bluuebunny/crossref_metadata_2025 huggingface dataset:
Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes
Authors: Lai Ping , Hille Susanne S , Subramanian Hariharan , Wiegmann Robert , Roser Pia , Müller Oliver J , Nikolaev Viacheslav O , De Jong Kirstie A
Published: December 2023

Aims

Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a), which forms a functional cardiomyocyte (CM) microdomain where 3′,5′-cyclic adenosine monophosphate (cAMP) produced upon β-adrenergic receptor (β-AR) stimulation leads to phospholamban (PLN) phosphorylation and facilitated Ca2+ re-uptake.

Methods and results

To visualize real-time cAMP dynamics in the direct vicinity of SERCA2a in healthy and diseased myocytes, we generated a novel mouse model on the leprdb background that stably expresses the Epac1-PLN Förster resonance energy transfer biosensor. Mice homozygous for the leprdb mutation (db/db) developed obesity and type 2 diabetes and presented with a HFpEF phenotype, evident by mild left ventricular hypertrophy and elevated left atria filling pressures. Live cell imaging uncovered a substantial β2-AR subtype stimulated cAMP response within the PLN/SERCA2a microdomain of db/db but not healthy control (db/+) CMs, which was accompanied by increased PLN phosphorylation and accelerated calcium re-uptake. Importantly, db/db CMs also exhibited a desensitization of β1-AR stimulated cAMP pools within the PLN/SERCA2a microdomain, which was accompanied by a blunted lusitropic effect, suggesting that the increased β2-AR control is an intrinsic compensatory mechanism to maintain PLN/SERCA2a-mediated calcium dynamics and cardiac relaxation. Mechanistically, this was due to a local loss of cAMP-degrading phosphodiesterase 4 associated specifically with the PLN/SERCA2a complex.

Conclusion

These newly identified alterations of cAMP dynamics at the subcellular level in HFpEF should provide mechanistic understanding of microdomain remodelling and pave the way towards new therapies.
Remnant cholesterol and risk of premature mortality: an analysis from a nationwide prospective cohort study
Authors: Li Likang , Lai Jun , Zhang Jingyi , Van Spall Harriette G C , Thabane Lehana , Lip Gregory Y H , Li Guowei
Published: December 2023

Aims

To explore the relationship between remnant cholesterol (RC) and the risk of premature mortality as well as life expectancy in the general population.

Methods

We included a total of 428 804 participants from the UK Biobank for analyses. Equivalent population percentiles approach based on the low-density lipoprotein cholesterol cut-off points was performed to categorize participants into three RC groups: low (with a mean RC of 0.34 mmol/L), moderate (0.53 mmol/L), and high (1.02 mmol/L). We used multivariable Cox proportional hazards models to evaluate the relationship between RC groups and the risk of premature mortality (defined as death before age 75 years). Life table methods were used to estimate life expectancy by RC groups.

Results

During a median follow-up of 12.1 years (Q1–Q3 11.0–13.0), there were 23 693 all-cause premature deaths documented, with an incidence of 4.83 events per 1000 person-years [95% confidence interval (CI): 4.77–4.89]. Compared with the low RC group, the moderate RC group was associated with a 9% increased risk of all-cause premature mortality [hazard ratio (HR) = 1.09, 95% CI: 1.05–1.14], while the high RC group had an 11% higher risk (HR = 1.11, 95% CI: 1.07–1.16). At the age of 50 years, high RC group was associated with an average 2.2 lower years of life expectancy for females, and an average 0.1 lower years of life expectancy for males when compared with their counterparts in the low RC group.

Conclusions

Elevated RC was significantly related to an increased risk of premature mortality and a reduced life expectancy. Premature death in the general population would benefit from measurement to aid risk stratification and proactive management of RC to improve cardiovascular risk prevention efforts.
Ablation for atrial fibrillation improves the outcomes in patients with heart failure with preserved ejection fraction
Authors: Xie Zhonglei , Qi Baozhen , Wang Zimu , Li Fuhai , Chen Chaofeng , Li Chaofu , Yuan Shuai , Yao Shun , Zhou Jingmin , Ge Junbo
Published: December 2023

Aims

Patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) have worse clinical outcomes than those with sinus rhythm (SR). We aim to investigate whether maintaining SR in patients with HFpEF through a strategy such as AF ablation would improve outcomes.

Methods and results

This is a cohort study that analysed 1034 patients (median age 69 [63–76] years, 46.2% [478/1034] female) with HFpEF and AF. Of these, 392 patients who underwent first-time AF ablation were assigned to the ablation group, and the remaining 642 patients, who received only medical therapy, were assigned to the no ablation group. The primary endpoint was a composite of all-cause death or rehospitalization for worsening heart failure. After a median follow-up of 39 months, the cumulative incidence of the primary endpoint was significantly lower in the ablation group compared to the no ablation group (adjusted hazard ratio [HR], 0.55 [95% CI, 0.37–0.82], P = 0.003) in the propensity score-matched model. Secondary endpoint analysis showed that the benefit of AF ablation was mainly driven by a reduction in rehospitalization for worsening heart failure (adjusted HR, 0.52 [95% CI, 0.34–0.80], P = 0.003). Patients in the ablation group showed a 33% relative decrease in atrial tachycardia/AF recurrence compared to the no ablation group (adjusted HR, 0.67 [95% CI, 0.54–0.84], P < 0.001).

