bluuebunny/crossref_metadata_2025 huggingface dataset:
Visible‐Light‐Induced Denitroalkylation of β‐Nitrostyrenes with Alkyl Boronic Acids
Authors: Xu Mingli , Zhao Chenyue , Huang Yongxiang , Hu Shuo , Cheng Dongping , Xu Xiaoliang
Published: November 2023

Without an additional activator, the visible‐light‐catalyzed denitroalkylation of β‐nitrostyrenes and alkyl boronic acids is reported. The efficient coupling of cyclic and secondary alkyl boronic acids with various aryl nitroolefins is realized, which gives aryl alkyl olefins in 47–87 % yields. A possible mechanism involving the fact that nitrite is released from β‐nitrostyrene upon irradiation and further activates alkyl boronic acids to generate alkyl radicals is proposed based on control experiments and a literature survey.
Mesoporous Cerium Oxide Nanoparticles with High Scavenging Properties of Reactive Oxygen Species for Treating Age‐Related Macular Degeneration
Authors: Choi Seung Woo , Kim Ye Eun , Kim Jaeyun
Published: November 2023

Age‐related macular degeneration (AMD), the leading cause of vision loss among older individuals, is characterized by damage to photoreceptors and retinal pigment epithelial cells (RPEs). Oxidative stress and chronic inflammation in the retina play notable roles in AMD pathogenesis, rendering them attractive therapeutic targets. Cerium oxide nanoparticles (CeNPs) have shown promise in scavenging reactive oxygen species (ROS) by mimicking antioxidant enzymes, whereas mesoporous materials have emerged as versatile drug carriers. Herein, mesoporous CeNPs (mCeNPs) that integrate the advantages of CeNPs and mesoporous materials are presented. The mCeNPs can be synthesized using 1,1′‐carbonyldiimidazole and imidazole in acetone without heating and pressurization. The resulting mCeNPs exhibit mesoporous structures comprising assembled small CeNPs, exerting excellent ROS‐scavenging capabilities, biocompatibility, and cytoprotective and anti‐inflammatory effects against H2O2‐induced damage in RPEs. Using a sodium iodate‐induced AMD mouse model, it is demonstrated that intravitreal mCeNP administration can exhibit disease‐preventive effects. These findings indicate the therapeutic potential of mCeNPs against AMD.
Makromolekulare Hydrazon Hauptkettenphotoschalter
Authors: Duy Thai Linh , Fanelli Julian , Munaweera Rangika , O'Mara Megan L. , Barner‐Kowollik Christopher , Mutlu Hatice
Published: November 2023

Hydrazone – bestehend aus einer dynamischen Iminbindung und einem sauren NH‐Proton – haben sich in letzter Zeit aufgrund ihrer Fähigkeit zur Bildung thermisch bistabiler (Z) bzw. (E) Isomere als vielseitige Potoschalter erwiesen. In diesem Artikel stellen wir zwei lichtsensitive Homopolymere vor, die strukturell unterschiedliche Hydrazone als sich wiederholende Einheiten in der Hauptkette enthalten und durch „Kopf‐Schwanz“‐Polymerisation mittels azyklischer Dien‐METathese (ADMET) synthetisiert wurden. Der Hauptunterschied der beiden Polymere liegt dabei im Design des Hydrazon‐Photoschalters, insbesondere in der Lage des aliphatischen Arms, der den Rotor mit dem aliphatischen Polymerrückgrat verbindet. Es zeigt sich, dass sich das hydrodynamische Volumen der Polymere in verdünnter Lösung während der Photoisomerisierung (λ=410 nm) in entgegengesetzter Weise ändert. Darüber hinaus zeigt sich nach der Photoisomerisierung eine Veränderung der Glasübergangs‐temperatur (Tg) um fast 10 °C bei beiden Polymeren, unabhängig vom Design des jeweiligen Hydrazon‐Monomers. Die hier vorgestellte Designstrategie erlaubt es, makromolekulare Eigenschaften durch Strukturänderungen photochemisch zu kontrollieren.
Effects of Size and Asymmetry on Catalase‐Powered Silica Micro/nanomotors
Authors: Sun Jun , Wu Jie , Ju Huangxian
Published: November 2023

Enzyme‐powered micro/nanomotors that can autonomously move in biological environment are attractive in the fields of biology and biomedicine. The fabrication of enzyme‐powered micro/nanomotors normally focuses on constructing Janus structures of micro/nanomaterials, based on the intuition that the Janus coating of enzymes can generate driving force from asymmetric catalytic reactions. Here, in the fabrication of catalase‐powered silica micro/nanomotors (C‐MNMs), an archetypical model of enzyme‐powered micro/nanomotors, we find the silica size rather than asymmetric coating of catalase determines the motion ability of C‐MNMs. The effects of size and asymmetry have been investigated by a series of C‐MNMs at various sizes (0.5, 2, 5 and 10 μm) and asymmetric levels (full‐, half‐ and most‐coated with catalase). The motion performance indicates that 500 nm and 2 μm C‐MNMs show obvious increases (varying from 134% to 618%) of diffusion coefficient, but C‐MNMs bigger than 5 μm have no self‐propulsion behaviour at all, regardless of asymmetric levels. In addition, although asymmetry facilitates enhanced diffusion of C‐MNMs, only 2 μm C‐MNMs are sensitive to asymmetric level. This work elucidates the primary and secondary roles of size and asymmetry in the preparation of C‐MNMs, paving the way to fabricate enzyme‐powered micro/nanomotors with high motion performance in future.
Reductive amination cascades in cell‐free and resting whole cell formats for valorization of lignin deconstruction products
Authors: Nain Priyanka , Dickey Roman M. , Somasundaram Vishal , Sulzbach Morgan , Kunjapur Aditya M.
Published: November 2023

