bluuebunny/crossref_metadata_2025 huggingface dataset:
An Adaptive Decoupling Register Control Method for Roll-to-Roll Printing Systems
Authors: Zhang Tao , He Zhanpeng , Zheng Ying , Chen Zhihua
Published: August 2023

Model-based decoupling control methods have been widely used in the register control of Roll-to-Roll (R2R) printing systems due to their advantage in dealing with couplings. While they achieve a certain decoupling effect, their registrations are influenced by the accuracy of the model and decoupling compensation. In this paper, a hybrid model is presented to calculate an appropriate compensation to eliminate the complex velocity-error relations in the R2R system, which consists of a general register error model and a data-based supplement model. Then, an adaptive decoupling control (ADC) method is proposed, in which the feedback gains are determined by solving a Riccati equation. The effectiveness of the hybrid model is validated by experiments, while the superior performance of the ADC is demonstrated by simulations. The results indicate that the hybrid model is more accurate than the general model and ADC method can rapidly reduce the register errors into a range of ±10 μm. In addition, simulated comparisons of ADC, direct decoupling proportional differential (DDPD), and improved DDPD control methods also show that the ADC owns the highest register precision and smoothest control signal.
Laminar Torsional Couette Flow Over a Wavy Disk
Authors: Sherikar Akshay , Disimile Peter J. , Toy Norman
Published: August 2023

A parametric study of laminar torsional Couette flow between a rotating flat disk and a stationary wavy disk is conducted using computer simulations. The waviness of the stationary disk, characterized by the parameter wave slope (WS), is increased across four cases to evaluate its influence. The resulting flow field is significantly different from torsional Couette flow between flat disks. Shear stress and pressure on the flat and wavy disks are sinusoidal with the same spatial frequency as the undulation. Their averages over one wavelength remain unaffected by the increase in WS. However, this is not the case with their amplitudes. A critical layer is observed approximately at a distance of 70% radius of the disk across which the effect of WS on shear amplitude is inverted. Furthermore, the sinusoidal shear on the flat disk is observed to be in destructive phase with respect to the shear on wavy disk. This is corroborated by the concave/convex distortion of the height-wise tangential velocity profile across the undulation. Alternately, the net radial velocity becomes biased either toward or away from the axis depending on angular location with respect to the undulation. The effect of increasing WS on the tangential velocity is in the form of small increments to the curvature of its height-wise profile, while the axial velocity, though it is orders of magnitude smaller than the tangential velocity, increases substantially with increase in WS.
New data to the fauna of Tydeidae (Acari: Prostigmata) of Western Siberia, Russia with discovery of secondary sexual dimorphism
Authors: Khaustov Alexander A.
Published: August 2023

The female and male of a new species, Brachytydeus elongatus sp. nov., are described from leaves of common reed (Phragmites australis) in Tyumen Oblast of Russia. Brachytydeus obnoxius (Kuznetsov and Zapletina) is recorded from Russia for the first time; B. inconstans (Kaźmierski) and B. ferulus (Baker) are recorded from Western Siberia for the first time. An unusual type of secondary sexual dimorphism in Brachytydeus elongatus sp. nov. is discussed.
A neural network-based method for spruce tonewood characterization
Authors: Badiane David Giuseppe , Gonzalez Sebastian , Malvermi Raffaele , Antonacci Fabio , Sarti Augusto
Published: August 2023

The acoustical properties of wood are primarily a function of its elastic properties. Numerical and analytical methods for wood material characterization are available, although they are either computationally demanding or not always valid. Therefore, an affordable and practical method with sufficient accuracy is missing. In this article, we present a neural network-based method to estimate the elastic properties of spruce thin plates. The method works by encoding information of both the eigenfrequencies and eigenmodes of the system and using a neural network to find the best possible material parameters that reproduce the frequency response function. Our results show that data-driven techniques can speed up classic finite element model updating by several orders of magnitude and work as a proof of concept for a general neural network-based tool for the workshop.
Amplitude modulation of acoustic waves in accelerating flows quantified using acoustic black and white hole analogues
Authors: Schenke Sören , Sewerin Fabian , van Wachem Berend , Denner Fabian
Published: August 2023

We investigate the amplitude modulation of acoustic waves in accelerating flows, a problem that is still not fully understood, but essential to many technical applications, ranging from medical imaging to acoustic remote sensing. The proposed modeling framework is based on a convective form of the Kuznetsov equation, which incorporates the background flow field and is solved numerically by a finite-difference method. Using acoustic black and white hole analogues as model systems, we identify a modulation of the wave amplitude which is shown to be driven by the divergence/convergence of the acoustic wave characteristics in an accelerating/decelerating flow, and which is distinct from the convective amplification accompanying an acoustic emitter moving at a constant velocity. To rationalize the observed amplitude modulation, a leading-order model is derived from first principles, leveraging a similarity of the wave characteristics and the wave amplitude with respect to a modified Helmholtz number. This leading-order model may serve as a basis for the numerical prediction and analysis of the behavior of acoustic waves in accelerating flows, by taking advantage of the notion that any accelerating flow field can be described locally as a virtual acoustic black or white hole.
Fundamental frequency disturbances in female and male singers' pitch glides through long tube with varied resistances
Authors: Sundberg Johan , Lã Filipa , Granqvist Svante
Published: August 2023

