Miracle-dz/UniFAR-FTUs huggingface dataset:
RALF1 peptide triggers biphasic root growth inhibition upstream of auxin biosynthesis

Significance Regulation of growth is crucial for overall plant development and its adaptation to environment. Peptide rapid alkalinization factors 1 (RALF1) and phytohormone auxin are key growth regulators with characteristic both rapid and long-term effects. However, the underlying mechanism and coordination of these signals are unclear. Our study reveals that those two signals trigger rapid growth inhibition (<1 min) by rapidly alkalinizing the apoplast, a result of rapid net H+ influx across the plasma membrane; nonetheless, their signaling mechanisms are independent. RALF1 sustains root growth inhibition long term by inducing auxin biosynthesis and signaling. These discoveries contribute to the understanding of rapid plant growth responses and hormone-peptide cross-talk for optimization of plant growth and architecture also relevant for agriculture applications.
The 2018 World Cancer Research Fund/American Institute for Cancer Research Score and cancer risk: a longitudinal analysis in the NIH-AARP Diet and Health Study.

BACKGROUND We examined associations between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations using the standardized 2018 WCRF/AICR Score and cancer risk among older U.S. adults. METHODS Participants included 215,102 adults in the NIH-AARP Diet and Health Study followed between 2004-2011 (mean 7.0 person-years). Scores (range: 0-7 points) were calculated from self-reported weight, physical activity, and diet and alcohol intake measures. Outcomes included 17 cancers reviewed by WCRF/AICR (cases: male n=11,066; female n=8,865) and top three U.S. cancers in males (total n=4,658; lung n=2,211; prostate n=920; colorectal n=1,527) and females (total n=5,957; lung n=1,475; post-menopausal breast n=3,546; colorectal n=936). Cox proportional hazard ratios (HRs) were estimated for score and cancer risk associations, stratifying by sex and smoking status. RESULTS Each one-point score increase was associated with 6-13% reduced cancer risk across combined outcomes, except for male never smokers' risk for top three cancers and male current smokers' risk for both combined cancer outcomes. Higher scores were associated with decreased lung cancer risk only among male former smokers (HR=0.84; 95%CI: 0.79-0.89) and female current smokers (HR=0.89; 95%CI: 0.82-0.96). Higher scores were associated with 7-19% decreased breast cancer risk across smoking strata and 10-14% decreased colorectal cancer risk among male and female never and former smokers. CONCLUSIONS Greater Recommendations adherence was associated with reduced cancer risk. IMPACT Findings emphasize the importance of considering combined contributions of multiple lifestyle factors for cancer prevention among older adults and the potential modifying role of smoking history.
Evaluation of Appendicular Muscle Mass in Sarcopenia in Older Adults Using Ultrasonography: A Systematic Review and Meta-Analysis

Background: The measurement of appendicular muscle mass is essential for the diagnosis of sarcopenia. Ultrasonography is an accurate and convenient method used to evaluate muscle mass. Objective: The aim of the study was to evaluate the diagnostic value of ultrasonography for appendicular muscle mass in sarcopenia in older adults and find out proper ultrasound parameters. Methods: Medline, Embase, Cochrane, and Web of Science databases were searched for relevant articles. Published studies on the validity and/or reliability of ultrasonography for quantifying muscle mass of the limbs in sarcopenia in the older population were included. A systematic review was conducted based on specific muscles and reference methods. A meta-analysis was conducted to assess the validity and reliability of the ultrasonography. Results: Forty articles were included in this review. There were nine, nine, nine, and four studies included in the qualitative synthesis for a diagnostic test, correlation coefficient, intra-class reliability, and inter-class reliability, respectively. The diagnostic value of rectus femoris (RF) or gastrocnemius (GM) thickness on ultrasonography for sarcopenia or low muscle mass was moderate (the area under summary receiver operating characteristic curve [SROC] = 0.76, 95% confidence interval [CI]: 0.72–0.79, SROC = 0.80, 95% CI: 0.76–0.83, respectively). The pooled correlation between muscle mass on dual-energy X-ray (DXA) or bioelectrical impedance analysis (BIA) and muscle thickness (MT) on ultrasound was moderate (r = 0.56, 95% CI: 0.49–0.62). There was a low-to-moderate correlation between muscle mass on DXA or BIA and cross-sectional area (CSA) on ultrasound (r = 0.267–0.584). The correlation was high to very high between muscle mass from DXA and the ultrasound-predicted formula (r = 0.85–0.963). The CSA from ultrasound had a high or very high correlation with that from computed tomography or magnetic resonance imaging (r = 0.826, intra (inter)-correlation coefficient [ICC] = 0.998–0.999). The respective meta-analyses showed good inter-rater and intra-rater reliabilities (ICC > 0.9). Conclusion: Ultrasonography is a reliable and valid diagnostic method for the quantitative assessment of appendicular muscle mass in sarcopenia in older people. The thickness and CSA of the RF or GM seem to be proper ultrasound parameters to predict muscle mass in sarcopenia. Multicenter studies with large samples and the application of new ultrasonic techniques will be the future research directions.
Rankin--Eisenstein classes and explicit reciprocity laws

