bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquiescence in the face of dispossession in the Mahindra World City Special Economic Zone, Tamil Nadu, India
Authors: Subramanyam Nidhi , Kudva Neema
Published: July 2020

Scholarship on community responses to land grabs for Special Economic Zones (SEZs) has overwhelmingly analysed cases of mobilization against SEZs or the subsequent trajectories of anti-dispossession struggles. We build on the role of the neoliberal broker state developed within this scholarship as well as theories on state and capital rescaling, and quiescence to power to explain the production of acquiescence to dispossession. Our in-depth case study of a large SEZ, the Mahindra World City (MWC) in Tamil Nadu, India, argues that acquiescence is produced in part by a multiscalar broker state that uses several intersecting strategies. These include threatening landowners with coercive eminent domain, facilitating market-based land acquisition by rescaled private capital that operates through a locally embedded network of brokers who persuade landowners, and utilizing the gains from brokerage to finance a populist welfare state that cushions the adverse impacts of dispossession. The use of customized market-based compensation further individualizes the experience of dispossession in an urbanizing context with no living memories of prior collective mobilization against dispossession. The multiscalar state thus intersects with rescaled capital in and through coercive, persuasive, and selected welfare strategies variously employed at the subnational and local scales to blunt resistance and produce acquiescence in the face of dispossession. Examining the decade long process of land acquisition in the MWC SEZ helps us theorize an evolving broker state and understand why it remains largely uncontested in contemporary rent-driven development.
Enhancer-gene rewiring in the pathogenesis of Quebec Platelet Disorder
Authors: Liang Minggao , Soomro Asim Usman , Tasneem Subia , Abatti Luis E , Alizada Azad , Yuan Xuefei , Uusküla-Reimand Liis , Antounians Lina , Alvi Sana Akhtar , Paterson Andrew David , Rivard Georges E , Scott Ian C , Mitchell Jennifer A , Hayward Catherine P M , Wilson Michael Davies
Published: July 2020

Quebec Platelet Disorder (QPD) is an autosomal dominant bleeding disorder with a unique, platelet-dependent gain-of-function defect in fibrinolysis, without systemic fibrinolysis. The hallmark feature of QPD is a >100-fold overexpression of PLAU specifically in megakaryocytes. This overexpression leads to >100-fold increased platelet stores of urokinase plasminogen activator (PLAU/uPA), subsequent plasmin-mediated degradation of diverse a-granule proteins, and platelet-dependent, accelerated fibrinolysis. The causative mutation is a 78kb tandem duplication of PLAU. How this duplication causes megakaryocyte-specific PLAU overexpression is unknown. To investigate the mechanism that causes QPD, we used epigenomic profiling, comparative genomics, and chromatin conformation capture approaches to study PLAU regulation in cultured megakaryocytes from QPD participants and unaffected controls. We show that the QPD duplication leads to ectopic interactions between PLAU and a conserved megakaryocyte enhancer found within the same topologically associating domain (TAD). Our results support a unique disease mechanism whereby the reorganization of subTAD genome architecture results in a dramatic, cell-type specific blood disorder phenotype.
NCOA4 is Regulated by HIF and Mediates Mobilization of Murine Hepatic Iron Stores After Blood Loss
Authors: Li Xiuqi , Lozovatsky Larisa , Sukumaran Abitha , Gonzalez Luis , Jain Anisha , Liu Dong , Ayala-Lopez Nadia , Finberg Karin E.
Published: July 2020

The mechanisms by which phlebotomy promotes the mobilization of hepatic iron stores are not well understood. NCOA4 (nuclear receptor coactivator 4) is a widely-expressed intracellular protein previously shown to mediate the autophagic degradation of ferritin. Here, we investigate a local requirement for NCOA4 in the regulation of hepatic iron stores and examine mechanisms of NCOA4 regulation. Hepatocyte-targeted Ncoa4 knockdown in non-phlebotomized mice had only modest effects on hepatic ferritin subunit levels and non-heme iron concentration. After phlebotomy, mice with hepatocyte-targeted Ncoa4 knockdown exhibited anemia and hypoferremia similar to control mice with intact Ncoa4 regulation, but showed a markedly impaired ability to lower hepatic ferritin subunit levels and hepatic non-heme iron concentration. This impaired hepatic response was observed even when dietary iron was limited. In both human and murine hepatoma cell lines, treatment with chemicals that stabilize hypoxia inducible factor (HIF), including desferrioxamine, cobalt chloride, and dimethyloxalylglycine, raised NCOA4 mRNA. This NCOA4 mRNA induction occurred within 3 hours, preceded a rise in NCOA4 protein, and was attenuated in the setting of dual HIF-1a and HIF-2a knockdown. In summary, we show for the first time that NCOA4 plays a local role in facilitating iron mobilization from the liver after blood loss and that HIF regulates NCOA4 expression in cells of hepatic origin. Because the prolyl hydroxylases that regulate HIF stability are oxygen and iron-dependent enzymes, our findings suggest a novel mechanism by which hypoxia and iron deficiency may modulate NCOA4 expression to impact iron homeostasis.
Prevalence and antibiogram of coagulase negative Staphylococci in bioaerosols from different indoors of a university in India
Authors: Kumari Himani , Chakraborti Trina , Singh Madhuri , Chakrawarti Maneet Kumar , Mukhopadhyay Kasturi
Published: July 2020

