bluuebunny/crossref_metadata_2025 huggingface dataset:
BHSeP35 Incidence and outcome of emergency presentation with complicated abdominal wall hernias: a retrospective study of 10 years in a District General Hospital
Authors: Anwar Kehkashan , Jadhav Sourabh , Mihailescu Andrei
Published: January 2025

Abdominal wall hernias including groin defects are a common surgical encounter in outpatient clinic , however there is an increasing number of emergency presentations with same problem to ED department seen in recent years.

It is known that best outcome on surgical pathologies is obtained when patient is operated on elective basis, with all necessary pre-optimization done before surgery . It is even more important to achieve pre-optimization steps when abdominal wall defects are repaired surgically, in order to obtain best possible outcomes.

Starting from this postulate, the authors of the study wanted to look at the outcomes of patients operated with any type of abdominal wall hernia in our hospital , who had an emergency presentation, over the last 10 years (2014–2023).

It is of common practice currently in UK to avoid mesh implantation when repairing a complicated hernia on emergency basis, particularly if any bowel involvement. At the same time, the current EHS guidelines advise using a prosthetic reinforcement on all ventral hernias over 1 cm diameter and in all groin hernias, in order to prevent recurrence.

Our retrospective audit looked at several parameters on all presentations with emergency hernias, as follows: immediate surgery vs delayed to elective list, open vs MIS approach, LOS, mesh vs primary stitch repair, long term outcome at follow-up including recurrence, chronic pain and other specific hernia complications.
BHSeP48 A review of outcomes following the establishment of a Complex Abdominal Wall Reconstruction (CAWR) Multi-Disciplinary Team (MDT) at Medway NHS Foundation Trust
Authors: Wilson Kendra , Umair Momina , Salem Reem , Dickson-Lowe Richard , Chan Shirley , Ahmed Ibrahim
Published: January 2025

Background

Medway ventral hernia patients have a high prevalence of co-morbidities, high Body Mass Index (BMI), recurrent hernias, multiple defects, mesh-explantation and stomas. Before CAWR MDT establishment, these patients were booked without standardized pre-operative pathways, experiencing delays and sub-optimal outcomes.

Methods

Prospective data of 55 patients were reviewed from February 2021 to February 2024 after the CAWR MDT was established. Median follow-up of 14 months. Outcome measures included compliance with Delphi consensus, MDT to surgery wait times, length of stay (LOS), complications, recurrences and EuraHS-Quality of Life (QoL) scores.

Results

MDT pre-operative planning achieved 99% guideline compliance. Key gaps were expert radiology, prehabilitation, and dietician input.

11 patients were unsuitable for surgery, another 6 referred to specialist centres.16 patients underwent surgery at Medway; 3 as emergencies. 42% had BMI ≥ 35, 60% required prehabilitation and median CeDAR (Carolina’s Equation for Determining Associated Risk) scores were 35% (IQR 22–43). Median time from MDT to elective repair was 6 months versus 2 months for emergencies. 38% of electives received ultrasound-guided Botulinum toxin injection into lateral abdominal wall musculature pre-operatively, median 47 days before surgery (IQR 40-61).

LOS was 5.5 days for electives versus 14 days after emergency repairs (P = 0.002). Recurrence odds were 10 times higher for emergencies (95% CI 2.5, 153), with 100% complication rates (Clavien-Dindo ≥3) versus 8% for electives. QoL scores were best for elective patients (36/90) compared to those awaiting repair (60/90) and emergency patients (54/90). Elective repairs utilized mesh (retromuscular) in 82% of cases (62% biological), versus 66% and 33% in emergencies respectively.

Conclusions

CAWR MDT enables structured decision-making, optimizes resources and improves patient outcomes. Findings advocated for radiologist and prehabilitation input and expedited elective repairs to prevent significant morbidity in emergencies.
WHO Disability Assessment Schedule 2.0: responsiveness in detecting long-term functional disability after surgery
Authors: Yabuno Yoko , Naito Yusuke , Ida Mitsuru , Ogata Soshiro , Kawaguchi Masahiko
Published: January 2025

Background

The WHO Disability Assessment Schedule (WHODAS) 2.0 is widely used for detecting postoperative functional disability. Its responsiveness for detecting disability has been evaluated at 1 year after surgery, with no long-term evaluation. The aim of this study was to examine the responsiveness of the WHO Disability Assessment Schedule in detecting functional disability at 5 years after surgery.

Methods

This study was a secondary analysis of a prospective observational study. Patients were enrolled who were aged 55 years or older and underwent elective non-cardiac surgery under general anaesthesia. They were asked to complete the 12-item WHO Disability Assessment Schedule and the Medical Outcome Study Short Form questionnaires before surgery and at 5 years after surgery. The correlation between changes in WHO Disability Assessment Schedule score and Medical Outcome Study Short Form physical score (change in physical component score) was evaluated using the Spearman rank correlation coefficient (ρ). The standardized response means were also calculated for typical subgroups for which functional disability was predicted to improve or decline and compared with the overall standardized response mean.

