bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Platelets and von Willebrand Factor in the Procoagulant Phenotype of Inflammatory Bowel Disease
Authors: Schellenberg Célia , Lagrange Jérémy , Ahmed Muhammad Usman , Arnone Djésia , Campoli Philippe , Louis Huguette , Touly Nina , Caron Bénédicte , Plénat François , Perrin Julien , Lenting Peter J , Regnault Véronique , Lacolley Patrick , Denis Cécile V , Peyrin-Biroulet Laurent
Published: November 2023

Aims

Although the risk of thrombosis is well documented for inflammatory bowel disease [IBD] patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Determining the factors responsible for the increased risk of thrombosis in IBD would help to improve the management of this frequent complication.

Methods

We studied the interplay between platelets, coagulation, and von Willebrand factor [VWF] in 193 IBD patients and in experimental models [acute and chronic] of colitis in wild-type and VWF-deficient mice.

Results

We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were also able to detect the presence of active VWF [VWF in its platelet-binding conformation; 3.2 ± 2.7 μg/mL] in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were <0.3 μg/mL. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also showed a significant worsening of colitis severity in both acute and chronic models.

Conclusion

Platelets and VWF [including its active form] appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in haemostasis differs from its role in colonic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.
Successful permanent pacemaker explantation after diagnosis and treatment of Lyme carditis complete heart block: a case report
Authors: Messner Christopher R , Amara Richard S
Published: November 2023

Background

Lyme carditis (LC) complete heart block (CHB) is typically treated with i.v. antibiotics without requiring permanent pacing. In patients with high degree atrioventricular (AV) block, suspicious index in Lyme carditis (SILC) scoring is highly sensitive for diagnosing LC.

Case summary

We present a case of CHB where a permanent pacemaker (PPM) was implanted prior to LC diagnosis. Suspicious index in Lyme carditis score was 2 at the time of exam, indicating a low risk for LC. However, per further discussion at follow-up, his score was retroactively increased to an intermediate risk of 4 and Lyme titres returned positive. An outpatient oral antibiotic regimen was given, and 2 months later, the patient had <0.1% V-pacing on interrogation with a subsequent unremarkable event monitor. The pacemaker was removed after considerations ensuring full conduction recovery. The patient is doing well at follow-up > 1 year.

Discussion

Lyme carditis spontaneous resolution of CHB is common. Once safe extraction parameters have been established, it is appropriate to engage patients without ongoing pacer requirements about explantation of their PPM. For CHB patients without clear aetiology, SILC scoring may be a predictive measure to help prevent unnecessary PPM placement in the future.
Cardiac arrest in seronegative idiopathic inflammatory myopathy: a case report
Authors: Srivatsav Varun , Khan Ambreen , Wardell Stephan
Published: November 2023

Background

Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases that are characterized by muscle injury. These disorders can cause cardiomyopathy and heart failure, myocarditis, and arrhythmias. However, only a few cases of cardiac arrest as a result of IIMs have been previously reported.

Case summary

A 46-year-old male presented with an out-of-hospital ventricular fibrillation cardiac arrest. A diagnosis of IIM had been made through a muscle biopsy performed 2 years before presentation. The patient had a positive anti-nuclear antibody but negative myositis-specific antibodies. His initial symptoms of IIM were mild and consisted of myalgias. His only cardiac symptoms were minor palpitations that occurred 3 years prior to the cardiac arrest, with a negative Holter monitor test result at that time. His cardiac catheterization was normal. He was suspected to have myocarditis, and a rheumatologist was consulted, following which the patient was initiated on intravenous immunoglobulin (IVIG). Cardiac magnetic resonance imaging demonstrated evidence of chronic myocarditis and an ejection fraction of 44%. He was initiated on goal-directed medical therapy for heart failure. A VVI implantable cardioverter defibrillator was implanted for secondary prevention. He was discharged and prescribed additional immunosuppression including further IVIG infusions, prednisone taper and rituximab infusions.

Discussion

Our case demonstrates that cardiac arrest in IIM is not only plausible, but can be the first major cardiac manifestation of the disease. When a diagnosis of IIM is made, patients require a thorough assessment of cardiac symptomatology and a low threshold for additional cardiac investigations.
The Limitations of Activity-Based Instruction to Improve the Productivity of Schooling
Authors: de Barros Andreas , Fajardo-Gonzalez Johanna , Glewwe Paul , Sankar Ashwini
Published: November 2023

