bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers to climate change and health research in India: a qualitative study
Authors: Shrikhande Shreya , Merten Sonja , Cambaco Olga , Lee Tristan T , Lakshmanasamy Ravivarman , Röösli Martin , Dalvie Mohammad Aqiel , Utzinger Jürg , Cissé Guéladio
Published: October 2023

Objectives

Almost a quarter of the global burden of disease and mortalities is attributable to environmental causes, the magnitude of which is projected to increase in the near future. However, in many low- and middle-income settings, there remains a large gap in the synthesis of evidence on climate-sensitive health outcomes. In India, now the world’s most populous country, little remains known about the impacts of climate change on various health outcomes. The objective of this study is to better understand the challenges faced in conducting climate change and health research in Puducherry, India.

Design and setting

In this study, we employed key informant interviews to deepen the understanding of the perceived research barriers in Puducherry. The findings were analysed using data-driven qualitative thematic analysis to elaborate the major perceived barriers to conducting environmental health research.

Participants

This study was conducted among 16 public health professionals, including medical researchers, and professionals involved in environmental policies and planning in Puducherry.

Results

We identify three key barriers faced by public health professionals as key stakeholders, namely: (1) political and institutional barriers; (2) education and awareness barriers; and (3) technical research barriers. We show there is a need, from the professionals’ perspective, to improve community and political awareness on climate change and health; strengthen technical research capacity and collaboration among researchers; and strengthen health surveillance, resource allocation and access to health data for research.

Conclusion

Evidence informed policies and interventions are a key element in the adaptation response for countries. In the context of the paucity of data on environmental health from India, despite recognised climate change related health vulnerabilities, these findings could contribute to the development and improvement of relevant interventions conducive to a strong research environment.
AN EPIDEMIC MODEL WITH SATURATED DIGITAL CONTACT TRACING FUNCTION: BIFURCATION AND ANALYSIS
Authors: DING SIBO , FU PENGBO , YUAN LINSHUANG
Published: October 2023

In this paper, we develop an epidemic model with a nonlinear function that describes the saturated digital contact tracing. The model is theoretically and numerically analyzed based on its dynamics. The model equilibria points and the basic reproduction number are obtained. However, the proposed model reveals both backward and forward bifurcation, and backward bifurcation occurs when the digital contact tracing saturation parameter is larger than a specific threshold. Real data are used to fit the model and estimate the parameter values. Sensitivity analysis reveals that interventions such as reducing the infection rate, enhancing quarantine efforts, and accelerating vaccination can effectively reduce the basic reproduction number, [Formula: see text]. Simulations show that improving tracing accuracy and encouraging greater participation in providing personal track information can effectively reduce the peak of undetected exposed individuals. Moreover, we analyze the expression for the specific threshold and determine that the increasing hospital resources and strengthening patient quarantine can reduce the potential occurrence of backward bifurcation. The analysis and simulations presented in this paper provide valuable suggestions for the prevention and control of the epidemic.
Joint Audio-Visual Attention with Contrastive Learning for More General Deepfake Detection
Authors: Zhang Yibo , Lin Weiguo , Xu Junfeng
Published: October 2023

With the continuous advancement of deepfake technology, there has been a surge in the creation of realistic fake videos. Unfortunately, the malicious utilization of deepfake poses a significant threat to societal morality and political security. Therefore, numerous researchers have proposed various deepfake detection methods. However, traditional deepfake approaches tend to focus on specific forgery features, such as artifacts or inconsistent actions, which can be vulnerable to specialized countermeasures. Recent studies show an intrinsic correlation between facial and audio cues, which can be exploited for deepfake detection. To address these challenges and enhance the robustness and generalization of deepfake detection algorithms, we propose a novel joint audio-visual deepfake detection model named AVA-CL, which is capable of detecting deepfakes in both audio and visual domains. Furthermore, exploiting the inherent correlation and consistency between audio and visual enhances the effectiveness of deepfake detection significantly. Through extensive experiments, we demonstrate that our proposed AVA-CL model outperforms many state-of-the-art (SOTA) methods with superior robustness and generalization capabilities. This research presents a promising approach for deepfake detection and reducing the harm caused by malicious use.
A primitive-based representation of dance: modulations by experience and perceptual validity
Authors: Leh Amalaswintha , Endres Dominik , Hegele Mathias
Published: October 2023

This study demonstrates that a temporal movement primitive model, trained with movements performed by dancers with different levels of experience, is able to generate natural-looking dance movements. The results suggest that motor experience in dance is associated not only with fewer temporal segments but also with an increase in the number of underlying movement building blocks. The recruitment of these primitives, which might be used to simplify movement production, additionally seems to become more consistent with experience.
Visual feedback decoding during bimanual circle drawing
Authors: Nazarahari Milad , Ajami Sahand , Jeon Soo , Arami Arash
Published: October 2023