The selective introduction of amine groups within deconstruction products of lignin could provide an avenue for valorizing waste biomass while achieving a green synthesis of industrially relevant building blocks from sustainable sources. Here, we built and characterized enzyme cascades that create aldehydes and subsequently primary amines from diverse lignin‐derived carboxylic acids using a carboxylic acid reductase (CAR) and an ω‐transaminase (TA). Unlike previous studies that have paired CAR and TA enzymes, here we examine multiple homologs of each of these enzymes and a broader set of candidate substrates. In addition, we compare the performance of these systems in cell‐free and resting whole‐cell biocatalysis formats using the conversion of vanillate to vanillyl amine as model chemistry. We also demonstrate that resting whole cells can be recycled for multiple batch reactions. We used the knowledge gained from this study to produce several amines from carboxylic acid precursors using one‐pot biocatalytic reactions, several of which we report for the first time. These results expand our knowledge of these industrially relevant enzyme families to new substrates and contexts for environmentally friendly and potentially low‐cost synthesis of diverse aryl aldehydes and amines.
A multi‐dimensional assessment of financial hardship of cancer patients using existing health system data
Authors: You Wen , Pilehvari Asal , Shi Ruoding , Cohn Wendy , Sheffield Christina , Chow Philip I‐Fon , Krukowski Becca Anne , Anderson Roger
Published: November 2023

Background

Existing financial hardship screening does not capture the multifaceted and dynamic nature of the problem. The use of existing health system data is a promising way to enable scalable and sustainable financial hardship screening.

Methods

We used existing data from 303 adult patients with cancer at the University of Virginia Comprehensive Cancer Center (2016–2018). All received distress screening and had a valid financial assistance screening based solely on household size‐adjusted income. We constructed a composite index that integrates multiple existing health system data (Epic, distress screening, and cancer registry) to assess comprehensive financial hardship (e.g., material conditions, psychological responses, and coping behaviors). We examined differences of at‐risk patients identified by our composite index and by existing single‐dimension criterion. Dynamics of financial hardship over time, by age, and cancer type, were examined by fractional probit models.

Results

At‐risk patients identified by the composite index were generally younger, better educated, and had a higher annual household income, though they had lower health insurance coverage. Identified periods to intervene for most patients are before formal diagnosis, 2 years, and 6 years after diagnosis. Within 2 years of diagnosis and more than 4 years after diagnosis appear critical for subgroups of patients who may suffer from financial hardship disparities.

Conclusion

Existing health system data provides opportunities to systematically measure and track financial hardship in a systematic, scalable and sustainable way. We find that the dimensions of financial hardship can exhibit different patterns over time and across patient subgroups, which can guide targeted interventions. The scalability of the algorithm is limited by existing data availability.
Involvement of the OTUB1‐YAP1 axis in driving malignant behaviors of head and neck squamous cell carcinoma
Authors: Jin Shengjian , Tsunematsu Takaaki , Horiguchi Taigo , Mouri Yasuhiro , Shao Wenhua , Miyoshi Keiko , Hagita Hiroko , Sarubo Motoharu , Fujiwara Natsumi , Qi Guangying , Ishimaru Naozumi , Kudo Yasusei
Published: November 2023

Background

Comprehending the molecular mechanisms underlying head and neck squamous cell carcinoma (HNSCC) is vital for the development of effective treatment strategies. Deubiquitinating enzymes (DUBs), which regulate ubiquitin‐dependent pathways, are potential targets for cancer therapy because of their structural advantages. Here we aimed to identify a potential target for HNSCC treatment among DUBs.

Methods

A screening process was conducted using RNA sequencing data and clinical information from HNSCC patients in the TCGA database. A panel of 88 DUBs was analyzed to identify those associated with poor prognosis. Subsequently, HNSCC cells were modified to overexpress specific DUBs, and their effects on cell proliferation and invasion were evaluated. In vivo experiments were performed to validate the findings.

Results

In HNSCC patients, USP10, USP14, OTUB1, and STAMBP among the screened DUBs were associated with a poor prognosis. Among them, OTUB1 showed the most aggressive characteristics in both in vitro and in vivo experiments. Additionally, OTUB1 regulated the stability and nuclear localization of YAP1, a substrate involved in cell proliferation and invasion. Notably, OTUB1 expression exhibited a positive correlation with the HNSCC‐YAP score in HNSCC cells.

Conclusions

This study highlights the critical role of OTUB1 in HNSCC progression via modulating YAP1. Targeting the OTUB1‐YAP1 axis holds promise as a potential therapeutic strategy for HNSCC treatment.
Effectiveness of SARS‐CoV‐2 testing strategies: A scoping review
Authors: Saif‐Ur‐Rahman KM , Movsisyan Ani , Kothari Kavita , Conway Thomas , Tierney Marie , Madden Caoimhe , Taneri Petek Eylul , O'Halloran Jane A. , Nurdin Nadra , Murphy Lena , Mulholland Deirdre , Tricco Andrea C. , Devane Declan
Published: November 2023

Introduction

Rapid identification of severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infections by testing potentially reduced coronavirus disease‐19 (COVID‐19) cases. Testing strategies varied across countries and during different stages of the pandemic. This scoping review aims to map the available evidence on the effectiveness of SARS‐CoV‐2 testing strategies for suspected cases and asymptomatic populations to inform the development of World Health Organization recommendations for SARS‐CoV‐2 testing strategies.

