bluuebunny/crossref_metadata_2025 huggingface dataset:
Parent proxy assessment of sibling quality of life following pediatric hematopoietic cell transplantation
Authors: Buchbinder David , Patel Sunita K. , Casillas Jacqueline N. , Nugent Diane J. , Neudorf Steven , Sender Leonard S. , Torno Lilibeth , Huszti Heather , Zeltzer Lonnie K. , Parsons Susan K.
Published: October 2019

Background

When a child undergoes hematopoietic cell transplantation (HCT), the impact extends to the entire family, including siblings. Assessment of the quality of life (QoL) of siblings is challenged by their general lack of availability for regular assessment by clinical providers. Thus, the use of parent proxy reporting may be useful. Our aim was to describe the QoL of siblings of HCT survivors, as reported by their parents, as well as to identify parent and family factors associated with lower sibling QoL.

Methods

A cross-sectional study was utilized to assess parent-reported QoL of the HCT recipient’s sibling (Short Form (SF)-10 Health Survey for Children and the Pediatric Symptom Checklist (PSC)-17). Parent QoL was assessed using the SF-12. Multivariable linear regression was used to explore hypothesized predictors of sibling QoL, including parent QoL, family impact/function (Impact on Family Scale, Family Adaptability and Cohesion Evaluation Scales, IV, and a question asking about financial problems) while adjusting for demographic and HCT characteristics.

Results

Ninety-seven siblings (55% males) with a mean age of 12 years (standard deviation [SD] 4 years) were assessed, representing HCT survivors, who were an average of 5 years (SD 4 years) post-HCT. Neither sibling psychosocial (mean 49.84, SD 10.70, p = 0.87) nor physical health scores (mean 51.54, SD 8.42, p = 0.08) differed from norms. Parent proxies reported behavioral/emotional problems (PSC-17 total score > 15) in 24% of siblings. While parental ratings of their own physical health (SF-12 were higher than norms (mean 53.04, SD 8.17, p = 0.0005), mental health scores were lower (mean 45.48, SD 10.45, p < 0.0001). In multivariable analysis, lower parent emotional functioning and adverse family function were associated with lower sibling QoL, as reported by parents.

Conclusions

While proxy-reported QoL of siblings did not differ significantly from normative data, both parent QoL and family function were associated with sibling QoL. Future research is needed to understand how siblings themselves perceive their QoL following HCT.
CD36 promotes the epithelial–mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β
Authors: Deng Min , Cai Xiaodong , Long Ling , Xie Linying , Ma Hongmei , Zhou Youjian , Liu Shuguang , Zeng Chao
Published: October 2019

Background

Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer.

Methods

Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis.

Results

In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer.

Conclusions

Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.
First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene
Authors: Oziębło Dominika , Sarosiak Anna , Leja Marcin L. , Budde Birgit S. , Tacikowska Grażyna , Di Donato Nataliya , Bolz Hanno J. , Nürnberg Peter , Skarżyński Henryk , Ołdak Monika
Published: October 2019

Background

Biallelic PTPRQ pathogenic variants have been previously reported as causative for autosomal recessive non-syndromic hearing loss. In 2018 the first heterozygous PTPRQ variant has been implicated in the development of autosomal dominant non-syndromic hearing loss (ADNSHL) in a German family. The study presented the only, so far known, PTPRQ pathogenic variant (c.6881G>A) in ADNSHL. It is located in the last PTPRQ coding exon and introduces a premature stop codon (p.Trp2294*).

Methods

A five-generation Polish family with ADNSHL was recruited for the study (n = 14). Thorough audiological, neurotological and imaging studies were carried out to precisely define the phenotype. Genomic DNA was isolated from peripheral blood samples or buccal swabs of available family members. Clinical exome sequencing was conducted for the proband. Family segregation analysis of the identified variants was performed using Sanger sequencing. Single nucleotide polymorphism array on DNA samples from the Polish and the original German family was used for genome-wide linkage analysis.

Results

Combining clinical exome sequencing and family segregation analysis, we have identified the same (NM_001145026.2:c.6881G>A, NP_001138498.1:p.Trp2294*) PTPRQ alteration in the Polish ADNSHL family. Using genome-wide linkage analysis, we found that the studied family and the original German family derive from a common ancestor. Deep phenotyping of the affected individuals showed that in contrast to the recessive form, the PTPRQ-related ADNSHL is not associated with vestibular dysfunction. In both families ADNSHL was progressive, affected mainly high frequencies and had a variable age of onset.

Conclusion

Our data provide the first confirmation of PTPRQ involvement in ADNSHL. The finding strongly reinforces the inclusion of PTPRQ to the small set of genes leading to both autosomal recessive and dominant hearing loss.
Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling
Authors: Ryu Ka-Young , Lee Hyun-ju , Woo Hanwoong , Kang Ri-Jin , Han Kyung-Min , Park HyunHee , Lee Sang Min , Lee Ju-Young , Jeong Yoo Joo , Nam Hyun-Wook , Nam Youngpyo , Hoe Hyang-Sook
Published: October 2019

Background

The FDA-approved small-molecule drug dasatinib is currently used as a treatment for chronic myeloid leukemia (CML). However, the effects of dasatinib on microglial and/or astrocytic neuroinflammatory responses and its mechanism of action have not been studied in detail.

