bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations Between Elevated Growth Differentiation Factor-15 and Sarcopenia Among Community-dwelling Older Adults
Authors: Kim Miji , Walston Jeremy D , Won Chang Won
Published: July 2021

Background

Growth differentiation factor 15 (GDF-15) is associated with disease progression, mitochondrial dysfunction, and mortality. Elevated GDF-15 level was recently reported to be associated with poorer physical performance in healthy adults. However, the association between serum GDF-15 level and sarcopenia in community-dwelling older adults has not been well characterized.

Methods

We conducted cross-sectional (n = 929) and 2-year prospective analyses (n = 788) among participants aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study. Participants with an estimated glomerular filtration rate of <60 mL/min/1.73 m2 were excluded. Appendicular lean mass was measured using dual-energy x-ray absorptiometry. Sarcopenia status was determined according to the Asian Working Group for Sarcopenia-2019 algorithm.

Results

At baseline, 16.6% of the participants had sarcopenia. Median GDF-15 concentration was higher in the sarcopenic group than in the non-sarcopenic group (1221 pg/mL vs 1019 pg/mL, p < .001). In the multivariate analysis adjusted for cardiometabolic risk and biological factors, the highest GDF-15 tertile (≥1245 pg/mL) had an increased likelihood of sarcopenia (odds ratio, 1.96; 95% confidence interval, 1.16–3.33) than the lowest tertile (<885 pg/mL). During the 2-year follow-up period, 67 (10.1%) individuals without sarcopenia at baseline developed sarcopenia. There were no significant associations between baseline serum GDF-15 levels and incident sarcopenia or its components (all p > .05).

Conclusions

Elevated GDF-15 was associated with prevalent sarcopenia but not able to predict incident sarcopenia in the 2-year follow-up. Further studies are needed to explore the pathophysiological roles of GDF-15 in the development of sarcopenia.
Later-Life Living Arrangements of Americans With and Without Children: A Life Table Approach
Authors: Raymo James M , Xu Xiao , Kim BoRin , Liang Jersey , Ofstedal Mary Beth
Published: July 2021

Objectives

This study describes living arrangement-specific life expectancy for older Americans with and without children, by sex and race/ethnicity.

Method

We use life tables from the Human Mortality Database and data from the Health and Retirement Study over a 17-year period (2000–2016) to calculate living arrangement-specific life expectancy at age 65 using Sullivan’s method. Results describe the lives of older Americans aged 65 and older with and without children in terms of the number of expected years of life in different living arrangements.

Results

With the exception of Hispanic men, older Americans without children spend over half of their remaining life living alone. Among the childless, it is White women and Black men who spend the largest percent of remaining life living alone (65% and 57%, respectively). Relative to parents, childless older Americans have an overall life expectancy at age 65 that is 1 year lower and spend 5–6 years more living alone and fewer years living with a spouse (8 years less for men and 5 years less for women). Childless older Americans spend more time in nursing homes, but average expected duration in this living arrangement is short and differences between those with and without children are small.

Discussion

This descriptive analysis demonstrates the fundamental ways in which children shape the lives of older Americans by showing that later-life living arrangements of childless Americans differ markedly from their counterparts with children. These results provide a valuable empirical foundation for broader efforts to understand relationships between childlessness, living arrangements, and well-being at older ages.
Combinatorial Ricci Flows with Applications to the Hyperbolization of Cusped 3-Manifolds
Authors: Feng Ke , Ge Huabin , Hua Bobo , Xu Xu
Published: July 2021

In this paper, we adopt combinatorial Ricci flow to study the existence of hyperbolic structure on cusped 3-manifolds. The long-time existence and the uniqueness for the extended combinatorial Ricci flow are proven for general pseudo 3-manifolds. We prove that the extended combinatorial Ricci flow converges to a decorated hyperbolic polyhedral metric if and only if there exists a decorated hyperbolic polyhedral metric of zero Ricci curvature, and the flow converges exponentially fast in this case. For an ideally triangulated cusped 3-manifold admitting a complete hyperbolic metric, the flow provides an effective algorithm for finding the hyperbolic metric.
On C0-Continuity of the Spectral Norm for Symplectically Non-Aspherical Manifolds
Authors: Kawamoto Yusuke
Published: July 2021

The purpose of this paper is to study the relation between the $C^0$-topology and the topology induced by the spectral norm on the group of Hamiltonian diffeomorphisms of a closed symplectic manifold. Following the approach of Buhovsky–Humilière–Seyfaddini, we prove the $C^0$-continuity of the spectral norm for complex projective spaces and negative monotone symplectic manifolds. The case of complex projective spaces provides an alternative approach to the $C^0$-continuity of the spectral norm proven by Shelukhin. We also prove a partial $C^0$-continuity of the spectral norm for rational symplectic manifolds. Some applications such as the Arnold conjecture in the context of $C^0$-symplectic topology are also discussed.
Incidence of Chronic Obstructive Pulmonary Disease in People With Human Immunodeficiency Virus and Their Parents and Siblings in Denmark
Authors: Ronit Andreas , Omland Lars H , Kronborg Gitte , Pedersen Gitte , Nielsen Lars , Mohey Rajesh , Wiese Lothar , Obel Niels , Ahlström Magnus G
Published: July 2021

Background

People with human immunodeficiency virus (PWH) may be at increased risk of several respiratory syndromes including chronic obstructive pulmonary disease (COPD). In matched cohort studies, we examined risk factors for COPD in PWH and their parents and siblings compared with population controls.

