bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Death Due to Melanoma and Other Causes in Patients With Thin Cutaneous Melanomas
Authors: Lo Serigne N. , Williams Gabrielle J. , Cust Anne E. , Ollila David W. , Varey Alexander H. R. , Ch’ng Sydney , Scolyer Richard A. , Thompson John F.
Published: December 2024

Importance

Most patients who present with primary cutaneous melanomas have thin tumors (≤1.0 mm in Breslow thickness, ie, pT1a and pT1b). Although their prognosis is generally considered to be excellent, there is limited precise information on the association of risk of death with specific Breslow measurements in thin lesions.

Objective

To assess the relative effect of a 0.8-mm Breslow thickness threshold with respect to the incidence of both melanoma-related and nonmelanoma-related death.

Design, Setting, and Participants

Registry data for all Australians diagnosed with thin invasive primary melanomas between 1982 and 2014 were analyzed. Data were extracted from all 8 Australian state and territory population-based cancer registries. Dates and causes of death were obtained from the Australian National Death Index. Adults diagnosed with a first invasive primary melanoma of 1.0 mm or smaller in thickness were included.

Exposure

First invasive primary melanoma between 1982 and 2014.

Main Outcomes and Measures

The primary outcomes were melanoma-related deaths and nonmelanoma-related deaths. Competing-risk regression analyses and cause-specific analyses were performed to investigate the relationships between Breslow thickness subcategory (<0.8 mm versus ≥0.8 mm by 0.1-mm increments) and the primary outcomes.

Results

Overall, a cohort of 144 447 participants was included. The median (range) age was 56 (18-101) years and 78 014 (54.0%) were men. Median (IQR) follow-up was 15.0 (9.5-23.3) years. Crude incidence rates of melanoma-related death 20 years after diagnosis were 6.3% (95% CI, 6.1%-6.5%) for the whole cohort, 6.0% (95% CI, 5.7%-6.2%) for tumors smaller than 0.8 mm, and 12.0% (95% CI, 11.4%-12.6%) for tumors 0.8 to 1.0 mm. The corresponding 20-year melanoma-specific survival rates were 91.9% (95% CI, 91.6%-92.1%), 94.2% (95% CI, 94.0%-94.4%), and 87.8% (95% CI, 87.3%-88.3%), respectively. On multivariable analysis, tumor thickness of 0.8 to 1.0 mm was significantly associated with both a greater absolute risk of melanoma-related death (subdistribution hazard ratio, 2.92; 95% CI, 2.74-3.12) and a greater rate of melanoma-related death (hazard ratio, 2.98; 95% CI, 2.79-3.18) than thinner tumors (<0.8 mm). Risk of death from nonmelanoma-related causes was not associated with Breslow thickness.

Conclusions and Relevance

In this study, the risk of melanoma-related death increased significantly for patients with primary tumors of 0.8 to 1.0 mm in thickness. The risk of death from nonmelanoma-ralated causes was similar across Breslow thicknesses of 0.1 to 1.0 mm. This analysis suggests that a 0.8-mm threshold for guiding the care of patients with thin primary melanomas.
Global Healthspan-Lifespan Gaps Among 183 World Health Organization Member States
Authors: Garmany Armin , Terzic Andre
Published: December 2024

Importance

Health-adjusted life expectancy, a measure of healthy longevity, lags longevity gains, resulting in a healthspan-lifespan gap.

Objective

To quantify the healthspan-lifespan gap across the globe, investigate for sex disparities, and analyze morbidity and mortality associations.

Design, Setting, and Participants

This retrospective cross-sectional study used the World Health Organization (WHO) Global Health Observatory as the global data source and acquired national-level data covering all continents. The 183 WHO member states were investigated. Statistical analysis was conducted from January to May 2024.

Exposures

Data represent 2 decades of longitudinal follow-up.

Main Outcomes and Measures

Changes in life expectancy and health-adjusted life expectancy, as well as the healthspan-lifespan gap were quantified for all participating member states. Gap assessment was stratified by sex. Correlations of the gap with morbidity and mortality were examined.

Results

The healthspan-lifespan gap has widened globally over the last 2 decades among 183 WHO member states, extending to 9.6 years. A sex difference was observed with women presenting a mean (SD) healthspan-lifespan gap of 2.4 (0.5) years wider than men (P < .001). Healthspan-lifespan gaps were positively associated with the burden of noncommunicable diseases and total morbidity, and negatively with mortality. The US presented the largest healthspan-lifespan gap, amounting to 12.4 years, underpinned by a rise in noncommunicable diseases.

Conclusions and Relevance

This study identifies growing healthspan-lifespan gaps around the globe, threatening healthy longevity across worldwide populations. Women globally exhibited a larger healthspan-lifespan gap than men.
Mechanical Behavior of Metastable β Ti–10V–2Fe–3Al Alloy with and without Presence of α Phase
Authors: Pereloma Elena , Nancarrow Mitchel J. B. , Bian Xiaohui , Naseri Ryan , Zhu Qiang , Smillie Lachlan , Saleh Ahmed A.
Published: December 2024

