bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Prenatally Diagnosed Periventricular Nodular Heterotopia in a Surviving Male Patient with FLNA Mutation
Authors: Tencer Jaclyn , Virupakshaiah Akash , Campbell Ian M. , Zackai Elaine H. , Zarnow Deborah , Agarwal Sonika
Published: February 2021

FLNA is a gene on the X chromosome that encodes Filamin A, a widely expressed protein crucial for forming the cell cytoskeleton and mediating cell signaling. Loss-of-function mutations have been associated with periventricular nodular heterotopia (PVNH) with associated epilepsy and intellectual deficits, as well as cardiovascular disease, connective tissue disorders, pulmonary disease, bleeding diathesis, and gastrointestinal disease. Alternatively, gain-of-function mutations have been described with otopalatodigital spectrum disorders.

The loss-of-function variants of FLNA associated with PVNH have historically been considered lethal in males, often prenatally or by the first year of life. However, more surviving males with FLNA variants are being described. Most of the surviving males have missense or distal truncating mutations or a degree of mosaicism. Others are thought to have splice site mutations or in-frame exon skipping leading to production of some degree of functional Filamin A as possible mechanisms of survival.

Here, we presented a case of a 20-month-old small but developmentally appropriate and healthy male infant who was prenatally diagnosed with PVNH, and postnatally found to have a nonsense variant of the FLNA gene. This mutation has not been previously clinically described or published to our knowledge.
Forty years of declining burglary in the United States: Explanation and evidence relating to the security hypothesis
Authors: Farrell Graham
Published: February 2021

Residential burglary in the United States has declined by over 80% across the last four decades, representing a major social phenomenon that remains largely unexplained. International research indicates a need for investigation of the security hypothesis. Here, 50 years of studies are examined chronologically. A consistent narrative emerges which indicates that household security, largely absent in the 1970s, improved gradually over time. Improvement occurred via several mechanisms: the increased prevalence, quality, coverage, and routine use of security fixtures and fittings. In addition, crime displacement declined over time as fewer households offered easy crime opportunities, and the average age of burglars increased as juveniles found burglary increasingly difficult. Hence the study concludes that gradual household security improvements played a central role in the decline in residential burglary. While the findings suggest a considerable revison is needed to our understanding of burglary and burglars, the likelihood that 50 years of diverse burglary research points in the same direction by chance, and without significant contrary evidence, seems remote. Further implications for theory, policy, and research are identified.
From Ethnic Nationalism to Cosmopolitan Mysticism: The Life and Works of Hossein Kazemzadeh Iranshahr (1884–1962)
Authors: Anzali Ata
Published: February 2021

This article examines the life and works of Hossein Kazemzadeh Iranshahr, focusing on the evolution of his thought from an ardent nationalist to a cosmopolitan mystic. It offers a detailed account of the spiritual transformation that Iranshahr went through around 1920 in Europe—a topic that has never been addressed in existing scholarship. It contextualizes his esoteric views, especially the influence of Theosophy on his thought in the context of the so-called “Occult Revival” in Weimar Germany. Finally, it discusses how Iranshahr's emerging spiritual worldview impacted his intellectual outlook, especially his views on religion, nationalism, civilization, and race.
Concussions, cuts and cracked bones: A systematic literature review on protective headgear and head injury prevention in Olympic boxing
Authors: Tjønndal Anne , Haudenhuyse Reinhard , de Geus Bas , Buyse Luk
Published: February 2021

In 2013, the International Boxing Association (AIBA) prohibited the use of headguards for elite male Olympic boxing competitions. Could the removal of the headguard from elite male boxing competitions potentially cause increased injury risk for boxers? The aim of the literature review is to analyse current knowledge about the use of protective headgear and injury prevention in boxing, in order to determine if there are increased injury risks associated with headguard use. Peer‐reviewed studies (language: English, Norwegian, Swedish, Danish and Dutch) published from 1980 and onwards were considered. Five academic databases and grey literature sources were searched, and articles were assessed for methodological quality. Only studies that included boxers as the study population with headguards as a factor were considered. A total of 39 articles were included in the review. The analysis of the reviewed literature indicates that headguards protect well against lacerations and skull fractures, while less is known about the protective effects against concussion and other traumatic brain injuries. Most of the analysed studies however use indirect evidence, obtained through self‐report or observational techniques with relatively small non‐representative samples. There are almost no randomised control trials, longitudinal research designs or samples from recreational boxing. Therefore, AIBA's decision to remove the headguard has to be seen with caution and injury rates among (male) boxers should be continuously evaluated.

Highlights

Research does not sufficiently support the statement that boxing without protective headgear is safer than boxing with a headguard.

Headguards protect well against facial cuts and skull fractures. The systematic review indicates that headguards provide some protection against linear impacts to the head. The headguards protective effects against concussion are however uncertain.

