bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the impact of critical attributes on hard drive failure times: Multi‐state models for left‐truncated and right‐censored semi‐competing risks data
Authors: Oakley Jordan L. , Forshaw Matthew , Philipson Pete , Wilson Kevin J.
Published: December 2023

The ability to predict failures in hard disk drives (HDDs) is a major objective of HDD manufacturers since avoiding unexpected failures may prevent data loss, improve service reliability, and reduce data center downtime. Most HDDs are equipped with a threshold‐based monitoring system named self‐monitoring, analysis and reporting technology (SMART). The system collects several performance metrics, called SMART attributes, and detects anomalies that may indicate incipient failures. SMART works as a nascent failure detection method and does not estimate the HDDs' remaining useful life. We define critical attributes and critical states for hard drives using SMART attributes and fit multi‐state models to the resulting semi‐competing risks data. The multi‐state models provide a coherent and novel way to model the failure time of a hard drive and allow us to examine the impact of critical attributes on the failure time of a hard drive. We derive dynamic predictions of conditional survival probabilities, which are adaptive to the state of the drive. Using a dataset of HDDs equipped with SMART, we find that drives are more likely to fail after entering critical states. We evaluate the predictive accuracy of the proposed models with a case study of HDDs equipped with SMART, using the time‐dependent area under the receiver operating characteristic curve (AUC) and the expected prediction error (PE). The results suggest that accounting for changes in the critical attributes improves the accuracy of dynamic predictions.
Circumstellar disk and the first generation of stars
Authors: Riaz Rafeel
Published: December 2023

Circumstellar disk (CD) around the first generation of stars have been numerically investigated here to see if the cooling regimes also play a role in the formation and evolution of the disk associated with the most massive protostars (MMPS). Also, an emphasis is given to exploring the effect of the initial turbulent motion of the metal‐free gas on the resulting morphology of the CD. For this, a systematic range of Mach number has been examined. It has been found that the disk‐to‐star mass ratio / is larger when the model evolution is based on the first H line cooling followed by subsequent cooling via collision‐induced emission than in the model where only H line cooling remains operative. Also, irrespective of the initial turbulence in the cloud, the former type of model yields a CD as massive as 7.66 M while the latter type produces a disk as massive as 1.29 M. Moreover, the inner part of the CD is found dominated by higher subsonic turbulent motions in the case of the former type of models than in the latter type. CDs around MMPS in both types of models show stable disk structures.
Recent advances in aggregation‐induced emission–active type I photosensitizers with near‐infrared fluorescence: From materials design to therapeutic platform fabrication
Authors: Xie Yili , Li Zhijia , Zhao Chunhui , Lv Ruizhi , Li Yan , Zhang Zhihong , Teng Muzhou , Wan Qing
Published: December 2023

Near‐infrared (NIR) fluorescence imaging–guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self‐aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π–π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence–guided type I PSs with aggregation‐induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE‐active PDT based on type I PSs. In this review, cutting‐edge advances focusing on AIE‐active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE‐active type I PSs are proposed.
Agar plate‐based activity assay for easy and fast screening of recombinant Pichia pastoris expressing unspecific peroxygenases
Authors: Schmitz Fabian , Röder Annika , Hoffrogge Maike , Urlacher Vlada B. , Koschorreck Katja
Published: December 2023

Unspecific peroxygenases (UPOs) are promising biocatalysts that catalyze oxyfunctionalization reactions without the need for costly cofactors. Pichia pastoris (reclassified as Komagataella phaffii) is considered an attractive host for heterologous expression of UPOs. However, integration of UPO‐expression cassettes into the genome via a single cross‐over yields recombinant Pichia transformants with different UPO gene copy numbers resulting in different expression levels. Selection of the most productive Pichia transformants by a commonly used screening in liquid medium in 96‐well plates is laborious and lasts up to 5 days. In this work, we developed a simple two‐step agar plate‐based assay to screen P. pastoris transformants for UPO activity with less effort, within shorter time, and without automated screening devices. After cell growth and protein expression on agar plates supplemented with methanol and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), an additional top agar layer supplemented with ABTS and peroxide is added. UPO activity is visualized within 15 min by formation of green zones around UPO‐secreting P. pastoris transformants. The assay was validated with two UPOs, AbrUPO from Aspergillus brasiliensis and evolved PaDa‐I from Agrocybe aegerita. The assay results were confirmed in a quantitative 96‐deep well plate screening in liquid medium.
Consumers' textile disposal practices and their perceived value in the circular economy: A platform focused ethnography approach
Authors: Pera Rebecca , Ferrulli Eliana
Published: December 2023

