bluuebunny/crossref_metadata_2025 huggingface dataset:
A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis
Authors: Huang Daoyuan , Zuo Yuesheng , Zhang Chen , Sun Guoqiang , Jing Ying , Lei Jinghui , Ma Shuai , Sun Shuhui , Lu Huifen , Zhang Xiaoli , Cai Yusheng , Zhang Weiqi , Gao Fei , Xiang Andy Peng , Izpisua Belmonte Juan Carlos , Liu Guang-Hui , Qu Jing , Wang Si
Published: November 2022

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing the first single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms’ Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
It’s Not the Message, It’s The Messenger: Organizational Identity and White Men’s Opposition to Women’s and African Americans’ Civic Participation
Authors: McVeigh Rory , Carbonaro William , Cannady Emmanuel
Published: November 2022

Theories of structural racism and sexism build from an assumption that members of privileged groups react negatively when non-privileged identities link to an agenda for change. We directly test that assumption with three online experiments administered to national samples of white men in the United States. Respondents evaluate web pages of (fictitious) civic organizations displaying agendas that could undermine race and gender hierarchies. We find that in each experiment, respondents are much more likely to disapprove of the organizational identity of the civic organizations if they are evaluating an organization that indicates it is a “Black Alliance,” or a “Women’s Alliance,” rather than simply an “Alliance.” Disapproval of the organizational identity, in turn, differentiates respondents in terms of their levels of support for the organization and its goals. Results across the three experiments are strikingly similar, reflecting the shared micro-level assumption in different macro-level theories.
Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis*
Authors: Richards-Belle Alvin , Hylands Mathieu , Muttalib Fiona , Taran Shaurya , Rochwerg Bram , Day Andrew , Mouncey Paul R. , Radermacher Peter , Couban Rachel , Asfar Pierre , Adhikari Neill K. J. , Lamontagne Francois
Published: November 2022

OBJECTIVES:

Balancing the risks of hypotension and vasopressor-associated adverse effects is a daily challenge in ICUs. We conducted a systematic review with meta-analysis to examine the effect of lower versus higher exposure to vasopressor therapy on mortality among adult ICU patients with vasodilatory hypotension.

DATA SOURCES:

We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from inception to October 15, 2021.

STUDY SELECTION:

We included randomized controlled trials of lower versus higher exposure to vasopressor therapy in adult ICU patients with vasodilatory hypotension without language or publication status limits.

DATA EXTRACTION:

The primary outcome was 90-day all-cause mortality, with seven prespecified subgroups. Secondary outcomes included shorter- and longer-term mortality, use of life-sustaining therapies, vasopressor-related complications, neurologic outcome, and quality of life at longest reported follow-up. We conducted random-effects meta-analyses to calculate summary effect measures across individual studies (risk ratio [RR] for dichotomous variables, mean difference for continuous variables, both with 95% CIs). The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. We registered this review on the International Prospective Register of Systematic Reviews (CRD42021224434).

DATA SYNTHESIS:

Of 3,403 records retrieved, 68 full-text articles were reviewed and three eligible studies included. Lower exposure to vasopressors probably lowers 90-day mortality but this is based on moderate-certainty evidence, lowered for imprecision (RR, 0.94; 95% CI, 0.87–1.02). There was no credible subgroup effect. Lower vasopressor exposure may also decrease the risk of supraventricular arrhythmia (odds ratio, 0.55; 95% CI, 0.36–0.86; low certainty).

CONCLUSIONS:

In patients with vasodilatory hypotension who are started on vasopressors, moderate-certainty evidence from three randomized trials showed that lower vasopressor exposure probably lowers mortality. However, additional trial data are needed to reach an optimal information size to detect a clinically important 10% relative reduction in mortality with this approach.
Corneal topography and tomography readings with mask wear during the COVID-19 pandemic
Authors: Zein Mike , Wylegala Adam , Sripawadkul Wathanee , Al Bayyat Ghada , Alvarez Osmel P. , Gutierrez Alejandro J. , Guerrero Miguel A. , Galor Anat , Karp Carol L.
Published: November 2022

Purpose:

To assess the effect of mask wear on corneal topography and tomography readings.

Setting:

Tertiary ophthalmic center.

Design:

Prospective, observational, comparative study.

Methods:

Subjects underwent imaging with the Tomey TMS-4a topographer and the Oculus Pentacam HR tomographer. Imaging was performed without a mask, and then testing was repeated while wearing 3 different masks: Halyard Level 2, Halyard Level 3, and KN95. Measurements during mask wear were compared with measurements without a mask. The Kruskal-Wallis analysis of variance grouped test was used to compare mean differences without vs with mask wear on measurements. The Chi-square test was used to compare frequency of differences between different masks and against-the-rule vs with-the-rule astigmatism. The frequencies of clinically significant changes in axis of astigmatism, magnitude of astigmatism, and mean keratometry (K) values were calculated.