Methods

BV2 microglial cells, primary astrocytes, or primary microglial cells were treated with dasatinib (100 or 250 nM) or vehicle (1% DMSO) for 30 min or 2 h followed by lipopolysaccharide (LPS; 200 ng/ml or 1 μg/ml) or PBS for 5.5 h. RT-PCR, real-time PCR; immunocytochemistry; subcellular fractionation; and immunohistochemistry were subsequently conducted to determine the effects of dasatinib on LPS-induced neuroinflammation. In addition, wild-type mice were injected with dasatinib (20 mg/kg, intraperitoneally (i.p.) daily for 4 days or 20 mg/kg, orally administered (p.o.) daily for 4 days or 2 weeks) or vehicle (4% DMSO + 30% polyethylene glycol (PEG) + 5% Tween 80), followed by injection with LPS (10 mg/kg, i.p.) or PBS. Then, immunohistochemistry was performed, and plasma IL-6, IL-1β, and TNF-α levels were analyzed by ELISA.

Results

Dasatinib regulates LPS-induced proinflammatory cytokine and anti-inflammatory cytokine levels in BV2 microglial cells, primary microglial cells, and primary astrocytes. In BV2 microglial cells, dasatinib regulates LPS-induced proinflammatory cytokine levels by regulating TLR4/AKT and/or TLR4/ERK signaling. In addition, intraperitoneal injection and oral administration of dasatinib suppress LPS-induced microglial/astrocyte activation, proinflammatory cytokine levels (including brain and plasma levels), and neutrophil rolling in the brains of wild-type mice.

Conclusions

Our results suggest that dasatinib modulates LPS-induced microglial and astrocytic activation, proinflammatory cytokine levels, and neutrophil rolling in the brain.
CD147 as a key mediator of the spleen inflammatory response in mice after focal cerebral ischemia
Authors: Jin Rong , Zhong Wei , Liu Shan , Li Guohong
Published: October 2019

Background

The splenic inflammatory response after cerebral ischemia has been implicated in secondary brain injury. We have recently reported that CD147 plays an important role in driving brain inflammation after ischemic stroke. In this study, we hypothesized that CD147 may play a role in the splenic inflammatory response after cerebral ischemia.

Methods

Transient (60 min) middle cerebral artery occlusion was induced in wild-type mice treated with an anti-CD147 antibody (αCD147) 1 h before ischemia onset. The splenic inflammatory response was evaluated at 4 and 24 h, representing the peak and early stage of splenic inflammatory activation in this model. Changes in mRNA and protein expression of CD147 and inflammatory markers were measured using RT-qPCR and western blot, respectively. Immune cells in the spleen and brain were measured using flow cytometry.

Results

CD147 expression was rapidly upregulated in the spleen at 4 and 24 h after ischemia onset. The splenic inflammatory response induced by cerebral ischemia was inhibited by αCD147 treatment as demonstrated by the reduced expression of cytokines (TNFα, IL-6, IL-1β) and monocyte chemoattractant protein-1 (MCP-1) in the spleen at 4 and 24 h after ischemia onset. Furthermore, reduced expression of Ly-6C and CCR2 coincided with a decrease in the number of Ly-6ChighMMs subset in the spleen at 4 h after ischemia onset. This suggests αCD147 treatment abrogates cerebral ischemia-induced inflammatory activation of splenic monocytes/macrophages (MMs). In addition, the experiment in splenectomized mice showed the spleen as the major source of infiltrated Ly-6ChighMMs subset in the ischemic brain and that brain infiltration of Ly-6ChighMMs was reduced by αCD147 treatment. These results reveal CD147 as a key mediator of the spleen’s inflammatory activation in response to cerebral ischemia.
Healthcare system indicators associated with modern contraceptive use in Ghana, Kenya, and Nigeria: evidence from the Performance Monitoring and Accountability 2020 data
Authors: Asaolu Ibitola , Nuño Velia Leybas , Ernst Kacey , Taren Douglas , Ehiri John
Published: October 2019

Background

Public health literature is replete with evidence on individual and interpersonal indicators of modern contraceptive use. There is, however, limited knowledge regarding healthcare system indicators of modern contraceptive use. This study assessed how the healthcare system influences use of modern contraceptive among women in Ghana, Kenya, and two large population states in Nigeria.

