bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the mechanism of trehalose: dual functions of PI3K/Akt and VPS34/mTOR pathways in porcine oocytes and cumulus cells
Authors: Cai Lian , Yoon Junchul David , Hwang Seon-Ung , Lee Joohyeong , Kim Eunhye , Kim Mirae , Hyun Saang-Yoon , Choi Hyerin , Oh Dongjin , Jeon Yubyeol , Hyun Sang-Hwan
Published: March 2022

Autophagy, an intracellular recycling system, is essential for the meiotic maturation of porcine oocytes. Trehalose has been reported as a novel mammalian target of rapamycin (mTOR)-independent autophagy inducer in many cells. Furthermore, we previously have demonstrated that trehalose supplementation during in vitro maturation of porcine oocytes improves the developmental competence of parthenogenetic embryos, possibly via autophagic activation, whereas the underlying mechanisms remain unclear. Therefore, the aim of this study was to address this issue. We found that trehalose plays a role as an autophagy activator by autophagic flux assay and determined that it promotes phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) inhibition and vacuolar protein sorting 34 (VPS34)/mTOR activation by immunoblotting, both in cumulus cells (CCs) and oocytes. However, interestingly, the effects and the mechanisms regulated by trehalose were different in them, respectively. In CCs, the autophagy was activated through the improvement of lysosomal function/autophagic clearance viability by upregulation of coordinated lysosomal expression and regulation genes via PI3K/Akt inhibition. Whereas in oocytes, autophagy was activated via induction of VPS34, which directly influences autophagosome formation, and the precise meiotic process was ensured via Akt inhibition and mTOR activation. Taken together, this study furtherly elucidates the novel detailed mechanism of trehalose during porcine oocyte maturation, thus laying the biological foundations for pharmacological application.
Evidence of seeding capacity of α-synuclein assemblies in infantile Krabbe disease
Authors: Kwatra Mohit , Kasanga Ella A. , Brundin Patrik
Published: March 2022

This scientific commentary refers to ‘Prion-like α-synuclein pathology in the brain of infants with Krabbe disease’ by Hatton et al. (https://doi.org/10.1093/brain/awac002).
Phosphorylated α-synuclein in skin Schwann cells: a new biomarker for multiple system atrophy
Authors: Donadio Vincenzo , Incensi Alex , Rizzo Giovanni , Westermark Gunilla T , Devigili Grazia , De Micco Rosa , Tessitore Alessandro , Nyholm Dag , Parisini Sara , Nyman Dag , Tedeschi Gioacchino , Eleopra Roberto , Ingelsson Martin , Liguori Rocco
Published: March 2022

Multiple system atrophy (MSA) is characterized by accumulation of phosphorylated α-synuclein (p-syn) as glial cytoplasmic inclusions in the brain and a specific biomarker for this disorder is urgently needed. We aimed at investigating if p-syn can also be detected in skin Remak non-myelinating Schwann cells (RSCs) as Schwann cell cytoplasmic inclusions (SCCi) and may represent a reliable clinical biomarker for MSA.

This cross-sectional diagnostic study evaluated skin p-syn in 96 patients: 46 with probable MSA (29 with parkinsonism type MSA and 17 with cerebellar type MSA), 34 with Parkinson's disease (PD) and 16 with dementia with Lewy bodies (DLB). We also included 50 healthy control subjects. Patients were recruited from five different medical centres. P-syn aggregates in skin sections were stained by immunofluorescence, followed by analyses with confocal microscopy and immuno-electron microscopy. All analyses were performed in a blinded fashion.

Overall, p-syn aggregates were found in 78% of MSA patients and 100% of patients with PD/DLB, whereas they could not be detected in controls. As for neuronal aggregates 78% of MSA patients were positive for p-syn in somatic neurons, whereas all PD/DLB patients were positive in autonomic neurons. When analysing the presence of p-syn in RSCs, 74% of MSA patients were positive, whereas no such SCCi could be observed in PD/DLB patients. Analyses by immuno-electron microscopy confirmed that SCCi were only found in cases with MSA and thus absent in those with PD/DLB.

In conclusion, our findings demonstrate that (i) fibrillar p-syn in RSCs is a pathological hallmark of MSA and may be used as a specific and sensitive disease biomarker; (ii) in Lewy body synucleinopathies (PD/DLB) only neurons contain p-syn deposits; and (iii) the cell-specific deposition of p-syn in the skin thus mirrors that of the brain in many aspects and suggests that non-myelinated glial cells are also involved in the MSA pathogenesis.
α-Amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor and RNA processing gene dysregulation are early determinants of selective motor neuron vulnerability in a mouse model of amyotrophic lateral sclerosis
Authors: Zanganeh Pardis F. , Barton Samantha K. , Lim Katherine , Qian Elizabeth L. , Crombie Duncan E. , Bye Christopher R. , Turner Bradley J.
Published: March 2022