Background

Staphylococci species are the major constituents of infectious bioaerosols, particularly methicillin-resistant Staphylococci (MRS) have serious health impacts. Here, the bacterial burden was quantified, especially prevalence of MRS in bioaerosols collected from indoors of Dr. B.R. Ambedkar Central Library (DBRACL) and Central Laboratory Animal Resources (CLAR) of Jawaharlal Nehru University, New Delhi, India. Air samplings from DBRACL and CLAR were done using the settle plate method and SKC biosampler, respectively.

Results

This study showed a maximum 6757 CFU/m2/hr of bacterial load in the DBRACL reading room, while unacceptable bacterial loads (> 1000 CFU/m3 of air) at different sites of CLAR. Further, at both the sampling sites the predominance of coagulase negative Staphylococci (CNS) was observed. A total 22 and 35 Staphylococci isolates were isolated from DBRACL and CLAR bioaerosols, respectively. Majority (16/22) of the Staphylococcal isolates from DBRACL belonged to human-associated Staphylococci where S. haemolyticus (5/22) was the most dominating species. However, in CLAR facility centre, animal-associated Staphylococci (19/35) were dominating, where S. xylosus (12/35) was the most dominating species. Further, antibiotic sensitivity tests revealed 41% MRS and 73% multidrug resistant (MDR) among airborne Staphylococci from DBRACL indoor bioaerosols. Similarly, in CLAR facility, approximately, 66% Staphylococci isolates were methicillin resistant, out of which 2 isolates showed high MIC value ≥ 16 μg/mL. Further, we confirmed the presence of 49% multidrug resistant Staphylococci in the indoor air of CLAR facility.

Conclusions

This study suggested that the exposure of workers and students in CLAR to such a high concentration of drug-resistant Staphylococci should not be undermined, as these bacterial concentrations are the direct representative of inhalable particulate matter (PM2.5) as per collection procedure. Simultaneously, passive sampling from DBRACL assessed the risks due to microbial contamination in particle agglomerates, which may deposit on the crucial surfaces such as wounds/ cuts or on the frequently used items.
Invasive non-typeable Haemophilus influenzae infection due to endometritis associated with adenomyosis
Authors: Nishimura Yoshito , Hagiya Hideharu , Kawano Kaoru , Yokota Yuya , Oka Kosuke , Iio Koji , Hasegawa Kou , Obika Mikako , Haruma Tomoko , Ono Sawako , Masuyama Hisashi , Otsuka Fumio
Published: July 2020

Background

The widespread administration of the Haemophilus influenzae type b vaccine has led to the predominance of non-typable H. influenzae (NTHi). However, the occurrence of invasive NTHi infection based on gynecologic diseases is still rare.

Case presentation

A 51-year-old Japanese woman with a history of adenomyoma presented with fever. Blood cultures and a vaginal discharge culture were positive with NTHi. With the high uptake in the uterus with 67Ga scintigraphy, she was diagnosed with invasive NTHi infection. In addition to antibiotic administrations, a total hysterectomy was performed. The pathological analysis found microabscess formations in adenomyosis.

Conclusions

Although NTHi bacteremia consequent to a microabscess in adenomyosis is rare, this case emphasizes the need to consider the uterus as a potential source of infection in patients with underlying gynecological diseases, including an invasive NTHi infection with no known primary focus.
Percutaneous fine-needle aspiration for pyogenic liver abscess (3-6 cm): a two-center retrospective study
Authors: He Shuangjun , Yu Jie , Wang Hairong , Chen Xuelian , He Zhanqiang , Chen Yi
Published: July 2020

Background

The role of ultrasonography-guided percutaneous fine-needle aspiration (PNA) for pyogenic liver abscess (PLA) remains without consensus, especially in abscesses 3 to 6 cm in diameter. The objective of this study was to evaluate the comparative effectiveness and safety of PNA combined with antibiotics.

Methods

This was a retrospective study of patients with PLA that were from 3 to 6 cm in diameter who treated at two medical centers in Shanghai, China, from January 2014 to March 2019. Patients were divided into groups treated by PNA plus antibiotics or antibiotics alone. Patients demographics and clinical data related diagnosis, antibiotic treatment, and patient outcomes were analyzed.