There is substantial emphasis on improving classroom practices, primarily through activity-based instruction, to increase the productivity of schooling. We study a large programme that seeks to promote mathematics learning in government primary schools in India. Through a cluster-randomised trial we find that the programme increased activity-based instruction, but yielded only muted impacts on learning. We provide a potential explanation: school value-added models suggest a negative relationship between activity-based instruction and test score gains. Our findings are robust to adding a community-engagement component to the intervention. These results highlight the limitations of activity-based instruction programmes for increasing school productivity.
Prognostic outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical epidermal growth factor receptor mutations
Authors: Chen Tao , Wen Jialiang , Li Yingze , Deng Jiajun , Zhong Yifan , Hou Likun , She Yunlang , Xie Dong , Chen Chang
Published: November 2023

OBJECTIVES

Limited data exist on the characteristics of atypical epidermal growth factor receptor (EGFR) mutations in early-stage lung cancer. Our goal was to elucidate the associations with outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical EGFR mutations.

METHODS

Eligible patients between 2014 and 2019 were retrospectively identified and grouped into exon20 insertion mutations and major atypical mutations, which included G719X, L861Q and S768I. Disease-free survival (DFS) was evaluated in the entire cohort and stratified by radiologic characteristics. Recurrence patterns were investigated and compared between groups. A competing risk model was used to estimate the cumulative incidence of recurrence.

RESULTS

A total of 710 patients were finally included. Among them, 289 (40.7%) patients had exon 20 insertion mutations and 421 (59.3%) patients had major atypical mutations. There was no significant difference regarding DFS (P = 0.142) between groups in the entire cohort. The interaction between mutation subtype and the presence of ground-glass opacities was significant (hazard ratio 2.00, 95% confidence interval 1.59–2.51, P < 0.001), indicating DFS between exon 20 insertion mutations and major atypical mutations may be different among subsolid and solid tumours. Survival analysis consistently revealed no significant difference in subsolid tumours (P = 0.680), but favourable DFS of exon 20 insertion mutations in solid tumours (P = 0.037). Furthermore, patients with exon 20 insertion mutations had a lower risk of developing bone metastases did those with radiologic solid tumours (Gray’s test, P = 0.012).

CONCLUSIONS

Exon 20 insertion mutations were correlated with favourable DFS and lower incidence of bone metastases in radiologic solid lung adenocarcinomas harbouring atypical EGFR mutations.
Predisposing factors for adrenal crisis in chronic adrenal insufficiency: a case–control study
Authors: Chifu Irina , Burger-Stritt Stephanie , Schrader Anna , Herterich Sabine , Freytag Janik , Kurlbaum Max , Vogg Nora , Werner Johanna , Quinkler Marcus , Hahner Stefanie
Published: November 2023

Objective

This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI).

Design

A case–control study involving 66 patients with AI analyzing the impact of glucocorticoid and mineralocorticoid exposure, adrenomedullary function, inflammatory parameters, and educational status on AC frequency. Patients were categorized into low (n = 32) and high (n = 34) AC frequency groups based on AC occurrence (below or 2 times above the average of the reported AC frequency of 8.3 AC/100 patient-years in a previous prospective study).

Methods

Parameters, including cortisol plasma profile and urinary steroid excretion after administration of the morning glucocorticoid dose, 24-h urinary steroid profiling, salivary cortisol profiling, and hair cortisol, estimated cortisol exposure. Polymorphisms (single nucleotide polymorphism [SNP]) of the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) associated with individual steroid sensitivity were assessed together with SNPs for 11β-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11β-hydroxysteroid dehydrogenase 2 (HSD11B2). Mineralocorticoid replacement was evaluated by serum and urinary electrolytes and osmolality, plasma–renin concentration, and ambulatory blood pressure levels. We additionally measured plasma and urinary catecholamines, serum levels of IL6 and hsCRP, and SNPs of IL6 and TNF-alpha. Patient knowledge of AC prevention was assessed by questionnaires.

Results

Frequent AC patients had higher daily glucocorticoid doses and hair cortisol levels, with no significant differences in other parameters investigated. AC frequency is inversely correlated with the frequency of self-reported adjustments of the glucocorticoid replacement.

Conclusion

Higher glucocorticoid dosages in high-risk patients, despite unaffected cortisol metabolism, may be linked to decreased cortisol sensitivity or impaired glucocorticoid absorption. Proactive dose adjustments show a protective effect against AC, regardless of biological vulnerability.
Changes in the swallowing pattern and tongue posture during the transition from deciduous to mixed dentition—a longitudinal ultrasonography study
Authors: Ovsenik Rok , Marolt Mušič Maja , Primožič Jasmina
Published: November 2023

Background

Given the importance that swallowing pattern and tongue posture might have in the aetiology of malocclusion, it appears important to be aware of the physiological changes of tongue function and its posture.

