bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Cancer Data Interoperability: The Promise of the Minimal Common Oncology Data Elements (mCODE) Initiative
Authors: Osterman Travis J. , Terry May , Miller Robert S.
Published: November 2020

PURPOSE

Because of expanding interoperability requirements, structured patient data are increasingly available in electronic health records. Many oncology data elements (eg, staging, biomarkers, documentation of adverse events and cancer outcomes) remain challenging. The Minimal Common Oncology Data Elements (mCODE) project is a consensus data standard created to facilitate transmission of data of patients with cancer.

METHODS

In 2018, mCODE was developed through a work group convened by ASCO, including oncologists, informaticians, researchers, and experts in terminologies and standards. The mCODE specification is organized by 6 high-level domains: patient, laboratory/vital, disease, genomics, treatment, and outcome. In total, 23 mCODE profiles are composed of 90 data elements.

RESULTS

A conceptual model was published for public comment in January 2019 and, after additional refinement, the first public version of the mCODE (version 0.9.1) Fast Healthcare Interoperability Resources (FHIR) implementation guide (IG) was presented at the ASCO Annual Meeting in June 2019. The specification was approved for balloting by Health Level 7 International (HL7) in August 2019. mCODE passed the HL7 ballot in September 2019 with 86.5% approval. The mCODE IG authors worked with HL7 reviewers to resolve all negative comments, leading to a modest expansion in the number of data elements and tighter alignment with FHIR and other HL7 conventions. The mCODE version 1.0 FHIR IG Standard for Trial Use was formally published on March 18, 2020.

CONCLUSION

The mCODE project has the potential to offer tremendous benefits to cancer care delivery and research by creating an infrastructure to better share patient data. mCODE is available free from www.mCODEinitiative.org . Pilot implementations are underway, and a robust community of stakeholders has been assembled across the oncology ecosystem.
Characterization of the Tumor Immune Microenvironment Identifies M0 Macrophage-Enriched Cluster as a Poor Prognostic Factor in Hepatocellular Carcinoma
Authors: Farha Mark , Jairath Neil K. , Lawrence Theodore S. , El Naqa Issam
Published: November 2020

PURPOSE

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and a high recurrence rate. The tumor immune microenvironment in HCC has been characterized as shifted toward immunosuppression. We conducted a genomic data-driven classification of immune microenvironment HCC subtypes. In addition, we demonstrated their prognostic value and suggested a potential therapeutic targeting strategy.

METHODS

RNA sequencing data from The Cancer Genome Atlas–Liver Hepatocellular Carcinoma was used (n = 366). Abundance of immune cells was imputed using CIBERSORT and visualized using unsupervised hierarchic clustering. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox regression. Differential expression and gene set enrichment analyses were conducted on immune clusters with poor OS and high programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) coexpression. A scoring metric combining differentially expressed genes and immune cell content was created, and its prognostic value and immune checkpoint blockade response prediction was evaluated.

RESULTS

Two clusters were characterized by macrophage enrichment, with distinct M0Hi and M2Hi subtypes. M2Hi ( P = .038) and M0Hi ( P = .018) were independently prognostic for OS on multivariable analysis. Kaplan-Meier estimates demonstrated that patients in M0Hi and M2Hi treated with sorafenib had decreased OS ( P = .041), and angiogenesis hallmark genes were enriched in the M0Hi group. CXCL6 and POSTN were overexpressed in both the M0Hi and the PD-1Hi/PD-L1Hi groups. A score consisting of CXCL6 and POSTN expression and absolute M0 macrophage content was discriminatory for OS (intermediate: hazard ratio [HR], 1.59; P ≤ .001; unfavorable: HR, 2.08; P = .04).

CONCLUSION

Distinct immune cell clusters with macrophage predominance characterize an aggressive HCC phenotype, defined molecularly by angiogenic gene enrichment and clinically by poor prognosis and sorafenib response. This novel immunogenomic signature may aid in stratification of unresectable patients to receive checkpoint inhibitor and antiangiogenic therapy combinations.
Reproductive and Perinatal Outcomes in Women with Congenital Adrenal Hyperplasia: A Population-based Cohort Study
Authors: Hirschberg Angelica Lindén , Gidlöf Sebastian , Falhammar Henrik , Frisén Louise , Almqvist Catarina , Nordenskjöld Agneta , Nordenström Anna
Published: November 2020

Context

Reduced fertility has been reported for women with congenital adrenal hyperplasia (CAH), especially for those with the salt-losing form. However, data are sparse on reproductive and perinatal outcomes in these women.

Objective

To investigate reproductive and perinatal outcomes in women with CAH.

Design and Setting

Population-based and nationwide study using the National CAH Register, the Total Population Register, and the Medical Birth Register of Sweden.

Participants

A total of 272 women with CAH due to 21-hydroxylase deficiency and 27 200 controls matched by sex, age, and place of birth. The median age was 31 years.

Main outcome measures

The proportion of CAH women that have given birth, and reproductive and perinatal outcomes.

Results

Of the 272 women with CAH, 69 gave birth to at least 1 child (25.4%), which was a lower frequency than for the controls (45.8%) (P < .001). Furthermore, women with CAH had fewer children than controls and were slightly older at birth of their first child. More women with CAH were diagnosed with gestational diabetes than controls, 4.9% versus 1.4% (P < .05), and more women with CAH were delivered through cesarean section, 51.4% versus 12.3% (P < .05). There was no difference in Apgar score or frequency of small-for-gestational age between children born to mothers with CAH and controls.

