bluuebunny/crossref_metadata_2025 huggingface dataset:
Tensile and compressive mechanical properties of nanocrystalline calcite with grain size effect
Authors: Luo Chaocai , Yang Xinhua , Li Jie
Published: November 2023

Calcite is one of the most main components of microbially induced calcium carbonate precipitation (MICP). With the in-depth research of MICP, the mechanical properties of nanocrystalline calcite attract much attention. In this paper, the deformation and failure behaviors of nanocrystalline calcite under a uniaxial tensile or compressive condition are studied by molecular dynamics simulation, and then the dominant deformation and failure mechanisms, as well as their grain size effect, are analyzed. The results show that the grain boundary densification dominates the elastic deformation, while the intragranular phase transition dominates the plastic deformation. Compared with single-crystal calcite, the elastic modulus of nanocrystalline calcite is significantly reduced and its ultimate strength is decreased by more than 50%. Nanocrystalline calcite has stronger plastic deformation ability in compression than in tension. Its tensile and compressive elastic moduli and peak stresses all increase with the average grain size. The effects of grain size on the limit stresses can be described by the inverse Hall–Petch equation. This study is helpful for tailoring the mechanical properties of MICP by the morphology of nanocrystalline calcite.
Real-World Adoption of Mental Health Support Among Adolescents: Cross-Sectional Analysis of the California Health Interview Survey
Authors: Zhao Xin , Schueller Stephen M , Kim Jeongmi , Stadnick Nicole A , Eikey Elizabeth , Schneider Margaret , Zheng Kai , Mukamel Dana B , Sorkin Dara H
Published: November 2023

Objective

We aim to examine: (a) the extent to which patterns of adoption of counseling services and digital mental health interventions (DMHIs) shifted in recent years (2019–2021); (b) the impact of distress on adoption of mental health support; and (c) reasons related to adolescents’ low adoption of DMHIs when experiencing distress.

Methods

Data were from three cohorts of adolescents aged 12–17 years (n = 847 in 2019; n = 1,365 in 2020; n = 1,169 in 2021) recruited as part of the California Health Interview Survey. We estimated logistic regression models to examine the likelihood of using mental health support as a function of psychological distress, sociodemographic characteristics, and cohorts. We also analyzed adolescents’ self-reported reasons for not trying DMHIs as a function of distress.

Results

The proportion of adolescents reporting elevated psychological distress (∼50%) was higher than those adopting counseling services (<20%) or DMHIs (<10%). A higher level of distress was associated with a greater likelihood of receiving counseling (OR = 1.15), and using DMHIs to connect with a professional (Odds ratio (OR) = 1.11) and for self-help (OR = 1.17). Among those experiencing high distress, adolescents’ top reason for not adopting an online tool was a lack of perceived need (19.2%).

Conclusion

Adolescents’ main barriers to DMHI adoption included a lack of perceived need, which may be explained by a lack of mental health literacy. Thoughtful marketing and dissemination efforts are needed to increase mental health awareness and normalize adoption of counseling services and DMHIs.
Invasive Group A Streptococcus in Infants Less Than 1-year of Age From 2012 to 2022: A Single-Center Experience
Authors: Nack Taylor , Vallejo Jesus G , Dunn James , Flores Anthony R , McNeil J Chase
Published: November 2023

The incidence of invasive Group A Streptococcus (iGAS) has varied throughout the COVID-19 pandemic. We reviewed iGAS infections in infants ≤1 year from 2012 to 2022. Twenty-five percent of cases occurred in the last quarter of 2022. Pneumonia (21.8%) was the most common presentation. Twenty-one patients (65.6%) were successfully transitioned to oral antibiotics.
Improving Donor Imputation Using the Prediction Power of Random Forests: a Combination of SwissCheese and missForest
Authors: Tripet Arnaud , Eustache Esther , Tillé Yves
Published: November 2023

Imputation procedures are frequently used to treat nonresponse. With random hot deck imputation, missing values are replaced by valid observed values from other units in the same dataset. The recently developed balanced nearest neighbor imputation method, implemented in the SwissCheese R package, generates random hot deck imputation under certain balancing constraints to decrease the variance of the total estimator, in the presence of multivariate nonresponse. The method relies on a notion of neighborhood between units, utilizing a distance measure that becomes difficult to define in high dimensions. In contrast to hot deck imputation methods, many imputation procedures obtain replacement values from prediction models fit from observed data. The missForest method, which uses random forests as prediction models, is an example of this approach. In this article, we propose a new approach that uses the two methods in a complementary manner. We refine the distance measure in the SwissCheese method using missForest predictions. Through a simulation study on empirical data from the Swiss Survey on Income and Living Conditions, we demonstrate reductions in Monte Carlo variance, bias, and mean squared error of the totals obtained by our proposed imputed estimator compared to those obtained using SwissCheese alone.
Compact stars with dark matter induced anisotropy in complexity-free background and effect of dark matter on GW echoes
Authors: Maurya S K , Singh Ksh Newton , Aziz Abdul , Ray Saibal , Mustafa Ghulam
Published: November 2023