Methods

We followed the standard methods for scoping reviews. We searched Medline (OVID), EMBASE (Elsevier), and Europe PMC using a comprehensive search strategy. The search was conducted in January 2023 and covered the period from January 2020 to January 2023. Two review authors independently screened the titles and abstracts, and full texts. Data were extracted onto a pilot‐tested form by a review author and cross‐checked by another review author. We provided a descriptive report summarizing the extracted data around the outcomes and created an interactive map of the available evidence using the evidence for policy and practice mapper.

Results

We identified 34,550 citations from the databases. After the screening, we included 17 studies from 11 countries for data extraction. The study designs were randomized controlled trials (n = 3), nonrandomized experimental studies (n = 3), cohort studies (n = 3), cross‐sectional studies (n = 4), self‐controlled case series (n = 1), and economic evaluations (n = 3).  Among the included studies, 14 used reverse transcription‐polymerase chain reaction and 10 studies used antigen‐detecting rapid diagnostic test. The settings of the studies were healthcare facilities (n = 8), communities (n = 4), schools, and workplaces (n = 3). Included studies considered symptomatic and asymptomatic individuals, or both, or asymptomatic contacts. Most of the studies (n = 14) reported the COVID‐19 positivity rate as the primary outcome. Other reported outcomes are the number of COVID‐19 cases (n = 11), number of hospitalizations and deaths (n = 3), and cost (n = 3).

Conclusion

We identified evidence gaps in the effectiveness of SARS‐CoV‐2 testing strategies, particularly in specific settings such as schools and long‐term care facilities. This scoping review provides a foundation for further research, allowing researchers and stakeholders to focus on addressing the identified gaps.
Low‐burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation
Authors: László Tamás , Kotmayer Lili , Fésüs Viktória , Hegyi Lajos , Gróf Stefánia , Nagy Ákos , Kajtár Béla , Balogh Alexandra , Weisinger Júlia , Masszi Tamás , Nagy Zsolt , Farkas Péter , Demeter Judit , Istenes Ildikó , Szász Róbert , Gergely Lajos , Sulák Adrienn , Borbényi Zita , Lévai Dóra , Schneider Tamás , Pettendi Piroska , Bodai Emese , Szerafin László , Rejtő László , Bátai Árpád , Dömötör Mária Á , Sánta Hermina , Plander Márk , Szendrei Tamás , Hamed Aryan , Lázár Zsolt , Pauker Zsolt , Radványi Gáspár , Kiss Adrienn , Körösmezey Gábor , Jakucs János , Dombi Péter J , Simon Zsófia , Klucsik Zsolt , Gurzó Mihály , Tiboly Márta , Vidra Tímea , Ilonczai Péter , Bors András , Andrikovics Hajnalka , Egyed Miklós , Székely Tamás , Masszi András , Alpár Donát , Matolcsy András , Bödör Csaba
Published: November 2023

TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next‐generation sequencing (NGS)‐based studies have identified frequent low‐burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low‐burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS‐based mutation analysis in a ‘real‐world’ cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high‐burden mutations, while 52% were low‐burden TP53 mutations. Low‐burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low‐burden TP53 mutation. Patients harbouring low‐burden TP53 mutations had significantly lower time to first treatment compared to patients with wild‐type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low‐burden TP53 mutations. By demonstrating that patients with sole low‐burden TP53 variants represent more than one‐third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting.
A multivariable analysis delineating hair color, hair dyeing, and hat wearing as predictors of level of cocaine and MDMA detection in human hair samples
Authors: Palamar Joseph J. , Cleland Charles M. , Vincenti Marco , Salomone Alberto
Published: November 2023

Research suggests that hair color, hair dyeing, and perspiration can bias hair test results regarding drug exposure, but research is needed to examine such associations in a multivariable manner. In this epidemiology study, adults were surveyed entering nightclubs and dance festivals in New York City, and 328 provided hair samples, which were analyzed using ultra‐high‐performance liquid chromatography–tandem mass spectrometry to determine the level of detection of cocaine and 3,4‐methylenedioxymethamphetamine (MDMA). Reporting use was not an inclusion criterion for analysis. We used two‐part multivariable models to delineate associations of hair color, past‐year hair dyeing, and frequency of past‐month hat wearing (which may increase perspiration) in relation to any vs. no detection of cocaine and MDMA as well as level of detection, controlling for hair length, self‐reported past‐year cocaine/ecstasy/MDMA use, and age, sex, and race/ethnicity. Those reporting having dyed their hair were at increased odds of having any level of cocaine detected (adjusted odds ratio [aOR] = 3.75, 95% CI confidence interval [CI]: 1.85–6.70), and compared to those with brown hair, those with blond(e) hair on average had lower levels of cocaine (ng/mg) detected (beta = −7.97, p = 0.025). Those reporting having dyed their hair were at increased odds of having any level of MDMA detected (aOR = 3.05, 95% CI: 1.44–6.48), and compared to those who reported never wearing a hat, those who reported wearing a hat daily or almost daily on average had lower levels of MDMA (ng/mg) detected (beta = −6.61, p = 0.025). This study demonstrates the importance of using multivariable models to delineate predictors of drug detection.
Fe Nanoparticles Decorated Pinewood‐Derived Carbon for Highly Efficient Electrocatalytic Conversion of Nitrite to Ammonia
Authors: Li Tengyue , He Xun , Cai Zhengwei , Fan Xiaoya , Dong Kai , Yao Yongchao , He Lang , Zheng Dongdong , Sun Shengjun , Luo Yongsong , Chen Junhao , Jiang Zhenju , Sun Xuping
Published: November 2023

