bluuebunny/crossref_metadata_2025 huggingface dataset:
Posterior mediastinal neurilemmoma accompanied by intrapulmonary sequestration in the left lower lobe
Authors: Yue Yang , Xin Hua , Xu Bao-Cen , Zhang Le-Ning , Zhao Wei
Published: July 2019

Rationale:

The presence of a mediastinal neurilemmoma accompanied by intrapulmonary sequestration is a rare occurrence. The clinical symptoms of a neurilemmoma depend on the site of the tumor. Diagnosis of pulmonary sequestration mainly depends on the presence of aberrant feeding arteries.

Patient concerns:

A 78-year-old woman was admitted to our hospital with a mediastinal space-occupying lesion of 50 years. Computed tomography and magnetic resonance imaging showed 2 roundish low-density shadows in the left posterior mediastinum.

Diagnosis:

The pathological findings of the upper cystic mass support the diagnosis of neurilemmoma. A branch of aorta was found supplying blood to the lower mass; it was considered a pulmonary sequestration.

Interventions:

Left-sided thoracotomy was planned to remove the chest space-occupying lesions. Two masses were completely removed. Severe adhesion between the left lower lobe and the diaphragm was successfully separated, the aberrant feeding vessel was properly managed, and the lower lobe was resected completely.

Outcomes:

The patient experienced remission of symptoms, had no significant postoperative complications, and was discharged from the hospital.

Lessons:

Special attention should be paid to neurological involvement of the neurilemmoma and the fragile feeding arteries of the intrapulmonary sequestration. Early diagnosis and treatment are important in such cases.
A case report detailing use of a new intraocular lens with advanced technology, designed specifically for patients with center-involving macular disorders
Authors: Borkenstein Andreas F. , Borkenstein Eva-Maria
Published: July 2019

Rationale:

Many studies have shown that cataract surgery can be performed safely and improve visual acuity, without increasing the risk of progression of existing age-related macular degeneration (AMD). Data are emerging for an intraocular lens (IOL) that utilizes an advanced optical design to optimize the image supplied to all areas of the macula and not just the foveal center, which may benefit patients with center-involving macular disorders.

Patient concerns:

An 83-year-old Caucasian female presented with poor contrast sensitivity and color perception with increasing glare over the preceding year.

Diagnosis:

She had a progressive cortical cataract and stable dry AMD in the left eye, and wet AMD in the right eye. In the left eye, preoperative best-corrected distance visual acuity (BCDVA) was 0.2 (decimal) and best-corrected near visual acuity (BCNVA) was 0.05 (decimal).

Interventions:

Standard small-incision phacoemulsification was performed in the left eye, with capsular bag implantation of EyeMax Mono (LEH Pharma, London, UK), a single-piece, soft, hydrophobic, acrylic IOL designed to optimize image quality across the macula, rather than a standard monofocal lens.

Outcomes:

At 6 months postoperation, visual acuity in the left eye had markedly improved, with a BCDVA of 0.5 (decimal) and a BCNVA of 0.2 (decimal).

Conclusion:

In this first case undertaken at our center (and the first in Austria), cataract extraction and EyeMax Mono implantation were performed safely, with good subjective and objective outcome measures consistent with the effects of image optimization across the macula. Further studies of this IOL in patients with center-involving macular disorders, such as AMD, are warranted.
Decreased expression of SLC16A12 mRNA predicts poor prognosis of patients with clear cell renal cell carcinoma
Authors: Mei Jie , Hu Kehan , Peng Xiafeng , Wang Huiyu , Liu Chaoying
Published: July 2019

Solute carrier family 16, member 12 (SLC16A12) is a highly -expressed protein in the kidney and has been reported to participate in the transport of creatine. However, the clinical values of SLC16A12 in clear cell renal cell carcinoma (ccRCC) have not been explored.

SLC16A12 RNA-seq data and clinical information were downloaded from the Cancer Genome Atlas (TCGA) database. We compared its expression in ccRCC and paracancerous tissues, then the result was further validated with our cohort. The impact on the clinical significance of SLC16A12 in ccRCC was also assessed.

Compared with paracancerous tissue, SLC16A12 was significantly downregulated in the tumor tissues both in mRNA and protein level. In TCGA cohort, SLC16A12 mRNA expression was associated with several clinicopathological parameters, including T stages (P < .001), M stages (P = .009), TNM stages (P < .001), and differentiated grades (P = .001). Kaplan–Meier analysis showed that the overall survival of patients with low expression of SLC16A12 mRNA was significantly worse than that of patients with high expression (P < .001). Furthermore, both univariate (HR = 0.371, 95%CI: 0.269–0.513, P < .001) and multivariate (HR = 0.485, 95%CI: 0.297–0.793, P = .004) Cox regression analyses suggested that low expression of SLC16A12 mRNA was an independent prognostic factor for patients with ccRCC.

Overall, we uncovered that decreased expression of SLC16A12 is a poor prognostic factor for patients with ccRCC. SLC16A12 might be a potential biomarker and therapeutic target in ccRCC.
Comparison of efficacy and safety of S-1 and capecitabine in patients with metastatic colorectal carcinoma
Authors: Chen Jianxin , Wang Junhui , Xu Tiancai
Published: July 2019

Background:

This study aimed to compare the efficacy and safety of S-1 and capecitabine in patients with metastatic colorectal carcinoma (mCRC).

