Miracle-dz/UniFAR-FTUs huggingface dataset:
Lymphocyte Doubling Time As A Key Prognostic Factor To Predict Time To First Treatment In Early-Stage Chronic Lymphocytic Leukemia

The prognostic role of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was recognized more than three decades ago when the neoplastic clone’s biology was almost unknown. LDT was defined as the time needed for the peripheral blood lymphocyte count to double the of the initial observed value. Herein, the LDT prognostic value for time to first treatment (TTFT) was explored in our prospective O-CLL cohort and validated in in two additional CLL cohorts. Specifically, newly diagnosed Binet stage A CLL patients from 40 Italian Institutions, representative of the whole country, were prospectively enrolled into the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540). Two independent cohorts of newly diagnosed CLL patients recruited respectively at the Division of Hematology in Novara, Italy, and at the Hospital Clinic in Barcelona, Spain, were utilized as validation cohorts. In the training cohort, TTFT of patients with LDT >12 months was significantly longer related to those with a shorter LDT. At Cox multivariate regression model, LDT ≤ 12 months maintained a significant independent relationship with shorter TTFT along with IGHV unmutated (IGHVunmut) status, 11q and 17p deletions, elevated β2M, Rai stage I-II, and NOTCH1 mutations. Based on these statistics, two regression models were constructed including the same prognostic factors with or without the LDT. The model with the LTD provided a significantly better data fitting (χ2 = 8.25, P=0.0041). The risk prediction developed including LDT had better prognostic accuracy than those without LDT. Moreover, the Harrell’C index for the scores including LDT were higher than those without LDT, although the accepted 0.70 threshold exceeded in both cases. These findings were also confirmed when the same analysis was carried out according to TTFT’s explained variation. When data were further analyzed based on the combination between LDT and IGHV mutational status in the training and validation cohorts, IGHVunmut and LDT>12months group showed a predominant prognostic role over IGHVmut LTD ≤ 12 months (P=0.006) in the O-CLL validation cohort. However, this predominance was of borden-line significance (P=0.06) in the Barcelona group, while the significant prognostic impact was definitely lost in the Novara group. Overall, in this study, we demonstrated that LDT could be re-utilized together with the more sophisticated prognostic factors to manage the follow-up plans for Binet stage A CLL patients.
Characterization of Tigecycline-Heteroresistant Klebsiella pneumoniae Clinical Isolates From a Chinese Tertiary Care Teaching Hospital

Tigecycline has been used as one of the therapeutic choices for the treatment of infections caused by multidrug-resistant Klebsiella pneumoniae. However, the emergence of tigecycline heteroresistance has led to great challenges in treating these infections. The purpose of this study was to investigate whether tigecycline-heteroresistant K. pneumoniae (TGCHR-Kp) exists in clinical isolates, and to further characterize the underlying molecular mechanisms involved in the development of tigecycline-resistant subpopulations. Of the 268 tigecycline-susceptible clinical K. pneumoniae isolates, 69 isolates were selected as tigecycline-heteroresistant candidates in the preliminary heteroresistant phenotypic selection by a modified disk diffusion method, and only 21 strains were confirmed as TGCHR-Kp by the population analysis profile (PAP). Pulsed-field gel electrophoresis (PFGE) analysis demonstrated that all the parental TGCHR-Kp isolates were clonally unrelated, and colonies confirmed as the heteroresistant subpopulation showed no significant differences from their respective parental TGCHR-Kp isolates. Efflux pump inhibitors reversed the tigecycline susceptibility in heteroresistant subpopulations. Mutations in the ramR and soxR genes lead to upregulation of the ramA and soxS transcriptional regulators, which in turn induced overexpression of the AcrAB-TolC efflux pump genes in TGCHR-Kps-resistant subpopulations. Moreover, mutations of rpsJ were also found in resistant subpopulations, which suggested that the rpsJ mutation may also lead to tigecycline resistance. Time-kill assays showed that the efficacy of tigecycline against TGCHR-Kps was weakened, whereas the number of resistant subpopulations was enriched by the presence of tigecycline. Our findings imply that the presence of TGCHR-Kps in clinical strains causes severe challenges for tigecycline therapy in clinical practice.
Consensus Guidelines for Advancing Coral Holobiont Genome and Specimen Voucher Deposition

