bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing a novel anti-cancer RXR agonist to attenuate murine acute GVHD and maintain graft-versus-leukemia responses
Authors: Thangavelu Govindarajan , Wang Chao , Loschi Michael , Saha Asim , Osborn Mark J. , Furlan Scott N. , Aoyama Kazutoshi , McDonald-Hyman Cameron , Aguilar Ethan G. , Janesick Amanda S. , Chandraratna Roshantha A. , Refaeli Yosef , Panoskaltsis-Mortari Angela , MacDonald Kelli P. , Hill Geoffrey R. , Zeiser Robert , Maillard Ivan , Serody Jonathan S. , Murphy William J. , Munn David H. , Blumberg Bruce , Brown Chrysothemis , Kuchroo Vijay , Kean Leslie S. , Hippen Keli L. , Noelle Randolph J. , Blazar Bruce R. 
Published: September 2020

AbstractThe nuclear receptor (NR) subclass, retinoid X receptors (RXRs), exert immunomodulatory functions that control inflammation and metabolism via homodimers and heterodimers, with several other NRs, including retinoic acid receptors. IRX4204 is a novel, highly specific RXR agonist in clinical trials that potently and selectively activates RXR homodimers, but not heterodimers. In this study, in vivo IRX4204 compared favorably with FK506 in abrogating acute graft-versus-host disease (GVHD), which was associated with inhibiting allogeneic donor T-cell proliferation, reducing T-helper 1 differentiation, and promoting regulatory T-cell (Treg) generation. Recipient IRX4204 treatment reduced intestinal injury and decreased IFN-γ and TNF-α serum levels. Transcriptional analysis of donor T cells isolated from intestines of GVHD mice treated with IRX4204 revealed significant decreases in transcripts regulating proinflammatory pathways. In vitro, inducible Treg differentiation from naive CD4+ T cells was enhanced by IRX4204. In vivo, IRX4204 increased the conversion of donor Foxp3− T cells into peripheral Foxp3+ Tregs in GVHD mice. Using Foxp3 lineage-tracer mice in which both the origin and current FoxP3 expression of Tregs can be tracked, we demonstrated that IRX4204 supports Treg stability. Despite favoring Tregs and reducing Th1 differentiation, IRX4204-treated recipients maintained graft-versus-leukemia responses against both leukemia and lymphoma cells. Notably, IRX4204 reduced in vitro human T-cell proliferation and enhanced Treg generation in mixed lymphocyte reaction cultures. Collectively, these beneficial effects indicate that targeting RXRs with IRX4204 could be a novel approach to preventing acute GVHD in the clinic.
A randomized phase 2 trial of pomalidomide in subjects failing prior therapy for chronic graft-versus-host disease
Authors: Curtis Lauren M. , Ostojic Alen , Venzon David J. , Holtzman Noa G. , Pirsl Filip , Kuzmina Zoya J. , Baird Kristin , Rose Jeremy J. , Cowen Edward W. , Mays Jacqueline W. , Mitchell Sandra A. , Parsons-Wandell Laura , Joe Galen O. , Comis Leora E. , Berger Ann , Pusic Iskra , Peer Cody J. , Figg William D. , Cao Liang , Gale Robert Peter , Hakim Frances T. , Pavletic Steven Z. 
Published: September 2020

