bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen receptor α as a predictive biomarker for survival in human papillomavirus-positive oropharyngeal squamous cell carcinoma
Authors: Kwon Soohyeon , Ahn Soon-Hyun , Jeong Woo-Jin , Jung Young Ho , Bae Yun Jung , Paik Jin Ho , Chung Jin-Haeng , Kim Hyojin 
Published: June 2020

Abstract
Background
Although oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infection has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential to design deintensification regimens. Here, we investigated estrogen receptor α (ERα) as a prognostic biomarker with therapeutic implications in OPSCC alongside factors associated with HPV infection.

Methods
We performed immunohistochemistry for ERα and p53 using formalin-fixed, paraffin-embedded tissues and assessed the HPV status using p16 immunohistochemistry and HPV DNA testing in 113 consecutive patients with OPSCC treated with surgical resection or radiotherapy/chemoradiotherapy.

Results
ERα expression and p53 alteration was observed in 35.4% and 21.2% OPSCCs; 45.6% and 1.3% p16+/HPV+ OPSCCs; and 11.5% and 76.9% p16− OPSCCs, respectively. These data suggest that OPSCC pathogenesis varies with HPV status. Furthermore, ERα expression was associated with improved overall survival (OS) in both HPV+ (p16+/HPV+ OPSCC) and p16+ (p16+ OPSCC irrespective of HPV status) models (p = 0.005 and p = 0.006, respectively) and with improved OS adjusted for stage (p = 0.037, hazard ratio: 0.109, 95% confidence interval 0.013–0.871) in the p16+ model.

Conclusions
ERα is a potential predictive biomarker for improved survival in both HPV+ and p16+ OPSCC models.
Perceptions and experiences of men and women towards acceptability and use of contraceptives in underserved areas of Karachi, Pakistan: a midline qualitative assessment of Sukh initiative, Karachi Pakistan
Authors: Saleem Sarah , Rizvi Narjis , Shahil Feroz Anam , Reza Sayyeda , Jessani Saleem , Abrejo Farina 
Published: June 2020

Abstract
Background
Family planning (FP) is an essential component of Sustainable Development Goals (SDG) and contributes directly to SDG targets 3.7 and 5.6. In Pakistan, contraceptive use has remained stagnant over the past 5 years. This change has been very slow when compared to the FP2020 pledge. The Sukh initiative project was conceived and implemented to alleviate these challenges by providing access to quality contraceptive methods in some underserved areas of Karachi, Pakistan. A qualitative study was conducted to understand the perceptions and experiences of men and women towards acceptability and contraceptive use.

Methods
A qualitative study was conducted at ten Sukh stations located in four towns of Karachi. Focus group discussions (FGDs) were conducted with married women of reproductive age (MWRA) and married men who received FP services through the Sukh initiative. Study participants were purposively sampled for focus group discussions (FGDs). Interview data was manually transcribed and analyzed using thematic analysis.

Results
A total of 20 FDGs (Men = 10 FGDs; MWRA = 10 FGDs) were conducted. Three overarching themes were identified: (I) Appropriateness and means to promote contraceptive use; (II) Equity and Accessibility to contraceptives; and (III) Perspective on available FP services. Generally, both men and women were informed about FP methods but women were more cognizant of FP information. The door to door services by community health workers in Sukh initiative areas was largely appreciated both by women and men as it has made the accessibility and availability of the information and services easy. Women suggested that the Sukh initiative should bring some strategies that can help men broaden their perspective towards FP. The study informed that the men feel left out from the FP programs. Therefore, male participants expressed keen interest in initiatives for men in their communities that would cater to their FP needs.

