bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic yet delicate: the dilemma of involving health workers in facilitating birth registration in Indonesia
Authors: Siagian Clara , Wandasari Wenny , Sahputra Feri , Kusumaningrum Santi
Published: November 2019

Background

Birth registration provides the basis for population data. Previous studies have examined that collaboration between the health sector and civil registration can help improve birth registration rate. However, there was a little exploration into health workers’ understanding of civil registration and vital statistics (CRVS) and their perceived role in it. This study aims to fill this gap by focusing on the perspective of both health personnel in a managerial position and those who are involved in direct service provision to the community. Finally, we discussed the opportunities and challenges to strengthen the birth registration presented by health workers’ diverse views.

Method

This study uses a qualitative approach through semi-structured in-depth interviews with 23 provincial to village health personnel in Pangkajene Kepulauan (Pangkep) district of South Sulawesi province. The participants were selected through consultation with the Department of Planning and the head of the Department of Health at provincial and district level based on the relevance of their position with CRVS. At the frontline level, the informants were identified using a snowballing technique and recommendation from community members.

Results

This study finds that at the village level, health workers perceive CRVS as important since it supports them in delivering healthcare to community members. They see identification document like birth certificate as crucial for healthcare seekers to access the government’s health insurance and with that, proper and affordable treatment. Some health workers have been facilitating birth registration on a discretionary basis. Local health officials agree that accurate birth data lead to effective planning and financing for healthcare services and insurance. Despite the positive perception of birth registration, the majority of health workers do not want the additional burden for registering births. Health officials, however, are more open to taking some responsibilities.

Conclusion

This study concludes that the level of health workers’ understanding and appreciation of the CRVS system provides opportunities to engage them systematically in birth registration. It recommends that institutionalizing health workers’ participation in birth registration must consider their current workload, revision of legal instruments, capacity building plan, and operable linkage with civil registration authority.
What constitutes patient-centred care for women: a theoretical rapid review
Authors: Ramlakhan Jessica U. , Foster Angel M. , Grace Sherry L. , Green Courtney R. , Stewart Donna E. , Gagliardi Anna R.
Published: November 2019

Background

Women experience disparities in health care delivery and outcomes. Patient-centred care for women (PCCW) is needed. This study examined how PCC has been conceptualized and operationalized in women’s health research.

Methods

We conducted a theoretical rapid review of PCCW in MEDLINE, EMBASE, CINAHL and SCOPUS from 2008 to 2018 for studies involving women aged 18 years or greater with any condition, and analyzed data using an established 6-domain framework of patient-centred communication.

Results

We included 39 studies, which covered the following clinical areas: maternal care, cancer, diabetes, HIV, endometriosis, dementia, distal radius fracture, overactive bladder, and lupus erythematosus. The 34 (87.2%) studies that defined or described PCC varied in the PCC elements they addressed, and none addressed all 6 PCC domains. Common domains were exchanging information (25, 73.5%) and fostering the patient-clinician relationship (22, 64.7%). Fewer studies addressed making decisions (16, 47.1%), enabling patient self-management (15, 44.1%), responding to emotions (12, 35.3%), or managing uncertainty (1, 2.9%). Compared with mixed-gender studies, those comprised largely of women more frequently prioritized exchanging information above other domains. Few studies tested strategies to support PCCW or evaluated the impact of PCCW; those that did demonstrated beneficial impact on patient knowledge, satisfaction, well-being, self-care and clinical outcomes.

Conclusions

Studies varied in how they conceptualized PCCW, and in many it was defined narrowly. Few studies examined how to implement or measure PCCW; thus, we lack insight on how to operationlize PCCW. Thus, further research is needed to confirm this, and whether PCCW differs across conditions, knowledge needed to inform policies, guidelines and measures aimed at improving health care and associated outcomes for women.
Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly
Authors: Shi Qing , Zhu Yasheng , Ma Jian , Chang Kun , Ding Dongling , Bai Yang , Gao Kun , Zhang Pingzhao , Mo Ren , Feng Kai , Zhao Xiaying , Zhang Liang , Sun Huiru , Jiao Dongyue , Chen Yingji , Sun Yinghao , Zhao Shi-min , Huang Haojie , Li Yao , Ren Shancheng , Wang Chenji
Published: November 2019

Background

The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. Stress granules (SG) assembly is an evolutionarily conserved strategy for survival of cells under stress, and often upregulated in human cancers. We investigated the role of SPOP mutations in aberrant activation of the SG in prostate cancer and explored the relevanve of the mechanism in therapy resistance.

Methods

We identified SG nucleating protein Caprin1 as a SPOP interactor by using the yeast two hybrid methods. A series of functional analyses in cell lines, patient samples, and xenograft models were performed to investigate the biological significance and clinical relevance of SPOP regulation of SG signaling in prostate cancer.

Results

The cytoplasmic form of wild-type (WT) SPOP recognizes and triggers ubiquitin-dependent degradation of Caprin1. Caprin1 abundance is elevated in SPOP-mutant expressing prostate cancer cell lines and patient specimens. SPOP WT suppresses SG assembly, while the prostate cancer-associated mutants enhance SG assembly in a Caprin1-dependent manner. Knockout of SPOP or expression of prostate cancer-associated SPOP mutants conferred resistance to death caused by SG inducers (e.g. docetaxel, sodium arsenite and H2O2) in prostate cancer cells.

