bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Pneumomediastinum Secondary to Undiagnosed Asthma in Military Adult
Authors: Klamfoth Jeanette , Koroscil Matthew
Published: August 2023

Spontaneous pneumomediastinum (SPM) is a rare but described complication of exercise-induced bronchoconstriction (EIB), more commonly observed in children with asthma. We present a 23-year-old active duty military male and avid distance runner who developed progressive radiating retrosternal chest pain preceded by wheezing and coughing paroxysm. A chest computed tomography revealed extensive pneumomediastinum. SPM results from increased intrathoracic pressure with alveolar rupture and subsequent tracking of air between fascial planes. Like most cases of SPM, our patient remained hemodynamically stable and responded well to conservative therapies with complete resolution. After thorough evaluation, undiagnosed asthma was determined to be the inciting etiology. The patient is now well controlled and symptom free on a daily low-dose inhaled corticosteroid without SPM reoccurrence. In young adult patients presenting with SPM, EIB and asthma should be considered on the differential diagnosis as appropriate medical therapy will improve symptoms and reduce risk of reoccurrence.
New-onset severe eosinophilic granulomatosis with polyangiitis following the third dose of mRNA COVID-19 vaccine: A case report
Authors: Mahdi Salah , Joudeh Anwar I , Raman Krishnamoorthy Sundara , Faqih Samia Ait , Alhatou Mohammed Ibrahim , Wadiwala Muhammad Faisal , Akhtar Mohammed , Lutf Abdo Qaid Ahmed
Published: August 2023

Eosinophilic granulomatosis with polyangiitis (EGPA) is a complex multifactorial disease that results in multisystemic inflammation of the small- and medium-sized arteries. The exact pathogenesis of this syndrome is poorly understood, but it is postulated to result from a combination of eosinophilic dysfunction, genetic predisposition, and the development of autoantibodies after exposure to an unknown stimulus. We describe a case of new-onset EGPA following the third dose of the Pfizer-BioNTech mRNA vaccine in an infection-naive middle-aged man with a background history of allergic respiratory symptoms. The patient developed acute onset of mononeuritis multiplex, pauci-immune glomerulonephritis, and leucocytoclastic vasculitis 10 days after receiving the booster dose. His laboratory markers including eosinophil count, antineutrophil cytoplasmic antibodies, and renal function tests improved markedly after the initiation of pulse steroid therapy and rituximab infusion. However, his peripheral muscle weakness and neuropathic pain did not respond to the initial therapy but improved later with intravenous cyclophosphamide and intravenous immunoglobulin. To the best of our knowledge, this is the fourth case report of post-coronavirus disease 2019 vaccination precipitation of EGPA. All reported cases including our report were in patients with previous allergic manifestations who received mRNA-based coronavirus disease 2019 vaccines, and all the patients developed mononeuritis multiplex at presentation. Despite the few reported cases of post-vaccination autoimmune phenomena, the temporal association between vaccination administration and disease onset does not indicate causality, given the mass vaccination programmes employed. However, the novel use of the mRNA platform in vaccine delivery necessitates vigilant monitoring by the scientific committee.
Incidence and Prevalence of Hepatitis C Virus Among HIV-Negative Gay and Bisexual Men Using HIV Pre-exposure Prophylaxis (PrEP): A Systematic Review and Meta-analysis
Authors: Traeger Michael W , Harney Brendan L , Sacks-Davis Rachel , van Santen Daniela K , Cornelisse Vincent J , Wright Edwina J , Hellard Margaret E , Doyle Joseph S , Stoové Mark A
Published: August 2023

Background

Gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) are at increased risk for sexually transmissible infections. Hepatitis C virus (HCV) risk among PrEP users is less clear. We explored HCV prevalence and incidence among cohorts of gay and bisexual men using PrEP and sources of heterogeneity across studies.

Methods

This was a systematic review and meta-analysis of open-label PrEP studies to April 2022 reporting HCV prevalence at baseline or incidence during follow-up among gay and bisexual men using PrEP. Pooled prevalence and incidence estimates were calculated using random-effects meta-analysis, and subgroup analyses were performed by study- and country-level characteristics, including availability of HCV direct-acting antiviral (DAA) therapy at time of study.

Results

Twenty-four studies from 9 countries were included, with a total sample of 24 733 gay and bisexual men. Pooled HCV antibody baseline prevalence was 0.97% (95% CI, 0.63%–1.31%), and pooled HCV RNA baseline prevalence was 0.38% (95% CI, 0.19%–0.56%). Among 19 studies reporting HCV incidence, incidence ranged from 0.0 to 2.93/100 person-years (py); the pooled estimate was 0.83/100py (95% CI, 0.55–1.11). HCV incidence was higher in 12 studies that began follow-up before broad DAA availability (1.27/100py) than in 8 studies that began follow-up after broad DAA availability (0.34/100py) and higher in studies in Europe compared with North America and Australia.