A combination of digital image correlation during uniaxial tensile testing with electron microscopy characterization of microstructure is used to study the details of mechanical behavior of the Ti–10V–2Fe–3Al (wt%) alloy with α phase amount variation from 0 to 20%. Although the triggering stress for deformation‐induced α″ martensite formation has increased and the extent of transformation reduced with an increase in α phase fraction, the deformation mechanism has not changed. The α″ martensite transformation starts from the initiation of single variants of martensite at grain boundaries and/or α/β interfaces in favorably oriented toward deformation axis β grains. It follows by self‐accommodation of strain by α″ martensite via formation of grids and V‐shaped arrangements of {111}α″ type I twins at higher tensile strains.
1D Flat Bands in Phosphorene Nanoribbons with Pentagonal Nature
Authors: Sun Shuo , You Jing‐Yang , Cai Zhihao , Su Jie , Yang Tong , Peng Xinnan , Wang Yihe , Geng Daiyu , Gou Jian , Huang Yuli , Duan Sisheng , Chen Lan , Wu Kehui , Wee Andrew T. S. , Feng Yuan Ping , Zhang Jia Lin , Lu Jiong , Feng Baojie , Chen Wei
Published: December 2024

Materials with flat bands can serve as a promising platform to investigate strongly interacting phenomena. However, experimental realization of ideal flat bands is mostly limited to artificial lattices or moiré systems. Here, a general way is reported to construct 1D flat bands in phosphorene nanoribbons (PNRs) with a pentagonal nature: penta‐hexa‐PNRs and penta‐dodeca‐PNRs, wherein the corresponding 1D flat bands are directly verified by using angle‐resolved photoemission spectroscopy. It is confirmed that the observed 1D flat bands originate from the electronic 1D zigzag and Lieb lattices, respectively, as revealed by the combination of bond‐resolved scanning tunneling microscopy, scanning tunneling spectroscopy, tight‐binding models, and first‐principles calculations. The study demonstrates a general way to construct 1D flat bands in 1D solid materials system, which provides a robust platform to explore strongly interacting phases of matter.
Spin‐Orbital Ordering Effects of Light Emission in Organic–Inorganic Hybrid Metal Halide Perovskites
Authors: Liu Liqun , Tang Yipeng , Ma Yuguang , Hu Bin
Published: December 2024

Organic–inorganic hybrid metal halide perovskites carrying strong spin‐orbital coupling (SOC) have demonstrated remarkable light‐emitting properties in spontaneous emission, amplified spontaneous emission (ASE), and circularly‐polarized luminescence (CPL). Experimental studies have shown that SOC plays an important role in controlling the light‐emitting properties in such hybrid perovskites. Here, the SOC consists of both orbital (L) and spin (S) momentum, leading to the formation of J (= L + S) excitons intrinsically involving orbital and spin momentum. In general, there are three issues in determining the effects of SOC on the light‐emitting properties of J excitons. First, when the J excitons function as individual quasi‐particles, the configurations of orbital and spin momentum directly decide the formation of bright and dark J excitons. Second, when the J excitons are mutually interacting as collective quasi‐particles, the exciton–exciton interactions can occur through orbital and spin momentum. The exciton–exciton interactions through orbital and spin momentum give rise to different light‐emitting properties, presenting SOC ordering effects. Third, the J excitons can develop ASE through coherent exciton–exciton interaction and CPL through exciton‐helical ordering effect. This review article discusses the SOC effects in spontaneous emission, ASE, and CPL in organic–inorganic hybrid metal halide perovskites.
Continuous Flow Synthesis of α‐Chloroketones from Esters
Authors: Brassart Léna , Manneveau Maxime , Poisson Thomas , Legros Julien , Huez Philippe , Forcato Massimiliano , Jubault Philippe , Chausset‐Boissarie Laëtitia
Published: December 2024

Herein, we report a novel and practical strategy to access α‐chloroketones from esters bearing diverse (hetero)aromatic, aliphatic, alkynyl and alkenyl substituents with transient chloromethyllithium under continuous flow conditions. This highly chemoselective method enables a fast (on a time scale of <5 s), efficient and straightforward access to a broad substrate scope (up to 99% yield) with a remarkable throughput of ∼10.6 g/h.
Green Hydrogen and Its Supply Chain. A Critical Assessment of the Environmental Impacts
Authors: Sola Antonella , Rosa Roberto , Ferrari Anna Maria
Published: December 2024

Green hydrogen produced via electrolysis powered by renewables can greatly contribute to achieving carbon neutrality. The analysis of 35 papers reporting the life cycle assessment (LCA) of green hydrogen supply chains confirms the lower greenhouse gas (GHG) emissions with respect to other hydrogen forms and conventional fossil fuel and carbon systems. However, the global warming potential of green hydrogen worsens if grid electricity is used to back up renewable sources. Green hydrogen is also responsible for water consumption and for land use, while offshore platforms may be responsible for the loss of marine biodiversity. Another potential environmental hotspot is the depletion of rare metals and critical materials employed in the electrolyzer and in the power generation plants. This issue is exacerbated by the lack of information about the management of the end‐of‐life stage of this equipment. Notably, the delivery along the supply chain is responsible for hydrogen leaks, whose environmental consequences are still uncertain.
MAM‐STAT3‐Driven Mitochondrial Ca+2 Upregulation Contributes to Immunosenescence in Type A Mandibuloacral Dysplasia Patients
Authors: Padhiar Arshad Ahmed , Yang Xiaohong , Zaidi Syed Aqib Ali , Li Zhu , Liao Jinqi , Shu Wei , Chishti Arif Ali , He Liangge , Alam Gulzar , Faqeer Abdullah , Ali Ilyas , Zhang Shuai , Wang Ting , Liu Tao , Zhou Meiling , Wang Gang , Zhou Yan , Zhou Guangqian
Published: December 2024