Results

Out of a total of 94 PLA patients, 42 (44.7%) patients received PNA combined with antibiotics, and 52 (55.3%) received antibiotics alone. There were no complications related to PNA. In the PNA group, 13 (31.7%) patients with negative blood culture and 8 (19.5%) patients without blood culture were microbiologically confirmed via aspiration. The time for temperature normalization (P < 0.001) and the reduction rate of C-reactive protein within the first week (P = 0.031) were significantly lower in the PNA group. In the multivariate analysis, treatment with PNA was more likely to result in clinical improvement of PLA (odds ratio = 0.33, 95% confidence intervals (CI): 0.11–0.96, P = 0.043).

Conclusions

PNA combined with antibiotics appears to be a safe, effective, and promising treatment for PLA of 3–6 cm in size. Furthermore, the technique allows for direct microbial sample, which can improve the selection of antibiotics.
A COVID-19 patient with multiple negative results for PCR assays outside Wuhan, China: a case report
Authors: Chen Li-Da , Li Hao , Ye Yu-Ming , Wu Zhi , Huang Ya-Ping , Zhang Wei-Liang , Lin Li
Published: July 2020

Background

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of major international concern. Real-time RT-PCR assays are recommended for diagnosis of COVID-19. Here we report a rare case of COVID-19 with multiple negative results for PCR assays outside Wuhan, China.

Case presentation

A 32-year old male was admitted to our hospital because of 6 days of unexplained fever on January 29, 2020. He had come from Wuhan city 10 days before admission. Five days before admission, no abnormality was noted in laboratory test, chest radiography, and nasopharyngeal swab test for the SARS-CoV-2 nucleic acid. The patient was treated with ibuprofen for alleviating fever. On admission, chest computed tomography showed multiple ground-glass opacities in right lower lung field. COVID-19 was suspected. Three times of nasopharyngeal swab specimens were collected after admission. However, none of the specimens were positive. The patient was confirmed with COVID-19 after fifth SARS-CoV-2 nucleic acid test. He was treated with lopinavir/ritonavir, recombinant human interferon alfa-2b inhalation, methylprednisolone. After 18 days of treatment, he was discharged with improved symptoms, lung lesions and negative results of nasopharyngeal swab.

Conclusion

This case reminds clinician that a patient with high clinical suspicion of COVID-19 but multiple negative RT-PCR result should not be taken out of isolation. A combination of patient’s exposure history, clinical manifestations, laboratory tests, and typical imaging findings plays a vital role in making preliminary diagnosis and guide early isolation and treatment. Repeat swab tests are helpful in diagnosis for this kind of patients.
Hospital physicians’ experiences with procalcitonin – implications for antimicrobial stewardship; a qualitative study
Authors: Christensen Ingrid , Haug Jon Birger , Berild Dag , Bjørnholt Jørgen Vildershøj , Jelsness-Jørgensen Lars-Petter
Published: July 2020

Background

Procalcitonin is an inflammatory biomarker that is sensitive for bacterial infections and a promising clinical decision aid in antimicrobial stewardship programs. However, there are few studies of physicians’ experiences concerning the use of PCT. The objective of this study was to investigate whether hospital physicians’ experience with procalcitonin after 18 months of use can inform the PCT implementation in antimicrobial stewardship programs.

Materials/methods

We deployed a qualitative approach using semi-structured interviews with 14 hospital physicians who had experience with procalcitonin in clinical practice. Interviews were audio-taped, transcribed verbatim and analysed using thematic analysis.

Results

Physicians reported a knowledge gap, which made them uncertain about the appropriate procalcitonin use, interpretation, and trustworthiness. Simultaneously, the physicians experienced procalcitonin as a useful clinical decision aid but emphasised that their clinical evaluation of the patient was the most important factor when deciding on antibiotic treatment.

Conclusions

Procalcitonin was regarded a helpful clinical tool, but the physicians called for more knowledge about its appropriate uses. Active implementation of unambiguous procalcitonin algorithms and physician education may enhance the utility of the test as an antimicrobial stewardship adjunct.
Barriers to maternal retention in HIV care in Ghana: key differences during pregnancy and the postpartum period
Authors: Sakyi Kwame S. , Lartey Margaret Y. , Kennedy Caitlin E. , Dension Julie A. , Mullany Luke C. , Owusu Prince G. , Sacks Emma , Hurley Emily A. , Surkan Pamela J.
Published: July 2020

Background

Maternal retention in HIV care is lower for women in the postpartum period than during pregnancy, but the reasons are poorly understood. We examined key differences in barriers to retention in HIV care during and after pregnancy.

Methods

We conducted semi-structured, in-depth interviews with 30 postpartum women living with HIV. Participants were recruited from two tertiary facilities implementing Option B+ for prevention of mother-to-child HIV transmission in Accra, Ghana. We collected data from mothers who had disengaged from HIV care and those who were still engaged in care. The interviews were analyzed using principles adapted from grounded theory.