Conclusions

This is, to our knowledge, the largest cohort designed to investigate reproductive and perinatal outcomes in women with CAH. We found the birth rate to be lower in women with CAH; gestational diabetes and cesarean section were more common, but perinatal outcomes were comparable with controls.
Sebastian Haffner’s Germanys
Authors: Bodenheimer Rosemarie
Published: November 2020

Sebastian Haffner’s Defying Hitler: A Memoir appears in the twenty-first century as a kind of time capsule, offering a personal and political analysis forged during the 1930s, when the endgame of the Nazi regime was not yet visible. Haffner attempts to account for the historical precursors of Nazism, beginning with the Great War–besotted children of his own generation, now hungering for another dose of public excitement, and moving back to the mistaken nationalism of Bismarck’s 1871 Reich. Haffner’s general view of German character as incapable of democracy, reliant on strong leaders, but not essentially anti-Semitic, sits uncomfortably with his more personal horror at the Nazi invasion of individual privacy. Defiant analysis yields to tragedy as the memoir goes on to represent individual capitulations to Nazi tactics, including Haffner’s own. Reflecting our current dilemma, his dramatic narrative puts us vividly in mind of the angry, fearful, strident, hopeless, hopeful, and courageous elements that contend, unresolved, during an unpredictable rush of threatening world events.
A service evaluation of a hospital-based specialist postnatal breastfeeding clinic
Authors: McGuinness Denise , Paul Gillian , Murtagh Rosemaree , O'Hagan Lorraine
Published: November 2020

Background

Breastfeeding is described as the gold standard of infant feeding and is beneficial to both infant and maternal health, reducing healthcare costs. Breastfeeding rates are low in Ireland. Interventions that support and protect breastfeeding are required.

Aim

To conduct a service evaluation of a hospital-based specialist postnatal breastfeeding clinic.

Methods

A telephone questionnaire was administered to 99 participants who attended a breastfeeding specialist clinic. Descriptive analysis was conducted on the quantitative data. The qualitative data was anonymised and subjected to thematic analysis.

Results

Of the 99 women, 99% were breastfeeding at 6 weeks, 92% at 3 months and 77% at 6 months, respectively. The majority of women attended with one breastfeeding challenge (63%) while 24% of women attended with two breastfeeding challenges.

Conclusions

Skilled professional breastfeeding support, in addition to peer support, is an effective and acceptable way to increase breastfeeding among women who present with common breastfeeding challenges.
Destitution in pregnancy: forced migrant women's lived experiences
Authors: Ellul Rosanna , McCarthy Rose , Haith-Cooper Melanie
Published: November 2020

Background

Forced migrant women are increasingly becoming destitute whilst pregnant. Destitution may exacerbate their poor underlying physical and mental health. There is little published research that examines this, and studies are needed to ensure midwifery care addresses the specific needs of these women. This study aimed to explore vulnerable migrant women's lived experience of being pregnant and destitute.

Methods

Six in-depth individual interviews with forced migrant women who had been destitute during their pregnancy were conducted over one year.

Results

A lack of food and being homeless impacted on women's physical and mental health. Women relied on support from the voluntary sector to fill the gaps in services not provided by their local authorities. Although midwives were generally kind and helpful, there was a limit to how they could support the women.

Conclusions

There is a gap in support provided by local authorities working to government policies and destitute migrant pregnant women should not have to wait until 34 weeks gestation before they can apply for support. Home office policy needs to change to ensure pregnant migrant women receive support throughout their pregnancy.
COVID-19: women with diabetes and hypertension during pregnancy
Authors: Hu Jiamiao , Danielli Marianna , Thomas Roisin C , Melford Sarah E , Gillies Clare L , Scott David A , Tan Bee K
Published: November 2020

Midwives should be prepared to create individualised care plans, share data and liase with other departments, to improve maternal and fetal outcomes for pregnant women with these conditions
Increasing physical activity in people with COPD
Authors: Armstrong Matthew
Published: November 2020

Levels of physical activity tend to be reduced in people with COPD. Matthew Armstrong discusses the benefits of improving activity levels in this group of patients

It is well acknowledged that levels of physical activity in patients with chronic obstructive pulmonary disease (COPD) are considerably lower than healthy-age matched individuals, with physical inactivity recognised as a key predictor of hospitalisation and mortality. Pulmonary rehabilitation (PR) has become a major tool for managing symptoms of COPD and the associated extra-pulmonary effects. However, inconsistencies surrounding its effectiveness in terms of improving physical activity remain due to the complex nature of physical activity. To overcome these inconsistencies, both pharmacological and behavioural interventions have been documented to aid improvements in physical activity, with behavioural interventions alongside PR found to be the most effective tool to promote levels of physical activity. Health professionals must therefore look to incorporate an interdisciplinary approach in order to best achieve improvements in physical activity levels in patients with COPD.
The role of orthopaedic trainees during the COVID-19 pandemic and impact on post-graduate orthopaedic education
Authors: Gonzi Gianluca , Gwyn Rhodri , Rooney Kathryn , Boktor Joseph , Roy Kunal , Sciberras Nadia C. , Pullen Huw , Mohanty Khitish
Published: November 2020

Aims

The COVID-19 pandemic has had a significant impact on the provision of orthopaedic care across the UK. During the pandemic orthopaedic specialist registrars were redeployed to “frontline” specialties occupying non-surgical roles. The impact of the COVID-19 pandemic on orthopaedic training in the UK is unknown. This paper sought to examine the role of orthopaedic trainees during the COVID-19 and the impact of COVID-19 pandemic on postgraduate orthopaedic education.