Methods

This study used data from Phase 1 of the Performance Monitoring and Accountability 2020. The analytical sample was limited to women with a need for contraception, defined as women of reproductive age (15 to 49 years) who wish to delay or limit childbirth. Therefore, this analysis consisted of 1066, 1285, and 1955 women from Nigeria, Ghana, and Kenya respectively. Indicators of healthcare assessed include user-fees, visit by health worker, type of health facility, multiple perinatal services, adolescent reproductive healthcare, density of healthcare workers, and regularity of contraceptive services. All analyses were conducted with SAS (9.4), with statistical significance set at p < 5%.

Results

The prevalence of modern contraceptive was 22.7, 33.2, and 68.9% in Nigeria, Ghana, and Kenya respectively. The odds of modern contraceptive use were higher among Nigerian women who lived within areas that provide adolescent reproductive healthcare (OR = 2.05; 95% C.I. = 1.05—3.99) and Kenyan women residing in locales with polyclinic or hospitals (OR = 1.91; 1.27—2.88). Also, the odds of contraceptive use were higher among Kenyan women who lived in areas with user-fee for contraceptive services (OR = 1.40; 1.07–1.85), but lower among Ghanaian women residing in such areas (OR = 0.46; 0.23—0.92). Lastly, the odds of modern contraceptive use were higher among women visited by a health-worker visit among women in Ghana (OR = 1.63; 1.11—2.42) and Nigeria (OR = 2.97; 1.56—5.67) than those without a visit.

Conclusion

This study found an association between country-specific indicators of healthcare and modern contraceptive use. Evidence from this study can inform policy makers, health workers, and healthcare organizations on specific healthcare factors to target in meeting the need for contraception in Ghana, Kenya, and Nigeria.
Vision does not always help stroke survivors compensate for impaired limb position sense
Authors: Herter Troy M. , Scott Stephen H. , Dukelow Sean P.
Published: October 2019

Background

Position sense is commonly impaired after stroke. Traditional rehabilitation methods instruct patients to visualize their limbs to compensate for impaired position sense.

Objective

Our goal was to evaluate how the use of vision influences impaired position sense.

Methods

We examined 177 stroke survivors, an average of 12.7 days (+/− 10 days (SD)) post-stroke, and 133 neurologically-intact controls with a robotic assessment of position sense. The robot positioned one limb (affected) and subjects attempted to mirror-match the position using the opposite limb (unaffected). Subjects completed the test without, then with vision of their limbs. We examined three measures of position sense: variability (Var), contraction/expansion (C/E) and systematic shift (Shift). We classified stroke survivors as having full compensation if they performed the robotic task abnormally without vision but corrected performance within the range of normal with vision. Stroke survivors were deemed to have partial compensation if they performed the task outside the range of normal without and with vision, but improved significantly with vision. Those with absent compensation performed the task abnormally in both conditions and did not improve with vision.

Results

Many stroke survivors demonstrated impaired position sense with vision occluded [Var: 116 (66%), C/E: 91 (51%), Shift: 52 (29%)]. Of those stroke survivors with impaired position sense, some exhibited full compensation with vision [Var: 23 (20%), C/E: 42 (46%), Shift: 32 (62%)], others showed partial compensation [Var: 37 (32%), C/E: 8 (9%), Shift: 3 (6%)] and many displayed absent compensation (Var: 56 (48%), C/E: 41 (45%), Shift: 17 (33%)]. Stroke survivors with an affected left arm, visuospatial neglect and/or visual field defects were less likely to compensate for impaired position sense using vision.

Conclusions

Our results indicate that vision does not help many stroke survivors compensate for impaired position sense, at least within the current paradigm. This contrasts with historical reports that vision helps compensate for proprioceptive loss following neurologic injuries.
Neural stimulation systems for the control of refractory epilepsy: a review
Authors: Bigelow Matthew D. , Kouzani Abbas Z.
Published: October 2019

Epilepsy affects nearly 1% of the world’s population. A third of epilepsy patients suffer from a kind of epilepsy that cannot be controlled by current medications. For those where surgery is not an option, neurostimulation may be the only alternative to bring relief, improve quality of life, and avoid secondary injury to these patients. Until recently, open loop neurostimulation was the only alternative for these patients. However, for those whose epilepsy is applicable, the medical approval of the responsive neural stimulation and the closed loop vagal nerve stimulation systems have been a step forward in the battle against uncontrolled epilepsy. Nonetheless, improvements can be made to the existing systems and alternative systems can be developed to further improve the quality of life of sufferers of the debilitating condition. In this paper, we first present a brief overview of epilepsy as a disease. Next, we look at the current state of biomarker research in respect to sensing and predicting epileptic seizures. Then, we present the current state of open loop neural stimulation systems. We follow this by investigating the currently approved, and some of the recent experimental, closed loop systems documented in the literature. Finally, we provide discussions on the current state of neural stimulation systems for controlling epilepsy, and directions for future studies.
An efficient and reproducible Agrobacterium-mediated transformation method for hexaploid wheat (Triticum aestivum L.)
Authors: Hayta Sadiye , Smedley Mark A. , Demir Selcen U. , Blundell Robert , Hinchliffe Alison , Atkinson Nicola , Harwood Wendy A.
Published: October 2019

Background

Despite wheat being a worldwide staple, it is still considered the most difficult to transform out of the main cereal crops. Therefore, for the wheat research community, a freely available and effective wheat transformation system is still greatly needed.

