bluuebunny/crossref_metadata_2025 huggingface dataset:
Dust masses for a large sample of core-collapse supernovae from optical emission line asymmetries: dust formation on 30-year time-scales
Authors: Niculescu-Duvaz Maria , Barlow M J , Bevan A , Wesson R , Milisavljevic D , De Looze I , Clayton G C , Krafton K , Matsuura M , Brady R
Published: July 2022

Modelling the red–blue asymmetries seen in the broad emission lines of core-collapse supernovae (CCSNe) is a powerful technique to quantify total dust mass formed in the ejecta at late times (>5 yr after outburst) when ejecta dust temperatures become too low to be detected by mid-infrared (IR) instruments. Following our success in using the Monte Carlo radiative transfer code damocles to measure the dust mass evolution in SN 1987A and other CCSNe, we present the most comprehensive sample of dust mass measurements yet made with damocles, for CCSNe aged between 4 and 60 yr after outburst. Our sample comprises multi-epoch late-time optical spectra taken with the Gemini/Gemini Multi-Object Spectrographs (GMOS) and Very Large Telescope (VLT) X-Shooter spectrographs, supplemented by archival spectra. For the 14 CCSNe that we have modelled, we confirm a dust mass growth with time that can be fit by a sigmoid curve that is found to saturate beyond an age of ∼30 yr, at a mass of 0.23$^{+0.17}_{-0.12}$ M⊙. For an expanded sample including dust masses found in the literature for a further 11 CCSNe and six CCSN remnants, the dust mass at saturation is found to be 0.42$^{+0.09}_{-0.05}$ M⊙. Uncertainty limits for our dust masses were determined from a Bayesian analysis using the affine invariant Markov chain Monte Carlo ensemble sampler emcee with damocles. The best-fitting line profile models for our sample all required grain radii between 0.1 and 0.5 $\mu$m. Our results are consistent with CCSNe forming enough dust in their ejecta to significantly contribute to the dust budget of the Universe.
Spatially resolved gas-phase metallicity in FIRE-2 dwarfs: late-time evolution of metallicity relations in simulations with feedback and mergers
Authors: Porter Lori E , Orr Matthew E , Burkhart Blakesley , Wetzel Andrew , Ma Xiangcheng , Hopkins Philip F , Emerick Andrew
Published: July 2022

We present an analysis of spatially resolved gas-phase metallicity relations in five dwarf galaxies ($\rm \mathit{M}_{halo} \approx 10^{11}\, {\rm M}_\odot$, $\rm \mathit{M}_\star \approx 10^{8.8}{-}10^{9.6}\, {\rm M}_\odot$) from the FIRE-2 (Feedback in Realistic Environments) cosmological zoom-in simulation suite, which include an explicit model for sub-grid turbulent mixing of metals in gas, near z ≈ 0, over a period of 1.4 Gyr, and compare our findings with observations. While these dwarf galaxies represent a diverse sample, we find that all simulated galaxies match the observed mass–metallicity (MZR) and mass–metallicity gradient (MZGR) relations. We note that in all five galaxies, the metallicities are effectively identical between phases of the interstellar medium (ISM), with 95 ${{\ \rm per\ cent}}$ of the gas being within ±0.1 dex between the cold and dense gas (T < 500 K and nH > 1 cm−3), ionized gas (near the H αT ≈ 104 K ridge-line), and nebular regions (ionized gas where the 10 Myr-averaged star formation rate is non-zero). We find that most of the scatter in relative metallicity between cold dense gas and ionized gas/nebular regions can be attributed to either local starburst events or metal-poor inflows. We also note the presence of a major merger in one of our galaxies, m11e, with a substantial impact on the metallicity distribution in the spatially resolved map, showing two strong metallicity peaks and triggering a starburst in the main galaxy.
LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response signalling to trigger dual DNA repair mechanisms
Authors: Yu Ruyuan , Hu Yameng , Zhang Shuxia , Li Xincheng , Tang Miaoling , Yang Meisongzhu , Wu Xingui , Li Ziwen , Liao Xinyi , Xu Yingru , Li Man , Chen Suwen , Qian Wanying , Gong Li-Yun , Song Libing , Li Jun
Published: July 2022

Sustaining DNA damage response (DDR) signalling via retention of DDR factors at damaged sites is important for transmitting damage-sensing and repair signals. Herein, we found that DNA damage provoked the association of ribosomes with IRES region in lncRNA CTBP1-DT, which overcame the negative effect of upstream open reading frames (uORFs), and elicited the novel microprotein DNA damage-upregulated protein (DDUP) translation via a cap-independent translation mechanism. Activated ATR kinase-mediated phosphorylation of DDUP induced a drastic ‘dense-to-loose’ conformational change, which sustained the RAD18/RAD51C and RAD18/PCNA complex at damaged sites and initiated RAD51C-mediated homologous recombination and PCNA-mediated post-replication repair mechanisms. Importantly, treatment with ATR inhibitor abolished the effect of DDUP on chromatin retention of RAD51C and PCNA, thereby leading to hypersensitivity of cancer cells to DNA-damaging chemotherapeutics. Taken together, our results uncover a plausible mechanism underlying the DDR sustaining and might represent an attractive therapeutic strategy in improvement of DNA damage-based anticancer therapies.
Insights into innate immune activation via PS-ASO–protein–TLR9 interactions
Authors: Pollak Adam J , Zhao Luyi , Vickers Timothy A , Huggins Ian J , Liang Xue-Hai , Crooke Stanley T
Published: July 2022

