Miracle-dz/UniFAR-FTUs huggingface dataset:
Cavity Formation is a Prognostic Indicator for Pathologic Stage I Invasive Lung Adenocarcinoma of ≥3 cm in Size

Background We investigated the correlation between cavity formation, prognosis, and tumor stage for pathologic stage I invasive lung adenocarcinomas (IADCs) ≤3 cm in size. Material/Methods 2106 candidates with pathologic stage I IADC were identified from Shanghai Chest Hospital between 2009 and 2014. There were 227 patients who were diagnosed as having cavity formation and another 1879 patients who were not (the non-cavitary lung cancer group). Kaplan-Meier analysis curves were conducted to compare the overall survival (OS) and relapse-free survival (RFS) between these 2 groups. Cox proportional hazards regression was performed to discover the independent risk factors of OS and RFS. Receiver operating characteristic (ROC) curve was done to determine the cutoff value of cavity size for predicting prognosis. Furthermore, subgroup analysis was stratified by the size of tumor and the 8th classification of T category. Results Compared with non-cavitary lung cancer group, patients with cavity formation were found to have a higher prevalence of male patients (P=0.015), older age patients (P=0.039), larger size tumors (P=0.004), and worse cancer relapse (P<0.001). Survival analysis found that patients with cavitary IADC had significantly shorter RFS than those with non-cavitary IADC (P=0.001). Further, subgroup analysis confirmed a significantly worse RFS in cavitary IADC group both in stage T1a (P=0.002) and T1b (P<0.001), but not for stage T1c (P=0.962) and T2a (P=0.364). Moreover, cavity formation was still less of a significant predictor of RFS in multivariable analysis (hazard ratio [HR] 1.810, 95% confidence level [CI] 1.229–2.665, P=0.003). The ROC curve showed that the best cutoff value of maximum diameter of the cavity for judging RFS was 5 mm (sensitivity: 0.500; specificity: 0.783). At the same time, multiple cavities were more likely to lead to recurrence (sensitivity: 0.605; specificity: 0.439). Conclusions Cavitary adenocarcinoma was a worse prognostic indicator compared with non-cavitary adenocarcinoma, especially for cavity >5 mm and multiple cavities. Thus, for stage T1a and T1b, cavitary and non-cavitary IADC should be considered separately.
HIV pretreatment drug resistance among cisgender MSM and transgender women from Lima, Peru

Transmitted, or any pretreatment drug resistance (TDR, PDR) can compromise efficacy of first‐line antiretroviral therapy (ART). In Peru, genotypic resistance testing is not routinely performed before ART initiation, and estimated PDR prevalence prior to 2012 ranged from 1.0% to 4.7%. We aimed to update estimates of PDR prevalence in men who have sex with men (cis‐MSM) and transgender women (TW).
Micronuclei Detection by Flow Cytometry as a High-Throughput Approach for the Genotoxicity Testing of Nanomaterials

Thousands of nanomaterials (NMs)-containing products are currently under development or incorporated in the consumer market, despite our very limited understanding of their genotoxic potential. Taking into account that the toxicity and genotoxicity of NMs strongly depend on their physicochemical characteristics, many variables must be considered in the safety evaluation of each given NM. In this scenario, the challenge is to establish high-throughput methodologies able to generate rapid and robust genotoxicity data that can be used to critically assess and/or predict the biological effects associated with those NMs being under development or already present in the market. In this study, we have evaluated the advantages of using a flow cytometry-based approach testing micronucleus (MNs) induction (FCMN assay). In the frame of the EU NANoREG project, we have tested six different NMs—namely NM100 and NM101 (TiO2NPs), NM110 (ZnONPs), NM212 (CeO2NPs), NM300K (AgNPs) and NM401 (multi-walled carbon nanotubes (MWCNTs)). The obtained results confirm the ability of AgNPs and MWCNTs to induce MN in the human bronchial epithelial BEAS-2B cell line, whereas the other tested NMs retrieved non-significant increases in the MN frequency. Based on the alignment of the results with the data reported in the literature and the performance of the FCMN assay, we strongly recommend this assay as a reference method to systematically evaluate the potential genotoxicity of NMs.
MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (i) modulator of YAP/TAZ expression and (ii) a regulator of EGFR signaling during osteoblast commitments. Starting from the observation on hMSCs and primary osteoblast cell lines (Nh-Ost) in which EMT genes and miR-33a displayed a specific expression, we performed a gain and loss of function study with miR-33a-5p and 3p on hMSCs cells and Nh-Ost. After 24 h of transfections, we evaluated the modulation of EMT and osteoblast genes expression by qRT-PCR, Western blot, and Osteoimage assays. Through bioinformatic analysis, we identified YAP as the putative target of miR-33a-3p. Its role was investigated by gain and loss of function studies with miR-33a-3p on hMSCs; qRT-PCR and Western blot analyses were also carried out. Finally, the possible role of EGFR signaling in YAP/TAZ modulation by miR-33a-3p expression was evaluated. Human MSCs were treated with EGF-2 and EGFR inhibitor for different time points, and qRT-PCR and Western blot analyses were performed. The above-mentioned methods revealed a balance between miR-33a-5p and miR-33a-3p expression during hMSCs osteoblast differentiation. The human MSCs phenotype was maintained by miR-33a-5p, while the maintenance of the osteoblast phenotype in the Nh-Ost cell model was permitted by miR-33a-3p expression, which regulated YAP/TAZ through the modulation of EGFR signaling. The inhibition of EGFR blocked the effects of miR-33a-3p on YAP/TAZ modulation, favoring the maintenance of hMSCs in a committed phenotype. A new possible personalized therapeutic approach to bone regeneration was discussed, which might be mediated by customizing delivery of miR-33a in simultaneously targeting EGFR and YAP signaling with combined use of drugs.
Measuring Primary and Secondary School Characteristics: A Group-Based Modeling Approach*