Results

In the analysis, 2596 patients were included. A moderate correlation (ρ = −0.47) existed between changes in WHO Disability Assessment Schedule and physical Medical Outcome Study Short Form scores. The overall standardized response mean was 0.17. The standardized response means for the patients with functional disability predicted to improve ranged from −0.45 to −0.67, whereas those for patients predicted to decline ranged from 0.17 to 0.56. These findings indicated high responsiveness.

Conclusion

The WHO Disability Assessment Schedule 2.0 has a high responsiveness at 5 years after surgery. It can be used to detect functional disability at 5 years after surgery.
Extracellular vesicles in burn injury: roles, mechanisms, and applications
Authors: Wang Min , Zhao Xinyu , Cui Yuyu , Gui Hengshuo , Wang Shuai , Liu Zhuang , Wang Xianwen
Published: January 2025

Burn injuries are associated with high morbidity and mortality, and severe burns trigger many pathophysiological reactions, such as metabolic changes, distributive shock, and inflammatory responses, which are potentially devastating to patients. Burn wound management necessitates infection prevention, anti-inflammation, pain management, and growth factor management, but significant obstacles remain. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types, including mammalian cells, plant cells, and even prokaryotes, They are widely involved in various biological processes, such as cell survival, neovascularization, and immunomodulation. EVs are abundant in components that can play a significant role in different stages of wound repair and at different subcellular levels simultaneously by transporting various active contents, such as proteins and nucleic acids. Moreover, EVs are detectable in many biofluids of burn injury patients and are thus regarded as novel biomarkers for monitoring therapeutic response and predicting prognosis. This review summarizes the biological roles of EVs and their mechanisms of action in burn injury are summarized. The prospects and opportunities for the clinical application of EVs in burn wounds are also discussed. This review will stimulate and guide additional in-depth studies of EVs in burn wound repair, provide a new therapy for burn wounds, and provide a reference and guidance for applying EVs in clinical wound repair.
Reversible Mg2+ insertion/deinsertion of rutile TiO2 in noncorrosive electrolytes
Authors: Yamamoto Keito , Thanh Truc Nguyen Thi , Shimizu Masahiro
Published: January 2025

Single-crystal rutile TiO2 with a spindle morphology was investigated as a negative electrode material for Mg-ion batteries. In the electrolyte with ethylene carbonate and diethyl carbonate typically used for Li-ion batteries, the rutile TiO2 exhibited reversible capacities of 163 and 94 mA h g−1 at the first cycle and 50th cycle, respectively. The spindle structure developed in the c-axis direction should contribute easier Mg2+ diffusion inside the structure to improve utilization of the active material.
Impact of COVID-19 on hospitalization for heart failure: a perspective from Victoria, Australia
Authors: Nguyen Dieu , Kavanagh Shane , Bowe Steve , Tan Elise , Moodie Marj , Gao Lan
Published: January 2025

Aims

The COVID-19 pandemic disrupted healthcare systems and possibly impacted the management of heart failure (HF). This study examined the impact of the pandemic on HF hospitalization activities, outcomes, and costs in Victoria, Australia.

Methods and results

Data on HF hospitalizations were acquired from the Victorian Admitted Episodes Dataset. All consecutive patients hospitalized for HF in both public and private hospitals in Victoria between February 2019 and March 2021 were extracted using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification. Data were analysed using descriptive analysis and interrupted time series analysis. A total of 85 564 completed admissions were identified, of which 45 080 were hospitalized in the pre-COVID-19 period and 40 484 were hospitalized in the COVID-19 impacted period. A higher average cost per completed admission in the COVID-19 impacted period was observed, while average length of stay (LOS) was not different between the two periods. It was revealed that monthly total LOS and hospitalization activity cost across all HF admissions dropped at the beginning of the pandemic and continued to decrease until the end of the observation period. However, these changes were not statistically significant.

Conclusion

The impacts of COVID-19 on HF hospitalization activities and associated outcomes at the beginning of the pandemic appeared relatively small and were not sustained. Further studies using other data (i.e. linkage data) are required to understand if, or how, the pandemic impacted on HF management in Australia, especially in the long COVID-19 era.
ZW Sex Chromosome Differentiation in Palaeognathous Birds Is Associated with Mitochondrial Effective Population Size but Not Mitochondrial Genome Size or Mutation Rate
Authors: Weinstein Brooke , Wang Zongji , Zhou Qi , Roy Scott William
Published: January 2025

Eukaryotic genome size varies considerably, even among closely related species. The causes of this variation are unclear, but weak selection against supposedly costly “extra” genomic sequences has been central to the debate for over 50 years. The mutational hazard hypothesis, which focuses on the increased mutation rate to null alleles in superfluous sequences, is particularly influential, though challenging to test. This study examines the sex chromosomes and mitochondrial genomes of 15 flightless or semiflighted palaeognathous bird species. In this clade, the nonrecombining portion of the W chromosome has independently expanded stepwise in multiple lineages. Given the shared maternal inheritance of the W chromosome and mitochondria, theory predicts that mitochondrial effective population size (Ne) should decrease due to increased Hill–Robertson interference in lineages with expanded nonrecombining W regions. Our findings support the extent of the nonrecombining W region with three indicators of reduced selective efficiency: (i) the ratio of nonsynonymous to synonymous nucleotide changes in the mitochondrion, (ii) the probability of radical amino acid changes, and (iii) the number of ancient, W-linked genes lost through evolution. Next, we tested whether reduced Ne affects mitochondrial genome size, as predicted by weak selection against genome expansion. We find no support for a relationship between mitochondrial genome size and expanded nonrecombining W regions, nor with increased mitochondrial mutation rates (predicted to modulate selective costs). These results highlight the utility of nonrecombining regions and mitochondrial genomes for studying genome evolution and challenge the general idea of a negative relation between the efficacy of selection and genome size.
Associations between regional supply and integration of home and community-based service providers and risk of institutionalization: Evidence from South Korea
Authors: Yun Sunghun , Kim Hongsoo
Published: January 2025