Results:

52 eyes were included in the study with a mean age of 34.71. Mask wear did not show statistically significant differences in mean topography and tomography measurements compared with without mask wear for all parameters. However, the majority, 53% (83/156) had a >10 degrees and 41% (64/156) had >15 degrees change in axis of astigmatism on topography when wearing a mask compared with no mask wear.

Conclusions:

Mask wear did not result in statistically significant mean changes in K readings on topography and tomography. However, the axis of astigmatism varied >10 degrees in most of the patients. Axis determination should be interpreted with caution regarding refractive surgery and/or toric intraocular lens planning in individuals whose measurements were obtained while wearing a mask.
Effect of surgical subcutaneous fat removal on leptin serum concentrations, lipid profile, glucose metabolism, insulin resistance, weight, and body mass index: A Meta-analysis.
Authors: Gómez-Sámano Miguel Ángel , Guerrero-Castillo Anna Paula , Abarca-Arroyo Jorge Antonio , Albuja-González Elena Cristina , García-Bonilla Hans Alessandro , Espinosa-Salazar Héctor Donaldo , Villanueva-Gómez-Crespo María Teresa , Catzin-Kuhlmann Andrés , López-Gatell Hugo , Tlapanco-Beltrán Cristina Aurora , Vera-Zertuche Juan Mauricio , León-Suárez Andrés , Telich-Tarriba José Eduardo , Cuevas-Ramos Daniel , Gómez-Pérez Francisco J , Gulias-Herrero Alfonso
Published: November 2022

INTRODUCTION:

Abdominal obesity has been associated with an increased risk of insulin resistance, metabolic syndrome, and diabetes. In contrast, central fat removal procedures like liposuction, lipectomy, and abdominoplasty are among the most common surgical procedures. Nevertheless, the impact of the latter on the former is controversial and understudied.

OBJECTIVE:

to explore the effect of subcutaneous fat elimination procedures on insulin resistance parameters and adipokine levels.

METHODS:

Relevant studies regarding the effects of surgical subcutaneous fat removal on glucose, insulin, adipokines, and lipid metabolism as well as blood pressure, were identified by searching PubMed and Ovid-Cochrane without limits in date, type of publication, or language. After the selection process, 24 studies were obtained. The results of the articles were summarized using descriptive statistics. For the final analysis, a randomized effects model was used to evaluate heterogeneity, averages and meta-analytic differences were expressed with a confidence interval (CI) of 95%.

RESULTS:

All studies reported a reduction in weight (-2.64 kg, 95%CI -4.32, -0.96, p=0.002, i2=36%, p of i2<0.001) and body mass index (BMI) after liposuction. A significant improvement in triglycerides (-10.06 mg/dL, 95%CI -14.03,-6.09, p<0.001, i2=48%, p of i2=0.05), serum glucose concentration (-4.25 mg/dL, 95%CI -5.93,-2.56, p<0.001, i2=68%, p of i2<0.001), serum insulin concentration (-2.86 μIU/mL, 95%CI -3.75,-1.97, p<0.001, i2=59%, p of i2=0.003), and serum leptin concentration (-7.70 ng/mL, 95%CI -11.49,-3.92, p=0.0001, i2=96%, p of i2<0.001) was consistently observed.

CONCLUSIONS:

We do confirm that in addition to weight loss, there is a significant decrease in leptin, triglyceride, glucose, and insulin serum concentrations after liposuction, a fact that should be considered in future discussions.
Quality of Life Improvement Following Blepharoplasty: A Prospective Study
Authors: Papadopulos Nikolaos A. , Archimandritis Theresa , Henrich Gerhard , Kovacs Laszlo , Machens Hans-Günther , Klöppel Markus
Published: November 2022

Background:

Our previous retrospective study indicates that esthetic surgery in general results in a significant improvement in Quality of life (QoL). This is the first indication-specific prospective evaluation of QoL after blepharoplasty using standardized and validated questionnaires.

Objectives:

To report changes in QoL after blepharoplasty prospectively with a 6-month follow-up.

Methods:

The same surgical team performed an esthetic blepharoplasty on 50 patients. Participants answered 1 set of questionnaires preoperatively and 6 months postoperatively. The instrument consisted of a self-developed indication-specific part specially designed for blepharoplasty and 4 validated and standardized testing instruments (FLZ, FPI-R, RSES, and PHQ-4) with norm data for German-speaking countries available.

Results:

This study reveals a high rate of satisfaction after blepharoplasty. 96% felt better about themselves and 94% would undergo the procedure again. Statistically significant increased values were found postoperatively in the items “income” (P=0.016), “family life” (P=0.028), “partner relationship” (P=0.039), “ability to relax” (P<0.001), “energy” (P<0.001), “hobbies” (P<0.001), and with their outer appearance in general (P=0.018). Blepharoplasty showed a statistically significant improvement in emotional stability (P=0.017) and a reduction in depressive symptoms (P<0.001). Our patients had statistically significantly higher self-esteem before (P<0.001) and after (P<0.001) the intervention.

