bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon‐like peptide‐1 analogues in monogenic syndromic obesity: Real‐world data from a large cohort of Alström syndrome patients
Authors: Ali Sadaf , Baig Shanat , Wanninayake Subadra , da Silva Xavier Gabriela , Dawson Charlotte , Paisey Richard , Geberhiwot Tarekegn
Published: December 2023

Aim

To examine the real‐world efficacy of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in monogenic obesity in patients with Alström syndrome (ALMS).

Methods

We screened 72 UK adult patients with ALMS and offered treatment to 34 patients meeting one of the following criteria: body mass index of 25 kg/m2 or higher, insulin resistance, suboptimal glycaemic control on antihyperglycaemic medications or non‐alcoholic fatty liver disease.

Results

In total, 30 patients, with a mean age of 31 ± 11 years and a male to‐female ratio of 2:1, completed 6 months of treatment with GLP‐1 RAs either in the form of semaglutide or exenatide. On average, treatment with GLP‐1 RAs reduced body weight by 5.4 ± 1.7 (95% confidence interval [CI] 3.6‐7) kg and HbA1c by 12 ± 3.3 (95% CI 8.7‐15.3) mmol/mol, equating to 6% weight loss (P < .01) and 1.1% absolute reduction in HbA1c (P < .01). Significant improvements were also observed in serum total cholesterol, triglycerides, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol and alanine aminotransferase. The improvement of metabolic variables in our cohort of monogenic syndromic obesity was comparable with data for polygenic obesity, irrespective of weight loss.

Conclusions

Data from our centre highlight the non‐inferiority of GLP‐1 RAs in monogenic syndromic obesity to the available GLP‐1 RA‐use data in polygenic obesity, therefore, these agents can be considered as a treatment option in patients with ALMS, as well as other forms of monogenic obesity.
The lived experience of weight loss maintenance in young people
Authors: Sides Nicola , Pringle Andy , Newson Lisa
Published: December 2023

Introduction

There continues to be an imbalance of research into weight loss and weight loss maintenance (WLM), with a particular lack of research into WLM in young people under 18 years. Failure to coherently understand WLM in young people may be a potential contributor to the underdeveloped guidance surrounding long‐term support. Furthermore, no research has investigated young people's preferences around WLM support following the attendance of a residential intensive weight loss intervention from a qualitative perspective. This study explored the influences of WLM in young people following a residential intensive weight loss intervention, considered how interventions could be improved and sought to develop recommendations for stakeholders responsible for designing WLM interventions.

Methods

The context in which this research is framed was taken from a residential Intensive Weight Loss Intervention for young people aged 8–17 years in England. Six semi‐structured interviews were carried out to understand the lived experience of WLM, including barriers and enablers influencing WLM, adopting an interpretative phenomenological analysis design.

Findings

Three superordinate themes were developed to explain the barriers and enablers to WLM; (1) Behavioural control and the psychosocial skills to self‐regulate WLM; (2) Delivering effective social support; and (3) Conflicting priorities and environmental triggers.

Conclusion

The findings of this research mirror that of other studies of WLM in young people, with the majority of young people struggling to maintain weight loss. However, by exploring the experience of WLM in young people through qualitative means, it was possible to understand the specific motivators and barriers influencing WLM behaviours in this context, providing recommendations to support WLM.

Patient or Public Contribution

The interview guide was developed in consultation with a young person from the intervention, and through discussions with the intervention stakeholders (delivery staff and management staff). The interview guide included topics such as knowledge and skills; experience of weight loss; reflections on weight maintenance, and experiences of daily life postintervention. We piloted the interview schedule with one young person who had consented to take part in the research. This first interview was used to check for understanding of questions and to assess the flow of the interview.
Geochronological and petrological investigations of Miocene felsic igneous rocks in the Amakusa Islands, southwest Japan: Possible extension of the Setouchi Volcanic Belt
Authors: Shinjoe Hironao , Orihashi Yuji , Akasaka Mana , Niki Sota , Sasaki Minoru , Hirata Takafumi
Published: December 2023

The opening of the Japan Sea led to the separation of southwest Japan from the Eurasian continent. Subsequent to this event, a diverse range of igneous activities occurred in southwest Japan. On the back‐arc side of the region, igneous activity commenced at approximately 22 Ma and persisted for an extended period. In the trench‐proximal region of southwest Japan, magmatism initiated around 15.6 Ma, immediately following the cessation of the Japan Sea opening, in correlation with the subduction of the Philippine Sea plate beneath southwest Japan. The Amakusa Islands in western Kyushu host felsic to intermediate igneous rocks with Miocene radiometric ages. There has been a debate regarding the attribution of the igneous rocks in Amakusa Island among the Miocene igneous rocks in southwest Japan. To address this issue, we conducted zircon U–Pb dating and analyzed the major‐ and trace‐element compositions of felsic igneous rocks in the Amakusa Islands to elucidate their characteristics. The obtained U–Pb ages range from 14.5 to 14.8 Ma, suggesting contemporaneity between magmatism in the Amakusa Islands and the Setouchi Volcanic Rocks in the trench‐proximal region of southwest Japan. The major and trace element compositions of the felsic igneous rocks exhibit similarities to the dacites of the Setouchi Volcanic Rocks. These findings support previous suggestions that the magmatism in the Amakusa Islands can be correlated with the Setouchi Volcanic Rocks, based on the discovery of a high‐Mg andesite dike and paleo‐stress analysis utilizing the direction of dikes and sills. Therefore, the Setouchi Volcanic Belt is proposed to extend further west than the previously identified Ohno volcanic rocks in eastern Kyushu. The subduction of the Shikoku Basin of the Philippine Sea plate toward western Kyushu supports the hypothesis that the Kyushu‐Palau Ridge was positioned west of Kyushu at ~15 Ma.
How the eyes respond to sounds
Authors: Hu Junchao , Vetter Petra
Published: December 2023

