bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult‐onset Still's disease in Western Australia: Epidemiology, comorbidity and long‐term outcome
Authors: Nossent Johannes , Raymond Warren , Keen Helen , Preen David B. , Inderjeeth Charles A.
Published: August 2022

Aim

Adult‐onset Still’s disease (ASD) is a rare, potentially life‐threatening autoinflammatory condition. As reported prevalence shows regional variation and long‐term outcome data are scarce, we investigated epidemiology and long‐term health outcomes of ASD in Western Australia (WA).

Methods

Population‐based cohort study using longitudinally linked administrative health data from all WA hospitals between 1999 and 2013 for ASD patients (ICD‐10‐AM M06.1) and controls matched for age, gender, and index year. Rate ratios and odds ratios (RR/OR) with 95% confidence intervals (CI) compared ASD patients with controls.

Results

The average ASD incidence (n = 52) was 0.22/100 000 with 2.4/100 000 point‐prevalence as of December 31, 2013. ASD patients (median age 41.5 years, 59.6% female) had higher odds of previous liver disease (OR 2.67, 95% CI 1.31‐5.45), fever (OR 54.10, 95% CI 6.60‐433.0), rash (OR 15.70, 95% CI 4.08‐60.80), and serious infections (OR 4.36, 95% CI 2.11‐22.80) than controls. Despite biological disease‐modifying antirheumatic drugs in 27% of patients, ASD patients had higher odds for joint replacement (n = 7, 13.5%) (OR 45.5, 95% CI 4.57‐93.70), osteoporosis (OR 31.3, 95% CI 3.43‐97), and serious infections (RR 5.68; 95% CI 6.61‐8.74) during follow up. However, crude mortality (11.5% vs 7.5%; P = 0.34), survival at 1 and 5 years (P= 0.78), and last modified Charlson Comorbidity score (median 2 vs 2) were similar between groups.

Conclusion

The epidemiology and demographics of ASD in Western Australia fall within the internationally reported range. ASD patients present increased rates of liver disease, rash, and serious infections before disease onset. Mortality following ASD was not increased for 5 years despite high rates of chronic arthritis requiring joint replacement, serious infections, and osteoporosis.
Canakinumab treatment in a young girl with refractory chronic recurrent multifocal osteomyelitis associated with pyoderma gangrenosum
Authors: Acierno Sabrina , Angrisani Francesca , Marino Achille , Caporali Roberto Felice , Cimaz Rolando , Giani Teresa
Published: August 2022

Background

Chronic recurrent multifocal osteomyelitis (CRMO) is a bone inflammatory disorder characterized by osteolytic, usually multiple, symmetric lesions. Diagnosis is one of exclusion, and no standardized therapies are available. Presumed deregulation of the interleukin (IL)‐1β axis, as observed in 2 monogenic autoinflammatory conditions such as Majeed syndrome (LPIN2 mutations) and deficiency of IL‐1 receptor antagonist (IL1RN mutations) with CRMO‐like bone involvement, suggests the blockade of IL‐1 as potentially useful also in this condition, even if scarce data are available.

Case presentation

We report the case of a 13‐year‐old girl affected by a multidrug‐resistant and pyoderma gangrenosum‐complicated CRMO treated with canakinumab, a human monoclonal antibody targeting IL‐1β.

Conclusion

In this young patient pyoderma gangrenosum and CRMO showed a rapid and satisfactory response to canakinumab, although over time a decreased efficacy in controlling bone disease was observed.
Unique and common TCR repertoire features of Ni2+‐, Co2+‐, and Pd2+‐specific human CD154 + CD4+ T cells
Authors: Riedel Franziska , Aparicio‐Soto Marina , Curato Caterina , Münch Lucas , Abbas Amro , Thierse Hermann‐Josef , Peitsch Wiebke K. , Luch Andreas , Siewert Katherina
Published: August 2022

Background

Apart from Ni2+, Co2+, and Pd2+ ions commonly trigger T cell‐mediated allergic contact dermatitis. However, in vitro frequencies of metal‐specific T cells and the mechanisms of antigen recognition remain unclear.

Methods

Here, we utilized a CD154 upregulation assay to quantify Ni2+‐, Co2+‐, and Pd2+‐specific CD4+ T cells in peripheral blood mononuclear cells (PBMC). Involved αβ T cell receptor (TCR) repertoires were analyzed by high‐throughput sequencing.

Results

Peripheral blood mononuclear cells incubation with NiSO4, CoCl2, and PdCl2 increased frequencies of CD154 + CD4+ memory T cells that peaked at ~400 μM. Activation was TCR‐mediated as shown by the metal‐specific restimulation of T cell clones. Most abundant were Pd2+‐specific T cells (mean 3.5%, n = 19), followed by Co2+‐ and Ni2+‐specific cells (0.6%, n = 18 and 0.3%, n = 20) in both allergic and non‐allergic individuals. A strong overrepresentation of the gene segment TRAV9‐2 was unique for Ni2+‐specific TCR (28% of TCR) while Co2+ and Pd2+‐specific TCR favorably expressed TRAV2 (8%) and the TRBV4 gene segment family (21%), respectively. As a second, independent mechanism of metal ion recognition, all analyzed metal‐specific TCR showed a common overrepresentation of a histidine in the complementarity determining region 3 (CDR3; 15% of α‐chains, 34% of β‐chains). The positions of the CDR3 histidine among metal‐specific TCR mirrored those in random repertoires and were conserved among cross‐reactive clonotypes.