Conclusions

Early reports of high HCV incidence among PrEP-using cohorts likely reflect enrollment of individuals based on specific risk-based eligibility criteria for smaller studies and enrollment before DAA scale-up. In contexts where both DAAs and PrEP have been implemented at scale, studies report lower HCV incidence. PrEP-specific HCV testing guidelines should be guided by local epidemiology.
Biologics to treat anaphylaxis
Authors: Yang Barbara C.
Published: August 2023

Purpose of review

The purpose of this literature review was to review the latest use of biologics in the management of anaphylaxis. The methodology was to highlight both the nonbiologic management of anaphylaxis and the biologic management and how they can be used in conjunction with each other.

Recent findings

As the phenotypes and endotypes of anaphylaxis are better portrayed, it furthers our understanding of the mechanisms of anaphylaxis. New applications of existing biologics to the prevention of anaphylaxis are described.

Anaphylaxis is a potentially life-threatening acute hypersensitivity reaction affecting up to 16.8% of the U.S. population. Acute management entails swift identification, removal of the causative agent, and the prevention of cardiovascular collapse, firstly with epinephrine. Adjunctive treatments such as antihistamines work to prevent anaphylaxis from recurring. Biologic management of anaphylaxis involves the use of large-molecule drugs such as monoclonal antibodies. Omalizumab, an IgG1 monoclonal antibody targeting unbound IgE, is the most prevalent and widely studied biologic in the prevention of anaphylaxis. Other monoclonal antibodies in development or approved for other indications, such as ligelizumab, quilizumab, MEDI4212, and dupilumab, may also have potential for preventing anaphylaxis through various mechanisms.
Management and outcomes of gastric leak after sleeve gastrectomy: results from the 2010–2020 national registry
Authors: Li Mengyi , Zeng Na , Liu Yang , Sun Xitai , Yang Wah , Liu Yanjun , Mao Zhongqi , Yao Qiyuan , Zhao Xiangwen , Liang Hui , Lou Wenhui , Ma Chiye , Song Jinghai , Wu Jianlin , Yang Wei , Zhang Pin , Zhu Liyong , Tian Peirong , Zhang Peng , Zhang Zhongtao
Published: August 2023

Background:

Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aim to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting.

Methods:

To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan–Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks.

Results:

A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population (P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgicalt reatment was significantly lower than those requring non-surgical treatment (P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor.

Conclusions:

Male sex, elevated waist circumference, hypoproteinaemia and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Estimation of SARS-CoV-2 Seroprevalence in Central North Carolina: Accounting for Outcome Misclassification in Complex Sample Designs
Authors: Vias Nishma P. , Cassidy Caitlin A. , Edwards Jessie K. , Xiong Khou , Beatty Parker Cherese , Aiello Allison E. , Boyce Ross M. , Shook-Sa Bonnie E.
Published: August 2023

Background:

Population-based seroprevalence studies are crucial to understand community transmission of COVID-19 and guide responses to the pandemic. Seroprevalence is typically measured from diagnostic tests with imperfect sensitivity and specificity. Failing to account for measurement error can lead to biased estimates of seroprevalence. Methods to adjust seroprevalence estimates for the sensitivity and specificity of the diagnostic test have largely focused on estimation in the context of convenience sampling. Many existing methods are inappropriate when data are collected using a complex sample design.

Methods:

We present methods for seroprevalence point estimation and confidence interval construction that account for imperfect test performance for use with complex sample data. We apply these methods to data from the Chatham County COVID-19 Cohort (C4), a longitudinal seroprevalence study conducted in central North Carolina. Using simulations, we evaluate bias and confidence interval coverage for the proposed estimator compared with a standard estimator under a stratified, three-stage cluster sample design.

Results:

We obtained estimates of seroprevalence and corresponding confidence intervals for the C4 study. SARS-CoV-2 seroprevalence increased rapidly from 10.4% in January to 95.6% in July 2021 in Chatham County, North Carolina. In simulation, the proposed estimator demonstrates desirable confidence interval coverage and minimal bias under a wide range of scenarios.

Conclusion:

We propose a straightforward method for producing valid estimates and confidence intervals when data are based on a complex sample design. The method can be applied to estimate the prevalence of other infections when estimates of test sensitivity and specificity are available.
Disparities in greenspace associated with sleep duration among adolescent children in Southern California
Authors: Zhong Charlie , Yin Xiaozhe , Fallah-Shorshani Masoud , Islam Talat , McConnell Rob , Fruin Scott , Franklin Meredith
Published: August 2023

Background:

More than half of adolescent children do not get the recommended 8 hours of sleep necessary for optimal growth and development. In adults, several studies have evaluated effects of urban stressors including lack of greenspace, air pollution, noise, nighttime light, and psychosocial stress on sleep duration. Little is known about these effects in adolescents, however, it is known that these exposures vary by socioeconomic status (SES). We evaluated the association between several environmental exposures and sleep in adolescent children in Southern California.

Methods:

In 2010, a total of 1476 Southern California Children’s Health Study (CHS) participants in grades 9 and 10 (mean age, 13.4 years; SD, 0.6) completed a questionnaire including topics on sleep and psychosocial stress. Exposures to greenspace, artificial light at night (ALAN), nighttime noise, and air pollution were estimated at each child’s residential address, and SES was characterized by maternal education. Odds ratios and 95% confidence intervals (95% CIs) for sleep outcomes were estimated by environmental exposure, adjusting for age, sex, race/ethnicity, home secondhand smoke, and SES.