Individuals with homozygous laminA/C p.R527C mutations manifest a severe form of Mandibuloacral dysplasia‐(MAD) and exhibit overlapping progeroid symptoms, for which the underlying molecular pathology remains unknown. Herein, it is shown that MAD patients achieved inflammaging with different pro‐inflammatory cytokines compared to progeria‐(HGPS) patient. Characterization of MAD iPSC‐derived Mesenchymal stem cells (MAD‐iMSC) uncovers deregulated mitochondrial Ca+2 as the primary cause of inflammaging, mediated through inflammasome formation rather than the cGAS‐STING pathway. Moreover, MAD‐iMSCs extracellular vesicles (EVs) can also upregulate mitochondrial Ca+2 in healthy cells. This deregulated Ca+2 homeostasis is indirectly mediated by mitochondrial calcium mediator, signal transducer, and activator of transcription‐3 (STAT3), situated on the mitochondrial associated membrane (MAM). Inflammaging is mitigated by various FDA‐approved MAM‐STAT3 upstream inhibitors, such as (Tocilizumab) or by correcting R527C mutation with CRISPR/CAS9. These results provide new insights into MAD disease and propose targeting defective mitochondrial Ca+2 homeostasis as a promising therapy for reversing immunosenescence.
The prevalence and outcomes of pre‐admission vitamin D levels in the management of proximal femur fractures
Authors: Rajeev Aysha , Hunter Connor , Krishnan Saurav , Ullah Atta , Koshy George ,   Gateshead Health Foundation NHS Trust
Published: December 2024

Objectives

The prevalence of low Vitamin D levels (<30 nmol/L) is about 15.7% globally. The aim of this study was to examine the prevalence of vitamin D deficiency in elderly patients with fragility fractures of the hip by estimating 25‐hydroxyvitamin D levels and to assess whether low vitamin D levels at the time of admission affect functional outcomes at 3 months and mortality at 28 days and 1 year.

Methods

We conducted a retrospective study of all patients admitted with a fracture of the neck of the femur between January 2018 and March 2022. Data were obtained from the National Hip Fracture Database (NHFD) and Medway software. A total of 1440 patients were included. Patient demographics, including age, sex, fracture pattern, vitamin D levels at the time of admission, functional status at 120 days, and mortality at 1 month and 1 year, were analyzed.

Results

The average age of the patients was 81.91 years (range 60–108). Of the patients, 1009 (70%) were female and 431 (30%) were male. Vitamin D levels were low in 796 patients (55.3%). Mobility significantly declined in patients with vitamin D deficiency within 3 months after surgery for proximal femur fractures. The 28‐day and one‐year mortality rates were 6.7% and 30.3%, respectively, in patients with low vitamin D levels, compared to 4.7% and 22.3% in those with normal levels. Patients with low vitamin D levels at the time of admission had higher mortality rates at both 28 days and 1 year compared to those with normal levels.

Conclusion

Our study demonstrates that low vitamin D levels at the time of admission for proximal femur fractures are associated with poorer functional mobility and higher perioperative and 1‐year mortality rates.
Potential New Expression Biomarkers for Anorexia Nervosa
Authors: Verebi Camille , Lebrun Nicolas , Petit Justine Vily , Viltart Odile , Duriez Philibert , Saint‐Pierre Benjamin , Gorwood Philip , Ramoz Nicolas , Bienvenu Thierry
Published: December 2024

Anorexia nervosa (AN) is a psychiatric disorder with an estimated heritability of around 70%. Although the largest meta‐analysis of genome‐wide association studies on AN identified independent risk‐conferring loci for the disorder, the molecular mechanisms underlying the genetic basis of AN remain to be elucidated. To investigate AN, we performed transcriptome profiling in peripheral blood mononuclear cells from 15 AN patients and 15 healthy controls. We validated our mean results in a mouse model of chronic food restriction, which mimics several aspects of AN. In this exploratory study, we identified 673 significantly differentially expressed genes in AN. Among these genes, we identified seven genes previously found to be dysregulated in IPSC‐derived neurons from AN individuals and the Vanin‐1 (Vnn1) gene, which appears to play an important role in the regulation of several metabolic pathways. We confirmed underexpression of Vnn1, particularly in the liver, in a mouse model of chronic food restriction. These results indicate that quantitative food restriction affects Vnn1 expression, suggesting that this gene may contribute to the anorexic phenotype in the chronic food restriction mouse model as well as in patients with AN. We believe that this report highlights promising candidate genes and gene pathways for AN, and although we did not obtain a significant result in the replication cohort, it identifies Vnn1 as a potential biomarker that may be used as a molecular target to predict and/or to understand AN.
Ectopic olfactory neuroblastoma is associated with increased frequency of syndrome of inappropriate antidiuretic hormone secretion and reduced disease control: Case series with systematic review and pooled analysis
Authors: Daloiso Antonio , Gaudioso Piergiorgio , Vinciguerra Alessandro , Turri‐Zanoni Mario , Testa Gabriele , Cazzador Diego , Lambertoni Alessia , Arosio Alberto Daniele , Contro Giacomo , Taboni Stefano , Rampinelli Vittorio , Piazza Cesare , Bignami Maurizio , Emanuelli Enzo , Battaglia Paolo , Bossi Paolo , Herman Philippe , Castelnuovo Paolo , Hanna Ehab Y. , Nicolai Piero , Mattavelli Davide , Ferrari Marco
Published: December 2024

Introduction

Olfactory neuroblastoma (ONB) is a rare malignant tumor originating from the olfactory neuroepithelium, typically within the sinonasal cavity. Cases of ONB originating outside of the olfactory cleft area are extremely rare and are referred to as “ectopic” (eONB), in contrast to “orthotopic” tumors (oONB). ONB has been associated with paraneoplastic syndromes (PNSs), including the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study investigate the association between eONB and SIADH and compared the prognosis of eONB to oONB.

Methods

A systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines was conducted, focusing on studies reporting eONB and oONB associated with SIADH. Data from four newly identified eONB cases were reported and a pooled analysis was performed. Statistical analyses were conducted to evaluate the prevalence of SIADH in eONB and oONB and to compare clinical outcomes in the two groups.

