Miracle-dz/UniFAR-FTUs huggingface dataset:
The association between severe obesity and characteristics of failed fertilized oocytes.

STUDY QUESTION Is the cytoskeletal and chromosomal organization of failed fertilized oocytes from severely obese patients (BMI ≥ 35 kg/m²) altered compared with that in patients with normal BMI (BMI 18.5-24.9 kg/m²)? SUMMARY ANSWER Compared with normal BMI patients, severe obesity was associated with a greater prevalence of spindle anomalies and non-aligned chromosomes in failed fertilized oocytes. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Obesity is associated with poor reproductive outcomes, but little is known regarding the underlying mechanisms. To address potential mechanisms, our study compared the cytoskeletal and chromosome organization in failed fertilized oocytes from severely obese and normal BMI patients. DESIGN The study population was drawn from IVF patients treated in a hospital-based infertility clinic between February 2010 and July 2011. The prevalence of meiotic spindle and chromosome alignment anomalies in failed fertilized oocytes from patients with severe obesity (i.e. Class II and III; BMI 35.0-50.1 kg/m²) was compared with those from patients with normal BMI (BMI 18.5-24.9 kg/m²). Oocytes were fixed and then labeled for tubulin, actin and chromatin. Spindle number and integrity, as well as chromosome alignment, were assessed using immunofluorescence microscopy and, in some cases, confocal microscopy. Generalized estimating equations were applied, which account for the correlation among oocytes from the same patient to estimate odds ratio (OR), 95% confidence intervals (CIs) and two-sided Wald P-values. Models were adjusted for continuous age at cycle start, cycle type (IVF or ICSI) and polycystic ovarian syndrome (PCOS) a priori. PARTICIPANTS AND SETTING University-affiliated infertility clinic. A total of 276 oocytes that failed to fertilize from 137 patients were evaluated: 105 oocytes from severely obese women (n = 47) and 171 oocytes from normal BMI patients (n = 90). MAIN RESULTS AND THE ROLE OF CHANCE (i) Significantly more oocytes from the severely obese group exhibited two spindles compared with those from the normal BMI group (58.9 versus 35.1%; OR = 2.68, CI = 1.39-5.15, P-value = 0.003). (ii) Among oocytes with a single spindle, those from severely obese patients showed a significantly higher prevalence of disarranged spindles with non-aligned chromosomes compared with those from normal BMI patients (28.6 versus 8.6%; OR = 4.58, CI = 1.05-19.86, P-value = 0.04). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION Inclusion of only failed fertilized oocytes, small sample size, unknown factors such as non-PCOS comorbidity. GENERALIZABILITY TO OTHER POPULATIONS For this study, by design, it is unclear whether the findings are generalizable to successfully fertilized oocytes, and whether this oocyte-level influence of obesity is generalizable to infertile women who do not undergo stimulation or, more broadly, to spontaneous conceptions in fertile women. STUDY FUNDING/COMPETING INTEREST(S) none. TRIAL REGISTRATION NUMBER n/a.
Philosophy and treatment in US critical care units

In this chapter, the evolution of critical care practice and advanced nursing roles are explored. An examination of factors that contribute to safe monitoring and treatment in critical care units includes certification processes and national support for critical care nursing practice, perspectives on patient and familyfocused care, and the evolution of rapid response team (RRT) roles in hospital settings.
Breast-cancer anti-estrogen resistance 4 (BCAR4) encodes a novel maternal-effect protein in bovine and is expressed in the oocyte of humans and other non-rodent mammals.

