bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of patriarchal culture on Somali women's participation in politics
Authors: Abdullahi Abdulkadir Mohamed , Williamson Kim , Ahmed Mohamed Yusuf
Published: September 2023

Motivation

The political progress has been slow. The patriarchal clan traditions perpetuate gender discrimination, bestowing absolute priority upon all men for public affairs, while clan women remain voiceless, voteless, and restricted to private (household) affairs.

Purpose

To better understand why, despite the minimal formal constraints on women's participation in political life, informal institutions and customs determine the social, economic, and cultural constraints on women such that they are often poorly equipped and/or reluctant to participate in public political activity.

Methods and approach

Based on secondary literature, the article seeks to explain how the influences of the clan patriarchal system exert a negative impact on the political participation of Somali women. It identifies four structural categories, cultural, social, economic, and political, by which patriarchy has persistently impeded the participation of Somali women in the nation's politics.

Findings

Although women have contested the patriarchal system in Somalia through their participation in public decision‐making processes in different sectors and their participation in politics, including an increasingly higher level of education and more participation in the labour force, their numbers are still insufficient compared to men.

Policy implications

Given that patriarchy has been identified throughout the world as one of the main obstacles to women's participation in political and socioeconomic processes, there is a need for official quotas for women's representation in politics to balance severe gender inequalities, achieve full realization of human rights and influence the issues raised and how political policies are shaped. There is also a need for political representation to imprint their competence as decision makers. The article sets out recommendations for tackling the four main structural barriers to achieving this, so that women can fully contribute to the development of Somalia, on a par with men.
Unveiling invisible farm‐to‐farmPRRSV‐2 transmission links and routes through transmission tree and network analysis
Authors: Pamornchainavakul Nakarin , Makau Dennis N. , Paploski Igor A. D. , Corzo Cesar A. , VanderWaal Kimberly
Published: September 2023

The United States (U.S.) swine industry has struggled to control porcine reproductive and respiratory syndrome (PRRS) for decades, yet the causative virus, PRRSV‐2, continues to circulate and rapidly diverges into new variants. In the swine industry, the farm is typically the epidemiological unit for monitoring, prevention, and control; breaking transmission among farms is a critical step in containing disease spread. Despite this, our understanding of farm transmission still is inadequate, precluding the development of tailored control strategies. Therefore, our objective was to infer farm‐to‐farm transmission links, estimate farm‐level transmissibility as defined by reproduction numbers (R), and identify associated risk factors for transmission using PRRSV‐2 open reading frame 5 (ORF5) gene sequences, animal movement records, and other data from farms in a swine‐dense region of the U.S. from 2014 to 2017. Timed phylogenetic and transmission tree analyses were performed on three sets of sequences (n = 206) from 144 farms that represented the three largest genetic variants of the virus in the study area. The length of inferred pig‐to‐pig infection chains that corresponded to pairs of farms connected via direct animal movement was used as a threshold value for identifying other feasible transmission links between farms; these links were then transformed into farm‐to‐farm transmission networks and calculated farm‐levelR‐values. The median farm‐level R was one (IQR = 1–2), whereas theRvalue of 28% of farms was more than one. Exponential random graph models were then used to evaluate the influence of farm attributes and/or farm relationships on the occurrence of farm‐to‐farm transmission links. These models showed that, even though most transmission events cannot be directly explained by animal movement, movement was strongly associated with transmission. This study demonstrates how integrative techniques may improve disease traceability in a data‐rich era by providing a clearer picture of regional disease transmission.
How does climate change affect small scale fisheries? A case study of the Lower Amazon in Brazil
Authors: Furtado Maura da Silva Costa , Queiroz Joaquim Carlos Barbosa , Bentes Bianca , Gouveia Nelson de Almeida , de Lima Marcus José Alves , Ruffino Mauro Luis , Isaac Victoria
Published: September 2023

Effects of global climate change on inland artisanal fisheries have received little attention from scientists. We investigated fisheries of the Lower Amazon in Brazil using a wavelet analysis of a 13‐year data series of fishery catches, environmental variables, and climatic indices, to determine how these variables affected catches of different species. The catch per unit of effort (CPUE) of gillnet and line fisheries increased over time. Relative humidity, latent heat, and sea surface temperatures influenced productivity of both fisheries. El Niño had a negative and immediate effect on gillnet CPUE, while its effect on line fishing was positive, with an eight month lag. Our findings indicate that fishery productivity was modulated by climate events, which influenced ecosystems and modified habitats and ecological niches, andthereby impacted fishery productivity.
The distributive politics of privately financed infrastructure agreements
Authors: Woodhouse Eleanor Florence
Published: September 2023

Privately financed infrastructure agreements (PFIAs) are increasingly being used across the globe, bringing private money into the delivery of public goods. How does introducing private actors to such a process change how we think about distributive politics? I investigate this question using both quantitative and qualitative analyses, uncovering a relationship consistent with PFIAs being used as distributive goods and exploring how the credit‐claim potential of PFIAs may affect their distributive use. My quantitative analyses (on 16 middle‐income countries) present evidence suggestive of a relationship between electoral variables and the likelihood of a PFIA being present in a district. In districts aligned with the national ruling party, PFIAs are more likely to be concentrated in swing districts than core districts. I find that this relationship is more pronounced for PFIAs that are more directly attributable to the government. My qualitative press analysis provides insights into how politicians use various features of PFIAs to create credit‐claiming opportunities.
Advancements in Nipah virus treatment: Analysis of current progress in vaccines, antivirals, and therapeutics
Authors: Mishra Gayatree , Prajapat Vishal , Nayak Debasis
Published: September 2023