Methods:

Eligible prospective clinical trials were searched and available data were extracted. Odds ratio and hazard ratio of available outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled for analysis.

Results:

A total of 6 studies including 828 patients were included. The results of pooled analysis showed no statistical difference in short-term efficacy including ORR (95% confidence interval [CI]: 0.68–1.19; P = .48) or DCR (95% CI: 0.65–1.29; P = .61), or long-term efficacy including PFS (95% CI: 0.75–1.08; P 
= .26) or OS (95% CI: 0.78–1.13; P 
= .50). Symptoms of diarrhea at any grade were more prevalent (95% CI: 1.21–2.29; P 
= .002) in patients treated with S-1, while hand-foot syndrome (HFS) at any grade (95% CI: 0.24–0.48; P < .0001) or high grade (95% CI: 0.09–0.48; P < .0001) was more frequent in capecitabine group. AEs including leucopenia, neutropenia, anemia, thrombocytopenia, vomiting, oral mucositis, stomatitis, elevated alanine transaminase, or peripheral neuropathy showed no statistical difference between S-1 and capecitabine group (all P > .05).

Conclusions:

This meta-analysis reveals that S-1 has comparable efficacy, lower risk of HFS and higher incidence of diarrhea compared to capecitabine for treatment in patients with mCRC.
Intermittent Fasting During Ramadan and Its Effects in Individuals With Metabolic Syndrome
Authors: Alinezhad-Namaghi Maryam , Eslami Saeid , Nematy Mohsen , Khoshnasab Adeleh , Rezvani Reza , Philippou Elena , Norouzy Abdolreza
Published: July 2019

This study evaluated the effect of intermittent fasting during Ramadan, the Muslim religious season of fasting, on body composition among 95 adults (65 male adults) with a mean age of 45.4 years with metabolic syndrome in Iran. The individuals were classified retrospectively into fasting and nonfasting groups based on fasting for a minimum of 10 days during Ramadan. Body composition, physical activity, and dietary intake were assessed both at baseline before the fast began and after Ramadan. Those who fasted a minimum of 10 days had significant reductions in body weight (−1.5 kg) and body mass index, body fat mass (−1.2 kg), fat free mass (−0.4 kg), skeletal muscle mass (−0.3 kg), and visceral fat area (−5.7 cm2). Also, they showed significant decreases in the total body water, intracellular water, 50-kHz whole-body phase angle (−0.13 degrees), and total physical activity. Fasting resulted in a 1.5-kg weight loss, of which the percentage losses were loss in body fat mass, 76%; body water loss, 18%; and protein loss, 6%, and also decrease in daily dietary intake during fasting in those who fasted. Fasting during Ramadan, which restricts the time of eating and caloric restriction, may be effective as dietary interventions in patients with metabolic syndrome to reduce body weight, fat mass, and visceral fat while retaining lean mass.
Validation of a Self-reported Food Frequency for Overweight and Obese Children, Using Parental 3-Day Food Records
Authors: Varagiannis Panagiotis , Magriplis Emmanuella , Risvas Grigoris , Vamvouka Katerina , Nisianaki Adamantia , Papageorgiou Anna , Pervanidou Panagiota , Chrousos Georgios , Zampelas Antonis
Published: July 2019

Background

Many studies derive dietary information from child self-reported Food Frequency Questionnaires (FFQs). This may be subjected to misreporting, especially among overweight and obese children.

Aim

The aim of this study was to examine the validity of data acquired from child-reported dietary intake using a semiquantitative FFQ developed for assessing dietary habits of overweight and obese children in Greece, using parental 3-day food records of child intakes.

Methods

Validation analysis was based on 106 (from total 115) children (41% boys and 59% girls). Children were asked to report the frequency of their dietary intake, using the FFQ provided. Parents were asked to keep a 3-day food record for their children’s intake. Correlations and significance between methods were assessed via Spearman correlation coefficient and Wilcoxon nonparametric pairwise comparisons, respectively. Agreement between the FFQ and the 3-day record was performed using Bland-Altman method.

Results

Significant correlations, ranging from 0.32 to 1 (all P < .05), were observed between food consumption reported in the FFQ and recorded in the 3-day dietary record. High correlation was found for fruits (ρ = 0.988), vegetables (ρ = 0.985), dairy (ρ = 0.702), meat (ρ = 0.958), fish (ρ = 0.841), starchy foods (ρ = 0.793), sweets (ρ = 1), and beverages (ρ = 0.978). Medium correlation was observed only between the consumption of legumes (ρ = 0.329). No significant differences were found between reported FFQ and 3-day dietary record for most food groups and beverages examined. Mean intake agreement was ranged from 90.6% to 98.1% (Bland-Altman).

Conclusions

The FFQ used appears to be a valid tool for investigating dietary intake of food among overweight and obese children.
The Burden of Unintentional Injury Mortality Among American Indians/Alaska Natives in Michigan, Minnesota, and Wisconsin
Authors: Porter Meghan A. , Cirillo Lilli Alexandra N. , Schellinger Chalyse N.
Published: July 2019

Objectives:

To characterize the burden of unintentional injury mortality among American Indians/Alaska Natives (AI/ANs) in Michigan, Minnesota, and Wisconsin and identify segments of the population that may especially benefit from policy and practice actions to reduce unintentional injury mortality risk factors.

