bluuebunny/crossref_metadata_2025 huggingface dataset:
Remimazolam and serious adverse events
Authors: Kempenaers Sander , Hansen Tom G. , Van de Velde Marc
Published: September 2023

Remimazolam is anticipated to be an interesting anaesthetic and sedative. It combines the pharmacodynamic properties of midazolam with pharmacokinetic properties similar to remifentanil. However, worrisome case reports of anaphylaxis, delayed emergence and re-sedation have emerged recently and necessitate further investigation.

PubMed (including MEDLINE) and EMBASE were searched for all studies reporting serious adverse events where remimazolam was administered for sedation or anaesthesia.

Thirty-six case reports and 73 trials were identified, involving a total of 6740 patients who received remimazolam. Hypotension was reported in 911 cases, delayed emergence in 68 cases, anaphylaxis in 10 cases and re-sedation in 8 cases. The incidence of hypotension seems to be lower compared with other anaesthetics, even in high-risk patients.

Delayed emergence might be related to the metabolism of remimazolam through carboxylesterase 1 (CES1), a tissue esterase predominant in the liver. There is significant interindividual variation, and it is inhibited by flavonoids, fatty acids and alcohol. Individual benzodiazepine sensitivity has also been reported. A higher BMI, older age and low plasma albumin concentration are risk factors for delayed emergence. Anaphylaxis might be related to a non-IgE-mediated effect of the excipient dextran-40 or a partially IgE-mediated reaction to remimazolam itself. Resedation has been reported after flumazenil reversal and is explained by the specific pharmacokinetic properties of flumazenil and remimazolam. Reversal by flumazenil should be reserved for and used carefully in patients with delayed emergence.

Visual Abstract

http://links.lww.com/EJA/A864.
Systematic Critical Review of Genetic Factors Associated with Cisplatin-induced Ototoxicity: Canadian Pharmacogenomics Network for Drug Safety 2022 Update
Authors: Scott Erika N. , Joseph Akshaya A. , Dhanda Angie , Tanoshima Reo , Brooks Beth , Rassekh S. Rod , Ross Colin J.D. , Carleton Bruce C. , Loucks Catrina M.
Published: September 2023

Background:

Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.

Methods:

An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.

Results:

Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.

Conclusions:

Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.
Axial Length Control Is Associated With a Choroidal Thickness Increase in Myopic Adolescents After Orthokeratology
Authors: Wang Zhiqian , Chen Jingyi , Kang Jingxiong , Niu Tongtong , Guo Lei , Fan Liying
Published: September 2023

Objective:

To investigate the changes in choroidal thickness and axial length after orthokeratology in adolescents with low-to-moderate myopia and to explore the relationship between choroidal thickness and axial length variation.

Methods:

Thirty eyes with low-to-moderate myopia were retrospectively studied, and optometric data were collected before and after 6 months of continuous orthokeratology. Axial length and choroidal and foveal thicknesses were measured using optical biometry and enhanced depth imaging–spectral domain optical coherence tomography, respectively.

Results:

Axial length in the low myopia group increased (P<0.001) after 6 months of orthokeratology, and the variation was greater than that in the moderate myopia group (P<0.05). The subfoveal choroidal thickness in low and moderate myopia groups increased (P<0.01), and the variation was greater in the moderate myopia group (P<0.05). Choroidal thickness in all seven measured spots increased, with the variation of subfovea, nasal 1 mm to fovea, and temporal 1 mm to fovea being statistically significant (P<0.001, P<0.05, and P<0.05). The change in axial length was negatively associated with subfoveal and average choroidal thicknesses (P<0.01).

Conclusion:

Adolescents with moderate myopia presented better axial length control after 6 months of orthokeratology. The choroidal thickness of low and moderate myopic eyes increased, and the variation was more significant in moderate myopic eyes. The axial length control effects can be associated with an increase in the subfoveal and average choroidal thickness.
Comparison between linear regression and four different machine learning methods in selecting risk factors for osteoporosis in a Chinese female aged cohort
Authors: Tzou Shiow-Jyu , Peng Chung-Hsin , Huang Li-Ying , Chen Fang-Yu , Kuo Chun-Heng , Wu Chung-Ze , Chu Ta-Wei
Published: September 2023

Background:

Population aging is emerging as an increasingly acute challenge for countries around the world. One particular manifestation of this phenomenon is the impact of osteoporosis on individuals and national health systems. Previous studies of risk factors for osteoporosis were conducted using traditional statistical methods, but more recent efforts have turned to machine learning approaches. Most such efforts, however, treat the target variable (bone mineral density [BMD] or fracture rate) as a categorical one, which provides no quantitative information. The present study uses five different machine learning methods to analyze the risk factors for T-score of BMD, seeking to (1) compare the prediction accuracy between different machine learning methods and traditional multiple linear regression (MLR) and (2) rank the importance of 25 different risk factors.

