bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective study of small-pelvis radiotherapy plus image-guided brachytherapy in stage I–II non-bulky cervical squamous cell carcinoma
Authors: Yoshimoto Yuya , Murata Kazutoshi , Irie Daisuke , Ando Ken , Adachi Akiko , Aoki Hiroshi , Hirakawa Takashi , Noda Shin-ei , Nakano Takashi , Ohno Tatsuya
Published: January 2022

We herein report a retrospective analysis of the efficacy of a combination therapy of pelvic irradiation that excluded the common iliac lymph nodes region and image-guided brachytherapy (IGBT) for non-bulky (≤4 cm) cervical cancer. Thirty-three patients with stage I–II cervical squamous cell carcinoma (≤4 cm) and without pelvic/para-aortic lymphadenopathy who were treated with definitive radiotherapy alone between February 2009 and September 2016 were included. The radiotherapy consisted of CT-based small-pelvis irradiation (whole pelvis minus common iliac lymph node area) of 20 Gy/10 fractions followed by pelvic irradiation with a midline block of 30 Gy/15 fractions and IGBT of 24 Gy/4 fractions (6 Gy/fraction for high-risk [HR] clinical target volume [CTV] D90%). In-room computed tomography (CT) imaging with applicator insertion was used for brachytherapy planning, with physical examinations and diagnostic magnetic resonance imaging (MRI) also being referred to for determination of HR CTV. Over a median follow-up of 60.5 months (range, 7–89), two patients developed distant recurrence and one developed local and distant recurrence. Two patients died from cervical cancer, one from hepatocellular carcinoma and one from non-cancerous disease. The 2/5-year local control (LC), progression-free survival (PFS) and overall survival (OS) rates were 100%/96.7%, 93.8%/90.6% and 93.9%/93.9%, respectively. No pelvic/para-aortic lymph node recurrence was observed. There were no late complications of grade 3 or higher in the small bowel, large bowel/rectum, or bladder. Our results suggest that a combination therapy of IGBT plus small-pelvis irradiation excluding common iliac lymph nodes provides reasonable clinical outcomes and can be a treatment option in non-bulky (≤4 cm) cervical squamous cell carcinoma.
BEBOP II: sensitivity to sub-Saturn circumbinary planets using radial-velocities
Authors: Standing Matthew R , Triaud Amaury H M J , Faria João P , Martin David V , Boisse Isabelle , Correia Alexandre C M , Deleuil Magali , Dransfield Georgina , Gillon Michaël , Hébrard Guillaume , Hellier Coel , Kunovac Vedad , Maxted Pierre F L , Mardling Rosemary , Santerne Alexandre , Sairam Lalitha , Udry. Stéphane
Published: January 2022

BEBOP is a radial-velocity survey that monitors a sample of single-lined eclipsing binaries, in search of circumbinary planets by using high-resolution spectrographs. Here, we describe and test the methods we use to identify planetary signals within the BEBOP data and establish how we quantify our sensitivity to circumbinary planets by producing detection limits. This process is made easier and more robust by using a diffusive nested sampler. In the process of testing our methods, we notice that contrary to popular wisdom, assuming circular orbits in calculating detection limits for a radial-velocity survey provides overoptimistic detection limits by up to $40{{\ \rm per\ cent}}$ in semi-amplitude with implications for all radial-velocity surveys. We perform example analyses using three BEBOP targets from our Southern HARPS survey. We demonstrate for the first time a repeated ability to reach a residual root mean squared scatter of $3\, \rm m\, s^{-1}$ (after removing the binary signal), and find that we are sensitive to circumbinary planets with masses down to that of Neptune and Saturn, for orbital periods up to $1000\, \rm d$.
Is FRB 191001 embedded in a supernova remnant?
Authors: Kundu Esha
Published: January 2022

Fast radio burst (FRB) 191001 is localized at the spiral arm of a highly star-forming galaxy with an observed dispersion measure (DM) of 507 $\mbox{pc cm$^{-3}$}$. Subtracting the contributions of the intergalactic medium and our Milky Way Galaxy from the total DM, one gets an excess of around 200 $\mbox{pc cm$^{-3}$}$, which may have been contributed by the host galaxy of the FRB. It is found in this work that the position of FRB 191001 is consistent with the distribution of supernovae (SNe) in the spiral arm of their parent galaxies. If this event is indeed due to an SN explosion, then, from the analysis of the SN contributions to the excess DM, a core-collapse (CC) channel is preferred over a thermonuclear runaway. For the CC explosion, depending on the density of the surrounding medium, the age of the central engine that powers the radio burst is within a couple of years to a few decades. However, the observed rotation measure of FRB 191001 does not confirm the fact that the radio burst has passed through the remnant of a young SN.
RNA modifications stabilize the tertiary structure of tRNAfMet by locally increasing conformational dynamics
Authors: Biedenbänder Thomas , de Jesus Vanessa , Schmidt-Dengler Martina , Helm Mark , Corzilius Björn , Fürtig Boris
Published: January 2022