Eye movements have been extensively studied with respect to visual stimulation. However, we live in a multisensory world, and how the eyes are driven by other senses has been explored much less. Here, we review the evidence on how audition can trigger and drive different eye responses and which cortical and subcortical neural correlates are involved. We provide an overview on how different types of sounds, from simple tones and noise bursts to spatially localized sounds and complex linguistic stimuli, influence saccades, microsaccades, smooth pursuit, pupil dilation, and eye blinks. The reviewed evidence reveals how the auditory system interacts with the oculomotor system, both behaviorally and neurally, and how this differs from visually driven eye responses. Some evidence points to multisensory interaction, and potential multisensory integration, but the underlying computational and neural mechanisms are still unclear. While there are marked differences in how the eyes respond to auditory compared to visual stimuli, many aspects of auditory‐evoked eye responses remain underexplored, and we summarize the key open questions for future research.
“You didn't ask, so you don't know”: Information and administrative burden in social benefit claims
Authors: Tarshish Noam , Holler Roni
Published: December 2023

Encounters with welfare state bureaucracy are often burdensome and might even result in administrative exclusion and non‐take up. With the growing scholarly interest in administrative burden experiences, a particular focus has been on learning costs, with evidence suggesting that difficulty obtaining reliable and useful information is one of their most fundamental aspects. We still lack a systematic conceptualization of bureaucratic information and its various dimensions. In this non‐representative exploratory study, we draw on interviews with 15 Israeli social benefit claimants to delve deeper into the nature of the information required in encounters with welfare state bureaucracy. Using thematic analysis, we identify five dimensions of such information: primary information on the existence of the benefit, as opposed to secondary procedural information on the claiming process; universal, wide‐ranging available information, in contrast to personalized information; one‐ versus two‐directional information transfer; covert, informal and dynamic, as opposed to overt, publicly available information; and finally, online versus offline information. We suggest that this exploratory conceptual framework can serve as a starting point for future studies to develop deeper understanding of the information citizens need in their encounters with welfare state bureaucracy.
EXPERIMENTAL STUDY OF THE PRESSURE DROP AND FLOODING IN A ROTATING PACKED BED REACTOR
Authors: Garba Usman , Rouzineau David , Meyer Michel
Published: December 2023

In conventional packed beds, mass transfer and flooding limitations lower the productivity of many processes. The almost zero sensitivity to variations in gravitational force has made centrifugal processes to have great potential for enhancing heterogeneous catalytic reactions. We studied a rotating packed bed (RPB) reactor as a gas/liquid contactor for multi-phase catalytic reactions. The scarcity of fundamental data on the hydrodynamics and mass transfer of the reactor limits the design, scale-up, and retrofitting of  RPB reactors. Hence, we focused on the hydrodynamic behavior of the device. Previous studies on RPB reactor flooding and operating limits dwelled on visual observations and pressure drop variations only. However, physical visualizations are subjective because RPB reactor pressure drop variations are too inconsistent to be used to determine the upper operating limit during their operations. A robust quantitative method of obtaining RPB reactor flooding limits based on the flow rate of the ejected liquid, supported by visual observation and pressure drop measurement, was presented. The aim was to identify, with greater certainty, RPB reactor hydrodynamic characteristics and provide a more standard method of identifying it. The average increase in single-phase pressure drop per unit increase in rotation speed in the range investigated was 0.75Pa/rpm, and the average increase in pressure drop per unit increase in gas flow rate was 4.11Pa/Nm3h-1 within the operating range investigated.
Internal Temperature Estimation of Lithium-Ion Battery Based on Improved Electro-Thermal Coupling Model and ANFIS
Authors: Wen Jianping , Li Zhensheng , Zhang Haodong , Zhang Chuanwei
Published: December 2023

