bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome editing approaches using reproductive cells/tissues in flowering plants
Authors: Toda Erika , Kato Norio , Higashiyama Tetsuya , Okamoto Takashi
Published: January 2023

Targeted mutagenesis via programmable nucleases including the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system has been broadly utilized to generate genome-edited organisms including flowering plants. To date, specific expression of Cas9 protein and guide RNA (gRNA) in reproductive cells or tissues is considered one of the most effective genome-editing approaches for heritable targeted mutagenesis. In this report, we review recent advances in genome editing methods for reproductive cells or tissues, which have roles in transmitting genetic material to the next-generation, such as egg cells, pollen grains, zygotes, immature zygotic embryos, and shoot apical meristems (SAMs). Specific expression of Cas9 proteins in initiating cells efficiently induces targeted mutagenesis viaAgrobacterium-mediated in planta transformation. In addition, genome editing by direct delivery of CRISPR/Cas9 components into pollen grains, zygotes, cells of embryos and SAMs has been successfully established to generate genome-edited plant lines. Notably, DNA-free genome editing by the delivery of Cas9-gRNA ribonucleoproteins (RNPs) is not associated with any legislative concerns about genetically modified organisms. In summary, the genome editing methods for reproductive cells or tissues have enormous potential for not only basic studies for plant reproduction but also applied sciences toward molecular plant breeding.
Placental circadian lincRNAs and spontaneous preterm birth
Authors: Zhou Guoli , Fichorova Raina N. , Holzman Claudia , Chen Bin , Chang Chi , Kasten Eric P. , Hoffmann Hanne M.
Published: January 2023

Long non-coding RNAs (lncRNAs) have a much higher cell- and/or tissue-specificity compared to mRNAs in most cases, making them excellent candidates for therapeutic applications to reduce off-target effects. Placental long non-coding RNAs have been investigated in the pathogenesis of preeclampsia (often causing preterm birth (PTB)), but less is known about their role in preterm birth. Preterm birth occurs in 11% of pregnancies and is the most common cause of death among infants in the world. We recently identified that genes that drive circadian rhythms in cells, termed molecular clock genes, are deregulated in maternal blood of women with spontaneous PTB (sPTB) and in the placenta of women with preeclampsia. Next, we focused on circadian genes-correlated long intergenic non-coding RNAs (lincRNAs, making up most of the long non-coding RNAs), designated as circadian lincRNAs, associated with sPTB. We compared the co-altered circadian transcripts-correlated lincRNAs expressed in placentas of sPTB and term births using two published independent RNAseq datasets (GSE73712 and GSE174415). Nine core clock genes were up- or downregulated in sPTB versus term birth, where the RORA transcript was the only gene downregulated in sPTB across both independent datasets. We found that five circadian lincRNAs (LINC00893, LINC00265, LINC01089, LINC00482, and LINC00649) were decreased in sPTB vs term births across both datasets (p ≤ .0222, FDR≤.1973) and were negatively correlated with the dataset-specific clock genes-based risk scores (correlation coefficient r = −.65 ∼ -.43, p ≤ .0365, FDR≤.0601). Gene set variation analysis revealed that 65 pathways were significantly enriched by these same five differentially expressed lincRNAs, of which over 85% of the pathways could be linked to immune/inflammation/oxidative stress and cell cycle/apoptosis/autophagy/cellular senescence. These findings may improve our understanding of the pathogenesis of spontaneous preterm birth and provide novel insights into the development of potentially more effective and specific therapeutic targets against sPTB.
Case report: Daratumumab for treatment of refractory late or chronic active antibody-mediated rejection in renal allograft recipients with high levels of de novo donor-specific antibodies
Authors: Zhu Lan , Guo Zhiliang , Zhao Daqiang , Sa Rula , Zhao Guangyuan , Guo Hui , Chen Gang
Published: January 2023

Background

Late or chronic active antibody-mediated rejection (AMR) associated with de novo donor-specific antibodies (dnDSA) after renal transplantation is a great clinical challenge because it is often resistant to conventional therapies. Daratumumab, an anti-CD38 monoclonal antibody that can deplete plasma cells, may be effective for the treatment of late or chronic active AMR.

Methods

We designed a novel regimen that included early intensive therapy with daratumumab plus plasmapheresis (PP)/intravenous immunoglobulins (IVIG) and later maintenance therapy with daratumumab alone, and used this regimen to treat late or chronic active AMR in two kidney transplant recipients with extremely high levels of anti-DQ7 dnDSA.

