bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Specific Targets for the Member States to Achieve the European Union's Goal of 50 per cent Reduction in Sales of Veterinary Antimicrobials by 2030
Authors: Beber Caetano Luiz , Aragrande Maurizio , Canali Massimo
Published: September 2024

This article proposes a tailored approach to reduce antimicrobial use (AMU) in livestock among EU countries, in alignment with the EU Farm‐to‐Fork initiative that targets a 50 per cent reduction by 2030. We argue against a one‐size‐fits‐all target and introduce country‐specific targets based on individual factors such as current antimicrobial sales, GDP, and livestock and human densities. Using data from the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), the article identifies countries with high densities of animals and humans, as well as high levels of AMU per livestock unit, such as Germany, Belgium, Italy, Spain and Poland, as needing to prioritise greater reduction efforts. The article also underlines the need for a more precise EU‐level indicator of AMU, as sales do not directly represent use. It suggests that specific targets and regulations should apply to antimicrobials classified as ‘Highest Priority Critically Important Antimicrobials’ by the WHO. The article recommends extending these targets to different sectors and even individual farms, with high‐consumption sectors and poorly performing farms making greater efforts. By considering these factors, the article aims to provide a fair and effective approach to reducing AMU, mitigate the risks associated with antimicrobial resistance, and contribute to achieving the Farm‐to‐Fork strategy AMU reduction target.
How do plant‐based milks compare to cow's milk nutritionally? An audit of the plant‐based milk products available in Australia
Authors: Harmer Isobel , Craddock Joel C. , Charlton Karen E.
Published: September 2024

Aim

This cross‐sectional study aims to explore the nutritional composition, cost, country of origin and fortification status of plant‐based milk products available for purchase in Illawarra supermarkets and make various comparisons between types of plant‐based milks and cow's milk.

Methods

Plant‐based milk information was collected from nutrition information panels on packaging and manufacturer websites. Product ingredient lists, including fortifiers, were analysed to estimate the nutrient composition of the identified plant‐based milks, including nutrients beyond those listed by manufacturers. Descriptive statistics were used to summarise the characteristics of the plant‐based milks identified in the audit. For non‐normally distributed data, a Kruskal–Wallis H test with pairwise multiple comparisons and a Bonferroni adjustment were undertaken to explore the differences between various types of plant‐based milk and cow's milk.

Results

One hundred twenty‐nine plant‐based milk products were identified in the audit, primarily almond, oat and soy‐based beverages. Of these, 80.6% were fortified with calcium; however, fortification with other micronutrients was less common, ranging from 27.1% being fortified with vitamin B12 and 3.1% being fortified with iodine. The median plant‐based milk cost was AU$3.5/L (Q1–Q3: AU$2.8–4.5/L) and 87.6% of products were Australian made. Overall, particularly due to low fortification rates, plant‐based milks identified in the audit had significantly lower levels of protein, sugar, iodine, phosphorus, zinc and vitamins A, B2 and B12 compared to cow's milk. However, there was no significant difference in protein content between soy milk and cow's milk.

Conclusions

The nutritional content of plant‐based milks identified in this audit varied, and in most instances, Australian plant‐based milks were found to be nutritionally different to cow's milk.
Vachellia xanthophloea, a New Native–Alien Tree Species Along the Orange River in Southern Namibia
Authors: Cunningham Peter Low , Cunningham Peter Low
Published: September 2024

Vachellia xanthophloea is often observed as a garden ornamental tree in gardens in towns and lodges throughout Namibia. Escapee plants were observed along the Orange River between Komsberg and Sendelingsdrift in southern Namibia and have insidiously invaded the riparian habitat without notice. It is viewed as a native–alien population and may detrimentally affect the local riparian ecology, therefore recommended that eradication be implemented immediately.
Board Gender Diversity and Workplace Safety: Evidence From Quasi‐Natural Experiments
Authors: Haidar Md Ismail , Hossain Saha Iqbal
Published: September 2024

Research Questions/Issue

This paper examines the impact of board gender diversity on workplace safety in an international setting from 2002 to 2019. Utilizing gender quotas on corporate boards as a quasi‐natural experiment, we explore the causal effects of gender diversity on workplace safety, highlighting the significant influence of corporate board gender quotas on corporate policies.

Research Findings/Results

Using a sample of 13,124 firm‐year observations from 48 countries, our findings reveal that gender quotas on corporate boards are linked to higher rates of work‐related injuries. The association is particularly strong in financially constrained firms, as well as in those with high workloads and low investments in workplace safety. In contrast, this effect is mitigated in firms located in countries with strong institutional frameworks and high union representation. The results hold across various regression specifications and remain robust when considering different measures of workplace injuries, board gender diversity, and additional control variables.

Theoretical Implications

Our study draws on gender behavior theory, social role theory, and gender socialization theory, with findings particularly aligning with gender behavior theory. It advances understanding of how changes in corporate governance structures related to board diversity influence workplace safety. This research underscores the importance of further empirical work to expand this area of study, suggesting valuable directions for future research through cross‐sectional and longitudinal analyses.