STUDY QUESTION Does BCAR4 have a role in mammalian embryo development? SUMMARY ANSWER Expression, localization and functional data support that BCAR4 is a maternal-effect protein in non-rodent mammals. WHAT IS KNOWN ALREADY BCAR4 was previously identified as an oocyte-specific gene in cattle, and as a marker of certain breast tumors in humans. STUDY DESIGN, SIZE, DURATION Human oocytes were obtained from patients undergoing IVF, but had failed to mature after ovarian stimulation. Dog oocytes were obtained from ovariectomized bitches. Pig, horse and bovine ovaries were obtained from commercial slaughterhouses for extraction of immature oocyte-cumulus complexes. In vivo matured bovine matured oocytes were obtained after ovulation induction and ovulation inducing treatment of Montbeliard heifers. MATERIALS, SETTING AND METHODS Expression at the RNA level was analyzed by reverse transcription coupled to polymerase chain reaction. Western blot and immunolabeling coupled to confocal or electronic microscopy were used to analyze bovine protein expression and intracellular localization. For the functional approach, short-interfering RNA were microinjected into mature bovine oocytes, followed by IVF; cleavage and embryo development were recorded. MAIN RESULTS AND THE ROLE OF CHANCE The BCAR4 gene is conserved in mammalian species from various orders and has been lost in rodents after divergence with lagomorphs. The transcript is expressed in the oocytes of humans and domestic species. We bring the first experimental evidence of the BCAR4 protein in mammals. In cattle, the protein is not detected in immature oocytes but starts to be synthesized during maturation, increases in the zygote and persists until the morula stage. The protein is detected throughout the cytoplasm in mature oocytes, concentrates in and around the pronuclei in the zygote, and appears to shuttle in and out of the nuclei starting in the 2-cell embryo; BCAR4 is also present at the junctions between blastomeres from 2-cell to morula. In our functional approach, targeting the BCAR4 transcript by small-interfering RNA significantly compromised development to the morula or/and blastocyst stages (P < 0.05, logistic regression). LIMITATIONS, REASONS FOR CAUTION As indicated above, protein expression and function were investigated in cattle and mostly in vitro matured oocytes were used. WIDER IMPLICATIONS OF THE FINDINGS This study provides a novel candidate gene whose mutation or deregulation may underlie certain cases of unexplained female infertility.
Anti-Müllerian hormone levels in girls and adolescents with Turner syndrome are related to karyotype, pubertal development and growth hormone treatment.

STUDY QUESTION In girls and adolescents with Turner syndrome (TS), is there a correlation between serum AMH levels and karyotype, spontaneous puberty and other biochemical markers of ovarian function, or growth hormone (GH) therapy? SUMMARY ANSWER Serum anti-Müllerian hormone (AMH) correlates with karyotype, pubertal development, LH, FSH and are measurable in a higher percentage of TS patients under GH therapy. WHAT IS KNOWN ALREADY Most girls with TS suffer from incomplete sexual development, premature ovarian failure and infertility due to abnormal ovarian folliculogenesis. Serum AMH levels reflect the ovarian reserve in females, even in childhood. STUDY DESIGN, SIZE, DURATION Cross-sectional study investigating 270 karyotype proven TS patients aged 0-20 years between 2009 and 2010. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Studies were conducted at three University Children's hospitals in Europe. Main outcome measures were clinical data concerning pubertal development as well as laboratory data including karyotype, serum AMH, LH, FSH, estradiol (E2), inhibin B and IGF. RESULTS AND THE ROLE OF CHANCE: Serum AMH was detectable in 21.9% of all TS girls and correlated strongly with karyotypes. A measurable serum AMH was found in 77% of TS girls with karyotype 45,X/46,XX, in 25% with 'other' karyotypes and in only 10% of 45,X TS girls. A strong relationship was also observed for measurable serum AMH and signs of spontaneous puberty such as breast development [adjusted odds ratio (OR) 19.3; 95% CI 2.1-175.6; P = 0.009] and menarche (crude OR 47.6; 95% CI 4.8-472.9; P = 0.001). Serum AMH correlated negatively with FSH and LH, but did not correlate with E2 and inhibin B. GH therapy increased the odds of having measurable AMH in TS (adjusted OR 4.1; 95% CI 1.9-8.8; P < 0.001). LIMITATIONS, REASONS FOR CAUTION The cross-sectional design of the study does not allow longitudinal interpretation of the data; for that further studies are needed. High percentage of non-measurable AMH levels in the cohort of TS require categorized analysis.
Tree mortality across biomes is promoted by drought intensity, lower wood density and higher specific leaf area.

Drought events are increasing globally, and reports of consequent forest mortality are widespread. However, due to a lack of a quantitative global synthesis, it is still not clear whether drought-induced mortality rates differ among global biomes and whether functional traits influence the risk of drought-induced mortality. To address these uncertainties, we performed a global meta-analysis of 58 studies of drought-induced forest mortality. Mortality rates were modelled as a function of drought, temperature, biomes, phylogenetic and functional groups and functional traits. We identified a consistent global-scale response, where mortality increased with drought severity [log mortality (trees trees-1 year-1 ) increased 0.46 (95% CI = 0.2-0.7) with one SPEI unit drought intensity]. We found no significant differences in the magnitude of the response depending on forest biomes or between angiosperms and gymnosperms or evergreen and deciduous tree species. Functional traits explained some of the variation in drought responses between species (i.e. increased from 30 to 37% when wood density and specific leaf area were included). Tree species with denser wood and lower specific leaf area showed lower mortality responses. Our results illustrate the value of functional traits for understanding patterns of drought-induced tree mortality and suggest that mortality could become increasingly widespread in the future.
Copper T380 intrauterine device for emergency contraception: highly effective at any time in the menstrual cycle.