Results

We have developed and optimised a reproducible Agrobacterium-mediated transformation system for the spring wheat cv ‘Fielder’ that yields transformation efficiencies of up to 25%. We report on some of the important factors that influence transformation efficiencies. In particular, these include donor plant health, stage of the donor material, pre-treatment by centrifugation, vector type and selection cassette. Transgene copy number data for independent plants regenerated from the same original immature embryo suggests that multiple transgenic events arise from single immature embryos, therefore, actual efficiencies might be even higher than those reported.

Conclusion

We reported here a high-throughput, highly efficient and repeatable transformation system for wheat and this system has been used successfully to introduce genes of interest, for RNAi, over-expression and for CRISPR–Cas9 based genome editing.
Neutral lipid storage disease with myopathy in China: a large multicentric cohort study
Authors: Zhang Wei , Wen Bing , Lu Jun , Zhao Yawen , Hong Daojun , Zhao Zhe , Zhang Cheng , Luo Yuebei , Qi Xueliang , Zhang Yingshuang , Song Xueqin , Zhao Yuying , Zhao Chongbo , Hu Jing , Yang Huan , Wang Zhaoxia , Yan Chuanzhu , Yuan Yun
Published: October 2019

Background

Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents skeletal myopathy, cardiomyopathy and the multiple organs dysfunction. Around 50 cases of NLSDM have been described worldwide, whereas the comprehensive understanding of this disease are still limited. We therefore recruit NLSDM patients from 10 centers across China, summarize the clinical, muscle imaging, pathological and genetic features, and analyze the genotype-phenotype relationship.

Results

A total of 45 NLSDM patients (18 men and 27 women) were recruited from 40 unrelated families. Thirteen patients were born from consanguineous parents. The phenotypes were classified as asymptomatic hyperCKemia (2/45), pure skeletal myopathy (18/45), pure cardiomyopathy (4/45), and the combination of skeletal myopathy and cardiomyopathy (21/45). Right upper limb weakness was the early and prominent feature in 61.5% of patients. On muscle MRI, the long head of the biceps femoris, semimembranosus and adductor magnus on thighs, the soleus and medial head of the gastrocnemius on lower legs showed the most severe fatty infiltration. Thirty-three families were carrying homozygous mutations, while seven families were carrying compound heterozygous mutations. A total of 23 mutations were identified including 11 (47.8%) point mutations, eight (34.8%) deletions and four (17.4%) insertions. c.757 + 1G > T, c.245G > A and c.187 + 1G > A were the three most frequent mutations. Among four groups of phenotypes, significant differences were shown in disease onset (< 20 years versus ≥20 years old, p = 0.003) and muscle pathology (with rimmed vacuoles versus without rimmed vacuoles, p = 0.001). PNPLA2 mutational type or functional defects did not show great impact on phenotypes.

Conclusion

We outline the clinical and genetic spectrum in a large cohort of NLSDM patients. Selective muscle fatty infiltration on posterior compartment of legs are characteristic of NLSDM. Chinese patients present with distinctive and relative hotspot PNPLA2 mutations. The disease onset age and pathological appearance of rimmed vacuoles are proved to be related with the clinical manifestations. The phenotypes are not strongly influenced by genetic defects, suggesting the multiple environmental risk factors in the development of NLSDM.
A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia
Authors: Liang Yuejuan , Chen Mengjie , Qin Lu , Wan Bing , Wang He
Published: October 2019

Microecology is an emerging discipline in recent years. The female reproductive tract is an important microecological region, and its microecological environment can directly affect women’s cervical health. This meta-analysis aimed to analyze the effects of vaginal microecology on Human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). PubMed and Web of Science were systematically searched for eligible publications from January 2000 to December 2017. Articles were selected on the basis of specific inclusion and exclusion criteria. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) with a 95% confidence interval (95% CI) were calculated. Thirteen eligible studies were selected to evaluate the association of vaginal microecology with HPV infection and CIN. The factors related to HPV infection were bacterial vaginosis (BV) (OR 2.57, 95% CI 1.78–3.71, P<0.05), Candida albicans (VVC) (OR 0.63, 95% CI 0.49–0.82, P < 0.05), Chlamydia trachomatis (CT) (OR 3.16, 95% CI 2.55–3.90, P < 0.05), and Ureaplasma urealyticum (UU) (OR 1.35, 95% CI 1.20–1.51, P < 0.05). BV was also related to CIN (OR 1.56, 95% CI 1.21–2.00, P < 0.05). This meta-analysis of available literature suggested an intimate association of vaginal microecology and HPV infection with CIN. BV, CT and UU were associated to increased HPV infection, VVC was associated to decreased HPV infection, Lactobacillus is not associated to increased HPV infection, BV was associated to increased CIN development risk. Further large-scale studies are needed to confirm our findings.
Prehospital administration of surfactant to a premature neonate in respiratory distress
Authors: Mize Charles Haviland , Dorji Lhab , Zafren Ken
Published: October 2019