Design:

Surveillance of mortality data from CDC WONDER and WISQARS online databases.

Setting:

The 3 states in the Indian Health Service (IHS) Bemidji Area: Michigan, Minnesota, and Wisconsin.

Participants:

AI/ANs and whites who died from unintentional injuries in 2011-2015 in Michigan, Minnesota, and Wisconsin.

Main Outcome Measure:

Unintentional injury mortality rates and AI/AN versus white unintentional injury mortality disparity ratios.

Results:

For all types of unintentional injury mortality, from 2011 to 2015, AI/ANs in the Bemidji Area died at an age-adjusted rate that was 77% higher than that for whites, a statistically significant difference. For AI/ANs in the 3-state area, the top cause of unintentional death was poisoning. The poisoning rate was a statistically significant 2.64 times as high for AI/ANs as that for whites, the highest disparity seen by type. When analyzed by age, gender, and rural/urban residence, unintentional injury mortality rates were almost always higher for AI/ANs. AI/ANs also had a much higher burden of years of potential life lost.

Conclusions:

Unintentional injury mortality significantly affects AI/ANs in the 3-state area and to a larger degree than for whites. However, some of the risk factors for unintentional injury are modifiable and, if addressed effectively, can reduce injury deaths. Governments, local leaders, organizations, and individuals can reduce AI/ANs' risk of unintentional injury by providing effective programming; encouraging or modeling behavior change; advocating for, creating, and enforcing laws and policies; and making infrastructure improvements. Increased attention to this topic and equitable efforts to reduce risk factors have great potential to reduce the burden of unintentional injury deaths for AI/ANs and all peoples.
Unilateral Absence of the Basal Ganglia on 123I-Ioflupane DaTScan
Authors: Baghdadi Yaser , Anh Se Jin , Brook Allan , Moadel Renee , Freeman Leonard M.
Published: July 2019

This 33-year-old man presented with hemorrhagic stroke manifesting with left hemiparesis and right ptosis. Angiography revealed no patent carotids. The anterior and middle cerebral arteries were filling collaterally through the posterior vertebrobasilar pathway. The presumptive diagnosis was moyamoya disease. The etiology of the bleeding was right basilar tip aneurysm that subsequently had partial coil placement. Months later, the neck of the aneurysm perforated and second coiling was performed. Later on follow-up, patient developed left hand tremor. A radionuclide DATscan revealed total absence of right-sided basal ganglia activity. A possible etiology was occlusion of the middle cerebral artery’s lenticulostriate branches.
Potential Causes of False-Negative Interpretations in 68Ga-PSMA PET/CT for the Detection of Local and Recurrent Prostate Cancer
Authors: Yakar Derya , Noordzij Walter , Kwee Thomas C.
Published: July 2019

68Ga-PSMA PET/CT has emerged as a highly promising diagnostic method for the evaluation of prostate cancer. Although it is increasingly recognized that its specificity is imperfect, data on false-negatives in the prostate have been underreported. We present 3 cases with false-negatives for local (recurrent) prostate cancer on 68Ga-PSMA PET/CT, using multiparametric MRI and histopathology as reference standard. Metal artifact of prostate gold markers placed for external beam radiation therapy, low level of PSMA uptake, and bladder spillover are potential causes of misinterpretation. Awareness of these diagnostic pitfalls may improve 68Ga-PSMA PET/CT interpretation.
Stem Cell Therapy and Hydrogen Sulfide: Conventional or Nonconventional Mechanisms of Action?
Authors: Jensen Amanda R. , Drucker Natalie A. , Olson Ken R. , Markel Troy A.
Published: July 2019

Purpose:

Hydrogen sulfide (H2S) has many beneficial biological properties, including the ability to promote vasodilation. It has been shown to be released from stem cells and increased by hypoxia. Therefore, H2S may be an important paracrine factor in stem cell-mediated intestinal protection. We hypothesized that H2S created through conventional pathways would be a critical component of stem cell-mediated intestinal protection after ischemic injury.

Methods:

Human bone marrow-derived mesenchymal stem cells (BMSCs) were transfected with negative control siRNA (Scramble), or with siRNA to CBS, MPST, or CTH. Knockdown was confirmed with PCR and H2S gas assessed with AzMC fluorophore. Eight-week-old male mice then underwent intestinal ischemia for 60 min, after which time, perfusion was restored. BMSCs from each of the above groups were then placed into the mouse abdominal cavity before final closure. After 24 h, mice were reanesthetized and mesenteric perfusion was assessed by Laser Doppler Imaging (LDI). Animals were then sacrificed and intestines excised, placed in formalin, paraffin embedded, and stained with H & E. Intestines were then scored with a common mucosal injury grading scale.

Results:

PCR confirmed knockdown of conventional H2S-producing enzymes (CBS, MPST, CTH). H2S gas was decreased in MPST and CTH-transfected cells in normoxic conditions, but was not decreased compared with Scramble in any of the transfected groups in hypoxic conditions. BMSCs promoted increased mesenteric perfusion at 24 h postischemia compared with vehicle. Transfected stem cells provided equivalent protection. Histologic injury was improved with BMSCs compared with vehicle. CBS, MPST, and CTH knockdown cell lines did not have any worse histological injury compared with Scramble.