Abstract
Steroid-refractory chronic graft-versus-host disease (cGVHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase 2 clinical trial (#NCT01688466) to determine the safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGVHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide 0.5 mg per day orally (n = 17; low-dose cohort) or 2 mg per day at a starting dose of 0.5 mg per day increasing to 2 mg per day over 6 weeks (n = 17; high-dose cohort). The primary endpoint was overall response rate (ORR) at 6 months according to the 2005 National Institutes of Health cGVHD Response Criteria. Thirty-two patients had severe sclerotic skin and received a median of 5 (range, 2-10) previous systemic therapies. ORR was 47% (95% confidence interval, 30-65) in the intention-to-treat analyses. All were partial responses, with no difference in ORR between the cohorts. ORR was 67% (45%-84%) in the 24 evaluable subjects at 6 months. Nine had improvement in National Institutes of Health joint/fascia scores (P = .018). Median change from the baseline in body surface area involvement of skin cGVHD was −7.5% (–10% to 35%; P = .002). The most frequent adverse events were lymphopenia, infection, and fatigue. Eight subjects in the high-dose cohort had dose decreases because of adverse events. There was 1 death in the low-dose cohort from bacterial pneumonia. Our data indicate antifibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and interleukin-2. Pomalidomide 0.5 mg per day is a safe and effective therapy for advanced corticosteroid-refractory cGVHD.
Analysis of risk factors for anastomotic leakage after lower rectal Cancer resection, including drain type: a retrospective single-center study
Authors: Kinugasa Tetsushi , Nagasu Sachiko , Murotani Kenta , Mizobe Tomoaki , Ochi Takafumi , Isobe Taro , Fujita Fumihiko , Akagi Yoshito 
Published: September 2020

Abstract
Background
We investigated the correlations between surgery-related factors and the incidence of anastomotic leakage after low anterior resection (LAR) for lower rectal cancer.

Methods
A total of 630 patients underwent colorectal surgery between 2011 and 2014 in our department. Of these, 97 patients (15%) underwent LAR and were enrolled in this retrospective study. Temporary ileostomy was performed in each patient.

Results
Anastomotic leakage occurred in 21 patients (21.7%). Univariate analysis showed a significant association between operative duration (p = 0.005), transanal hand-sewn anastomosis (p = 0.014), and operation procedure (p = 0.019) and the occurrence of leakage. Multivariate regression reanalysis showed that underlying disease (p = 0.044), transanal hand-sewn anastomosis (p = 0.019) and drain type (p = 0.025) were significantly associated with the occurrence of leakage. The propensity-score analysis showed that closed drainage were 6.3 times more likely to have anastomotic leakage than open drainage in relation to the amount of postoperative drainage (ml), according to the inverse probability of treatment-weighted analysis.

Conclusions
Our results indicate that underlying disease, transanal hand-sewn anastomosis, and closed drain may be a risk and predictive factors for anastomotic leakage after LAR for lower rectal cancer. The notable finding was that closed drainage was related to the occurrence of anastomotic leakage and closed drainage was correlated with less volume of postoperative drain discharge than open drain.
Plasmid mediated penicillin and tetracycline resistance among Neisseria gonorrhoeae isolates from Kenya
Authors: Kivata Mary Wandia , Mbuchi Margaret , Eyase Fredrick , Bulimo Wallace Dimbuson , Kyanya Cecilia Katunge , Oundo Valerie , Mbinda Wilton Mwema , Sang Willy , Andagalu Ben , Soge Olusegun O. , McClelland Raymond Scott , Distelhorst John 
Published: September 2020