Conclusion

Among patients with HFpEF and AF, the strategy of AF ablation to maintain SR was associated with a lower risk of the composite outcome of all-cause death or rehospitalization for worsening heart failure.
Lakes-scale pattern of eukaryotic phytoplankton diversity and assembly process shaped by electrical conductivity in central Qinghai-Tibet Plateau
Authors: Zhu Huan , Xiong Xiong , Liu Benwen , Liu Guoxiang
Published: December 2023

Phytoplankton are the main primary producers in aquatic ecosystems and play an important role in food web and geochemical cycles. Its diversity, community structure, and assembly process are influenced by several factors. Alpine lake ecosystems are relatively weak and extremely sensitive to global climate change. However, the impact of climate change on phytoplankton in Qinghai-Tibet Plateau lakes and their responses are still unclear. In this study, we analyzed the diversity, environmental drivers, and assembly process of phytoplankton community in the central QTP lakes. The phytoplankton of these lakes can be primarily distinguished into freshwater and brackish types, with significant differences in species diversity and community dissimilarity. Both shared nearly same key environmental factors that significantly affecting phytoplankton such as EC, and brackish lakes were also positively correlative with TN. Stochastic process was predominant in phytoplankton assembly. Additionally, freshwater and brackish lakes were dominated by dispersal limitation and heterogeneous selection respectively. Alpine lakes had significant EC thresholds, and their diversity and assembly processes changed significantly around the thresholds. The present findings have important implications for understanding and predicting the response of lake phytoplankton communities to climate change and for making decisions to protect the ecological resources of alpine lakes.
Functional guilds and drivers of diversity in seaweed-associated bacteria
Authors: Khan Tahsin , Song Weizhi , Nappi Jadranka , Marzinelli Ezequiel M , Egan Suhelen , Thomas Torsten
Published: December 2023

Comparisons of functional and taxonomic profiles from bacterial communities in different habitats have suggested the existence of functional guilds composed of taxonomically or phylogenetically distinct members. Such guild membership is, however, rarely defined and the factors that drive functional diversity in bacteria remain poorly understood. We used seaweed-associated bacteria as a model to shed light on these important aspects of community ecology. Using a large dataset of over 1300 metagenome-assembled genomes from 13 seaweed species we found substantial overlap in the functionality of bacteria coming from distinct taxa, thus supporting the existence of functional guilds. This functional equivalence between different taxa was particularly pronounced when only functions involved in carbohydrate degradation were considered. We further found that bacterial taxonomy is the dominant driver of functional differences between bacteria and that seaweed species or seaweed type (i.e. brown, red and green) had relatively stronger impacts on genome functionality for carbohydrate-degradation functions when compared to all other cellular functions. This study provides new insight into the factors underpinning the functional diversity of bacteria and contributes to our understanding how community function is generated from individual members.
Genomes of nine biofilm-forming filamentous strains of Cyanobacteria (genera Jaaginema, Scytonema, and Karukerafilum gen. nov.) isolated from mangrove habitats of Guadeloupe (Lesser Antilles)
Authors: Halary Sébastien , Duval Charlotte , Marie Benjamin , Bernard Cécile , Piquet Bérénice , Gros Olivier , Bourguet-Kondracki Marie-Lise , Duperron Sébastien
Published: December 2023

Biofilm-forming cyanobacteria are abundant in mangrove ecosystems, colonizing various niches including sediment surface and periphyton where they can cover large areas, yet have received limited attention. Several filamentous isolates were recently isolated from Guadeloupe, illustrating the diversity and novelty present in these biofilms. In this study, nine strains belonging to three novel lineages found abundantly in Guadeloupe biofilms are characterized by genome sequencing, morphological and ultrastructural examination, metabolome fingerprinting and searched for secondary metabolites biosynthesis pathways. Assignation of two lineages to known genera is confirmed, namely Scytonema and Jaaginema. The third lineage corresponds to a new Coleofasciculales genus herein described as Karukerafilum gen. nov. The four strains belonging to this genus group into two subclades, one of which displays genes necessary for nitrogen fixation as well as the complete pathway for geosmin production. This study gives new insights into the diversity of mangrove biofilm-forming cyanobacteria, including genome-based description of a new genus and the first genome sequence available for the genus Jaaginema.
Under the influence: system-level effects of alcohol industry-funded health information organizations
Authors: Maani Nason , CI van Schalkwyk May , Petticrew Mark
Published: December 2023

