bluuebunny/crossref_metadata_2025 huggingface dataset:
Can firm R&D benefit from digital technologies? Evidence from Chinese high-speed rail industry
Authors: Jiang Zihao , Shi Jiarong
Published: July 2023

Purpose

As an emerging socio-technical paradigm, high-speed railways profoundly change individuals' lifestyle and allow for the shift toward a green transportation. Digital technologies open an opportunity window for the development of enterprises. This study aims to clarify the impact of firm digitalization on the innovation efficiency of the Chinese high-speed rail industry. In addition, human capital is the important non-physical capital of enterprises. The authors also elucidate the moderating role of human capital on the above relationship.

Design/methodology/approach

Based on the data of Chinese high-speed railway listed companies from 2015 to 2021, this study explores the impact of digital transformation on the innovation efficiency, and further clarifies the boundary role of human capital with two-way fixed effect regression models.

Findings

The empirical results indicate that digital transformation has a positive impact on the innovation efficiency of the Chinese high-speed railway enterprises. Furthermore, human capital significantly enhances the above relationship. In addition, digital transformation fosters the innovation efficiency of small- and medium-sized enterprises and private-owned enterprises, but the correlation coefficients between digital transformation and the innovation efficiency of large enterprises and state-owned enterprises are not significant.

Originality/value

This is one of the earliest studies to explore how digital technologies shape R&D activities. From the perspective of relative efficiency, this study evaluates the effectiveness of digital transformation and provides empirical evidence for the formulation and implementation of corporate digital strategies. Moreover, this study links human capital with digital transformation and identifies condition factors that affect the effectiveness of digital transformation, thereby supplementing existing knowledge.
Examining theories, mediators and moderators in financial well-being literature: a systematic review and future research agenda
Authors: Bashir Ifra , Qureshi Ishtiaq Hussain
Published: July 2023

Purpose

The United Nation's 2030 mission provides scholars, practitioners and governments with a valuable framework to direct their research in a way that tackles societal issues. Towards this aim, some key Sustainable Development Goals focus on improving the well-being of humans and societies; however, the literature dealing with individual financial well-being is still underdeveloped and fragmented. To address this significant research gap, this paper reviews the literature on financial well-being. It provides an in-depth analysis of different theories, mediators and moderators employed in financial well-being studies to deepen the theoretical framework and widen the scope of financial well-being research.

Design/methodology/approach

Using the Web of Science Core Collection database (WoS), the literature on financial well-being was reviewed (n = 32) following a systematic review approach.

Findings

Findings revealed that (a) there is a limited application of theories in financial well-being studies (n = 19) with the majority of studies (n = 15) employing only one theory; (b) twenty-one different theories were used with the maximum number of theories employed by any study was four; (c) the theory of planned behavior was the most commonly used (n = 4); (d) While a reasonable number of studies examine mediators and moderators in antecedents-financial well-being relationships, studies examining mediators and moderators relationships in financial well-being-outcomes relationships are limited. Based on these findings, this review identified a need for future theory-based financial well-being research and examining the role of underlying and intervening mechanisms in antecedents-financial well-being-outcomes relationships.

Originality/value

The study concludes by suggesting some relevant theories and prospective variables that can explain potential financial well-being relationships. To the best of the author's knowledge, this is the first review on the use of theories, mediators and moderators in financial well-being studies.
The Financially Material Effects of Mandatory Nonfinancial Disclosure
Authors: GIBBONS BRIAN
Published: July 2023

Complaints from institutional investors suggest that principles‐based disclosure regimes that rely on financial materiality standards produce inadequate nonfinancial environmental and social (E&S) information. Using the staggered introduction of 40 country‐level regulations that mandate disclosure, I document that reporting E&S information relates to increased investment from institutional owners and has material effects on firms’ investment and financing decisions. Firms mandated to disclose E&S information allocate more investment toward long‐term, innovative projects and raise more equity capital. Evidence indicates that disclosure attracts long‐term–oriented institutional clientele with E&S preferences, which then feeds back on firm decision making. Although the effects of nonfinancial disclosure are similar to those of improved financial disclosure, this clientele mechanism is unique. Taken together, these results suggest that jurisdictions that rely solely on financial materiality disclosure standards create nonfinancial information frictions with material effects on investors and firm decision making.
The effect of violent conflict on calorie consumption and dietary quality in Iraq
Authors: Parigi Marta
Published: July 2023

By combining 2012 Living Standard Measurement Survey cross‐sectional survey responses and georeferenced conflict data, this study quantifies the effect of violent conflict on food security and dietary quality in Iraq. Specifically, it estimates the effect of physical insecurity on different food security dimensions, including caloric consumption and household dietary diversity. Because disrespecting war‐related foreign national cemeteries is a war crime that discourages nearby fighting, instrumenting conflict intensity by the exogenous variation in distance between these sites and household place of residence addresses potential sources of bias. The instrumental variable analysis confirms the positive (negative) effect of conflict—deriving from state, non‐state and one‐sided violence (e.g., attacks by the Islamic State)—on per capita caloric consumption (household dietary diversity), which although counterintuitive is unsurprising given Iraq's relatively high‐income levels and changes in dietary pattern. Given that the primary driver of conflict's positive effect on calories is increased consumption of carbohydrates and, to a lesser extent, saturated fat, these results suggest that in countries transitioning to Western‐style diets, violent conflict may drive the population toward an unhealthier diet, contributing heavily to a growing national prevalence of nutrition‐related non‐communicable diseases.
Effect of short neuropeptide F signaling on larval feeding in Mythimna separata
Authors: Li Mei‐Mei , Yang Qi , Chen Li‐Hui , Li Yan‐Ying , Wu Jun‐Xiang , Xu Xiang‐Li
Published: July 2023

