bluuebunny/crossref_metadata_2025 huggingface dataset:
Streptococcus canis genomic epidemiology reveals the potential for zoonotic transfer
Authors: Pagnossin Davide , Weir William , Smith Andrew , Fuentes Manuel , Coelho Juliana , Oravcova Katarina
Published: March 2023

Streptococcus canis

, a multi-host pathogen commonly isolated from dogs and cats, has been occasionally reported in severe cases of human infection. To address the gap in knowledge on its virulence and host tropism, we investigated

S. canis

genomic epidemiology and report the results of this analysis for the first time. We analysed 59

S

.

canis

whole genome sequences originating from a variety of host species, comprising 39 newly sequenced isolates from UK sources, along with all (n=20) publicly available genomes. Antimicrobial resistance (AMR) phenotype was determined for all 39 available isolates. Genomes were screened for determinants of resistance and virulence. We created a core SNP phylogeny and compared strain clustering to multi-locus sequence typing (MLST) and

S. canis

M-like protein (SCM) typing. We investigated the dataset for signals of host adaptation using phylogenetic analysis, accessory genome clustering and pan-genome-wide association study analysis. A total of 23 % (9/39) of isolates exhibited phenotypic resistance to lincosamides, macrolides and/or tetracyclines. This was complemented by the identification of AMR-encoding genes in all genomes: tetracycline (tetO 14 %, 8/59; and tetM 7 %, 4/59) and lincosamide/macrolide (ermB, 7 %, 4/59). AMR was more common in human (36 %, 4/11) compared to companion animal (18 %, 5/28) isolates. We identified 19 virulence gene homologues, 14 of which were present in all strains analysed. In an

S. canis

strain isolated from a dog with otitis externa we identified a homologue of

S. pyogenes

superantigen SMEZ. The MLST and SCM typing schemes were found to be incapable of accurately representing core SNP-based genomic diversity of the

S. canis

population. No evidence of host adaptation was detected, suggesting the potential for inter-species transmission, including zoonotic transfer.
Interleukin-1 regulates follicular T cells during the germinal center reaction
Authors: Belbezier Aude , Engeroff Paul , Fourcade Gwladys , Vantomme Helene , Vaineau Romain , Gouritin Bruno , Bellier Bertrand , Brocheriou Isabelle , Tchitchek Nicolas , Graff-Dubois Stephanie , Klatzmann David
Published: March 2023

Antibody production by plasma cells and generation of long-term memory B-cells are positively regulated by Tfh cells and negatively regulated by Tfr cells in germinal centers. However, the precise role of Tfr cells in controlling antibody production is still unclear. We have previously shown that Tfh and Tfr cells both express IL-1R1, while only Tfr cells express the IL-1R2 decoy and IL-1Ra antagonist receptors. To study the role of these receptors in the regulation of the B cell response by Tfh and/or Tfr cells, we generated mice with knockout of IL-1 receptors in Tfh and/or Tfr cells and measured antibody production and cell activation upon immunization. We showed that IL-1β concentration is increased in the draining lymph node after immunization. Antigen-specific antibody levels and cell activation phenotypes indicated that IL-1β can activate both Tfh and Tfr cells through IL-1R1 stimulation. Surprisingly, IL-1R2 and IL-1Ra expression on Tfr cells does not block IL-1 activation of Tfh cells, but rather prevents IL-1/IL-1R1-mediated early activation of Tfr cells. IL-1Rs similarly regulate antibody response against autoantigens and its related pathophysiology in an experimental lupus model. Altogether, these results show that IL-1R1 inhibitory receptors expressed by Tfr cells prevent their own activation and suppressive function, thus licensing IL-1-mediated activation of Tfh cells after immunization.

One Sentence Summary

Functional knockout of IL-1 agonist (R1) and antagonist (R2 and Ra) receptors reveals that IL-1-R2 and -Ra on Tfr cells prevent their own early activation to license the expansion and activation of Tfh cells after immunization.
Molecular Mechanisms of Na+-driven Bile Acid Transport in Human NTCP
Authors: Lu Xiaoli , Huang Jing
Published: March 2023

Human Na+taurocholate co-transporting protein (hNTCP) is a key bile salt transporter to maintain enterohepatic circulation and is responsible for the recognition of hepatitis B and D viruses (HBV/HDV). Despite recent cryo-EM studies revealing open-pore and inward-facing states of NTCP stabilized by antibodies, the transport mechanism remains largely unknown. To address this knowledge gap, we used molecular dynamics (MD) and enhanced sampling Metadynamics simulations to elucidate the intrinsic mechanism of hNTCP-mediated taurocholate acid (TCA) transport driven by Na+-binding. We uncovered three TCA binding modes, including one that closely matched the limited cryo-EM density observed in the open-pore hNTCP. We also captured several key hNTCP conformations in the substrate transport cycle, particularly including an outward-facing, substrate-bound state. Furthermore, we provided thermodynamic evidence supporting that changes in the Na+-binding state drive the TCA transport by exploiting the amphiphilic nature of the substrate and modulating the protein environment, thereby enabling the TCA molecule to flip through. Understanding these mechanistic details of Na+-driven bile acid transport may aid in the development of hNTCP-targeted therapies for liver diseases.
Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow niche
Authors: Lewis Sloan A. , Doratt Brianna M , Qiao Qi , Blanton Madison B. , Grant Kathleen A. , Messaoudi Ilhem
Published: March 2023

