bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Aberrant Data Variability on Drug–Placebo Separation and Drug/Placebo Response in an Acute Schizophrenia Clinical Trial
Authors: Kott Alan , Brannan Stephen , Wang Xingmei , Daniel David 
Published: August 2021

AbstractObjectiveIn the current posthoc analyses, we evaluated the impact of markers of aberrant data variability on drug placebo separation and placebo and drug response in an acute schizophrenia clinical trial.MethodsPositive and negative syndrome scale data were obtained from a phase 2, randomized, double-blind, placebo controlled trial in hospitalized adults with schizophrenia experiencing an acute exacerbation. We assessed the impact of a total of six markers of aberrant data variability: erratic ratings, unusually large postbaseline improvement, high and low mean square successive difference (MSSD), identical and nearly identical ratings and compared the drug placebo difference, drug and treatment response at last visit in affected subjects vs those not affected. All analyses were conducted using generalized linear models.ResultsIn this posthoc analysis, drug placebo separation decreased with the presence of most markers of aberrant data variability. The only exception was high MSSD was associated with significant increase in the signal. In the affected subjects, the presence of indicators of increased data variability augmented the response to placebo, in the case of large postbaseline change and high MSSD, significantly. The presence of indicators of decreased variability numerically but not statistically decreased the response to placebo. Similar findings were observed in the drug treatment group with the exception of erratic ratings that numerically but not statistically decreased the response to the drug.DiscussionThe presence of most indicators of aberrant data variability had a detrimental effect on drug-placebo separation and showed different effects on placebo and treatment response.
LncRNA DUXAP10 Upregulation and the Hedgehog Pathway Activation Are Critically Involved in Chronic Cadmium Exposure-Induced Cancer Stem Cell-Like Property
Authors: Lin Hsuan-Pei , Wang Zhishan , Yang Chengfeng 
Published: August 2021

Abstract
Cadmium (Cd) is a well-known lung carcinogen. However, the mechanism of Cd carcinogenesis remains to be clearly defined. Cd has been shown to act as a weak mutagen, suggesting that it may exert tumorigenic effect through nongenotoxic ways, such as epigenetic mechanisms. Long noncoding RNAs (lncRNAs) refer to RNA molecules that are longer than 200 nucleotides in length but lack protein-coding capacities. Regulation of gene expressions by lncRNAs is considered as one of important epigenetic mechanisms. The goal of this study is to investigate the mechanism of Cd carcinogenesis focusing on the role of lncRNA dysregulations. Cd-induced malignant transformation of human bronchial epithelia BEAS-2B cells was accomplished by a 9-month low-dose Cd (CdCl2, 2.5 µM) exposure. The Cd-exposed cells formed significantly more colonies in soft agar, displayed cancer stem cell (CSC)-like property, and formed tumors in nude mice. Mechanistically, chronic low-dose Cd exposure did not cause significant genotoxic effects but dysregulated lncRNA expressions. Further Q-PCR analysis confirmed the significant upregulation of the oncogenic lncRNA DUXAP10 in Cd-transformed cells. DUXAP10 knockdown in Cd-transformed cells significantly reduced their CSC-like property. Further mechanistic studies showed that the Hedgehog pathway is activated in Cd-transformed cells and inhibition of this pathway reduces Cd-induced CSC-like property. DUXAP10 knockdown caused the Hedgehog pathway inactivation in Cd-transformed cells. Furthermore, Pax6 expression was upregulated in Cd-transformed cells and Pax6 knockdown significantly reduced their DUXAP10 levels and CSC-like property. In summary, these findings suggest that the lncRNA DUXAP10 upregulation may play an important role in Cd carcinogenesis.
Total Vaginal Hysterectomy With Uterosacral Ligament Suspension Compared With Supracervical Hysterectomy With Sacrocervicopexy for Uterovaginal Prolapse
Authors: Giugale Lauren E. , Melnyk Alexandra I. , Ruppert Kristine M. , Napoe Gnankang S. , Lavelle Erin S. , Bradley Megan S. 
Published: August 2021

OBJECTIVE:
To compare prolapse recurrence after total vaginal hysterectomy with uterosacral ligament suspension to recurrence after supracervical hysterectomy with mesh sacrocervicopexy for the primary management of uterovaginal prolapse.