Many daily activities involve bimanual coordination while simultaneous movement of the hands may result in interference with their movements. Here, we studied whether the central nervous system could use the relevant information in composite feedback, i.e., a weighted sum of positional information of nonvisible and visible hands, to improve the movement of the nonvisible hand. Our results suggest the ability to decode and associate task-relevant information from the composite feedback.
Asymmetric and Cubic Nonlinear Energy Sink Inerters for Mitigating Wind-Induced Responses of High-Rise Buildings
Authors: Wang Qinhua , Wu Huaxiao , Qiao Haoshuai , Yu Xianfeng , Huang Peng
Published: October 2023

Flexible high-rise buildings with low damping are prone to excessive vibration under strong wind loads. To explore a light-weight control device having desirable mitigation effects on responses and sound robustness against deviations in tuning parameters, the performance of two novel inerter-integrated nonlinear energy sinks (NESIs), i.e., asymmetric nonlinear energy sink inerter (Asym NESI) and cubic NESI, on wind-induced vibration control of super high-rise buildings is assessed in the present work. Based on the wind loads obtained from wind tunnel tests, a super high-rise building with a 300 m height is taken as the host structure in the numerical case study. The results show that Asym NESI can achieve reduction ratios of 38.5% and 11.3% on extreme acceleration and displacement, respectively, while the sensitivity indices of Asym NESI on displacement and acceleration control are only 70.5% and 62.5% of those of tuned mass damper inerter (TMDI) having identical mitigation effects. Although the sensitivity indices of cubic NESI are only 5.5% and 29.8% of those of TMDI, the moderate mitigation effects and large nonlinear stiffness ratio may prohibit its practical implementation. Overall, Asym NESI could be an alternative to TMDI due to the same mitigation effects but better robustness against possible detuning.
Analysis of Injury Severity of Drivers Involved Different Types of Two-Vehicle Crashes Using Random-Parameters Logit Models with Heterogeneity in Means and Variances
Authors: Wu Qiang , Song Dongdong , Wang Chenzhu , Chen Fei , Cheng Jianchuan , Easa Said M. , Yang Yitao , Yang Wenchen
Published: October 2023

This study proposes random-parameters multinomial logit models, with heterogeneity in means and variances, to explore the differences in the factors influencing injury severities of drivers involved in different types of two-vehicle crashes. The models are verified using crash data from the United Kingdom (UK) over three years (2016–2018). Three types of crashes are separately identified (car-car, car-truck, and truck-truck crashes). In this study, a wide variety of potential variables, including the driver, vehicle, road, and environmental characteristics, are considered, with two possible injury-severity outcomes: severe and slight injury. The results show that unobserved heterogeneity existed for young drivers in both car-car and truck-truck crash models and the 30 mph speed limit in the three separate models. Remarkably variations are observed in crashes involving different types of vehicles. The driver’s age and gender, speeding, sideswipes, presence of junctions, weekdays, unlit, and weather conditions significantly impact driver-injury severities in various types of vehicle crashes. These findings are expected to help policymakers seek to improve highway safety and implement proper safety countermeasures.
Findings of Cardiovascular Workup of Kidney Transplant Candidates: A Retrospective Study of a Single-Center in Saudi Arabia
Authors: Arabi Ziad , Tawhari Mohammed H. , Al Rajih Haneen S. , Youssouf Talha M. , Abdulgadir Mohamad Y.
Published: October 2023

Background. There are limited data about the prevalence of cardiovascular (CV) risk factors and the findings of CV workup among kidney transplant (KTx) recipients (KTRs) in Saudi Arabia. Methods. A single-center retrospective study of KTRs who underwent KTx from 2017 to 2020 was performed. We reviewed the prevalence of CV risk factors and the results of the pre-KTx CV workup which was derived from the American Heart Association guidelines. Results. We included 254 KTRs. The mean age was 43.1 ± 15.9 years, and 55.5% were men and 79.5% were living-donor KTRs. Pre-emptive KTx was 9.8%, peritoneal dialysis was 11.8%, and hemodialysis was 78.3% (arteriovenous fistula: 33.1% versus hemodialysis catheter: 66.9%). The mean dialysis vintage was 4.8 ± 3.3 years for deceased-donor KTRs versus 2.4 ± 2.6 years for living-donor KTRs. CV risk factors were hypertension: 76%, diabetes: 40.6% (type 1 : 25.2% versus type 2 : 74.7%), hyperlipidemia (low-density lipoprotein >2.6 mmol/L): 40.2%, coronary artery disease (CAD): 12.6%, smoking: 9.1%, peripheral vascular disease: 2.8%, and cerebral vascular disease: 2.4%. The prevalence of obesity stage 1 was 19.7% and obesity stage 2 was 4%. Left ventricular hypertrophy was present in 38.5%. The ejection fraction was abnormal (<55%) in 22%. Abnormal wall motion was present in 34 patients (13.4%). A cardiac (PET-CT) stress test was conducted on 129 patients (50.8%) which showed abnormal perfusion in 37 patients (28.7%). Out of those who required PET-CT, 18.6% had a coronary artery calcium scoring (CACS) of more than 400, 41.8% had a CACS of zero, 29.4% had a CACS of 1–100, and 14.7% had a CACS of 100–400. Coronary angiogram was required in only 41 patients (16.1%), 12 (29.3%) required coronary interventions, 25 (61%) were treated medically, and 4 (9.8%) did not have any CAD. CT scans of pelvic arteries were performed in 118 patients (46.5%). It showed moderate or severe calcifications in only 7 patients (5.9%), whereas it was normal in 97 patients (82.2%), or it showed only mild calcifications in 14 patients (11.9%). Conclusion. This study outlines the prevalence of CV risk factors and the findings of the pretransplant CV workup among KTx candidates who underwent KTx. Multicenter national studies will be helpful to validate the generalizability of these findings.
Rapid Separation of Asiatic Acid, Quercetin, and Kaempferol from Traditional Chinese Medicine Centella asiatica (L.) Urban Using HSCCC-Semi-Prep-HPLC and the Assessment of Their Potential as Fatty Acid Synthase Inhibitors
Authors: Xia Binbin , Li Yali , Liu Yang , Sun Wenfang , Chen Jing , Li Liushui , Pang Jingyao , Liu Xianjun , Chen Shicai , Cheng Hua
Published: October 2023