Chronic alcohol drinking rewires circulating monocytes and tissue-resident macrophages towards heightened inflammatory states with compromised anti-microbial defenses. As these effects remain consistent in short-lived monocytes after a 1-month abstinence period it is unclear whether these changes are restricted to the periphery or mediated through alterations in the progenitor niche. To test this hypothesis, we profiled monocytes/macrophages and hematopoietic stem cell progenitors (HSCP) of the bone marrow compartment from rhesus macaques after 12 months of ethanol consumption using a combination of functional assays and single cell genomics. Bone marrow-resident monocytes/macrophages from ethanol-consuming animals exhibited heightened inflammation. Differentiation of HSCPin vitrorevealed skewing towards monocytes expressing neutrophil-like markers with heightened inflammatory responses to bacterial agonists. Single cell transcriptional analysis of HSCPs showed reduced proliferation but increased inflammatory markers in mature myeloid progenitors. We observed transcriptional signatures associated with increased oxidative and cellular stress as well as oxidative phosphorylation in immature and mature myeloid progenitors. Single cell analysis of the chromatin landscape showed altered drivers of differentiation in monocytes and progenitors. Collectively, these data indicate that chronic ethanol drinking results in remodeling of the transcriptional and epigenetic landscapes of the bone marrow compartment leading to altered functions in the periphery.
Consolidated Bioprocessing of Lignocellulosic Biomass Poplar to Produce Short-Chain Esters byClostridium thermocellum
Authors: Seo Hyeongmin , Singh Priyanka , Wyman Charles E. , Cai Charles M. , Trinh Cong T.
Published: March 2023

Consolidated bioprocessing (CBP) of lignocellulosic biomass using cellulolytic microorganisms presents a promising sustainable and economical biomanufacturing platform where enzyme production, biomass hydrolysis, and fermentation to produce biofuels, biochemicals, and biomaterials occur in a single step. However, understanding and redirecting metabolism of microorganisms to be compatible with CBP to produce non-native metabolites are limited. In this study, we metabolically engineered a cellulolytic thermophileClostridium thermocellumand demonstrated its compatibility with CBP integrated with a mild Co-solvent Enhanced Lignocellulosic Fractionation (CELF) pretreatment for conversion of hardwood poplar into short-chain esters (i.e., ethyl acetate, ethyl isobutyrate, isobutyl acetate, isobutyl isobutyrate) with broad use as solvents, flavors, fragrances, and biofuels. A recombinantC. thermocellumengineered with deletion of carbohydrate esterases and stable overexpression of a thermostable alcohol acetyltransferase improved the target esters production without compromised deacetylation activities. We discovered these esterases exhibited promiscuous thioesterase activities and their deletion improved ester production by increasing isobutanol flux and rerouting the native electron and carbon fermentative metabolism besides their known major function of ester degradation. The total ester production could be further enhanced up to 80-fold and the composition of short-chain esters could be modified by deleting lactate biosynthesis and/or CELF-pretreated poplar under different pretreatment conditions.
Robust immunogenicity of a third BNT162b2 vaccination against SARS-CoV-2 Omicron variant in a naïve New Zealand cohort
Authors: Lavender Brittany , Hooker Caitlin , Frampton Chris , Williams Michael , Carson Simon , Paterson Aimee , McGregor Reuben , Moreland Nicole J. , Gell Katie , Priddy Frances H. , Wiig Kjesten , Le Gros Graham , Ussher James E. , Brewerton Maia
Published: March 2023

The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted. This adult cohort of 298 participants, oversampled for at-risk populations, was composed of 29% Māori and 28% Pacific peoples, with 40% of the population aged 55+. A significant proportion of the cohort was obese and presented with at least one comorbidity. Sera were collected 28 days and 6 months post second vaccination and 28 days post third vaccination. SARS-CoV-2 anti-S IgG titres and neutralising capacity using surrogate viral neutralisation assays against variants of concern, including Omicron BA.1, were investigated. The incidence of SARS-CoV-2 infection, within our cohort, prior to third vaccination was very low (<6%). This study found a third vaccine significantly increased the mean SARS-CoV-2 anti-S IgG titres, for every demographic subgroup, by a minimum of 1.5-fold compared to titres after two doses. Diabetic participants experienced a greater increase (∼4-fold) in antibody titres after their third vaccination, compared to non-diabetics (increase of ∼2-fold). This corrected for the deficiency in antibody titres within diabetic participants which was observed following two doses. A third dose also induced a neutralising response against Omicron variant BA.1, which was absent after two doses. This neutralising response improved regardless of age, BMI, ethnicity, or diabetes status. Participants aged ≥75 years consistently had the lowest SARS-CoV-2 anti-S IgG titres at each timepoint, however experienced the greatest improvement after three doses compared to younger participants. This study shows that in the absence of prior SARS-CoV-2 infection, a third Pfizer-BioNTech BNT162b2 vaccine enhances immunogenicity, including against Omicron BA.1, in a cohort representative of at-risk groups in the adult New Zealand population.
Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease
Authors: Gerber Janina Lara , Guzmán Suria Itzel Morales , Worf Lorenz , Hubbe Petra , Kopp Jürgen , Peschek Jirka
Published: March 2023