In this paper we introduce a new way to conceptualize and measure the educational resources that young people encounter as they make their way from kindergarten to high school graduation. Using recent methodological advances in group-based modeling and a unique data set, we empirically test for and identify a series of categorically distinct school quality trajectories. We find that these trajectories vary significantly in terms of their intercept and slope, their prevalence within the sampled population, and in the sociodemographic makeup of their constituent members. We then present an extended empirical example illustrating relationships between school quality trajectories and important post-secondary educational outcomes, both before and after controlling for static, single-year measures of primary and secondary school characteristics. Our results suggest that the chronology of students’ exposures to different educational resources is significantly associated with college enrollment, college selectivity, and, in some instances, college completion.
Plasma Vitamin C and Cancer Mortality in Kidney Transplant Recipients

There is a changing trend in mortality causes in kidney transplant recipients (KTR), with a decline in deaths due to cardiovascular causes along with a relative increase in cancer mortality rates. Vitamin C, a well-known antioxidant with anti-inflammatory and immune system enhancement properties, could offer protection against cancer. We aimed to investigate the association of plasma vitamin C with long-term cancer mortality in a cohort of stable outpatient KTR without history of malignancies other than cured skin cancer. Primary and secondary endpoints were cancer and cardiovascular mortality, respectively. We included 598 KTR (mean age 51 ± 12 years old, 55% male). Mean (SD) plasma vitamin C was 44 ± 20 μmol/L. At a median follow-up of 7.0 (IQR, 6.2–7.5) years, 131 patients died, of which 24% deaths were due to cancer. In Cox proportional hazards regression analyses, vitamin C was inversely associated with cancer mortality (HR 0.50; 95%CI 0.34–0.74; p < 0.001), independent of potential confounders, including age, smoking status and immunosuppressive therapy. In secondary analyses, vitamin C was not associated with cardiovascular mortality (HR 1.16; 95%CI 0.83–1.62; p = 0.40). In conclusion, plasma vitamin C is inversely associated with cancer mortality risk in KTR. These findings underscore that relatively low circulating plasma vitamin C may be a meaningful as yet overlooked modifiable risk factor of cancer mortality in KTR.
Perception of Auditory Distance in Normal-Hearing and Moderate-to-Profound Hearing-Impaired Listeners

The auditory system allows the estimation of the distance to sound-emitting objects using multiple spatial cues. In virtual acoustics over headphones, a prerequisite to render auditory distance impression is sound externalization, which denotes the perception of synthesized stimuli outside of the head. Prior studies have found that listeners with mild-to-moderate hearing loss are able to perceive auditory distance and are sensitive to externalization. However, this ability may be degraded by certain factors, such as non-linear amplification in hearing aids or the use of a remote wireless microphone. In this study, 10 normal-hearing and 20 moderate-to-profound hearing-impaired listeners were instructed to estimate the distance of stimuli processed with different methods yielding various perceived auditory distances in the vicinity of the listeners. Two different configurations of non-linear amplification were implemented, and a novel feature aiming to restore a sense of distance in wireless microphone systems was tested. The results showed that the hearing-impaired listeners, even those with a profound hearing loss, were able to discriminate nearby and far sounds that were equalized in level. Their perception of auditory distance was however more contracted than in normal-hearing listeners. Non-linear amplification was found to distort the original spatial cues, but no adverse effect on the ratings of auditory distance was evident. Finally, it was shown that the novel feature was successful in allowing the hearing-impaired participants to perceive externalized sounds with wireless microphone systems.
Modulatory effects of the supplementary motor area (SMA) on primary motor cortex outputs.