Electrochemical nitrite (NO2−) reduction reaction (NO2−RR) presents a sustainable approach for the electrochemical synthesis of ammonia (NH3), concurrently facilitating the removal of NO2− contaminants. Developing NO2−RR electrocatalysts with high NH3 selectivity and satisfactory NH3 yield poses a significant challenge. Herein, we present Fe nanoparticles decorated pinewood‐derived carbon (Fe/PC) as a highly proficient electrocatalyst for the conversion of NO2− to NH3. The well‐designed Fe/PC electrocatalyst achieves an impressive NH3 yield of 21924.6 μg h−1 cm−2 and a high Faradic efficiency of 91.5 % under ambient conditions. Notably, the Fe/PC catalyst exhibits robust stability in both prolonged electrolysis and cyclic electrolysis assessments.
Highly Versatile Preparation of Imidazo[1,5‐a]quinolines and Characterization of Their Photoluminescent Properties
Authors: Kulhanek Niclas , Martin Niklas , Göttlich Richard
Published: November 2023

In this work, we describe a simple and robust synthetic approach for the formation of 1,3‐substituted imidazo[1,5‐a]quinolines. This was achieved by developing a mild and selective bromination with N‐bromosuccinimide (NBS) in 3‐position of the imidazole ring. This was followed by a Negishi coupling, which we performed with various coupling partners, resulting in a wide range of different combinations, usually unattainable by other approaches and similar coupling reactions. Fluorescence measurements identified beneficial substitution patterns for the future use of imidazo[1,5‐a]quinolines in optical applications, such as organic light‐emitting diodes (OLEDs).
Hybrid primary puncture in stapler‐assisted total laryngectomy
Authors: Galli Jacopo , Perna Luca , Rossi Giorgia , Corina Luigi , Parrilla Claudio
Published: November 2023

In Video S1, a new surgical technique for hybrid primary tracheoesophageal (TE) puncture in stapler‐assisted total laryngectomy is shown. The video describes the surgical steps of the procedure and illustrates some tips and tricks. The procedure incorporates an upper mini‐pharyngotomy to enable retrograde placement of the voice prosthesis (VP), eliminating the need for rigid esophagoscopy. This has made it possible to exploit, without additional risks, the potential of the stapler combined with primary TE puncture and VP placement. In our experience, this hybrid procedure in stapler‐assisted total laryngectomy is not related to adverse events such as pharyngocutaneous fistula (PCF), hypertonicity, and functional complications. Therefore, it can be considered a valid technique that allows for easy insertion of a primary voice prosthesis also in case of mechanical sutures.
The effect of hemodialysis with cool dialysate on nausea in hemodialysis patients: A randomized clinical trial
Authors: Arghide Yasem , Faraji Azam , Raygani Ali Akbar Vaisi , Salari Nader , Omrani Hamidreza , Mohammadi Mohammad Mehdi
Published: November 2023

Background and Aims

Experiencing nausea leads to decreased self‐esteem and social isolation in hemodialysis patients and affects all aspects of their quality of life. Nausea and vomiting make hemodialysis unpleasant for patients leading to premature termination of hemodialysis. Therefore, based on this necessity, the present study was conducted to determine the effect of hemodialysis with cool dialysate on nausea in hemodialysis patients.

Methods

In this clinical trial, 60 eligible patients receiving hemodialysis were randomly assigned to the control (30 participants) and intervention (30 participants) groups. In the control group, the patients received standard hemodialysis (37°C) for three sessions. Simultaneously, patients in the intervention group received hemodialysis with a cold solution (of 36°C) for three sessions. The patients' nausea and shivering rates were measured using the visual analog scale and the shivering standard assessment scale, respectively. Both groups were evaluated before and after 1 week of intervention. The study did not include blinding. The trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the number IRCT20200530047597N1. The present study was financially supported by Kermanshah University of Medical Sciences, Kermanshah, Iran (no. 990220). Data were analyzed using SPSS‐25 software.

Findings

The independentttest showed no statistically significant difference between the two control and experimental groups regarding the nausea rate in the three evaluation times (p < 0.05). Nevertheless, nausea severity decreased significantly after the intervention in the two groups. However, the rate of nausea in the intervention group with cold solution decreased more compared to the control group. Moreover, no patient in the intervention group experienced shivering during hemodialysis with a cool dialysate.

Conclusion

According to the results of this study, it can be stated that the use of cold hemodialysis to control nausea in patients undergoing hemodialysis requires further studies and can be recommended as a nonpharmacological treatment to manage the treatment costs in case of efficiency.
Factors associated with poor sleep quality among construction workers in Arba Minch town, Ethiopia: A cross‐sectional study
Authors: Wendimu Debisa E. , Meshesha Solomon G.
Published: November 2023

Background and Aims

Sleep is critical for human physical and cognitive health. Even though poor sleep quality had a major negative impact on workers' health and safety, there is a scarcity of study that attempts to demonstrate its magnitude and causative factors in labor‐intensive environments.