Practical Implications

The findings provide critical insights for policymakers considering the implementation of gender quotas in boardrooms. Additionally, this research highlights the need for further exploration of unexamined aspects within governance studies, which will significantly influence future policy debates, legislative processes, and corporate practices in promoting gender diversity and enhancing workplace safety.
Mendelian randomization analysis of the association between childhood overweight or obesity and gestational diabetes mellitus
Authors: Jiang Huaiyan , Zhang Kun , Zhang Xi
Published: September 2024

Objective

To investigate the association between childhood overweight or obesity and gestational diabetes mellitus (GDM).

Methods

Data were sourced from the Genome‐Wide Association Studies database on childhood body mass index (BMI), with 39 620 samples and 8 173 382 single‐nucleotide polymorphisms (SNPs), and GDM, with 143 441 samples, including 12 332 GDM cases and 20 149 608 SNPs. Mendelian randomization (MR) was conducted, including inverse variance weighting (IVW), MR‐Egger regression, and the weighted median method. Statistical heterogeneity among SNPs was assessed using Cochran's Q test. MR‐Egger's intercept, the MR‐Pleiotropy RESidual Sum and Outlier (PRESSO) test, and funnel plots were used to evaluate pleiotropy. The leave‐one‐out method tested the robustness of the IVW results by excluding individual SNPs.

Results

Fifteen SNPs highly related to childhood BMI were identified. IVW analysis indicated that higher childhood BMI is a significant risk factor for GDM (odds ratio 1.50 [95% confidence interval 1.20–1.87]; p < 0.001). The direction of the β value derived from the weighted median method analysis was consistent with that from the IVW analysis. Cochran's Q test showed statistical heterogeneity among SNPs highly related to childhood BMI (p = 0.001), thus prioritizing IVW analysis results. The MR‐Egger regression intercept, MR‐PRESSO test, and funnel plot analyses demonstrated no horizontal pleiotropy among SNPs highly related to childhood BMI. The leave‐one‐out analysis indicated that the MR analysis results were largely unchanged after the exclusion of individual SNPs.

Conclusion

Elevated childhood BMI is associated with an increased risk of developing GDM, underscoring the need to address childhood obesity as a preventive strategy. Effective interventions to reduce childhood obesity could be crucial in mitigating this risk.
POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic‐atonic seizures and ataxia
Authors: Symonds Joseph D. , Park Kristen L. , Mignot Cyril , Macleod Stewart , Armstrong Martin , Ashrafian Houman , Bernard Geneviève , Brown Kathleen , Brunklaus Andreas , Callaghan Mary , Classen Georg , Cohen Julie S. , Cutcutache Ioana , de Sainte Agathe Jean‐Madeleine , Dyment David , Elliot Katherine S. , Isapof Arnaud , Joss Shelagh , Keren Boris , Marble Michael , McTague Amy , Osmond Matthew , Page Matthew , Planes Marc , Platzer Konrad , Redon Sylvia , Reese James , Saenz Margarita , Smith‐Hicks Constance , Stobo Daniel , Stockhaus Christian , Vuillaume Marie‐Laure , Wolf Nicole I. , Wakeling Emma L. , Yoon Grace , Knight Julian C. , Zuberi Sameer M.
Published: September 2024

Objective

POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non‐coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures.

The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants.

Methods

We used online gene‐matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas.

Results

All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic‐atonic, atypical absence, or tonic‐clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic‐atonic seizures (EMAtS) in seven patients and “probable EMAtS” in two more.

Seizures were treatment resistant in all cases. Three patients became seizure‐free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset.

Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3).

Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13).

Significance

POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients.
Gender gap in investment performance revisited: The role of attention
Authors: Davydov Denis , Eskner Karl , Peltomäki Jarkko
Published: September 2024

This paper revisits the effect of gender on portfolio performance, exploring the hypothesis that investors may derive fewer benefits from increased financial attention due to disparities in financial confidence. Using data from trading accounts of over 745,000 investors, we find that the difference in investment performance between men and women depends on the level of attention that they pay to their portfolios. Furthermore, our results indicate that the positive effects of investor attention are primarily attributable to young men, who appear to benefit the most from heightened attentiveness.
An urbanized phantom tributary subsidizes river–riparian communities of a mainstem gravel‐bed river
Authors: Negishi J. N. , Song Y. Y. , Matsubara I. , Morisaki N.
Published: September 2024

Urbanization transforms natural river channels, and surface water of some rivers disappeared over time. How and whether the subsurface domains of the original waterways and aquifers connecting them (a phantom of historical landscape) are functional is not known. This study examined the effects of tributary groundwater inflow on the response of river–riparian organisms in an alluvial mainstem river in northern Japan, where the tributary disappeared over the course of urban landscape transformation.