Methods

A 42-point questionnaire was designed, validated, and disseminated via e-mail and an instant-messaging platform.

Results

A total of 101 orthopaedic trainees, representing the four nations (Wales, England, Scotland, and Northern Ireland), completed the questionnaire. Overall, 23.1% (23/101) of trainees were redeployed to non-surgical roles. Of these, 73% (17/23) were redeployed to intensive treatment units (ITUs), 13% (3/23) to A/E, and 13%(3/23%) to general medicine. Of the trainees redeployed to ITU 100%, (17/17) received formal induction. Non-deployed or returning trainees had a significant reduction in sessions. In total, 42.9% (42/101) % of trainees were not timetabled into fracture clinic, 53% (53/101) of trainees had one allocated theatre list per week, and 63.8%(64/101) of trainees did not feel they obtained enough experience in the attached subspecialty and preferred repeating this. Overall, 93% (93/101) of respondents attended at least one weekly online webinar, with 79% (79/101) of trainees rating these as useful or very useful, while 95% (95/101) trainees attended online deanery teaching which was rated as more useful than online webinars (p = 0.005)

Conclusion

Orthopaedic specialist trainees occupied an important role during the COVID-19 pandemic. COVID-19 has had a significant impact on orthopaedic training. It is imperative this is properly understood to ensure orthopaedic specialist trainees achieve competencies set out in the training curriculum. Cite this article: Bone Joint Open 2020;1-11:676–682.
Design and implementation of an acute Trauma and Orthopaedic ePlatform (TOP) referral system utilising existing secure technology during the COVID-19 pandemic
Authors: McIntyre Tom Vincent , Kelly Enda Gerard , Clarke Trevor , Green Connor J.
Published: November 2020

Introduction

Virtual fracture clinics (VFCs) are being increasingly used to offer safe and efficient orthopaedic review without the requirement for face-to-face contact. With the onset of the COVID-19 pandemic, we sought to develop an online referral pathway that would allow us to provide definitive orthopaedic management plans and reduce face-to-face contact at the fracture clinics.

Methods

All patients presenting to the emergency department from 21March 2020 with a musculoskeletal injury or potential musculoskeletal infection deemed to require orthopaedic input were discussed using a secure messaging app. A definitive management plan was communicated by an on-call senior orthopaedic decision-maker. We analyzed the time to decision, if further information was needed, and the referral outcome. An analysis of the orthopaedic referrals for the same period in 2019 was also performed as a comparison.

Results

During the study period, 295 patients with mean age of 7.93 years (standard error (SE) 0.24) were reviewed. Of these, 25 (9.8%) were admitted, 17 (5.8%) were advised to return for planned surgical intervention, 105 (35.6%) were referred to a face-to-face fracture clinic, 137 (46.4%) were discharged with no follow-up, and seven (2.4%) were referred to other services. The mean time to decision was 20.14 minutes (SE 1.73). There was a significant difference in the time to decision between patients referred to fracture clinic and patients discharged (mean 25.25 minutes (SE 3.18) vs mean 2.63 (SE 1.42); p < 0.005). There were a total of 295 referrals to the fracture clinic for the same period in 2019 with a further 44 emergency admissions. There was a statistically significant difference in the weekly referrals after being triaged by the VFC (mean 59 (SE 5.15) vs mean 21 (SE 2.17); p < 0.001).

Conclusion

The use of an electronic referral pathway to deliver a point of care virtual fracture clinic allowed for efficient use of scarce resources and definitive management plan delivery in a safe manner. Cite this article: Bone Joint Open 2020;1-6:293–301.
Transformation from a traditional model to a virtual model of care in orthopaedic surgery
Authors: King Dominic , Emara Ahmed K. , Ng Mitchell K. , Evans Peter J. , Estes Kelly , Spindler Kurt P. , Mroz Thomas , Patterson Brendan M. , Krebs Viktor E. , Pinney Stephen , Piuzzi Nicolas S. , Schaffer Jonathan L.
Published: November 2020

Virtual encounters have experienced an exponential rise amid the current COVID-19 crisis. This abrupt change, seen in response to unprecedented medical and environmental challenges, has been forced upon the orthopaedic community. However, such changes to adopting virtual care and technology were already in the evolution forecast, albeit in an unpredictable timetable impeded by regulatory and financial barriers. This adoption is not meant to replace, but rather augment established, traditional models of care while ensuring patient/provider safety, especially during the pandemic. While our department, like those of other institutions, has performed virtual care for several years, it represented a small fraction of daily care. The pandemic required an accelerated and comprehensive approach to the new reality. Contemporary literature has already shown equivalent safety and patient satisfaction, as well as superior efficiency and reduced expenses with musculoskeletal virtual care (MSKVC) versus traditional models. Nevertheless, current literature detailing operational models of MSKVC is scarce. The current review describes our pre-pandemic MSKVC model and the shift to a MSKVC pandemic workflow that enumerates the conceptual workflow organization (patient triage, from timely care provision based on symptom acuity/severity to a continuum that includes future follow-up). Furthermore, specific setup requirements (both resource/personnel requirements such as hardware, software, and network connectivity requirements, and patient/provider characteristics respectively), and professional expectations are outlined. MSKVC has already become a pivotal element of musculoskeletal care, due to COVID-19, and these changes are confidently here to stay. Readiness to adapt and evolve will be required of individual musculoskeletal clinical teams as well as organizations, as established paradigms evolve.