Background and Objectives

To examine whether the regional density of integrated home and community-based services (HCBS) providers affects long-term care (LTC) service utilization pattern and institutionalization risk in South Korea.

Research Design and Methods

This observational study utilized data from the National Health Insurance Service (NHIS) on individuals aged 65 and older who became newly eligible for LTC insurance benefits in 2018. The final sample excluded individuals admitted to long-term care hospitals during the previous year or those living away from home, resulting in a total of 91,302 individuals included in the study. We analyzed the impact of regional HCBS and integrated care provider density on four outcomes: choice of HCBS over LTC facilities (LTCF) as first LTC service, intensity and comprehensiveness of HCBS use, and risk of institutionalization within a year.

Results

Higher regional densities of integrated care providers are associated with increased odds of using HCBS as the first LTC service (Odds Ratio 1.066, model 1, p<0.01). Increased density was also associated with higher odds of using multiple HCBS (Odds Ratio 1.108, model 1, p<0.01). Additionally, higher density of integrated care providers was associated to decreased risk of institutionalization into LTC facilities (Hazard Ratio 0.98, model 1, p<0.01).

Discussion and Implications

The density integrated care providers significantly reduce institutionalization rates, by increasing the possibility of choosing HCBS over LTCF as their first LTC service and using a more comprehensive combination of HCBS services. Further investment in integrated care models may enhance the effectiveness of LTC systems.
Intact N-glycopeptide analysis of human platelets reveals a Glycostructure important for platelet function
Authors: Zhu Hui-Jun , Dong Hang-Yan , Qian Cheng-Rui , Ma Qin-Qin , Li Rui-Shu , Fu Min , He Ye , Lu Ping
Published: January 2025

Glycosylation is an important posttranslational modification in platelets, and the glycosylation pattern is critical for platelet function. To date, the exploration of the roles of various glycoforms in specific platelet functions is largely lacking. In this study, a global analysis of intact N-glycopeptides in human platelets was performed to map all the glycopeptides, glycosites and glycans of platelets. The glycopeptides were enriched by the ZIC- hydrophilic interaction chromatography method and then analyzed by Liquid Chromatography–Tandem Mass Spectrometry analysis. A total of 1,425 intact glycopeptides belonging to 190 N-glycoproteins from human platelets were identified. Moreover, 358 glycans modified 328 glycosites from those glycoproteins. Functional analysis revealed that these glycoproteins are involved mainly in processes and pathways related to platelet adhesion. Among the proteins in these adhesion-related annotations, von Willebrand factor, thrombospondin 1and glycoprotein V were found to contain a possible Lewis y structure, and this finding was further verified by immunoprecipitation assays. As a blood group-related antigen, Lewis y was previously reported to exist in human platelets, but its function remains unclear. Since the glycosylation of von Willebrand factor, thrombospondin 1 and glycoprotein V is involved in platelet–collagen adhesion, the importance of Lewis y on platelet function was evaluated by adhesion assays, which demonstrated that the blockade of Lewis y on platelets decreased the adhesion of platelets to collagen I under both static and flow conditions.
Extraction and characterization of gelatin from acoupa weakfish skins (Cynoscion acoupa) pretreated with EDTA
Authors: Barbosa Jhonatas Rodrigues , Santos Freitas Maurício Madson , Fátima Henriques Lourenço Lúcia
Published: January 2025

The growth of the fish production chain in the Amazon region brought large investments, generating jobs and income. However, accompanied by economic growth, there was an increase in the accumulation of organic waste without any management and use. Here, we present an elegant solution for efficient recovery of high Bloom gelatin from fish skin (Cynoscion acoupa). A new method has been employed using skin pretreatment with EDTA and reflux extraction with acidified water. The protocol was efficient in gelatin recovery, with a maximum yield of 82%. In addition, we reduce the extraction time to a maximum of 1 h, being able to produce high bloom gelatin, with excellent technological properties. Gelatin showed a high correlation between structural amino acids such as proline and hydroxyproline and pseudoplastic rheological behaviour, with high viscosity. The method is scalable and can be applied to expand socioeconomic opportunities in the Amazon.
P20 Evaluation of cefepime/enmetazobactam against MDR Enterobacterales
Authors: Richards J R , Wooton M , Ward J R
Published: January 2025

Background

Cefepime/enmetazobactam is a fourth generation cephalosporin in combination with a novel penicillanic acid sulfone ESBL inhibitor. Cefepime is stable to AmpC β-lactamases (class C) and OXA-48-like carbapenemases (class D) whilst enmetazobactam has activity against most class A β-lactamases (TEM, SHV, CTX-M). Limited activity has been reported against KPC carbapenemases and no activity seen against metallo-β-lactamases (class B). Cefepime/enmetazobactam is approved for use as treatment for complicated urinary tract infections (cUTI), pyelonephritis, hospital acquired pneumonia (HAP) and ventilator acquired pneumonia (VAP). The aim of this study was to understand the activity of cefepime/enmetazobactam against UK isolates of MDR Enterobacterales.

