bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: clinical assessment of suspected drug‐induced liver injury and its management
Authors: Vuppalanchi Raj , Ghabril Marwan 
Published: October 2022

SummaryBackgroundIdisyncratic drug‐induced liver injury (DILI) is a rare instance of liver injury after exposure to an otherwise safe drug or herbal or dietary supplement. DILI can be associated with significant morbidity and mortality. Furthermore, it is an important consideration in drug development due to safety concerns.Aims and MethodsTo highlight pearls and pitfalls to aid clinicians in diagnosing DILI and surmising the management options. We also share the best practices from personal insights developed from decades long participation in the causality assessment committee meetings of the DILI Network.ResultsDILI lacks a diagnostic test and is currently diagnosed through a process of exclusion of competing aetiologies of liver injury. This requires a high degree of suspicion to consider the possibility of DILI, skill in ruling out the obvious and less obvious competing liver insults, and an understanding of the expected phenotypes of DILI. The facets of DILI cover multiple aspects, including the latency, liver injury pattern, course of injury, and associated autoimmune or immuno‐allergic features. Care for patients with DILI is geared towards stopping the offending drug and symptom management that include the use of corticosteroids in select cases.ConclusionThe diagnosis of DILI is challenging and is primarily made through a carefully crafted patient interview, temporal relationship with the implicated drug or supplement, and exclusion of competing aetiology. LiverTox is a useful resource for clinicians to review the literature and recognise the likelihood of the implicated agent in causing DILI.
Internationalization strategies of multi‐product firms: The role of technology
Authors: Baumgarten Daniel , Irlacher Michael , Mayr‐Dorn Karin 
Published: October 2022

AbstractHigh‐performance firms typically have two features in common: (i) they produce in more than one country and (ii) they produce more than one product. In this paper, we analyze the internationalization strategies of multi‐product firms. Guided by several new stylized facts, we develop a theoretical model to determine optimal modes of market access at the firm–product level. We find that the most productive firms sell core varieties via foreign direct investment and export products with intermediate productivity. Shocks to trade costs and technology affect the endogenous decision to export or produce abroad at the product‐level and, in turn, the relative productivity between parents and affiliates.
Frequency of cardiac arrhythmias in horses during straight and untethered swimming
Authors: Santosuosso Emma , David Florent , Massie Shannon , Filho Silvio A. , McCrae Persephone , Johnson Sarah , Leguillette Renaud 
Published: October 2022

AbstractBackgroundCardiac arrhythmias have not been previously reported in horses while swimming.ObjectivesTo describe the type and frequency of encountered arrhythmias during repetitive swimming cycles.Study designDescriptive observational study.MethodsSixteen horses swam five pool lengths (75 m), each separated by an active recovery walk. Continuous electrocardiograms (ECGs) were recorded (n = 80) and analysed during the pre‐swim, swim and active‐recovery periods. Arrhythmias were categorised as sinus arrhythmia (SA), sinus block, sinus pause (compensatory and non‐compensatory), second degree atrioventricular block (2AVB) for physiological arrhythmias, supraventricular premature depolarisation (SVPD) and ventricular premature depolarisation (VPD) for non‐physiological arrhythmias. A linear mixed‐effects model was used to examine the effects of repetitive swim lengths on arrhythmias and swimming parameters. Data were reported as median [interquartile range].ResultsFifteen horses (94%) experienced at least one arrhythmia; however, the frequency remained low and 2AVB were only observed during the pre‐swim period. The swimming heart rate (HR) was 162 bpm [141;173]. Sinus blocks, sinus pauses, SA, SVPD and VPD were all recorded at least once during swimming. Except for one VPD couplet, all premature depolarisations were isolated. During active‐recovery, the HR was 105 bpm [103;106], with SA observed in 13 horses (81%), isolated SVPD in six horses (38%), sinus pause in one horse (6%) but no VPD present.Main limitationsLimited number of horses precluding population prevalence assessment.Conclusion and clinical importanceHigh‐quality underwater ECGs were acquired in swimming horses for the first time. The frequency of arrhythmias remained low and rare pathological arrhythmias were observed during repetitive swimming and active‐recovery cycles. Swimming with active‐recovery periods is not a high‐risk cardio‐arrhythmic exercise.
mTORC2 contributes to systemic autoimmunity
Authors: Zhou Xian , Qi Haiyu , Li Meilu , Li Yanfeng , Zhu Xingxing , Amin Shreyasee , Alexander Mariam , Diadhiou Catherine , Davidson Anne , Zeng Hu 
Published: October 2022