Cite this article: Bone Joint Open 2020;1-6:272–280.
Inpatient and outpatient opioid requirements after total joint replacement are strongly influenced by patient and surgical factors
Authors: Roebke Austin J. , Via Garrhett G. , Everhart Joshua S. , Munsch Maria A. , Goyal Kanu S. , Glassman Andrew H. , Li Mengnai
Published: November 2020

Aims

Currently, there is no single, comprehensive national guideline for analgesic strategies for total joint replacement. We compared inpatient and outpatient opioid requirements following total hip arthroplasty (THA) versus total knee arthroplasty (TKA) in order to determine risk factors for increased inpatient and outpatient opioid requirements following total hip or knee arthroplasty.

Methods

Outcomes after 92 primary total knee (n = 49) and hip (n = 43) arthroplasties were analyzed. Patients with repeat surgery within 90 days were excluded. Opioid use was recorded while inpatient and 90 days postoperatively. Outcomes included total opioid use, refills, use beyond 90 days, and unplanned clinical encounters for uncontrolled pain. Multivariate modelling determined the effect of surgery, regional nerve block (RNB) or neuraxial anesthesia (NA), and non-opioid medications after adjusting for demographics, ength of stay, and baseline opioid use.

Results

TKAs had higher daily inpatient opioid use than THAs (in 5 mg oxycodone pill equivalents: median 12.0 vs 7.0; p < 0.001), and greater 90 day use (median 224.0 vs 100.5; p < 0.001). Opioid refills were more likely in TKA (84% vs 33%; p < 0.001). Patient who underwent TKA had higher independent risk of opioid use beyond 90 days than THA (adjusted OR 7.64; 95% SE 1.23 to 47.5; p = 0.01). Inpatient opioid use 24 hours before discharge was the strongest independent predictor of 90-day opioid use (p < 0.001). Surgical procedure, demographics, and baseline opioid use have greater influence on in/outpatient opioid demand than RNB, NA, or non-opioid analgesics.

Conclusion

Opioid use following TKA and THA is most strongly predicted by surgical and patient factors. TKA was associated with higher postoperative opioid requirements than THA. RNB and NA did not diminish total inpatient or 90-day postoperative opioid consumption. The use of acetaminophen, gabapentin, or NSAIDs did not significantly alter inpatient opioid requirements. Cite this article: Bone Joint Open 2020;1-7:398–404.
30-day outcomes in hip fracture patients during the COVID-19 pandemic compared to the preceding year
Authors: Macey Alistair R. M. , Butler Joanna , Martin Sean C. , Tan Ting Yang , Leach William J. , Jamal Bilal
Published: November 2020

Aims

To establish if COVID-19 has worsened outcomes in patients with AO 31 A or B type hip fractures.

Methods

Retrospective analysis of prospectively collected data was performed for a five-week period from 20 March 2020 and the same time period in 2019. The primary outcome was mortality at 30 days. Secondary outcomes were COVID-19 infection, perioperative pulmonary complications, time to theatre, type of anaesthesia, operation, grade of surgeon, fracture type, postoperative intensive care admission, venous thromboembolism, dislocation, infection rates, and length of stay.

Results

In all, 76 patients with hip fractures were identified in each group. All patients had 30-day follow-up. There was no difference in age, sex, American Society of Anesthesiologists (ASA) classification or residence at time of injury. However, three in each group were not fit for surgery. No significant difference was found in 30-day mortality; ten patients (13%) in 2019 and 11 patients (14%) in 2020 (p = 0.341). In the 2020 cohort, ten patients tested positive for COVID-19, two (20%) of whom died. There was no significant increase in postoperative pulmonary complications. Median time to theatre was 20 hours (interquartile range (IQR) 16 to 25) in 2019 versus 23 hours (IQR 18 to 30) in 2020 (p = 0.130). Regional anaesthesia increased from 24 (33%) cases in 2019 to 46 (63%) cases in 2020, but ten (14%) required conversion to general anaesthesia. In both groups, 53 (70%) operations were done by trainees. Hemiarthroplasty for 31 B type fractures was the most common operation. No significant difference was found for intensive care admission or 30-day venous thromboembolism, dislocation or infection, or length of stay.

Conclusion

Little information exists on mortality and complications after hip fracture during the COVID-19 pandemic. At the time of writing, no other study of outcomes in the UK has been published. Cite this article: Bone Joint Open 2020;1-7:415–419.
Stream Sediments Geochemical Exploration in Wadi El Reddah area, Northeastern Desert, Egypt
Authors: Mira Hamed Ibrahim , Hussein Hussein Kamal , Tawfik Sameh Zakaria , Abed Neveen Salah
Published: November 2020

Wadi El Reddah representing a semi-closed basin, extends in the N-S direction. It has only one outlet at the northern tip while the wadi collects floodwater from internal tributaries along wall rocks. The present study discusses the relationship between geology and geochemistry data to detect anomalous radioactive locations. The geochemical maps show the mineralization areas with abnormal rare metal contents. This led to two uranium occurrences (GXXIII and GXXIV) at Gabal Gattar in the perthitic leucogranite. At Wadi El Reddah, high contents of pathfinder elements (REE, Y, Zn, Nb and As) were discovered at the southern and eastern boundaries. This may be attributed to the presence of alkali feldspar granite at Gabal Gattar at the upstream of Wadi El Reddah and also to the sharp contact between Gabal Gattar and Hammamat Sedimentary rocks. A strong positive correlation coefficient between Fe2Ot and or Al2O3 with Zr, Hf, Nb, Ta, REE, U, Rb, and Th reflects their association with thematization processes.
Incoherent color digital holography with computational coherent superposition for fluorescence imaging [Invited]
Authors: Tahara Tatsuki , Koujin Takako , Matsuda Atsushi , Ishii Ayumi , Ito Tomoyoshi , Ichihashi Yasuyuki , Oi Ryutaro
Published: November 2020