Methods:

The study sample includes 24 412 women older than 55 years with 25 related variables, applying traditional MLR and five different machine learning methods: classification and regression tree, Naïve Bayes, random forest, stochastic gradient boosting, and eXtreme gradient boosting. The metrics used for model performance comparisons are the symmetric mean absolute percentage error, relative absolute error, root relative squared error, and root mean squared error.

Results:

Machine learning approaches outperformed MLR for all four prediction errors. The average importance ranking of each factor generated by the machine learning methods indicates that age is the most important factor determining T-score, followed by estimated glomerular filtration rate (eGFR), body mass index (BMI), uric acid (UA), and education level.

Conclusion:

In a group of women older than 55 years, we demonstrated that machine learning methods provide superior performance in estimating T-Score, with age being the most important impact factor, followed by eGFR, BMI, UA, and education level.
Incidence of Vulvar Lichen Sclerosus and of Cancer Among Vulvar Lichen Sclerosus Patients: Does Socioeconomic Status Have a Role?
Authors: Borghi Alessandro , Ferretti Stefano , Pacetti Lucrezia , Falcini Fabio , Corazza Monica
Published: September 2023

Objective

Socioeconomic status (SES) impacts on the incidence of many inflammatory diseases and cancers, but there is no evidence on its implication in vulvar lichen sclerosus (VLS). The authors aimed to assess possible associations between SES and both occurrence of VLS and cancer occurrence among VLS patients.

Materials and Methods

A retrospective cohort of women resident in the province of Ferrara, Italy, affected with VLS diagnosed between 2001 and 2020, was investigated for assessing any association of SES with VLS and cancer incidence. The SES was expressed through an ecological-based deprivation index identifying 5 subgroups.

Result

Four-hundred women were diagnosed with VLS during the study period, with double the number of cases in the second decade (2011–2020) compared with the first (2001–2010). More VLS patients belonged to the high rather than the low SES groups (p = .032). From VLS diagnosis to 2018 (1,958.4 total person*years at risk), 22 patients received their first diagnosis of cancer, mainly the skin, breast, and vulva. No significant differences in cancer incidence were found between high/medium-high and low/medium-low SES subjects.

Conclusions

The fact that more VLS patients belonged to the highest socioeconomic classes may be due to a more frequent diagnosis in those with greater health seeking behavior and resources. An involvement of SES-related factors in VLS pathophysiological background can also be taken into consideration. Both the lack of marked social and economic differences in the study area and the availability of free visits and screening may account for the lack of association between SES and cancer development.
Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein
Authors: Lai Quirino , Ito Takashi , Iesari Samuele , Ikegami Toru , Nicolini Daniele , Larghi Laureiro Zoe , Rossi Massimo , Vivarelli Marco , Yoshizumi Tomoharu , Hatano Etsurou , Lerut Jan
Published: September 2023

Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52–2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48–2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26–3.35; p=0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.
Feasibility of a selective targeted strategy of HIV testing in emergency departments: a before-after study
Authors: González del Castillo Juan , Mirò Emília , Miguens Iria , Trenc Patricia , Espinosa Begoña , Piedrafita Lourdes , Pérez Elías María Jesús , Moreno Santiago , García Federico , Villamor Alberto , Carbó Míriam , Gené Emili , Mirò Òscar ,   on behalf of the Emergency HIV network investigators
Published: September 2023

Background and importance

The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic.

Objective

To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis.

Design

This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios.

Settings and participants

Patients attended 34 Spanish EDs.

Intervention or exposure

The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results.

Outcome measures and analysis

The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI).

Main results

HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90–104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143–322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30–125%) increase of positive HIV tests.

Conclusion

Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.
Gastrointestinal Biomarkers and Their Association with Feeding in the First Five Days of Pediatric Critical Illness
Authors: Veldscholte Karlien , Hulst Jessie M. , Eveleens Renate D. , de Jonge Rogier C.J. , de Koning Barbara A.E. , van den Berg Sjoerd A.A. , van der Wal Ronald , Ruijter George J.G. , Rizopoulos Dimitris , Vanhorebeek Ilse , Gunst Jan , Casaer Michaël , Van den Berghe Greet , Joosten Koen F.M. , Verbruggen Sascha C.A.T.
Published: September 2023

Objectives:

Predicting the patients’ tolerance to enteral nutrition (EN) would help clinicians optimize individual nutritional intake. This study investigated the course of several gastrointestinal (GI) biomarkers and their association with EN advancement (ENA) longitudinally during pediatric intensive care unit (PICU) admission.