Amyotrophic lateral sclerosis is a late-onset adult neurodegenerative disease, although there is mounting electrophysiological and pathological evidence from patients and animal models for a protracted preclinical period of motor neuron susceptibility and dysfunction, long before clinical diagnosis. The key molecular mechanisms linked to motor neuron vulnerability in amyotrophic lateral sclerosis have been extensively studied using transcriptional profiling in motor neurons isolated from adult mutant superoxide dismutase 1 mice. However, neonatal and embryonic motor neurons from mutant superoxide dismutase 1 mice show abnormal morphology and hyperexcitability, suggesting preceding transcriptional dysregulation. Here, we used RNA sequencing on motor neurons isolated from embryonic superoxide dismutase 1G93A mice to determine the earliest molecular mechanisms conferring neuronal susceptibility and dysfunction known in a mouse model of amyotrophic lateral sclerosis. Transgenic superoxide dismutase 1G93A mice expressing the spinal motor neuron homeobox HB9:green fluorescent protein reporter allowed unambiguous identification and isolation of motor neurons using fluorescence-activated cell sorting. Gene expression profiling of isolated motor neurons revealed transcriptional dysregulation in superoxide dismutase 1G93A mice as early as embryonic Day 12.5 with the majority of differentially expressed genes involved in RNA processing and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-mediated glutamate receptor signalling. We confirmed dysregulation of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor Subunit 2, at transcript and protein levels, in embryonic superoxide dismutase 1G93A mouse motor neurons and human motor neurons derived from amyotrophic lateral sclerosis patient induced pluripotent stem cells harbouring pathogenic superoxide dismutase 1 mutations. Mutant superoxide dismutase 1 induced pluripotent stem cell-derived motor neurons showed greater vulnerability to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-mediated excitotoxicity, consistent with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor Subunit 2 downregulation. Thus, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor Subunit 2 deficiency leading to enhanced α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor signalling, calcium influx, hyperexcitability, and chronic excitotoxicity is a very early and intrinsic property of spinal motor neurons that may trigger amyotrophic lateral sclerosis pathogenesis later in life. This study reinforces the concept of therapeutic targeting of hyperexcitability and excitotoxicity as potential disease-modifying approaches for amyotrophic lateral sclerosis.
Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells
Authors: Mise Yuka , Hamanishi Junzo , Daikoku Takiko , Takamatsu Shiro , Miyamoto Taito , Taki Mana , Yamanoi Koji , Yamaguchi Ken , Ukita Masayo , Horikawa Naoki , Abiko Kaoru , Murakami Ryusuke , Furutake Yoko , Hosoe Yuko , Terakawa Jumpei , Kagabu Masahiro , Sugai Tamotsu , Osakabe Mitsumasa , Fujiwara Hiroshi , Matsumura Noriomi , Mandai Masaki , Baba Tsukasa
Published: March 2022

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.
Working with “Wogs”: Aliens, Denizens and the Machinations of Denialism
Authors: Gilroy Paul
Published: March 2022

This article uses a discussion of the currency of the word “wog” in Britain to identify a pivotal, racialized position used to contain alien incomers so as to exclude them from belonging to the national community. The argument invites readers to focus on the affective energy specifically endowed in contemporary European “populist” politics by race-talk and the anti-Muslim rhetoric which share common roots in absolutist conceptions of culture and “ethnicity.” It is suggested that those developments have conditioned the digital and virtual politics of contemporary racism. They connect with the deployment of machine learning and the growing application of Artificial Intelligence to build trans-national networks among White supremacists and ultranationalists in order to promote their allyship and coordinate their activities.
Metabolic and functional connectivity provide unique and complementary insights into cognition-connectome relationships
Authors: Voigt Katharina , Liang Emma X , Misic Bratislav , Ward Phillip G D , Egan Gary F , Jamadar Sharna D
Published: March 2022

A major challenge in current cognitive neuroscience is how functional brain connectivity gives rise to human cognition. Functional magnetic resonance imaging (fMRI) describes brain connectivity based on cerebral oxygenation dynamics (hemodynamic connectivity), whereas [18F]-fluorodeoxyglucose functional positron emission tomography (FDG-fPET) describes brain connectivity based on cerebral glucose uptake (metabolic connectivity), each providing a unique characterization of the human brain. How these 2 modalities differ in their contribution to cognition and behavior is unclear. We used simultaneous resting-state FDG-fPET/fMRI to investigate how hemodynamic connectivity and metabolic connectivity relate to cognitive function by applying partial least squares analyses. Results revealed that although for both modalities the frontoparietal anatomical subdivisions related the strongest to cognition, using hemodynamic measures this network expressed executive functioning, episodic memory, and depression, whereas for metabolic measures this network exclusively expressed executive functioning. These findings demonstrate the unique advantages that simultaneous FDG-PET/fMRI has to provide a comprehensive understanding of the neural mechanisms that underpin cognition and highlights the importance of multimodality imaging in cognitive neuroscience research.
Heightened Microbial Translocation Is a Prognostic Biomarker of Recurrent Tuberculosis
Authors: Kumar Nathella Pavan , Moideen Kadar , Viswanathan Vijay , Sivakumar Shanmugam , Ahamed Shaik Fayaz , Ponnuraja C , Hissar Syed , Kornfeld Hardy , Babu Subash
Published: March 2022

Background

Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known.