Mythimna separata is a notorious phytophagous pest which poses serious threats to cereal crops owing to the gluttony of the larvae. Because short neuropeptide F (sNPF) and its receptor sNPFR are involved in a diversity of physiological functions, especially in functions related to feeding in insects, it is a molecular target for pest control. Herein, an sNPF and 2 sNPFRs were identified and cloned from M. separata. Bioinformatics analysis revealed that the sNPF and its receptors had a highly conserved RLRFamide C‐terminus and 7 transmembrane domains, respectively. The sNPF and its receptor genes were distributed across larval periods and tissues, but 2 receptors had distinct expression patterns. The starvation‐induced assay elucidated that sNPF and sNPFR expression levels were downregulated under food deprivation and recovered with subsequent re‐feeding. RNA interference knockdown of sNPF, sNPFR1, and sNPFR2 by injection of double‐stranded RNA into larvae not only suppressed food consumption and increased body size and weight, but also led to decrease of glycogen and total lipid contents, and increase of trehalose compared with double‐stranded green fluorescent protein injection. Furthermore, molecular docking was performed on the interaction mode between sNPFR protein and its ligand sNPF based on the 3‐dimensional models constructed by AlphaFold; the results indicated that both receptors were presumably activated by the mature peptide sNPF‐2. These results revealed that sNPF signaling played a considerably vital role in the feeding regulation of M. separata and represents a potential control target for this pest.
Learning curve of lung dose optimization in intensity‐modulated radiotherapy for locally advanced non‐small cell lung cancer
Authors: Igari Mitsunobu , Abe Takanori , Iino Misaki , Saito Satoshi , Aoshika Tomomi , Ryuno Yasuhiro , Ohta Tomohiro , Hirai Ryuta , Kumazaki Yu , Noda Shin‐ei , Kato Shingo
Published: July 2023

Background

Intensity‐modulated radiotherapy (IMRT) has been increasingly used for patients with locally advanced non‐small cell lung cancer (LA‐NSCLC). However, there are some barriers to implementing IMRT for LA‐NSCLC, including the complexity of treatment plan optimization. This study aimed to evaluate the learning curve of lung dose optimization in IMRT for LA‐NSCLC and identify the factors that affect the degree of achievement of lung dose optimization.

Methods

We retrospectively evaluated 40 consecutive patients with LA‐NSCLC who received concurrent chemoradiotherapy at our institution. These 40 patients were divided into two groups: 20 initially treated patients (earlier group) and 20 subsequently treated patients (later group). Patient and tumor characteristics were compared between the two groups. The dose‐volume parameter ratio between the actually delivered IMRT plan and the simulated three‐dimensional conformal radiotherapy plan was also compared between the two groups to determine the learning curve of lung dose optimization.

Results

The dose‐volume parameter ratio for lung volume to receive more than 5 Gy (lung V5) and mean lung dose (MLD) significantly decreased in later groups. The spread of the beam path and insufficient optimization of dose coverage of planning target volume (PTV) might cause poor control of lung V5, MLD.

Conclusions

A learning curve for lung dose optimization was observed with the accumulation of experience. Appropriate techniques, such as restricting the beam path and ensuring dose coverage of PTV during the optimization process, are essential to control lung dose in IMRT for LA‐NSCLC.
Decomposing the effect of trade on the gender wage gap
Authors: Benguria Felipe , Ederington Josh
Published: July 2023

This paper uses variation in exposure to increased Chinese imports in Brazil to investigate the impact of trade on gender wage inequality. First, using Brazilian census data, we find that rising imports reduced the gender wage gap in Brazilian local labour markets. Next, using Oaxaca–Blinder decompositions, we show that this reduction in the wage gap was largely explained by trade increasing the share of female workers in higher‐paying occupations. Finally, we use a matched employer–employee data set to investigate how individual workers adjust to the trade shock. Similar to the local labour market analysis, we find that male workers exposed to increased import competition saw a larger decline in both wages and cumulative earnings relative to female workers. In addition, we uncover an interesting asymmetry in that, while male workers exhibited much higher degrees of industry mobility in response to the trade shock, female workers exhibited an equal if not higher degree of occupational mobility.
Totality of evidence of the effectiveness of repurposed therapies for COVID‐19: Can we use real‐world studies alongside randomized controlled trials?
Authors: Mandema Jaap , Montgomery Hugh , Dron Louis , Fu Shuai , Russek‐Cohen Estelle , Bromley Christina , Mouksassi Samer , Lalonde Amy , Springford Aaron , Tsai Larry , Ambery Phil , McNair Doug , Qizilbash Nawab , Pocock Stuart , Zariffa Névine
Published: July 2023