We present color fluorescence imaging using an incoherent digital
holographic technique in which holographic multiplexing of multiple
wavelengths is exploited. Self-interference incoherent digital
holography with a single-path in-line configuration and the
computational coherent superposition scheme are adopted to obtain
color holographic three-dimensional information of self-luminous
objects with a monochrome image sensor and no mechanical scanning. We
perform not only simultaneous color three-dimensional sensing of
multiple self-luminous objects but also color fluorescence imaging of
stained biological samples. Color fluorescence imaging with an
improved point spread function is also demonstrated experimentally by
adopting a Fresnel incoherent correlation holography system.
Rapid and label-free urine test based on surface-enhanced Raman spectroscopy for the non-invasive detection of colorectal cancer at different stages
Authors: Lin Jinyong , Huang Zongwei , Lin Xueliang , Wu Qiong , Quan Kerun , Cheng Yanming , Zheng Mingzhi , Xu Jiaying , Dai Yitao , Qiu Hejin , Lin Duo , Feng Shangyuan
Published: November 2020

The concept of being able to urinate in a cup and screen for colorectal cancer (CRC) is fascinating to the public at large. Here, a simple and label-free urine test based on surface-enhanced Raman spectroscopy (SERS) was employed for CRC detection. Significant spectral differences among normal, stages I-II, and stages III-IV CRC urines were observed. Using discriminant function analysis, the diagnostic sensitivities of 95.8%, 80.9%, and 84.3% for classification of normal, stages I-II, and stages III-IV CRC were achieved in training model, indicating the great promise of urine SERS as a rapid, convenient and noninvasive method for CRC staging detection.
Enhanced rotation sensing and exceptional points in a parity–time-symmetric coupled-ring gyroscope
Authors: Grant Matthew J. , Digonnet Michel J. F.
Published: November 2020

Enhancement in rotation sensitivity is achieved in a parity–time-symmetric gyroscope consisting of a ring with gain coupled to a lossy ring, operated below laser threshold and in the vicinity of its exceptional point (EP). An external laser and a conventional readout system are used to measure the large rotation-induced shifts in resonance frequency known to occur in this device. A complete model of the rotation sensitivity is derived that accounts for gain saturation caused by the large circulating power. Compared to a single-ring gyro, the sensitivity is enhanced by a factor of

∼

300

when the inter-ring coupling is tuned to its EP value

κ

EP

, and

∼

2400

when it is decreased from

κ

EP

, even though the Sagnac frequency shift is then much smaller.

∼

40

%

of this 2400-fold enhancement is assigned to a new sensing mechanism where rotation alters the gain saturation. These results show that this compact gyro has a far greater sensitivity than a conventional ring gyro, and that this improvement arises mostly from the gain compensating the loss, as opposed to the enhanced Sagnac frequency shift from the EP. This gyro is also shown to be much more stable against gain fluctuations than a single-ring gyro with gain.
Design-flexible entanglement of two distant quantum dots bridged by dark whispering gallery modes
Authors: Zhao Yanhui
Published: November 2020

We present a flexible design to realize the entanglement between two distant semiconductor quantum dots (QDs) embedded in separated photonic crystal nanobeam cavities. When bridged by a largely detuned microring cavity, photonic supermodes between two distant nanobeam cavities are formed via whispering gallery modes (WGMs). Due to the large detuning, WGMs in the microring exhibit almost no photonic excitation, showing the “dark WGMs.” With the dyadic Green’s functions of the nano-structure and the resolvent operators of the Hamiltonian, we numerically investigate the entanglement dynamics of two distant QDs. Furthermore, we prove that the entanglement can be tuned by adjusting the distances between the cavities. Such a scheme paves an efficient way for realizing a scalable quantum network in a solid-state system.
Strain sensitivity of dielectric polarization to doping in a host: guest medium
Authors: Datta Kanak , Deotare Parag B
Published: November 2020

In this work, we show controlled spatial and spectral modulation of local dielectric polarization in amorphous organic Alq3: DCM host: guest medium. We use self-strained silicon-dioxide microbeams to apply tensile strain on thin films at different DCM doping. From the measured spectral shift of the emission peak, we estimate the orientational polarizability (and in turn dielectric polarizability) in the strained host: guest medium at different guest doping. Orientational polarizability in the thin film follows a linear relationship with applied tensile strain at different guest material doping while the strain sensitivity shows an inverse relationship with guest doping.
Design of a wideband terahertz metamaterial absorber based on Pythagorean-tree fractal geometry
Authors: Bilal R. M. H. , Naveed M. A. , Baqir M. A. , Ali M. M. , Rahim A. A.
Published: November 2020