Methods

We examined the presence of microbial translocation in a cohort of newly diagnosed, sputum smear, and culture positive individuals with drug-sensitive PTB. Participants were followed up for a year following the end of anti-tuberculosis treatment. They were classified as cases (in the event of recurrence, n = 30) and compared to age and gender matched controls (in the event of successful, recurrence free cure; n = 51). Plasma samples were used to measure the circulating microbial translocation markers. All the enrolled study participants were treatment naïve, HIV negative and with or without diabetes mellitus.

Results

Baseline levels of lipopolysaccharide (LPS) (P = .0002), sCD14 (P = .0191), and LPS-binding protein (LBP) (P < .0001) were significantly higher in recurrence than controls and were associated with increased risk for recurrence, whereas intestinal fatty acid binding protein (I-FABP) and Endocab showed no association. Receiver operating characteristic (ROC) curve analysis demonstrated the utility of these individual microbial markers in discriminating recurrence from cure with high sensitivity, specificity, and area under the curve (AUC).

Conclusions

Recurrence following microbiological cure in PTB is characterized by heightened baseline microbial translocation. These markers can be used as a rapid prognostic tool for predicting recurrence in PTB.
Hepatitis C Virus Reinfection Following Direct-Acting Antiviral Treatment in the Prison Setting: The SToP-C Study
Authors: Carson Joanne M , Dore Gregory J , Lloyd Andrew R , Grebely Jason , Byrne Marianne , Cunningham Evan , Amin Janaki , Vickerman Peter , Martin Natasha K , Treloar Carla , Martinello Marianne , Matthews Gail V , Hajarizadeh Behzad ,   Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) Study Group, Loveday Stuart , Dore Gregory , Lloyd Andrew , Grebely Jason , Butler Tony , Chambers Georgina , Treloar Carla , Byrne Marianne , Donnelly Roy , McGrath Colette , Bowman Julia , Trevethan Lee , Lagios Katerina , Grant Luke , Murrell Terry , Bath Nicky , Tawil Victor , Stevens Annabelle , Topp Libby , Churchill Alison , Pinnock Kate , Martin Natasha , Drew Steven , Harrod Mary , Dore Gregory , Lloyd Andrew , Hajarizadeh Behzad , Butler Tony , Marks Pip , Tamaddoni Mahshid , Obeid Stephanie , Mercade Gerard Estivill , Martinez Maria , Byrne Marianne , Rawlinson William , Yeang Malinna , Wynn Matthew , Willenborg Christiana , Smith Angela , Williams Ronella , Cooper Brigid , Somes Kelly , Burns Carina , Lobo Camilla , Conroy Karen , McCredie Luke , Café Carolyn , Anlezark Jodie
Published: March 2022

Background

Injection drug use (IDU) following treatment for hepatitis C virus (HCV) infection may lead to reinfection, particularly if access to harm reduction services is suboptimal. This study assessed HCV reinfection risk following direct-acting antiviral therapy within Australian prisons that had opioid agonist therapy (OAT) programs but did not have needle and syringe programs (NSPs).

Methods

The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study enrolled people incarcerated in 4 prisons between 2014 and 2019. Participants treated for HCV were followed every 3–6 months to identify reinfection (confirmed by sequencing). Reinfection incidence and associated factors were evaluated.

Results

Among 388 participants receiving treatment, 161 had available posttreatment follow-up and were included in analysis (92% male; median age, 33 years; 67% IDU in prison; median follow-up 9 months). Among those with recent (in the past month) IDU (n = 71), 90% had receptive needle/syringe sharing. During 145 person-years (PY) of follow-up, 18 cases of reinfection were identified. Reinfection incidence was 12.5/100 PY (95% confidence interval [CI]: 7.9–19.8) overall, increasing to 28.7/100 PY (95% CI: 16.3–50.6) among those with recent IDU and needle/syringe sharing. In adjusted analysis, recent IDU with needle/syringe sharing was associated with increased reinfection risk (adjusted hazard ratio [aHR], 4.74 [95% CI: 1.33–16.80]; P = .016) and longer HCV testing interval with decreased risk (ie, chance of detection; aHR, 0.41 per each month increase [95% CI: .26–.64]; P < .001).

Conclusions

A high rate of HCV reinfection was observed within prison. Posttreatment surveillance and retreatment are ­essential to limit the impact of reinfection. High-coverage OAT and NSPs should be considered within prisons.

Clinical Trials Registration

NCT02064049
Evaluation of the Latent Tuberculosis Care Cascade Among Public Health Clinics in the United States
Authors: Holzman Samuel B , Perry Allison , Saleeb Paul , Pyan Alexandra , Keh Chris , Salcedo Katya , Narita Masahiro , Ahmed Amina , Miller Thaddeus L , Pettit April C , Khurana Renuka , Whipple Matthew , Katz Dolly , Largen Angela , Krueger Amy , Shah Maunank ,   Tuberculosis Epidemiologic Studies Consortium
Published: March 2022

Background

Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions.

Methods

We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016–2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion.

