Miracle-dz/UniFAR-FTUs huggingface dataset:
A retrospective cohort study of obstetric complications and birth outcomes in women with polycystic ovarian syndrome

Abstract Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women and a high risk factor for adverse pregnancy complications. Therefore, we aimed to analyse the relationship between PCOS and pregnancy complications in a large sample from China. Additionally, since obesity and assisted reproductive technology (ART) are common in women with PCOS, we also aimed to determine whether both of these factors increased the complication incidence for women with PCOS. A retrospective cohort study that included 1357 pregnant women with PCOS and 6940 without PCOS was performed. Our results indicated women with PCOS had higher incidence of gestational diabetes mellitus (GDM), hypertension, postpartum haemorrhage, preterm birth, macrosomia and cervical incompetence. Additionally, obesity was associated with an increased incidence of hypertension and GDM in women with PCOS generally. ART did not result in an increase in the obstetric complication rate in women with PCOS. In conclusion, PCOS appeared to result in an increased risk of adverse pregnancy complications. Obesity may further increase the risks of hypertension and GDM among women with PCOS. However, ART did not increase the risk of pregnancy complications, which suggests that ART is a relatively safe and effective method to address infertility problems in women with PCOS. IMPACT STATEMENT What is already known on this subject? There are several studies evaluating the associations of PCOS with the risk of pregnancy complications. However, reports about the risk of pregnancy complications between PCOS women with and without obesity or ART are limited. What do the results of this study add? PCOS appeared to increase the risk of adverse pregnancy complications, including GDM, pregnancy-induced hypertension, postpartum haemorrhage, preterm birth, macrosomia and cervical incompetence. Obesity further increased the risks of hypertension and GDM in women with PCOS, but it did not increase the incidence of macrosomia and postpartum haemorrhage. Additionally, ART did not increase the risk of adverse pregnancy complications among women with PCOS, except for postpartum haemorrhage. What are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because it showed that PCOS independently increased the risk of adverse pregnancy complications in a large sample of patients. Second, obesity is a high risk factor for adverse complications in pregnant women with PCOS. Third, ART is a relatively safe and effective method for addressing infertility problems for women with PCOS.
Lower incidence of clinical allergy with PEG‐asparaginase upfront versus the sequential use of native E. coli asparaginase followed by PEG‐ASP in pediatric patients with acute lymphoblastic leukemia

Asparaginase (ASP) is an essential component for the acute lymphoblastic leukemia (ALL) treatment, but toxicities, such as allergy, frequently limit its use. Although the potentially lower PEG‐ASP formulation immunogenicity, few studies with conflicting results have compared the allergy incidence between Escherichia coli‐ASP and PEG‐ASP in the same protocol. We aimed at comparing the allergy incidence in children receiving native E. coli‐ASP versus PEG‐ASP within the same clinical protocol (Spanish Society of Pediatric Hematology and Oncology ALL‐SEHOP‐PETHEMA 2013). One hundred and twenty‐six children (1–19 years) diagnosed with ALL from 2013 to 2020 were included. Patients in group 1 received a sequential scheme of native E. coli‐ASP 10,000 IU/m2 intramuscularly (IM) followed by PEG‐ASP 1000 IU/m2 IM. Patients in group 2 received PEG‐ASP 1000 IU/m2 IM upfront. Clinical allergy incidence was compared between both groups. Serum ASP activity (SAA) was measured in a subgroup of patients, and silent inactivation was recorded. The cumulative incidence of clinical allergy was significantly higher in group 1 (native followed by PEG‐ASP) than in group 2 (PEG‐ASP upfront), 24.7% versus 4.1% (p = 0.0085). Adequate ASP activity was achieved with PEG‐ASP 1000 IU/m2 dose in most patients (median SAA 412.5 and 453.0 IU/L at days 7 and 14). The incidence of silent inactivation in PEG‐ASP upfront patients was very low. PEG‐ASP‐used upfront was associated with a lower incidence of clinical allergy than that observed in the sequential use of native E. coli‐ASP followed by PEG‐ASP. PEG‐ASP at 1000 IU/m2 was effective in achieving enough ASP activity in most patients.
Effects of COVID-19 Lockdown on Tumour Burden of Melanoma and Cutaneous Squamous Cell Carcinoma