Conclusion:

Our prospective study shows that blepharoplasty increases most aspects of QoL significantly, has a positive effect on emotional and physical well-being, and reduces the incidence of depressive symptoms and anxiety.
Short-term Outcomes of Laparoscopic and Open Distal Pancreatectomy Using Propensity Score Analysis
Authors: Ota Masato , Asakuma Mitsuhiro , Taniguchi Kohei , Ito Yuri , Komura Kazumasa , Tanaka Tomohito , Yamakawa Kazuma , Ogura Takeshi , Nishioka Daisuke , Hirokawa Fumitoshi , Uchiyama Kazuhisa , Lee Sang-Woong
Published: November 2022

Objective:

This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database.

Background:

Reports on the benefits of laparoscopic distal pancreatectomy include 2 randomized controlled trials; however, large-scale, real-world data are scarce.

Methods:

We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the inhospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the 2 groups.

Results:

From 5502 eligible patients, we created a pseudopopulation of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower inhospital mortality during the period of admission (0.0% vs 0.7%, P<0.001) and within 30 days (0.0% vs 0.2%, P=0.001), incidence of reoperation during the period of admission (0.7% vs 1.7%, P=0.018), postpancreatectomy hemorrhage (0.4% vs 2.0%, P<0.001), ileus (1.1% vs 2.8%, P=0.007), and shorter postoperative length of stay (17 vs 20 d, P<0.001).

Conclusions:

The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of inhospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as postpancreatectomy hemorrhage and ileus.
Modulation of Monocyte Response by MicroRNA-15b/106a/374a During Antibody-mediated Rejection in Kidney Transplantation
Authors: Tinel Claire , Lamarthée Baptiste , Gazut Stéphane , Van Loon Elisabet , Von Tokarski Florent , Benon Aurélien , Sauvaget Virginia , Garcia-Paredes Victor , Ménager Mickaël , Morin Lise , Aouni Laïla , Cagnard Nicolas , Rabant Marion , Legendre Christophe , Terzi Fabiola , Essig Marie , Gwinner Wilfried , Naesens Maarten , Marquet Pierre , Anglicheau Dany
Published: November 2022

Background.

Increasing evidence suggest that microRNAs are involved in the physiopathology of acute or chronic renal disease. In kidney transplantation, as key regulators of cellular homeostasis, microRNAs may be involved in the regulation of immune cell function and the allograft response. Here, we investigated the change in circulating microRNA expression profile and their involvement in the profound transcriptional changes associated with antibody-mediated rejection (AMR).

Methods.

Blood samples were collected at the time of the 710 kidney allograft biopsies at 4 European transplant centers. Messenger RNA and microRNA profiling analyses were performed in a discovery-to-validation study within 3 independent cohorts encompassing N = 126, N = 135, and N = 416 patients, respectively.

Results.

Compared with samples with no AMR, 14 microRNAs were significantly decreased in AMR samples. Among them, expression levels of microRNA-15b, microRNA-106a, and microRNA-374a gradually decreased with the severity of AMR lesions. From their in silico–predicted target genes, a high proportion proved to be significantly upregulated in the paired transcriptomic analysis. Gene ontology analyses of microRNA-15b/-106a/-374a suggested enrichment in myeloid-related pathways, which was further refined by in silico and ex vivo transcriptomic analyses, showing a specific origin from classical CD14+ monocytes. Finally, human CD14+ monocytes were subjected to transduction by antago-microRNAs to mimic AMR pathology. MicroRNA-15b/-106a/-374a impairment resulted in cellular activation with an increased expression of CD69, CRIM1, IPO7, and CAAP1, direct and common targets of the 3 microRNAs.

Conclusions.

Together, our data provide new insights into circulating microRNAs as markers and key players in AMR, and they suggest monocyte involvement in this process.
Pathways of Antigen Recognition by T Cells in Allograft Rejection
Authors: Carnel Natacha , Lancia Hyshem H. , Guinier Claire , Benichou Gilles
Published: November 2022

The adaptive immune response leading to the rejection of allogeneic transplants is initiated and orchestrated by recipient T cells recognizing donor antigens. T-cell allorecognition is mediated via 3 distinct mechanisms: the direct pathway in which T cells recognize allogeneic major histocompatibility complex (MHC) molecules on donor cells, the indirect pathway through which T cells interact with donor peptides bound with self-MHC molecules on recipient antigen-presenting cells, and the recently described semidirect pathway whereby T cells recognize donor MHC proteins on recipient antigen-presenting cells. In this article, we present a description of each of these allorecognition pathways and discuss their role in acute and chronic rejection of allogeneic transplants.
Impact of Recipient Age at Liver Transplant on Long-term Outcomes
Authors: Niazi Shehzad K. , Brennan Emily , Spaulding Aaron , Crook Julia , Borkar Shalmali , Keaveny Andrew , Vasquez Adriana , Gentry Melanie T. , Schneekloth Terry , Taner C. Burcin
Published: November 2022

Background.