AbstractThe development of many systemic autoimmune diseases, including systemic lupus erythematosus, is associated with overactivation of the type I interferon (IFN) pathway, lymphopenia and increased follicular helper T (Tfh)‐cell differentiation. However, the cellular and molecular mechanisms underlying these immunological perturbations remain incompletely understood. Here, we show that the mechanistic target of rapamycin complex 2 (mTORC2) promotes Tfh differentiation and disrupts Treg homeostasis. Inactivation of mTORC2 in total T cells, but not in Tregs, greatly ameliorated the immunopathology in a systemic autoimmunity mouse model. This was associated with reduced Tfh differentiation, B‐cell activation, and reduced T‐cell glucose metabolism. Finally, we show that type I IFN can synergize with TCR ligation to activate mTORC2 in T cells, which partially contributes to T‐cell lymphopenia. These data indicate that mTORC2 may act as downstream of type I IFN, TCR and costimulatory receptor ICOS, to promote glucose metabolism, Tfh differentiation, and T‐cell lymphopenia, but not to suppress Treg function in systemic autoimmunity. Our results suggest that mTORC2 might be a rational target for systemic autoimmunity treatment.
The immunoregulatory role of IL‐35 in patients with interstitial lung disease
Authors: Osuna‐Gómez Rubén , Barril Silvia , Mulet Maria , Zamora Atenza Carlos , Millan‐Billi Paloma , Pardessus Ana , Brough Douglas E. , Sabzevari Helen , Semnani Roshanak T. , Castillo Diego , Vidal Silvia 
Published: October 2022

AbstractPulmonary fibrosis involves various types of immune cells and soluble mediators, including TGF‐β and IL‐35, a recently identified heterodimeric cytokine that belongs to the IL‐12 cytokine family. However, the effect of regulatory IL‐35 may play an important role in fibrotic diseases. The aim of this paper is to explore the immunoregulatory role of IL‐35 in the development of fibrosis in interstitial lung disease (ILD). To gain a better understanding of this issue, the concentrations of IL‐35 and different profibrotic cytokines in fibrotic (F‐ILD) and non‐fibrotic (NF‐ILD) patients by ELISA were compared to that of intracellular IL‐35 and IL‐17 on CD4+ T cells stimulated in the presence of BAL or with different ratios of recombinant IL‐35 (rIL‐35) and TGF‐β (rTGF‐β), which were evaluated by flow cytometry. We observed that BAL concentration of IL‐35 was lower in F patients (p < 0.001) and was negatively correlated with concentrations of TGF‐β (p < 0.001) and IL‐17 (p < 0.001). In supplemented cell cultures, BAL from NF but not F patients enhanced the percentage of IL‐35 + CD4+ T (p < 0.001) cells and decreased the percentage of IL‐17 + CD4+ T cells (p < 0.001). The percentage of IL‐35 + CD4+ T cells correlated positively with BAL concentration of IL‐35 (p = 0.02), but correlated negatively with BAL concentrations of IL‐17 (p = 0.007) and TGF‐β (p = 0.01). After adjusting the concentrations of recombinant cytokines to establish a TGF‐β: IL‐35 ratio of 1:4, an enhanced percentage of IL‐35 + CD4+ T cells (p < 0.001) but a decreased percentage of IL‐17 + CD4+ T cells (p < 0.001) was observed. After adding recombinant IL‐35 to the BAL from F patients until a 1:4 ratio of TGF‐β: IL‐35 was reached, a significantly increased percentage of IL‐35 + CD4+ T cells (p < 0.001) and a decreased percentage of IL‐17 + CD4+ T cells (p = 0.003) was found. These results suggest that IL‐35 may induce an anti‐fibrotic response, regulating the effect of TGF‐β and the inflammatory response on CD4+ T cells. In addition, the TGF‐β: IL‐35 ratio in BAL has been shown to be a potential biomarker to predict the outcome of F patients with ILD.
Melt‐quenched oxide glasses with ultrahigh Young's modulus and small thermal expansion coefficient
Authors: Hayashi Katsuki , Mitsui Kazuki , Shimizu Tatsuki , Kado Rikiya , Umada Takumi , Koike Akio , Yoshida Satoshi , Inaba Seiji , Saitoh Akira 
Published: October 2022