Broadband absorption in the terahertz regime is a challenge and onerous to realize with a single layer metasurface. Self-similarity in fractal structures are exploiting metamaterial characteristics that offer a promising platform to design wideband microwave and optical devices. This paper presents a metamaterial absorber that consists of fractal geometry of Pythagorean-tree. The proposed metamaterial absorber demonstrates the wideband absorptivity in a terahertz spectrum ranging from 7.5–10 THz. Both transverse electric (TE)–and transverse magnetic(TM)–mode are taken up under different obliquity incidence angles to deeply study the angular dependence on absorption features of the Pythagorean-tree fractal meta-absorber (PTFMA). A numerical approach of interference theory is employed to verify the simulation results of the designed PTFMA. Further, the performance of the PTFMA was analyzed in terms of the figure of merit (FOM) and operational bandwidth (OBW) for different geometric parameters. Furthermore, surface electric field patterns and current distributions were studied to understand the absorption mechanism of the suggested PTFMA. The designed absorber would be a promising contender for bolometers, THz detection, and communication.
Ribosome biogenesis is a downstream effector of the oncogenic U2AF1-S34F mutation
Authors: Akef Abdalla , McGraw Kathy , Cappell Steven D. , Larson Daniel R.
Published: November 2020

U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) forms a heterodimeric complex with U2AF2 that is primarily responsible for 3ʹ splice site selection. U2AF1 mutations have been identified in most cancers but are prevalent in Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), and the most common mutation is a missense substitution of serine-34 to phenylalanine (S34F). The U2AF heterodimer also has a noncanonical function as a translational regulator. Here, we report that the U2AF1-S34F mutation results in specific misregulation of the translation initiation and ribosome biogenesis machinery. The net result is an increase in mRNA translation at the single-cell level. Among the translationally up-regulated targets of U2AF1-S34F is Nucleophosmin 1 (NPM1), which is a major driver of myeloid malignancy. Depletion of NPM1 impairs the viability of the U2AF1-S34F mutant cells and causes ribosomal RNA (rRNA) processing defects, thus indicating an unanticipated synthetic interaction between U2AF1, NPM1, and ribosome biogenesis. Our results establish a unique molecular phenotype for the U2AF1 mutation that recapitulates translational misregulation in myeloid disease.
A proteomic survey of microtubule-associated proteins in a R402H TUBA1A mutant mouse
Authors: Leca Ines , Phillips Alexander William , Hofer Iris , Landler Lukas , Ushakova Lyubov , Cushion Thomas David , Dürnberger Gerhard , Stejskal Karel , Mechtler Karl , Keays David Anthony
Published: November 2020

Microtubules play a critical role in multiple aspects of neurodevelopment, including the generation, migration and differentiation of neurons. A recurrent mutation (R402H) in the α-tubulin geneTUBA1Ais known to cause lissencephaly with cerebellar and striatal phenotypes. Previous work has shown that this mutation does not perturb the chaperone-mediated folding of tubulin heterodimers, which are able to assemble and incorporate into the microtubule lattice. To explore the molecular mechanisms that cause the disease state we generated a new conditional mouse line that recapitulates the R402H variant. We show that heterozygous mutants present with laminar phenotypes in the cortex and hippocampus, as well as a reduction in striatal size and cerebellar abnormalities. We demonstrate that homozygous expression of the R402H allele causes neuronal death and exacerbates a cell intrinsic defect in cortical neuronal migration. Microtubule sedimentation assays coupled with quantitative mass spectrometry demonstrated that the binding and/or levels of multiple microtubule associated proteins (MAPs) are perturbed by the R402H mutation including VAPB, REEP1, EZRIN, PRNP and DYNC1l1/2. Consistent with these data we show that the R402H mutation impairs dynein-mediated transport which is associated with a decoupling of the nucleus to the microtubule organising center. Our data support a model whereby the R402H variant is able to fold and incorporate into microtubules, but acts as a gain of function by perturbing the binding of MAPs.
In vivo miRNA knockout screening identifies miR-190b as a novel tumor suppressor
Authors: Hong Hui , Yao Shun , Zhang Yuanyuan , Ye Yi , Li Cheng , Hu Liang , Sun Yihua , Huang Hsin-Yi , Ji Hongbin
Published: November 2020

MicroRNAs (miRNAs) play important roles in the development of various cancers including lung cancer which is one of the devastating diseases worldwide. How miRNAs function in de novo lung tumorigenesis remains largely unknown. We here developed a CRISPR/Cas9-mediated dual guide RNA (dgRNA) system to knockout miRNAs in genetically engineered mouse model (GEMM). Through bioinformatic analyses of human lung cancer miRNA database, we identified 16 downregulated miRNAs associated with malignant progression and performed individual knockout with dgRNA system in KrasG12D/Trp53L/L (KP) mouse model. Using this in vivo knockout screening, we identified miR-30b and miR-146a, which has been previously reported as tumor suppressors and miR-190b, a new tumor-suppressive miRNA in lung cancer development. Over-expression of miR-190b in KP model as well as human lung cancer cell lines significantly suppressed malignant progression. We further found that miR-190b targeted the Hus1 gene and knockout of Hus1 in KP model dramatically suppressed lung tumorigenesis. Collectively, our study developed an in vivo miRNA knockout platform for functionally screening in GEMM and identified miR-190b as a new tumor suppressor in lung cancer.
Dual genome-wide CRISPR knockout and CRISPR activation screens identify mechanisms that regulate the resistance to multiple ATR inhibitors
Authors: Schleicher Emily M. , Dhoonmoon Ashna , Jackson Lindsey M. , Clements Kristen E. , Stump Coryn L. , Nicolae Claudia M. , Moldovan George-Lucian
Published: November 2020