Non-CpG PS-ASOs can activate the innate immune system, leading to undesired outcomes. This response can vary—in part—as a function of 2′modifications and sequence. Here we investigated the molecular steps involved in the varied effects of PS-ASOs on the innate immune system. We found that pro-inflammatory PS-ASOs require TLR9 signaling based on the experimental systems used. However, the innate immunity of PS-ASOs does not correlate with their binding affinity with TLR9. Furthermore, the innate immune responses of pro-inflammatory PS-ASOs were reduced by coincubation with non-inflammatory PS-ASOs, suggesting that both pro-inflammatory and non-inflammatory PS-ASOs can interact with TLR9. We show that the kinetics of the PS-ASO innate immune responses can vary, which we speculate may be due to the existence of alternative PS-ASO binding sites on TLR9, leading to full, partial, or no activation of the pathway. In addition, we found that several extracellular proteins, including HMGB1, S100A8 and HRG, enhance the innate immune responses of PS-ASOs. Reduction of the binding affinity by reducing the PS content of PS-ASOs decreased innate immune responses, suggesting that PS-ASO–protein complexes may be sensed by TLR9. These findings thus provide critical information concerning how PS-ASOs can interact with and activate TLR9.
ERECTA regulates seed size independently of its intracellular domain via MAPK-DA1-UBP15 signaling
Authors: Wu Xuedan , Cai Xingbo , Zhang Baowen , Wu Shuting , Wang Ruiju , Li Na , Li Yunhai , Sun Yu , Tang Wenqiang
Published: July 2022

Seed size is determined by the coordinated growth of the embryo, endosperm, and integument. Growth of the integument is initiated by signal molecules released from the developing endosperm or embryo. Although recent studies have identified many components that regulate seed size by controlling integument growth, the upstream signals and the signal transduction pathway that activate these components after double fertilization are unclear. Here, we report that the receptor-like kinase ERECTA (ER) controls seed size by regulating outer integument cell proliferation in Arabidopsis thaliana. Seeds from er mutants were smaller, while those from ER-overexpressing plants were larger, than those of control plants. Different from its role in regulating the development of other organs, ER regulates seed size via a novel mechanism that is independent of its intracellular domain. Our genetic and biochemical data show that a MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) signaling pathway comprising MAPK-KINASE 4/5, MAPK 3/6 (MPK3/6), DA1, and UBIQUITIN SPECIFIC PROTEASE 15 (UBP15) functions downstream of ER and modulates seed size. MPK3/6 phosphorylation inactivates and destabilizes DA1 to increase the abundance of UBP15, promoting outer integument cell proliferation and increasing seed size. Our study illustrates a nearly completed ER-mediated signaling pathway that regulates seed size and will help uncover the mechanism that coordinates embryo, endosperm, and integument growth after double fertilization.
Cooperative innovation and crises: Foreign subsidiaries, state-owned enterprises, and domestic private firms
Authors: García-Sánchez Antonio , Rama Ruth
Published: July 2022

This article studies whether foreign subsidiaries (FSs) are able to cooperate for innovation with local partners during good and harsh economic times. It also enquires as to whether these companies and different types of domestic firms displayed similar cooperative behaviour during 2004–16. The period is divided into three sub-periods (boom, downturn, and recovery), and three logit models with panel data of a representative sample of Spanish firms are proposed. The ability of FSs to cooperate for innovation is maintained throughout the business cycle. These firms are better at cooperating than are unaffiliated firms but not significantly better than domestic business groups. State-owned enterprises strongly outperform both FSs and domestic private firms during the boom, the downturn, and the recovery. Unaffiliated domestic firms manage to cooperate during the boom and the recovery but not during the downturn. Predictors of cooperative innovation vary throughout the business cycle. The results contain policy implications.
Leading nutrient foraging strategies shaping by root system characteristics along the elevations in rubber (Hevea brasiliensis) plantations
Authors: Duan Mengcheng , Li Liang , Ding Gaigai , Ma Zeqing
Published: July 2022