Methods:

This is a secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit randomized controlled trial. EN was started early and increased gradually. The cholecystokinin (CCK), leptin, glucagon, intestinal fatty acid-binding protein 2 (I-FABP2), and citrulline plasma concentrations were measured upon PICU admission, day 3 and day 5. ENA was defined as kcal EN provided as % of predicted resting energy expenditure. The course of the biomarkers and ENA was examined in patients with samples on all time points using Friedman and Wilcoxon signed-rank tests. The association of ENA with the biomarkers was examined using a 2-part mixed-effects model with data of the complete population, adjusted for possible confounders.

Results:

For 172 patients, median age 8.6 years (first quartile; third quartile: 4.2; 13.4), samples were available, of which 55 had samples on all time points. The median ENA was 0 (0; 0) on admission, 14.5 (0.0; 43.8) on day 3, and 28.0 (7.6; 94.8) on day 5. During PICU stay, CCK and I-FABP2 concentrations decreased significantly, whereas glucagon concentrations increased significantly, and leptin and citrulline remained stable. None of the biomarkers was longitudinally associated with ENA.

Conclusions:

Based on the current evidence, CCK, leptin, glucagon, I-FABP2, and citrulline appear to have no added value in predicting ENA in the first 5 days of pediatric critical illness.
A Forensic Case of Suicide Ingestion of Paraquat Herbicide
Authors: Tambuzzi Stefano , Vacchiano Laura , Gentile Guendalina , Boracchi Michele , Zoja Riccardo , Migliorini Arnaldo Stanislao
Published: September 2023

Paraquat (PQ) is one of the most widely used herbicides in the world, and poisoning is generally associated with accidental, suicidal, or homicidal events. Therefore, in the forensic context, PQ could be in various ways involved as a possible cause of death of a subject. However, even though its systemic toxicity is known, the biological effects exerted on individual viscera have been explored only to some extent, especially in case of victim's survival. Therefore, a case concerning a suicidal ingestion of PQ with survival of 3 days was deemed of interest. Clinical toxicological analyses confirmed acute PQ intoxication, and after the death of the victim, an autopsy was performed showing local and systemic signs of ingestion of a caustic substance. Histologic examination revealed marked cellular damage to the major viscera, particularly the gastroesophageal tract, liver, kidneys, and lungs, with initial alveolar fibrosis noted despite the patient's short survival. This finding represents a new element in the context of PQ lung injury, as it has not been previously documented in the literature. Thus, histological findings in lethal intoxications after survival can reveal specific peculiarities still unknown and, therefore, assume transversal relevance not only at forensic but also clinical level.
Reduced Postdischarge Incidents After Implementation of a Hospital-to-Home Transition Intervention for Children With Medical Complexity
Authors: Huth Kathleen , Hotz Arda , Emara Norah , Robertson Bryanna , Leaversuch Marissa , Mercer Alexandra N. , Khan Alisa , Campos Maria-Lucia , Liss Isabella , Hahn Phillip D. , Graham Dionne A. , Rossi Laura , Thomas Margaret V. , Elias Nahel , Morris Marie , Glader Laurie , Pinkham Amy , Bardsley Kristin M. , Wells Sarah , Rogers Jayne , Berry Jay G. , Mauskar Sangeeta , Starmer Amy J.
Published: September 2023

Objectives

Prior research suggests that errors occur frequently for patients with medical complexity during the hospital-to-home transition. Less is known about effective postdischarge communication strategies for this population. We aimed to assess rates of 30-day (1) postdischarge incidents and (2) readmissions and emergency department (ED) visits before and after implementing a hospital-to-home intervention.

Methods

We conducted a prospective intervention study of children with medical complexity discharged at a children’s hospital from April 2018 to March 2020. A multistakeholder team developed a bundled intervention incorporating the I-PASS handoff framework including a postdischarge telephone call, restructured discharge summary, and handoff communication to outpatient providers. The primary outcome measure was rate of postdischarge incidents collected via electronic medical record review and family surveys. Secondary outcomes were 30-day readmissions and ED visits.

