Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

ABSTRACT To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic- and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups of genes with characteristic protein phenotypes, such as genes encoding cytoplasmic granular proteins, nuclear envelope and cytoskeletal proteins, cell adhesion proteins, and proteins involved in the cell cycle and apoptosis illustrate the profound differences among the various cell states. In addition to the transcriptome analyses, companion karyotyping by M-FISH of undifferentiated HL-60/S4 cells revealed a plethora of chromosome alterations, compared with normal human cells. The present mRNA profiling provides important information related to nuclear shape changes (e.g., granulocyte lobulation), deformability of the nuclear envelope and linkage between the nuclear envelope and cytoskeleton during induced myeloid chromatin differentiation.
Connexin 43 upregulation by dioscin inhibits melanoma progression via suppressing malignancy and inducing M1 polarization

Connexin 43 (Cx43), a vital gap junction protein in tumor microenvironment (TME), is a novel molecular target for melanoma chemotherapeutics due to its tumor suppressive function. Dioscin, an herbal steroidal saponin, exerts anti‐tumor effects while the underlying mechanism is unclear. Using WB, FACS, and immunofluorescence methodologies, we found dioscin significantly activated the transcription and translation of Cx43 via the retinoid acid signaling pathway and simultaneously enhanced the transporting function of Cx43. Through stimulating Cx43, dioscin remarkably suppressed the migratory and invasive capacities of B16 cells, and notably decreased pluripotency markers of cancer stem cells and epithelial‐to‐mesenchymal transition in B16 cells and animal tumor tissues. Conversely, dioscin improved the secretion of pro‐inflammatory cytokines (IL‐6, TNFα, and IL‐1β), and the phagocytic capacity of tumor‐associated macrophages by increasing M2‐to‐M1 phenotype transition. More strikingly, even in Cx43 functional deficient B16 and RAW264.7 cells, dioscin still dramatically reversed the aggravated tumor malignancy and reduced macrophage phagocytic activity. Two classical metastasis animal models were utilized in vivo and results showed that dioscin showed significant anti‐metastatic effects, which is closely related to the expression of Cx43 either in in situ tumor or metastatic lung nodes. In conclusion, dioscin targets Cx43 to suppress the tumor cell malignancy and activate macrophage sensitivity, thereby targeting melanoma microenvironment.
Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow‐up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country‐specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68–1.15; p‐trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69–1.14; p‐trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79–1.26; p‐trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98–1.53; p‐trend = 0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.
Bowel vaginoplasty: a systematic review

Abstract Among surgical procedures for constructing a neovagina, positive outcomes are reported in literature for bowel vaginoplasty for male-to-female transgenders and patients with vaginal aplasia. This systematic review shows outcomes of bowel vaginoplasty procedures, and rates the quality of evidence of the included studies. A search of the literature was performed in PubMed, Medline, Cochrane Library and SveMed+, in accordance with the PRISMA statement, between January 2016 and February 2018. The PICOS (patients, intervention, comparator, outcomes and study design) approach was used as inclusion criteria. Among 251 analyzed studies only 34 met inclusion criteria. Quality of evidence and methodology were rated according to GRADE and MINORS, respectively. Data from the included studies were extracted based on study characteristics, participants? specifics, type of intervention/treatment and type of outcome measures into data extraction forms. All studies were non-randomized with a high risk of bias and very low quality of evidence according to GRADE. Vaginal reconstruction with isolated bowel segments provides a self-lubricating neovagina with low rates of failure and revision, and without routine dilatation need. Furthermore, the use of laparoscopic techniques offers a better postoperative cosmetic appearance of the abdomen and a shorter hospital stay. Vaginoplasty using bowel segment is a safe and effective procedure that obtains excellent long-term results as reported by the included studies. Despite that further researches are needed improving methodology with larger populations, retrospective qualitative studies and report of outcome measurements using standardized evaluation tools as the Female Sexual Function Index.
Digitalis use and lung cancer risk by histological type in men

Lung cancer risk and tumor characteristics differ between sexes. Estrogen has been suggested to counteract lung cancer development. We aimed to test the hypothesis that digitalis use decreases lung cancer risk due to its estrogenic and other anticancer properties in men. This was a nationwide Swedish population‐based cohort study between July 1, 2005 and December 31, 2013. Data on the use of digitalis and organic nitrates in all male individuals were derived from the Swedish Prescribed Drug Registry. New lung cancer diagnoses among cohort participants were identified from the Swedish Cancer Registry. Cox proportional hazards regression was employed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of lung cancer in digitalis users (exposed participants) compared to users of organic nitrates without digitalis medication (unexposed participants). The study cohort contained 74,437 digitalis users and 297,301 organic nitrates users. Long‐term use (≥2 years) of digitalis was associated with decreased HRs of total lung cancer (HR 0.55, 95% CI 0.39–0.79) and squamous cell carcinoma (HR 0.40, 95% CI 0.19–0.87). This large and population‐based study suggests decreased risks of lung cancer overall and squamous cell carcinoma associated with long‐term use of digitalis in men.
Mortality In Thalassemic Patients From Solapur District, Maharashtra State, India