METHODS:
We conducted a retrospective cohort study of women undergoing uterovaginal prolapse repair at an academic center from 2009 to 2019. Women who underwent vaginal hysterectomy with uterosacral ligament suspension or laparoscopic supracervical hysterectomy with mesh sacrocervicopexy were included. The primary outcome was composite prolapse recurrence (prolapse beyond the hymen or retreatment with pessary or surgery). Secondary outcomes included mesh complications, time to recurrence, and overall reoperation for either prolapse recurrence or mesh complication. We used propensity scoring with a 2:1 ratio of sacrocervicopexy to uterosacral suspension.

RESULTS:
The cohort consisted of 654 patients, of whom 228 (34.9%) underwent uterosacral suspension and 426 (65.1%) underwent sacrocervicopexy. The median follow-up was longer for the sacrocervicopexy group (230 vs 126 days, P<.001) and less than 1 year for both groups. The uterosacral group had a greater proportion of composite prolapse recurrence (14.9% [34/228] vs 8.7% [37/426], P=.02) and retreatment for recurrent prolapse (7.5% [17/228] vs 2.8% [12/426], P=.02). The uterosacral group demonstrated a shorter time to prolapse recurrence on multivariable Cox regression (hazard ratio 3.14, 95% CI 1.90–5.16). There were 14 (3.3%) mesh complications in the sacrocervicopexy group. Overall reoperation was similar between groups (4.8% [11/228] vs 3.8% [16/426], P=.51).

CONCLUSION:
Total vaginal hysterectomy with uterosacral ligament suspension was associated with higher rate of, and shorter time-to-prolapse recurrence compared with supracervical hysterectomy with mesh sacrocervicopexy.
Intrauterine Adhesions After Chlamydia Infection With a Levonorgestrel-Releasing Intrauterine Device in Place
Authors: Schaub Amelia M. , Pisarska Margareta D. , Wright Kelly N. 
Published: August 2021

BACKGROUND:
Little is known about the long-term reproductive effects of pelvic infection when a levonorgestrel-releasing intrauterine device (LNG-IUD) is in situ. Society guidelines do not recommend removing an LNG-IUD during pelvic infection.

CASE:
A 37-year-old woman presented with primary infertility, and the only contributing factor was intrauterine adhesions in the shape of an IUD. She was known to previously have an LNG-IUD and was treated for asymptomatic chlamydia infection while the IUD was in place. After lysis of adhesions, she successfully conceived spontaneously.

CONCLUSION:
Data on long-term reproductive effects of pelvic infection with an LNG-IUD in situ are not available, and there may be consequences affecting the intrauterine milieu requiring further studies and potential counseling.
What is the Interobserver Reliability of an Ultrasound-enhanced Physical Examination of the Hip in Infants? A Prospective Study on the Ease of Acquiring Skills to Diagnose Hip Dysplasia
Authors: Jejurikar Neha , Moscona-Mishy León , Rubio Mónica , Cavallaro Romina , Castañeda Pablo 
Published: August 2021

Abstract

Background
Developmental dysplasia of the hip (DDH) is the most common disorder found in newborns. The consequences of DDH can be mitigated with early diagnosis and nonoperative treatment, but existing approaches do not address the current training deficit in making an early diagnosis.

Question/purpose
Can ultrasound be taught to and used reliably by different providers to identify DDH in neonates?

Methods
This was a prospective observational study of a series of neonates referred for an evaluation of their hips. An experienced clinician trained three second examiners (a pediatric orthopaedic surgeon, an orthopaedic resident, and a pediatrician) in performing an ultrasound-enhanced physical examination. The 2-hour training process included video and clinical didactic sessions aimed to teach examiners to differentiate between stable and unstable hips in newborns using ultrasound. The experienced clinician was a pediatric orthopaedic surgeon who uses ultrasound regularly in clinical practice. Materials required for training include one ultrasound device. A total of 227 infants (454 hips) were examined by one of the three second examiners and the experienced clinician (gold standard) to assess reliability. Of the 454 hips reviewed, there were 18 dislocations, 24 unstable hips, and 63 dysplastic hips, and the remainder had normal findings. The cohort was composed of a series of patients younger than 6 months referred to a specialty pediatric orthopaedic practice.