A 2.8‐km lowland segment of the mainstem gravel‐bed river was examined for water properties and the river–riparian food web. In addition, watershed‐wide water sampling was conducted to isotopically distinguish several types of groundwater that contributed to the hyporheic water in the study segment. Altitude had a clear effect on the hydrogen/oxygen stable isotope ratios in the river water collected across the watershed.

Groundwater unique both in chemical and isotopic signatures occurred in several spots within the study segment, and its properties resembled and its upwelling locations matched groundwater from a tributary river whose surface channel disappeared 60 years ago. Positive numerical increases in abundance and/or a sign of nitrogen transfer in river–riparian communities (algae, invertebrates and riparian trees) originating from groundwater high in nitrate with elevated nitrogen stable isotope ratios were found.

We demonstrated that tributary groundwater with unique chemical properties manifested by an urban watershed river network continued to have trophic effects on biota across the river–riparian boundary in the mainstem river, even after urbanization transformed the tributary into a phantom river. We highlighted the legacy effects of landscape transformation in the subsurface domain and the significance of scrutinizing the past landscape and hydrological connectivity at the watershed scale in urban environments.
Exploring the Safewards Programme to Reduce Restrictive Practices in Residential Aged Care: Protocol for a Pilot and Feasibility Study
Authors: Dawson Suzanne , Oster Candice , Page Michael , George Stacey
Published: September 2024

Introduction

Restrictive practice use in residential aged care homes internationally is unacceptably high. Although policies and legislation mandate the reduction or elimination of restrictive practices, there remains a gap in knowledge regarding strategies that have been effective in achieving a sustained reduction in restraint use. There is an urgent need to identify effective and feasible interventions that aged care staff can implement in everyday practice to reduce restraint use. Safewards is an evidence‐based programme that has demonstrated effectiveness in reducing conflict and restrictive practice use in inpatient psychiatric settings and has the potential to address the issue of restraint use in aged care homes. This study aims to evaluate the feasibility of Safewards in reducing restrictive practices in residential aged care homes.

Methods

This pilot and feasibility study will adopt a mixed methods process and outcomes evaluation. Safewards will be implemented in two Australian residential aged care homes. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will be used to evaluate implementation outcomes. Additionally, the Consolidated Framework for Implementation Research will be used to guide qualitative data collection (including semi‐structured interviews with residents/family members, aged care leaders and staff) and explain the facilitators and barriers to effective implementation.

Conclusion

This study will provide pilot evidence on the feasibility of the Safewards programme in residential aged care homes. Understanding the processes and adaptations for implementing and evaluating Safewards in residential aged care will inform a future trial in aged care to assess its effectiveness. More broadly, the findings will support the implementation of an international aged care policy of reducing restrictive practices in residential aged care.

Patient or Public Contribution

A person with lived experience of caring for someone with dementia is employed as a Safewards facilitator and is a member of the steering committee. Residents and family members will be invited to participate in the project steering committee and provide feedback on their experience of Safewards.

Trial Registration

ACTRN12624000044527.
How maternal factors shape the immune system of breastfed infants to alleviate food allergy: A systematic and updated review
Authors: Wu Yuhong , Chen Bihua , Wu Huan , Gao Jinyan , Meng Xuanyi , Chen Hongbing
Published: September 2024

What infants eat early in life may shape the immune system and have long‐standing consequences on the health of the host during later life. In the early months post‐birth, breast milk serves as the exclusive and optimal nourishment for infants, facilitating crucial molecular exchanges between mother and infant. Recent advances have uncovered that some maternal factors influence breastfed infant outcomes, including the risk of food allergy (FA). To date, accumulated data show that breastfed infants have a lower risk of FA. However, the issue remains disputed, some reported preventive allergy effects, while others did not confirm such effects, or if identified, protective effects were limited to early childhood. The disputed outcomes may be attributed to the maternal status, as it determines the compounds of the breast milk that breastfed infants are exposed to. In this review, we first detail the compounds in breast milk and their roles in infant FA. Then, we present maternal factors resulting in alterations in breast milk compounds, such as maternal health status, maternal diet intake, and maternal food allergen intake, which subsequently impact FA in breastfed infants. Finally, we analyze how these compounds in breast milk alleviated the infant FA by mother‐to‐infant transmission. Altogether, the mechanisms are primarily linked to the synergetic and direct effects of compounds in breast milk, via promoting the colonization of gut microbiota and the development of the immune system in infants.
Global prevalence of teething problems in infants and children—A systematic review and meta‐analysis
Authors: Garima Jhunjhunwala , Mathur Vijay Prakash , Tewari Nitesh , Rahul Morankar , Sultan Farheen , Haldar Partha , Bansal Kalpana , Upadhyay Ashish Datt
Published: September 2024

Background

Eruption of primary teeth is associated with local and systemic manifestations. Understanding the global prevalence is necessary to formulate the standard guidelines for management.

Aim

To evaluate the global prevalence of problems associated with teething in infants and children aged 0–36 months.