Materials and methods

Cefepime/enmetazobactam MICs were determined on 203 clinical Enterobacterales using broth micro dilution (BMD) according to International Standard 20776-1. All isolates were resistant third generation cephalosporin and/or carbapenems, due to native and plasmid-mediated AmpC β-lactamases, ESBLs, OXA-48-like carbapenemases and efflux mechanisms. Ceftazidime-avibactam was tested concomitantly. Clinically derived susceptibility testing data for carbapenems, cephalosporins and aminoglycosides was also collected. EUCAST v14 clinical breakpoints were used to interpret MICs.

Results

Overall cefepime/enmetazobactam susceptibility was 94.1% and resistance 5.9%. Cefepime/enmetazobactam susceptibility for third generation cephalosporin resistant Enterobacterales, harbouring either a CTX-M ESBL, hyper-expressed native (intrinsic) AmpC β-lactamase or plasmid-mediated AmpC β-lactamase was 96.1%, 92% and 100%, respectively. Overall ceftazidime/avibactam susceptibility was 99%. For those isolates harbouring an OXA-48-like carbapenemase (without CTX-M but possibly some native AmpC activity) the cefepime/enmetazobactam susceptibility was 100%. Whilst the percentage cefepime/enmetazobactam susceptibility in isolates containing OXA-48-like carbapenemase and a CTX-M enzymes was 89.1%. For Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae, cefepime/enmetazobactam susceptibility was 98.8%, 87.1% and 83.3%, respectively. For all other species susceptibility was 100%. Only 12 (5.9%) isolates exhibited cefepime/enmetazobactam resistance, with MICs ranging from 8 mg/L to >128 mg/L. However, seven of these isolates had MICs just above the breakpoint (8 mg/L). Resistance mechanisms present were CTX-M ESBL or AmpC alongside efflux.

Conclusions

Cefepime/enmetazobactam has good activity against third generation cephalosporin and carbapenem resistant Enterobacterales. The agent has excellent activity against all third generation cephalosporin resistance mechanisms (native and plasmid-mediated AmpC and ESBL) as well as carbapenem resistance due to OXA-48 like carbapenemases and efflux.
The association between clinical trial participation, drug costs, and performance in the Oncology Care Model
Authors: Canavan Maureen E , Westvold Sarah , Csik Valerie , Franks Jeffrey , Rocque Gabrielle , Gross Cary P , Adelson Kerin B
Published: January 2025

It has long been assumed that academic oncology practices are disadvantaged in value-based payment programs because of patient complexity and research costs. This assumption has not been tested. The Oncology Care Model (OCM) was a Medicare alternative payment model, which sought to curb costs while improving care. We assessed the impact of clinical trial participation on 2 outcomes: (1) cost and (2) practice performance among 3 participating National Cancer Institute–designated cancer centers using a random effects meta-analysis. The mean total Medicare cost per episode was $42 225 for clinical trial episodes and $34 937 for nonclinical trial episodes. Despite higher total costs, clinical trial episodes were more likely to be under spending targets than non–clinical trial episodes (odds ratio = 0.37, 95% confidence interval = 0.25 to 0.48). Drug costs in clinical trial episodes were lower than in nonclinical trial episodes, although this was only statistically significant at the largest volume practice. In conclusion, clinical trials may offer an advantage in value-based programs.
Abdominal pseudohernia caused by thoracic disk herniation: case series and review of the literature
Authors: Massé G , Al Khaldi M , Schwenter F , Boudier-Revéret M , Sebajang H
Published: January 2025

Intervertebral thoracic disk herniation (TDH) is a rare occurrence and presents with a wide variety of symptoms. Errors in diagnosis are thought to be frequent due to the variable clinical presentations. We herein present two unusual cases of TDH presenting with abdominal pseudohernias, abdominal pain, and hypoesthesia along the T11-T12 dermatomes due to TDH at the same level. Both patients were managed conservatively, using a combination of analgesics and muscle relaxants. At 10 months of follow-up, the first patient reported complete resolution of abdominal bulge and no residual pain. The second patient reported residual paresthesia of T11-T12 dermatome, with non-limiting back pain and almost complete resolution of abdominal bulge. In conclusion, TDH may present with an abdominal wall bulge mimicking hernia, hypoesthesia, and radicular pain along the affected dermatome. Conservative management can be considered as first-line treatment.
Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence
Authors: Tang Weicheng , Wang Kaichen , Feng Yourong , Tsui Kuan-Hao , Singh Keshav K , Stout Michael B , Wang Shixuan , Wu Meng
Published: January 2025