A research agenda is proposed. Priority areas include a focus on longitudinal research designs, randomized control trials, samples from recreational competitive boxing, as well as further research into coaches' and athletes' experiences and perspectives on headguards and injuries.
Bardeen black hole surrounded by perfect fluid dark matter *
Authors: Zhang He-Xu , Chen Yuan , Ma Tian-Chi , He Peng-Zhang , Deng Jian-Bo
Published: February 2021

We derive an exact solution for a spherically symmetric Bardeen black hole surrounded by perfect fluid dark matter (PFDM). By treating the magnetic charge g and dark matter parameter

as thermodynamic variables, we find that the first law of thermodynamics and the corresponding Smarr formula are satisfied. The thermodynamic stability of the black hole is also studied. The results show that there exists a critical radius

where the heat capacity diverges, suggesting that the black hole is thermodynamically stable in the range

. In addition, the critical radius

increases with the magnetic charge g and decreases with the dark matter parameter

. Applying the Newman-Janis algorithm, we generalize the spherically symmetric solution to the corresponding rotating black hole. With the metric at hand, the horizons and ergospheres are studied. It turns out that for a fixed dark matter parameter

, in a certain range, with the increase of the rotation parameter a and magnetic charge g, the Cauchy horizon radius increases while the event horizon radius decreases. Finally, we investigate the energy extraction by the Penrose process in a rotating Bardeen black hole surrounded by PFDM.
Categorization of two-loop Feynman diagrams in the
𝒪α2 correction to

*
Authors: Li Zhao , Wang Yefan , Wu Quan-feng
Published: February 2021

The

process is the dominant process for the Higgs boson production at the future Higgs factory. In order to match the analysis on the Higgs properties with highly precise experiment data, it will be crucial to include the theoretical prediction to the full next-to-next-to-leading order electroweak effect in the production rate

. In this inspiring work, we categorize the two-loop Feynman diagrams of the

correction to

into 6 categories according to relevant topological structures. Although 25377 diagrams contribute to the

correction in total, the number of the most challenging diagrams with seven denominators is 2250, which contain only 312 non-planar diagrams with 155 independent types. This categorization could be a valuable reference for the complete calculation in future.
Outdoor Courier Lockboxes in Summer Are a Significant Source of Preanalytical Error
Authors: Dibbern Megan E , Pierre Christina C , Wiencek Joesph R
Published: February 2021

Objectives

To determine the impact of short-term (<4-hour) exposure of summer-like temperatures on lithium heparin (uncentrifuged and centrifuged) samples stored in outdoor courier lockboxes in the Mid-Atlantic United States.

Methods

Healthy adults (n = 8) were recruited to investigate the impact of the short-term exposure of lithium heparin samples (centrifuged and uncentrifuged) inside 2 LabLocker-KF300 courier lockboxes placed outside in direct sunlight during summer. Each courier lockbox was monitored every 5 minutes with a temperature data logger and contained either the standard number (n = 2) of cold packs (cold) or no standard cold packs (warm). Acceptable tolerance limits were defined for each analyte by significant change limit (SCL) analysis (P < .05), as previously described.

Results

Significant changes were identified in each study condition for warm and cold lockbox conditions. Aspartate aminotransferase, glucose, lactate dehydrogenase, and potassium commonly crossed SCLs from mean baseline (t0) in the majority of conditions.

Conclusions

Outdoor courier lockboxes are an underrecognized source of preanalytical error.
SATB2 Is Expressed in a Subset of Pulmonary and Thymic Neuroendocrine Tumors
Authors: Vrana Julie A , Boland Jennifer M , Terra Simone B S P , Xie Hao , Jenkins Sarah M , Mansfield Aaron S , Molina Julian R , Cassivi Stephen D , Roden Anja C
Published: February 2021

Objectives

To evaluate SATB2 expression and prognostic implications in a large cohort of thoracic neuroendocrine tumors.

Methods

Surgical pathology files (1995-2017) and an institutional thymic epithelial tumor database (2010-2020) were searched for resected neuroendocrine tumors. Cases were stained with SATB2 (clone EP281). Percent SATB2-positive tumor cells and expression intensity were scored.

Results

In the lung, SATB2 was expressed in 5% or more of tumor cells in 29 (74.4%) of 39 small cell carcinomas and 9 (22.5%) of 40 atypical and 26 (40.6%) of 64 typical carcinoid tumors. SATB2 percent tumor cell expression and intensity were higher in small cell carcinomas than in carcinoid tumors (both P < .001, respectively). After adjusting for tumor subtype, SATB2 expression did not correlate with outcome. In the thymus, four (100%) of four atypical carcinoid tumors and one large cell neuroendocrine carcinoma but no small cell carcinoma (n = 2) expressed SATB2 in 5% or more of tumor cells.