Conclusions:

Knocking down conventional H2S-producing enzymes only impacted gas production in normoxic conditions. When cells were transfected in hypoxic conditions, as would be expected in the ischemic intestines, H2S gas was not depressed. These data, along with unchanged perfusion and histological injury parameters with conventional enzyme knockdown, would indicate that alternative H2S production pathways may be initiated during hypoxic and/or ischemic events.
Hepatic Ablation Promotes Colon Cancer Metastases in an Immunocompetent Murine Model
Authors: Jones Edward L. , Halpern Alison L. , Carmichael Heather , Wikiel Krzysztof J. , Jones Teresa S. , Moore John T. , Robinson Thomas N. , Barnett Carlton C.
Published: July 2019

Objective:

To determine the impact of radiofrequency (RF) and microwave (MW) energy compared to direct cautery on metatstatic colon cancer growth.

Background:

Hepatic ablation with MW and RF energy creates a temperature gradient around a target site with temperatures known to create tissue injury and cell death. In contrast, direct heat application (cautery) vaporizes tissue with a higher site temperature but reduced heat gradient on surrounding tissue. We hypothesize that different energy devices create variable zones of sublethal injury that may promote tumor recurrence. To test this hypothesis we applied MW, RF, and cautery to normal murine liver with a concomitant metastatic colon cancer challenge.

Methods:

C57/Bl6 mice received hepatic thermal injury with MW, RF, or cautery to create a superficial 3-mm lesion immediately after intrasplenic injection of 50K MC38 colon cancer cells. Thermal imaging recorded tissue temperature during ablation and for 10 seconds after energy cessation. Hepatic tumor location and volume was determined at day 7.

Results:

Cautery demonstrated the highest maximum tissue temperatures (129°C) with more rapid return to baseline compared to MW or RF energy. All mice had metastasis at the ablation site. Mean tumor volume was significantly greater in the MW (95.3 mm3; P = 0.007) and RF (55.7 mm3; P = 0.015) than cautery (7.13 mm3). There was no difference in volume between MW and RF energy (P = 0.2).

Conclusions:

Hepatic thermal ablation promotes colon cancer metastasis at the injury site. MV and RF energy result in greater metastatic volume than cautery. These data suggest that the method of energy delivery promotes local metastasis.
Real-World Effectiveness and Safety of Fingolimod in Patients With Relapsing Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina
Authors: Patrucco Liliana , Cristiano Edgardo , Sánchez Francisco , Miguez Jimena , Rojas Juan Ignacio
Published: July 2019

Objectives

The aim of this prospective observational postmarketing study was to evaluate fingolimod effectiveness in a real-world setting in Buenos Aires, Argentina.

Methods

Relapsing remitting multiple sclerosis patients who had been prescribed fingolimod owing to treatment failure and had at least greater than or equal to 24 months of follow-up were included during August 2013 and June 2018. Three-monthly clinical evaluations and 12-monthly magnetic resonance were performed. Demographic and clinical variables were described as well as the safety and the effectiveness outcomes that included the proportion of patients free from clinical relapses, from disability progression, from new or enlarging T2 or T1 gadolinium-enhancing lesions on annual magnetic resonance imaging, and from any disease activity during the follow-up.

Results

A total of 97 patients were included (68% female [n = 66]; mean ± SD age, 30 ± 10.5 years; mean ± SD disease duration, 6.5 ± 3.1 years; mean ± SD Expanded Disability Status Scale, 3.5 ± 1; mean ± SD fingolimod use, 30 ± 13 months [range, 18–56 months]). One hundred percent (97) used previous disease-modifying therapy, mainly interferons (87%; n = 84). Fourteen patients (14.4%) discontinued/withdrew fingolimod (10 owing to disease activity and 4 owing to tolerance and personal decisions). Eighty-two percent were free from clinical relapses, and 85% were free from disability progression; 75% of patients remained free from new or newly enlarging T2 lesions, and 78% of patients were free from gadolinium enhancing lesions. The proportion of patients free from any disease activity was 54%.

Conclusions

The effectiveness of fingolimod in a newly real-world setting was consistent with information provided from phase III clinical trials.
Asymptomatic filariasis and leprosy co-morbidity in a patient with suspected Guillain–Barrè syndrome: the first case report of an incidental finding in a slit-skin smear
Authors: Nag Soumyabrata , Gupta Sneha , Sisodia Juhi , Misra Richa
Published: July 2019

Introduction. Lymphatic filariasis (LF) and leprosy are both endemic in India. These diseases are on the World Health Organization (WHO) list of neglected tropical diseases (NTDs), as they affect the most marginalized communities in the world, resulting in deformities and functional limitation. We report the first case of asymptomatic filariasis and leprosy co-morbidity in a patient with suspected Guillain–Barré syndrome.

Case presentation. A 55-year-old male who was a farmer by occupation presented to the Neurology Outpatient Department (OPD) of our institute with complaints of weakness in all four limbs for the last 15 days. After admission, a detailed history revealed that the patient had been taking multi-drug therapy (MDT) for leprosy for the previous 6 months. After symptomatic management of the presenting complaints, the patient was sent to the Department of Microbiology for a consultation and six-site slit-skin sampling. The initial screening of Ziehl–Neelsen (ZN)-stained smears under a 10× objective led to the incidental finding of sheathed structures resembling microfilaria (Mf) on the smear made from ear lobules. In addition, short acid-fast bacilli (AFB) were also observed under the oil-immersion objective.