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.
Interventional resealing of preterm premature rupture of the membranes: a systematic review and meta-analysis

Abstract Objective To compare the effectiveness and outcomes of interventional resealing of membranes, “amniopatch” for spontaneous vs. iatrogenic preterm premature rupture of the membranes (sPPROM and iPPROM). Methods We performed a systematic review of literature involving an electronic search of the following databases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Scopus. An indirect meta-analysis was then performed to compare the obstetric, maternal, fetal, and neonatal outcomes of amniopatch between the sPPROM and iPPROM groups. Results The mean gestational age (GA) at the time rupture was 17.8 ± 1.8 and 25.2 ± 3.8 weeks for iPPROM and sPPROM, respectively, p = . 005. Mean GA at the time of amniopatch procedure was 19.2 ± 2.07 weeks for iPPROM and 23 ± 3.1 weeks of gestation for sPPROM, p = . 023. The rates of fluid re-accumulation (sPPROM 26% and iPPROM 53%, p = .09) were comparable between the sPPROM and iPPROM groups. Neonatal outcomes except for the rate of IUFD were also comparable between the groups. The incidence of IUFD was significantly higher in the iPPROM group (ES: 24%; 95% CI: 8.00–44.0%; p < .001), compared to sPPROM (ES: 0%; 95% CI: 0.00–4.00%). Obstetric and maternal outcomes were comparable between the two groups. Conclusions Amniopatch appears to be a feasible and safe procedure for PPROM treatment. Further research is warranted to investigate the effectiveness of this procedure and establish a standardized criterion for the appropriate selection of patients that could benefit from this intervention.
Involvement of the effect of renal hypoperfusion medications on vancomycin trough concentration: A secondary analysis using a retrospective observational data

This study examined the association between vancomycin (VCM) trough concentration and confounding factors including renal hypoperfusion medications which include angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, loop/thiazide diuretics, or non‐steroidal anti‐inflammatory drugs. This secondary analysis included patients aged >15 years who were administered VCM intravenously between June 2015 and August 2017 at the Tokyo Women's Medical University Medical Center East. We investigated predictors for three (initial, mean, and final) dose‐normalized VCM trough concentration (dose‐normalized VCMtrough) as outcome using a multiple linear regression analysis. In total, 208 patients were analysed (use of loop/thiazide diuretics: 48 [23%]). Multiple linear regression analysis revealed that the initial dose‐normalized VCMtrough was negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.028) and positively correlated with the use of loop/thiazide diuretics (p = 0.003). Meanwhile, there was a positive correlation between the mean dose‐normalized VCMtrough and age (p = 0.023). The mean dose‐normalized VCMtrough was negatively correlated with eGFR (p < 0.001) and serum albumin (p < 0.001). The final dose‐normalized VCMtrough was positively associated with age (p = 0.034) and negatively associated with eGFR (p = 0.032) and serum albumin (p = 0.007). Clinicians should closely monitor VCM trough concentration while receiving VCM and loop/thiazide diuretics.
A Phase 1/2 Randomized, Placebo-Controlled Trial of Romidespin in Persons With HIV-1 on Suppressive Antiretroviral Therapy