The main objective of this study was to rapidly separate asiatic acid (AA), quercetin (QCN), and kaempferol (KPL) from Centella asiatica (L.) Urban using high-speed counter-current chromatography (HSCCC) in tandem with the UV detector of semipreparative high-performance liquid chromatography (Semi-Prep-HPLC) and to evaluate their potential as inhibitors of fatty acid synthetase (FAS). To efficiently prepare large amounts of AA, QCN, and KPL from Centella asiatica (L.) Urban, rapid and simple methods by HSCCC were established respectively based on the partition coefficients (K values) of crude samples. The conditions of HSCCC-Semi-Prep-HPLC for the large-scale separation of AA, QCN, and KPL from Centella asiatica (L.) Urban were established and optimized. This included selecting the solvent system, flow rate, rotation speed, and so on. HSCCC-Semi-Prep-HPLC was successfully applied to separate and purify AA, QCN, and KPL, with n-hexane-n-butanol-methanol-water (3 : 1 : 3 : 3, V : V : V : V) as the solvent system for AA, which was detected at a wavelength of 210 nm with the stationary phase retention of 70%, and with n-hexane-ethyl acetate-methanol-water (0.8 : 0.9 : 1.2 : 1, V : V : V : V) as the solvent system for the co-separation of QCN and KPL, which was detected at a wavelength of 254 nm with the stationary phase retention of 65%. AA could be isolated at a large scale with high purity (>91.0%) in only one-step HSCCC-Semi-Prep-HPLC separation (within 150 min) under the optimized conditions. Meanwhile, QCN and KPL could be simultaneously isolated at a large scale with high purity (>99.1%) by another one-step HSCCC-Semi-Prep-HPLC separation (within 240 min) under the optimized conditions. The assessment of inhibition potential revealed that AA exhibited the strongest inhibitory effect on FAS, with an IC50 of 9.52 ± 0.76 μg/mL. Madecassic acid (MA) followed closely with IC50 values of 10.84 ± 0.92 μg/mL. QCN and KPL showed similar and relatively weaker inhibitory effects on FAS, with IC50 values of 43.09 ± 2.98 μg/mL and 36.90 ± 1.83 μg/mL, respectively. Overall, the HSCCC-Semi-Prep-HPLC method proved to be a highly efficient and reliable technique for separating AA, QCN, and KPL from Centella asiatica (L.) Urban, and the isolated compounds showed potential as FAS inhibitors.
Sequential Geometric Programming Method for Parameter Estimation of a Nonlinear System in Microbial Continuous Fermentation
Authors: Xu Gongxian , Liu Zijia
Published: October 2023

This paper addresses the problem of parameter estimation for the microbial continuous fermentation of glycerol to 1,3-propanediol. A nonlinear dynamical system is first presented to describe the microbial continuous fermentation. Some mathematical properties of the dynamical system in the microbial continuous fermentation are also presented. A parameter estimation model is proposed to estimate the parameters of the dynamical system. The proposed estimation model is a large-scale, nonlinear, and nonconvex optimization problem if the number of experimental groups is large. A sequential geometric programming (SGP) method is proposed to efficiently solve the parameter estimation problem. The results indicated that our proposed SGP method can yield smaller errors between the experimental and calculated steady-state concentrations than the existing seven methods. For the five error indices considered, that is, the concentration errors of biomass, glycerol, 1,3-propanediol, acetic acid, and ethanol, the results obtained using the proposed SGP method are better than those obtained using the methods in the literature (Xiu et al., Gao et al., Sun et al., Sun et al., Li and Qu, Wang et al., and Zhang and Xu), with improvements of approximately 71.86–95.03%, 52.08–94.87%, 99.70–99.98%, 5.39–90.29%, and 12.67–80.83%, respectively. This concludes that the established dynamical system can better describe the microbial continuous fermentation. We also present that our established dynamical system has multiple positive steady states in some fermentation conditions. We observe that there are two regions of multiple positive steady states at relatively high values of substrate glycerol concentration in feed medium.
Nanoporous Double-Gyroid Structure from ABC Triblock Terpolymer Thick Films
Authors: Aissou Karim , Coronas Maximilien , Hermida-Merino Daniel , Solano Eduardo , Cot Didier , Roualdes Stéphanie , Bouyer Denis , Quemener Damien
Published: October 2023