Nipah virus (NiV) causes severe encephalitis in humans. Three NiV strains NiV‐Malaysia (NiVM), NiV Bangladesh (NiVB), and NiV India (NiVI reported in 2019) have been circulating in South‐Asian nations. Sporadic outbreak observed in South‐East Asian countries but human to human transmission raises the concern about its pandemic potential. The presence of the viral genome in reservoir bats has further confirmed that NiV has spread to the African and Australian continents. NiV research activities have gained momentum to achieve specific preparedness goals to meet any future emergency—as a result, several potential vaccine candidates have been developed and tested in a variety of animal models. Some of these candidate vaccines have entered further clinical trials. Research activities related to the discovery of therapeutic monoclonal antibodies (mAbs) have resulted in the identification of a handful of candidates capable of neutralizing the virion. However, progress in discovering potential antiviral drugs has been limited. Thus, considering NiV's pandemic potential, it is crucial to fast‐track ongoing projects related to vaccine clinical trials, anti‐NiV therapeutics. Here, we discuss the current progress in NiV‐vaccine research and therapeutic options, including mAbs and antiviral medications.
Novel approaches for leadless pacemaker implantation in the extra‐cardiac Fontan cohort: Options to avoid leaded systems or epicardial pacing
Authors: Goulden Christopher J. , Khanra Dibbendhu , Llewellyn Jennifer , Rao Archana , Evans Alison , Ashrafi Reza
Published: September 2023

Background

Fontan surgery, a palliative procedure for single ventricle patients, often leads to the need for permanent pacing. Epicardial pacing has limitations, while transvenous pacing carries risks in the Fontan circulation. This case series introduces a novel approach of leadless pacemaker implantation in the extra‐cardiac Fontan (ECF) cohort to overcome these limitations.

Methods

The study includes four cases of leadless pacemaker (Micra™) implantation in patients with ECF. Procedures were performed under general anesthesia with guidance from trans‐esophageal echocardiography. Various access routes were used, including trans‐carotid and trans‐fenestration approaches. Procedural details, parameters, and follow‐up data were collected.

Results

All leadless pacemaker implantations were successful, with satisfactory electrical parameters and stable pacing postprocedural outcomes during short‐term follow‐up. One patient required closure of their fenestration for symptomatic desaturation post procedurally.

Conclusions

Leadless pacemaker implantation via trans‐carotid and trans‐fenestration approaches appears to be a feasible back up option for pacing in Fontan patients where other options have been exhausted or there is a patient choice to avoid surgery. These techniques provide an option to avoid leaded systems or epicardial pacing, reducing the need for multiple thoracotomies and addressing challenges associated with surgical pacing leads. Further studies are needed to evaluate long‐term outcomes and assess the broader application of leadless pacemakers in the Fontan population.
Nonrenewable resource use sustainability and public debt
Authors: Clootens Nicolas , Magris Francesco
Published: September 2023

The sustainability of resource use and the management of public finances are both long‐run issues that are linked to each other through savings decisions. To study them conjointly, this paper introduces a public debt stabilization constraint in an overlapping generation model in which nonrenewable resources constitute a necessary input in the production function and belong to agents. It shows that stabilization of public debt at a high level (as share of capital) may prevent the existence of a sustainable development path, that is, a path on which per capita consumption is not decreasing. Public debt thus appears as a threat to sustainable development. It also shows that higher public debt‐to‐capital ratios (and public expenditures‐to‐capital ones) are associated with lower growth. Two transmission channels are identified. As usual, public debt crowds out capital accumulation. In addition, public debt tends to increase resource use which reduces the rate of growth. We also provide a numerical analysis of the dynamics that shows that the economy is characterized by saddle path stability. Finally, we show that the public debt‐to‐capital ratio may be calibrated to implement the social planner optimal allocation according to which the growth rate is increasing in the degree of patience.
Simvastatin induces human gut bacterial cell surface genes
Authors: Escalante Veronica , Nayak Renuka R. , Noecker Cecilia , Babdor Joel , Spitzer Matthew , Deutschbauer Adam M. , Turnbaugh Peter J.
Published: September 2023

Drugs intended to target mammalian cells can have broad off‐target effects on the human gut microbiota with potential downstream consequences for drug efficacy and side effect profiles. Yet, despite a rich literature on antibiotic resistance, we still know very little about the mechanisms through which commensal bacteria evade non‐antibiotic drugs. Here, we focus on statins, one of the most prescribed drug types in the world and an essential tool in the prevention and treatment of high circulating cholesterol levels. Prior work in humans, mice, and cell culture support an off‐target effect of statins on human gut bacteria; however, the genetic determinants of statin sensitivity remain unknown. We confirmed that simvastatin inhibits the growth of diverse human gut bacterial strains grown in communities and in pure cultures. Drug sensitivity varied between phyla and was dose‐dependent. We selected two representative simvastatin‐sensitive species for more in‐depth analysis: Eggerthella lenta (phylum: Actinobacteriota) and Bacteroides thetaiotaomicron (phylum: Bacteroidota). Transcriptomics revealed that both bacterial species upregulate genes in response to simvastatin that alter the cell membrane, including fatty acid biogenesis (E. lenta) and drug efflux systems (B. thetaiotaomicron). Transposon mutagenesis identified a key efflux system in B. thetaiotaomicron that enables growth in the presence of statins. Taken together, these results emphasize the importance of the bacterial cell membrane in countering the off‐target effects of host‐targeted drugs. Continued mechanistic dissection of the various mechanisms through which the human gut microbiota evades drugs will be essential to understand and predict the effects of drug administration in human cohorts and the potential downstream consequences for health and disease.
Stability of Three‐Dimensional Printed Custom‐Made Metaphyseal Cone for Tibial Bone Defects Reconstruction: A Finite Element Analysis and Biomechanical Study
Authors: Wang Xinguang , Li Xinyu , Wang Cheng , Geng Xiao , Chen Bo , Dong Ziyang , Li Yang , Zhao Minwei , Li Zijian , Li Feng , Wang Caimei , Tian Hua
Published: September 2023