Results

Both patients had a limited clinical response to the early treatment with rituximab and PP/IVIG (with or without splenic irradiation); however, they had a remarkable decrease in anti-DQ7 DSA (MFI value from ~20,000 to ~5,000) after 2-3 months of intensive therapy with daratumumab plus PP/IVIG. Over 20 months of follow-up, patient 1 maintained a low DSA (as low as 1,572) and normal renal function on daratumumab maintenance therapy. Patient 2 retained a low DSA and improved renal function and pathological lesions within one year after treatment but then deteriorated because of acute T cell-mediated rejection.

Conclusions

Our daratumumab-based regimen has shown promising results in the treatment of refractory late active or chronic active AMR in renal transplant recipients with high-level dnDSA. This may provide a reference for better use of daratumumab in the treatment of late or chronic active AMR.
Weight cycling induces innate immune memory in adipose tissue macrophages
Authors: Caslin Heather L. , Cottam Matthew A. , Piñon Jacqueline M. , Boney Likem Y. , Hasty Alyssa H.
Published: January 2023

Introduction

Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease. We previously reported that male mice retain obesity-associated immunological changes even after weight loss, suggesting that immune cells may remember the state of obesity. Therefore, we hypothesized that cycles of weight gain and loss, otherwise known as weight cycling, can induce innate memory in adipose macrophages.

Methods

Bone marrow derived macrophages were primed with palmitic acid or adipose tissue conditioned media in a culture model of innate immune memory. Mice also put on low fat or high fat diets over 14-27 weeks to induce weight gain, weight loss, and weight cycling.

Results

Priming cells with palmitic acid or adipose tissue conditioned media from obese mice increased maximal glycolysis and oxidative phosphorylation and increased LPS-induced TNFα and IL-6 production. Palmitic acid effects were dependent on TLR4 and impaired by methyltransferase inhibition and AMPK activation. While weight loss improved glucose tolerance in mice, adipose macrophages were primed for greater activation to subsequent stimulation by LPS ex vivo as measured by cytokine production. In the model of weight cycling, adipose macrophages had elevated metabolism and secreted higher levels of basal TNFα, suggesting that weight loss can also prime macrophages for heighted activation to weight regain.

Discussion

Together, these data suggest that weight loss following obesity can prime adipose macrophages for enhanced inflammation upon weight regain. This innate immune memory response may contribute to worsened glucose tolerance following weight cycling.
A practical pCO2 estimation and carbonate dynamics at an event of hypoxic water upwelling in Tokyo Bay
Authors: Endo Masanori , Zhao Yue , Nakamura Wataru , Sasaki Jun
Published: January 2023

Urban bays have been considered to have a high CO2 absorption function due to the high nutrient load and resultant primary production. It is expected to enhance the function by promoting a blue carbon policy co-beneficial with strengthening ecosystem services such as fisheries. Estimates of CO2 absorption in urban bays have been based mostly on fragmentary information from shipboard observations, and an evaluation based on continuous observation of water quality is necessary considering the large spatiotemporal variability of such bay environment. In particular, Tokyo Bay has a specific feature of water pollution problem of hypoxia and anoxia leading to emitting high CO2. Bottom hypoxic and anoxic waters develop from early summer to autumn in the central part of the bay and enclosed areas such as navigation channels and borrow pits. It is known that pCO2 becomes very high in these waters, and their upwelling (called blue tide in the bay from the discoloration of the sea surface) is thought to cause high CO2 emissions; however, the actual situation is unknown. We developed a practical method for continuous estimation of pCO2 by appropriately combining continuous observation of water quality using sensors and measurements of carbonate parameters by water sampling. The results show that a highly reproducible and practical method for continuous estimation of pCO2 was possible by combining in situ salinity and pH meters and the total alkalinity and calc. pH measured by a total alkalinity titrator for water samples. This method was then applied to the duration of blue tide that occurred in the head of the bay in the summer and autumn of 2021. The pCO2 in the surface water was found to increase significantly and exceed 2000 µatm due to the upwelling of anoxic bottom water containing high pCO2. Mean CO2 emissions of approximately +2150 and +1540 µmol m-2 h-1 were observed at two stations during the upwelling period. The mean values rose to +2390 and +2190 µmol m-2h-1 with the blue tide and lowered to +810 and +1120 µmol m-2 h-1 without it, suggesting that high CO2 emissions may occur due to upwelling, especially with blue tides.
Notoginsenoside Fc ameliorates renal tubular injury and mitochondrial damage in acetaminophen-induced acute kidney injury partly by regulating SIRT3/SOD2 pathway
Authors: Wei Miaomiao , Gao Yuancheng , Cheng Dongsheng , Zhang Haiying , Zhang Wei , Shen Yilan , Huang Qunwei , An Xiaoning , Wang Bing , Yu Zhonghai , Wang Niansong , Chen Hongbo , Xu Youhua , Gui Dingkun
Published: January 2023