This study builds on the Circular Economy paradigm which recognises consumers as key stakeholders in extending textiles' lifespan. The paper unfolds how consumers engage in the textile disposal practices of reuse, repair, donate and resell. In doing so, consumers create a value‐in‐disposition, here conceptualised as the enhanced value that consumers generate through the process of transforming depleted textiles into new meaningful ones. This research adopts a multimethod platform focused ethnography that combines textual, visual and audio data, generated in the domestic environment, which facilitates contextual and situational insights. The findings highlight that value‐in‐disposition goes far beyond the utilitarian aspects (e.g. economic or functional) and includes social, aesthetic, emotional and moral value dimensions, which contribute in building an overarching environmental value. The study shows that consumer disposal practices not only reduce waste but also favour consumer empowerment through the transformation of unused/depleted resources into new value. Finally, the article provides specific managerial insights on the design of textile products and services to encourage consumer engagement in reuse, repair, donation, and resell practices, supporting companies in the Circular Economy uptake.
Ten tips for successful assessment of risk of bias in randomized trials using the RoB 2 tool: Early lessons from Cochrane
Authors: Moore Theresa H. M. , Higgins Julian P. T. , Dwan Kerry
Published: December 2023

Introduction

RoB 2 is a tool used by systematic reviewers to assess risk of bias in randomized trials. Over a period of 19 months working as editors for Cochrane, we saw many instances where users of RoB 2 frequently applied the tool in ways the developers had not intended, despite availability of detailed guidance, webinars and FAQs.

Methods

In this paper we highlight the ten main issues that we observed, with the aims of optimising the application of the RoB 2 tool, avoiding some of the frequent misapplications of the tool.

Results

Issues noted included failure to state an effect of interest, applying the tool to an entire study rather than to a specific numerical result, omitting key signaling questions and relying on outdated views of causes of bias.

Conclusion

Such omissions and misapplications can lead to overly harsh or lenient assessments of bias with potential to change the confidence we have in an evidence base of randomized trials. We recommend that teams planning to use RoB 2 include at least one member familiar with the RoB 2 detailed guidance and that they use the free resources, such as webinars and FAQs, from the developers of RoB 2 and Cochrane. Our ten tips should be useful to non‐Cochrane systematic reviewers as well as to peer reviewers and editors in Cochrane and other journals.
Conventional maxillary denture versus maxillary implant‐supported overdenture opposing mandibular implant‐supported overdenture: Patient's satisfaction
Authors: Niakan Somayeh , Mahgoli Hosseinali , Afshari Aylar , Mosaddad Seyed Ali , Afshari Aysooda
Published: December 2023

Objectives

This study sought to determine the impact of age, gender, and use of maxillary implant‐supported overdenture (UISOD) versus conventional denture (CMD) opposing mandibular implant‐supported overdenture (LISOD) and the number of years the patient has used their prosthesis on the ratings of satisfaction. This study aimed to assess the long‐term influence of different factors on patients' satisfaction with LISODs needing a maxillary prosthesis, helping dentists choose a treatment pathway that leads to a higher satisfaction rate.

Material and Methods

This cross‐sectional study included 84 participants. They were treated with LISOD opposing either CMD or UISOD from 2015 to 2020. They were all eligible to participate in the study. An oral health impact profile (OHIP‐14) questionnaire was given to each patient and filled out by them. OHIP‐14 scores were gathered and went under statistical analysis with PASS‐11 software to determine the relationship between patients' satisfaction with the scores.

Results

Age and gender had no significant influence on how satisfied patients were. Patients with maxillary overdentures showed more satisfaction than the CMD group (p < .05). Moreover, patients' satisfaction decreased with increasing years of prostheses usage (p < .05).

Conclusions

This study demonstrated that satisfaction is related to the type of maxillary prosthesis (conventional or implant‐supported) used opposing LISODs and the number of years the patient had used the prostheses.
Understanding sensitivity and cross‐reactivity of xylazine lateral flow immunoassay test strips for drug checking applications
Authors: Sisco Edward , Nestadt Danielle F. , Bloom Madeline B. , Schneider Kristin E. , Elkasabany Rae A. , Rouhani Saba , Sherman Susan G.
Published: December 2023

The continued prevalence of xylazine in the illicit drug market has necessitated development of quick and simple methods for identification, including lateral flow immunoassays (also known as “test strips”), like those frequently used to detect fentanyl. This study explored the drug checking applicability of the first publicly available xylazine test strips (XTS) using four sub‐studies: reproducibility (i.e., consistency of positive results in a highly‐concentrated xylazine solution); limit of detection on a calibration curve of xylazine concentrations; cross‐reactivity against 77 commonly encountered drugs, cutting agents, and other structurally similar compounds; and applicability for analyzing community‐acquired samples—where 100 drug residue samples were analyzed using XTS, direct analysis in real time mass spectrometry (DART‐MS), and gas chromatography tandem mass spectrometry (GC–MS/MS). XTS consistently detected xylazine at concentrations ≥2.5 μg/ml, and XTS results were reproducible. Sensitivity and specificity of XTS were calculated by comparing expected versus obtained results based on xylazine concentration of community‐acquired samples measured by GC‐MS/MS. XTS consistently detected xylazine in samples with concentration >2 μg/ml and yielded a sensitivity of 0.974, specificity of 1.00, and overall accuracy of 0.986. Cross‐reactivity with lidocaine, a common cutting agent, and lack of XTS reactivity with other α2‐agonists found in the illicit drug supply highlight the need to offer consumers comprehensive drug checking services that identify a range of substances and better inform them about drug contents.
The treatment of dissociative identity disorder in an eating disorder residential treatment setting
Authors: Brewerton Timothy D. , Perlman Molly M. , Gavidia Ismael , Suro Giulia
Published: December 2023