We construct three-variable $p$-adic families of Galois cohomology classes attached to Rankin convolutions of modular forms, and prove an explicit reciprocity law relating these classes to critical values of L-functions. As a consequence, we prove finiteness results for the Selmer group of an elliptic curve twisted by a 2-dimensional odd irreducible Artin representation when the associated $L$-value does not vanish.
SARS-CoV-2 Omicron escapes mRNA vaccine booster-induced antibody neutralisation in patients with autoimmune rheumatic diseases: an observational cohort study

Objectives This study investigates whether COVID-19 vaccines can elicit cross-reactive antibody responses against the Omicron variant in patients with autoimmune rheumatic diseases (ARDs). Methods This observational cohort study comprised 149 patients with ARDs and 94 healthcare workers (HCWs). Blood samples were obtained at enrolment, a median of 15 weeks after the second vaccine dose or 8 weeks after the third dose. The functional cross-neutralisation capacity of sera was measured using the Omicron variant receptor-binding domain-ACE2 binding inhibition assay. We assessed the incidence of breakthrough infections and the potential correlation with neutralising responses in participants after receiving third doses. The association of time-from-vaccine and neutralising responses in sera was predicted using linear regression analysis. Results The mean cross-neutralising responses against the Omicron variant developed after the second dose was 11.5% in patients with ARDs and 18.1% in HCWs (p=0.007). These responses were significantly lower in patients with ARDs than in HCWs after the third dose (26.8% vs 50.3%, p<0.0001). Only 39.2% of the patient sera showed functional neutralisation capacity to the Omicron variant and cross-neutralising responses were shown to be poorly correlated with anti-spike immunoglobulin G titres. Within 6 weeks of immunological assessments, significantly lower Omicron-neutralising responses were detected in sera from patients with ARDs who developed breakthrough infections compared with those who did not (p=0.018). Additionally, a relative decline was implied in neutralising responses against the Omicron variant as a reference to the wild-type virus during 120 days since the third vaccination, with a predicted decay rate of −0.351%/day (95% CI, −0.559 to −0.144, p=0.001). Conclusions Striking antibody evasion manifested by the Omicron variant in patients with ARDs and current vaccine-induced immunity may not confer broad protection from Omicron breakthrough infection, highlighting the need for further research on vaccine effectiveness in patients with immune dysfunctions.
Single-Level Total Disc Replacement: Mid- to Long-Term Outcomes

Background Total disc replacement (TDR) has been shown to be effective for the treatment of lumbar degenerative disc disease (DDD) in carefully selected patients. Previous studies have demonstrated high rates of patient satisfaction and improvement in patient-reported outcome measures (PROMs) compared with preoperative status but most have short-term follow-up or small cohort sizes only. Objective The aim of this study is to report mid- to long-term PROMs from the treatment of symptomatic single-level lumbar DDD with TDR. Methods Data collected prospectively concerning single-level TDR performed via an anterior approach were included for analysis. A preoperative assessment was obtained followed by postoperative follow-up assessments at 3, 6, and 12 months, and yearly follow-up thereafter. PROMs included patient satisfaction, visual analog score back and leg, Oswestry Disability Index, and Roland-Morris Disability Questionnaire. Results A total of 211 patients (118 men, 93 women) operated on between June 1997 and July 2015 were included in this study. Minimum follow-up was 4 years. The average age was 42.2 (range 24–87) years and median follow-up 96 interquartile range 72–132, range 48–120) months. The operative levels were L5-S1 (160, 75.8%) and L4-L5 (61, 24.2%). Both statistically and clinically significant improvements observed postoperatively were maintained at 10 years. In addition, 92% of patients reported either good (n = 29) or excellent satisfaction (n = 155) with treatment at final review. Conclusions This study shows that single-level lumbar TDR used appropriately in selected patient results in clinically significant improvements in pain and function, well above the minimum clinically important difference, and good to excellent satisfaction in most patients. Further study to define long-term outcomes and survivorship is required. Clinical Relevance Statistically significant and clinically relevant improvements can be achieved by single-level lumbar TDR, in the treatment of single-level discogenic axial low back pain, with or without radiculopathy. These outcomes are sustained in the mid- to long-term followup periods. Level of Evidence 4.
The association between PI3K, JAK/STAT pathways with the PDL‐1 expression in prostate cancer