Accurate estimation of the internal temperature of lithium-ion batteries plays an important role in the development of a suitable battery thermal management system, safeguarding the healthy and safe operation of batteries and improving battery performance. In order to accurately estimate the internal temperature of the battery, this paper proposes a method for estimating the internal temperature of lithium-ion batteries based on an improved electro-thermal coupling model and an Adaptive Network-Based Fuzzy Inference System (ANFIS). First, a parameterization method of the electrical model is proposed, and an electrical model whose parameters are affected by temperature and SOC is established. Second, to overcome the complex nonlinear modeling problem of lithium-ion batteries, the ANFIS thermal model is established. Then, an improved electro-thermal coupling model for lithium-ion batteries is established by combining the proposed electrical model and the ANFIS thermal model to improve the accuracy of estimating the internal temperature of the battery. Finally, the effectiveness of the proposed method is verified by simulation and experiment.
Conformal coating of macroscopic nanoparticle compacts with ZnO via atomic layer deposition
Authors: Greenberg Benjamin L. , Anderson Kevin P. , Jacobs Alan G. , Cendejas Austin J. , Hajzus Jenifer R. , Patterson Eric A. , Wollmershauser James A. , Feigelson Boris N.
Published: December 2023

Conformal atomic layer deposition (ALD) inside macroscopic nanoporous solids with aspect ratios greater than 103 can require ALD reactant exposures on the order of 103 Torr-s or greater. For some ALD chemistries, such large exposures raise the concern of non-self-limiting deposition. In the case of ZnO ALD from diethylzinc (DEZ) and H2O, exposures in the 10–103 Torr-s range have resulted in metallic Zn deposition at typical temperatures used for ZnO ALD on wafers (e.g., ∼180 °C). This Zn deposition can be suppressed by lowering the deposition temperature, but this slows H2O desorption and, thus, can necessitate impractically long purge times. In this work, we use static-dose ALD with DEZ and H2O exposures >104 Torr-s to deposit ZnO inside Al2O3 nanoparticle compacts (NPCs) with 50.5 ± 0.3% porosity, 100 nm NP diameter, 1.55 ± 0.05 mm thickness, and an aspect ratio of 7800 ± 200 (based on the half-thickness), and we explore a novel approach to the deposition temperature, T: T is cycled between 160 °C (for H2O purges) and 120 °C (for all other steps). For comparison, we also deposit ZnO with T held constant at 120 or 160 °C. Whereas the T = 160 °C process results in Zn metal deposition and nonuniform infiltration, the temperature-cycled process yields apparently self-limiting ZnO deposition at a growth per cycle (GPC) of ∼2.1 Å/cyc, forming an electrically conductive ZnO network that is uniform throughout the thickness of the NPC, with the exception of some ZnO depletion near the NPC surfaces, possibly due to the (unoptimized) long DEZ purge time. The T = 120 °C process produces similar results, although the GPC is slightly elevated, indicating diminished removal of H2O and/or OH during purges. We employ scanning electron microscopy with energy-dispersive x-ray spectroscopy, x-ray diffractometry, electrical resistivity measurements, and ALD chamber pressure analysis in our comparison of the three ALD processes.
New-onset movement disorder in the immediate postpartum period
Authors: Wikeley Sarah , Bacon Imogen , Greer Orene , Evans Matthew , Hasan Rizwan , Pathak Sangeeta
Published: December 2023

This case report describes a woman who developed involuntary, uncoordinated movements of her face and limbs following a spontaneous vaginal delivery, complicated by postpartum haemorrhage. Using systematic assessment with multidisciplinary team input, a differential diagnosis was proposed and relevant investigations were undertaken. Atypical eclamptic or generalised seizures were excluded clinically and neuroimaging ruled out an intracranial vascular event such as stroke or venous sinus thrombosis. Local anaesthetic systemic toxicity was managed empirically with intravenous lipid emulsion and intravenous fluids. A diagnosis of drug-induced dyskinesia was made, most likely secondary to ondansetron, with which dystonias and myoclonus have been described. This woman’s symptoms were transient and resolved within 2 hours.

This case presented a complex differential diagnosis, highlighting the paucity of guidance available. We propose a diagnostic algorithm to aid in the identification of acute involuntary movements in pregnancy and the puerperium.
Recommendations for laboratory workflow that better support centralised amalgamation of genomic variant data: findings from CanVIG-UK national molecular laboratory survey
Authors: Allen Sophie , Loong Lucy , Garrett Alice , Torr Bethany , Durkie Miranda , Drummond James , Callaway Alison , Robinson Rachel , Burghel George J , Hanson Helen , Field Joanne , McDevitt Trudi , McVeigh Terri P , Bedenham Tina , Bowles Christopher , Bradshaw Kirsty , Brooks Claire , Butler Samantha , Del Rey Jimenez Juan Carlos , Hawkes Lorraine , Stinton Victoria , MacMahon Suzanne , Owens Martina , Palmer-Smith Sheila , Smith Kenneth , Tellez James , Valganon-Petrizan Mikel , Waskiewicz Erik , Yau Michael , Eccles Diana M , Tischkowitz Marc , Goel Shilpi , McRonald Fiona , Antoniou Antonis C , Morris Eva , Hardy Steven , Turnbull Clare
Published: December 2023

Background

National and international amalgamation of genomic data offers opportunity for research and audit, including analyses enabling improved classification of variants of uncertain significance. Review of individual-level data from National Health Service (NHS) testing of cancer susceptibility genes (2002–2023) submitted to the National Disease Registration Service revealed heterogeneity across participating laboratories regarding (1) the structure, quality and completeness of submitted data, and (2) the ease with which that data could be assembled locally for submission.