The creation of nanostructured materials with a triply periodic minimal surface (TPMS), defined as a zero mean curvature surface having periodicity in three-dimensional space, is an emerging solution to optimize transport (i.e., the ion-conductivity and hydraulic permeability) through the next-generation of electrolyte and ultrafiltration (UF) membranes. Here, we used an amphiphilic ABC-type block copolymer (BCP) (namely, polystyrene-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) (PS-b-P2VP-b-PEO)) to generate symmetric thick films (~8 μm) composed entirely of a TPMS-based structure, consisting of a PS matrix with a double gyroid (DG) minimal surface and hydrophilic stimuli-responsive (P2VP/PEO) nanochannels. To produce the core/shell DG-structured monoliths, we used a process combining the nonsolvent-induced phase separation (NIPS) process with a solvent vapor annealing (SVA) treatment. From such symmetric ABC-type BCP-thick films generated by NIPS-SVA, a mean hydraulic permeability as high as 514 L h-1 m-2 bar-1 was measured. This mean value was revealed to be nearly equal to that of asymmetric PS-b-P2VP-b-PEO membranes manufactured by NIPS, which have a substructure with an implicit irregular and random distribution of the internal pore structure and a skin layer with P2VP/PEO nanopores arranged into a hexagonal array.
Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma
Authors: Zhao Tiansuo , Jiang Tingting , Li Xiaojia , Chang Shaofei , Sun Qihui , Kong Fanyang , Kong Xiangyu , Wei Fang , He Jie , Hao Jihui , Xie Keping
Published: October 2023

Purpose:

Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains.

Experimental Design:

Gene expression and its association with clinicopathologic characteristics of patients with PDA and mouse models were analyzed using IHC. Protein expression and their regulation were measured by Western blot and immunoprecipitation analyses. Protein interactions were determined using gain- and loss-of-function assays and molecular methods, including chromatin immunoprecipitation, co-immunoprecipitation, and dual luciferase reporter.

Results:

There was concomitant overexpression of both GRP78 and HIF-1α in human and mouse PDA tissues and cells. Glucose deprivation increased the expression of GRP78 and HIF-1α, particularly colocalization in nucleus. Induction of HIF-1α expression by glucose deprivation in PDA cells depended on the expression of and its own interaction with GRP78. Mechanistically, increased expression of both HIF-1α and LDHA under glucose deprivation was caused by the direct binding of GRP78 and HIF-1α protein complexes to the promoters of HIF-1α and LDHA genes and transactivation of their transcriptional activity.

Conclusions:

Protein complex of GRP78 and HIF-1α directly binds to HIF-1α own promoter and LDHA promoter, enhances the transcription of both HIF-1α and LDHA, whereas glucose deprivation increases GRP78 expression and further enhances HIF-1α and LDHA transcription. Therefore, crosstalk and integration of hypoxia- and hypoglycemia-responsive signaling critically impact PDA metabolic reprogramming and therapeutic resistance.
Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma
Authors: McCrury Mason , Swafford Kennith , Shuttleworth Sydnye L. , Mehdi Syed Hassan , Acharya Baku , Saha Debasmita , Naceanceno Kevin , Byrum Stephanie D. , Storey Aaron J. , Xu Ying-Zhi , Doshier Claire , Patel Vijay , Post Ginell R. , De Loose Annick , Rodriguez Analiz , Shultz Leonard D. , Zhan Fenghuang , Yoon Donghoon , Frett Brendan , Kendrick Samantha
Published: October 2023

Expression of the serine/threonine kinase never in mitosis gene A (NIMA)–related kinase 2 (NEK2) is essential for entry into mitosis via its role in facilitating centrosome separation. Its overactivity can lead to tumorigenesis and drug resistance through the activation of several oncogenic pathways, including AKT. Although the cancer-enabling activities of NEK2 are documented in many malignancies, including correlations with poor survival in myeloma, breast, and non–small cell lung cancer, little is known about the role of NEK2 in lymphoma. Here, in tumors from patients with diffuse large B-cell lymphoma (DLBCL), the most common, aggressive non-Hodgkin lymphoma, we found a high abundance of NEK2 mRNA and protein associated with an inferior overall survival. Using our recently developed NEK2 inhibitor, NBI-961, we discovered that DLBCL cell lines and patient-derived cells exhibit a dependency on NEK2 for their viability. This compromised cell fitness was directly attributable to efficient NEK2 inhibition and proteasomal degradation by NBI-961. In a subset of particularly sensitive DLBCL cells, NBI-961 induced G2/mitosis arrest and apoptosis. In contrast, an existing indirect NEK2 inhibitor, INH154, did not prevent NEK2 autophosphorylation, induce NEK2 proteasomal degradation, or affect cell viability. Global proteomics and phospho-proteomics revealed that NEK2 orchestrates cell-cycle and apoptotic pathways through regulation of both known and new signaling molecules. We show the loss of NEK2-sensitized DLBCL to the chemotherapy agents, doxorubicin and vincristine, and effectively suppressed tumor growth in mice. These studies establish the oncogenic activity of NEK2 in DLBCL and set the foundation for development of anti-NEK2 therapeutic strategies in this frequently refractory and relapse-prone cancer.
TABLE 1 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