Objectives

The study aimed to assess changes of the swallowing pattern and tongue posture during the transition from the deciduous to mixed dentition and the association between them.

Materials and Methods

The study included 57 subjects aged 5.87 ± 0.5 with normal occlusion, orofacial functions, no history of trauma, or orthodontic treatment. Ultrasonography was used for the assessment of tongue posture and swallowing pattern, where the spontaneous act of swallowing was recorded. To evaluate the possible effect of incisors’ eruption, the swallowing pattern and tongue posture ultrasonograms were compared at the deciduous (DD), early mixed (EMD), and intermediate mixed (IMD) timepoints.

Results

A significant association between the swallowing pattern and tongue posture at the DD and IMD timepoint was found. Moreover, the visceral swallowing pattern decreases with age (odds ratio [OR] = 0.777), as well as with a prolonged phase IIa (OR = 0.071), while it increases when the tongue is postured on the mouth floor (OR = 5.020).

Limitations

The young age of the investigated subjects, direct contact of the probe, and the determination of the rest phase of the tongue were considered limitations.

Conclusions

No statistically significant changes in swallowing pattern and tongue posture occurred during the transition period; however, a significant association between the swallowing pattern and tongue posture among subjects with normal occlusion, regardless of the dentition phase was detected.
Natural unemployment and activity rates in Italy: flow-based determinants and implications for price dynamics
Authors: D’Amuri Francesco , De Philippis Marta , Guglielminetti Elisa , Lo Bello Salvatore
Published: November 2023

Despite the magnitude and cyclicality of transitions into and out of the labour force, the literature generally considers unemployment as a sufficient statistic of labour market slack. We question this view by jointly estimating natural unemployment and participation rates through a Phillips curve informed by structural labour market flows. Focusing on Italy, a country where flows into and out of the labour force are particularly large, we find that the participation margin accounts for a significant share of total slack and explains one-third of the missing inflation that followed the 2011 Sovereign Debt Crisis. Exploiting a reform that sharply and unexpectedly increased the statutory retirement age and expanded labour supply without directly affecting unemployment, we confirm that neglecting the participation gap biases inflation forecasts.
Long-term performance of single-connector (DF4) implantable defibrillator leads
Authors: Ibrahim Rand , Al-Gibbawi Mounir , Mekary Wissam , Bhatia Neal Kumar , Kiani Soroosh , Westerman Stacy B , Shah Anand D , Lloyd Michael S , Leal Miguel , De Lurgio David B , Patel Anshul M , Tompkins Christine , Leon Angel R , Merchant Faisal M , El-Chami Mikhael F
Published: November 2023

Aims

Single-connector (DF4) defibrillator leads have become the predominantly implanted transvenous implantable cardioverter-defibrillator lead. However, data on their long-term performance are derived predominantly from manufacturer product performance reports.

Methods and results

We reviewed medical records in 5289 patients with DF4 leads between 2011 and 2023 to determine the frequency of lead-related abnormalities. We defined malfunction as any single or combination of electrical abnormalities requiring revision including a sudden increase (≥2×) in stimulation threshold, a discrete jump in high-voltage impedance, or sensing of non-physiologic intervals or noise. We documented time to failure, predictors of failure, and management strategies. Mean follow-up after implant was 4.15 ± 3.6 years (median = 3.63), with 37% of leads followed for >5 years. A total of 80 (1.5%) leads demonstrated electrical abnormalities requiring revision with an average time to failure of 4 ± 2.8 years (median = 3.5). Of the leads that malfunctioned, 62/80 (78%) were extracted and replaced with a new lead and in the other 18 cases, malfunctioned DF4 leads were abandoned, and a new lead implanted. In multivariable models, younger age at implant (OR 1.03 per year; P < 0.001) and the presence of Abbott/St. Jude leads increased the risk of malfunction.

Conclusion

DF4 defibrillator leads demonstrate excellent longevity with >98.3% of leads followed for at least 5 years still functioning normally. Younger age at implant and lead manufacturer are associated with an increased risk of DF4 lead malfunction. The differences in lead survival between manufacturers require further investigation.
Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties
Authors: Iravanian Shahriar , Uzelac Ilija , Shah Anand D , Toye Mikael J , Lloyd Michael S , Burke Michael A , Daneshmand Mani A , Attia Tamer S , Vega John David , El-Chami Mikhael F , Merchant Faisal M , Cherry Elizabeth M , Bhatia Neal K , Fenton Flavio H
Published: November 2023

Aims

The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts.

Methods and results

We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel.