Source-filter interaction can disturb vocal fold vibration frequency. Resonance frequency/bandwidth ratios (Q-values) may affect such interaction. Occurrences of fundamental frequency (fo) disturbances were measured in ascending pitch glides produced by four female and five male singers phonating into a 70 cm long tube. Pitch glides were produced with varied resonance Q-values of the vocal tract + tube compound (VT + tube): (i) tube end open, (ii) tube end open with nasalization, and (iii) with a piece of cotton wool in the tube end (conditions Op, Ns, and Ct, respectively). Disturbances of fo were identified by calculating the derivative of the low-pass filtered fo curve. Resonance frequencies of the compound VT+tube system were determined from ringings and glottal aspiration noise observed in narrowband spectrograms. Disturbances of fo tended to occur when a partial was close to a resonance of the compound VT+tube system. The number of such disturbances was significantly lower when the resonance Q-values were reduced (conditions Ns and Ct), particularly for the males. In some participants, resonance Q-values seemed less influential, suggesting little effect of source-filter interaction. The study sheds light on factors affecting source-filter interaction and fo control and is, therefore, relevant to voice pedagogy and theory of voice production.
Collegiate Athletes’ Perceptions of the Connection Between Mental Health and Sport Performance: A Qualitative Investigation
Authors: Beebe Kelzie E. , Petrie Trent A. , Kiefer Heather R. , Slavin Lindsey E. , Arnold Macey L.
Published: August 2023

Prevalence of mental health (MH) concerns among young adults is high and continues to increase. As a specific subset of young adults, National Collegiate Athletic Association (NCAA) athletes seem to experience these concerns at a similar or greater prevalence rate than their nonathlete, age-matched peers. Yet, how MH affects sport performance has not been robustly studied, and existing studies have not included the diversity of identities present in the collegiate athlete population. Thus, via online survey, this study explored the beliefs of 249 collegiate athletes representing diverse identities and sports regarding how MH affects sport performance. Regardless of demographic variable, 96.4%–100.0% of participants believed that MH affects sport performance. Three themes were identified: (a) collegiate athletes affirm that MH affects sport performance, (b) collegiate athletes’ perceptions of how MH affects sport performance, and (c) collegiate athletes believe that being a collegiate athlete exacerbates their MH concerns. The universality of endorsement and the themes represent novel findings that warrant further exploration of the MH–sport performance connection.
Motor Unit Firing Properties During Force Control Task and Associations With Neurological Tests in Children
Authors: Okudaira Masamichi , Takeda Ryosuke , Hirono Tetsuya , Nishikawa Taichi , Kunugi Shun , Watanabe Kohei
Published: August 2023

The present study aimed to clarify the development of motor unit (MU) firing properties and the association between those neural properties and force steadiness (FS)/neurological tests in 6- to 12-year-old children. Fifty-eight school-aged children performed maximal voluntary knee extension contraction, a submaximal FS test at 10% of maximal voluntary knee extension contraction, knee extension reaction time to light stimulus test, and single-leg standing test, and data from 38 children who passed the criteria were subject to analysis. During the FS test, high-density surface electromyography was recorded from the vastus lateralis muscle to identify individual MU firing activity. FS was improved with an increase in age (r = −.540, P < .001). The MU firing rate (MUFR) was significantly decreased with an increase in age (r = −.343, P = .035). MUFR variability was not associated with age. Although there was no significant correlation between FS and MUFR, FS was significantly correlated with MUFR variability even after adjustment for the effect of age (r = .551, P = .002). Neither the reaction time nor the single-leg standing test was correlated with any MU firing properties. These findings suggest that MUFR variability makes an important contribution to precise force control in children but does not naturally develop with age.
Development of Upper-Extremity Morphological Asymmetries in Male and Female Elite Youth Tennis Players: A Longitudinal Study
Authors: Chapelle Laurent , D’Hondt Eva , Rommers Nikki , Clarys Peter
Published: August 2023

Purpose: This 2-year longitudinal study examined the development of upper-extremity bone mineral density (BMD), bone mineral content (BMC), and lean mass (LM) asymmetry magnitudes in male and female youth tennis players. Methods: Dominant and nondominant upper-extremity BMD, BMC, and LM values of 49 male and 31 female players were measured yearly using dual X-ray absorptiometry. From these values, asymmetry magnitudes were calculated and expressed as a percentage. Maturity offset was estimated using anthropometric measurements. Linear mixed effect models examined the development of BMD, BMC, and LM asymmetry magnitudes according to players’ maturity offset, sex, and training volume. Results: Adjusted for sex and training volume, a 1-year increment in maturity offset was associated with a significant increase in BMD (1.3% [2.2%]; P < .001) and BMC (0.6% [2.4%]; P = .011) asymmetry magnitudes. Male players displayed significantly higher LM asymmetry magnitudes (Δ3.2% [8.4%]; P = .002) compared with their female counterparts. Training volume was not significantly associated with asymmetry magnitude development. Conclusion: In contrast to LM, male and female youth tennis players’ upper-extremity bones are still responsive to mechanical loading with a significant increase in BMD and BMC asymmetry magnitudes according to maturity offset.
FIRRM cooperates with FIGNL1 to promote RAD51 disassembly during DNA repair
Authors: Pinedo-Carpio Edgar , Dessapt Julien , Beneyton Adèle , Sacre Lauralicia , Bérubé Marie-Anne , Villot Romain , Lavoie Elise G. , Coulombe Yan , Blondeau Andréanne , Boulais Jonathan , Malina Abba , Luo Vincent M. , Lazaratos Anna-Maria , Côté Jean-François , Mallette Frédérick A. , Guarné Alba , Masson Jean-Yves , Fradet-Turcotte Amélie , Orthwein Alexandre
Published: August 2023

