Miracle-dz/UniFAR-FTUs huggingface dataset:
A small UTX stabilization domain of Trr is conserved within mammalian MLL3-4/COMPASS and is sufficient to rescue loss of viability in null animals

In this study, Rickel et al. identified essential histone methylatransferase-independent functions of Trr, used a screen to identify a minimal Trr domain sufficient to rescue Trr-null lethality, and demonstrated that this domain binds and stabilizes Utx in vivo. Their findings show that COMPASS-dependent UTX stabilization is an essential noncatalytic function of Trr/MLL3/MLL4, suggesting that stabilizing UTX could be a therapeutic strategy for cancers with MLL3/4 loss-of-function mutations.
The Direct and Indirect Impact of SARS-CoV-2 Infections on Neonates

Supplemental Digital Content is available in the text. Background: The impact of SARS-CoV-2 on neonates remains largely unknown in low- and middle-income countries (LMICs). We provide an epidemiologic and clinical report of SARS-CoV-2 infections in neonates hospitalized in Bangladesh. Methods: Outborn neonates admitted to Dhaka Shishu Hospital, a tertiary-care referral hospital, between 29 March and 1 July were screened for SARS-CoV-2. We reviewed clinical data, including chest radiograph and laboratory reports, and conducted SARS-CoV-2 genome sequencing. Patients were followed-up for 27–75 days. A subset of caregivers was also tested. Results: Of 83 neonates tested, 26 were positive (median age 8 days). Most neonates were admitted with diagnosis unrelated to SARS-CoV-2: 11 presented with serious non-communicable diseases, 7 with early-onset sepsis, 5 with late-onset sepsis and 2 with pneumonia. In 3 of 5 chest radiograph, infiltrates and ground-glass or patchy opacities were noted. Two neonates developed metabolic acidosis, one developed disseminated intravascular coagulation. Most SARS-CoV-2 positive neonates were referred to government-designated COVID-19 hospitals, leading to gaps in treatment. Twenty-three neonates could be followed-up: 12 were healthy, 8 died and 3 were still seeking medical care. Of 9 caregivers tested, 8 were positive. Conclusions: SARS-CoV-2 may have serious adverse effects on children born in LMICs. The virus likely contributed directly to two deaths, but the remaining 6 neonates who died had serious comorbidities. Positive SARS-CoV-2 test results led to gaps in immediate clinical care for other morbidities, which likely contributed to adverse outcomes. This case series emphasizes the need to understand COVID-19 in neonates in LMICs and its indirect impacts.
Occurrence of polytene chromosomes in the bicellular and mature pollen grains of endangered plant species Pancratium maritimum L. (Amaryllidaceae)

AbstractEndoreduplication is a modified form of mitotic cycle in which repeated rounds of DNA replication occur without chromosome segregation and cell division, leading to formation of larger and thicker chromosomes called polytenics. In the present study, spontaneous formation of polytene chromosomes in the generative nuclei of pollen grains of Amaryllidaceae, and presumably in angiosperms, was described for the first time. For this purpose, microspores and mature pollens of the endangered species Pancratium maritimum L. were examined by light and transmission electron microscopy with a special reference to the observation of polytenic nuclei. Polytene chromosomes were detected in most of the generative cells of young bicellular pollen grains and mature pollen grains found in some anther locules, but they were rare or absent in the other anther locules. Polytenization of chromosomes did not follow the same pattern in all of the pollen grains. Polytene structures found in the developing pollen grains of .
Pregnancy with giant ovarian dysgerminoma