STUDY QUESTION Does the efficacy of placing a copper intrauterine device (IUD) for emergency contraception (EC) to prevent pregnancy depend on menstrual cycle timing and timing of unprotected intercourse (UPI)? SUMMARY ANSWER If the urine pregnancy test is negative prior to IUD placement, the copper IUD is highly effective for EC at any point in the menstrual cycle. WHAT IS KNOWN ALREADY The use of the Copper T380A for EC has been encouraged by the failure of oral EC methods to decrease rates of unintended pregnancy and the documented success of the IUD in reducing unintended pregnancies. However scant data exist regarding the efficacy and safety of IUD insertion for EC when accounting for menstrual cycle timing and time since UPI. STUDY DESIGN, SIZE, DURATION This is a secondary analysis of data obtained from a previously published prospective cohort study of women who received the Copper T380A IUD for EC between July 1997 and January 2000. We included 1840 participants according to the study inclusion criteria of a known last menstrual period (LMP) and cycle lengths of 25-35 days. PARTICIPANTS/MATERIALS, SETTING, METHODS The original study included women aged between 18 and 44 years who presented for EC at 18 sites throughout China and who had regular menstrual cycles between 24 and 42 days, a known LMP, UPI within 120 h (5 days) and a negative urine pregnancy test (cutoff <25 IU/ml). Women with uncertain LMP dates were excluded. This study included only participants with cycle lengths of 25-35 days. MAIN RESULTS AND THE ROLE OF CHANCE Among the 1840 participants with usual cycle lengths of 25-35 days, 850 (46.2%) had their IUD inserted following UPI in the expected fertile window and 84 (4.6%) had the insertion >5 days after the predicted ovulation day and 52 (2.8%) had the insertion >5 days after UPI. There were no pregnancies in the first month among the 1771 women who had information available regarding their 1-month follow-up pregnancy test. LIMITATIONS, REASONS FOR CAUTION This was a secondary analysis of an observational study, and thus participants were not randomized to an alternative postcoital method. There were a small number of women who had UPI >5 days after their predicted ovulation day thus limiting the confidence of assuring a low risk of pregnancy in this situation. The ovulation day was calculated based on the LMP prior to IUD insertion and not on the subsequent first day of menses following IUD insertion. WIDER IMPLICATIONS OF THE FINDINGS If the urine pregnancy test is negative prior to IUD placement, the copper IUD is likely to be effective for EC at almost any point in the menstrual cycle. STUDY FUNDING/COMPETING INTEREST(S) The original study was funded by the UNDP/UNPFA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction. The donors and sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, writing of the report or the decision to submit the paper for publication.
CD133 and CD44 expression patterns in gliomas and meningiomas

CD133 ve CD44 sirasiyla glioblastoma multiforme (GBM) ve meningiomlarda genis olcude tespit edilen hucre yuzey isaret molekulleridir. Yakin zamandaki molekuler calismalar CD133 muspet GBM hucrelerinin kanser kok hucrelerinin sahip oldugu dusunulen „kendini yenileme ve yineleme‟ ozelliklerine sahip olduklarini gostermistir. Benzer sekilde, CD44 yuzey isaretinin de degisik meningioma alttiplerinde oldugu bilinmektedir ve birkac calismada CD44 miktariyla meningioma invazyonu arasinda iliski oldugu bildirilmistir. Bu baglamda, CD133 ve CD44 hucre yuzey isaret molekullerinin sirasiyla GBM ve meningiomlardaki sunulma bicimlerini ve bu molekullerin potansiyel kanser kok hucreleriyle olan iliskilerini vurgulamayi amacladik
Low back pain and widespread pain in primary health care: Early access to physical therapy, treatment and prognostic factors

Low back pain (LBP) and widespread pain (WP) are common and incur considerable costs to society mainly due to work disability. Identification of prognostic factors, intervention and early access to care seems important for influencing and preventing pain and disability in LBP and WP but further knowledge is warranted. The overall purpose of the present thesis was to obtain knowledge about a) prevalence and characteristics for WP in chronic LBP (CLBP), b) prognostic factors for activity and work status, c) the effect of function based intervention on health status and body functions in patients with WP or fibromyalgia, and d) the effect of early access to physical therapy for subacute LBP.
Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis.