Results

eONB had a significantly higher prevalence of SIADH (18.3%) compared to oONB (2.0%; p < 0.0001). Patients with eONB were younger, with a slight predominance of females. Recurrence‐free survival and time‐to‐recurrence of eONB were worse than oONB, independently of other prognosticators.

Conclusions

eONB is associated with a significantly higher incidence of SIADH than oONB, suggesting distinct biological characteristics. Moreover, patients with eONB had worse prognostic outcomes. Further research is needed to understand the underlying mechanisms and improve management strategies for eONB.
Optical Control of TRPM8 Channels with Photoswitchable Menthol
Authors: Becker Jasmin , Ellerkmann Clara S. , Schmelzer Hannah , Hermann Christian , Lützel Kyra , Gudermann Thomas , Konrad David B. , Trauner Dirk , Storch Ursula , Mederos y Schnitzler Michael
Published: December 2024

Transient receptor potential melastatin 8 (TRPM8) channels are well known as sensors for cold temperatures and cooling agents such as menthol and icilin and these channels are tightly regulated by the membrane lipid phosphoinositol‐4,5‐bisphosphate (PIP2). Since TRPM8 channels emerged as promising drug targets for treating pain, itching, obesity, cancer, dry eye disease, and inflammation, we aimed at developing a high‐precision TRPM8 channel activator, to achieve spatiotemporal control of TRPM8 activity with light. In this study, we designed, synthesized and characterized the first photoswitchable TRPM8 activator azo‐menthol (AzoM). AzoM enables optical control of endogenously and heterologously expressed TRPM8 channels with UV and blue light which is demonstrated by performing patch‐clamp experiments. Moreover, AzoM facilitates the reliable determination of activation, inactivation, and deactivation kinetics thereby providing further insights into the channel gating. Using AzoM, the specific roles of individual amino acids for AzoM or PIP2 binding and for sensitization by PIP2 can be elucidated. Altogether, AzoM represents as a high‐precision pharmaceutical tool for reversible control of TRPM8 channel function that enhances our biophysical understanding of TRPM8 channels and holds the potential to support the development of novel pharmaceuticals.
Remote On‐Paper Electrochemiluminescence‐Based High‐Safety and Multilevel Information Encryption
Authors: Fu Wenxuan , Qi Min , Rong Yidan , Lin Chukai , Guo Weiliang , Su Bin
Published: December 2024

The escalating needs in information protection underscore the urgency of developing advanced encryption strategies. Herein we report a novel chemical approach that enables information encryption by on‐paper electrochemiluminescence (ECL). Dendritic porous silica nanospheres modified with polyetherimide and bovine serum albumin were prepared as the chemical ink to write the secret message on a paper. Attaching the paper to an electrode, immersing it in a solution containing tris(2,2′‐bipyridyl)ruthenium (Ru(bpy)32+) and then applying a suitable voltage, a remote “catalytic route” electrochemical reaction produces ECL that functions as the key to decrypt and visualize the message by imaging. In addition, proteins can be also used as the biological ink to write the secret message, which is then decrypted by a combined use of immunochemistry and ECL imaging as two keys. We believe the ECL‐based strategy holds great promise in high‐safety and multilevel information encryption, as it is protected not only by encoding, like conventional invisible inks, but also by the unique ECL decoding approach.
Cationic Lignin and Cellulose Fiber Incorporated Polyvinyl Alcohol Film
Authors: Phansamarng Pratchaya , Bacchus Ameena , Hassan Pour Fatemeh , Kongvarhodom Chutima , Fatehi Pedram
Published: December 2024

Polyvinyl alcohol (PVA) films are widely used in industry, but they have limitations in mechanical strength, UV‐blocking, and antibacterial performance. This research addresses these challenges by integrating kraft lignin (KL) derivative and cellulose fibers (CFs) into PVA films. The results confirmed that KL enhanced UV blocking and hydrophobicity, but it reduced porosity and water absorption. Cationic KL (CKL) further improved UV‐blocking, hydrophilicity, antibacterial properties, and decreased oxygen permeability of the films. CF in PVA enhanced UV‐blocking and mechanical properties. It also improved hydrophilicity, aiding water absorption in lignin‐containing PVA films. CF also increased Young's modulus, oxygen permeability, and antibacterial properties. A 5 wt.% concentration of CF significantly enhanced oxygen barrier properties and mechanical strength, even though it reduced UV‐blocking. These findings highlighted the positive impact of lignin and cellulose derivatives in PVA films. However, due to high water absorption, these films may not be suitable for food packaging requiring moisture resistance.
Kinetics and energetics of biodiesel oxidation stability: The impact of Uapaca kirkiana‐derived natural antioxidants
Authors: Kahimbi Henry , Kichonge Baraka , Kivevele Thomas
Published: December 2024