Results

Participants’ experiences and narratives showed that retention in HIV care was more challenging during the postpartum period than during pregnancy. Poor maternal physical health (from birth complications and cesarean section), socio-cultural factors (norms about newborn health and pregnancy), and economic difficulties linked to childbirth (such as unemployment, under-employment, and debt) made the costs of retention in HIV care more economically and socially expensive in the postpartum period than during pregnancy. Some participants also shared that transportation costs and resulting dependence on a partner to pay increased during the postpartum period because of a strong shift in maternal preference for private modes of transportation due to HIV stigma and the desire to protect the newborn. These factors played a larger role in the postpartum period than during pregnancy and created a significant barrier to retention. A conceptual model of how these factors interrelate, the synergy between them, and how they affect retention in the postpartum period is presented.

Conclusions

In Ghana, lower retention in HIV care in the postpartum period compared to in pregnancy may be primarily driven by social, economic, and newborn health factors. Multifaceted economic-based and stigma-reduction interventions are needed to increase retention in maternal HIV care after childbirth.
Maternity health professionals’ perspectives of cord clamp timing, cord blood banking and cord blood donation: a qualitative study
Authors: Peberdy Lisa , Young Jeanine , Massey Debbie , Kearney Lauren
Published: July 2020

Background

Parents today have several options for the management of their infant’s cord blood during the third stage of labour. Parents can choose to have their infant’s cord clamped early or to have deferred cord clamping. If the cord is clamped early, cord blood can be collected for private cord blood banking or public cord blood donation for use later if needed. If cord clamping is deferred, the placental blood physiologically transfuses to the neonate and there are physiological advantages to this. These benefits include a smoother cardiovascular transition and increased haemoglobin levels while not interfering with the practice of collecting cord blood for gases if needed. The aim of this study is to explore Australian maternity health professionals’ perspectives towards cord clamp timing, cord blood banking and cord blood donation.

Methods

Fourteen maternity health professionals (midwives and obstetricians) from both private and public practice settings in Australia participated in semi-structured interviews either in person or by telephone. Interviews were transcribed and data analysed using thematic analysis.

Results

Overall there was strong support for deferred cord clamping, and this was seen as important and routinely discussed with parents as part of antenatal care. However, support did not extend to the options of cord blood banking and donation and to routinely informing parents of these options even when these were available at their birthing location.

Conclusion

Formalised education for maternity health professionals is needed about the benefits and implications of cord blood banking and cord blood donation so that they have the confidence to openly discuss all options of cord clamp timing, cord blood banking and cord blood donation to facilitate informed decision-making by parents.
The experiences of receiving a diagnosis of attention deficit hyperactivity disorder during adulthood in Japan: a qualitative study
Authors: Aoki Yumi , Tsuboi Takashi , Furuno Takehiko , Watanabe Koichiro , Kayama Mami
Published: July 2020

Background

Although the number of adults with attention deficit hyperactivity disorder (ADHD) has increased considerably in recent years, there are few qualitative investigations of the experiences of adults with adult-diagnosed ADHD in Japan. This study aimed to explore in depth the diagnosis-related experiences and needs of such adults.

Methods

Participants were 12 psychiatric outpatients aged 23–55 years diagnosed with ADHD during adulthood. Individual semi-structured interviews were conducted to examine participants’ experiences of receiving, and subsequently coping with, an ADHD diagnosis. A thematic analysis of the interview data was performed.

Results

Six themes emerged: difficulties in accepting the diagnosis, interest in ADHD, feelings of relief, identity concerns, dealing with symptoms, and acceptance of ADHD. Despite initial negative reactions, participants were willing to learn about the disorder, spending time seeking ADHD-related information and sharing it with loved ones. Participants felt relieved after the diagnosis, as they realized why they had experienced long-term problems and incorrect labeling. However, participants also had identity concerns. They gradually began to accept their ADHD symptoms and deal with them better.

Conclusions

The results suggest that, when treating individuals with adult-diagnosed ADHD, it is important to promote self-understanding and reduce negative attitudes toward ADHD; to provide appropriate, brief, evidence-based information about ADHD; and to give individuals sufficient time to think about their ADHD symptoms, how they have affected their daily lives, and how to cope with them in the future.
Implementing a system for the real-time risk assessment of patients considered for intensive care
Authors: Dahella Simarjot S. , Briggs James S. , Coombes Paul , Farajidavar Nazli , Meredith Paul , Bonnici Timothy , Darbyshire Julie L. , Watkinson Peter J.
Published: July 2020

Background

Delay in identifying deterioration in hospitalised patients is associated with delayed admission to an intensive care unit (ICU) and poor outcomes. For the HAVEN project (HICF ref.: HICF-R9–524), we have developed a mathematical model that identifies deterioration in hospitalised patients in real time and facilitates the intervention of an ICU outreach team. This paper describes the system that has been designed to implement the model. We have used innovative technologies such as Portable Format for Analytics (PFA) and Open Services Gateway initiative (OSGi) to define the predictive statistical model and implement the system respectively for greater configurability, reliability, and availability.