OS within KRAS-variant patients by as-treated cetuximab
Supplementary Data Table 6 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

Worst Overall Treatment-Related Adverse Event by KRAS Analysis Inclusion Status
Supplementary Data Table 5 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

Best Observed Response by KRAS Analysis Inclusion Status
Supplementary Data Table 15 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

Worst Treatment-Related Toxicity within KRAS-Variant Patients By Cetuximab
Supplementary Data Table 14 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

Worst Treatment-Related Toxicity within Non-variant Patients By Cetuximab Assignment
Supplementary Data Table 13 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

Worst Treatment-Related Toxicity Logistic Regression Model of KRAS and As-Treated RT Interaction
Supplementary Data Table 10 from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

Overall Survival within non-variant Patients Cetuximab Assignment
Data from The Inherited KRAS-variant as a Biomarker of Cetuximab Response in NSCLC
Authors: Weidhaas Joanne B. , Hu Chen , Komaki Ritsuko , Masters Gregory A. , Blumenschein George R. , Chang Joe Y. , Lu Bo , Dicker Adam P. , Bogart Jeffrey A. , Garces Yolanda I. , Narayan Samir , Robinson Clifford G. , Kavadi Vivek S. , Greenberger Joel S. , Koprowski Christopher D. , Welsh James , Gore Elizabeth M. , MacRae Robert M. , Paulus Rebecca , Bradley Jeffrey D.
Published: October 2023

AbstractPurpose:
RTOG 0617 was a phase III randomized trial for patients with unresectable stage IIIA/IIIB non–small cell lung cancer comparing standard-dose (60 Gy) versus high-dose (74 Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617.
Experimental Design:
From RTOG 0617, 328 of 496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran—Mantel–Haenzel tests and multivariable logistic regression models were used. All statistical tests were two sided, and a P value <0.05 was considered significant.
Results:
A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients—while the hazard of death was higher in cetuximab-treated patients within year 1 [HR = 3.37, 95% confidence interval (CI): 1.13–10.10, P = 0.030], death was lower from year 1 to 4 (HR = 0.33, 95% CI: 0.11–0.97, P = 0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR = 1.59, 95% CI: 1.11–2.28, P = 0.012).
Conclusions/Discussion:
Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy.
Significance:
The KRAS-variant is the first functional, inherited miRNA-disrupting variant identified in cancer. Our findings support that cetuximab has a potentially beneficial impact on KRAS-variant patients treated with radiation. The work confirms prior evidence that KRAS-variant patients are a subgroup who are especially sensitive to radiation. These findings further support the potential of this class of variants to enable true treatment personalization, considering the equally important endpoints of response and toxicity.
Verhaltenstherapeutische Behandlung von Perfektionismus: Ein Überblick über Forschungsstand und praktisches Vorgehen
Authors: Wegerer Melanie
Published: October 2023

Hintergrund: Perfektionismus stellt einen wichtigen transdiagnostischen prädisponierenden sowie aufrechterhaltenden Faktor bei einer Reihe psychischer Störungen dar. Zudem kann Perfektionismus die Behandlung psychischer Störungen erschweren und zu Behandlungsresistenz beitragen. Im vorliegenden Artikel werden verhaltenstherapeutische Ansätze zur Reduktion perfektionistischer Muster erläutert. Zudem wird auf Besonderheiten der therapeutischen Beziehungsgestaltung sowie auf die Ätiologie und mögliche Funktionalitäten perfektionistischer Muster eingegangen. Zusammenfassung: Die Wirksamkeit klassisch kognitiv-verhaltenstherapeutischer Interventionen für die Reduktion von Perfektionismus wurde in einer Reihe von Studien nachgewiesen. Neuere Untersuchungen zeigen zudem den (potentiellen) Nutzen von Interventionen, die der dritten Welle der Verhaltenstherapie zuzuordnen sind (wie achtsamkeitsbasierte, schematherapeutische oder selbstmitgefühlbasierte Ansätze) – jedoch besteht hier noch ein Mangel an Studien mit ausreichender methodischer Qualität. Kernaussage: Zwar stehen zur Behandlung von Perfektionismus eine Reihe verschiedener verhaltenstherapeutischer Ansätze zur Verfügung, doch sollten zukünftige Studien verstärkt untersuchen, welche Interventionen sich bei welchen Patient*innen-Charakteristika als besonders indiziert zeigen.
Factors Associated with Discharge against Medical Advice among Acute Stroke Patients: Analysis of the Nationwide Emergency Department Sample
Authors: Patel Karan , Taneja Kamil , Wolfe Jared , Oak Solomon , Favilla Christopher , Siegler James E.
Published: October 2023