Conclusions

SATB2 (clone EP281) is expressed in a large subset of pulmonary and thymic neuroendocrine tumors and therefore does not appear to be a useful marker to identify the origin of neuroendocrine tumors. Validation studies are needed, specifically including thymic neuroendocrine tumors, as the expression pattern might be different in those tumors.
Presence of a dominant native shrub is associated with minor shifts in the function and composition of grassland communities in a northern savannah
Authors: Peetoom Heida Isaac , Brown Charlotte , Dettlaff Margarete A , Oppon Kenneth J , Cahill James F
Published: February 2021

Ecosystems are spatially heterogenous in plant community composition and function. Shrub occurrence in grasslands is a visually striking example of this, and much research has been conducted to understand the functional implications of this pattern. Within savannah ecosystems, the presence of tree and shrub overstories can have significant impacts on the understory herbaceous community. The exact outcomes, however, are likely a function of the spatial arrangement and traits of the overstory species. Here we test whether there are functional linkages between the spatial patterning of a native shrub and the standing biomass, community composition, and overall nutrient cycling of a neighbouring grassland understory communities within the Aspen Parkland of central Alberta, Canada. In a paired grassland-shrub stand study, we found the native shrub, Elaeagnus commutata, has relatively few stand-level impacts on the composition and standing biomass of the ecosystem. One factor contributing to these limited effects may be the overdispersion of shrub stems at fine spatial scales, preventing areas of deep shade. When we looked across a shrub density gradient and incorporated shrub architecture into our analyses, we found these shrub traits had significant associations with species abundance and root biomass in the understory community. These results suggest that stem dispersion patterns, as well as local stand architecture, are influential in determining how shrubs may affect their herbaceous plant understory. Thus, it is important to incorporate shrub spatial and architectural traits when assessing shrub-understory interactions.
The functional impact of nuclear reorganization in cellular senescence
Authors: Rocha Azucena , Dalgarno Audrey , Neretti Nicola
Published: February 2021

Cellular senescence is the irreversible cell cycle arrest in response to DNA damage. Because senescent cells accumulate with age and contribute to chronic inflammation, they are promising therapeutic targets for healthspan extension. The senescent phenotype can vary depending on cell type and on the specific insults that induce senescence. This variability is also reflected in the extensive remodeling of the genome organization within the nucleus of senescent cells. Here, we give an overview of the nuclear changes that occur in different forms of senescence, including changes to chromatin state and composition and to the three-dimensional organization of the genome, as well as alterations to the nuclear envelope and to the accessibility of repetitive genomic regions. Many of these changes are shared across all forms of senescence, implicating nuclear organization as a fundamental driver of the senescent state and of how senescent cells interact with the surrounding tissue.
Children Speaking against Home Arrest: Decolonising Racial Penologies
Authors: Shalhoub-Kevorkian Nadera
Published: February 2021

Home arrest (HA), an alternative rehabilitative sentence to the more punitive disposal of imprisonment, is utilised in a range of ways by criminal justice regimes across the world. However, its implementation contains the potential for intimate political intrusion. This paper engages with forty-one testimonials gathered from Palestinian children, young people (aged 12–18 years) and their families, examining their experiences under HA in Occupied East Jerusalem. The analysis of their voices reveals how HA has affected children and young people’s intimate spaces, psyches and behaviour, and dismembered their relationships and sense of belonging. It simultaneously uncovers creative manifestations of freedom and the refusal to accept HA’s destructive consequences. The paper draws on children’s own understandings of HA as a violent technology of control, rethinks the role of social work in violent contexts and offers new insights on intervention. It suggests that in settler colonial militarised contexts, HA serves as a racialised disciplinary practice that poses major ethical challenges for critical social work practice. The paper concludes by underscoring the importance of encouraging social workers to engage with the anti-oppressive social work agenda and to examine their positions and ethics in politically complex realities.
A case report: extensive myocardial calcification and non-ischaemic cardiomyopathy related to past sepsis
Authors: Lim Anthony , Be Kim Kuy , Wong Chiew
Published: February 2021

Background

Diffuse myocardial calcification following severe sepsis is a rare complication whose long-term effects are not well-understood.

Case summary

A 51-year-old man presented with a 6-month history of worsening dyspnoea on a background of sepsis 9 years prior. His initial echocardiogram showed moderate systolic dysfunction and a mildly dilated left ventricle. Cardiac computed tomography showed signs of mild coronary artery disease without significant stenosis, but the diffuse extensive left ventricular (LV) mid-myocardial calcification was visible. Cardiac magnetic resonance imaging showed diffuse extensive LV mid-myocardial late gadolinium enhancement in keeping with the calcification. He was diagnosed with non-ischaemic cardiomyopathy. He was commenced on appropriate anti-failure medical therapy, maintains New York Heart Association functional class II functional status, and has received a prophylactic implantable cardioverter-defibrillator.