Conclusions

SG assembly is aberrantly elevated in SPOP-mutated prostate cancer. SPOP mutations cause resistance to cellular stress induced by chemtherapeutic drug such as docetaxel in prostate cancer.
LncRNA H19 induced by helicobacter pylori infection promotes gastric cancer cell growth via enhancing NF-κB-induced inflammation
Authors: Zhang Yifeng , Yan Jin , Li Chao , Wang Xiaoyong , Dong Yu , Shen Xiaoran , Zhang Ximei
Published: November 2019

Background

The aim of this study was to investigate the role of long non-coding RNA (lncRNA) H19 in gastric cancer (GC) with Helicobacter pylori (H. pylori).

Methods

H19 expression in peripheral blood from H. pylori+/− GC patients and healthy donors (control) as well as in GC tissues and cells were detected by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. The levels of pro-inflammatory cytokines were determined by ELISA. The protein levels of IκBα, p-IκBα and p65 were determined by western blotting.

Results

H19 expression was upregulated in H. pylori-infected GC tissues and cells. Furthermore, H. pylori promoted GC cell viability, migration, invasion and inflammatory response. Moreover, H19 overexpression promoted the proliferation, migration and invasion of H. pylori-infected GC cells via enhancing NF-κB-induced inflammation.

Conclusions

LncRNA H19 promotes H. pylori-induced GC cell growth via enhancing NF-κB-induced inflammation.
Mono-institutional phase 2 study of innovative Stereotactic Body RadioTherapy targeting PArtial Tumor HYpoxic (SBRT-PATHY) clonogenic cells in unresectable bulky non-small cell lung cancer: profound non-targeted effects by sparing peri-tumoral immune microenvironment
Authors: Tubin Slavisa , Khan Mohammad K. , Salerno Gerardo , Mourad Waleed F. , Yan Weisi , Jeremic Branislav
Published: November 2019

Background

Radiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC.

Materials and methods

Sixty patients considered inoperable or unsuitable for radical radio-chemotherapy were enrolled and treated using the following 3 regimens: SBRT-PATHY (group I, n = 20 patients), recommended standard of care chemotherapy (group II, n = 20 patients), and institutional conventional palliative radiotherapy (group III, n = 20 patients).

Results

Median follow-up was 13 months. The 1-year overall survival was 75, 60, and 20% in groups 1, 2 and 3, respectively (p = 0.099). The 1-year cancer specific survival was 90, 60, and 20% in groups 1, 2, and 3, respectively (p = 0.049). Bulky tumor control rate was 95% for SBRT-PATHY compared with 20% in the other two groups. BE and AE were seen by SBRT-PATHY in 95 and 45% of patients, respectively. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p < 0.001) independent of age, sex, performance status, histology, stage, treated bulky site and tumor diameter. SBRT-PATHY resulted in lower toxicity (p = 0.026), and improved symptom control (p = 0.018) when compared to other two treatment options.

Conclusion

SBRT-PATHY improved treatment outcomes in unresectable NSCLC and should be investigated in larger trials.

Present study has been retrospectively registered on 8th of August 2019 by the ethic committee for Austrian region „Kärnten “in Klagenfurt (AUT), under study number A 31/19.
Incontinentia pigmenti burden scale: designing a family burden questionnaire
Authors:   the Filière Maladies Rares en Dermatologie, Taieb Charles , Hadj-Rabia Smail , Monnet Jacques , Bennani Mohammed , Bodemer Christine
Published: November 2019

Background

Incontentia pigmenti (IP) is a rare multisystem disorder of ectodermal origin comprising skin, dental, ocular and central nervous system features. Symptomatic treatments are adapted to each family according to the patient’s disability. Due to its rarity, the family IP burden in its broadest sense (psychological, social, economic and physical) has not yet been evaluated.

Aim

To design a questionnaire allowing assessing the family burden of IP (F’BoIP).

Method

A questionnaire was developed using a standardized methodology for designing quality of life questionnaires according to the following steps: conception, development, and validation. A multidisciplinary working group was designed, including experts in questionnaire development, dermatologists specialised in IP patient care and representatives of the French IP association. A cultural and linguistic validation into US English was conducted, based on the original French version.

Results

A 20-item conceptual questionnaire was generated. Subsequent confirmatory analyses produced a 20-item questionnaire grouped into four domains, demonstrating internal consistency (Cronbach’s alpha: 0.93), reproducibility and high reliability. The F’BoIP questionnaire significantly correlated with other validated questionnaires: Family Dermatology Life Quality Index (F-DLQI), Perceived Stress Scale (PSS) and SF-12 mental and SF12 physical scores, indicating good external validity.