Introduction: Patients discharged against medical advice have been shown to have worse outcomes across a host of different conditions. However, risk factors related to increased odds of discharge against medical advice remain understudied in patients who suffer from acute cerebral infarction. Methods: We retrospectively examined the 2019 National Emergency Department Sample Database for stroke patients. Multivariable logistic regression was used to estimate associations between patient- and hospital-level factors and the outcome of discharge against medical advice. Results: Of the 603,623 encounters for acute ischemic stroke, 8,858 (1.5%) were discharged against medical advice. Predictors of discharge against medical advice were lower income quartile and having either Medicaid insurance (odds ratio [OR] 1.32, 95% confidence interval [CI]: 1.10–1.58) or being uninsured (OR 1.28, 95% CI: 1.03–1.58). Vascular comorbidities associated with discharge against medical advice included prior tobacco use (OR 1.60, 95% CI: 1.45–1.78) and coronary artery disease (OR 1.19, 95% CI: 1.04–1.35). Treatment with thrombectomy (OR 0.33, 95% CI: 0.13–0.78) or systemic thrombolysis (OR 0.39, 95% CI: 0.23–0.66) was inversely associated with discharge against medical advice. A high modified Charlson comorbidity index (3+ vs. 0, OR 0.49, 95% CI: 0.42–0.56) was also associated with a lower odds of discharge against medical advice. Presenting to a Northeastern hospital had the highest rate of discharge against medical advice, when compared to other regions (p < 0.05). Conclusions: Certain patient-level, socioeconomic, and regional factors were associated with discharge against medical advice following acute stroke. These patient- and systems-level factors warrant heightened attention in order to optimize acute care and secondary prevention strategies.
Retrograde Intrarenal Surgery Learning Curves of Urology Residents Supervised by an Experienced Endourologist: An RIRSearch Study
Authors: Şahin Mehmet Fatih , Ozman Oktay , Cakir Hakan , Cinar Onder , Akgul Murat , Basatac Cem , Simsekoglu Muhammed Fatih , Teke Kerem , Yazici Cenk Murat , Sancak Eyup Burak , Önal Bülent , Akpinar Haluk
Published: October 2023

Introduction: Although retrograde intrarenal surgery (RIRS) is being performed with increasing frequency, there are only a limited number of studies about the learning curve (LC). This study aimed to analyze the LC of RIRS for five surgeons who underwent the same training. Materials and Methods: The data of the 410 patients who underwent RIRS between April 2017 and 2022 in a single institution, which were performed consecutively by five surgeons, were analyzed. All 50 cases performed by each surgeon were included and numbered consecutively and separately, according to the date of the operation. The combined stone-free rate (SFR) was calculated for each surgeon’s cases in the same row, and the LCs were created using moving average and cumulative sum (CUSUM) analyses. Separate multivariable analyses identified each period’s (LC vs. beyond) characteristics. Results: The LCs from the combined SFRs reached a plateau after approximately 50 cases for both the CUSUM and the moving average. The effect of stone burden on SFR was more evident in the first 50 cases compared to subsequent cases in the multivariable analyses (p = 0.001 and p = 0.047, respectively). Case order and stone density were independent factors in the first 50 cases (OR: 1.02 [95% CI 1.00–1.04], p = 0.04 and OR: 0.99 [95% CI 0.99–1.00], p = 0.04) but not significant in subsequent cases (OR: 0.97 [95% CI 0.94–1.00], p = 0.1 and OR: 1.00 [95% CI 0.99–1.00], p = 0.7, respectively). Compared to single locations except the lower calyx, the unfavorable effect of the multiple-stone localization on SFR grew in strength after the 50th case (OR: 0.42 [95% CI 0.23–0.78], p = 0.01 and OR: 0.20 [95% CI 0.09–0.46], p < 0.001, respectively). Conclusions: This is the first study reporting on the RIRS LCs of urology residents. While stone burden, density, and multiple-stone localization were the factors determining SFR in the learning period, after completing the LC, the effect of stone burden weakened and multiple-stone localization became stronger.
Clinical, Radiological, and Histopathological Findings of Post-Exenterated Mucormycosis Specimens
Authors: Ramasamy Vidhyadevi , Saudhamini Shiguru , Shanmugasundaram Sakthisankari , Manayil Athira
Published: October 2023