Objective

Child maltreatment, dissociation and dissociative disorders have been noted in relationship to eating disorders (EDs) for decades, and their co‐occurrence generally is associated with greater morbidity, self‐harm and mortality. The concomitant presentation of dissociative identity disorder (DID) with an ED (ED + DID) is especially challenging, and there is limited information on approaches to and the effects of integrated treatment for this serious comorbidity, especially in higher levels of care. There are also limited treatment resources for such patients, since they are often turned away from specialty units due to lack of expertise with or bias toward one or the other disorder.

Method

We report our experience with a case series of 18 patients with DSM‐5 defined ED + DID (mean age (SD) = 32.6 (11.8) years) admitted to residential treatment (RT) and assessed using validated measures for symptoms of ED, major depression (MD), PTSD, state–trait anxiety, quality of life (QOL), age of ED onset, and family involvement during treatment. All patients received integrated, multimodal, trauma‐focused approaches including those based on DID practice guidelines, principles of cognitive processing therapy (CPT), and other evidence‐based approaches. Fifteen of 18 patients also completed discharge reassessments, which were compared to admission values using paired t‐tests.

Results

Following integrated, trauma‐focused RT, patients with ED + DID demonstrated statistically significant improvements in all measures, with medium (anxiety) to high (ED, PTSD, MD, QOL) effect sizes.

Discussion

These results provide positive proof of concept that patients with ED + DID can be effectively treated in a specialty, trauma‐focused ED program at higher levels of care.

Public Significance

EDs and dissociative identity disorder (DID) are related conditions, but little is known about treating patients with both conditions. We describe the clinical features and integrated treatment of 18 such patients, 15 of whom completed discharge assessments. Significant clinical improvements were found in multiple domains (ED, PTSD, mood, anxiety, quality of life), which demonstrate positive proof of concept that ED + DID can be effectively treated in a specialty, trauma‐focused ED program.
Assessing habitat quality at Poyang Lake based on InVEST and Geodetector modeling
Authors: Yuan Wenrui , Chen Lingkang , Chen Haixia , Deng Shaofu , Ji Hong , Liang Fenshuo
Published: December 2023

Poyang Lake is an essential natural wetland in the Yangtze River basin and plays a vital role in maintaining the ecosystem function and ecological security in the middle and lower reaches of the Yangtze River. However, the relative importance and spatial heterogeneity of the impacts of human activities and land use changes on ecological security needs to be further explored. Here, we analyzed the habitat quality level around Poyang Lake in 2022 and explored the factors of habitat quality change from a geographical perspective. The land use structure changes around the Poyang Lake basin from 2000 to 2022 were quantitatively analyzed, and then the relative importance and spatial heterogeneity of each factor on ecological security changes were investigated using geographic probes. The results show that (1) The worst quality habitat (0–0.1) consists mainly of construction land (1624.9 km2) with an area of 1634.64 km2; (2) Construction land continues to increase with the most significant change, and the dynamic land use attitude is 0.47. Grassland and mudflats have the greatest decrease. The increase in cultivated land in different periods is mainly due to the shift of water surface and forest land; (3) The drivers of habitat quality in Poyang Lake were significantly influenced by the interaction of socioeconomic factors. The explanatory power of population density interacting with the total year‐end population and population density interacting with administrative area exceeded 0.84. These values were higher than the explanatory power of each individual factor, indicating that habitat quality was primarily associated with population density, total year‐end population, and administrative area. These results suggest that human activities contribute to the degradation of wetlands around Poyang Lake. This study has significant reference value for coordinating human–land relationships in Poyang Lake, optimizing land management policy, and improving the sustainable development of cities.
Zfp36l1 establishes the high‐affinity CD8 T‐cell response by directly linking TCR affinity to cytokine sensing
Authors: Petkau Georg , Mitchell Twm J. , Evans Marian Jones , Matheson Louise , Salerno Fiamma , Turner Martin
Published: December 2023