Methods

In May 2023, we undertook a closed online survey of 51 clinical scientists who provided consensus responses representing all 17 of 17 NHS molecular genetic laboratories in England and Wales which undertake NHS diagnostic analyses of cancer susceptibility genes. The survey included 18 questions relating to ‘next-generation sequencing workflow’ (11), ‘variant classification’ (3) and ‘phenotypical context’ (4).

Results

Widely differing processes were reported for transfer of variant data into their local LIMS (Laboratory Information Management System), for the formatting in which the variants are stored in the LIMS and which classes of variants are retained in the local LIMS. Differing local provisions and workflow for variant classifications were also reported, including the resources provided and the mechanisms by which classifications are stored.

Conclusion

The survey responses illustrate heterogeneous laboratory workflow for preparation of genomic variant data from local LIMS for centralised submission. Workflow is often labour-intensive and inefficient, involving multiple manual steps which introduce opportunities for error. These survey findings and adoption of the concomitant recommendations may support improvement in laboratory dataflows, better facilitating submission of data for central amalgamation.
An Efficient Sentiment Classification Method with the Help of Neighbors and a Hybrid of RNN Models
Authors: Salman Al-Tameemi Israa K. , Feizi-Derakhshi Mohammad-Reza , Pashazadeh Saeed , Asadpour Mohammad
Published: December 2023

Some texts that are challenging to recognize on their own may become more understandable in a neighborhood of related texts with similar contexts. Motivated by this intuition, a novel deep text sentiment classification (DTSC) model is proposed to improve the model’s performance by incorporating the neighborhood of related texts. Our framework uses a nonparametric approach to construct neighborhoods of related texts based on Jaccard similarities. Then, a new deep recurrent neural network architecture is proposed, comprising two distinct modules: bidirectional long short-term memory (Bi-LSTM) and gated recurrent unit (GRU). The proposed model aims to effectively capture informative features from the input text and its neighbors. The result of each module is processed through the maximum operation, which selects the most pertinent data. Finally, the extracted features are concatenated and subjected to classification to achieve accurate sentiment prediction. Previous studies have commonly employed a parametric approach to represent textual metadata. However, our approach utilizes a nonparametric approach, enabling our model to perform strongly even when the text vocabulary varies between training and testing. The proposed DTSC model has been evaluated on five real-world sentiment datasets, achieving 99.60% accuracy on the Binary_Getty (BG) dataset, 98.32% accuracy on the Binary_iStock (BIS) dataset, 96.13% accuracy on Twitter, 82.19% accuracy on the multi-view sentiment analysis (MVSA) dataset, and 87.60% accuracy on the IMDB dataset. These findings demonstrate that the proposed model outperforms established baseline techniques in terms of model evaluation criteria for text sentiment classification.
The Associations among Destructive Leadership, Job Demands and Resources, and Burnout among Nurses: A Cross-Sectional Survey Study
Authors: Palvimo Tuuli , Vauhkonen Anneli , Hult Marja
Published: December 2023

Background. Nurses demonstrate high burnout prevalence. Moreover, destructive leadership, as well as job demands and resources, are associated with burnout. However, these associations, particularly in the context of nursing, warrant further investigation. Objective. To explore the associations of destructive leadership, as well as job demands and resources, with burnout in registered nurses. Design. A cross-sectional survey. Participants. 2115 registered nurses in Finland. Methods. The self-administered questionnaire survey was distributed nationwide to 106,000 members of the Finnish trade union for health and social care professionals via an online newsletter in February 2023. Nurses’ burnout was measured with the Burnout Assessment Tool (BAT). The data were analysed through descriptive statistics and linear regression analysis. Results. Destructive leadership and job demands were positively associated with burnout (β = 0.39 and 0.32, respectively; both p<0.001), whereas job resources and burnout were negatively associated (β = −0.41, p<0.001). The associations of destructive leadership and job demands with burnout became less positive when job resources were added to the regression model (β = 0.21 and 0.14, respectively; both p<0.001). Conclusions. Job resources led to the greatest reduction in burnout among registered nurses. Moreover, job resources reduced burnout by diminishing the negative effects of destructive leadership and job demands. Providing a sufficient amount of job resources might reduce burnout and diminish the negative effects of destructive leadership and job demands among nurses. These relationships warrant examination in other cultural settings.
Examining the Interplay of Labour Productivity Policies and Industrial-Energy-Environmental Policy Goals
Authors: Ross Andrew G. , McGregor Peter G. , Swales J. Kim , Roy Graeme
Published: December 2023