Abstract Rationale: Dysgerminoma is an extraordinarily rare neoplasm arising from the malignant germ cells of the ovary. Early antenatal diagnosis and proper management of the neoplasm to improve maternal-neonatal results are the considerable challenges facing the gyne-oncologist. We summarize the clinical features and discuss treatment strategies of the ovary dysgerminoma (OD). Besides, we also review the literature on OD in PubMed, Web of Science Core Collection, Library of Congress, and LISTA from 1939 to 2019 to evaluate its clinical characteristics, feto-maternal compromise, management, and fertility outcome. Patient concerns: A 25-year-old pregnant woman reported lower abdominal pain and vomiting. Diagnosis: The patient was diagnosed as right OD. Interventions: She received a cesarean section due to severe abdominal pain, delivered a healthy girl at 38 C 4 weeks of gestation, and accepted fertility-preserving surgery. However, the patient refused chemotherapy postoperatively. Outcomes: The patient was followed up 42 days, 3 months, and 6 months after surgery, and no tumor recurrence was observed. Lessons: OD has non-specificity characteristics, including age, symptoms, image date, and tumor marks. However, these abnormal indicators may provide some evidence for accurate antenatal diagnosis. The management strategies should be considered comprehensively on an individual basis, and fertility-preserving surgery should be carried out in the second trimester if further pregnancy is desired. Adjuvant chemotherapy needs to be applied to the treatment of OD patients with The International Federation of Gynecology and Obstetrics (FIGO) stages II, III, and IV and timely chemotherapy is suggested if there are several weeks before the expected date of delivery. The overall prognosis of OD patients is excellent.
Functional characterization of the HMP‐P synthase of Legionella pneumophila (Lpg1565)

The production of the pyrimidine moiety in thiamine synthesis, 2‐methyl‐4‐amino‐5‐hydroxymethylpyrimidine phosphate (HMP‐P), has been described to proceed through the Thi5‐dependent pathway in Saccharomyces cerevisiae and other yeast. Previous work found that ScThi5 functioned poorly in a heterologous context. Here we report a bacterial ortholog to the yeast HMP‐P synthase (Thi5) was necessary for HMP synthesis in Legionella pneumophila. Unlike ScThi5, LpThi5 functioned in vivo in Salmonella enterica under multiple growth conditions. The protein LpThi5 is a dimer that binds pyridoxal‐5′‐phosphate (PLP), apparently without a solvent‐exposed Schiff base. A small percentage of LpThi5 protein co‐purifies with a bound molecule that can be converted to HMP. Analysis of variant proteins both in vivo and in vitro confirmed that residues in sequence motifs conserved across bacterial and eukaryotic orthologs modulate the function of LpThi5.
Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases

Abstract Sterol biosynthesis, primarily associated with eukaryotic kingdoms of life, occurs as an abbreviated pathway in the bacterium Methylococcus capsulatus. Sterol 14α-demethylation is an essential step in this pathway and is catalyzed by cytochrome P450 51 (CYP51). In M. capsulatus, the enzyme consists of the P450 domain naturally fused to a ferredoxin domain at the C-terminus (CYP51fx). The structure of M. capsulatus CYP51fx was solved to 2.7 Å resolution and is the first structure of a bacterial sterol biosynthetic enzyme. The structure contained one P450 molecule per asymmetric unit with no electron density seen for ferredoxin. We connect this with the requirement of P450 substrate binding in order to activate productive ferredoxin binding. Further, the structure of the P450 domain with bound detergent (which replaced the substrate upon crystallization) was solved to 2.4 Å resolution. Comparison of these two structures to the CYP51s from human, fungi, and protozoa reveals strict conservation of the overall protein architecture. However, the structure of an “orphan” P450 from nonsterol-producing Mycobacterium tuberculosis that also has CYP51 activity reveals marked differences, suggesting that loss of function in vivo might have led to alterations in the structural constraints. Our results are consistent with the idea that eukaryotic and bacterial CYP51s evolved from a common cenancestor and that early eukaryotes may have recruited CYP51 from a bacterial source. The idea is supported by bioinformatic analysis, revealing the presence of CYP51 genes in >1,000 bacteria from nine different phyla, >50 of them being natural CYP51fx fusion proteins.
MR Imaging Features of Middle Cranial Fossa Encephaloceles and Their Associations with Epilepsy