Programmed cell death protein‐1/programmed death‐ligand‐1 (PD‐1/PDL‐1) signalling pathway has gained attention in prostate cancer. The relationship between pSTAT‐1, pSTAT‐3 expressions and PTEN loss with PDL‐1 expression was assessed and the effects of the pathways on prostate cancer prognosis were evaluated. Patients who underwent radical prostatectomy between 2011 and 2017 were included in our study. Prostatectomy materials were evaluated using immunohistochemical staining of pSTAT‐1, pSTAT‐3, PTEN, and PDL‐1. The relationship between PDL‐1 and pSTAT‐1, pSTAT‐3 expressions and PTEN loss was evaluated. Additionally, factors affecting biochemical recurrence‐free survival and clinical progression‐free survival were analysed. Within100 patients, 9 of 11 patients with PDL‐1 expression also had intermediate‐high pSTAT‐1 staining intensity, and those with PDL‐1 expression had higher pSTAT‐1 staining intensity than those without (81.9% vs. 56.2%, p = 0.014). In univariate analysis, pSTAT‐1, pSTAT‐3 and PDL‐1 expressions had significant impact on biochemical recurrence‐free and clinical progression‐free survival. In multivariate analysis, pSTAT‐1 staining intensity with radical prostatectomy ISUP grade in terms of biochemical recurrence‐free survival and the pSTAT‐1 H‐score with radical prostatectomy ISUP grade in terms of clinical progression‐free survival were independent risk factors. Moderate‐high expression of pSTAT‐1 was closely associated with PDL‐1 expression, and pSTAT‐1 was also a predictor of biochemical recurrence and clinical progression.
Amisulpride Augmentation in Schizophrenia Patients with Poor Response to Olanzapine: A 4-week, Randomized, Rater-Blind, Controlled, Pilot Study

Objective The purpose of this study was to compare the efficacy and tolerability of continued olanzapine (OLA) versus amisulpride (AMI) augmentation in schizophrenic patients with poor response to OLA monotherapy. Methods The present 4-week, randomized, rater-blinded study included 25 patients with schizophrenia who were partially or completely unresponsive to treatment with OLA monotherapy. Eligible subjects were randomly assigned at a 11 ratio to continuation of OLA monotherapy (OLA group) or OLA with AMI augmentation (AMI group). Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 1, 2, and 4 weeks. Results The changes in PANSS total score and PANSS-positive subscale score were significantly different (p < 0.05) between the OLA and AMI groups. The differences between the two groups in PANSS-negative subscale, PANSS-general subscale, Brief Psychiatric Rating Scale, and Clinical Global Impression-Severity (CGI-S) scale scores were not statistically significant. Conclusion AMI augmentation could be an effective strategy for patients with schizophrenia who show inadequate early response to OLA monotherapy.
Educational Technologies for Teaching Social Skills to Individuals With Schizophrenia: Scoping Review

Schizophrenia interventions incorporate improving quality of life and social functioning. Educational technologies are a potential treatment method for social skills development among individuals with schizophrenia. The objective of the study is to provide an overview of the characteristics and range of approaches of educational technologies in the context of social skills for individuals with schizophrenia. A scoping review methodological framework was applied. Search strategy was conducted on Ovid MEDLINE® and CINAHL Plus. Data were synthesized using a charting form for a logical, descriptive summary of results. The search yielded 771 results and 23 included studies that met eligibility criteria. The data showed persons with schizophrenia respond well to educational technologies to address illness self-management. Using technology in conjunction with traditional evidence-based interventions demonstrates promising results to improve social skills functioning. Occupational therapists can use educational technologies to decrease the gap in health care services and improve social support for individuals with schizophrenia.
Long-Term Effect of Physical Exercise on the Risk for Hospitalization and Death in Dialysis Patients