Background. Romidepsin (RMD) is a histone deacetylase inhibitor reported to reverse HIV-1 latency. We sought to identify doses of RMD that were safe and induced HIV-1 expression. Enrollees HIV-1 copies/mL antiretroviral therapy. Measurements included RMD levels, plasma viremia by single-copy HIV-1 RNA assay, HIV-1 DNA, cell-associated unspliced HIV-1 RNA (CA-RNA), acetylation of histone H3-lysine-9 (H3K9ac + ), and phosphorylation of transcription factor P-TEFb. Wilcoxon tests were used for comparison. Results. In the single-dose cohorts 1–3, 43 participants enrolled (36 participants 0.5, 2, 5 mg/m 2 RMD; 7 placebo) and 16 enrolled in the multidose cohort 4 (13 participants 5 mg/m 2 RMD; 3 placebo). One grade 3 event (neutropenia) was possibly treatment related. No significant changes in viremia were observed in cohorts 1–4 compared to placebo. In cohort 4, pharmacodynamic effects of RMD were reduced proportions of CD4 + T cells 24 hours after infusions 2–4 (median, −3.5% to −4.5%) vs placebo (median, 0.5% to 1%; P ≤ .022), and increased H3K9ac + and phosphorylated P-TEFb in CD4 + T cells vs placebo ( P ≤ .02). Conclusions. RMD infusions were safe but did not increase plasma viremia or unspliced CA-RNA despite pharmacodynamic effects on CD4 + T cells.
Prognostic factors, symptom evolution, and quality of life of posttraumatic trigeminal neuropathy

Supplemental Digital Content is Available in the Text. Sixty percent of patients with posttraumatic trigeminal neuropathies had a persistent injury. Painful or persistent symptoms were related to decreased HRQoL. Recovery from neurosensory deficits is dependent on sex, the initiating event, sensory profile, and injured nerve branch.
Cucurbitacin B enhances apoptosis in gefitinib resistant non-small cell lung cancer by modulating the miR-17-5p/STAT3 axis

Tyrosine kinase inhibitors, such as gefitinib, are currently widely used as targeted therapeutics for non-small cell lung cancer (NSCLC). Although drug resistance has become a major obstacle to successful treatment, mechanisms underlying resistance to gefitinib remain unclear. Therefore, the present study aimed to investigate the impact of adjunctive cucurbitacin B (CuB) on gefitinib resistance (GR) in the PC9 cell line, including identifying underlying mechanisms. Reverse transcription-quantitative PCR demonstrated significant downregulation of microRNA (miR)-17-5p expression in GR PC9 cells (PC9/GR), and this could be reversed by CuB. During combination treatment with CuB and gefitinib at IC25, PC9/GR cell proliferation was downregulated, and apoptosis was upregulated. The presence of a miR-17-5p inhibitor negated the effects of CuB and gefitinib, whereas the presence of a miR-17-5p mimic enhanced them. Luciferase assays demonstrated that the hypothetical target gene, signal transducer and activator of transcription 3 (STAT3), was directly targeted by miR-17-5p. Moreover, significant elevation of the STAT3 protein and phosphorylation levels in PC9/GR cells was reversed by the addition of CuB, despite a lack of change in STAT3 transcription level. During combined treatment with CuB and gefitinib at IC25, the STAT3 protein expression was negatively associated with the expression of miR-17-5p. Overexpression of STAT3 increased proliferation and decreased apoptosis and the protein levels of apoptosis-related factors cleaved caspase-3 and cleaved caspase-9 of PC9/GR cells. Findings indicated that STAT3 protein and phosphorylation levels became elevated in response to gefitinib, and that CuB-induced miR-17-5p expression led to STAT3 degradation, thereby ameliorating GR. In summary, CuB reduced the proliferation of GR PC9 cells by modulating the miR-17-5p/STAT3 axis, and may represent a promising potential novel strategy for the reversal of GR.
Psychological Distress During the Retirement Transition and the Role of Psychosocial Working Conditions and Social Living Environment