AbstractThe well‐known Makishima–Mackenzie relationship, consisting of two terms of the dense packing structure and dissociation energy regarding bonding in constituent oxides, enables fabricating oxide glasses with ultrahigh Young's modulus (∼140 GPa) and a small coefficient of thermal expansion (CTE) (∼4 ppm/K). The effects of increasing MgO and Ta2O5 contents in an MgO–Ta2O5–Al2O3–SiO2–B2O3 glass system using a conventional melt‐quenching method are revealed. The essential oxides of Al2O3 and Ta2O5 are primarily suitable for dense packing structures dominated by a large coordination number of oxygens. The substitution of CaO by MgO results in high dissociation energy when the glass composition falls in the peraluminous regime (Al2O3/[MgO + CaO] > 1). A small CTE is realized by increasing the molar ratio of Al2O3/MgO. According to magic‐angle spinning‐nuclear magnetic resonance spectra, mechanically and thermally functional oxide glasses depend on their structures. These findings facilitate the development of glass substrate applications without thermal dilatation.
Ultralow dielectric loss in Tb + Ta‐modified TiO2 giant dielectric ceramics via designing defect chemistry
Authors: Fan Jiangtao , Yang Tiantian , Cao Yongfan , Liang Jiyan 
Published: October 2022

AbstractThe environment‐friendly materials exhibiting colossal permittivity play an increasingly important role in the electronics industry. In this work, (Tb0.5Ta0.5)xTi1−xO2 (x = 0, 0.005, 0.01, 0.02, and 0.04) ceramics with new defect clusters were fabricated to enhance the dielectric response. Significantly, all ceramic samples exhibit large dielectric constants (εr > 104), whereas the ceramic with x = 0.005 exhibits an ultralow loss (tan δ) of about 0.008 at room temperature and 1 kHz. The origins of its excellent dielectric properties were revealed by XRD, X‐ray photoelectron spectroscopy, and dielectric response analysis, which were mainly caused by defective dipoles associated with oxygen vacancies (). These defective dipoles limiting the long‐range hopping of electrons lead to the electron pinning effect. Additionally, the frequency spectrum under DC bias and conductivity behavior suggests that grain boundary and electrode effects also contribute to the dielectric constant. This study not only explores the dielectric response properties of a new giant dielectric (Tb0.5Ta0.5)xTi1−xO2 ceramics but also offers a candidate material suitable for ceramics capacitors.
Comparative trophic ecology of two sympatric guitarfishes Pseudobatos (Chondrichthyes, Rhinobatidae) from Southeast Brazil, southwestern Atlantic
Authors: Chelotti Luiza de David , Gadig Otto Bismarck Fazzano 
Published: October 2022

AbstractThe present study compares the trophic ecology of two guitarfishes (Pseudobatos percellens and Pseudobatos horkelii) from the continental shelf of the São Paulo State, Brazil, caught by the bottom pair trawls between 2007 and 2009. These two sympatric species are under different threat categories, “Vulnerable” and “Critically Endangered,” respectively, according to Brazilian agencies. Thus, any study considering trophic ecology parameters is pivotal in understanding the trophic ecology role of such species in the ecosystem. The authors analysed 500 stomachs of P. percellens and 108 of P. horkelii, quantifying with dietary indexes: numerical (%N), gravimetric (%W), frequency of occurrence (%FO) and the prey‐specific index of relative importance (%PSIRI). For P. percellens and P. horkelii, 26 and 14 different prey items were found, respectively. Crustacea and Teleostei were the most important prey items for both species, indicating a specialist feeding behaviour due to their low niche amplitude. The results provide evidence related to ontogenetic dietary shift in P. percellens and individual‐level diet specialization in both species. These two benthic‐demersal elasmobranchs are important mesopredators (3,7 for P. percellens, and 3,5 for P. horkelii) in the study area, with high trophic‐level values.
Differential effect of anticoagulation according to cognitive function and frailty in older patients with atrial fibrillation
Authors: Wang Weijia , Lessard Darleen , Kiefe Catarina I. , Goldberg Robert J. , Parish David , Helm Robert , Trymbulak Katherine , Mehawej Jordy , Abu Hawa , Bamgbade Benita A. , Hayward Robert , Gore Joel , Gurwitz Jerry H. , McManus David D. , Saczynski Jane S. 
Published: October 2022