How individual T cells compete for and respond to IL‐2 at the molecular level, and, as a consequence, how this shapes population dynamics and the selection of high‐affinity clones is still poorly understood. Here we describe how the RNA binding protein ZFP36L1, acts as a sensor of TCR affinity to promote clonal expansion of high‐affinity CD8 T cells. As part of an incoherent feed‐forward loop, ZFP36L1 has a nonredundant role in suppressing multiple negative regulators of cytokine signaling and mediating a selection mechanism based on competition for IL‐2. We suggest that ZFP36L1 acts as a sensor of antigen affinity and establishes the dominance of high‐affinity T cells by installing a hierarchical response to IL‐2.
Status of epilepsy care delivery and referral in clinics, hospitals, and epilepsy centers in Japan: A nationwide survey
Authors: Tokumoto Kentaro , Terada Kiyohito , Kawaguchi Norihiko , Nishida Takuji , Yamano Mitsuhiko , Aoyagi Tomoo , Tadokoro Yuji , Usui Naotaka , Inoue Yushi
Published: December 2023

Objective

Collaboration among medical facilities is crucial to deliver comprehensive epilepsy care to a diverse and large population of people with epilepsy. We conducted a survey among medical facilities of various sizes throughout Japan to investigate the status of epilepsy care delivery, functioning, and referral.

Methods

With the cooperation of the Japan Neurological Society (1428 facilities), Japanese Neurosurgical Society (3489 specialists), and Epilepsy Care Network (948 facilities), a questionnaire was mailed to 5865 locations that provide epilepsy care in Japan. The facilities were classified into clinics (19 beds or less), small hospitals (SH, 20–199 beds), large hospitals (LH, 200 beds or more), and epilepsy centers (EC). The status of epilepsy care delivery, functioning, and referral was compared among the four groups.

Results

Responses were received from 1014 facilities (17.3% response rate). After excluding duplicate responses, 957 facilities were analyzed (394 clinics, 149 SH, 388 LH, 26 EC). EC responded “manageable” in more items of epilepsy care functions in general, especially those related to epilepsy surgery, compared to LH with similar facility size. However, EC responded being less manageable in psychiatric service (61.5%), dietary therapy (46.2%), rehabilitation (53.8%), and patient employment support (61.5%). The percentage of facilities that responded “always able to refer” was highest in clinics (67.6%) and the lowest in EC (40%). Referral difficulties were more commonly encountered in EC, and less common in clinics. In EC, the most common reason for inability to refer was patient or family refusal (64%).

Significance

We have clarified the epilepsy care delivery, functioning, and referral in facilities of various sizes in Japan. This study highlights the issues of downward referral and patient stagnation in EC, which have not received much attention.

Plain Language Summary

A nationwide survey of healthcare facilities ranging in size from small clinics to large hospitals in Japan examined medical care delivery and patient referrals related to epilepsy. Compared to other facilities, epilepsy centers provided a variety of medical services to people with epilepsy but were inadequate in addressing psychiatric symptoms, providing dietary therapy, rehabilitation, and patient employment support. Referrals from epilepsy centers to other medical facilities were often refused by patients and their families. This results in patient crowding at epilepsy centers
RAKSHAM: Responsive approach to Knock‐off scavenging hackers and attack mitigation
Authors: Bhardwaj Sonam , Dave Mayank
Published: December 2023

With the increasing interconnectivity of devices and systems in the Internet of Things (IoT) landscape, the importance of cybersecurity has grown significantly. This work presents a comprehensive solution that combines deceptive techniques and AI‐based detection to strengthen the security of IoT networks against sophisticated cyber threats. Deceptive techniques, such as the utilization of honeypots, deceptive IoT devices, and deceptive network traffic, are deliberately employed with the aim of misleading potential attackers. However, the effectiveness of these systems is often challenged by highly skilled attackers and the complexities associated with allocating resources. To address these challenges, “RAKSHAM” is a unique approach to improving the security of IoT networks. It combines deceptive techniques with AI‐based detection mechanisms, minimizing false positives and operational outages in IoT networks. This approach utilizes Eigenvector Centrality (EVC) to identify nodes with a higher risk level. It also evaluates the performance of an AI‐based attack detection model. The AI model, which utilizes a Convolutional Neural Network (CNN), demonstrates exceptional efficacy in the detection of attacks with 99% accuracy and a minimal attack success probability rate of 0.10. RAKSHAM offers a pragmatic and efficient solution for securing IoT networks by accurately detecting attacks and minimizing false positives and operational outages.
Comparison of automated and manual quantification methods for neuromelanin‐sensitive MRI in Parkinson's disease
Authors: Shaff Nicholas , Erhardt Erik , Nitschke Stephanie , Julio Kayla , Wertz Christopher , Vakhtin Andrei , Caprihan Arvind , Suarez‐Cedeno Gerson , Deligtisch Amanda , Richardson Sarah Pirio , Mayer Andrew R. , Ryman Sephira G.
Published: December 2023