Conclusion

We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.
Relationship between health-related determinants and adherence to breast and colorectal cancer screening: a population-based study in Flanders, Belgium
Authors: Ferrari Allegra , Tran Thuy Ngan , Hoeck Sarah , Peeters Marc , Goossens Mathijs , Van Hal Guido
Published: November 2023

Background

Despite the recognized benefits of structured cancer screening, tests outside organized screening programs are common. Comprehensive reports on outside program screening in Europe are lacking, but the Flemish breast cancer (BC) and colorectal cancer (CRC) screening programs monitor data on non-organized tests prescribed by GPs and specialists.

Methods

Using data at aggregated level, logistic regression was used to examine the relationship between health care utilization and screening coverage in 308 Flemish municipalities during 2015–18.

Results

With regards to BC, municipalities with higher rates of gynecologists’ visits had lower odds of coverage inside (−8%) and higher odds of coverage outside (+17%) the program. By contrast, municipalities with higher rates of GP visits, had higher odds of coverage inside (+6%) and lower odds of coverage outside (−7%) the program. As for CRC, municipalities with higher rates of visits gastroenterologists’ visits had lower odds of coverage inside (−3%). Instead, municipalities with higher rates of GP visits, had higher odds of coverage both inside (+2%) and outside (+5%) the program. Municipalities with higher percentages of people with chronic conditions had higher odds of coverage within both the BC and CRC programs (+5% and +3%), and lower odds of outside screening (−7% and −6%). Municipalities with higher percentages of people 65+ with dementia and with mood disorders had, respectively, higher odds (+13% and +5%) and lower odds (−3% and −4%) of coverage inside both the BC and CRC programs.

Conclusion

Our findings underscore the impact of healthcare utilization on cancer screening coverage at the municipal level in Flanders.
Chicken manure application alters microbial community structure and the distribution of antibiotic-resistance genes in rhizosphere soil of Cinnamomum camphora forests
Authors: Chen Deqiang , Zou Jiawei , Chen Dexing , He Xin , Zhang Cuili , Li Jinwei , Lan Siren , Liu Zhong-Jian , Zou Shuangquan , Qian Xin
Published: November 2023

The distribution of antibiotic-resistance genes (ARGs) in environmental soil is greatly affected by livestock and poultry manure fertilization, the application of manure will lead to antibiotic residues and ARGs pollution, and increase the risk of environmental pollution and human health. Cinnamomum camphora is an economically significant tree species in Fujian Province, China. Here, through high-throughput sequencing analysis, significant differences in the composition of the bacterial community and ARGs were observed between fertilized and unfertilized rhizosphere soil. The application of chicken manure organic fertilizer significantly increased the relative abundance and alpha diversity of the bacterial community and ARGs. The content of organic matter, soluble organic nitrogen, available phosphorus, nitrate reductase, hydroxylamine reductase, urease, acid protease, β-glucosidase, oxytetracycline, and tetracycline in the soil of C. camphora forests have significant effects on bacterial community and ARGs. Significant correlations between environmental factors, bacterial communities, and ARGs were observed in the rhizosphere soil of C. camphora forests according to Mantel tests. Overall, the findings of this study revealed that chicken manure organic fertilizer application has a significant effect on the bacterial community and ARGs in the rhizosphere soil of C. camphora forests, and several environmental factors that affect the bacterial community and ARGs were identified.
Evaluating the Performance of Widely Used Phylogenetic Models for Gene Expression Evolution
Authors: Dimayacyac Jose Rafael , Wu Shanyun , Jiang Daohan , Pennell Matt
Published: November 2023

Phylogenetic comparative methods are increasingly used to test hypotheses about the evolutionary processes that drive divergence in gene expression among species. However, it is unknown whether the distributional assumptions of phylogenetic models designed for quantitative phenotypic traits are realistic for expression data and importantly, the reliability of conclusions of phylogenetic comparative studies of gene expression may depend on whether the data is well described by the chosen model. To evaluate this, we first fit several phylogenetic models of trait evolution to 8 previously published comparative expression datasets, comprising a total of 54,774 genes with 145,927 unique gene–tissue combinations. Using a previously developed approach, we then assessed how well the best model of the set described the data in an absolute (not just relative) sense. First, we find that Ornstein–Uhlenbeck models, in which expression values are constrained around an optimum, were the preferred models for 66% of gene–tissue combinations. Second, we find that for 61% of gene–tissue combinations, the best-fit model of the set was found to perform well; the rest were found to be performing poorly by at least one of the test statistics we examined. Third, we find that when simple models do not perform well, this appears to be typically a consequence of failing to fully account for heterogeneity in the rate of the evolution. We advocate that assessment of model performance should become a routine component of phylogenetic comparative expression studies; doing so can improve the reliability of inferences and inspire the development of novel models.
Comparison of transcriptome-wide N6-methyladenosine profiles from healthy trio families reveals regulator-mediated methylation alterations
Authors: Li Yini , Liu Hang , He Chuan , Ma Lijia
Published: November 2023