The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility and dysfunction across multiple organs. Research has demonstrated that cellular senescence in various cell types within the ovary can trigger a decline in ovarian function through distinct stress responses, resulting in ovarian aging. This review explores how cellular senescence may contribute to ovarian aging and reproductive failure. Additionally, we discuss the factors that cause ovarian cellular senescence, including the accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, and exposure to chemotherapy. Furthermore, we discuss senescence in six distinct cell types, including oocytes, granulosa cells, ovarian theca cells, immune cells, ovarian surface epithelium and ovarian endothelial cells, inside the ovary and explore their contribution to the accelerated ovarian aging. Lastly, we describe potential senotherapeutics for the treatment of ovarian aging and offer novel strategies for ovarian longevity.
A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei
Authors: Jonsdottir Thorey K , Paoletta Martina S , Ishizaki Takahiro , Hernandez Sophia , Ivanova Maria , Herrera Curbelo Alicia , Saiki Paulina A , Selinger Martin , Das Debojyoti , Henriksson Johan , Bushell Ellen S C
Published: January 2025

Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able to target about half of the genome in the more genetically tractable rodent malaria parasite Plasmodium berghei. To overcome this limitation, we have developed a scalable CRISPR system called P. berghei high-throughput (PbHiT), which uses a single cloning step to generate targeting vectors with 100-bp homology arms physically linked to a guide RNA (gRNA) that effectively integrate into the target locus. We show that PbHiT coupled with gRNA sequencing robustly recapitulates known knockout mutant phenotypes in pooled transfections. Furthermore, we provide an online resource of knockout and tagging designs to target the entire P. berghei genome and scale-up vector production using a pooled ligation approach. This work presents for the first time a tool for high-throughput CRISPR screens in Plasmodium for studying the parasite’s biology at scale.
Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors
Authors: Bremer Juliane , Franco Pamela , Menstell Joelle Aline , Tey Shelisa , Zajt Kamil Kajetan , Popzhelyazkova Klimentina , Nolte Kay , Schlegel Jürgen , Pedro Maria Teresa , Osterloh Anja , Delev Daniel , Hohenhaus Marc , Scholz Christoph , Schnell Oliver , Beck Juergen , Weis Joachim , Heiland Dieter Henrik
Published: January 2025

Background

Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells. Here, we aimed at determining the spatial and biological heterogeneity of PNSTs.

Methods

We performed spatial transcriptomics on formalin-fixed paraffin-embedded diseased peripheral nerve tissue. We used spatial clustering and weighted correlation network analysis to construct niche-similarity networks and gene expression modules. We determined differential expression in primary pathologies, analysed pathways to investigate the biological significance of identified meta-signatures, integrated the transcriptional data with histological features and existing single cell data, and validated expression data by immunohistochemistry.

Results

We identified distinct transcriptional signatures differentiating PNSTs. Immune cell infiltration, APOD and perineurial fibroblast marker expression highlighted the neurofibroma component of hybrid PNSTs (HPNSTs). While APOD was evenly expressed in neurofibromatous tumor tissue in both, HPNST and pure neurofibromas, perineurial fibroblast markers were evenly expressed in HPNST, but restricted to the periphery in plexiform neurofibromas. Furthermore, we provide a spatial cellular differentiation map for MPNST, locating Schwann cell precursors, neural crest-like cells and those with mesenchymal transition.

Conclusions

This pilot study shows that applying spatial transcriptomics to PNSTs provides important insight into their biology. It helps establishing new markers and provides spatial information about cellular composition and distribution of cellular differentiation states. By integrating morphological and high-dimensional molecular data it can improve PNSTs classification in the future.
Big Data Bayesian Truths: No Vancomycin Trough Concentration Target is Sufficiently Precise for Safety or Efficacy
Authors: Shiau Justin , Roy Sharmeen , Sabourenkov Paul , Scheetz Marc H
Published: January 2025

Introduction

Therapeutic drug monitoring is standard of care for vancomycin because of the known efficacy and safety exposure window [i.e. area under the concentration-time curve (AUC) of 400-600 mg*24hours/L]. Despite guideline recommendations, AUCs are infrequently calculated because of the perceived adequacy of trough (Cmin) concentrations. Yet, the percentage of real-world patients with goal measured vancomycin trough concentrations that achieve target vancomycin AUC remains unknown.

Methods

A large cohort of internationally represented adult patients treated with vancomycin in 2021 and 2022 and therapeutic drug monitoring performed had data anonymized via an electronic clearinghouse at DoseMe. Unique patients, dosing events, and measured Cmin were identified. Patient individualized AUC was calculated using a Bayesian method with 4 validated models. For each dosing event, Cmin and AUC pairs were compared and categorized as “low”, “target”, and “high” using the therapeutic ranges for Cmin of 15-20 mg/L and AUC of 400-600 mg*24hours/L.

Results

In 2022, 17,711 adult patients from the European Union (4.9%), Australia (4.0%), and the United States (91.1%) with 26,769 measured trough levels obtained. Categorical disagreement between Cmin and AUC was 34.3%, with most disagreement (7,959 Cmin levels, 30%) occurring with low Cmin but target AUC. Only 23% of paired Cmin and AUC were within range. AUC was variable for all trough categories (i.e. low, target, and high).