Results:

An interquartile range (IQR) increase in greenspace decreased the odds of not sleeping at least 8 hours (odds ratio [OR], 0.86 [95% CI, 0.71, 1.05]). This association was significantly protective in low SES participants (OR, 0.77 [95% CI, 0.60, 0.98]) but not for those with high SES (OR, 1.16 [95%CI, 0.80, 1.70]), interaction P = 0.03. Stress mediated 18.4% of the association among low SES participants.

Conclusions:

Residing in urban neighborhoods of greater greenness was associated with improved sleep duration among children of low SES but not higher SES. These findings support the importance of widely reported disparities in exposure and access to greenspace in socioeconomically disadvantaged populations.
DETECTION OF VITRECTOR SHAVINGS ON OPTICAL COHERENCE TOMOGRAPHY
Authors: Silvasi Truman L. , Omari Amro A. , Sitto Mina M. , Gupta Chirag K. , Williams George A.
Published: August 2023

Purpose:

To describe multiple retained intraocular foreign bodies felt to be from a vitrectomy instrument.

Methods:

Observational case report.

Patient:

A 66-year-old man with history of rhegmatogenous retinal detachment repaired with pars plana vitrectomy, scleral buckle, endolaser, and fluid–air exchange presented with dyschromatopsia in the right eye.

Results:

Optical coherence tomography demonstrated metallic vitrector shavings detected on optical coherence tomography above the optic nerve head and macula. Repeat optical coherence tomography 9 months later demonstrated movement of the vitrector shavings throughout the vitreous.

Conclusion:

We demonstrate retained intraocular foreign body shavings, which are rarely seen after vitrectomy. These can be confirmed using optical coherence tomography.
Artificial intelligence enabled smart digital eye wearables
Authors: RaviChandran Narrendar , Teo Zhen Ling , Ting Daniel S.W.
Published: August 2023

Purpose of review

Smart eyewear is a head-worn wearable device that is evolving as the next phase of ubiquitous wearables. Although their applications in healthcare are being explored, they have the potential to revolutionize teleophthalmology care. This review highlights their applications in ophthalmology care and discusses future scope.

Recent findings

Smart eyewear equips advanced sensors, optical displays, and processing capabilities in a wearable form factor. Rapid technological developments and the integration of artificial intelligence are expanding their reach from consumer space to healthcare applications. This review systematically presents their applications in treating and managing eye-related conditions. This includes remote assessments, real-time monitoring, telehealth consultations, and the facilitation of personalized interventions. They also serve as low-vision assistive devices to help visually impaired, and can aid physicians with operational and surgical tasks.

Wearables such as smart eyewear collects rich, continuous, objective, individual-specific data, which is difficult to obtain in a clinical setting. By leveraging sophisticated data processing and artificial intelligence based algorithms, these data can identify at-risk patients, recognize behavioral patterns, and make timely interventions. They promise cost-effective and personalized treatment for vision impairments in an effort to mitigate the global burden of eye-related conditions and aging.
Argon Cold Plasma Use and Driveline Infection in Left Ventricular Assist Device Implant Recipients
Authors: Lauenroth Volker , Zittermann Armin , Lucke Stefan , Gummert Jan F. , Morshuis Michiel
Published: August 2023

We conducted a prospective open-labeled, clinical trial, with a two-by-two factorial design, of argon cold plasma (ACP) application and two different types of driveline positioning for the prevention of driveline infection (DLI) in patients with a left ventricular assist device (LVAD) implant. Here, we present the results of ACP application versus no ACP application. Eighty patients were allocated to the control group (no preventive ACP use; n = 40) or ACP group (preventive ACP use for 30 days post-LVAD implantation; n = 40). Patients were followed up for 1 year. The secondary endpoint was survival on device. Preventive ACP use improved 30 day freedom from DLI significantly (100% vs. 85%; p = 0.012); results remained significant at 6 months (92% vs. 69%, p = 0.007) and were 55% and 60%, respectively (p = 0.65) at 1 year follow-up. With respect to survival on device, results in the control and ACP groups did not differ significantly at 30 days (97.5% vs. 100%, respectively; p = 0.32), but tended to be lower in the control group than in the ACP group at 1 year follow-up (74% vs. 90%, respectively; p = 0.09). In conclusion, preventive ACP use was able to significantly reduce DLI both during the application period and up to 6 months after LVAD implantation.
Barriers to Receiving Follow-up Care Among Childhood Cancer Survivors
Authors: Bossert Sharon , Borenzweig William , Benedict Catherine , Cerise Jane E. , Siembida Elizabeth J. , Fish Jonathan D.
Published: August 2023