Design

PubMed, LILACS, Web of Science, Scopus, and EMBASE were searched on May 31, 2023, and it was updated on January 31, 2024. Gray literature and reference search were performed. Cross‐sectional, case–control, and cohort studies done in hospital or community settings, reporting the prevalence of signs and symptoms during the eruption of primary teeth in infants aged 0–36 months, were included. Two reviewers extracted data using a pre‐piloted sheet. Data were analyzed and pooled by using random‐effects meta‐analyses.

Results

Twenty‐five studies were included. The global prevalence of teething problems was 80.0% (95% confidence interval [CI]: 67.8–89.9). The most common local symptom was increased biting (65.9%, 95% CI 37.5–89.3), and irritability (60.7%, 95% CI 50.6–70.3) was the most common general symptom.

Conclusion

The pooled prevalence of teething problems was estimated to be 80%. There was a variability in the prevalence of teething problems based on geographic location.
Hepatic retransplantation: University of Nebraska Medical Center experience
Authors: Saito S. , Langnas A. N. , Stratta R. J. , Wood R. P. , Shaw B. W. , Matsuno T. , Markin R. S.
Published: September 2024

The lack of an artificial liver makes liver retransplantation a unique, life‐saving procedure when all the other alternatives to save a failed graft have been exhausted. On the other hand, the shortage of donors in line with the increasing number of end‐stage liver disease patients who are waiting in long recipient lists represents a dilemma and raises the question of most appropriate recipient selection. In this report, we retrospectively analyzed the results of 350 primary, 48 secondary, and 5 tertiary hepatic transplants performed between July 1985 and January 1990 at University of Nebraska Medical Center. The same immunosuppression protocol was used in each case and the maintenance immunosuppressive therapy consisted of cyclosporine (CyA) and steroids. The overall survival rate of 80.5% at 1 year which was achieved in the primary grafting group was significantly better than the secondary grafting group (63.0%, p<0.05). However, this difference was not significant in pediatric patients and their survival rates were 73.8% and 71.6% in primary and secondary grafting groups, respectively. When the retransplanted patients were considered as deaths unless secondary grafting was performed, the overall patient survival rate of 69.7% in primary grafting group at 1 yr increased to 77.8% in the retransplanted group and this difference was significant (p<0.05). Blood loss and operating time were found to be lower in the retransplanted group. Furthermore, the decrease of the operating time in the retransplanted pediatric patients reached statistical significance (p<0.05). Retransplantation of the liver, when compared with primary grafting, was not associated with any further technical difficulties and in the light of our results appeared to be even less troublesome, particularly in early retransplants. In conclusion, we believe that retransplantation of the liver has a significant impetus on patient survival and there are firm grounds for optimism about its future.
Complex partial seizure, an unusual complication of cyclosporine in renal transplantation
Authors: Arora P. , Kohli A. , Kher V. , Sharma R. K. , Gupta A. , Bhandari M.
Published: September 2024

We report a case of a renal allograft recipient who developed complex partial seizure at a maintenance dose of cyclosporine, which reversed following cyclosporine withdrawal. This type of seizure at low dose (2.5 mg/kg) has not been reported previously.
Extracorporeal shock wave lithotripsy in the renal transplant patient: A case report and review of literature
Authors: Rhoderick Traci M. , Yang Harold C. , Escobar Francisco S. , Belis John A. , Gifford Robert R. M.
Published: September 2024

Renal allograft lithiasis is a rare complication of renal transplantation, which in the past has required various invasive procedures for adequate stone fragmentation and dissolution. Noninvasive techniques such as extracorporeal shock wave lithotripsy (ESWL) can now be extended to the renal transplant patient. Five cases have been previously reported in which ESWL was used effectively for dissolution of renal allograft calculi. We now report a 6th case in which a calculus, initially identified 2 weeks after renal transplantation, was effectively fragmented 3 years later using ESWL. Based on our experience and the reviewed composite experience in the literature, ESWL is a safe therapy for renal allograft calculi.
Appropriate allocation of pediatric donor kidneys
Authors: Kockelbergh R. C. , Francis D. M. A. , Millar R. J. , Walker R. G. , Jones C. , Becker G.
Published: September 2024

Optimal allocation of pediatric donor kidneys is controversial. We reviewed the outcome of transplanting pediatric donor kidneys into children and adults, together with the outcome of transplanting adult kidneys into adults and children, with the aim of identifying the most appropriate donor‐recipient combinations. Three‐year graft survival was 73% in 23 adults transplanted with pediatric kidneys, 87% in 23 adults given adult kidneys, 93% in 15 children who received adult kidneys, but only 64% in 11 children who received pediatric kidneys (p <0.05). All single kidneys from donors less than 2.5 years of age failed because of acute rejection early after transplantation. The study does not support the allocation of pediatric kidneys specifically to children and questions the use of single kidneys from very small donors.
Characterization of cellular human anti‐porcine xenoreactivity
Authors: Kumagai‐Braesch Makiko , Satake Masahiro , Korsgren Olle , Andersson Arne , Möller Erna
Published: September 2024