Objective: The aim of the present study is to surveying the mortality in thalassemic patients from Solapur District, Maharashtra State, India. Methods: Present observational survey study, one hundred twenty five clinically proved by their medical reports, cases of thalassemic children's with age 6 months to 18 Years, coming for to get blood transfusion from different parts of Solapur district. Results: The results indicates that the increased mortality during 11-15 years of age. As a result, transfusional iron overload can cause increased morbidity and premature mortality in thalassemia patients. This study will be helpful in further defining the morbidity and mortality in thalassemic patients. DOI: http://dx.doi. org/10.3329/bjms.v11i3. 11717 Bangladesh Journal of Medical Science Vol. 11 No. 03 July’12
Species composition and habitat characterization of mosquito (Diptera: Culicidae) larvae in semi-urban areas of Dhaka, Bangladesh

Mosquito larvae are purely aquatic and develop in water bodies, the type of which is more or less specific to each species. Therefore, a study was carried out to identify the habitat characters of different mosquito species along with their species composition in semi-urban area of Dhaka in Bangladesh during the month of May and June 2012. A total of 6088 mosquito larvae belonging to 12 species (Aedes aegypti, Aedes albopictus, Anopheles barbirostris, Anopheles peditaeniatus, Anopheles vagus, Culex gelidus, Culex hutchinsoni, Culex quinquefasciatus, Culex tritaeniorhynchus, Mansonia annulifera, Mansonia uniformis, and Toxorhynchites splendens) under 5 genera were collected from 14 different types of habitats. Culex quinquefsciatus was the dominant (21.7/500 ml) species followed by Cx. tritaeniorhynchus (10.53/500 ml). Dissolved oxygen and chlorophyll a were the preeminent predictors for the abundance of all collected mosquito larvae except Ae. aegypti. Water temperature was positively associated with the breeding of An. vagus (r = 0.421, p = <0.001), An. barbirostris (r = 0.489, p = <0.001) and An. peditaeniatus (r = 0.375, p = <0.001). Water depth, distance from nearest house, emergent plant coverage, and alkalinity were found as the basis of larval abundance. Every Culex species and Tx. splendens (r = 0.359, p = 0.001) were found positively associated with chemical oxygen demand, while Mn. annulifera showed negative association (r = −0.115, p = 0.0297). This study also highlighted that various physicochemical factors affect the presence or abundance of mosquito larvae.
Efficacy and safety of anti‐EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: a systematic review and meta‐analysis of randomized controlled trials

Agents targeting epidermal growth factor receptor (EGFR) are used to treat head and neck squamous cell carcinoma (HNSCC); however, their efficacy and safety is poorly understood. Here we evaluated the efficacy and safety of anti‐EGFR agents administered concurrently with standard therapies for HNSCC. Randomized controlled trials that evaluated addition of EGFR targeted therapy versus standard therapy alone were included. The primary outcome was overall survival (OS). Secondary outcomes were progression‐free survival (PFS), overall response rate (ORR), locoregional control, and severe adverse events (SAEs, grade ≥ 3). Sixteen eligible trials with 4031 patients were included. Addition of anti‐EGFR regimens to standard therapy significantly improved OS of patients with HNSCC (HR = 0.89; 95% CI, 0.82–0.96), with a moderately elevated rate of SAEs (RR = 1.08; 95% CI, 1.03–1.13). Subgroup analysis indicated that the survival benefit was observed when cetuximab was administered concurrently with radiotherapy (RT) for stage III/IV patients (HR = 0.76; 95% CI, 0.61–0.94; p = 0.01), or with chemotherapy for recurrent or metastatic (R/M) HNSCC (HR = 0.86; 95% CI, 0.78–0.95; p = 0.005). Significantly increased ORR (RR = 1.51; 95% CI 1.05–2.18) and PFS (HR = 0.72; 95% CI, 0.59–0.88) were found in R/M HNSCC patients treated with anti‐EGFR plus chemotherapy, while no significant improvements were found in stage III/IV patients treated with anti‐EGFR plus standard therapy. In conclusion, addition of cetuximab to standard therapy may improve outcomes for R/M HNSCC patients, while causing a moderate increase in SAEs. For stage III/IV patients, anti‐EGFR mAb plus RT can improve OS compared with RT alone, while replacement of chemotherapy with EGFR mAb or adding EGFR mAb to combined chemotherapy and RT did not improve outcomes.
Right hemisphere syndrome is in the eye of the beholder