Conclusions

Induced CD154 expression allows a fast and comprehensive detection of Ni2+‐, Co2+‐, and Pd2+‐specific CD4+ T cells. Distinct TCR repertoire features underlie the frequent activation and cross‐reactivity of human metal‐specific T cells.
Helsinki in Zion: Hospital ethics committees and political gatekeeping in Israel/Palestine
Authors: Shalev Guy
Published: August 2022

This article looks at six months of the author's repeated attempts to obtain the approval of three Helsinki Committees (HCs, Israeli hospitals’ research ethics committees) to conduct ethnographic research with Palestinian physicians in Israeli hospitals. While the research was eventually approved and carried out in two of these institutions, correspondence with HC representatives, as well as evidence of their informal moves with institutions’ management, reflect their perceptions of the risks the study posed. In the Israeli hospital, acknowledging Palestinian political subjectivity challenges the definition of Israeli nationhood as exclusively Jewish and contaminates the allegedly politically neutral medical sphere. These committees exerted their power to serve their institutions and state ideology. This, I argue, should not be understood as anomalous instances of negligence. I show how the committees’ censorship was attuned to the Declaration of Helsinki as their guiding text and Zionism as their underlying ideology. Embedded in the powerful regimes of ethics, bureaucracy, science, and health, ethics committees employ “unarmed power” that is beyond critique. They are well‐oiled “anti‐politics machines,” rearticulating political concerns into a depoliticized moral discourse. As such, they not only limit academic inquiry but also redefine, in political terms, the realm of the moral.
Management of prolonged meconium evacuation in preterm infants: A survey‐based analysis in German Neonatal Intensive Care Units
Authors: Lange Matthias , Figura Yannick , Böhne Carolin , Beske Florian , Bohnhorst Bettina , Heep Axel
Published: August 2022

Aim

Due to the functional immaturity of bowel motility, a delayed passage frequently requires evacuation of meconium in preterm infants. Often rectal enemas and oral laxatives are used to manage these bowel evacuation disorders.

Methods

An online survey was sent to all 163 high‐level Neonatal Intensive Care Units (NICUs) in Germany. The participants were queried on rectal enemas, laxative therapy and outcome incidences.

Results

A total of 110/163 (67.5%) hospitals participated in the study. 103/110 (93.6%) participating sites applied rectal enemas in cases of delayed meconium evacuation and 63/110 (57.3%) additionally used oral laxatives. In total, 15 different solutions and 7 different application systems were used for rectal instillation. Preterm infants receiving enemas within the first 48 hours after birth were found to have a significantly lower incidence of FIP (p = 0.006). Altogether 8 different oral laxatives were utilised.

Conclusion

Therapeutic approaches to the management of prolongated meconium evacuation differ widely among German NICUs. Our survey highlights the diversity of applied substances, means of application and differences in duration and frequency of interventions. Macrogol was commonly used in neonates as an oral laxative despite the lack of approval from the manufacturer.
A risk calculator to predict suicide attempts among individuals withearly‐onsetbipolar disorder
Authors: Goldstein Tina R. , Merranko John , Hafeman Danella , Gill Mary Kay , Liao Fangzi , Sewall Craig , Hower Heather , Weinstock Lauren , Yen Shirley , Goldstein Benjamin , Keller Martin , Strober Michael , Ryan Neal , Birmaher Boris
Published: August 2022

Objectives

To build a one‐year risk calculator (RC) to predict individualized risk for suicide attempt in early‐onset bipolar disorder.

Methods

Youth numbering 394 with bipolar disorder who completed ≥2 follow‐up assessments (median follow‐up length = 13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide attempt over follow‐up was assessed via the A‐LIFE Self‐Injurious/Suicidal Behavior scale. Predictors from the literature on suicidal behavior in bipolar disorder that are readily assessed in clinical practice were selected and trichotomized as appropriate (presence past 6 months/lifetime history only/no lifetime history). The RC was trained via boosted multinomial classification trees; predictions were calibrated via Platt scaling. Half of the sample was used to train, and the other half to independently test the RC.

Results

There were 249 suicide attempts among 106 individuals. Ten predictors accounted for >90% of the cross‐validated relative influence in the model (AUC = 0.82; in order of relative influence): (1) age of mood disorder onset; (2) non‐suicidal self‐injurious behavior (trichotomized); (3) current age; (4) psychosis (trichotomized); (5) socioeconomic status; (6) most severe depressive symptoms in past 6 months (trichotomized none/subthreshold/threshold); (7) history of suicide attempt (trichotomized); (8) family history of suicidal behavior; (9) substance use disorder (trichotomized); (10) lifetime history of physical/sexual abuse. For all trichotomized variables, presence in the past 6 months reliably predicted higher risk than lifetime history.