Results

There were 199 total incidents and the most common were medication related (60%), equipment issues (15%), and delays in scheduling/provision of services (11%). The I-PASS intervention was associated with a 36.4% decrease in the rate of incidents per discharge (1.51 versus 0.95, P = 0.003). There were fewer nonharmful errors and quality issues after intervention (1.27 versus 0.85 per discharge, P = 0.02). The 30-day ED visit rate was significantly lower after intervention (12.6% versus 3.4%, per 100 discharges, P = 0.05). Thirty-day readmissions were 15.8% versus 10.2% postintervention (P = 0.32).

Conclusions

A postdischarge communication intervention for patients with medical complexity was associated with fewer postdischarge incidents and reduced 30-day ED visits. Standardized postdischarge communication may play an important role in improving quality and safety in the transition from hospital-to-home for vulnerable populations.
Associations Between Hospitalist Shift Busyness, Diagnostic Confidence, and Resource Utilization: A Pilot Study
Authors: Gupta Ashwin B. , Greene M. Todd , Fowler Karen E. , Chopra Vineet I.
Published: September 2023

Objectives

Hospitalized patients are at risk for diagnostic errors. Hospitalists caring for these patients are often multitasking when overseeing patient care. We aimed to measure hospitalist workload and understand its influences on diagnostic performance in a real-world clinical setting.

Methods

We conducted a single-center, prospective, pilot observational study of hospitalists admitting new patients to the hospital. Hospitalists completed an abridged Mindful Attention Awareness Tool and a survey about diagnostic confidence at shift completion. Data on differential diagnoses and resource utilization (e.g., laboratory, imaging tests ordered, and consultations) were collected from the medical record. The number of admissions and paging volume per shift were used as separate proxies for shift busyness. Data were analyzed using linear mixed effects models (continuous outcomes) or mixed effects logistic regression (dichotomous outcomes).

Results

Of the 53 hospitalists approached, 47 (89%) agreed to participate; complete data were available for 37 unique hospitalists who admitted 160 unique patients. Increases in admissions (odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82; P = 0.04) and pages (odds ratio, 1.11; 95% CI, 1.02 to 1.21; P = 0.01) were associated with increased odds of hospitalists finding it “difficult to focus on what is happening in the present.” Increased pages was associated with a decrease in the number of listed differential diagnoses (coefficient, −0.02; 95% CI, −0.04 to −0.003; P = 0.02).

Conclusions

Evaluation of hospitalist busyness and its associations with factors that may influence diagnosis in a real-world environment was feasible and demonstrated important implications on physician focus and differential diagnosis.
Adverse Event Reporting of Commonly Used Gender-Specific Implantable Medical Devices in the United States
Authors: Pierce Hudson , Ahsan Muhammad Danyal , Martinez Diaz Susana , Cho Ahra , Asfaw Tirsit , Mao Jialin , Anger Jennifer , Chughtai Bilal
Published: September 2023

Background

Evidence suggests that more women are harmed by implantable medical devices than men. It is unknown whether this difference includes gender-specific devices.

Methods

In this study, we examine the differences in reported adverse events between 6 female- and 5 male-specific implantable devices from the Manufacturer and User Facility Device Experience (MAUDE) database from 1993 to 2018. Primary endpoints were injury type (life-threatening, disability, death) and the rate of device evaluation by the manufacturer. Proportions of valid entries across these variables were compared using either the Fisher exact test or χ2 test.

Results

Female-specific devices had higher rates of life-threatening outcomes (1.6% versus 0.3%, P < 0.001), disabilities (5.0% versus 4.3%, P < 0.001), and deaths (0.6% versus 0.1%, P < 0.001) compared with the male-specific devices. Of the 8159 devices that were evaluated by the manufacturer, 56% were female specific while 44% were male specific. Female-specific devices were evaluated far less frequently by the manufacturer (4.5% versus 38.2%, P < 0.001).

Conclusions

Increased adverse events reports for female-specific devices and associated high-grade complications necessitates improved postmarket surveillance.
Evidence supporting the use of therapeutic drug monitoring of ganciclovir in transplantation
Authors: Wong Diana D. , Ho Su Ann , Domazetovska Ana , Yong Michelle K. , Rawlinson William D.
Published: September 2023

Purpose of review

This review describes current knowledge of ganciclovir (GCV) and valganciclovir (ValGCV) pharmacokinetic/pharmacodynamic characteristics, highlighting the likely contribution from host genetic factors to interpatient variability. The evidence and challenges surrounding optimization of drug dosing through therapeutic drug monitoring (TDM) are examined, with recommendations made.