Results

The HAVEN system has been deployed as part of a research project in the Oxford University Hospitals NHS Foundation Trust. The system has so far processed > 164,000 vital signs observations and > 68,000 laboratory results for > 12,500 patients and the algorithm generated score is being evaluated to review patients who are under consideration for transfer to ICU. No clinical decisions are being made based on output from the system. The HAVEN score has been computed using a PFA model for all these patients. The intent is that this score will be displayed on a graphical user interface for clinician review and response.

Conclusions

The system uses a configurable PFA model to compute the HAVEN score which makes the system easily upgradable in terms of enhancing systems’ predictive capability. Further system enhancements are planned to handle new data sources and additional management screens.
A comparison of the associations between adiposity and lipids in Malawi and the United Kingdom
Authors: Soares Ana Luiza G. , Banda Louis , Amberbir Alemayehu , Jaffar Shabbar , Musicha Crispin , Price Alison J. , Crampin Amelia C. , Nyirenda Moffat J. , Lawlor Deborah A.
Published: July 2020

Background

The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK).

Methods

We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies.

Results

Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men.

Conclusions

Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.
Genome Scale Metabolic Model of the versatile methanotroph Methylocella silvestris
Authors: Bordel Sergio , Crombie Andrew T. , Muñoz Raúl , Murrell J. Colin
Published: July 2020

Background

Methylocella silvestris is a facultative aerobic methanotrophic bacterium which uses not only methane, but also other alkanes such as ethane and propane, as carbon and energy sources. Its high metabolic versatility, together with the availability of tools for its genetic engineering, make it a very promising platform for metabolic engineering and industrial biotechnology using natural gas as substrate.

Results

The first Genome Scale Metabolic Model for M. silvestris is presented. The model has been used to predict the ability of M. silvestris to grow on 12 different substrates, the growth phenotype of two deletion mutants (ΔICL and ΔMS), and biomass yield on methane and ethanol. The model, together with phenotypic characterization of the deletion mutants, revealed that M. silvestris uses the glyoxylate shuttle for the assimilation of C1 and C2 substrates, which is unique in contrast to published reports of other methanotrophs. Two alternative pathways for propane metabolism have been identified and validated experimentally using enzyme activity tests and constructing a deletion mutant (Δ1641), which enabled the identification of acetol as one of the intermediates of propane assimilation via 2-propanol. The model was also used to integrate proteomic data and to identify key enzymes responsible for the adaptation of M. silvestris to different substrates.

Conclusions

The model has been used to elucidate key metabolic features of M. silvestris, such as its use of the glyoxylate shuttle for the assimilation of one and two carbon compounds and the existence of two parallel metabolic pathways for propane assimilation. This model, together with the fact that tools for its genetic engineering already exist, paves the way for the use of M. silvestris as a platform for metabolic engineering and industrial exploitation of methanotrophs.
Identification of a three-miRNA signature as a novel prognostic model for papillary renal cell carcinoma
Authors: Li Ge , Yang Haifan , Cheng Yong , Zhao Xin , Li Xu , Jiang Rui
Published: July 2020

Background

Papillary renal cell carcinoma (pRCC) accounting for near 20% of renal cell carcinoma is the second most common histological subtype. MiRNAs have been demonstrated to played significant roles on predicting prognosis of patients with tumors. An appropriate and comprehensive miRNAs analysis based on a great deal of pRCC samples from The Cancer Genome Atlas (TCGA) will provide perspective in this field.

Methods

We integrated the expression of mRNAs, miRNAs and the relevant clinical data of 321 pRCC patients recorded in the TCGA database. The survival-related differential expressed miRNAs (sDEmiRs) were estimated by COX regression analysis. The high-risk group and the low-risk group were separated by the median risk score of the risk score model (RSM) based on three screened sDEmiRs. The target genes, underlying molecular mechanisms of these sDEmiRs were explored by computational biology. The expression levels of the three sDEmiRs and their correlations with clinicopathological parameters were further validated by qPCR.

Results

Based on univariate COX analysis (P < 0.001), eighteen differential expressed miRNAs (DEmiRs) were remarkably related with the overall survival (OS) of pRCC patients. Three sDEmiRs with the most significant prognostic values (miR-34a-5p, miR-410-3p and miR-6720-3p) were employed to establish the RSM which was certified as an independent prognosis factor and closely correlated with OS. In the verification of clinical samples, the overexpression of miR-410-3p and miR-6720-3p were detected to be associated with the advanced T-stages, while miR-34a-5p showed the reversed results.