Conclusions
This qualitative study provided a unique opportunity to understand the perceptions of men and women towards the phenomena of contraceptive use. The study identified the need for trained and qualified female and male healthcare providers and well-established health facilities alongside door-to-door services.
Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression
Authors: Aleksandrova Lily R. , Wang Yu Tian , Phillips Anthony G. 
Published: June 2020

AbstractAccumulating evidence implicates dysregulation of hippocampal synaptic plasticity in the pathophysiology of depression. However, the effects of ketamine on synaptic plasticity and their contribution to its mechanism of action as an antidepressant, are still unclear. We investigated ketamine’s effects on in vivo dorsal hippocampal (dHPC) synaptic plasticity and their role in mediating aspects of antidepressant activity in the Wistar-Kyoto (WKY) model of depression. dHPC long-term potentiation (LTP) was significantly impaired in WKY rats compared to Wistar controls. Importantly, a single low dose (5 mg/kg, ip) of ketamine or its metabolite, (2R,6R)-HNK, rescued the LTP deficit in WKY rats at 3.5 h but not 30 min following injection, with residual effects at 24 h, indicating a delayed, sustained facilitatory effect on dHPC synaptic plasticity. Consistent with the observed dHPC LTP deficit, WKY rats exhibited impaired hippocampal-dependent long-term spatial memory as measured by the novel object location recognition test (NOLRT), which was effectively restored by pre-treatment with both ketamine or (2R,6R)-HNK. In contrast, in WKYs, which display abnormal stress coping, ketamine, but not (2R,6R)-HNK, had rapid and sustained effects in the forced swim test (FST), a commonly used preclinical screen for antidepressant-like activity. The differential effects of (2R,6R)-HNK observed here reveal a dissociation between drug effects on FST immobility and dHPC synaptic plasticity. Therefore, in the WKY rat model, restoring dHPC LTP was not correlated with ketamine’s effects in FST, but importantly, may have contributed to the reversal of hippocampal-dependent cognitive deficits, which are critical features of clinical depression. Our findings support the theory that ketamine may reverse the stress-induced loss of connectivity in key neural circuits by engaging synaptic plasticity processes to “reset the system”.
Intraventricular IL-17A administration activates microglia and alters their localization in the mouse embryo cerebral cortex
Authors: Sasaki Tetsuya , Tome Saki , Takei Yosuke 
Published: June 2020

AbstractViral infection during pregnancy has been suggested to increase the probability of autism spectrum disorder (ASD) in offspring via the phenomenon of maternal immune activation (MIA). This has been modeled in rodents. Maternal T helper 17 cells and the effector cytokine, interleukin 17A (IL-17A), play a central role in MIA-induced behavioral abnormalities and cortical dysgenesis, termed cortical patch. However, it is unclear how IL-17A acts on fetal brain cells to cause ASD pathologies. To assess the effect of IL-17A on cortical development, we directly administered IL-17A into the lateral ventricles of the fetal mouse brain. We analyzed injected brains focusing on microglia, which express IL-17A receptors. We found that IL-17A activated microglia and altered their localization in the cerebral cortex. Our data indicate that IL-17A activates cortical microglia, which leads to a cascade of ASD-related brain pathologies, including excessive phagocytosis of neural progenitor cells in the ventricular zone.
Clinical and bacteriological profile of diabetic foot infections in a tertiary care
Authors: Goh Teik Chiang , Bajuri Mohd Yazid , C. Nadarajah Sivapathasundaram , Abdul Rashid Abdul Halim , Baharuddin Suhaila , Zamri Kamarul Syariza 
Published: June 2020

AbstractBackgroundDiabetic foot infection is a worldwide health problem is commonly encountered in daily practice. This study was conducted to identify the microbiological profile and antibiotic sensitivity patterns of causative agents identified from diabetic foot infections (DFIs). In addition, the assessment included probable risk factors contributing to infection of ulcers that harbour multidrug‐resistant organisms (MDROs) and their outcomes.MethodsWe carried out a prospective analysis based on the DFI samples collected from 2016 till 2018. Specimens were cultured with optimal techniques in addition to antibiotic susceptibility based on recommendations from The Clinical and Laboratory Standards Institute (CLSI). A total of 1040 pathogens were isolated with an average of 1.9 pathogens per lesion in 550 patients who were identified with having DFIs during this interval.ResultsA higher percentage of Gram‐negative pathogens (54%) were identified as compared with Gram‐positive pathogens (33%) or anaerobes (12%). A total of 85% of the patients were found to have polymicrobial infections.Pseudomonas aeruginosa(19%),Staphylococcus aureus(11%) and Bacteroides species (8%) appeared to be the predominant organisms isolated. In the management of Gram‐positive bacteria, the most efficacious treatment was seen with the use of Vancomycin, while Imipenem and Amikacin proved to be effective in the treatment of Gram‐negative bacteria.ConclusionDFI's are common among Malaysians with diabetes, with a majority of cases displaying polymicrobial aetiology with multi‐drug resistant isolates. The data obtained from this study will be valuable in aiding future empirical treatment guidelines in the treatment of DFIs. This study investigated the microbiology of DFIs and their resistance to antibiotics in patients with DFIs that were managed at a Tertiary Care Centre in Malaysia.
Health-related quality of life of children and their parents 2 years after critical illness: pre-planned follow-up of the PEPaNIC international, randomized, controlled trial
Authors: Hordijk José , Verbruggen Sascha , Vanhorebeek Ilse , Güiza Fabian , Wouters Pieter , Van den Berghe Greet , Joosten Koen , Dulfer Karolijn 
Published: June 2020