Methods

Using data from national registries, competing risk regression models were constructed and used to calculate adjusted hazard ratios (aHRs) for COPD. We evaluated the effect of human immunodeficiency virus characteristics, smoking, and educational attainment on COPD incidence in PWH.

Results

A total of 226 PWH and 1029 population controls were diagnosed with COPD during 63 661 and 562 171 person-years of follow-up. PWH had increased risk of being diagnosed with COPD compared to controls (aHR, 2.02 [95% confidence interval, 1.75–2.33]). Parents and siblings of PWH were also more likely to be diagnosed with COPD compared to controls. CD4+ T-cell counts were not associated with COPD, but unsuppressed viral replication, smoking status, and educational attainment were associated with COPD in PWH. No COPD diagnoses were registered in PWH with high educational attainment and absence of smoking

Conclusions

PWH have an increased risk of being diagnosed with COPD, as have their parents and siblings. This seems to be driven primarily by smoking and low socioeconomic status.
Gender differences in survival among low birthweight newborns and infants in sub-Saharan Africa: a systematic review
Authors: Gebremeskel Akalewold T , Fantaye Arone W , Faust Lena , Obegu Pamela , Yaya Sanni
Published: July 2021

In sub-Saharan Africa, low birthweight (LBW) accounts for three-quarters of under-five mortality and morbidity. However, gender differences in survival among LBW newborns and infants have not yet been systematically examined. This review examines gender differences in survival among LBW newborns and infants in the region. Ovid Medline, Embase, CINAHL, Scopus and Global Health databases were searched for qualitative, quantitative and mixed methods studies. Studies that presented information on differences in mortality or in morbidity between LBW male and female newborns or infants were eligible for inclusion. The database search yielded 4124 articles, of which 11 were eligible for inclusion. A narrative synthesis method was used to summarize the findings of the included studies. Seven studies reported more LBW male deaths, three studies reported more LBW female deaths and one study did not disaggregate the deaths by gender. Nine of the 11 studies that examined gender differences in mortality did not find significant evidence of gender differences in mortality among LBW newborns and infants. Likewise, no significant differences were found for gender differences in morbidity among this population. The review findings suggest a need for further research on this topic given the potential significance on child health and developmental goals.
Comparison of phenotypic antimicrobial susceptibility testing results and WGS-derived genotypic resistance profiles for a cohort of ESBL-producing Escherichia coli collected from Canadian hospitals: CANWARD 2007–18
Authors: Golden Alyssa R , Karlowsky James A , Walkty Andrew , Baxter Melanie R , Denisuik Andrew J , McCracken Melissa , Mulvey Michael R , Adam Heather J , Bay Denice , Zhanel George G
Published: July 2021

Objectives

To determine whether the genotypic resistance profile inferred from WGS could accurately predict phenotypic resistance for ESBL-producing Escherichia coli isolated from patient samples in Canadian hospital laboratories.

Methods

As part of the ongoing CANWARD study, 671 E. coli were collected and phenotypically confirmed as ESBL producers using CLSI M100 disc testing criteria. Isolates were sequenced using the Illumina MiSeq platform, resulting in 636 high-quality genomes for comparison. Using a rules-based approach, the genotypic resistance profile was compared with the phenotypic resistance interpretation generated using the CLSI broth microdilution method for ceftriaxone, ciprofloxacin, gentamicin and trimethoprim/sulfamethoxazole.

Results

The most common genes associated with non-susceptibility to ceftriaxone, gentamicin and trimethoprim/sulfamethoxazole were CTX-M-15 (n = 391), aac(3)-IIa + aac(6′)-Ib-cr (n = 121) and dfrA17 + sul1 (n = 169), respectively. Ciprofloxacin non-susceptibility was most commonly attributed to alterations in both gyrA (S83L + D87N) and parC (S80I + E84V), with (n = 187) or without (n = 197) aac(6′)-Ib-cr. Categorical agreement (susceptible or non-susceptible) between actual and predicted phenotype was 95.6%, 98.9%, 97.6% and 88.8% for ceftriaxone, ciprofloxacin, gentamicin and trimethoprim/sulfamethoxazole, respectively. Only ciprofloxacin results (susceptible or non-susceptible) were predicted with major error (ME) and very major error (VME) rates of <3%: ciprofloxacin (ME, 1.5%; VME, 1.1%); gentamicin (ME, 0.8%–31.7%; VME, 4.8%); ceftriaxone (ME, 81.8%; VME, 3.0%); and trimethoprim/sulfamethoxazole (ME, 0.9%–23.0%; VME, 5.2%–8.5%).