Introduction: A sharp upsurge in the number of coronavirus disease-associated mucormycosis cases was noted during the second wave of coronavirus disease in India. The fungal hyphae spread from the nasal mucosa, orbit to the brain, hence otherwise called rhino-orbito-cerebral mucormycosis (ROCM). Prompt diagnosis and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome. This study is done to enumerate the clinical, radiological, and histopathological findings of post-exenterated specimens of ROCM. Methods: This is a non-randomized cross-sectional study conducted at a tertiary care center. Ten post-exenterated specimens were examined histopathologically for the involvement of the central retinal artery, superior ophthalmic vein (SOV), optic nerve, muscle, and orbital fat showing necrosis. Clinical findings of these 10 patients were studied retrospectively for visual loss, proptosis, extraocular movements for muscle involvement, scleral necrosis, and fundus findings for artery or vein occlusions. Preoperative magnetic resonance imaging (MRI) findings like the number of orbital quadrants showing soft tissue thickening or tissue enhancement, diffusion restriction in the optic nerve, soft tissue enhancement seen at the orbital apex or superior orbital fissure, loss of flow void in the left internal carotid artery, enlargement of the SOV containing filling defect on post-contrast images were noted. Results: Optic nerve involvement was seen in 100% patients clinically, 70% on MRI, and 50% on histopathological examination (HPE). Muscle involvement was seen in 100% patients clinically, 90% on MRI, and 80% on HPE. None of the patients had scleral necrosis clinically. Scleral tenting was seen in 20% patients on MRI and 20% on HPE. Clinically, central retinal artery involvement was seen in 40%, and cilioretinal artery involvement was seen in 10%. MRI could not give much information on artery involvement. Clinically, none of them had central retinal vein occlusion. 20% had an enlarged SOV seen on MRI. HPE showed vascular involvement in 90% of the specimens. Conclusion: Clinical, radiological, and histopathological findings play a major role in the diagnosis, staging, and follow-up of ROCM.
Interaction between Serum Cotinine and Magnesium Intake with Childhood Asthma: A Cross-Sectional Study
Authors: Cao Jianwei , Liu Meiling , Wang Zhongquan , Huang Ying , Zheng Kaijun
Published: October 2023

Introduction: Serum cotinine and magnesium intake are often associated with childhood asthma. This study evaluated the interaction between serum cotinine and magnesium intake and childhood asthma. Methods: This cross-sectional study included 14,159 subjects from the National Health and Nutrition Examination Survey 2005–2018. Serum cotinine levels were classified according to the lower quartile: ≤0.2089 ng/mL as low level and >0.2089 ng/mL as high level. Magnesium intake was categorized as high (>98 mg/1,000 kcal) or low level (≤98 mg/1,000 kcal) based on the upper quartile. Weighted logistic regression analyses were adopted to analyze the association between cotinine, magnesium intake, and childhood asthma. Additionally, the combined effect of cotinine and magnesium intake on childhood asthma risk was examined. The stratified analyses were based on gender, body mass index, and family history of asthma to further examine the relationship between cotinine, magnesium intake, and childhood asthma. Results: The prevalence of asthma was approximately 17.56%. Compared to low-level cotinine, high-level cotinine was associated with asthma (odds ratio [OR] = 1.25, 95% confidence interval (CI): 1.04–1.50). Low-level magnesium intake was related to asthma compared with high-level magnesium intake (OR = 1.21, 95% CI: 1.04–1.40). Using interaction analysis, we also found that the combined effect of cotinine and magnesium intake was associated with childhood asthma risk, and the interaction between high-level cotinine and low-level magnesium intake was associated with the highest risk of childhood asthma (OR = 1.35, 95% CI: 1.04–1.74). Additionally, this interaction was also found in males, overweight/non-overweight, and those with family history of asthma. Conclusion: There was an interaction between serum cotinine and magnesium intake on childhood asthma. The results suggested that implementing smoking bans in certain settings (e.g., communities, schools) and promoting the consumption of magnesium-rich foods may be effective strategies for preventing childhood asthma.
Exogenous Insulin Antibody Syndrome in a Pediatric Patient: Successful Treatment with Mycophenolate Mofetil
Authors: Saba Leslie , Fatica Erica M. , Orandi Amir B. , Pittock Siobhan T. , Creo Ana L.
Published: October 2023

Introduction: Exogenous insulin antibody syndrome (EIAS) rarely occurs in type 1 diabetes and should be considered in those with blood glucose levels outside the target range requiring greater than 2 units/kg/day of insulin without obesity. We describe the novel treatment of this condition using mycophenolate mofetil monotherapy in a pediatric patient in the outpatient setting. Case Presentation: A 17-year-old Caucasian male with type 1 diabetes experienced an abrupt increase in insulin requirements from 1.7 to 3.3 units/kg/day. Total insulin level was 7 µIU/mL with free insulin of 4.8 µIU/mL (68% of the total insulin), suggesting the presence of insulin antibodies. Switching from insulin aspart to glulisine was unsuccessful as insulin requirements increased to 4.4 units/kg/day. Treatment with oral mycophenolate mofetil decreased insulin requirements to 1.4 units/kg/day after 7 months. Total and free insulin levels improved to 5.2 and 4.6 µIU/mL, respectively (free insulin was 88% of total insulin). No adverse effects were encountered. Conclusion: Mycophenolate mofetil monotherapy is successful in safely treating EIAS in a pediatric patient.
A Rare Case of Cardioembolic Spinal Stroke in a Young Female: Case Report
Authors: Mendel Rom , Tsirkin Irina , Soikher Eugene , Haratz Salo
Published: October 2023