A plethora of modified nucleotides extends the chemical and conformational space for natural occurring RNAs. tRNAs constitute the class of RNAs with the highest modification rate. The extensive modification modulates their overall stability, the fidelity and efficiency of translation. However, the impact of nucleotide modifications on the local structural dynamics is not well characterized. Here we show that the incorporation of the modified nucleotides in tRNAfMet from Escherichia coli leads to an increase in the local conformational dynamics, ultimately resulting in the stabilization of the overall tertiary structure. Through analysis of the local dynamics by NMR spectroscopic methods we find that, although the overall thermal stability of the tRNA is higher for the modified molecule, the conformational fluctuations on the local level are increased in comparison to an unmodified tRNA. In consequence, the melting of individual base pairs in the unmodified tRNA is determined by high entropic penalties compared to the modified. Further, we find that the modifications lead to a stabilization of long-range interactions harmonizing the stability of the tRNA’s secondary and tertiary structure. Our results demonstrate that the increase in chemical space through introduction of modifications enables the population of otherwise inaccessible conformational substates.
The transcriptional elongation factor CTR9 demarcates PRC2-mediated H3K27me3 domains by altering PRC2 subtype equilibrium
Authors: Chan Ngai Ting , Huang Junfeng , Ma Gui , Zeng Hao , Donahue Kristine , Wang Yidan , Li Lingjun , Xu Wei
Published: January 2022

CTR9 is the scaffold subunit in polymerase-associated factor complex (PAFc), a multifunctional complex employed in multiple steps of RNA Polymerase II (RNAPII)-mediated transcription. CTR9/PAFc is well known as an evolutionarily conserved elongation factor that regulates gene activation via coupling with histone modifications enzymes. However, little is known about its function to restrain repressive histone markers. Using inducible and stable CTR9 knockdown breast cancer cell lines, we discovered that the H3K27me3 levels are strictly controlled by CTR9. Quantitative profiling of histone modifications revealed a striking increase of H3K27me3 levels upon loss of CTR9. Moreover, loss of CTR9 leads to genome-wide expansion of H3K27me3, as well as increased recruitment of PRC2 on chromatin, which can be reversed by CTR9 restoration. Further, CTR9 depletion triggers a PRC2 subtype switch from the less active PRC2.2, to the more active PRC2.1 with higher methyltransferase activity. As a consequence, CTR9 depletion generates vulnerability that renders breast cancer cells hypersensitive to PRC2 inhibitors. Our findings that CTR9 demarcates PRC2-mediated H3K27me3 levels and genomic distribution provide a unique mechanism that explains the transition from transcriptionally active chromatin states to repressive chromatin states and sheds light on the biological functions of CTR9 in development and cancer.
FILER: a framework for harmonizing and querying large-scale functional genomics knowledge
Authors: Kuksa Pavel P , Leung Yuk Yee , Gangadharan Prabhakaran , Katanic Zivadin , Kleidermacher Lauren , Amlie-Wolf Alexandre , Lee Chien-Yueh , Qu Liming , Greenfest-Allen Emily , Valladares Otto , Wang Li-San
Published: January 2022

Querying massive functional genomic and annotation data collections, linking and summarizing the query results across data sources/data types are important steps in high-throughput genomic and genetic analytical workflows. However, these steps are made difficult by the heterogeneity and breadth of data sources, experimental assays, biological conditions/tissues/cell types and file formats. FILER (FunctIonaL gEnomics Repository) is a framework for querying large-scale genomics knowledge with a large, curated integrated catalog of harmonized functional genomic and annotation data coupled with a scalable genomic search and querying interface. FILER uniquely provides: (i) streamlined access to >50 000 harmonized, annotated genomic datasets across >20 integrated data sources, >1100 tissues/cell types and >20 experimental assays; (ii) a scalable genomic querying interface; and (iii) ability to analyze and annotate user’s experimental data. This rich resource spans >17 billion GRCh37/hg19 and GRCh38/hg38 genomic records. Our benchmark querying 7 × 109 hg19 FILER records shows FILER is highly scalable, with a sub-linear 32-fold increase in querying time when increasing the number of queries 1000-fold from 1000 to 1 000 000 intervals. Together, these features facilitate reproducible research and streamline integrating/querying large-scale genomic data within analyses/workflows. FILER can be deployed on cloud or local servers (https://bitbucket.org/wanglab-upenn/FILER) for integration with custom pipelines and is freely available (https://lisanwanglab.org/FILER).
Matching anticancer compounds and tumor cell lines by neural networks with ranking loss
Authors: Prasse Paul , Iversen Pascal , Lienhard Matthias , Thedinga Kristina , Bauer Chris , Herwig Ralf , Scheffer Tobias
Published: January 2022