In this work, we consider the vanishing complexity factor scenario which has opened up a whole new way of generating solutions to the Einstein field equations for the spherically symmetric structure of celestial bodies. By using this very rare condition on the system of two metric potentials, viz. gtt and grr, we make reduce it to a uni-metric potential system satisfying all physical conditions. Along with this, we further have considered that the space–time is deformed by dark matter (DM) content in DM haloes resulting into perturbations in the gtt and grr metric potentials. This DM deformation is mathematically done by the complete geometric decoupling method where the decoupling parameter β decides the amount of DM content. In connection to the claimed post-merger object in the GW170817 event we have argued that if these compact stars were in galactic DM haloes with the assumption that the radius remains the same, the compactness factor can grow within the range 1/3 to 4/9 and therefore can generate gravitational waves (GW) echoes. Additionally, we have presented effect of β on the generation of GW echoes in accordance with the observational constraints related to the compact stars GW190814, PSR J0740+6620, PSR J1614−2230, Cen X-3, and LMC X-4.
Exploring the multiband gravitational wave background with a semi-analytic galaxy formation model
Authors: Li Zhencheng , Jiang Zhen , Fan Xi-Long , Chen Yun , Gao Liang , Guo Qi , Yu Shenghua
Published: November 2023

An enormous number of compact binary systems, spanning from stellar to supermassive levels, emit substantial gravitational waves during their final evolutionary stages, thereby creating a stochastic gravitational wave background (SGWB). We calculate the merger rates of stellar compact binaries and massive black hole binaries using a semi-analytic galaxy formation model – Galaxy Assembly with Binary Evolution (GABE) – in a unified and self-consistent approach, followed by an estimation of the multiband SGWB contributed by those systems. We find that the amplitudes of the principal peaks of the SGWB energy density are within one order of magnitude ΩGW ∼ 10−9–10−8. This SGWB could easily be detected by the Square Kilometre Array (SKA), as well as by the planned interferometric detectors, such as the Einstein Telescope and the Laser Interferometer Space Antenna (LISA). The energy density of this background varies as ΩGW ∝ f2/3 in the SKA band. The shape of the SGWB spectrum in the frequency range ∼[10−4,1] Hz could allow the LISA to distinguish the black hole seed models. The amplitude of the SGWB from merging stellar binary black holes at ∼100 Hz is approximately 10 and 100 times greater than those from merging binary neutron stars and neutron-star–black-hole mergers, respectively. Note that, since the cosmic star formation rate density predicted by GABE is somewhat lower than the observational results by ∼0.2 dex at z < ∼2, the amplitude of the SGWB in the frequency range ∼[1, 104] Hz may be underestimated by a similar factor at most.
Mergers of black hole binaries driven by misaligned circumbinary discs
Authors: Martin Rebecca G , Lepp Stephen , Zhang Bing , Nixon C J , Childs Anna C
Published: November 2023

With hydrodynamical simulations we examine the evolution of a highly misaligned circumbinary disc around a black hole binary including the effects of general relativity. We show that a disc mass of just a few per cent of the binary mass can significantly increase the binary eccentricity through von-Zeipel–Kozai–Lidov (ZKL) like oscillations provided that the disc lifetime is longer than the ZKL oscillation time-scale. The disc begins as a relatively narrow ring of material far from the binary and spreads radially. When the binary becomes highly eccentric, disc breaking forms an inner disc ring that quickly aligns to polar. The polar ring drives fast retrograde apsidal precession of the binary that weakens the ZKL effect. This allows the binary eccentricity to remain at a high level and may significantly shorten the black hole merger time. The mechanism requires the initial disc inclination relative to the binary to be closer to retrograde than to prograde.
Cerebral venous thrombosis: a practical review
Authors: Borhani-Haghighi Afshin , Hooshmandi Etrat
Published: November 2023

The evolution of the Coronavirus Disease-2019 pandemic and its vaccination raised more attention to cerebral venous thrombosis (CVT). Although CVT is less prevalent than arterial stroke, it results in larger years of life lost. CVT is more common in women and young patients. Predisposing factors are categorized as transient factors such as pregnancy, puerperium, oral contraceptive pills, trauma, and dehydration; and permanent factors such as neoplastic, vasculitic, thrombophilic, hematologic conditions, infectious causes such as severe acute respiratory syndrome coronavirus-2 infection and HIV. The most common manifestations are headache, seizures, focal neurologic deficits, altered level of consciousness, and cranial nerve palsies. The most common syndromes are stroke-like, raised-intracranial-pressure (ICP), isolated-headache, and encephalopathy, which may have overlaps. Diagnosis is mostly based on computed tomography, magnetic resonance imaging, and their respective venous sequences, supported by blood results abnormalities such as D-dimer elevation. Treatment includes the prevention of propagation of current thrombus with anticoagulation (heparin, or low molecular weight heparinoids and then warfarin, or direct oral anticoagulants), decreasing ICP (even by decompressive craniotomy), and treatment of specific underlying diseases.
Studying the impact of deuteron non-elastic breakup on 93Zr + d reaction cross sections measured at 28 MeV/nucleon
Authors: Chillery Thomas , Hwang Jongwon , Dozono Masanori , Imai Nobuaki , Michimasa Shin’ichiro , Sumikama Toshiyuki , Chiga Nobuyuki , Ota Shinsuke , Nakayama Shinsuke , Ahn Deuk Soon , Beliuskina Olga , Chikaato Kazuya , Fukuda Naoki , Hayakawa Seiya , Ideguchi Eiji , Iribe Kotaro , Iwamoto Chihiro , Kawase Shoichiro , Kawata Keita , Kitamura Noritaka , Kusaka Kensuke , Masuoka Shoichiro , Miki Hareru , Miyatake Hiroari , Nagae Daisuke , Nakajima Ryo , Nakano Keita , Ohtake Masao , Omika Shunichiro , Ong Hooi Jin , Otsu Hideaki , Sakurai Hiroyoshi , Schrock Philipp , Shimizu Hideki , Shimizu Yohei , Sun Xiaohui , Suzuki Daisuke , Suzuki Hiroshi , Takaki Motonobu , Takechi Maya , Takeda Hiroyuki , Takeuchi Satoshi , Teranishi Takashi , Tsunoda Rieko , Wang He , Watanabe Yukinobu , Watanabe Yutaka X , Wimmer Kathrin , Yako Kentaro , Yamada Hiroki , Yamada Kazunari , Yamaguchi Hidetoshi , Yang Lei , Yanagihara Rikuto , Yanagisawa Yoshiyuki , Yoshida Hiroya , Yoshida Koichi , Shimoura Susumu
Published: November 2023