When it comes to root and mycorrhizal associations that define resource acquisition strategy, there is a need to identify the leading dimension across root physiology, morphology, architecture and whole plant biomass allocation to better predict the plant’s responses to multiple environmental constraints. Here, we developed a new framework for understanding the variation in roots and symbiotic fungi by quantifying multiple-scale characteristics, ranging from anatomy to the whole plant. We chose the rubber (Hevea brasiliensis) grown at three elevations to test our framework and to identify the key dimensions for resource acquisition. Results showed that the quantities of absorptive roots and root system architecture, rather than single root traits, played the leading role in belowground resource acquisition. As the elevation increased from the low to high elevation, root length growth, productivity and root mass fraction (RMF) increased by 2.9-, 2.3- and 13.8-fold, respectively. The contribution of RMF to the changes in total root length was 3.6-fold that of specific root length (SRL). Root architecture exhibited higher plasticity than anatomy and morphology. Further, mycorrhizal colonization was highly sensitive to rising elevations with a non-monotonic pattern. By contrast, both leaf biomass and specific leaf area (traits) co-varied with increasing elevation. In summary, rubber trees changed root system architecture by allocating more biomass and lowering the reliance on mycorrhizal fungi rather than improving single root efficiency in adapting to high elevation. Our framework is instructive for traits-based ecology; accurate assessments of forest carbon cycling in response to resource gradient should account for the leading dimension of root system architecture.
Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis
Authors: Xu Junhua , Zhong Yanfeng , Yin Haoyang , Linneman John , Luo Yixuan , Xia Sijian , Xia Qinyi , Yang Lei , Huang Xingtao , Kang Kang , Wang Jun , Niu Yanqin , Li Li , Gou Deming
Published: July 2022

Objective:

Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension.

Methods:

We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia.

Results:

We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group.

Conclusion:

We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo.
Virtual Reality in Treatment for Psychological Problems in First-Line Health care Professionals Fighting COVID-19 Pandemic
Authors: Pan Xiao , Zhang Ying-Cheng , Ren Ding , Lu Li , Wang Yi-Hao , Li Guan-Xiong , Xiao Ying , Zhou Hong-Yu , Bai Yong-Hai
Published: July 2022

Virtual reality therapy (VRT) is a new psychotherapeutic approach integrating virtual reality technology and psychotherapy. This case series aimed to study effectiveness of VRT in treating psychological problems. We described four cases of first-line health care professionals with emerging clinically significant early psychological problems during the COVID-19 outbreak, and specifically received the VRT treatment. We compared the Patient Health Questionnaire 9 items (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), PHQ-15, and Athens Insomnia Scale to evaluate psychological symptoms and sleep quality before and after sessions. All four cases showed a reduction in scale comparison. General scores of the PHQ-9 reduced 65%, GAD-7 reduced 52.17%, PHQ-15 decreased 38.17%, and scores of the Athens Insomnia Scale reduced 67.44%. Meanwhile, a reduction in depression, anxiety, psychosomatic, and sleeping symptoms was also found, which decreased 76.92% in general. These results are highly significant statistically. This case series demonstrated the effectiveness of VRT on psychological problems as a promising approach to apply on various psychological distress and disorders.
Relationships Among Depression, Online Self-Disclosure, Social Media Addiction, and Other Psychological Variables Among Hungarian University Students
Authors: Piko Bettina F. , Kiss Hedvig , Rátky Dóra , Fitzpatrick Kevin M.
Published: July 2022

In the digital age, besides the well-known contributors to depression, more research is needed on certain activities of social media, such as online self-disclosure. Using an online survey, we examine the associations of depression with social media addiction, online self-disclosure, loneliness, and life satisfaction among a sample of Hungarian university students (N = 301, aged between 18 and 30 years). There were no sex differences in depression scores. Findings showed the following: a) lonely students; b) those less satisfied with their lives; c) those sharing negative information; and d) those that engage in deep self-disclosure are more likely to report depressive symptomatology. Although social media addiction was a correlate of depression in bivariate analyses, it became nonsignificant when online self-disclosure and other psychological variables were introduced to the model. A more careful accounting of these relationships is needed to more wisely use social media when disclosing information about ourselves.
Effectiveness of Topical ρ-Kinase Inhibitors in Veterans with Severe Glaucoma on Maximally Tolerated Medical Therapy
Authors: Kianian Reza , Hulbert Samuel W. , Law Simon K. , Giaconi JoAnn
Published: July 2022

SIGNIFICANCE

The real-world pharmacological use of netarsudil shows that it can produce a clinically significant decrease in intraocular pressure for a small group of patients, even if they are already taking three or four other hypotensive glaucoma medication classes.

PURPOSE

This study aimed to assess the effectiveness of netarsudil in reducing intraocular pressure among veterans with advanced glaucoma on maximally tolerated medical therapy.

METHODS

All patients with glaucoma who received netarsudil between June 2018 and April 2020 from the West Los Angeles Veterans Administration Medical Center were reviewed. Inclusion criteria included a minimum of one intraocular pressure measurement in each of two time windows (within and after 4 months of netarsudil use). Exclusion criteria included medication nonadherence, change in treatment plan before post-treatment intraocular pressure could be obtained, corneal disease precluding reliable measurement, outside follow-up, and loss to follow-up. Intraocular pressure at baseline and that at two time windows were compared using analyses of variance. Relationships between intraocular pressure and number of baseline medications and concurrent statin therapy were evaluated. Netarsudil tolerability was reported.