BACKGROUND AND PURPOSE: Middle cranial fossa encephaloceles are an increasingly recognized cause of epilepsy; however, they are also often encountered on neuroimaging in patients with no history of seizure. We characterized the MR imaging features of middle cranial fossa encephaloceles in seizure and nonseizure groups with the hope of uncovering features predictive of epileptogenicity. MATERIALS AND METHODS: Seventy-seven patients with middle cranial fossa encephaloceles were prospectively identified during routine clinical practice of neuroradiology at a tertiary care hospital during an 18-month period. Thirty-five of 77 (45%) had a history of seizure, 20/77 (26%) had temporal lobe epilepsy, and 42/77 (55%) had no history of seizures. Middle cranial fossa encephalocele features on MR imaging were characterized, including depth, area, number, location, presence of adjacent encephalomalacia, and degree of associated parenchymal morphologic distortion. MR imaging features were compared between the seizure and nonseizure groups. RESULTS: No significant difference in MR imaging features of middle cranial fossa encephaloceles was seen when comparing the seizure and nonseizure groups. Comparison of just those patients with temporal lobe epilepsy (n = 20) with those with no history of seizure (n = 42) also found no significant difference in MR imaging features. CONCLUSIONS: Anatomic MR imaging features of middle cranial fossa encephaloceles such as size, number, adjacent encephalomalacia, and the degree of adjacent parenchymal morphologic distortion may not be useful in predicting likelihood of epileptogenicity.
An Early-Onset Subgroup of Type 2 Diabetes: A Multigenerational, Prospective Analysis in the Framingham Heart Study

OBJECTIVE To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring. RESEARCH DESIGN AND METHODS In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)–control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes. RESULTS Among the participants in two generations (N = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (P < 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10–2.97, P = 0.02) of cardiovascular death and 1.75-fold odds (0.96–3.21, P = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P = 0.09 for cardiovascular death; P = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73–6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50–3.19). CONCLUSIONS Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.
A wheeze recognition algorithm for practical implementation in children

Background The detection of wheezes as an exacerbation sign is important in certain respiratory diseases. However, few highly accurate clinical methods are available for automatic detection of wheezes in children. This study aimed to develop a wheeze detection algorithm for practical implementation in children. Methods A wheeze recognition algorithm was developed based on wheezes features following the Computerized Respiratory Sound Analysis guidelines. Wheezes can be detected by auscultation with a stethoscope and using an automatic computerized lung sound analysis. Lung sounds were recorded for 30 s in 214 children aged 2 months to 12 years and 11 months in a pediatric consultation room. Files containing recorded lung sounds were assessed by two specialist physicians and divided into two groups: 65 were designated as “wheeze” files, and 149 were designated as “no-wheeze” files. All lung sound judgments were agreed between two specialist physicians. We compared wheeze recognition between the specialist physicians and using the wheeze recognition algorithm and calculated the sensitivity, specificity, positive predictive value, and negative predictive value for all recorded sound files to evaluate the influence of age on the wheeze detection sensitivity. Results The detection of wheezes was not influenced by age. In all files, wheezes were differentiated from noise using the wheeze recognition algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value of the wheeze recognition algorithm were 100%, 95.7%, 90.3%, and 100%, respectively. Conclusions The wheeze recognition algorithm could identify wheezes in sound files and therefore may be useful in the practical implementation of respiratory illness management at home using properly developed devices.
Race/Ethnicity, Cumulative Midlife Loss and Carotid Atherosclerosis in Middle-Aged Women.