The deuteron is a loosely bound system that can easily break up into its constituent proton and neutron whilst in the presence of Coulomb and nuclear fields. Previous experimental studies have shown that this breakup process has a significant impact on residual-nucleus production from deuteron bombardment in the high-energy range of 50–210 MeV/nucleon. However, there remains a lack of cross-section data at energies below 50 MeV/nucleon. The current study determined 93Zr + d reaction cross sections under inverse kinematics at approximately 28 MeV/nucleon using the BigRIPS separator, OEDO beamline, and SHARAQ spectrometer. Cross sections from this research were compared with previous measurements and theoretical calculations. The experimental results show a large enhancement of the production cross sections of residual nuclei, especially those produced from a small number of particle emissions, compared to the proton-induced reaction data at similar bombarding energy. The DEURACS calculation, which quantitatively takes deuteron-breakup effects into account, reproduces the data well. As a long-lived fission product, 93Zr remains a challenge for nuclear-waste disposal and treatment. This study’s low-energy data may assist future consideration of nuclear-waste treatment facilities, where 93Zr + d may feasibly transmute the waste into short-lived/stable nuclei.
Neural tracking of social hierarchies in adolescents’ real-world social networks
Authors: Dai Junqiang , Jorgensen Nathan A , Duell Natasha , Capella Jimmy , Maza Maria T , Kwon Seh-Joo , Prinstein Mitchell J , Lindquist Kristen A , Telzer Eva H
Published: November 2023

In the current study, we combined sociometric nominations and neuroimaging techniques to examine adolescents’ neural tracking of peers from their real-world social network that varied in social preferences and popularity. Adolescent participants from an entire school district (N = 873) completed peer sociometric nominations of their grade at school, and a subset of participants (N = 117, Mage = 13.59 years) completed a neuroimaging task in which they viewed peer faces from their social networks. We revealed two neural processes by which adolescents track social preference: (1) the fusiform face area, an important region for early visual perception and social categorization, simultaneously represented both peers high in social preference and low in social preference; (2) the dorsolateral prefrontal cortex (DLPFC), which was differentially engaged in tracking peers high and low in social preference. No regions specifically tracked peers high in popularity and only the inferior parietal lobe, temporoparietal junction, midcingulate cortex and insula were involved in tracking unpopular peers. This is the first study to examine the neural circuits that support adolescents’ perception of peer-based social networks. These findings identify the neural processes that allow youths to spontaneously keep track of peers’ social value within their social network.
Associations Between Structural Covariance Network and Antipsychotic Treatment Response in Schizophrenia
Authors: Tsugawa Sakiko , Honda Shiori , Noda Yoshihiro , Wannan Cassandra , Zalesky Andrew , Tarumi Ryosuke , Iwata Yusuke , Ogyu Kamiyu , Plitman Eric , Ueno Fumihiko , Mimura Masaru , Uchida Hiroyuki , Chakravarty Mallar , Graff-Guerrero Ariel , Nakajima Shinichiro
Published: November 2023

Background and Hypothesis

Schizophrenia is associated with widespread cortical thinning and abnormality in the structural covariance network, which may reflect connectome alterations due to treatment effect or disease progression. Notably, patients with treatment-resistant schizophrenia (TRS) have stronger and more widespread cortical thinning, but it remains unclear whether structural covariance is associated with treatment response in schizophrenia.

Study Design

We organized a multicenter magnetic resonance imaging study to assess structural covariance in a large population of TRS and non-TRS, who had been resistant and responsive to non-clozapine antipsychotics, respectively. Whole-brain structural covariance for cortical thickness was assessed in 102 patients with TRS, 77 patients with non-TRS, and 79 healthy controls (HC). Network-based statistics were used to examine the difference in structural covariance networks among the 3 groups. Moreover, the relationship between altered individual differentiated structural covariance and clinico-demographics was also explored.