Results

Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range [IQR] 20–46). A median of 35% of participants were US-born at each site (IQR 11–78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US–born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis).

Conclusions

Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.
Rejoinder: Mises’s attempt to scientifically reject socialism failed
Authors: Camarinha Lopes Tiago
Published: March 2022

In this rejoinder to Bylund, Lingle and Packard, I explain why Mises’s attempt to scientifically reject socialism failed, commenting on the two specific points they have raised in their reply to my article ‘Technical or Political: the socialist economic calculation debate’.
Universal Clinician Device for improving risk prediction and management of patients with atrial fibrillation: an assumed benefit analysis
Authors: van Husen Georg , Virdone Saverio , Pieper Karen , Kayani Gloria , Fox Keith A A
Published: March 2022

Aim

Atrial fibrillation (AF) management guidelines advise using risk tools to optimize AF treatment. This study aims to develop a dynamic and clinically applicable digital device to assess stroke and bleeding risk, and to facilitate outcome improvements in AF patients. The device will provide tailored treatment recommendations according to easily attainable individual patient data.

Methods and Results

This Universal Clinician Device (UCD) was created using the GARFIELD-AF registry using a split sample approach. The GARFIELD-AF risk tool was adapted with two modifications. First, predictors with ≥1000 missing data points were separated, allowing expected risks estimation. Second, recommendations for modifiable risk factors and associated 2-year outcome estimates were incorporated. Outcomes of interest were all-cause mortality, non-haemorrhagic stroke/systemic embolism (SE), and major bleeding. All patients were randomized to a derivation (n = 34853) and validation cohort (n = 17165). In the derivation cohort, predictors were identified using least absolute shrinkage and selection operator regression. Cox models were fitted with the selected parameters. The UCD demonstrated superior predictive power compared with CHA2DS2VASc for all-cause mortality [0.75(0.75–0.76) vs. 0.71(0.70–0.72)] and non-haemorrhagic stroke/SE [0.68(0.66–0.70) vs. 0.65(0.63–0.67)], and with HAS-BLED for major bleeding [0.69(0.67–0.71) vs. 0.64(0.62–0.65)]. Universal Clinician Device recommendations reduced all-cause mortality (8.45–5.42%) and non-haemorrhagic stroke/SE (2.58–1.50%). Patients with concomitant diabetes and chronic kidney disease benefitted further, reducing mortality risk from 13.15% to 8.67%. One-third of patients with a CHA2DS2VASc score of >1 had the lowest risk of stroke.

Conclusion

The UCD simultaneously predicts mortality, stroke, and bleeding risk in patients using easily attainable individual clinical data and guideline-based optimized treatment plans.

Clinical Trial Registration

URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF: NCT01090362
Challenges and experiences of general practitioners during the course of the Covid-19 pandemic: a northern Italian observational study—cross-sectional analysis and comparison of a two-time survey in primary care
Authors: Mahlknecht Angelika , Barbieri Verena , Engl Adolf , Piccoliori Giuliano , Wiedermann Christian J
Published: March 2022

Background

General practitioners (GPs) have been among the frontline workers since the outbreak of the Covid-19 pandemic. Reflecting and analyzing the ongoing pandemic response of general practice provides essential information and serves as a precondition for outlining future health policy strategies.

Objective

To investigate the effects of the pandemic on GPs’ daily work and well-being and to describe needs for improvement in primary care highlighted by the pandemic.

Methods

A 2-time cross-sectional online survey involving GPs in a northern Italian region was conducted in September 2020 and March/April 2021.

Results

Eighty-four GPs (29.6% of invited GPs) participated in the first survey, and 41 GPs (14.4%) in the second survey. Most GPs experienced a notable workload increase which was tendentially higher during the advanced stages of the pandemic. A notable increase between the first and the second survey was noted regarding the frequency of Covid-related patient contacts and phone calls. Communication with health authorities and hospitals was rated as improvable. Psychological distress among GPs tended to increase over time; female GPs were more affected in the first survey. Most practices introduced major changes in their workflow, mainly appointment-based visits and separating Covid-19-suspected patients. Availability of protective equipment considerably increased over time. In the second survey, the GPs felt more prepared to self-protection and outpatient treatment of Covid-affected patients.

Conclusion

The work of GPs has been substantially impacted by the ongoing Covid-19 pandemic. Efforts should be undertaken to efficiently strengthen primary care which plays an important role in pandemic events.
Role of Human Leukocyte Antigen Allele Sharing in Human Papillomavirus Infection Transmission Among Heterosexual Couples: Findings From the HITCH Cohort Study
Authors: Louvanto Karolina , Baral Prativa , Burchell Ann , Ramanakumar Agnihotram , El-Zein Mariam , Tellier Pierre Paul , Coutlée Francois , Roger Michel , Franco Eduardo L
Published: March 2022

Background

Human leukocyte antigen (HLA) polymorphism influences innate and adaptive immune responses. Among heterosexual couples in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study, we examined whether allele sharing in a couple predicted the partners’ infections with the same human papillomavirus (HPV) type.