Methods

A cross‐sectional study design was employed. A total of 423 individuals were selected using a simple random sampling technique, starting from April 1, 2020 to May 1, 2020. Interviews were administered using the validated and pretested Pittsburgh Sleep Quality Index (PSQI) tool. EpiData version 4.4.3.1 was used for data entry and SPSS version 25 for analysis. To associate factors with poor sleep quality binary logistic regression model was fitted at 95% confidence interval (CI). A p < 0.25 and p < 0.05 were used to declare association in bivariable and multivariable analysis, respectively.

Results

A total of 415 building construction workers take part in this study, with a response rate of 98.1%. A PSQI global score showed 66.3% (95% CI: [0.63, 0.71]) of construction workers suffering from poor sleep quality. Working hours, work experience, previous injury status, managerial support on occupational safety and health, cigarette smoking, and job satisfaction were the factors that were associated with poor sleep quality significantly.

Conclusions

Two‐thirds of construction workers suffer from poor sleep quality. Risk factors include shorter working years, longer working hours, prior injury, lack of managerial support, cigarette smoking, and low job satisfaction. Efficient health education and promotion through taking the identified associated factors into account could help reduce poor sleep quality.
Numerical modeling and optimization of perforated twisted tape insert based on hybrid ANSYS‐RSM approach
Authors: Kadbhane Snehal Vasant , Pangavhane Dilip R.
Published: November 2023

Heat exchangers have a wider scope in numerous applications, such as space heating, chemical industries, power stations, and so on. Due to heat loss and the thermal properties of the materials involved, the overall performance of a heat exchanger is questionable. Therefore, studies related to heat transfer techniques are appreciated in the research community. Thus, the present study numerically investigates the heat transfer performance of a horizontal heat pipe equipped with hexagonal perforated twisted tape inserts. Further, the numerical solutions of Nusselt number (Nu), friction factor (f), and thermal performance factor (TPF) are optimized with the help of response surface methodology (RSM). The parameters investigated in this study are Reynolds number (Re), which varies between 500 and 1500, input heat supply (Q) between 100 and 1000 W, and pitch ratio (3.2, 4, and 5.2). ANSYS fluid flow fluent was used to perform flow simulations for three different twisted tape inserts: horizontal, vertical, and alternate hexagon perforations. Optimum solutions are obtained at 1000 W heat supply, 1500 Re, and p/di = 4 from alternatively perforated twisted tape inserts. The optimum Nu, f, and TPF achieved are 119.545, 0.437, and 1.82, respectively. Also, the proposed RSM optimization method is evidenced with a maximum of 2.673% error during the confirmatory test.
A retrospective study to investigate the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis with ulcerative colitis
Authors: Ito Ayumi , Murasugi Shun , Yonezawa Maria , Omori Teppei , Nakamura Shinichi , Tokushige Katsutoshi
Published: November 2023

Background and Aims

Primary sclerosing cholangitis has a poor prognosis and can be accompanied by ulcerative colitis. Infection control is essential, so immunosuppressive drugs should ideally be preferably. Granulocyte and monocyte adsorptive apheresis does not suppress the immune system and is used to treat ulcerative colitis. Therefore, this study investigated the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis and ulcerative colitis.

Methods

We retrospectively evaluated data from patients with primary sclerosing cholangitis with ulcerative colitis who visited our hospital from April 2000 to December 2022 and underwent granulocyte and monocyte adsorptive apheresis (n = 10, number of treatment cycles = 15). Study endpoints were remission induction rate and safety, assessed as changes in liver functions and adverse events.

Results

Seven of the 10 patients were male. The median (min‐max) age was 23 (18‐77) years. The most common disease type was right‐dominant pancolitis. Remission occurred after 86.6% of cycles (13/15). Serum alkaline phosphatase and Aspartate transaminase were significantly lower after treatment (P = .0124, P = .002), and no negative effects on liver function were seen. The only adverse events were headache (n = 1) and decreased blood pressure (n = 1).

Conclusions

Granulocyte and monocyte adsorptive apheresis has high efficacy for intestinal lesions and improves alkaline phosphatase and aspartate transaminase levels (high levels are a poor prognosis factor). It appears to be a treatment option in patients with primary sclerosing cholangitis associated with ulcerative colitis.
Cell‐free DNA extraction from urine of lung cancer patients and healthy individuals: Evaluation of a simple method using sample volume up‐scaling
Authors: Ruppert Tilman , Roth Andreas , Kollmeier Jens , Mairinger Thomas , Frost Nikolaj
Published: November 2023

Background

Urine holds promise as a source for cell‐free DNA (cfDNA) analysis of cancer genetics due to its nature as a self‐collectable biospecimen available in large quantities. However, pre‐analytical variables such as preservation of cfDNA or efficiency of up‐scaling specimen volume need to be better explored to increase analysis sensitivity.

Patients and Methods

Initially effects of pH levels on cfDNA stability of urine preserved with EDTA were investigated in three healthy probands. Furthermore, the efficiency of urine volume up‐scaling was examined using a simple DNA extraction method and cfDNA in urine of 32 individuals. Quantification was performed by PCR detection of three relevant targets used for EGFR and KRAS gene mutational analysis.

Results

Only samples preserved with EDTA at alkaline pH levels showed cfDNA stability of up to 10 days at room temperature. Moreover, it was found that increasing the volume up to 100 mL was highly efficient. A similar amount of copies was detected in three different gene sites in all specimens indicating both a good availability and a non‐random distribution pattern across genes. Since the median cfDNA copy number was 1642 copies/mL, abundance of cfDNA in this type of liquid biopsy is low.