Interstrand DNA cross-links (ICLs) represent complex lesions that compromise genomic stability. Several pathways have been involved in ICL repair, but the extent of factors involved in the resolution of ICL-induced DNA double-strand breaks (DSBs) remains poorly defined. Using CRISPR-based genomics, we identified FIGNL1 interacting regulator of recombination and mitosis (FIRRM) as a sensitizer of the ICL-inducing agent mafosfamide. Mechanistically, we showed that FIRRM, like its interactor Fidgetin like 1 (FIGNL1), contributes to the resolution of RAD51 foci at ICL-induced DSBs. While the stability of FIGNL1 and FIRRM is interdependent, expression of a mutant of FIRRM (∆WCF), which stabilizes the protein in the absence of FIGNL1, allows the resolution of RAD51 foci and cell survival, suggesting that FIRRM has FIGNL1-independent function during DNA repair. In line with this model, FIRRM binds preferentially single-stranded DNA in vitro, raising the possibility that it directly contributes to RAD51 disassembly by interacting with DNA. Together, our findings establish FIRRM as a promoting factor of ICL repair.
Brain rhythms control microglial response and cytokine expression via NF-κB signaling
Authors: Prichard Ashley , Garza Kristie M. , Shridhar Avni , He Christopher , Bitarafan Sara , Pybus Alyssa , Wang Yunmiao , Snyder Emma , Goodson Matthew C. , Franklin Tina C. , Jaeger Dieter , Wood Levi B. , Singer Annabelle C.
Published: August 2023

Microglia transform in response to changes in sensory or neural activity, such as sensory deprivation. However, little is known about how specific frequencies of neural activity, or brain rhythms, affect microglia and cytokine signaling. Using visual noninvasive flickering sensory stimulation (flicker) to induce electrical neural activity at 40 hertz, within the gamma band, and 20 hertz, within the beta band, we found that these brain rhythms differentially affect microglial morphology and cytokine expression in healthy animals. Flicker induced expression of certain cytokines independently of microglia, including interleukin-10 and macrophage colony-stimulating factor. We hypothesized that nuclear factor κB (NF-κB) plays a causal role in frequency-specific cytokine and microglial responses because this pathway is activated by synaptic activity and regulates cytokines. After flicker, phospho–NF-κB colabeled with neurons more than microglia. Inhibition of NF-κB signaling down-regulated flicker-induced cytokine expression and attenuated flicker-induced changes in microglial morphology. These results reveal a mechanism through which brain rhythms affect brain function by altering microglial morphology and cytokines via NF-κB.
A wide megafauna gap undermines China’s expanding coastal ecosystem conservation
Authors: Li Xincheng , Wang Hanchen , McCauley Douglas J. , Altieri Andrew H. , Silliman Brian R. , Lefcheck Jonathan S. , Wu Jihua , Li Bo , He Qiang
Published: August 2023

To fulfill sustainable development goals, many countries are expanding efforts to conserve ecologically and societally critical coastal ecosystems. Although megafauna profoundly affect the functioning of ecosystems, they are neglected as a key component in the conservation scheme for coastal ecosystems in many geographic contexts. We reveal a rich diversity of extant megafauna associated with all major types of coastal ecosystems in China, including 218 species of mammals, birds, reptiles, cephalopods, and fish across terrestrial and marine environments. However, 44% of these species are globally threatened, and 78% have not yet been assessed in China for extinction risk. More worrisome, 73% of these megafauna have not been designated as nationally protected species, and <10% of their most important habitats are protected. Filling this wide “megafauna gap” in China and globally would be a leading step as humanity strives to thrive with coastal ecosystems.
Radar remote sensing reveals potential underestimation of rainfall erosivity at the global scale
Authors: Dai Qiang , Zhu Jingxuan , Lv Guonian , Kalin Latif , Yao Yuanzhi , Zhang Jun , Han Dawei
Published: August 2023

Rainfall kinetic energy (RKE) constitutes one of the most critical factors that drive rainfall erosivity on surface soil. Direct measurements of RKE are limited, relying instead on the empirical relations between kinetic energy and rainfall intensity (
KE-I
relation), which have not been well regionalized for data-scarce regions. Here, we present the first global rainfall microphysics–based RKE (