Little is known on why adherence to follow-up care in childhood cancer survivors (CCS) is lacking. This study characterized barriers to adherence to follow-up care among CCS, identified sociodemographic correlates of barriers, and examined whether barriers to follow-up care relate to health-related quality of life. Adult CCS (N=84) were anonymously surveyed via REDCap using the Barriers to Care Questionnaire (BCQ) and the Quality of Life Scale–Cancer Survivor (QOL-CS). Both descriptive and correlation analyses were conducted. The median BCQ total score was 88.5 (interquartile ranges:78.4 to 95.7), with the greatest barriers reported in the Skills (eg, ease of navigating the healthcare system) and Pragmatism subscales (eg, cost). There was a statistically significant correlation between the BCQ total score and the QOL-CS total score (rs=0.47, P<0.0001) and the physical, psychological, and social QOL-CS subscales (all P’s<0.05). The results found that barriers to follow-up care for CCS are mostly related to cost and appointment logistics, and that more barriers to care is associated with lower health-related quality of life among CCS. Identifying barriers to follow-up care is the first step in improving adherence, which would allow for earlier detection of late effects of cancer therapy and thereby result in reductions in morbidity and mortality.
Invasive Fungal Infections in Children With Acute Myeloid Leukemia: A Single-center Experience Over 19 Years
Authors: Avcu Gulhadiye , Karadas Nihal , Goktepe Sebnem Onen , Bal Zumrut Sahbudak , Metin Dilek Yesim , Polat Suleyha Hilmioglu , Aydinok Yesim , Karapinar Deniz Yilmaz
Published: August 2023

Objective:

Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality in children with acute myeloid leukemia (AML). This study aimed to evaluate the incidence, risk factors, etiology, and outcome of IFIs in children with AML and the effect of mold-active antifungal prophylaxis.

Materials and Methods:

We retrospectively reviewed pediatric patients treated for AML between January 2004 and December 2022. Proven, probable, or possible IFIs were defined using standardized definitions of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) classification published at 2008.

Results:

A total of 298 febrile neutropenia episodes from 78 patients were evaluated. Proven, probable, and possible IFI rates were 3%, 2.6%, and 9.4%, respectively. Profound neutropenia was detected in 18 (58%) and prolonged neutropenia in 20 (64.5%) of the IFI episodes.. Invasive aspergillosis accounted for the majority of IFI episodes; however, non-albicans Candida spp. were the most isolated pathogens in the proven group. Patients with relapsed AML were particularly at risk for the development of IFI (P=0.02). A significant decrease in IFI episodes was achieved with mold-active antifungal prophylaxis with voriconazole (P=0.01, odds ratio: 0.288, %95 CI:0.104-0.797). The overall mortality was 35.8%, and the IFI-attributable mortality rate was 25%. In the multivariate analysis, relapsed disease was the most significant risk factor associated with mortality (P=0.006, odds ratio:4.745; 95% CI: 1.573-14.316).

Conclusion:

Mold-active prophylaxis reduced the rate of IFIs in this cohort however IFI-related mortality was still high as 25% in pediatric AML patients. Relapsed AML was the most significant risk factor associated with mortality.
Body Mass Index, Obesity, and Mortality—Part II
Authors: Sanders Lisa M. , Mestre Luis M. , Ejima Keisuke , Mehta Tapan , Keith Scott W. , Maki Kevin C. , Allison David B.
Published: August 2023

The relationship of obesity with mortality rate, and subsequently, the impact of weight loss on mortality, has been questioned by researchers for many years. Although weight loss in an individual with obesity can improve metabolic outcomes, the impacts on mortality are less clear. This has caused some to question the importance of weight loss because most individuals who lose weight through diet and lifestyle interventions gain all or a substantial portion of the weight back within 5 years. Furthermore, individuals who attempt to lose weight again may enter weight cycling (yo-yo dieting), which some have suggested may be detrimental to metabolism, eating behaviors, quality of life, and, ultimately, mortality rate. Beyond weight loss and weight cycling, the relationship between diet composition and dietary patterns has also been investigated for their relationship to longevity and mortality. This narrative review will examine the existing human and animal research evaluating the relationship between weight loss, weight cycling, and dietary composition on mortality and longevity, and identify research gaps that still exist.
Understanding the (Fake) Meat Debates
Authors: Broad Garrett M.
Published: August 2023

The topic of “alternative proteins,” a field comprised of both plant-based animal product alternatives and the nascent field of cellular agriculture (eg, cultivated meat), has become a flashpoint for contemporary food system debate. This article introduces the “alternative protein ideological circle” as a framework for understanding the nature of this contestation, as well as the key stakeholder groups who animate the landscape. It argues that perspectives on alternative proteins coalesce around 2 primary ideological poles: (1) meat attachment or carnism, the extent to which people believe or do not believe that eating animals is a natural, normal, and necessary part of contemporary life; and (2) sociotechnical imaginaries, divided between techno-optimistic “wizards” and technoskeptical “prophets.” From there, 4 key stakeholder groups emerge: (1) the “high-tech vegans” (techno-optimists with low levels of carnism); (2) the “ecomodernists” (techno-optimists with high levels of carnism); (3) the “good foodies” (technoskeptics with low levels of carnism); and (4) the “carnivore traditionalists” (technoskeptics with high levels of carnism). The article offers illustrative examples of these groups, drawing from popular media and advocacy. It concludes with reflections on the implications of this framework for nutrition research and practice.
Repurposing the atypical type I-G CRISPR system for bacterial genome engineering
Authors: Shangguan Qilin , White Malcolm F.
Published: August 2023