There is now an established body of evidence that the alcohol industry seeks to obstruct public health policies that could affect the availability, affordability or marketing of alcohol. In parallel, the alcohol industry is active in funding corporate social responsibility initiatives, with a particular focus on ‘responsible drinking’ campaigns, often facilitated by national-level charities established and/or funded by the alcohol industry and associated organizations. While evidence continues to grow regarding biases in the content produced by such health information organizations, they remain active in partnerships with government health departments on national health promotion campaigns and provide a range of health-related information to the public, community organizations and schools. To understand the implications of such access for policymakers, researchers and the public, there is a need to consider the wider, system-level influences of such organizations and their place in wider alcohol industry strategies. In this article, we describe evolving evidence of the direct and indirect strategic effects of such organizations and demonstrate how they serve key roles in the alcohol industry through their existence, content, partnerships and public profiles. We end by considering the implications for how we conceptualize charities established or funded (entirely or partly) by harmful commodity industries, and to what extent current conflicts of interest guidelines are sufficiently effective.
Immunogenicity and Safety Following 1 Dose of AS01E-Adjuvanted Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults: A Phase 3 Trial
Authors: Schwarz Tino F , Hwang Shinn-Jang , Ylisastigui Pedro , Liu Chiu-Shong , Takazawa Kenji , Yono Makoto , Ervin John E , Andrews Charles P , Fogarty Charles , Eckermann Tamara , Collete Delphine , de Heusch Magali , De Schrevel Nathalie , Salaun Bruno , Lambert Axel , Maréchal Céline , Olivier Aurélie , Nakanwagi Phoebe , Lievens Marc , Hulstrøm Veronica
Published: December 2023

Background

The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine for older adults (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds.

Methods

This ongoing phase 3 study in ≥60-year-olds evaluates immune persistence until 3 years after RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until 1 year post–dose 1.

Results

In total, 1653 participants were vaccinated. One month post–dose 1, neutralization titers increased 10.5-fold (RSV-A) and 7.8-fold (RSV-B) vs pre–dose 1. Titers then declined to levels 4.4-fold (RSV-A) and 3.5-fold (RSV-B) above pre–dose 1 at month 6 and remained 3.1-fold (RSV-A) and 2.3-fold (RSV-B) above pre–dose 1 levels after 1 year. RSVPreF3-binding immunoglobulin G levels and CD4+ T-cell frequencies showed similar kinetics. Solicited administration-site and systemic adverse events (mostly mild to moderate and transient) were reported by 62.2% and 49.5% of participants. Serious adverse events were reported by 3.9% of participants within 6 months post–dose 1; 1 case was considered vaccine related.

Conclusions

One RSVPreF3 OA dose elicited cell-mediated and RSV-A– and RSV-B–specific humoral immune responses that declined over time but remained above pre–dose 1 levels for at least 1 year. The vaccine was well tolerated with an acceptable safety profile.

Clinical Trials Registration. NCT04732871 (ClinicalTrials.gov).
A preliminary survey reveals that common viruses are found at low titers in a wild population of honey bees (Apis mellifera)
Authors: Dickey Myra , Whilden Mckaela , Ellis Jordan Twombly , Rangel Juliana
Published: December 2023

A major threat to honey bee (Apis mellifera Linnaeus, Hymenoptera: Apidae) health continues to be parasitism by the mite Varroa destructor, which has been linked to high colony losses worldwide. Besides feeding on developing and adult bees, Varroa is also a prolific vector of honey bee-associated viruses. Because they live in unmanaged conditions, wild honey bee colonies are not treated against Varroa, which has enabled the natural selection of more mite-tolerant bees. To date, few studies have explored the prevalence of viruses in unmanaged colonies. The Welder Wildlife Refuge (WWR) in Texas is a unique site to study the viral landscape of unmanaged honey bees in the United States. The goals of this study were to identify and quantify viruses in wild colonies at the WWR, to examine changes in the prevalence of viruses in these colonies over time, and to compare the presence and titers of viruses between wild colonies at the WWR and those from the nearest managed apiary. We collected bees from colonies at the WWR in 2013, 2016, and 2021, and analyzed selected viruses for their presence and titers via quantitative polymerase chain reaction. In 2021, we also sampled bees from the nearest managed apiary for comparison. We found low average virus titers in all wild colonies sampled, and no difference in virus titers between colonies at the WWR and those from the managed apiary. Our study indicates that virus titers in wild colonies at the WWR are similar to those found in nearby colonies, and that these titers fluctuate over time.
Gender diversity at academic conferences—the case of the International Communication Association
Authors: Braun Maike , Heintz Laura , Kruschinski Simon , Trepte Sabine , Scharkow Michael
Published: December 2023

Gender diversity and the lack of women in leadership in academia have been issues of academic interest for decades. However, little is known about gender diversity at academic conferences as an essential aspect of academia. We investigated 86,719 contributions to International Communication Association (ICA) conferences over the past 18 years with regard to female and male authorship and how it changed following the introduction of childcare, during the global pandemic, and under female division leadership. Lastly, we analyzed divisions/interest groups, authors’ gender, and national affiliation. We found that the proportion of female authors is high in all conference years and is representative of ICA membership. We found differences in how women and men are represented across divisions, countries of author affiliation, based on the availability of childcare, and during the global pandemic. We discuss implications at societal, organizational, and individual levels.
Experiences of working from home: umbrella review
Authors: Hall Charlotte E. , Brooks Samantha K. , Mills Freya , Greenberg Neil , Weston Dale
Published: December 2023

Introduction: The concept of “working from home” is extremely topical following the COVID-19 pandemic; therefore, it is unsurprising that there has been an increased interest in collating research related to homeworking. This has been carried out by multiple reviews, all with slightly different research aims and methodologies. Collating the findings from the available reviews is therefore highly beneficial to establish the experience of homeworking to create recommendations for the future of home-based work.