AbstractBackgroundTreatment of gonorrhea is complicated by the development of antimicrobial resistance inNeisseria gonorrhoeae(GC) to the antibiotics recommended for treatment.Knowledge on types of plasmids and the antibiotic resistance genes they harbor is useful in monitoring the emergence and spread of bacterial antibiotic resistance. In Kenya, studies on gonococcal antimicrobial resistance are few and data on plasmid mediated drug resistance is limited. The present study characterizes plasmid mediated resistance inN. gonorrhoeaeisolates recovered from Kenya between 2013 and 2018.MethodsDNA was extracted from 36 sub-cultured GC isolates exhibiting varying drug resistance profiles. Whole genome sequencing was done on Illumina MiSeq platform and reads assembledde-novousing CLC Genomics Workbench. Genome annotation was performed using Rapid Annotation Subsystem Technology. Comparisons in identified antimicrobial resistance determinants were done using Bioedit sequence alignment editor.ResultsTwenty-four (66.7%) isolates had both β-lactamase (TEM) and TetM encoding plasmids. 8.3% of the isolates lacked both TEM and TetM plasmids and had intermediate to susceptible penicillin and tetracycline MICs. Twenty-six (72%) isolates harbored TEM encoding plasmids. 25 of the TEM plasmids were of African type while one was an Asian type. Of the 36 isolates, 31 (86.1%) had TetM encoding plasmids, 30 of which harbored American TetM, whereas 1 carried a Dutch TetM. All analyzed isolates had non-mosaicpenAalleles. All the isolates expressing TetM were tetracycline resistant (MIC> 1 mg/L) and had increased doxycycline MICs (up to 96 mg/L). All the isolates had S10 ribosomal protein V57M amino acid substitution associated with tetracycline resistance. No relation was observed between PenB and MtrR alterations and penicillin and tetracycline MICs.ConclusionHigh-level gonococcal penicillin and tetracycline resistance in the sampled Kenyan regions was found to be mediated by plasmid borneblaTEMandtetMgenes. While the African TEM plasmid, TEM1 and American TetM are the dominant genotypes, Asian TEM plasmid, a new TEM239 and Dutch TetM have emerged in the regions.
HIV prevention is not all about HIV – using a discrete choice experiment among women to model how the uptake and effectiveness of HIV prevention products may also rely on pregnancy and STI protection
Authors: Vickerman Peter , Quaife Matthew , Kilbourne-Brook Maggie , Mvundura Mercy , Eakle Robyn , Terris-Prestholt Fern 
Published: September 2020

Abstract
Introduction
In sub-Saharan Africa, considerable HIV-burden exists among women. Anti-retroviral (ARV) based prevention products could decrease this burden, and their uptake could be increased if they also protect against pregnancy and sexually transmitted infections (STI).

Methods
A discrete choice experiment (DCE) was undertaken in South Africa (2015) through a household survey of adult females (n = 158) and adolescent girls (n = 204) who self-reported HIV-negative status. The DCE was used to project the uptake (percentage using product) of oral pre-exposure prophylaxis (PrEP), vaginal rings, and injectable long-lasting ARV agents among these women, and how uptake could depend on whether these products protect against pregnancy or STI acquisition. Uptake estimates were used to model how each product could decrease a women’s HIV acquisition risk.

Results
In adolescent women, there will be limited uptake (< 6% for any product) and impact (< 4% decrease in HIV acquisition risk) of new products unless they provide pregnancy protection, which could quadruple use and impact. Adult women have weaker preference for pregnancy protection, with moderate use (< 17% for each) and impact (< 14 percentage point decrease) if they only provide HIV protection. All women had highest preference for injectable ARVs, with oral PrEP having high preference if injectable ARVs are not available. Adult women will use the ring, but adolescent women will not. Importantly, even with three additional prevention products, all providing pregnancy and STI protection, > 14% of women will remain unprotected and > 31% of the baseline acquisition risk will remain.

Conclusions
Incorporating multiple prevention components into new ARV-based prevention products may increase their uptake and impact among women.
Differences in mortality in patients undergoing surgery for infective endocarditis according to age and valvular surgery
Authors: Østergaard Lauge , Smerup Morten Holdgaard , Iversen Kasper , Jensen Andreas Dalsgaard , Dahl Anders , Chamat-Hedemand Sandra , Bruun Niels Eske , Butt Jawad Haider , Bundgaard Henning , Torp-Pedersen Christian , Køber Lars , Fosbøl Emil 
Published: September 2020

Abstract
Background
Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival and reduce complications, but the balance between benefit and harm is difficult and may be closely related to age and type of surgical intervention. We aimed to examine how age and type of left-sided surgical intervention modified mortality in patients undergoing surgery for IE.

Methods
By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment 2000–2017. Patients were grouped by age < 60 years, 60–75 years, and ≥ 75 years. Multivariable adjusted Cox proportional hazard analysis was used to examine factors associated with 90-day mortality.