The age of a liver transplant (LT) candidate is one of many variables used in the transplant selection process. Most research about the age at transplant has used prespecified age ranges or categories in assessing associations with transplant outcomes. However, there is a lack of knowledge about the age at transplant and survival. This study aimed to examine associations of age at transplant as a continuous variable, in conjunction with other patient and disease-related factors, with patient and graft survival after LT.

Methods.

We used the Standard Transplant Analysis and Research data to identify LT recipients between January 2002 and June 2018. Cox regression models with a restricted cubic spline term for age examined associations with graft and patient survival after LT. We assessed the interactions of age with recipients’ sex, race/ethnicity, region, indication for transplant, body mass index, model for end-stage liver disease score, diabetes, functional status at transplant, and donor risk index.

Results.

Age at the time of LT showed a nonlinear association with both graft and patient survival. Each demographic, clinical, transplant-related, and donor-related factor influenced these relationships differently.

Conclusions.

Our results suggest that some older LT candidates may be better than some younger candidates and that clinicians should not exclusively use age to determine who receives LT.
Unrelated Stem Cell Donor HLA Match Likelihoods in the US Registry Incorporating HLA-DPB1 Permissive Mismatching
Authors: Gragert Loren , Spellman Stephen , Shaw Bronwen , Maiers Martin
Published: November 2022

Donor-recipient HLA matching at the DPB1 locus improves the outcomes of hematopoietic cell transplantation (HCT). Retrospective outcomes studies found that in transplants matched for all 8 alleles of the A, B, C, and DRB1 loci at high resolution (8-of-8 match), few transplants were also allele-matched at the DPB1 locus. DPB1 allele matching was thought to be logistically impractical, however a DPB1-permissive mismatch model based on T-cell epitope (TCE) reactivity expands the proportion of suitable donors. To understand the likelihood of success for finding a DPB1-permissive donor, we sought to expand population genetic match likelihood models for the US unrelated donor registry, National Marrow Donor Program (NMDP). After extending HLA haplotype frequency estimates to include the DPB1 locus, our models found that the likelihood of having a DPB1-permissive donor was not much lower than the 8-of-8 match likelihoods. A maximum of 5 additional donors would need to be typed to find a more optimal DPB1-permissive donor at least 90% of the time. Linkage disequilibrium patterns between the DPB1 locus and other classical HLA loci varied markedly by haplotype and population, indicating that the known recombination hotspot between DQ and DP gene complexes has not had uniform impact, thus DPB1-permissive donors are easier to identify within minority populations. DPB1 TCE categories were highly predictable from HLA typing at other loci when imputed with extended haplotype frequency data. Our overall results indicate that registry search strategies that seek a more optimally matched HCT donor encompassing HLA-DPB1 permissibility are likely to be highly productive.

KEY POINTS

HLA-DPB1 permissive donors are available for nearly all patients that have an 8/8 allele match

DPB1-permissive donors will be easier to identify among 8/8 allele matches for minority patients relative to White patients
The prevalence and factors associated with premature birth among post-delivery women in the Mbeya region: An analytical cross-sectional study
Authors: Mawolle Glory Godfrey , Moshi Fabiola Vincent
Published: November 2022

In Tanzania, there was an increase of prematurity rate from 11.4% in 2014 up to 16.60% in 2016 (1). This is a hospital based analytical cross-sectional study which involved biopsychosocial model, which focused on identifying prevalence and associated factors for preterm births among post-delivery women in Mbeya region, one of Tanzania regions. This study involved hospitals in Mbeya urban, Mbeya rural, Chunya, Kyela, Mbarali, Rungwe, Busokelo and Tukuyu districts, where the prevalence of preterm births in Mbeya found to be 39.1%. The study pointed out that factors associated with preterm births were child spacing of <24months (AOR=3.058; 95% CI = 1.026-9.116: p-value 0.045), non-effective use of malaria prophylaxis during pregnancy (AOR=5.418; 95% CI =1. p-value 0.008), twin pregnancy (AOR=4.657; 95% CI =2.112-10.223, p-value < 0.001), violence during pregnancy (AOR=2.059; p-value 0.048), lack of social support (AOR=1.993; p-value 0.022) and use of pica during pregnancy (AOR=1.880; p-value 0.029).