Methods

We tested genital samples from 271 couples for 36 HPV genotypes by polymerase chain reaction. We used direct DNA sequencing to type HLA-B07, -DRB1, -DQB1 and -G. Generalized estimating equations were used to examine the associations between the extent of allele sharing and HPV type concordance in which at least 1 of the partners was HPV positive.

Results

We identified 106 different HLA alleles. The most common HLA alleles among couples were G*01:01:01 (95.6%), G*01:01:02 (60.1%), DQB1*03:01 (57.2%), and DRB1*07:01 (46.9%). Allele sharing was as follows: 19.6% shared none, 43.2% shared 1 only, 25.1% shared 2, and 12.5% shared 3–5. Irrespective of HLA class, grouped or in combination, the extent of allele sharing was not a significant predictor of type-specific HPV concordance in a couple (odds ratio, 1.1 [95% confidence interval, .5–2.1], for 3–5 vs none).

Conclusions

We found no evidence that the extent of HLA allele concordance influences the likelihood of HPV transmission in newly formed heterosexual couples.
Beyond Roll-Call Voting: Sponsorship Dynamics at the UN General Assembly
Authors: Seabra Pedro , Mesquita Rafael
Published: March 2022

Research on the United Nations General Assembly (UNGA) has often privileged analyses on voting patterns, that is, how countries position themselves whenever a resolution is brought to a vote in each plenary session. However, voted resolutions comprise only a fraction of UNGA output, and much is still unknown about how countries behave before casting any votes. What takes place prior to and leading up to the adoption of resolutions? Even though the study of draft sponsorship remains underdeveloped, it can comprise a more valid empirical strategy to infer state preferences. This research note introduces the UN General Assembly Sponsorship Dataset, which encompasses the sponsorship behavior of every UNGA member from 2009 to 2019. We develop two novel empirical indices, priority and ownership, in order to ascertain draft relevance for each member state. We also use the new data to test longstanding arguments over vote-buying and North versus South coalitions in the UNGA. Our findings confirm mainstream conclusions for the former but challenge prevailing assumptions on the latter.
Co-transfer of last-line antibiotic resistance and virulence operons by an IncFIBk-FII-X3-ColKP3 hybrid plasmid in Klebsiella pneumoniae
Authors: Liu Congcong , Dong Ning , Zeng Yu , Lu Jiayue , Chen Jiawei , Wang Yao , Cai Chang , Chen Kaichao , Chen Gongxiang , Shen Zhangqi , Chen Sheng , Zhang Rong
Published: March 2022

Objectives

To characterize a clinical Klebsiella pneumoniae isolate from China co-harbouring tet(X4), blaOXA-181 and the aerobactin operon on an IncFIBk-FII-X3-ColKP3 hybrid plasmid.

Methods

A tigecycline-resistant strain was recovered from the intestinal sample of a patient. It was subjected to antimicrobial susceptibility testing, conjugation assay, virulence testing, WGS, bioinformatics analysis, plasmid stability testing and fitness cost testing.

Results

The strain K. pneumoniae T877 was resistant to tigecycline, intermediate to piperacillin/tazobactam and ertapenem, and positive for tet(X), blaOXA-181 and the virulence-associated operon iutAiucABCD, which were located on the same plasmid, named pKPT877-hybrid. It was 99.96% identical to the IncFIBk-FII plasmid pSCH6109-Vir (accession number CP050860) from K. pneumoniae strain SCH6109 at 96% coverage with the absence of a 50 kb region on pKPT877-hybrid; this region was highly homologous to the 51 kb IncX3-ColKP3-type, blaOXA-181-carrying plasmid pOXA181-191773 (accession number CP080367). Plasmid pKPT877-hybrid was conjugatively transferable to the ST11 K. pneumoniae strains FJ8 and KP04. pKPT877-hybrid did not have a significant impact on the fitness cost and could be maintained stably in T877.

Conclusions

We report for the first time (to the best of our knowledge) the co-transfer of last-line antibiotic resistance determinants [tet(X4) and blaOXA-181] and the aerobactin operon (iutAiucABCD) by a mobile IncFIBk-FII-X3-ColKP3 hybrid plasmid, which can be stably maintained in K. pneumoniae strains, even in the absence of antibiotic selective pressure. Once the plasmid transfers to a K. pneumoniae with porin deficiency, the strain might have high levels of resistance to carbapenems and tigecycline, which are the last line of defence against infections. Heightened and continuous efforts are needed to control its dissemination.
Combining human and machine intelligence for clinical trial eligibility querying
Authors: Fang Yilu , Idnay Betina , Sun Yingcheng , Liu Hao , Chen Zhehuan , Marder Karen , Xu Hua , Schnall Rebecca , Weng Chunhua
Published: March 2022

Objective

To combine machine efficiency and human intelligence for converting complex clinical trial eligibility criteria text into cohort queries.