Neuromelanin‐sensitive magnetic resonance imaging quantitative analysis methods have provided promising biomarkers that can noninvasively quantify degeneration of the substantia nigra in patients with Parkinson's disease. However, there is a need to systematically evaluate the performance of manual and automated quantification approaches. We evaluate whether spatial, signal‐intensity, or subject specific abnormality measures using either atlas based or manually traced identification of the substantia nigra better differentiate patients with Parkinson's disease from healthy controls using logistic regression models and receiver operating characteristics. Inference was performed using bootstrap analyses to calculate 95% confidence interval bounds. Pairwise comparisons were performed by generating 10,000 permutations, refitting the models, and calculating a paired difference between metrics. Thirty‐one patients with Parkinson's disease and 22 healthy controls were included in the analyses. Signal intensity measures significantly outperformed spatial and subject specific abnormality measures, with the top performers exhibiting excellent ability to differentiate patients with Parkinson's disease and healthy controls (balanced accuracy = 0.89; area under the curve = 0.81; sensitivity =0.86; and specificity = 0.83). Atlas identified substantia nigra metrics performed significantly better than manual tracing metrics. These results provide clear support for the use of automated signal intensity metrics and additional recommendations. Future work is necessary to evaluate whether the same metrics can best differentiate atypical parkinsonism, perform similarly in de novo and mid‐stage cohorts, and serve as longitudinal monitoring biomarkers.
Long‐term vinasse application enhanced the initial dissipation of atrazine and ametryn in a sugarcane field in Tucumán, Argentina
Authors: Portocarrero Rocio de los Ángeles , Chalco Vera Jorge , Vallejo Juan Inocencio , De Gerónimo Eduardo , Costa José Luis , Aparicio Virginia Carolina
Published: December 2023

The production of sugarcane bioethanol generates large volumes of vinasse, an effluent whose final disposal can produce an environmental impact that is of concern. The long‐term disposal of vinasse in sugarcane fields could challenge crop management, such as the performance of traditional herbicides, by changing soil properties. This study aimed to evaluate the effect of long‐term vinasse application on the field and the dissipation of atrazine and ametryn herbicides in a subtropical sugarcane agroecosystem, and to discuss the potential processes involved in it. Vinasse affected soil properties by increasing pH (12%), electrical conductivity (160%), and soil organic carbon (25%) at 0–10 cm depth of soil. Differences in the herbicide calculated sorption coefficient (Kd) varied according to the pedotransfer function applied and the herbicide type (atrazine or ametryn). During the first seven days after herbicide application, the soil underwent long‐term vinasse application and increased atrazine and ametryn dissipation 45% and 33%, respectively, compared with the conventional fertilization scheme (control). The Pesticide Root Zone Model revealed that dissipation was mediated mainly by the degradation process rather than transport or other processes. The long‐term application of vinasse in a typical sugarcane field of Tucumán, Argentina decreased the potential groundwater pollution of triazines and, adversely, reduced their bioavailability for weed control. For this, the present study presents original information about how long‐term treatment with vinasse may require an adaptation of conventional management practices such as the application of herbicides in Argentina and other sugarcane‐producing regions. Integr Environ Assess Manag 2024;20:1075–1086. © 2023 SETAC
1064nm Nd:YAG laser promotes chondrocytes regeneration and cartilage reshaping by upregulating local estrogen levels
Authors: Zhu Yingjie , Zhou Xueqing , Peng Xieling , Li Hantao , Wang Hongshun , Guo Ziwei , Xiong Yang , Xu Jiaqi , Ni Xiangrong , Qi Xiangdong
Published: December 2023

Cartilage is frequently used as a scaffolds for repairing and reconstructing body surface organs. However, after successful plastic surgery, transplanted cartilage scaffolds often exhibit deformation and absorption over time. To enhance the shaping stability of cartilage scaffolds and improve patients' satisfaction after reconstructions, we employed the ear folding models in New Zealand rabbits to confirm whether the 1064nm neodymium‐doped yttrium aluminum garnet (Nd:YAG) laser could promote cartilage reshaping. There was an increase in collagen and aromatase (Cyp19) expression within the ear cartilage after laser treatment. Moreover, we have found that the Cyp19 inhibitor can inhibit the laser's effect on cartilage shaping and reduce collagen and Cyp19 expression. The overall findings suggest that treatment with 1064nm Nd:YAG laser irradiation can enhance estrogen levels in local cartilage tissues by upregulating Cyp19 expression in chondrocytes through photobiomodulation, thereby promoting the proliferation and collagen secretion of chondrocytes to improve cartilage reshaping and stability.
When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit
Authors: Wölfel Eva M. , Bartsch Benjamin , Koldehoff Jasmin , Fiedler Imke A. K. , Dragoun‐Kolibova Sofie , Schmidt Felix N. , Krug Johannes , Lin Mei‐Chun , Püschel Klaus , Ondruschka Benjamin , Zimmermann Elizabeth A. , Jelitto Hans , Schneider Gerold , Gludovatz Bernd , Busse Björn
Published: December 2023

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age‐related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case‐control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back‐scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three‐point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J‐integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Medical emergencies in a dental school clinic – A 12‐year review and lessons learned
Authors: D'Innocenzo Richard , Sethi Amit , Uribe‐Rivera Armando , Dang Rushil R. , Cook Abigail , Joshi Prajakta , Lakis Sally , Bhagania Manish K.
Published: December 2023

Purpose

The aims of this study were to estimate the type and frequency of different medical emergencies that occurred over the study period (twelve years) and discuss the lessons learned and the modifications made in the curriculum to better equip dental students and faculty in their management.