The study outcome revealed that the prevalence of preterm births in Mbeya Region is even higher. Therefore, to minimize or eliminate the problem a deliberate effort to come up with strategies to improve family planning, applications of antimalaria prophylaxis, stop the use of pica and violence during pregnancy was highly recommended.
Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents
Authors: Invernizzi Azzurra , Rechtman Elza , Oluyemi Kristie , Renzetti Stefano , Curtin Paul , Colicino Elena , Ambrosi Claudia , Mascaro Lorella , Patrono Alessandra , Corbo Daniele , Cagna Giuseppa , Gasparotti Roberto , Reichenberg Abraham , Tang Cheuk Y. , Smith Donald R. , Placidi Donatella , Lucchini Roberto G. , Wright Robert O. , Horton Megan K.
Published: November 2022

Adolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal-associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross-sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics (global and local efficiency) in adolescents. In 193 participants (53% females, ages: 15-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting-state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age. We observed significant negative associations between the metal mixture and GE and LE (βGE= -0.076, 95% CI [-0.122, -0.031]; βLE= -0.051, 95% CI [-0.095, -0.006]). Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE. Our results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal.
A cost-effectiveness of Fecal DNA methylation test for colorectal cancer screening in Saudi Arabia
Authors: Yang Zhongzhou , Shi Mang , Liu Mengping , Wang Zhe , Huang Hui , Wang Shunyao , Zheng Xiaoyuan , Liu Yanyan , Liu Na , Li Yantao , Lau Eric , Zhu Shida
Published: November 2022

Background

In the Saudi Arabia, we estimated the cost-effectiveness between fecal DNA methylation test (FDMT) and fecal immunochemical testing (FIT) to detect colorectal cancer (CRC) and precancerous lesions in the national screening program.

Participants and methods

A Markov model was used from 45 to 74 years old CRC screening to compare the cost-effectiveness with the FDMT vs FIT. We predicated the longitudinal participation patterns in the perfect adherence vs organized programs screening covered by national budgets. Outcomes incorporated the incidence rates and mortality rates, cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) under the perfect adherence as well as incidence and mortality forecast within 3, 6 and 9 years.

Results

Under the perfect adherence, the total cost of FDMT was cheaper 38.16% than FIT and extends 0.22 QALYs per person. Furthermore, FDMT was more cost-effective as ICERs ($1487.30 vs $1982.42 per QALY saved) compared with FIT test. Therefore, FDMT test dominated than FIT every year (more costly and less effective). Compared with the organized FDMT programs (6.6% initial positive rate and 54% coloscopy compliance rate), the FIT program (5.8% initial positive rate and 48% coloscopy compliance rate) had 6.25 times to 7.76 times on the incidence rates; 5.12 times to 12.19 times on the mortality rates among 3, 6 and 9 years prediction.

Conclusions

Through the Markov model, we compared FDMT was less costly and more effective than the FIT test under the perfect and organized adherence within nine years prediction. It implied that FDMT might the novel cost-effective tool for Saudi Arabia national screening program.
The effectiveness of grass, birch, and mugwort pollen allergen immunotherapy over 18 years: A national cohort study in Denmark
Authors: Bager Peter , Poulsen Gry , Wohlfahrt Jan , Melbye Mads
Published: November 2022

Background

Long-term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) has been studied for different durations. We studied effectiveness over 18 years using nationwide register-data for Denmark.

Methods

A register-based cohort study using data on filled prescriptions, 1995-2018, Denmark. In a cohort of 1.1 million intranasal corticosteroid spray users (proxy for AR), we matched users treated with grass, birch or mugwort (GBM) AIT 1:2 with non-treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti-allergic nasal spray during the pollen season in the treated vs. non-treated group modelled in a logistic generalized estimating equations analysis using an autoregressive correlation structure and adjusted for years since baseline (one year categories).

Results

Among 7,914 AR patients treated with GBM AIT, the OR of using nasal spray 0-5 years after baseline was reduced when compared with 15,520 non-treated AR individuals (0-2 years, odds ratio (OR) 0.81(0.76-0.85); 3-5 years, OR 0.82(0.77-0.87)), but was close to unity or higher thereafter (6-9 years, OR 0.96(0.91-1.03); 10-18 years, OR 1.15(1.06-1.24). In post-hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use (0-2 years, OR 0.59 (0.54-0.64); 3-5 years, OR 0.64 (0.59-0.71); 6-9 years, 0.82 (0.75-0.91); 10-18 years, 0.95 (0.84-1.08), and in patients using nasal spray in the last pollen season (0-2 years, OR 0.76 (0.72-0.80); 3-5 years 0.84 (0.78-0.91); 6-9 years, OR 0.94 (0.86-1.03); 10-18 years, 0.90 (0.81-1.00)) as opposed to patients who did not use nasal spray in the last pollen season. The post-hoc findings were likewise more consistent for eye drop and oral antihistamine users (secondary outcomes).