The cellular xenoimmune reactivity of human responder cells reactive against porcine stimulator cells has been characterized. The xenogeneic mixed lymphocyte bulk culture reactivity is slightly lower than the allogeneic response but peak reactivity occurs with similar kinetics and secondary responses of primed lymphocytes are comparable. The xeno‐MLR was directed against pig MHC class II molecules as indicated by blocking using specific monoclonal antibodies. Production of IL‐2 was delayed and significantly lower in the xeno‐MLR. The low proliferative xenoresponse could not be restored by the addition of human IL‐2. Characterization of lymphoblasts and of small lymphocytes derived from xcno‐ and from allogeneic mixed cultures showed that xeno‐ and alloreactivity involves similar proportions of CD4+, CD8+ and CD3+ cells and that similar frequencies of responder cells expressed HLA‐DR and CD25 in the two test systems. Determinations of proliferative and of cytotoxic lymphocyte precursor frequencies demonstrated that the proliferative xenoreactivc responder cells were approximately 10‐fold lower but the frequency of cytotoxic precursor cells considerably higher than the allogeneic precursors. Similar tests were performed on enriched lymphocyte subpopulations. Both allo‐ and xenospecific proliferative reactivity was approximately 10 × higher in the population of CD4+ cells compared to the CD8+ population. However, tests for cytotoxic precursors showed that xenoreactive cells were more frequent than alloreactive cells; this was true for both the CD8+ and the CD4+ cell populations. We conclude that human anti‐porcine xenoreactivity shares major characteristics with allogeneic responses but also that there exist differences that need to be elucidated further.
Characterization of humoral human anti‐porcine xenoreactivity
Authors: Satake Masahiro , Kumagai‐Braesch Makiko , Korsgren Olle , Andersson Arne , Möller Erna
Published: September 2024

The presence and specificity of natural xenoreactive human anti‐pig antibodies was studied. Titers of cytotoxic antibodies reactive with porcine blood lymphocytes were similar in sera from healthy controls, patients with high titers of HLA alloantibodies, uremic patients, diabetic uremic patients, kidney allografted patients on maintenance immunosuppressive therapy, patients who had been splenectomized and in bone marrow transplanted patients 6 months after transplantation. Similar titers were also recorded in patients with various autoimmune disorders, such as SLE and RA; there was no correlation to autoantibody titers. Furthermore, we found no correlation to natural isohemagglutinins; absorption with adequate human red cells did not reduce activity. However, absorption with pig red blood cells reduced the titer significantly and absorption with pig platelets completely abolished reactivity. Finally, antibodies were also present in cord blood samples indicating an endogenous ligand as an activating substance for antibody production. Most sera contained only IgM cytotoxic antibodies, but some also had a weak non‐IgM cytotoxic titer. Fluorescence studies with pig blood lymphocytes indicated that even sera that did not contain non‐IgM cytotoxic antibodies had IgG and IgA antibodies reactive with pig cells. Direct immunofluorescence experiments were also carried out to demonstrate the presence of target structures for naturally reactive antibodies on fetal pig islet cells. Pig blood lymphocytes were sensitive to ADCC‐mediated killing by IgG natural antibodies, whereas fetal pig islet cells were resistant. However, using adequate positive controls, such as anti‐pig MHC class I antibodies, it was shown that fetal pig islet cells can be sensitive to ADCC‐mediated killing. Finally, lysostrip and fluorostrip experiments were performed to test whether pig MHC antigens contain target determinants, possibly as oligosaccharide side chains, for natural antibodies. We found that pig MHC class I antigens do not contain such determinants.
Relief of hepatic vein stenosis by balloon angioplasty after living‐related donor liver transplantation
Authors: Egawa Hiroto , Tanaka Koichi , Uemoto Sinjl , Someda Hitoshl , Moriyasu Fuminori , Sano Kaoru , Nishlzawa Fumio , Ozawa Kazue
Published: September 2024

We have experienced 5 hepatic vein stenoses in 3 children (8 to 23 months old) after living‐related liver transplantation (total 48 liver transplants for 48 children between June 1990 and November 1992). The initial symptoms of hepatic vein stenosis were ascites and/or edema. The blood flow of hepatic vessels was monitored by duplex sonography. The mean velocity of the hepatic vein and the portal vein was decreased and flow wave pattern of the stenotic hepatic vein was flat. The patients were treated by percutaneous transhepatic balloon angioplasty. After a successful angioplasty, the mean velocity of the hepatic vein and portal vein increased and pulsatile waves returned to the hepatic vein. Arterial ketone body ratio (acetoacetate/3‐hydroxybutylate) increased, promptly followed by recovery of other liver function tests. In 1 patient, this complication occurred three times with intervals of 7 months and 3 months between episodes of hepatic vein stenosis. In conclusion, hepatic vein flow should be monitored routinely with duplex sonography after living‐related donor liver transplantation. Percutaneous transhepatic balloon angioplasty is a primary treatment for the stenosis.
OKT3: Immunology, production, purification, and pharmacokinetics
Authors: Roitt Ivan M.
Published: September 2024