Conclusions

This RC holds promise as a clinical and research tool for prospective identification of individualized high‐risk periods for suicide attempt in early‐onset bipolar disorder.
Factors associated with person‐centered care during pregnancy and birth for Black women and birthing people in California
Authors: Altman Molly R. , Afulani Patience A. , Melbourne Daphina , Kuppermann Miriam
Published: August 2022

Introduction

In the United States, adverse birth outcomes are most prevalent among Black women and birthing people, who are known to experience increased mistreatment and disrespect in care. The purpose of this paper is to describe findings from a study that used two validated scales to examine factors associated with experiences of person‐centered care during pregnancy and birth among Black birthing people in California.

Methods

We used data from 234 Black women and birthing people who were recruited between January and September 2020 as part of a validation study for the Person‐Centered Prenatal Care (PCPC) and the Person‐Centered Maternity Care (PCMC‐US) scales. Bivariate and multivariate analyses were conducted to examine the associations between PCPC and PCMC‐US scores and sociodemographic, health‐related, and care‐related factors.

Results

The factors associated with lower PCPC scores were having foreign‐born parents, having public or no insurance, part‐time employment, unstable housing, late start of prenatal care (in the second or third trimester), poorer self‐rated health (less than very good), and lack of continuity of care with prenatal providers. Factors associated with lower PCMC‐US scores were having public insurance, late start of prenatal care, longer length of stay in facility following birth, poorer self‐rated health, lack of continuity of care between prenatal care and birth providers, and racial discordance with birth provider.

Conclusions

Our analysis highlights the contributions of intersecting identities as well as health‐related and care‐related factors to Black birthing people's experiences of care in California. Continuity of care and provider racial concordance, in particular, were shown to improve pregnancy and birth experiences.
Real‐life efficacy and safety of idelalisib in 55 double‐refractory follicular lymphoma patients
Authors: Isidori Alessandro , Loscocco Federica , Visani Giuseppe , Paolasini Sara , Scalzulli Potito , Musto Pellegrino , Perrone Tommasina , Guarini Attilio , Pastore Domenico , Mazza Patrizio , Tonialini Lorenzo , Pavone Vincenzo , De Santis Gaetano , Tarantini Giuseppe
Published: August 2022

Idelalisib, a reversible inhibitor of PI3Kδ (phosphoinositide‐3 kinase delta), showed remarkable activity in the phase II DELTA trial, leading to its approval by the European Medicines Agency (EMA) in patients with relapsed/refractory (R/R) follicular lymphoma (FL). However, real‐life data on idelalisib are scarce. We treated 55 double‐refractory FL patients with idelalisib in a real‐life setting. With a median exposure to idelalisib of 10 months (range 1–43), overall response rate was 73%, the highest ever reported. Non‐haematological toxicities were mild and manageable. At 12 months, 80% of patients were alive, and 72% disease‐free. The efficacy and safety of idelalisib was confirmed in a real‐life setting.
A review on computer‐aided chemogenomics and drug repositioning for rationalCOVID‐19 drug discovery
Authors: Maghsoudi Saeid , Taghavi Shahraki Bahareh , Rameh Fatemeh , Nazarabi Masoomeh , Fatahi Yousef , Akhavan Omid , Rabiee Mohammad , Mostafavi Ebrahim , Lima Eder C. , Saeb Mohammad Reza , Rabiee Navid
Published: August 2022

Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment―either experimentally or computationally―to enlarge practical application window. The emergence of computational methods, particularly computer‐aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time‐consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross‐species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system‐based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants.
MOG‐antibody‐associated disorder with hypothalamic lesions associated with hypersomnia and decrease of orexin in CSF: A case report
Authors: Menjo Kanako , Ashida Shinji , Murata Shohei , Tanaka Eijirou , Fujii Chihiro , Tanaka Masami , Tanaka Keiko , Kanbayashi Takashi , Mizuno Toshiki
Published: August 2022

Background

Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) is an inflammatory disorder of the central nervous system. Here, we are the first to report a MOGAD patient with hypersomnolence caused by bilateral hypothalamic lesions.

Case presentation

The case involved a 51‐year‐old female patient with MOGAD who showed hypersomnolence. She had been diagnosed with MOGAD at 50 years old and admitted due to the development of optic neuritis and encephalitis while under corticosteroid and immunosuppressant treatment. These were improved after the introduction of intravenous methylprednisolone and plasma exchange. The orexin level in the cerebrospinal fluid (CSF) was decreased to 142.2 pg/mL (<200 pg/mL) upon admission and improved to a normal level (298.3 pg/mL) after immunotherapy. Bilateral hypothalamic lesions and reduction of the orexin level in the CSF were considered associated with hypersomnia.

Conclusion

The orexin level in CSF was useful to monitor hypothalamic dysfunction in a patient with MOGAD.
Population pharmacokinetics of everolimus in adult liver transplant patients: Comparison to tacrolimus disposition and extrapolation to pediatrics
Authors: Itohara Kotaro , Yano Ikuko , Nakagawa Shunsaku , Sugimoto Mitsuhiro , Hirai Machiko , Yonezawa Atsushi , Imai Satoshi , Nakagawa Takayuki , Hira Daiki , Ito Takashi , Hata Koichiro , Hatano Etsuro , Terada Tomohiro , Matsubara Kazuo
Published: August 2022