Results
Ultrasound-enhanced physical examination of the hip was easily taught, and the results were reliable among different levels of providers. The intraclass correlation coefficient between the gold-standard examiner and the other examiners for all hips was 0.915 (p = 0.001). When adjusting for only the binary outcome of normal versus abnormal hips, the intraclass correlation coefficient was 0.97 (p = 0.001). Thus, the agreement between learners and the experienced examiner was very high after learners completed the course.

Conclusion
After a 2-hour course, physicians were able to understand and reliably examine neonatal children using ultrasound to assess for DDH. The success of the didactic approach outlined in this study supports the need for ultrasound-enhanced examination training for the diagnosis of DDH in orthopaedic surgery and pediatric residency core curriculums. Training programs would best be supported through established residency programs. Expansion of training more residents in the use of ultrasound-enhanced physical examinations would require a study to determine its efficacy. This finding highlights the need for further research in implementing ultrasound-enhanced physical examinations on a broader scale.

Level of Evidence
Level II, diagnostic study.
The clinical features and prognostic outcomes of primary mediastinal yolk sac tumors
Authors: Qin Li , Zhu Menglin , Wang Tiejun , Wang Hongli , Pan Qin , He Du 
Published: August 2021

Abstract
Primary mediastinal yolk sac tumors (PMYSTs) are a rare occurrence. As such, the clinicopathological features, treatment, and prognosis, of this disease still remain unclear. In this study, we aimed to provide further information relating to this rare malignancy in order to facilitate the creation of more specific clinical guidelines for the diagnosis and treatment of patients with PMYSTs.
In this retrospective study, we recruited 15 patients who had been diagnosed with PMYST from four medical institutions to create a population-based cohort. We then used Kaplan-Meier analysis and the log-rank test to investigate and compare overall survival (OS) and progression-free survival (PFS).
A total of 15 cases were identified. The mean age was 27.3 years (range: 19–34 years). The estimated 1- and 2-year PFS rates were 66.7% and 60.0%, respectively. The 1- and 2-year OS rates were both 73.3%. Computer tomography scans revealed tumors were located in the anterior middle mediastinum (5 cases), the anterior superior mediastinum (1 case), the left anterior mediastinum (3 cases), and the right anterior mediastinum (6 cases). Of the 15 patients receiving extended resections, the majority (40.0%) underwent tumor resection, partial pericardiotomy, pulmonary wedge resection, and mediastinal lymphadenectomy. R0 resections were achieved in eleven patients. Four patients underwent R2 resection and experienced postoperative complications, including pneumonia (2 cases), atelectasis (1 case), and bronchopleural fistula (1 case). Four patients developed postoperative lung metastasis. Three patients died due to progressive diseases. Disease recurred in all patients at a median of 8.0 months (range: 6.0–11.0 months).
PMYST is a rare but highly malignant tumor with a poor prognosis. Tumor resection, with optimal extended surgical management, may provide patients with the best chance of a cure although postoperative complications relating to the pulmonary systems should be treated with caution.
Effects of depth of neuromuscular blockade on the BIS-guided propofol requirement
Authors: Nam Sun Woo , Oh Ah-Young , Koo Bon-Wook , Kim Bo Young , Han Jiwon , Chung Sung Hoon 
Published: August 2021

Abstract

Background:
Deep neuromuscular blockade is considered beneficial for improving the surgical space condition during laparoscopic surgery. Adequacy of the surgical space condition may affect the anesthetists’ decision regarding titration of depth of anesthesia. We investigated whether deep neuromuscular blockade reduces the propofol requirement under bispectral index monitoring compared to moderate neuromuscular blockade.

Methods:
Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to a moderate or deep group. A train-of-four count of 1–2 in the moderate group, and a post-tetanic count of 1–2 in the deep group, were maintained by continuous infusion of rocuronium. The induction and maintenance of anesthesia were achieved by target-controlled infusion of propofol and remifentanil. The dose of propofol was adjusted to maintain the bispectral index in the range of 40–50. The remifentanil dose was titrated to maintain the systolic blood pressure to within 20% of the ward values.

