bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental and human health implications of metal(loid)s: Source identification, contamination, toxicity, and sustainable clean-up technologies
Authors: Kumar Pankaj , Gacem Amel , Ahmad Mohammad Tauheed , Yadav Virendra Kumar , Singh Snigdha , Yadav Krishna Kumar , Alam Md Mottahir , Dawane Vinars , Piplode Satish , Maurya Parul , Ahn Yongtae , Jeon Byong-Hun , Cabral-Pinto Marina M.S.
Published: August 2022

Environmental pollution is becoming more prevalent in both human life and the ecosystem. The increased use of fossil fuels, mining, and the burning of wastes, as well as industrial wastewater discharge, are polluting natural resources such as water, soil, and air. Metals (loid)s (Cu, Cr, Cd, Zn, Ni, Pb, Hg, Sb, Sn, and As) contribute to several ecological problems when exposed to humans and the environment resulting in serious health and environmental risks. The pollution of aquatic and terrestrial sites with these elements is an issue of environmental as well as public health significance. The present review highlights environmental problems instigated by the toxic metal (loid)s, their source, and respective health/environmental concern along with the importance of creating low-cost, environmentally acceptable clean-up technologies for treating household and industrial wastewater. Various physical, chemical, biological, and/or biochemical as well as their various combinations have been described from the sustainable technological point of view. Techniques such as ion exchange, membrane filtration, photocatalysis, bioremediation, phytoremediation, economical biosorbents, and nanomaterials have been discussed in detail along with respective recent case studies to gain a significant inside towards the solution of the environmental problems focused and action-oriented sustainable technologies development. Thus, this article significantly provides a deep insight into metal (loid)s toxicity, source identification, and their influences on the ecosystem and human health along with conventional and sustainable clean-up technologies.
A novel anoikis-related gene signature predicts prognosis in patients with head and neck squamous cell carcinoma and reveals immune infiltration
Authors: Chi Hao , Jiang Puyu , Xu Ke , Zhao Yue , Song Bingyu , Peng Gaoge , He Bingsheng , Liu Xin , Xia Zhijia , Tian Gang
Published: August 2022

Background: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with a poor prognosis for advanced tumors. Anoikis play a key role in cancer metastasis, facilitating the detachment and survival of cancer cells from the primary tumor site. However, few studies have focused on the role of anoikis in HNSC, especially on the prognosis.

Methods: Anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals were used to identify HNSCC subtypes and to construct a prognostic model for HNSCC patients. Also, we explored the immune microenvironment and enrichment pathways between different subtypes. Finally, we provide clinical experts with a novel nomogram based on ANRGs, with DCA curves indicating the potential clinical benefit of the model for clinical strategies.

Results: We identified 69 survival-related HNSCC anoikis-related DEGs, from which 7 genes were selected to construct prognostic models. The prognostic risk score was identified as an independent prognostic factor. Functional analysis showed that these high and low risk groups had different immune status and drug sensitivity. Next risk scores were combined with HNSCC clinicopathological features together to construct a nomogram, and DCA analysis showed that the model could benefit patients from clinical treatment strategies.

Conclusion: The predictive seven-gene signature and nomogram established in this study can assist clinicians in selecting personalized treatment for patients with HNSCC.
Comparative transcriptome analysis of brain and gonad reveals reproduction-related miRNAs in the giant prawn, Macrobrachium rosenbergii
Authors: Xia Jiao , Liu Dong , Zhou Wenzong , Yi Shaokui , Wang Xinhai , Li Beilei , Jawad Muhammad , Xu Haijing , Gui Lang , Li Mingyou
Published: August 2022

Macrobrachium rosenbergii (M. rosenbergii), as a species of common prawn, is a delicacy that is consumed all over the world. By interacting with the target gene 3′-untranslated region (3'-UTR), microRNAs (miRNAs) regulate its expression and ultimately participate in the regulation of reproductive development. However, research focusing on miRNA regulation during gonadal development in M. rosenbergii received very little attention. To explore the association between miRNA and reproduction, we performed RNA sequencing (RNA-seq) on brain and gonad organs in male and female M. rosenbergii. A total of 494 miRNAs were obtained in RNA-seq, including 31 and 59 differentially expressed (DE) miRNAs in the brain and gonads, respectively. Furthermore, 9 DE miRNAs were randomly selected from the brain and gonads, and qRT-PCR was conducted to validate the results of RNA-seq. Interestingly, dpu-miR-133 was found to be substantially expressed in the male brain and testis but poorly expressed in the female brain, ovary, and other organs. Analysis of dpu-miR-133 by Targetscan and MiRanda predicted to target 5-HT1. Furthermore, the dual-luciferase reporter assay manifested that dpu-miR-133 can combine with 5-HT1. Overall, our research work provides basic data for further study on the miRNA-mediated regulation of brain, gonad, and reproductive development of study M. rosenbergii.
Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome
Authors: Pane Fabrizio , Lefevre Guillaume , Kwon Namhee , Bentley Jane H. , Yancey Steven W. , Steinfeld Jonathan
Published: August 2022