The academic and policy-oriented literature increasingly quantifies the wider effects of energy policy on the macroeconomy. However, the spillovers from economic policies to energy use are less frequently recognised, meaning that many policymakers who strive to improve productivity whilst simultaneously targeting emission reduction fail to consider these interactions. This paper addresses this issue by using simulation results generated by introducing an exogenous increase in labour productivity in a computable general equilibrium model calibrated with data from the United Kingdom. Theoretical analysis suggests that increasing labour productivity can have positive or negative effects on employment levels and energy use. However, the simulation results show that in the context of a developed open economy, improved labour efficiency will increase employment, a key policy objective, but simultaneously increase energy use. A key policy implication is that this work highlights the need for policy frameworks that explicitly acknowledge and quantify the interconnections between national economic policy strategies and energy policy objectives. Secondly, it shows that in practice, policies to reduce carbon emissions need to be strengthened alongside policies to improve productivity successfully implemented.
Fig S5 from Pharmacodynamic Analysis of BTK Inhibition in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib
Authors: Alsadhan Anfal , Cheung Jean , Gulrajani Michael , Gaglione Erika M. , Nierman Pia , Hamdy Ahmed , Izumi Raquel , Bibikova Elena , Patel Priti , Sun Clare , Covey Todd , Herman Sarah E.M. , Wiestner Adrian
Published: December 2023

Rate of change in percent free BTK per day.
Supplemental Figure Legends from Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization
Authors: Holdhoff Matthias , Guner Gunes , Rodriguez Fausto J. , Hicks Jessica L. , Zheng Qizhi , Forman Michael S. , Ye Xiaobu , Grossman Stuart A. , Meeker Alan K. , Heaphy Christopher M. , Eberhart Charles G. , De Marzo Angelo M. , Arav-Boger Ravit
Published: December 2023

Figure legends for Supplemental Figures 1-5.
Supplemental Figure 2 from Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization
Authors: Holdhoff Matthias , Guner Gunes , Rodriguez Fausto J. , Hicks Jessica L. , Zheng Qizhi , Forman Michael S. , Ye Xiaobu , Grossman Stuart A. , Meeker Alan K. , Heaphy Christopher M. , Eberhart Charles G. , De Marzo Angelo M. , Arav-Boger Ravit
Published: December 2023

Telomeric DNA detection by CISH. CISH assay targeting human telomeric DNA showing strong nuclear signals (arrows) in tumor cells. Original magnification, x 200.
Supplemental Figure 1 from Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization
Authors: Holdhoff Matthias , Guner Gunes , Rodriguez Fausto J. , Hicks Jessica L. , Zheng Qizhi , Forman Michael S. , Ye Xiaobu , Grossman Stuart A. , Meeker Alan K. , Heaphy Christopher M. , Eberhart Charles G. , De Marzo Angelo M. , Arav-Boger Ravit
Published: December 2023

CMV detection by CISH and IHC from CMV negative and positive cells with varying multiplicity of infection (M0I).
Supplemental Table 3 from Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer
Authors: Siemens Helge , Neumann Jens , Jackstadt Rene , Mansmann Ulrich , Horst David , Kirchner Thomas , Hermeking Heiko
Published: December 2023

PDF file - 1532K,Summary of the associations of the nodal-status (absence of lymph-node metastases N0 vs. presence of lymph-node metastases N+) with the markers analyzed in this study. Mean differences, 95% confidence interval (CI) and p-values were calculated using a paired t-test
Supplemental Materials from Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms
Authors: El Charif Omar , Mapes Brandon , Trendowski Matthew R. , Wheeler Heather E. , Wing Claudia , Dinh Paul C. , Frisina Robert D. , Feldman Darren R. , Hamilton Robert J. , Vaughn David J. , Fung Chunkit , Kollmannsberger Christian , Mushiroda Taisei , Kubo Michiaki , Gamazon Eric R. , Cox Nancy J. , Huddart Robert , Ardeshir-Rouhani-Fard Shirin , Monahan Patrick , Fossa Sophie D. , Einhorn Lawrence H. , Travis Lois B. , Dolan M. Eileen
Published: December 2023

Figure S1; Tables S1-S4
Supplemental Figure 1 from Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer
Authors: Siemens Helge , Neumann Jens , Jackstadt Rene , Mansmann Ulrich , Horst David , Kirchner Thomas , Hermeking Heiko
Published: December 2023

PDF file - 2577K, Supplemental Figure 1. Map of the human miR-34a gene locus indicating the transcriptional start site (TSS), histone H3K27 acetylation and CpG islands modified from the UCSC genome browser (Feb. 2009 GRCh37/hg19)
Supplementary Table S1 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

Structure-activity relationship studies of the inhibition of KRAS G12D/GST-RBD binding.
Figure S6 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

Effects of KRB-456 on cell viability in human pancreatic cancer cells that harbor KRAS G12D (Panc0403 cells), KRAS G12V (Capan1 cells), KRAS G12C (MiaPaCa2 cells), and KRAS WT (BxPc3 cells).
FIGURE 7 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