Visual Abstract Background and objectives In the EXerCise Introduction to Enhance Performance in Dialysis (EXCITE) trial, a simple, personalized 6-month walking exercise program at home during the day off of dialysis improved the functional status and the risk for hospitalization in patients with kidney failure. In this post-trial observational study, we tested whether the same intervention was associated with a lower long-term risk of death or hospitalization (combined end point) during a follow-up extended up to 36 months. Design, setting, participants, & measurements In total, 227 patients (exercise, n=104; control, n=123) completed the 6-month trial and entered the post-trial observational study. Data were analyzed by unadjusted and adjusted Cox regression analyses and Bayesian analysis. Results In the long-term observation (up to 36 months), 134 events were recorded (eight deaths not preceded by hospitalization and 126 hospitalizations, which were followed by death in 38 cases). The long-term risk for hospitalization or death was 29% lower (hazard ratio, 0.71; 95% confidence interval, 0.50 to 1.00), and in an analysis stratified by adherence to the walking exercise program during the 6-month trial, the subgroup with high adherence (>60% of prescribed sessions) had a 45% lower risk as compared with the control group (hazard ratio, 0.55; 95% confidence interval, 0.35 to 0.87). A Bayesian analysis showed that the posterior probability of a hazard ratio of 0.71 (95% confidence interval, 0.50 to 1.00) for the risk of the composite outcome observed in the post-trial observational study was 93% under the conservative prior and 97% under the optimistic prior. Sensitivity analyses restricted to the risk of hospitalization only or censoring patients at the time of transplantation fully confirmed these findings. Conclusions A simple, personalized, home-based, low-intensity exercise program was associated with a lower risk of hospitalization. Clinical Trial registry name and registration number: EXerCise Introduction to Enhance Performance in Dialysis (EXCITE), NCT01255969
Systems pharmacology approaches in herbal medicine research: a brief review

Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.
Oncology provider experiences during the COVID-19 pandemic

Purpose The COVID-19 pandemic upended nearly all aspects of daily life and of medical care, placing a double burden of professional and personal concerns on those who provide medical care. We set out to assess the burden of the pandemic on provider outlook and understand how cancer survivorship providers experienced rapid changes to practice. Methods We distributed a survey through the American College of Surgeons Commission on Cancer (CoC) to its accredited organizations in mid-October 2020. We included questions on provider characteristics, changes in patient care practices resulting from the pandemic, worry about COVID-19, and concern about impact on cancer survivors. Results Of the n = 607 participants, three-quarters were female and three-quarters were White. Only 2.1% of participants reported having had COVID-19, but 43% reported anxiety about getting COVID-19 and over a quarter experienced sadness or depression, anxiety about the future, changes to sleep, difficulty concentrating, or social isolation. Approximately half of providers also expressed significant concern about progression of cancer in patients who experienced care delays or were afraid of accessing in-person care. In terms of changes to survivorship care, respondents reported changes to visitor policies, delays or cancellations, and efforts to reduce in-person visits. Conclusions COVID-19 has taken a significant toll on front-line healthcare professionals, including oncologists and cancer care allied health professionals. Findings support proactive mental health support of healthcare professionals as well as emergency preparedness to manage delays to care for cancer patients in the event of future unexpected pandemics.
Silver nanoparticles adversely affect the swimming behavior of European Whitefish (Coregonus lavaretus) larvae within the low µg/L range

ABSTRACT The aim of this study was to determine the effects of silver nanoparticles (AgNPs; speciation: NM-300 K) in the lab on the behavior of larvae in European Whitefish (Coregonus lavaretus), a relevant model species for temperate aquatic environments during alternating light and darkness phases. The behavioral parameters measured included activity, turning rate, and distance moved. C. lavaretus were exposed to AgNP at nominal concentrations of 0, 5, 15, 45, 135, or 405 µg/L (n = 33, each) and behavior was recorded using a custom-built tracking system equipped with light sources that reliably simulate light and darkness. The observed behavior was analyzed using generalized linear mixed models, which enabled reliable detection of AgNP-related movement patterns at 10-fold higher sensitivity compared to recently reported standard toxicological studies. Exposure to 45 µg/L AgNPs significantly resulted in hyperactive response patterns for both activity and turning rates after an illumination change from light to darkness suggesting that exposure to this compound triggered escape mechanisms and disorientation-like behaviors in C. lavaretus fish larvae. Even at 5 µg/L AgNPs some behavioral effects were detected, but further tests are required to assess their ecological relevance. Further, the behavior of fish larvae exposed to 135 µg/L AgNPs was comparable to the control for all test parameters, suggesting a triphasic dose response pattern. Data demonstrated the potential of combining generalized linear mixed models with behavioral investigations to detect adverse effects on aquatic species that might be overlooked using standard toxicological tests.
Treatment for relapsed acute promyelocytic leukemia: what is the best post-remission treatment?

Background Arsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking. Methods We evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC). Results The ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%, P=0.878). Among these patients, seven received salvage allogeneic HSCT; six remained alive. The other seven patients received ATO without HSCT. Five died from disease progression, and two survived and have been in mCR2 since. Conclusion Post-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.