Conclusion

These findings support AUC therapeutic drug monitoring and challenge Cmin as an adequate vancomycin AUC proxy. Since no trough concentration or range was sufficiently precise to ensure AUC targets, we suggest direct calculation of AUC.
Four Matters of Interpretation: The Constitutional Phenomenon in Comparative Studies
Authors: Kuo Ming-Sung
Published: January 2025

This article takes a close look at the state of comparative constitutional studies as constitutional scholarship is taking a comparative turn. It first surveys the field and identifies four varieties – doctrinal, law-and-society, documentary, and cultural – of constitutional comparison and then critically investigates the state of comparative constitutional studies. Through this two-stage engagement, this article aims to make two main analytical points. First, at the core of each of the four varieties of comparative constitutional studies lies an interpretive exercise oriented by its distinctive purpose. Second, the social sciences’ growing influence on constitutional comparison has entailed a myth of scientism in the field, which may inadvertently impoverish comparative constitutional studies as a whole. It concludes with a cautionary note on the comparative turn in studying constitutional ordering. With its prevalent focus on formal institutions and norms in constitutional orders, the comparative turn may unwittingly limit studies of the multifaceted constitutional phenomenon.
Ovarian clear cell carcinoma: open questions on the management and treatment algorithm
Authors: Rosso Roberta , Turinetto Margherita , Borella Fulvio , Chopin Nicolas , Meeus Pierre , Lainè Alexandra , Ray-Coquard Isabelle , Le Saux Olivia , Ferraioli Domenico
Published: January 2025

Ovarian clear cell carcinoma (OCCC) accounts for ~10% of all epithelial ovarian cancers and is considered a different entity from the more common high-grade serous ovarian carcinoma (HGSC), with distinct clinical presentations, different risk, and prognostic factors, and specific molecular features. Most OCCCs are diagnosed at an early stage and show favorable outcomes, in contrast to those diagnosed at advanced stages, which exhibit intrinsic resistance to platinum-based chemotherapy regimens and a very poor prognosis. The standard treatment of advanced OCCC is currently based on primary debulking surgery followed by platinum-based chemotherapy according to recent international guidelines. However, these recommendations are extrapolated from several trials mainly featuring a large cohort of HGSC, with only a small minority of OCCC. Because of its rarity, many questions remain unanswered regarding the surgical and medical treatment. Lymph node staging, fertility-sparing treatment, the use of targeted therapies and radiotherapy as well as the adjuvant treatment for early-stage disease and second or further lines of chemotherapy are still under debate. This review aims to address these unresolved issues, by providing a comprehensive overview of the current data on this disease, and to suggest possible directions for future research.
Introduction
Authors: Garrod Raphaële
Published: January 2025

Bodily functions in Rabelais have polarized its scholarly reception. Both Bakhtinian, carnivalesque interpretations and satirical ones assume their opposition to higher, intellectual and spiritual activities: a contrast repeated in the ideological and hermeneutical pitting of high humanism against popular culture, of literal against spiritual meanings. However, a third way opened by Jeanneret and others has highlighted the continuum between these polar opposites. In Renaissance medicine, animation results from a spirited physiology whose integrated operations—breathing, digesting, thinking—define the dynamism of the human ingenium as inborn nature and wit, this source of invention. By envisaging man as an ingenious animal, Rabelais’s fictions investigate the physiological production of culture as invention. The following chapters sketch various figures of this investigation in a selection of episodes from Gargantua and the Quart livre. The poetics best suited to it was that of the Renaissance grotesque ornament—a metamorphic, antiquarian, ironically reflexive art form.
Situating Islamic Reform
Authors: Bashir Haroon
Published: January 2025

The concept of reform (Islāh; Tajdīd) has existed throughout Islamic history. The idea of human errancy and the need to renew traditions is certainly not novel within Islamic thought, as Islam views itself as a corrective to previous ‘adulterated’ traditions. To this end, Muslim scholarship has often attempted to chart out the great reformers of the Islamic tradition, attributing key scholars to different centuries. This chapter explores the primary components of the nineteenth-century reform movement. It explores what led to reformist scholarship emerging, and how this movement differed from those that preceded it, situating these discourses during the period of European Colonialism.
Striking the Right Balance
Authors: Bussey Erica
Published: January 2025

The Special Criminal Court (SCC) in the Central African Republic (CAR), a ‘hybrid’ tribunal wholly grounded within the national justice system, has a majority of national judges and nationals in key staff positions. At the opposite end of the spectrum, the Kosovo Specialist Chambers (KSC), by design, has no national judges or staff. In the middle there are uneasy compromises—the proposed Hybrid Court for South Sudan (HCSS), as well as several of the first-wave of hybrids such as the Special Court for Sierra Leone (SCSL) and the Extraordinary Chambers in the Courts of Cambodia (ECCC). Against the backdrop of these two opposite models, and by looking at case studies from several tribunals, this chapter examines the rationales for including and for excluding national judges and staff in hybrid tribunals, with an emphasis on the question of legitimacy, and the effects of these choices on internal and external resilience. The chapter also breaks down the national and international components of hybrid tribunals, with an emphasis on the effects of the regionalization of the composition of judges and staff on the legitimacy of recently created tribunals, as well as on other questions relating to personnel who fall between the narrow ‘national’ and ‘international’ categories, such as those from the diaspora.
The Premise of Capacity Building in the Special Court for Sierra Leone, the Extraordinary Chambers in the Courts of Cambodia, and the Bosnian War Crimes Chamber
Authors: Jimenez Ezequiel
Published: January 2025