RNA ligases of the RTCB-type play an essential role in tRNA splicing, the unfolded protein response and RNA repair. RTCB is the catalytic subunit of the pentameric human tRNA ligase complex. RNA ligation by the tRNA-ligase complex requires GTP-dependent activation of RTCB. This active site guanylylation reaction relies on the activation factor Archease. The mechanistic interplay between both proteins has remained unknown. Here, we report a biochemical and structural analysis of the human RTCB-Archease complex in the pre- and post-activation state. Archease reaches into the active site of RTCB and promotes the formation of a covalent RTCB-GMP intermediate through coordination of GTP and metal ions. During the activation reaction, Archease prevents futile RNA substrate binding to RTCB. Moreover, monomer structures of Archease and RTCB reveal additional states within the RNA ligation mechanism. Taken together, we present structural snapshots along the reaction cycle of the tRNA ligase complex.
Delineating disorder-general and disorder-specific dimensions of psychopathology from functional brain networks in a developmental clinical sample
Authors: Voldsbekk Irene , Kjelkenes Rikka , Dahl Andreas , Holm Madelene C. , Lund Martina J. , Kaufmann Tobias , Tamnes Christian K. , Andreassen Ole A. , Westlye Lars T. , Alnæs Dag
Published: March 2023

The interplay between functional brain network maturation and psychopathology during development remains elusive. To establish the structure of psychopathology and its neurobiological mechanisms, mapping of both shared and unique functional connectivity patterns across developmental clinical populations is needed. We investigated shared associations between resting-state functional connectivity and psychopathology in children and adolescents aged 5-21 (n=1689). Specifically, we used partial least squares (PLS) to identify latent variables (LV) between connectivity and both symptom scores and diagnostic information. We also investigated associations between connectivity and each diagnosis specifically, controlling for other diagnosis categories. PLS identified five significant LVs between connectivity and symptoms, mapping onto the psychopathology hierarchy. The first LV resembled a general psychopathology factor, followed by dimensions of internalising-externalising, neurodevelopment, somatic complaints, and thought problems. Another PLS with diagnostic data revealed one significant LV, resembling a cross-diagnostic case-control pattern. The diagnosis-specific PLS identified a unique connectivity pattern for autism spectrum disorder (ASD). All LVs were associated with distinct patterns of functional connectivity. These dimensions largely replicated in an independent sample (n=420) from the same dataset, as well as to an independent cohort (n = 3504). This suggests that covariance in developmental functional brain networks supports transdiagnostic dimensions of psychopathology.
Long-term duration of protection of ancestral-strain monovalent vaccines and effectiveness of the bivalent BA.1 boosters against COVID-19 hospitalisation during a period of BA.5, BQ.1, CH.1.1. and XBB.1.5 circulation in England
Authors: Møller Kirsebom Freja Cordelia , Andrews Nick , Stowe Julia , Ramsay Mary , Bernal Jamie Lopez
Published: March 2023

Background

Bivalent BA.1 booster vaccines were offered to adults aged 50 years and older and clinically vulnerable individuals as part of the autumn COVID-19 booster vaccination programme 2022 in England.

Methods

A test-negative case-control study was used to estimate the duration of protection of the monovalent vaccines against hospitalisation as compared to those unvaccinated. In addition, the incremental VE of the bivalent BA.1 booster vaccines was estimated relative to those with waned immunity where the last dose was at least 6 months prior amongst those aged 50 years and older.

Findings

The protection conferred by the monovalent vaccines was well maintained long-term: absolute VE against hospitalisation amongst those aged 65 years and older who had received at least 3 doses plateaued from 6 months after the last dose at around 50%. Incremental VE (in addition to the protection from earlier vaccines) of the bivalent BA.1 boosters against hospitalisation peaked at 53.0% (95% C.I.; 47.9-57.5%) (equivalent to an absolute VE of approximately 75%) before waning to around 35.9% (95% C.I.; 31.4-40.1%) after 10 or more weeks.

Interpretation

This study provides evidence of the long-term duration of protection of the monovalent vaccines, suggesting individuals at lower risk of severe disease who did not receive a booster in autumn 2022 may not require regular re-vaccination. Furthermore, this study finds good evidence that the bivalent BA.1 booster vaccines are highly effective against hospitalisation amongst those aged 50 years and older with the sub-lineages of Omicron present in the autumn/winter of 2022 in England.

Funding

None.
The association between audit firm attributes and key audit matters readability
Authors: Hussin Norazian , Md Salleh Mohd Fairuz , Ahmad Azlina , Rahmat Mohd Mohid
Published: March 2023

Purpose

This study aims to examine the relationship between the attributes of audit firms (Big 4, audit fees, busy season, audit firm tenure and audit partner gender) and the impact of these attributes on key audit matters (KAM) readability in Malaysia.