Conclusion

Predictable sensitivities with different urine volumes on the ground of detectable cfDNA in our study population revealed that up‐scaling (>5 mL) is mandatory if the mutation allele frequency is less than 1%.
Agarose biodegradation by deep‐sea bacterium Vibrio natriegens WPAGA4 with the agarases through horizontal gene transfer
Authors: Zhang Mengyuan , Tong Xiufang , Wang Wenxin , Wang Jianxin , Qu Wu
Published: November 2023

This study aimed to reveal the importance of horizontal gene transfer (HGT) for the agarose‐degrading ability and the related degradation pathway of a deep‐sea bacterium Vibrio natriegens WPAGA4, which was rarely reported in former works. A total of four agarases belonged to the GH50 family, including Aga3418, Aga3419, Aga3420, and Aga3472, were annotated and expressed in Escherichia coli cells. The agarose degradation products of Aga3418, Aga3420, and Aga3472 were neoagarobiose, while those of Aga3419 were neoagarobiose and neoagarotetraose. The RT‐qPCR analysis showed that the expression level ratio of Aga3418, Aga3419, Aga3420, and Aga3472 was stable at about 1:1:1.5:2.5 during the degradation, which indicated the optimal expression level ratio of the agarases for agarose degradation by V. natriegens WPAGA4. Based on the genomic information, three of four agarases and other agarose‐degrading related genes were in a genome island with a G + C content that was obviously lower than that of the whole genome of V. natriegens WPAGA4, indicating that these agarose‐degrading genes were required through HGT. Our results demonstrated that the expression level ratio instead of the expression level itself of agarase genes was crucial for agarose degradation by V. natriegens WPAGA4, and HGT occurred in the deep‐sea environment, thereby promoting the deep‐sea carbon cycle and providing a reference for studying the evolution and transfer pathways of agar‐related genes.
A systematic review and meta‐analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols
Authors: Wu Trudy C. , Smith Clayton P. , Li Joshua S. , Burton Jason , Jackson Nicholas J. , Tao Randa , Ludmir Ethan B. , Raldow Ann C.
Published: November 2023

Background and Objectives

Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR).

Methods

We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random‐effect meta‐analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1‐, 3‐, and 5‐year recurrence‐free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest.

Results

A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1‐year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61–0.91), and 91% (95% CI, 0.87–0.94), respectively. There was no 1‐year OS difference detected among the three groups. pCR was not associated with OS in the meta‐regression. Pooled 3‐ and 5‐year OS among all studies was 72% and 61%, respectively.

Conclusions

The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta‐regression, pCR was not a surrogate marker for survival.
Comparison of optical coherence tomography and in vivo reflectance confocal microscopy with dermoscopy for the diagnosis and management of nonmelanoma skin cancer: A randomized controlled trial
Authors: Hobelsberger Sarah , Steininger Julian , Laske Jörg , Berndt Katja , Meier Friedegund , Beissert Stefan , Gellrich Frank Friedrich
Published: November 2023

Background

Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) can yield improved diagnostic accuracy of nonmelanoma skin cancer (NMSC) in comparison with dermoscopy alone.

Objectives

The aim of this study was to compare the diagnostic performance of OCT and RCM together and individually with that of dermoscopy.

Methods

Patients with lesions suspicious for NMSC were randomized into two groups in a prospective, single‐centre study. In the intervention group (IG), every lesion was examined with dermoscopy, OCT and RCM, while in the control group (CG), every lesion was examined with dermoscopy alone.

Results

A total of 365 lesions of 250 patients (105 female, 145 male) were included in the study. A total of 208 basal cell carcinomas (BCCs), 65 squamous cell carcinomas (SCCs) and 31 SCCs in situ were examined histologically. The IG involved significantly fewer biopsies than the CG (14 vs. 27, p = 0.029) and required fewer additional inpatient stays due to positive biopsy results (2 vs. 12, p = 0.001). For the diagnosis of BCC, diagnostic accuracy was 81% with dermoscopy, 84% with OCT, 83% with RCM and 85% with the combination of OCT and RCM (OCT/RCM). The diagnostic accuracy of OCT for BCC subtypes was as follows: superficial, 89%; nodular, 79%; sclerodermiform, 82%; and nodular‐cystic BCC, 75%. For the diagnosis of SCC, diagnostic accuracy was 85% with dermoscopy, 87% with OCT, 89% with RCM and 87% with OCT/RCM. For the diagnosis of in situ SCC, diagnostic accuracy was 87% with dermoscopy, 89% with OCT, 89% with RCM and 91% with OCT/RCM.

Conclusions

Diagnostic accuracy increased with OCT and RCM and was even higher when both methods were used together. OCT and RCM could facilitate optimization of lesion management by reducing the number of punch biopsies and reducing additional inpatient stays due to positive biopsy results.
The Breakdown of Blood‐Labyrinth Barrier Makes it Easier for Drugs to Enter the Inner Ear
Authors: Ke Yujie , Ma Xin , Jing Yuanyuan , Diao Tongxiang , Yu Lisheng
Published: November 2023

Purpose

This study aimed to investigate dynamic change of permeability of blood‐labyrinth barrier (BLB) after noise exposure and its effect on the drug delivery efficiency of systemic administration.