Coral research is being ushered into the genomic era. To fully capitalize on the potential discoveries from this genomic revolution, the rapidly increasing number of high-quality genomes requires effective pairing with rigorous taxonomic characterizations of specimens and the contextualization of their ecological relevance. However, to date there is no formal framework that genomicists, taxonomists, and coral scientists can collectively use to systematically acquire and link these data. Spurred by the recently announced “Coral symbiosis sensitivity to environmental change hub” under the “Aquatic Symbiosis Genomics Project” - a collaboration between the Wellcome Sanger Institute and the Gordon and Betty Moore Foundation to generate gold-standard genome sequences for coral animal hosts and their associated Symbiodiniaceae microalgae (among the sequencing of many other symbiotic aquatic species) - we outline consensus guidelines to reconcile different types of data. The metaorganism nature of the coral holobiont provides a particular challenge in this context and is a key factor to consider for developing a framework to consolidate genomic, taxonomic, and ecological (meta)data. Ideally, genomic data should be accompanied by taxonomic references, i.e., skeletal vouchers as formal morphological references for corals and strain specimens in the case of microalgal and bacterial symbionts (cultured isolates). However, exhaustive taxonomic characterization of all coral holobiont member species is currently not feasible simply because we do not have a comprehensive understanding of all the organisms that constitute the coral holobiont. Nevertheless, guidelines on minimal, recommended, and ideal-case descriptions for the major coral holobiont constituents (coral animal, Symbiodiniaceae microalgae, and prokaryotes) will undoubtedly help in future referencing and will facilitate comparative studies. We hope that the guidelines outlined here, which we will adhere to as part of the Aquatic Symbiosis Genomics Project sub-hub focused on coral symbioses, will be useful to a broader community and their implementation will facilitate cross- and meta-data comparisons and analyses.
The Contribution of Word-, Sentence-, and Discourse-Level Abilities on Writing Performance: A 3-Year Longitudinal Study

Writing is a foundational skill throughout school grades. This study analyzed the development of different levels of written language (word, sentence, and discourse) and explored the relationship between these levels and writing performance. About 95 Portuguese students from two cohorts—Grades 4–7 (n = 47) 6–9 (n = 48)—were asked to produce a descriptive text two times, with a 3-year interval. The produced texts were used to assess spelling, syntactic correctness and complexity, and descriptive discourse as well as text length and quality. The main results showed that there were improvements from Grades 4 to 7 and 6 to 9 in word- and sentence-level skills, along with increases in some dimensions of the descriptive discourse. Moreover, the older cohort performed better than the younger cohort in terms of spelling, syntactic complexity, and text quality, but not in terms of syntactic correctness, one dimension of the descriptive discourse, and text length. Regression analyses showed that writing performance was predicted by word and sentence levels in the younger cohort only, and by discourse-level variables in both cohorts. Overall, despite indicating a generalized growth in writing skills throughout schooling, this study also highlighted the areas that may need additional attention from teachers, mainly in terms of the descriptive features.
Suppression of miR-130a-3p Attenuates Oxygen–Glucose Deprivation/Reoxygenation-Induced Dendritic Spine Loss by Promoting APP

Background Cerebral stroke induces neuronal dysfunction as a consequence of neuronal morphology changes. Emerging evidence suggests that microRNAs (miRNAs) may play an important role in regulating dysfunction in stroke, yet there are still few studies examining the association between whole blood miRNAs and neuronal morphology. The present study aimed to ascertain the potential roles and mechanisms of action of miR-130a-3p in ischemic stroke. Methods The miRNA datasets of peripheral serum in the GEO database and the mRNA datasets of the human brain after ischemia were analyzed to identify differentially expressed RNAs, and their functions were verified in cultured neurons in vitro. Furthermore, the target gene was validated by dual-luciferase reporter assay, RT-PCR, Western blot, and immunofluorescence experiments. The identified miRNA was further verified by the OGD test to restore neuronal changes after ischemia through APP. Results The expression of whole blood miR-130a-3p was found significantly lower in participants with ischemic stroke than in controls by analyzing expression profiling datasets of cerebral ischemia stroke obtained from the Gene Expression Omnibus (GEO) DataSets portal, which was confirmed in the MCAO model in mice. Furthermore, GO analysis showed that miR-130a-3p might directly affect neuronal function. Indeed, we demonstrated that miR-130a-3p played a central role in the inhibition of dendritic morphogenesis and in the growth of dendritic spines in vitro. We also confirmed that miR-130a-3p could regulate the expression of APP by luciferase reporter assay, RT-PCR, Western blot, and immunofluorescence experiments, which were consistent with the bioinformatic analysis. Last but not least, we also demonstrated that reducing miR-130a-3p expression partially rescued neuronal morphological changes after OGD in vitro. Conclusion miR-130a-3p is a potential biomarker of cerebral stroke, can affect neuronal morphology through APP, and promote the repair of neurons by promoting APP expression after cerebral ischemia.
The Daily Mile in practice: implementation and adaptation of the school running programme in a multiethnic city in the UK

