Miracle-dz/UniFAR-FTUs huggingface dataset:
EGFR amplification is a putative resistance mechanism for NSCLC–LM patients with TKI therapy and is associated with poor outcome

Background Leptomeningeal metastases (LM) have become increasingly common in non-small cell lung cancer (NSCLC) patients who harbor epidermal growth factor receptor (EGFR) mutation treated with EGFR-TKI and are correlated with inferior prognosis. Evidence in prior research demonstrated that EGFR amplification was more likely presented in advanced clinical stages and was associated with worse survival. However, whether EGFR amplification is a prognostic marker in NSCLC–LM is still inconclusive. Methods This study enrolled patients diagnosed with NSCLC–LM from June 2019 to September 2021 and who had received previous EGFR-TKI at Guangdong Sanjiu Brain Hospital. Cerebrospinal fluid (CSF) samples were collected and subjected to targeted next-generation sequencing of 168 cancer-related genes. Clinical characteristics and overall survival (OS) were compared in patients with and without EGFR amplification. Results This study enrolled 53 NSCLC–LM patients, all of whom had EGFR mutations. TP53 and EGFR amplifications are the two most frequent mutations in the study cohort, presenting at 72% (38 of 53) and 40% (21 of 53), respectively. The rate of EGFR amplification was much higher at the time of leptomeningeal progression than at initial diagnosis (p < 0.01). Karnoskfy performance status was poorer (p = 0.021), and CSF pressure was higher (p = 0.0067) in patients with EGFR amplification than those without. A multivariable Cox proportional hazard regression model showed that EGFR amplification was an independent prognostic factor for poorer OS (8.3 vs. 15 months; p = 0.017). The median OS was shorter in NSCLC–LM patients with mutated TP53 than those with wild-type TP53, but the difference was not statistically significant (10 vs. 17.3 months, p = 0.184). Conclusions EGFR gene amplification could be a potential resistance mechanism to EGFR-TKI failure in NSCLC–LM and is associated with inferior clinical outcomes.
Virulence of Blumeria graminis f. sp. tritici in Brazil, South Africa, Turkey, Russia, and Australia

The globally distributed causal agent of powdery mildew on wheat, Blumeria graminis f. sp. tritici (Bgt), is one of the most rapidly adapting plant pathogens and requires monitoring for shifts in virulence to wheat resistance (Pm) genes. Virulence frequencies were assessed in a total of 346 Bgt isolates from several countries that had either lately recorded increasing powdery mildew epidemics (Brazil, South Africa, and Australia) or not recently been surveyed (Turkey and Russia). The results were compared to previously published surveys of United States and Egyptian Bgt (390 isolates). Many of the Pm genes that have potentially been employed longer (Pm1a–Pm17) were shown to have lost effectiveness, and the complexity of virulence to those genes was higher among Brazilian isolates than those from any other country. Some cases of high virulence frequency could be linked to specific Pm gene deployments, such as the widespread planting of cultivar Wyalkatchem (Pm1a) in Australia. Virulence was also assessed to a set of Pm genes recently introgressed from diploid and tetraploid wheat relatives into a hexaploid winter wheat background and not yet commercially deployed. The isolate collections from Fertile Crescent countries (Egypt and Turkey) stood out for their generally moderate frequencies of virulence to both the older and newer Pm genes, consistent with that region’s status as the center of origin for both host and pathogen. It appeared that the recently introgressed Pm genes could be the useful sources of resistance in wheat breeding for other surveyed regions.
Identification of genetic loci conferring seed coat color based on a high-density map in soybean