The CRISPR-Cas system functions as a prokaryotic immune system and is highly diverse, with six major types and numerous sub-types. The most abundant are type I CRISPR systems, which utilize a multi-subunit effector, Cascade, and a CRISPR RNA (crRNA) to detect invading DNA species. Detection leads to DNA loading of the Cas3 helicase-nuclease, leading to long-range deletions in the targeted DNA, thus providing immunity against mobile genetic elements (MGE). Here, we focus on the type I-G system, a streamlined, 4-subunit complex with an atypical Cas3 enzyme. We demonstrate that Cas3 helicase activity is not essential for immunity against MGE in vivo and explore applications of the

Thioalkalivibrio sulfidiphilus

Cascade effector for genome engineering in

Escherichia coli

. Long-range, bidirectional deletions were observed when the lacZ gene was targeted. Deactivation of the Cas3 helicase activity dramatically altered the types of deletions observed, with small deletions flanked by direct repeats that are suggestive of microhomology mediated end joining. When donor DNA templates were present, both the wild-type and helicase-deficient systems promoted homology-directed repair (HDR), with the latter system providing improvements in editing efficiency, suggesting that a single nick in the target site may promote HDR in

E. coli

using the type I-G system. These findings open the way for further application of the type I-G CRISPR systems in genome engineering.
Non-operative management of uncomplicated appendicitis in children: a randomised, controlled, non-inferiority study evaluating safety and efficacy
Authors: Adams Susan Elizabeth , Perera Meegodage Roshell Swindri , Fung Saskia , Maxton Jordon , Karpelowsky Jonathan
Published: August 2023

Background

Appendicitis is the commonest paediatric surgical emergency. Adult studies suggest non-operative management (NOM) may have a place in care. There have been no adequately powered randomized controlled trials in children. Objective: to determine the safety and efficacy of NOM for paediatric simple appendicitis.

Methods

A non-inferiority randomized controlled trial was conducted comparing operative (OM) to NOM of SA in children aged five-15 years. Primary outcome was treatment success (no unplanned or unnecessary operation, or complication) at 30 days and 12 months, with a non-inferiority margin of 15%. (anzctr.org.au:ACTRN12616000788471).

Results

From 11 June 2016 to 30 November 2020, 222 children were randomized: 94 (42·34%) to OM and 128 (57·66%) to NOM. Non-inferiority of NOM was not demonstrated at either time point, with 45.67% of NOM patients subsequently undergoing operation. There was no significant difference in complications (p=0.399).

Conclusions

While noninferiority was not shown, NOM was safe, with no difference in adverse outcomes between the two groups. Further research to refine the place of NOM of simple appendicitis in children is required, including nuanced patient selection, longer term evaluation, the place of choice, and the acceptability of the treatment for children and their carers.

Level of evidence

Level 1

Highlights

What is currently known

There have been multiple studies examining the role of non-operative management (NOM) with antibiotics alone for appendicitis in adults, with inconclusive evidence regarding its non-inferiority to operative management. There have only been three pilot randomized control trial to date in children.

What this study adds

This is the first adequately powered randomized controlled trial in children. While non-inferiority was not shown, non-operative management was safe, and associated with significantly shorter time away from school and usual activities.
SARS-CoV-2 in 30 Months, Indonesia’s Data Tells: Study from a Reference Laboratory in North Jakarta and Its Reflection for Regional to National COVID-19 Situation
Authors: Kaisar Maria Mardalena Martini , Widowati Tria Asri , Kristin Helen , Jonnatan Sheila , Surja Sem Samuel , Tjoa Enty , Venna  , Wijaya Jullyanny Waty , Thantry Anita Devi K. , Martin Ivonne , Ali Soegianto
Published: August 2023

Atma Jaya Catholic University of Indonesia (AJCUI) COVID-19 Laboratory has become a reference testing site, which contributed to prevent the SARS-CoV-2 transmission in Indonesia. Through the LSSR and CARE, the Indonesian government has implemented moderate yet arguably successful policies to combat this pandemic. This study aims to assess and strengthen public health management while enhancing our understanding of the dynamics of COVID-19. We analyzed the correlation between policies enforced in controlling COVID-19 from July 2020–December 2022 to the positivity rate and viral intensity. AJCUI, DKI Jakarta, Indonesia demonstrated a similar trend in COVID-19 prevalence. Government policy on mobility restrictions has substantially reduced the positivity rate in Indonesia within the period of study. Our study interpreted that the Ct value in the positive case population of AJCUI data correlated positively with DKI Jakarta and Indonesia; subsequently, it has the potential to serve as an early warning for an anticipated wave. Despite the coverage of vaccines, AJCUI and DKI Jakarta positivity rates are shifting due to evolving virus variants. Altogether, the comprehensively recorded data would enable an understanding of COVID-19 dynamics, serve as a model for unprecedented disaster and public health management in general.
Postural control in girls practicing volleyball is different than in non-playing peers: comparison of data on the center of pressure and ground reaction forces
Authors: Borzucka Dorota , Kręcisz Krzysztof , Kuczyński Michał
Published: August 2023