Conclusion

The F’BoIP questionnaire is the first specific tool to assess the family burden of IP and can be used by both family members of IP patients and by health care professionals. It is a valuable tool which evaluates medical and nonmedical strategies to improve the daily life of families affected by this orphan disease.
The balance between mitotic death and mitotic slippage in acute leukemia: a new therapeutic window?
Authors: Ghelli Luserna di Rorà Andrea , Martinelli Giovanni , Simonetti Giorgia
Published: November 2019

Mitosis is the process whereby an eukaryotic cell divides into two identical copies. Different multiprotein complexes are involved in the fine regulation of cell division, including the mitotic promoting factor and the anaphase promoting complex. Prolonged mitosis can result in cellular division, cell death, or mitotic slippage, the latter leading to a new interphase without cellular division. Mitotic slippage is one of the causes of genomic instability and has an important therapeutic and clinical impact. It has been widely studied in solid tumors but not in hematological malignancies, in particular, in acute leukemia. We review the literature data available on mitotic regulation, alterations in mitotic proteins occurring in acute leukemia, induction of prolonged mitosis and its consequences, focusing in particular on the balance between cell death and mitotic slippage and on its therapeutic potentials. We also present the most recent preclinical and clinical data on the efficacy of second-generation mitotic drugs (CDK1-Cyclin B1, APC/CCDC20, PLK, Aurora kinase inhibitors). Despite the poor clinical activity showed by these drugs as single agents, they offer a potential therapeutic window for synthetic lethal combinations aimed to selectively target leukemic cells at the right time, thus decreasing the risk of mitotic slippage events.
DNMT3b/OCT4 expression confers sorafenib resistance and poor prognosis of hepatocellular carcinoma through IL-6/STAT3 regulation
Authors: Lai Ssu-Chuan , Su Yu-Ting , Chi Ching-Chi , Kuo Yung-Che , Lee Kam-Fai , Wu Yu-Chih , Lan Pei-Chi , Yang Muh-Hwa , Chang Te-Sheng , Huang Yen-Hua
Published: November 2019

Background

The inflammatory cytokine interleukin-6 (IL-6) is critical for the expression of octamer-binding transcription factor 4 (OCT4), which is highly associated with early tumor recurrence and poor prognosis of hepatocellular carcinomas (HCC). DNA methyltransferase (DNMT) family is closely linked with OCT4 expression and drug resistance. However, the underlying mechanism regarding the interplay between DNMTs and IL-6-induced OCT4 expression and the sorafenib resistance of HCC remains largely unclear.

Methods

HCC tissue samples were used to examine the association between DNMTs/OCT4 expression levels and clinical prognosis. Serum levels of IL-6 were detected using ELISA assays (n = 144). Gain- and loss-of-function experiments were performed in cell lines and mouse xenograft models to determine the underlying mechanism in vitro and in vivo.

Results

We demonstrate that levels of DNA methyltransferase 3 beta (DNMT3b) are significantly correlated with the OCT4 levels in HCC tissues (n = 144), and the OCT4 expression levels are positively associated with the serum IL-6 levels. Higher levels of IL-6, DNMT3b, or OCT4 predicted early HCC recurrence and poor prognosis. We show that IL-6/STAT3 activation increases DNMT3b/1 and OCT4 in HCC. Activated phospho-STAT3 (STAT-Y640F) significantly increased DNMT3b/OCT4, while dominant negative phospho-STAT3 (STAT-Y705F) was suppressive. Inhibiting DNMT3b with RNA interference or nanaomycin A (a selective DNMT3b inhibitor) effectively suppressed the IL-6 or STAT-Y640F-induced increase of DNMT3b-OCT4 and ALDH activity in vitro and in vivo. The fact that OCT4 regulates the DNMT1 expressions were further demonstrated either by OCT4 forced expression or DNMT1 silence. Additionally, the DNMT3b silencing reduced the OCT4 expression in sorafenib-resistant Hep3B cells with or without IL-6 treatment. Notably, targeting DNMT3b with nanaomycin A significantly increased the cell sensitivity to sorafenib, with a synergistic combination index (CI) in sorafenib-resistant Hep3B cells.

Conclusions

The DNMT3b plays a critical role in the IL-6-mediated OCT4 expression and the drug sensitivity of sorafenib-resistant HCC. The p-STAT3 activation increases the DNMT3b/OCT4 which confers the tumor early recurrence and poor prognosis of HCC patients. Findings from this study highlight the significance of IL-6-DNMT3b–mediated OCT4 expressions in future therapeutic target for patients expressing cancer stemness-related properties or sorafenib resistance in HCC.
Impact of rewarming rate on the mortality of patients with accidental hypothermia: analysis of data from the J-Point registry
Authors: Watanabe Makoto , Matsuyama Tasuku , Morita Sachiko , Ehara Naoki , Miyamae Nobuyoshi , Okada Yohei , Jo Takaaki , Sumida Yasuyuki , Okada Nobunaga , Nozawa Masahiro , Tsuruoka Ayumu , Fujimoto Yoshihiro , Okumura Yoshiki , Kitamura Tetsuhisa , Ohta Bon
Published: November 2019

Background

Accidental hypothermia (AH) is defined as an involuntary decrease in core body temperature to < 35 °C. The management of AH has been progressing over the last few decades, and numerous techniques for rewarming have been validated. However, little is known about the association between rewarming rate (RR) and mortality in patients with AH.