In patients with hypereosinophilic syndrome (HES), mepolizumab reduces the incidence of HES-related clinical signs and symptoms (flares). However, reports characterizing flare manifestations are limited. The double-blind, parallel-group 200622 trial (NCT02836496) enrolled patients ≥12 years old with HES for ≥6 months, ≥2 flares in the previous year, and screening blood eosinophil count ≥1000 cells/μL. Patients maintained ≥4 weeks stable HES therapy, before randomization (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. This post hoc analysis investigated flare manifestations and duration by re-examining the Core Assessments form and narrative recorded for each flare during the study. Flare symptoms were retrospectively categorized into constitutional, dermatological, respiratory, nasal, gastrointestinal, neurologic and other. The most frequently reported flare symptoms were constitutional (94% of flares), dermatological (82% of flares) and respiratory (72% of flares); flares reported in patients receiving mepolizumab compared with placebo were generally similar in terms of the frequency of symptoms reported. Mepolizumab was associated with a shorter median (range) duration of flares (10.0 [4, 126] days) versus placebo (26.0 [1, 154] days). In patients with HES, flares were associated with symptoms linked to multiple organ systems highlighting the challenges faced for treating flares.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT02836496, identifier NCT02836496.
Activation mechanisms of monocytes/macrophages in adult-onset Still disease
Authors: Tsuboi Hiroto , Segawa Seiji , Yagishita Mizuki , Toko Hirofumi , Honda Fumika , Kitada Ayako , Miki Haruka , Ohyama Ayako , Hagiwara Shinya , Kondo Yuya , Matsumoto Isao , Sumida Takayuki
Published: August 2022

Adult onset Still disease (AOSD) is a systemic inflammatory disorder characterized by skin rash, spiking fever, arthritis, sore throat, lymphadenopathy, and hepatosplenomegaly. Although the etiology of this disease has not been fully clarified, both innate and acquired immune responses could contribute to its pathogenesis. Hyperactivation of macrophages and neutrophils along with low activation of natural killer (NK) cells in innate immunity, as well as hyperactivation of Th1 and Th17 cells, whereas low activation of regulatory T cells (Tregs) in acquired immunity are involved in the pathogenic process of AOSD. In innate immunity, activation of monocytes/macrophages might play central roles in the development of AOSD and macrophage activation syndrome (MAS), a severe life-threating complication of AOSD. Regarding the activation mechanisms of monocytes/macrophages in AOSD, in addition to type II interferon (IFN) stimulation, several pathways have recently been identified, such as the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)-pattern recognition receptors (PRRs) axis, and neutrophil extracellular traps (NETs)-DNA. These stimulations on monocytes/macrophages cause activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain (NLRP) 3 inflammasomes, which trigger capase-1 activation, resulting in conversion of pro-IL-1β and pro-IL-18 into mature forms. Thereafter, IL-1β and IL-18 produced by activated monocytes/macrophages contribute to various clinical features in AOSD. We identified placenta-specific 8 (PLAC8) as a specifically increased molecule in monocytes of active AOSD, which correlated with serum levels of CRP, ferritin, IL-1β, and IL-18. Interestingly, PLAC8 could suppress the synthesis of pro-IL-1β and pro-IL-18 via enhanced autophagy; thus, PLAC8 seems to be a regulatory molecule in AOSD. These findings for the activation mechanisms of monocytes/macrophages could shed light on the pathogenesis and development of a novel therapeutic strategy for AOSD.
A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19
Authors: Singh Shivani , Saavedra-Avila Noemi Alejandra , Tiwari Sangeeta , Porcelli Steven A.
Published: August 2022

Bacillus Calmette-Guerin (BCG) has been used as a vaccine against tuberculosis since 1921 and remains the only currently approved vaccine for this infection. The recent discovery that BCG protects against initial infection, and not just against progression from latent to active disease, has significant implications for ongoing research into the immune mechanisms that are relevant to generate a solid host defense against Mycobacterium tuberculosis (Mtb). In this review, we first explore the different components of immunity that are augmented after BCG vaccination. Next, we summarize current efforts to improve the efficacy of BCG through the development of recombinant strains, heterologous prime-boost approaches and the deployment of non-traditional routes. These efforts have included the development of new recombinant BCG strains, and various strategies for expression of important antigens such as those deleted during the M. bovis attenuation process or antigens that are present only in Mtb. BCG is typically administered via the intradermal route, raising questions about whether this could account for its apparent failure to generate long-lasting immunological memory in the lungs and the inconsistent level of protection against pulmonary tuberculosis in adults. Recent years have seen a resurgence of interest in the mucosal and intravenous delivery routes as they have been shown to induce a better immune response both in the systemic and mucosal compartments. Finally, we discuss the potential benefits of the ability of BCG to confer trained immunity in a non-specific manner by broadly stimulating a host immunity resulting in a generalized survival benefit in neonates and the elderly, while potentially offering benefits for the control of new and emerging infectious diseases such as COVID-19. Given that BCG will likely continue to be widely used well into the future, it remains of critical importance to better understand the immune responses driven by it and how to leverage these for the design of improved vaccination strategies against tuberculosis.
Wnt5A signaling supports antigen processing and CD8 T cell activation
Authors: Sarraf Tresa Rani , Sen Malini
Published: August 2022