Computational drug sensitivity models have the potential to improve therapeutic outcomes by identifying targeted drug components that are likely to achieve the highest efficacy for a cancer cell line at hand at a therapeutic dose. State of the art drug sensitivity models use regression techniques to predict the inhibitory concentration of a drug for a tumor cell line. This regression objective is not directly aligned with either of these principal goals of drug sensitivity models: We argue that drug sensitivity modeling should be seen as a ranking problem with an optimization criterion that quantifies a drug’s inhibitory capacity for the cancer cell line at hand relative to its toxicity for healthy cells. We derive an extension to the well-established drug sensitivity regression model PaccMann that employs a ranking loss and focuses on the ratio of inhibitory concentration and therapeutic dosage range. We find that the ranking extension significantly enhances the model’s capability to identify the most effective anticancer drugs for unseen tumor cell profiles based in on in-vitro data.
Egg consumption and risks of all-cause and cause-specific mortality: a dose–response meta-analysis of prospective cohort studies
Authors: Yang Peng-Fei , Wang Chun-Rui , Hao Fa-Bao , Peng Yang , Wu Jing-Jing , Sun Wei-Ping , Hu Jie-Jun , Zhong Guo-Chao
Published: January 2022

Context

Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the dose-response association of egg consumption with risk of mortality has not been determined.

Objective

To determine the potential dose-response association of egg consumption with risk of mortality in the general population.

Data Sources

The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021.

Data Extraction

Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system.

Data Analysis

Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01–1.15) for all-cause mortality, 1.07 (95%CI, 0.97–1.18) for cardiovascular disease–caused mortality, and 1.16 (95%CI, 1.04–1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease–caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011).

Conclusions

Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.
Comparison of the Clinical Outcomes of Patients With Positive Xpert Carba-R Tests for Carbapenemase-Producing Enterobacterales According to Culture Positivity
Authors: Seo Hyeonji , Lee Jeong-Young , Ryu Seung Hee , Kwak Sun Hee , Kim Eun Ok , Bae Seongman , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Sung Heungsup , Kim Mi-Na , Kim Yang Soo , Jung Jiwon
Published: January 2022

Background

We aimed to compare the clinical outcomes of patients with positive Xpert Carba-R assay results for carbapenemase-producing Enterobacterales (CPE) according to CPE culture positivity.

Methods

We retrospectively collected data for patients with positive CPE (positive Xpert Carba-R or culture) who underwent both tests from August 2018 to March 2021 in a 2700-bed tertiary referral hospital in Seoul, South Korea. We compared the clinical outcomes of patients positive for Xpert Carba-R according to whether they were positive (XPCP) or negative (XPCN) for CPE culture.

Results

Of 322 patients with CPE who underwent both Xpert Carba-R and culture, 313 (97%) were positive for Xpert Carba-R for CPE. Of these, 87 (28%) were XPCN, and 226 (72%) were XPCP. XPCN patients were less likely to have a history of previous antibiotic use (75.9% vs 90.3%; P = .001) and to have Klebsiella pneumoniae carbapenemase (21.8% vs 48.9%; P < .001). None of the XPCN patients developed infection from colonization within 6 months, whereas 13.4% (29/216) of the XPCP patients did (P < .001). XPCN patients had lower transmission rates than XPCP patients (3.0% [9/305] vs 6.3% [37/592]; P = .03). There was no significant difference in CPE clearance from positive culture results between XPCN and XPCP patients (40.0% [8/20] vs 26.7% [55/206]; P = .21).

Conclusions

Our study suggests that XPCN patients had lower rates of both infection and transmission than XPCP patients. The Xpert Carba-R assay is clinically useful not only for rapid identification of CPE but also for predicting risks of infection and transmission when performed along with culture.
Marital Status, Living Arrangement, and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings from CALGB 89803 (Alliance)
Authors: Lee Seohyuk , Ma Chao , Zhang Sui , Ou Fang-Shu , Bainter Tiffany M , Niedzwiecki Donna , Saltz Leonard B , Mayer Robert J , Whittom Renaud , Hantel Alexander , Benson Al , Atienza Daniel , Kindler Hedy , Gross Cary P , Irwin Melinda L , Meyerhardt Jeffrey A , Fuchs Charles S
Published: January 2022

Background

Limited and conflicting findings have been reported regarding the association between social support and colorectal cancer (CRC) outcomes. We sought to assess the influences of marital status and living arrangement on survival outcomes among patients with stage III colon cancer.

Patients and Methods

We conducted a secondary analysis of 1082 patients with stage III colon cancer prospectively followed in the CALGB 89803 randomized adjuvant chemotherapy trial. Marital status and living arrangement were both self-reported at the time of enrollment as, respectively, married, divorced, separated, widowed, or never-married, and living alone, with a spouse or partner, with other family, in a nursing home, or other.