Study Results

Patients with non-TRS exhibited greater structural covariance compared with HC, mainly in the fronto-temporal and fronto-occipital regions, while there were no significant differences in structural covariance between TRS and non-TRS or HC. Higher individual differentiated structural covariance was associated with lower general scores of the Positive and Negative Syndrome Scale in the non-TRS group, but not in the TRS group.

Conclusions

These findings suggest that reconfiguration of brain networks via coordinated cortical thinning is related to treatment response in schizophrenia. Further longitudinal studies are warranted to confirm if greater structural covariance could serve as a marker for treatment response in this disease.
The accumulation–metabolism nexus: internationalization, labour–capital relations, and material flows of French capitalism since the post-war era
Authors: Cahen-Fourot Louison , Magalhães Nelo
Published: November 2023

We investigate the links between accumulation and socio-metabolic regimes by studying French capitalism from socio-economic and material perspectives since 1948. We characterize its social metabolism both in domestic and footprint approaches. The periodization of accumulation regimes in terms of Fordism and finance-led capitalism translates into material terms. The offshore materiality of finance-led capitalism partly substitutes for and partly complements the more domestic materiality inherited from Fordism. The transition phase between the two socio-metabolic regimes clearly corresponds to the emergence of the offshoring–financialization nexus of French capitalism, indicating the shift from Fordism to finance-led capitalism. We highlight strong inter-linkages between accumulation and material dynamics and discuss how materials may be instrumental in shaping accumulation regimes. We therefore introduce the concept of accumulation–metabolism nexus. This work illustrates the relevance of combining institutionalist macroeconomics with Material Flow Analysis.
Christian Nationalism and Opposition to Reallocating Police Funding to Other Social Services
Authors: Liberman Jessica , Lehman Derek , Kawakami Atsuko
Published: November 2023

In the wake of several high-profile cases of police use of excessive force, renewed critiques of policing have emerged from the Defund the Police movement. Yet, the movement has faced fierce opposition from Americans who subscribe to a color-blind logic that racial inequality in policing and society as a whole reflect differences in merit. In assessing Americans’ use of color-blind racism, support for public spending on social services, and support for punitive social control, scholars have recently emphasized the role of Christian nationalist ideology. Building on this recent work, we use data from the 2021 General Social Survey (GSS), a nationally representative survey of Americans, to test the relationship between adherence to Christian nationalist ideology and opposition to reducing funding for police departments and moving those funds to mental health, housing, and other social services. We find that respondents who score higher on an index of Christian nationalism hold greater odds of opposing shifting funding from police departments, independent of other measures of political and religious orientations. We also consider interactions between Christian nationalist ideology, race, and color-blind racial ideology.
HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies
Authors: Zhang Hang , Bull Rowena A , Quadeer Ahmed Abdul , McKay Matthew R
Published: November 2023

The Hepatitis C virus (HCV) envelope glycoprotein E1 forms a non-covalent heterodimer with E2, the main target of neutralizing antibodies. How E1–E2 interactions influence viral fitness and contribute to resistance to E2-specific antibodies remain largely unknown. We investigate this problem using a combination of fitness landscape and evolutionary modeling. Our analysis indicates that E1 and E2 proteins collectively mediate viral fitness and suggests that fitness-compensating E1 mutations may accelerate escape from E2-targeting antibodies. Our analysis also identifies a set of E2-specific human monoclonal antibodies that are predicted to be especially resilient to escape via genetic variation in both E1 and E2, providing directions for robust HCV vaccine development.
Suicide Ideation and Attempt Among People With HIV: A Statewide Population-level Cohort Analysis Between 2005 and 2020
Authors: Mi Tianyue , Zhang Jiajia , Yang Xueying , Chen Shujie , Weissman Sharon , Olatosi Bankole , Li Xiaoming
Published: November 2023

Background:

Risk factors for suicidality among people with HIV (PWH) may evolve over their disease course, particularly as they develop comorbidities such as mental health disorders over time.

Setting:

This study compared the leading risk factors of suicide ideation/attempt among PWH in South Carolina across different combination antiretroviral therapy (cART) eras.

Methods:

A statewide cohort of PWH who were diagnosed between 2005 and 2016, with a follow-up record until 2020, was involved in the study. A Cox proportional hazards model was used to examine the association of suicide ideation/attempt and predictors, including demographics, HIV-related characteristics, and mental health conditions.

Results:

Among 8567 PWH, the incidence of suicide ideation/attempt increased from 537.7 per 100,000 person-years [95% confidence interval (CI): 460.2 to 615.1] in the early cART cohort (2005–2008) to 782.5 (95% CI: 697.6 to 867.4) in the late cART cohort (2009–2016). Leading risk factors of suicide ideation/attempt changed across the cART cohort. In the early cART cohort, PWH with suicide ideation/attempt were more likely to be White and diagnosed with bipolar disorder (P’s < 0.05). In the late cART cohort, suicide ideation/attempt was positively associated with transmission through injection drug use, anxiety, posttraumatic stress disorder, schizophrenia, and personality disorder (P’s < 0.05).