The N6-methyladenosine (m6A) modification is a highly conserved RNA modification found in eukaryotic messenger RNAs (mRNAs). It plays a vital role in regulating various biological processes. Dysregulation of m6A modifications has been linked to a range of complex genetic diseases in humans. However, there has been a lack of comprehensive characterization and comparison of m6A modifications at the transcriptome-wide level within families. To address this gap, we profiled transcriptome-wide m6A methylation in 18 individuals across 6 Yoruba trio families. The m6A methylomes of these 18 individuals revealed that m6A modifications in children showed greater similarity to each other than to their parents. This suggests that m6A modifications are influenced by multiple factors rather than solely determined by genetic factors. Additionally, we found that mRNAs exhibiting m6A modifications specific to children were enriched in cell cycle control processes, while those with m6A modifications specific to parents were associated with chromatin modifications. Furthermore, our analysis on the interactions between differentially expressed m6A-related regulatory genes and age-related genes suggested that age might be one of the factors influencing m6A modifications. In summary, our study provided a valuable dataset that highlighted the differences and functional diversity of m6A modifications within and between trio families.
Differential Impact of Smoking on Methylome and Transcriptome in Crohn’s Disease and Ulcerative Colitis
Authors: Yan Ang Qi , Plichta Damian , Kim Sean , Hyun-A Kim Iris , Gregory Sadie , Xia Yan , Lau Helena , Xavier Ramnik , Ananthakrishnan Ashwin N
Published: November 2023

Background

Smoking is an environmental factor that differentially impacts Crohn’s disease (CD) and ulcerative colitis (UC). The mechanism of impact of smoking on disease risk and clinical outcomes remains to be established.

Methods

This study used a prospective cohort of patients with CD or UC. Self-reported smoking status was validated using serum cotinine measurement. We profiled methylation changes in peripheral blood using the Illumina Methylation BeadChip. Transcriptomic profiling was performed on ileal and colonic tissue using an Illumina TruSeq platform. We compared the methylation and transcriptional changes in current, former, and never smokers stratified by disease type.

Results

Our cohort included 200 patients with CD or UC with methylation profiles and 160 with transcriptomic data. The mean serum cotinine level was higher in current compared with former or never smokers. Epigenetic changes common to both CD and UC included hypomethylation at AHRR. Smoking-associated MGAT3 hypomethylation was associated with severe disease course only in UC, while IER3 hypomethylation was associated with worse course only in CD. Smoking downregulated several inflammatory pathways in UC. Current smoking in CD but not in UC was associated with upregulation of several genes mediating Paneth cell function. Genes with opposite direction of effects in CD and UC include HSD3B2 and GSTA1.

Conclusions

Our findings suggest both common and differential effects of cigarette smoking on CD and UC. Paneth cell dysfunction may mediate adverse impact of smoking on CD. Bile acid and oxidative stress pathways may be relevant for the differential effect of smoking on CD and UC.
Reconstructive surgery for severe breast asymmetry post-paediatric cardiovascular operation by anterolateral thoracotomy
Authors: Ishii Naohiro , Ko Takanori , Shimabukuro Makoto , Matsuzaki Kyoichi
Published: November 2023

Breast maldevelopment is a troublesome long-term complication of anterolateral thoracotomies, and several cases of this event have been reported. However, breast reconstruction in such cases has not yet been reported in detail, and solutions for managing this event remain unexplained. Herein, we present a case of breast maldevelopment after anterolateral thoracotomy, in which symmetrical breasts were successfully obtained by breast reconstruction based on autologous tissue transfer. The surgical approach prior to pleurotomy in anterolateral thoracotomy, particularly when performed on female infant patients, must be modified to prevent postoperative breast malformation.
Impact of lung cancer screening on surgical stage distribution and surgical practice: a regional analysis of patients operated in and out of a screening program
Authors: Gooseman Michael R , Tentzeris Vasileios , Bulliment Kerry L , Qadri Syed S A , Callister Matthew E J , Milton Richard , Chaudhuri Nilanjan , Tcherveniakov Peter , Papagiannopoulos Kostas , Cowen Michael E , Brunelli Alessandro
Published: November 2023

OBJECTIVES

The aim of this study was to assess variations in surgical stage distribution in 2 centres within the same UK region. One centre was covered by an active screening program started in November 2018 and the other was not covered by screening.

METHODS

Retrospective analysis of 1895 patients undergoing lung resections (2018–2022) in 2 centres. Temporal distribution was tested using Chi-squared for trends. A lowess curve was used to plot the proportion of stage 1A patients amongst those operated over the years.