Despite considerable progress in understanding biodiesel autoxidation inhibition, the kinetics and energetics of the inhibition reactions involving natural antioxidants remain underexplored. Most existing research on natural antioxidants has focused on enhancing oxidation stability and other fuel properties. This study aimed to investigate the oxidative stability of croton biodiesel (CBD) and assess the kinetics and energetics of natural antioxidants derived from the roots, pulp, and fruit peels of the Uapaca kirkiana plant. The oxidation stability of biodiesel samples was assessed using the OXITEST method at temperatures of 90, 100, 110, and 120 °C. These tests enabled the calculation of kinetic parameters such as reaction rates and activation energies, crucial for understanding the inhibition role of antioxidants during oxidative degradation. Activation energy for antioxidant consumption, determined using the Arrhenius equation, was found to be 81.39 kJ mol−1 for fruit peel extracts, 77.73 kJ mol−1 for pulp extracts, and 63.85 kJ mol−1 for root bark extracts. The higher activation energy for fruit peel extracts suggests that they are more effective at preventing oxidation, especially under high‐temperature conditions. Enthalpy, entropy, and Gibbs free energy parameters were calculated using the Eyring equation, indicating a nonspontaneous endothermic process for the antioxidant samples. The study found an inverse relationship between antioxidant concentration and rate constants, demonstrating the antioxidants' effectiveness in slowing down the oxidation process. These kinetics and energetics analyses provide detailed insights into how antioxidants function, facilitating the optimization, selection, and validation of their efficiency in stabilizing biodiesel.
Systematic review and meta‐analysis of the pelvic organ prolapse and vaginal prolapse among the global population
Authors: Mudalige Tharanga , Pathiraja Vindya , Delanerolle Gayathri , Cavalini Heitor , Wu Shuqi , Taylor Julie , Kurmi Om , Elliot Kathryn , Hinchliff Sharron , Atkinson Carol , Potocnik Kristina , Briggs Paula , Saraswat Lucky , Kemp Helen Felicity , Eleje George , Hock Toh Teck , Benetti‐Pinto Cristina Laguna , Muhammad Irfan , Kareem Rabia , Bouchareb Yassine , Phiri Peter , Zhang Ruishu , Weng Yunfei , Aggarwal Ieera , Shi Jian Qing , Shetty Ashish , Litchfield Ian , Rathnayake Nirmala , Elneil Sohier
Published: December 2024

Background

Pelvic organ prolapse (POP) occurs when one or more pelvic organs (uterus, bowel, bladder or top of the vagina) descend from their normal position and bulge into the vagina. Symptoms include pelvic discomfort, fullness, and changes in bladder or bowel function. Treatment ranges from conservative approaches to surgery, depending on symptom severity. Surgical methods include vaginal wall repair, with or without hysterectomy, or via laparoscopic, robotic or open techniques. Common complications include bleeding, infection, and urinary or bowel dysfunction.

Methods

A systematic review was conducted, and a protocol was registered with PROSPERO (CRD42022346051). Publications from 30 April 1980 to 30 April 2023 were retrieved from multiple databases. Data were analysed using random‐effects and common‐effects models with subgroup and sensitivity analyses.

Findings

Forty‐four studies met the inclusion criteria, with 29 studies used for meta‐analysis of vaginal prolapse surgery outcomes. Sixteen studies focused on patients who had undergone hysterectomy alongside prolapse repair.

Interpretation

Patients who underwent vaginal prolapse surgery with hysterectomy experienced higher operative and postoperative complication rates than those without hysterectomy. Increased risks included hospital readmission, POP recurrence and re‐operation. The review highlighted a lack of diversity in terms of ethnicity, age and comorbidity status, which are essential to fully understanding the impact of POP. Future research should focus on these underrepresented factors.
Monitoring of the Biotechnological Production of Dihydroxyacetone Using a Low‐Field 1H NMR Spectrometer
Authors: Mahler Lukas , Tasdemir Ebru , Nickisch‐Hartfiel Anna , Mayer Christian , Jaeger Martin
Published: December 2024

The concept of sustainable production necessitates the utilization of waste and by‐products as raw materials, the implementation of biotechnological processes, and the introduction of automated real‐time monitoring for efficient use of resources. One example is the biocatalyzed conversion of the reusable by‐product glycerin by acetic acid bacteria to dihydroxyacetone (DHA), which is of great importance to the cosmetic industry. The application of compact spectrometers enables the rapid measurement of samples while simultaneously reducing the consumption of resources and energy. Yet, this approach requires comprehensive data preprocessing and, on occasion, multivariate data analysis. For the process monitoring of the production of DHA, a low‐field 1H nuclear magnetic resonance (NMR) spectrometer was implemented in on‐line mode. Small‐volume samples were taken from a bypass and transferred to the spectrometer by an autosampler. Complete analysis within minutes allowed real‐time process control. To this purpose, reliable automated spectral preprocessing preceded the creation of a univariate model. The model enabled the acquisition of process knowledge from chemical kinetics and facilitated the tracking of both substrate and product concentrations, requiring independent calibration. As a second multivariate approach, principal component analysis was utilized to monitor the process in a semi‐quantitative manner without the necessity for calibration. The results of this study are beneficial for real‐time monitoring applications with the objective of exerting control over the process in question while minimizing expenditure.
Project‐Based Learning in Bioprocess Engineering: MATLAB Software as a Tool for Industrial‐Scale Bioreactor Design
Authors: González‐Cortés José Joaquín , Cantero Domingo , Ramírez Martín
Published: December 2024

The project‐based learning (PBL) methodology has proven to be a valuable pedagogical approach in engineering programs for decades. However, a significant gap remains in the application of such methodologies in the field of bioprocess engineering. This study addresses this gap by exploring the implementation and outcomes of innovative PBL methodology in the context of bioprocess engineering education. The educational innovation involved the study of a bioprocess at the industrial scale, which comprises the definition of the culture medium, the operational units of the process, the design of the bioreactor with the assistance of MATLAB software, and the performance of a techno‐economic analysis. The results over eight academic years (441 students) demonstrated consistently high average grades in case studies (8.9 ± 0.3 out of 10), indicating successful student navigation of PBL challenges. The students’ positive feedback highlighted the satisfaction and effectiveness of the methodology in promoting collaboration, enhancing comprehension, and preparing students for real‐world scenarios. Overall, this study provides valuable insights into the successful implementation of PBL in bioprocess engineering education, highlighting its potential for fostering active learning, practical skill development, and student engagement. These findings contribute to the growing body of literature on innovative pedagogical approaches in engineering education and underscore the importance of ongoing evaluation and refinement for enhancing student learning outcomes.
Mogamulizumab‐Associated Autoimmune Diseases: Insights From FAERS Database Analysis
Authors: Zhang Genshan , Zhang Haokun , Fu Jie , Cao Zhixin
Published: December 2024

Background

Mogamulizumab is a monoclonal antibody targeting the C‐C chemokine receptor 4, used to treat T‐cell malignancies such as cutaneous T‐cell lymphoma, adult T‐cell leukemia/lymphoma, and peripheral T‐cell lymphoma. However, real‐world studies on mogamulizumab‐associated adverse events (AEs) are limited.