Conclusions

Our rules-based approach for predicting a resistance phenotype from WGS performed well for ciprofloxacin, with categorical agreement of 98.9%, an ME rate of 1.5% and a VME rate of 1.1%. Although high categorical agreements were also obtained for gentamicin, ceftriaxone and trimethoprim/sulfamethoxazole, ME and/or VME rates were ≥3%.
User-centered design of a scalable, electronic health record-integrated remote symptom monitoring intervention for patients with asthma and providers in primary care
Authors: Rudin Robert S , Perez Sofia , Rodriguez Jorge A , Sousa Jessica , Plombon Savanna , Arcia Adriana , Foer Dinah , Bates David W , Dalal Anuj K
Published: July 2021

Objective

To determine user and electronic health records (EHR) integration requirements for a scalable remote symptom monitoring intervention for asthma patients and their providers.

Methods

Guided by the Non-Adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework, we conducted a user-centered design process involving English- and Spanish-speaking patients and providers affiliated with an academic medical center. We conducted a secondary analysis of interview transcripts from our prior study, new design sessions with patients and primary care providers (PCPs), and a survey of PCPs. We determined EHR integration requirements as part of the asthma app design and development process.

Results

Analysis of 26 transcripts (21 patients, 5 providers) from the prior study, 21 new design sessions (15 patients, 6 providers), and survey responses from 55 PCPs (71% of 78) identified requirements. Patient-facing requirements included: 1- or 5-item symptom questionnaires each week, depending on asthma control; option to request a callback; ability to enter notes, triggers, and peak flows; and tips pushed via the app prior to a clinic visit. PCP-facing requirements included a clinician-facing dashboard accessible from the EHR and an EHR inbox message preceding the visit. PCP preferences diverged regarding graphical presentations of patient-reported outcomes (PROs). Nurse-facing requirements included callback requests sent as an EHR inbox message. Requirements were consistent for English- and Spanish-speaking patients. EHR integration required use of custom application programming interfaces (APIs).

Conclusion

Using the NASSS framework to guide our user-centered design process, we identified patient and provider requirements for scaling an EHR-integrated remote symptom monitoring intervention in primary care. These requirements met the needs of patients and providers. Additional standards for PRO displays and EHR inbox APIs are needed to facilitate spread.
Influence of a novel consensus bacterial 6-phytase variant on mineral digestibility and bone ash in young growing pigs fed diets with different concentrations of phytate-bound phosphorus
Authors: Espinosa Charmaine D , Oliveira Maryane S F , Velayudhan Deepak E , Dersjant-Li Yueming , Stein Hans H
Published: July 2021

A 20-d experiment was conducted to test the hypothesis that phytase increases nutrient digestibility, bone ash, and growth performance of pigs fed diets containing 0.23%, 0.29%, or 0.35% phytate-bound P. Within each level of phytate, five diets were formulated to contain 0, 500, 1,000, 2,000, or 4,000 phytase units (FTU)/kg of a novel phytase (PhyG). Three reference diets were formulated by adding a commercial Buttiauxella phytase (PhyB) at 1,000 FTU/kg to diets containing 0.23%, 0.29%, or 0.35% phytate-bound P. A randomized complete block design with 144 individually housed pigs (12.70 ± 4.01 kg), 18 diets, and 8 replicate pigs per diet was used. Pigs were adapted to diets for 15 d followed by 4 d of fecal collection. Femurs were collected on the last day of the experiment. Results indicated that diets containing 0.35% phytate-bound P had reduced (P < 0.01) digestibility of Ca, P, Mg, and K compared with diets containing less phytate-bound P. Due to increased concentration of total P in diets with high phytate, apparent total tract digestible P and bone ash were increased by PhyG to a greater extent in diets with 0.29% or 0.35% phytate-bound P than in diets with 0.23% phytate-bound P (interaction, P < 0.05). At 1,000 FTU/kg, PhyG increased P digestibility and bone P more (P < 0.05) than PhyB. The PhyG increased (P < 0.01) pig growth performance, and pigs fed diets containing 0.35% or 0.29% phytate-bound P performed better (P < 0.01) than pigs fed the 0.23% phytate-bound P diets. In conclusion, the novel phytase (i.e., PhyG) is effective in increasing bone ash, mineral digestibility, and growth performance of pigs regardless of dietary phytate level.
Migration and invention in the Age of Mass Migration
Authors: Diodato Dario , Morrison Andrea , Petralia Sergio
Published: July 2021