Abstract
Background
Pediatric intensive care unit (PICU) survivors are at risk for prolonged morbidities interfering with daily life. The current study examined parent-reported health-related quality of life (HRQoL) in former critically ill children and parents themselves and aimed to determine whether withholding parenteral nutrition (PN) in the first week of critical illness affected children’s and parents’ HRQoL 2 years later.

Methods
Children who participated in the pediatric early versus late parenteral nutrition in critical illness (PEPaNIC) trial and who were testable 2 years later (n = 1158) were included. Their HRQoL outcomes were compared with 405 matched healthy controls. At PICU admission, children had been randomly assigned to early-PN or late-PN. In the early-PN group, PN was initiated within 24 h after PICU admission. In the late-PN group, PN was withheld for up to 1 week in the PICU. Parents completed the Infant Toddler Quality of Life Questionnaire (ITQOL; age 2–3 years) or the Child Health Questionnaire-Parent Form 50 (CHQ-PF50; age 4–18 years). Besides, they completed the Health Utility Index (HUI) and the Short Form Health Survey (SF-12) regarding their child’s and their own HRQoL, respectively.

Results
For the total age group of 786 post-PICU survivors, parents reported lower scores for almost all HRQoL scales compared to healthy children. Age-specifically, younger critically ill children (2.5 to 3 years old) scored worse for growth and development and older children (4–18 years old) scored worse for role functioning and mental health. Parents’ own mental and physical HRQoL was comparable to that of healthy control parents. No HRQoL differences were found between children in the late-PN and those in the early-PN group.

Conclusions
Parent-reported HRQoL of children 2 years after critical illness was impaired compared with healthy controls. In relation to their child’s HRQoL, parents reported impairments in emotions, personal time, and family activities; however, their own HRQoL was not impaired. Withholding PN in the first week during critical illness had no impact on longer-term HRQoL of the child.

Trial registration
Clinical trials, NCT01536275. Registered 22 February 2012
3D genome architecture coordinates trans and cis regulation of differentially expressed ear and tassel genes in maize
Authors: Sun Yonghao , Dong Liang , Zhang Ying , Lin Da , Xu Weize , Ke Changxiong , Han Linqian , Deng Lulu , Li Guoliang , Jackson David , Li Xingwang , Yang Fang 
Published: June 2020

Abstract
Background
Maize ears and tassels are two separate types of inflorescence which are initiated by similar developmental processes but gradually develop distinct architectures. However, coordinated trans and cis regulation of differentially expressed genes determining ear and tassel architecture within the 3D genome context is largely unknown.

Results
We identify 56,055 and 52,633 open chromatin regions (OCRs) in developing maize ear and tassel primordia using ATAC-seq and characterize combinatorial epigenome features around these OCRs using ChIP-seq, Bisulfite-seq, and RNA-seq datasets. Our integrative analysis of coordinated epigenetic modification and transcription factor binding to OCRs highlights the cis and trans regulation of differentially expressed genes in ear and tassel controlling inflorescence architecture. We further systematically map chromatin interactions at high-resolution in corresponding tissues using in situ digestion-ligation-only Hi-C (DLO Hi-C). The extensive chromatin loops connecting OCRs and genes provide a 3D view on cis- and trans-regulatory modules responsible for ear- and tassel-specific gene expression. We find that intergenic SNPs tend to locate in distal OCRs, and our chromatin interaction maps provide a potential mechanism for trait-associated intergenic SNPs that may contribute to phenotypic variation by influencing target gene expression through chromatin loops.