Antigen processing and antigen-specific CD8 T cell activation form part and parcel of cell-mediated immunity to infections. Yet, several lacunae remain in our understanding of how antigen processing and CD8 T cell response are coordinated. In this study, using mouse bone marrow-derived dendritic cells (BMDC) as antigen-presenting cells and Ovalbumin (OVA)/DQ-Ovalbumin (DQ-OVA) as model antigen we demonstrated that Wnt5A signaling in BMDC supports antigen processing/presentation and concomitant CD8 T cell activation through regulation of actin and proteasome dynamics. Recombinant Wnt5A conditioning of BMDC and associated actin assembly facilitated DQ-OVA processing, which was inhibited by the proteasome inhibitor MG132. Moreover, Wnt5A depletion led to a significant reduction in OVA processing and presentation. Impaired DQ-OVA processing in Wnt5A depleted BMDC correlated with altered dynamics of both actin and the proteasome regulator PA28α-PA28β, and reduced association of DQ-OVA with actin and proteasome subunits. Inhibited OVA processing/presentation in the Wnt5A depleted BMDC also resulted in subdued activation of OVA-sensitized CD8 T cells in co-culture with the BMDC. In concurrence with these findings, we demonstrated reduced OVA processing and impaired CD8 T cell response to OVA immunization in Wnt5A heterozygous mice lacking a copy of the Wnt5A gene in comparison to the wild-type cohorts. Taken together, our results reveal a crucial requirement of Wnt5A signaling in antigen processing/presentation and CD8 T cell activation, thus unveiling a vital regulatory node of cell-mediated immunity, unidentified thus far.
1-Bit dual-polarized ultrathin lens antennas based on Huygens’ metasurface
Authors: Xue Chunhua , He Qingqi , Li Teng , Gao Xi
Published: August 2022

In this paper 1-bit dual-polarized ultra-thin lens antennas are presented based on Huygens’ principle. The unit cell provides two-state transmission phase compensation for dual-polarized waves. By tuning state 0 away from resonance and state 1 near Huygens’ resonance, the 180° transmission phase difference between the two states is achieved. In the frequency range of 27.5–28.5 GHz, the transmission phase difference between the two states of the unit cell is 180° ± 20°, and the transmission amplitude is greater than −2 dB. Using the proposed unit cell, three ultrathin 1-bit Huygens’ metasurface antennas comprising 33 × 33 unit cells with single beams pointing separately at 0°, 15°, and 30° are designed, fabricated and measured. Simulated and measured results show that the proposed 1-bit transmitarray antenna can achieve single-beam patterns, which is useful for the development of reconfigurable transmission and digital metasurface antennas in the future.
LQR and LQG-Kalman active control comparison of smart structures with finite element reduced-order modeling and a Monte Carlo simulation
Authors: El Khaldi Loukmane , Sanbi Mustapha , Saadani Rachid , Rahmoune Miloud
Published: August 2022

The present contribution presents a comparison between two types of controls, namely, the optimal linear quadratic regulator (LQR) and the Kalman-LQG controller using the model order reduction process. Due to numerical constraints, the models of structures have been reduced so that the design of controllers and/or estimators could be performed. The proposed method results in a significant reduction in computational costs for dynamic analysis without compromising on accuracy. Transforming the full order state-space resulting from finite element space to a lower model reduces the simulation time with a few degrees of freedom and helps to implement easily the control without changes in the dynamics of the structure. The estimator Kalman is used here in order to estimate the modal states of the system that are used in modal analysis. In this context, a one-side cantilever Timoshenko beam is chosen with perfectly bonded piezoelectric layers of actuators and sensors to apply this comparison. The Monte Carlo simulation was used to improve the number and location selection of piezoelectric sensors on the chosen beam model. Neglecting environmental effects, numerical results relating to this comparison without and with model order reduction are established. Simulation results are presented to illustrate the effectiveness of the proposed vibration control algorithm for the studied beam.
Ingestion of spinosad-containing toxic sugar bait alters Aedes albopictus vector competence and vectorial capacity for dengue virus
Authors: Alomar Abdullah A. , Eastmond Bradley H. , Rapti Zoi , Walker Edward D. , Alto Barry W.
Published: August 2022

Dengue virus (DENV) is a highly prevalent vector-borne virus that causes life-threatening illnesses to humans worldwide. The development of a tool to control vector populations has the potential to reduce the burden of DENV. Toxic sugar bait (TSB) provides a form of vector control that takes advantage of the sugar-feeding behavior of adult mosquitoes. However, studies on the effect of ingestion of toxins in TSB on vector competence and vectorial capacity for viruses are lacking. This study evaluated vector competence for DENV serotype-1 of Aedes albopictus at 7 and 14 days post-ingestion of TSB formulated with spinosad (of bacteria origin) as an oral toxin. Our results and others were modeled to estimate effects on Ae. albopictus vectorial capacity for DENV. Ingestion of TSB caused a reduction in survival of females, but increased mosquito susceptibility to DENV infection, disseminated infection, and transmission. However, this increase in vector competence was obviated by the reduction in survival, leading to a lower predicted vectorial capacity. The findings of this study highlight the importance of evaluating the net impact of TSB ingestion on epidemiological parameters of vectorial capacity in the context of vector control efforts to reduce the risk of transmission of vector-borne viruses.
Therapeutic efficacy against Mycobacterium tuberculosis using ID93 and liposomal adjuvant formulations
Authors: Baldwin Susan L. , Reese Valerie A. , Larsen Sasha E. , Pecor Tiffany , Brown Bryan P. , Granger Brian , Podell Brendan K. , Fox Christopher B. , Reed Steven G. , Coler Rhea N.
Published: August 2022