Materials and Methods

Criteria2Query (C2Q) 2.0 was developed to enable real-time user intervention for criteria selection and simplification, parsing error correction, and concept mapping. The accuracy, precision, recall, and F1 score of enhanced modules for negation scope detection, temporal and value normalization were evaluated using a previously curated gold standard, the annotated eligibility criteria of 1010 COVID-19 clinical trials. The usability and usefulness were evaluated by 10 research coordinators in a task-oriented usability evaluation using 5 Alzheimer’s disease trials. Data were collected by user interaction logging, a demographic questionnaire, the Health Information Technology Usability Evaluation Scale (Health-ITUES), and a feature-specific questionnaire.

Results

The accuracies of negation scope detection, temporal and value normalization were 0.924, 0.916, and 0.966, respectively. C2Q 2.0 achieved a moderate usability score (3.84 out of 5) and a high learnability score (4.54 out of 5). On average, 9.9 modifications were made for a clinical study. Experienced researchers made more modifications than novice researchers. The most frequent modification was deletion (5.35 per study). Furthermore, the evaluators favored cohort queries resulting from modifications (score 4.1 out of 5) and the user engagement features (score 4.3 out of 5).

Discussion and Conclusion

Features to engage domain experts and to overcome the limitations in automated machine output are shown to be useful and user-friendly. We concluded that human–computer collaboration is key to improving the adoption and user-friendliness of natural language processing.
Assessing and addressing COVID-19 information needs via a weather application
Authors: McKillop Mollie M , VanHouten Courtney , Bales Carol , Felix Winnie , Hekmat Rezzan , Purcell Jackson Gretchen
Published: March 2022

We describe implementation and usage of a coronavirus disease 2019 (COVID-19) digital information hub delivered through the widely adopted The Weather Company (TWC) application and explore COVID-19 knowledge, behaviors, and information needs of users. TWC deployed the tool, which displayed local case counts and trends, in March 2020. Unique users, visits, and interactions with tool features were measured. In August 2020, a cross-sectional survey assessed respondent characteristics, COVID-19 knowledge, behaviors, and preferences. TWC COVID-19 hub averaged 1.97 million unique users with over 2.6 million visits daily and an average interaction time of 1.63 min. Respondents reported being knowledgeable about COVID-19 (92.3%) and knowing relevant safety precautions (90.9%). However, an average of 35.3% of respondents reported not increasing preventive practices across behaviors surveyed due to information about COVID-19. In conclusion, we find a free weather application delivered COVID-19 data to millions of Americans. Despite confidence in knowledge and best practices for prevention, over one-third of survey respondents did not increase practice of preventive behaviors due to information about COVID-19.
Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids With Incident Colorectal Cancer
Authors: Loftfield Erikka , Falk Roni T , Sampson Joshua N , Huang Wen-Yi , Hullings Autumn , Murphy Gwen , Weinstein Stephanie J , Albanes Demetrius , Freedman Neal D , Sinha Rashmi
Published: March 2022

Background

Human studies investigating the prospective relationship between microbial metabolites and colorectal cancer (CRC) risk are lacking. We tested whether higher serum bile acids (BAs) and lower short-chain fatty acids (SCFAs) were associated with CRC risk.

Methods

In baseline serum collected more than 30 years before a CRC diagnosis, we quantified concentrations of 15 BAs and 6 SCFAs using targeted liquid chromatography with tandem mass spectrometry  assays in 1:1 matched cases and controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (men: n = 262 cases; women: n = 233 cases) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (men: n = 598 cases). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for BA and SCFA quartiles and summary measures with CRC overall and by anatomic location using multivariable conditional logistic regression models. PLCO analyses were stratified by sex. All statistical tests were 2-sided.

Results

In PLCO women, 7 BAs were strongly associated with increased CRC risk, including the secondary BAs, deoxycholic (ORQ4 v Q1 = 2.85, 95% CI = 1.45 to 5.60, Qtrend = 0.011), glycodeoxycholic (OR Q4 v Q1 = 3.45, 95% CI = 1.79 to 6.64, Qtrend = 0.006), taurodeoxycholic (OR Q4 v Q1 = 2.36, 95% CI = 1.22 to 4.55, Qtrend = 0.023), and glycolithocholic acid (ORQ4 v Q1 = 2.71, 95% CI = 1.41 to 5.22, Qtrend = 0.015). Women in the highest compared with lowest quartile of total SCFAs had a 45% lower risk of CRC (OR = 0.55, 95% CI = 0.31 to 0.98, Ptrend = .03). Associations for total BAs and SCFAs were strongest among women with proximal colon cancer. No statistically significant associations were observed for BA or SCFA measures among men.