A comprehensive explanation of the relationship between postural control and athletic performance requires evaluating body balance in athletes of different performance levels. To fill this gap in relation to volleyball, the aim of this study was to compare the balance of intermediate adolescent female players (VOL, n=61) with inactive peers (CON, n=57). The participants were investigated in normal quiet stance during 30 s trials on a Kistler force plate. The traditional spatial (amplitude and mean speed) and temporal (frequency, fractality and entropy) indices were computed for ground reaction forces (GRF) and center-of-pressure (COP) time-series. The spatial parameters of the both time-series did not discriminate the two groups. However, the temporal GRF parameters revealed much lower values in VOL than in CON (p<.0001). This leads to three important conclusions regarding posturography applications. First, GRF and COP provide different information regarding postural control. Second, measures based on GRF are more sensitive to changes in balance (at least those related to volleyball training and perhaps to similar training and sports activity regimens). And third, the indicators calculated on the basis of these two time series can complement each other and thus enrich the insight into the relationship between balance and sports performance level.
The therapeutic effect of diet and dietary ingredients on cellular senescence in animals and humans: A systematic review
Authors: Guan Lihuan , Eisenmenger Anna , Crasta Karen C. , Sandalova Elena , Maier Andrea B.
Published: August 2023

Background

Cellular senescence is a permanent state of cell cycle arrest and has been regarded as a therapeutic target for ageing and age-related diseases. Several senotherapeutic agents have been proposed, including compounds derived from natural products which hold the translational potential to promote healthy ageing. It is largely unclear whether cellular senescence could be targeted by dietary interventions. This systematic review examined diets and dietary ingredients and their association with cellular senescence load in animal models and humans, with an intent to identify dietary interventions with senotherapeutic potential.

Methods

The databases PubMed and Embase were systematically searched for key terms related to cellular senescence, senescence markers, diets, nutrients and bioactive compounds. Intervention and observational studies on human and animal models investigating the effects of diets or dietary ingredients via oral administration on cellular senescence load were included. The studies were screened using the Covidence systematic review software. Study design, methods and results were extracted. Biomaterials used for senescence detection were categorized into physiological systems. The SYRCLE’s risk of bias tool and Cochrane risk of bias tool v2.0 were used to assess the risk of bias for animal and human studies respectively.

Results

Out of 5707 identified articles, 82 articles consisting of 78 animal studies and 4 human studies aimed to reduce cellular senescence load using dietary interventions. In animal studies, the most-frequently used senescence model was normal ageing (26 studies), followed by D- galactose-induced models (17 studies). Resveratrol (8 studies), vitamin E (4 studies) and soy protein isolate (3 studies) showed positive effects on reducing the level of senescence markers such as p53, p21, p16 and senescence-associated ß-galactosidase in various tissues of physiological systems. In three out of four human studies, ginsenoside Rg1 had no positive effect on reducing senescence in muscle tissues after exercise. The risk of bias for both animal and human studies was largely unclear.

Conclusion

Resveratrol, vitamin E and soy protein isolate are promising senotherapeutics studied in animal models. Studies testing dietary interventions with senotherapeutic potential in humans are limited and translation is highly warranted.
ISMI-VAE: A Deep Learning Model for Classifying Disease Cells Using Gene Expression and SNV Data
Authors: Li Han , Wang Ying , Lai Yongxuan , Zeng Feng , Yang Fan
Published: August 2023

Various studies have linked several diseases, including cancer and Covid-19, to single nucleotide variations (SNV). Although scRNA-seq technology can provide SNV and gene expression data, few studies have integrated and analyzed these multimodal data. To address this issue, this paper introduces Interpretable Single-cell Multimodal Data Integration Based on Variational Autoencoder (ISMI-VAE). ISMI-VAE leverages latent variable models that utilize the characteristics of SNV and gene expression data to overcome high noise levels, and uses deep learning techniques to integrate multimodal information, map them to a low-dimensional space, and classify disease cells. Moreover, ISMI-VAE introduces an attention mechanism to reflect feature importance and analyze genetic features that could potentially cause disease. Experimental results on three cancer data sets and one Covid-19 data set demonstrate that ISMI-VAE surpasses the baseline method in terms of both effectiveness and interpretability, and can effectively identify disease-causing gene features.
Identification of putative druggable pockets in PRL3, a significant oncology target, usingin silicoanalysis
Authors: Bennett Grace M. , Starczewski Julia , dela Cerna Mark Vincent C.
Published: August 2023