Methods

Disproportionality analyses were performed to assess the safety profile of mogamulizumab based on data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for the period spanning from October 2018 to December 2023. The research investigated demographic characteristics, the onset timing of AEs, and the safety implications associated with mogamulizumab use.

Results

A total of 1182 significant preferred terms were identified among the 3661 mogamulizumab‐associated AE reports collected from the FAERS database. The frequently reported AEs including rash, infusion‐related reaction, and pyrexia were in line with drug instruction. Notably, several unexpectedly significant AEs were also found, including pemphigoid (ROR = 5.69 [95% CI 1.83–17.66]), unstable angina (ROR = 20.56 [95% CI 8.54–49.5]), bulbar palsy (ROR = 238.36 [95% CI 75.22–755.31]), myositis (ROR = 12.65 [95% CI 5.67–28.19]), and various autoimmune diseases such as autoimmune hepatitis (ROR = 21.33 [95% CI 11.08–41.07]), myocarditis (ROR = 15.29 [95% CI 8.67–26.97]), glomerulonephritis (ROR = 22.49 [95% CI 7.24–69.9]), nephrotic syndrome (ROR = 7.63 [95% CI 2.46–23.67]), myasthenia gravis (ROR = 8.54 [95% CI 3.2–22.77]), and autoimmune thyroiditis (ROR = 11.81 [95% CI 3.8–36.68]).

Conclusion

This study replicated previously identified AEs associated with mogamulizumab and uncovered additional signals of AEs, particularly emphasizing the risks associated with autoimmune diseases. It is essential to exercise vigilance in monitoring the occurrence of these AEs during the use of mogamulizumab in clinical practice.
LRP1B Suppresses Immunotherapy Efficacy in Lung Adenocarcinoma by Preventing Ferroptosis
Authors: Ke Zi‐Hao , Chen Ying , Yu Tao , Zhang Qi , Xiang Yan , Lu Kai‐Hua
Published: December 2024

Background

Immune biomarkers for non‐small‐cell lung cancer (NSCLC) are programmed death ligand 1 (PD‐L1) and tumor mutational burden (TMB). However, they cannot accurately predict the effectiveness of immunotherapy. Identifying appropriate biomarkers that can differentiate between beneficiary groups is imperative.

Methods

We identified lipoprotein receptor–related protein 1B (LRP1B) mutation as a potential biomarker for immunotherapy by analyzing clinical data, combined with bioinformatics analysis. The effects of LRP1B on ferroptosis were assessed using qRT‐PCR, Western blotting, CCK‐8 assay, and flow cytometry. The potential mechanism underlying the regulation of ferroptosis by LRP1B was elucidated using qRT‐PCR, Western blotting, ChIP, and dual‐luciferase reporter gene assays.

Results

Through the collection and analysis of clinical data, we had established that LRP1B mutations are closely associated with immunotherapy. Bioinformatics analysis revealed significant differences in the expression levels of PD‐L1 and TMB between patients with LRP1B mutation and wild‐type patients in lung adenocarcinoma (LUAD). Furthermore, we observed that patients with LRP1B mutation in LUAD had significantly higher levels of tumor‐infiltrating lymphocytes (TILs) than wild‐type patients. In addition, we found that patients with LRP1B mutation in LUAD had significantly prolonged progression‐free survival (PFS) compared to wild‐type patients. However, the differences of PD‐L1 expression, TILs, and PFS were not observed in patients with LRP1B mutation in lung squamous cell carcinoma (LUSC). These findings provided strong evidence that LRP1B mutation was a potential biomarker for immunotherapy in LUAD. Moreover, our in vivo experiments indicated that knockdown of LRP1B enhanced the efficacy of mPD‐1, and mechanistic studies revealed that LRP1B regulated the sensitivity of cells to ferroptosis by modulating the expression of SLC7A11 through altering the phosphorylation level of STAT3. Further analysis revealed that LRP1B knockdown promoted immunotherapy in vivo.

Conclusions

Our results confirmed that LRP1B affected the efficacy of immunotherapy by modulating the sensitivity of NSCLC cells to ferroptosis. LRP1B mutations represent a highly promising immunotherapeutic biomarker for NSCLC.
Gene Expression Profiling of Pancreatic Ductal Adenocarcinoma Arising From Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Ziaziaris William A. , Lim Christopher S. H. , Sioson Loretta , Gill Anthony J. , Samra Jaswinder S. , Sahni Sumit , Mittal Anubhav
Published: December 2024

Introduction

Intraductal papillary mucinous neoplasms (IPMNs) are diverse premalignant tumors of the pancreas. They progress stepwise from adenoma to carcinoma and offer an opportunity for intervention prior to malignant transformation into pancreatic ductal adenocarcinoma (PDAC). The current study aimed to identify differentially expressed genes (DEGs) in invasive PDAC‐associated IPMN vs. noninvasive IPMN to understand the potential molecular changes involved in malignant transformation of IPMN into PDAC.