Conclusion

The study developed a RSM based on the identified sDEmiRs with significant prognosis prediction values for pRCC patients. The results pave the avenue for establishing and optimizing a reliable and referable risk assessing model and provide novel insight into the researches of biomarkers and clinical treatment strategies.
Cyclin H predicts the poor prognosis and promotes the proliferation of ovarian cancer
Authors: Peng Chen , Yang Yansong , Ji Li , Yang Panpan , Yang Xiaoqing , Zhang Yuquan
Published: July 2020

Background

Cell cycle dysregulation plays a key role in the pathogenesis of malignant tumors. As a part of the CDK-activating kinase (CAK) trimeric complex, cyclin H is necessary to regulate the cell cycle and proliferation. This investigation aims to characterize the clinical significance and the biological functions of cyclin H in ovarian cancer.

Methods

Immunohistochemical staining was performed on 60 ovarian cancer cases, and a correlation between cyclin H expression and the clinical characteristics of ovarian cancer was analyzed. The function of cyclin H in ovarian cancer was further explored using HO8910 cells and a subcutaneous xenograft model of nude mice.

Result

Cyclin H was slightly expressed in grade 1 ovarian cancer but highly expressed in grade 2 and grade 3 cancerous tissues. The Spearman’s rank correlation analysis showed that the expression of cyclin H is positively correlated with the tumor grade, the FIGO stage, histological grade, and the peritoneal metastasis of ovarian cancer and is also positively correlated with the Ki67 and p-CDK2 in ovarian cancer. Additionally, we found that the five-year survival rate was higher in patients expressing low cyclin H than those expressing high cyclin H. Further, knockdown of cyclin H was achieved using an shRNA in HO8910 ovarian cancer cell line. Silencing cyclin H resulted in a G1/S cell cycle arrest in ovarian cancer cells suppressing its growth. The Ki67 expression was also decreased in cyclin H silenced ovarian cancer.

Conclusion

These results suggest that high expression of cyclin H predicts the poor prognosis and promotes the growth of ovarian cancer by regulating the cell cycle.
Reducing harm through the development of good preparation practices for the injection of slow release morphine sulphate capsules
Authors: Keijzer Lenneke
Published: July 2020

Background

It is not always easy to advise people who inject drugs (PWID) on how to prepare their drugs in a way that is associated with reduced harm. This is particularly true for pharmaceutical drugs that are not meant to be injected. Our objective was to find “good preparation practices” for slow release morphine sulphate capsules, namely preparation methods that reduce harm, that are evidence-based and acceptable to PWID.

Methods

In the laboratory, morphine sulphate capsules were prepared using both a cold and lukewarm preparation technique, two contact and stirring durations (1 min and 20 s) and 4 different filters (cotton filter, Sterifilt, Sterifilt+ and a wheel filter). The following outcomes were compared: particle reduction and morphine content in the filtrate, as well as filtration ease and time.

Results

The lukewarm method and a stirring and contact time of 1 min were associated with a considerably higher morphine yield than both the cold method and the stirring time of only 20 s. Moreover, the suspension obtained was easy to filter using membrane filters. Particle reduction was important with all three membrane filters tested. Using the lukewarm method, morphine recovery was 86% for the wheel filter, 89% for the Sterifilt and 99% for the Sterifilt+.

Conclusions

The provision of a method that is easy to use, reduces harms associated to the injection of insoluble particles and recovers virtually all the active drug has a large chance to be adopted by people who use drugs. This type of “best practices” can be provided by drug workers and by people who use drugs to actively promote harm reduction.
Oxidized cell-free DNA as a stress-signaling factor activating the chronic inflammatory process in patients with autism spectrum disorders
Authors: Shmarina Galina V. , Ershova Elizaveta S. , Simashkova Natalia V. , Nikitina Svetlana G. , Chudakova Julia M. , Veiko Natalia N. , Porokhovnik Lev N. , Basova Anna Y. , Shaposhnikova Antonina F. , Pukhalskaya Daria A. , Pisarev Vladimir M. , Korovina Natalia J. , Gorbachevskaya Natalia L. , Dolgikh Olga A. , Bogush Marina , Kutsev Sergey I. , Kostyuk Svetlana V.
Published: July 2020

Background

Autism spectrum disorders (ASD) are known to be associated with an inflammatory process related to immune system dysfunction. This study’s aim was to investigate the role of cell-free DNA in chronic inflammatory process in ASD patients.

Methods

The study included 133 ASD patients and 27 healthy controls. Sixty-two ASD patients were demonstrated to have mild-to-moderate disease severity (group I) and 71 individuals to have severe ASD (group II). Plasma cell-free (cf) DNA characteristics, plasma cytokine concentrations, expression of the genes for NFкB1 transcription factor and pro-inflammatory cytokines TNFα, IL-1β and IL-8 in peripheral blood lymphocytes (PBL) of ASD patients, and unaffected controls were investigated. Additionally, in vitro experiments with oxidized DNA supplementation to PBL cultures derived from ASD patients and healthy controls were performed.