African-American women have elevated rates of cardiovascular disease compared to women of other race/ethnicities, and race/ethnicity-related stressors may play a role. We examined the association between an understudied race/ethnicity-related stressor, midlife loss (e.g. deaths of friends/family members) and a marker of cardiovascular risk, carotid intima media thickness (IMT) in 1,410 African-American, White, Chinese and Hispanic women from the Study of Women's Health Across the Nation. Participants were queried about losses annually over 12 years (1996-2013), with IMT assessed Year 12-13 via ultrasound. Linear regression models examined associations between cumulative upsetting losses and IMT, adjusting for covariates. In minimally-adjusted models in the full cohort, ≥3 upsetting losses (versus none) were associated with IMT (β = .03, 95% confidence interval (CI):. 01, . 05, p=. 0003). Results were more robust among African-American (β=.042, 95% CI:.01, .07, p<.009), than White (β=.014, 95% CI:-.01, .03, p=.21), Chinese (β=.036, 95% CI:-.03, .10, p=.25), or Hispanic women (β=.036, 95% CI:-.07, .14, p=.51), although associations among racial/ethnic minority women overall were of similar magnitude. Results persisted in fully-adjusted models (p for interaction with race/ethnicity=.04). Findings suggest that midlife loss may be one pathway through which race/ethnicity impacts cardiovascular risk for African-American women, and potentially Chinese and Hispanic women as well.
Interspecific abundance-occupancy relationships : a test of mechanisms using microcosms

1. Several hypotheses have been proposed to account for the widely observed positive interspecific relationship between the local abundance and number of sites occupied. Here we provide a test of some of these hypotheses using data from microcosm communities of protists, in which sets of individual communities are linked by varying rates of dispersal. 2. Positive relationships between abundance and occupancy were found over all the dispersal rate treatments, including those with no between-community dispersal. 3. Species tended to be consistent in their position in the abundance-occupancy relationship, both within and between treatments. 4. The design of the experiment makes it unlikely that (i) sampling artefacts, (ii) geographical range position, (iii) niche breadth, (iv) resource availability, or (v) vital rates mechanisms are appropriate, or sole explanations for the observed patterns, though biotic heterogeneity complicates the interpretation of (ii)-(v). 5. The results fail to support the specific hypotheses based on metapopulation dynamics, but suggest that occupancy may be driven by local abundance, combined with a very general (not specifically metapopulation-structured) set of extinction and colonization processes.
The Impact of Diabetes on Outcomes and Health Care Costs Following Anterior Cervical Discectomy and Fusion

Study Design: Retrospective cohort study. Objectives: Anterior cervical discectomy and fusion (ACDF) is commonly used to treat an array of cervical spine pathology and is associated with good outcomes and low complication rates. Diabetes mellitus (DM) is a common comorbidity for patients undergoing ACDF, but the literature is equivocal about the impact it has on outcomes. Because DM is a highly prevalent comorbidity, it is crucial to determine if it is an associated risk factor for outcomes after ACDF procedures. Methods: Patients at a single institution from 2008 to 2016 undergoing ACDF were compared on the basis of having a prior diagnosis of DM versus no DM. The 2 cohorts were compared utilizing univariate tests and multivariate logistic and linear regressions. Results: Data for 2470 patients was analyzed. Diabetic patients had significantly higher Elixhauser scores (P < .0001). Univariate testing showed diabetic patients were more likely to suffer from sepsis (0.82% vs 0.10%, P = .03) and bleeding complications (3.0% vs 1.5%, P = .04). In multivariate analyses, diabetic patients had higher rates of non–home discharge (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.07-1.75, P = .013) and prolonged length of stay (OR = 1.95, 95% CI = 1.25-3.05, P = .003), but similar complication (OR = 1.46, 95% CI = 0.85-2.52, P = .17), reoperation (OR = 0.77, 95% CI = 0.33-1.81, P = .55), and 90-day readmission (OR = 1.53, 95% CI = 0.97-2.43) rates compared to nondiabetic patients. Direct cost was also shown to be similar between the cohorts after adjusting for patient, surgical, and hospital-related factors (estimate = −$30.25, 95% CI = −$515.69 to $455.18, P = .90). Conclusions: Diabetic patients undergoing ACDF had similar complication, reoperation, and readmission rates, as well as similar cost of care compared to nondiabetic patients.
Effect of arsenite and growth in biofilm conditions on the evolution of Thiomonas sp. CB2