Everolimus has recently been used to prevent graft rejection in liver transplantation and reduces the incidence of kidney dysfunction caused by calcineurin inhibitors. In this study, a population pharmacokinetic analysis was conducted to improve the individualization of everolimus therapy. Japanese post‐liver transplant patients whose blood everolimus concentrations were measured between March 2018 and December 2020 were included in this study. A nonlinear mixed‐effect modeling program was used to explore covariates that affect everolimus pharmacokinetics. Individual everolimus pharmacokinetic parameters estimated by the post‐hoc Bayesian analysis using the final model were compared with the tacrolimus dose per trough concentration (D/C) ratio in each patient. The final model was extrapolated to pediatric liver transplant patients for external evaluation. A total of 937 concentrations from 87 adult patients were used in the model‐building process. Everolimus clearance was significantly affected by the estimated glomerular filtration rate, concomitant use of fluconazole, sex, as well as total daily dose of everolimus (TDM effect). The estimated individual apparent clearance of everolimus by the post‐hoc Bayesian analysis was moderately correlated with the D/C ratio of tacrolimus in each patient (R2 = 0.330, p < 0.0001). The estimation accuracy in pediatric patients was considerably high, except for one infant out of 13 patients. In conclusion, population pharmacokinetic analysis clarified several significant covariates for everolimus pharmacokinetics in liver transplant patients. Everolimus pharmacokinetics moderately correlated with tacrolimus pharmacokinetics and could be extrapolated from adult to pediatric patients by body size correction, except for infants.
Repertoires of citizen action in hybrid settings
Authors: Gaventa John
Published: August 2022

Motivation

In recent years, a growing literature has emerged analysing how organized citizen action can achieve more accountable and inclusive governance. While this literature is mostly focused on relatively open, democratic, or more stable contexts, often in western democracies, only a small proportion of the world's population lives in such settings. Rather, authoritarianism is growing and democratic spaces are closing globally.

Purpose

This article explores how hybrid political settings—those which have both democratic and non‐democratic features, fragmented authority, and closing civic space—affect strategies of citizen action.

Methods and approach

Drawing from a large number of single and comparative case studies of citizen action, mainly from Mozambique, Myanmar, Nigeria, and Pakistan, the article builds on work by Tilly and Tarrow on repertoires of contention. Based on these, the article develops a typology of eight repertoires of citizen action through which citizens may express their grievances and attempt to hold authorities to account.

Findings

The literature suggests that there may be little space for contentious social and political action in closed or authoritarian settings. This article finds, however, that a rich and diverse tapestry of citizen action may be seen in the “hybrid” settings (those which have both democratic and non‐democratic features). Shaped by political opportunities as well as by key trigger events, these repertoires will vary according to their visibility and their level of “ruliness” and may shift or re‐enforce one another over time, contributing to building blocks for broader accountability and democratic governance.

Policy implications

Policy and donor interventions aimed at supporting citizen‐led action for accountability have often focused on the most visible and ruly of these strategies. However, we find that the more hidden or more unruly forms of action are important in and of themselves and help to create building blocks for broader changes. For those who are interested in supporting citizen‐led accountability, mapping these broader repertoires will be important to understand the full range of accountability strategies available, going beyond more commonly understood approaches.
Pathogenicity of three Botryosphaeriaceae fungi, Diplodia scrobiculata, Diplodia mutila, and Dothiorella californica, isolated from coast redwood (Sequoia sempervirens) in California
Authors: Lee Christopher A. , Rooney‐Latham Suzanne , Brown Albre A. , McCormick Megan , Baston David
Published: August 2022

Three Botryosphaeriaceae species, not previously recorded on coast redwood, were detected from native redwood stands in Humboldt Co., CA during general surveys between 2014 and 2017. Pathogenicity experiments with three of these fungi, Diplodia scrobiculata, Diplodia mutila, and Dothiorella californica, were performed on 2‐year‐old redwood seedlings to fulfil Koch's postulates and prove pathogenicity. Only D. scrobiculata produced lesions significantly longer than control lesions, although they were generally smaller than those of more virulent Botryosphaeriaceae pathogens in previous studies. In a separate pathogenicity study of D. scrobiculata on younger seedlings without secondary growth, inoculations on wounded stems resulted in black lesions that were much more externally obvious than the wound inoculations on lignified stems after 90 days. However, no lesions developed on non‐wounded stems of younger seedlings. Lesion lengths caused by D. scrobiculata were consistent between the two studies. On one wound‐inoculated, non‐woody seedling, D. scrobiculata was recovered from asymptomatic stem tissue 2 cm below the inoculation site, indicating possible pathogen latency. These experiments indicate that there are more Botryosphaeriaceae fungi involved in coast redwood dieback than previously known and confirm the pathogenicity of D. scrobiculata on primary and secondary tissue of coast redwood.
(E)‐Trust and Its Function: Why We Shouldn't Apply Trust and Trustworthiness to Human–AI Relations
Authors: Al Pepijn
Published: August 2022