Abstract Objectives Mental health is determined by social, biological, and cultural factors and is sensitive to life transitions. We examine how psychosocial working conditions, social living environment, and cumulative risk factors are associated with mental health changes during the retirement transition. Method We use data from the Finnish Retirement and Aging study on public sector employees (n = 3,338) retiring between 2014 and 2019 in Finland. Psychological distress was measured with the General Health Questionnaire annually before and after retirement and psychosocial working conditions, social living environment, and accumulation of risk factors at the study wave prior to retirement. Results Psychological distress decreased during the retirement transition, but the magnitude of the change was dependent on the contexts individuals retire from. Psychological distress was higher among those from poorer psychosocial working conditions (high job demands, low decision authority, job strain), poorer social living environment (low neighborhood social cohesion, small social network), and more cumulative risk factors (work/social/both). During the retirement transition, greatest reductions in psychological distress were observed among those with poorer conditions (work: absolute and relative changes, p [Group × Time interactions] < .05; social living environment and cumulative risk factors: absolute changes, p [Group × Time interactions] < .05). Discussion Psychosocial work-related stressors lead to quick recovery during the retirement transition but the social and cumulative stressors have longer-term prevailing effects on psychological distress. More studies are urged incorporating exposures across multiple levels or contexts to clarify the determinants of mental health during the retirement transition and more generally at older ages.
Executive Functions in Aging: An Experimental and Computational Study of the Wisconsin Card Sorting and Brixton Spatial Anticipation Tests

ABSTRACT In order to explore the effect of normal aging on executive function, we tested 25 younger adults and 25 neurologically healthy older adults on the Wisconsin Card Sorting Test (WCST) and the Brixton Spatial Anticipation Test (BRXT), two classic tests of executive function. We found that older participants were more likely than younger participants to err on both tasks, but the additional errors of older participants tended to be related to task set maintenance and rule inference rather than perseveration. We further found that the tendency to perseverate (across all participants) on the WCST was related to the tendency to produce stimulus or response perseverations on the BRXT, rather than any tendency to perseverate on BRXT rule application. Finally, on both tasks, older participants were also slower, particularly on trials following an error, than younger participants. To explore the neurocomputational basis for the observed behaviours we then extended an existing model of schema-modulated action selection on the WCST to the BRXT. We argue on the basis of the model that the performance of older participants on both tasks reflects a slower update of schema thresholds within the basal ganglia, coupled with a decrease in sensitivity to feedback.
The Impact of COVID-19 on Plastic Surgery Home Program Match Rates

Background Historically, integrated plastic surgery is one of the most competitive specialties in the residency match. In the 2020–2021 residency application cycle, plastic surgery programs were forced to adjust how they select applicants because of the COVID-19 pandemic disrupting visiting subinternships. We hypothesize that a higher proportion of plastic surgery applicants matched at their home institution during the 2020–2021 application cycle secondary to the implementation of COVID-19–related restrictions. Methods Between March 24 and 27, 2021, we used publicly available, online plastic surgery–specific spreadsheets to analyze plastic surgery applicant information over the course of 3 application cycles (2018–2019, 2019–2020, and 2020–2021) for the top 50 plastic surgery programs. We collected data corresponding to the matched plastic surgery applicants' medical school, the institution at which they matched, and whether they had previous communication with their matched program. Results Our search yielded information on 128 applicants from the 2019 match cycle, 129 applicants from the 2020 match cycle, and 133 applicants from the 2021 application cycle. In 2019 and 2020, 15 (11.7%) and 22 (17.1%) plastic surgery applicants matched at their home program, respectively. In 2021, 32 (24.1%) of plastic surgery applicants matched at their home program (P = 0.032). When stratified by reputation rank, home program match rates among programs ranked 1–25 in 2021 had a large increase over the 2020 match cycle (28.4% vs 16.7%), whereas the home match rates of programs ranked 26–50 in 2021 (17.3%) held level with that of 2020 (17.6%). Conversely, for those not matched to their home programs, only 20 (19.8%) in 2021 reported having had any prior contact with their matched programs compared with 54 (50.5%) in 2020 (P < 0.001). Conclusions The 2020–2021 plastic surgery application cycle matched a significantly higher proportion of applicants at their home institution. With the temporary discontinuation of visiting subinternships during the 2020–2021 application cycle, it is likely that both plastic surgery programs and applicants compensate for this loss of in-person exposure by turning to home applicants and home institutions, respectively.
Testing for adaptive radiation: A new approach applied to Madagascar frogs *