RESULTS

The surgical populations in the 2 centres were similar. In the screening unit (SU), we observed a 18% increase in the proportion of patients with clinical stage IA in the recent phase compared to the early phase (59% vs 50%, P = 0.004), whilst this increase was not seen in the unit without screening. This difference was attributable to an increase of cT1aN0 patients in the SU (16% vs 11%, P = 0.035) which was not observed in the other unit (10% vs 8.2%, P = 0.41). In the SU, there was also a three-fold increase in the proportion of sublobar resections performed in the recent phase compared to the early one (35% vs 12%, P < 0.001). This finding was not evident in the unit without screening.

CONCLUSIONS

Lung cancer screening is associated with a higher proportion of lung cancers being detected at an earlier stage with a consequent increased practice of sublobar resections.
Unconditionally stable small stencil enriched multiple point flux approximations of heterogeneous diffusion problems on general meshes
Authors: Coatléven Julien
Published: November 2023

We derive new multiple point flux approximations (MPFA) for the finite volume approximation of heterogeneous and anisotropic diffusion problems on general meshes, in dimensions 2 and 3. The resulting methods are unconditionally stable while preserving the small stencil typical of MPFA finite volumes. The key idea is to solve local variational problems with a well-designed stabilization term from which we deduce conservative flux instead of directly prescribing a flux formula and solving the usual flux continuity equations. The boundary conditions of our local variational problems are handled through additional cell-centered unknowns, leading to an overall scheme with the same number of unknowns than first-order discontinuous Galerkin methods. Convergence results follow from well-established frameworks, while numerical experiments illustrate the good behavior of the method.
Associations Between HIV and Severe Mpox in an Atlanta Cohort
Authors: Aldred Bruce , Scott Jane Y , Aldredge Amalia , Gromer Daniel J , Anderson Albert M , Cartwright Emily J , Colasanti Jonathan A , Hall Betsy , Jacob Jesse T , Kalapila Aley , Kandiah Sheetal , Kelley Colleen F , Lyles Robert H , Marconi Vincent C , Nguyen Minh Ly , Rebolledo Paulina A , Sheth Anandi N , Szabo Brittany , Titanji Boghuma K , Wiley Zanthia , Workowski Kimberly , Cantos Valeria D
Published: November 2023

Background

In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH).

Methods

We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox.

Results

Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200 copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01–6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200 copies/mL had 2.10 (95% CI, 1.00–4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis.

Conclusions

PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment.
Impact of Intravenous Fat Emulsion Choice on Candida Biofilm, Hyphal Growth, and Catheter-Related Bloodstream Infections in Pediatric Patients
Authors: Alvira-Arill Gustavo R , Willems Hubertine M E , Fortwendel Jabez P , Yarbrough April , Tansmore Jessica , Sierra Caroline M , Bashqoy Ferras , Stultz Jeremy S , Peters Brian M
Published: November 2023

Background

Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs.

Methods

Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients.

Results

Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11, HGC1, and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non-albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval, .46–3.26]).

Conclusions

MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6-dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed.
Utilizing a Quality Improvement Approach to Improve Positioning of Acute Burn Patients
Authors: Freeman Catherine E , Yoo Junhwi , Slater Julia C
Published: November 2023

Patient positioning, using “anti-deformity positioning,” is a standard practice in burn rehabilitation to assist with edema management, scar contracture prevention, and wound healing. Consistently providing proper positioning requires the combined effort of the multidisciplinary burn team. Our primary goal was to increase the frequency that patients were correctly positioned to over 90%. At a medium-sized, academic burn unit, random audits were conducted by burn lead therapists on the compliance of proper patient positioning over 6 months. Using this data as a trigger, a quality improvement project was designed using the Plan-Do-Study-Act (PDSA) cycle. Surveys were distributed to therapy and nursing staff to identify barriers to proper positioning. Effects on positioning compliance postintervention were monitored. In the 6 months prior to intervention, the average correct positioning was 76%. Surveys identified the following barriers to care: nursing needed more education and the approach was too heavily reliant on nursing efforts alone. To address this, therapists provided education to all nurses, communicated daily about positioning expectations, shifted the project to a multidisciplinary approach, and made changes in therapy workflow. The median compliance improved from 79% to 91% (P < .05). Coordinating efforts of the entire burn team improve consistency for positioning in burn patients. Utilizing the PDSA cycle allowed us to identify areas for improvement and develop appropriate interventions to increase education for nursing staff and workflow improvements for therapists. Following the completion of our interventions, we were able to obtain an immediate improvement in our patient positioning compliance.
Transmission accuracy–axial backlash–fatigue life-driven tolerance optimization of planetary roller screw mechanism
Authors: Liu Genshen , Wei Peitang , Liu Huaiju , Du Xuesong , Hu Rui , He Huilin , Zhou Pengliang , Tan Xiaoqing
Published: November 2023