This chapter examines the premise of capacity building within the hybrid tribunal model and analyses the experience of the Special Court for Sierra Leone (SCSL), the ongoing trials in the Extraordinary Chambers in the Courts of Cambodia (ECCC), and the unique judicial set up in the War Crimes Chamber (WCC) within the Court of Bosnia Herzegovina (BiH) with the backing of the International Tribunal for the Former Yugoslavia (ICTY). Tasked with prosecuting war crimes, genocide, and crimes against humanity, the hybrid tribunal model contemplates the premise of rebuilding domestic judicial capacity through a mix of applicable domestic and international law, knowledge transfer between local and foreign judicial personnel, and infrastructure investment, to bring the judicial process closer to victims in post-conflict situations. However, the experiences in Sierra Leone, Cambodia, and Bosnia Herzegovina highlight the varied implementation of the capacity-building element of the hybrid tribunal model, uncovering issues of operational clarity hybrid tribunals’ mandate to rebuild domestic judicial systems as well as the level of impact and resources allocated for this mammoth task. Given the re-emergence of the hybrid tribunal model to address situations where an accountability gap persists, strengthening the premise of the capacity-building element in the hybrid tribunal model is paramount for processes aimed at developing resilient states based on the rule of law and the right of access to justice.
Molding Military Loyalty
Authors: Peifer Douglas Carl
Published: January 2025

State authority rests on a mix of coercion, popularity, and tradition. The overwhelming majority of German soldiers, sailors, and airmen fought doggedly for the Third Reich as long as they were able to do so. This chapter explores how Hitler and the German military nurtured loyalty and suppressed dissent. It argues that consent and conformity were as important as coercion in preventing desertion. Much of the working class came to embrace the idea of a German people’s community (Volksgemeinschaft), with German schools and the Hitler Youth cultivating Nazi worldviews in the younger generation before they entered the military. Once in the military, loyalty to comrades in arms (Kameradschaft), notions of masculinity, and a mix of traditional and ethnic nationalism made the idea of desertion repugnant to all but a few.
Situating the Deserter in Postwar German Consciousness
Authors: Peifer Douglas Carl
Published: January 2025

Assessing the crime of desertion in the context of the Third Reich’s war of aggression took decades of debate, changing and evolving over time. It would be debated between the two Germanies, and it pitted different segments of society against one another: survivors and perpetrators, playwrights and judges, and those who had stayed in the ranks and those who had not. This chapter analyzes the contested meaning attached to the Wehrmacht deserter in Germany from its defeat to the twenty-first century. It examines how postwar authors such as Alfred Andersch and the Gruppe 47 portrayed the deserter, how courts dealt with the matter, how assessments of the National Committee for a Free Germany evolved, and how the Filbinger Affair ignited a national debate about recognizing and rehabilitating those who had deserted Hitler’s Wehrmacht.
“Like a Human Being”
Authors: Riccardi Ricky
Published: January 2025

This chapter focuses on how Louis Armstrong was arrested and its aftermath. In 1910, the Chinatown section of Louis’s Third Ward neighborhood was rocked by a fire which was a beacon for looters, including 15-year-old Henry Smith, who targeted a building filled with brass. Armstrong was taking a chance by joining Smith’s crew, but the lure of making money off some stolen brass was too good to pass up. The chapter considers the issue of juvenile delinquency, especially in the African American community. It provides an overview of Armstrong living with the Jewish Karnofsky family between jobs to support his family.
“I Would Gladly Live It Over Again”
Authors: Riccardi Ricky
Published: January 2025

This chapter discusses the aftermath of Louis Armstrong leaving the Waif’s Home. Louis might have been sad to leave the Waif’s Home and sadder to not be with his mother, but it was probably best for him to be living at Willie Armstrong’s home. However, eventually, he returned home to his mother after his father concluded that his expenses were too heavy for both his original family and Armstrong. The chapter considers the conflicting reports regarding this period of Armstrong’s life, particularly with regard to music. Armstrong’s foundation of singing and comedy was secure, but he hadn’t had any real opportunities to hear good ragtime since he left the Waif's Home in June 1914.
“The Memory of the Bullies and Trouble Makers”
Authors: Riccardi Ricky
Published: January 2025

This chapter discusses Louis Armstrong’s first gig, where he played and sang at Andrew H. Pons’s place. It details the level of violence occurring at the location due to the feud between Pons and Joe Segreto. Eventually, Armstrong began to form a small addiction to his neighborhood’s nightlife. Armstrong was now at a crossroads and could have easily ended up like one of his old Waif’s Home friends if he had made the wrong choices. The chapter then provides an overview of Armstrong’s writing about bullies and troublemakers he met in his life. It notes the vague details related to whether Armstrong played during the funeral of Arthur Brown, one of Armstrong’s classmates at Fisk School.
“Son, You Got a Chance”
Authors: Riccardi Ricky
Published: January 2025