Objectives

The reconstruction of bone defects in tibial revision knee arthroplasty is challenging. In this study, we evaluated the primary stability of a novel three‐dimensional (3D)‐printed custom‐made metaphyseal cone for Anderson Orthopedic Research Institute (AORI) IIb or III bone defect reconstruction in tibial revision knee arthroplasty using the combination of finite‐element analysis and biomechanical experiments.

Methods

In the finite‐element analysis, AORI II b and III medial tibial bone defects were designed at varying depths. A novel 3D‐printed custom‐made metaphyseal cone was designed and used to reconstruct the bone defect with or without a stem in simulated revision total knee arthroplasty (RTKA). A no‐stem group and a stem group were established (based on whether a stem was used or not). Von Mises stress and micromotion were calculated with varying depths of bone defects, ranging from 5 mm to 35 mm, and then micromotions at the bone–implant interface were calculated and compared with the critical value of 150 μm. In the biomechanical experiment, the no‐stem group was used, and the same bone defects were made in four synthetic tibias using patient‐specific instruments. Micromotions at the bone–implant interface were investigated using a non‐contact optical digital image correlation system and compared with the critical value of 150 μm.

Results

When the bone defect was <30 mm, micromotions at the bone–implant interface in the finite‐element analysis were all below 150 μm both in the stem groups and no‐stem groups, whereas those in the biomechanical experiment were also below 150 μm in the no‐stem group.

Conclusions

The 3D‐printed custom‐made metaphyseal cone in RTKA has excellent primary stability and does not require stems in reconstructing tibial AORI type IIb or III bone defects with a depth of <30 mm.
Risk Factors for Significant Intraoperative Blood Loss during Anterior Cervical Decompression and Fusion for Degenerative Cervical Diseases
Authors: Yuan Hong , Zhao Yuanhang , Hu Yin , Liu Zhonghua , Chen Yu , Wang Hongwei , Yu Hailong , Xiang Liangbi
Published: September 2023

Objectives

Anterior cervical decompression and fusion (ACF) has become a widely accepted surgical treatment for degenerative cervical diseases, but occasionally, significant intraoperative blood loss (SIBL), which is defined as IBL of 500 mL or more, will occur. We aimed to investigate the independent risk factors for SIBL during ACF for degenerative cervical diseases.

Methods

We enrolled 1150 patients who underwent ACF for degenerative cervical diseases at our hospital between 2013 and 2019. The patients were divided into two groups: the SIBL group (n = 38) and the non‐SIBL group (n = 1112). Demographic, surgical and radiographic data were recorded prospectively to investigate the independent risk factors for SIBL. For counting data, the chi‐square test or Fisher's exact probability test was used. Student's t‐test or the Mann–Whitney rank sum test was used for comparisons between groups of measurement data. Univariate analysis and multivariate logistic regression analysis were further used to analyze the significance of potential risk factors.

Results

The incidence of SIBL during ACF was 3.3% (38/1150). A multivariate analysis revealed that female sex (odds ratio [OR], 6.285; 95% confidence interval [CI], 2.707–14.595; p < 0.001), corpectomy (OR, 3.872; 95% CI, 1.616–9.275; p = 0.002), duration of operation ≥150 min (OR, 8.899; 95% CI, 4.042–19.590; p < 0.001), C3 involvement (OR, 4.116; 95% CI, 1.808–9.369; p = 0.001) and ossification of posterior longitudinal ligament (OPLL) at the surgical level (OR, 6.007; 95% CI, 2.218–16.270; p < 0.001) were independent risk factors for SIBL. Patients with SIBL had more days of first‐degree/intensive nursing (p = 0.003), longer length of stay (p = 0.003) and higher hospitalization costs (p = 0.023).

Conclusion

Female sex, corpectomy, duration of operation, C3 involvement and OPLL at the surgical level were independent risk factors for SIBL during ACF. SIBL in ACF was associated with more days of first‐degree/intensive nursing, longer length of stay and higher hospitalization costs.
Agencies on the parliamentary radar: Exploring the relations between media attention and parliamentary attention for public agencies using machine learning methods
Authors: Boon Jan , Wynen Jan , Daelemans Walter , Lemmens Jens , Verhoest Koen
Published: September 2023