Materials and methods

A retrospective study was conducted to evaluate all medical emergencies that needed activation of the response team at our school from 2008 to 2020.

Results

The emergency response system was activated 250 times during the 12‐year period. There were 132 medical emergencies in the pre‐doctoral clinic and 105 events in the post‐doctoral clinic (p 0.0680). Most of the emergencies occurred in patients between 45 and 64 years of age. Syncope occurs most often followed by adverse cardiovascular, respiratory, anxiety, and hypoglycemic events.

Conclusions

Medical emergencies occurring in a dental school provide a unique opportunity for students to gain experience in their management. The key lies in preparing the students and faculty to prevent them from occurring, but should these occur, then they should be able to promptly recognize symptoms and institute prompt intervention.
Assessment of copper nanoparticles treatment on male accessory reproductive organs and epididymis in a mouse model: A morphological and biochemical study
Authors: Nicy Vanrohlu , Gurusubramanian Guruswami , Roy Vikas K.
Published: December 2023

Although the usage of nanoparticles has expanded substantially in recent years, and it causes the detrimental effect on the various organs. CuNPs are widely used in commercial applications. There has been minimal investigation into the possibly harmful effects of CuNPs on the accessory reproductive organs. Thus, the present study aimed to investigate the effect of CuNPs on the male reproductive organs like epididymis, vas deferens, seminal vesicle and prostate of mice. The mice were exposed orally to CuNPs at three doses 10, 100, and 200 mg/kg for 70 days. Our results showed that the organs index of only vas deferens and prostate reduced at 200 mg/kg group compared to the control. However, the histological study showed degenerative changes in the epididymis at higher doses like distortion in the tubules. The sperm parameters were also decreased in the 200 mg/kg CuNPs group. The vas deferens in 100 and 200 mg/kg treatment groups exhibited detachment of luminal epithelium and with a few or no spermatozoa in the higher dose group. The seminal vesicle and prostate also showed degenerative changes like atrophy, hyperplasia, and scant secretary materials. Furthermore, CuNPs also increased the oxidative stress and decreased antioxidant enzymes in vas deferens and seminal vesicles at higher dose. Caput epididymis showed decreased GPx enzymes in all the groups. However, MDA and GPx in corpus, cauda, and prostate did not show any significant variations among all the groups. In conclusion, our results suggest that CuNPs can manifest the detrimental effect of the male accessory organs and epididymis in a dose and tissue dependent manner. Since, detrimental effects were observed only at higher dose, thus, uses of CuNPs would be safe for reproductive organs at lower dose, even for the prolonged duration.
Surface modification of lipid nanoparticles for gene therapy
Authors: Tafech Belal , Mohabatpour Fatemeh , Hedtrich Sarah
Published: December 2023

Gene therapies have the potential to target and effectively treat a variety of diseases including cancer as well as genetic, neurological, and autoimmune disorders. Although we have made significant advances in identifying non‐viral strategies to deliver genetic cargo, certain limitations remain. In general, gene delivery is challenging for several reasons including the instabilities of nucleic acids to enzymatic and chemical degradation and the presence of restrictive biological barriers such as cell, endosomal and nuclear membranes. The emergence of lipid nanoparticles (LNPs) helped overcome many of these challenges. Despite its success, further optimization is required for LNPs to yield efficient gene delivery to extrahepatic tissues, as LNPs favor accumulation in the liver after systemic administration. In this mini‐review, we provide an overview of current preclinical approaches in that LNP surface modification was leveraged for cell and tissue targeting by conjugating aptamers, antibodies, and peptides among others. In addition to their cell uptake and efficiency‐enhancing effects, we outline the (dis‐)advantages of the different targeting moieties and commonly used conjugation strategies.
Femicide in Northern Ireland during the COVID‐19 lockdown: A model for differentiating male offender characteristics
Authors: Johnston Rea , Synnott John , Ioannou Maria , Ashton Sally‐Ann
Published: December 2023