Seed coat color is a typical evolutionary trait. Identification of the genetic loci that control seed coat color during the domestication of wild soybean could clarify the genetic variations between cultivated and wild soybean. We used 276 F10 recombinant inbred lines (RILs) from the cross between a cultivated soybean (JY47) and a wild soybean (ZYD00321) as the materials to identify the quantitative trait loci (QTLs) for seed coat color. We constructed a high-density genetic map using re-sequencing technology. The average distance between adjacent markers was 0.31 cM on this map, comprising 9,083 bin markers. We identified two stable QTLs (qSC08 and qSC11) for seed coat color using this map, which, respectively, explained 21.933 and 26.934% of the phenotypic variation. Two candidate genes (CHS3C and CHS4A) in qSC08 were identified according to the parental re-sequencing data and gene function annotations. Five genes (LOC100786658, LOC100801691, LOC100806824, LOC100795475, and LOC100787559) were predicted in the novel QTL qSC11, which, according to gene function annotations, might control seed coat color. This result could facilitate the identification of beneficial genes from wild soybean and provide useful information to clarify the genetic variations for seed coat color in cultivated and wild soybean.
Bifidobacterium longum CECT 7894 Improves the Efficacy of Infliximab for DSS-Induced Colitis via Regulating the Gut Microbiota and Bile Acid Metabolism

Background: Recent evidence suggests that the changes in gut microbiota and its metabolites could predict the clinical response of anti-tumor necrosis factor (TNF) agents, such as infliximab (IFX). However, whether manipulation of the gut microbiota can enhance the efficacy of anti-TNF agents remains unclear. Here, we aim to evaluate the effect of a probiotic strain, Bifidobacterium longum (B. longum) CECT 7894, on IFX efficacy for dextran sulfate sodium (DSS)-induced colitis in mice and attempt to explore the potential involved mechanisms. Methods: C57BL/6 mice were treated with phosphate-buffered saline (PBS) or B. longum CECT 7894 (5 × 108 CFU/day) once daily by gavage for 5 days and subsequently induced acute colitis by 3% (w/v) DSS in drinking water. The efficacies of IFX combined with or without B. longum CECT 7894 were assessed by weight loss, fecal consistency, colon length, and histopathological changes. Immunohistochemistry (IHC) was used to examine the expression of tight junction proteins (TJPs) in colonic tissues. The microbiota composition was characterized through 16 S rRNA gene sequencing. Fecal bile acids (BAs) levels were analyzed by targeted metabolomics. Results: B. longum CECT 7894 improved the efficacy of IFX for DSS-induced colitis as evidenced by decreased weight loss, disease activity index (DAI) scores, colon length shortening, histological damage, increased ZO-1, and Occludin expressions as compared with mice that received IFX only. B. longum CECT 7894 modified the composition and structure of the gut microbiota community in DSS-induced colitis mice. B. longum CECT 7894 increased the relative abundances of genera Bifidobacterium, Blautia, Butyricicoccus, Clostridium, Coprococcus, Gemmiger, and Parabacterioides, and reduced the relative abundances of bacteria genera Enterococcus and Pseudomonas. Furthermore, B. longum CECT 7894 changed the BAs metabolism by increasing the abundance of secondary BAs, such as a-MCA, ß-MCA, LCA, CDCA, UDCA, HCA, isoLCA, isoalloLCA. The covariance analysis revealed the upregulated secondary BAs were positively associated with the increased abundance of bacteria that contained bile salt hydrolases (BSH) and 7α-dehydroxylases genes. Conclusion: B. longum CECT 7894 improved the efficacy of IFX for DSS-induced colitis via regulating the gut microbiota composition and bile acid metabolism. Probiotics supplementation may provide a possibility to improve the clinical response of anti-TNF agents in IBD management.
COVID-19 Vaccine Hesitancy Among Health Care Workers in Thailand: The Comparative Results of Two Cross-Sectional Online Surveys Before and After Vaccine Availability