The news media frame political debate about public agencies, and enable legislators with incomplete information to monitor and act upon agency (mal)performance. While studies show that the news media matters for parliamentary attention, the contingent nature of this relation has been understudied. Building on agenda‐setting theory, this study theorizes that the effect of newspaper coverage is contingent on the sentiment of coverage, the majority vs. opposition role of legislators, and the locus (committee vs. plenaries) of parliamentary questions. Supervised machine learning methods allow to code sentiment towards agencies in newspapers and parliament, after which a balanced panel relates these data to the questioning behavior of legislators in parliament over time. Results show that media attention for public agencies precedes parliamentary attention. Sentiment matters, as positive media attention, was related to (positive) parliamentary attention in the same month. Negative media attention had broader and more enduring influences on parliamentary questioning behavior.
A retrospective analysis to evaluate if KIR B haplotype donors associate with a reduced risk of relapse in patients with haematological malignancies following haploidentical transplantation at the Blood and Bone Marrow Transplant Unit at Hammersmith Hospital ICHNHST
Authors: Byrnes Christopher Paul , Hastings Andrew , Lacej Ira , Palanicawandar Renuka , Olavarria Eduardo , Anand Arthi
Published: September 2023

Relapse is a major cause of treatment failure in haploidentical haematopoietic progenitor cell transplant (HPCT) with PTCy. Natural killer cells suppress graft versus host disease and mediate the graft versus leukaemia effect, driven by killer cell immunoglobulin‐like receptors (KIRs). Emerging research suggests that donor KIR genotype may influence graft outcome in haploidentical transplants with varying impacts between patient cohorts. This study investigates whether donors with greater KIR B motifs associate with outcomes such as greater relapse‐free survival (RFS), overall survival (OS), nonrelapse mortality (NRM), acute graft versus host disease (GvHD) and infection. The study cohort included 98 haploidentical donor–recipient (D/R) pairs (myeloablative n = 37, RIC n = 61) with various haematological malignancies, receiving primary T‐cell replete haploidentical HSCT with PTCγ. Following KIR SSO genotyping, donors are categorised into neutral (n = 63) or better and best (n = 35), based on KIR B motif content. Kaplan–Meier and Cox regression survival functions are performed to investigate associations with outcomes. Our results show that the better and best category has significantly poorer RFS (p = 0.013; hazard ratio [HR] 3.16, 95% CI 1.21–8.24: p = 0.018). The greater risk of relapse associated with poorer OS (p = 0.011; HR 2.24, 95% CI 1.18–4.24: p = 0.01) in the better and best category. The competing KIR receptor‐ligand and missing licensing proof models failed to predict transplant outcomes. Here, we show neutral donors associate with favourable outcomes in T‐cell replete haplo‐HPCT with PTCγ after categorisation using the KIR B content model, due to the increased risk of relapse associated with the use of better and best donors.
Transfusion‐associated adverse events incidence and severity after the implementation of an active hemovigilance program with 24 h follow‐up. A prospective cohort study
Authors: Bueno José L. , Bocanegra Ana B. , Sánchez Isabel , Mateos José M. , Puyuelo Alba , García Erce José A. , Villanueva Héctor , Reaño María M. , Núñez Lucía , Losa Azucena , Arias Ana , Aguilar Miriam , Richart Luis A. , Martínez Fátima , Salgado Rosario , Royuela Ana , Cruz‐Bermúdez Juan L. , Fernández Roberto , Forés Rafael , Fornet Inocencia , Ojeda Emilio , Cabrera Rafael , Duarte Rafael F.
Published: September 2023

Background

Hemovigilance (HV) is usually based on voluntary reports (passive HV). Our aim is to ascertain credible incidence, severity, and mortality of transfusion‐associated adverse events (TAAEs) using an active HV program.

Study Design and Methods

Prospective cohort study to estimate transfusion risk after 46,488 transfusions in 5830 patients, using an active HV program with follow‐up within the first 24 h after transfusion. We compared these results to those with the previously established passive HV program during the same 30 months of the study. We explored factors associated with the occurrence of TAAEs using generalized estimating equations models.

Results

With the active HV program TAAEs incidence was 57.3 (95% CI, 50.5–64.2) and mortality 1.1 (95% CI, 0.13–2.01) per 10,000 transfusions. Incidence with the new surveillance model was 14.0 times higher than with the passive. Most events occurred when transfusions had already finished (60.2%); especially pulmonary events (80.4%). Three out of five deaths and 50.3% of severe TAAEs were pulmonary. In the multivariate analysis surgical patients had half TAAEs risk when compared to medical patients (OR, 0.53; 95% CI, 0.34–0.78) and women had nearly twice the risk of a pulmonary event compared to men (OR, 1.84; 95% CI, 1.03–3.32). Patient's age, blood component type, or blood component shelf‐life were unrelated to TAAEs risk.

Discussion

Active hemovigilance programs provide additional data which may lead to better recognition and understanding of TAAEs and their frequency and severity.
Sodium channel endocytosis drives axon initial segment plasticity
Authors: Fréal Amélie , Jamann Nora , Ten Bos Jolijn , Jansen Jacqueline , Petersen Naomi , Ligthart Thijmen , Hoogenraad Casper C. , Kole Maarten H. P.
Published: September 2023