Mycobacterium tuberculosis (M.tb) has led to approximately 1.3 million deaths globally in 2020 according to the World Health Organization (WHO). More effective treatments are therefore required to prevent the transmission of M.tb. Although Bacille Calmette–Guérin (BCG), a prophylactic vaccine against M.tb, already exists, other vaccines are being developed that could help boost BCG’s noted incomplete protection. This includes ID93 + GLA-SE, an adjuvanted protein vaccine which is being tested in Phase 2 clinical trials. The aim of this study was to test new lipid-based adjuvant formulations with ID93 in the context of a therapeutic vaccine, which we hypothesize would act as an adjunct to drug treatment and provide better outcomes, such as survival, than drug treatment alone. The recent success of another adjuvanted recombinant protein vaccine, M72 + AS01E (GlaxoSmithKline Biologicals), which after 3 years provided approximately 50% efficacy against TB pulmonary disease, is paving the way for new and potentially more effective vaccines. We show that based on selected criteria, including survival, T helper 1 cytokine responses, and resident memory T cells in the lung, that a liposomal formulation of GLA with QS-21 (GLA-LSQ) combined with ID93 provided enhanced protection over drug treatment alone.
First report on the metabolic characterization of Sterigmatocystin production by select Aspergillus species from the Nidulantes section in Foeniculum vulgare
Authors: Mahata Pranab Kumar , Dass Regina Sharmila , Gunti Lokanadhan , Thorat Pooja Appasaheb
Published: August 2022

Spices are typically grown in climates that support the growth of toxigenic fungi and the production of mycotoxins. The Aspergilli described in this study, as well as the sterigmatocystin (STC) detected, are causes for concern due to their potential to induce food poisoning. One of the most well-known producers of the carcinogenic STC is Aspergillus nidulans. This research explores the occurrence of STC-producing fungi in Foeniculum vulgare, a spice that is marketed in India and other parts of the world. This innovative study details the mycotoxigenic potential of five Aspergilli belonging to Section Nidulantes, namely Aspergillus latus (02 isolates), Emericella quadrilineata (02 isolates), and Aspergillus nidulans (01 isolate), with respect to STC contamination. These five isolates of Aspergilli were screened to produce STC on yeast extract sucrose (YES) medium in a controlled environment with regard to light, temperature, pH, and humidity, among other variables. The expression patterns of regulatory genes, namely, aflR, laeA, pacC, fluG, flbA, pksA, and mtfA were studied on the Czapek–Dox agar (CDA) medium. STC biosynthesis by the test isolates was done in potato dextrose broth (PDB) under optimum conditions, followed by the extraction and purification of the broth using ethyl acetate. High-performance liquid chromatography (HPLC) with an ultraviolet (UV) detector was utilized to detect compounds in eluted samples. F. vulgare contains Aspergilli that have been shown to have mycotoxigenic potential, which can accumulate in the spice during its active growth and thereby cause the elaboration of mycotoxins.
Evolving role of seneca valley virus and its biomarker TEM8/ANTXR1 in cancer therapeutics
Authors: Corbett Virginia , Hallenbeck Paul , Rychahou Piotr , Chauhan Aman
Published: August 2022

Oncolytic viruses have made a significant inroad in cancer drug development. Numerous clinical trials are currently investigating oncolytic viruses both as single agents or in combination with various immunomodulators. Oncolytic viruses (OV) are an integral pillar of immuno-oncology and hold potential for not only delivering durable anti-tumor responses but also converting “cold” tumors to “hot” tumors. In this review we will discuss one such promising oncolytic virus called Seneca Valley Virus (SVV-001) and its therapeutic implications. SVV development has seen seismic evolution over the past decade and now boasts of being the only OV with a practically applicable biomarker for viral tropism. We discuss relevant preclinical and clinical data involving SVV and how bio-selecting for TEM8/ANTXR1, a negative tumor prognosticator can lead to first of its kind biomarker driven oncolytic viral cancer therapy.
Altered membrane properties but unchanged intrinsic excitability and spontaneous postsynaptic currents in an aged APPswe/PS1dE9 model of Alzheimer’s disease
Authors: Ohline Shane M. , Liu Xinhuai , Ibrahim Mohamed F. , Mockett Bruce M. , Empson Ruth M. , Abraham Wickliffe C. , Iremonger Karl J. , Jones Peter P.
Published: August 2022

Neuronal hyperexcitability in Alzheimer’s disease (AD) models is thought to either contribute to the formation of amyloid beta plaques or result from their formation. Neuronal hyperexcitability has been shown in the cerebral cortex of the widely used young APPswe/PS1dE9 mice, which have accelerated plaque formation. However, it is currently unclear if hyperexcitability also occurs in CA1 hippocampal neurons of aged animals in this model. In the present work, we have compared intrinsic excitability and spontaneous synaptic inputs from CA1 pyramidal cells of 8-month-old APPswe/PS1dE9 and wildtype control mice. We find no change in intrinsic excitability or spontaneous postsynaptic currents (PSCs) between groups. We did, however, find a reduced input resistance and an increase in hyperpolarization-activated sag current. These results are consistent with findings from other aged AD model mice, including the widely used 5xFAD and 3xTg. Together these results suggest that neuronal hyperexcitability is not a consistent feature of all AD mouse models, particularly at advanced ages.
Assessment of the individual and compounding effects of marginalization factors on injury severity, discharge location, recovery, and employment outcomes at 1 year after traumatic brain injury
Authors: Garduño-Ortega Olga , Li Huihui , Smith Michelle , Yao Lanqiu , Wilson Judith , Zarate Alejandro , Bushnik Tamara
Published: August 2022

Objective

The aim of this study is to examine the effect of eight distinct marginalized group memberships and explore their compounding effect on injury severity, recovery, discharge location, and employment outcomes 1-year after traumatic brain injury (TBI).