Introduction The arrival of COVID-19 vaccines in Thailand has supported the fight against the COVID-19 pandemic. This study examined COVID-19 vaccine acceptance among health care workers (HCWs) in Thailand before and after vaccines' availability and investigated factors (both enablers and barriers) affecting their decisions. Methods Two online self-administered questionnaires were distributed to HCWs in two time-periods: (1) the pre-vaccine arrival period (prior to COVID-19 vaccines' arrival in Thailand, January 28 to February 16, 2021); and (2) the post-vaccine arrival period (April 21 to May 9, 2021). Descriptive analyses and multinomial logistic regression were conducted to examine factors associated with vaccine hesitancy. Results There were 55,068 respondents in the pre-vaccine arrival period and 27,319 respondents in the post-vaccine arrival period. In the pre-vaccine arrival period, 55.0% of respondents were willing to accept the vaccines, 35.4% were uncertain, and 9.6% declined. In the post-vaccine arrival period, ~16% already received two doses of either the Sinovac or AstraZeneca vaccine, and 43% were administered one dose. Approximately 12% of those who had received the first dose were uncertain or not willing to accept the second dose. Demographic and socio-demographic factors of participants, including their sex, place of residence, and whether they were frontline COVID-19 workers, were found to be the significant factors explaining vaccination hesitancy. Moreover, when comparing the pre-vaccine arrival and post-vaccine arrival periods, it was found that older HCWs were more likely to decline a COVID-19 vaccine in the pre-vaccine arrival period; on the other hand, older HCWs were less likely to decline or be uncertain to receive a COVID-19 vaccine in the post-vaccine arrival period. Conclusion Information on HCWs' acceptance of COVID-19 vaccines, including who is more likely to accept the vaccines, could assist in planning vaccine allocation to both HCWs and the general public, who often believe HCWs' recommendations. This study's findings set out how policies can be addressed to reduce vaccine hesitancy. This study also highlights HCWs' characteristics (including gender, work region, occupation, and history of receiving influenza vaccination) and the reasons they cited for their vaccine acceptance or hesitance.
Effectiveness of aerobic and resistance training on the motor symptoms in Parkinson's disease: Systematic review and network meta-analysis

Background/objectives Aerobic and resistance training are common complementary therapies to improve motor symptoms in people with Parkinson's disease (PD), and there is still a lack of advice on which intensity and period of aerobic or resistance training is more appropriate for people with PD. Therefore, a network meta-analysis was conducted to assess the comparative efficacy of aerobic and resistance training of different intensities and cycles on motor symptoms in patients with Parkinson's disease. Methods Based on several biomedical databases, a search strategy system was conducted to retrieve randomized controlled trials (RCTs) without language restrictions. A network meta-analysis with a frequentist approach was conducted to estimate the efficacy and probability rankings of aerobic and resistance training on Parkinson's patients. What's more, a range of analyses and assessments, such as routine meta-analyses and risk of bias, were performed as well. Results Twenty trials with 719 patients evaluating 18 different therapies were identified. Through the Unified Parkinson's Disease Motor Rating Scale, (UPDRS III); 6-minute walk test, (6MWT); 10-meter walk test, (TWM); and time up and go (TUG) and Quality of Life Scale-39 (PDQ-39), to explore the effects of different intensity resistance and aerobic exercise on PD. As a result, short period high intensity resistance movement (standard mean difference (SMD) = −0.95, 95% confidence interval (CI) −1.68 to −0.22) had significantly decreased the Unified Parkinson's Disease Motor Rating Scale (UPDRS III). Short period high intensity resistance exercise showed similar superiority in other indices; also, aerobic and resistance training of different cycle intensities produced some efficacy in PD patients, both in direct and indirect comparisons. Conclusion For patients with moderate to mild Parkinson's symptoms, short periods high intensity resistance training may provide complementary therapy for PD, and aerobic or resistance training of varying intensity and periodicity may be recommended as exercise prescription for PD patients. However, more large scale and high quality clinical trials are needed to confirm the effectiveness of this exercise therapy in the future. Systematic Review Registration https://www.crd. york.ac. uk/PROSPERO/, identifier: CRD42022324824.
Matcha green tea targets the gut–liver axis to alleviate obesity and metabolic disorders induced by a high-fat diet

Obesity induced by a high-fat diet (HFD) is an increasing global health problem, leading to many metabolic syndromes. As the emerging food additive rich in tea polyphenols, theanine, caffeine, and so on, matcha green tea has gained more and more popularity for its outstanding potential in ameliorating metabolic disorders. This study investigated the composition and antioxidant activity of matcha green tea and further explored its effects on gut–liver axis homeostasis in an HFD-induced obese mouse model. Male (7–8 weeks old) C57BL/6J mice were divided into four groups with the following dietary supplementation for 8 weeks: a normal chow diet (NCD), a normal chow diet+1.0% matcha (NCM), a high-fat diet (HFD), and a high-fat diet+1.0% matcha (HFM). The results demonstrated that matcha green tea ameliorated the development of obesity, lipid accumulation, and hepatic steatosis induced by HFD. Subsequently, dietary matcha supplementation restored the alterations in fecal bile acid profile and gut microbial composition. Meanwhile, the levels of mRNA expression in hepatocytes demonstrated that matcha intervention made significant regulatory on the multiple metabolic pathways of hosts involved in glucose, lipid, and bile acid metabolism. These findings present new evidence for matcha green tea as an effective nutritional strategy to mitigate obesity and relevant metabolic disorders through the gut–liver axis.
Increased functional connectivity of white-matter in myotonic dystrophy type 1