Background: Specific information about prevalence and patterns of deficits associated with right hemisphere brain damage (RHD) is incomplete. A recent large-scale study of inpatients in a United States rehabilitation centre (Lehman Blake, Duffy, Myers & Tompkins, 2002) provided initial estimates of deficit prevalence and co-occurrence. The data obtained were based on information from multiple medical disciplines, and may not adequately reflect the typical caseload seen by US speech-language pathologists (SLP). Differences in how professionals view RHD may influence whether patients are appropriately referred for services. Aims: The first aim was to evaluate whether prevalence and patterns of deficits differ when diagnoses are made by SLPs versus other disciplines. The second aim was to examine whether the presence of certain deficits is associated with referrals to SLP. Methods and Procedures: A retrospective chart review was conducted examining medical records for 122 adults with RHD in an inpatient rehabilitation unit. Diagnoses were obtained from speech-language pathology versus a group of other medical professionals, including neurology/physiatry, neuropsychology, and occupational therapy. Frequencies and cluster analyses were computed for both groups of diagnosticians to examine differences between groups. Relationships between performance on a screening measure of mental status and cognitive/communicative diagnoses were examined to determine if there were obvious connections between specific disorders and referrals to SLP. Outcomes and Results: Diagnoses of pragmatic and communicative deficits were made more often by SLPs, while the other professionals more often diagnosed deficits in attention, visuoperception, and learning/memory. Moderate-strong correlations between diagnoses from the two groups were obtained only for deficits of attention, linguistics, and neglect. Referral to SLP was not related to performance on a general mental status screening test. Patients who presented with neglect, aprosodia, or deficits in interpersonal interactions were more likely to be referred to SLP than when these deficits were absent. Conclusions: This study raises the question of how to ensure appropriate referrals to SLP when referring professionals may not always identify the communicative disorders exhibited by individuals with RHD. A descriptive definition of right hemisphere syndrome and a consistent set of terminology would facilitate communication about right hemisphere deficits within and across disciplines. A broader scope of referrals to SLP would increase the number of patients who receive appropriate care for their cognitive and communicative deficits.
A Critical Evaluation of Long-Term Aesthetic Outcomes of Fronto-Orbital Advancement and Cranial Vault Remodeling in Nonsyndromic Unicoronal Craniosynostosis

Background: This study reports long-term aesthetic outcomes with fronto-orbital advancement and cranial vault remodeling in treating unicoronal synostosis over a 35-year period. Methods: Retrospective review was performed on patients with isolated unicoronal synostosis from 1977 to 2012. Demographic, preoperative phenotypic, and long-term aesthetic outcomes data were analyzed with chi-squared and Fisher’s exact test for categorical data and Wilcoxon rank-sum and Kruskal-Wallis rank for continuous data. Results: A total of 238 patients were treated; 207 met inclusion criteria. None underwent secondary intervention for intracranial pressure. At definitive intervention, there 96 (55 percent) Whitaker class I patients, 11 (6 percent) class II, 62 (35 percent) class III, and six (3 percent) class IV. Nasal root deviation and occipital bossing each conferred an increased risk of Whitaker class III/IV [OR, 4.4 (1.4 to 13.9), p = 0.011; OR, 2.6 (1.0 to 6.8), p = 0.049]. Patients who underwent bilateral cranial vault remodeling with extended unilateral bandeau were less likely Whitaker class III/IV at latest follow-up compared with those undergoing strictly unilateral procedures [OR, 0.2 (0.1 to 0.7), p = 0.011]. Overcorrection resulted in decreased risk of temporal hollowing [OR, 0.3 (0.1 to 1.0), p = 0.05]. Patients with 5 years or more of follow-up were more likely to develop supraorbital retrusion [OR, 7.2 (2.2 to 23.4), p = 0.001] and temporal hollowing [OR, 3.7 (1.5 to 9.6), p = 0.006] and have Whitaker class III/IV outcomes [OR, 4.9 (1.8 to 12.8), p = 0.001]. Conclusion: Traditional fronto-orbital advancement and cranial vault remodeling appears to mitigate risk of intracranial pressure but may lead to aesthetic shortcomings as patients mature, namely fronto-orbital retrusion and temporal hollowing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Protection of Candida parapsilosis from neutrophil killing through internalization by human endothelial cells