Methods

Individuals with medically confirmed, complicated mild-severe TBI (N = 300) requiring inpatient rehabilitation care between the ages of 18 and 65 were recruited at two urban (public and private) health systems between 2013 and 2019. Data were collected from self-report and medical record abstraction. Marginalized group membership (MGM) includes racial and ethnic minority status, less than a high school diploma/GED, limited English proficiency, substance abuse, homelessness, psychiatric hospitalizations, psychiatric disorders, and incarceration history. Membership in four or more of these groups signifies high MGM. In addition, these factors were explored individually. Unadjusted and adjusted linear and logistic regressions and Kruskal–Wallis tests were used to assess the associations of interest in RStudio.

Results

After adjusting for age, sex, and cause of injury, compared to TBI patients with low MGM, those with high MGM experience significantly longer post-traumatic amnesia (95% CI = 2.70, 16.50; p = 0.007) and are significantly more likely to have a severe TBI (per the Glasgow-Coma Scale) (95% CI = 1.70, 6.10; p ≤ 0.001) than a complicated mild-moderate injury. Individuals with high MGM also are significantly less likely to be engaged in competitive paid employment 1 year after injury (95% CI = 2.40, 23.40; p = 0.001). Patients with high MGM are less likely to be discharged to the community compared to patients with low MGM, but this association was not significant (95% CI = 0.36, 1.16; p = 0.141). However, when assessing MGMs in isolation, certain associations were not significant in unadjusted or adjusted models.

Conclusion

This exploratory study's findings reveal that when four or more marginalization factors intersect, there is a compounding negative association with TBI severity, recovery, and employment outcomes. No significant association was found between high MGM and discharge location. When studied separately, individual MGMs had varying effects. Studying marginalization factors affecting individuals with TBI has critical clinical and social implications. These findings underline the importance of addressing multidimensional factors concurrent with TBI recovery, as the long-term effects of TBI can place additional burdens on individuals and their economic stability.
Brain hemispheres with right temporal lobe damage swap dominance in early auditory processing of lexical tones
Authors: Wei Yarui , Liang Xiuyuan , Guo Xiaotao , Wang Xiaoxiao , Qi Yunyi , Ali Rizwan , Wu Ming , Qian Ruobing , Wang Ming , Qiu Bensheng , Li Huawei , Fu Xianming , Chen Lin
Published: August 2022

Labor division of the two brain hemispheres refers to the dominant processing of input information on one side of the brain. At an early stage, or a preattentive stage, the right brain hemisphere is shown to dominate the auditory processing of tones, including lexical tones. However, little is known about the influence of brain damage on the labor division of the brain hemispheres for the auditory processing of linguistic tones. Here, we demonstrate swapped dominance of brain hemispheres at the preattentive stage of auditory processing of Chinese lexical tones after a stroke in the right temporal lobe (RTL). In this study, we frequently presented lexical tones to a group of patients with a stroke in the RTL and infrequently varied the tones to create an auditory contrast. The contrast evoked a mismatch negativity response, which indexes auditory processing at the preattentive stage. In the participants with a stroke in the RTL, the mismatch negativity response was lateralized to the left side, in contrast to the right lateralization pattern in the control participants. The swapped dominance of brain hemispheres indicates that the RTL is a core area for early-stage auditory tonal processing. Our study indicates the necessity of rehabilitating tonal processing functions for tonal language speakers who suffer an RTL injury.
On the state-dependent nature of odor perception
Authors: Shanahan Laura K. , Kahnt Thorsten
Published: August 2022

The olfactory system—and odor perception by extension—is susceptible to state-dependent influences. This review delves into human behavioral research in this area, and also touches on mechanistic evidence and examples from animal work. The review summarizes studies on the impact of satiety state on olfaction, highlighting the robust effects of food intake on the perceived pleasantness of food odors and olfactory decision-making. The impacts of other behavioral states on olfaction are also discussed. While research in this area is more limited, preliminary evidence suggests that odor perception is altered by circadian state, sleep deprivation, and mood. The flexibility in olfactory function described here can be considered adaptive, as it serves to direct behavior toward stimuli with high state-dependent value.
Ultrasound radiomics model-based nomogram for predicting the risk Stratification of gastrointestinal stromal tumors
Authors: Zhuo Minling , Guo Jingjing , Tang Yi , Tang Xiubin , Qian Qingfu , Chen Zhikui
Published: August 2022