More than 30 million people migrated to the USA between late-ninetieth and early-twentieth century, and thousands became inventors. Drawing on a novel dataset of immigrant inventors in the USA, we assess the city-level impact of immigrants’ patenting and their contribution to the technological specialization of the receiving US regions between 1870 and 1940. Our results show that native inventors benefited from the inventive activity of immigrants. In addition, we show that the knowledge transferred by immigrants gave rise to new and previously not exiting technological fields in the US regions where immigrants moved to.
History of the AsianLymantriaspecies Program: A Unique Pathway Risk Mitigation Strategy
Authors: Mastro Victor C , Munson A Steve , Wang Baode , Freyman Tamara , Humble Leland M
Published: July 2021

Changes in grain trading between Russian Far Eastern ports and North America in the late 1980s and early 1990s led to introductions of Lymantria dispar asiatica (Vnukovskij), formerly called the Asian gypsy moth (AGM), and the recognition of a new pathway for its transport. Unlike the pathways commonly used and regulated for commodities and for packaging material containing pest organisms, this presented a unique pathway for AGM. Vessels departing from the Russia Far East transiting to ports on the west coast of the United States (US) and Canada (CA) were infested with life stages of AGM and related species. Upon arrival in North America, eggs oviposited on the surfaces of the ships and its cargo hatched with larvae ballooning to vegetation surrounding port areas leading to the potential establishment of AGM populations. A multi layered monitoring and inspection program was developed to mitigate this risk of introduction, initially for Russian Far Eastern ports, and eventually to include specified areas of other Asian countries. In this article, we summarize and review the integral parts of this mitigation program, which include: risk assessments, AGM monitoring in foreign and domestic ports, vessel cleaning and certification by a government Plant Protection Organization (PPO) or its proxy, AGM surveillance, and eradication of introduced AGM in ports and other areas within the United States and Canada. The uniqueness of this program is characterized by its complexity, which involves coordinated efforts of PPOs, the use of various inspection organizations, and the support of ocean transportation industries.
Risk of death due to other causes is lower among octogenarians with non-small cell lung cancer after wedge resection than lobectomy/segmentectomy
Authors: Mimae Takahiro , Miyata Yoshihiro , Yoshimura Kenichi , Tsutani Yasuhiro , Imai Kentaro , Ito Hiroyuki , Nakayama Haruhiko , Ikeda Norihiko , Okada Morihito
Published: July 2021

Objective

We aimed to determine the influences of surgical procedures on the postoperative death of octogenarians with clinical Stage IA non-small cell lung cancer excluding cT1mi.

Methods

We compared overall survival and the cumulative incidence of death due to all and other causes among 1 130 279, and 191 consecutive patients aged ≤79 and ≥80 years after lobectomy, segmentectomy and wedge resection at three institutions. Death due to other causes was defined as death due to any cause except non-small cell lung cancer.

Results

The median followup was 53 months. The 5-year overall survival rates for patients aged ≥ 80 and ≤ 79 years after lobectomy, segmentectomy and wedge resection were respectively, 78.0% (95% confidence interval, 63.8%–87.2%) versus 91.2% (95% confidence interval, 89.0%–92.9%), 68.1% (95% confidence interval, 45.2%–83.1%) versus 90.0% (95% confidence interval, 84.6%–93.5%), and 62.7% (95% confidence interval, 44.0–76.7%) versus 84.4% (95% confidence interval, 76.3%–89.9%) (P < 0.01 for all). The cumulative incidence of death due to other causes after wedge resection was similar between patients aged ≥ 80 and ≤ 79 years (P = 0.45), but significantly higher in those aged ≥ 80, than ≤ 79 years after lobectomy or segmentectomy (P = 0.00015 and 0.00091, respectively).

Conclusions

The influence of wedge resection on death due to other causes was lower than that of lobectomy or segmentectomy in patients with non-small cell lung cancer aged ≥ 80 years. Wedge resection might be a useful option for octogenarians even if they can tolerate lobectomy/segmentectomy to avoid postoperative death due to causes other than non-small cell lung cancer.
Deep Learning for Mortgage Risk*
Authors: Sadhwani Apaar , Giesecke Kay , Sirignano Justin
Published: July 2021

We examine the behavior of mortgage borrowers over several economic cycles using an unprecedented dataset of origination and monthly performance records for over 120 million mortgages originated across the United States between 1995 and 2014. Our deep learning model of multi-period mortgage delinquency, foreclosure, and prepayment risk uncovers the highly nonlinear influence on borrower behavior of an exceptionally broad range of loan-specific and macroeconomic variables down to the zip-code level. In particular, most variables strongly interact. Prepayments involve the greatest nonlinear effects among all events. We demonstrate the significant implications of the nonlinearities for risk management, investment management, and mortgage-backed securities.
BIG DATA AND DIGITAL MARKETS CONTESTABILITY: THEORY OF HARM AND DATA ACCESS REMEDIES
Authors: Krämer Jan , Schnurr Daniel
Published: July 2021