Methods: An umbrella review was carried out. In June 2022, literature searches were conducted across 4 electronic databases. Published reviews of literature that used a systematic process, were focused on working from home populations, and detailed factors that could be related to the personal experience of homeworking (eg, barriers, facilitators, advantages, disadvantages) were included.

Results: A total of 1930 records were screened and 6 review articles were included. Results report on the following sections: working environment (eg, workplace design, space conditions), personal impact (eg, satisfaction, career impact), and health (eg, physical health, well-being) including a total of 19 themes. Mixed findings were apparent for nearly all included themes, highlighting the need to consider individual and contextual circumstances when researching working from home.

Conclusions: This review establishes the importance of retaining flexibility while homeworking for employees, managers, and organizations. Essentially, a one-size-fits-all approach to working from home is impractical as individual circumstances limit application. Eight recommendations for the future of working from home are suggested.
Clinical effectiveness of trigger point acupuncture on chronic neck and shoulder pain (katakori) with work productivity loss in office workers: a randomized clinical trial
Authors: Minakawa Yoichi , Miyazaki Shogo , Waki Hideaki , Akimoto Yoshiko , Itoh Kazunori
Published: December 2023

Objectives: To evaluate whether trigger point acupuncture (TrPA) is beneficial for office workers who have reduced job performance (presenteeism) due to chronic neck and shoulder pain (katakori).

Methods: A 4-week single-center randomized controlled trial was conducted on 20 eligible female office workers with chronic neck and shoulder pain of at least 3-month duration. The control group implemented only workplace-recommended presenteeism measures, whereas the intervention group received TrPA up to 4 times per month in addition to the presenteeism measures recommended by each workplace. The major outcome measure was the relative presenteeism score on the World Health Organization Health and Work Performance (WHO-HPQ). The secondary outcome measures were pain intensity (numerical rating scale), absolute presenteeism (WHO-HPQ), anxiety and depression (Hospital Anxiety and Depression Scale; HADS), catastrophic thoughts related to pain (Pain Catastrophizing Scale; PCS), and sleep (Athens Insomnia Scale; AIS).

Results: All 9 cases in the intervention group and 11 cases in the control group were analyzed. TrPA up to 4 times per month reduced the intensity of neck and shoulder pain by 20% (P < .01, d = 1.65) and improved labor productivity (relative presenteeism value) by 0.25 (P < .01, d = 1.33) compared with the control group over 1 month. No significant differences were observed between the 2 groups in terms of absolute presenteeism score, HADS, PCS, or AIS.

Conclusions:These results suggest that regular intervention with TrPA may be effective in the relative presenteeism score before and after the intervention and the degree of neck and shoulder pain over 28 days compared with the control group.
Can you See? Actuality Entailments in the Present
Authors: Dieuleveut Anouk
Published: December 2023

This paper argues that English present ability modal statements like “I can see Saturn” are ambiguous in the same way as past ability statements like “I was able to lift a fridge”: they can express either a general ability (‘I have the ability to see Saturn, in general’), or have an actualized (episodic) interpretation (‘I'm seeing Saturn, right now’). The challenge is to explain why in the present, actualized interpretations are only licensed when the modal's prejacent is a perception verb like see, and not with other predicates: “I can watch Saturn” only has the general ability reading available, and not the actualized one. I propose that (i) similar to what has been shown for past modal statements in the literature on Actuality Entailments (AEs) (Bhatt 1999), the ambiguity depends on grammatical aspect: general ability readings are due to the imperfective, which “removes” AEs by having the event occur in worlds introduced by a generic operator (Bhatt 1999), and actualized readings are due to the perfective, which directly combines with the prejacent event across the modal (Hacquard 2009); (ii) The usual unavailability of actualized interpretations in the present comes from the Present Perfective Paradox (Malchukov 2009): perfective aspect is incompatible with present tense, because the event time, a time interval, cannot be contained within the punctual speech time. (iii) Perception verbs are special in that they, and only they, are able to combine with perfective in the present, either because the PPP does not arise at all, or because they allow a specific type of aspectual coercion. This also explains their behavior in (non-modal) simple present sentences. A second challenge is that actualized interpretations in the present appear to occur exclusively with ability modals, and not when modals express other root flavors (e.g. teleological or deontic). I propose that this restriction is due to a further temporal orientation constraint.
Seroepidemiology of Human Tularemia—Systematic Review and Meta-analysis of Seroprevalence Studies
Authors: Mattatia Chantal , Agyeman Philipp K A , Schöbi Nina , Aebi Simon , Duppenthaler Andrea , Büttcher Michael , Aebi Christoph
Published: December 2023

Background

Seroepidemiologic studies of human tularemia have been conducted throughout the northern hemisphere. The purposes of this study were (1) to provide an overview of Francisella tularensis seroprevalence data, and (2) to generate an estimate of the proportion of study participants whose infection remained subclinical.