The population of the Kingdom of Bhutan is scattered in small villages throughout the eastern Himalaya. Infants born prematurely in villages have no access to neonatal intensive care until they are transported to the national referral hospital, a process that once took hours, if not days. After the introduction of a helicopter critical-care retrieval team, we were able to send a trained team to a remote location that successfully administered surfactant and initiated critical care to a premature, extreme low birth weight infant in severe respiratory distress in the first hour of life. Although the infant was in shock and in a near-arrest state at the time the team arrived, he made an excellent recovery after resuscitation by the team.
Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination
Authors: Antonio-Nkondjio Christophe , Ndo Cyrille , Njiokou Flobert , Bigoga Jude D. , Awono-Ambene Parfait , Etang Josiane , Ekobo Albert Same , Wondji Charles S.
Published: October 2019

Malaria still has a devastating impact on public health and welfare in Cameroon. Despite the increasing number of studies conducted on disease prevalence, transmission patterns or treatment, there are to date, not enough studies summarising findings from previous works in order to identify gaps in knowledge and areas of interest where further evidence is needed to drive malaria elimination efforts. The present study seeks to address these gaps by providing a review of studies conducted so far on malaria in Cameroon since the 1940s to date. Over 250 scientific publications were consulted for this purpose. Although there has been increased scale-up of vector control interventions which significantly reduced the morbidity and mortality to malaria across the country from a prevalence of 41% of the population reporting at least one malaria case episode in 2000 to a prevalence of 24% in 2017, the situation is not yet under control. There is a high variability in disease endemicity between epidemiological settings with prevalence of Plasmodium parasitaemia varying from 7 to 85% in children aged 6 months to 15 years after long-lasting insecticidal nets (LLINs) scale-up. Four species of Plasmodium have been recorded across the country: Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Several primate-infecting Plasmodium spp. are also circulating in Cameroon. A decline of artemisinin-based combinations therapeutic efficacy from 97% in 2006 to 90% in 2016 have been reported. Several mutations in the P. falciparum chloroquine resistance (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1) genes conferring resistance to either 4-amino-quinoleine, mefloquine, halofanthrine and quinine have been documented. Mutations in the Pfdhfr and Pfdhps genes involved in sulfadoxine-pyrimethamine are also on the rise. No mutation associated with artemisinin resistance has been recorded. Sixteen anopheline species contribute to malaria parasite transmission with six recognized as major vectors: An. gambiae, An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti. Studies conducted so far, indicated rapid expansion of DDT, pyrethroid and carbamate resistance in An. gambiae, An. coluzzii, An. arabiensis and An. funestus threatening the performance of LLINs. This review highlights the complex situation of malaria in Cameroon and the need to urgently implement and reinforce integrated control strategies in different epidemiological settings, as part of the substantial efforts to consolidate gains and advance towards malaria elimination in the country.
The impact of sex and disease classification on patient-reported outcome measures in axial spondyloarthritis: a descriptive prospective cross-sectional study
Authors: Andreasen Rikke A. , Kristensen Lars E. , Egstrup Kenneth , Baraliakos Xenofon , Strand Vibeke , Horn Hans Christian , Hansen Inger M. J. , Christensen Robin , Ellingsen Torkell
Published: October 2019

Background

The aim of this study was to explore the impact of sex and disease classification on outcomes in axial spondyloarthritis (axSpA) patients, including both radiographic (r-) axSpA and non-radiographic (nr-) axSpA, in males and females, respectively.

Methods

AxSpA patients were consecutively recruited from two rheumatology outpatient university clinics. We explored how sex and axSpA disease classification affected patient-reported outcome measures (PROMs). General linear models were used to investigate if there was an association between the continuous variables and each of the main effects of interest (sex and axSpA classification), as well as the possible interaction between them. Categorical outcome measures were analyzed with the use of logistic regression with the same fixed effects. We analyzed the relationship between tender point count (TPC) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The prevalence of extra-articular manifestations (EAMs) and the Charlson Comorbidity Index (CCI) were determined.

Results

According to the protocol, a total of 100 outpatients with axSpA were enrolled (r-axSpA males 30, r-axSpA females 10, nr-axSpA males 25, nr-axSpA females 35). The BASDAI scores appeared higher among nr-axSpA females (median [Q1; Q3], 47 [21; 60]) compared with the combined median for the 3 other subgroups 25 [12; 25]. Female sex was associated with a higher number of tender point count (TPC, P < 0.001). TPC and BASDAI were correlated for female nr-axSpA patients (r = 0.44, P = 0.008) and male nr-axSpA patients (r = 0.56, P = 0.003). Being classified as nr-axSpA was associated with a lower SF-36 Mental Component Summary (median for the 4 subgroups: nr-axSpa females 46.7, nr-axSpA males 52.3 vs. r-axSpA males 56.9 and r-axSpA females 50.4). EAMs were frequent (up to 50%). The CCI was low in all 4 subgroups, and no difference in the CCI between the subgroups was observed (P = 0.14). However, male sex had a significant impact on the CCI (P = 0.03).