Results

Over a median follow-up of 7.6 years, divorced/separated/widowed patients experienced worse outcomes relative to those married regarding disease free-survival (DFS) (hazards ratio (HR), 1.44 (95% CI, 1.14-1.81); P =.002), recurrence-free survival (RFS) (HR, 1.35 (95% CI, 1.05-1.73); P = .02), and overall survival (OS) (HR, 1.40 (95% CI, 1.08-1.82); P =.01); outcomes were not significantly different for never-married patients. Compared to patients living with a spouse/partner, those living with other family experienced a DFS of 1.47 (95% CI, 1.02-2.11; P = .04), RFS of 1.34 (95% CI, 0.91-1.98; P = .14), and OS of 1.50 (95% CI, 1.00-2.25; P =.05); patients living alone did not experience significantly different outcomes.

Conclusion

Among patients with stage III colon cancer who received uniform treatment and follow-up within a nationwide randomized clinical trial, being divorced/separated/widowed and living with other family were significantly associated with greater colon cancer mortality. Interventions enhancing social support services may be clinically relevant for this patient population.

Trial Registration

ClinicalTrials.gov Identifier: NCT00003835
Gender Ramifications of a Weberian Bureaucracy: A Feminist Appraisal of the United States Department of Agriculture
Authors: Viswanath Shilpa , Samanta Aritree
Published: January 2022

In the field of public administration, a feminist appraisal of Weber’s bureaucracy has transpired gradually. In this article, we examine the gender ramifications of Weberian bureaucracy, with a specific focus on the United States Department of Agriculture (USDA). Using the feminist critique of the field at large, and the framework of bureau men and settlement women in particular, we critically analyze Weber’s ideas of an ideal bureaucracy. Our central contribution is intermeshing Stiver’s critical perspectives with the theoretical frames of feminist phenomenology and feminist standpoint theory to craft a feminist model for appraising the agricultural bureaucracy in the United States. In doing so, we demonstrate how women farmers’ and landowners’ approach to agriculture and farm management is fundamentally different in values and orientation than the USDA’s Weberian bureaucratic approach which dictates the design and implementation of agricultural policy.
Transition between vacuum and finite-density states in the infinite-dimensional Bose–Hubbard model with spatially inhomogeneous dissipation
Authors: Asai Shiono , Goto Shimpei , Danshita Ippei
Published: January 2022

We analyze the dynamics of the infinite-dimensional Bose–Hubbard model with spatially inhomogeneous dissipation in the hardcore boson limit by solving the Lindblad master equation with use of the Gutzwiller variational method. We consider dissipation processes that correspond to inelastic light scattering in the case of Bose gases in optical lattices. We assume that the dissipation is applied to half of the lattice sites in a spatially alternating manner. We focus on steady states at which the system arrives after long time evolution. We find that when the average particle density is varied, the steady state exhibits a transition between a state in which the sites without dissipation are vacuum and one containing a finite number of particles at those sites. We associate the transition with the notion that the sites with dissipation tend towards a local state at infinite temperature.
Exercise and Manual Therapy for the Treatment of Primary Headache: An Umbrella and Mapping Review
Authors: Varangot-Reille Clovis , Suso-Martí Luis , Dubuis Valentin , Cuenca-Martínez Ferran , Blanco-Díaz María , Salar-Andreu Cristina , Casaña Jose , Calatayud Joaquín
Published: January 2022

Objective

The main aim of this study was to assess through systematic review the efficacy of exercise and manual therapy (MT) interventions in individuals with primary headache.

Methods

In this umbrella review, 2 authors reviewed systematic reviews by searching the Cochrane Database of Systematic Reviews, MEDLINE, PEDro, Web of Science, and Google Scholar. Systematic reviews that evaluated the effectiveness of MT. Exercise-based interventions, or both in patients with primary headaches were included. Methodological quality was analyzed using the ROBIS scale, and the strength of evidence was established according to the Grading Criteria of the Physical Activity Guidelines Advisory Committee.

Results

Thirty-one systematic reviews containing 79 trials and involving 9103 patients were included. The 7 exercise-related systematic reviews reported beneficial effects on primary headache based on unclear to moderate evidence. Of the 23 MT-related systematic reviews, 11 reported enhanced effectiveness compared with usual care; however, overall heterogeneity and risk of bias were high. Systematic reviews that evaluated the effectiveness of MT, exercise-based interventions, or both in patients with primary headaches were included.

Conclusion

Results show that exercise could be an effective therapy for the treatment of primary headache, with moderate to limited quality of evidence regarding the positive effects in terms of pain intensity and frequency and duration of headache. Moderate quality of evidence was found regarding the ability of MT to reduce pain intensity in patients with tension-type headaches, but quality of evidence was limited in terms of frequency of headache and disability and pain reduction in patients with migraine.