The ataxia telangiectasia and Rad3-related (ATR) protein kinase is a key regulator of the cellular response to DNA damage. Due to increased amount of replication stress, cancer cells heavily rely on ATR to complete DNA replication and cell cycle progression. Thus, ATR inhibition is an emerging target in cancer therapy, with multiple ATR inhibitors currently undergoing clinical trials. Here, we describe dual genome-wide CRISPR knockout and CRISPR activation screens employed to comprehensively identify genes that regulate the cellular resistance to ATR inhibitors. Specifically, we investigated two different ATR inhibitors, namely VE822 and AZD6738, in both HeLa and MCF10A cells. We identified and validated multiple genes that alter the resistance to ATR inhibitors. Importantly, we show that the mechanisms of resistance employed by these genes are varied, and include restoring DNA replication fork progression, and prevention of ATR inhibitor-induced apoptosis. In particular, we describe a role for MED12-mediated inhibition of the TGFβ signaling pathway in regulating replication fork stability and cellular survival upon ATR inhibition. Our dual genome-wide screen findings pave the way for personalized medicine by identifying potential biomarkers for ATR inhibitor resistance.
Genetic engineering of sex chromosomes for batch cultivation of non-transgenic, sex-sorted males
Authors: Das Siba R. , Maselko Maciej , Upadhyay Ambuj , Smanski Michael J.
Published: November 2020

The field performance of Sterile Insect Technique (SIT) is improved by sex-sorting and releasing only sterile males. This can be accomplished by resource-intensive separation of males from females by morphology. Alternatively, sex-ratio biasing genetic constructs can be used to selectively remove one sex without the need for manual or automated sorting, but the resulting genetically engineered (GE) control agents would be subject to additional governmental regulation. Here we describe and demonstrate a genetic method for the batch production of non-GE males. This method could be applied to generate the heterogametic sex (XY, or WZ) in any organism with chromosomal sex determination. We observed up to 100% sex-selection with batch cultures of more than 103individuals. Using a stringent transgene detection assay, we demonstrate the potential of mass production of transgene free males.
Opposing functions of Fng1 and the Rpd3 HDAC complex in H4 acetylation in Fusarium graminearum
Authors: Jiang Hang , Xia Aliang , Ye Meng , Ren Jingyi , Li Dongao , Liu Huiquan , Wang Qinhu , Lu Ping , Wu Chunlan , Xu Jin-Rong , Jiang Cong
Published: November 2020

Histone acetylation, balanced by histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes, affects dynamic transitions of chromatin structure to regulate transcriptional accessibility. However, little is known about the interplay between HAT and HDAC complexes in Fusarium graminearum, a causal agent of Fusarium Head Blight (FHB) that uniquely contains chromosomal regions enriched for house-keeping or infection-related genes. In this study, we identified the ortholog of the human inhibitor of growth (ING1) gene in F. graminearum (FNG1) and found that it specifically interacts with the FgEsa1 HAT of the NuA4 complex. Deletion of FNG1 led to severe growth defects and blocked conidiation, sexual reproduction, DON production, and plant infection. The fng1 mutant was normal in H3 acetylation but significantly reduced in H4 acetylation. A total of 34 spontaneous suppressors of fng1 with faster growth rate were isolated. Most of them were still defective in sexual reproduction and plant infection. Thirty two of them had mutations in orthologs of yeast RPD3, SIN3, and SDS3, three key components of the yeast Rpd3L HDAC complex. Four mutations in these three genes were verified to suppress the defects of fng1 mutant in growth and H4 acetylation. The rest two suppressor strains had a frameshift or nonsense mutation in a glutamine-rich hypothetical protein that may be a novel component of the FgRpd3 HDAC complex in filamentous fungi. FgRpd3, like Fng1, localized in euchromatin. Deletion of FgRPD3 resulted in severe growth defects and elevated H4 acetylation. In contract, the Fgsds3 deletion mutant had only a minor reduction in growth rate but FgSIN3 appeared to be an essential gene. RNA-seq analysis revealed that 48.1% and 54.2% of the genes with altered expression levels in the fng1 mutant were recovered to normal expression levels in two suppressor strains with mutations in FgRPD3 and FgSDS3, respectively. Taken together, our data showed that Fng1 is important for H4 acetylation as a component of the NuA4 complex and functionally related to the FgRpd3 HDAC complex for transcriptional regulation of genes important for growth, conidiation, sexual reproduction, and plant infection in F. graminearum.
Clinical impact of monocyte distribution width and neutrophil-to-lymphocyte ratio for distinguishing COVID-19 and influenza from other upper respiratory tract infections: A pilot study
Authors: Lin Hui-An , Lin Sheng-Feng , Chang Hui-Wen , Lee Yuarn-Jang , Chen Ray-Jade , Hou Sen-Kuang
Published: November 2020

The coronavirus disease 2019 (COVID-19) has become a pandemic. Rapidly distinguishing COVID-19 from other respiratory infections is a challenge for first-line health care providers. This retrospective study was conducted at the Taipei Medical University Hospital, Taiwan. Patients who visited the outdoor epidemic prevention screening station for respiratory infection from February 19 to April 30, 2020, were evaluated for blood biomarkers to distinguish COVID-19 from other respiratory infections. Monocyte distribution width (MDW) ≥ 20 (odds ratio [OR]: 8.39, p = 0.0110, area under curve [AUC]: 0.703) and neutrophil-to-lymphocyte ratio (NLR) < 3.2 (OR: 4.23, p = 0.0494, AUC: 0.673) could independently distinguish COVID-19 from common upper respiratory tract infections (URIs). Combining MDW ≥ 20 and NLR < 3.2 was more efficient in identifying COVID-19 (AUC: 0.840). Moreover, MDW ≥ 20 and NLR > 5 effectively identified influenza infection (AUC: 0.7055). Thus, MDW and NLR can distinguish COVID-19 from influenza and URIs.
The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite
Authors: Chaves Mariana M. , Lee Sang Hun , Kamenyeva Olena , Ghosh Kashinath , Peters Nathan C. , Sacks David
Published: November 2020