Recent findings

Pharmacokinetic studies of current dosing guidelines have shown high interindividual and intraindividual variability of GCV concentrations. This is sometimes associated with a slow decline in cytomegalovirus (CMV) viral load in some transplant recipients. A high incidence of GCV-associated myelosuppression has limited the use of this drug in the transplant setting. Patient groups identified to benefit from GCV TDM include pediatric patients, cystic fibrosis with lung transplantation, obese with kidney transplantation, and patients with fluctuating renal function or on hemodialysis. The emergence of refractory resistant CMV, particularly in immune compromised patients, highlights the importance of appropriate dosing of these antivirals. Host genetic factors need to be considered where recently, two host genes were shown to account for interpatient variation during ganciclovir therapy. Therapeutic Drug Monitoring has been shown to improve target antiviral-level attainment. The use of TDM may guide concentration-based dose adjustment, potentially improving virological and clinical outcomes. However, evidence supporting the use of TDM in clinical practice remains limited and further study is needed in the transplant cohort.

Further studies examining novel biomarkers are needed to guide target concentrations in prophylaxis and treatment. The use of TDM in transplant recipients is likely to improve the clinical efficacy of current antivirals and optimize outcomes in transplant recipients.
Transplant Outcomes After Exposure of Deceased Kidney Donors to Contrast Medium
Authors: Chotkan Kinita A. , Hilbrands Luuk B. , Putter Hein , Konjin Cynthia , Schaefer Brigitte , Beenen Ludo F.M. , Pol Robert A. , Braat Andries E.
Published: September 2023

Background.

The administration of contrast medium is associated with acute kidney injury; however, the effect of exposure of a deceased organ donor to contrast medium on kidney transplant outcomes has been poorly studied.

Methods.

A retrospective analysis of all deceased kidney donors between 2011 and 2021 and their corresponding recipients in the Netherlands was conducted. Multivariable analyses were performed to assess the associations between contrast medium exposure and delayed graft function (DGF)/graft survival. Linear mixed models were used to assess the differences in mean estimated glomerular filtration rate values in recipients 1 to 6 y after transplantation.

Results.

In total, 2177 donors and 3638 corresponding kidney graft recipients were included. Twenty-four percent of the donors (n = 520) were exposed to contrast medium, corresponding to 23% of recipients (n = 832). DGF was observed in 36% (n = 1321) and primary nonfunction in 3% (n = 122) of recipients. DGF rates for donation after brain death (DBD) and donation after circulatory death (DCD) donors showed no significant effect of contrast medium exposure (P = 0.15 and P = 0.60 for DBD and DCD donors, respectively). In multivariable analyses, contrast medium administration was not significantly associated with a higher DGF risk (odds ratio 1.06; 95% confidence interval, 0.86-1.36; P = 0.63) nor was a significant predictor for death-censored graft failure (hazard ratio 1.01; 95% confidence interval, 0.77-1.33; P = 0.93). Linear mixed models showed no difference in mean estimated glomerular filtration rate values in recipients 1 to 6 y posttransplantation (P = 0.78).

Conclusions.

This study indicates that contrast medium administration in DBD and DCD donors has no negative effect on early and long-term kidney graft function.
Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation
Authors: Sakanoue Ichiro , Okamoto Toshihiro , Ayyat Kamal S. , Yun James J. , Farver Carol F. , Fujioka Hisashi , Date Hiroshi , McCurry Kenneth R.
Published: September 2023

Background.

Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts.

Methods.

Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion.

Results.

The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control.

Conclusions.

The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.
Harvester ant colonies differ in collective behavioural plasticity to regulate water loss
Authors: Gordon D. M. , Steiner E. , Das Biplabendu , Walker N. S.
Published: September 2023

Collective behavioural plasticity allows ant colonies to adjust to changing conditions. The red harvester ant (
Pogonomyrmex barbatus
), a desert seed-eating species, regulates foraging activity in response to water stress. Foraging ants lose water to evaporation. Reducing foraging activity in dry conditions sacrifices food intake but conserves water. Within a year, some colonies tend to reduce foraging on dry days while others do not. We examined whether these differences among colonies in collective behavioural plasticity persist from year to year. Colonies live 20–30 years with a single queen who produces successive cohorts of workers which live only a year. The humidity level at which all colonies tend to reduce foraging varies from year to year. Longitudinal observations of 95 colonies over 5 years between 2016 and 2021 showed that differences among colonies, in how they regulate foraging activity in response to day-to-day changes in humidity, persist across years. Approximately 40% of colonies consistently reduced foraging activity, year after year, on days with low daily maximum relative humidity; approximately 20% of colonies never did, foraging as much or more on dry days as on humid days. This variation among colonies may allow evolutionary rescue from drought due to climate change.
Analysis of wavenumber resonances for the Rayleigh system in a half space
Authors: de Hoop Maarten V. , Iantchenko Alexei
Published: September 2023