Design/methodology/approach

The auditor's reports and financial data were analysed from a sample of FTSE 100 Malaysia-listed companies for the fiscal years 2017–2019, consisting of 258 observations. Panel regression analyses were conducted to evaluate the possible associations between audit firm attributes and KAM readability. The Flesch reading ease score and Coleman–Liau index were applied to measure KAM readability.

Findings

The findings show that female audit partners significantly impact KAM readability; further analysis also revealed that companies audited by Big 4 audit firms and higher audit fees tend to report a more readable KAM disclosure in the FTSE 100 in Malaysia.

Originality/value

The regression results provide empirical evidence of the influence of audit firm attributes on KAM readability. This study also examined important corporate governance players, such as external auditors and those charged with governance, who form the audit committee's qualities when analysing the determinants of KAM reporting variations in Malaysia.
Transnational education, labor market outcomes and graduate employability: a scoping review
Authors: Schueller Jessica
Published: March 2023

Purpose

This scoping review aims to survey literature that covers employability preparation and labor market outcomes for graduates from transnational higher education institutions.

Design/methodology/approach

This scoping literature review uses career ecosystems as a theoretical framework and the context-input-process-outcomes model as a conceptual framework.

Findings

This scoping review confirms a limited research base of approximately 50 sources that primarily use qualitative methods and socio-economic theories to center the student voice and focus on international branch campuses in the Middle East and Asia. Notably, there is a lack of focus on staff experiences regarding the process of preparing students for employment. The review also demonstrates the need for more research on career processes and outcomes in transnational higher education.

Research limitations/implications

This scoping review is relevant to higher education institutions seeking to meet the challenges of preparing graduates for more than one national labor market. It has implications for universities' ability to attract students, develop relevant labor market preparation programming and understand whether the institution is addressing local employment needs. For researchers, it offers insight and impetus into the area of inquiry regarding transnational education, graduate labor market outcomes and employability.

Practical implications

Practical implications are drawn for students, parents, policymakers and transnational and non-transnational higher education institutions, as well as those who are engaged in providing international education and career advice.

Social implications

This review offers insight into developing labor market-relevant TNE programming, which may be helpful both for host and home country transnational education stakeholders interested in impact.

Originality/value

This is one of the first reviews to systematically address literature about employability preparation and labor market outcomes for graduates from transnational higher education institutions; in using career ecosystems theory, this review offers a bridge between international higher education and career studies.
From entrepreneurial leadership to new product development performance: A study of the Coleman bathtub model
Authors: Sultan Madeeha , Hussain Ghulam , Ismail Wan Khairuzzaman Wan , Rashid Muhammad Amir
Published: March 2023

Purpose

This study aims to examine the relationship between entrepreneurial leadership (EL) and new product development performance (NPDP) at the firm level (level 2) of analysis and employee’s creativity (EC) at the cross level (level 1) of analysis. It also examines the serial mediations of (1) intrinsic motivation (IM)-EC and (2) creative self-efficacy (CSE)-EC on the relationship between EL and NPDP.

Design/methodology/approach

A systematic random sampling technique was used to collect data through self-administered surveys from leaders and employees of small and medium-sized enterprises (SMEs) in Pakistan’s IT sector. Analysis was conducted on net responses from 114 leaders and 476 employees.

Findings

The results revealed significant positive associations between EL and NPDP at the firm level of analysis and EC at the cross level of analysis. The results of the cross-level serial mediations show that (1) IM and EC, and (2) CSE and EC serially mediate the relationship between EL and NPDP.

Originality/value

This study is among the few to use the Coleman bathtub model to show top-down and bottom-up relationships. The study extends and complements the multilevel perspective on leadership and new product development research by simultaneously examining the relationships between EL and NPDP at the individual and firm levels.
Does export structure enhance the growth gains from foreign investment? Evidence from the ECOWAS region
Authors: Haini Hazwan , Wei Loon Pang , Raimi Lukman
Published: March 2023

Purpose

This study aims to examine whether diversified economies enhance the growth benefits from foreign direct investment (FDI). Diversified economies benefit from stable export earnings, stable investment composition and greater factor endowments through forward and backward linkages that can leverage superior foreign technology embedded in FDI. This is crucial as many African economies suffer from dependency while FDI is concentrated in the primary sector.

Design/methodology/approach

The authors use a dataset of 15 Economic Community of West African States from 1995 to 2020 and compile variables from various sources, including an export diversification index measured using the Herfindahl–Hirschman index of product concentration. The authors use a growth regression model estimated using dynamic panel estimators to control for endogeneity and simultaneity issues.

Findings

The results show that the effects of direct FDI are insignificant to growth considering diversification and controlling for other confounding factors. Meanwhile, diversification is associated with growth, which highlights the importance of industrial policy. More importantly, the authors find that the marginal effects of FDI are positively and significantly associated with growth when diversification levels are low, implying that production structure matters for the FDI–growth nexus in developing economies.