Conclusion

Patients treated with GBM AIT in routine care to a higher degree stopped using anti-allergic nasal spray 0-5 years after starting the standard three years of therapy. Post-hoc analyses suggested results were more consistent among patients with persistent AR.
The State-Level Association Between Safe Haven Laws and Rates of Infant Mortality in the United States
Authors: Thomas Kathryn A. , Kaminsky Chloe J.
Published: November 2022

Context

Although the United States has safe haven laws, which allow mothers to safely relinquish their babies to designated safety points, rates of infant mortality remain significantly higher in the United States than other similarly developed countries. The current study is seeking to explore the state-level association between safe haven laws and infant mortality in the United States utilizing a legal epidemiological approach.

Methods

Several sources of publicly available data were combined to examine the state-level association between safe haven laws and rates of infant mortality. A backward stepwise regression was used to determine whether certain safe haven laws significantly predicted rates of infant mortality, while controlling for demographic variables.

Findings

After controlling for demographic variables including rates of health insurance and poverty, safe haven laws stating that only the mother can relinquish a child, laws that protect parents from criminal liability, and laws requiring the provider to provide legal information and referrals significantly predicted rates of infant mortality, with the total model accounting for 70.1% of variance in infant mortality.

Conclusions

Several elements of safe haven laws significantly predicted higher rates of infant mortality, including laws stating that only the mother may relinquish the child, laws that do not protect parents from criminal liability, and laws requiring a provider to provide legal information and referrals. These results have important implications for policymakers considering the reform of the safe haven laws. It is especially important to evaluate the effectiveness and origins of safe haven laws in the wake of the overturn ofRoe v. Wade. Future studies should longitudinally examine how changes in safe haven laws lead to changes in rates of infant mortality.

Policy Points

⍰ This is the first study to use a legal epidemiological approach to examine the state-level impact of specific elements of safe haven laws on rates of infant mortality.

⍰ Several elements of safe haven laws significantly predicted higher rates of infant mortality, including laws stating that only the mother may relinquish the child, laws that do not protect parents from criminal liability, and laws requiring a provider to provide legal information and referrals. These results have important implications for policymakers considering the reform of safe haven laws, which is especially important in the wake of the overturn ofRoe v. Wade.
Evaluation of the effectiveness of mass drug administration strategies for reducing scabies burden in Monrovia, Liberia: An agent-based modelling approach
Authors: Tellioglu Nefel , Chisholm Rebecca H. , Campbell Patricia Therese , Collinson Shelui , Timothy Joseph , Kollie Karsor , Zayzay Samuel , Devine Angela , McVernon Jodie , Marks Michael , Geard Nicholas
Published: November 2022

Background

Scabies is a parasitic infestation with high global burden. Mass drug administrations (MDAs) are recommended for communities with a scabies prevalence of >10%. Quantitative analyses are needed to demonstrate the likely effectiveness of MDA recommendations. In this study, we compare the effectiveness of differing MDA strategies, supported by improved treatment access, on scabies prevalence in Monrovia, Liberia.

Methods

We developed an agent-based model of scabies transmission calibrated to demographic and epidemiological data from Monrovia. We used this model to compare the effectiveness of MDA scenarios for achieving scabies elimination and reducing scabies burden, as measured by time until recrudescence following delivery of an MDA and disability-adjusted-life-years (DALYs) averted. We also investigated the additional impact of improving access to scabies treatment following delivery of an MDA.

Results

Our model showed that 3 rounds of MDA delivered at 6-month intervals and reaching 80% of the population could reduce prevalence below 2% for 3 years following the final round, before recrudescence. When MDAs were followed by increased treatment uptake, prevalence was maintained below 2% indefinitely. Increasing the number of and coverage of MDA rounds increased the probability of achieving elimination and the DALYs averted.

Conclusions

Our results suggest that acute reduction of scabies prevalence by MDA can support a transition to improved treatment access. This study demonstrates how modelling can be used to estimate the expected impact of MDAs by projecting future epidemiological dynamics and health gains under alternative scenarios.

We use an agent-based model to demonstrate that mass drug administration (MDA) programs can achieve sustained reduction in scabies prevalence. However, effective MDAs must be accompanied by systemic changes that increase the rate of scabies treatment to prevent recrudescence.
Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment
Authors: França Lucas G. S. , Ciarrusta Judit , Gale-Grant Oliver , Fenn-Moltu Sunniva , Fitzgibbon Sean , Chew Andrew , Falconer Shona , Dimitrova Ralica , Cordero-Grande Lucilio , Price Anthony N , Hughes Emer , O’Muircheartaigh Jonathan , Duff Eugene , Tuulari Jetro J , Deco Gustavo , Counsell Serena J , Hajnal Joseph V , Nosarti Chiara , Arichi Tomoki , Edwards A David , McAlonan Grainne , Batalle Dafnis
Published: November 2022

Brain dynamic functional connectivity characterises transient connections between brain regions, changing over time. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n= 324) and preterm-born (n= 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.
Oral bioavailability and metabolism of hydroxytyrosol from food supplements
Authors: Bender Cecilia , Strassmann Sarah , Golz Christian
Published: November 2022

Table olives and olive oils are the main dietary sources of hydroxytyrosol (HT), a natural antioxidant compound that has emerged as a potential aid in protection against cardiovascular risk. Bioavailability studies with olive oils showed that HT is bioavailable from its free form and from conjugated forms like oleuropein and its aglycone. Still, its low dietary intake, poor bioavailability, and high inter-individual variability after absorption through the gastrointestinal tract hamper its full benefits.