Impact

Exercise could be an effective treatment in patients with primary headache. Manual therapy showed limited evidence to reduce pain intensity in patients with tension-type headache. It is not possible to establish a preferential exercise protocol or MT program, so psychosocial and behavioral variables need to be considered in future studies.
ASSESSMENT OF OCCUPATIONAL EXPOSURE LEVELS OF CLEANING PRODUCT MANUFACTURING FACTORY WORKERS TO ELECTROMAGNETIC FIELDS
Authors: Cerezci Osman , Kanberoglu Baha , Yener Suayb Cagri
Published: January 2022

Determination of the levels of the electromagnetic field of frequency between 0 Hz and 300 GHz bands in the working area and the evaluation of the results measured in terms of international standards is now essential according to the regulation of working safety and health. In this study, electromagnetic field measurements were performed in a cleaning product manufacturing factory with 400 workers. Electric and magnetic field measurements were performed at 10 different departments of the factory with extremely low-frequency and broadband (radiofrequency) frequencies. Obtained values are shown and analysed with graphs and compared by the International Commission on Non-Ionizing Radiation Protection and National Information Technology and Communication Authority (Turkey) limits. Also, an assessment is made for the occupational electromagnetic field levels in the factory and recommendations are suggested for the lowest risk occurrence and providing a healthier working environment for workers.
Learning to Discern the Voices of Gods, Spirits, Tulpas, and the Dead
Authors: Luhrmann Tanya M , Alderson-Day Ben , Chen Ann , Corlett Philip , Deeley Quinton , Dupuis David , Lifshitz Michael , Moseley Peter , Peters Emmanuelle , Powell Adam , Powers Albert
Published: January 2022

There are communities in which hearing voices frequently is common and expected, and in which participants are not expected to have a need for care. This paper compares the ideas and practices of these communities. We observe that these communities utilize cultural models to identify and to explain voice-like events—and that there are some common features to these models across communities. All communities teach participants to “discern,” or identify accurately, the legitimate voice of the spirit or being who speaks. We also observe that there are roughly two methods taught to participants to enable them to experience spirits (or other invisible beings): trained attention to inner experience, and repeated speech to the invisible other. We also observe that all of these communities model a learning process in which the ability to hear spirit (or invisible others) becomes more skilled with practice, and in which what they hear becomes clearer over time. Practice—including the practice of discernment—is presumed to change experience. We also note that despite these shared cultural ideas and practices, there is considerable individual variation in experience—some of which may reflect psychotic process, and some perhaps not. We suggest that voice-like events in this context may be shaped by cognitive expectation and trained practice as well as an experiential pathway. We also suggest that researchers could explore these common features both as a way to help those struggling with psychosis, and to consider the possibility that expectations and practice may affect the voice-hearing experience.
Examining the impact of employment status on sleep quality during the COVID-19 pandemic in two low-income neighborhoods in Pittsburgh, PA
Authors: Baird Matthew D , Dubowitz Tamara , Cantor Jonathan , Troxel Wendy M
Published: January 2022

Study Objectives

African Americans have faced disproportionate socioeconomic and health consequences associated with the COVID-19 pandemic. The current study examines employment and its association with sleep quality during the initial months of the pandemic in a low-income, predominantly African American adult sample.

Methods

In the early months of COVID-19 (March to May 2020), we administered a survey to an ongoing, longitudinal cohort of older adults to assess the impact of COVID-related changes in employment on self-reported sleep quality (N = 460; 93.9% African American). Participants had prior sleep quality assessed in 2018 and a subset also had sleep quality assessed in 2013 and 2016. Primary analyses focused on the prevalence of poor sleep quality and changes in sleep quality between 2018 and 2020, according to employment status. Financial strain and prior income were assessed as moderators of the association between employment status and sleep quality. We plotted trend lines showing sleep quality from 2013 to 2020 in a subset (n = 339) with all four waves of sleep data available.

Results

All participants experienced increases in poor sleep quality between 2018 and 2020, with no statistical differences between the employment groups. However, we found some evidence of moderation by financial strain and income. The trend analysis demonstrated increases in poor sleep quality primarily between 2018 and 2020.

Conclusions

Sleep quality worsened during the pandemic among low-income African American adults. Policies to support the financially vulnerable and marginalized populations could benefit sleep quality.
Improvements in cognitive function and quantitative sleep electroencephalogram in obstructive sleep apnea after six months of continuous positive airway pressure treatment
Authors: D’Rozario Angela L , Hoyos Camilla M , Wong Keith K H , Unger Gunnar , Kim Jong Won , Vakulin Andrew , Kao Chien-Hui , Naismith Sharon L , Bartlett Delwyn J , Grunstein Ronald R
Published: January 2022

Study Objectives

Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function.

Methods

We studied 167 patients with OSA (age 50 ± 13, AHI 35.0 ± 26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline.

Results

Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment.