Introduction

Mitochondria dysfunction is one of the primary causes of tubular injury in acute kidney injury (AKI). Notoginsenoside Fc (Fc), a new saponin isolated from Panax notoginseng, exhibited numerous pharmacological actions. However, the beneficial effects of Fc on renal tubular impairment and mitochondrial dysfunction in AKI have not been fully studied.

Methods

In this study, we established acetaminophen (APAP)-induced AKI model in mice to examine the therapeutic impacts of Fc on AKI.

Results

Our results showed that Fc could decrease the levels of the serum creatinine (Scr), blood urea nitrogen (BUN) and Cystatin C in mice with AKI. Fc also ameliorated renal histopathology, renal tubular cells apoptosis and restored expression of apoptosis-related proteins such as Bax, Bcl-2 and caspase3 (C-caspase3). Additionally, Fc increased the protein expression of SIRT3 and SOD2 in kidneys from mice with AKI. In vitro studies further showed Fc reduced the apoptosis of HK-2 cells exposure to APAP, attenuated the loss of mitochondrial membrane potential and decreased the formation of mitochondrial superoxide. Fc also partly restored the protein expression of Bax, Bcl-2, C-Caspase3, SIRT3, and SOD2 in HK-2 cells exposure to APAP.

Conclusion

In summary, Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of SIRT3/SOD2 pathway.
Influence of structural features and feruloylation on fermentability and ability to modulate gut microbiota of arabinoxylan in in vitro fermentation
Authors: Li Zhongxia , Zhang Huibin , He Li , Hou Yaqin , Che Yingjuan , Liu Tian , Xiong Shaobai , Zhang Xuguang , Luo Shunjing , Liu Chengmei , Chen Tingting
Published: January 2023

Introduction

Arabinoxylan (AX) is a versatile polysaccharide that shows various effects in modulating gut microbiota and health. The influence of arabinoxylan carbohydrate structural feature and feruloylation on fermentability and the effect of modulation of gut microbiota of AX was not clear.

Methods

Arabinoxylans from rice bran and corn bran (RAX and CAX), and their deferulyolated counterpart dRAX and dCAX were fermented using an in vitro fermentation model. Structural information was determined based on monosaccharide composition. Gas production of fermentation products, SCFAs production, pH change, and microbiota change were measured.

Results

RAX and dRAX posessed lower A/X ratio compared with CAX and dCAX. The gas and total SCFAs production were lower in RAX and dRAX, and the butyrate production were higher in RAX and dRAX compared with CAX and dCAX. Butyrate production was lower at dRAX compared to RAX. On the other hand, butyrate production was higher in dCAX than in CAX. The microbiota shift were different for the four fibers.

Discussion

The AXs from rice have a higher A/X ratio than the AXs from maize, suggesting more branching and a more complex side chain. The structural difference was crucial for the difference in fermentation pattern. Different Bacteroides species are responsible for the utilization of rice AXs and corn AXs. Although feruloylation had a minor effect on the overall fermentation pattern, it significantly affected butyrate production and alpha diversity. dRAX promoted less butyrate than RAX, which is associated with a significantly lower amount of Faecalibacterium prausnitzi. dCAX promoted more butyrate than CAX, which may be associated with a lower amount of Bacteroides ovatus and a higher amount of Blautia in dCAX compared to CAX. The effects of feruloylation on the fermentation pattern and the resulted microbiota shift of AX varied depending on the carbohydrate structure.
Phenylalanine-arginine β-naphthylamide could enhance neomycin-sensitivity on Riemerella anatipestifer in vitro and in vivo
Authors: Liu Shiqi , Liu Junfa , Fu Ning , Kornmatitsuk Bunlue , Yan Zhuanqiang , Luo Junrong
Published: January 2023