Conclusion. We emphasize that a high index of suspicion and thorough screening of smears by a microbiologist is essential in specimens obtained from any body site.
Characterization of Escherichia coli obtained from patients undergoing peritoneal dialysis and diagnosed with peritonitis in a Brazilian centre
Authors: Dias Regiane C. B. , Vieira Melissa A. , Moro Ana C. , Ribolli Danilo F. M. , Monteiro Aydir C. M. , Camargo Carlos H. , Tiba-Casas Monique R. , Soares Flávia B. , dos Santos Luis F. , Montelli Augusto C. , da Cunha Maria de Lourdes R. de S. , Barretti Pasqual , Hernandes Rodrigo T.
Published: July 2019

Purpose. This study aimed to characterize 27

Escherichia coli

isolates obtained from peritoneal dialysis (PD)-related peritonitis that occurred at the University Hospital of Botucatu Medical School, Brazil, between 1997 and 2015.

Methodology. These isolates were characterized regarding the occurrence of 22 virulence factor-encoding genes, antimicrobial resistance and biofilm production. We then evaluated whether these factors influenced the clinical outcome.

Results. Over an 18-year period, 726 episodes of PD-related peritonitis were diagnosed, with 27 of them (3.7 %) being due to

E. coli

. The majority of the isolates were classified in phylogroups B1 (33.3 %), B2 (30.0 %) or F (18.0 %). fimH (100.0 %), ompT (66.7 %) and irp2 (51.9 %) were the most prevalent genes, while papA, papC, iha, sat, irp2, iucD, ireA, ibe10, ompT and kpsMTII were significantly more prevalent among isolates belonging to phylogroups B2 and F (P<0.05). Non-susceptibility to quinolones was detected in six isolates, which harboured chromosomal and/or plasmid-mediated quinolone resistance determinants, while two CTX-M extended-spectrum β-lactamase-producing

E. coli

were identified. Virulence factor-encoding genes (alone or in combination) and antimicrobial resistance were not associated with non-resolution outcomes. However, there was a trend for the ability to produce biofilm to be associated with treatment failure, although this association was not statistically significant.

Conclusion. The

E. coli

isolates were heterogeneous in terms of the features investigated, and were susceptible to most of the antimicrobial drugs tested, despite the unsuccessful treatment observed in more than 50.0 % of the patients. Studies including more cases could help to clarify if biofilm production can influence the outcome in patients with PD-related peritonitis.
Early assessment of molecular progression and response by whole-genome circulating tumor DNA in advanced solid tumors
Authors: Davis Andrew A. , Iams Wade T. , Chan David , Oh Michael S. , Lentz Robert W. , Peterman Neil , Robertson Alex , Shah Abhik , Srivas Rohith , Wilson Timothy , Lambert Nicole , George Peter , Wong Becky , Wood Haleigh , Close Jason , Tezcan Ayse , Nesmith Ken , Tezcan Haluk , Chae Young Kwang
Published: July 2019

Treatment response assessment for patients with advanced solid tumors is complex and existing methods require greater precision. Current guidelines rely on imaging, which has known limitations, including the time required to show a deterministic change in target lesions. Serial changes in whole-genome (WG) circulating tumor DNA (ctDNA) were used to assess response or resistance to treatment early in the treatment course. 96 patients with advanced cancer were prospectively enrolled (91 analyzed and 5 excluded), and blood was collected before and after initiation of a new, systemic treatment. Plasma cell-free DNA libraries were prepared for either WG or WG bisulfite sequencing. Longitudinal changes in the fraction of ctDNA were quantified to retrospectively identify molecular progression (MP) or major molecular response (MMR). Study endpoints were concordance with first follow-up imaging (FFUI) and stratification of progression-free survival (PFS) and overall survival (OS). Patients with MP (n=13) had shorter PFS (median 62d vs. 310d) and OS (255d vs. not reached). Sensitivity for MP to identify clinical progression was 54% and specificity was 100%. MP calls were from samples taken a median of 28d into treatment and 39d before FFUI. Patients with MMR (n=27) had longer PFS and OS compared to those with neither call (n=51). Molecular response assessment can potentially enable early switching to potentially effective therapies, therefore minimizing side effects and costs associated with additional cycles of ineffective treatment. MMR may present a novel endpoint to target to improve long-term patient outcomes.
Use of viral load to improve survey estimates of known HIV-positive status and antiretroviral treatment coverage in Kenya
Authors: Young Peter W. , Zielinski-Gutierrez Emily , Wamicwe Joyce , Mukui Irene , Kim Andrea A. , Waruru Anthony , Zeh Clement , Kretzschmar Mirjam E. , De Cock Kevin M.
Published: July 2019

Objective

To compare alternative methods of adjusting self-reported knowledge of HIV-positive status and antiretroviral (ARV) therapy use based on undetectable viral load (UVL) and ARV detection in blood.

Design

Post hoc analysis of nationally-representative household survey to compare alternative biomarker-based adjustments to population HIV indicators.