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational “real‐world studies” (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID‐19) pandemic. Comparing results between them offers a unique opportunity to determine the potential value and contribution of each. A learning review of these parallel evidence channels in COVID‐19, based on quantitative modeling, can help improve speed and reliability in the evaluation of repurposed therapeutics in a future pandemic. Analysis of all‐cause mortality data from 249 observational RWS and RCTs across eight treatment regimens for COVID‐19 showed that RWS yield more heterogeneous results, and generally overestimate the effect size subsequently seen in RCTs. This is explained in part by a few study factors: the presence of RWS that are imbalanced for age, gender, and disease severity, and those reporting mortality at 2 weeks or less. Smaller studies of either type contributed negligibly. Analysis of evidence generated sequentially during the pandemic indicated that larger RCTs drive our ability to make conclusive decisions regarding clinical benefit of each treatment, with limited inference drawn from RWS. These results suggest that when evaluating therapies in future pandemics, (1) large RCTs, especially platform studies, be deployed early; (2) any RWS should be large and should have adequate matching of known confounders and long follow‐up; (3) reporting standards and data standards for primary endpoints, explanatory factors, and key subgroups should be improved; in addition, (4) appropriate incentives should be in place to enable access to patient‐level data; and (5) an overall aggregate view of all available results should be available at any given time.
Low‐density lipoprotein cholesterol in adolescents and young adults with type 1 diabetes: Data from the Australasian Diabetes Data Network registry
Authors: James S. , Donaghue K. C. , Perry L. , Lowe J. , Colman P. G. , Craig M. E. ,   the Australasian Diabetes Data Network (ADDN) Study Group
Published: July 2023

Aim

To determine low‐density lipoprotein cholesterol (LDL‐C) screening frequency and levels, and factors associated with elevated LDL‐C, in Australasian youth with type 1 diabetes (T1D).

Methods

Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16–25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL‐C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL‐C across all visits.

Results

A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL‐C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL‐C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL‐C continuously was associated with older age (OR = 0.07; 0.01–0.13, p = 0.02), female sex (OR = 0.31; 0.18–0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01–0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06–0.39, p < 0.001).

Conclusions

LDL‐C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population.
Are brief febrile seizures benign? A systematic review and narrative synthesis
Authors: Gould Laura , Delavale Victoria , Plovnick Caitlin , Wisniewski Thomas , Devinsky Orrin
Published: July 2023

Febrile seizures affect 2%–5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained death. We compared rates of mortality, neurodevelopmental disorders, and neuropathology in young children with simple and complex febrile seizures to healthy controls. We systematically reviewed studies of 3‐ to 72‐month‐old children with simple or complex febrile seizures ≤30 min. We searched studies with outcome measures on mortality, neurodevelopment, or neuropathology through July 18, 2022. Bias risk was assessed per study design. Each outcome measure was stratified by study design. PROSPERO registration is CRD42022361645. Twenty‐six studies met criteria reporting mortality (11), neurodevelopment (11), and neuropathology (13), including 2665 children with febrile seizures and 1206 seizure‐free controls. Study designs varied: 15 cohort, 2 cross‐sectional, 3 case–control, 5 series, and 1 case report. Mortality outcomes showed stark contrasts. Six cohort studies following children after febrile seizure (n = 1348) reported no deaths, whereas four child death series and 1 case report identified 24.1% (108/449) deaths associated with simple (n = 104) and complex (n = 3) febrile seizures ≤30 min. Minor hippocampal histopathological anomalies were common in sudden deaths with or without febrile seizure history. Most electroencephalography (EEG) studies were normal. Neuroimaging studies suggested increased right hippocampal volumes. When present, neurodevelopmental problems usually preexisted febrile‐seizure onset. Risk bias was medium or high in 95% (18/19) of cohort and case–control studies vs medium to low across remaining study designs. Research on outcomes after simple or brief complex febrile seizures is limited. Cohort studies suffered from inadequate sample size, bias risk, and limited follow‐up durations to make valid conclusions on mortality, neurodevelopment, and neuropathology. Sudden death registries, focused on a very small percentage of all cases, strongly suggest that simple febrile seizures are associated with increased mortality. Although most children with febrile seizures have favorable outcomes, longer‐term prospective studies are needed.
Exploring the landscape of synthetic IL‐6‐type cytokines
Authors: Scheller Jürgen , Ettich Julia , Wittich Christoph , Pudewell Silke , Floss Doreen M. , Rafii Puyan
Published: July 2023

Interleukin‐6 (IL‐6)‐type cytokines not only have key immunomodulatory functions that affect the pathogenesis of diseases such as autoimmune diseases, chronic inflammatory conditions, and cancer, but also fulfill important homeostatic tasks. Even though the pro‐inflammatory arm has hindered the development of therapeutics based on natural‐like IL‐6‐type cytokines to date, current synthetic trends might pave the way to overcome these limitations and eventually lead to immune‐inert designer cytokines to aid type 2 diabetes and brain injuries. Those synthetic biology approaches include mutations, fusion proteins, and inter‐cytokine swapping, and resulted in IL‐6‐type cytokines with altered receptor affinities, extended target cell profiles, and targeting of non‐natural cytokine receptor complexes. Here, we survey synthetic cytokine developments within the IL‐6‐type cytokine family and discuss potential clinical applications.
Social cynicism, greenwashing, and trust in green clothing brands
Authors: Policarpo Manoela Costa , Apaolaza Vanessa , Hartmann Patrick , Paredes Mario R. , D'Souza Clare
Published: July 2023