Conclusions
Our comprehensive epigenome annotations and 3D genome maps serve as valuable resource and provide a deep understanding of the complex regulatory mechanisms of genes underlying developmental and morphological diversities between maize ear and tassel.
Fast-track- recovery surgery with a whey-protein-infused carbohydrate-loading drink pre-operatively and early oral feeding post-operatively among surgical gynaecological cancer patients: study protocol of an open-labelled, randomised controlled trial
Authors: Ho Chiou Yi , Ibrahim Zuriati , Abu Zaid Zalina , Mat Daud Zulfitri ‘Azuan , Md Yusop Nor Baizura 
Published: June 2020

Abstract
Introduction
There has been growing evidence on the favourable outcomes of fast-track-recovery (FTR) surgery; to expedite recovery, minimise complications, and reduce the length of hospital stay for surgical patients. However, there is lack of evidence on the effectiveness of FTR in surgical gynaecological cancer (GC) patients. Most of the previous studies did not focus on feeding composition in the FTR surgery protocol. This study aims to determine the effectiveness of FTR feeding with a whey-protein-infused carbohydrate-loading drink pre-operatively and early oral feeding post-operatively on post-operative outcomes among surgical GC patients.

Methods/design
This open-labelled, randomised controlled trial (RCT) will randomly allocate patients into intervention and control groups. Ambulated Malaysian aged over 18 years and scheduled for elective surgery for (suspected) GC, will be included in this study. The intervention group will be given whey-protein-infused carbohydrate-loading drinks on the evening before their operation and 3 h before their operation as well as started on early oral feeding 4 h post-operatively. The control group will be fasted overnight pre-operation and only allowed plain water, and return to a normal diet is allowed when bowel sounds return post-operatively. The primary outcomes of study are length of post-operative hospital stay, length of clear-fluid tolerance, solid-food tolerance and bowel function. Additional outcome measures are changes in nutritional status, biochemical profile and functional status. Data will be analysed on an intention-to-treat basis.

Trial registration
ClinicalTrials.gov, ID: NCT03667755. Retrospectively registered on 12 September 2018;
Protocol version: version 3 dated 27 September 2017.
Comparative therapeutic index, lethal time and safety margin of various toxicants and snake antivenoms using newly derived and old formulas
Authors: Saganuwan Saganuwan Alhaji 
Published: June 2020

Abstract
Objective
The assessment of clinical efficacy and toxicity is very important in pharmacology and toxicology. The effects of psychostimulants (e.g. amphetamine), psychotomimetics (e.g. Cannabis sativus) and snake antivenoms are sometimes unpredictable even at lower doses, leading to serious intoxication and fatal consequences. Hence, there is need to re-assess some formulas for calculation of therapeutic index, lethal time and safety margin with a view to identifying therapeutic agents with remarkable toxicity potentials.

Results
The therapeutic index formula $$\left[ {T_{1} = 3\left( {W_{a} \times 10^{ - 4} } \right)} \right]$$

T
1

=
3

W
a

×

10

-
4

was derived from T1 = LD50/ED50 and ED50 = $$\frac{{LD_{50} }}{3} x W_{a} \times 10^{ - 4}$$

L

D
50

3

x

W
a

×

10

-
4

. Findings have shown that, therapeutic index is a function of death reversal (s), safety factor (10−4) and weight of animal (Wa). However, the new safety margin formula $$\left[ {MS = \sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}} \times \frac{1}{{ED_{99} }}} \right]$$