Methods

We reclassified HIV-positive participants aged 15–64 years in the 2012 Kenya AIDS Indicator Survey (KAIS) that were unaware of their HIV-positive status by self-report as aware and on antiretroviral treatment if either ARVs were detected or viral load was undetectable (<550 copies/mL) on dried blood spots. We compared self-report to adjustments for ARVs measurement, UVL, or both.

Results

Treatment coverage among all HIV-positive respondents increased from 31.8% for self-report to 42.5% [95% confidence interval (CI) 37.4–47.8] based on ARV detection alone, to 42.8% (95% CI 37.9–47.8) when ARV-adjusted, 46.2% (95% CI 41.3–51.1) when UVL-adjusted and 48.8% (95% CI 43.9–53.8) when adjusted for either ARV or UVL. Awareness of positive status increased from 46.9% for self-report to 56.2% (95% CI 50.7– 61.6) when ARV-adjusted, 57.5% (95% CI 51.9–63.0) when UVL-adjusted, and 59.8% (95% CI 54.2–65.1) when adjusted for either ARV or UVL.

Conclusions

Undetectable viral load, which is routinely measured in surveys, may be a useful adjunct or alternative to ARV detection for adjusting survey estimates of knowledge of HIV status and antiretroviral treatment coverage.
Hospital Resource Utilization in Epilepsy: Disparities in Rural vs Urban Care
Authors: Bensken Wyatt P. , Norato Gina , Khan Omar I.
Published: July 2019

Objective

This study assessed differences in resource utilization during epilepsy and seizure related hospitalizations in urban versus rural environments, to identify potential disparities in care for people living with epilepsy in rural communities.

Methods

A 10 year (2001 to 2011) state-wide hospital discharge database was used. Cost, length of stay, illness severity, and procedure use were compared between urban facilities, rural facilities, and epilepsy centers. Comparison across three separate years helped to identify differences between facility type as well as to assess practices changes within facilities over time.

Results

Average total charges between the three types of facilities was significantly different, with epilepsy centers having the highest average charge per patient, followed by urban and rural facilities (corrected p-values < 0.001). Illness severity was similar between the three groups, with the exception that epilepsy centers had a higher proportion of major severity cases. Length of stay remained fairly consistent across all three years for epilepsy centers (mean: 4.75 days), while decreasing for urban facilities (means: 4.39 to 3.72) and ultimately decreasing for rural facilities (mean: 3.31 to 3.09). Rates of procedure utilization revealed CT scan use persisted longer at rural facilities compared to urban facilities, while EEG and vEEG was low at rural facilities. vEEG was relatively restricted to epilepsy centers and had an initial substantial rise in use over the years and was associated with corresponding greater surgical procedure rates.

Significance

This study indicates a measurable difference between epilepsy centers, urban facilities, and rural facilities in cost and procedure utilization while caring for patients during epilepsy- and seizure-related hospitalizations. If these conclusions are valid, they support that persons living with epilepsy who live in rural communities and utilize these services receive care that is considered suboptimal when compared to urban centers or epilepsy centers.
Multidimensional factors predicting exclusive breastfeeding in Ethiopia: evidence from a meta-analysis of studies in the past 10 years
Authors: Habtewold Tesfa Dejenie , Endalamaw Aklilu , Mohammed Shimels Hussien , Mulugeta Henok , Dessie Getenet , Kassa Getachewu Mullu , Asmare Yared , Tadesse Mesfin , Alemu Yihun Mulugeta , Sharew Niguse Tadesse , Tura Abera Kenay , Tegegne Balewgizie Sileshi , Alemu Sisay Mulugeta
Published: July 2019

Background

In Ethiopia, the prevalence of exclusive breastfeeding (EBF) is 60.1%, which is lower than the national Health Sector Transformation Plan 2016-2020, National Nutrition Program 2016–2020 and WHO global target. This may be attributed to multidimensional factors.

Objective

The aim of this meta-analysis was to investigate the association between EBF and educational status, household income, marital status, media exposure, and parity in Ethiopia.

Methods

Databases used were PubMed, EMBASE, Web of Science, SCOPUS, CINAHL and WHO Global health library, and key terms were searched using interactive searching syntax. It was also supplemented by manual searching. Observational studies published between September 2000 and March 2019 were included. The methodological quality of studies was examined using the Newcastle-Ottawa Scale (NOS) for cross-sectional studies. Data were extracted using the Joanna Briggs Institute (JBI) data extraction tool. To obtain the pooled odds ratio (OR), extracted data were fitted in a random-effects meta-analysis model. Statistical heterogeneity was quantified using Cochran’s Q test, τ2, and I2 statistics. Additional analysis conducted includes Jackknife sensitivity analysis, cumulative meta-analysis, and meta-regression analysis.

Results

Out of 553 studies retrieved, 31 studies fulfilled our inclusion criteria. Almost all studies were conducted on mothers with newborn less than 23 months. Maternal educational status (OR = 1.39; p = 0.03; 95% CI = 1.03 - 1.89; I2 = 86.11%), household income (OR = 1.27; p = 0.02; 95% CI = 1.05 - 1.55; I2 = 60.9%) and marital status (OR = 1.39; p = 0.02; 95% CI = 1.05 - 1.83; I2 = 76.96%) were found to be significantly associated with EBF. We also observed an inverse dose-response relationship of EBF with educational status and income. Significant association was not observed between EBF and parity, media exposure and paternal educational status.