This research develops a theoretical model of the effect of social cynicism as a personality trait on trust in green clothing brands. We conducted an online survey of a representative Australian sample to test the hypothesized relationships. Our findings confirmed that social cynicism affected green brand trust negatively and that this effect can be explained by an increase in perceived greenwashing. Conspicuous consumption moderates this indirect influence. This mediated influence decreased when conspicuous consumption was more salient. Findings provide important practical insights for brand managers intending to avoid a decrease in brand trust regarding garments marketed with sustainability claims.
Who benefits from computerized learning progress assessment in reading education? Evidence from a two‐cohort pre–post design
Authors: Schmitterer A. M. Alexandra , Tetzlaff Leonard. D. , Hasselhorn Marcus , Brod Garvin
Published: July 2023

Background

Learning Progress Assessments (LPA) have been developed to help teachers individualize their curriculum. The use of LPA is facilitated by an increasing number of computerized LPA tools. However, little is known about student factors that influence the effectiveness of computerized LPA.

Objectives

In this study, we explored whether a computerized LPA that focused on reading comprehension was differentially effective depending on students' initial reading comprehension abilities. Moreover, effects of the LPA implementation on underlying or related form‐based literacy skills (i.e., decoding, spelling) were explored.

Methods

The development of reading and spelling skills of 668 third graders was assessed in 41 LPA and 36 control classes in a pretest–posttest design. We used multi‐level modelling to analyse effects of the LPA on reading comprehension, decoding, and spelling skills, and tested whether these effects were qualified by students' initial achievement level.

Results

The LPA treatment proved beneficial for improving reading comprehension but not for improving decoding or spelling. Children with low levels of reading comprehension at the beginning of the school year benefitted particularly from LPA.

Takeaways

Teachers seem to make use of the data offered by the computerized LPA to identify children with reading comprehension difficulties. For these children, an accelerated increase in reading comprehension ability was observed. Results also suggest that this effect is specific to the literacy skill measured by the LPA and does not generalize to underlying or related literacy skills (i.e., decoding, spelling).
A risk‐scoring model for the differential diagnosis of lentigo maligna and other atypical pigmented facial lesions of the face: The facial iDScore
Authors: Tognetti Linda , Cartocci Alessandra , Żychowska Magdalena , Savarese Imma , Cinotti Elisa , Pizzichetta Maria Antonietta , Moscarella Elvira , Longo Caterina , Farnetani Francesca , Guida Stefania , Paoli John , Lallas Aimilios , Tiodorovic Danica , Stanganelli Ignazio , Magi Serena , Dika Emi , Zalaudek Iris , Suppa Mariano , Argenziano Giuseppe , Pellacani Giovanni , Perrot Jean Luc , Miracapillo Chiara , Rubegni Giovanni , Cevenini Gabriele , Rubegni Pietro
Published: July 2023

Background

Due to progressive ageing of the population, the incidence of facial lentigo maligna (LM) of the face is increasing. Many benign simulators of LM and LMM, known as atypical pigmented facial lesions (aPFLs—pigmented actinic keratosis, solar lentigo, seborrheic keratosis, seborrheic‐lichenoid keratosis, atypical nevus) may be found on photodamaged skin. This generates many diagnostic issues and increases the number of biopsies, with a subsequent impact on aesthetic outcome and health insurance costs.

Objectives

Our aim was to develop a risk‐scoring classifier‐based algorithm to estimate the probability of an aPFL being malignant. A second aim was to compare its diagnostic accuracy with that of dermoscopists so as to define the advantages of using the model in patient management.

Materials and Methods

A total of 154 dermatologists analysed 1111 aPFLs and their management in a teledermatology setting: They performed pattern analysis, gave an intuitive clinical diagnosis and proposed lesion management options (follow‐up/reflectance confocal microscopy/biopsy). Each case was composed of a dermoscopic and/or clinical picture plus metadata (histology, age, sex, location, diameter). The risk‐scoring classifier was developed and tested on this dataset and then validated on 86 additional aPFLs.

Results

The facial Integrated Dermoscopic Score (iDScore) model consisted of seven dermoscopic variables and three objective parameters (diameter ≥ 8 mm, age ≥ 70 years, male sex); the score ranged from 0 to 16. In the testing set, the facial iDScore‐aided diagnosis was more accurate (AUC = 0.79 [IC 95% 0.757–0.843]) than the intuitive diagnosis proposed by dermatologists (average of 43.5%). In the management study, the score model reduced the number of benign lesions sent for biopsies by 41.5% and increased the number of LM/LMM cases sent for reflectance confocal microscopy or biopsy instead of follow‐up by 66%.