Methods

Gadopentetate dimeglumine (Gd‐DTPA) and dexamethasone (DEX) were used as tracers, and magnetic resonance imaging (MRI) and immunofluorescence were used to observe the change of the BLB after strong noise exposure in guinea pigs. High‐performance liquid chromatography‐mass spectrometry (LC–MS) was used to observe the effect of the breakdown of BLB after noise exposure on the drug delivery efficiency of intravenous DEX. The guinea pigs were divided into 6 groups: normal group (N), 1, 3, 5, 8, and 12 days after noise exposure groups (P1, P3, P5, P8, P12), with 5 animals in each group.

Results

The BLB changes dynamically after noise exposure. Increased permeability of the blood‐endolymph barrier, the endolymph‐perilymph barrier, and the blood‐nerve barrier was observed at days 1–3, 1–5, and 1–8, respectively, after noise exposure in guinea pigs. Higher drug concentration in the cochlear tissue was obtained by intravenous administration of DEX in guinea pigs during the time window of increased permeability of the BLB.

Conclusion

After noise exposure, the increased BLB permeability makes it easier for drugs to enter the inner ear from blood. In guinea pigs, 1–8 days after strong noise exposure, the drug delivery efficiency of systemic administration increased. After 8 days, the efficiency gradually returned to normal level. 1–8 days after noise exposure may be the best intervention time for systemic administration.

Level of Evidence

NA Laryngoscope, 134:2377–2386, 2024
Validation and cross‐cultural adaptation of the Arabic version of the self‐reported mini olfactory questionnaire (Self‐MOQ)
Authors: Alfallaj Rayan , Almousa Hisham , Alsubaie Nawaf , Akkielah Yara , Mesallam Tamer A. , Sumaily Ibrahim , Alsaleh Saad
Published: November 2023

Background

A simple self‐assessment screening questionnaire for olfactory dysfunction is direly needed in Rhinology practice, and this questionnaire should be accessible to affected individuals. The self‐reported mini olfactory questionnaire (Self‐MOQ), constructed to fill this gap, could be an important tool, especially in the era of telemedicine.

Objectives

The aim of this study was to assess the validity and reliability of the Arabic version of the self‐reported mini olfactory questionnaire (Self‐MOQ) in patients with olfactory dysfunction.

Methodology

This cross‐sectional study included all adult patients who visited a rhinology clinic between January and June 2023 with a complaint of olfactory dysfunction and a control group. The participants completed a questionnaire that included items on demographics, risk factors of olfactory dysfunction, the olfaction VAS, SNOT‐22, and Arabic Self‐MOQ. The Self‐MOQ was forward‐ and back‐translated by qualified professional translators familiar with American English and Arabic.

The reliability of the Arabic Self‐MOQ was evaluated using Cronbach's α. The test–retest reliability was assessed by estimating the intraclass correlation coefficient (ICC) for the total Arabic Self‐MOQ score and the individual items. The discriminative ability was examined by comparing the scores of the case and control groups. The construct validity was assessed by comparing the Arabic Self‐MOQ to the olfaction VAS.

Results

The study sample included 307 respondents (196 cases and 111 controls; 34 undertook the retest). The Cronbach's α coefficients were 0.92 (total Self‐MOQ) and considered excellent. The ICC for the total Self‐MOQ score was 0.87 (95% CI: 0.757, 0.933; p < .001), which indicated good test–retest reliability. Strong correlations were observed between the Self‐MOQ items and VAS scores (r = 0.732, p < .001), (r = 0.689, p < .001).

Conclusion

The current investigation showed the Arabic version of the Self‐MOQ to be a reliable tool for olfactory dysfunction screening.
Proposal of Pseudo‐Capping Effects by Polymer–Polymer Interaction through Preparation of Stereocomplex Pseudo‐Polyrotaxane with Cyclodextrin and PEG‐PLA Triblock Copolymers
Authors: Choi Jaeyeong , Ajiro Hiroharu
Published: November 2023

ABA types triblock copolymers, specifically poly(L‐lactide)‐co‐poly(ethylene glycol)‐co‐poly(L‐lactide) (PLLA‐PEG‐PLLA) and poly(D‐lactide)‐co‐poly(ethylene glycol)‐co‐poly(D‐lactide) (PDLA‐PEG‐PDLA), are employed for stereocomplexes (SCs) formation. These SCs are subsequently utilized as axles, in conjunction with various cyclodextrins (CDs) as ring moieties to create pseudo‐polyrotaxane (PPRX). The authors referred to this new construct as “SC PPRX”, to distinguish it from the earlier study, denoted as “PPRX SC”, which primarily focuses on SC within the PPRX. When attempting to form PPRXs in aqueous solutions, the authors encountered challenges related to the inclusion of CDs due to the robust presence of the SC structure. However, by using mixed solvents, such as water/acetone (10/1, v/v), a partial relaxation of the SC structure is observed. This allows for the successful inclusion of CDs, thereby facilitating the PPRX formation. These observations highlight the significance of axle–axle interaction, which, in this case, prevailed over axle–ring interactions in determining the outcome of the formation process. The authors propose the term, ‘SC pseudo‐capping effect’ to describe this unique phenomenon, underscoring the role of interactions among polymer chains, including polymer–polymer and axle–axle interactions, in shaping the architecture of rotaxanes. This study thus unveils a novel dimension of polymer‐polymer interactions within the realm of rotaxane.
Nurse‐led care for people with early rheumatoid arthritis: Interview study with thematic analysis
Authors: Sweeney Anne‐Marie Tetsche , Flurey Caroline A. , McCabe Candy S. , Robson Joanna C. , Richards Pamela , Ndosi Mwidimi
Published: November 2023

Aims

To develop an understanding of what comprises nurse‐led care in early rheumatoid arthritis from the perspective of rheumatology nurse specialists in England.