Premotor areas of primates are specialized cortical regions that can contribute to hand movements by modulating the outputs of the primary motor cortex (M1). The goal of the present work was to study how the supplementary motor area (SMA) located within the same hemisphere (i.e. ipsilateral SMA or iSMA) or the opposite hemisphere (i.e. contralateral or cSMA) modulate the outputs of M1. We used paired-pulse protocols with intracortical stimulations in sedated cebus monkeys. A conditioning stimulus in iSMA or cSMA was delivered simultaneously or prior to a test stimulus in M1 with different interstimulus intervals (ISIs) while recording electromyographic activity in hand and forearm muscles. The pattern of modulation from iSMA and cSMA shared some clear similarities. In particular, both areas predominantly induced facilitatory effects on M1 outputs with shorter ISIs and inhibitory effects with longer ISIs. However, the incidence and strength of facilitatory effects was greater for iSMA than cSMA. We then compared the pattern of modulatory effects from SMA to the ones from the dorsal and ventral premotor cortices (PMd and PMv) collected in the same series of experiments. Among premotor areas, the impact of SMA on M1 outputs was always weaker than the one of either PMd or PMv, and this regardless of the hemisphere, or the ISI tested. These results show that SMA exerts a unique set of modulations on M1 outputs, which could support its specific function for the production of hand movements.
Rejection of psychiatric treatment

attenders has been seen unwittingly for the last time? Is this cause for relief or concern. In general terms our study demonstrated that patients lost to follow-up are less ill, more likely to be employed and more likely to have the support of a marital relationship, and as such this is not a cause for concern. However in economic terms, failure to attend the clinic is wasteful in terms of staff time and may result in unnecessary home visits. The role of out-patient services has gradually changed over the years from being an adjunct to inpatient treatment (Kessel & Hassall, 1965) to having adopted a more independent role and being engaged in the diagnosis and treatment of a wide range of psychiatric disorders (Johnson, 1973). It is important to establish which patients fail to make use of the service so that the out-patient resources are fully utilised, and so that alternative provision can be made for those patients who do not make full use of the existing services. Further prospective studies will be required to establish more information about patients who are 149
PREVALENCE AND SUBJECTIVE OUTCOME

he aim of this study was to determine the prevalence of deep venous thrombosis (DVT) following lower limb arthroplasty and to assess whether this adversely affected satisfaction, relief from pain, or the level of mobility as perceived by patients. Six hundred and ten consecutive recipients of primary total hip replacement (THR) or total knee replacement (TKR) underwent routine post-operative venography. The functional outcome had already been assessed at one year by using the Regional Arthroplasty Database questionnaire, the results of which were correlated to venographic records. The combined prevalence of DVT after THR and TKR in the patients, who did not receive chemical thromboprophylaxis, was 46.4%. Thrombus was identified in 57.6% of those with a TKR and in 33.5% of patients with a THR. Proximal thrombus was found in 11.0% of TKRs and in 14.8% of THRs. One year after surgery, patients who had a DVT established by venography did not report higher levels of immobility (p = 0.07), discomfort (p = 0.12) or dissatisfaction (p = 0.23) when compared to those with patent venous systems. This suggests that the prevalence of DVT following TKR/THR without chemical thromboprophylaxis is high and these findings are consistent with the literature. However, patients did not perceive thrombosis to compromise their overall outcome. This challenges the belief that DVT is associated with morbidity and calls for further comprehensive research in this area. The low morbidity of the lower limb associated with DVT in these patients does not support the use of chemical thromboprophylaxis.
Micronutrient powder use in Arequipa, Peru: Barriers and enablers across multiple levels

Abstract In Peru, nearly half of children aged 6–36 months were diagnosed with anaemia in 2017. To address this disease, the Peruvian Ministry of Health implemented a national programme in 2014, distributing free micronutrient powders (MNPs) to all children of this age. However, rates of childhood anaemia remain high. The aim of this study was to explore factors at all levels of the Social‐Ecological Model that affect MNP use and adherence in Arequipa, an Andean city with childhood anaemia rates higher than the national average. We conducted in‐depth interviews with 20 health personnel and 24 caregivers and 12 focus group discussions with 105 caregivers. We identified numerous barriers, including negative side effects (constipation, vomiting, and diarrhoea), poor taste of MNP, lack of familial and peer support for its use, insufficient informational resources provided by the health system, and limited human resources that constricted health personnel abilities to implement MNP programming successfully. Facilitators identified included concern about the long‐term effects of anaemia, support from organizations external to the health system, well‐coordinated care within the health system, and provision of resources by the Ministry of Health. We found that community or organizational and societal factors were key to limited MNP use and adherence, specifically the limited time health personnel have to address caregivers' doubts during appointments and the lack of informational resources outside of these appointments. Potential policy implications could be to increase informational resources available outside of individualized counselling by strengthening existing collaborations with community organizations, increasing media coverage, and providing group counselling.
Eradicating metastatic cancer and the eco-evolutionary dynamics of Anthropocene extinctions.