Conclusions

The facial iDScore can be proposed as a feasible tool for managing patients with aPFLs.
Poor recognition and undertreatment of anemia in patients with chronic kidney disease managed in primary care
Authors: Xu Yang , Evans Marie , Mazhar Faizan , Ärnlöv Johan , Cockburn Elinor , Barany Peter , Carrero Juan‐Jesus
Published: July 2023

Background

Anemia is a common complication of chronic kidney disease (CKD), but limited awareness and treatment options may hinder its management among CKD patients followed in primary care.

Methods

We evaluated adults with CKD stages 3–5 attending primary care in Stockholm, Sweden, 2012–2018. We assessed the incidence of anemia, clinical reactions, and association with subsequent major adverse cardiovascular events (MACE) and death.

Results

We identified 45,637 patients with CKD stages 3–5 free from anemia (mean age 78 years; 64% females; 79% CKD stage 3b). During a median follow‐up of 2.4 years, 26% of patients developed anemia, and 10.4% developed severe anemia (hemoglobin <10 g/dL). Within 6 months from the anemia event, iron tests were infrequent; ferritin and transferrin saturation were tested in 27% and 11% of anemia cases, respectively, and 49% and 24% of severe anemia cases. Few patients were recognized with a clinical diagnosis (15% of anemia cases; 68% of severe anemias). Only 19% of patients with anemia received treatment, primarily iron (10%) and blood transfusions (7%); erythropoietin‐stimulating agent use was anecdotal (∼1%). Treatment rates for severe anemia were higher, but 43% of patients still failed to receive treatment. Developing anemia was associated with a higher risk of MACE and death.

Conclusion

Anemia was common and associated with adverse outcomes among patients with CKD stages 3–5 managed in primary care. Iron stores were infrequently tested, and a large proportion of patients with anemia remained untreated/under‐recognized.
Syllable‐final /s/ as an index of language, gender, and ethnicity in a contact variety of Mexican Spanish
Authors: Welker Craig
Published: July 2023

This study of syllable‐final /s/ reduction in a 55‐speaker corpus of Spanish in Juchitán, México, a contact variety, uses both language contact and social processes to explain its results. Contact with the indigenous Isthmus Zapotec language leads to decreased rates of syllable‐final /s/ retention, creating a locally salient n+1‐order index between “Zapotecness” and /s/ reduction that influences the indexical field for syllable‐final /s/ reduction. Zapotec identity is associated with tradition and femininity. Therefore, in this new indexical field, syllable‐final /s/ reduction comes to directly index Zapotec language dominance and indirectly index both femininity and tradition. This leads feminine and elderly speakers to reduce /s/ more frequently than “less feminine” and young speakers, even though the opposite pattern is usually found in other varieties. The results show, therefore, that language contact can influence the indexical field typically linked to socially meaningful variation and thereby cause unexpected patterns of variation to emerge.
Neuromuscular junction denervation and terminal Schwann cell loss in the hTDP‐43 overexpression mouse model of amyotrophic lateral sclerosis
Authors: Alhindi Abrar , Shand Megan , Smith Hannah L. , Leite Ana S. , Huang Yu‐Ting , van der Hoorn Dinja , Ridgway Zara , Faller Kiterie M. E. , Jones Ross A. , Gillingwater Thomas H. , Chaytow Helena
Published: July 2023

Aims

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with complex aetiology. Despite evidence of neuromuscular junction (NMJ) denervation and ‘dying‐back’ pathology in models of SOD1‐dependent ALS, evidence in other genetic forms of ALS is limited by a lack of suitable animal models. TDP‐43, a key mediator protein in ALS, is overexpressed in neurons in Thy1‐hTDP‐43WT mice. We therefore aimed to comprehensively analyse NMJ pathology in this model of ALS.

Methods

Expression of TDP‐43 was assessed via western blotting. Immunohistochemistry techniques, alongside NMJ‐morph quantification, were used to analyse motor neuron number, NMJ denervation status and terminal Schwann cell morphology.

Results

We present a time course of progressive, region‐specific motor neuron pathology in Thy1‐hTDP‐43WT mice. Thy1‐driven hTDP‐43 expression increased steadily, correlating with developing hindlimb motor weakness and associated motor neuron loss in the spinal cord with a median survival of 21 days. Pronounced NMJ denervation was observed in hindlimb muscles, mild denervation in cranial muscles but no evidence of denervation in either forelimb or trunk muscles. NMJ pathology was restricted to motor nerve terminals, with denervation following the same time course as motor neuron loss. Terminal Schwann cells were lost from NMJs in hindlimb muscles, directly correlating with denervation status.

Conclusions

Thy1‐hTDP‐43WT mice represent a severe model of ALS, with NMJ pathology/denervation of distal muscles and motor neuron loss, as observed in ALS patients. This model therefore provides an ideal platform to investigate mechanisms of dying‐back pathology, as well as NMJ‐targeting disease‐modifying therapies in ALS.
ACE2 expression and spike S1 protein‐mediated immune responses in oral mucosal cells
Authors: Akagi Misaki , Ohta Kouji , Fukada Shohei , Sakuma Miyuki , Naruse Takako , Nakagawa Takayuki , Ono Shigehiro , Nishi Hiromi , Shigeishi Hideo , Aikawa Tomonao
Published: July 2023

Objectives

ACE2, known as a host receptor involved with SARS‐CoV‐2 infection, binds to viral spike proteins for host cell entry. However, details regarding its induction and function in oral mucosal cells remain unknown.