RESULTS

Of 200 patients prescribed netarsudil, 42 patients (eyes) met the enrollment criteria. The mean age of these patients was 75.7 years (95% confidence interval [CI], 73.0 to 78.4 years), 64% were of African descent, 79% had open-angle glaucoma, and the mean number of baseline medications was 3.7 (95% CI, 3.5 to 3.9). Baseline intraocular pressure of 17.2 mmHg (95% CI, 16.1 to 18.2 mmHg) decreased to 15.1 mmHg (95% CI, 14.0 to 16.2 mmHg; P < .001), and a reduction of >20% was seen in 30.9% of patient after 4 months of netarsudil therapy. Intraocular pressure reduction was not associated with number of baseline medications or systemic statin use.

CONCLUSIONS

Netarsudil may produce a clinically significant intraocular pressure reduction in up to a third of the patients with advanced glaucoma already on maximally tolerated medical therapy.
Temporal trends and outcomes of peripheral artery disease revascularization and amputation among the HIV population
Authors: Teng Alexandra E. , Kennedy Kevin F. , Parikh Rushi V. , Armstrong Ehrin J. , Hsue Priscilla Y. , Secemsky Eric A.
Published: July 2022

Objective:

With antiretroviral therapy, people with HIV (PWH) are developing age-related diseases, including peripheral arterial disease (PAD). This study examined frequency and outcomes of peripheral vascular intervention (PVI) and primary amputation in PWH.

Design:

We used the National Inpatient Sample (NIS) database to examine demographics, comorbidities, and temporal trends among PVI and primary amputation admissions by HIV status from 2012 to 2018.

Methods:

Inverse probability of treatment weighting was used to calculate adjusted odds of in-hospital death and amputation. Cost of hospitalization and length of stay were compared by HIV status and revascularization approach.

Results:

Of the 347 824 hospitalizations for PVI/amputation, 0.6% were PWH, which was stable over time. PWH had more renal and hepatic disease, whereas uninfected individuals had more traditional PAD risk factors. 55.2% of HIV+ admissions were endovascular compared with 49.3% in HIV− admissions, and 28.9% of the HIV+ admissions were elective compared with 42.1% among HIV−. HIV status did not impact amputation following PVI. In-hospital death was similar between groups following PVI or primary amputation. PWH had lower costs of hospitalization and a trend towards shorter hospital stays.

Conclusion:

Although PWH are developing more age-related chronic illnesses, the number of PAD-associated procedures has remained flat. Despite being younger with fewer traditional PAD risk factors, PWH had higher rates of unplanned PVI admissions and endovascular revascularization but similar in-hospital outcomes. These findings suggest PWH have different risk factors for PAD and are likely underdiagnosed and undertreated, whereas those who are treated have similar outcomes to the general population.
Tenofovir disoproxil fumarate and coronavirus disease 2019 outcomes in men with HIV
Authors: Li Guilin , Park Lesley S. , Lodi Sara , Logan Roger W. , Cartwright Emily J. , Aoun-Barakat Lydia , Casas Juan P. , Dickerman Barbra A. , Rentsch Christopher T. , Justice Amy C. , Hernán Miguel A.
Published: July 2022

Objective:

To compare the risk of coronavirus disease 2019 (COVID-19) outcomes by antiretroviral therapy (ART) regimens among men with HIV.

Design:

We included men with HIV on ART in the Veterans Aging Cohort Study who, between February 2020 and October 2021, were 18 years or older and had adequate virological control, CD4+ cell count, and HIV viral load measured in the previous 12 months, and no previous COVID-19 diagnosis or vaccination.

Methods:

We compared the adjusted risks of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-related hospitalization, and intensive care unit (ICU) admission by baseline ART regimen: tenofovir alafenamide (TAF)/emtricitabine (FTC), tenofovir disoproxil fumarate (TDF)/FTC, abacavir (ABC)/lamivudine (3TC), and other. We fit pooled logistic regressions to estimate the 18-month risks standardized by demographic and clinical factors.

Results:

Among 20 494 eligible individuals, the baseline characteristics were similar across regimens, except that TDF/FTC and TAF/FTC had lower prevalences of chronic kidney disease and estimated glomerular filtration rate <60 ml/min. Compared with TAF/FTC, the estimated 18-month risk ratio (95% confidence interval) of documented SARS-CoV-2 infection was 0.65 (0.43, 0.89) for TDF/FTC, 1.00 (0.85, 1.18) for ABC/3TC, and 0.87 (0.70, 1.04) for others. The corresponding risk ratios for COVID-19 hospitalization were 0.43 (0.07, 0.87), 1.09 (0.79, 1.48), and 1.21 (0.88, 1.62). The risk of COVID-19 ICU admission was lowest for TDF/FTC, but the estimates were imprecise.

Conclusion:

Our study suggests that, in men living with HIV, TDF/FTC may protect against COVID-19-related events. Randomized trials are needed to investigate the effectiveness of TDF as prophylaxis for, and early treatment of, COVID-19 in the general population.
The contribution of late HIV diagnosis on the occurrence of HIV-associated tuberculosis
Authors: Girardi Enrico , Caro-Vega Yanink , Cozzi-Lepri Alessandro , Musaazi Joseph , Carriquiry Gabriela , Castelnuovo Barbara , Gori Andrea , Manabe Yukari C. , Gotuzzo José Eduardo , D’arminio Monforte Antonella , Crabtree-Ramírez Brenda , Mussini Cristina
Published: July 2022

Objectives:

To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials.