Activity-dependent plasticity of the axon initial segment (AIS) endows neurons with the ability to adapt action potential output to changes in network activity. Action potential initiation at the AIS highly depends on the clustering of voltage-gated sodium channels, but the molecular mechanisms regulating their plasticity remain largely unknown. Here, we developed genetic tools to label endogenous sodium channels and their scaffolding protein, to reveal their nanoscale organization and longitudinally image AIS plasticity in hippocampal neurons in slices and primary cultures. We find that
N
-methyl-
d
-aspartate receptor activation causes both long-term synaptic depression and rapid internalization of AIS sodium channels within minutes. The clathrin-mediated endocytosis of sodium channels at the distal AIS increases the threshold for action potential generation. These data reveal a fundamental mechanism for rapid activity-dependent AIS reorganization and suggests that plasticity of intrinsic excitability shares conserved features with synaptic plasticity.
Density-discriminating chromatic x-ray imaging based on metal halide nanocrystal scintillators
Authors: Hu Xudong , Luo Sihan , Leng Jing , Wang Chujie , Chen Yiyang , Chen Jun , Li Xiaoming , Zeng Haibo
Published: September 2023

X-ray imaging based on a single gray level shows visual blind parts and affects accurate judgment in some situations. Color-cognized x-ray imaging will boost the recognition capability, which has not yet been reported. Here, we propose a quartz-assisted chromatic x-ray imaging model based on metal halide nanocrystal (NC) stacked scintillators. Mutually inactive (BA)
2
PbBr
4
:Mn and Cs
3
Cu
2
I
5
:Tl enable x-ray energy- or density-dependent radioluminescence (RL) color variation. The upper scintillator light yield and the bottom scintillator transmittance are enhanced by elaborate in situ passivation of phenethylamine bromide and NC orientation regulation, respectively. Imaging targets with different densities are distinguished on RL spectra, and the color coordinates shift linearly on CIE 1931. An algorithm balances the image details of different gray areas and enhances the visual perception by color filling. This work provides color recognition between objects with different densities and takes a step toward chromatic x-ray imaging applied to practical scenarios.
Sulfonium-based precise alkyl transposition reactions
Authors: Chen Jian , Liu Shilu , Su Shuaisong , Fan Rong , Zhang Ruirui , Meng Wei , Tan Jiajing
Published: September 2023

S
-adenosyl-
L
-methionine (SAM), a sulfonium-based cofactor, plays an important role in numerous biological processes as methyl donor. Inspired by the function of sulfonium motif in this nature’s synthetic toolkit, we here present an aryne-activation strategy that the sulfonium intermediates in situ generated from thioethers display unique reactivity toward alkyl group transposition. Experimental and theoretical studies indicate that the reaction occurs in an intermolecular fashion where the TfO
−
-incorporated [K(18-crown-6)] complex acts as a key promoter for this thermodynamically favored process. Next, a series of robust, easy-to-prepare sulfonium salts are designed and developed as electrophilic alkylation reagents accordingly. Both systems feature for broad scope, excellent selectivity, and simple operation. Moreover, we highlight the synthetic value through molecular editing and late-stage modification of complex scaffolds or even active pharmaceutical ingredients.
Interferon-stimulated gene TDRD7 interacts with AMPK and inhibits its activation to suppress viral replication and pathogenesis
Authors: Chakravarty Sukanya , Subramanian Gayatri , Popli Sonam , Veleeparambil Manoj , Fan Shumin , Chakravarti Ritu , Chattopadhyay Saurabh
Published: September 2023

Many viruses activate cellular autophagy in infected cells to facilitate their replication. Recently, we identified an interferon (IFN)-stimulated gene (ISG) Tudor domain containing 7 (TDRD7), which inhibits viral replication by blocking autophagy pathway. Here, we present a molecular mechanism for TDRD7 action and its relative contribution to protection against viral pathogenesis. TDRD7 inhibited the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a kinase required for initiating autophagy. Mechanistically, TDRD7 interacted directly with AMPK in the cytosolic compartment. Domain-mapping analyses revealed C-terminal Tudor domain of TDRD7 interacted with auto-inhibitory domain of AMPK. Deletion of Tudor domains abolished anti-AMPK and antiviral activities of TDRD7. We evaluated physiological relevance of TDRD7 function against viral replication using newly engineered TDRD7 knockout mice and the derived primary cells. TDRD7 knockout primary cells displayed increased AMPK activation, which led to a higher viral load. Subsequently, TDRD7 knockout mice showed enhanced susceptibility upon intranasal Sendai virus infection. Therefore, our study revealed a new antiviral function of IFN, mediated by TDRD7-AMPK, inhibiting viral replication and pathogenesis.

IMPORTANCE

Virus infection triggers induction of interferon (IFN)-stimulated genes (ISGs), which ironically inhibit viruses themselves. We identified Tudor domain-containing 7 (TDRD7) as a novel antiviral ISG, which inhibits viral replication by interfering with autophagy pathway. Here, we present a molecular basis for autophagy inhibitory function of TDRD7. TDRD7 interacted with adenosine monophosphate (AMP)-activated protein kinase (AMPK), the kinase that initiates autophagy, to inhibit its activation. We identified domains required for the interaction; deleting AMPK-interacting domain blocked antiAMPK and antiviral activities of TDRD7. We used primary cells and mice to evaluate the TDRD7-AMPK antiviral pathway. TDRD7-deficient primary mouse cells exhibited enhanced AMPK activation and viral replication. Finally, TDRD7 knockout mice showed increased susceptibility to respiratory virus infection. Therefore, our study revealed a new antiviral pathway of IFN and its contribution to host response. Our results have therapeutic potential; a TDRD7-derived peptide may be an effective AMPK inhibitor with application as antiviral agent.
Essential function of alveolin
Pf
IMC1g in the
Plasmodium falciparum
asexual blood stage
Authors: Cepeda Diaz Ana Karla , Rudlaff Rachel M. , Farringer Madeline , Dvorin Jeffrey D.
Published: September 2023