Treatment of mice with KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels and induces apoptosis in KRAS G12D PDXs from patients with pancreatic cancer. A, Tumor biopsies from patient G160 were subcutaneously implanted into NSG mice as described in Materials and Methods, and when the average tumor volume reached 200 mm3, the mice were treated either with vehicle (mice V1, V2, V3) or 5 mpk KRB-456 (mice KRB1, KRB2, KRB3) as described in Materials and Methods. Two hours after treatment, tumors were harvested and lysates were processed for Western blotting as described in Materials and Methods. * and ** designates blots from different gels. B and C, Quantification of the Western blots. P values were determined by Student t test, * designates P < 0.05. The actual P values were 0.016 (P-MEK/MEK), 0.010 (P-ATK(S473)/AKT), 0.012 (P-ATK(T308)/AKT), 0.037 (P-S6/S6), 0.069 (P-ERK/ERK), 0.097 (CASPASE3/b-ACTIN), and 0.019 (PARP/b-ACTIN). Error bars represent SE.
FIGURE 5 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

Effects of KRB-456 on cell viability, levels of KRAS bound to GTP, binding of KRAS to RAF1, and the levels of P-MEK and P-ERK in human pancreatic cancer cells that harbor KRAS G12D. Human pancreatic cancer cell lines Panc0203 and Panc1 were treated with the indicated concentrations of KRB-456 and processed for viability assays (72 hours), Panc0203 (open circles) and Panc1 (closed circles; A), GST-RBD pulldown (“G” designates GST-RBD only with no lysate added; B), immuno-precipitation with RAS antibody and blotting with RAF1 and KRAS antibodies (C), and Panc0203 and Panc01 cells were treated with 0, 1, 3, and 10 µmol/L KRB-456 for 2 hours and processed for Western blotting as described in Materials and Methods (D).
FIGURE 2 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

SAR studies of the inhibition of KRAS G12D/GST-RBD binding. The top four confirmed hits from Fig. 1 were all derivatives of gibberellic acid and were evaluated for their potency to inhibit GTP-KRAS G12D/GST-RBD binding by GST pulldown assays. Concentration–response experiments identified IB-21 L (KRB-456; IC50 = 0.26 µmol/L) as the most potent compound followed by IB-21G (IC50 = 0.36 µmol/L), IB-21J (IC50 = 2.02 µmol/L), and IIA-15D (IC50 = 10.82 µmol/L).
FIGURE 1 from Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors
Authors: Kazi Aslamuzzaman , Ranjan Alok , Kumar M.V. Vasantha , Agianian Bogos , Garcia Chavez Martin , Vudatha Vignesh , Wang Rui , Vangipurapu Rajanikanth , Chen Liwei , Kennedy Perry , Subramanian Karthikeyan , Quirke Jonathan C.K. , Beato Francisca , Underwood Patrick W. , Fleming Jason B. , Trevino Jose , Hergenrother Paul J. , Gavathiotis Evripidis , Sebti Said M.
Published: December 2023

Alpha screen and GST pulldown assays identify disruptors of the binding of mt KRAS G12D to the RBD of RAF1. A, Alpha screen was used in a one-compound (10 µmol/L)-one well 384-well plate format to identify KRAS G12D/RBD binding disruptors from a natural product-inspired 560 synthetic compound library. The compounds were ranked from highest to lowest based on % inhibition of the KRAS G12D/RBD binding. B, The top ranked 56 hits (10% of the 560-compound library) from the alpha screen were selected for confirmation by a GST pulldown assay, and six of these were found to inhibit the binding of KRAS G12D to GST-RBD potently (77% to 100%) whereas the remaining 50 compounds weakly inhibited the interaction (0% to 31%).
Place in the Novel Ziryāb by Maqbūl al-ʿAlawī
Authors: al-Sarani Khalid S. , al-Mutazz Nuha S.
Published: December 2023

This study investigates the style of the novelist Maqbūl al-ʿAlawī in his interaction with place in his novel Ziryāb, place being seen as one of the most important elements of the novel. It is shown how place affects the reader and how it carries out several tasks and represents several values. Place played a part in making events and depicting some symbols. The study answers several questions: it considers the sorts of places in which the novel’s events unfold. What is the role of place in the formation of events among other things? Are some places more important than others? For what reasons does the novelist lean toward some places instead of others? The study investigates the manner in which place supports the narrative or decreases its value.
Recircumscription of Lopholejeunea sikkimensis (Lejeuneaceae: Marchantiophyta) and its varieties in India
Authors: - PRIYANKA , SINGH S.K. , PANDEY ARUN K.
Published: December 2023

The taxonomy of Lopholejeunea sikkimensis var. tenuicostata, L. sikkimensis var. kumaunii and L. sikkimensis var. dentata is evaluated. Based on study of numerous collections of L. sikkimensis, followed by comparison with the protologues of the varieties, we conclude that var. tenuicostata and var. kumaunii are not distinct from the typical variety. Hence both the varieties are placed here under synonymy of L. sikkimensis. Lopholejeunea sikkimensis var. dentata, however, is accepted as a distinct taxon. A detailed revised taxonomic description of L. sikkimensis is provided along with line drawing illustration and photographic plate for future identification and reference.
David Meagher (1956–2023)
Authors: CAIRNS ANDI , FRANKS ANDREW , KLAZENGA NIELS
Published: December 2023