Conclusions

Serum concentrations of BAs, particularly downstream microbial metabolites of cholic acid, were strongly associated with increased risk of CRC among women.
Deconstructing Burnout at the Intersections of Race, Gender, and Generation in Local Government
Authors: Barboza-Wilkes Cynthia J , Le Thai V , Resh William G
Published: March 2022

In recent years, there have been multiple calls for public administration scholars to adopt an intersectional approach to the study of diversity within public organizations. This paper empirically examines the simultaneous influence of multiple dimensions of individual identity on employee burnout. We advance a better understanding of disparities in individual well-being outcomes for public servants. Using conservation of resource (COR) theory and applied intersectionality, we systematically measure and model differential vulnerabilities to emotional exhaustion, depersonalization, and loss of personal accomplishment for individuals at the intersection of gender, racial, and generational identities. Using survey data on local government employees across two neighboring large cities in California, we use ordinary least squares and ordered logit models to estimate the impact of intersectional identities on different dimensions of burnout. Our results show that younger generations of women of color are particularly vulnerable to burnout, but the experience of burnout is not uniform across groups, with each dimension of burnout revealing different vulnerable groups. These findings highlight the importance of deconstructing burnout into its discrete dimensions to better understand the experience of different socio-demographic groups of employees and develop culturally competent strategies to better support an increasingly diverse public workforce.
A Hierarchy of Medical Countermeasures Against Biological Threats
Authors: Biggs Adam T , Littlejohn Lanny F
Published: March 2022

Introduction

Emerging biological threats represent a serious challenge for force health protection (FHP). Against a novel biological threat, medical countermeasures are the first line of defense. However, as exposed by global pandemic conditions, there are significant complications when administering medical countermeasures against novel threats. One such limitation involved the lack of any guiding structure to discuss and deliberate upon the relative value of employing different countermeasures either alone or in tandem. For example, both personal protective equipment and prophylactic medication can provide some protection, but how are individual protections weighed against operational capabilities and FHP initiatives? The goal of this review is to provide a hierarchical organizing structure to the different medical countermeasures available in response to emerging biological threats.

Materials and Methods

This review used no explicit inclusion or exclusion criteria for its literature review. References are provided for illustrative purposes to represent different components of the medical hierarchy.

Discussion

The hierarchy presented here is organized around a resource-durability structure that functions as a push–pull mechanism. Specifically, lower levels of the hierarchy require more resources to sustain FHP conditions while also providing less durable protection. These countermeasures require continual reapplication, and so resources become conceived as much in time and effort to apply as in exhaustible supplies. Higher-order countermeasures require less resources investment as a single application can provide weeks, months, or years of protection. Moreover, higher-order protections are less likely to interfere with military operational capabilities, which further support their classification as superior countermeasures to sustain FHP. The five levels of the hierarchy are presented here as follows, organized from lowest to highest value as a medical countermeasure: (1) Sanitization, (2) personal protective equipment, (3) prophylaxis, (4) vaccines, and (5) optimized immune system. Rationale and descriptions identify how each higher-order countermeasure is superior to its lower-order counterparts while noting that optimizing FHP will likely require employing multiple countermeasures at different levels. The discussion concludes with an overview as to how different countermeasures were employed to various degrees during a novel global pandemic.

Conclusions and Future Uses

Identifying medical countermeasures is important to optimizing FHP. Different countermeasures have different advantages, and the hierarchy distinguishes between inferior and superior countermeasures through the push–pull style mechanism of resource-durability assessment. Future deployment and development should focus on superior countermeasures to maximize medical protections and operational readiness while understanding the relative value and complications inherent with different countermeasures.
Dealing with density discontinuities in planetary SPH simulations
Authors: Ruiz-Bonilla S , Borrow J , Eke V R , Kegerreis J A , Massey R J , Sandnes T D , Teodoro L F A
Published: March 2022

Density discontinuities cannot be precisely modelled in standard formulations of smoothed particles hydrodynamics (SPH) because the density field is defined smoothly as a kernel-weighted sum of neighbouring particle masses. This is a problem when performing simulations of giant impacts between proto-planets, for example, because planets typically do have density discontinuities both at their surfaces and at any internal boundaries between different materials. The inappropriate densities in these regions create artificial forces that effectively suppress mixing between particles of different material and, as a consequence, this problem introduces a key unknown systematic error into studies that rely on SPH simulations. In this work, we present a novel, computationally cheap method that deals simultaneously with both of these types of density discontinuity in SPH simulations. We perform standard hydrodynamical tests and several example giant impact simulations, and compare the results with standard SPH. In a simulated Moon-forming impact using 107 particles, the improved treatment at boundaries affects at least 30${{\ \rm per\ cent}}$ of the particles at some point during the simulation.
LYRA – II. Cosmological dwarf galaxy formation with inhomogeneous Population III enrichment
Authors: Gutcke Thales A , Pakmor Rüdiger , Naab Thorsten , Springel Volker
Published: March 2022

We present the simulation of a $2\times 10^{9}\, \mathrm{M}_{\odot }$ halo mass cosmological dwarf galaxy run to z = 0 at 4 solar mass gas resolution with resolved supernova feedback. We compare three simple subgrid implementations for the inhomogeneous chemical enrichment from Population III stars and compare them to constraints from Local Group dwarf galaxies. The employed model, LYRA, is a novel high-resolution galaxy formation model built for the moving mesh code arepo, which is marked by a resolved multiphase interstellar medium, single stars, and individual supernova events. The resulting reionization relic is characterized by a short (<1.5 Gyr) star formation history that is repeatedly brought to a standstill by violent bursts of feedback. Star formation is reignited for a short duration due to a merger at z ≈ 4 and then again at z ≈ 0.2−0 after sustained gas accretion. Our model z = 0 galaxy matches the stellar mass, size, stellar kinematics, and metallicity relations of Local Group dwarf galaxies well. The dark matter profile does not exhibit a core in any version of the model. We show that the host halo masses of Population III stars affect the assembly history of dwarf galaxies. This manifests itself through the initial gaseous collapse in the progenitor haloes, affecting the central density of the stellar component and through the accretion of luminous substructure.
On positively charged dust in the coma of comet 67P
Authors: Vigren E , Eriksson A I , Bergman S
Published: March 2022