Objectives The aim of this study was to generate new evidence on how The Daily Mile (TDM), a popular school-based running programme in the UK, is implemented in a diverse and multiethnic city in the UK and also the barriers faced by non-implementer schools. Design Mixed method cross-sectional study (including survey data collection and qualitative interviews). Setting Primary schools in a multiethnic city in the East Midlands, UK. Participants Forty-two schools in Leicester city completed an online survey, and five teaching staff from five schools took part in follow-up semistructured qualitative interviews. Results Overall, 40.5% of schools who completed the survey reported having never implemented TDM, and 96.0% of implementer schools reported delivering TDM on three or more days per week. Reported barriers included space limitations and safety issues, timetabling and curriculum pressures, and pupil and teacher attitudes. Facilitators of implementation were teacher engagement and school culture/ethos, communication of the initiative and substantial delivery adaptations. Conclusions The findings from this study, based on data from schools in a multiethnic city in the UK, suggest that implementation of TDM is variable, and is influenced by a range of factors related to the school context, as well as the characteristics of TDM itself.
Efficient Hydrogen Delivery for Microbial Electrosynthesis via 3D-Printed Cathodes

The efficient delivery of electrochemically in situ produced H2 can be a key advantage of microbial electrosynthesis over traditional gas fermentation. However, the technical details of how to supply large amounts of electric current per volume in a biocompatible manner remain unresolved. Here, we explored for the first time the flexibility of complex 3D-printed custom electrodes to fine tune H2 delivery during microbial electrosynthesis. Using a model system for H2-mediated electromethanogenesis comprised of 3D fabricated carbon aerogel cathodes plated with nickel-molybdenum and Methanococcus maripaludis, we showed that novel 3D-printed cathodes facilitated sustained and efficient electromethanogenesis from electricity and CO2 at an unprecedented volumetric production rate of 2.2 LCH4 /Lcatholyte/day and at a coulombic efficiency of 99%. Importantly, our experiments revealed that the efficiency of this process strongly depends on the current density. At identical total current supplied, larger surface area cathodes enabled higher methane production and minimized escape of H2. Specifically, low current density (<1 mA/cm2) enabled by high surface area cathodes was found to be critical for fast start-up times of the microbial culture, stable steady state performance, and high coulombic efficiencies. Our data demonstrate that 3D-printing of electrodes presents a promising design tool to mitigate effects of bubble formation and local pH gradients within the boundary layer and, thus, resolve key critical limitations for in situ electron delivery in microbial electrosynthesis.
Psychosocial Adjustment and Mental Distress Associated With In-Game Purchases Among Japanese Junior High School Students