RKE
MPH

) flux retrieved from radar reflectivity at different frequencies. The results suggest that

RKE
MPH

flux outperforms the
RKE
estimates derived from a widely used empirical
KE-I
relation (

RKE
KE-I

) validated using ground disdrometers. We found a potentially widespread underestimation of

RKE
KE-I

, which is especially prominent in some low-income countries with ~20% underestimation of RKE and the resultant rainfall erosivity. Given the evidence that these countries are subject to greater rainfall-induced soil erosion, these underestimations would mislead conservation practices for sustainable development of terrestrial ecosystems.
A whole-genome reference panel of 14,393 individuals for East Asian populations accelerates discovery of rare functional variants
Authors: Choi Jaeyong , Kim Sungjae , Kim Juhyun , Son Ho-Young , Yoo Seong-Keun , Kim Chang-Uk , Park Young Jun , Moon Sungji , Cha Bukyoung , Jeon Min Chul , Park Kyunghyuk , Yun Jae Moon , Cho Belong , Kim Namcheol , Kim Changhoon , Kwon Nak-Jung , Park Young Joo , Matsuda Fumihiko , Momozawa Yukihide , Kubo Michiaki ,   Biobank Japan Project, Kim Hyun-Jin , Park Jin-Ho , Seo Jeong-Sun , Kim Jong-Il , Im Sun-Wha
Published: August 2023

Underrepresentation of non-European (EUR) populations hinders growth of global precision medicine. Resources such as imputation reference panels that match the study population are necessary to find low-frequency variants with substantial effects. We created a reference panel consisting of 14,393 whole-genome sequences including more than 11,000 Asian individuals. Genome-wide association studies were conducted using the reference panel and a population-specific genotype array of 72,298 subjects for eight phenotypes. This panel yields improved imputation accuracy of rare and low-frequency variants within East Asian populations compared with the largest reference panel. Thirty-nine previously unidentified associations were found, and more than half of the variants were East Asian specific. We discovered genes with rare protein-altering variants, including
LTBP1
for height and
GPR75
for body mass index, as well as putative regulatory mechanisms for rare noncoding variants with cell type–specific effects. We suggest that this dataset will add to the potential value of Asian precision medicine.
Multiple approaches of cellular metabolism define the bacterial ancestry of mitochondria
Authors: Geiger Otto , Sanchez-Flores Alejandro , Padilla-Gomez Jonathan , Degli Esposti Mauro
Published: August 2023

We breathe at the molecular level when mitochondria in our cells consume oxygen to extract energy from nutrients. Mitochondria are characteristic cellular organelles that derive from aerobic bacteria and carry out oxidative phosphorylation and other key metabolic pathways in eukaryotic cells. The precise bacterial origin of mitochondria and, consequently, the ancestry of the aerobic metabolism of our cells remain controversial despite the vast genomic information that is now available. Here, we use multiple approaches to define the most likely living relatives of the ancestral bacteria from which mitochondria originated. These bacteria live in marine environments and exhibit the highest frequency of aerobic traits and genes for the metabolism of fundamental lipids that are present in the membranes of eukaryotes, sphingolipids, and cardiolipin.
Anti–phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell immunotherapy
Authors: Zheng Chunxiong , Zhong Qingguo , Yi Ke , Kong Huimin , Cao Fangfang , Zhuo Chenya , Xu Yanteng , Shi Run , Ju Enguo , Song Wantong , Tao Yu , Chen Xiaoyuan , Li Mingqiang
Published: August 2023

Equipping multiple functionalities on adoptive effector cells is essential to overcome the complex immunological barriers in solid tumors for superior antitumor efficacy. However, current cell engineering technologies cannot endow these functionalities to cells within a single step because of the different spatial distributions of targets in one cell. Here, we present a core-shell anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) to achieve one-step multiplexing cell engineering for multifunctional cell construction. Through fusing with the M1 macrophage membrane, ARMFUL inserts an anti-CD47 (aCD47)–modified lipid shell onto the surface and simultaneously delivers colony-stimulating factor 1 receptor inhibitor BLZ945-loaded core into the cytoplasm. The surface-presenting aCD47 boosts macrophage's phagocytosis against the tumor by blocking CD47. The cytoplasm-located BLZ945 prompts its polarization resistance to M2 phenotype in the immunosuppressive microenvironment via inactivating the intracellular M2 polarization signaling pathway. This ARMFUL provides a versatile cell engineering platform to customize multimodal cellular functions for enhanced adoptive cell therapy.
Comparison of SARS-CoV-2 entry inhibitors based on ACE2 receptor or engineered Spike-binding peptides
Authors: Llewellyn George N. , Chen Hsu-Yu , Rogers Geoffrey L. , Huang Xiaoli , Sell Philip J. , Henley Jill E. , Cannon Paula M.
Published: August 2023