AbstractBackgroundIn older patients with atrial fibrillation (AF), cognitive impairment and frailty are prevalent. It is unknown whether the risk and benefit of anticoagulation differ by cognitive function and frailty.MethodsA total of 1244 individuals with AF with age ≥65 years and a CHADSVASC score ≥2 were recruited from clinics in Massachusetts and Georgia between 2016 and 18 and followed until 2020. At baseline, frailty status and cognitive function were assessed. Hazard ratios of anticoagulation on physician adjudicated outcomes were adjusted by the propensity for receiving anticoagulation and stratified by cognitive function and frailty status.ResultsThe average age was 75.5 (± 7.1) years, 49% were women, and 86% were prescribed oral anticoagulants. At baseline, 528 (42.4%) participants were cognitively impaired and 172 (13.8%) were frail. The adjusted hazard ratios of anticoagulation for the composite of major bleeding or death were 2.23 (95% confidence interval: 1.08–4.61) among cognitively impaired individuals and 0.94 (95% confidence interval: 0.49–1.79) among cognitively intact individuals (P for interaction = 0.08). Adjusted hazard ratios for anticoagulation were 1.84 (95% confidence interval: 0.66–5.13) among frail individuals and 1.39 (95% confidence interval: 0.84–2.40) among not frail individuals (P for interaction = 0.67).ConclusionCompared with no anticoagulation, anticoagulation is associated with more major bleeding episodes and death in older patients with AF who are cognitively impaired.
Unmet health‐related needs of community‐dwelling older adults during COVID‐19 lockdown in a diverse urban cohort
Authors: Perry Laura , Scheerens Charlotte , Greene Meredith , Shi Ying , Onion Zoe , Bayudan Evamae , Stern Rachel J. , Gilissen Joni , Chodos Anna H. 
Published: October 2022

AbstractBackgroundShelter‐in‐place orders during the COVID‐19 pandemic created unmet health‐related and access‐related needs among older adults. We sought to understand the prevalence of these needs among community‐dwelling older adults.MethodsWe performed a retrospective chart review of pandemic‐related outreach calls to older adults between March and July 2020 at four urban, primary care clinics: a home‐based practice, a safety net adult medicine clinic, an academic geriatrics practice, and a safety net clinic for adults living with HIV. Participants included those 60 or older at three sites, and those 65 or older with a chronic health condition at the fourth. We describe unmet health‐related needs (the need for medication refills, medical supplies, or food) and access‐related needs (ability to perform a telehealth visit, need for a call back from the primary care provider). We performed bivariate and multivariate analyses to examine the association between unmet needs and demographics, medical conditions, and healthcare utilization.ResultsSixty‐two percent of people had at least one unmet need. Twenty‐six percent had at least one unmet health‐related need; 14.0% needed medication refills, 12.5% needed medical supplies, and 3.0% had food insecurity. Among access‐related needs, 33% were not ready for video visits, and 36.4% asked for a return call from their provider. Prevalence of any unmet health‐related need was the highest among Asian versus White (36.4% vs. 19.1%) and in the highest versus lowest poverty zip codes (30.8% vs. 18.2%). Those with diabetes and COPD had higher unmet health‐related needs than those without, and there was no change in healthcare utilization.ConclusionsDuring COVID, we found that disruptions in access to services created unmet needs among older adults, particularly for those who self‐identified as Asian. We must foreground the needs of this older population group in the response to future public health crises.
Solar Light Responsive Graphitic Carbon Nitride Coupled Porphyrin Photocatalyst that Uses for Solar Fine Chemical Production
Authors: Mishra Shaifali , Yadav Rajesh K. , Singh Satyam , Chaubey Surabhi , Singh Pooja , Singh Chandani , Gupta Sarvesh Kumar , Gupta Shivani , Tiwary Dhanesh , Kim Tae Wu 
Published: October 2022

AbstractPhotocatalysis is a defendable manner for production of several organic chemicals, energy and its storage from solar energy. For the evolution of metal free, cost‐effective catalyst a 2D composite has been appear as a photocatalyst. Here, we had reported the synthesis of a light harvesting composite as a photocatalyst which was assembled by a poly‐condensation mechanism between graphitic carbon nitride and tetrakis(4‐nitrophenyl) porphyrin and the resulting composite manifest the excellent light harvesting properties, suitable energy band and low charge recombination. The photocatalyst [(NO2)4TPP@g‐C3N4] enables the efficient photocatalytic production of nicotinamide adenine dinucleotide (NADH) from consumed NAD+ also the production of organic chemicals like 4‐methoxybenzylimines from 4‐methoxybenzylamines. The photocatalytic efficiency of the photocatalyst was estimated by the percentage of NADH regeneration and the percentage yield of organic transformations. It shows the tetrakis(4‐nitrophenyl) porphyrin could enhance the charge transfer capacity of graphitic carbon nitride which shows excellent photocatalysis activities and organic transformations.
Developing a shared supplier with endogenous spillovers
Authors: Veldman Jasper , Anderson Edward , Pulles Niels J. , Gaalman Gerard 
Published: October 2022