Femicide, the lethal form of gender‐based violence against women, is a global health crisis that transcends class and ethnicity. To date, there is no working model for differentiating male femicide offenders within Northern Ireland (NI); therefore, the current study aimed to do this, focusing on the timeframe of the COVID‐19 lockdown in 2020. The research has drawn on newspaper articles reporting on the 11 NI femicides perpetrated over a period of 20 months. These crimes were content analysed for the presence or absence of 16 pre‐identified offender variables. The data was analysed using a multi‐dimensional scaling procedure called Smallest Space Analysis (SSA). Two distinct themes emerged: Chronic Criminal Abuser and Mentally Disturbed. The qualitative data obtained on offender characteristics aligned with the preliminary model for differentiation. Forensic implications pertinent to risk assessment and management are considered. It is argued that NI adopt an active violence against women and girls (VAWG) strategy to effectively tackle the issue of Femicide. Future research may consider a retrospective study of NI Femicide offenders to firmly establish the types of offenders committing femicide for targeted resource allocation.
Intraoral Microscopic Versus Robot‐Assisted Sialolithotomy and Sialendoscopy for Submandibular Stones
Authors: Seif‐Elnasr Mahmoud , Magdy Emad A. , Fung Ethan , Deot Neal S. , Marzouk Mark F.
Published: December 2023

Objective

Sialendoscopy has remained the standard of treatment for sialolithiasis; however, large stones impacted in the submandibular gland hilum often require an intra‐oral combined approach.

Methods

Patients treated for submandibular hilar sialolithiasis from 2015 to 2021 at two tertiary centers were stratified into two groups based on the surgical technique: Intraoral Microscopic‐Assisted Sialolithotomy (IMAS) versus Robot‐Assisted Sialolithotomy and Sialendoscopy (RASS). We compared the characteristics of retrieved stones, surgical success rate, operative time, and post‐operative complications in both techniques. True surgical success was defined as successful stone extraction without reoccurrence within 12 months.

Results

The RASS technique was attempted in 60 patients and successful in 56 (93.3%) cases whereas the IMAS technique was performed in 52 patients and successful in 48 (92.3%) cases. The longest dimension of the predominant retrieved calculi was 9.6 ± 3.1 mm (range, 5–18 mm) for the robotic technique and 10 ± 4.8 mm (range, 5–30 mm) for the microscopic technique. The operative time for the robotic technique excluding robot setup time was 70.6 ± 24.8 min compared to 61.9 ± 42.4 min for microscopic technique (p = 0.018). No major adverse outcomes were reported; however, temporary lingual paresthesia was found in ten robotic (16.7%) and five microscopic (9.6%) cases.

Conclusion

The two techniques were comparable in terms of efficacy and safety for large stones. The robot has the advantage of intraoral high dynamic maneuverability and improved surgeon posture while the microscopic technique has the advantage of intraoral tactile feedback. The procedure was significantly shorter in duration with the microscope.

Level of Evidence

3 Laryngoscope, 134:2170–2176, 2024
Effects of Para‐ or Meta‐Aromatic Amide Units on the Microstructure, Thermal, Mechanical, Rheological, and Dielectric Properties of Thermotropic Liquid Crystalline Poly(ester amide)s
Authors: Song Young‐Gi , Park Jin‐Hyeok , Tang Feng , Kim Seok‐ju , Eomm Tae‐Gyeong , Seo Minyoung , Jeong Young Gyu
Published: December 2023

The impact of para‐ and meta‐aromatic amide repeat units on the microstructure, thermal behavior, mechanical properties, rheological characteristics, and dielectric properties of thermotropic liquid crystalline poly(ester amide)s (TPEAs) is reported. For this purpose, two distinct series of TPEAs are synthesized using 75.0 mol% of 4‐hydroxybenzoic acid (HBA) and 25.0–17.5 mol% of 6‐hydroxy‐2‐naphtoic acid (HNA) with 0.0–7.5 mol% terephthalic acid/para‐acetylaminophenol (TPA/PAP) or isophthalic acid/para‐acetylaminophenol (IPA/PAP) are synthesized via bulk polycondensation reaction. Infrared and electron microscopic data reveal the existence of intermolecular hydrogen bonds and associated fibrillar structures of TPEAs with TPA/PAP‐ or IPA/PAP‐based aromatic amide units. Accordingly, the glass transition temperatures, dynamic storage moduli, and melt viscosities of TPEAs increased with the increment of the aromatic amide units, although they are higher for TPEAs with IPA/PAP‐derived units, compared to TPEAs with TPA/PAP‐derived units. The melting temperatures of TPEAs increase with the para‐aromatic amide unit owing to the intermolecular hydrogen bonding and the rigid linearity, whereas the melting points decrease with the meta‐aromatic amide unit due to the structural nonlinearity. Interestingly, the dielectric constants and losses of TPEAs decrease with the aromatic amide unit content, which is even dominant for TPEAs with IPA/PAP‐based repeat units. TPEAs can be thus utilized as super‐engineering plastics, industrial fibers, printed circuit board materials, etc., requiring enhanced mechanical and thermal transition properties but lower dielectric constants and losses.
Biomarkers and experimental models for cancer immunology investigation
Authors: Xu Hengyi , Jia Ziqi , Liu Fengshuo , Li Jiayi , Huang Yansong , Jiang Yiwen , Pu Pengming , Shang Tongxuan , Tang Pengrui , Zhou Yongxin , Yang Yufan , Su Jianzhong , Liu Jiaqi
Published: December 2023