With increasing resistance of SARS-CoV-2 variants to antibodies, there is interest in developing entry inhibitors that target essential receptor-binding regions of the viral Spike protein and thereby present a high bar for viral resistance. Such inhibitors could be derivatives of the viral receptor, ACE2, or peptides engineered to interact specifically with the Spike receptor-binding pocket. We compared the efficacy of a series of both types of entry inhibitors, constructed as fusions to an antibody Fc domain. Such a design can increase protein stability and act to both neutralize free virus and recruit effector functions to clear infected cells. We tested the reagents against prototype variants of SARS-CoV-2, using both Spike pseudotyped vesicular stomatitis virus vectors and replication-competent viruses. These analyses revealed that an optimized ACE2 derivative could neutralize all variants we tested with high efficacy. In contrast, the Spike-binding peptides had varying activities against different variants, with resistance observed in the Spike proteins from Beta, Gamma, and Omicron (BA.1 and BA.5). The resistance mapped to mutations at Spike residues K417 and N501 and could be overcome for one of the peptides by linking two copies in tandem, effectively creating a tetrameric reagent in the Fc fusion. Finally, both the optimized ACE2 and tetrameric peptide inhibitors provided some protection to human ACE2 transgenic mice challenged with the SARS-CoV-2 Delta variant, which typically causes death in this model within 7–9 days.

IMPORTANCE

The increasing resistance of SARS-CoV-2 variants to therapeutic antibodies has highlighted the need for new treatment options, especially in individuals who do not respond to vaccination. Receptor decoys that block viral entry are an attractive approach because of the presumed high bar to developing viral resistance. Here, we compare two entry inhibitors based on derivatives of the ACE2 receptor, or engineered peptides that bind to the receptor-binding pocket of the SARS-CoV-2 Spike protein. In each case, the inhibitors were fused to immunoglobulin Fc domains, which can further enhance therapeutic properties, and compared for activity against different SARS-CoV-2 variants. Potent inhibition against multiple SARS-CoV-2 variants was demonstrated
in vitro
, and even relatively low single doses of optimized reagents provided some protection in a mouse model, confirming their potential as an alternative to antibody therapies.
SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models
Authors: Mykytyn Anna Z. , Breugem Tim I. , Geurts Maarten H. , Beumer Joep , Schipper Debby , van Acker Romy , van den Doel Petra B. , van Royen Martin E. , Zhang Jingshu , Clevers Hans , Haagmans Bart L. , Lamers Mart M.
Published: August 2023

SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters cells via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for Omicron in a monkey kidney cell line, experiments with protease inhibitors showed that Omicron (BA.1 and XBB1.5) did not use cathepsins for entry into human airway organoids and instead utilized TTSPs. Likewise, CRISPR-edited intestinal organoids showed that entry of Omicron BA.1 relied on the expression of the serine protease TMPRSS2 but not cathepsin L or B. Together, these data force us to rethink the concept that Omicron has adapted to cathepsin-mediated entry and indicate that TTSP inhibitors should not be dismissed as prophylactic or therapeutic antiviral strategy against SARS-CoV-2.

IMPORTANCE

Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Whereas earlier studies using cell lines suggested that the Omicron variant of SARS-CoV-2 has changed its protease usage, from cell surface type II transmembrane serine proteases (TTSPs) to endosomal cathepsins, we report that this is not the case in human airway and intestinal organoid models, suggesting that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlighting the importance of relevant human
in vitro
cell models.
APOBEC3 degradation is the primary function of HIV-1 Vif determining virion infectivity in the myeloid cell line THP-1
Authors: Ikeda Terumasa , Shimizu Ryo , Nasser Hesham , Carpenter Michael A. , Cheng Adam Z. , Brown William L. , Sauter Daniel , Harris Reuben S.
Published: August 2023

HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4
+
T lymphocytes and macrophages. Previous studies have demonstrated that the apolipoprotein B mRNA editing enzyme polypeptide-like 3 (APOBEC3, A3) family of proteins (at least A3D, A3F, A3G, and stable A3H haplotypes) contribute to HIV-1 restriction in CD4
+
T lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this antiviral activity by degrading A3 enzymes allowing HIV-1 replication in infected cells. In addition to A3 proteins, Vif also targets other cellular proteins in CD4
+
T lymphocytes, including PPP2R5 proteins. However, whether Vif primarily degrades only A3 proteins during viral replication is currently unknown. Herein, we describe the development and characterization of
A3F
-,
A3F/A3G
-, and
A3A
-to-
A3G
-null THP-1 cells. In comparison to Vif-proficient HIV-1, Vif-deficient viruses have substantially reduced infectivity in parental and
A3F
-null THP-1 cells, and a more modest decrease in infectivity in
A3F/A3G
-null cells. Remarkably, disruption of A3A–A3G protein expression completely restores the infectivity of Vif-deficient viruses in THP-1 cells. These results indicate that the primary function of Vif during infectious HIV-1 production from THP-1 cells is the targeting and degradation of A3 enzymes.