Due to their active roles in regulating phosphorylations, protein tyrosine phosphatases (PTP) have emerged as attractive targets in diseases characterized by aberrant phosphorylations such as cancers. The activity of the phosphatase of regenerating liver 3, PRL3, has been linked to several oncogenic and metastatic pathways, particularly in breast, ovarian, colorectal, and blood cancers. Development of small molecules that directly target PRL3, however, has been challenging. This is partly due to the lack of structural information on how PRL3 interacts with its inhibitors. Here, computational methods are used to bridge this gap by evaluating the druggability of PRL3. In particular, web-based pocket prediction tools, DoGSite3 and FTMap, were used to identify binding pockets using structures of PRL3 currently available in the Protein Data Bank. Druggability assessment by molecular dynamics simulations with probes was also performed to validate these results and to predict the strength of binding in the identified pockets. While several druggable pockets were identified, those in the closed conformation show more promise given their volume and depth. These two pockets flank the active site loops and roughly correspond to pockets predicted by molecular docking in previous papers. Notably, druggability simulations predict the possibility of low nanomolar affinity inhibitors in these sites implying the potential to identify highly potent small molecule inhibitors for PRL3. Putative pockets identified here can be leveraged for high-throughput virtual screening to further accelerate the drug discovery against PRL3 and development of PRL3-directed therapeutics.
Divergent patterns of healthy aging across human brain regions at single-cell resolution reveal links to neurodegenerative disease
Authors: Duffy Megan F. , Ding Jinhui , Langston Rebekah G. , Shah Syed I. , Nalls Mike A. , Scholz Sonja W. , Whitaker D. Thad , Auluck Pavan K. , Marenco Stefano , Gibbs J. Raphael , Cookson Mark R.
Published: August 2023

Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) to examine changes in cell proportions and transcriptomes in four different brain regions, each from 12 donors aged 20-30 years (young) or 60-85 years (old). We sampled 155,192 nuclei from two cortical regions (entorhinal cortex and middle temporal gyrus) and two subcortical regions (putamen and subventricular zone) relevant to neurodegenerative diseases or the proliferative niche. We found no changes in cellular composition of different brain regions with healthy aging. Surprisingly, we did find that each brain region has a distinct aging signature, with only minor overlap in differentially associated genes across regions. Moreover, each cell type shows distinct age-associated expression changes, including loss of protein synthesis genes in cortical inhibitory neurons, axonogenesis genes in excitatory neurons and oligodendrocyte precursor cells, enhanced gliosis markers in astrocytes and disease-associated markers in microglia, and genes critical for neuron-glia communication. Importantly, we find cell type-specific enrichments of age associations with genes nominated by Alzheimer’s disease and Parkinson’s disease genome-wide association studies (GWAS), such as apolipoprotein E (APOE), and leucine-rich repeat kinase 2 (LRRK2) in microglia that are independent of overall expression levels across cell types. We present this data as a new resource which highlights, first, region- and cell type-specific transcriptomic changes in healthy aging that may contribute to selective vulnerability and, second, provide context for testing GWAS-nominated disease risk genes in relevant subtypes and developing more targeted therapeutic strategies. The data is readily accessible without requirement for extensive computational support in a public website,https://brainexp-hykyffa56a-uc.a.run.app/

Graphical Abstract

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Highlights

Establishment of a single nuclei atlas of human aging in four brain regions

Each region and cell type exhibits a unique aging-associated transcriptome signature

Gene expression changes occur in absence of overt cell loss and are categorically unique across cell types

Neurological disease-associated genes have age-associated expression patterns in specific cell types in the context of healthy aging
Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion
Authors: Flores Andrew J. , Bartlett Mitchell J. , Samtani Grace , Seaton Blake T. , Sexauer Morgan R. , Weintraub Nathan C. , Siegenthaler James R. , Lu Dong , Heien Michael L. , Porreca Frank , Sherman Scott J. , Falk Torsten
Published: August 2023

Levels of the opioid peptide dynorphin, an endogenous ligand selective for kappa-opioid receptors (KORs), its mRNA and pro-peptide precursors are differentially dysregulated in Parkinson’s disease (PD) and following the development of L-DOPA-induced dyskinesia (LID). It remains unclear whether these alterations contribute to the pathophysiological mechanisms underlying PD motor impairment and the subsequent development of LID, or whether they are part of compensatory mechanisms. We sought to investigate nor-BNI, a KOR antagonist, 1) in the dopamine (DA)-depleted PD state, 2) during the development phase of LID, and 3) via measuring of tonic levels of striatal DA. While nor-BNI (3 mg/kg;s.c.) did not lead to functional restoration in the DA-depleted state, it affected the dose-dependent development of abnormal voluntary movements (AIMs) in response to escalating doses of L-DOPA in a rat PD model with a moderate striatal 6-hydroxdopamine (6-OHDA) lesion. We tested five escalating doses of L-DOPA (6, 12, 24, 48, 72 mg/kg;i.p.), and nor-BNI significantly increased the development of AIMs at the 12 and 24 mg/kg L-DOPA doses. However, after reaching the 72 mg/kg L-DOPA, AIMs were not significantly different between control and nor-BNI groups. In summary, while blocking KORs significantly increased the rate of development of LID induced by chronic, escalating doses of L-DOPA in a moderate-lesioned rat PD model, it did not contribute further once the overall severity of LID was established. While we observed an increase of tonic DA levels in the moderately lesioned dorsolateral striatum, there was no tonic DA change following administration of nor-BNI.