This study aimed to develop and evaluate a nomogram based on an ultrasound radiomics model to predict the risk grade of gastrointestinal stromal tumors (GISTs). 216 GIST patients pathologically diagnosed between December 2016 and December 2021 were reviewed and divided into a training cohort (n = 163) and a validation cohort (n = 53) in a ratio of 3:1. The tumor region of interest was depicted on each patient’s ultrasound image using ITK-SNAP, and the radiomics features were extracted. By filtering unstable features and using Spearman’s correlation analysis, and the least absolute shrinkage and selection operator algorithm, a radiomics score was derived to predict the malignant potential of GISTs. a radiomics nomogram that combines the radiomics score and clinical ultrasound predictors was constructed and assessed in terms of calibration, discrimination, and clinical usefulness. The radiomics score from ultrasound images was significantly associated with the malignant potential of GISTs. The radiomics nomogram was superior to the clinical ultrasound nomogram and the radiomics score, and it achieved an AUC of 0.90 in the validation cohort. Based on the decision curve analysis, the radiomics nomogram was found to be more clinically significant and useful. A nomogram consisting of radiomics score and the maximum tumor diameter demonstrated the highest accuracy in the prediction of risk grade in GISTs. The outcomes of our study provide vital insights for important preoperative clinical decisions.
Clinical outcomes of robotic-assisted laparoscopic partial nephrectomy with renal hypothermia perfusion by renal artery balloon catheter in treating patients with complex renal tumors
Authors: Bai YuChen , Yang YunKai , Wei HaiBin , Quan Jing , Wei Fei , Zhang Qi , Liu Feng
Published: August 2022

Objective

This study aimed to investigate the safety and efficacy of renal hypothermic perfusion by renal artery balloon catheter during robot-assisted laparoscopic partial nephrectomy (P-RALPN) for patients with complex renal tumors.

Materials and methods

We retrospectively identified 45 patients with complex renal tumors who received standard robot-assisted laparoscopic partial nephrectomy (S-RALPN) and 11 patients treated with P-RALPN from September 2017 to October 2021. Preoperative patients’ characteristics and intraoperative surgical parameters including operating time, blood loss, hospitalization, pre- and post-surgical glomerular filtration rate (GFR), and postoperative survival time were collected and compared between the two groups. The patients’ body temperature, real-time kidney temperature, and short-term renal function were analyzed in the P-RALPN group.

Results

There was no statistically significant difference on median intraoperative estimated blood loss and postoperative hospitalization between the two groups. Patients who received P-RALPN had a slightly longer operative time than those who received S-RALPN (103.1 versus 125.9; p = 0.09). In the P-RALPN group, the volume of perfusion solution was 533.2 ml (range, 255.0–750.0 ml), the median temperature of kidney was 22.6°C (range, 21.7–24.1°C) after the kidney cools down, and the median minimum intraoperative temperature of patients was 36.1°C (range 35.2–36.7°C). The ischemia time in the S-RALPN group was markedly lower than that in the P-RALPN group (21.5 versus 34.8; p < 0.01). However, the loss of GFR was much higher for the S-RALPN group after the surgery. (28.9 versus 18.4; p < 0.01). Importantly, patients had similar postoperative survival time between the two groups (p = 0.42; HR = 0.27).

Conclusion

P-RALPN is a safe and feasible surgery in the treatment of patients with complex renal tumors, which provides a new operative approach for clinicians to treat these patients.
Eligibility, uptake and response to germline genetic testing in women with DCIS
Authors: Turza Lauren , Lovejoy Leann A. , Turner Clesson E. , Shriver Craig D. , Ellsworth Rachel E.
Published: August 2022

Background

Ductal carcinoma in situ (DCIS) is a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for recurrence. Uptake of genetic testing and subsequent surgical intervention in women with DCIS has not been well-studied. The aim of this study was to evaluate test eligibility parameters, uptake of clinical testing, impact on surgical decision making and second cancer events (SCE) in women with DCIS.

Methods

Four-hundred eighty-four women diagnosed with unilateral DCIS 2001-2020 were eligible for this study. Demographic, commercial genetic test results and surgical procedures were extracted from the database. Test-eligibility was assigned using National Comprehensive Cancer Network (NCCN) criteria. Panel genetic testing was performed in the research laboratory across 94 cancer predisposition genes. Statistical analyses were performed using Fisher’s exact tests and Chi-square analyses with p < 0.05 defining significance.

Results

Forty-four percent of women were test-eligible at diagnosis of which 63.4% pursued genetic testing before definitive surgery; 9.9% pursued testing only after a second cancer event. Bilateral mastectomy (BM) was significantly higher (p<0.001) in women who had testing before definitive surgery (46.9%) compared to those who had testing afterword (10.8%) and in women who underwent testing before definitive surgery with PV (75%) compared to those without PV (37.5%. p=0.045). Of the 39 women with PV, 20 (51.3%) were detected only in the research setting, with 7 (17.9%) of these women not eligible for genetic testing based on NCCN criteria. In women who did not undergo BM at diagnosis, SCE were significantly higher (p=0.001) in women with PV (33.3%) compared to those without PV (11.9%).