Design:

We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk.

Methods:

People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy. The risk of TB was compared in LP (accessing care with CD4+ cell count ≤350 cells/μl) vs. nonlate presentation using survival curves and a weighted Cox regression. We emulated two strategies: initiating ART with CD4+ cell count less than 350 cells/μl vs. CD4+ cell count at least 350 cells/μl (late initiation). We estimated TB attributable risk and population attributable fraction up to 5 years from the emulated date of randomization.

Results:

Twenty thousand one hundred and twelve patients and 1936 TB cases were recorded. Over 50% of TB cases were diagnosed at presentation for HIV care. More than 50% of the incident cases of TB after ART initiation were attributable to late presentation; nearly 70% of TB cases during the first year of follow-up could be attributed to late presentation and more than 50%, 5 years after first attending HIV care.

Conclusion:

Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry.
Routine programmatic data show a positive population-level impact of HIV self-testing: the case of Côte d’Ivoire and implications for implementation
Authors: Simo Fotso Arlette , Johnson Cheryl , Vautier Anthony , Kouamé Konan Blaise , Diop Papa Moussa , Silhol Romain , Maheu-Giroux Mathieu , Boily Marie-Claude , Rouveau Nicolas , Doumenc-Aïdara Clémence , Baggaley Rachel , Ehui Eboi , Larmarange Joseph
Published: July 2022

Objectives:

We estimate the effects of ATLAS's HIV self-testing (HIVST) kit distribution on conventional HIV testing, diagnoses, and antiretroviral treatment (ART) initiations in Côte d’Ivoire.

Design:

Ecological study using routinely collected HIV testing services program data.

Methods:

We used the ATLAS's programmatic data recorded between the third quarter of 2019 and the first quarter of 2021, in addition to data from the President's Emergency Plan for AIDS Relief dashboard. We performed ecological time series regression using linear mixed models. Results are presented per 1000 HIVST kits distributed through ATLAS.

Results:

We found a negative but nonsignificant effect of the number of ATLAS’ distributed HIVST kits on conventional testing uptake (−190 conventional tests; 95% confidence interval [CI]: −427 to 37). The relationship between the number of HIVST kits and HIV diagnoses was significant and positive (+8 diagnosis; 95% CI: 0 to 15). No effect was observed on ART initiation (−2 ART initiations; 95% CI: −8 to 5).

Conclusions:

ATLAS’ HIVST kit distribution had a positive impact on HIV diagnoses. Despite the negative signal on conventional testing, even if only 20% of distributed kits are used, HIVST would increase access to testing. The methodology used in this paper offers a promising way to leverage routinely collected programmatic data to estimate the effects of HIVST kit distribution in real-world programs.
Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens
Authors: Bannister Wendy P. , Mast T. Christopher , de Wit Stéphane , Gerstoft Jan , Wiese Lothar , Milinkovic Ana , Hadziosmanovic Vesna , Clarke Amanda , Rasmussen Line D. , Lacombe Karine , Schommers Philipp , Staub Thérèse , Zagalo Alexandra , Portu Joseba J. , Tau Luba , Calmy Alexandra , Cavassini Matthias , Gisinger Martin , Borodulina Elena , Mocroft Amanda , Reekie Joanne , Peters Lars
Published: July 2022

Background:

Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study.

Methods:

PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010–2019 with baseline and ≥1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease [CVD], malignancies, diabetes mellitus [DM] and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m2 decrease, ±1 kg/m2 stable, >1 kg/m2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure.

Results:

6721 PWH were included; 72.3% were male, median age 48 years (interquartile range [IQR] 40–55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years [IQR 2.6–6.7]).

100 CVDs, 149 malignancies, 144 DMs, and 257 deaths were observed with incidence rates 4.4, 6.8, 6.6, 10.6 per 1000 person-years of follow-up, respectively. Compared to stable BMI, >1 kg/m2 increase was associated with increased risk of DM (adjusted incidence rate ratio [IRR]: 1.96, 95% confidence interval [CI]: 1.36–2.80) and >1 kg/m2 decrease with increased risk of death (adjusted IRR: 2.33, 95% CI: 1.73–3.13). No significant associations were observed between BMI changes and CVD or malignancies.

Conclusions:

A BMI increase was associated with DM and a decrease associated with death.
Characteristics of patients admitted to the ICU with Kaposi sarcoma herpesvirus-associated diseases
Authors: Hansen Megan E. , Mangusan Ralph , Lurain Kathryn , Odeny Thomas , George Jomy , Lu Crystal , Manion Maura , Widell Anaida , Ekwede Irene , Whitby Denise , Gulley James L. , Kadri Sameer S. , Elinoff Jason M. , Barochia Amisha , Torabi-Parizi Parizad , Uldrick Thomas S. , Yarchoan Robert , Ramaswami Ramya
Published: July 2022

Objective:

There are four conditions caused by Kaposi sarcoma herpesvirus (KSHV): Kaposi sarcoma, KSHV-associated multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and KSHV inflammatory cytokine syndrome (KICS). These KSHV-associated disorders (KADs) often occur in people with HIV and can lead to multiorgan dysfunction requiring admission to the ICU. However, little is known about patient outcomes in this setting.