IMPORTANCE

HIV-1 Vif neutralizes the HIV-1 restriction activity of A3 proteins. However, it is currently unclear whether Vif has additional essential cellular targets. To address this question, we disrupted
A
3
A
to
A
3
G
genes in the THP-1 myeloid cell line using CRISPR and compared the infectivity of wild-type HIV-1 and Vif mutants with the selective A3 neutralization activities. Our results demonstrate that the infectivity of Vif-deficient HIV-1 and the other Vif mutants is fully restored by ablating the expression of cellular A3A to A3G proteins. These results indicate that A3 proteins are the only essential target of Vif that is required for fully infectious HIV-1 production from THP-1 cells.
Exhaled CO2monitoring to guide non-invasive ventilation at birth: a systematic review
Authors: Monnelly Vix , Josephsen Justin B , Isayama Tetsuya , de Almeida Maria Fernanda B , Guinsburg Ruth , Schmölzer Georg M , Rabi Yacov , Wyckoff Myra H , Weiner Gary , Liley Helen G , Solevåg Anne Lee
Published: August 2023

Objective

Measuring exhaled carbon dioxide (ECO2) during non-invasive ventilation at birth may provide information about lung aeration. However, the International Liaison Committee on Resuscitation (ILCOR) only recommends ECO2detection for confirming endotracheal tube placement. ILCOR has therefore prioritised a research question that needs to be urgently evaluated: ‘In newborn infants receiving intermittent positive pressure ventilation by any non-invasive interface at birth, does the use of an ECO2monitor in addition to clinical assessment, pulse oximetry and/or ECG, compared with clinical assessment, pulse oximetry and/or ECG only, decrease endotracheal intubation in the delivery room, improve response to resuscitation, improve survival or reduce morbidity?’.

Design

Systematic review of randomised and non-randomised studies identified by Ovid MEDLINE, Embase and Cochrane CENTRAL search until 1 August 2022.

Setting

Delivery room.

Patients

Newborn infants receiving non-invasive ventilation at birth.

Intervention

ECO2measurement plus routine assessment compared with routine assessment alone.

Main outcome measures

Endotracheal intubation in the delivery room, response to resuscitation, survival and morbidity.

Results

Among 2370 articles, 23 were included; however, none had a relevant control group. Although studies indicated that the absence of ECO2may signify airway obstruction and ECO2detection may precede a heart rate increase in adequately ventilated infants, they did not directly address the research question.

Conclusions

Evidence to support the use of an ECO2monitor to guide non-invasive positive pressure ventilation at birth is lacking. More research on the effectiveness of ECO2measurement in addition to routine assessment during non-invasive ventilation of newborn infants at birth is needed.

PROSPERO registration number

CRD42022344849.
Is neglect of self-clearance biasing TB vaccine impact estimates?
Authors: Scarponi Danny , Clark Rebecca A , Weerasuriya Chathika Krishan , Emery Jon , Houben Rein M G J , White Richard , McCreesh Nicky
Published: August 2023

Background

Mathematical modelling has been used extensively to estimate the potential impact of new tuberculosis vaccines, with the majority of existing models assuming that individuals withMycobacterium tuberculosis(Mtb) infection remain at lifelong risk of tuberculosis disease. Recent research provides evidence that self-clearance of Mtb infection may be common, which may affect the potential impact of new vaccines that only take in infected or uninfected individuals. We explored how the inclusion of self-clearance in models of tuberculosis affects the estimates of vaccine impact in China and India.

Methods

For both countries, we calibrated a tuberculosis model to a scenario without self-clearance and to various scenarios with self-clearance. To account for the current uncertainty in self-clearance properties, we varied the rate of self-clearance, and the level of protection against reinfection in self-cleared individuals. We introduced potential new vaccines in 2025, exploring vaccines that work in uninfected or infected individuals only, or that are effective regardless of infection status, and modelling scenarios with different levels of vaccine efficacy in self-cleared individuals. We then estimated the relative disease incidence reduction in 2050 for each vaccine compared with the no vaccination scenario.

Findings

The inclusion of self-clearance increased the estimated relative reductions in incidence in 2050 for vaccines effective only in uninfected individuals, by a maximum of 12% in China and 8% in India. The inclusion of self-clearance increased the estimated impact of vaccines only effective in infected individuals in some scenarios and decreased it in others, by a maximum of 14% in China and 15% in India. As would be expected, the inclusion of self-clearance had minimal impact on estimated reductions in incidence for vaccines that work regardless of infection status.

Interpretations

Our work suggests that the neglect of self-clearance in mathematical models of tuberculosis vaccines does not result in substantially biased estimates of tuberculosis vaccine impact. It may, however, mean that we are slightly underestimating the relative advantages of vaccines that work in uninfected individuals only compared with those that work in infected individuals.
Global environmental risk factors of schizophrenia: a study protocol for systematic review and meta-analysis of cohort studies
Authors: Mahdavinoor Seyyed Muhammad Mahdi , Mollaei Aghil , Farhang Sara
Published: August 2023

Introduction

Schizophrenia is a chronic, complex and severe psychiatric disorder affecting millions of people every year and inflicting different costs to the individual, family and community. A growing body of evidence has introduced several genetic and environmental factors and their interactions as aetiological factors of schizophrenia. The goal of this systematic review and meta-analysis is to present an updated representation of the global environmental risk factors of schizophrenia.