We present a comprehensive analysis of wavenumber resonances or leaking modes associated with the Rayleigh operator in a half space containing a heterogeneous slab, being motivated by seismology. To this end, we introduce Jost solutions on an appropriate Riemann surface, a boundary matrix and a reflection matrix in analogy to the studies of scattering resonances associated with the Schrödinger operator. We analyse their analytic properties and characterize the distribution of these wavenumber resonances. Furthermore, we show that the resonances appear as poles of the meromorphic continuation of the resolvent to the nonphysical sheets of the Riemann surface as expected.
Complex field reversal dynamics in nanomagnetic systems
Authors: Saccone Michael , Caravelli Francesco
Published: September 2023

Nanomagnetic materials, built from thin, patterned films of ferromagnetic materials, began as analogues to frustrated magnetism. Their low energy of operation and emergent properties make them strong candidates for physics-based devices. A recent model of how nanomagnetic domains flip, the Glauber mean-field model, is used here to understand how systems of nanomagnets evolve when opposed by external field. This reversal can be expressed in an analytical form in the case of one-dimensional chains and trees at zero temperature, where the cascade of spin flips gives rise to harmonic power spectra. The same cascades in two and three dimensions form fractal field reversal clusters whose shape depends on the strength of the field and the tuning of interactions between nanomagnets.
Investigation of the influence of macrozones in titanium alloys on the propagation and scattering of ultrasound
Authors: Yeoh W. Y. , Lan B. , Lowe M. J. S.
Published: September 2023

The presence of macrozones (or micro-textured regions) in Ti-6Al-4V (Ti-64) was shown to be a potential cause to the onset of cold dwell fatigue which reduces fatigue life significantly. Past research has demonstrated the potential of using ultrasonic testing for macrozone characterization, with the variation of ultrasound attenuation, backscatter and velocity in the presence of macrozones. However, due to the complexity of the microstructure, some physical phenomena that were observed are still not well understood. In this study, we propose the use of finite-element polycrystalline models to provide us with a means to systematically study the wave-macrozone interaction. Through this investigation performed using two-dimensional models, we are able to identify important correlations between macrozone characteristics (size, shape and texture) and ultrasound responses (attenuation, backscatter and velocity). The observed behaviours are then validated experimentally, and we also highlight how this understanding can potentially aid with the characterization of macrozones in Ti-64 samples.
Modelling of pressure-induced magnetic and magnetocaloric effects in dissipative magnetic shape memory alloy systems
Authors: Kumar Avinash , Haldar Krishnendu
Published: September 2023

This article presents a coupled magneto-thermo-mechanical model of pressure-dependent magneto-caloric effect (MCE) and magnetization responses for polycrystalline magnetic shape memory alloys (MSMA). Coupled constitutive equations are derived from a Helmholtz free energy function in a consistent thermodynamic way. The hysteretic and dissipative characteristics of phase transformations in MSMAs are captured by the internal state variables approach with their evolution equations. A relation of adiabatic temperature change is established for such a dissipative material system. The model is calibrated and validated with the existing experimental data. The validated constitutive model is then exploited to predict MCEs at different pressure and magnetic field level. Some predicted results are compared with the available experimental data.
The spectral underpinnings of pathogen spread on animal networks
Authors: Fountain-Jones Nicholas M. , Silk Mathew , Appaw Raima Carol , Hamede Rodrigo , Rushmore Julie , VanderWaal Kimberly , Craft Meggan E. , Carver Scott , Charleston Michael
Published: September 2023

Predicting what factors promote or protect populations from infectious disease is a fundamental epidemiological challenge. Social networks, where nodes represent hosts and edges represent direct or indirect contacts between them, are important in quantifying these aspects of infectious disease dynamics. However, how network structure and epidemic parameters interact in empirical networks to promote or protect animal populations from infectious disease remains a challenge. Here we draw on advances in spectral graph theory and machine learning to build predictive models of pathogen spread on a large collection of empirical networks from across the animal kingdom. We show that the spectral features of an animal network are powerful predictors of pathogen spread for a variety of hosts and pathogens and can be a valuable proxy for the vulnerability of animal networks to pathogen spread. We validate our findings using interpretable machine learning techniques and provide a flexible web application for animal health practitioners to assess the vulnerability of a particular network to pathogen spread.
The origins of colour patterns in fossil insects revealed by maturation experiments
Authors: Wang Shengyu , McNamara Maria E. , Wang Bo , Hui Hejiu , Jiang Baoyu
Published: September 2023