Methods:

A retrospective study of patients with KADs admitted to the ICU between 2010 and 2021 was conducted, examining KAD admission diagnoses, HIV characteristics, selected cytokine profiles, and ICU interventions. Primary outcomes were 60-day and median overall survival from ICU admission to death from any cause.

Results:

Forty-seven patients (all but one with HIV coinfection) were included. At ICU admission, 44 patients (94%) were on antiretroviral therapy with a median CD4+ count of 88 cells/μl and HIV viral load of 23 copies/ml. The most common presentation was respiratory failure alone (19%) or with hypotension (17%). Twenty-two (47%) patients had presumed KICS (with or without Kaposi sarcoma) at admission and an additional KAD was diagnosed in 36% of these patients. IL-6 levels did not vary across KAD subtype. Twenty (43%) patients received KAD-directed therapy in the ICU. Sixty-day survival was 70% and median overall survival was 9 months.

Conclusion:

The majority of patients with HIV and KADs admitted to the ICU had well controlled HIV. Additional KAD were diagnosed during ICU admission in a proportion of patients who presented with presumed KICS. Critical illness did not preclude a subset of patients from receiving KAD-directed therapy in the ICU.
COVID19 in hematological patients and telemedicine: lessons learned across Europe and the US
Authors: Mussetti Alberto , Peric Zinaida , Figueroa Cesar
Published: July 2022

Purpose of review

To describe the state-of-the-art of telemedicine in hematology through the description of most relevant studies published in the pre-COVID19 and during the COVID19 era.

Recent findings

Telemedicine has recently gained momentum in hematology due to the COVID19 pandemic. Due to a necessary improvement of domiciliary follow-up of patients during the pandemic and an increase in technologies able to offer telemedicine, the number of studies has increased in the last 2 years. Telemedicine showed the potential to improve the monitoring of both benign and malignant hematological diseases. Patients affected by thalassemias, hemophilias and/or myeloproliferative diseases were monitored successfully with telemedicine platform. For higher-risk patients such as high-dose chemotherapy or stem cell transplantation, better platforms are needed (e.g. use of wearable devices systems). Also, telemedicine showed to be useful for the follow-up of hematological patients with COVID19.

Despite the clear potential advantages of telemedicine for the follow-up of hematological patients, more evidence is required before adopting this approach in larger cohorts of patients. Larger- and higher-quality studies are highly needed in this setting.
A work in progress: antimicrobial stewardship in solid organ transplant patient populations
Authors: Tessier Jeffrey
Published: July 2022

Purpose of review

To review recent medical literature addressing antimicrobial stewardship in solid organ transplant (SOT) recipients.

Recent findings

Few studies with a strict focus on SOT patients have been published to date. Team-based antimicrobial stewardship interventions in SOT populations do have beneficial impacts on antimicrobial stewardship-relevant outcomes. Several studies have compared SOT-specific antibiograms to widely accepted hospital antibiograms; these studies all have found important differences in resistance rates among bacterial pathogens. Novel biomarkers like virome monitoring for assessing the net state of immunosuppression hold promise for individualized antimicrobial stewardship interventions.

SOT patients are an understudied population with respect to antimicrobial stewardship interventions. Current antimicrobial stewardship interventions for SOT patients are largely extrapolated from studies in general patient populations and may not accurately reflect SOT-specific infection risks or outcomes. Antimicrobial stewardship interventions do impact SOT-relevant care goals but require significantly more research to achieve the depth and reach of antimicrobial stewardship interventions developed for general populations.
The implications of the COVID-19 pandemic for long term care facilities
Authors: Yen Muh-Yong , Schwartz Jonathan , Hsueh Po-Ren
Published: July 2022

Purpose of review

Despite advances in infection prevention and control and breakthroughs in vaccination development, challenges remain for long-term care facilities (LTCFs) as they face a likely future of emerging infectious diseases. To ensure the safety of LTCF residents from the current and future pandemics, we identify lessons learned from the coronavirus disease 2019 (COVID-19) experience for improving future prevention and response efforts.

Recent findings

In addition to high disease susceptibility among LTCF residents, LTCF vulnerabilities include a lack of pandemic preparedness, a lack of surge capacity in human, material and testing resources, and poorly designed buildings. External sources of vulnerability include staff working in multiple LTCFs and high COVID-19 rates in surrounding communities. Other challenges include poor cooperation between LTCFs and the other components of health systems, inadequately enforced regulations, and the sometimes contradictory interests for-profit LTCFs face between protecting their residents and turning a profit.