In a randomized, controlled, blind, cross-over study, we investigated the impact of HT metabolism and bioavailability by comparing two olive-derived watery supplements containing different doses of HT (30.58 and 61.48 mg of HT/dosage, respectively); additionally, HT-fortified olive oil was used in the control group. To this aim, plasma and urine samples were evaluated in 12 healthy volunteers following the intake of a single dose of the supplements or fortified olive oil. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 hours after intake. HT and its metabolites were analyzed by UHPLC-DAD-MS/MS.

Pharmacokinetic results showed that dietary HT administered through the food supplements is bioavailable and biovailability increases with the administered dose. After intake, homovanillic acid, HT-3-O-sulfate, and 3,4-dihydroxyphenylacetic acid are the main metabolites found both in plasma and urine. The maximum concentrations in plasma peaked 30 minutes after intake.

Being the bioavailability of a compound a fundamental prerequisite for its effect, these results promise a good potential of both food supplements for the protection against oxidative stress and the consequent cardiovascular risk.
Trends and determinants of Acute Respiratory Infection symptoms among Under-five children in Cambodia: Analysis of 2000 to 2014 Cambodia Demographic and Health Surveys
Authors: Um Samnang , Pin Punleak , Vang Daraden , Chau Darapheak
Published: November 2022

INTRODUCTION

Acute Respiratory Infections (ARI) is public health concern. According to the World Health Organization (WHO), ARI is responsible for 3.5% of all diseases in the world and more than 808,000 (15%) of all under-five deaths worldwide in 2017. ARI continues to be one of the leading causes of childhood morbidity and mortality in Cambodia, particularly among children under five of age. We aimed to assess the trends over time of ARI symptoms and examine the socio-demographic, behavioral, and environmental factors associated with ARI symptoms among Cambodian children aged 0-59 months across 2000, 2005, 2010, and 2014.

METHODS

We used existing children’s data from the Cambodia Demographic and Health Survey (CDHS) with a total of children ages 0-59 months included 7,828 in 2000, 7,621 in 2005, 7,727 in 2010, and 6,864 in 2014, respectively. All statistical estimations were carried out using STATA V16, within the survey-specific command “svy” using the standard sampling weight (v005/1,000,000), clustering, and stratification. We used simple and multiple logistic regression to determine the main predictors of ARI symptoms.

RESULTS

ARI symptoms in the previous two weeks in children aged 0-59 months in Cambodia decreased from 19.9% in 2000 to 8.6% in 2005 to 6.4% in 2010, then fewer at 5.5% in 2014. The main factors that increased the likelihood of ARI symptoms were children ages 6-11 months [AOR=1.91; 95% CI: 1.53-2.38], 12-23 months [AOR=1.79; 95% CI: 1.46-2.20], and 24-35 months [AOR=1.41; 95% CI: 1.13-1.76], mothers who smoke cigarette [AOR=1.61; 95% CI: 1.27-2.05], and children born into households had non-improved toilets [AOR=1.20; 95% CI: 0.99-1.46]. However, the following factors were found to be associated with decreased odds of having ARI symptoms: Mothers with higher education [AOR=0.45; 95% CI: 0.21-0.94], breastfeeding children [AOR=0.87; 95% CI: 0.77-0.98], and children born into richest wealth quantile [AOR=0.73; 95% CI: 0.56-0.95], respectively. Survey years in 2005 [AOR=0.36; 95% CI: 0.31-0.42], 2010 [AOR=0.27; 95% CI: 0.22-0.33], 2014 [AOR=0.24; 95% CI: 0.19-0.30].