Method

This was a multicentre chart review study of patients with AH visiting the emergency department of 12 institutions in Japan from April 2011 to March 2016 (Japanese accidental hypothermia network registry, J-Point registry). We retrospectively registered patients using the International Classification of Diseases, Tenth Revision code T68: ‘hypothermia’. We excluded patients whose body temperatures were unknown or ≥ 35 °C, who could not be rewarmed, whose rewarmed temperature or rewarming time was unknown, those aged < 18 years, or who or whose family members had refused to join the registry. RR was calculated based on the body temperature on arrival at the hospital, time of arrival at the hospital, the documented temperature during rewarming, and time of the temperature documentation. RR was classified into the following five groups: ≥2.0 °C/h, 1.5–< 2.0 °C/h, 1.0–< 1.5 °C/h, 0.5–< 1.0 °C/h, and < 0.5 °C/h. The primary outcome of this study was in-hospital mortality. The association between RR and in-hospital mortality was evaluated using multivariate logistic regression analysis.

Result

During the study, 572 patients were registered in the J-Point registry, and 481 patients were included in the analysis. The median body temperature on arrival to the hospital was 30.7 °C (interquartile range [IQR], 28.2 °C–32.4 °C), and the median RR was 0.85 °C/h (IQR, 0.53 °C/h–1.31 °C/h). The in-hospital mortality rates were 19.3% (11/57), 11.1% (4/36), 14.4% (15/104), 20.1% (35/175), and 34.9% (38/109) in the ≥2.0 °C/h, 1.5–< 2.0 °C/h, 1.0–< 1.5 °C/h, 0.5–< 1.0 °C/h, and < 0.5 °C/h groups, respectively. Multivariate regression analysis revealed that in-hospital mortality rate increased with each 0.5 °C/h decrease in RR (adjusted odds ratio, 1.49; 95% confidence interval, 1.15–1.94;Ptrend < 0.01).

Conclusion

This study showed that slower RR is independently associated with in-hospital mortality.
Unique fine scale village spatial-temporal distributions of Anopheles farauti differ by physiological state and sex
Authors: Pollard Edgar J. M. , Russell Tanya L. , Apairamo Allan , Burkot Thomas R.
Published: November 2019

Background

The ecology of many mosquitoes, includingAnopheles farauti, the dominant malaria vector in the southwest Pacific including the Solomon Islands, remains inadequately understood. Studies to map fine scale vector distributions are biased when trapping techniques use lures that will influence the natural movements of mosquitoes by attracting them to traps. However, passive collection methods allow the detailed natural distributions of vector populations by sex and physiological states to be revealed.

Methods

The barrier screen, a passive mosquito collection method along with human landing catches were used to recordAn. farautidistributions over time and space in two Solomon Island villages from May 2016 to July 2017.

Results

Temporal and spatial distributions of over 15,000 mosquitoes, including males as well as unfed, host seeking, blood-fed, non-blood fed and gravid females were mapped. These spatial and temporal patterns varied by species, sex and physiological state. Sugar-fedAn. farautiwere mostly collected between 10–20 m away from houses with peak activity from 18:00 to 19:00 h. MaleAn. farautiwere mostly collected greater than 20 m from houses with peak activity from 19:00 to 20:00 h.

Conclusions

Anopheles farautisubpopulations, as defined by physiological state and sex, are heterogeneously distributed in Solomon Island villages. Understanding the basis for these observed heterogeneities will lead to more accurate surveillance of mosquitoes and will enable spatial targeting of interventions for greater efficiency and effectiveness of vector control.
Effects of enriched endogenous omega-3 fatty acids on age-related hearing loss in mice
Authors: Honkura Yohei , Suzuki Jun , Sakayori Nobuyuki , Inada Hitoshi , Kawase Tetsuaki , Katori Yukio , Osumi Noriko
Published: November 2019

Objective

Dietary intervention is a practical prevention strategy for age-related hearing loss (AHL). Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may be effective in prevention of AHL due to their anti-inflammatory and tissue-protective functions. Age-related changes in the hearing function of wild-type and Fat-1 transgenic mice derived from the C57BL/6N strain, which can convert omega-6 PUFAs to n-3 PUFAs and consequently produce enriched endogenous n-3 PUFAs, were investigated to test the efficacy of n-3 PUFAs for AHL prevention.

Results

At 2 months, the baseline auditory brainstem response (ABR) thresholds were the same in Fat-1 and wild-type mice at 8–16 kHz but were significantly higher in Fat-1 mice at 4 and 32 kHz. In contrast, the ABR thresholds of Fat-1 mice were significantly lower at 10 months. Moreover, the ABR thresholds of Fat-1 mice at low-middle frequencies were significantly lower at 13 months (12 kHz). Body weights were significantly reduced in Fat-1 mice at 13 months, but not at 2, 10, and 16–17 months. In conclusion, enriched endogenous n-3 PUFAs produced due to the expression of the Fat-1 transgene partially alleviated AHL in male C57BL/6N mice.
Cytotoxic T-lymphocyte antigen-4 +49A/G polymorphisms in Sudanese adults with type 1 diabetes and latent autoimmune diabetes
Authors: Alshareef Shimos A. , Omar Saeed M. , Hamdan Hamdan Z. , Adam Ishag
Published: November 2019

Objectives

This study was conducted to assess the association of T-lymphocyte-associated protein 4 (CTLA-4 +49A/G) variant with Latent autoimmune diabetes in adults (LADA) in Eastern Sudan. The study included 24 LADA, 240 patients with type 1 diabetes mellitus (T1DM), and 240 healthy controls. Genotyping for CTLA-4 +49A/G was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