Background Myotonic dystrophy type 1 (DM1) is the most common and dominant inherited neuromuscular dystrophy disease in adults, involving multiple organs, including the brain. Although structural measurements showed that DM1 is predominantly associated with white-matter damage, they failed to reveal the dysfunction of the white-matter. Recent studies have demonstrated that the functional activity of white-matter is of great significance and has given us insights into revealing the mechanisms of brain disorders. Materials and methods Using resting-state fMRI data, we adopted a clustering analysis to identify the white-matter functional networks and calculated functional connectivity between these networks in 16 DM1 patients and 18 healthy controls (HCs). A two-sample t-test was conducted between the two groups. Partial correlation analyzes were performed between the altered white-matter FC and clinical MMSE or HAMD scores. Results We identified 13 white-matter functional networks by clustering analysis. These white-matter functional networks can be divided into a three-layer network (superficial, middle, and deep) according to their spatial distribution. Compared to HCs, DM1 patients showed increased FC within intra-layer white-matter and inter-layer white-matter networks. For intra-layer networks, the increased FC was mainly located in the inferior longitudinal fasciculus, prefrontal cortex, and corpus callosum networks. For inter-layer networks, the increased FC of DM1 patients is mainly located in the superior corona radiata and deep networks. Conclusion Results demonstrated the abnormalities of white-matter functional connectivity in DM1 located in both intra-layer and inter-layer white-matter networks and suggested that the pathophysiology mechanism of DM1 may be related to the white-matter functional dysconnectivity. Furthermore, it may facilitate the treatment development of DM1.
Reliable and Valid Robotic Assessments of Hand Active and Passive Position Sense in Children With Unilateral Cerebral Palsy

Impaired hand proprioception can lead to difficulties in performing fine motor tasks, thereby affecting activities of daily living. The majority of children with unilateral cerebral palsy (uCP) experience proprioceptive deficits, but accurately quantifying these deficits is challenging due to the lack of sensitive measurement methods. Robot-assisted assessments provide a promising alternative, however, there is a need for solutions that specifically target children and their needs. We propose two novel robotics-based assessments to sensitively evaluate active and passive position sense of the index finger metacarpophalangeal joint in children. We then investigate test-retest reliability and discriminant validity of these assessments in uCP and typically developing children (TDC), and further use the robotic platform to gain first insights into fundamentals of hand proprioception. Both robotic assessments were performed in two sessions with 1-h break in between. In the passive position sense assessment, participant's finger is passively moved by the robot to a randomly selected position, and she/he needs to indicate the perceived finger position on a tablet screen located directly above the hand, so that the vision of the hand is blocked. Active position sense is assessed by asking participants to accurately move their finger to a target position shown on the tablet screen, without visual feedback of the finger position. Ten children with uCP and 10 age-matched TDC were recruited in this study. Test-retest reliability in both populations was good (intraclass correlation coefficients (ICC) >0.79). Proprioceptive error was larger for children with uCP than TDC (passive: 11.49° ± 5.57° vs. 7.46° ± 4.43°, p = 0.046; active: 10.17° ± 5.62° vs. 5.34° ± 2.03°, p < 0.001), indicating discriminant validity. The active position sense was more accurate than passive, and the scores were not correlated, underlining the need for targeted assessments to comprehensively evaluate proprioception. There was a significant effect of age on passive position sense in TDC but not uCP, possibly linked to disturbed development of proprioceptive acuity in uCP. Overall, the proposed robot-assisted assessments are reliable, valid and a promising alternative to commonly used clinical methods, which could help gain a better understanding of proprioceptive impairments in uCP, facilitating the design of novel therapies.
Would victims blame victims? Effects of ostracism, sexual objectification, and empathy on victim blaming