Results:
A total of 82 patients were included in the analyses. The mean±SD dose of propofol was 7.54 ± 1.66 and 7.42 ± 1.01 mg·kg−1·h−1 in the moderate and deep groups, respectively (P = .104). The mean±SD dose of remifentanil was 4.84 ± 1.74 and 4.79 ± 1.77 μg kg−1 h−1 in the moderate and deep groups, respectively (P = .688). In comparison to the moderate group, the deep group showed significantly lower rates of intraoperative patient movement (42.9% vs 22.5%, respectively, P = .050) and additional neuromuscular blocking agent administration (76% vs 53%, respectively, P = .007). Postoperative complications, including pulmonary complications, wound problems and reoperation, were not different between the two groups.

Conclusion:
Deep neuromuscular blockade did not reduce the bispectral index-guided propofol requirement compared to moderate neuromuscular blockade during laparoscopic colon surgery, despite reducing movement of the patient and the requirement for a rescue neuromuscular blocking agent.

Trial registration:
Clinicaltrials.gov (NCT03890406)
Negative impact of COVID-19 associated health system shutdown on patients diagnosed with colorectal cancer: a retrospective study from a large tertiary center in Ontario, Canada
Authors: Forse Catherine L. , Petkiewicz Stephanie , Teo Iris , Purgina Bibianna , Klaric Kristina-Ana , Ramsay Tim , Wasserman Jason K. 
Published: August 2021

AbstractBackgroundIn March 2020, a directive to halt all elective and non-urgent procedures was issued in Ontario, Canada because of COVID-19. The directive caused a temporary slowdown of screening programs including surveillance colonoscopies for colorectal cancer (CRC). Our goal was to determine if there was a difference in patient and tumour characteristics between CRC patients treated surgically prior to the COVID-19 directive compared to CRC patients treated after the slowdown.MethodsCRC resections collected within the Champlain catchment area of eastern Ontario in the six months prior to COVID-19 (August 1, 2019-January 31, 2020) were compared to CRC resections collected in the six months post-COVID-19 slowdown (August 1, 2020-January 31, 2021). Clinical (e.g. gender, patient age, tumour site, clinical presentation) and pathological (tumour size, tumour stage, nodal stage, lymphovascular invasion) features were evaluated using chi square tests, T-tests and Mann-Whitney tests where appropriate.Results343 CRC specimens were identified (175 pre-COVID-19, 168 post-COVID-19 slowdown). CRC patients treated surgically post-COVID-19 slowdown had larger tumours (44 mm vs. 35 mm; p = 0.0048) and were more likely to have presented emergently (24% vs .10%; p < 0.001). While there was a trend towards higher tumour stage, nodal stage, and clinical stage, these differences did not reach statistical significance. Other demographic and pathologic variables including patient gender, age, and tumour site were similar between the two cohorts.InterpretationThe COVID-19 slowdown resulted in a shift in the severity of disease experienced by CRC patients in Ontario. Pandemic planning in the future should consider the long-term consequences to cancer diagnosis and management.
Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing post-COVID-19
Authors: Cassar Mark Philip , Tunnicliffe Elizabeth M. , Petousi Nayia , Lewandowski Adam J. , Xie Cheng , Mahmod Masliza , Abd Samat Azlan Helmy , Evans Rachael A. , Brightling Christopher E. , Ho Ling-Pei , Piechnik Stefan K. , Talbot Nick P. , Holdsworth David , Ferreira Vanessa M. , Neubauer Stefan , Raman Betty 
Published: August 2021

AbstractBackgroundThe longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19.MethodsFifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months.FindingsAt 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1(marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET.By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (−4·3 mls/m2,P=0·005) decreased and RV ejection fraction (+3·2%,P=0·0003) increased. Native T1and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures.InterpretationIn patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.FundingNIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.
Epidemiology of 869,220 varicose vein surgeries over 12 years in Brazil: trends, costs and mortality rate
Authors: Silva Marcela Juliano , Sposato Louzada Andressa Cristina , Alexandrino da Silva Marcelo Fiorelli , Cassino Portugal Maria Fernanda , Teivelis Marcelo Passos , Wolosker Nelson 
Published: August 2021