Results

Genotypes distribution of CTLA-4 in controls was in accordance with the HWE (P > 0.05). The frequency of mutation (both homozygous and heterozygous) of CTLA-4 +49A/G (AG + GG) was significantly higher in LADA compared with T1DM and the controls [19 (79.1%) vs. 100 (41.7%) vs. 78 (32.5%), P < 0.001]. It was significantly higher when LADA was compared with T1DM [19 (79.1%) vs. 100 (41.7%), P = 0.018, OR = 3.21, 95% CI 1.16–8.89] and when LADA was compared with the controls [19 (79.1%) vs. 78 (32.5%), P = 0.001, OR = 4.49, 95% CI 1.62–12.42]. The rate of heterozygous mutation of the CTLA-4 +49A/G (AG) was significantly higher in LADA compared with T1DM and the controls [16 (66.7%) vs. 85 (35.4%) vs. 70 (29.2%), P < 0.001]. It was significantly higher when LADA was compared with T1DM [16 (66.7%) vs. 85 (35.4%), P = 0.002, OR = 3.64, 95% CI 1.49–8.87] and when LADA was compared with the controls [16 (66.6%) vs. 85 (35.4%), P = 0.001, OR = 4.85, 95% CI 1.98–11.86].
The utility of PAX8 and SATB2 immunohistochemical stains in distinguishing ovarian mucinous neoplasms from colonic and appendiceal mucinous neoplasm
Authors: Aldaoud Najla , Erashdi Madiha , AlKhatib Sohaib , Abdo Nour , Al-Mohtaseb Alia , Graboski-Bauer Ashley
Published: November 2019

Objectives

It is challenging to distinguish between primary ovarian mucinous tumors and metastatic mucinous neoplasms from the lower gastrointestinal tract, including appendiceal tumors. A combination of PAX8 and SATB2 immunohistochemical stains can be used as a diagnostic tool to distinguish between these cases.

Results

Immunostaining for SATB2, PAX8, CK7, CK20 and CDX2 was performed on 50 ovarian mucinous neoplasms (OMN) (39 cystadenomas, 4 borderline and 7 adenocarcinomas), 63 mucinous colorectal carcinoma (CRC), and 9 appendiceal mucinous neoplasms (AMN) [8 low grade appendiceal mucinous neoplasms (LAMN) and 1 adenocarcinoma]. PAX8 was positive in 32% of OMN and negative in all CRC and AMN cases. SATB2 was expressed in 2.0% of OMN, 77.8% of AMN, and 49.2% of CRC cases. CK7 was positive in 78.0% of OMN, 33.3% of AMN, and 9.5% of CRC cases. CK20 was expressed in 24.0% of OMN, 88.9% of OMN, and 87.3% of CRC cases. CDX2 was positive in 14.0% of OMN, 100% of AMN, and 90.5% of CRC cases. PAX8 can differentiate between OMN and AMN with high specificity but low sensitivity. CDX2 is the most sensitive marker for CRC and AMN, whereas SATB2 has better specificity.
Perturbations in imprinted methylation from assisted reproductive technologies but not advanced maternal age in mouse preimplantation embryos
Authors: Kindsfather Audrey J. , Czekalski Megan A. , Pressimone Catherine A. , Erisman Margaret P. , Mann Mellissa R. W.
Published: November 2019

Background

Over the last several decades, the average age of first-time mothers has risen steadily. With increasing maternal age comes a decrease in fertility, which in turn has led to an increase in the use of assisted reproductive technologies by these women. Assisted reproductive technologies (ARTs), including superovulation and embryo culture, have been shown separately to alter imprinted DNA methylation maintenance in blastocysts. However, there has been little investigation on the effects of advanced maternal age, with or without ARTs, on genomic imprinting. We hypothesized that ARTs and advanced maternal age, separately and together, alter imprinted methylation in mouse preimplantation embryos. For this study, we examined imprinted methylation at three genes, Snrpn, Kcnq1ot1, and H19, which in humans are linked to ART-associated methylation errors that lead to imprinting disorders.

Results

Our data showed that imprinted methylation acquisition in oocytes was unaffected by increasing maternal age. Furthermore, imprinted methylation was normally acquired when advanced maternal age was combined with superovulation. Analysis of blastocyst-stage embryos revealed that imprinted methylation maintenance was also not affected by increasing maternal age. In a comparison of ARTs, we observed that the frequency of blastocysts with imprinted methylation loss was similar between the superovulation only and the embryo culture only groups, while the combination of superovulation and embryo culture resulted in a higher frequency of mouse blastocysts with maternal imprinted methylation perturbations than superovulation alone. Finally, the combination of increasing maternal age with ARTs had no additional effect on the frequency of imprinted methylation errors.