With an increasing use of artificial intelligence (AI) systems, theorists have analyzed and argued for the promotion of trust in AI and trustworthy AI. Critics have objected that AI does not have the characteristics to be an appropriate subject for trust. However, this argumentation is open to counterarguments. Firstly, rejecting trust in AI denies the trust attitudes that some people experience. Secondly, we can trust other non‐human entities, such as animals and institutions, so why can we not trust AI systems? Finally, human–AI trust is criticized based on a conception of human–human trust, which does not recognize the distinctiveness of the human–AI relationship. This article aims to refute these counterarguments based on the genealogical analyses of ‘trust’ and ‘trustworthiness’ of Karen Jones and Thomas Simpson, who show that trust and trustworthiness help to overcome vulnerabilities. This function of trust gives reason to use human–human trust as a standard. For this function, it is important that trustees are responsive to trust. While animals and institutions could be responsive, narrow AI systems are unable to be responsive to trust. Therefore, we should not apply trust to AI and instead direct our trust to those who can be responsive to and held responsible for our trust.
Permissive parenting mediates parental stress and child emotions in families of children with Down syndrome
Authors: Faught Gayle G. , Phillips B. Allyson , Conners Frances A.
Published: August 2022

Background

Parenting styles mediate parental stress and child emotions in families of typically developing (TD) children. Our main aim was to study these relations in families of children with Down syndrome (DS), who in past research reported increased parental stress and permissive parenting.

Method

Our sample included 100 parents of children with DS and 72 parents of TD children age 4–12 years. Parents completed online surveys of parental adjustment and emotion regulation (ER), parenting styles, and child ER and mood.

Results

Parents of children with DS reported more distress and permissive parenting than parents of TD children. Within parents of children with DS, there was an indirect effect of parental stress on child emotions through permissive parenting. This effect was partly conditional upon parental ER and positive adjustment.

Conclusions

Results have implications for distressed parents of children with DS whose families may benefit from improved coping strategies and increased support.
Butyrylcholinesterase distribution in the mouse gastrointestinal tract: An immunohistochemical study
Authors: Severi Ilenia , Abbatelli Silvia , Perugini Jessica , Di Mercurio Eleonora , Senzacqua Martina , Giordano Antonio
Published: August 2022

Butyrylcholinesterase (BChE) is a hydrolytic enzyme that together with acetylcholinesterase (AChE) belongs to the cholinesterase family. Whereas AChE has a well‐established role in regulating cholinergic neurotransmission in central and peripheral synapses, the physiological role of BChE remains elusive. In this morphological immunohistochemical and double‐label confocal microscopy study we investigated the distribution of BChE in the mouse gastrointestinal tract. BChE‐positive cells were detected in the liver (both in hepatocytes and cholangiocytes), in the keratinised layers of the squamous epithelium of the oesophagus and forestomach, in the oxyntic mucosa of the stomach, in the mucus‐secreting cells of duodenal Brunner glands and the small and large intestinal mucosa. Interestingly, BChE‐positive cells were often detected close to gastrointestinal proliferative niches. In the oxyntic mucosa, the close proximity of ghrelin‐producing and BChE‐positive parietal cells suggests that BChE may be involved in ghrelin hydrolysation through paracrine action. To our knowledge, this is the first comprehensive morphological study performed to gain insight into the physiological role of BChE in the gastrointestinal tract.
Unraveling the relation between vitiligo, Interleukin 17, and serum amyloid A
Authors: Ahmed Aliaa Abd Elsalam , Mikhael Nancy Wadie , Elfallah Asmaa Adel , Hamed Ahmed Mohammed
Published: August 2022

Background

There is debate concerning the precise etiopathogenesis of vitiligo. According to certain theories, a series of inflammatory responses that mediate the loss of melanocytes are caused by both cellular and humoral immune responses. It has also been demonstrated that Interleukin 17 (IL‐17) promotes melanocyte death and inhibits melanogenesis through different mechanisms. Serum Amyloid A (SAA) levels are over‐expressed in autoimmune diseases. Th17 cytokines are regulated by serum amyloid A proteins.

Aims

To measure serum levels of IL‐17 and SAA in vitiligo patients aiming to explain their possible role in disease pathogenesis and the other aim is to correlate their levels with disease activity and severity.

Methods

This study included 60 vitiligo patients and 40 healthy age and sex controls. Enzyme‐linked immunosorbent assay was used to measure serum levels of SAA and IL‐17.

Results

This study revealed significant increase in levels of serum IL‐17 and SAA in patients than controls (p < 0.05). Both markers showed significant positive correlations with VASI score and duration of vitiligo; only IL‐17 showed statistically significant positive correlation with VIDA scores. Patients with vitiligo showed a statistically significant positive connection between serum IL‐17 levels and SAA (γ = 0.992, p‐value <0.05).

Conclusion

Increased serum level of IL‐17 and SAA in vitiligo patients together with their positive relation to vitiligo severity and the duration of the disease show that these two markers play a key role in the vitiligo development.
Ostomy‐related problems and their impact on quality of life of Saudi ostomate patients: A mixed‐methods study
Authors: Alenezi Aishah , Livesay Karen , McGrath Ian , Kimpton Amanda
Published: August 2022

Aim and objective

The aim of this study is to explore the health‐related quality of life outcomes and ostomy‐related obstacles among patients with ostomy in Saudi Arabia.

Background

Negative effects on quality of life for patients following ostomy creation are a globally important health concern. Paucity of understanding factors that influenced quality of care after ostomy surgery hinders the ability of healthcare providers to offer appropriate care to improve patient's quality of care.