2.Structured AbstractObjectivesto assess the total numbers of surgical procedures performed between 2008 and 2019 for the treatment of varicose veins in the Public Health System, which exclusively insures more than 160 million Brazilians, the distribution of surgeries over time, as well as its costs and mortality rates.Study designretrospective cross-sectional population-based studyMaterials and Methodspublic and open data referring to all surgeries to treat chronic venous disease between 2008 and 2019 were extracted from the database of the Brazilian Public Health System.ResultsIn total, 869,220 surgeries were performed to treat chronic venous disease in public hospitals and outpatient clinics in Brazil, with an average rate of 4.5 surgeries per 10,000 inhabitants per year. From 2015 on, we observed a slight downward trend in the total number of procedures. The total amount reimbursed by the government was US$ 232,775,518.11. A total of 49 deaths were registered following varicose vein surgery, corresponding to a mortality rate of 0.0056%.Conclusionsa total of 869,220 surgeries performed to treat chronic venous disease over twelve years, with an overall rate of 4.52 procedures per 10,000 inhabitants per year. The mortality rate was very low, 0.0056%.
ExhauFS: exhaustive search-based feature selection for classification and survival regression
Authors: Nersisyan Stepan , Novosad Victor , Galatenko Alexei , Sokolov Andrey , Bokov Grigoriy , Konovalov Alexander , Alekseev Dmitry , Tonevitsky Alexander 
Published: August 2021

AbstractMotivationFeature selection is one of the main techniques used to prevent overfitting in machine learning applications. The most straightforward approach for feature selection is exhaustive search: one can go over all possible feature combinations and pick up the model with the highest accuracy. This method together with its optimizations were actively used in biomedical research, however, publicly available implementation is missing.ResultsWe present ExhauFS – the user-friendly command-line implementation of the exhaustive search approach for classification and survival regression. Aside from tool description, we included three application examples in the manuscript to comprehensively review the implemented functionality. First, we executed ExhauFS on a toy cervical cancer dataset to illustrate basic concepts. Then, a multi-cohort microarray and RNA-seq breast cancer datasets were used to construct gene signatures for 5-year recurrence classification. Finally, Cox survival regression models were used to fit isomiR signatures for overall survival prediction for patients with colorectal cancer.AvailabilitySource codes and documentation of ExhauFS are available on GitHub: https://github.com/s-a-nersisyan/ExhauFS.Contactsnersisyan@hse.ru
The heterogeneity of the DNA damage response landscape determines patient outcomes in ovarian cancer
Authors: Walker TDJ , Faraahi ZF , Price MJ , Hawarden A , Waddell CA , Russell B , Jones DM , McCormick A , Gavrielides N , Tyagi S , Woodhouse LC , Whalley B , Roberts C , Crosbie EJ , Edmondson RJ 
Published: August 2021

AbstractDefective DNA damage response (DDR) pathways allow cancer cells to accrue genomic aberrations and evade normal cellular growth checkpoints. Defective DDR also determines response to chemotherapy. However, the interaction and overlap between the two double strand repair pathways and the three single strand repair pathways is complex, and has remained poorly understood.Here we show that, in ovarian cancer, a disease hallmarked by chromosomal instability, explant cultures show a range of DDR abrogation patterns. Defective homologous recombination (HR) and non-homologous end joining (NHEJ) are near mutually exclusive with HR deficient (HRD) cells showing increased abrogation of the single strand repair pathways compared to NHEJ defective cells.When combined with global markers of DNA damage, including mitochondrial membrane functionality and reactive oxygen species burden, the pattern of DDR abrogation allows the construction of DDR signatures which are predictive of bothex vivocytotoxicity, and more importantly, patient outcome.SignificanceHolistic assessment of the DDR is possible, shows improved ability to predict response to chemotherapy over single pathway assessment, and is applicable to a variety of ovarian cancer types. Such an assessment has clinical utility in settings of therapeutic dilemma such as retreatment for relapse.