Method and analysis

This protocol is developed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guideline. We will systematically search the databases such as PubMed, Scopus, Web of Science, PsycINFO and Embase until 30 September 2022. We include Cohort studies that have reported one or more risk factors of schizophrenia. We will also search Google Scholar search engine and references lists of included articles. Extracting the relevant data and assessing the quality of the included studies will be independently performed by different authors of our team. The risk of bias for the included studies will be evaluated using Newcastle-Ottawa Scale. Subgroup analysis, meta-regression or sensitivity analysis will be our solution to deal with heterogeneity between studies. We will use a funnel diagram as well as Begg and Egger tests to check for possible publication bias.

Ethics and dissemination

Ethical approval is not required because there will be no primary data collection or human involvement. The results of this study will be published in an international peer-reviewed journal.

PROSPERO registration number

CRD42022359327.
Derivation and external validation of a risk score for clinically important declines in health and function among two longitudinal cohorts of women in the mid-life
Authors: Solomon Daniel H , Santacroce Leah , Shadyab Aladdin , Haring Bernhard , Burnett-Bowie Sherri-Ann M , Karvonen-Gutierrez Carrie , Colvin Alicia , Jackson Rebecca , LeBoff Meryl S , Ruppert Kristine , Valencia Celina I , Avis Nancy E , Manson JoAnn E
Published: August 2023

Objectives

Women in mid-life often develop chronic conditions and experience declines in physical health and function. Identifying factors associated with declines provides opportunity for targeted interventions. We derived and externally validated a risk score for clinically important declines over 10 years among women ages 55–65 using the Physical Component Summary Score (PCS) of the SF-36.

Design

Derivation and validation of a risk score.

Setting

Two longitudinal cohorts from sites in the USA were used.

Participants

Women from the Study of Women’s Health Across the Nation (SWAN) and women from the Women’s Health Initiative (WHI) Observational Study and/or clinical trials.

Outcome measures

A clinically important decline over 10 years among women ages 55–65 using the PCS of the SF-36 predictors was measured at the beginning of the 10 years of follow-up.

Results

Seven factors—lower educational attainment, smoking, higher body mass index, history of cardiovascular disease, history of osteoarthritis, depressive symptoms and baseline PCS level—were found to be significant predictors of PCS decline among women in SWAN with an area under the curve (AUC)=0.71 and a Brier Score=0.14. The same factors were associated with a decline in PCS in WHI with an AUC=0.64 and a Brier Score=0.18. Regression coefficients from the SWAN analysis were used to estimate risk scores for PCS decline in both cohorts. Using a threshold of a 30% probability of a significant decline, the risk score created a binary test with a specificity between 89%–93% and an accuracy of 73%–79%.

Conclusions

Seven clinical variables were used to create a valid risk score for PCS declines that was replicated in an external cohort. The risk score provides a method for identifying women at high risk for a significant mid-life PCS decline.
Impact of armed conflicts on HIV treatment outcomes in sub-Saharan Africa: protocol for a systematic review and meta-analysis
Authors: Kebede Hafte Kahsay , Gesesew Hailay , Ward Paul
Published: August 2023

Introduction

Armed conflicts have significant negative impacts on the entire healthcare system in general and HIV care system in particular. Sub-Saharan Africa is suffering from a disproportionate double burden of armed conflict and HIV infection. Nevertheless, the impact of the armed conflict on the HIV treatment outcomes in conflict settings in sub-Saharan Africa has not been thoroughly and systematically synthesised. This protocol outlines a review that aims to summarise the available evidence on the impact of armed conflict on HIV treatment outcomes in sub-Saharan Africa.

Methods and analysis

A systematic review of all quantitative studies that assess the impact of armed conflicts on HIV treatment outcomes will be conducted. The systematic search will start with a preliminary search of Google Scholar, followed by implementation of the full search strategy across five databases (MEDLINE, PubMed, CINAHL, SCOPUS and Web of Science) and the screening of titles and abstracts then relevant full texts. Bibliographies will be reviewed to identify additional relevant studies. We will include studies conducted in sub-Saharan Africa that were published in English between 1 January 2002 and 31 December 2022. Methodological validity of the included studies will be assessed using standardised critical appraisal instruments from the Joanna Briggs Institute (JBI) Meta-Analysis of Statistics Assessment and Review Instrument. Data will be extracted using standardised JBI instruments and analysed through narrative synthesis, and meta-analyses and regression. Heterogeneity will be assessed using I2and Χ2tests.

Ethics and dissemination

Since this study will not involve gathering primary data, formal ethical approval is not required. Journal publications, conference presentations and a media release will be used to share the study findings.

PROSPERO registration number

CRD42022361924.
COVID-19 era-related e-learning: a cross-sectional web-scale study of cyberchondria, internet addiction and anxiety-related symptomatology among university nursing students
Authors: Mrayyan Majd T , Alkhawaldeh Ja'far M , Alfayoumi Imad , Algunmeeyn Abdullah , Abunab Hamzeh Y , Suliman W A , Abu Hasheesh Mohammad , Shudifat Raed
Published: August 2023

Objective

The study assessed COVID-19 era-related e-learning cyberchondria, internet addiction and anxiety-related symptomatology among nursing students. The relationships, predictors and differences between the studied concepts were measured.