This chapter focuses on Louis Armstrong’s chances after leaving the secure employment of the Marable band. The Orchard Cabaret engagement solidified the close friendship between Armstrong and Arthur “Zutty” Singleton. Aside from trying to avoid his ex-wife, rmstrong was honored to be asked to join Oscar “Papa” Celestin’s Tuxedo Brass Band in the latter part of 1921. As Armstrong’s reputation grew, he became an in-demand sub with the city’s other popular brass bands, always making an impact with each parade he played. The chapter then reviews Armstrong’s upbringing beyond the blues and jazz up until his decision to go to Chicago to play with his idol, King Oliver.
“I Always Played Pretty under Him”
Authors: Riccardi Ricky
Published: January 2025

This chapter provides an overview of Louis Armstrong’s arrival in Chicago. It introduces the band members Armstrong was to play with alongside Joe Oliver. Oliver’s music had an equally life-changing effect on the many young Black musicians who frequented the Lincoln Gardens. Oliver also occasionally took Armstrong out on the town to hear Chicago’s other jazz bands, including Will Bottoms’s Dreamland Café, where the orchestra was led by violinist Mae Brady. The chapter also mentions Armstrong meeting white musicians from downtown Chicago and enjoying their music. It then elaborates on the influence of Bill “Bojangles” Robinson on Armstrong’s eventual stage persona.
“Awful Glorious Days”
Authors: Riccardi Ricky
Published: January 2025

This chapter examines Louis Armstrong’s growing career. It notes how Armstrong’s Stompers remained at the Sunset Café throughout the summer of 1927, finally winning the approval of Dave Peyton. Armstrong began doubling with the orchestra of pianist Clarnece Jones at the Metropolitan Theater. . Armstrong was still featuring early Hot Five, but OKeh was hoping for similar hits and they weren’t finding them, even with a new Hot Seven batch of recordings. The chapter then discusses how Armstrong conquered the Savoy and decided to record for OKeh again to make history.
Legacy, Part I
Authors: Walker Paul
Published: January 2025

This chapter investigates the influence of both the preludes and the fugues on later composition and pedagogy. Composers whose works show significant influence from The Well-Tempered Clavier include Mozart in the eighteenth century, Mendelssohn and Schumann in the nineteenth, and Hindemith and Shostakovich in the twentieth. Although the Paris Conservatory has, since its founding, relied on its own in-house model for the teaching of fugue (the so-called fugue d’école), Bach’s fugues were taken as the standard in the Leipzig Conservatory under Mendelssohn’s directorship around the middle of the nineteenth century and quickly became the universal authority for most of the musical world, a status they enjoy to this day. The preludes served as models for keyboard études in the first half of the nineteenth century, but since that time have exerted less influence than the fugues.
The Wars of the Lord
Authors: Tuininga Matthew J.
Published: January 2025

The Wars of the Lord: The Puritan Conquest of America’s First People tells the story of how the English Puritans came to dominate the native peoples of New England. The Puritans believed that by colonizing the new world they were advancing Christ’s kingdom, waging a spiritual war against the Devil, and liberating Native Americans from sin and darkness. They attempted to colonize the natives in a manner consistent with justice and peace. When Indians resisted colonization, as during the Pequot War (1636-1637), the Puritans interpreted such attacks as an assault on Christ’s kingdom and responded ruthlessly. For the most part, therefore, Indians pursued cooperation through trade and diplomacy. Missionaries such as John Eliot worked hard to convert Indians to Christianity, and thousands did become Christians. Though a series of crises repeatedly brought the region to the brink of war, Indians and Puritans managed to avoid a major conflict until the catastrophe of King Philip’s War (1675-1676). After suffering a series of major disasters, the English and their Indian allies ultimately crushed their Indian opposition. The war left the English in a dominant position over all Indians, including those who had converted to Christianity or supported the English during the war.
The Lord Has Cleared Our Title
Authors: Tuininga Matthew J.
Published: January 2025

This chapter describes how disease devastated native populations and the English colonies expanded. Puritans believed God used diseases like smallpox to clear native land for his people. Entire Indian communities were nearly wiped out, opening regions like the Connecticut Valley for settlement. Numerous parties laid claim to the valley, including the Pequots, local Indians, Dutch traders, Plymouth, and a new English colony named Saybrook, founded at the mouth of the Connecticut River. Roger Williams challenged the morality of colonization and was banished from Massachusetts, leading him to establish what would become Rhode Island.
The Pocumtuck War
Authors: Tuininga Matthew J.
Published: January 2025

This chapter describes how the colonies struggled to bring recalcitrant sachems to submit to English dominion while pressuring Indians to sell additional land. Massachusetts repeatedly prevented the colonies from going to war without just grounds, undermining the unity of the United Colonies. When the Pocumtuck War broke out among various Indian communities, it exacerbated the division among the colonies, with Connecticut sympathizing with Uncas and Massachusetts sympathizing with the Narragansetts. But the colonies’ common interests – especially their desire for land – eventually led them to form a common front against the Narragansetts. After a series of Narragansett depredations, the United Colonies imposed punitive reparations on the Narragansetts. The Narragansetts were forced to mortgage their land to the Atherton Company to pay the debt, and the Atherton Company soon claimed all Narragansett land.