Conclusion

Collectively, increasing maternal age with or without superovulation had no effect of imprinted methylation acquisition at Snrpn, Kcnq1ot1, and H19 in oocytes. Furthermore, during preimplantation development, while ARTs generated perturbations in imprinted methylation maintenance in blastocysts, advanced maternal age did not increase the burden of imprinted methylation errors at Snrpn, Kcnq1ot1, and H19 when combined with ARTs. These results provide cautious optimism that advanced maternal age is not a contributing factor to imprinted methylation errors in embryos produced in the clinic. Furthermore, our data on the effects of ARTs strengthen the need to advance clinical methods to reduce imprinted methylation errors in in vitro-produced embryos.
MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway
Authors: Liu Feng , Qiu Haibo , Xue Ming , Zhang Shi , Zhang Xiwen , Xu Jingyuan , Chen Jianxiao , Yang Yi , Xie Jianfeng
Published: November 2019

Background

An uncontrolled inflammatory response is a critical pathophysiological feature of sepsis. Mesenchymal stem cells (MSCs) induce macrophage phenotype polarization and reduce inflammation in sepsis. MSC-secreted transforming growth factor beta (TGF-β) participated in the immune modulatory function of MSCs. However, the underlying mechanism of MSC-secreted TGF-β was not fully elucidated in regulation macrophage M2-like polarization.

Methods

The paracrine effects of MSCs on macrophage polarization were studied using a co-culture protocol with LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs. The effect of TGF-β in the co-culture system was blocked by the TGF-β receptor inhibitor. To determine the role of MSC-secreted TGF-β, we used recombinant TGF-β to culture with LPS-stimulated RAW264.7 cells. In addition, we employed antibody microarray analysis to determine the mechanisms of MSC secreted TGF-β on LPS-stimulated RAW264.7 cell/mouse peritoneal macrophage M2-like polarization. Furthermore, we used an Akt inhibitor and a FoxO1 inhibitor to inhibit the Akt/FoxO1 pathway. The nuclear translocation of FoxO1 was detected by Western blot.

Results

MSCs induced LPS-stimulated RAW264.7 cell/mouse peritoneal macrophage polarization towards the M2-like phenotype and significantly reduced pro-inflammatory cytokine levels via paracrine, which was inhibited by TGF-β receptor inhibitor. Furthermore, we found that MSC-secreted TGF-β enhanced the macrophage phagocytic ability. The antibody microarray analysis and Western blot verified that TGF-β treatment activated the Akt/FoxO1 pathway in LPS-stimulated macrophages, TGF-β-induced FoxO1 nuclear translocation and obviously expressed in the cytoplasm, the effects of TGF-β regulatory effects on LPS-stimulated macrophage were inhibited by pre-treatment with Akt inhibitor and FoxO1 inhibitor.

Conclusions

TGF-β secreted by MSCs could skew LPS-stimulated macrophage polarization towards the M2-like phenotype, reduce inflammatory reactions, and improve the phagocytic ability via the Akt/FoxO1 pathway, providing potential therapeutic strategies for sepsis.
Post-fire fuel succession in a rare California, USA, closed-cone conifer
Authors: McNamara Bret A. , Kane Jeffrey M. , Greene David F.
Published: November 2019

Background

Increasing frequency and size of wildfires over the past few decades have prompted concerns that populations of obligate seeding species may be vulnerable to repeat, short-interval fires that occur prior to these species reaching maturity. The susceptibility of populations to this risk is partially dependent on the amount and characteristics of fuel loading over time and their influence on fire behavior and effects. This study characterized fuel dynamics and modeled fire behavior across a time-since-fire chronosequence in stands of the rare, serotinous conifer, Baker cypress (Hesperocyparis bakeri [Jeps.] Bartel), ranging in age between 3 and 147 years post fire.

Results

Litter and fine woody fuel loading (1- to 100-hour) were highest in the 10-year-old and 147-year-old stands, while coarse fuel loading (1000-hour) peaked in the 10-year-old stand and subsequently decreased with time since fire. Duff loading consistently increased with time since fire. Cone production had not occurred in the first 10 yr of stand development. Foliar moisture content in Baker cypress was inversely correlated with stand age, and older foliage had lower moisture content than younger foliage. Modeled surface fire behavior was highest in the 10-year-old and 107-year-old stands in accordance with higher litter, fine woody fuel, or shrub fuel accumulation. While foliar moisture content was higher in younger stands and influenced the critical fireline intensity, we did not observe changes in fire type.

Conclusions

Fine-fuel loading in Baker cypress stands followed a U-shaped pattern over time (first decreasing, then stable, then increasing), consistent with findings in other forests with stand-replacing fire regimes. Our results indicated that early-successional stages of Baker cypress forests have sufficient fuels to allow for the spread of wildfire and 10-year-old stands could burn with substantive fire behavior prior to cone production. Whenever possible, we recommend suppressing wildfire in stands less than 20 yr old to avoid substantial decreases or local extirpation of these rare Baker cypress populations. Our results highlight the importance of knowing the cone production patterns, fuel dynamics, and corresponding fire behavior over the development of obligate-seeder species to assess the risk of population loss due to short-interval fires.
Uptake and accumulation of di-n-butyl phthalate in six leafy vegetables under hydroponic conditions
Authors: Li Yong , Yan Huang-qian , Yu Xiang-yang
Published: November 2019