Methods

This mixed‐methods study was undertaken through survey (COHQOL‐Q Arabic version) for collecting the quantitative data (n = 421) and semi‐structured interview for collecting qualitative data (n = 12). This study employed STROBE and GRAMMS checklists.

Results

Multiple health‐related quality of life challenges was indicated by Saudi patients with intestinal stomas. Ostomy surgery interferes with religious practice in Muslim people, particularly obtaining Hajj worship and fasting for Ramadan. The overall QOL mean score was moderate level (M = 7.57) for ostomy patients in Saudi Arabia. The highest domain mean score was the social well‐being (M = 7.84) and the lowest in the physical well‐being (M = 7.18). Reshaping of religious practices, apprehension and adaptation to living with a stoma were the most common themes that participants discussed related to ostomy issues they experienced following ostomy surgery.

Conclusion

The study findings reported a greater understanding of challenges that patients with stoma experience in Saudi Arabia. The process of the adaptation and the change of their lifestyle also affects patient's quality of life. The healthcare providers can use the study results to create a supportive intervention strategy that needed for maximise QOL for people with stoma.

Relevance to clinical practice

This study identifies issues associated with stoma creation among Saudi people and can help in planning and providing the required nursing care which may support in the reduction of predictable problems. Recommendations for future studies related to nursing professional practice are indicated.
Digging into legal archaeology: a methodology for case study research
Authors: NOTTINGHAM EMMA
Published: August 2022

Traditional legal scholarship has been dominated by doctrinal analysis. When cases are analysed, attention has commonly focused upon the legal issues, judicial reasoning, and case outcome. However, alternative approaches can lead to new or different conclusions. Legal archaeology is a type of micro‐level case study research that examines a case in its socio‐historical context, using mainly original sources, to construct a more detailed case narrative than that presented in the case report. Rather than trying to fit newly discovered evidence to pre‐existing doctrine or respond to a research question, legal archaeology focuses on the subjective, variable nature of cases and captures their uniqueness. Reflecting on a legal archaeology study previously undertaken by the author in addition to existing works, this article emphasizes the importance of legal archaeology as a tool for case study research and suggests a four‐stage approach for the process of investigation that could be replicated by scholars in future.
Using the primal approach to derive the second‐best rules for different public services in a general competitive growth model
Authors: Jin Ge
Published: August 2022

In this paper we establish a general competitive growth model which includes public consumption services and public productive services, which are financed by capital and labor income taxes. By using the primal approach, we derive the second‐best rules for both types of public services and compare them with the conventional first‐best rules. Particularly, we find that the second‐best rule for public consumption generally differs from the conventional rule due to distortionary taxation. Whether the conventional rule represents an under‐ or over‐supply of public consumption depends on the form of preference. Finally, by solving a specific example theoretically and numerically, we show that the absolute difference of the first‐ and second‐best ratios of public‐to‐private consumption increases with an increase in distorting taxes as long as the two ratios differ.
DLK1‐directed chimeric antigen receptor T‐cell therapy for hepatocellular carcinoma
Authors: Zhai Yangyang , He Kunyan , Huang Liyu , Shang Xuyang , Wang Guangxing , Yuan Guandou , Han Ze‐Guang
Published: August 2022

Background

Delta‐like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1‐directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1‐positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy.

Methods

We first characterized a homemade anti‐human DLK1 monoclonal antibody, sequenced the single‐chain Fragment variable (scFv) and integrated it into the second‐generation CAR lentiviral vector, and then developed the DLK1‐directed CAR‐T cells. The cytotoxic activities of DLK1‐directed CAR‐T cells against different HCC cells were evaluated in vitro and in vivo.

Results

The genetically modified human T cells with the DLK1‐directed CARs produced cytotoxic activity against DLK1‐positive HCC cells. Additionally, the DLK1‐directed CARs enhanced T cell proliferation and activation in a DLK1‐dependent manner. Interestingly, the DLK1‐targeted CAR‐T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh‐7.

Conclusion

DLK1‐directed CAR‐T cells specifically suppresses DLK1‐positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR‐T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy.
Factors that influence women's engagement with breastfeeding support: A qualitative evidence synthesis
Authors: Bengough Theresa , Dawson Shoba , Cheng Hui‐Lin , McFadden Alison , Gavine Anna , Rees Rebecca , Sacks Emma , Hannes Karin
Published: August 2022

Breastfeeding is an integral part of early childhood interventions as it can prevent serious childhood and maternal illnesses. For breastfeeding support programmes to be effective, a better understanding of contextual factors that influence women's engagement and satisfaction with these programmes is needed. The aim of this synthesis is to suggest strategies to increase the level of satisfaction with support programmes and to better match the expectations and needs of women. We systematically searched for studies that used qualitative methods for data collection and analysis and that focused on women's experiences and perceptions regarding breastfeeding support programmes. We applied a maximum variation purposive sampling strategy and used thematic analysis. We assessed the methodological quality of the studies using a modified version of the CASP tool and assessed our confidence in the findings using the GRADE‐CERQual approach. We included 51 studies of which we sampled 22 for in‐depth analysis. Our sampled studies described the experiences of women with formal breastfeeding support by health care professionals in a hospital setting and informal support as for instance from community support groups. Our findings illustrate that the current models of breastfeeding support are dependent on a variety of contextual factors encouraging and supporting women to initiate and continue breastfeeding. They further highlight the relevance of providing different forms of support based on socio‐cultural norms and personal backgrounds of women, especially if the support is one‐on‐one. Feeding decisions of women are situated within a woman's personal situation and may require diverse forms of support.
Anaemia, anthropometric undernutrition and associated factors among mothers with children younger than 2 years of age in the rural Dale district, southern Ethiopia: A community‐based study
Authors: Kebede Tsigereda B. , Mengesha Selamawit , Lindtjorn Bernt , Engebretsen Ingunn Marie S.
Published: August 2022