This article analyses the crucial role of user data for digital markets contestability and presents policy proposals devised to address growing concerns about the dominance of data-rich incumbents in digital markets. To this end, we discuss a data-driven theory of harm that would warrant ex-ante data access regulation and highlight that niche entry and growth should be the primary economic policy objective in digital markets characterized by strong data-driven network effects. We then evaluate regulatory data access remedies with respect to the involved economic trade-offs and their effectiveness for promoting niche entry and growth. Firstly, we analyse remedies that would limit the collection of user data by data-rich incumbents such as data silos and line of business restrictions. Secondly, we consider remedies that facilitate sharing of (user) data by opening up access to raw behavioural user data collected by data-rich incumbents. In particular, we propose a dual approach with two complementary types of data access remedies: bulk sharing of broad anonymized raw user data and continuous, real-time data portability of deep raw data that contain personally identifiable information. Finally, we comment on the recent proposal for a Digital Markets Act by the European Commission with respect to our findings.
Clostridioides difficile and the Microbiota Early in Life
Authors: Semon Alexa K , Keenan Orlaith , Zackular Joseph P
Published: July 2021

Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease, including pseudomembranous colitis and toxic megacolon, healthy infants are asymptomatically colonized at high rates. The mechanisms leading to high colonization rates and infant protection from C. difficile are currently unknown; however, the ecology and metabolic state of the intestinal microbiome are factors known to influence C. difficile pathogenesis. In this review, we will examine the aspects of the early-life microbiome that may contribute to the incidence of C. difficile and protection from disease manifestation in infants. We will also discuss whether features of the adult microbiota that enable and restrict C. difficile are prevalent during early-life colonization.
International dental tourism in a post-COVID era: pre-travel advice
Authors: Felkai Peter P , Flaherty Gerard , Felkai Thomas
Published: July 2021

The most significant risk of dental tourism is the timing of air travel after dental interventions in order to avoid the pain or injury caused by barotrauma. Usually the minimum waiting time should be 24 h, but in some cases, it can be up to 2 weeks.
Mass Spectrometry–Based Detection of Beta Lactam Hydrolysis Enables Rapid Detection of Beta Lactamase Mediated Antibiotic Resistance
Authors: Suhandynata Raymond T , Lund Kyle , Caraballo-Rodríguez Andrés M , Reed Sharon L , Dorrestein Pieter C , Fitzgerald Robert L , Bevins Nicholas J
Published: July 2021

Objective

Antibiotic resistance by beta lactamase expression is a serious and growing threat. We aimed to determine whether beta-lactamase activity is detectable in urine specimens to enable faster identification of resistance.

Methods

Urine specimens from patients with extended spectrum beta lactamase (ESBL)-expressing urinary infections were incubated with beta lactam antibiotics. Beta lactam hydrolysis was determined by mass spectrometry methods.

Results

Ceftriaxone hydrolysis was observed in 45 of 45 ESBL-containing specimens from patients not treated with a beta lactamase inhibitor before specimen collection. Ceftriaxone hydrolysis was not observed in 108 of 108 non-ESBL-containing specimens. Spiking studies show that beta lactam hydrolysis can be observed within 30 minutes. Beta lactam hydrolysis is evidenced by mass spectrometry preceded by either liquid chromatography or matrix-assisted laser desorption ionization specimen processing methods.

Conclusion

Clinically significant beta lactamase activity is detectable directly from urine specimens. The described methods would enable the detection of beta lactam resistance 24 to 48 hours sooner than culture based methods.
Ultracompact X-ray binaries with He star companions
Authors: Wang Bo , Chen Wen-Cong , Liu Dong-Dong , Chen Hai-Liang , Wu Cheng-Yuan , Tang Wen-Shi , Guo Yun-Lang , Han Zhan-Wen
Published: July 2021

Ultracompact X-ray binaries (UCXBs) are low-mass X-ray binaries with hydrogen-deficient mass donors and ultrashort orbital periods. They have been suggested to be the potential Laser Interferometer Space Antenna (LISA) sources in the low-frequency region. Several channels for the formation of UCXBs have been proposed so far. In this paper, we carried out a systematic study on the He star donor channel, in which a neutron star (NS) accretes matter from a He main-sequence (MS) star through Roche lobe overflow, where the mass transfer is driven by the gravitational wave radiation. First, we followed the long-term evolution of the NS+He MS binaries by employing the stellar evolution code Modules for Experiments in Stellar Astrophysics (mesa ), and thereby obtained the initial parameter spaces for the production of UCXBs. We then used these results to perform a detailed binary population synthesis approach to obtain the Galactic rates of UCXBs through this channel. We estimate the Galactic rates of UCXBs appearing as LISA sources to be ${\sim} 3.1\!-\!11.9\, \rm Myr^{-1}$ through this channel, and the number of such UCXB-LISA sources in the Galaxy can reach about 1–26 calibrated by observations. This work indicates that the He star donor channel may contribute significantly to the Galactic UCXB formation rate. We found that the evolutionary tracks of UCXBs through this channel can account for the location of the five transient sources with relatively long orbital periods quite well. We also found that such UCXBs can be identified by their locations in the mass-transfer rate versus the orbital period diagram.
The COP9 signalosome subunit 3 is necessary for early embryo survival by way of a stable protein deposit in mouse oocytes
Authors: Israel Steffen , Drexler Hannes C A , Fuellen Georg , Boiani Michele
Published: July 2021