Conclusion

Pursuit of genetic testing and subsequent use of risk-reducing surgeries in women with PV was suboptimal in women with a primary diagnosis of DCIS. In conjunction, >50% of PV were detected only in the research setting. Because omission of genetic testing in women with DCIS may represent a lost opportunity for prevention, genetic testing at the time of diagnosis should be standard for all women with DCIS.
Emerging PD-1/PD-L1 targeting immunotherapy in non-small cell lung cancer: Current status and future perspective in Japan, US, EU, and China
Authors: Mizuno Takaaki , Katsuya Yuki , Sato Jun , Koyama Takafumi , Shimizu Toshio , Yamamoto Noboru
Published: August 2022

Non-small cell lung cancer (NSCLC), one of the deadliest types of cancers worldwide, has been the target of immunotherapy due to its high immune antigenicity. With the addition of immune-checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 antibodies, as an indispensable and powerful regimen for the treatment of this lethal disease, the median survival time for patients with stage IV NSCLC is approximately 2 years. In contrast, the response rate to ICIs remains less than 50%, even if the patients are selected using biomarkers such as PD-L1. Pharmaceutical companies have begun to develop additional anti-PD-1/PD-L1 antibodies to overcome resistance and are devising further immunotherapy combinations. More than 20 anti-PD-1/PD-L1antibodies have been approved or are currently in development. Numerous combination therapies are under development, and several combination therapies have provided positive results in randomized controlled trials. This review aimed to examine the current status of approved and investigational anti-PD-1/PD-L1antibodies for NSCLC in Japan, the United States, the European Union, and China. Further, this review discusses the challenges and future perspectives for developing new ICIs in alignment with the global developments in Japan.
Establishing a prognostic model of ferroptosis- and immune-related signatures in kidney cancer: A study based on TCGA and ICGC databases
Authors: Han Zhijun , Wang Hao , Long Jing , Qiu Yanning , Xing Xiao-Liang
Published: August 2022

Background

Kidney cancer (KC) is one of the most challenging cancers due to its delayed diagnosis and high metastasis rate. The 5-year survival rate of KC patients is less than 11.2%. Therefore, identifying suitable biomarkers to accurately predict KC outcomes is important and urgent.

Methods

Corresponding data for KC patients were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. Systems biology/bioinformatics/computational approaches were used to identify suitable biomarkers for predicting the outcome and immune landscapes of KC patients.

Results

We found two ferroptosis- and immune-related differentially expressed genes (FI-DEGs) (Klotho (KL) and Sortilin 1 (SORT1)) independently correlated with the overall survival of KC patients. The area under the curve (AUC) values of the prognosis model using these two FI-DEGs exceeded 0.60 in the training, validation, and entire groups. The AUC value of the 1-year receiver operating characteristic (ROC) curve reached 0.70 in all the groups.

Conclusions

Our present study indicated that KL and SORT1 could be prognostic biomarkers for KC patients. Whether this model can be used in clinical settings requires further validation.
Body composition change during neoadjuvant chemotherapy for breast cancer
Authors: Jang Min Kyeong , Park Seho , Park Chang , Doorenbos Ardith Z. , Go Jieon , Kim Sue
Published: August 2022

Background

Sarcopenia is receiving attention in oncology as a predictor of increased chemotherapy toxicities. Research into body composition change during neoadjuvant chemotherapy for breast cancer is both urgently needed and generally lacking. This study assessed sarcopenia prevalence before and after neoadjuvant chemotherapy using CT imaging, evaluated body composition changes during neoadjuvant chemotherapy, and determined predictors of sarcopenia status after neoadjuvant chemotherapy for breast cancer.

Materials and Methods

In this retrospective, descriptive study, we used data collected from 2017 to 2020 to measure body composition parameters on cross-sectional CT slices for 317 Korean women with breast cancer patients before and at completion of neoadjuvant chemotherapy. Changes in skeletal muscle index, visceral fat index, subcutaneous fat index, and sarcopenia were assessed and correlated, and multivariate logistic regression was conducted to identify predictive factors associated with sarcopenia status at completion of neoadjuvant chemotherapy.

Results

Of the 80 breast cancer patients (25.2%) who had sarcopenia before beginning neoadjuvant chemotherapy, 64 (80.0%) retained their sarcopenia status after chemotherapy. Weight, body mass index, body surface area, and visceral fat index showed significant increases after neoadjuvant chemotherapy; notably, only skeletal muscle index significantly decreased, showing a reduction of 0.44 cm2/m2 (t (316) = 2.15, p <.5). Lower skeletal muscle index at baseline was associated with greater loss of muscle mass during neoadjuvant chemotherapy (r = −.24, p <.001). Multivariate logistic regression showed that baseline sarcopenia status was the only significant predictor of sarcopenia status after neoadjuvant chemotherapy (p <.001). Specifically, the log odds of sarcopenia after neoadjuvant chemotherapy were 3.357 higher in the baseline sarcopenia group than in the group without baseline sarcopenia (β = 3.357, p <.001).

Conclusion

Sarcopenia during neoadjuvant chemotherapy can be obscured by an increasing proportion of fat in body composition if clinical assessment focuses on only body mass index or body surface area rather than muscle mass. For breast cancer patients who have sarcopenia when they begin neoadjuvant chemotherapy, the risk of muscle mass loss during treatment is alarmingly high. To reduce masking of muscle mass loss during treatment, comprehensive evaluation of body composition, beyond body surface area assessment, is clearly needed.
Endoscopic transorbital approach to the cavernous sinus: Cadaveric anatomy study and clinical application (‡SevEN-009)
Authors: Jung In-Ho , Yoo Jihwan , Choi Seonah , Lim Seung Hoon , Ko JaeSang , Roh Tae Hoon , Hong Je Beom , Kim Eui Hyun
Published: August 2022

Objective

Cavernous sinus (CS) invasion is frequently encountered in the management of skull base tumors. Surgical treatment of tumors in the CS is technically demanding, and selection of an optimal surgical approach is critical for maximal tumor removal and patient safety. We aimed to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the CS based on a cadaveric study.