Methods

We conducted a systematic review of F tularensis seroprevalence studies according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed, Embase, and Web of Science covering the period from 1951 to 2023.

Results

The weighted pooled seroprevalence among 44 486 participants recruited in 52 studies was 3.7% (95% confidence interval [CI], 2.7–5.1). Reported seroprevalences ranged between 0.2% and 31.3%. Occupational activities associated with an increased likelihood of exposure (risk ratio, 3.51 [95% CI, 3.2–3.86]) and studies from North America versus Europe and Asia (4.53 [4.15–4.94]) were associated with significantly increased seropositive rates. Twenty-eight data sets (47%) reported clinical information on a total of 965 seropositive participants. The weighted pooled estimate for subclinical seropositivity was 84.4% (95% CI, 72.9%–991.7%). Studies from F tularensis type A areas (risk ratio, 0.37 [95% CI, .27–.51) and studies from sites where pulmonary tularemia prevailed (0.38 [.28–.51]) reported lower subclinical seropositivity rates than studies from type B areas and from areas of predominance of (ulcero)glandular or oropharyngeal tularemia, respectively.

Conclusions

Throughout the northern hemisphere, only a small proportion of study participants showed serologic evidence of exposure to F tularensis. Eight of 10 seropositive participants had no historical evidence of past clinical tularemia.
Macro-Level Pluralism
Authors: Rubin Ruth Bloch , Elinson Gregory , TerBeek Calvin
Published: December 2023

As is true of many social-scientific traditions, political history is populated by scholars who run the methodological gamut, from those who rely on finely textured narrative accounts to those who employ advanced computational tools, statistical analyses, and formal models. But, as this chapter argues, what is distinctive about political history is that its methodological pluralism is a feature of the field in aggregate, rather than a characteristic of its most influential component studies. This macro-level pluralism has helped political historians to address some of the fundamental challenges of working with historical data. Perhaps more importantly, it represents a profitable alternative to the way political scientists have tended to think about mixed-methods research.
The spatiotemporal pattern of surface ozone and its impact on agricultural productivity in China
Authors: Chen Xiaoguang , Gao Jing , Chen Luoye , Khanna Madhu , Gong Binlei , Auffhammer Maximilian
Published: December 2023

The slowing of agricultural productivity growth globally over the past two decades has brought a new urgency to detect its drivers and potential solutions. We show that air pollution, particularly surface ozone (O3), is strongly associated with declining agricultural total factor productivity (TFP) in China. We employ machine learning algorithms to generate estimates of high-resolution surface O3 concentrations from 2002 to 2019. Results indicate that China's O3 pollution has intensified over this 18-year period. We coupled these O3 estimates with a statistical model to show that rising O3 pollution during nonwinter seasons has reduced agricultural TFP by 18% over the 2002–2015 period. Agricultural TFP is projected to increase by 60% if surface O3 concentrations were reduced to meet the WHO air quality standards. This productivity gain has the potential to counter expected productivity losses from 2°C warming.
A tomato bushy stunt virus–based vector for simultaneous editing and sensing to survey the host antiviral RNA silencing machinery
Authors: DeMell April , Mendoza Maria R , Scholthof Herman B
Published: December 2023

A tomato bushy stunt virus (TBSV)–derived vector system was applied for the delivery of CRISPR/Cas9 gene editing materials, to facilitate rapid, transient assays of host–virus interactions involved in the RNA silencing pathway. Toward this, single guide RNAs designed to target key components of the virus-induced host RNA silencing pathway (AGO2, DCL2, HEN1) were inserted into TBSV-based GFP-expressing viral vectors TBSV-GFP (TG) and its P19 defective mutant TGΔP19. This produced rapid, efficient, and specific gene editing in planta. Targeting AGO2, DCL2, or HEN1 partially rescued the lack of GFP accumulation otherwise associated with TGΔP19. Since the rescue phenotypes are normally only observed in the presence of the P19 silencing suppressor, the results support that the DCL2, HEN1, and AGO2 proteins are involved in anti-TBSV RNA silencing. Additionally, we show that knockdown of the RNA silencing machinery increases cargo expression from a nonviral binary Cas9 vector. The TBSV-based gene editing technology described in this study can be adapted for transient heterologous expression, rapid gene function screens, and molecular interaction studies in many plant species considering the wide host range of TBSV. In summary, we demonstrate that a plant virus can be used to establish gene editing while simultaneously serving as an accumulation sensor for successful targeting of its homologous antiviral silencing machinery components.
Real-time monitoring of the amyloid β1–42 monomer-to-oligomer channel transition using a lipid bilayer system
Authors: Numaguchi Yuri , Tsukakoshi Kaori , Takeuchi Nanami , Suzuki Yuki , Ikebukuro Kazunori , Kawano Ryuji
Published: December 2023