Investigations of genes required in early mammalian development are complicated by protein deposits of maternal products, which continue to operate after the gene locus has been disrupted. This leads to delayed phenotypic manifestations and underestimation of the number of genes known to be needed during the embryonic phase of cellular totipotency. Here we expose a critical role of the gene Cops3 by showing that it protects genome integrity during the 2-cell stage of mouse development, in contrast to the previous functional assignment at postimplantation. This new role is mediated by a substantial deposit of protein (94th percentile of the proteome), divided between an exceptionally stable cortical rim, which is prevalent in oocytes, and an ancillary deposit in the embryonic nuclei. Since protein abundance and stability defeat prospects of DNA- or RNA-based gene inactivation in oocytes, we harnessed a classical method next to an emerging method for protein inactivation: antigen masking (for functional inhibition) versus TRIM21-mediated proteasomal degradation, also known as ‘Trim away’ (for physical removal). Both resulted in 2-cell embryo lethality, unlike the embryos receiving anti-green fluorescent protein. Comparisons between COPS3 protein-targeted and non-targeted embryos revealed large-scale transcriptome differences, which were most evident for genes associated with biological functions critical for RNA metabolism and for the preservation of genome integrity. The gene expression abnormalities associated with COPS3 inactivation were confirmed in situ by the occurrence of DNA endoreduplication and DNA strand breaks in 2-cell embryos. These results recruit Cops3 to the small family of genes that are necessary for early embryo survival. Overall, assigning genes with roles in embryogenesis may be less safe than assumed, if the protein products of these genes accumulate in oocytes: the inactivation of a gene at the protein level can expose an earlier phenotype than that identified by genetic techniques such as conventional gene silencing.
SNO 2020 diversity survey: defining demographics, racial biases, career success metrics and a path forward for the field of neuro-oncology
Authors: Chukwueke Ugonma N , Vera Elizabeth , Acquaye Alvina , Hervey-Jumper Shawn L , Odia Yazmin , Klesse Laura J , Dunbar Erin , Sharma Akanksha , Fonkem Ekokobe , Thomas Alissa A , Werbowetski-Ogilvie Tamra E , Camelo-Piragua Sandra , Gatson Na Tosha N , de la Fuente Macarena I , Armstrong Terri S , Porter Alyx B , Jackson Sadhana
Published: July 2021

Background

Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals.

Methods

In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population.

Results

The 386 respondents were predominantly female (58%) with a median age range of 40–49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field.

Conclusions

The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.
Inhibition of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress
Authors: Sharma Pratibha , Xu Jihong , Williams Katie , Easley Michelle , Elder J Brad , Lonser Russell , Lang Frederick F , Lapalombella Rosa , Sampath Deepa , Puduvalli Vinay K
Published: July 2021

Background

Tumor-specific metabolic processes essential for cell survival are promising targets to potentially circumvent intratumoral heterogeneity, a major resistance factor in gliomas. Tumor cells preferentially using nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway for synthesis of NAD, a critical cofactor for diverse biological processes including cellular redox reactions, energy metabolism, and biosynthesis. NAMPT is overexpressed in most malignancies, including gliomas, and can serve as a tumor-specific target.

Methods

Effects of pharmacological inhibition of NAMPT on cellular oxygen consumption rate, extracellular acidification, mitochondrial respiration, cell proliferation, invasion, and survival were assessed through in vitro and ex vivo studies on genetically heterogeneous glioma cell lines, glioma stem-like cells (GSCs), and mouse and human ex vivo organotypic glioma slice culture models.

Results

Pharmacological inhibition of the NAD salvage biosynthesis pathway using a highly specific inhibitor, KPT-9274, resulted in the reduction of NAD levels and related downstream metabolites, inhibited proliferation, and induced apoptosis in vitro in cell lines and ex vivo in human glioma tissue. These effects were mediated by mitochondrial dysfunction, DNA damage, and increased oxidative stress leading to apoptosis in GSCs independent of genotype, IDH status, or MGMT promoter methylation status. Conversely, NAMPT inhibition had minimal in vitro effects on normal human astrocytes (NHA) and no apparent in vivo toxicity in non-tumor-bearing mice.