These challenges can be addressed in the post-COVID-19 period through systemic reforms. Governments should establish comprehensive health networks that normalize mechanisms for prediction/preparedness and response/recovery from disruptive events including pandemics. In addition, governments should facilitate cooperation among public and private sector health systems and institutions while utilizing advanced digital communication technologies. These steps will greatly reduce the threat to LTCFs posed by emerging infectious diseases in future.
Epidemiological Study of Neonatal Congenital Microtia in Shandong Province, China, 2011–2020
Authors: Sun Pengfei , Lin Qian , Zhang Min , Liu Zhenzhong , Zhu Lingdong
Published: July 2022

Objective:

Congenital microtia is a common congenital disease in newborns. The specific cause of congenital microtia is currently unknown. The main objective of this study is to elucidate the epidemiological characteristics of congenital microtia and explore the possible etiology of congenital microtia.

Methods:

Part of the newborn data from 2011 to 2020 in Shandong Province Birth Defects Monitoring Hospitals were randomly selected. The software GraphPad Prism 9 was used to analyze the data and draw figures.

Results:

A total of 4247 infants were diagnosed with congenital malformation among 149,525 newborns randomly selected from the Shandong Province Birth Defects Monitoring Hospitals. Among them, a total of 115 infants were diagnosed with congenital microtia. The mean incidence of microtia during 10 years was 76.14±21.93 per 100,000 infants. The mean incidence of microtia in infants with congenital malformation was 2.67±0.75%. The average incidence of male and female infants with microtia during 10 years were 86.93±23.22 and 64.18±32.71 per 100,000 infants, respectively. In terms of maternal age, the older the mother, the higher the incidence of microtia. In terms of the place of residence, rural infants have a higher incidence of microtia than urban infants.

Conclusions:

The average incidence of microtia was 76.14±21.93 per 100,000 infants in Shandong Province, China, 2011–2020. The female-to-male incidence ratio was 1.45:1. The authors recommend that women choose to give birth at the age of 25 to 29. They hope that the government will take measures to improve the medical and health conditions in rural areas and improve parenting knowledge in rural areas. This can effectively reduce the prevalence of microtia in infants.
Bioprotective potential of lactic acid bacteria and their metabolites against enterotoxigenic Escherichia coli
Authors: Oliveira Gabriel Souza , Freire Herbert Pina Silva , Romano Carla Cristina , Rezende Rachel Passos , Evangelista Alberto Gonçalves , Meneghetti Camila , Costa Leandro Batista
Published: July 2022

Escherichia coli

is one of the main pathogens that impacts swine production. Given the need for methods for its control, the in vitro effect of lactic acid bacteria (LAB) and their metabolites against

E. coli

F4 was evaluated through cell culture and microbiological analysis. The strains

Limosilactobacillus fermentum

5.2,

Lactiplantibacillus plantarum

6.2, and

L. plantarum

7.1 were selected. To evaluate the action of their metabolites, lyophilized cell-free supernatants (CFS) were used. The effect of CFS was evaluated in HT-29 intestinal lineage cells; in inhibiting the growth of the pathogen in agar; and in inhibiting the formation of biofilms. The bioprotective activity of LAB was evaluated via their potential for autoaggregation and coaggregation with

E. coli

. The CFS did not show cytotoxicity at lower concentrations, except for

L. fermentum

5.2 CFS, which is responsible for cell proliferation at doses lower than 10 mg ml−1. The CFS were also not able to inhibit the growth of

E. coli

F4 in agar; however, the CFS of

L. plantarum

7.1 resulted in a significant decrease in biofilm formation at a dose of 40 mg ml−1. Regarding LAB, their direct use showed great potential for autoaggregation and coaggregation in vitro, thus suggesting possible effectiveness in animal organisms, preventing

E. coli

fixation and proliferation. New in vitro tests are needed to evaluate lower doses of CFS to control biofilms and confirm the bioprotective potential of LAB, and in vivo tests to assess the effect of LAB and their metabolites interacting with animal physiology.
Decline of intrinsic cerebrospinal fluid outflow in healthy humans with age detected by non-contrast spin-labeling MRI
Authors: Malis Vadim , Bae Won C. , Yamamoto Asako , McEvoy Linda K. , McDonald Marin A. , Miyazaki Mitsue
Published: July 2022

Background

Clearance of cerebrospinal fluid (CSF) is important for the removal of toxins from the brain, with implication for neurodegenerative diseases. Imaging evaluation of CSF outflow in humans has been limited, relying on injections of contrast agents. Objective of this study was to introduce a novel spin-labeling magnetic resonance imaging (MRI) technique to detect and quantify the movement of endogenously tagged CSF without administration of tracer or contrast media, and use the technique to evaluate CSF outflow in normal human subjects with varying ages.

Methods

This study was performed on a clinical 3-Tesla MRI scanner in healthy subjects (10 males and 6 females; mean age, 47.6 ± 18.9 years; range, 19-71 years) with informed consent. Our non-contrast spin-labeling MRI technique applies a tag pulse on the brain hemisphere, including subarachnoid space, dura mater, brain parenchyma, and images the outflow of the tagged CSF into the superior sagittal sinus. We obtained 3-dimensional images in real time, which was analyzed to determine tagged-signal changes in different regions of the brain involved in CSF outflow or clearance. Additionally, the signal changes over time were fit to a signal curve to determine quantitative flow metrics such as relative CSF flow and volume. These were correlated against subject age to determine aging effects.