Conclusions

Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.
Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience
Authors: Macías-Sánchez María del Mar , Morata-Tarifa Cynthia , Cuende Natividad , Cardesa-Gil Ana , Cuesta-Casas María Ángeles , Pascual-Cascon María Jesús , Pascual Antonia , Martín-Calvo Carmen , Jurado Manuel , Perez-Simón José Antonio , Espigado Ildefonso , Garzón López Sebastián , Carmona Sánchez Gloria , Mata-Alcázar-Caballero Rosario , Sánchez-Pernaute Rosario
Published: January 2022

Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.
The effects of differing nutritional levels and body condition score on scrotal circumference, motility, and morphology of bovine sperm
Authors: Harrison Taylor D , Chaney Elizabeth M , Brandt Kiernan J , Ault-Seay Taylor B , Schneider Liesel G , Strickland Lew G , Schrick F Neal , McLean Kyle J
Published: January 2022

Bulls often experience various levels of nutrient availability throughout the year. Nutritional management is a critical factor on overall ejaculate composition and the ability to get females pregnant. We hypothesized that differing nutritional levels and body condition score (BCS) affect reproductive fertility parameters in bulls. Mature Angus bulls (n = 11) were individually housed and randomly assigned to one of two dietary regimens: 1) over-fed (n = 5) or 2) restricted (n = 6). Bulls were fed the same ration at different volumes to achieve desired effects resulting in eight individual treatments: gain to an over-fed body condition score ([BCS]; GO), gain after nutrient restriction (GR), loss after an over-fed BCS (LO), loss from nutrient restriction (LR), maintenance at ideal adiposity (BCS = 6) after overfeeding (IMO), maintenance at ideal adiposity after nutrient restriction (IMR), maintenance at an over-fed BCS (BCS = 8; MO), and maintenance at a restricted BCS (BCS = 4; MR). Body weight (BW) and BCS were recorded every 2 wk to monitor bull weight and BCS changes. Scrotal circumference was measured every 28 d. Body fat and sperm motility and morphology were evaluated every 84 d. Scrotal circumference, motility, and morphology were normalized to the initial value of each bull. Thus, allowing the individual bull to serve as a control. Statistical analyses were conducted with PROC GLIMMIX of SAS as a complete randomized design to determine if treatment influenced BW, BCS, scrotal circumference, motility, morphology, and adipose thickness. Scrotal circumference (P < 0.001) had the least amount of deviation from initial during the LR (0.29 ± 0.44) treatment and the greatest during the MO (3.06 ± 0.44), LO (2.28 ± 0.44), MR (2.43 ± 0.44), GR (3.03 ± 0.44), and IMR (2.91 ± 0.44) treatments. Sperm motility was not affected by nutritional treatments (P = 0.55). Both head and total defects of sperm differed (P = 0.02) due to nutritional treatments. Increased head abnormalities occurred during the LO (37.60 ± 8.61) treatment, with no differences between the other treatments. Total defects increased during the LO (43.80 ± 9.55) treatment with similar increases in bulls during the GR (29.40 ± 9.55) and IMR (35.60 ± 9.55) treatments. In conclusion, male fertility was impacted when a deviation from a BCS of 6 occurred which could be detrimental to reproductive and beef production efficiency.
Acceptability and feasibility of an online physical activity program for women over 50: a pilot trial
Authors: Wallbank Geraldine , Sherrington Catherine , Hassett Leanne , Kwasnicka Dominika , Chau Josephine Y , Phongsavan Philayrath , Grunseit Anne , Martin Fiona , Canning Colleen G , Baird Marian , Shepherd Roberta , Tiedemann Anne
Published: January 2022

Regular physical activity benefits health across the lifespan. Women in middle-age often juggle carer and work responsibilities, are often inactive, and may benefit from tailored support to increase physical activity. Establish the acceptability, feasibility, and impact on physical activity of a scalable program for women 50+ years.

This pilot trial randomized participants to immediate program access, or to a wait-list control. Active Women over 50 Online program included: (1) study-specific website, (2) 8 emails or 24 SMS motivation-based messages, (3) one telephone health-coaching session. Outcomes, at 3 months, were acceptability (recommend study participation, intervention uptake), feasibility (recruitment, reach, completion), intervention impact (physical activity), intervention impressions. At baseline, 62 participants of mean (SD) age 59 (±7) years took 7459 (±2424) steps/day and most (92%) reported ≥2 medical conditions. At 3 months, acceptability and impact data were available for 52 (84%) and 57 (92%) participants, respectively. Study participation was recommended by 83% of participants. Participants mostly agreed to receive health coaching (81%) and messages (87%: email = 56%, SMS = 44%), opened 82% of emails and accessed the website 4.8 times on average. Respondents reported the intervention supported their physical activity. Intervention participants were more likely to increase steps from baseline by 2000+/day (OR: 6.31, 95% CI: 1.22 to 32.70, p = .028) than controls, and trended toward more light-intensity (p = .075) and moderate-vigorous intensity physical activity (p = .11). The Active Women over 50 Online program demonstrated acceptability and feasibility among the target population, and effectiveness in some domains in the short term. Results warrant further testing in a full-scale RCT.
Pediatric Rheumatic Heart Disease in a Middle-Income Country: A Population-Based Study
Authors: Zahari Norazah , Yeoh Si Ling , Muniandy Siva Rao , Mat Bah Mohd Nizam
Published: January 2022

Introduction

Rheumatic heart disease (RHD), a debilitating complication from rheumatic fever, remains a problem in low- and middle-income countries. This study describes the incidence, prevalence, modifiable risk factors for severe RHD and immediate outcome of pediatric RHD.