Conclusions

Pharmacological NAMPT inhibition by KPT9274 potently targeted genetically heterogeneous gliomas by activating mitochondrial dysfunction. Our preclinical results provide a rationale for targeting the NAMPT-dependent alternative NAD biosynthesis pathway as a novel clinical strategy against gliomas.
Self-evaluating participatory research projects: A content validation of the InSPIRES online impact evaluation tool
Authors: Gignac Florence , Gresle Anne-Sophie , Santoro Lamelas Valeria , Yepes-Baldó Montserrat , de la Torre Leonardo , Pinazo Maria-Jesus
Published: July 2021

Research projects involving science shops and citizen science in their promotion of participatory approaches are flourishing globally. However, an instrument evaluating the impacts of such approaches at different stages of a participatory research processes has yet to be validated. The InSPIRES H2020 project developed an impact evaluation tool for just this purpose, consisting of 64 items that reflect upon the dimensions of knowledge democracy, citizen-led research, participatory dynamics, transformative change, and integrity. In this article, we seek to test the content validity of this tool and to provide recommendations that can ensure its validity. A panel of nine experts was created to evaluate each item as regards the following three criteria: representativeness, relevance, and clarity. The Aiken’s V and Wilson Score methods were used to assess the tool’s content validity based on the experts’ ratings. Experts’ written comments were also reviewed. At the panel level, 75% of the items were considered satisfactory in relation to each of the three validity criteria. However, at the population level, 72% of the items suggested that parts of the tool were not valid and required revision. The main suggestions from the experts pointed to the need to reformulate items in which the separation between science and society appeared reinforced and to develop more items about the gender perspective of a research project. The revised version of the tool should serve as a well-founded, comprehensive evaluation instrument for on-going and future projects whose goal is to self-reflect and compare participatory research processes.
Social thinking is for doing: the posterior cerebellum supports predictions of social actions based on personality traits
Authors: Haihambo Naem , Ma Qianying , Baeken Chris , Deroost Natacha , Baetens Kris , Heleven Elien , Overwalle Frank Van
Published: July 2021

Can we predict the future by reading others’ minds? This study explores whether attributing others’ personality traits facilitates predictions about their future actions and the temporal order of these future actions. Prior evidence demonstrated that the posterior cerebellar crus is involved in identifying the temporal sequence of social actions and the person’s traits they imply. Based on this, we hypothesized that this area might also be recruited in the reverse process; that is, knowledge of another person’s personality traits supports predictions of temporal sequences of others’ actions. In this study, participants were informed about the trait of a person and then had to select actions that were consistent with this information and arrange them in the most likely temporal order. As hypothesized, the posterior cerebellar crus 1 and crus 2 were strongly activated when compared to a control task which involved only the selection of actions (without temporal ordering) or which depicted non-social objects and their characteristics. Our findings highlight the important function of the posterior cerebellar crus in the prediction of social action sequences in social understanding.
Predictors of Lack of Relapse After Random Discontinuation of Oral and Long-acting Injectable Antipsychotics in Clinically Stabilized Patients with Schizophrenia: A Re-analysis of Individual Participant Data
Authors: Schoretsanitis Georgios , Kane John M , Correll Christoph U , Rubio Jose M
Published: July 2021

Objective

To quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment.

Methods

We re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of “relapse-free” individuals by the end of follow-up (median = 118 days, IQR = 52.0–208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for >5 half-lives of the stabilizing antipsychotic, and studied predictors of “rebound psychosis” in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal.

Results

29.9% (95%CI = 23.2–38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65–21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4–46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19–2.00), female sex (aHR = 1.37, 95%CI = 1.08–1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68–4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5–7.1). “Rebound psychosis” did not show predictors.

Conclusions and relevance

Our results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk.
The all-E. coliTXTL toolbox 3.0: new capabilities of a cell-free synthetic biology platform
Authors: Garenne David , Thompson Seth , Brisson Amaury , Khakimzhan Aset , Noireaux Vincent
Published: July 2021

The new generation of cell-free gene expression systems enables the prototyping and engineering of biological systems in vitro over a remarkable scope of applications and physical scales. As the utilization of DNA-directed in vitro protein synthesis expands in scope, developing more powerful cell-free transcription–translation (TXTL) platforms remains a major goal to either execute larger DNA programs or improve cell-free biomanufacturing capabilities. In this work, we report the capabilities of the all-E. coli TXTL toolbox 3.0, a multipurpose cell-free expression system specifically developed for synthetic biology. In non-fed batch-mode reactions, the synthesis of the fluorescent reporter protein eGFP (enhanced green fluorescent protein) reaches 4 mg/ml. In synthetic cells, consisting of liposomes loaded with a TXTL reaction, eGFP is produced at concentrations of >8 mg/ml when the chemical building blocks feeding the reaction diffuse through membrane channels to facilitate exchanges with the outer solution. The bacteriophage T7, encoded by a genome of 40 kb and ∼60 genes, is produced at a concentration of 1013 PFU/ml (plaque forming unit/ml). This TXTL system extends the current cell-free expression capabilities by offering unique strength and properties, for testing regulatory elements and circuits, biomanufacturing biologics or building synthetic cells.
Pathogenic characteristics and treatment in 43 cases of acute colchicine poisoning
Authors: Lu Xiaoxia , Liu Yanqing , Wang Chunyan , Dong Jianguang , Bai Lili , Zhang Chengcheng , Zhang Renzheng , Sun Chengwen , Qiu Zewu
Published: July 2021

Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5–0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries， include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration.
Consensus in Brazil on the renaming of leprosy to Hansen's disease
Authors: Delboni Lucas , Deps Patrícia
Published: July 2021

Brazil has been at the forefront in replacing the stigmatising term ‘leprosy’ with the non-pejorative alternative ‘Hansen's disease’ (‘hanseníase’), with use of the former word prohibited by law since 1995. This change followed decades of advocacy, including by civil society organisations representing people affected by the disease. A survey of people affected by Hansen's disease in Brazil found that 111/112 respondents preferred the alternative term, supporting the view that consideration of non-stigmatising terminology that respects the wishes of people affected by the disease should be part of the WHO Global Leprosy (Hansen's disease) Strategy to achieve ‘zero stigma’ by 2030.
Integrated Strategies for Durable Rice Blast Resistance in Sub-Saharan Africa
Authors: Mutiga Samuel K. , Rotich Felix , Were Vincent M. , Kimani John M. , Mwongera David T. , Mgonja Emmanuel , Onaga Geoffrey , Konaté Kadougoudiou , Razanaboahirana Claudine , Bigirimana Joseph , Ndayiragije Alexis , Gichuhi Emily , Yanoria Mary J. , Otipa Miriam , Wasilwa Lusike , Ouedraogo Ibrahima , Mitchell Thomas , Wang Guo-Liang , Correll James C. , Talbot Nicholas J.
Published: July 2021

Rice is a key food security crop in Africa. The importance of rice has led to increasing country-specific, regional, and multinational efforts to develop germplasm and policy initiatives to boost production for a more food-secure continent. Currently, this critically important cereal crop is predominantly cultivated by small-scale farmers under suboptimal conditions in most parts of sub-Saharan Africa (SSA). Rice blast disease, caused by the fungus Magnaporthe oryzae, represents one of the major biotic constraints to rice production under small-scale farming systems of Africa, and developing durable disease resistance is therefore of critical importance. In this review, we provide an overview of the major advances by a multinational collaborative research effort to enhance sustainable rice production across SSA and how it is affected by advances in regional policy. As part of the multinational effort, we highlight the importance of joint international partnerships in tackling multiple crop production constraints through integrated research and outreach programs. More specifically, we highlight recent progress in establishing international networks for rice blast disease surveillance, farmer engagement, monitoring pathogen virulence spectra, and the establishment of regionally based blast resistance breeding programs. To develop blast-resistant, high yielding rice varieties for Africa, we have established a breeding pipeline that utilizes real-time data of pathogen diversity and virulence spectra, to identify major and minor blast resistance genes for introgression into locally adapted rice cultivars. In addition, the project has developed a package to support sustainable rice production through regular stakeholder engagement, training of agricultural extension officers, and establishment of plant clinics.
Single Treatment, Single Depth Superficial Microfocused Ultrasound with Visualization for Rhytid Improvement
Authors: Lowe Stephen
Published: July 2021

Background:

Standard lifting and tightening protocols with microfocused ultrasound with visualization (MFU-V, Ultherapy) comprise the use of multiple transducer depths. We developed a shortened, single depth treatment protocol for patients seeking skin rejuvenation.

Methods:

Single-center, prospective case series. Subjects with static periorbital wrinkles, perioral wrinkles, or accordion lines had a single MFU-V treatment comprising up to 340 lines (periorbital 120, perioral 100, and accordion 120) with the superficial depth transducer (10.0 MHz/1.5 mm). Efficacy was assessed using established rating scales as well as clinician- and subject-reported Global Aesthetic Improvement Scales at baseline, 90, and 180 days, and each subject served as their own control. Adverse events were documented.

Results:

Nine subjects, women aged 38–64, received treatment. At 180 days, post treatment clinicians reported visible improvements in periorbital lines (6/6 cases), accordion lines (5/6 cases), and perioral lines (3/6 cases). Subjects’ self-assessments mirrored those of the clinicians, reporting improvements in accordion lines (5/6 cases improved, 1/6 cases much improved), periorbital lines (3/6 cases improved, 3/6 cases much improved) and perioral lines (2/6 cases improved, 2/6 cases much improved). Subject-rated satisfaction was high (accordion lines 6/6 cases, periorbital lines 4/6 cases and perioral lines 4/6 cases). All subjects experienced mild, transient erythema; in one subject, wheals persisted for 24 hours, resolving on application of mild topical corticosteroid.

Conclusions:

Shortened protocol, single depth MFU-V treatment was well-tolerated. It provided aesthetic improvements in periorbital and accordion lines, and to a lesser extent in perioral lines. Its utility as a noninvasive therapy for superficial skin rejuvenation warrants further investigation.