In-game purchases, including microtransactions and loot box spending, are the monetization systems of free-to-play online games. Although some studies have suggested that excessive in-game purchases increase the risk of psychosocial maladjustment and mental distress as well as predict future problematic gaming and gambling practices, empirical studies on problematic behavioral patterns related to in-game purchasing among adolescents are lacking. This study sought to explore whether knowing the style of in-game purchases (non-purchase, planned purchase, or unplanned purchase) could be useful when characterizing maladaptive behavior among adolescents from the perspective of psychosocial adjustment and mental distress. A total of 335 junior high school students (aged 12–15 years) participated in the survey and completed a questionnaire assessing daily online gaming usage, in-game purchases, psychosocial adjustment, and mental distress. The results showed that (1) 30.7% of students had previously made in-game purchases, and at least 14.0% had made unplanned in-game purchases; (2) 19.2% of the users who had made unplanned purchases had spent greater than or equal to their actual monthly allowance within the past month, and (3) unplanned purchase gamers exhibited more behavioral problems and peer problems regarding psychosocial adjustment compared to planned purchase gamers, and more overall difficulties compared to non-purchasers. Meanwhile, more hyperactivity/inattention was seen among in-game purchasers compared to non-purchasers, regardless of whether the purchase was planned or unplanned. These findings support that understanding whether adolescents make unplanned in-game purchases could be a useful approach to describing the characteristics of online gamers with maladaptive tendencies.
The Association Between Variability in Electrolytes and the In-Hospital Mortality in Critically Ill Children in Pediatric Intensive Care Units

Objective: This study aimed to explore the association between the variability in electrolytes and the in-hospital mortality in critically ill children admitted into intensive care units (ICUs). Design: This is a retrospective case–control study. Setting and Participants: Total of 11,245 children have been admitted to ICUs of Children's Hospital of Zhejiang University from 2010 to 2018. Methods: The coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) were calculated as variability indices. High variability was defined as having values in the highest quartile for each parameter. Age, sex, diagnoses of disease, and surgical treatment were adjusted in the multivariable-adjusted logistic regression model. Results: A total of 11,245 children were included, and 660 patients died in the hospital. The median (P25, P75) potassium, sodium, and chloride of all patients were 3.8 (3.58, 4.09), 136.83 (135.11, 138.60), and 108.67 (105.71, 111.17), respectively. U-shaped relationships between the mean, lowest, and highest levels of potassium, sodium, and chloride and the in-hospital mortality were observed. The lowest mortality was noted when serum potassium, sodium, and chloride were between ~3.5 and 5.0, 135 and 145, and 105 and 115 mmol/l, respectively. The areas under the curve (AUCs) of three indices of variability in electrolytes were larger than those of the mean and lowest levels of electrolytes in predicting the in-hospital mortality. In the multivariable-adjusted model, the odds ratios and 95% confidence interval (CI) of the in-hospital mortality were 3.14 (2.44–4.04) for one parameter, 5.85 (4.54–7.53) for two parameters, and 10.32 (7.81–13.64) for three parameters compared with subjects having no parameters of high variability measured as the CV. The results were consistent when the variability was determined using the SD and VIM (all P for trend <0.001). Consistent results were noted in various subgroup analyses. Conclusions: This study showed that individuals with higher variability of each parameter were related with higher risk of in-hospital mortality. There was a linear association between the number of high variability parameters and the in-hospital mortality. The variability of electrolytes might be a good predictor for in-hospital mortality of children in ICUs.
Interleukin 32 Promotes Foxp3+ Treg Cell Development and CD8+ T Cell Function in Human Esophageal Squamous Cell Carcinoma Microenvironment

Proinflammatory cytokine interleukin 32 (IL-32) is involved in infectious diseases and cancer, but what subtypes of immune cells express IL-32 and its roles in tumor microenvironment (TME) have not been well discussed. In this study, we applied bioinformatics to analyze single-cell RNA sequencing data about tumor-infiltrating immune cells from esophageal squamous cell carcinoma (ESCC) TME and analyzed IL-32 expression in different immune cell types. We found CD4+ regulatory T cells (Treg cells) express the highest level of IL-32, while proliferating T and natural killer cells expressed relatively lower levels. Knocking down of IL-32 reduced Foxp3 and interferon gamma (IFNγ) expressions in CD4+ and CD8+ T cells, respectively. IL-32 was positively correlated with Foxp3, IFNG, and GZMB expression but was negatively correlated with proliferation score. IL-32 may have a contradictory role in the TME such as it promotes IFNγ expression in CD8+ T cells, which enhances the antitumor activity, but at the same time induces Foxp3 expression in CD4+ T cells, which suppresses the tumor immune response. Our results demonstrate different roles of IL-32 in Treg cells and CD8+ T cells and suggest that it can potentially be a target for ESCC cancer immunosuppressive therapy.
Supernumerary lacrimal puncta: Case series