Discussion

Diffuse myocardial calcification might be associated with long-term development of non-ischaemic cardiomyopathy. The benefit of monitoring such patients for long-term effects is not routine, but should be considered.
Syncope triggered by atrial flutter in a patient with a pacemaker: cross-stimulation—a case report
Authors: Durán-Bobin Olga , Crespo-Mancebo Francisco , Elices-Teja Juliana , González-Juanatey Carlos
Published: February 2021

Background

Syncope in a patient with a pacemaker is a serious event requiring urgent action to ascertain its cause. Around 5% of cases are due to a pacemaker system malfunction.

Case summary

An 82-year-old man underwent dual-chamber permanent pacemaker implantation due to intermittent high-degree atrioventricular block (AVB) in sinus rhythm. Nine months later, the patient reported episodes of syncope. The chest X-ray showed both leads to be at their expected positions. The electrocardiography (ECG) showed common atrial flutter. Ventricular capture during pacing in atrial demand pacing (AAI) mode confirmed cross-stimulation due to the switching of the atrial and ventricular leads at the pacemaker header.

Discussion

Cross-stimulation is a rare possibility in a differential diagnosis of causes of syncope. The diagnosis is frequently made during the procedure or a few hours later. The lack of symptoms during 9 months in this case was likely due to the patient having normal sinus rhythm with preserved AV conduction most of the time, as well as ventricular capture from the atrial lead related to non-sensed P waves. When atrial arrhythmias occurred, the sensing of the F waves inhibited ventricular pacing. In order to avoid this complication, in patients with intermittent bradycardia, pacing at a slightly higher heart rate during implantation of the device should be recommended to see the chamber paced with the surface ECG connected to the device interrogator. The ECG and electrogram (EGM) should correlate during device interrogation in order to identify this complication.)
‘Pave-and-crack’ technique for the recanalization of severely calcified occlusive aorto-ilio-femoral disease in type-III Leriche syndrome: a case report
Authors: Giusca Sorin , Schmidt Andrej , Korosoglou Grigorios
Published: February 2021

Background 

Leriche syndrome is the result of the atherosclerotic occlusion of the distal aorta that may also involve pelvic arteries. The standard treatment for this condition is considered surgical with various techniques available for establishing appropriate flow to both limbs. However, due to the technical advances in the last decades, endovascular approaches are now also capable to tackle such lesions. The ‘pave-and-crack’ technique enables the treatment of severely calcified lesions. This two-step procedure consists of firstly placing a covered stent prothesis (VIABAHN) into the severely calcified segment, which is afterwards aggressively dilated with high-pressure balloons. Subsequently, an interwoven nitinol SUPERA stent with high radial forces is placed within the prothesis.

Case summary 

Herein, we describe the case of an 81-year-old male patient, who presented with critical limb-threatening ischaemia of his right leg. Doppler ultrasound revealed a long occlusion of the right external iliac artery, common femoral, superficial femoral, and deep femoral artery. The lesion was successfully tackled using antegrade and retrograde punctures and the ‘pave-and-crack’ technique.

Discussion 

The ‘pave-and-crack’ technique is an endovascular approach for the treatment of severe circumferential calcified lesions. Based on this technique covered stents are initially placed to prevent vessel rupture, which might occur during the aggressive balloon dilatation. Subsequently, the covered stents are relined by interwoven Supera stents, which provide high radial force preventing recoil and restenosis.
Spatial population trends and economic development in Puerto Rico, 1765–2010
Authors: Marein Brian
Published: February 2021

I use data for consistently defined municipalities to describe spatial patterns in population growth in Puerto Rico across all stages of economic development and rule by Spain and then the United States. The spatial distribution of population began to resemble the modern distribution after the turn of the twentieth century, around the time that municipal population densities diverged. Municipal population growth was positively correlated with crop production in the preindustrial era and was negatively correlated with agricultural employment from 1899 to 1970. Urbanization commenced around 1900, decades earlier than generally believed and before most of the Caribbean and Central America.
Incorporating spatiotemporal variability in multispecies survey design optimization addresses trade-offs in uncertainty
Authors: Oyafuso Zack S , Barnett Lewis A K , Kotwicki Stan
Published: February 2021

In designing and performing surveys of animal abundance, monitoring programs often struggle to determine the sampling intensity and design required to achieve their objectives, and this problem greatly increases in complexity for multispecies surveys with inherent trade-offs among species. To address these issues, we conducted a multispecies stratified random survey design optimization using a spatiotemporal operating model and a genetic algorithm that optimizes both the stratification (defined by depth and longitude) and the minimum optimal allocation of samples across strata subject to prespecified precision limits. Surveys were then simulated under those optimized designs and performance was evaluated by calculating the precision and accuracy of a resulting design-based abundance index. We applied this framework to a multispecies fishery-independent bottom trawl survey in the Gulf of Alaska, USA. Incorporating only spatial variation in the optimization failed to produce population estimates within the prespecified precision constraints, whereas including additional spatiotemporal variation ensured that estimates were both unbiased and within prespecified precision constraints. In general, results were not sensitive to the number of strata in the optimized solutions. This optimization approach provides an objective quantitative framework for designing new, or improving existing, survey designs for many different ecosystems.
Per-recruit modelling of pulse fisheries: comment on “Modelling pulse fishery systems in data-limited situations”
Authors: Hart Deborah R
Published: February 2021