This study describes the observation of the transformation of monomeric amyloid β1–42 (Aβ42) into oligomers in a lipid membrane utilizing a lipid bilayer system for electrophysiological measurement. The relevance of oligomers and protofibrils in Alzheimer's disease (AD) is underscored given their significant neurotoxicity. By closely monitoring the shift of Aβ42 from its monomeric state to forming oligomeric channels in phospholipid membranes, we noted that this transformation transpired within a 2-h frame. We manipulated the lipid membrane's constitution with components such as glycerophospholipid, porcine brain total lipid extract, sphingomyelin (SM), and cholesterol (Chol.) to effectively imitate nerve cell membranes. Interesting findings showcased Chol.'s ability to foster stable oligomeric channel formation in the lipid membrane, with SM and GM1 lipids potentially enhancing channel formation as well. Additionally, the study identified the potential of a catechin derivative, epigallocatechin gallate (EGCG), in obstructing oligomerization. With EGCG present in the outer solution of the Aβ42-infused membrane, a noteworthy reduction in channel current was observed, suggesting the successful inhibition of oligomerization. This conclusion held true in both, prior and subsequent, stages of oligomerization. Our findings shed light on the toxicity of oligomers, promising invaluable information for future advancements in AD treatment strategies.
Migration and the Value of Social Networks
Authors: Blumenstock Joshua E , Chi Guanghua , Tan Xu
Published: December 2023

How do social networks influence the decision to migrate? Prior work suggests two distinct mechanisms that have historically been difficult to differentiate: as a conduit of information, and as a source of social and economic support. We disentangle these mechanisms using a massive “digital trace” dataset that allows us to observe the migration decisions made by millions of individuals over several years, as well as the complete social network of each person in the months before and after migration. These data allow us to establish a new set of stylized facts about the relationship between social networks and migration. Our main analysis indicates that the average migrant derives more social capital from “interconnected” networks that provide social support than from “extensive” networks that efficiently transmit information.
Oral Nifedipine Versus Intravenous Labetalol for Hypertensive Emergencies During Pregnancy: A Systematic Review and Meta-analysis
Authors: Li Lin , Xie Wenxia , Xu Hao , Cao Lei
Published: December 2023

(Abstracted from J Matern Fetal Neonatal Med 2023;36(2):2235057)

Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal death. Severe pregnancy hypertension is defined as 160/110 mm Hg.
Efficacy of minimally invasive reduction with cerclage fixation in spiral or oblique subtrochanteric femoral fractures: A retrospective cohort study comparing cables and wires
Authors: Kook Incheol , Park Ki-Chul , Kim Keong Yoon , Jung Ilyun , Hwang Kyu Tae
Published: December 2023

OBJECTIVE:

To compare the outcomes of a minimally invasive reduction (MIR) technique using a cable and a wire in spiral or oblique subtrochanteric femoral fractures (SFF).

METHODS

Design:

Retrospective cohort study

Setting:

Two University Hospitals

Patient Selection Criteria:

Skeletally mature patients with spiral or oblique SFF (OTA/AO 32A1 and 32A2) treated with intramedullary nailing and MIR with a cerclage wire passer using either a single-loop cable or cerclage wire or MIR without cable or wire between May 2016 and November 2021.

Outcome Measures and Comparisons: Coronal and sagittal interfragmentary gap, neck-shaft angle, coronal and sagittal angulation, fracture union, time to union, and Radiographic Union Score for Hip (RUSH) at 6 months post-operation were compared.

RESULTS:

A total of 46 patients were included, with 16 each in the cable and wire groups and 14 in the non-wiring group. There were no differences in demographics (p>0.05), fracture classification (p=0.710), or operative data (p>0.05) between the three groups. The cable group showed significantly better coronal (p=0.003) and sagittal (p=0.003) interfragmentary gap, shorter union time (p<0.001), and higher 6-month RUSH score (p<0.001) among the three groups. There were no significant differences in outcome measures between the wire and non-wiring groups (all p>0.05). No mechanical complications or reoperations were observed in all three groups.

Conclusions:

Minimally invasive reduction using a cable is more effective than wire or non-wiring reduction to improve reduction quality and promote bone union in SFF.

Level of evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Corrective Open-wedge Valgus Proximal Humerus Lengthening Osteotomy. Technique and Case Series
Authors: Goetti Patrick , Aibinder William R. , Rollick Natalie R. , Rouleau Dominique M. , Faber Kenneth J.
Published: December 2023

Symptomatic varus malunion after proximal humeral fractures is associated with weakness and painful limitation of shoulder range of motion. When there is conformity of the articular surface and no avascular necrosis, a head-preserving procedure is best indicated. Arthroscopic arthrolysis, subacromial decompression, and tuberoplasty have been described for the treatment of mild deformity. In cases with more severe deformity, corrective extracapsular lateral closing wedge valgus osteotomy has been reported as a reliable treatment option, in terms of both pain relief and improved function. While this procedure adequately restores rotator cuff tensioning, it is associated with a shortening of the lever arm to the deltoid muscle, secondary to a loss of humeral length. We describe our technique and results with a vascular-sparing, medial open-wedge osteotomy, using a structural allograft and lateral locking plate. In our opinion, this procedure is safe and effective, with the potential to improve functional outcomes in young and active patients.
Prediction of Long-Term Physical, Mental, and Cognitive Problems Following Critical Illness: Development and External Validation of the PROSPECT Prediction Model*
Authors: van Sleeuwen Dries , Zegers Marieke , Ramjith Jordache , Cruijsberg Juliette K. , Simons Koen S. , van Bommel Daniëlle , Burgers-Bonthuis Dominique , Koeter Julia , Bisschops Laurens L. A. , Janssen Inge , Rettig Thijs C. D. , van der Hoeven Johannes G. , van de Laar Floris A. , van den Boogaard Mark
Published: December 2023

OBJECTIVES:

ICU survivors often suffer from long-lasting physical, mental, and cognitive health problems after hospital discharge. As several interventions that treat or prevent these problems already start during ICU stay, patients at high risk should be identified early. This study aimed to develop a model for early prediction of post-ICU health problems within 48 hours after ICU admission.