In the current research, we examined whether ostracism and sexual objectification affect the tendency to blame the victim of sexual harassment. Previous research concerning victim blame examined the attribution of blame considering the characteristics of the victim, the perpetrator, and the relation between them. However, no research to date examined whether situational factors of the perceiver can affect their perception and judgment of blame. We propose that sexual objectification and ostracism may elicit empathy toward the victim, and in turn, reduce victim blame. In two experimental studies, women were instructed to imagine interacting with a videotaped man who either gazed at their body (objectification), away from them (ostracism), or at their face (treated well). Then, they were asked to read a newspaper article (study 1) or watch a video (study 2) portraying encounters in which the man's sexual advances continued after the woman expressed discomfort and lack of interest. In study 1, we found that sexually objectified women attributed less blame to the woman compared with the women who were treated well, with ostracized women falling in between and marginally different from both. In study 2, using mediation analysis we found an indirect effect such that sexually objectified women experienced greater empathy toward the victim, which was associated with reduced attribution of blame. It appears that greater similarity between the situation of the perceiver and the situation of the victim elicits greater empathy. This adds to the previous knowledge that personality similarities result in higher empathy.
Case report: Combined therapy of bilateral subthalamic nucleus deep brain stimulation and spinal cord stimulation significantly improves motor function in a patient with multiple system atrophy with predominant parkinsonism

Multiple system atrophy with predominant parkinsonism (MSA-P) is a highly incapacitating disease with a short life expectancy and symptomatic therapy is still limited. In this report, we presented the case of a 65-year-old woman with a 3-year history of severe rigidity, bradykinesia, and gait dysfunction alongside severe freezing of gait diagnosed with MSA-P. She underwent combined therapy of bilateral subthalamic nucleus deep brain stimulation (DBS) and low-thoracic spinal cord stimulation (SCS). The double-blind evaluation of the Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III and 7-m Timed Up and Go at follow-ups showed her cardinal parkinsonian symptoms benefit significantly from DBS stimulation, while the improvement of SCS was mainly embodied in lower-limb symptoms. The combined stimulation achieved a better improvement of motor function than either DBS or SCS stimulation alone. Most notably, the improvement of lower-limb symptoms was significantly enhanced by the combined stimulation.
Pediatric uveitis: Role of the pediatrician

The challenges of childhood uveitis lie in the varied spectrum of its clinical presentation, the often asymptomatic nature of disease, and the evolving nature of the phenotype alongside normal physiological development. These issues can lead to delayed diagnosis which can cause significant morbidity and severe visual impairment. The most common ocular complications include cataracts, band keratopathy, glaucoma, and macular oedema, and the various associated systemic disorders can also result in extra-ophthalmic morbidity. Pediatricians have an important role to play. Their awareness of the various presentations and etiologies of uveitis in children afford the opportunity of prompt diagnosis before complications arise. Juvenile Idiopathic Arthritis (JIA) is one of the most common associated disorders seen in childhood uveitis, but there is a need to recognize other causes. In this review, different causes of uveitis are explored, including infections, autoimmune and autoinflammatory disease. As treatment is often informed by etiology, pediatricians can ensure early ophthalmological referral for children with inflammatory disease at risk of uveitis and can support management decisions for children with uveitis and possible underling multi-system inflammatory disease, thus reducing the risk of the development of irreversible sequelae.
Identification of a novel RMST-ALK rearrangement in advanced lung adenocarcinoma and durable response to ceritinib: A case report

Next-generation sequencing technology has enabled the identification of fusion partners of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer, and various ALK fusion partners have been confirmed. Here, a novel rhabdomyosarcoma 2-associated transcript (RMST)-ALK rearrangement was identified in an 80-year-old Chinese man with advanced lung adenocarcinoma. The patient was prescribed ceritinib and achieved a partial response, which has been sustained for more than 18 months. This is the first report of the RMST-ALK rearrangement, and we showed that a patient with lung adenocarcinoma carrying this rearrangement can benefit from ceritinib treatment; therefore, this is a significant finding in clinical practice.