A pulse fishery is one where fishing occurs during a short period each year and is zero for the rest of the year. Grüss et al. proposed a continuous per-recruit model for such fisheries. However, this analysis is based on per-recruit equations that were derived under the assumption that fishing mortality is constant in time and, thus, do not apply to fisheries where F varies, such as a pulse fishery. A correct continuous per-recruit formulation for pulse fisheries is derived. In most cases, the continuous per-recruit model can be closely approximated by a discrete model, where the integrals are replaced by sums. A modification in the Baranov catch equation for pulse fisheries is also derived that can used to compute annual exploitation rates.
Quality of maternal and newborn hospital care in Brazil: a quality improvement cycle using the WHO assessment and quality tool
Authors: Pessa Valente Emanuelle , Barbone Fabio , de Melo E Lima Tereza Rebecca , de Mascena Diniz Maia Paula Ferdinanda Conceição , Vezzini Francesca , Tamburlini Giorgio
Published: February 2021

Background

Increasing efforts toward quality improvement (QI) are necessary in low- and middle-income countries (LMICs) to reduce maternal and perinatal mortality and morbidity and to promote respectful care. In Brazil, perinatal health indicators are below targets in several states despite universal access to perinatal services and very high rates of institutional births, indicating poor quality of care (QoC) as a key issue to be addressed. However, research efforts to develop and test QoC improvement interventions are scarce.

Objectives

We assessed the effects of a 1-year comprehensive QI cycle using a World Health Organization (WHO) assessment and quality tool on maternal and newborn care at hospital level and documented QIs obtained after a 1-year comprehensive QI cycle.

Methods

Uncontrolled, unblinded, pre–post study carried out in six maternity hospitals in Pernambuco, Brazil, accounting for 29 128 live births in 2014. A standards-based and participatory approach based on a WHO quality assessment and improvement tool for maternal and neonatal care at hospital level was used. A national team of assessors supervised by international experts carried out baseline and final assessments. An action plan was developed and implemented to address key quality gaps emerging from the baseline assessment and from two supportive supervision visits.

Results

At baseline, hospitals presented a variety of quality gaps, the majority common to all participating centers. Gaps in case management of normal and complicated deliveries and in respectful and holistic care were predominant, in both teaching/tertiary and secondary care hospitals. After one year, several improvements were observed, particularly in respectful care during labor and at delivery, in case management of normal labor and delivery and in neonatal care.

Conclusions

A systematic participatory approach based on a WHO tool produced important QIs in a relatively short time and should be considered for use for large-scale QI programs in Brazil and other LMICs. Its comprehensive, peer-to-peer and action-oriented nature and its capability to document QI over time and to build a QI culture represent important comparative advantages over other QI interventions.
Choosing Appropriate Technique for Nasal Reconstruction in Challenging Cases of Panfacial Burn: Treatment Algorithm
Authors: Hesamirostami Mohammadhossein , Sarparast Leila , Radfar Azar , Hesamirostami Sami , Hosseinzadeh Ahmad Zaghi , Yousefnezhad Omid
Published: February 2021

The nose is one of the most challenging facial parts to reconstruct. Its asymmetries, defects, or disharmonies are easily noticeable. The complex contours, highlights, shadows, and special shape of its subunits make nasal reconstruction more difficult in panfacial burn than that of nonburned ones. This retrospective study was conducted at Zare Hospital. Twenty-five panfacial burn cases with nasal defects were studied from 2010 to 2019. Profile photos were manipulated by Adobe Photoshop. Based on the difference between the burn-related shortened nasal length and the expected photoshopped one, the severity of the short nose was detected, and the strategy of the surgery was determined. Of the 25 cases, 10 cases with normal nasal length and projection, or mild short nose with minimal alar rim, tip and/or columellar defect underwent nasal reconstruction with skin and/or composite graft. Nine patients with normal nasal length or mild to moderate short nose but moderate to severe alar defect underwent reconstruction with turndown flap plus skin and/or composite graft. Pre-expanded forehead flap (n = 1) and delayed scarred or skin grafted forehead flap (n = 5) were used for six patients with severe short nose defect. There are several procedural alternatives for the reconstruction of burn-related mild to moderate nasal deformity. For severe and deep panfacial burn, delayed forehead flap seems safe with acceptable color and texture harmony. Our designed algorithm could potentially improve the selection of proper nasal reconstruction techniques and assist novice surgeons.
A Systematic Review and Meta-Analysis of Cancer Patients Affected by a Novel Coronavirus
Authors: Venkatesulu Bhanu Prasad , Chandrasekar Viveksandeep Thoguluva , Girdhar Prashanth , Advani Pragati , Sharma Amrish , Elumalai Thiraviyam , Hsieh Cheng En , Elghazawy Hagar I , Verma Vivek , Krishnan Sunil
Published: February 2021

Background

Cancer patients with coronavirus disease 2019 (COVID-19) have been reported to have double the case fatality rate of the general population.