Results

The data indicates that ASD patients have demonstrated increased cfDNA concentration in their circulation. cfDNA of patients with severe ASD has been characterized by a high abundance of oxidative modification. Furthermore, ASD patients of both groups have shown elevated plasma cytokine (IL-1β, IL-8, IL-17A) levels and heightened expression of genes for NFкB1 nuclear factor and pro-inflammatory cytokines TNFα, IL-1β, and IL-8 in PBL. In vitro experiments have shown that NF-κB/cytokine mRNA expression profiles of ASD patient PBL treated with oxidized DNA fragments were significantly different from those of healthy controls.

Conclusions

It may be proposed that oxidized cfDNA plays a role of stress-signaling factor activating the chronic inflammatory process in patients with ASD.
Risk factors for iliopsoas impingement after total hip arthroplasty using a collared femoral prosthesis
Authors: Qiu Jiandi , Ke Xiurong , Chen Shanxi , Zhao Liben , Wu Fanghui , Yang Guojing , Zhang Lei
Published: July 2020

Background

The relationship between collar design of a femoral component and iliopsoas impingement (IPI) after total hip arthroplasty (THA) is still underrecognized. The purpose of our study was to determine the possible risk factors for IPI related to the femoral component, when using a collared femoral prosthesis.

Methods

A total of 196 consecutive THA patients (206 hips) using a collared femoral prosthesis were reviewed retrospectively after exclusion of the factors related to acetabular component and femoral head. The patients were divided into +IPI and −IPI group according to the presence of IPI. Radiological evaluations were performed including femoral morphology, stem positioning, and collar protrusion length (CPL). Multivariate regression analysis was performed to assess the risk factors for IPI.

Results

At a minimum follow-up of 1 year, IPI was observed in 15 hips (7.3%). Dorr type C proximal femur was found in nine hips (60%) in the +IPI group and in 28 hips in the −IPI group (14.7%, p < 0.001). The mean stem anteversion in the +IPI group was significantly greater than that in the −IPI group (19.1° vs. 15.2°, p < 0.001), as well as the mean CPL (2.6 mm vs. − 0.5 mm, p < 0.001). The increased stem anteversion (OR = 1.745, p = 0.001) and CPL (OR = 13.889, p = 0.001) were potential risk factors for IPI.

Conclusions

The incidence of IPI after THA is higher than expected when using a collared femoral prosthesis. Among the factors related to collared femoral prosthesis, excessively increased stem anteversion and prominent collar protrusion are independent predictors for IPI. In addition, high risk of IPI should be carefully considered in Dorr type C bone, despite that femoral morphology is not a predictive factor.

Level of evidence

Level IV, clinical cohort study
DT2216—a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas
Authors: He Yonghan , Koch Raphael , Budamagunta Vivekananda , Zhang Peiyi , Zhang Xuan , Khan Sajid , Thummuri Dinesh , Ortiz Yuma T. , Zhang Xin , Lv Dongwen , Wiegand Janet S. , Li Wen , Palmer Adam C. , Zheng Guangrong , Weinstock David M. , Zhou Daohong
Published: July 2020

Background

Patients with advanced T cell lymphomas (TCLs) have limited therapeutic options and poor outcomes in part because their TCLs evade apoptosis through upregulation of anti-apoptotic Bcl-2 proteins. Subsets of TCL cell lines, patient-derived xenografts (PDXs), and primary patient samples depend on Bcl-xL for survival. However, small molecule Bcl-xL inhibitors such as ABT263 have failed during clinical development due to on-target and dose-limiting thrombocytopenia.

Methods

We have developed DT2216, a proteolysis targeting chimera (PROTAC) targeting Bcl-xL for degradation via Von Hippel-Lindau (VHL) E3 ligase, and shown that it has better anti-tumor activity but is less toxic to platelets compared to ABT263. Here, we examined the therapeutic potential of DT2216 for TCLs via testing its anti-TCL activity in vitro using MTS assay, immunoblotting, and flow cytometry and anti-TCL activity in vivo using TCL cell xenograft and PDX model in mice.

Results

The results showed that DT2216 selectively killed various Bcl-xL-dependent TCL cells including MyLa cells in vitro. In vivo, DT2216 alone was highly effective against MyLa TCL xenografts in mice without causing significant thrombocytopenia or other toxicity. Furthermore, DT2216 combined with ABT199 (a selective Bcl-2 inhibitor) synergistically reduced disease burden and improved survival in a TCL PDX mouse model dependent on both Bcl-2 and Bcl-xL.

Conclusions

These findings support the clinical testing of DT2216 in patients with Bcl-xL-dependent TCLs, both as a single agent and in rational combinations.
Hypoxia induced ferritin light chain (FTL) promoted epithelia mesenchymal transition and chemoresistance of glioma
Authors: Liu Junhui , Gao Lun , Zhan Na , Xu Pengfei , Yang Ji’an , Yuan Fan’en , Xu Yang , Cai Qiang , Geng Rongxin , Chen Qianxue
Published: July 2020

Background

Hypoxia, a fundamental characteristic of glioma, is considered to promote tumor malignancy by inducing process of epithelial mesenchymal transition (EMT). Ferritin Light Chain (FTL) is one of the iron metabolism regulators and is overexpressed in glioma. However, relationship between hypoxia and FTL expression and its role in regulating EMT remains unclear.