Firms who buy from suppliers often engage in supplier development to reduce the supplier's production cost. Being aware that their efforts may benefit a rival firm when there is a shared supplier, some buyers only invest in “specific supplier development,” that is, in those processes or technologies where spillover cannot occur. Other buyers willingly accept the spillover that arises from supplier development, and invest in “generic supplier development.” Our game‐theoretic model captures a buyer's choice to invest in these distinct supplier development types as a way to endogenize spillovers. In contrast to the literature, this paper considers the benefits of investing in a combination (i.e., portfolio) of cost‐reducing generic and specific supplier development. We demonstrate how supplier development affects a shared supplier's wholesale pricing decisions; whereas generic supplier development lowers wholesale prices equally across buyers, specific supplier development only lowers the wholesale price of the investing party. Our model shows that buyers should treat the spillovers from generic supplier development as an investment opportunity rather than a threat. In equilibrium, a buyer will always invest in a portfolio of both supplier development types, and having a better generic than specific investment capability may even make generic supplier development the most prevalent option for him, depending on the level of competition. Moreover, even if the buyers can commit to only investing in specific supplier investment, the resulting equilibrium gives lower buyer profits than a portfolio that includes generic investments. We also find that the presence of specific investments may raise generic supplier development, benefiting all supply chain actors. However, incorporating specific supplier development into a supplier development portfolio or a commitment to investment in only specific supplier development can lead to a prisoner's dilemma in terms of buyer profits. We show how investment capabilities and competitive intensity drive the buyers' investment decisions and supply chain actors' profits. The paper's main results also hold for asymmetric generic investment capabilities, though we highlight that the least capable buyer will free‐ride on his rival's investments, consequently making him earn higher profits.
Neuropsychiatric outcomes and caregiver distress in primary progressive aphasia
Authors: Seckin Mustafa , Yıldırım Elif , Demir İlayda , Orhun Ömer , Bülbül Ezgi , Velioğlu H. Aziz , Öktem Öget , Yeşilot Nilüfer , Çoban Oğuzhan , Gürvit Hakan 
Published: October 2022

BackgroundIn this study, we aimed to outline the neuropsychiatric consequences of primary progressive aphasia (PPA) and to understand how neuropsychiatric symptomatology affects distress in caregivers.MethodsThe Neuropsychiatric Inventory (NPI) including the distress index (NPI‐Distress) was used. Additional information about the caregiver burden was obtained using Zarit Burden Interview (ZBI). NPI, NPI‐Distress, and ZBI data from 17 patients with a clinical diagnosis of PPA were compared with 10 stroke aphasia patients. Neuropsychiatric symptomatology was investigated based on three clusters; Mood, Frontal/Comportmental, and Psychotic/Disruptive. Additionally, the Activities of Daily Living Questionnaire (ADLQ) was used to outline the functional impairment. Twelve healthy controls were included to compare the neurocognitive test scores with PPA and stroke aphasia groups.ResultsA greater number of neuropsychiatric symptoms were observed in the PPA group compared to the stroke aphasia group. The number of symptoms in Mood, and Frontal/Comportmental clusters were greater than the number of symptoms in Psychotic/Disruptive clusters in the PPA group, whereas no significant relationship between the number of symptoms and symptom clusters was found in the stroke aphasia group. In the PPA group, a strong correlation was found between the NPI‐Frequency × Severity scores and the NPI‐Distress scores. Moreover, the NPI‐Distress scores in the PPA group strongly correlated with the ZBI scores. Scores for anxiety, irritability/lability, and apathy had a stronger correlation with the NPI‐Distress scores compared to the other NPI symptoms. The Communication subscale was the most impaired domain in the PPA group. Travel, and Employment and Recreation subscales showed greater functional impairment in the stroke aphasia group compared to the PPA group.ConclusionsNeuropsychiatric symptoms in PPA in our study were more frequent than previously reported. Furthermore, the distress index of the NPI was not only correlated with the severity of the neuropsychiatric symptoms but also reflected the overall burden on the caregivers in the PPA group.