Methods

A systematic search of PubMed, Embase, and Cochrane Central was done for studies on cancer patients with COVID-19. Pooled proportions were calculated for categorical variables. Odds ratio (OR) and forest plots (random-effects model) were constructed for both primary and secondary outcomes.

Results

This systematic review of 38 studies and meta-analysis of 181 323 patients from 26 studies included 23 736 cancer patients. Our meta-analysis shows that cancer patients with COVID-19 have a higher likelihood of death (n = 165 980, OR = 2.54, 95% confidence interval [CI] = 1.47 to 4.42), which was largely driven by mortality among patients in China. Cancer patients were more likely to be intubated. Among cancer subtypes, the mortality was highest in hematological malignancies (n = 878, OR = 2.39, 95% CI = 1.17 to 4.87) followed by lung cancer (n = 646, OR = 1.83, 95% CI = 1.00 to 3.37). There was no association between receipt of a particular type of oncologic therapy and mortality. Our study showed that cancer patients affected by COVID-19 are a decade older than the normal population and have a higher proportion of comorbidities. There was insufficient data to assess the association of COVID-19–directed therapy and survival outcomes in cancer patients.

Conclusion

Cancer patients with COVID-19 disease are at increased risk of mortality and morbidity. A more nuanced understanding of the interaction between cancer-directed therapies and COVID-19–directed therapies is needed. This will require uniform prospective recording of data, possibly in multi-institutional registry databases.
Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome
Authors: Napoletani Giorgia , Vigli Daniele , Cosentino Livia , Grieco Maddalena , Talamo Maria Cristina , Lacivita Enza , Leopoldo Marcello , Laviola Giovanni , Fuso Andrea , d’Erme Maria , De Filippis Bianca
Published: February 2021

Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene, characterized by severe behavioral and physiological impairments for which no cure is available. The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25 mg/kg/day for 7 days) was proved to rescue neurobehavioral alterations in a mouse model of RTT. In the present study, we aimed at gaining insight into the mechanisms underpinning the efficacy of 5-HT7R pharmacological stimulation by investigating its epigenetic outcomes in the brain of RTT female mice bearing a truncating MeCP2 mutation. Treatment with LP-211 normalized the reduced histone H3 acetylation and HDAC3/NCoR levels, and increased HDAC1/Sin3a expression in RTT mouse cortex. Repeated 5-HT7R stimulation also appeared to strengthen the association between NCoR and MeCP2 in the same brain region. A different profile was found in RTT hippocampus, where LP-211 rescued H3 hyperacetylation and increased HDAC3 levels. Overall, the present data highlight a new scenario on the relationship between histone acetylation and serotoninergic pathways. 5-HT7R is confirmed as a pivotal therapeutic target for the recovery of neuronal function supporting the translational value of this promising pharmacological approach for RTT.
Down-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus suppresses OVCAR-3 cells proliferation and induction of apoptosis by Wnt/β-catenin
Authors: Sun Lingna , Cui Yuping , Jiang Kongdi , Li Juan
Published: February 2021

Objectives

Ovarian cancer is a lethal gynecological malignancy. Long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was reported to have a critical role in cancer advancement. The ANRIL-mediated oncogenic underlying molecular mechanisms are not fully understood in ovarian cancer. We aimed to study ANRIL silencing effects on the proliferation and apoptosis of OVCAR-3 cells.

Methods

The ANRIL was Knockdown by transfection of OVCAR-3 cells with si-RNA against ANRIL. MTT assay and cell death ELISA kit were used to evaluate cellular proliferation and apoptosis. The expression levels of ANRIL, pro-and anti-apoptotic genes were assessed using q-RT-PCR. Western blotting was used to assess Wnt/β-catenin signalling pathway.

Key findings

ANRIL down-regulating in OVCAR-3 cell lines resulted in significant inhibition of cellular proliferation, apoptosis induction, as well as suppression of cellular invasion. Besides, knockdown of ANRIL led to pro-apoptotic genes up-regulation, Bad and Bax and anti-apoptotic genes down-regulation, Bid and Bcl-2. More importantly, we observed that ANRIL inhibition suppressed the vital components expression of the Wnt/β-catenin cascade.