Mothers in resource‐poor settings are affected by different forms of undernutrition. However, the nutritional status of mothers in rural areas, particularly after delivery, is not well documented. This study assessed haemoglobin levels and body mass index (BMI) of mothers with children below 2 years of age in a rural district of southern Ethiopia. Factors associated with low haemoglobin levels and low BMI were analysed. A community‐based cross‐sectional study was conducted among 931 mother‐child pairs. Structured and standard questionnaires were used to collect data on background information, 24 h dietary recalls, and household food insecurity. Anthropometric and haemoglobin level assessments were performed. Anaemia was defined as haemoglobin levels below 12.0 g/dl, and anthropometric undernutrition was defined as a BMI <18.5 kg/m2. Multilevel linear regression was used to determine associations. Out of 931 mothers, 12.8% were anaemic and 12.6% had a BMI <18.5 kg/m2. The prevalence of minimum dietary diversity was 37.8%. The majority (78.5%) of the households were food insecure. Weight (β 0.02; 95% CI: 0.003−0.03), dietary diversity (β 0.08; 95% CI: 0.03−0.12) and secondary school attendance (β 0.34; 95% CI: 0.08−0.59) were associated with the mothers' haemoglobin level. Dietary diversity (β 0.08; 95% CI: 0.01−0.16) and household's wealth (β 0.6; 95% CI: 0.27−0.94) were associated with the mothers' BMI. Findings suggest that education and community‐based nutrition interventions must be strengthened to ensure household food security. Implementation of the national food‐based strategies should be considered, to improve the dietary diversity and nutritional status of mothers.
Are Fiscal Multipliers Estimated with Proxy‐SVARs Robust?*
Authors: Angelini Giovanni , Caggiano Giovanni , Castelnuovo Efrem , Fanelli Luca
Published: August 2022

We estimate government spending and tax multipliers in the United States via a flexible proxy‐SVAR model, where identification is achieved by combining fiscal and non‐fiscal instruments with additional parametric restrictions. We find that, while the spending multiplier is robustly estimated to be larger than one across different models, the estimate of the tax multiplier is sensitive to the combination of instruments that we use. We unveil that the key factor behind these heterogeneous estimates is the assumption of orthogonality between total factor productivity (our main non‐fiscal proxy) and the tax shock. If this assumption is imposed, the tax multiplier is around one. If it is not imposed, the tax multiplier is three times as large. Our results point to the need of accounting for the large uncertainty surrounding the tax multiplier for the design of optimal fiscal policies.
Delayed medical care due to transportation barriers among US children with atopic dermatitis
Authors: Zheng David X. , Cwalina Thomas B. , Mulligan Kathleen M. , Gallo Marin Benjamin , O'Connell Katie A. , Shah Sonal D. , Kwatra Shawn G. , Mostaghimi Arash
Published: August 2022

Our objective was to examine the prevalence and predictors of delayed medical care due to transportation barriers among children with atopic dermatitis (AD) living in the United States (US). We analyzed data from the 1998–2018 National Health Interview Survey, a nationally representative survey of US households. In 2018, transport‐delayed care was reported for 3.4% of US children with AD, representing approximately 279,000 children annually given the National Health Interview Survey's weighted survey design, and was more common among patients of lower socioeconomic status. Targeted interventions aimed at reducing transportation barriers to healthcare among at‐risk AD patients may reduce health disparities related to AD.
Changes in arterial blood vessels and VEGF and Ang‐1 expression in pregnant and non‐pregnant yak uterine caruncle
Authors: Long Min , Cui Yan , Pang Xin , Wang Biao , He Junfeng , Zhang Qian , Yu Sijiu , Bai Xuefeng
Published: August 2022

We investigated the structural features of arterial blood vessels in yak uterine caruncle and the effects of the expression of vascular regulation‐related factors on angiogenesis in pregnant and non‐pregnant yak uterus. Three‐dimensional specimens of the uterine artery of non‐pregnant and pregnant yaks were produced to observe and measure the distribution characteristics and number of arterial vessels in the uterus and caruncle in the two periods. The uterine caruncle structure was observed and analysed by haematoxylin–eosin staining. The expression features of vascular endothelial growth factor (VEGF) and angiopoietin‐1 (Ang‐1) in the uterine caruncle were detected with immunohistochemistry, quantitative real‐time PCR (qRT‐PCR) and western blotting. The length and number of blood vessels in the caruncle were increased, the degree of curvature was decreased, and the folding was more complicated during pregnancy as compared with that during non‐pregnancy. The immunohistochemical results demonstrated that VEGF and Ang‐1 were mainly expressed strongly in the mucosal epithelial cytoplasm. The glandular lumen of the uterine gland, lymphocytes and the media and adventitia of blood vessels are widely distributed, and they are all positive. VEGF and Ang‐1 mRNA and protein levels were highest in pregnancy, followed by that in the luteal phase and in the follicular phase, and three stages were significantly different (p < .05). These findings provide an anatomical reference and theoretical basis for improving the diagnosis and treatment of yak reproductive disorders and other diseases in high‐altitude and low‐oxygen environments.
Linebreeding as a system of stock breeding to improve the productive qualities of horses of the Kushum breed
Authors: Rzabayev Tolybek S. , Assanbayev Tolegen Sh. , Rzabayev Serikbay , Bazargaliyev Alibek , Rzabayev Kalybek S.
Published: August 2022