Originality/value

Previous studies have overlooked the role of export production structure on the FDI–growth nexus. Many developing economies are dependent on primary exports and suffer from dependency, which implies lower levels of factor endowments. As such, this reduces the growth gains from FDI. The authors provide new empirical evidence on the importance of export production structure on the FDI–growth nexus.
Signature reliability scrutiny of domestic refrigerator
Authors: Naaz Sadiya , Ram Mangey , Kumar Akshay
Published: March 2023

Purpose

The purpose of this paper is to evaluate the reliability and structure function of refrigeration complex system consisted of four components in complex manner.

Design/methodology/approach

Although, a variety of methodologies have been used to assess the refrigeration system's reliability function that has proven to be effective, the universal generating function approach is the basis of this research study, which is used in the calculation of a domestic refrigeration system with four separate components that are related in series and parallel with a corresponding sample to form a complex machine.

Findings

In this paper, signature reliability of the refrigeration system has been evaluated with the universal generating function technique. There are four components present in the proposed system in complex (series and parallel) manner. The tail signature, signature, Barlow–Proschan index, expected lifetime and expected cost of independent identically distributed are all computed.

Originality/value

This is the first study of domestic refrigeration system to examine the signature reliability with the help of universal generating function techniques with various measures. Refrigeration systems are an essential process in industries and home applications as they perform cooling or the maintain temperature at the desired value. A cycle of refrigeration consists of four main components such as, heat exchange, compression and expansion with a refrigerant flowing through the units within the cycle.
Experimental and numerical study of the settlement behavior of soil reinforced by stone columns
Authors: Hadri Soumaya , Rehab Bekkouche Souhila , Messast Salah
Published: March 2023

Purpose

The paper aims to present an experimental and numerical investigation of the load–settlement behavior of soil reinforced by stone column, as well as to evaluate the plane strain unit cell model for the analysis of stone columns.

Design/methodology/approach

The numerical analysis was done using both axisymmetric and plane strain models. The elastic perfectly plastic behavior of Mohr–Coulomb was adopted for both soil and column material. The numerical results of this study were validated by the comparison with the in-situ measurements of a full-scale loading test on a stone column. This study also evaluated the effect of different parameters involved in the design of a stone column, including Young’s modulus of the column material, column diameter, spacing between the stone columns and Poisson’s ratio of the column material.

Findings

After the numerical simulation, the results from both axisymmetric and plane strain models are quite comparable. In addition, the numerical results revealed that the stone column with low spacing, a large diameter and a high Young’s modulus indicated better behavior against the settlement.

Originality/value

The axisymmetric unit cell model was used in many numerical studies on the behavior of stone columns. In the present work, a field load test on stone column was simulated using a plane strain unit cell model. This research adds that the plane strain unit cell model can be used to predict the settlement of reinforced soil with stone columns.
Psychosocial interventions aimed at family members caring for patients with cancer in the palliative period: A systematic review
Authors: Yıldız Manolya , Terzioğlu Candan , Ayhan Fatma
Published: March 2023

Aim

The purpose of this systematic review is to examine evidence‐based psychosocial intervention research aimed at family members caring for patients with cancer in the palliative period.

Method

In this systematic review, randomized controlled psychosocial intervention studies for the family member caring for patients with cancer published between January 1, 2016 and July 30, 2021 were reviewed. PubMed (including MEDLINE), Cochrane, APA PsycNet, ProQuest, Science Direct, TR Index, and Wiley Online Library databases were scanned. Eight publications were identified following a database review for English language articles published from 2016 to 2021. Sample, methods, content, and outcomes of included interventions are summarized.

Results

Only eight of the 4652 articles examined met the inclusion criteria. Psychosocial interventions such as mindfulness exercises, stress management, acceptance and commitment therapy, cognitive behavioral intervention, and meaning‐centered psychotherapy for cancer caregivers were applied for relatives caring for patients with cancer in the palliative period.

Conclusion

Psychosocial interventions applied to family members caring for patients with cancer during the palliative period lead to improvements in depressive symptoms, stress levels, the caregiver burden, quality of life, self‐efficacy, coping skills, and awareness levels.
S1‐guideline cutaneous and subcutaneous leiomyosarcoma
Authors: Helbig Doris , Dippel Edgar , Erdmann Michael , Frisman Alexander , Kage Paula , Leiter Ulrike , Mentzel Thomas , Seidel Clemens , Weishaupt Carsten , Ziemer Mirjana , Ugurel Selma
Published: March 2023

Superficial leiomyosarcomas (LMS) are rare skin cancers (2–3% of cutaneous sarcomas) that originate from dermally located hair follicle muscles, dartos or areolar muscles (cutaneous/dermal LMS), or from vascular muscle cells of the subcutaneous adipose tissue (subcutaneous LMS). These superficial LMS are distinct from LMS of the deep soft tissues. Leiomyosarcomas are typically localized at the lower extremities, trunk or capillitium, and present as painful, erythematous to brownish nodules. Diagnosis is made by histopathology. The treatment of choice for primary LMS is complete (R0) microscopically controlled excision, with safety margins of 1 cm in dermal LMS, and 2 cm in subcutaneous LMS, if possible. Non‐resectable or metastatic LMS require individual treatment decisions. After R0 resection with 1 cm safety margins, the local recurrence rate of dermal LMS is very low, and metastasis is very rare. Subcutaneous LMS, very large, or incompletely excised LMS recur and metastasize more frequently. For this reason, clinical follow‐up examinations are recommended every six months for cutaneous LMS, and every three months for subcutaneous LMS within the first two years (in subcutaneous LMS including locoregional lymph node sonography). Imaging such as CT/MRI is indicated only in primary tumors with special features, recurrences, or already metastasized tumors.
Real‐time continuous glucose monitoring immediately after severe hypoglycaemia requiring emergency medical services: A randomised controlled trial
Authors: Uduku Chukwuma , Pendolino Valentina , Jugnee Narvada , Oliver Nick , Fothergill Rachael , Reddy Monika
Published: March 2023