Curative therapy for metastatic cancers is equivalent to causing extinction of a large, heterogeneous, and geographically dispersed population. While eradication of dinosaurs is a dramatic example of extinction dynamics, similar application of massive eco-evolutionary force in cancer treatment is typically limited by host toxicity. Here, we investigate the evolutionary dynamics of Anthropocene species extinctions as an alternative model for curative cancer therapy. Human activities can produce extinctions of large, diverse, and geographically distributed populations. The extinction of a species typically follows a pattern in which initial demographic and ecological insults reduce the size and heterogeneity of the population. The surviving individuals, with decreased genetic diversity and often fragmented ecology, are then vulnerable to small stochastic perturbations that further reduce the population until extinction is inevitable. We hypothesize large, diverse, and disseminated cancer populations can be eradicated using similar evolutionary dynamics. Initial therapy is applied to reduce population size and diversity and followed by new treatments to exploit the eco-evolutionary vulnerability of small and/or declining populations. Mathematical models and computer simulations demonstrate initial reductive treatment followed immediately by demographic and ecological perturbations, similar to the empirically derived treatment of pediatric Acute Lymphocytic Leukemia, can consistently achieve curative outcomes in non-pediatric cancers.
Correlation of CpG methylation of the Pdcd1 gene with PD‐1 expression on CD8+ T cells and medical laboratory indicators in chronic hepatitis B infection

The negative signal provided by some co‐inhibitory factors such as programmed cell death‐1 (PD‐1) has been associated with chronic hepatitis B (CHB) infection induced‐T cell exhaustion, although the correlation of CpG methylation of the Pdcd1 gene with PD‐1 expression and medical laboratory indicators in CHB infection has not yet been elucidated.
Trends in Leadership at Spine Surgery Fellowships.

STUDY DESIGN Cross-sectional study. OBJECTIVE To illustrate demographic trends among spine fellowship leaders (FLs). SUMMARY OF BACKGROUND DATA No previous study in the orthopaedic literature has analyzed the demographic characteristics or past surgical training of FL in an orthopaedic sub-specialty. We attempt to illustrate demographic trends among spine fellowship leadership including fellowship directors (FDs) and co-fellowship directors (co-FDs). We also highlight the institutions that have trained these leaders at various levels. METHODS Our search for FDs was constructed from the 2018-2019 North American Spine Surgery (NASS) Fellowship Directory. Datapoints gathered included: age, gender, residency/fellowship training location, time since training completion until FD appointment, length in FD role, and personal research H-index. RESULTS We identified 103 FLs consisting of 67 FDs, 19 co-FDs, and another 16 individuals with a synonymous leadership title. 96.1% (99) of the leadership consisted of males while 3.9% (4) were female. The mean age was 52.9 years old and the mean h-index of the FLs was 23.8. FLs were trained in orthopaedic surgery (n = 89), neurosurgery (n = 13), or combined orthopaedic surgery and neurosurgery training (n = 1). The top fellowships programs producing future FLs were: Case Western Reserve University, Cleveland (n = 10), Washington University, St. Louis (n = 9), and Rothman Institute, Thomas Jefferson University, Philadelphia (n = 7). CONCLUSION Spine surgery fellowship directors are more likely to have graduated from certain residency and fellowship programs. This finding could be a result of the training provided by these centers or the institution's predilection to select applicants that are more likely to later seek academic leadership roles post-training. LEVEL OF EVIDENCE 4.
A single plasmid based CRISPR interference in Synechocystis 6803 – A proof of concept

We developed a simple method to apply CRISPR interference by modifying an existing plasmid pCRISPathBrick containing the native S. pyogenes CRISPR assembly for Synechocystis PCC6803 and named it pCRPB1010. The technique presented here using deadCas9 is easier to implement for gene silencing in Synechocystis PCC6803 than other existing techniques as it circumvents the genome integration and segregation steps thereby significantly shortens the construction of the mutant strains. We executed CRISPR interference against well characterized photosynthetic genes to get a clear phenotype to validate the potential of pCRPB1010 and presented the work as a “proof of concept”. Targeting the non-template strand of psbO gene resulted in decreased amount of PsbO and 50% decrease in oxygen evolution rate. Targeting the template strand of psbA2 and psbA3 genes encoding the D1 subunit of photosystem II (PSII) using a single spacer against the common sequence span of the two genes, resulted in full inhibition of both genes, complete abolition of D1 protein synthesis, complete loss of oxygen evolution as well as photoautotrophic growth arrest. This is the first report of a single plasmid based, completely lesion free and episomal expression and execution of CRISPR interference in Synechocystis PCC6803.