Materials and Methods

Archived tissue and data from 12 patients with histologically proven invasive PDAC arising from IPMN specimens were assessed. Gene expression analysis was performed on RNA extracted from macro‐dissected tissue specimens using the NanoString nCounter PanCancer Progression assay. Statistical and pathway analysis was performed using SPSS v28 and Ingenuity Pathway Analysis, respectively.

Results

A total of 159 genes had significantly (p < 0.05, q < 0.05) different expression in PDAC arising from IPMN compared with that from IPMN alone (91 overexpressed and 68 underexpressed). Interestingly, 14 of top 10 over‐ and underexpressed genes were predicted to translate secretory proteins, with SignalP scores approaching 1. A number of differential canonical pathways (e.g., LXR/RXR activation pathway, glycolysis I gluconeogenesis I, and hepatic fibrosis) and potential upstream regulators (e.g., TGFB1, THBS2, etc.) were also identified.

Conclusion

A differential gene expression profile between PDAC arising from IPMN and IPMN alone was identified. Pathway analysis identified potential mechanisms involved in malignant transformation of IPMN to PDAC.
Sequential Dual Guide Catheter Technique for Chronic Total Occlusion Interventions in Patients With Prior Coronary Artery Bypass Graft Surgery
Authors: Al‐Ogaili Ahmed , Chu A. J. , Sandoval Yader , Brilakis Emmanouil S.
Published: December 2024

Triple arterial access is sometimes necessary for complete visualization of the collateral circulation and distal vessel anatomy, and to facilitate the retrograde approach in complex chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass surgery (CABG) and multiple sources of collaterals. We present two CTO PCI cases in prior CABG patients with complex occlusions supplied by multiple sources of collaterals for which a “sequential dual guide technique” was used, reducing the number of necessary arterial access points from three to two.
A Case of BRASH Syndrome Presenting With Refractory Hyperkalemia Requiring Intermittent Hemodialysis
Authors: Khadka Bikash , Poudel Saroj , Khanal Kishor , Regmi Ashim , Ghimire Anup , Shrestha Sharad , KC Shirish , Nepal Rohini ,   Doctors on Wheels (DOW)
Published: December 2024

BRASH syndrome characterized by bradycardia, renal dysfunction, atrioventricular nodal blockade (AVNB), shock, and hyperkalemia presents diagnostic and management challenges due to its complex pathophysiology and varied clinical presentations. We describe a 90‐year‐old woman with a history of multiple comorbidities who was on beta blockers bisoprolol for heart failure, presented with shock, refractory hyperkalemia along with bradycardia that required intermittent hemodialysis. Initial management involved aggressive hyperkalemia medical therapy and fluid resuscitation, with subsequent consideration of renal replacement therapy hemodialysis following collaboration with a multidisciplinary team, including cardiology and nephrology specialists. Despite aggressive medical management for hyperkalemia, some cases of BRASH syndrome may remain challenging to treat, requiring intermittent hemodialysis highlighting the need for further research and understanding of this complex clinical entity to improve treatment outcomes.
Spontaneous Tumor Lysis Syndrome in an Undifferentiated Uterine Sarcoma: A Case Report and Review of the Literature
Authors: Valizadeh Zahra , Farshchi Parisa
Published: December 2024

Tumor lysis syndrome (TLS), as an oncologic emergency, may rarely occur in patients with solid organ neoplasms and without previous cancer therapy. Physicians should be highly aware of the possibility of TLS, with special attention in patients having bulky tumors, irrespective of recent treatment with cytotoxic agents for its prompt prevention and treatment.
Giant Primary Choledocholithiasis: A Rare Case Report and Comprehensive Review of Literature
Authors: Lamichhane Samiksha , KC Suraj , Mishra Nishant , Devkota Shritik , Kumar Abhijeet , Gupta Rakesh Kumar
Published: December 2024

Choledocholithiasis is the second most common complication of gallstone disease. Giant primary choledocholithiasis is a rare occurrence. Ultrasonography is the initial mode of imaging, and endoscopic ultrasound is considered superior to other modalities. Endoscopic retrograde cholangiopancreatography can be used for stone extraction. Other treatment modalities include laparoscopic or open common bile duct (CBD) exploration. Many institutions in underdeveloped countries still practice open CBD exploration. Factors such as larger stone diameter, edema of the CBD, and the presence of multiple lithiasis can influence the treatment approach. In this article we are presenting a case of 62 years‐old‐female with no any known comorbidities had presented to emergency with severe upper quadrant pain and giant choledocholithiasis was diagnosed in ultrasound and computed tomography scan with no other features of complications and patient successfully underwent open CBD exploration with intraoperative choledochoscopy and primary closure.
Red Room Temperature Phosphorescence in Non‐Aromatic Carbonized Polymer Dots
Authors: Kang Chunyuan , Tao Songyuan , Yang Fan , Zheng Chengyu , Li Xiaoyu , Yang Bai
Published: December 2024