OKT3 is a monoclonal antilymphocyte antibody produced by a murine hybridoma technique. It differs from polyclonal antilymphocyte antibody preparations in that it is specific for one epitope of the T lymphocyte and is a pure product with batch‐to‐batch standardization. OKT3 binds to the CD3/T‐cell receptor complex, which is located on the surface of mature T lymphocytes and is involved in antigen recognition and cell activation. It appears to produce its potent immunosuppressant effect by: 1) opsonization of circulating T cells; 2) modulation of the CD3/T‐cell receptor complex on T cells; and possibly 3) T‐cell apoptosis. OKT3 also activates T cells and produces the cytokine release syndrome observed with first‐time administration of the drug. OKT3 has a half‐life of approximately 18 h, far shorter than that of human immunoglobulin.
Late recurrence of Wegener's granulomatosis presenting as tracheal stenosis in a renal transplant patient
Authors: Boubenider S. A. , Akhtar M. , Alfurayh O. , Algazlan S. , Taibah K. , Qunibi W.
Published: September 2024

An unusual case of a 46‐year‐old man who had end‐stage renal disease due to crescenlic glomerulonephritis that was treated by a cadaveric renal allograft is presented. About 18 months post‐Tx, the patient developed severe tracheal stenosis which, on biopsy, revealed granulation tissue and chronic inflammation. After another 18 months he developed necrotizing glomerulonephritis involving the renal allograft and an inflammatory retro‐orbital pseudotumor. The latter, on biopsy, revealed granulomatous vasculitis characteristic of Wegener's granulomatosis. This diagnosis was further confirmed by strongly positive anti‐ncutrophil antibodies with diffuse granular cytoplasmic immunofluorescence (C‐ANCA). The patient was treated successfully with cyclophosphamide therapy.
Intraoperative increment of platelet‐activating factor in clinical liver transplantation
Authors: Hashikura Yasuhiko , Kawasaki Seiji , Matsunami Hidetoshi , Ikegami Toshihiko , Makuuchi Masatoshi
Published: September 2024

Recent studies have shown that platelet‐activating factor (PAF) is involved in ischemia/reperfusion injury to the liver. We therefore examined changes in PAF in recipients during liver transplantation. The level of PAF increased after portal venous reperfusion, except in one case where veno‐venous bypass was applied. A marked elevation was noted in another case where portal congestion occurred due to outflow block, followed by prolonged graft dysfunction. These results suggest that elevation of the PAF level is related to portal congestion, and that PAF might be involved in postoperative liver graft dysfunction.
Correlation of serum basic fetoprotein with acute rejection in kidney transplantation
Authors: Seguchi T. , Nakano E. , Kameoka H. , Takahara S. , Namiki M. , Ishibashi M. , Okuyama A.
Published: September 2024

We monitored serum BFP, a broad‐spectrum tumor marker, in 36 patients with kidney transplantation. Scrum BFP was elevated in close association with acute rejection and dropped to a normal level after reversal of rejection. As Western blot analysis has revealed that BFP is present in the normal kidney, it is believed that serum BFP may be useful for the detection of various types of renal damage such as acute rejection.
Monitoring of the cellular immune system in patients with biventricular assist devices awaiting cardiac transplantation
Authors: Hummel Manfred , Döcke Wolf‐Dietrich , Friedel Norbert , von Baehr Rüdiger , Hetzer Roland , Volk Hans‐Dieter
Published: September 2024

Lack of objective parameters to predict the clinical course and outcome are a major problem in managing the patients selected for BVAD‐support as a bridge to heart transplantation. This study was intended to assess whether cellular immune parameters have a predictive value for the clinical result of VAD‐support. Various cellular immune markers were monitored by multiparameter cytofluorometry in 30 patients who received a VAD system (Berlin Heart). We did not find significant differences in preoperative values of immune parameters between groups of survivors (n= 14) and non‐survivors (n= 16). All 9 patients who died of septic multiple organ failure (MOF) had shown increased levels of T‐cell activation (CD 71, CD 25, HLA‐DR) as well as leukocytosis and 7 patients who died of noninfectious complications (mostly hemorrhage or cerebral complications) had exhibited T‐lymphopenia. Seven of 9 patients who died of septic MOF had extremely decreased levels of HLA‐DR+ monocytes (<30%) while all 14 survivors and all 7 patients who died of noninfectious complications showed almost normal monocytic HLA‐DR antigen expression, antigen‐presenting capacity and cytokine secretion. These observations point to the reduced antimicrobial immunity (“immunoparalysis”) in the non‐survivors and may explain the fatal course of infection in these individuals. The in vitro results of restitution experiments call for new therapeutic strategies to improve the survival of VAD‐patients.
Treatment of the Budd‐Chiari syndrome with orthotopic liver transplantation and long‐term anticoagulation
Authors: Knoop M. , Lemmens H.‐P. , Bechstein W. O. , Blumhardt G. , Schattenfroh N. , Keck H. , Neuhaus P.
Published: September 2024