The planetary roller screw mechanism (PRSM) is an advanced linear transmission device. The relationship between tolerance allocation and performance risk still remains elusive, which is a challenge for its future applications. This work proposes a novel transmission accuracy–axial backlash–fatigue life-driven tolerance optimization method for the screw, roller, and nut of PRSM. A computational framework for PRSM transmission accuracy, axial backlash, and fatigue life calculation is developed to work on the parametric variation of design parameters including the eccentric, pitch, nominal diameter, and flank angle. Combinations of parametric variation are obtained by the Latin hypercube sampling-based tolerance statistical model to rapidly evaluate PRSM performance risk under operation conditions and tolerance parameters. The optimal tolerance parameters with the expanded width of tolerance interval and the minimum PRSM performance risk probability are obtained using the non-dominated sorting genetic algorithm. Results reveal that PRSM performance risk probabilities change from 89.25 to 68.72% and 58.1 to 56.86%, with 29.94 and 17.38% tolerance interval width increase under the high-precision and heavy-loading operation cases studied, respectively.
Unveiling the Mind of the Machine
Authors: Clegg Melanie , Hofstetter Reto , de Bellis Emanuel , Schmitt Bernd H
Published: November 2023

Previous research has shown that consumers respond differently to decisions made by humans versus algorithms. Many tasks, however, are not performed by humans anymore but entirely by algorithms. In fact, consumers increasingly encounter algorithm-controlled products, such as robotic vacuum cleaners or smart refrigerators, which are steered by different types of algorithms. Building on insights from computer science and consumer research on algorithm perception, this research investigates how consumers respond to different types of algorithms within these products. This research compares high-adaptivity algorithms, which can learn and adapt, versus low-adaptivity algorithms, which are entirely pre-programmed, and explore their impact on consumers' product preferences. Six empirical studies show that, in general, consumers prefer products with high-adaptivity algorithms. However, this preference depends on the desired level of product outcome range—the number of solutions a product is expected to provide within a task or across tasks. The findings also demonstrate that perceived algorithm creativity and predictability drive the observed effects. This research highlights the distinctive role of algorithm types in the perception of consumer goods and reveals the consequences of unveiling the mind of the machine to consumers.
“A Vile Custom”: The Strange Career of William Osler’s “Professional Notes”
Authors: Healey Jenna
Published: November 2023

In 1882, William Osler wrote “Professional Notes among the Indian Tribes about Great Slave Lake, NWT,” a fantastical essay that purportedly described the sexual and obstetric customs of Indigenous peoples residing in the Canadian Northwest. Originally prepared as a prank, “Professional Notes,” along with Osler’s alter ego Egerton Yorrick Davis, became an elaborate inside joke that circulated widely among the medical elite for decades after Osler’s death. In this essay, I trace the history and afterlife of “Professional Notes,” considering both the colonial context of its creation as well as the reasons for its enduring popularity. I argue that “Professional Notes” both reflected and reinforced the anti-Indigenous racism that permeated the medical profession, particularly during its consolidation in the late nineteenth and early twentieth century. I also make a methodological argument for the study of joking within the history of medicine, presenting “Professional Notes” as a powerful example of the role humour has played in shaping medical culture.
Physical activity and checkpoint inhibition: association with toxicity and survival
Authors: Verheijden Rik J , Cabané Ballester Anna , Smit Karel C , van Eijs Mick J M , Bruijnen Cheryl P , van Lindert Anne S R , Suijkerbuijk Karijn P M , May Anne M
Published: November 2023

Background

Although animal experiments suggest beneficial effects of physical activity (PA) on antitumor immunity, little is known about the effects of PA on immune checkpoint inhibitor (ICI) toxicity and effectiveness in humans. We assessed the association of PA with immune-related adverse events (irAE) and survival in patients undergoing ICI.

Methods

Patients receiving ICI who completed the Dutch short questionnaire to assess health enhancing physical activity (SQUASH) questionnaire at the start of treatment as part of the prospective UNICIT study in an academic hospital were included. PA was quantified by calculating total metabolic equivalent task hours per week (total PA) and hours per week of moderate- to vigorous-intensity PA during sport and leisure time (MVPA-SL). Associations of PA with severe irAE occurrence within 1 year and overall survival (OS) were evaluated using logistic regression and Cox proportional hazard regression, respectively, with adjustment for probable confounders.