The uptake and accumulation of di-n-butyl phthalate (DBP) in six leafy vegetables was investigated under hydroponic conditions. The test vegetables were six varieties of Brassica campestris ssp., including Kangresijiqing (KRSJQ), Xiadiqing (XDQ), Ziyoucai (ZYC), Aijiaohuang (AJH), Shanghaiqing (SHQ) and Gaogengbai (GGB). The root concentration factor (RCF), translocation factor (TF) and transpiration stream concentration factor (TSCF) were calculated in order to compare the difference of uptake and accumulation behaviours of DBP in vegetable varieties. The results showed that DBP was easily concentrated in vegetable roots, but was poorly translocated from the roots to the shoots. Among the six vegetables, the ability of concentrating DBP from the solution to shoots was the highest in GGB, followed by ZYC, KRSJQ, AJH, SHQ and XDQ. High concentrations of DBP (5.0 mg/L) seem to inhibit normal physiological activity in the vegetables, which resulted in a higher RCF and a lower TF and TSCF than in low-concentration treatment. The results will help to evaluate the safety of agricultural products and to provide evidence for screening DBP pollution-safe vegetable cultivars.

Graphical abstract
Preliminary results of the acute Heart Failure registry in the DELTA region of Egypt (DELTA-HF): a database and a quality initiative project
Authors: Elasfar Abdelfatah , Shaheen Sherif , El-Sherbeny Wafaa , Elsokkary Hatem , Elhefnawy Suzan , Al-Setiha Mohammed
Published: November 2019

Background

Data about heart failure in Egypt is scarce. We aimed to describe the clinical characteristics and diagnostic and treatment options in patients with acute heart failure in the Delta region of Egypt and to explore the gap in the management in comparison to the international guidelines.

Results

DELTA-HF is a prospective observational cohort registry for all consecutive patients with acute heart failure (AHF) who were admitted to three tertiary care cardiac centers distributed in the Delta region of Egypt. All patients were recruited in the period from April 2017 to May 2018, during which, data were collected and short-term follow-up was done.

A total of 220 patients (65.5% were males with a median age of 61.5 years and 50.9% had acute decompensation on top of chronic heart failure) was enrolled in our registry. The risk factors for heart failure included rheumatic valvular heart disease (10.9%), smoking (65.3%), hypertension (48.2%), diabetes mellitus (42.7%), and coronary artery disease (28.2%). Left ventricular ejection fraction (LVEF) was less than 40% in 62.6%. Etiologies of heart failure included ischemic heart disease (58.1%), valvular heart disease (16.3%), systemic hypertension (9.1%), and dilated non-ischemic cardiomyopathy (15.5%). Exacerbating factors included infections (28.1%), acute coronary syndromes (25.5%), non-compliance to HF medications (19.6%), and non-compliance to diet (23.2%) in acute decompensated heart failure (ADHF) patients. None of our patients had been offered heart failure device therapy and only 50% were put on beta-blockers upon discharge. In-hospital, 30 days and 90 days all-cause mortality were 18.2%, 20.7%, and 26% respectively.

Conclusions

There is a clear gap in the management of patients with acute heart failure in the Delta region of Egypt with confirmed under-utilization of heart failure device therapy and under-prescription of guideline-directed medical therapies particularly beta-blockers. The short-term mortality is high if compared with Western and other local registries. This could be attributed mainly to the low-resource health care system in this region and the lack of formal heart failure management programs.
Postoperative 320 multi-slice computed tomography in assessment of pedicle screw insertion in thoraco-lumbar fixation
Authors: Salama Alsiagy A. , Amin Mohamed A. , Soliman Ahmed Y. , El-Tantaway Ahmed
Published: November 2019

Background

Pedicle screw instrumentation is used widely in lumbar spine for stabilization to enhance arthrodesis and has been accepted in the thoracic spine in recent years. The purpose of this study was to assess the value of postoperative 320 multi-slice computed tomography (MSCT) in assessment of pedicle screw placement in patients with spinal fixation with clinical and surgical correlation.

Results

A total of 340 pedicular screws were inserted to 70 cases. 286 (84.12%) were in, 54 screws (15.88%) were violated, and revision surgeries were required for 5 displaced screws. On axial, coronal reconstruction and three-dimensional (3D) reformatted CT images 36, 47, and 54 displaced screws were detected, respectively. Both sensitivity and specificity for 3D reformatted images were 100%. For axial image, they were 97.6% and 89.4%, respectively, compared with surgical findings in 5 revised screws.

Conclusion

Multi-slice CT scan is a valuable and valid postoperative assessment tool of accuracy of spinal pedicle screw placement.
A systematic, science-driven approach for predicting subsurface properties
Authors: Rose Kelly Kathleen , Bauer Jennifer R. , Mark-Moser MacKenzie
Published: November 2019