Highlights

Mild L-DOPA-induced dyskinesia develops in moderately lesioned parkinsonian rats

In the moderately-lesioned dorsolateral striatum tonic dopamine is increased

Antagonizing dynorphin does not affect parkinsonian motor symptoms in rodents

Antagonizing dynorphin increases rate of development of L-DOPA-induced dyskinesia

Tonic dopamine in dorsolateral striatum is unchanged after antagonizing dynorphin
Interdependence of plasma membrane nanoscale dynamics of a kinase and its cognate substrate underliesArabidopsisresponse to viral infection
Authors: Jolivet Marie-Dominique , Deroubaix Anne-Flore , Boudsocq Marie , Abel Nikolaj B. , Rocher Marion , Robbe Terezinha , Wattelet-Boyer Valérie , Huard Jennifer , Lefebvre Dorian , Lu Yi-Ju , Day Brad , Saias Grégoire , Ahmed Jahed , Cotelle Valérie , Giovinazzo Nathalie , Gallois Jean-Luc , Yamaji Yasuyuki , German-Retana Sylvie , Gronnier Julien , Ott Thomas , Mongrand Sébastien , Germain Véronique
Published: August 2023

Plant viruses represent a risk to agricultural production and as only a few treatments exist, it is urgent to identify resistance mechanisms and factors. In plant immunity, plasma membrane (PM)-localized proteins play an essential role in sensing the extracellular threat presented by bacteria, fungi or herbivores. Viruses are intracellular pathogens and as such the role of the plant PM in detection and resistance against viruses is often overlooked. We investigated the role of the partially PM-bound Calcium-dependent protein kinase 3 (CPK3) in viral infection and we discovered that it displayed a specific ability to hamper viral propagation over CPK isoforms that are involved in immune response to extracellular pathogens. More and more evidence support that the lateral organization of PM proteins and lipids underlies signal transduction in plants. We showed here that CPK3 diffusion in the PM is reduced upon activation as well as upon viral infection and that such immobilization depended on its substrate, Remorin (REM1.2), a scaffold protein. Furthermore, we discovered that the viral infection induced a CPK3-dependent increase of REM1.2 PM diffusion. Such interdependence was also observable regarding viral propagation. This study unveils a complex relationship between a kinase and its substrate that contrasts with the commonly described co-stabilisation upon activation while it proposes a PM-based mechanism involved in decreased sensitivity to viral infection in plants.
De novo production of an antitumor precursor actinocin and other medicinal molecules from kynurenine pathway inEscherichia coli
Authors: Sharma Komal , Ghiffary Mohammad Rifqi , Lee GaRyoung , Kim Hyun Uk
Published: August 2023

Kynurenine pathway has a potential to convert L-tryptophan into multiple medicinal molecules. This study aims to explore the biosynthetic potential of kynurenine pathway for the efficient production of actinocin, an antitumor precursor selected as a proof-of-concept target molecule. Kynurenine pathway is first constructed inEscherichia coliby testing various combinations of biosynthetic genes from four different organisms. Metabolic engineering strategies are next performed to improve the production by inhibiting a competing pathway, and enhancing intracellular supply of a cofactorS-adenosyl-L-methionine, and ultimately to produce actinocin from glucose. Metabolome analysis further suggests additional gene overexpression targets, which finally leads to the actinocin titer of 719 mg/L.E. colistrain engineered to produce actinocin is further successfully utilized to produce 350 mg/L of kynurenic acid, a neuroprotectant, and 1401 mg/L of 3-hydroxyanthranilic acid, an antioxidant, also from glucose. These competitive production titers demonstrate the biosynthetic potential of kynurenine pathway as a source of multiple medicinal molecules. The approach undertaken in this study can be useful for producing other molecules associated with kynurenine pathway.
Cell-type-specific gene expression and regulation in the cerebral cortex and kidney of atypicalSetbp1S858RSchinzel Giedion Syndrome mice
Authors: Whitlock Jordan H. , Soelter Tabea M. , Howton Timothy C. , Wilk Elizabeth J. , Oza Vishal H. , Lasseigne Brittany N.
Published: August 2023

Schinzel Giedion Syndrome (SGS) is an ultra-rare autosomal dominant Mendelian disease presenting with abnormalities spanning multiple organ systems. The most notable phenotypes involve severe developmental delay, progressive brain atrophy, and drug-resistant seizures. SGS is caused by spontaneous variants inSETBP1, which encodes for the epigenetic hub SETBP1 transcription factor (TF).SETBP1variants causing classical SGS cluster at the degron, disrupting SETBP1 protein degradation resulting in toxic accumulation, while those located outside cause milder atypical SGS. Due to the multi-system phenotype, we evaluated gene expression and regulatory programs altered in atypical SGS by snRNA-seq of cerebral cortex and kidney ofSetbp1S858Rheterozygous mice (corresponds to the human likely pathogenicSETBP1S867Rvariant) compared to matched wild-type mice by constructing cell-type-specific regulatory networks.Setbp1was differentially expressed in excitatory neurons, but known SETBP1 targets were differentially expressed and regulated in many cell types. Our findings suggest molecular drivers underlying neurodevelopmental phenotypes in classical SGS also drive atypical SGS, persist after birth, and are present in the kidney. Our results indicate SETBP1’s role as an epigenetic hub leads to cell-type-specific differences in TF activity, gene targeting, and regulatory rewiring. This research provides a framework for investigating cell-type-specific variant impact on gene expression and regulation.