Results

In total, 251 patients were included, with a median follow-up of 20 months. Moderate and high levels of total PA were associated with lower odds of severe irAE occurrence compared to low levels of total PA (adjusted OR: 0.34 [95% CI = 0.12 to 0.90] and 0.19 [95% CI = 0.05 to 0.55], respectively). Moderate and high levels of total PA were also associated with prolonged survival (adjusted HR: 0.58 [95% CI = 0.32 to 1.04] and 0.48 [95% CI = 0.27 to 0.89], respectively). Similar associations were observed in patients who performed more MVPA-SL.

Conclusions

Higher physical activity levels at the start of ICI treatment are associated with lower risk of severe irAEs and probably prolonged survival. Randomized controlled trials are needed to investigate whether patients indeed benefit from increasing PA levels after diagnosis.
Multiple proceedings and abuse of procedure on BRI disputes
Authors: Gotsiridze Mariam
Published: November 2023

This article argues that specific mechanisms and best practices should be adopted by different players in the Belt and Road Initiative (BRI) dispute resolution ecosystem to mitigate the risks of multiple proceedings and abuse of procedure. Specifically, (i) states should enhance their multilateral and bilateral treaty practices; (ii) arbitral institutions should enhance their arbitral rules as well as cooperate with each other; and (iii) states should direct more efforts to dispute prevention and amicable dispute settlement. This article will explain what these best practices and mechanisms are. The ‘The BRI’ section will provide a general background on the nature and architecture of the BRI. The ‘Problem of multiple proceedings and abuse of procedure’ section will discuss the notion of multiple proceedings and abuse of procedure. The ‘Potential of multiple, parallel proceedings and abuse of procedure on BRI projects’ section will focus on possible multiple proceedings and abuse of procedure on BRI disputes. The ‘Possible solutions and recommendations’ section will identify possible solutions and provide recommendations. Conclusions section will draw final conclusions.
The precarity of the police powers doctrine in investment arbitration: Rockhopper v Italy
Authors: Carvosso Rhys
Published: November 2023

This article analyses the reasoning of the ICSID tribunal in Rockhopper v Italy with respect to the police powers doctrine. It contends that, in upholding the investors’ claim that the Italian government had unlawfully expropriated their investment in an oil and gas field off the Italian coast by passing a law banning hydrocarbon exploitation and refusing their application for a production permit on that basis, the Tribunal approached the police powers doctrine in an insufficiently clear and rigorous way. First, the Tribunal’s reasons were scant and lacked any articulation of the content of the doctrine or engagement with the extensive body of relevant arbitral jurisprudence and scholarship, making it difficult to comprehend how the doctrine was understood and why it was rejected. Secondly, the Tribunal’s assessment of the validity of Italy’s regulatory purpose, being the only aspect of the doctrine with which it engaged, lacked careful engagement with the evidence. As a result of these shortcomings, the Tribunal’s reasons lend a precarity to the police powers doctrine which belies its relatively settled status in investor-state arbitration and reveals the need for greater rigour and lucidity in its future application.
Soil prokaryotic characterization in response to natural moisture gradient in the temperate grassland ecosystems
Authors: Chen Xin , Wang Yujue , Shen Yuting , Sang Weiguo , Xiao Nengwen , Xiao Chunwang
Published: November 2023

Soil moisture, which is an important factor affecting ecosystem function, can maintain microbial activity and ultimately change the microbial community by altering vegetation diversity and controlling the diffusion and transport of soil nutrients. To explore the effects of soil water content (SWC) on soil prokaryotic community, we established a study area covering a natural soil moisture gradient and subdivided it into high (HW, 4.80 ± 1.18%), medium (MW, 2.17 ± 0.09%) and low water contents (LW, 1.85 ± 0.14%) in the grassland ecosystem along the south shore of Hulun Lake in Inner Mongolia, China. Environmental factors were determined by field surveys and laboratory analyses. Soil prokaryotes were determined by high-throughput sequencing techniques. Vegetation characteristics and soil physicochemical properties had a significant effect on prokaryotic richness diversity, and SWC was the most important factor influencing prokaryotic richness diversity. In the MW, the number of differential prokaryotes was lowest, and prokaryotic microorganisms had the highest diversity and relative abundance at the phylum level, which may reflect less intrinsic variation and higher overall activity of the prokaryotic community in the MW. In addition, HW and LW had lower prokaryotic diversity and relative abundance at the phylum level, and phenotypic predictions for both groups indicated a more tolerant prokaryotic community. In summary, the prokaryotic community responded significantly to the natural moisture gradients in grassland ecosystems along the south shore of Hulun Lake, and both too high and too low soil moisture increased prokaryotic stress resistance.