IMPORTANCE Two meta-analyses conclude that finasteride treatment of androgenic alopecia (AGA) is safe but do not assess quality of safety reporting. OBJECTIVE To assess safety reporting for clinical trial reports of finasteride for AGA. DATA SOURCES MEDLINE, ClinicalTrials.gov, and a clinical data repository for an academic medical center. STUDY SELECTION Published clinical trial reports for finasteride treatment of AGA. DATA EXTRACTION AND SYNTHESIS For each trial, we assessed quality of adverse event reporting, extracted the number and type of adverse events in treatment and placebo groups, and assessed duration of safety evaluation and adequacy of blinding. Two observers independently extracted the data; differences were resolved by consensus. We assessed generalizability in a large cohort of men prescribed finasteride, 1.25 mg/d or less, by assessing for eligibility in the finasteride-AGA pivotal trials. MAIN OUTCOMES AND MEASURES Quality was assessed as adequate, partially adequate, inadequate, or no events reported. We used funnel plots of the hazard ratio to assess bias. RESULTS Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for AGA, only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer's full prescribing information and 33% took finasteride for more than 1 year. CONCLUSIONS AND RELEVANCE Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.
STEM SCHOOLS VS. NON-STEM SCHOOLS: COMPARING STUDENTS MATHEMATICS STATE BASED TEST PERFORMANCE

The purpose of this study is to determine how students who participated in T-STEM schools performed on the Texas Assessment of Knowledge and Skills (TAKS) mathematics test compared to their corresponding peers who particiapted in traditional public schools in Texas. The present study included 18 T-STEM schools, and 18 matched non-STEM schools. The sample for this study is 1887 students who were in 11th grade in 2011. A hierarchical linear model (HLM) was used to compare students' mathematics scores. This study also investigates if students who come from traditionally underserved subpopulation incrase their mathematics score by particiapting in T-STEM schools. Results revelaed that the mean matheamtics scores on TAKS of STEM and non-STEM schools were not statsitically significantly different from each other, but participating STEM schools resulted in statistically significantly increase on Hispanic students' mean matheamtics score relative to referance group (White, male, high-SES background, non-STEM).
Modern contraceptive preferences among women accessing family planning services at a specialist hospital in North Central Nigeria

BACKGROUND: It is contended that no community can rise out of destitution to dignity in the absence of family planning. An awareness of the importance of family planning in reducing maternal and perinatal morbidity and mortality and the dearth of information on contraceptive use in this region prompted this study. METHOD: It is a retrospective descriptive study of the contraceptive preference of women attending family planning (FP) clinic at Dalhatu Araf Specialist Hospital (DASH) Lafia Nasarawa State Nigeria. RESULT: Out of 937 women attending the FP clinic 908 were reviewed with 4 inconclusive data. Contraceptive usage rate was 32.6% of deliveries in the hospital. The women who were mostly married (99.9%) full time housewives (73.5%) and grandmultipara (48.7%) had a mean age of 29 +or- 6.1 years. Contraceptive preferences were mainly for implants (40.5%) and injectables (40%) with only 0.5% using condoms. These preferences remain the same when the women were stratified into age groups. CONCLUSION: Usage in the facility may seem relatively high but a lot more needs to be done to increase access to contraception. A well focused organized statewide family planning policy is urgently needed to remedy the current situation in the state a policy that can be extended nationwide.
Betamethasone therapy in ataxia telangiectasia: unraveling the rationale of this serendipitous observation on the basis of the pathogenesis

Ataxia telangiectasia (A‐T) is a rare autosomal recessive disorder characterized by progressive neurological dysfunction. To date, only supportive care aimed to halt the progressive neurodegeneration is available for the treatment. Recently, an improvement of neurological signs during short‐term treatment with betamethasone has been reported. To date, the molecular and biochemical mechanisms by which the steroid produces such effects have not yet been elucidated. Therefore, a review of the literature was carried out to define the potential molecular and functional targets of the steroid effects in A‐T. Glucocorticoids (GCs) are capable of diffusing into the CNS by crossing the blood–brain barrier (BBB) where they exert effects on the suppression of inflammation or as antioxidant. GCs have been shown to protect post‐mitotic neurons from apoptosis. Eventually, GCs may also modulate synaptic plasticity. A better understanding of the mechanisms of action of GCs in the brain is needed, because in A‐T during the initial phase of cell loss the neurological impairment may be rescued by interfering in the biochemical pathways. This would open a new window of intervention in this so far incurable disease.
Reversal of ophthalmic artery flow as a predictor of intracranial hemodynamic compromise: implication for prognosis of severe carotid stenosis

High‐grade cervical carotid stenosis (70–99%) or occlusion often accompanies reversed ophthalmic artery flow (ROAF), but its potential clinical significances remain poor understood. This study assessed ROAF and the related variables caused by carotid hemodynamic compromise in patients with unilateral severe cervical carotid stenosis.
Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma.

IMPORTANCE Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors. OBJECTIVE To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples. DESIGN, SETTING, AND PARTICIPANTS Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015. MAIN OUTCOMES AND MEASURES The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability. RESULTS Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients. CONCLUSIONS AND RELEVANCE Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing. Continuous dosing may be required to fully inhibit the HH pathway and achieve clinical response.