Conclusions:

Mental health conditions have emerged as more prominent risk factors for suicide ideation/attempt in the late cART cohort. Enhanced access to psychiatric care could facilitate the early identification of mental health conditions, enabling timely counseling or psychosocial interventions that may mitigate mental health issues and, consequently, reduce the likelihood of suicide ideation/attempts among PWH.
Factors Associated With Antiretroviral Adherence Among Youth Living With HIV
Authors: Arnold Elizabeth Mayfield , Kamal Susan , Rotheram-Borus Mary Jane , Bridges S. Kate , Gertsch William , Norwood Peter , Swendeman Dallas ,   the Adolescent Medicine Trials Network (ATN) CARES Team
Published: November 2023

Background:

Youth living with HIV (YLH) have an increased risk for psychosocial stressors that can affect their antiretroviral (ARV) adherence. We examined factors associated with self-reported ARV adherence among YLH ages 12–24 years old.

Setting:

YLH (N = 147) were recruited in Los Angeles, CA, and New Orleans, LA from 2017 to 2020.

Methods:

YLH whose self-reported recent (30 days) ARV adherence was “excellent” or “very good” were compared with nonadherent YLH on sociodemographic, clinical, and psychosocial factors using univariate and multivariate analyses.

Results:

Participants were predominantly male (88%), and 81% identified as gay, bisexual, transgender, queer, or other. The mean duration on ARV was 27 months (range 0–237 months). Most YLH (71.2%) self-reported being adherent, and 79% of those who self-reported adherence were also virally suppressed (<200 copies/mL). Multivariate analysis indicated being adherent was significantly associated with white race [aOR = 8.07, confidence intervals (CI): 1.45 to 74.0], Hispanic/Latinx ethnicity [aOR = 3.57, CI: 1.16 to 12.80], more social support [aOR = 1.11, CI: 1.05 to 1.18], and being on ARV for a shorter duration [aOR = 0.99, CI: 0.97 to 0.99]. Mental health symptoms, substance use, age, and history of homelessness or incarceration were unrelated to adherence.

Conclusions:

Enhancing efforts to provide support for adherence to non-white youth, and those with limited social support and who have been on ARV treatment longer, may help increase viral suppression among YLH.
Text-message based assessment of 90-day modified Rankin Scale after Stroke
Authors: Abbasi Mohammad Hossein , Yuan Kristy , Kasner Scott E. , McPartland Ellen , Owens Karrima C. , Sloane Kelly L.
Published: November 2023

Background

The modified Rankin scale (mRS) is commonly used to measure disability after stroke, traditionally assessed through telephone or in-person evaluation. Here, we investigated the validity of mRS assessment through automated text-messaging as an alternative method to traditional assessments.

Methods

Two hundred and fifty patients admitted to 3 hospitals within the University of Pennsylvania Health System with ischemic or hemorrhagic stroke were enrolled. Participants received automated text-messages sent 48 hours prior to their outpatient appointment at about 90-days post-stroke. The mRS scores were assigned based on participant responses to 2-4 text questions eliciting yes/no responses. The mRS was then evaluated in-person or by telephone interview for comparison. Responses were compared with kappa(κ).

Results

One hundred and forty-two patients (57%) completed the study. Spontaneous response rate to text messages was 46% and up to 72% with an additional direct in-person or phone call reminder. Agreement was substantial (quadratic-weighted κ=0.87) between responses derived from the automated text messaging and traditional interviews. Agreement for distinguishing functional independence (mRS 0-2) from dependence (mRS 3-5) was substantial (unweighted κ=0.79).

Conclusion

An automated text messaging system is a feasible and highly reliable for determining mRS and can serve as an alternative to traditional in-person or telephone assessment.
Diagnostic efficacy of hand-held digital refractometer for determining total serum protein in indigenous sheep of Pakistan
Authors: Sharif Madiha , Lashari Mushtaq Hussain , Farooq Umer , Idris Musadiq , Afzal Muhaammad Abrar
Published: November 2023

The study was designed to ascertain the diagnostic efficacy of hand-held digital refractometer in determining total protein. The Sipli sheep (n=141) were grouped as per gender (females=99, males=29) and age (G1=up till 1 year, G2=from 1 to 2 years, G3=above 2 years). The results regarding the overall mean (±SE) values and RIs for the TPs attained through serum chemistry analyzer (TP1) and hand-held digital refractometer (TP2) were non-significantly (P≤0.05) different (59.2±1.6g/L and 59.8±0.5g/L, respectively). However, the RIs were quite different between the two TPs being 45.1-95.7g/L and 57.0-67.0g/L for TP1 and TP2, respectively. Similar results were seen for gender-wise and group-wise results. On the contrary, the results regarding correlation coefficient and logilinear regression showed a negative correlation between the two TPs (r=-0.0244) with an adjusted r-square of 0.059 (5.9% probability). Furthermore, the results for Cronbach alpha and intraclass correlation coefficient between TP1 and TP2 showed that the values for single measure and average values were lower between TP1 and TP2 being - 0.135 and −0.313. Bland and Altman test between TP1 and TP2 also showed a weak level of agreement between the two methods of detecting TP. A proportional bias on the distribution of data around the mean difference line was noticed between TP1 and TP2 (Mean= 0.5; 95% CI= 39.8 to −40.9) with a standard deviation of biasness being 20.58. In a nutshell, the hand-held digital refractometer cannot be used as an on-farm POCT device for determining serum TP in sheep. However, certain other models of refractometers with higher sensitivity and specificity may be utilized in future studies to establish these conclusions for other species of livestock.
PD-1 signaling uncovers a pathogenic subset of T cells in inflammatory arthritis
Authors: Straube Johanna , Bukhari Shoiab , Lerrer Shalom , Winchester Robert , Henick Brian , Dragovich Matthew , Mor Adam
Published: November 2023