Methods

This population-based and observational cohort study reviewed pediatric RHD patients (0–18 years) from the Sabah Pediatric Rheumatic Heart Registry from 2015 till 2018.

Results

A total of 188 RHD were reviewed with 120 new cases. The incidence of RHD is 2.19 [95% confidence interval (CI): 1.83–2.61] per 100 000 population, with a rising trend over time. Meanwhile, the prevalence of RHD was 13.78 (95% CI: 11.92–15.86) per 100 000 pediatric population. The majority of patients were from indigenous groups (59.0%), male (56.4%) with a mean age of 14.3 (3.31) years. About 77.9% had the lowest household income, and a significant proportion lived in overcrowded conditions. At diagnosis, 59% were diagnosed with severe RHD. There is heightened risk but no statistical significance between modifiable factors (low weight and height percentile at diagnosis, lowest income group, renting a house, overcrowding and healthcare access of more than 5 km) with severe RHD. Severe RHD is significantly associated with risk for intervention (p = 0.016). Sixteen (13.8%) patients required surgical intervention. About 97.6% of patients were on intramuscular benzathine penicillin G with 84.5% compliance.

Conclusion

The rising prevalence and incidence of pediatric RHD in Sabah, with the most being severe RHD at diagnosis, necessitates the development of an echocardiographic screening and a comprehensive national disease program.
Vibrio gazogenes Inhibits Aflatoxin Production Through Downregulation of Aflatoxin Biosynthetic Genes in Aspergillus flavus
Authors: Kandel Shyam L. , Jesmin Rubaiya , Mack Brian M. , Majumdar Rajtilak , Gilbert Matthew K. , Cary Jeffrey W. , Lebar Matthew D. , Gummadidala Phani M. , Calvo Ana M. , Rajasekaran Kanniah , Chanda Anindya
Published: January 2022

Aspergillus flavus is an opportunistic pathogen of oilseed crops such as maize, peanut, cottonseed, and tree nuts and produces carcinogenic secondary metabolites known as aflatoxins during seed colonization. Aflatoxin contamination not only reduces the value of the produce but is also a health hazard to humans and animals. Previously, we observed inhibition of A. flavus aflatoxin biosynthesis on exposure to the marine bacterium Vibrio gazogenes ( Vg). In this study, we used RNA sequencing to examine the transcriptional profiles of A. flavus treated with both live and heat-inactivated dead Vg and control samples. Fungal biomass, total accumulated aflatoxins, and expression profiles of genes constituting secondary metabolite biosynthetic gene clusters were determined at 24, 30, and 40 h after treatment. Statistically significant reductions in total aflatoxins were detected in Vg-treated samples as compared with control samples at 40 h. However, no statistical difference in fungal biomass was observed on these treatments. The Vg treatments were most effective on aflatoxin biosynthesis, as was reflected in significant downregulation of most genes in the aflatoxin gene cluster, including the aflatoxin pathway regulator gene, aflR. Along with aflatoxin genes, we also observed significant downregulation in some other secondary metabolite gene clusters, including cyclopiazonic acid and aflavarin, suggesting that the treatment could inhibit other secondary metabolites as well. Finally, a weighted gene correlation network analysis identified an upregulation of 10 genes that were most strongly associated with Vg-dependent aflatoxin inhibition and provide a novel starting point in understanding the mechanisms that result in this phenomenon.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.
A Pilot Study of the Generalizability of Preclinical Entrustment Assessments in Undergraduate Medical Education
Authors: Meyer Eric G. , Boulet John R. , Monahan Patrick B. , Durning Steven J. , Uijtdehaage Sebastian
Published: January 2022

Purpose

The reproducibility and consistency of assessments of entrustable professional activities (EPAs) in undergraduate medical education (UME) have been identified as potential areas of concern. EPAs were designed to facilitate workplace-based assessments by faculty with a shared mental model of a task who could observe a trainee complete the task multiple times. In UME, trainees are frequently assessed outside the workplace by faculty who only observe a task once.

Method

In November 2019, the authors conducted a generalizability study (G-study) to examine the impact of student, faculty, case, and faculty familiarity with the student on the reliability of 162 entrustment assessments completed in a preclerkship environment. Three faculty were recruited to evaluate 18 students completing 3 standardized patient (SP) cases. Faculty familiarity with each student was determined. Decision studies were also completed. Secondary analysis of the relationship between student performance and entrustment (scoring inference) compared average SP checklist scores and entrustment scores.