Spinal cord infarction (SCI) is a rare neurovascular disorder often presented with acute spinal cord syndrome. The diagnosis is generally made clinically, with appropriate neuroimaging to confirm the diagnosis and exclude other causes. We present an unusual case of a 48-year-old woman with no relevant past medical history, admitted with acute paraparesis and a spinal cord infarct on magnetic resonance imaging. A thorough investigation revealed asymptomatic unknown heart failure secondary to hypertrophic cardiomyopathy, suggestive of a cardioembolic etiology. The patient was treated with anticoagulation and improved significantly with physical rehabilitation.
A Single-Institution Retrospective Series of SARS-CoV-2 Infection in Adult Glioma Patients
Authors: Lanman Tyler , Ruiz Amber N. , Nagpal Seema
Published: October 2023

A subset of cancer patients is particularly vulnerable to SARS-CoV-2 infection; however, real-world outcomes-based data on primary central nervous system tumor patients is sparse. This retrospective series describes a cohort of adult glioma patients seen at Stanford Cancer Center between January 1, 2020, and June 30, 2022 who contracted SARS-CoV-2, which, to our knowledge, currently represents the largest single-institution comprehensive analysis of this patient population. We performed a retrospective search of patients seen in the Stanford Neuro-Oncology clinic, identifying 29 cases of COVID-19 amongst glioma patients and extracted clinical data via individual chart review. At the time of COVID-19 diagnosis, 15 patients had been vaccinated against SARS-CoV-2, 8 patients were taking dexamethasone, and 8 were undergoing cancer-specific treatment. Obesity, prior tobacco use, and diabetes were the most common comorbidities. Cough, sore throat, and congestion were the most common symptoms. Five patients were admitted to the hospital and two received COVID-19-specific treatment. None died from COVID-related causes or complications. Our data suggest that glioma patients seen at Stanford Cancer Center do not experience an exceptionally high COVID-19 infectivity, hospitalization, or mortality rate, especially when compared to other vulnerable populations such as lung cancer patients. High vaccination rates, adherence to COVID-19 guidelines, and low prevalence of comorbidities may have contributed to these results.
André-Thomas (1867–1963), Initiator of Neonatal Neurology
Authors: Walusinski Olivier
Published: October 2023

After a brilliant career as a clinician and anatomopathologist, André-Thomas (1868–1963) spent the last 30 years of his life validating the components of neurological examinations of newborns and infants. This novel approach was developed through long examinations of several hundreds of normal and sick children, notably those with anencephaly. By combining his vast knowledge of physiology with the results of his experimental work, André-Thomas built the foundations of a speciality that did not exist before his time: neuropaediatrics. His Études neurologiques (neurological studies), medical in nature but also very literary, echoing his illustrious predecessors of the 19th century, made him a transmitter of knowledge, a man of transition, from the anatomoclinical method of the 19th century to the standardised investigation techniques of the 20th century.
Association of Familial Hyperkalemia and Hypertension with Proximal Renal Tubular Acidosis and Epileptic Seizures
Authors: Shirin Neta , Rabinowitz Grace , Blatt Ilan , Karlish Steven J.D. , Farfel Zvi , Mayan Haim
Published: October 2023

Introduction: Familial hyperkalemic hypertension (FHHt) is an inherited disease characterized by hyperkalemia, hypertension, and hyperchloremic acidosis (HCA). The primary defect is a hyperactive sodium chloride co-transporter, expressed in the renal distal tubule. FHHt is caused by mutation in either WNK1, WNK4, KLHL3, or Cul3. The mechanism of HCA is not completely understood. Methods: Clinical and genetic data were collected from the largest family with FHHt described in the literature. Urine ammonia was measured in 26 family members. Epilepsy was diagnosed clinically. Results: Of the 85 family members, 44 are affected by the Q565E WNK4 mutation, and 28 are newly described. In genetically engineered mice, urinary ammonium was decreased. In our study, urine ammonium did not change. In 11 unaffected subjects, urine ammonia per creatinine was 8.013 ± 3.620 mm/mm, and in 15 subjects affected by FHHt, it was 8.990 ± 4.300 mm/mm (p = 0.546, not significant). Due to the large family size and prolonged follow-up, rare conditions can be identified. Indeed, two children have genetic generalized epilepsy and one child has migraine. The prevalence of epilepsy is 4.545% (2/44) much higher than in the general population (0.681%). This difference is statistically significant (χ2 with Yates correction = 5.127, p = 0.023). Conclusions: We provide further evidence that the origin of HCA in FHHt lies in the proximal renal tubule. The association of FHHt with epilepsy leads us to speculate that the raised serum K in susceptible subjects may cause a rise in CSF K, and extracellular cerebral K, leading to epilepsy.