Conclusions

In summary, patients with r-axSpA, regardless of sex, appeared less affected on most PROMs compared with nr-axSpA patients. However, female sex was associated with a higher number of TPC. TPC could possibly confound disease activity outcomes such as BASDAI, and one can consider different thresholds for defining high disease activity depending on the patient’s sex.

Trial registration

The trial is registered and approved by the Region of Southern Denmark’s Ethics Committee (S-20150219). Registered 19 February 2015.
Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial
Authors: Omidian Mahsa , Djalali Mahmoud , Javanbakht Mohammad Hassan , Eshraghian Mohammad Reza , Abshirini Maryam , Omidian Parisa , Alvandi Ehsan , Mahmoudi Maryam
Published: October 2019

Background

Several researches have recommended vitamin D possible health benefits on diabetic complications development, but a few number of studies have been accomplished on the molecular and cellular mechanisms. Certain cellular pathways modification and also some transcription factors activation may protect cells from hyperglycemia condition induced damages. This study purpose was to determine the vitamin D supplementation effect on some key factors [advanced glycation end products (AGEs) signaling pathway] that were involved in the diabetic complications occurrence and progression for type-2 diabetes participants.

Methodology

48 type-2 diabetic patients (T2DM) randomly divided into two groups (n = 24 per group), receiving: 100-µg vitamin D or placebo for 3 months. At this study beginning and the end, the receptor expression for advanced glycation end products (RAGE) and glyoxalase I (GLO1) enzyme from peripheral blood mononuclear cells (PBMCs) and AGEs and tumor necrosis factor-α (TNF-α) serum levels were measured by the use of real-time PCR and ELISA methods, respectively.

Results

This study results demonstrated that vitamin D supplementation could down-regulate RAGE mRNA [fold change = 0.72 in vitamin D vs. 0.95 in placebo) P = 0.001)]. In addition, no significant changes were observed for GLO1 enzyme expression (P = 0.06). This study results also indicated that vitamin D serum level significantly increased in vitamin D group (P < 0.001). Moreover, AGES and TNF-α serum levels significantly reduced in vitamin D group, but they were remained unchanged in the placebo group.

Conclusion

In conclusion, vascular complications are more frequent in diabetic patients, and vitamin D treatment may prevent or delay the complications onset in these patients by AGEs serum level and RAGE gene expression reducing.

Trial registration NCT03008057. Registered December 2016
Risky sexual behavior practice and associated factors among secondary and preparatory school students of Aksum town, northern Ethiopia, 2018
Authors: Girmay Alem , Mariye Teklewoini
Published: October 2019

Objective

As adolescence is a stage in which human beings face once throughout a lifetime and it is the experimental period for this reason risky sexual behavior is common among young people, and it has several sexual and reproductive health consequences. But it doesn’t get enough attention the status of risky sexual behavior practice and factors’ contributing to it, so this study aimed to identify the prevalence of risky sexual behavior and factors associated with it.

Results

From the total respondents 115 (23.7%) had history of sexual intercourse and the mean age for sexual initiation is 15.48 ± 1.99 year. From whom 110 (98.2%) had sexual contact below the age of 18 and only 68 (60.8%) initiate first sex by their own willing. Overall 97 (19.6%) had practiced risky sexual behaviors. Students not facing peer pressure were 0.36 times less likely to develop risk sexual behavior (AOR = 0.357, 95% CI 0.172, 0.744).
Burden of Shigella spp and Vibrio spp, and their antibiotic sensitivity pattern in the patients with acute gastroenteritis in tertiary care hospital in Nepal
Authors: Sah Shiv Kumar , Basnet Shreejana , Shrestha Sushma , Ghale Kusum , Tamang Sabita , Mandal Dipendra Kumar , Pun Sher Bahadur
Published: October 2019

Objectives

The present study aims to investigate the etiology, clinical profile and resistance pattern of the isolated pathogens in Nepalese adults with acute gastroenteritis. This cross-sectional study was conducted at Sukraraj Tropical and Infectious Disease Hospital, from April 2016 to Sep 2017. Subjects’ ages 14 or above, presenting with gastroenteritis with positive stool culture were enrolled for analysis.