Background

PD-1 is an immune checkpoint on T cells and interventions to block this receptor result in T cell activation and enhanced immune response to tumors. Paired to that, and despite a decade of research, approaches to treat autoimmunity with PD-1 agonists still need to be more successful. To resolve this, new methods must be developed to augment PD-1 function beyond engaging the receptor.

Methods

We conducted a flow cytometry analysis of T cells isolated from the peripheral blood and synovial fluid of patients with rheumatoid arthritis. In addition, we performed a genome-wide CRISPR/Cas9 screen to identify genes associated with PD-1 signaling. We further analyzed genes involved in PD-1 signaling using publicly available bulk and single-cell RNA sequencing datasets.

Results

Our screen confirmed known regulators in proximal PD-1 signaling and, importantly, found an additional 1,112 unique genes related to PD-1 ability to inhibit T cell functions. These genes were strongly associated with the response of cancer patients to PD-1 blockades and with high tumor immune dysfunction and exclusion scores, confirming their role downstream of PD-1. Functional annotation revealed that more significant genes uncovered were those associated with known immune regulation processes. Remarkably, these genes were considerably downregulated in T cells isolated from patients with inflammatory arthritis, supporting their overall inhibitory functions. A study of rheumatoid arthritis single-cell RNA sequencing data demonstrated that five genes, KLRG1, CRTAM, SLAMF7, PTPN2, and KLRD1, were downregulated in activated and effector T cells isolated from synovial fluids. Back-gating these genes to canonical cytotoxic T cell signatures revealed PD-1+HLA-DRHIGHKLRGLOWT cells as a novel inflammatory subset of T cells.

Conclusion

We concluded that PD-1+HLA-DRHIGHKLRGLOWT cells are a potential target for future PD-1 agonists to treat inflammatory diseases. Our study uncovers new genes associated with PD-1 downstream functions and, therefore, provides a comprehensive resource for additional studies that are much needed to characterize the role of PD-1 in the synovial subset of T cells.
Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response
Authors: Nyirenda James , Hardy Olympia , Da Silva Filho João , Herder Vanessa , Attipa Charalampos , Ndovi Charles , Siwombo Memory , Namalima Takondwa , Suwedi Leticia , Nyasulu Watipenge , Ngulube Thokozile , Nyirenda Deborah , Mvaya Leonard , Phiri Joseph , Chasweka Dennis , Eneya Chisomo , Makwinja Chikondi , Phiri Chisomo , Ziwoya Frank , Tembo Abel , Makwangwala Kingsley , Khoswe Stanley , Banda Peter , Morton Ben , Hilton Orla , Lawrence Sarah , dos Reis Monique Freire , Melo Gisely Cardoso , de Lacerda Marcus Vinicius Guimaraes , Costa Fabio Trindade Maranhão , Monteiro Wuelton Marcelo , de Lima Ferreira Luiz Carlos , Johnson Carla , McGuinness Dagmara , Jambo Kondwani , Haley Michael , Kumwenda Benjamin , Palmarini Massimo , Barnes Kayla G. , Denno Donna M. , Voskuijl Wieger , Kamiza Steve , Couper Kevin , Marti Matthias , Otto Thomas , Moxon Christopher A.
Published: November 2023

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19 but there is almost no data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. We used histology and high-dimensional imaging to characterise fatal lung disease in Malawian adults with (n=9) and without (n=7) Covid19, and generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved Covid19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in the Malawi cohort, by response to interferon-gamma (IFN-γ) in lung-resident alveolar macrophages, in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes. HIV status had minimal impact on histology or immunopathology. Our study provides data resources and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.
An enzyme activation network provides evidence for extensive regulatory crosstalk between metabolic pathways
Authors: Al Zubaidi Sultana Mohammed , Nasar Muhammad Ibtisam , Ralser Markus , Notebaart Richard A. , Alam Mohammad Tauqeer
Published: November 2023