Possessing high meat and dairy productivity and good reproductive and adaptive qualities to year‐round grazing, the Kushum breed plays an exceptional role in the improvement of productive qualities in horse herding in Kazakhstan and the former Soviet republics. The aim of the study was to develop breeding methods for creating new highly productive breeding lines for the Kushum breed horses. The leading method was linebreeding, which is based on the systematic use of remarkable animals, the offspring of which will accumulate and develop all the desired qualities and traits. The practical significance of the study lies in the fact that new highly productive breeding lines of the Kushum horse have been created. On this basis, a new intra‐breed type of horses with increased live weight, high productivity and adaptive qualities for winter grazing in the Republic of Kazakhstan was created. The results of the study were introduced in farms engaged in breeding Kushum horses. Highly productive stallions of the Kushum breed of new genotypes are sold in horse breeding farms of the republic. These studies are used in the development of a comprehensive plan for selection and breeding work and a scientifically grounded system for conducting productive horse breeding in the Republic of Kazakhstan. The scientific novelty of the study lies in the creation of new highly productive breeding lines of stallions of the Kushum breed Krepysh and Grom, as well as in substantiating the creation of the Samotsvet line with high adaptive qualities.
Identification of the novel HLA‐DQB1*04:02:01:18 allele in a Maharashtrian individual from India
Authors: D'Silva Selma Z. , Tambe Manisha , Pinto Andrea , Singh Meenakshi
Published: August 2022

The novel allele HLA‐DQB1*04:02:01:18 differs from HLA‐DQB1*04:02:01:04 by a nucleotide change at position; gDNA 2789 A → G.
User‐centered road network traffic analysis with MobilityDB
Authors: Sakr Mahmoud , Zimányi Esteban , Vaisman Alejandro , Bakli Mohamed
Published: August 2022

Performance indicators of road networks are a long‐lasting topic of research. Existing schemes assess network properties such as the average speed on road segments and the queuing time at intersections. The increasing availability of user trajectories, collected mainly using mobile phones with a variety of applications, creates opportunities for developing user‐centered performance indicators. Performing such an analysis on big trajectory data sets remains a challenge for the existing data management systems, because they lack support for spatiotemporal trajectory data. This article presents an end‐to‐end solution, based on MobilityDB, a novel moving object database system that extends PostgreSQL with spatiotemporal data types and functions. A new class of indicators is proposed, focused on the users' experience. The indicators address the network design, the traffic flow, and the driving comfort of the motorists. Furthermore, these indicators are expressed as analytical MobilityDB queries over a big set of real vehicle trajectories.
A pulmonary endothelial amplification loop aggravates ex‐vivo transfusion‐related acute lung injury via increased toll‐like receptor 4 and intra‐cellular adhesion molecule‐1 expression
Authors: Morsing Sofia K. H. , Zeeuw van der Laan Eveline , van Stalborch Annemarieke D. , van Buul Jaap D. , Kapur Rick , Vlaar Alexander P.
Published: August 2022

Background

Transfusion‐Related Acute Lung Injury (TRALI) is a life‐threatening complication of blood transfusions characterized by pulmonary endothelial cell damage and edema, with a high incidence in critically ill patients. The pathophysiology of TRALI is unresolved, but can generally be hypothesized to follow a 2‐hit model in which the first hit is elicited by the underlying clinical condition of the patient (e.g., inflammation, which can be reflected by LPS in experimental models), and the second hit is delivered by the blood transfusion product (e.g., HLA class I antibodies). Here, we report a synergistic role for LPS and HLA class I antibody binding to pulmonary endothelium resulting in enhanced inflammatory responses.

Materials and Methods

Pulmonary endothelial cells were treated with PBS or low‐dose LPS, exclusively or in combination with anti‐HLA class I. Endothelial surface expression of HLA class I, TLR4, and inflammatory marker ICAM‐1 were measured, and trans‐endothelial migration (TEM) of neutrophils was investigated.

Results

LPS treatment of pulmonary endothelium enhanced HLA class I antibody binding, and combined LPS and HLA class I antibody binding enhanced TLR4 (LPS receptor) and ICAM‐1 expression on the endothelial cell surface. Low‐dose LPS and HLA antibody together also increased neutrophil TEM under physiological flow by on average 5‐fold.

Conclusion

We conclude that LPS and anti‐HLA class I antibody have the ability to activate the pulmonary endothelium into a spiral of increasing inflammation, opening the opportunity to potentially block TLR4 to prevent or reduce the severity of TRALI in vivo.