Results

G-study analysis revealed that entrustment assessments struggled to achieve moderate reliability. The student accounted for 30.1% of the variance in entrustment scores with minimal influence from faculty and case, while the relationship between student and faculty accounted for 26.1% of the variance. G-study analysis also revealed a difference in generalizability between assessments by unfamiliar (φ = 0.75) and familiar (φ = 0.27) faculty. Subanalyses showed that entrustment assessments by familiar faculty were moderately correlated to average SP checklist scores (r = 0.44, P < .001), while those by unfamiliar faculty were weakly correlated (r = 0.16, P = .13).

Conclusions

While faculty and case had a limited impact on the generalizability of entrustment assessments made outside the workplace in UME, faculty who were familiar with a student’s ability had a notable impact on generalizability and potentially on the scoring validity of entrustment assessments, which warrants further study.
Association Between Prenatal Cannabis Use and Psychotropic Medication Use in Pregnant Patients With Depression and Anxiety
Authors: Hirschtritt Matthew E. , Avalos Lyndsay A. , Sarovar Varada , Ridout Kathryn K. , Goler Nancy C. , Ansley Deborah R. , Satre Derek D. , Young-Wolff Kelly C.
Published: January 2022

Objectives

This cross-sectional study examined associations between prenatal cannabis use and prescribed psychotropic medication use among pregnant patients with depression or anxiety in a large, integrated healthcare system.

METHODS

Study patients had a confirmed pregnancy and a depressive or anxiety disorder defined by International Classification of Diseases codes between 2012 and 2018 at Kaiser Permanente Northern California. Patients were screened for prenatal substance use via a self-reported questionnaire and urine toxicology test as part of standard prenatal care. Generalized estimating equation models tested for associations between prenatal cannabis use and any dispensation of antidepressants, benzodiazepines, and hypnotics during gestation. Models were stratified by diagnosis (depression or anxiety) and depression symptom severity.

Results

This study included 35,047 pregnancies (32,278 patients; 17.6% aged <25 years, 48.1% non-Hispanic White). Adjusting for patient age, income, race/ethnicity, and depression symptom severity, the 12.6% of patients who screened positive for prenatal cannabis use demonstrated higher odds of prenatal benzodiazepine (adjusted odds ratios [aOR] = 1.40; 95% confidence interval [CI] = 1.20–1.62) and hypnotic (aOR = 1.28; 95% CI = 1.11–1.48), but not antidepressants (aOR = 1.05, 95% CI = 0.96–1.14) use. This pattern persisted when diagnostic groups were examined separately. The odds of prenatal benzodiazepine and hypnotic use associated with prenatal cannabis use were higher among pregnancies with severe depression symptom severity (31.8% of the sample).

CONCLUSIONS

Among pregnant patients with depression or anxiety, prenatal cannabis use was associated with higher odds of prenatal benzodiazepine and hypnotic use. As patients may be using cannabis to address depression and anxiety, prescribers should remain vigilant for under- or untreated psychiatric symptoms among pregnant patients and provide evidence-based treatments.
Effect of body size and intensive blood pressure management on cardiovascular and serious adverse events
Authors: Pei Junyu , Wang Xiaopu , Zheng Keyang , Su Wen , Hu Xinqun
Published: January 2022

Background:

Previous studies have shown that obese hypertensive patients have a lower risk of cardiovascular events than normal-weight patients, and that the performed hypertension treatment affects cardiovascular outcomes depending on the patient's body size. This study aimed to investigate the relationship between the BMI and cardiovascular outcomes and safety endpoints in hypertensive patients with intensive or standard blood pressure (BP) management.

Methods:

We used data from the Systolic Blood Pressure Intervention Trial (SPRINT). Cox proportional hazards models were used to analyze the data. The primary endpoint was cardiovascular disease (CVD) death, and the safety endpoint was serious adverse events.

Results:

In total, 9284 patients were included in our analysis. Thirty-seven patients in the intensive arm and 65 patients in the standard arm had CVD death. After multivariable adjustment, the BMI was not associated with the incidence of CVD death in the standard arm [hazard ratio 0.96, 95% confidence interval (CI) 0.91–1.02]. In the intensive arm, the incidence of CVD death decreased (hazard ratio 0.86, 95% CI 0.78–0.96) first and, then, increased (hazard ratio 1.15, 95% CI 1.07–1.25) with an increase in the BMI (inflection point, 32.33 kg/m2).

Conclusion:

Intensive BP management in overweight, class I, and class II obese patients significantly reduced the cardiovascular outcomes without increasing the safety risks. Nevertheless, further clinical evidence is needed to verify the effectiveness of intensive BP management in patients with normal weight and class III obesity.