The cytoskeleton of
Plasmodium
parasites is essential for replication, motility, and infectivity.
Plasmodium falciparum
leverages a family of cytoskeletal proteins known as alveolins to meet these diverse needs. The functional role of individual alveolins in
Plasmodium
blood stages, however, remains unexplored. Here, we demonstrate that the alveolin
Pf
IMC1g (PF3D7_0525800) is essential for
P. falciparum
asexual replication. Unlike alveolins studied in mosquito stages,
Pf
IMC1g does not play an important role in determining cell shape.
Pf
IMC1g-deficient parasites exhibit only minor defects during segmentation, with most merozoites being indistinguishable from wild type by super-resolution fluorescence microscopy, ultrastructure expansion microscopy, and electron microscopy. In the current study, we demonstrate that the absence of
Pf
IMC1g leads to parasite death shortly after merozoite internalization into red blood cells (RBCs).
Pf
IMC1g-deficient parasites egress and enter new RBCs but fail to develop into rings and die. We hypothesize that the primary role of
Pf
IMC1g is to maintain structural integrity, protecting parasites from incurring damage during the process of internalization. Along with the dispensability of
Pf
IMC1g for merozoite cell shape, we report new findings about the architecture of
Plasmodium
alveolins including the localization of
Pf
IMC1e and 1f to the basal complex.

Importance

Infection by the
Plasmodium falciparum
parasite is responsible for the most severe form of human malaria. The asexual blood stage of the parasite, which occurs inside human red blood cells, is responsible for the symptoms of malaria and is the target of most antimalarial drugs.
Plasmodium
spp. rely on their highly divergent cytoskeletal structures to scaffold their cell division, sustain the mechanical stress of invasion, and survive in both the human bloodstream and the mosquito. We investigate the function of a class of divergent intermediate filament-like proteins called alveolins in the clinically important blood stage. The functional role of individual alveolins in
Plasmodium
remains poorly understood due to pleiotropic effects of gene knockouts and redundancy among alveolins. We evaluate the localization and essentiality of the four asexual-stage alveolins and find that
Pf
IMC1g and
Pf
IMC1c are essential. Furthermore, we demonstrate that
Pf
IMC1g is critical for survival of the parasite post-invasion.
Precision detection of recent HIV infections using high-throughput genomic incidence assay
Authors: Faraci Gina , Park Sung Yong , Love Tanzy M. T. , Dubé Michael P. , Lee Ha Youn
Published: September 2023

HIV incidence is a key measure for tracking disease spread and identifying populations and geographic regions where new infections are most concentrated. The HIV sequence population provides a robust signal for the stage of infection. Large-scale and high-precision HIV sequencing is crucial for effective genomic incidence surveillance. We produced 1,034 full-length envelope gene sequences from a seroconversion cohort by conducting HIV microdrop sequencing and measuring the genomic incidence assay’s genome similarity index (GSI) dynamics. The measured dynamics of 9 of 12 individuals aligned with the GSI distribution estimated independently using 417 publicly available incident samples. We enhanced the capacity to identify individuals with recent infections, achieving predicted detection accuracies of 92% (89%–94%) for cases within 6 months and 81% (74%–87%) for cases within 9 months. These accuracy levels agreed with the observed detection accuracy intervals of an independent validation data set. Additionally, we produced 131 full-length envelope gene sequences from eight individuals with chronic HIV infection. This analysis confirmed a false recency rate (FRR) of 0%, which was consistent with 162 publicly available chronic samples. The mean duration of recent infection (MDRI) was 238 (209–267) days, indicating an 83% improvement in performance compared to current recent infection testing algorithms. The shifted Poisson mixture model was then used to estimate the time since infection, and the model estimates showed an 88% consistency with the days post infection derived from HIV RNA test dates and/or seroconversion dates. HIV microdrop sequencing provides unique prospects for large-scale incidence surveillance using high-throughput sequencing.

Importance

Accurate identification of recently infected individuals is vital for prioritizing specific populations for interventions, reducing onward transmission risks, and optimizing public health services. However, current HIV-specific antibody-based methods have not been satisfactory in accurately identifying incident cases, hindering the use of HIV recency testing for prevention efforts and partner protection. Genomic incidence assays offer a promising alternative for identifying recent infections. In our study, we used microdroplet technologies to produce a large number of complete HIV envelope gene sequences, enabling the accurate detection of early infection signs. We assessed the dynamics of the incidence assay’s metrics and compared them with statistical models. Our approach demonstrated high accuracy in identifying individuals with recent infections, achieving predicted detection rates exceeding 90% within 6 months and over 80% within 9 months of infection. This high-resolution method holds significant potential for enhancing the effectiveness of HIV incidence screening for case-based surveillance in public health initiatives.
Supplemental Material: Insights into initial continental rifting of marginal seas from seismic evidence for slab relics in the mid-mantle of the Woodlark rift, southwestern Pacific
Authors: Yu Youqiang , al. et
Published: September 2023

Figures S1–S9 and Table S1.
Supplemental Material: Products and dynamics of lava-snow explosions: The 16 March 2017 explosion at Mount Etna, Italy
Authors: Cioni Raffaello , et al.
Published: September 2023