CONCLUSION

The trends of ARI symptoms among children under five in Cambodia significantly decreased from 2000-2014. Mothers who smoke cigarettes, young children ages (6-35 months), and household unimproved toilet facilities are factors that independently increased the likelihood that children would develop ARI symptoms. Inversely, factors were found to be associated with decreased odds of having ARI symptoms: Mothers with higher education, breastfeeding children, and children born into the richest wealth quantile and Survey years. Therefore, government and child family programs must promote maternal education, particularly infant breastfeeding. The government ought to support maternal education and infant breastfeeding in the interest of early childhood care.
Modeling analysis of COVID 19-related delays in colorectal cancer screening on simulated clinical outcomes
Authors: Wilson Lesley-Ann Miller , Vahdat Vahab , Brooks Durado , Limburg Paul
Published: November 2022

Objective

Colorectal cancer (CRC) screening disruptions observed during the COVID-19 pandemic put patients at risk for more advanced-stage disease when diagnosed. This budget impact simulation model assessed increased use of multi-target stool DNA [mt-sDNA] or fecal immunochemical [FIT] tests to offset disruption in colonoscopy screening due to COVID-19 in adults at average-risk for CRC, from a United States payer perspective

Main outcomes and measures

Compared to the base case (S0; 85% colonoscopy and 15% non-invasive tests), the estimated number of missed CRCs and advanced adenomas (AAs) were determined for four COVID-19-affected screening scenarios: S1, 9 months of CRC screening at 50% capacity, followed by 21 months at 75% capacity; S2, S1 followed by increasing stool-based testing by an average of 10% over 3-years; S3, 18 months of CRC screening at 50% capacity, followed by 12 months of 75% capacity; and S4, S3 followed by increasing stool-based testing by an average of 13% over 3-years.

Results

Increasing the proportional use of mt-sDNA improved AA detection by 6.0% (Scenario 2 versus 1) to 8.4% (Scenario 4 versus 3) and decreased the number of missed CRCs by 15.1% to 17.3%, respectively. Increasing FIT utilization improved the detection of AAs by 3.3% (Scenario 2 versus 1) to 4.6% (Scenario 4 versus 3) and decreased the number of missed CRCs by 12.9% to 14.9%, respectively. Across all scenarios, the number of AAs detected was higher for mt-sDNA than for FIT, and the number of missed CRCs was lower for mt-sDNA than for FIT.

Conclusions and relevance

Using home-based stool tests for average-risk CRC screening can mitigate the consequences of reduced colonoscopy screening resulting from the COVID-19 pandemic. Use of mt-sDNA led to fewer missed CRCs and more AAs detected, compared to FIT.

Key Points

Question

What is the impact of increasing the use of stool-based screening tests for colorectal cancer (CRC) during the COVID-19 pandemic in the United States?

Findings

In this simulation model, increasing the use of stool-based screening tests increased the number of advanced adenomas detected and decreased the number of missed CRC cases. Use of multi-target stool DNA (mt-sDNA) resulted in a higher number of advanced adenomas detected and a lower number of missed CRC cases compared to fecal immunochemical testing (FIT).

Meaning

Increased use of mt-sDNA led to fewer missed CRC cases and more advanced adenomas detected, compared to FIT, when simulating reduced colonoscopy screening resulting from the COVID-19 pandemic.
Research Letter: Association between long COVID symptoms and employment status
Authors: Perlis Roy H. , Trujillo Kristin Lunz , Safarpour Alauna , Santillana Mauricio , Ognyanova Katherine , Druckman James , Lazer David
Published: November 2022

Background

Symptoms of Coronavirus-19 (COVID-19) infection persist beyond 2 months in a subset of individuals, a phenomenon referred to as long COVID, but little is known about its functional correlates and in particular the relevance of neurocognitive symptoms.

Method

We analyzed a previously-reported cohort derived from 8 waves of a nonprobability-sample internet survey called the COVID States Project, conducted every 4-8 weeks between February 2021 and July 2022. Primary analyses examined associations between long COVID and lack of full employment or unemployment, adjusted for age, sex, race and ethnicity, education, urbanicity, and region, using multiple logistic regression with interlocking survey weights.

Results

The cohort included 15,307 survey respondents ages 18-69 with test-confirmed COVID-19 at least 2 months prior, of whom 2,236 (14.6%) reported long COVID symptoms, including 1,027/2,236 (45.9%) reporting either ‘brain fog’ or impaired memory. Overall, 1,418/15,307 (9.3%) reported being unemployed, including 276/2,236 (12.3%) of those with long COVID and 1,142/13,071 (8.7%) of those without; 8,228 (53.8%) worked full-time, including 1,017 (45.5%) of those with long COVID and 7,211 (55.2%) without. In survey-weighted regression models, presence of long COVID was associated with being unemployed (crude OR 1.44, 95% CI 1.20-1.72; adjusted OR 1.23, 95% CI 1.02-1.48), and with lower likelihood of working full-time (crude OR 0.73, 95% CI 0.64-0.82; adjusted OR 0.79, 95% CI 0.70 -0.90). Among individuals with long COVID, the presence of cognitive symptoms – either brain fog or impaired memory – was associated with lower likelihood of working full time (crude OR 0.71, 95% CI 0.57-0.89, adjusted OR 0.77, 95% CI 0.61-0.97).

Conclusion

Long COVID was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. Presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to respond to long COVID, and particularly the associated neurocognitive symptoms.