Materials and Methods

We examined ACE2 expression and its induction by transfected mimic nucleotides and pro‐inflammatory cytokines in oral keratinocytes (RT7) and fibroblasts (GT1). Subsequently, the effects of viral spike S1 protein via ACE2 on CXCL10 expression induced by pro‐inflammatory cytokines in both cells were examined.

Results

ACE2 was constitutively expressed in RT7 and GT1. Transfected Poly(I:C) and Poly(dA:dT) increased ACE2 expression in those cells, while knockdown of RIG‐I decreased ACE2 expression induced by those transfected ds nucleotides. IFN‐γ and TNF‐α enhanced transfected ds nucleotides‐induced ACE2 expression in RT7 but not GT1. S1 protein alone did not affect CXCL10 expression in either cell type, whereas it enhanced IFN‐β‐induced CXCL10 in both, while immune responses of IFN‐γ‐ and TNF‐α‐induced CXCL10 enhanced by S1 protein were different between RT7 and GT1. Finally, knockdown of ACE2 decreased cytokines and S1 protein mediated‐CXCL10 levels in both cells.

Conclusions

ACE2 in oral mucosal cells may contribute to development of infection and inflammation in cooperation with pro‐inflammatory cytokines following SARS‐CoV‐2 invasion.
Melatonin enhances KCl salinity tolerance by maintaining K+ homeostasis in Malus hupehensis
Authors: Sun Zhijuan , Li Jianyu , Guo Dianming , Wang Tianchao , Tian Yike , Ma Changqing , Liu Xiaoli , Wang Caihong , Zheng Xiaodong
Published: July 2023

Large amounts of potash fertilizer are often applied to apple (Malus domestica) orchards to enhance fruit quality and yields, but this treatment aggravates KCl‐based salinity stress. Melatonin (MT) is involved in a variety of abiotic stress responses in plants. However, its role in KCl stress tolerance is still unknown. In the present study, we determined that an appropriate concentration (100 μm) of MT significantly alleviated KCl stress in Malus hupehensis by enhancing K+ efflux out of cells and compartmentalizing K+ in vacuoles. Transcriptome deep‐sequencing analysis identified the core transcription factor gene MdWRKY53, whose expression responded to both KCl and MT treatment. Overexpressing MdWRKY53 enhanced KCl tolerance in transgenic apple plants by increasing K+ efflux and K+ compartmentalization. Subsequently, we characterized the transporter genes MdGORK1 and MdNHX2 as downstream targets of MdWRKY53 by ChIP‐seq. MdGORK1 localized to the plasma membrane and enhanced K+ efflux to increase KCl tolerance in transgenic apple plants. Moreover, overexpressing MdNHX2 enhanced the KCl tolerance of transgenic apple plants/callus by compartmentalizing K+ into the vacuole. RT–qPCR and LUC activity analyses indicated that MdWRKY53 binds to the promoters of MdGORK1 and MdNHX2 and induces their transcription. Taken together, our findings reveal that the MT‐WRKY53‐GORK1/NHX2‐K+ module regulates K+ homeostasis to enhance KCl stress tolerance in apple. These findings shed light on the molecular mechanism of apple response to KCl‐based salinity stress and lay the foundation for the practical application of MT in salt stress.
Ursolic acid‐rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease
Authors: Daga Maiara A. , Nicolau Scheila T. , Jurumenha‐Barreto Juliana , Lima Lucas B. S. , Cabral Isaac L. , Pivotto Ana Paula , Stefanello Amanda , Amorim João P. A. , Hoscheid Jaqueline , Silva Edson A. , Ayala Thaís S. , Menolli Rafael A.
Published: July 2023

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti‐inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 μg/mL; LC50 26.73 ± 1.2 μg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE‐treated animals had a worsening compared to non‐treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti‐inflammatory effect of CPE, demonstrated by the higher IL‐10 and IL‐4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti‐inflammatory activity.
Theoretical and numerical analysis of a chaotic model with nonlocal and stochastic differential operators
Authors: Koca İlknur , Atangana Abdon
Published: July 2023

A set of nonlinear ordinary differential equations has been considered in this paper. The work tries to establish some theoretical and analytical insights when the usual time-deferential operator is replaced with the Caputo fractional derivative. Using the Caratheodory principle and other additional conditions, we established that the system has a unique system of solutions. A variety of well-known approaches were used to investigate the system. The stochastic version of this system was solved using a numerical approach based on Lagrange interpolation, and numerical simulation results were produced.
The Effect of Spherical Hybrid Silica–Molybdenum Disulfide on the Lubricating Characteristics of Castor Oil
Authors: Verma Gulshan , Harsha A. P. , Khatri O. P.
Published: July 2023