Conclusion

Our findings showed that down-regulation of lncRNA ANRIL resulted in the effective suppression of OVCAR-3 cell proliferation and invasion and induction of apoptosis by preventing Wnt/β-catenin signal transduction.
Association of SLC22A1,SLCO1B3 Drug Transporter Polymorphisms and Smoking with Disease Risk and Cytogenetic Response to Imatinib in Patients with Chronic Myeloid Leukemia
Authors: Mohammadi Fatemeh , Rostami Golale , Assad Dlnya , Shafiei Mohammad , Hamid Mohammad , Jalaeikhoo Hasan
Published: February 2021

Objective

To determine whether polymorphisms of SLC22A1 and SLCO1B3 genes could predict imatinib (IM) response and chronic myeloid leukemia (CML) risk.

Methods

We genotyped SLC22A1 (c.480G > C, c.1222A > G) and SLCO1B3 (c.334T > G, c.699G > A) polymorphisms in 132 patients with CML and 109 sex- and age-matched healthy subjects. The patients were evaluated for cytogenetic response by standard chromosome banding analysis (CBA).

Results

Polymorphism analysis showed significant increased risk of IM resistance for SLC22A1c.1222AG (P = .03; OR = 2.2), SLCO1B3c.334TT/TG genotypes (P = .007; OR = 4.37) and 334T allele (P = .03; OR = 2.86). The double combinations of SLC22A1c.480CC and c.1222AG polymorphisms with SLCO1B3c.334TT/TG were significantly associated with complete cytogenetic response (CCyR) (P <.05; OR> 7). The interaction between all polymorphisms and smoking were associated with CML development and IM resistance (P ≤.04; OR> 3).

Conclusions

Our study results suggest the influence of SLC22A1 and SLCO1B3 polymorphisms and the interaction of smoking on CML development and IM response.
Downregulation of aromatase plays a dual role in preeclampsia
Authors: Zhu Dawei , Huang Jie , Gu Xing , Li Li , Han Jian
Published: February 2021

Preeclampsia (PE) is a gestational disease, which seriously impairs maternal and infant health. However, the pathogenesis of PE remains unclear. The aromatase (CYP19A1) in placenta converts androgens from maternal and fetal adrenal glands to estrogen. Therefore, this change in the aromatase expression or function and the subsequent change of steroids in the placenta could be related to the pathophysiology of PE. In this study, we first analyzed the expression of CYP19A1 in clinical placental tissues as well as the level of sex hormones in corresponding serum samples. The results showed that the expression of aromatase in the placenta of PE patients was relatively low and accompanied by a sex hormone imbalance. Subsequently, animal experiments showed that ischemia and hypoxia lead to a low expression of CYP19A1, and that PE-like symptoms appear in pregnant mice following decreased or inhibited CYP19A1 expression. It was also found that, with the downregulation of CYP19A1 expression, the invasion and migration abilities of trophoblast cells were enhanced, which benefited placental implantation. However, alongside this, apoptosis and the inflammatory response were also increased, which was detrimental to placental development. Phosphoproteomic analyses revealed that the activation of the PI3K/AKT signaling pathway may play a key role in these processes. In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE.
Xenogeneic silencing relies on temperature-dependent phosphorylation of the host H-NS protein in Shewanella
Authors: Liu Xiaoxiao , Lin Shituan , Liu Tianlang , Zhou Yiqing , Wang Weiquan , Yao Jianyun , Guo Yunxue , Tang Kaihao , Chen Ran , Benedik Michael J , Wang Xiaoxue
Published: February 2021

Lateral gene transfer (LGT) plays a key role in shaping the genome evolution and environmental adaptation of bacteria. Xenogeneic silencing is crucial to ensure the safe acquisition of LGT genes into host pre-existing regulatory networks. We previously found that the host nucleoid structuring protein (H-NS) silences prophage CP4So at warm temperatures yet enables this prophage to excise at cold temperatures in Shewanella oneidensis. However, whether H-NS silences other genes and how bacteria modulate H-NS to regulate the expression of genes have not been fully elucidated. In this study, we discovered that the H-NS silences many LGT genes and the xenogeneic silencing of H-NS relies on a temperature-dependent phosphorylation at warm temperatures in S. oneidensis. Specifically, phosphorylation of H-NS at Ser42 is critical for silencing the cold-inducible genes including the excisionase of CP4So prophage, a cold shock protein, and a stress-related chemosensory system. By contrast, nonphosphorylated H-NS derepresses the promoter activity of these genes/operons to enable their expression at cold temperatures. Taken together, our results reveal that the posttranslational modification of H-NS can function as a regulatory switch to control LGT gene expression in host genomes to enable the host bacterium to react and thrive when environmental temperature changes.
MR1 overexpression correlates with poor clinical prognosis in glioma patients
Authors: Kubica Phillip , Lara-Velazquez Montserrat , Bam Marpe , Siraj Seema , Ong Irene , Liu Peng , Priya Raj , Salamat Shahriar , Brutkiewicz Randy R , Dey Mahua
Published: February 2021

Background

Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma.