Enzyme activation by cellular metabolites plays a pivotal role in regulating metabolic processes. Nevertheless, our comprehension of such activation events on a global network scale remains incomplete. In this study, we conducted a comprehensive investigation into the optimization of cell-intrinsic activation interactions withinSaccharomyces cerevisiae. To achieve this, we integrated a genome-scale metabolic model with enzyme kinetic data sourced from the BRENDA database. Our objective was to map the distribution of enzyme activators throughout the cellular network. Our findings indicate that virtually all biochemical pathways encompass enzyme activators, frequently originating from disparate pathways, thus revealing extensive regulatory crosstalk between metabolic pathways. Indeed, activators have short pathway lengths, indicating they are activated quickly upon nutrient shifts, and in most instances, these activators target key enzymatic reactions to facilitate downstream metabolic processes. Interestingly, non-essential enzymes exhibit a significantly higher degree of activation compared to their essential counterparts. This observation suggests that cells employ enzyme activators to finely regulate secondary metabolic pathways that are only required under specific conditions. Conversely, the activator metabolites themselves are more likely to be essential components, and their activation levels surpass those of non-essential activators. In summary, our study unveils the widespread importance of enzymatic activators, and suggests that feed-forward activation of conditional metabolic pathways through essential metabolites mediates metabolic plasticity.
Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling
Authors: Saunders Nell , Monel Blandine , Cayet Nadège , Archetti Lorenzo , Moreno Hugo , Jeanne Alexandre , Marguier Agathe , Wai Timothy , Schwartz Olivier , Fréchin Mathieu
Published: November 2023

Assessing the impact of SARS-CoV-2 on organelle dynamics allows a better understanding of the mechanisms of viral replication. We combine label-free holo-tomographic microscopy (HTM) with Artificial Intelligence (AI) to visualize and quantify the subcellular changes triggered by SARS-CoV-2 infection. We study the dynamics of shape, position and dry mass of nucleoli, nuclei, lipid droplets (LD) and mitochondria within hundreds of single cells from early infection to syncytia formation and death. SARS-CoV-2 infection enlarges nucleoli, perturbs LD, changes mitochondrial shape and dry mass, and separates LD from mitochondria. We then used Bayesian statistics on organelle dry mass states to define organelle cross-regulation (OCR) networks and report modifications of OCR that are triggered by infection and syncytia formation. Our work highlights the subcellular remodeling induced by SARS-CoV-2 infection and provides a new AI-enhanced, label-free methodology to study in real-time the dynamics of cell populations and their content.
Human microbiota is a reservoir of SARS-CoV-2 advantageous mutations
Authors: Cao Birong , Wang Xiaoxi , Yin Wanchao , Gao Zhaobing , Xia Bingqing
Published: November 2023

SARS-CoV-2 mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape, are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we show that the human microbiota may contribute to mutations in variants of concern (VOCs). We identified a mutation and adjacent 6 amino acids (aa) in a viral mutation fragment (VMF) and searched for homologous fragments (HFs) in the National Center for Biotechnology Information (NCBI) database. Among the approximate 8000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is a 12-fold higher than the natural variable proportion. Approximately 70% of these bacterial species belong to the human microbiota, are primarily distributed in the gut or lung and exhibit a composition pattern similar to that of COVID-19 patients. Importantly, SARS- CoV-2 RNA-dependent RNA polymerase (RdRp) replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. Collectively, SARS-CoV-2 may acquire mutations from the human microbiota, resulting in alterations in the binding sites or antigenic determinants of the original virus. Our study sheds light on the evolving mutational mechanisms of SARS-CoV-2.
Insulin at the Intersection of Thermoregulation and Glucose Homeostasis
Authors: Winn Nathan C. , Schleh Michael W. , Garcia Jamie N. , Lantier Louise , McGuinness Owen P. , Blair Joslin A. , Hasty Alyssa H. , Wasserman David H.
Published: November 2023

Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which are fundamental for thermogenic processes. The purpose of this work was to determine the interaction of ambient temperature induced changes in energy expenditure (EE) on the insulin sensitivity of glucose fluxes. Short-term and adaptive responses to thermoneutral temperature (TN, ∼28°C) and room (laboratory) temperature (RT, ∼22°C) were studied in mice. This range of temperature does not cause detectable changes in circulating catecholamines or shivering and postabsorptive glucose homeostasis is maintained. We tested the hypothesis that a decrease in EE that occurs with TN causes insulin resistance and that this reduction in insulin action and EE is reversed upon short term (<12h) transition to RT. Insulin-stimulated glucose disposal (Rd) and tissue specific glucose uptake were assessed combining isotopic tracers with hyperinsulinemic-euglycemic clamps. EE and insulin-stimulated Rd are both decreased (∼50%) in TN-adapted vs RT-adapted mice. When RT-adapted mice are switched to TN, EE rapidly decreases and Rd is reduced by ∼50%. TN-adapted mice switched to RT exhibit a rapid increase in EE, but whole body insulin-stimulated Rd remains at the low rates of TN-adapted mice. In contrast, whole body glycolytic flux rose with EE. This higher EE occurs without increasing glucose uptake from the blood, but rather by diverting glucose from glucose storage to glycolysis. In addition to adaptations in insulin action, ‘insulin-independent’ glucose uptake in brown fat is exquisitely sensitive to thermoregulation. These results show that insulin action adjusts to non-stressful changes in ambient temperature to contribute to the support of body temperature homeostasis without compromising glucose homeostasis.

Highlights

Energy expenditure and insulin-mediated glucose fluxes are reduced in thermoneutral (TN)-adapted mice versus room ‘laboratory’ temperature (RT)-adapted mice.

Reduced insulin sensitivity manifests in TN mice regardless of whether they are TN-adapted or short-term transitioned from RT-adapted to TN.

TN-adapted mice are resistant to the RT-induced increase in whole-body insulin sensitivity even though metabolic rate is increased.