Many fossil insects show monochromatic colour patterns that may provide valuable insights into ancient insect behaviour and ecology. Whether these patterns reflect original pigmentary coloration is, however, unknown, and their formation mechanism has not been investigated. Here, we performed thermal maturation experiments on extant beetles with melanin-based colour patterns. Scanning electron microscopy reveals that melanin-rich cuticle is more resistant to degradation than melanin-poor cuticle: with progressive maturation, melanin-poor cuticle regions experience preferential thinning and loss, yet melanin-rich cuticle remains. Comparative analysis of fossil insects with monotonal colour patterns confirms that the variations in tone correspond to variations in preserved cuticle thickness. These preserved colour patterns can thus be plausibly explained as melanin-based patterning. Recognition of melanin-based colour patterns in fossil insects opens new avenues for interpreting the evolution of insect coloration and behaviour through deep time.
Comparative analysis of the spatial distribution of brain metastases across several primary cancers using machine learning and deep learning models
Authors: Mahmoodifar Saeedeh , Pangal Dhiraj J. , Mason Jeremy , Salhia Bodour , Neman Josh , Zada Gabriel , Newton Paul K.
Published: September 2023

Objective

Brain metastases (BM) are associated with poor prognosis and increased mortality rates, making them a significant clinical challenge. Therefore, studying BMs can aid in developing better diagnostic tools for their early detection and monitoring. Systematic comparisons of anatomical distributions of BM from different primary cancers, however, remain largely unavailable.

Methods

To test the hypothesis that anatomical BM distributions differ based on primary cancer type, we analyze the spatial coordinates of BMs for five different primary cancer types along principal component (PC) axes which optimizes their largest spread along each of the three PC axes. Data used in this analysis is taken from the International Radiosurgery Research Foundation (IRRF) and all patients underwent gamma-knife radiosurgery (GKRS) for the treatment of BMs which are labeled based on the primary cancer types Breast, Lung, Melanoma, Renal, and Colon. The dataset consists of six features including sex, age, target volume, and stereotactic Cartesian coordinates X, Y, and Z of a total of 3949 intracranial metastases. We employ PC coordinates to reduce the dimensionality of our dataset and highlight the distinctions in the anatomical spread of BMs between various cancer types. We utilized different Machine Learning (ML) algorithms: Random Forest (RF), Support Vector Machine (SVM), and TabNet Deep Learning (DL) model to establish the relationship between primary cancer diagnosis, spatial coordinates of BMs, age, and target volume.

Results

Our findings demonstrate that the first principal component (PC1) exhibits a greater alignment with the Y axis, followed by the Z axis, with a minimal correlation observed with the X axis. Based on our analysis of the PC1 versus PC2 plots, we have determined that the pairs of Breast and Lung cancer, as well as Breast and Renal cancer, exhibit the most notable distinctions in their anatomical spreading patterns. In contrast, we find that the pairs of Renal and Lung cancer, as well as Lung and Melanoma, were most similar in their patterns. Our ML and DL results indicate high accuracy in distinguishing the distribution of BM for different primary cancers, with the SVM algorithm achieving a 97% accuracy rate when using a polynomial kernel and TabNet a 96% accuracy. The RF algorithm ranks PC1 as the most important discriminating feature.

Conclusions

Taken together, the results demonstrate an accurate multiclass machine learning classification with respect to the distribution of brain metastases.
DNA Tetrahedral Nanocages as a Promising Nanocarrier for Dopamine Delivery in Neurological Disorders
Authors: Singh Ramesh , Kansara Krupa , Mandal Sandip , Varshney Ritu , Gupt Sharad , Kumar Ashutosh , Maiti Prabal K , Bhatia Dhiraj
Published: September 2023