Methods

Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression.

Results

MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma.

Conclusions

Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.
Adolescent and young adult neuro-oncology: a comprehensive review
Authors: Yeo Kee Kiat , Burgers Darcy E , Brodigan Katelynn , Fasciano Karen , Frazier A Lindsay , Warren Katherine E , Reardon David A
Published: February 2021

Adolescent and young adult (AYA; ages 15-39) patients represent a population that experiences significant challenges in cancer care and research, exemplified by poorer clinical outcomes as well as unmet psychosocial and reproductive health needs. Despite central nervous system (CNS) tumors being one of the most common malignancies diagnosed in the age group, there is a clear paucity of AYA CNS tumor-specific publications, especially those related to the unique psychosocial and reproductive health needs of this population of patients. In this review, we examine various aspects of AYA oncological care including tumor biology, clinical outcome, clinical trials enrollment rate, site of care, unique psychosocial needs, and oncofertility. We assess the current state of these issues, highlight areas of deficiencies, and outline the steps needed to address these concerns. We emphasize the importance of comprehensive molecular testing as part of the diagnostic work-up, expansion of clinical trial availability, access to psychosocial care and oncofertility expertise, and the development of AYA-specific clinical research to define best practices and advancing care for this population.
The Response Measures to the Coronavirus Disease 2019 Outbreak in China
Authors: Qu Junyan , Lv Xiaoju
Published: February 2021

For China, the coronavirus disease 2019 (COVID-19) outbreak is a major public health emergency with the fastest spread, the most extensive infection, and the hardest to contain over the past 70 years. The different organizations and institutions in China have taken unprecedented public health responses to interrupt the virus transmission in the past several months. The outbreak in China was under control, but the number of confirmed cases abroad is still rising. Coronavirus disease 2019 has presented a global pandemic. We summarized the response measures adopted by different organizations at different levels (country, province, and hospital) in China, such as setting up an effective integrated system for disease prevention and control, effective deployment of medical staff, adjusting measures according to local conditions, establishing Fangcang hospitals, strengthening scientific research on COVID-19, epidemic prevention knowledge education, mass rapid testing for severe acute respiratory syndrome coronavirus 2, and correct personal protection including high compliance of wearing masks, hoping to provide some help for disease control in some regions.
Small business training to improve management practices in developing countries: re-assessing the evidence for ‘training doesn’t work’
Authors: McKenzie David
Published: February 2021

Despite the popularity of business training among policy-makers, its use has faced increasing scepticism. Most of the first randomized experiments could not detect statistically significant impacts of training on firm profits or sales. I reassess the evidence for whether small business training works, incorporating more recent results. A meta-analysis of these estimates shows that training increases profits and sales on average by 5–10 per cent. This is in line with what is optimistic to expect, but impacts of this magnitude are too small for most experiments to detect. I then discuss five approaches for improving the effectiveness of traditional training by incorporating gender, kaizen methods, localization and mentoring, heuristics, and psychology. The challenge is then how to deliver a quality programme on a cost-effective basis at a much larger scale. Three possible approaches to scaling up training are discussed: using the market, using technology, or targeting and funnelling firms.
Stomatal morphology and physiology explain varied sensitivity to abscisic acid across vascular plant lineages
Authors: Gong Lei , Liu Xu-Dong , Zeng Yuan-Yuan , Tian Xue-Qian , Li Yan-Lu , Turner Neil C , Fang Xiang-Wen
Published: February 2021

Abscisic acid (ABA) can induce rapid stomatal closure in seed plants, but the action of this hormone on the stomata of fern and lycophyte species remains equivocal. Here, ABA-induced stomatal closure, signaling components, guard cell K+ and Ca2+ fluxes, vacuolar and actin cytoskeleton dynamics, and the permeability coefficient of guard cell protoplasts (Pf) were analyzed in species spanning the diversity of vascular land plants including 11 seed plants, 6 ferns, and 1 lycophyte. We found that all 11 seed plants exhibited ABA-induced stomatal closure, but the fern and lycophyte species did not. ABA-induced hydrogen peroxide elevation was observed in all species, but the signaling pathway downstream of nitric oxide production, including ion channel activation, was only observed in seed plants. In the angiosperm faba bean (Vicia faba), ABA application caused large vacuolar compartments to disaggregate, actin filaments to disintegrate into short fragments and Pf to increase. None of these changes was observed in the guard cells of the fern Matteuccia struthiopteris and lycophyte Selaginella moellendorffii treated with ABA, but a hypertonic osmotic solution did induce stomatal closure in fern and the lycophyte. Our results suggest that there is a major difference in the regulation of stomata between the fern and lycophyte plants and the seed plants. Importantly, these findings have uncovered the physiological and biophysical mechanisms that may have been responsible for the evolution of a stomatal response to ABA in the earliest seed plants.