Item S1: List of websites hosting the three videos discussed in the text. Item S2: UAS video footage of the lava flow and the deposit of the explosion. Figure S1: Effects of the explosions. Figure S2: Relative abundance of the different clast lithologies in the different samples. Figure S3. Shape parameters relative to grain-size class. Figure S4: Density distribution for the different lithologies of the coarse material. Figure S5: Pre-eruption topography of the area invaded by the lava flow. Table S1: Sample list. Data S1: Field and laboratory data. 
Actinomycosis withFusobacteriumempyema
Authors: Sykes Christopher , Barik Milan , Kastelik Jack
Published: September 2023

Actinomyces, are gram-positive, non-spore forming anaerobic or microaerophilic species. Empyema due to actinomycosis is relatively rare and can be difficult to diagnose as the presenting symptoms may be indolent and the micro-organism may be difficult to culture. This case report describes a patient presenting with dyspnoea, weight loss and lethargy. The chest radiograph, CT and thoracic ultrasound revealed a left-sided pleural effusion. A chest drain was inserted under ultrasound guidance. The pleural fluid was macroscopically consistent with pus and microbiology showed growth of gram-positive bacilli,Actinomyces meyerias well as theFusobacteriumspecies. The patient was treated with a drainage of the pleural fluid, a prolonged course of antibiotics and made a good recovery. The awareness that theActinomycesspecies and theFusobacteriumspecies through their synergistic interaction may cause empyema, may lead to a timely diagnosis and treatment.
New-onset minimal change disease following the Moderna COVID-19 vaccine
Authors: Kobayashi Nobuteru , Fujisawa Hajime , Kumagai Jiro , Tanabe Madoka
Published: September 2023

We report the case of nephrotic syndrome after COVID-19 vaccination. The patient was a man in his 30s with no comorbidities other than atopic dermatitis. Over the course of 2 weeks after the first COVID-19 vaccination, systemic oedema gradually appeared. He was referred to the nephrology department for investigation of the systemic oedema. On admission, he presented with pitting oedema in his lower extremities. Initial examinations revealed massive urinary protein and decreased serum albumin, at 13.9 g/g Cr and 1.5 g/dL, respectively. Renal biopsy was performed, and minimal change disease was diagnosed. Prednisolone 60 mg/day was promptly started on the 5th day of hospitalisation, and complete remission was achieved on the 12th day. Prednisolone was once tapered off in 1.5 years successfully though minimal change disease was relapsed in 1 month after the steroid withdrawal.
Lady Windermere syndrome with haemoptysis: suspected pulmonary aspergilloma and MAC pulmonary disease
Authors: Nazarenko Natalia , Borkowski Pawel , Berges Melissa Morales , Varrias Dimitrios
Published: September 2023

We present a case of a woman in her 70s, with a history ofMycobacterium aviumcomplex (MAC) pulmonary disease, pectus excavatum, s-shaped thoracolumbar scoliosis, bronchiectasis of the right middle lobe, lingula of left upper lobe, and malnutrition with low body mass index of 14 kg/m2, who presented to the hospital due to worsening shortness of breath and small volume haemoptysis over 2 weeks. The patient was diagnosed with pulmonary MAC infection for the first time in 1999 without known history of pulmonary disease. Later on, it was complicated by massive haemoptysis requiring bronchial artery embolisation; however, she was unable to complete an oral antibiotic regimen due to gastrointestinal adverse reactions. Chest CT identified a newly found mass in the left upper lobe bulla, consistent with a radiological finding of aspergilloma. We present a rare symptoms constellation, described as ‘Lady Windermere syndrome’ and chronic untreated MAC infection progressing from reticulonodular changes to fibrocavitary lung disease and suspected aspergilloma formation.
Impact of the COVID-19 pandemic on antipsychotic prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: a federated analysis of 59 million patients’ primary care records in situ using OpenSAFELY
Authors: Macdonald Orla , Green Amelia , Walker Alex , Curtis Helen , Croker Richard , Brown Andrew , Butler-Cole Ben , Andrews Colm , Massey Jon , Inglesby Peter , Morton Caroline , Fisher Louis , Morley Jessica , Mehrkar Amir , Bacon Sebastian , Davy Simon , Evans David , Dillingham Iain , Ward Tom , Hulme William , Bates Chris , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , O'Hanlon Shaun , Eavis Alex , Jarvis Richard , Avramov Dima , Parkes Nasreen , Wood Ian , Goldacre Ben , Mackenna Brian
Published: September 2023

Background

The COVID-19 pandemic affected how care was delivered to vulnerable patients, such as those with dementia or learning disability.

Objective

To explore whether this affected antipsychotic prescribing in at-risk populations.

Methods

With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We calculated the monthly prevalence of antipsychotic prescribing in these groups, as well as the incidence of new prescriptions in each month.

Findings

The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30 to 83.19) in January–March 2019 to 90.1 (95% CI 89.68 to 90.60) in October–December 2021 and from 154.61 (95% CI 153.79 to 155.43) to 166.95 (95% CI 166.23 to 167.67) in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29 to 123.66) to 119.29 (95% CI 118.68 to 119.91) and from 54.91 (95% CI 54.52 to 55.29) to 51.04 (95% CI 50.74 to 51.35), respectively.