Results

Of total 153 patients, 47.72% subjects confirmed the presence of bacterial infection.Vibrio cholerae spp andShigellaspp were detected in 36.6% and 23.28% respectively. The most common resistance amongVibrio cholerae was to nitrofurantoin (92.8%), cotrimoxazole (92.8%) and nalidixic acid (92.8%). Among 17 isolates ofShigellaspp, the most frequent drug resistant was observed in ampicillin (64.7%), nalidixic acid (58.8%), ceftriaxone (47%). Chloramphenicol (94.1%), tetracycline (88.2%), and cotrimoxazole (82.3%) were found to be the most sensitive towards this pathogen. High rate of diarrhea due to bacterial infection, especiallyShigellaspp andVibriospp and their high rate of drug resistance emphasize an urgent need of designing a surveillance system for antimicrobial resistance in Nepalese setting.
Prevalence and antimicrobial susceptibility profile of Salmonella and Shigella among food handlers working in food establishment at Hawassa city, Southern Ethiopia
Authors: Awol Neja , Nigusse Demiss , Ali Musa
Published: October 2019

Objective

The aim of this study was to determine the prevalence ofSalmonellaandShigella, antibiotic susceptibility profile and associated factors among food handlers working in food establishment from June to December 2018 at Hawassa city, Southern Ethiopia.

Results

Out of the 236 food handlers screened for stool culture, 5 (2.12%) were positive forSalmonellaspecies and all of them were negative forShigellaspecies. AllSalmonellaspecies isolated were susceptible to ciprofloxacin and ceftriaxone but among the five isolatedSalmonellaspecies, 4 (80%), 3 (60%), 2 (40%), 2 (40%), and 2 (40%) were resistant to tetracycline, ampicillin, amoxicillin–clavulanic acid, cotrimoxazole, and chloramphenicol respectively. Only food handlers hand washing the habit after toilet had a significant association with the prevalence ofSalmonellaspecies (P = 0.03).
Hypermethylation of mismatch repair gene hMSH2 associates with platinum-resistant disease in epithelial ovarian cancer
Authors: Tian Hua , Yan Li , Xiao-fei Li , Hai-yan Sun , Juan Chen , Shan Kang
Published: October 2019

Purpose

One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance.

Methods

By initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of thehMSH2gene was discovered hypermethylated in the platinum-resistant group. The effect ofhMSH2methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels ofhMSH2upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect thehMSH2mRNA and protein expression in extended 150 patients.

Results

RRBS assay discovered an upstream region from − 1193 to − 1125 ofhMSH2was significant hypermethylated in resistant EOC patients (P = 1.06 × 10−14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. KnockdownhMSH2reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation ofhMSH2upstream region with platinum resistance. Spearman’s correlation analysis revealed a significantly negative connection between methylation level ofhMSH2upstream region and its expression. The Kaplan-Meier analyses showed the high methylation ofhMSH2promoter region, and its low expressions are associated with worse survival. In multivariable models,hMSH2low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85–2.31).

Conclusion

The hypermethylation ofhMSH2upstream region is associated with platinum resistant in EOC, and low expression ofhMSH2may be an index for the poor prognosis.
Neurochemical sex differences in adult ADHD patients: an MRS study
Authors: Endres Dominique , Tebartz van Elst Ludger , Maier Simon J. , Feige Bernd , Goll Peter , Meyer Simon A. , Matthies Swantje , Domschke Katharina , Lange Thomas , Sobanski Esther , Philipsen Alexandra , Nickel Kathrin , Perlov Evgeniy
Published: October 2019

Objective

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients.

Methods

We studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach.

Results

For the ACC, the signals of Cre (p = 0.008) and t-Cho (p = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre:p = 0.033; t-Cho:p = 0.040). For the Glx signal, an interaction of sex and age could also be observed (p = 0.033). For cerebellar neurometabolites, the signals of t-Cho (p = 0.049) and Glx (p = 0.049) showed significant effects of the factor sex.

Conclusion

This is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.
Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors
Authors: Liu Xuechao , Wang Guangfeng , Yan Xianglei , Qiu Haibo , Min Ping , Wu Miaoyi , Tang Chunyang , Zhang Fei , Tang Qiuqiong , Zhu Saijie , Qiu Miaozhen , Zhuang Wei , Fang Douglas D. , Zhou Zhiwei , Yang Dajun , Zhai Yifan
Published: October 2019

Background

Imatinib shows limited efficacy in patients with gastrointestinal stromal tumors (GISTs) carrying secondary KIT mutations. HQP1351, an orally bioavailable multikinase BCR-ABL inhibitor, is currently in clinical trials for the treatment of T315I mutant chronic myelogenous leukemia (CML), but the potential application in imatinib-resistant GISTs carrying secondary KIT mutations has not been explored.

Methods

The binding activities of HQP1351 with native or mutant KIT were first analyzed. Imatinib-sensitive GIST T1 and imatinib-resistant GIST 430 cells were employed to test the in vitro antiproliferative activity. Colony formation assay, cell migration assay and cell invasion assay were performed to evaluate the clonogenic, migration and invasion ability respectively. Flow cytometry and western blot analysis were used to detect cell apoptosis, cell cycle and signaling pathway. In vivo antitumor activity was evaluated in mouse xenograft models derived from GIST cell lines.