Results
We included 1767 patients with IE undergoing surgery, 735 patients < 60 years (24.1% female), 766 patients 60–75 years (25.8% female), and 266 patients ≥75 years (36.1% female). The proportions of patients undergoing surgery were 35.3, 26.9, and 9.1% for patients < 60 years, 60–75 years, and > 75 years, respectively. Mortality at 90 days were 7.5, 13.9, and 22.3% (p < 0.001) for three age groups. In adjusted analyses, patients 60–75 years and patients ≥75 years were associated with a higher mortality, HR = 1.84 (95% CI: 1.48–2.29) and HR = 2.47 (95% CI: 1.88–3.24) as compared with patients < 60 years. Factors associated with 90-day mortality were: mitral valve surgery, a combination of mitral and aortic valve surgery as compared with isolated aortic valve surgery, age, diabetes, and prosthetic heart valve implantation prior to IE admission.

Conclusions
In patients undergoing surgery for IE, mortality increased significantly with age and 1 in 5 died above age 75 years. Mitral valve surgery as well as multiple valve interventions augmented mortality further.
ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women
Authors: Cerda-Flores Ricardo M. , Camarillo-Cárdenas Karen Paola , Gutiérrez-Orozco Gabriela , Villarreal-Vela Mónica Patricia , Garza-Guajardo Raquel , Ponce-Camacho Marco Antonio , Castruita-Ávila Ana Lilia , González-Guerrero Juan Francisco , Rodríguez-Sánchez Iram Pablo , Calderón-Garcidueñas Ana Laura , Rodríguez-Gutierrez Hazyadee Frecia , Arellano-Barrientos Juan Carlos , Gutierrez Oscar Vidal , Saldaña Hugo Alberto Barrera , Garza-Rodríguez María Lourdes 
Published: September 2020

AbstractBackgroundAdiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) ofADIPOQin Mexican women with BC and to determine if they show an association with it.MethodsDNA samples from 397 patients and 355 controls were tested for theADIPOQgene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy–Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299.ResultsWe found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13–3.51, TT vs. GG; OR, 1.53; 95% CI 1.12–2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk.ConclusionsIdentification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.
RNA-Seq identifies condition-specific biological signatures of ischemia-reperfusion injury in the human kidney
Authors: Park Meeyoung , Kwon Chae Hwa , Ha Hong Koo , Han Miyeun , Song Sang Heon 
Published: September 2020

Abstract
Background
Acute kidney injury (AKI) is defined as a sudden event of kidney failure or kidney damage within a short period. Ischemia-reperfusion injury (IRI) is a critical factor associated with severe AKI and end-stage kidney disease (ESKD). However, the biological mechanisms underlying ischemia and reperfusion are incompletely understood, owing to the complexity of these pathophysiological processes. We aimed to investigate the key biological pathways individually affected by ischemia and reperfusion at the transcriptome level.

Results
We analyzed the steady-state gene expression pattern of human kidney tissues from normal (pre-ischemia), ischemia, and reperfusion conditions using RNA-sequencing. Conventional differential expression and self-organizing map (SOM) clustering analyses followed by pathway analysis were performed. Differential expression analysis revealed the metabolic pathways dysregulated in ischemia. Cellular assembly, development and migration, and immune response-related pathways were dysregulated in reperfusion. SOM clustering analysis highlighted the ischemia-mediated significant dysregulation in metabolism, apoptosis, and fibrosis-related pathways, while cell growth, migration, and immune response-related pathways were highly dysregulated by reperfusion after ischemia. The expression of pro-apoptotic genes and death receptors was downregulated during ischemia, indicating the existence of a protective mechanism against ischemic injury. Reperfusion induced alterations in the expression of the genes associated with immune response such as inflammasome and antigen representing genes. Further, the genes related to cell growth and migration, such as AKT, KRAS, and those related to Rho signaling, were downregulated, suggestive of injury responses during reperfusion. Semaphorin 4D and plexin B1 levels were also downregulated.