This investigation demonstrates the effect of a structural hybrid of spherical silica and lamellar molybdenum disulfide (MoS2) combined to form a sphere used as an antifriction and antiwear additive in vegetable oil in steel-on-steel tribopair. Hybrids demonstrated improved dispersion stability due to the deposition of lightweight silica on the surface of hydrothermally prepared 2D sheets of MoS2. The concentration of nanohybrid was optimized for optimal lubricant performance, and the best region of test space is presented in this work. At the optimum concentration, the coefficient of friction (COF) was 0.03236, with an average wear volume of 2.16 × 10−12 m3. The synergism of the particles significantly reduces friction and wear. The collision of the hybrid spheres with the surface has an immediate effect on it. The broken sphere of wear debris was observed under scanning electron microscopy. The wear debris analysis indicates that the lubrication mechanism begins with the rolling of hybrid spheres and ends with the rolling and sliding of silica and MoS2.
The Relationship of Resilience, Self-Compassion, and Social Support to Psychological Distress in Women Collegiate Athletes During COVID-19
Authors: Mikesell Matthew , Petrie Trent A. , Chu Tsz Lun (Alan) , Moore E. Whitney G.
Published: July 2023

Given how COVID-19 had caused significant increases in collegiate athletes’ psychological distress, we examined the extent to which such distress may have been ameliorated by the athletes’ psychosocial resources (e.g., resilience). We used structural equation modeling to examine the direct and indirect relationships of resilience, self-compassion, and social support to women collegiate athletes’ (N = 3,924; 81.2% White) psychological distress; athletes completed measures of these constructs from mid-April to mid-May 2020. Analyses revealed significant direct effects: More supported (β = −0.12 to −0.19), self-compassionate (β = −0.48 to −0.53), and resilient (β = −0.21 to −0.35) athletes experienced less psychological distress (R2 = .61–.65). Further, self-compassion and social support were related indirectly (and inversely) to psychological distress through higher levels of resilience. These psychosocial resources appear to have played a positive role in how athletes coped with the pandemic, being associated with less psychological distress. These findings have application beyond the pandemic, providing direction for how sport psychology professionals may assist athletes in maintaining their well-being.
Targeting the Siglec–sialic acid axis promotes antitumor immune responses in preclinical models of glioblastoma
Authors: Schmassmann Philip , Roux Julien , Buck Alicia , Tatari Nazanin , Hogan Sabrina , Wang Jinyu , Rodrigues Mantuano Natalia , Wieboldt Ronja , Lee Sohyon , Snijder Berend , Kaymak Deniz , Martins Tomás A. , Ritz Marie-Françoise , Shekarian Tala , McDaid Marta , Weller Michael , Weiss Tobias , Läubli Heinz , Hutter Gregor
Published: July 2023

Glioblastoma (GBM) is the most aggressive form of primary brain tumor, for which effective therapies are urgently needed. Cancer cells are capable of evading clearance by phagocytes such as microglia- and monocyte-derived cells through engaging tolerogenic programs. Here, we found that high expression of sialic acid–binding immunoglobulin-like lectin 9 (Siglec-9) correlates with reduced survival in patients with GBM. Using microglia- and monocyte-derived cell-specific knockouts of Siglec-E, the murine functional homolog of Siglec-9, together with single-cell RNA sequencing, we demonstrated that Siglec-E inhibits phagocytosis by these cells, thereby promoting immune evasion. Loss of Siglec-E on monocyte-derived cells further enhanced antigen cross-presentation and production of pro-inflammatory cytokines, which resulted in more efficient T cell priming. This bridging of innate and adaptive responses delayed tumor growth and resulted in prolonged survival in murine models of GBM. Furthermore, we showed the combinatorial activity of Siglec-E blockade and other immunotherapies demonstrating the potential for targeting Siglec-9 as a treatment for patients with GBM.
Short- and Long-Read Sequencing Reveals the Presence and Evolution of an IncF Plasmid Harboring
bla
CTX-M-15
and
bla
CTX-M-27
Genes in Escherichia coli ST131
Authors: Cave Rory , Ter-Stepanyan Mary M. , Mkrtchyan Hermine V.
Published: July 2023

Combining short and long reads from whole-genome sequencing analysis provided a genetic context for uncommon genes of clinical importance to better understand transmission and evolutionary features of ESBL-producing uropathogenic
E. coli
(UPEC) ST131 isolates recovered in Armenia. Using hybrid genome assembly in countries lacking genomic surveillance studies can inform us about new lineages not seen in other countries with genes encoding high virulence and antibiotic resistance harbored on mobile genetic elements.
Adenocarcinoma involving the urinary bladder
Authors: Wang Pule , Joiner Michael , Dzul Stephen , Miller Steven Raymond
Published: July 2023

A man in his 70s previously diagnosed with an adenocarcinoma of the prostate, received external beam radiation therapy (EBRT) and brachytherapy 11 years ago. Ten years later, he developed urinary symptoms and a cystoscopy identified a bladder neck tumour. A transurethral resection of a bladder tumour was performed, and pathology revealed a high-grade adenocarcinoma consistent with a colorectal primary. A colonoscopy was unremarkable, and imaging studies showed tumour involving the bladder and prostate. Tumour markers and a CARIS genomic prevalence score also favoured a colorectal cancer primary.