Aims

Severe hypoglycaemia requiring emergency medical services remains prevalent despite advances in all aspects of diabetes self‐management. Real‐time continuous glucose monitoring (RTCGM) technologies can reduce the risk of severe hypoglycaemia for adults with type 1 diabetes, but the impact of these devices has not been assessed in the acute phase after an episode of severe hypoglycaemia.

Methods

We recruited and randomised 35 adults with type 1 diabetes in the acute period after an episode of severe hypoglycaemia requiring emergency medical services and randomised participants to RTCGM with alerts and alarms, or usual care with self‐monitored blood glucose for 12 weeks with intermittent blinded CGM. The primary outcome was the difference between groups in percentage time spent in hypoglycaemia (≤3.0 mmol/L, 55 mg/dL).

Results

Thirty participants completed the study (median (IQR) age, duration of diabetes, and BMI was 43 (36–56) years, 26 (19–37) years, and 24.9 (21.9–29.0) kg/m2, respectively). Sufficient CGM data was available for 15 participants in RT‐CGM group and 8 in SMBG group for the primary outcome analysis. The RTCGM group had a significantly larger reduction in exposure to glucose below 3.0 mmol/L (RTCGM −0.16 [−1.23 to 0.01] vs. SMBG 1.58 [0.41 to 3.48], p = 0.03) and episodes of nocturnal hypoglycaemia (RT‐CGM −0.03 [−0.15 to 0.02] vs. SMBG 0.05 [−0.03 to 0.40], p = 0.02). Episodes of severe hypoglycaemia were significantly lower in the RTCGM group (RTCGM 0.0 vs. SMBG 4.0, p 0.04).

Conclusions

RTCGM implemented acutely after an episode of severe hypoglycaemia is feasible and clinically effective with important implications for hypoglycaemia management pathways and self‐monitoring cost effectiveness.
The association of gait speed and self‐reported difficulty walking with social isolation: A nationally‐representative study
Authors: Kuang Kathy , Huisingh‐Scheetz Megan , Miller Matthew J. , Waite Linda , Kotwal Ashwin A.
Published: March 2023

Background

Mobility assessments are commonly used among older adults as risk stratification for falls, preoperative function, frailty, and mortality. We determined if gait speed and self‐reported difficulty walking are similarly associated with social isolation and loneliness, which are key markers of social well‐being and linked to health outcomes.

Methods

We used 2015–2016 data from the National Social life Health and Aging Project (NSHAP), an in‐person nationally‐representative survey of 2640 community‐dwelling adults ≥65 years old. We measured gait speed (timed 3‐m walk: unable to walk, ≥5.7 s, and <5.7 s), and self‐reported difficulty walking one block or across the room (unable, “much,” “some,” or “no” difficulty). Social measures included loneliness (3‐item UCLA scale), social isolation (12‐item scale), and individual social activities (frequency socializing, religious participation, community participation, and volunteering). We used logistic regression to determine the adjusted probability of each social measure by gait speed and difficulty walking, adjusting for sociodemographic and health characteristics, and tested for interaction terms with age.

Results

Participants were on average 75 years old (SD = 7.1), 54% female, 9% Black/African American, and 6% Hispanic. Difficulty walking one block was associated with (p < 0.05): social isolation (much difficulty: 26% vs no difficulty: 18%), low socializing (33% vs 19%), low volunteering (67% vs 53%), low community participation (54% vs 43%), low religious participation (51% vs 46%), and loneliness (25% vs 14%). Difficulty walking across the room was similarly strongly associated with social isolation and individual activities. The association between self‐reported difficulty walking and social isolation was stronger at older ages (p‐value of interaction <0.001).

Conclusions

Self‐reported mobility difficulty is a widely used clinical assessment that is strongly associated with loneliness and social isolation, particularly at older ages. Among persons with limited mobility, clinicians should consider a careful social history to identify social needs and interventions addressing mobility to enhance social connections.
Oxybutynin gel versus nanoemulgel for treating primary palmar hyperhidrosis: A pilot double‐blind randomized controlled trial
Authors: Saki Nasrin , Shakouri Negin , Rastaghi Fatemeh , Hosseini Seyed Ali , Alipour Shohreh , Ahramiyanpour Najmeh
Published: March 2023

Introduction

Palmar hyperhidrosis or excessive palmar sweating can reduce one's quality of life as it is associated with significant physical and occupational disabilities. We compared the gel and nanoemulgel of oxybutynin in treating these patients.