Conclusions

In this meta-analysis, we depicted the relevant effect of maternal education, income, and marital status on EBF. Therefore, multifaceted, effective, and evidence-based efforts are needed to increase national breastfeeding rates in Ethiopia.
Analyzing the Reversal Hypothesis of Obesity with Education: A Cross-Sectional Study of Adult Females in 34 Low- and Lower-Middle-Income Countries
Authors: Tang Cynthia Y. , Woldu Henok G. , Sheets Lincoln R.
Published: July 2019

Setting

Obesity, once considered an epidemic of the developed world, is now becoming an even more prominent problem than underweight in low and lower middle income countries (LLMICs). Ample literature has shown that as a country’s income increases, the burden of obesity shifts from the rich to the poor. This is known as the “Reversal Hypothesis.” Many studies have explored the effects of various social determinants of health on obesity, but few have studied education as an independent variable on female obesity across LLMICs.

Objective

Globally, adult females have a higher prevalence of obesity and the obesity shift occurs more quickly for women than for men. We aim to address this disparity and contribute towards the reversal hypothesis by exploring the association of education and obesity in women in LLMICs.

Design

In this cross-sectional study, we used a multi-national and multi-year database from the publicly available Demographic and Health Surveys program with data from 34 LLMICs. Education levels are standardized across countries during survey collection.

Results

Our age-adjusted prevalence ratio (AA-PR) analysis shows that women in LLMICs with higher education have a significantly greater prevalence of obesity than women with no education. We analyzed this phenomenon by individual nations, continents, and income classifications. Educated women living in low income countries are 5.12 times more obese than uneducated women (AA-PR, 95% CI=4.75, 5.53) and 3.42 times more obese in lower middle income countries (AA-PR, 95% CI=3.31, 3.54).

Conclusion

These findings highlight a need for more studies and policy attention focusing on female education levels, among other factors, to understand, predict, and prevent obesity in LLMICs.

ARTICLE SUMMARY

Strengths and limitations of this study

A rigorous sample size of 943,947 adult females in 34 LLMIC countries was utilized to study the association between adult female obesity and education level.

Age-adjusted and age-and-wealth-adjusted prevalence ratios of obesity were analyzed based on 34 individual nations, three continents, and two major income categories.

This study includes the most recent data available through the Demographic and Health Surveys program, which standardizes education levels during data collection, allowing for comparison between all surveyed countries.

This study is limited by the relatively small number of countries for which data is available through the DHS dataset, and thus, further research will be needed to show whether these results are generalizable to other LLMICs.
CpG-creating Mutations are Costly in Many Human Viruses
Authors: Caudill Victoria R. , Qin Sarina , Winstead Ryan , Kaur Jasmeen , Tisthammer Kaho , Pineda E. Geo , Carja Oana , Eggo Rosalind M , Koelle Katia , Lythgoe Katrina , Roy Scott , Allen Nicole , Aviles Milo , Baker Brittany A. , Bauer William , Bermudez Shannel , Carlson Corey , Catalan Francisca L. , Chemel Angeline Katia , Evans Dwayne , Fiutek Natalie , Fryer Emily , Goodfellow Samuel Melvin , Hecht Mordecai , Hopp Kellen , Hopson E. Deshawn , Jaberi Amirhossein , Kinney Christen , Lao Derek , Le Adrienne , Lo Jacky , Lopez Alejandro G. , López Andrea , Lorenzo Fernando G , Luu Gordon T , Mahoney Andrew R , Melton Rebecca L. , Nascimento Gabriela Do , Pradhananga Anjani , Rodrigues Nicole S. , Shieh Annie , Sims Jasmine , Singh Rima , Sulaeman Hasan , Thu Ricky , Tran Krystal , Tran Livia , Winters Elizabeth J. , Wong Albert , Pennings Pleuni S.
Published: July 2019

Mutations can occur throughout the virus genome and may be beneficial or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly that similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses.
The consequences of lipid remodelling of adipocyte cell membranes being functionally distinct from global lipid storage during obesity
Authors: Liu Ke-di , Acharjee Animesh , Hinz Christine , Liggi Sonia , Murgia Antonio , Denes Julia , Gulston Melanie K , Wang Xinzhu , Chu Yajing , West James A. , Glen Robert C , Roberts Lee D. , Murray Andrew J. , Griffin Julian L.
Published: July 2019

Obesity is a complex disorder where the genome interacts with diet and environmental factors to ultimately influence body mass, composition and shape. Numerous studies have investigated how bulk lipid metabolism of adipose tissue changes with obesity, and in particular how the composition of triglycerides (TGs) changes with increased adipocyte expansion. However, reflecting the analytical challenge posed by examining non-TG lipids in extracts dominated by TGs, the glycerophospholipid (PL) composition of cell membranes has been seldom investigated. PLs contribute to a variety of cellular processes including maintaining organelle functionality, providing an optimised environment for membrane-associated proteins and as pools for metabolites (e.g. choline for one-carbon metabolism and for methylation of DNA). We have conducted a comprehensive lipidomic study of white adipose tissue in mice who become obese either through genetic modification (ob/ob), diet (high fat diet) or a combination of the two using both solid phase extraction and ion mobility to increase coverage of the lipidome. Composition changes in seven classes of lipid (free fatty acids, diglycerides, TGs, phosphatidylcholines, lyso-phosphatidylcholines, phosphatidylethanolamines, and phosphatidylserines) correlated with perturbations in one-carbon metabolism and transcriptional changes in adipose tissue. We demonstrate that changes in TGs that dominate the overall lipid composition of white adipose tissue are distinct from diet-induced alterations of PLs, the predominant components of the cell membranes. PLs correlate better with transcriptional and one-carbon metabolism changes within the cell, suggesting the compositional changes that occur in cell membranes during adipocyte expansion have far-reaching functional consequences.
NK cells prevent the formation of teratomas derived from human induced pluripotent stem cells
Authors: Benabdallah Basma , Désaulniers-Langevin Cynthia , Colas Chloé , Li Yuanyi , Guimont Jean V. , Haddad Elie , Beauséjour Christian
Published: July 2019

