measures, and almost all doping prevention measures enabled their participants to increase their physical and health literacy. No conclusion can be drawn as to whether doping prevention measures based on constructivist ideas are superior to cognitivist approaches or a combination of both. Nevertheless, programs that actively engage their participants appear superior to lecture-based knowledge transfer. Most of the prevention measures offered a benefit-orientation so that participants can achieve added value, besides trying to initiate health-promoting change through rejection. Because of the lack of sustained changes, a further modification in doping prevention seems necessary. The review results support the value of primary prevention. Doping prevention measures should enable tailored learning and development options in the sense of more meaningful differentiation to individual needs. The implementation in a school context or an online setting is promising and sees doping as a problem for society. The review highlights the importance of accompanying evaluation measures to identify efficient prevention components that promote health and protect young people.
Following the Science to Generate Well-Being: Using the Highest-Quality Experimental Evidence to Design Interventions

The second wave of devastating consequences of the COVID-19 pandemic has been linked to dramatic declines in well-being. While much of the well-being literature is based on descriptive and correlational studies, this paper evaluates a growing body of causal evidence from high-quality randomized controlled trials (RCTs) that test the efficacy of positive psychology interventions (PPIs). This systematic review analyzed the findings from 25 meta-analyses, 42 review papers, and the high-quality RCTs of PPIs designed to generate well-being that were included within those studies. Findings reveal PPIs have the potential to generate well-being even during a global pandemic, with larger effect sizes in non-Western countries. Four exemplar PPIs—that have been tested with a high-quality RCT, have positive effects on well-being, and could be implemented during a global pandemic—are presented and discussed. Future efforts to generate well-being can build on this causal evidence and emulate the most efficacious PPIs to be as effective as possible at generating well-being. However, the four exemplars were only tested in WEIRD (Western, Educated, Industrial, Rich, and Democratic) countries but seem promising for implementation and evaluation in non-WEIRD contexts. This review highlights the overall need for more rigorous research on PPIs with more diverse populations and in non-WEIRD contexts to ensure equitable access to effective interventions that generate well-being for all.
The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network “Depot Study” was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions—conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently—showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders.
Current Understanding of the “Insight” Phenomenon Across Disciplines

Despite countless anecdotes and the historical significance of insight as a problem solving mechanism, its nature has long remained elusive. The conscious experience of insight is notoriously difficult to trace in non-verbal animals. Although studying insight has presented a significant challenge even to neurobiology and psychology, human neuroimaging studies have cleared the theoretical landscape, as they have begun to reveal the underlying mechanisms. The study of insight in non-human animals has, in contrast, remained limited to innovative adjustments to experimental designs within the classical approach of judging cognitive processes in animals, based on task performance. This leaves no apparent possibility of ending debates from different interpretations emerging from conflicting schools of thought. We believe that comparative cognition has thus much to gain by embracing advances from neuroscience and human cognitive psychology. We will review literature on insight (mainly human) and discuss the consequences of these findings to comparative cognition.
Variation of Stem Radius in Response to Defoliation in Boreal Conifers

In the long term, defoliation strongly decreases tree growth and survival. Insect outbreaks are a typical cause of severe defoliation. Eastern spruce budworm (Choristoneura fumiferana Clem.) outbreaks are one of the most significant disturbances of Picea and Abies boreal forests. Nevertheless, in boreal conifers, a 2-year defoliation has been shown to quickly improve tree water status, protect the foliage and decrease growth loss. It suggests that defoliation effects are time-dependent and could switch from favorable in the short term to unfavorable when defoliation duration exceeds 5–10 years. A better understanding of the effect of defoliation on stem radius variation during the needle flushing time-window could help to elucidate the relationships between water use and tree growth during an outbreak in the medium term. This study aims to assess the effects of eastern spruce budworm (Choristoneura fumiferana Clem.) defoliation and bud phenology on stem radius variation in black spruce [Picea mariana (Mill.) B.S.P.] and balsam fir [Abies balsamea (L.) Mill. ] in a natural stand in Quebec, Canada. We monitored host and insect phenology, new shoot defoliation, seasonal stem radius variation and daytime radius phases (contraction and expansion) from 2016 to 2019. We found that defoliation significantly increased stem growth at the beginning of needle flushing. Needles flushing influenced the amplitude and duration of daily stem expansion and contraction, except the amplitude of stem contraction. Over the whole growing season, defoliation increased the duration of stem contraction, which in turn decreased the duration of stem expansion. However, the change (increase/decrease) of the duration of contraction/expansion reflects a reduced ability of the potential recovery from defoliation. Black spruce showed significantly larger 24-h cycles of stem amplitude compared to balsam fir. However, both species showed similar physiological adjustments during mild stress, preventing water loss from stem storage zones to support the remaining needles’ transpiration. Finally, conifers react to defoliation during a 4-year period, modulating stem radius variation phases according to the severity of the defoliation.
Protective Effect of Mannitol on Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-Analysis

Introduction Cisplatin, a chemotherapeutic drug, is widely used for the treatment of various malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity, which is controversial. This study aimed to evaluate the efficacy and safety of a hydration regimen containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis. Methods Potential records from PubMed, EMBASE, Cochrane Library, and ClinicalTrials that met the inclusion criteria were included from inception to May 2021. Cochrane Collaboration tools were used to assess the risk of bias in the included studies. Jadad’s and NOS scores were applied to assess the quality of randomized controlled trials (RCTs) and case-control studies. A random-effects model or fixed-effects model was used depending on the heterogeneity. Subgroup analyses were performed to evaluate the potential study characteristics. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated. Results Four RCTs and seven case-control studies involving 4168 patients were included. Pooled results showed that mannitol use could reduce the incidence of cisplatin-induced nephrotoxicity (OR = 0.66, 95% CI [0.45–0.97], p = 0.03), especially reducing grade 3 nephrotoxicity events according to CTCAE 4.0 (OR = 0.37,95% CI [0.16–0.84]). Moreover, mannitol use was not significantly associated with creatinine clearance, serum creatine, and electrolyte disturbance (p > 0.05). Gastrointestinal cancer (OR = 0.36, 95% CI [0.15–0.83], p = 0.02) and urinary tract cancer (OR = 0.32,95% CI [0.14–0.73], p = 0.007) may be more sensitive to mannitol, although the test for overall effect was significantly different (OR = 0.66, 95% CI [0.49–0.89], p = 0.007). For patients with diabetes and hypertension, mannitol may worsen renal function (OR = 1.80, 95% CI [1.18–2.72], p = 0.006; OR = 2.19, 95% CI [1.50, 3.19], p < 0.0001, respectively). Mannitol may have a better protective effect when doses of mannitol were ≥ 25 g (OR = 0.58, 95% CI [0.39–0.88], p = 0.01) and doses of cisplatin < 75 mg/m2 (OR = 0.59, 95% CI [0.36–0.94], p = 0.03). It revealed that mannitol use was likely to cause nausea or vomiting (OR = 1.86, 95% CI [1.20–2.89], p = 0.006). Conclusion Current evidence revealed that mannitol was an effective and safe drug to reduce cisplatin-induced nephrotoxicity events, especially Grade 3 events. However, it may cause more nausea/vomiting events and deteriorate renal function in patients with diabetes or hypertension. We also found that mannitol had the best effect when mannitol was ≥ 25 g in total or cisplatin was < 75 mg/m2. Meanwhile, mannitol may have a better effect on gastrointestinal and urinary tract cancers. Systematic Review Registration crd. york. ac. uk/PROSPERO, CRD 42021253990