The Budd‐Chiari syndrome (BCS) with hepatic vein occlusion is a rare disorder that can effectively be treated with orthotopic liver transplantation. In this retrospective analysis we report on 7 patients who received 9 liver grafts for terminal BCS. One patient died after 4 months due to cytomegalovirus‐pneumonia. The actuarial survival rate is 85.7% compared to more than 90% in all other 376 patients transplanted between September 1988 and April 1993 at our institution. Anticoagulation management consisted of early postoperative intravenous heparin and continuation with dicoumarin. One patient with thrombocytosis received hydroxyurea. Under this regimen one postoperative hemorrhage requiring laparotomy was observed. Discontinuation of oral anticoagulation due to gastrointestinal bleeding caused hepatic artery and portal vein thrombosis in 1 patient who had to be relransplanted. One recurrence requiring retransplantalion as well was due to an insufficient dicoumarin intake. In conclusion, terminal BCS represents a good indication for orthotopic liver transplantation with a closely‐monitored anticoagulation to avoid such adverse side effects as thrombosis and hemorrhage.
Epithelial‐ and endothelial‐cell specificity of renal graft infiltrating T cells
Authors: Deckers Joan GM , Daha Mohamed R , Van der Kooij Sandra W , Van der Woude Fokko J
Published: September 2024

Previously, we have shown that rejecting renal allografts are infiltrated by tissue‐specific T cells that in vitro kill proximal tubular epithelial cells (PTEC), while donor‐derived splenocytes are not af fected. In the current unique study we assessed the reactivity of graftinfiltrating T cells (GIC) for three different donor‐derived cell types. Cytotoxicity of GIC was tested against PTEC, as well as donor‐derived gonadal vein endothelial cells (GOVEC) and splenocytes. T cells lysed PTEC, GOVEC and splenocytes expressing a mismatched donor HLA antigen, HLA‐A29(19). Interestingly, PTEC and GOVEC, not splenocytes, expressing none of the donor HLA antigens were also killed. T cell clones, obtained by limiting dilution cloning of the GIC line, could be divided into different categories: clones recognizing both PTEC and GOVEC expressing the mismatched HLA‐A29(19), clones recognizing either PTEC or GOVEC expressing the mismatched HLA‐A29(19) and also clones specifically recognizing PTEC or GOVEC independent of donor HLA antigen expression. In conclusion, T cell clones with specificities for either epithelial or endothelial cells exist, leaving a role for tissue‐specific antigens in allograft rejection.
Health‐related quality of life and symptom frequency before and after lung transplantation
Authors: MacNaughton Kathleen L , Rodrigue James R , Cicale Michael , Staples E Mark
Published: September 2024

Health‐related quality of life (HRQOL) and symptom frequency and severity were assessed in 17 lung transplant recipients both prior to and following the procedure. Using standardized assessment techniques we found that the following components of QOL significantly improved post‐transplantation: physical functioning, general health, vitality and social functioning. Both prior to and following transplantation, lung transplant recipients had significantly lower scores on all health‐related quality of life indices when compared with a normative sample. Perhaps as a consequence of immunosuppression medication, recipients reported increased frequency of symptomatology following the procedure; however, considered together the symptoms were not reported as significantly more problematic following transplantation. These findings document improved HRQOL for lung transplant recipients and provide useful information for patients considering this potentially life‐saving treatment option.
A pharmacoeconomic analysis of Neoral without intravenous cyclosporine in liver transplantation in Canada
Authors: Hemming Alan W , Cattral Mark S , Greig Paul D , Meisner Janice , Turcotte Louis , Lilly Leslie B , Levy Gary A
Published: September 2024

Neoral, a microemulsion formulation of cyclosporin A (CSA). has improved absorption compared to Sandimmune and has allowed induction of immunosuppression in liver transplantation (LT) without the use of intravenous (IV) CSA. The improved bioavailability with less interand intra‐patient dosing variability coupled with the lack of requirement for IV CSA may provide a mechanism for cost savings when Neoral is used for induction immunosuppression. This retrospective case‐control study compares the relative costs associated with Neoral induction without IV CSA versus induction with IV CSA followed by oral CSA in adult liver transplant recipients. Twenty consecutive patients receiving Neoral 12‐15 mg/kg per d were compared to a control group of 21 patients receiving IV CSA followed by oral CSA for induction. Both groups received the same rapidly tapered dose of methylprednisilone. Health care resource utilization was assigned based on days in hospital and acute rejection episodes (ARE). Hospital per diem rates at specified care levels were used to assign costs associated with hospital stay, while a previously developed case‐costing model was used to assign costs to episodes of acute rejection. All patients were followed for a 3‐month period post‐transplant. Although there was a trend towards shorter hospital stay in the Neoral group the majority of cost savings were achieved by reducing costs associated with episodes of acute rejection. There were seven and 19 episodes of ARE in the Neoral and IV CSA groups respectively (p <0.05.) A separate cost effective assessment of the effect of reducing rejection by decision tree analysis demonstrated a cost reduction of $2162 per patient. The savings achieved with Neoral proved robust on sensitivity analysis. The change of practice to an induction immunosuppression regimen of Neoral without IV CSA has achieved a cost savings in adult liver transplantation at our center.
Donor cerebral tissue pulmonary emboli in a functioning transplanted lung
Authors: Simonetti Vincent A , Basha Michael A , Allenspach Lisa , Klosterman Kathleen G , Nakhleh Raouf , Higgins Robert SD
Published: September 2024