There is substantial experimental evidence to indicate that Leishmania infections that are transmitted naturally by the bites of infected sand flies differ in fundamental ways from those initiated by needle inocula. We have used flow cytometry and intravital microscopy (IVM) to reveal the heterogeneity of sand fly transmission sites with respect to the subsets of phagocytes in the skin that harbor L. major within the first hours and days after infection. By flow cytometry analysis, dermis resident macrophages (TRMs) were on average the predominant infected cell type at 1 hr and 24 hr. By confocal IVM, the co-localization of L. major and neutrophils varied depending on the proximity of deposited parasites to the presumed site of vascular damage, defined by the highly localized swarming of neutrophils. Some of the dermal TRMs could be visualized acquiring their infections via transfer from or efferocytosis of parasitized neutrophils, providing direct evidence for the “Trojan Horse” model. The role of neutrophil engulfment by dermal TRMs and the involvement of the Tyro3/Axl/Mertk family of receptor tyrosine kinases in these interactions and in sustaining the anti-inflammatory program of dermal TRMs was supported by the effects observed in neutrophil depleted and in Axl-/-Mertk-/- mice. The Axl-/-Mertk-/- mice also displayed reduced parasite burdens but more severe pathology following L. major infection transmitted by sand fly bite.
Textos de Finanças Públicas
Authors: Andrade Fernando Rocha
Published: November 2020

A obra recolhe um conjunto de textos tratando os temas integrados no programa da disciplina de Finanças Públicas I da licenciatura em Direito da FDUC. Os temas abordados são o (i) objeto das Finanças Públicas (ii) o papel do estado como agente económico (iii) os fundamentos para a provisão pública de bens (iv) o conceito de Orçamento do Estado - evolução, funções, regras de organização, caracterização na Constituição (v) o equilíbrio orçamental (vi) o processo orçamental (vii) a lei do orçamento (viii) a execução orçamental.
Karanténpedagógia a magyar közoktatásban
Authors: Fekete Tamás , Porkoláb Ádám
Published: November 2020

Jelen tanulmányunkban a magyar közoktatásban, a digitális átállás 2 hónapja alatt gyűjtött tapasztalatokról szeretnénk számot adni, melyet a koronavírus-világjárvány keltett. Ehhez – a helyzet aktualitása miatt – egy intézményi belső kérdőív (N = 243), valamint középiskolai diákokat és felsőoktatásban részt vevő hallgatókat érintő, saját kérdőíves vizsgálatunk (N = 163) eredményeit elemezzük. A vizsgálatok összesen 406 főt érintettek. A témában keletkezett más kutatások megállapításainak áttekintése mellett megosztjuk személyes, gyakorló pedagógusokként szerzett tapasztalatainkat is. Célunk az, hogy a pedagógustársadalom és a szaktudomány számára összegzett és tudományos módszerekkel is alátámasztott helyzetelemzést nyújthassunk. Tanulmányunkban nem volt célunk az egyes korcsoportok és oktatási szereplők összevetése, hanem a közöttük megfigyelhető hasonlóságokra és általánosan kirajzolódó trendekre koncentráltunk.
Sleep Disturbances and Hip Fractures
Authors: Marks Ray
Published: November 2020

Hip fractures, which remain highly prevalent among the elderly and produce enormous social and economic costs, have not truly abated in prevalence despite years of research that outlines a multitude of preventable risk factors and intervention programs. This review aimed to examine if sleep disturbances have a bearing on the risk of incurring a hip fracture directly or indirectly, among older adults. The specific aim was to explore and summarize what we know, and how this might inform future research and practice. To this end, PUBMED, Web of Science, Scopus, and Google Scholar data bases were searched to uncover available data representing the topic of sleep in relation to hip fractures among the elderly. Articles of note were scrutinized and summarized in narrative form. Results showed very few studies on the topic prevail, even with no restriction on years examined, and of these, discordant, rather than any solid uniform conclusions prevail. It is concluded there is a need to explore this topic carefully, including both the direct, as well as the indirect impact of sleep that may place an older adult at heightened risk for a fall and hip fracture injury as well as subsequent fractures.
Mental Health Scenario of Climate Migrant Women among Slum Dwellers in Dhaka City
Authors: Amjad Karisma
Published: November 2020

Climate change is a global challenge which is likely to affect the mankind in substantial ways. Not only climate change is expected to affect physical health, it is also likely to affect mental health. Increased frequency of disasters with climate change can lead to posttraumatic stress disorder, adjustment disorder, and depression. Changes in climate may require population to migrate, which can lead to acculturation stress. It can also lead to increased rates of physical illnesses, which secondarily would be associated with psychological distress. Using a qualitative approach, this research explores the mental health status of migrant women in two urban slum areas in Dhaka city. The purpose of this study is to perform a review of existing secondary data and present mental health scenario of climate migrant women among slum dwellers and amplified gaps in knowledge regarding psychological health care system in Bangladesh. It is found that there is a lack of mental health preparedness and response in majority parts in the country specially the city slum, where aid cannot be reached to the sufferers. The paper concludes with a discussion of what can and should be done to tackle the expected mental health issues consequent to climate change and migration.