Adaptive radiation is a key topic at the intersection of ecology and evolutionary biology. Yet the definition and identification of adaptive radiation both remain contentious. Here, we introduce a new approach for identifying adaptive radiations that combines key aspects of two widely used definitions. Our approach compares evolutionary rates in morphology, performance, and diversification between the candidate radiation and other clades. We then apply this approach to a putative adaptive radiation of frogs from Madagascar (Mantellidae). We present new data on morphology and performance from mantellid frogs, then compare rates of diversification and multivariate evolution of size, shape, and performance between mantellids and other frogs. We find that mantellids potentially pass our test for accelerated rates of evolution for shape, but not for size, performance, or diversification. Our results demonstrate that clades can have accelerated phenotypic evolution without rapid diversification (dubbed “adaptive non‐radiation”). We also highlight general issues in testing for adaptive radiation, including taxon sampling and the problem of including another adaptive radiation among the comparison clades. Finally, we suggest that similar tests should be conducted on other putative adaptive radiations on Madagascar, comparing their evolutionary rates to those of related clades outside Madagascar. Based on our results, we speculate that older Madagascar clades may show evolutionary patterns more similar to those on a continent than an island.
Is race important in genomic classification of hematological neoplasms?

In recent years, genome‐based classifications for hematological neoplasms have been proposed successively and proved to be more accurate than histologic classifications. However, some previous studies have reported the racial differences of genetic landscape in persons with hematological neoplasms including myelodysplastic syndromes (MDS), which may cause a genomic classification based on a particular ethnic group does not operate in other races. To determine whether race plays an important role in the genomic‐based classification, we validated a newly proposed genomic classification of MDS (J Clin Oncol.2021; JCO2001659), which was based on a large European database, in Chinese patients from our center. Our results showed significant differences between Chinese and European patients including proportion of each group to overall cohort when applying this novel genomic classification. Our data indicate that a genomic classification of hematological neoplasms probably should be revised according to specific genetic features in different races.
Outcomes of pregnancy during immunotherapy treatment for cancer: Analysis of clinical trials sponsored by the National Cancer Institute.

Despite expanding indications for immunotherapeutic agents, there is limited understanding about their clinical effects on pregnancy outcomes. Generally, pregnant cancer patients are excluded from clinical trials, and inadvertent pregnancies on trial result in patients being taken off due to concerns for fetal toxicity. To answer this question of pregnancy outcomes on immunotherapy-based trials, we performed a retrospective analysis of the National Cancer Institute's (NCI) Cancer Therapy Evaluation Program-Adverse Event Reporting System (CTEP-AERS) for unexpected pregnancies during NCI-CTEP sponsored immunotherapy clinical trials between 2011 and 2020. We identified 9 female patients who had unexpected pregnancies, of whom 7 chose to take their pregnancies to term. All 7 pregnancies resulted in vaginal births of apparently normal infants. This is the first report of pregnancy outcomes in multiple female patients exposed to immunotherapy. Our data suggest the need for further research to better evaluate and define contraception recommendations during immunotherapy treatment for cancer.
Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID

ABSTRACT The epidermis of Caenorhabditis elegans is an essential tissue for survival because it contributes to the formation of the cuticle barrier as well as facilitating developmental progression and animal growth. Most of the epidermis consists of the hyp7 hypodermal syncytium, the nuclei of which are largely generated by the seam cells, which exhibit stem cell-like behaviour during development. How seam cell progenitors differ transcriptionally from the differentiated hypodermis is poorly understood. Here, we introduce Targeted DamID (TaDa) in C. elegans as a method for identifying genes expressed within a tissue of interest without cell isolation. We show that TaDa signal enrichment profiles can be used to identify genes transcribed in the epidermis and use this method to resolve differences in gene expression between the seam cells and the hypodermis. Finally, we predict and functionally validate new transcription and chromatin factors acting in seam cell development. These findings provide insights into cell type-specific gene expression profiles likely associated with epidermal cell fate patterning.