Conclusion and implications

We observed a spike in antipsychotic prescribing in the dementia and care home groups, which correlated with lockdowns and was likely due to prescribing of antipsychotics for palliative care. We observed gradual increases in antipsychotic use in dementia and care home patients and decreases in their use in patients with learning disability or autism.
Low interobserver agreement among subspecialised breast pathologists in evaluating HER2-low breast cancer
Authors: Turashvili Gulisa , Gao Yuan , Ai Di (Andy) , Ewaz Abdulwahab M , Gjeorgjievski Sandra Gjorgova , Wang Qun , Nguyen Thi T A , Zhang Chao , Li Xiaoxian
Published: September 2023

Aims

Metastatic HER2-low breast cancer (HLBC) can be treated by trastuzumab deruxtecan. Assessment of low levels of HER2 protein expression suffers from poor interobserver reproducibility. The aim of the study was to evaluate the interobserver agreement among subspecialised breast pathologists and develop a practical algorithm for assessing HLBC.

Methods

Six breast pathologists (4 juniors, 2 seniors) evaluated 106 HER2 immunostained slides with 0/1+expression. Two rounds (R1, R2) of ring study were performed before and after training with a modified Ki-67 algorithm, and concordance was assessed.

Results

Agreement with 5% increments increased from substantial to almost perfect (R1: 0.796, R2: 0.804), and remained substantial for three categories (<1% vs 1%–10% vs >10%) (R1: 0.768, R2: 0.764). Seniors and juniors had almost perfect agreement with 5% increments (R1: 0.859 and 0.821, R2: 0.872 and 0.813). For the three categories, agreement remained almost perfect among seniors (R1: 0.837, R2: 0.860) and substantial among juniors (R1: 0.792, R2: 0.768). Binary analysis showed suboptimal agreement, decreasing for both juniors and seniors from substantial (R1: 0.650 and 0.620) to moderate (R2: 0.560 and 0.554) using the 1% cut-off, and increasing from moderate to substantial (R1: 0.478, R2: 0.712) among seniors but remaining moderate (R1: 0.576, R2: 0.465) among juniors using the 10% cut-off. The average scoring time per case was higher (72 vs 92 s).

Conclusions

Subspecialised breast pathologists have suboptimal agreement for immunohistochemical evaluation of HLBC using the modified Ki-67 methodology. An urgent need remains for a new assay/algorithm to reliably evaluate HLBC.
Endophytic fungi of soybean (Glycine max (L.) Merr.) and their potential applications
Authors: Abdelmagid Ahmed , Hou Anfu , Wijekoon Champa
Published: September 2023

Endophytes are microorganisms residing inside plants and are mostly transmitted by seeds. In this study, we used internal transcribed spacer metagenomic sequencing analysis to investigate the fungal endophyte profile of seeds harvested from three different soybean genotypes (OT 13-08, AC Proteus, and AC Harmony) grown in Manitoba, Canada. Protein and oil contents of these genotypes were different from each other. Out of the three soybean genotypes tested, AC Harmony showed the highest level (71.85%) of predicted fungal endophyte taxonomic units classified up to the genus level. At the species level analysis, 20 predicted microorganisms were common in all genotypes. In addition, AC Harmony included the most diverse potential number (90) of endophyte species. The potential roles of the identified endophytes were further studied and the differential roles were observed based on previous evidence. This study will give insight into fungal endophytes in Canadian soybean genotypes for potential applications in agriculture.
Naturalness: past, present, and future
Authors: Craig Nathaniel
Published: September 2023

We assess the state of naturalness in high-energy physics and summarize recent approaches to the three major naturalness problems: the cosmological constant problem, the electroweak hierarchy problem, and the strong CP problem.
Sparsification Lower Bounds for List
H
-Coloring
Authors: Chen Hubie , Jansen Bart M. P. , Okrasa Karolina , Pieterse Astrid , Rzążewski Paweł
Published: September 2023

We investigate the

List
H
-Coloring

problem, the generalization of graph coloring that asks whether an input graph 
G
admits a homomorphism to the undirected graph 
H
(possibly with loops), such that each vertex 
v
∈
V
(
G
) is mapped to a vertex on its list 
L
(
v
) ⊆
V
(
H
). An important result by Feder, Hell, and Huang [JGT 2003] states that

List
H
-Coloring

is polynomial-time solvable if 
H
is a so-called
bi-arc graph
, and NP-complete otherwise. We investigate the NP-complete cases of the problem from the perspective of polynomial-time sparsification: can an
n
-vertex instance be efficiently reduced to an equivalent instance of bitsize 

\(\mathcal {O} (n^{2-\varepsilon })\)

(
n
2-ɛ
) for some ɛ > 0? We prove that if 
H
is not a bi-arc graph, then

List
H
-Coloring

does not admit such a sparsification algorithm unless

\(\mathsf {NP \subseteq coNP/poly}\)

. Our proofs combine techniques from kernelization lower bounds with a study of the structure of graphs 
H
which are not bi-graphs.
Contributions of the Basal Ganglia to Visual Perceptual Decisions
Authors: Ding Long
Published: September 2023

The basal ganglia (BG) make up a prominent nexus between visual and motor-related brain regions. In contrast to the BG's well-established roles in movement control and value-based decision making, their contributions to the transformation of visual input into an action remain unclear, especially in the context of perceptual decisions based on uncertain visual evidence. This article reviews recent progress in our understanding of the BG's contributions to the formation, evaluation, and adjustment of such decisions. From theoretical and experimental perspectives, the review focuses on four key stations in the BG network, namely, the striatum, pallidum, subthalamic nucleus, and midbrain dopamine neurons, which can have different roles and together support the decision process.