The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting the need for highly effective biomarkers and reproducible experimental models. Current immunotherapy biomarkers encompass surface protein markers such as PD‐L1, genetic features such as microsatellite instability, tumor‐infiltrating lymphocytes, and biomarkers in liquid biopsy such as circulating tumor DNAs. Experimental models, ranging from 3D in vitro cultures (spheroids, submerged models, air–liquid interface models, organ‐on‐a‐chips) to advanced 3D bioprinting techniques, have emerged as valuable platforms for cancer immunology investigations and immunotherapy biomarker research. By preserving native immune components or coculturing with exogenous immune cells, these models replicate the tumor microenvironment in vitro. Animal models like syngeneic models, genetically engineered models, and patient‐derived xenografts provide opportunities to study in vivo tumor‐immune interactions. Humanized animal models further enable the simulation of the human‐specific tumor microenvironment. Here, we provide a comprehensive overview of the advantages, limitations, and prospects of different biomarkers and experimental models, specifically focusing on the role of biomarkers in predicting immunotherapy outcomes and the ability of experimental models to replicate the tumor microenvironment. By integrating cutting‐edge biomarkers and experimental models, this review serves as a valuable resource for accessing the forefront of cancer immunology investigation.
Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers
Authors: Liang Nan , Wu Mian , Gao Yining , Yang Shaoling , Lin Xiaojing , Sun Hang , Liang Ningning , Yin Huiyong , Qu Shen , Chen Haibing
Published: December 2023

Background

Oral inosine loading is a new method to evaluate the effects of purine on urate metabolism. However, individuals respond differently to acute purine intake, and the effects on the metabolism of other purines remain to be explored.

Methods

35 male participants are recruited. Participants received 500 mg of inosine orally after an overnight fast, and blood and urine samples are collected before and at various time points over 180 min after inosine administration.

Results

The serum urate concentration is significantly different between the hyperuricemia (n = 14) and non‐hyperuricemia (n = 16) groups before inosine intake, but there is no in urate change after inosine intake. When grouped according to the baseline estimated glomerular filtration rate (eGFR), the increase in urate level in the high‐eGFR group is significantly higher than that in the low‐eGFR group (p  =  0.047). The high‐eGFR group showed higher levels of serum xanthine and xanthine oxidase (XOD), the key enzyme in urate synthesis, after inosine loading (p < 0.01).

Conclusions

The increase in urate level is positively related to eGFR after oral acute inosine administration, which may have been due to a higher level of XOD.
Glutamate measurements using edited MRS
Authors: Saleh Muhammad G. , Prescot Andrew , Chang Linda , Cloak Christine , Cunningham Eric , Subramaniam Punitha , Renshaw Perry F. , Yurgelun‐Todd Deborah , Zöllner Helge J. , Roberts Timothy P. L. , Edden Richard A. E. , Ernst Thomas
Published: December 2023

Purpose

To demonstrate J‐difference coediting of glutamate using Hadamard encoding and reconstruction of Mescher‐Garwood‐edited spectroscopy (HERMES).

Methods

Density‐matrix simulations of HERMES (TE 80 ms) and 1D J‐resolved (TE 31–229 ms) of glutamate (Glu), glutamine (Gln), γ‐aminobutyric acid (GABA), and glutathione (GSH) were performed. HERMES comprised four sub‐experiments with editing pulses applied as follows: (A) 1.9/4.56 ppm simultaneously (ONGABA/ONGSH); (B) 1.9 ppm only (ONGABA/OFFGSH); (C) 4.56 ppm only (OFFGABA/ONGSH); and (D) 7.5 ppm (OFFGABA/OFFGSH). Phantom HERMES and 1D J‐resolved experiments of Glu were performed. Finally, in vivo HERMES (20‐ms editing pulses) and 1D J‐resolved (TE 31–229 ms) experiments were performed on 137 participants using 3 T MRI scanners. LCModel was used for quantification.

Results

HERMES simulation and phantom experiments show a Glu‐edited signal at 2.34 ppm in the Hadamard sum combination A+B+C+D with no overlapping Gln signal. The J‐resolved simulations and phantom experiments show substantial TE modulation of the Glu and Gln signals across the TEs, whose average yields a well‐resolved Glu signal closely matching the Glu‐edited signal from the HERMES sum spectrum. In vivo quantification of Glu show that the two methods are highly correlated (p < 0.001) with a bias of ∼10%, along with similar between‐subject coefficients of variation (HERMES/TE‐averaged: ∼7.3%/∼6.9%). Other Hadamard combinations produce the expected GABA‐edited (A+B–C–D) or GSH‐edited (A–B+C–D) signal.

Conclusion

HERMES simulation and phantom experiments show the separation of Glu from Gln. In vivo HERMES experiments yield Glu (without Gln), GABA, and GSH in a single MRS scan.