Design

In 2021, a quantitative cross‐sectional research design using a web survey with a sample size of 333 nursing students yielded a response rate of 70%.

Results

Nursing students had a moderate level of cyberchondria, low to moderate internet addiction, a moderate to severe level of anxiety and depression, and a normal stress level. Demographic characteristics, cyberchondria, internet addiction and anxiety-related symptomatology were significantly correlated. Grade point average, age, type of organisation where the students were trained and level of education were significant predictors of the studied variables. Significant differences in the studied concepts were found based on the sample’s characteristics such as gender, type of organisations or universities where the students were trained or studied, and age.

Conclusion

Cyberchondria, internet addiction, depression, anxiety and stress symptomatology are troublesome. Higher education organisations might benefit from examining the variables of interest and investigating the relations between internet addiction and depression and anxiety symptomatology among nursing students. Such research will aid in tailoring treatments to assist vulnerable students by targeting counselling and educational efforts toward building a future generation of nurses with reduced cyberchondria, internet addiction and anxiety-related symptomatology.
Efficacy and safety of Android artificial pancreas system use at home among adults with type 1 diabetes mellitus in China: protocol of a 26-week, free-living, randomised, open-label, two-arm, two-phase, crossover trial
Authors: Lei Mengyun , Lin Beisi , Ling Ping , Liu Zhigu , Yang Daizhi , Deng Hongrong , Yang Xubin , Lv Jing , Xu Wen , Yan Jinhua
Published: August 2023

Introduction

Do-it-yourself artificial pancreas system (DIY APS) is built using commercially available insulin pump, continuous glucose monitoring (CGM) and an open-source algorithm. Compared with commercial products, DIY systems are affordable, allow personalised settings and provide updated algorithms, making them a more promising therapy for most patients with type 1 diabetes mellitus (T1DM). Many small and self-reported observational studies have found that their real-world use was associated with potential metabolic and psychological benefits. However, rigorous-designed studies are urgently needed to confirm its efficacy and safety.

Methods and analysis

In this 26-week randomised, open-label, two-arm, two-phase, crossover trial, participants aged 18–75 years, with T1DM and glycated haemoglobin (HbA1c) 7–11%, will use AndroidAPS during one 12-week period and sensor-augmented pump during another 12-week period. This study will recruit at least 24 randomised participants. AndroidAPS consists of three components: (1) real-time CGM; (2) insulin pump; (3) AndroidAPS algorithm implemented in Android smartphone. The primary endpoint is time in range (3.9–10.0 mmol/L) derived from CGM. The main secondary endpoints include percentage of sensor glucose values below, within and above target range; mean sensor glucose value; measures of glycaemic variability and centralised HbA1c. Safety endpoints mainly include the frequency of hypoglycaemia events, diabetic ketoacidosis and other serious adverse events.

Ethics and dissemination

This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. There will be verbal and written information regarding the trial given to each participant. The study will be disseminated through peer-reviewed publications and conference presentations.

Overall status

Recruiting.

Study start

11 February 2023.

Primary completion

31 July 2024.

Trial registration number

ClinicalTrials.gov Registry (NCT05726461).
What happened to health labour markets during COVID-19? Insights from the analysis of cross-sectional survey data on the perceptions of medical doctors in Brazil
Authors: Russo Giuliano , de Oliveira Bruno Luciano Carneiro Alves Lucian , Cassenote Alex J Flores , Scheffer Mário C
Published: August 2023

Objectives

To examine physicians’ perceptions of changing employment opportunities in Brazil, and gain an insight into labour markets in low/middle-income countries (LMICs) during the pandemic.

Study design

Descriptive and inferential analysis of a quantitative dataset from a representative cross-sectional survey of physicians of two Brazilian states.

Settings

São Paulo and Maranhão states in Brazil.

Participants

Representative sample of 1183 physicians.

Outcome measures

We estimated prevalence and 95% CIs for physicians’ perceptions of changes in demand and supply of doctors, as well as changes in prices of medical services for facilities of practice in the two states, stratified by public, private and dual-practice physicians.

Results

Most doctors reported increased job opportunities in the public sector (54.9%, 95% CI 52.0% to 57.7%), particularly in Maranhão state (65.0%, 95% CI 60.9% to 68.9%). For the private sector, increased opportunities were reported only in large private hospitals (46.7%, 95% CI 43.9% to 49.6%) but not in smaller clinics. We recorded perceptions of slight increases in availability of doctors in Maranhão, particularly in the public sector (51.4%, 95% CI 43.2% to 59.5%). Younger doctors recounted increased vacancies in the public sector (64%, 95% CI 58.1% to 68.1%), older doctors only in walk-in clinics in Maranhão (47.5%, 95% CI 39.9% to 55.1%). Those working directly with patients with COVID-19 saw opportunities in public hospitals (65%, 95% CI 62.3% to 68.4%) and in large private ones (55%, 95% CI 51.8% to 59.1%).

Conclusions

Our findings hint that health labour markets in LMICs may not necessarily shrink during epidemics, and that impacts will depend on the balance of public and private services in national health systems.