The patient refused surgery and underwent chemoradiation with a combination of EBRT and brachytherapy with concurrent capecitabine. Imaging studies obtained 6 months after reirradiation revealed an enlarged left-sided mesorectal lymph node concerning for disease recurrence. The lymph node was treated with Stereotactic Body Radiation Therapy and his post-treatment imaging revealed a response to treatment with no other evidence of disease.
Metastatic renal cell carcinoma to the small bowel 6 years postnephrectomy
Authors: Kim David , Reed Gasinee , Ellis Kelsey Kay , Loden Jason
Published: July 2023

Renal cell carcinoma (RCC) is an unpredictable malignancy, with 25%–30% of patients developing metastatic disease. The most common sites of metastasis are the lung, bones, liver and brain, with small intestine metastasis being minimally reported in the literature. This report describes a case of small bowel obstruction caused by metastatic RCC in a male patient in his 60 s who had previously undergone a radical nephrectomy with adjuvant pembrolizumab therapy 6 years prior. The patient underwent a diagnostic laparoscopy converted to a laparotomy due to the complexity of the case. During surgical exploration, an enterectomy and end-to-end anastomosis were performed. This case emphasises the possibility of RCC metastasising to the small intestine, which may present with small bowel obstruction, while highlighting the importance of patient education for early detection to improve prognosis. Additionally, this report discusses treatment options for managing RCC metastasis to the small intestine.
Workplace socioeconomic characteristics and coronary heart disease: a nationwide follow-up study
Authors: Forsberg Per-Ola , Ohlsson Henrik , Sundquist Kristina
Published: July 2023

Objectives

Important gaps in previous research include a lack of studies on the association between socioeconomic characteristics of the workplace and coronary heart disease (CHD).

We aimed to examine two contextual factors in association with individuals’ risk of CHD: the mean educational level of all employees at each individual’s workplace (educationwork) and the neighbourhood socioeconomic characteristics of each individual’s workplace (neighbourhood SESwork).

Design

Nationwide follow-up/cohort study.

Setting

Nationwide data from Sweden.

Participants

All individuals born in Sweden from 1943 to 1957 were included (n=1 547 818). We excluded individuals with a CHD diagnosis prior to 2008 (n=67 619), individuals without workplace information (n=576 663), individuals lacking residential address (n=4139) and individuals who had unknown parents (n=7076). A total of 892 321 individuals were thus included in the study (426 440 men and 465 881 women).

Primary and secondary outcome measures

The outcome variable was incident CHD during follow-up between 2008 and 2012. The association between educationworkand neighbourhood SESworkand the outcome was explored using multilevel and cross-classified logistic regression models to determine ORs and 95% CIs, with individuals nested within workplaces and neighbourhoods. All models were conducted in both men and women and were adjusted for age, income, marital status, educational attainment and neighbourhood SESresidence.

Results

Low (vs high) educationworkwas significantly associated with increased CHD incidence for both men (OR 1.29, 95% CI 1.23 to 1.34) and women (OR 1.38, 95% CI 1.29 to 1.47) and remained significant after adjusting for potential confounders. These findings were not replicable for the variable neighbourhood SESwork.

Conclusions

Workplace socioeconomic characteristics, that is, the educational attainment of an individual’s colleagues, may influence CHD risk, which represents new knowledge relevant to occupational health management at workplaces.
Clinical course and outcomes in adults with co-occurring hypertrophic cardiomyopathy and hypertension: a scoping review protocol
Authors: Arabadjian Milla , Nicolas Barnaby , Montgomery Sophie , Pleasure Mitchell , Collins Maxine , Reuter Maria , Massera Daniele , Shimbo Daichi , Sherrid Mark
Published: July 2023

Introduction

Hypertension affects 40%–60% of adults with hypertrophic cardiomyopathy (HCM), the most common inherited cardiac condition. It can be a diagnostic confounder for HCM, contributing to delayed diagnosis. Clinically, treatment of co-occurring hypertension and HCM poses challenges as first-line and second-line antihypertensive medications are often contraindicated in HCM. The clinical course in adults with hypertension and HCM is also not well understood, and studies examining patient outcomes in this population are equivocal. In this paper, we aim to outline the protocol of a scoping review, a type of literature review, to systematically synthesise existing knowledge on adults with co-occurring HCM and hypertension, highlighting knowledge and evidence gaps, and identifying future research directions to optimise outcomes in this population.

Methods and analysis

This review is guided by Arksey and O’Malley’s conceptual framework on conducting scoping reviews. We will search five electronic databases (PubMed, CINAHL, Scopus, Embase and Web of Science) and reference lists of publications to identify eligible articles focusing on medical therapy, clinical course or outcomes in adults with HCM and hypertension, between 2011 and 2023. Our search strategy and presentation of results will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review guideline. First, two independent reviewers will screen articles, by title and abstract, followed by a full-text screen to identify eligible articles. Relevant data will be extracted and synthesised.

Ethics and dissemination

Ethical approval is not required for this review as it is a secondary data collection of published articles and does not involve human subject participation. We will present results of this review at relevant professional conferences and patient-centred educational events. Results will be published in a peer-reviewed journal.

Trial registration number

https://osf.io/cy8qb/?view_only=98197f4850584e51807ff9b62533a706.