Dopamine is a neurotransmitter in the central nervous system that is essential for many bodily and mental processes, and a lack of it can cause Parkinson’s disease. DNA tetrahedral (TD) nanocages are promising in bio-nanotechnology, especially as a nanocarrier. TD is highly programmable, biocompatible, and capable of cell differentiation and proliferation. It also has tissue and blood-brain barrier permeability, making it a powerful tool that could overcome potential barriers in treating neurological disorders. In this study, we used DNA-TD as a carrier for Dopamine to cells and zebrafish embryos. We investigated the mechanism of complexation between TD and dopamine hydrochloride using gel electrophoresis, fluorescence and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and molecular dynamic (MD) simulation tools. Further, we demonstrate these Dopamine-loaded DNA tetrahedral nanostructures’ cellular uptake and differentiation ability in SH-SY5Y neuroblastoma cells. Furthermore, we extended the study to zebrafish embryos as a model organism to examine survival and uptake. The research provides valuable insights into the complexation mechanism and cellular uptake of dopamine-loaded DNA tetrahedral nanostructures, paving the way for further advancements in nanomedicine for Parkinson’s disease and other neurological disorders.
Single-crystal quality data from polycrystalline samples: finding the needle in the haystack
Authors: Bear Joseph Charles , Terzoudis Nikitas , Cockcroft Jeremy Karl
Published: September 2023

Multi-grain crystallography, traditionally performed at synchrotron sources in association with high-pressure studies, has new relevance with respect to laboratory single-crystal X-ray diffraction, in which crystals can be grown rapidly in situ, and a preliminary dataset analysed and solved in a matter of minutes. Subsequently, a full-sphere of IUCr-quality data can then be collected in a few hours. To demonstrate the applicability of laboratory multi-grain crystallography with Cu Kα X-rays, co-crystals of hexafluorobenzene and pyrrole were grown rapidly by cooling a 1:1 liquid mixture in an X-ray capillary on the diffractometer. The software is able to identify a single unit cell from as few as 10% of the diffraction spots from a small number of diffraction frames. Once a unit cell is identified, a full crystal structure solution is rapidly obtained by collecting a small amount of data to a resolution of ca 1 Å. The co-crystal obtained from the 1:1 mixture showed that hexafluorobenzene and pyrrole crystallize in a 3:4 ratio, in contrast to the columnar 1:1 adduct structures typified by hexafluorobenzene and benzene. The generality of our multi-grain approach for samples that are liquid at room temperature (and form a polycrystalline solid mass on cooling) is further demonstrated by investigating and solving the 1:1 co-crystal formed between hexafluorobenzene and pyridine.
Aditya Kumar: Office Politics and Managing Upwards
Authors: Gupta Vishal , Premapuri Priyanka
Published: September 2023

The case describes the predicament of Aditya Kumar, Vice President of Marketing at Green Living India Technologies Private Limited (GLIT), an organisation working in arena of sustainable products and technology. Aditya Kumar, who has had an excellent academic background and a fast track promotion after seven months of joining the company, is harshly criticized by his boss Rajiv Nanda, Chief Marketing Officer. Aditya Kumar and Rajiv Nanda have different personalities and work styles. Aditya has a different opinion for some of Rajiv's initiatives and he does not agree to Rajiv's revenue projections which he finds to be over-estimated. Aditya has succeeded in his previous role but he has failed to adapt his work style and establish an effective relationship with his new boss that may lead to his position being removed from the organisation.
Razorpay: Providing Payment Convenience to Disruptors
Authors: Ganjoo Divya , Mukherjee Saral , Mukhopadhyay Sandip
Published: September 2023

Razorpay is a four-year-old Indian B2B fintech startup in digital payments which is venturing into digital lending. It aims to simplify digital payment flows involved in acceptance, processing, and disbursement of payments through superior technology and automation. This case details how Razorpay creates value for businesses by offering service convenience in B2B space. Razorpay started as a payment solutions provider, primarily known for their payment gateway. Over time the market for digital payment in India has matured, with multiple providers offering similar products making it difficult for Razorpay to sustain its growth by using technological leadership and service differentiation. To maintain its growth trajectory, Razorpay has launched multiple new products in the digital payment space as well as announced a foray into creating a marketplace for digital lending through launch of Razorpay Capital. The case provides details of the growth of Razorpay and its move from its core strength of payment gateway
Sanctity of Oral Agreements: MWB Business Exchange Centres Ltd v Rock Advertising Ltd
Authors: Pathak Akhileshwar
Published: September 2023

The founding principle of contracts is the freedom of the parties. The parties are free to choose their terms and follow any modality of communication, oral or written. As they can freely make a contract, they can freely modify or unmake it. Written contracts have a clause, No Oral Modification Clause (NOM Clause), precluding oral modifications of the contract. Irrespective of it, business persons make oral agreements modifying the contract, and later, dispute its validity. If the parties are free to contract, why should the oral agreement not be binding? In a NOM Clause then, ineffective? The United Kingdom Supreme Court, in MWB Business Exchange Centres Ltd v Rock Advertising Ltd, explores this fundamental question on contract law.