Supernumerary lacrimal punctum is rare, and very few cases have been reported. Most patients are asymptomatic, but in some excessive tearing could be a symptom. In addition, obstruction of the canaliculi causing canaliculitis has been reported. We describe four cases in detail with their presentations and diagnosis. The first patient presented with a right eye lesion and during examination, the left eye was less than mid dilated compared to that of the right eye. Further examination of the left eye revealed two left lower lid puncta. In another patient who was evaluated for diabetic retinopathy, two left lower lid puncta that shared the same canaliculus were noted. Furthermore, two lower lid puncta were found in a patient who came for cataract follow-up. Finally, in a patient who was following up in the retinal clinic, two lower lid puncta were documented. Probing to the accessory punctum showed that the canaliculus had an immediate horizontal course, unlike the rest of the puncta which showed a vertical then a horizontal course. Furthermore, in the accessory punctum, there was a soft stop, around 4 mm of the inserting probe. In summary, supernumerary lacrimal punctum is rare, and ophthalmologists need to be aware of this abnormality.
Corneal biomechanical properties in hyperthyroidism and thyroid eye disease

PURPOSE: The purpose of this study is to compare the corneal biomechanical properties of hyperthyroids without ophthalmopathy (HWO), thyroid eye disease (TED), and euthyroid participants. METHODS: In this prospective comparative study, one eye per patient included in the analysis and according to exclusion criteria, 38 eyes of 40 HWO patients, 31 eyes of 40 TED patients, and 150 eyes of 160 age- and sex-matched euthyroid participants were enrolled. All participants were evaluated by an endocrinologist and oculoplastic surgeon for evaluation of thyroid function and orbitopathy, respectively. Measurements of corneal biomechanical properties were performed using ocular response analyzer and Corvis ST tonometers. RESULTS: In the HWO group, applanation-1 length (A1 L), applanation-2 velocity (A2V) (P < 0.001), and corneal resistant factor (P = 0.043) were higher than the control group and corneal hysteresis (CH) was lower (P = 0.018). In the TED group, A1 L, A2V (P < 0.001), and highest concavity radius (HCR) (P = 0.027) were higher than the control group, and the CH (P = 0.007) and highest concavity deformation amplitude (HCDA) (P = 0.001) were lower. Furthermore, the level HCDA in the TED group was lower than HWO group (P = 0.011). The level of upper scleral show and palpebral fissure had a negative correlation with CH and HCDA. The amount of exophthalmos level had a positive correlation with HCR. CONCLUSION: Corneal biomechanical properties in the HWO and TED groups were different from the normal euthyroid individuals and may be taken into account in managing situation like glaucoma and refractive surgeries.
Low back pain prevalence and associated risk factors among medical students at four major medical colleges in Saudi Arabia

Aim: The aim of this study was to determine the prevalence of low back pain (LBP) and to identify risk factors associated with LBP among medical students. Materials and Methods: A cross-sectional study was conducted among 2021 medical students from four medical colleges in Saudi Arabia during the academic year 2019–2020. A self-administered questionnaire was conducted and included three sections: demographic data, risk factors of LBP, and prevalence of LBP (during lifetime, past 12 months, and past 7 days). Data were analyzed using SPSS. Results: A total of 2021 medical students responded to our survey. The participants were 57.1% female and 42.9% male. Most of the students' ages (76.3%) ranged from 20 to 24 years. Medical students younger than 20 and older than 24 were 21.8% and 1.9%, respectively. The prevalence of LBP was 80.7% at any time, 67.6% in the past 12 months, and 38.2% in the past 7 days. Females were found to have higher prevalence of LBP than males (P < 0.0001), 95% confidence interval (CI) (1.37, 2.04). History of physical trauma to the back was significantly associated with LBP (P < 0.0001), 95% CI (1.32, 2.40). A lack of daily exercise was also found to be associated with LBP (P = 0.015), 95% CI (1.05, 1.55). LBP affected the daily functions, such as walking and sleeping, of 30.1% of medical students. Around 11% of medical students sought medical care because of LBP. Conclusions: We conclude that the prevalence of LBP is high among Saudi medical students. LBP seemed to be higher in females and associated with history of back trauma. Back care awareness should be emphasized among medical students.