Methods

Immunohistochemistry (IHC), western blot and public datasets were used to evaluate FTL level in glioma. Wound healing, transwell assays, CCK8, annexin V staining assay were used to measure migration, invasion, proliferation and apoptosis of glioma cells in vitro. Interaction between HIF1A and FTL was assessed by luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. Subcutaneous xenograft model was established to investigate in vivo growth.

Results

FTL expression was enriched in high grade glioma (HGG) and its expression significantly associated with IDH1/2 wildtype and unfavorable prognosis of glioma patients. FTL expression positively correlated with HIF1A in glioma tissues and obviously increased in U87 and U251 cells under hypoxia in a time-dependent manner. Mechanistically, HIF-1α regulates FTL expression by directly binding to HRE-3 in FTL promoter region. Furthermore, we found that knockdown FTL dramatically repressed EMT and reduced migration and invasion of glioma by regulating AKT/GSK3β/ β-catenin signaling both in vitro and in vivo. Moreover, our study found downregulation FTL decreased the survival rate and increased the apoptosis of glioma cells treated with temozolomide (TMZ). FTL expression segregated glioma patients who were treated with TMZ or with high MGMT promoter methylation into survival groups in TCGA dataset. Patients with methylated MGMT who had high FTL expression presented similar prognosis with patients with unmethylated MGMT.

Conclusion

Our study strongly suggested that hypoxia-inducible FTL was a regulator of EMT and acted not only as a prognostic marker but also a novel biomarker of response to TMZ in glioma.
The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial
Authors: Cioccari Luca , Luethi Nora , Bailey Michael , Shehabi Yahya , Howe Belinda , Messmer Anna S. , Proimos Helena K. , Peck Leah , Young Helen , Eastwood Glenn M. , Merz Tobias M. , Takala Jukka , Jakob Stephan M. , Bellomo Rinaldo ,   for the ANZICS Clinical Trials Group and the SPICE III Investigators, Shehabi Yahya , Arabi Yaseen , Bass Frances , Bellomo Rinaldo , Erickson Simon , Howe Belinda , Kadiman Suhaini , McArthur Colin , Murray Lynnette , Reade Michael , Seppelt Ian , Takala Jukka , Webb Steve A. , Wise Matthew P. , Shehabi Yahya , Howe Belinda , Bellomo Rinaldo , Arabi Yaseen M. , Bailey Michael J. , Bass Frances , Kadiman Suhaini , McArthur Colin , Murray Lynnette , Reade Michael , Seppelt Ian , Takala Jukka , Webb Steve A. , Wise Matthew P. , Bailey Michael J. , Howe Belinda D. , Murray Lynette , Singh Vanessa
Published: July 2020

Background

Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting.

Methods

In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4).

Results

Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio.

Conclusions

In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP.

Trial registration

The SPICE III trial was registered at ClinicalTrials.gov (NCT01728558).
Fractional modeling and control in a delayed predator-prey system: extended feedback scheme
Authors: Li Shuai , Huang Chengdai , Guo Shuli , Song Xinyu
Published: July 2020

This paper’s goal is to delve into the fractional modeling and bifurcation control for a predator-prey model with prey dispersal and gestation delay. First, the bifurcation criteria for the uncontrolled system are obtained by viewing gestation delay as a bifurcation parameter. It is revealed that gestation delay can induce periodic oscillations. Then, an extended feedback controller is deeply conceived to suppress Hopf bifurcation for the underlying system. The results reflect that the stability behaviors of the uncontrolled system are saliently enhanced by adjusting feedback gain and feedback delay if other coefficients are fixed. To protrude the correctness and excellent feature of our works, two simulation examples are eventually carried out.
Higher-dimensional physical models with multimemory indices: analytic solution and convergence analysis
Authors: Jaradat Imad , Alquran Marwan , Abdel-Muhsen Ruwa , Momani Shaher , Baleanu Dumitru
Published: July 2020

The purpose of this work is to analytically simulate the mutual impact for the existence of both temporal and spatial Caputo fractional derivative parameters in higher-dimensional physical models. For this purpose, we employ the γ̅-Maclaurin series along with an amendment of the power series technique. To supplement our idea, we present the necessary convergence analysis regarding the γ̅-Maclaurin series. As for the application side, we solved versions of the higher-dimensional heat and wave models with spatial and temporal Caputo fractional derivatives in terms of a rapidly convergent γ̅-Maclaurin series. The method performed extremely well, and the projections of the obtained solutions into the integer space are compatible with solutions available in the literature. Finally, the graphical analysis showed a possibility that the Caputo fractional derivatives reflect some memory characteristics.