Results

HQP1351 potently inhibited both wild-type and mutant KIT kinases. In both imatinib-resistant and sensitive GIST cell lines, HQP1351 exhibited more potent or equivalent antiproliferative activity compared with ponatinib, a third generation BCR-ABL and KIT inhibitor. HQP1351 led to more profound inhibition of cell colony formation, cell migration and invasion, cell cycle arrest and cell apoptosis than ponatinib. Furthermore, HQP1351 also inhibited p-KIT, p-AKT, p-ERK1/2, and p-STAT3 to a higher extent than ponatinib. Finally, in xenograft tumor models derived from imatinib-resistant GIST cancer cell lines, HQP1351 exhibited antitumor activity superior to ponatinib.

Conclusions

Collectively, our in vitro and in vivo results suggest that the therapeutic application of HQP1351 in imatinib-resistant GIST patients deserves further investigation in clinical trials.
Coefficient bounds for certain subclasses of starlike functions
Authors: Cho Nak Eun , Kumar Virendra , Kwon Oh Sang , Sim Young Jae
Published: October 2019

The conjecture proposed by Raina and Sokòł [Hacet. J. Math. Stat. 44(6):1427–1433 (2015)] for a sharp upper bound on the fourth coefficient has been settled in this manuscript. An example is constructed to show that their conjectures for the bound on the fifth coefficient and the bound related to the second Hankel determinant are false. However, the correct bound for the latter is stated and proved. Further, a sharp bound on the initial coefficients for normalized analytic function f such that $zf'(z)/f(z)\prec \sqrt{1+\lambda z}$
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Positive solutions to second-order singular nonlocal problems: existence and sharp conditions
Authors: Ma Shiqi , Zhang Xuemei
Published: October 2019

In this paper we consider sharp conditions onωandffor the existence of$C^{1}[0,1]$C1[0,1]positive solutions to a second-order singular nonlocal problem$u''(t)+\omega (t)f(t,u(t))=0$u″(t)+ω(t)f(t,u(t))=0,$u(0)=u(1)=\int _{0} ^{1}g(t)u(t)\,dt$u(0)=u(1)=∫01g(t)u(t)dt; it turns out that this case is more difficult to handle than two point boundary value problems and needs some new ingredients in the arguments. On the technical level, we adopt the topological degree method.
Dynein activating adaptor BICD2 controls radial migration of upper-layer cortical neurons in vivo
Authors: Will Lena , Portegies Sybren , van Schelt Jasper , van Luyk Merel , Jaarsma Dick , Hoogenraad Casper C.
Published: October 2019

For the proper organization of the six-layered mammalian neocortex it is required that neurons migrate radially from their place of birth towards their designated destination. The molecular machinery underlying this neuronal migration is still poorly understood. The dynein-adaptor protein BICD2 is associated with a spectrum of human neurological diseases, including malformations of cortical development. Previous studies have shown that knockdown of BICD2 interferes with interkinetic nuclear migration in radial glial progenitor cells, and that Bicd2-deficient mice display an altered laminar organization of the cerebellum and the neocortex. However, the precise in vivo role of BICD2 in neocortical development remains unclear. By comparing cell-type specific conditional Bicd2 knock-out mice, we found that radial migration in the cortex predominantly depends on BICD2 function in post-mitotic neurons. Neuron-specific Bicd2 cKO mice showed severely impaired radial migration of late-born upper-layer neurons. BICD2 depletion in cortical neurons interfered with proper Golgi organization, and neuronal maturation and survival of cortical plate neurons. Single-neuron labeling revealed a specific role of BICD2 in bipolar locomotion. Rescue experiments with wildtype and disease-related mutant BICD2 constructs revealed that a point-mutation in the RAB6/RANBP2-binding-domain, associated with cortical malformation in patients, fails to restore proper cortical neuron migration. Together, these findings demonstrate a novel, cell-intrinsic role of BICD2 in cortical neuron migration in vivo and provide new insights into BICD2-dependent dynein-mediated functions during cortical development.
Study of a periodic spectral fluctuation existing in a fibered optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS)
Authors: Luo Zhifu , Tan Zhongqi , Long Xingwu
Published: October 2019

A special periodic spectral fluctuation is observed during the study of a fibered high sensitivity optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS) for the measurement of trace gas. This spectral fluctuation is different from some phenomenon observed in former OF-CEAS which contain a resonant cavity with V-shaped configuration, such as the etalon effect and the spectral ripple effect. To reveal why this phenomenon happens and how it works, a series of hypothesis are proposed and tested, and the results show that the multi-beam interference of resonance light at the input mirror of the resonant cavity is the main reason for this phenomenon. Based on the multi-beam interference theory, a mathematical modeling of this phenomenon is built, and the theoretical analyses agree well with the experimental results. Some methods to eliminate this phenomenon are proposed and implemented, and the 1σ noise equivalent absorption coefficient of 7.6 × 10− 10 cm− 1 Hz-1/2 is attained with this robust and compact OF-CEAS system.