Materials and Methods

This pilot study was performed as a double‐blind controlled randomized clinical trial at Shahid Faghihi Hospital, Shiraz, Iran. In two randomly allocated groups of 15, patients diagnosed with primary palmar hyperhidrosis by an attending dermatologist applied half a fingertip (roughly 0.25 g) of 1% oxybutynin topical gel or 1% oxybutynin nanoemulgel to both palms every 12 h for one month. The Hyperhidrosis Disease Severity Scale (HDSS), Visual Analog Scale (VAS), and Dermatology Life Quality Index (DLQI) were used to assess the patients at the beginning and end of the study. Statistical analysis was performed using SPSS version 25.

Results

The groups were similar in terms of age (p = 0.800), sex (p = 0.096), and baseline HDSS, VAS, and DLQI scores. The mean HDSS scores decreased significantly (p = 0.001) over time in patients receiving the gel (3.00 ± 1.00 vs. 2.33 ± 0.61) or nanoemulgel (2.92 ± 0.82 vs. 2.14 ± 0.53), without a significant difference between the groups. The same was true for the VAS and DLQI scores. Three patients in each group experienced transient, self‐limited anticholinergic side effects (p = 0.983).

Conclusion

Oxybutynin gel and nanoemulgel offer equal safety and similar efficacy in reducing the disease severity and increasing the quality of life of patients with palmar hyperhidrosis.
Uncovering genetic causes of hypophosphatemia
Authors: Puente‐Ruiz Nuria , Docio Pablo , Unzueta María T. García , Lavín Bernardo A. , Maiztegi Ainhoa , Vega Ana Isabel , Piedra María , Riancho‐Zarrabeitia Leyre , Mateos Fátima , Gonzalez‐Lamuño Domingo , Valero Carmen , Riancho José A.
Published: March 2023

Background

Chronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population.

Methods

By combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17–55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR).

Results

We identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X‐linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities.

Conclusion

Genetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype.
Association between device‐measured stepping behaviors and cardiometabolic health markers in middle‐aged women: The Australian Longitudinal Study on Women's Health
Authors: Wei Le , Ahmadi Matthew N. , Chan Hsiu‐Wen , Chastin Sebastien , Hamer Mark , Mishra Gita D. , Stamatakis Emmanuel
Published: March 2023

The associations between different types and contexts of stepping behaviors and cardiometabolic (CM) health markers are unclear. This study aimed to examine the associations of daily total, walking, stair, incidental and purposeful steps with cardiometabolic risk. A total of 943 women (mean age ± SD = 44.1 ± 1.6 years) from the Australian Longitudinal Study on Women's Health (ALSWH) were included in this cross‐sectional study. Daily total, walking, stair, incidental, and purposeful steps were measured using thigh‐worn accelerometry. Outcomes comprised of CM markers of adiposity, blood pressure, resting heart rate, lipids, glycaemia, and the composite CM score. We used generalized linear modeling and multiple linear regression to assess the associations. We observed that all stepping behaviors were beneficial to CM health, for example, compared to the lowest quartile (Q1), the change of the composite CM score across low to high quartile of purposeful steps was −0.12 (Q2, 95% CI: −0.41, 0.17), −0.16 (Q3, −0.46, 0.14), and −0.36 (Q4, −0.66, −0.05). Stair steps showed linear associations with blood pressure and adiposity biomarkers, for example, the change of quartile of waist circumference was −1.45 cm (Q2, −4.35, 1.44), −3.56 cm (Q3, −6.52, −0.60), and −7.08 cm (Q4, −10.31, −3.86). Peak 30‐min walking intensity showed independent association with adiposity biomarkers (p linear < 0.001 and p = 0.002 for waist circumference and BMI, respectively). Our study showed that all stepping forms were beneficial to CM health. Higher stair steps and peak 30‐min walking cadence were associated with a steep decline of adiposity biomarkers. Purposeful steps showed more consistent associations with CM biomarkers than incidental steps.
The causal nexus between innovation and economic growth: An OECD study
Authors: Dhar Bablu Kumar , Shaturaev Jakhongir , Kurbonov Khayrilla , Nazirjon Rajabov
Published: March 2023

Objective

Innovation contributes to economic growth by generating new ideas and improving production processes. At the same time, countries with high economic growth have the freedom to promote innovation. This article aims to examine the causal relationship between innovation and economic growth.

Method

An innovation index was constructed using factors of innovation, utilizing principal component analysis. The study used Granger causality to investigate the causal relationship between innovation and economic growth. The sample comprised 34 OECD countries during the period 1961–2018.

Results

The results showed that the United States had the highest innovation index, while Luxembourg had the highest economic growth. The study found both unidirectional and bidirectional causal relationships between innovation and economic growth.