The safe utilization of induced pluripotent stem cell-derivatives in clinic is tributary to the complete elimination of the risk of forming teratomas after transplantation. The extent by which such a risk exists in immune competent hosts is mostly unknown. Here, using humanized mice reconstituted with fetal hematopoietic stem cells and autologous thymus tissue (Hu-BLT) or following the adoptive transfer of peripheral blood mononuclear cells (PBMCs) (Hu-AT), we evaluated the capacity of immune cells to prevent or eliminate teratomas derived from human induced pluripotent stem cells (hiPSCs). Our results showed that the injection of hiPSCs failed to form teratomas in Hu-AT mice reconstituted with allogeneic or autologous PBMCs or purified NK cells alone. However, teratomas were observed in Hu-AT mice reconstituted with autologous PBMCs depleted from NK cells. In line with these results, Hu-BLT which do not have functional NK cells could not prevent the growth of autologous teratomas. Finally, we found that established teratomas were not targeted by NK cells and instead were efficiently rejected by allogeneic but not autologous T cells in Hu-AT mice. Overall, our findings suggest that autologous hiPSC-derived therapies are unlikely to form teratomas in the presence of NK cells.
Genomic properties of structural variants and short tandem repeats that impact gene expression and complex traits in humans
Authors: Jakubosky David , D’Antonio Matteo , Bonder Marc Jan , Smail Craig , Donovan Margaret K.R. , Greenwald William W. Young , D’Antonio-Chronowska Agnieszka , Matsui Hiroko ,   i2QTL Consortium, Stegle Oliver , Smith Erin N. , Montgomery Stephen B. , DeBoever Christopher , Frazer Kelly A.
Published: July 2019

Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we show that different SV classes and STRs differentially impact gene expression and complex traits. Functional differences between SV classes and STRs include their genomic locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We also identified a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and showed they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that impact gene expression and human traits.
Dissection of Catalytic Site in Crucial Gut Microbiome Enzyme: Bile Salt Hydrolase
Authors: Yadav Yashpal , Tiwari Mrityunjay K. , Chand Deepak , Boral Debjoyati , Pundle Archana , Ramasamy Sureshkumar
Published: July 2019

Bile Salt Hydrolases (BSHs) are enzymes from enteric bacteria that catalyze the hydrolysis of Bile Acids and consequently promote the reduction of cholesterol level in the mammalian body. Out of several reported BSHs, the Enterococcus faecalis BSH (EfBSH) has been reported to have the highest enzymatic activity. Herein, we have investigated the mechanistic details of the EfBSH activity. The study was carried out employing two mutants of EfBSH: E269A and R207A, which shows differential catalytic activity. The mutant E269A exhibits significant loss in the BSH activity with an increased affinity towards the substrate as compared to R207A mutant. Further, R207A was found to be involved in allostery with an increased EfBSH activity towards tauro-conjugated bile acids. The structural and electrostatic force analyses of the active sites of the E269A mutant and the wild type EfBSH (wt EfBSH) revealed that the interaction between Glu21 and Arg207 is the determining factor in maintaining the dynamic allostery and high activity of EfBSH.
Bayesian Correlation is a robust similarity measure for single cell RNA-seq data
Authors: Sanchez-Taltavull Daniel , Perkins Theodore J. , Dommann Noelle , Melin Nicolas , Keogh Adrian , Candinas Daniel , Stroka Deborah , Beldi Guido
Published: July 2019

Assessing similarityis highly important for bioinformatics algorithms to determine correlations between biological information. A common problem is that similarity can appear by chance, particularly for low expressed entities. This is especially relevant in single cell RNA-seq (scRNA-seq) data because read counts are much lower compared to bulk RNA-seq.

Recently, aBayesian correlationscheme, that assigns low similarity to genes that have low confidence expression estimates, has been proposed to assess similarity for bulk RNA-seq. Our goal is to extend the properties of the Bayesian correlation in scRNA-seq data by considering 3 ways to compute similarity. First, we compute the similarity of pairs of genes over all cells. Second, we identify specific cell populations and compute the correlation in those populations. Third, we compute the similarity of pairs of genes over all clusters, by considering the total mRNA expression.

We demonstrate that Bayesian correlations are more reproducible than Pearson correlations. Compared to Pearson correlations, Bayesian correlations have a smaller dependence on the number of input cells. We show that the Bayesian correlation algorithm assigns high similarity values to genes with a biological relevance in a specific population.

We conclude that Bayesian correlation is a robust similarity measure in scRNA-seq data.