Results

We observed the signal of the tagged CSF moving from the subarachnoid space to the dura mater and parasagittal dura, and finally draining into the superior sagittal sinus. In addition, there was strong evidence of a direct pathway by which tagged CSF flows directly from the subarachnoid space to the superior sagittal sinus, via the lateral wall of superior sagittal sinus. Furthermore, quantitative CSF outflow metrics were shown to decrease significantly with age.

Conclusions

We demonstrated a novel non-invasive MRI technique to evaluate CSF clearance in humans. In this study, we identified possible two CSF clearance pathways, and determined normative values and decline of CSF flow metrics in normal ages. Our work provides a new opportunity to better understand the relationships of these CSF clearance pathways in ages, which may be a significant factor in the age-related prevalence of neurodegenerative diseases.

Funding

This study was supported by the National Institutes of Health grants: RF1AG076692 (MM) and R01HL154092 (MM); and made possible by a grant from Canon Medical Systems. Corp., Japan.

Clinical trial

Not applicable.
Exploring the emergence of morphological asymmetries around the brain’s Sylvian fissure: a longitudinal study of shape variability in preterm infants
Authors: de Vareilles H , Rivière D , Pascucci M , Sun Z , Fischer C , Leroy F , Tataranno ML , Benders MJNL , Dubois J , Mangin JF
Published: July 2022

Brain folding patterns vary within the human species, but some folding properties are common across individuals, including the Sylvian fissure’s inter-hemispheric asymmetry. Contrarily to the other brain folds (sulci), the Sylvian fissure develops through the process of opercularization, with the frontal, parietal and temporal lobes growing over the insular lobe. Its asymmetry may be related to the leftward functional lateralization for language processing, but the time-course of these asymmetries’ development is still poorly understood. In this study, we investigated refined shape features of the Sylvian fissure and their longitudinal development in 71 infants born extremely preterm (mean gestational age at birth: 26.5 weeks) and imaged once before and once at term-equivalent age (TEA). We additionally assessed asymmetrical sulcal patterns at TEA in the perisylvian and inferior frontal regions, neighbor to the Sylvian fissure. While reproducing renown strong asymmetries in the Sylvian fissure, we captured an early encoding of its main asymmetrical shape features, and we observed global asymmetrical shape features representative of a more pronounced opercularization in the left-hemisphere, contrasting with the previously reported right-hemisphere advance in sulcation around birth. This added novel insights about the processes governing early-life brain folding mechanisms, potentially linked to the development of language-related capacities.

Highlights

-

Shape features can be isolated to describe quantitatively the development of the Sylvian fissure

-

Strong asymmetries are encoded as soon as 30 weeks of post-menstrual age

-

The process of opercularization is more pronounced in the left hemisphere
Model training periods impact estimation of COVID-19 incidence from wastewater viral loads
Authors: Daza–Torres Maria L. , Montesinos-López J. Cricelio , Kim Minji , Olson Rachel , Bess C. Winston , Rueda Lezlie , Susa Mirjana , Tucker Linnea , García Yury E. , Schmidt Alec J. , Naughton Colleen , Pollock Brad H. , Shapiro Karen , Nuño Miriam , Bischel Heather N.
Published: July 2022

Background

Wastewater-based epidemiology (WBE) has been deployed broadly as an early warning tool for emerging COVID-19 outbreaks. WBE can inform targeted interventions and identify communities with high transmission, enabling quick and effective response. As wastewater becomes an increasingly important indicator for COVID-19 transmission, more robust methods and metrics are needed to guide public health decision making.

Objectives

The aim of this research was to develop and implement a mathematical framework to infer incident cases of COVID-19 from SARS-CoV-2 levels measured in wastewater. We propose a classification scheme to assess the adequacy of model training periods based on clinical testing rates and assess the sensitivity of model predictions to training periods.

Methods

We present a Bayesian deconvolution method and linear regression to estimate COVID-19 cases from wastewater data. We described an approach to characterize adequacy in testing during specific time periods and provided evidence to highlight the importance of model training periods on the projection of cases. We estimated the effective reproductive number (Re) directly from observed cases and from the reconstructed incidence of cases from wastewater. The proposed modeling framework was applied to three Northern California communities served by distinct wastewater treatment plants.

Results

Both deconvolution and linear regression models consistently projected robust estimates of prevalent cases andRefrom wastewater influent samples when assuming training periods with adequate testing. Case estimates from models that used poorer-quality training periods consistently underestimated observed cases.

Discussion

Wastewater surveillance data requires robust statistical modeling methods to provide actionable insight for public health decision-making. We propose and validate a modeling framework that can provide estimates of COVID-19 cases andRefrom wastewater data that can be used as tool for disease surveillance including quality assessment for potential training data.