Design

Qualitative study.

Methods

Semi‐structured telephone interviews with rheumatology nurse specialists in England were conducted in Summer 2020. Interviews were audio‐recorded, transcribed verbatim and analysed using reflexive thematic analysis.

Reporting follows the appropriate elements of consolidated criteria for reporting qualitative research.

Results

Sixteen nurses were recruited and interviews lasted 30–60 min. Four themes with 14 subthemes were identified.

A specialist service delivered by experienced rheumatology nurses

Specialist care is provided by experienced nurse specialists with a high degree of autonomy in the rheumatology multidisciplinary team context.

Addressing patients' complex care needs

Care is evidence‐based and aims to start treatment, keep in treatment, educate and support. Access to psychology expertise is needed.

Care with compassion using person‐centred, holistic and empathetic approaches

Nurses create patient relationships and a positive therapeutic environment. Nurse‐led telephone advice lines are essential for treatment adjustment, patient support and empowerment.

Continued evaluation and development of the service

Consultations are reviewed, and patients are asked for feedback. The COVID‐19 pandemic caused disruption, but changes streamlined procedures and improved documentation and communication.

Conclusion

Nurse‐led care in early rheumatoid arthritis is a specialist service delivered with compassion, addressing complex care needs and using person‐centred approaches. This study identifies key aspects of care in early disease from the nurse perspective.
Conversion of N‐Acetylglucosamine to 3‐Acetamido‐5‐Acetylfuran over Al‐Exchanged Montmorillonite
Authors: Yamazaki Kiyoyuki , Hiyoshi Norihito , Yamaguchi Aritomo
Published: November 2023

3‐Acetamido‐5‐acetylfuran (3A5AF) is a potential platform compound for the production of nitrogen‐containing pharmaceuticals and chemicals. 3A5AF can be obtained by dehydration of chitin or its monomer, N‐acetylglucosamine (NAG). Here, we examined the use of solid catalysts for the dehydration of NAG to 3A5AF to achieve a more economical process that uses a recyclable catalyst. NAG was dehydrated using various solid catalysts in the presence of NaCl and N,N‐dimethyl acetamide as solvent at 433 K. The yield of 3A5AF with the solid catalysts decreased in the following order: Al‐exchanged montmorillonite>H‐ZSM‐5 (SiO2/Al2O3=40)>H‐montmorillonite (K‐10)>Amberlyst15>H‐ZSM‐5 (SiO2/Al2O3=300)>TiO2>γ‐Al2O3>ZrO2>SiO2 ⋅ MgO>Na‐montmorillonite. The highest yield of 3A5AF (14 %) was obtained with the Al‐exchanged montmorillonite. The montmorillonite catalysts were characterized by using inductively coupled plasma optical emission spectroscopy, energy‐dispersive X‐ray spectroscopy, N2 adsorption, Fourier‐transformed infrared spectroscopy, X‐ray diffraction, and 27Al magic‐angle spinning nuclear magnetic resonance spectroscopy (MAS‐NMR). In addition, a combined catalyst of Al‐exchanged montmorillonite and Cl− from synthetic hydrotalcite was found to be an active and recyclable solid catalyst for NAG dehydration to 3A5AF.
Evaluating the Current Ability of ChatGPT to Assist in Professional Otolaryngology Education
Authors: Zalzal Habib G. , Cheng Jenhao , Shah Rahul K.
Published: November 2023

Objective

To quantify ChatGPT's concordance with expert Otolaryngologists when posed with high‐level questions that require blending rote memorization and critical thinking.

Study Design

Cross‐sectional survey.

Setting

OpenAI's ChatGPT‐3.5 Platform.

Methods

Two board‐certified otolaryngologists (HZ, RS) input 2 sets of 30 text‐based questions (open‐ended and single‐answer multiple‐choice) into the ChatGPT‐3.5 model. Responses were rated on a scale (correct, partially correct, incorrect) by each Otolaryngologist working simultaneously with the AI model. Interrater agreement percentage was based on binomial distribution for calculating the 95% confidence intervals and performing significance tests. Statistical significance was defined as P < .05 for 2‐sided tests.

Results

In testing open‐ended questions, the ChatGPT model had 56.7% of initially answering questions with complete accuracy, and 86.7% chance of answer with some accuracy (corrected agreement = 80.1%; P < .001). For repeat questions, ChatGPT improved to 73.3% with complete accuracy and 96.7% with some accuracy (corrected agreement = 88.8%; P < .001). For multiple‐choice questions, the ChatGPT model performed substantially worse (43.3% correct).

Conclusion

ChatGPT currently does not provide reliably accurate responses to sophisticated questions in Otolaryngology. Professional societies must be aware of the potential of this tool and prevent unscrupulous use during test‐taking situations and consider guidelines for clinical scenarios. Expert clinical oversight is still necessary for myriad use cases (eg, hallucination).
Detecting local spots in network materials prone to mechanical failure
Authors: Wu Zhao , Markert Bernd , Bamer Franz
Published: November 2023

The prediction of the onset of fracture is a challenging issue in the mechanics of disordered materials. In this contribution, we show that the fracture process in network glasses, such as silica glass, turns out to be a complex phenomenon that originates from specific spots that have the size of a few hundred atoms only. We apply pure shear deformation to identify local rearrangement spots prone to material damage. These spots are analyzed using stress drop steps, originally used for densely packed disordered systems.