Described by a leading Australian botanist as ‘Australia’s most competent bryologist’, David Meagher’s broad knowledge of Australian bryophytes was extraordinary. He was well-respected by bryologists around the world for his MSc research on the leafy liverwort genus Bazzania, and his PhD thesis on the bryophytes of Lord Howe Island. In the last twenty years, David published over 60 papers, most with him as the single author but several in collaboration with other Australian bryologists. He described twelve new species of Bazzania, including nine in Australia, two in Papua New Guinea and one in New Zealand. With colleagues he named two new moss species and reported several range extensions and new records in the Australian Wet Tropics. David’s fieldwork on flora and fauna extended to Tasmania, Victoria, New South Wales, Queensland, Lord Howe Island, the Kermadec Islands in the South Pacific, and the mid-west of the USA.
Bazzania polita sp. nov., a rare New Zealand species (Lepidoziaceae, Marchantiophyta) with an assessment of branching type as a character
Authors: GLENNY DAVID , FISH STELLA
Published: December 2023

Bazzania polita sp. nov. is described from New Zealand from two collections. It resembles B. exempta in having leafy branches that are predominantly ventral-intercalary, but the leaves are more broadly rectangular, and the dorsal leaf margin is more ampliate. The underleaves of B. polita are connate with the leaves on both sides versus free in B. exempta, and they are toothed as well as lobed versus lobed but untoothed in B. exempta. Neither leaves nor underleaves of B. polita are caducous (leaves are caducous in B. exempta). The hyaline portion of the underleaf surface and the leaf margins of B. polita are asperulate, versus smooth throughout in B. exempta. Seven New Zealand species that commonly have leafy ventral-intercalary branches were sampled for variation between populations. In five species the proportion of leafy ventral-intercalary branches varied a great deal, suggesting that branching type in these species is environmentally influenced. If a species with a high proportion of leafy ventral-intercalary branches is known from a single specimen, it cannot be concluded that this is a constant feature of the species.
The original description, authorship and typification of Hapsidophrys smaragdina (Serpentes, Colubridae)
Authors: DENZER WOLFGANG
Published: December 2023

In the current herpetological literature, the original authorship of Hapsidophrys smaragdina is assigned to Schlegel (1837). In this note, evidence is produced that the authorship needs to be attributed to H. Boie in F. Boie, 1827. Furthermore, an earlier lectotype designation is proven invalid and the possible designation of a neotype is suggested.
Popular Protests in the Mzab in Light of Intercommunity Conflicts and Ordinary Practices (Algeria)
Authors: Hadj-Moussa Ratiba
Published: December 2023

The Mzab region in the Algerian south has seen numerous clashes between the Mozabite and Arab communities. The most important of these were in 2013–2015. This article considers these clashes as an expression of the problematic of integrating the Saharan regions into the Algerian national fabric, and its interlocking with the end of a political cycle, which has tended to obscure the emergence of new generations of actors. It proposes that these intercommunal conflicts belong to the conjunction between these macro-level dimensions and much more everyday levels, which serve as the substrate not only of the realization of the clashes but also of their justification. The article documents how the ordinary, where the distance between the groups is marked in the everyday, is mobilized in the demands for a “just” state; and how, in the slow unfolding and production of clashes, the state becomes at once their invisibilized third term and their center.
Application of artificial intelligence-based dual source CT scanning in the differentiation of lung adenocarcinoma in situ and minimally invasive adenocarcinoma
Authors: Liu Lihong , Ni Zhihua , Zhang Jian , Zhao Junsong , Shen Jieyun
Published: December 2023

Background and Objective: Lung adenocarcinoma is the most common type of lung cancer with highly incidence and mortality. Due to the overlap of morphological features, it is difficult to distinguish clinically between preinvasive lesions (in situ adenocarcinoma, AIS) and invasive lesions (minimally invasive adenocarcinoma, MIA), which appear as ground glass cloudy nodules. This study was performed to probe the application value of artificial intelligence (AI)-based dual source CT scanning in the differentiation of AIS as well as MIA.

Methods: The clinical data of 136 patients in Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to January 2022 were retrospectively analyzed. The accuracy of AI in distinguishing lung AIS (n=76) and MIA (n=60) were analyzed. The effectiveness of AI in detecting nodules and its diagnostic efficacy for AIS and MIA were explored.

Results: The proportion of patients with clear and regular lesion boundaries in AIS was higher than that in MIA. The mean lesion diameter of AIS patients was shorter than MIA patients. There was no difference in the CT value between AIS and MIA in the ground glass nodule density area of pure ground glass nodule and mixed ground glass nodule, but the CT value of the solid nodule density area in AIS was lower. The occurrence of pulmonary vascular abnormality, air bronchogram sign, and pleural depression in AIS patients were lower than MIA patients. The detection rate of AI for lung adenocarcinoma with nodule diameter ≤ 5 mm, complete solid nodules and ground glass nodules was significantly higher than radiologists. The sensitivity, specificity, positive prediction rate, negative prediction rate and accuracy of AI detection were significantly higher than radiologists.