Conclusions
We show that specific biological pathways were distinctively involved in ischemia and reperfusion during IRI, indicating that condition-specific therapeutic strategies may be imperative to prevent severe kidney damage after IRI in the clinical setting.
Pregnancy vs. paycheck: a qualitative study of patient’s experience with employment during pregnancy at high risk for preterm birth
Authors: Wheeler Sarahn M. , Massengale Kelley E. C. , Adewumi Konyin , Fitzgerald Thelma A. , Dombeck Carrie B. , Swezey Teresa , Swamy Geeta K. , Corneli Amy 
Published: September 2020

Abstract
Background
Pregnant women with a history of preterm birth are at risk for recurrence, often requiring frequent prenatal visits for close monitoring and/or preventive therapies. Employment demands can limit uptake and adherence to recommended monitoring and preterm birth prevention therapies.

Method
We conducted a qualitative descriptive study using in-depth interviews (IDIs) of pregnant women with a history of preterm birth. IDIs were conducted by trained qualitative interviewers following a semi-structured interview guide focused on uncovering barriers and facilitators to initiation of prenatal care, including relevant employment experiences, and soliciting potential interventions to improve prompt prenatal care initiation. The IDIs were analyzed via applied thematic analysis.

Results
We described the interview findings that address women’s employment experiences. The current analysis includes 27 women who are majority self-described as non-Hispanic Black (74%) and publically insured (70%). Participants were employed in a range of professions; food services, childcare and retail were the most common occupations. Participants described multiple ways that being pregnant impacted their earning potential, ranging from voluntary work-hour reduction, involuntary duty hour reductions by employers, truncated promotions, and termination of employment. Participants also shared varying experiences with workplace accommodations to their work environment and job duties based on their pregnancy. Some of these accommodations were initiated by a collaborative employee/employer discussion, others were initiated by the employer’s perception of safe working conditions in pregnancy, and some accommodations were based on medical recommendations. Participants described supportive and unsupportive employer reactions to requests for accommodations.

Conclusions
Our findings provide novel insights into women’s experiences balancing a pregnancy at increased risk for preterm birth with employment obligations. While many women reported positive experiences, the most striking insights came from women who described negative situations that ranged from challenging to potentially unlawful. Many of the findings suggest profound misunderstandings likely exist at the patient, employer and clinical provider level about the laws surrounding employment in pregnancy, safe employment responsibilities during pregnancy, and the range of creative accommodations that often allow for continued workplace productivity even during high risk pregnancy.
Maternal birth preparedness and complication readiness in the Greater Accra region of Ghana: a cross-sectional study of two urban health facilities
Authors: Klobodu Cynthia , Milliron Brandy-Joe , Agyabeng Kofi , Akweongo Patricia , Adomah-Afari Augustine 
Published: September 2020

Abstract
Background
High maternal mortality ratios remain a critical public health concern in Ghana. Birth preparedness and complication readiness (BP/CR), which is a component of focused antenatal care, is a safe motherhood strategy intended to promote skilled birth attendance by helping women and their families plan for pregnancy and childbirth, thereby reducing maternal mortality. The objective of this study was to determine the level of BP/CR and to assess factors associated with maternal BP/CR in the Greater Accra Region of Ghana.

Method
A cross sectional descriptive quantitative study was carried out among 300 postnatal women attending the Adabraka Polyclinic and the Greater Accra Regional Hospital both within Accra, the capital city of Ghana. Data were collected with a structured questionnaire which assessed socio-demographic, health facility/provider and social support factors and their associations with BP/CR. Levels of BP/CR were assessed using validated tools. Data from 300 women were analyzed using STATA version 15.0. Logistic regression analysis was conducted to establish associations between BP/CR and socio-demographic, health facility/provider and social support factors.

Results
Approximately 234 (78%) of the women were birth prepared. Strong predictors of BP/CR included having ≥4 antenatal clinic visits (aOR 2.63; 95% CI 1.03–6.73), being employed (aOR 4.07; 95% CI 1.49–11.11) and belonging to maternal health promoting clubs or groups during the antenatal period (aOR 3.00; 95% CI 1.07–8.40) .

Conclusion
BP/CR is generally high among the study population. Predictors of BP/CR are multifactorial and found to cut across all aspects assessed in the study. Therefore, the creation of a BP/CR tool is recommended to routinely monitor trends in maternal birth preparedness in antenatal clinics. This may help to sustain and improve current levels and indicators of BP/CR.