As human exploration of the subsurface increases, there is a need for better data- and knowledge-driven methods to improve prediction of subsurface properties. Present subsurface predictions often rely upon disparate and limited a priori information. Even regions with concentrated subsurface exploration still face uncertainties that can obstruct safe and efficient exploration of the subsurface. Uncertainty may be reduced, even for areas with little or no subsurface measurements, using methodical, science-driven geologic knowledge and data. We have developed a hybrid spatiotemporal statistical-geologic approach, subsurface trend analysis (STA), that provides improved understanding of subsurface systems. The STA method assumes that the present-day subsurface is not random, but is a product of its history, which is a sum of its systematic processes. With even limited data and geologic knowledge, the STA method can be used to methodically improve prediction of subsurface properties. To demonstrate and validate the improved prediction potential of the STA method, it was applied in an analysis of the northern Gulf of Mexico. This evaluation was prepared using only existing, publicly available well data and geologic literature. Using the STA method, this information was used to predict subsurface trends for in situ pressure, in situ temperature, porosity, and permeability. The results of this STA-based analysis were validated against new reservoir data. STA-driven results were also contrasted with previous studies. Both indicated that STA predictions were an improvement over other methods. Overall, STA results can provide critical information to evaluate and reduce risks, identify and improve areas of scarce or discontinuous data, and provide inputs for multiscale modeling efforts, from reservoir scale to basin scale. Thereby, the STA method offers an ideal framework for guiding future science-based machine learning and natural language processing to optimize subsurface analyses and predictions.
Brittleness index calculation based on amplitude-variation-with-offset inversion for coal-bed methane reservoir: A case study of the Qinshui Basin, China
Authors: Haibo Wu , Yan Cheng , Pingsong Zhang , Shouhua Dong , Yaping Huang
Published: November 2019

The brittleness index (BI) is an important parameter for coal-bed methane (CBM) reservoir fracturing characterization. Most published studies have relied on petrophysical and well-log data to estimate the geomechanical properties of reservoir rocks. The major drawback of such methods is the lack of control away from well locations. Therefore, we have developed a method of combining BI calculation from well logs with that inverted from 3D seismic data to overcome the limitation. A real example is given here to indicate the workflow. A traditional amplitude-variation-with-offset (AVO) inversion was conducted first. BI for the CBM reservoir was then calculated from the Lamé constants inverted from prestack seismic data through a traditional AVO inversion method. We build an initial low-frequency model based on the well-log data. Comparison of the seismic inverted BI at the target reservoir and BI extracted from the well-log data showed satisfactory results. This method has been proved to be efficient and effective enough at identifying BI sweet spots in CBM reservoirs.
Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age
Authors: Rank Cecilie U. , Wolthers Benjamin O. , Grell Kathrine , Albertsen Birgitte K. , Frandsen Thomas L. , Overgaard Ulrik M. , Toft Nina , Nielsen Ove J. , Wehner Peder S. , Harila-Saari Arja , Heyman Mats M. , Malmros Johan , Abrahamsson Jonas , Norén-Nyström Ulrika , Tomaszewska-Toporska Beata , Lund Bendik , Jarvis Kirsten B. , Quist-Paulsen Petter , Vaitkevičienė Goda E. , Griškevičius Laimonas , Taskinen Mervi , Wartiovaara-Kautto Ulla , Lepik Kristi , Punab Mari , Jónsson Ólafur G. , Schmiegelow Kjeld
Published: November 2019

PURPOSE

Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.

PATIENTS AND METHODS

We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.

RESULTS

Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.

CONCLUSION

Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
Radiotherapy to enhance T-cell infiltration and efficacy of PD-L1 blockade in murine orthotopic models of head and neck cancer.
Authors: Oweida Ayman , Lennon Shelby , Calame Dylan , Bhatia Shilpa , Raben David , Heasley Lynn , Nemenoff Raphael , Karam Sana
Published: November 2019

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Background: Cancers of the head and neck (HNC) represent some of the most debilitating and aggressive tumors. Radiotherapy (RT) is the primary treatment modality for locally advanced HNC, but less than 50% of patients treated with RT survive to 5 years. Clinical trials with the immune checkpoint inhibitor PD-L1 have shown considerable promise, but on its own has only yielded a 20% response rate. RT has the potential to transform the tumor microenvironment promoting infiltration of T-cells in poorly immunogenic tumors and activating T-cells in tumors with pre-existing T-cell populations. We hypothesized that the combination of PD-L1 inhibition with radiation can enhance therapeutic efficacy through re-invigoration of exhausted T-cells. Methods: Tumor cells were injected into the right buccal mucosa. Treatment was initiated when established tumors were observed. Forty mice per tumor model were randomized to IgG2b control, anti PD-L1, RT alone or RT+anti PD-L1. Anti PD-L1 was started 3 days before RT (single dose of 10Gy) and maintained for 3 weeks. For mechanistic studies, mice received the same treatment but were euthanized 72 hours after RT. Flow cytometric analysis of T-cell expression of PD-1, CTLA-4, FOXP3, CD44 and IFNG was performed on freshly harvested tumors and regional lymph nodes. Results: Tumor-bearing mice formed aggressive tumors with regional lymph node metastasis. Mice treated with RT or anti PD-L1 had slightly improved survival whereas mice treated with RT+anti-PD-L1 had significantly improved survival (p = 0.0007). Tumor control was significantly improved in the RT+anti-PD-L1 group compared to other groups. Anti PD-L1 alone did not improve tumor control. Average tumor volume on day 23 was 175±60.1 mm3 in the RT+anti-PD-L1 group compared to 623±91.0 mm3 in the PD-L1 group. Flow cytometric analysis revealed that this is mediated by enhancement in T-cell infiltration. Analysis of T-cell activation showed increased expression of CD44 and IFNG. Conclusions: Our results show a critical role for RT in mediating sensitivity to PD-L1 inhibition in HNC. In combination with anti PD-L1, RT significantly increased survival and tumor control compared to either modality alone.