DESIGN:

Prospective cohort study in seven Dutch ICUs.

SETTING/PATIENTS:

ICU patients older than 16 years and admitted for greater than or equal to 12 hours between July 2016 and March 2020.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Outcomes were physical problems (fatigue or ≥ 3 new physical symptoms), mental problems (anxiety, depression, or post-traumatic stress disorder), and cognitive impairment. Patient record data and questionnaire data were collected at ICU admission, and after 3 and 12 months, of 2,476 patients. Several models predicting physical, mental, or cognitive problems and a composite score at 3 and 12 months were developed using variables collected within 48 hours after ICU admission. Based on performance and clinical feasibility, a model, PROSPECT, predicting post-ICU health problems at 3 months was chosen, including the predictors of chronic obstructive pulmonary disease, admission type, expected length of ICU stay greater than or equal to 2 days, and preadmission anxiety and fatigue. Internal validation using bootstrapping on data of the largest hospital (n = 1,244) yielded a C-statistic of 0.73 (95% CI, 0.70–0.76). External validation was performed on data (n = 864) from the other six hospitals with a C-statistic of 0.77 (95% CI, 0.73–0.80).

CONCLUSIONS:

The developed and externally validated PROSPECT model can be used within 48 hours after ICU admission for identifying patients with an increased risk of post-ICU problems 3 months after ICU admission. Timely preventive interventions starting during ICU admission and follow-up care can prevent or mitigate post-ICU problems in these high-risk patients.
Semiparametric Allocation of Subjects to Cohort Strata
Authors: Walker Alexander M. , Russo Massimiliano , Schneeweiss Maria C. , Glynn Robert J.
Published: December 2023

Background:

We illustrate a method for stratum assignment in small cohort studies that avoids modeling assumptions.

Methods:

Off-the-shelf software (rgenoud) made stratum assignments to minimize a loss function built on within-stratum and population-adjusted Euclidean distances.

Results:

In 100 trials using simulated data of 300 records with a binary treatment and four dissimilar covariate treatment predictors, minimizing a loss based on Euclidean distance reduced covariate imbalance by a median of 99%. Stratification by propensity score and weighting records by the inverse of their probability of treatment reduced imbalance by 76%–89% and 83%–94%, respectively. Loss minimization applied to a cohort of 361 children undergoing immunotherapy achieved nearly complete elimination of covariate differences for important treatment predictors.

Conclusion:

With the availability of semiparametric stratum-assignment algorithms, analysts can tailor loss functions to meet design goals. Here, a loss function that emphasized covariate balance performed well under limited testing.
Intrahepatic neutrophil accumulation and extracellular trap formation are associated with posthepatectomy liver failure
Authors: Brunnthaler Laura , Pereyra David , Brenner Miriam , Santol Jonas , Herrmann Lukas , Schrottmaier Waltraud C. , Pirabe Anita , Schmuckenschlager Anna , Kim Sarang , Kern Anna Emilia , Huber Felix Xaver , Michels Lisa Emilie , Brostjan Christine , Salzmann Manuel , Hohensinner Philipp , Kain Renate , Gruenberger Thomas , Starlinger Patrick , Assinger Alice
Published: December 2023

Background:

Posthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is incompletely understood, especially as underlying liver disease, detectable in the majority of patients, critically affects hepatic regeneration. Here we explored intrahepatic neutrophil accumulation and neutrophil extracellular traps (NETs) in patients with PHLF and validated the functional relevance of NETs in a murine partial hepatectomy (PHx) model.

Methods:

We investigated the influx of neutrophils, macrophages, eosinophils, and mast cells and the presence of their respective extracellular traps in liver biopsies of 35 patients undergoing hepatectomy (10 patients with PHLF) before and after the initiation of liver regeneration by fluorescence microscopy. In addition, NET formation and neutrophil activation were confirmed by plasma analysis of 99 patients (24 patients with PHLF) before and up to 5 days after surgery. Furthermore, we inhibited NETs via DNase I in a murine PHx model of mice with metabolically induced liver disease.

Results:

We detected rapid intrahepatic neutrophil accumulation, elevated levels of myeloperoxidase release, and NET formation in regenerating human livers, with a significantly higher increase of infiltrating neutrophils and NETs in patients with PHLF. Circulating markers of neutrophil activation, including elastase, myeloperoxidase, and citrullinated histone H3, correlated with markers of liver injury. In a murine PHx model, we showed that the inhibition of NET accelerated hepatocyte proliferation and liver regeneration.