TN-adapted mice switched to RT meets increased thermogenic needs, not by increasing glucose uptake, but by partitioning a greater fraction of glucose from glycogen storage to glycolysis.

Brown fat glucose uptake sensitively increases with RT and decreases with TN by an insulin-independent mechanism.
Flowtigs: safety in flow decompositions for assembly graphs
Authors: Sena Francisco , Ingervo Eliel , Khan Shahbaz , Prjibelski Andrey , Schmidt Sebastian , Tomescu Alexandru I.
Published: November 2023

Adecompositionof a network flow is a set of weighted paths whose superposition equals the flow. The problem of characterising and computing safe walks for flow decompositions has so far seen only a partial solution by restricting the flow decomposition to consist of paths, and the graph to be directed and acyclic (DAG). However, the problem of decomposing into closed walks in a general graph (allowing cycles) is still open.

In this paper, we give a simple and linear-time-verifiable complete characterisation (flowtigs) of walks that aresafein such general flow decompositions, i.e. that are subwalks of any possible flow decomposition. Our characterisation generalises over the previous one for DAGs, using a more involved proof of correctness that works around various issues introduced by cycles. We additionally provide an optimalO(mn)-time algorithm that identifies all maximal flowtigs and represents them inside a compact structure. We also implement this algorithm and show that it is very fast in practice.

On the practical side, we study flowtigs in the use-case of metagenomic assembly. By using the species abundances as flow values of the metagenomic assembly graph, we can model the possible assembly solutions as flow decompositions into weighted closed walks.

Compared to reporting unitigs or maximal safe walks based only on the graph structure (structural contigs), reporting flowtigs results in a notably more contiguous assembly. Specifically, on shorter contigs (75-percentile), we get an improvement in assembly contiguity of up to 99% over unitigs, and on the 50-percentile of contiguity we get an improvement of up to 17% over unitigs. These improvements that flowtigs bring over unitigs are 4–14× larger that what structural contigs bring over unitigs.
Sexually dimorphic role of diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus
Authors: Shetty Sanutha , Duesman Samuel J. , Patel Sanil , Huyhn Pacific , Shroff Sanjana , Das Anika , Chowhan Disha , Sebra Robert , Beaumont Kristin , McAlpine Cameron S. , Rajbhandari Prashant , Rajbhandari Abha K.
Published: November 2023

Scientific evidence underscores the influence of biological sex on the interplay between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress jointly contribute to metabolic dysregulation in both males and females. To address this gap, our study aimed to investigate the combined effects of a high-fat diet (HFD) and repeated footshock stress on fear-related behaviors and metabolic outcomes in male and female mice. Using a robust rodent model that recapitulates key aspects of post-traumatic stress disorder (PTSD), we subjected mice to footshock stressor followed by weekly reminder footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. Our findings revealed that HFD impaired fear memory extinction in male mice that received initial stressor but not in female mice. Blood glucose levels were influenced by both diet and sex, with HFD-fed female mice displaying elevated levels that returned to baseline in the absence of stress, a pattern not observed in male mice. Male mice on HFD exhibited higher energy expenditure, while HFD-fed female mice showed a decreased respiratory exchange ratio (RER). Sex-specific alterations in pro-inflammatory markers and abundance of hematopoietic stem cells were observed in chronically stressed mice on an HFD in different peripheral tissues, indicating the manifestation of distinct comorbid disorders. Single-nuclei RNA sequencing of the ventromedial hypothalamus from stressed mice on an HFD provided insights into sex-specific glial cell activation and cell-type-specific transcriptomic changes. In conclusion, our study offers a comprehensive understanding of the intricate interactions between stress, diet, sex, and various physiological and behavioral outcomes, shedding light on a potential brain region coordinating these interactions.
Mapping responses to focal injections of bicuculline in the lateral parafacial region identifies core regions for maximal generation of active expiration
Authors: Pisanski Annette , Prostebby Mitchell , Dickson Clayton T. , Pagliardini Silvia
Published: November 2023

The lateral parafacial area (pFL) is a crucial region involved in respiratory control, particularly in generating active expiration through an expiratory oscillatory network. Active expiration involves rhythmic abdominal (ABD) muscle contractions during late-expiration, increasing ventilation during elevated respiratory demands. The precise anatomical location of the expiratory oscillator within the ventral medulla’s rostro-caudal axis is debated. While some studies point to the caudal tip of the facial nucleus (VIIc) as the oscillator’s core, others suggest more rostral areas. Our study employed bicuculline (a GABA-A receptor antagonist) injections at various pFL sites (-0.2 to +0.8mm from VIIc) to investigate the impact of GABAergic disinhibition on respiration. These injections consistently elicited ABD recruitment, but the response strength varied along the rostro-caudal zone. Remarkably, the most robust and enduring changes in tidal volume, minute ventilation and combined respiratory responses occurred at more rostral pFL locations (+0.6/+0.8 mm from VIIc). Multivariate analysis of the respiratory cycle further differentiated between locations, revealing the core site for active expiration generation. Our study advances our understanding of neural mechanisms governing active expiration and emphasizes the significance of investigating the rostral pFL region.