Achieving red organic room temperature phosphorescence (RTP) remains a significant challenge, especially in a non‐aromatic system. Herein, red RTP with emission at 605 and 645 nm is achieved through inducing and confining carboxyl dimer association (CDA), a unique hydrogen‐bonded coupling red phosphorescence unit, in non‐aromatic carbonized polymer dots (CPDs). The CPDs are synthesized via microwave method by using polyacrylic acid (PAA), succinic acid (SA), and traces of phosphoric acid as precursors. Small molecule SA can flexibly enter the polymer cluster of PAA and pair with the isolated carboxyl groups to form CDA. The intrinsic local carbonized structure formed in CPDs can effectively stabilize CDA to achieve red RTP. The red afterglow can last for 1 s to naked eye, and the corresponding lifetimes for emission at 605 and 645 nm were 61 and 45 ms, respectively, after 365 nm excitation off. This work not only reported the non‐aromatic red organic RTP materials for the first time, but also explored CPDs as an effective platform for achieving such non‐aromatic long‐wavelength RTP.
Gold‐Catalyzed Access to Pyrrolo‐ and (Aryl)Indolo‐Fused Phenazines
Authors: Hüßler Christopher , Dietl Martin C. , Scherr Matthias , Blaum Immanuel E. , Stuntebeck Hanno , Trogemann Lea , Schmidt Sophia , Kahle Justin , Krämer Petra , Rominger Frank , Rudolph Matthias , Hashmi A. Stephen K.
Published: December 2024

Novel fused phenazines were synthesized through a combination of gold‐catalyzed hydroamination and cascade cyclization reactions towards azaacenes. In total, 30 new compounds were synthesized and investigated with respect to their structural and optoelectronic properties. In solution, these targets exhibit strong green to red emission, with quantum yields of up to 60 %. The emission wavelength can be finely adjusted by the choice of solvent due to their solvatochromic behavior, as demonstrated with a representative example.
Holistic Management of Wastewater Pollution Through Biological Treatment: A Sustainable Future
Authors: Chatterjee Bidisha , Baruah Stootee , Chatterjee Deepsikha , Dey Sharadia , Mitra Arup Kumar
Published: December 2024

The global population is increasing at an elevated speed leading to the expansion of urbanization at the cost of environmental degradation, especially aquatic ecosystem pollution due to the enhanced discharge of wastewater. These aquatic ecosystems are primarily polluted by potentially toxic elements, polyaromatic hydrocarbons, dyes, plastics, pesticides, organic compounds, and molecules present in fertilizers, household wastes, industrial effluents, and sewage discharge. The enhanced deterioration of water bodies has led to the search for natural solutions for a sustainable ecosystem. The utilization of the natural microbial flora of the aquatic ecosystem for remediation, more popularly known as bioremediation, is of global interest because of its cost‐effectiveness and eco‐friendly approach. Bioremediation can be broadly categorized into bacterial remediation, mycoremediation, and phytoremediation and is more commonly studied for soil pollution. However, in this review, we discuss bioremediation techniques and mechanisms with respect to water pollution. Aquatic microbes utilize the toxic components present in wastewater as a substrate for their own metabolism by acting as a biologically active methylator or by chemical alteration of the toxicants into less harmful products, thus degrading the toxic environmental pollutants into nontoxic products thereby eliminating their detrimental effects. Microalgae used in phytoremediation also help to elevate the dissolved oxygen level in the aquatic ecosystem thereby reducing the probability of eutrophication. This review represents the study of diverse pollutants remediation and a method involving microbial consortia in a bioreactor for optimum efficacy at minimum cost.
Efficacy, safety, and pharmacokinetics of teclistamab in Chinese patients with relapsed/refractory multiple myeloma from the China cohort of MajesTEC‐1
Authors: Cai Zhen , Xia Zhongjun , He Ai‐Li , Dong Yu‐Jun , Wang Yafei , Liao Aijun , Song Yang , Song MM Juanjuan , Uhlar Clarissa , Chastain Katherine , Watkins Latisha , Luo Xinchao , Huang Lin , Niu Zhuolu , Quijano Cardé Natalia A. , Guo Yue , Xu Hongmei , Verona Raluca I. , Zhou Longen , Li Jingyun , Fu Weijun , Niu Ting , Du Juan
Published: December 2024

Introduction

Teclistamab, the first approved B‐cell maturation antigen‐directed bispecific antibody for treatment of triple‐class exposed relapsed/refractory multiple myeloma, demonstrated deep, durable responses with a manageable safety profile in the pivotal MajesTEC‐1 cohort (NCT03145181/NCT04557098). Efficacy, safety, and pharmacokinetics from the MajesTEC‐1 China cohort are reported.

Methods

Patients received teclistamab 1.5 mg/kg subcutaneously weekly after step‐up dosing; patients could switch to less frequent dosing with continued response.

Results

In the China cohort (N = 26; median age, 66 years; median prior lines of therapy, 5) 15‐month median follow‐up, overall response rates, very good partial response or better, and complete response or better (≥CR) were 76.9%, 76.9%, and 57.7%, respectively. Median time to first response and ≥CR were 1.4 and 6.3 months, respectively; among patients with ≥CR and have available MRD samples, MRD negativity was achieved in 14/15 (93.3%) patients. Median duration of response, progression‐free survival, and overall survival were not reached; 12‐month duration of response, progression‐free survival, and overall survival rates were 78.5%, 68.0%, and 83.5%, respectively. The safety profile was consistent with the pivotal cohort. Although infections occurred in 96.2% of patients, incidence decreased over time with six patients experiencing infections for >12 to 18 months. There were no discontinuations because of adverse events and no dose reductions. Ten patients switched to less frequent dosing. Teclistamab serum concentrations were consistent with the pivotal cohort, with a slightly lower mean pharmacokinetics profile.

Conclusions

Teclistamab demonstrated efficacy and safety profiles in the China cohort consistent with the pivotal cohort, supporting teclistamab as a promising treatment option for triple‐class exposed relapsed/refractory multiple myeloma in China.
Feasibility challenges for automated electronic health record‐to‐electronic data capture technologies
Authors: Stetson Peter D.
Published: December 2024

Electronic health record‐to‐electronic data capture is a possible solution for automating electronic health record data extraction. Significant challenges to the feasibility of full automation remain, especially for multicentered trials.