Conclusions:

Patients with PHLF showed accelerated intrahepatic neutrophil infiltration and NET formation, which were associated with liver damage. Further, we identified postsurgical myeloperoxidase levels as predictive markers for adverse outcomes and observed that blocking NETs in a murine PHx model accelerated tissue regeneration.
BILATERAL UVEITIS, RETINAL PERIPHLEBITIS, AND OPTIC NEURITIS ASSOCIATED WITH NON-PINEAL CENTRAL NERVOUS SYSTEM GERMINOMA
Authors: Liu Tianyu , Chebolu Apoorv P. , Chung Caroline W. , Kruszewski Adam M. , Bhatt Nirali , Brucker Alexander J.
Published: December 2023

Purpose:

The aim of this study was to report a case of bilateral uveitis, retinal periphlebitis, and optic neuritis associated with a non-pineal central nervous system germinoma.

Methods:

This is a case report.

Results:

A 32-year-old man presented with episodes of acute painless visual disturbance in each eye and was found to have decreased VA, abnormal color vision, an afferent pupillary defect in the left eye, bilateral optic disc edema, perivenous sheathing, and candle-wax dripping exudates. Optical coherence tomography revealed bilateral intraretinal fluid and posterior vitreous hyperreflective opacities. Fluorescein angiography revealed bilateral optic disc leakage without active small vessel leakage. Magnetic resonance imaging of the brain and orbits revealed enhancing periventricular lesions and enhancement of the left optic nerve and bilateral perioptic nerve sheaths, posterior globes, and optic nerve heads. Brain biopsy was consistent with a central nervous system germinoma. His ocular signs and symptoms improved with chemotherapy for the germinoma.

Conclusion:

Central nervous system germinomas, including those located outside the pineal region, can be associated with optic neuritis, uveitis, and periphlebitis including characteristic candle-wax dripping exudates. Ocular signs and symptoms typically improve with treatment of the underlying germinoma.
Assessing the role of robotic surgery versus laparoscopic surgery in patients with a diagnosis of endometriosis: A meta-analysis
Authors: Song Zhihua , Li Songtao , Luo Mei , Li Hongjun , Zhong Hanzhi , Wei Shaobin
Published: December 2023

Background:

Surgical management of endometriosis can be carried out with the traditional standard laparoscopic technique or the robotic surgery technique; however, it is not clear if there is a significant difference between techniques. This meta-analysis aims to evaluate and compare the impact of robotic and standard laparoscopic techniques in endometriosis regarding the clinical outcome.

Methods:

Studies comparing robotic surgery to laparoscopic surgery for endometriosis were among the studies from various languages that met the inclusion criteria. Using dichotomous and continuous random-effect models, the results of these investigations (surgery time, hospitalization time, blood loss, complications, and conversion rate) were examined, and the mean difference with 95% confidence intervals was computed.

Results:

Eight studies from 2013 to 2022 were selected for the current analysis including 1741 patients with endometriosis. The studied data revealed a statistically significant (P = .01) lower operation time related to laparoscopic surgery compared with the robotic technique. In addition, the hospitalization time of laparoscopic surgery is significantly (P = .03) lower than that of robotic surgery. On the other hand, blood loss, rehospitalization, postoperative and intraoperative complications, and conversion rates were not significantly different between both techniques. Heterogeneity values were variable according to the analysis factor, from 0% to 91%.

Conclusion:

Both robotic and standard laparoscopic techniques have similar outcomes regarding blood loss, rehospitalization, conversion rate, and rate of complication. However, the substantial difference between techniques was in favor of standard laparoscopic surgery regarding operation and hospitalization time.
Research trends and hotspots of exercise for people with sarcopenic: A bibliometric analysis
Authors: Zang Wanli , Chen Haohao , Yan Jin , Li Dong , Xiao Ningkun , Zheng Xiaoqin , Zhang Zezhong
Published: December 2023

This study aimed to analyze the trends and themes in exercise and sarcopenia research using a bibliometric approach. The Web of Science citation database was used to identify papers published on exercise and sarcopenia. The retrieved data on institutions, journals, countries, authors, journal distribution, and keywords were analyzed scientometric ally using CiteSpace and VOSviewer. 2895 papers were included according to our specified inclusion criteria eventually. The data showed an upward trend in the number of published articles on exercise and sarcopenia. The countries with the highest number of publications were the United States, Japan, and England; research institutions were mainly composed of universities in Europe and the United States, and high-producing authors formed major collaborative teams, but cross-geographical and cross-institutional collaboration was not apparent; research was closely focused on 3 aspects: resistance exercise, resistance combined with other forms of exercise, and exercise combined with nutritional supplementation, of which resistance exercise was a particular focus; and recently, the research hotspots were mainly the effects of exercise on grip strength. The most cited articles were consensus guidelines published by the working group on sarcopenia in the elderly from different continents. The prevention and rehabilitation of sarcopenia in the elderly are gaining attention. Current primary exercise therapies for sarcopenia and exercise combined with nutritional supplementation have significant advantages and the potential to delay muscle decay. This suggests a promising area for future research that could benefit from further advances.