Thiomonas bacteria are ubiquitous at acid mine drainage sites and play key roles in the remediation of water at these locations by oxidizing arsenite to arsenate, favouring the sorption of arsenic by iron oxides and their coprecipitation. Understanding the adaptive capacities of these bacteria is crucial to revealing how they persist and remain active in such extreme conditions. Interestingly, it was previously observed that after exposure to arsenite, when grown in a biofilm, some strains of Thiomonas bacteria develop variants that are more resistant to arsenic. Here, we identified the mechanisms involved in the emergence of such variants in biofilms. We found that the percentage of variants generated increased in the presence of high concentrations of arsenite (5.33 mM), especially in the detached cells after growth under biofilm-forming conditions. Analysis of gene expression in the parent strain CB2 revealed that genes involved in DNA repair were upregulated in the conditions where variants were observed. Finally, we assessed the phenotypes and genomes of the subsequent variants generated to evaluate the number of mutations compared to the parent strain. We determined that multiple point mutations accumulated after exposure to arsenite when cells were grown under biofilm conditions. Some of these mutations were found in what is referred to as ICE19, a genomic island (GI) carrying arsenic-resistance genes, also harbouring characteristics of an integrative and conjugative element (ICE). The mutations likely favoured the excision and duplication of this GI. This research aids in understanding how Thiomonas bacteria adapt to highly toxic environments, and, more generally, provides a window to bacterial genome evolution in extreme environments.
Clinical Outcomes and Predictors in Patients With Unresectable Colorectal Cancer Liver Metastases Following Salvage Percutaneous Radiofrequency Ablation: A Single Center Preliminary Experience

Purpose: The purpose of this study was to investigate the clinical efficacy of salvage percutaneous radiofrequency ablation in patients with unresectable colorectal cancer liver metastases. Methods: The cohort consisted of 81 patients with 126 colorectal cancer liver metastases who underwent radiofrequency ablation between January 2012 and September 2016. The clinical data and ablation data were retrospectively analyzed. The local tumor progression-free survival, overall survival, and prognostic factors were analyzed using the log-rank test and Cox regression model. Results: The technique success rate was 99.21%. The primary efficacy rate was 100% at the 1-month follow-up. Minor complications were observed in 2 patients, which recovered within 1 week. The median local tumor progression-free survival time of all patients was 29.8 months. The absence of subsequent chemotherapy was an independent predictor of a shorter local tumor progression-free survival time (P < 0.001, hazard ratio: 2.823, 95% confidence interval: 1.603, 4.972). The median overall survival time was 26.8 months. A lesion size greater than 3 cm (P = 0.011, hazard ratio: 2.112, 95% confidence interval: 1.188, 3.754) and the presence of early local tumor progression (P = 0.011, hazard ratio: 2.352, 95% confidence interval: 1.217, 4.545) were related to a shorter survival time. Conclusions: Percutaneous radiofrequency ablation is safe in patients with colorectal cancer liver metastases refractory from chemotherapy. Subsequent chemotherapy is important to enhance local control. Small lesions and favorable early responses are related to prolonged overall survival.
Design, synthesis and activity against Staphylococcus epidermidis of 5‐chloro‐2‐ or 5‐chloro‐4‐methyl‐9H‐xanthen‐9‐one and some of its derivatives

Ten new xanthone derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3: 5‐chloro‐2‐((4‐(2‐hydroxyethyl)piperazin‐1‐yl)methyl)‐9H‐xanthen‐9‐one dihydrochloride, exhibiting MIC of 0.8 µg/ml against ATCC 12228 strain, compared to linezolid (0.8 µg/ml), ciprofloxacin (0.2 µg/ml) or trimethoprim and sulfamethoxazole (0.8 µg/ml). For the most active compound 3, genotoxicity assay with use of Salmonella enterica serovar Typhimurium revealed safety in terms of genotoxicity at concentration 75 µg/ml and antibacterial activity against Salmonella at all higher concentrations. A final in silico prediction of skin metabolism of compound 3 seems promising, indicating stability of the xanthone moiety in the metabolism process.