Conclusion: AI-based dual source CT scanning can clearly show the morphological characteristics of lung adenocarcinoma, which is helpful for the differential diagnosis of lung AIS as well as MIA.

doi: https://doi.org/10.12669/pjms.40.3.8454

How to cite this: Liu L, Ni Z, Zhang J, Zhao J, Shen J. Application of artificial intelligence-based dual source CT scanning in the differentiation of lung adenocarcinoma in situ and minimally invasive adenocarcinoma. Pak J Med Sci. 2024;40(3):271-276.  doi: https://doi.org/10.12669/pjms.40.3.8454

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Moral injury and the four pillars of bioethics
Authors: Heston Thomas F , Pahang Joshuel A
Published: December 2023

Healthcare providers experience moral injury when their internal ethics are violated. The routine and direct exposure to ethical violations makes clinicians vulnerable to harm. The fundamental ethics in health care typically fall into the four broad categories of patient autonomy, beneficence, nonmaleficence, and social justice. Patients have a moral right to determine their own goals of medical care, that is, they have autonomy. When this principle is violated, moral injury occurs. Beneficence is the desire to help people, so when the delivery of proper medical care is obstructed for any reason, moral injury is the result. Nonmaleficence, meaning do no harm, has been a primary principle of medical ethics throughout recorded history. Yet today, even the most advanced and safest medical treatments are associated with unavoidable, harmful side effects. When an inevitable side effect occurs, the patient is harmed, and the clinician is also at risk of moral injury. Social injustice results when patients experience suboptimal treatment due to their race, gender, religion, or other demographic variables. While minor ethical dilemmas and violations routinely occur in medical care and cannot be eliminated, clinicians can decrease the prevalence of a significant moral injury by advocating for the ethical treatment of patients, not only at the bedside but also by addressing the ethics of political influence, governmental mandates, and administrative burdens on the delivery of optimal medical care. Although clinicians can strengthen their resistance to moral injury by deepening their own spiritual foundation, that is not enough. Improvements in the ethics of the entire healthcare system are necessary to improve medical care and decrease moral injury.
Photodetachment rates for O⁻ and O₂⁻ in the D layer of the ionosphere as function of solar zenith angle and solar activity
Authors: Kozlov Stanislav , Lyakhov Andrey
Published: December 2023

We present the results of calculation of photodetachment rates for negative ions in the D layer of the ionosphere, using recent photodetachment cross-section measurements. The calculations have been made for the standard atmosphere by means of the TUV (Terrestrial UltraViolet) code. We have obtained dependences of the photodetachment rates on altitude and solar zenith angle. The nonlinear nature of these dependences causes similar variations in the role of the photodetachement processes with altitude and solar zenith angle as compared to other processes in the middle atmosphere and the lower ionosphere, especially under terminator conditions. Calculations with solar spectrum for 2011–2020 for the summer/winter solstice and the spring/autumn equinox have shown no quantitative difference between the photodetachement rates for ions in the D layer of the ionosphere.
Influence of the magnetic field and the mean flow configuration on spatial structure and growth rate of normal modes
Authors: Mordvinov Vladimir , Devyatova Elena , Tomozov Vladimir
Published: December 2023

The first part of the work presents the results of numerical experiments with the magnetohydrodynamic model of “shallow water” to assess the degree of influence of the magnetic field on the development of instabilities conditioned by a combination of inhomogeneities in the mean flow and the mean magnetic field. Normal mode calculations have confirmed the earlier obtained result on the different influence of weak and strong magnetic fields on the instability of differential rotation. Calculations have shown that a weak magnetic field stabilizes the development of instabilities, whereas a strong magnetic field, on the contrary, enhances the instability. Azimuthal inhomogeneities of differential rotation in all cases contribute to the development of instabilities. In the second part of the work, we examine the spatial structure of normal modes and make an attempt to interpret the torsional oscillations observed in the atmospheres of Earth and the Sun. Calculations have shown that regular axisymmetric disturbances can be caused by the formation of a cyclonic vortex above the pole, which is characteristic of Earth's atmosphere and, possibly, of the Sun's atmosphere. The least damped normal mode of a stable polar cyclone has a structure of torsional oscillations. Flow anomalies and the development of an anticyclonic eddy in winter at midlatitudes destroy torsional oscillations and lead to a rapid amplification of normal modes, which are more complex in structure.
Preparation and Characterization of Organosiloxanes with A Liquid Crystalline Trans-4-Pentylcyclohexanoate Moiety
Authors: Wu Li-Chuan , Lin Chih-Hung
Published: December 2023

In the course of this research, we successfully created three series of liquid crystalline compounds featuring the trans-cyclohexane structure. One series of compounds featured a double bond at the terminal position of the molecules, whereas the remaining two series incorporated disiloxane and trisiloxane groups. Each series comprised five spacers of different lengths, specifically 3, 4, 5, 6, and 11 methylene units. We identified the structures of the synthesized compounds using Nuclear Magnetic Resonance spectroscopy and characterized their liquid crystalline behavior through thermal analysis and polarized optical microscopy. The results revealed that both the length of the spacer and the presence of siloxane groups significantly influenced the liquid crystal phase transitions, transition temperatures, and temperature ranges. These findings provide valuable insights for designing and developing new liquid crystal materials with tailored properties for various applications.