M
S
=

L

T
50

L

D
50

3

×

1

E

D
99

derived from LT50 = $$\frac{{LD_{50} }}{{D_{1}^{p} }}$$

L

D
50

D

1

p

and MS = $$\frac{{LD_{1} }}{{ED_{99} }}$$

L

D
1

E

D
99

shows that safety margin is a function of cube root of ratio between LT50 and LD50 and ED100th. Concentration (k) of toxicant at the receptor $$\left[ {K = \sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}} \times \frac{1}{{T^{n} }}} \right]$$

K
=

L

T
50

L

D
50

3

×

1

T
n

derived from D1 × Tn = K and LD1 = $$\sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}}$$

L

T
50

L

D
50

3

shows that therapeutic index, lethal time and safety margin is a function of drug or toxicant concentration at the receptor, the drug-receptor interaction and dose of toxicant or drug administered at a particular time.
SOCRATES: an online tool leveraging a social contact data sharing initiative to assess mitigation strategies for COVID-19
Authors: Willem Lander , Van Hoang Thang , Funk Sebastian , Coletti Pietro , Beutels Philippe , Hens Niel 
Published: June 2020

AbstractObjectiveEstablishing a social contact data sharing initiative and an interactive tool to assess mitigation strategies for COVID-19.ResultsWe organized data sharing of published social contact surveys via online repositories and formatting guidelines. We analyzed this social contact data in terms of weighted social contact matrices, next generation matrices, relative incidence and R$$_{0}$$0. We incorporated location-specific physical distancing measures (e.g. school closure or at work) and capture their effect on transmission dynamics. All methods have been implemented in an online application based on R Shiny and applied to COVID-19 with age-specific susceptibility and infectiousness. Using our online tool with the available social contact data, we illustrate that physical distancing could have a considerable impact on reducing transmission for COVID-19. The effect itself depends on assumptions made about disease-specific characteristics and the choice of intervention(s).
Ochratoxigenic fungi and Ochratoxin A determination in dried grapes marketed in Tunisia
Authors: Chebil Samir , Rjiba-Bahri Wafa , Oueslati Souheib , Ben Ismail Hanen , Ben-Amar Anis , Natskoulis Pantelis 
Published: June 2020

Abstract
Purpose
With the present work, we aimed to assess the occurrence of ochratoxigenic fungi and Ochratoxin A (OTA) in dried grapes from Tunisia.

Methods
Dried grapes samples (n = 90) were investigated for the presence of ochratoxigenic fungi, which were further characterized at the species level through amplification of the internal transcribed spacer (ITS) region and polymerase chain reaction (PCR) product sequencing. Fungal isolates were tested for their ochratoxigenic potential by high-performance liquid chromatography with fluorescence detection (HPLC-FLD), as well as dried grapes samples after an immunoaffinity column (IAC) clean-up procedure.

Results
Black Aspergilli isolates were the dominant genre among the filamentous fungi found in dried grapes samples and were the only OTA-producing fungi encountered. Aspergillus niger aggregate were the most frequently found isolates reaching 70%, 80%, and 85% in dried grapes samples from regions of Kelibia, Sfax, and Rafraf, respectively, while covered 100% of the relevant mycobiota found in imported samples. Aspergillus carbonarius isolates were found only in Sfax’s and Kelibia’s samples, while uniseriate Aspergilli were found between 7 and 20% in dried grapes from Kelibia, Sfax, and the imported samples. The in vitro OTA production test showed that 88.9% of OTA-producing isolates belonged to A. carbonarius with OTA levels varying from 0.06 to 1.32 μg/g of Czapek Yeast Agar (CYA). The remaining OTA-producing fungi (11.1 %) belonged to A. niger aggregate group having a maximum OTA potential of 2.88 μg/g CYA, and no uniseriate Aspergilli isolate was able to produce OTA. All dried grapes samples were free of OTA presence.

Conclusion
According to the present study’s findings, no OTA contamination was recorded in the investigated samples from Tunisian market. Nevertheless, the presence of strong OTA producers A. carbonarius in samples originated from the two out of three studied Tunisian regions, as well the high incidences of Aspergillus niger aggregate group with an attested potential for OTA production in all samples, necessitates further research on Tunisian dried grapes. Additionally, a continuous analysis of staple food of the Mediterranean diet is imperative to insure the best quality for the consumers and prevent potential health problems.