Candida parapsilosis is a fungal pathogen that is associated with hematogenously disseminated disease in premature neonates, acutely ill or immunocompromised patients. In cell culture, C. parapsilosis cells are actively and avidly endocytosed by endothelial cells via actin polymerization mediated by N-WASP. Here we present evidence that C. parapsilosis that were internalized by endothelial cells remained alive, and avoided being acidified or otherwise damaged via the host cell. Internalized fungal cells reproduced intracellularly and eventually burst out of the host endothelial cell. When neutrophils were added to endothelium and C. parapsilosis, they patrolled the endothelial surface and efficiently killed most adherent fungal cells prior to endocytosis. But after endocytosis by endothelial cells, internalized fungal cells evaded neutrophil killing. Silencing endothelial N-WASP blocked endocytosis of C. parapsilosis and left fungal cells stranded on the cell surface, where they were susceptible to neutrophil killing. These observations suggest that for C. parapsilosis to escape from the bloodstream, fungi may adhere to and be internalized by endothelial cells before being confronted and phagocytosed by a patrolling leukocyte. Once internalized by endothelial cells, C. parapsilosis may safely replicate to cause further rounds of infection. Immunosurveillance of the intravascular lumen by leukocytes crawling on the endothelial surface and rapid killing of adherent yeast may play a major role in controlling C. parapsilosis dissemination and infected endothelial cells may be a significant reservoir for fungal persistence.
Effectiveness of Conservative Therapy and Helmet Therapy for Positional Cranial Deformation

Background: The authors investigated the effectiveness of conservative (repositioning therapy with or without physical therapy) and helmet therapy, and identified factors associated with treatment failure. Methods: A total of 4378 patients evaluated for deformational plagiocephaly and/or deformational brachycephaly were assigned to conservative (repositioning therapy, n = 383; repositioning therapy plus physical therapy, n = 2998) or helmet therapy (n = 997). Patients were followed until complete correction (diagonal difference <5 mm and/or cranial ratio <0.85) or 18 months. Rates of correction were calculated, and independent risk factors for failure were identified by multivariate analysis. Results: Complete correction was achieved in 77.1 percent of conservative treatment patients; 15.8 percent required transition to helmet therapy (n = 534), and 7.1 percent ultimately had incomplete correction. Risk factors for failure included poor compliance (relative risk, 2.40; p = 0.009), advanced age (relative risk, 1.20 to 2.08; p = 0.008), prolonged torticollis (relative risk, 1.12 to 1.74; p = 0.002), developmental delay (relative risk, 1.44; p = 0.042), and severity of the initial cranial ratio (relative risk, 1.41 to 1.64; p = 0.044) and diagonal difference (relative risk, 1.31 to 1.48; p = 0.027). Complete correction was achieved in 94.4 percent of patients treated with helmet therapy as first-line therapy and in 96.1 percent of infants who received helmets after failed conservative therapy (p = 0.375). Risk factors for helmet failure included poor compliance (relative risk, 2.42; p = 0.025) and advanced age (relative risk, 1.13 to 3.08; p = 0.011). Conclusions: Conservative therapy and helmet therapy are effective for positional cranial deformation. Treatment may be guided by patient-specific risk factors. In most infants, delaying helmet therapy for a trial of conservative treatment does not preclude complete correction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
Reply to Argüelles

To the Editor, It is very much appreciated that Dr. Juan-Carlos Arg€ uelles has critiqued our review of the trehalose pathway as an antifungal target. In his letter, he cogently has emphasized and identified several issues which are important to the creation and completion of trehalose and its enzymes as fungicidal targets. This enthusiasm to exploit this pathway is clearly expressed by the critique. In fact, in his title that includes the statement, “the picture is still incomplete,” he has issued the challenge that our review tried to articulate. It is true that the “picture is not yet a masterpiece. ” This result will occur when we have discovered a potent antifungal agent at this mechanistic site. We hope our review suggests that it is both possible and of outstanding worth to complete this picture.
Stepped Care: A Promising Treatment Strategy for Mandated Students

Over the past decade, there has been a steady increase in the number of mandated students who have been referred to campus alcohol programs for violating campus alcohol policies. However, the severity of alcohol use and problems varies widely in mandated students, indicating that a “one size fits all” delivery of treatment may be inappropriate. Instead, an approach that tailors treatment may be more clinically effective, efficient, and cost-effective. Stepped care assigns individuals to different levels of treatment based on personal characteristics. This article discusses the promise of implementing stepped care with mandated students. We review previous applications of stepped care in the alcohol field, along with empirically validated interventions that could be incorporated into this approach. In addition, we address several issues to be considered when implementing stepped care with mandated students.