Cerebral tissue pulmonary embolus (CTPE) is a rare event following severe blunt or penetrating head trauma and is often complicated by coagulation disturbances and hemorrhage. Donor cerebral tissue pulmonary embolism has been reported to cause lethal, early graft dysfunction in lung transplant recipients. We report a case of donor cerebral tissue pulmonary embolism in a 41‐year‐old female single lung transplant recipient with excellent post‐operative graft function.
Acute rejection following renal transplantation. Evidence that severity is the best predictor of subsequent graft survival time
Authors: Pelletier Ronald P , Cosio Fernando , Henry Mitchell L , Bumgardner Ginny L , Davies Elizabeth A , Elkhammas Elmahdi A , Ferguson Ronald M
Published: September 2024

Timely recognition of risk factors influencing graft survival time following kidney transplantation could facilitate the development of clinical interventions that would increase the longevity of graft survival. To identify these risk factors, we performed a retrospective analysis of the clinical outcome of 1949 renal transplants performed at The Ohio State University Transplant Program between 22 September 1982 and 14 June 1996. The number of acute rejection (AR) episodes was most predictive of shorter graft survival time. The first AR episode severity (indexed using the difference between post‐treatment serum creatinine (RxCr) and baseline serum creatinine (BCr), or DeltaCr= RxCr BCr) was the best predictor of graft survival time (r = 0.27, p<0.0001) in patients experiencing AR. Subsequent AR episodes occurred more frequently in patients with a higher DeltaCr. However, DeltaCr was the best predictor of graft survival time (r = 0.44, p < 0.0001) in patients who had only one AR episode. The severity of the first AR episode (DeltaCr) correlated with the risk of subsequent AR episodes, the severity of a second AR episode and the average of mean blood pressures obtained after, but not before, the first AR episode. Therefore, we conclude that the severity of the first AR episode was the best predictor of renal allograft survival time in all patients experiencing AR, independent of subsequent AR episodes and correlated with subsequent clinical events which also influence renal allograft survival time. Thus, early diagnosis and aggressive treatment of the first AR episode are warranted to minimize AR severity and thereby maximize subsequent graft survival time.

Conclusions

The severity of the first acute rejection episode following renal transplantation is the best determinant of graft survival time and correlates with subsequent clinical events which could further reduce graft survival time.
Predicting the potential associations between circRNA and drug sensitivity using a multisource feature‐based approach
Authors: Yin Shuaidong , Xu Peng , Jiang Yefeng , Yang Xin , Lin Ye , Zheng Manyu , Hu Jinpeng , Zhao Qi
Published: September 2024

The unique non‐coding RNA molecule known as circular RNA (circRNA) is distinguished from conventional linear RNA by having a longer half‐life, greater degree of conservation and inherent solidity. Extensive research has demonstrated the profound impact of circRNA expression on cellular drug sensitivity and therapeutic efficacy. There is an immediate need for the creation of efficient computational techniques to anticipate the potential correlations between circRNA and drug sensitivity, as classical biological research approaches are time‐consuming and costly. In this work, we introduce a novel deep learning model called SNMGCDA, which aims to forecast the relationships between circRNA and drug sensitivity. SNMGCDA incorporates a diverse range of similarity networks, enabling the derivation of feature vectors for circRNAs and drugs using three distinct calculation methods. First, we utilize a sparse autoencoder for the extraction of drug characteristics. Subsequently, the application of non‐negative matrix factorization (NMF) enables the identification of relationships between circRNAs and drugs based on their shared features. Additionally, the multi‐head graph attention network is employed to capture the characteristics of circRNAs. After acquiring the characteristics from these three separate components, we combine them to form a unified and inclusive feature vector for each cluster of circRNA and drug. Finally, the relevant feature vectors and labels are inputted into a multilayer perceptron (MLP) to make predictions. The outcomes of the experiment, obtained through 5‐fold cross‐validation (5‐fold CV) and 10‐fold cross‐validation (10‐fold CV), demonstrate SNMGCDA outperforms five other state‐of‐art methods in terms of performance. Additionally, the majority of case studies have predominantly confirmed newly discovered correlations by SNMGCDA, thereby emphasizing its reliability in predicting potential relationships between circRNAs and drugs.
A critical view on five rules of how behavioural experiments could be run
Authors: Schuster Stefan
Published: September 2024

In everyday life it can be tempting to follow some convenient rules, but it is important to sometimes pause and to consider whether these rules are actually useful: Do they help or obscure our understanding of the full beauty of animal behavior?