Moment analysis of ion spectrograms measured by the Ion Composition Analyser (ICA) in the coma of comet 67P typically produces an ion number density estimate markedly lower than the number density of free electrons as measured by the Mutual Impedance Probe and the dual Langmuir Probe. While there are good reasons to distrust the ion density moment estimate in these circumstances, the issue cannot yet be considered fully understood and it is of interest to see whether any natural non-instrumental cause is possible. An obvious such cause would be whether a significant fraction of the positive charge density resides in positively charged dust grains that are not measured by the ICA. Here, we show that this scenario is highly unlikely, even near perihelion where photoemission is the strongest. In our semi-analytical grain charging model, we balance the current contributions to grains of photoelectron emission and electron attachment so as to find the expected charge state for a grain of a given radius. The charge state is affected by the ambient electron number density, the electron temperature, and the heliocentric distance. While at times the bulk of the dust population around comet 67P could be charged positive, dust charging, including photoelectron emission, should have a negligible influence on the overall ionization balance in the cometary coma simply because the dust particles are not ubiquitous enough.
Star-forming S0 Galaxies in SDSS-MaNGA: fading spirals or rejuvenated S0s?
Authors: Rathore Himansh , Kumar Kavin , Mishra Preetish K , Wadadekar Yogesh , Bait Omkar
Published: March 2022

We investigate the origin of rare star formation in an otherwise red-and-dead population of S0 galaxies, using spatially resolved spectroscopy. Our sample consists of 120 low redshift (z < 0.1) star-forming S0 (SF-S0) galaxies from the SDSS-IV MaNGA DR15. We have selected this sample after a visual inspection of deep images from the DESI Legacy Imaging Surveys DR9 and the Subaru/HSC-SSP survey PDR3 to remove contamination from spiral galaxies. We also construct two control samples of star-forming spirals (SF-Sps) and quenched S0s (Q-S0s) to explore their evolutionary link with the star-forming S0s. To study star formation at resolved scales, we use dust-corrected H α luminosity and stellar density (Σ⋆) maps to construct radial profiles of star formation rate (SFR) surface density (ΣSFR) and specific SFR (sSFR). Examining these radial profiles, we find that star formation in SF-S0s is centrally dominated as opposed to disc-dominated star formation in spirals. We also compared various global (size–mass relation, bulge-to-total luminosity ratio) and local (central stellar velocity dispersion) properties of SF-S0s to those of the control sample galaxies. We find that SF-S0s are structurally similar to the quenched S0s and are different from star-forming spirals. We infer that SF-S0s are unlikely to be fading spirals. Inspecting stellar and gas velocity maps, we find that more than $50{{\ \rm per\ cent}}$ of the SF-S0 sample shows signs of recent galaxy interactions such as kinematic misalignment, counter-rotation, and unsettled kinematics. Based on these results, we conclude that in our sample of SF-S0s, star formation has been rejuvenated, with minor mergers likely to be a major driver.
Forecasting the potential of weak lensing magnification to enhance LSST large-scale structure analyses
Authors: Mahony Constance , Fortuna Maria Cristina , Joachimi Benjamin , Korn Andreas , Hoekstra Henk , Schmidt Samuel J ,   LSST Dark Energy Science Collaboration, Alonso David , Singh Sukhdeep , Ricci Marina , Hildebrandt Hendrik , Duncan Christopher , Johnston Harry
Published: March 2022

Recent works have shown that weak lensing magnification must be included in upcoming large-scale structure analyses, such as for the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST), to avoid biasing the cosmological results. In this work, we investigate whether including magnification has a positive impact on the precision of the cosmological constraints, as well as being necessary to avoid bias. We forecast this using an LSST mock catalogue and a halo model to calculate the galaxy power spectra. We find that including magnification has little effect on the precision of the cosmological parameter constraints for an LSST galaxy clustering analysis, where the halo model parameters are additionally constrained by the galaxy luminosity function. In particular, we find that for the LSST gold sample (i < 25.3) including weak lensing magnification only improves the galaxy clustering constraint on Ωm by a factor of 1.03, and when using a very deep LSST mock sample (i < 26.5) by a factor of 1.3. Since magnification predominantly contributes to the clustering measurement and provides similar information to that of cosmic shear, this improvement would be reduced for a combined galaxy clustering and shear analysis. We also confirm that not modelling weak lensing magnification will catastrophically bias the cosmological results from LSST. Magnification must therefore be included in LSST large-scale structure analyses even though it does not significantly enhance the precision of the cosmological constraints.