Methods

Five cadaveric heads were used for dissection under the ETOA in the comparison with the endoscopic endonasal approach (EEA) and the microscopic transcranial approach (TCA). The CS was exposed, accessed, and explored, first using the ETOA, followed by the EEA and TCA. A dedicated endoscopic system aided by neuronavigation guidance was used for the procedures. During the ETOA, neurovascular structures inside the CS were approached through different surgical triangles.

Results

After completing the ETOA with interdural dissection, the lateral wall of the CS was fully exposed. The lateral and posterior compartments of the CS, of which accessibility is greatly limited under the EEA, were effectively approached and explored under the ETOA. The anteromedial triangle was the largest window via which most of the lateral compartment was freely approached. The internal carotid artery and abducens nerve were also observed through the anteromedial triangle and just behind V1. During the ETOA, the approaching view through the supratrochlear and infratrochlear triangles was more directed towards the posterior compartment. After validation of the feasibility and safety based on the cadaveric study, ETOA was successfully performed in a patient with a pituitary adenoma with extensive CS invasion.

Conclusions

Based on the cadaveric study, we demonstrated that the lateral CS wall was reliably accessed under the ETOA. The lateral and posterior compartments of the CS were effectively explored via surgical triangles under the ETOA. ETOA provides a unique and valuable surgical route to the CS with a promising synergy when used with EEA and TCA. Our experience with a clinical case convinces us of the efficacy of the ETOA during surgical management of skull base tumors with CS-invasion.
Case report: Novel compound heterozygous missense mutations in the DDHD2 gene in a Chinese patient associated with spastic paraplegia type 54
Authors: Xu Xin , Lu Fen , Du Senjie , Zhao Xiaoke , Li Hongying , Zhang Li , Tang Jian
Published: August 2022

Background

Spastic paraplegia type 54 (SPG54) is a rare inherited autosomal recessive disorder, and a complex hereditary spastic paraplegia (HSP) caused by mutations in the phospholipase DDHD2 gene. SPG54 is characterized by early onset of spastic paraplegia, intellectual disability and dysplasia of corpus callosum.

Case presentation

We report a 9 years and 5 months old Chinese girl with progressive spasm of the lower limbs, muscle weakness and intellectual disability. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia and thinning of the corpus callosum. According to the Wechsler Intelligence Scale, her IQ is 42. By whole exome sequencing, novel compound heterozygous missense mutations in the DDHD2 gene [c.168G>C, p.(Trp56Cys) and c.1505T>C, p.(Phe502Ser)] were identified in the proband. Comparative amino acid sequence alignment across different species revealed that Trp56 and Phe502 in the DDHD2 protein were highly conserved during evolution. And multiple in silico prediction tools suggested that both mutations were deleterious.

Conclusions

Our study reports a very rare case of complicated HSP caused by two novel compound heterozygous mutations in the DDHD2 gene. Our findings expand the genetic spectrum of SPG54.
Examination on the risk factors of cholangiocarcinoma: A Mendelian randomization study
Authors: Chen Lanlan , Fan Zhongqi , Sun Xiaodong , Qiu Wei , Mu Wentao , Chai Kaiyuan , Cao Yannan , Wang Guangyi , Lv Guoyue
Published: August 2022

Background: Several risk factors have been identified for CCA, however, whether such associations were causal remains unknown.

Methods: Mendelian randomization (MR) has been applied to examine the causal relationship between 26 putative risk factors and CCA. The genetic variants for each risk factor were extracted from their corresponding genome-wide association study (GWAS) if they reached the genome-wide significance (p-value < 5 × 10−8). The genetic associations with CCA were obtained from the publicly available GWAS with the largest sample size. Mainly, inverse-variance weighted (IVW) has been adopted to estimate the causal effect on CCA. Both multivariable and mediation MR analyses were carried out to detect independent factors.

Results: Three putative risk factors can causally elevate the risk of CCA after FDR correction, including liver fat content (LFC), non-alcoholic fatty liver disease (NAFLD), and cholelithiasis. The odds of CCA would increase per 1-SD increase in the liver fat content (LFC) (OR = 2.12 [1.66, 2.71]) and logOR of NAFLD. The genetic liability to cholelithiasis would increase the risk of CCA as well (OR = 2.17 [1.47, 3.20]). They were still significant in other methods. The multivariable MR analysis indicated that genetically-elevated LFC should increase the risk of CCA independently of cholelithiasis (OR = 1.88 [1.39, 2.55]). In the mediation MR analysis, the indirect effect was not significant when treating cholelithiasis as the mediator (indirect OR = 0.95 [0.85, 1.07]).

Conclusion: This MR study identified that gallstone and liver fat accumulation are two independent risk factors of CCA, suggesting two modifiable ways of preventing CCA.