Conclusions

The study highlights the importance of innovation in driving economic growth and provides insights into the complex and dynamic relationship between these two variables. The findings could be useful for policymakers in designing effective strategies to promote innovation and foster economic growth in their respective countries.
GBIF falls short of providing a representative picture of the global distribution of insects
Authors: Garcia‐Rosello Emilio , Gonzalez‐Dacosta Jacinto , Guisande Cástor , Lobo Jorge M.
Published: March 2023

The Global Biodiversity Information Facility (GBIF) is the largest databank on primary biodiversity data. We examined the completeness and geographical biases for all insect data on GBIF to determine its representativeness. Our results demonstrate that GBIF is far from providing a reliable representation about the global distribution of insects. Despite the growing number of records during the last years, few spatial units are well‐surveyed. At coarse resolutions, 34% of the world terrestrial cells lack data and barely 0.5% have completeness values above 90%. Insects are crucial in many ecological functions, and their alarming decline makes it more pressing to have a representative sample to improve our predictive capacity. However, the dynamic nature of species distributions and the strength of anthropogenic forces call for immediate conservation decisions that cannot wait for the empirical data on the identity and distribution of insects.
PI(4,5)P
2
-dependent regulation of endothelial tip cell specification contributes to angiogenesis
Authors: Davies Elizabeth M. , Gurung Rajendra , Le Kai Qin , Roan Katherine T. T. , Harvey Richard P. , Mitchell Geraldine M. , Schwarz Quenten , Mitchell Christina A.
Published: March 2023

Dynamic positioning of endothelial tip and stalk cells, via the interplay between VEGFR2 and NOTCH signaling, is essential for angiogenesis. VEGFR2 activates PI3K, which phosphorylates PI(4,5)P
2
to PI(3,4,5)P
3
, activating AKT; however, PI3K/AKT does not direct tip cell specification. We report that PI(4,5)P
2
hydrolysis by the phosphoinositide-5-phosphatase, INPP5K, contributes to angiogenesis. INPP5K ablation disrupted tip cell specification and impaired embryonic angiogenesis associated with enhanced DLL4/NOTCH signaling. INPP5K degraded a pool of PI(4,5)P
2
generated by PIP5K1C phosphorylation of PI(4)P in endothelial cells. INPP5K ablation increased PI(4,5)P
2
, thereby releasing β-catenin from the plasma membrane, and concurrently increased PI(3,4,5)P
3
-dependent AKT activation, conditions that licensed
DLL4
/
NOTCH
transcription. Suppression of PI(4,5)P
2
in
INPP5K
-siRNA cells by
PIP5K1C
-siRNA, restored β-catenin membrane localization and normalized AKT signaling. Pharmacological NOTCH or AKT inhibition in vivo or genetic β-catenin attenuation rescued angiogenesis defects in INPP5K-null mice. Therefore, PI(4,5)P
2
is critical for β-catenin/DLL4/NOTCH signaling, which governs tip cell specification during angiogenesis.
Theropod dinosaur facial reconstruction and the importance of soft tissues in paleobiology
Authors: Cullen Thomas M. , Larson Derek W. , Witton Mark P. , Scott Diane , Maho Tea , Brink Kirstin S. , Evans David C. , Reisz Robert
Published: March 2023

Large theropod dinosaurs are often reconstructed with their marginal dentition exposed because of the enormous size of their teeth and their phylogenetic association to crocodylians. We tested this hypothesis using a multiproxy approach. Regressions of skull length and tooth size for a range of theropods and extant varanid lizards confirm that complete coverage of theropod dinosaur teeth with extraoral tissues (gingiva and labial scales) is both plausible and consistent with patterns observed in living ziphodont amniotes. Analyses of dental histology from crocodylians and theropod dinosaurs, including
Tyrannosaurus rex
, further indicate that the most likely condition was complete coverage of the marginal dentition with extraoral tissue when the mouth was closed. This changes our perceptions about the appearance and oral configuration of these iconic predators and has broad implications for our interpretations of other terrestrial animals with large teeth.
Fix the backlash against public health
Authors: Gostin Lawrence O. , Wetter Sarah
Published: March 2023

Societies generally have reacted to deadly epidemics by strengthening health systems, including laws. Under American federalism (the constitutional division of power between states and the federal government), individual states hold primary public health powers. State legislatures have historically granted health officials wide-ranging authority. After the anthrax attacks in the United States in 2001, the US Centers for Disease Control and Prevention (CDC) supported the Model State Emergency Health Powers Act, which granted public health officials even more expansive powers to declare a health emergency and respond swiftly. But all that ended with COVID-19, as state legislatures and courts gutted this authority. The next pandemic could be far deadlier than COVID-19, but when the public looks to federal and state governments to protect them, they may find that health officials have their hands tied behind their backs.
Ghost Fiber Optic 3D Endoscopy
Authors: Belinsky A. V. , Gostev P. P. , Magnitskiy S. A. , Chirkin A. S.
Published: March 2023

A new type of ghost fiber optic endoscopy has been proposed to obtain ghost images of three-dimensional optically transparent objects. The method is based on spatial and temporal correlation of light beams formed in a bundle of single-mode fibers exposed in the transverse direction to femtosecond laser pulses. Resolution in the depth of an object is ensured by an original algorithm to reconstruct images, which involves both the properties of femtosecond radiation and the features of light propagation in an inhomogeneous scattering medium. The effectiveness of the proposed method has been confirmed by a numerical simulation by an example of an octahedron with a layered structure.