Riemerella anatipestifer is an important duck pathogen responsible for septicemia and infectious serositis, which has caused great economic losses to the duck industry. Phenylalanine-arginine β-naphthylamide (PAβN) is an efflux pump inhibitor, which mainly reduces the efflux effect by competing with antibiotics for efflux pump channels. Here, we found that R. anatipestifer strain GD2019 showed resistances to gentamicin, amikacin, kanamycin, and neomycin. Notably, PAβN could significantly reduce the Minimal inhibitory concentrations (MICs) of neomycin on the GD2019 strain. Moreover, PAβN combined with neomycin significantly decreased bacterial loads, relieved pathological injury and increase survival rate (p < 0.05) for the ducks lethally challenged by the GD2019 strain. Therefore, our results suggested, in vitro and in vivo, PAβN could reduce neomycin-resistant of R. anatipestifer. Importantly, finding of this study provide a new approach for treating antibiotic-resistant R. anatipestifer infection.
Plasma enzymatic activity, proteomics and peptidomics in COVID-19-induced sepsis: A novel approach for the analysis of hemostasis
Authors: Dos Santos Fernando , Li Joyce B. , Juocys Nathalia , Mazor Rafi , Beretta Laura , Coufal Nicole G. , Lam Michael T. Y. , Odish Mazen F. , Irigoyen Maria Claudia , O’Donoghue Anthony J. , Aletti Federico , Kistler Erik B.
Published: January 2023

Introduction: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation).

Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained for the collection of blood samples and de-identified use of the data. Blood samples were collected at multiple time points and analyzed to quantify a) the circulating proteome and peptidome by mass spectrometry; b) the aminopeptidase activity in plasma; and c) the endopeptidase activity in plasma using fluorogenic substrates that are cleaved by trypsin-like endopeptidases, specific clotting factors and plasmin. The one patient who died was diagnosed with bacterial superinfection on day 7 after beginning of the study.

Results: Spikes in protease activity (factor VII, trypsin-like activity), and corresponding increases in the intensity of peptides derived by hydrolysis of plasma proteins, especially of fibrinogen degradation products and downregulation of endogenous protease inhibitors were detected on day 7 for the patient who died. The activity of the analyzed proteases was stable in survivors.

Discussion: The combination of multiomics and enzymatic activity quantification enabled to i) hypothesize that elevated proteolysis occurs in COVID-19-induced septic shock with bacterial superinfection, and ii) provide additional insight into malfunctioning protease-mediated systems, such as hemostasis.
A Siamese tracker with “dynamic–static” dual-template fusion and dynamic template adaptive update
Authors: Sun Dongyue , Wang Xian , Man Yingjie , Deng Ningdao , Peng Zhaoxin
Published: January 2023

In recent years, visual tracking algorithms based on Siamese networks have attracted attention for their desirable balance between speed and accuracy. The performance of such tracking methods relies heavily on target templates. Static templates cannot cope with the adverse effects of target appearance change. The dynamic template method, with a template update mechanism, can adapt to the change in target appearance well, but it also causes new problems, which may lead the template to be polluted by noise. Based on the DaSiamRPN and UpdateNet template update networks, a Siamese tracker with “dynamic–static” dual-template fusion and dynamic template adaptive update is proposed in this paper. The new method combines a static template and a dynamic template that is updated in real time for object tracking. An adaptive update strategy was adopted when updating the dynamic template, which can not only help adjust to the changes in the object appearance, but also suppress the adverse effects of noise interference and contamination of the template. The experimental results showed that the robustness and EAO of the proposed method were 23% and 9.0% higher than those of the basic algorithm on the VOT2016 dataset, respectively, and that the precision and success were increased by 0.8 and 0.4% on the OTB100 dataset, respectively. The most comprehensive real-time tracking performance was obtained for the above two large public datasets.
The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with clinical outcomes of viral encephalitis
Authors: He Qiang , Wang Shuo , Chen Haoan , Long Lili , Xiao Bo , Hu Kai
Published: January 2023

Background

The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are used as prognostic biomarkers for many diseases. In this study, we aimed to explore the possibility of using ratios of NLR and MLR to predict the prognosis of viral encephalitis (VE).

Methods

A total of 81 patients with an initial diagnosis of VE who were admitted to our hospital from January 2018 to January 2021 were retrospectively analyzed. A routine blood test within 24 h of admission was utilized to determine the ratios of NLR and MLR for each patient. The modified Rankin Scale (mRS) at 12 months after discharge was used to evaluate patients' clinical prognosis and the patients were divided into the group of good prognosis (mRS ≤ 1) and the group of poor prognosis (mRS ≥ 2) according to the mRS scores. Univariate and multivariable regression analyses were used to differentiate and assess independent prognostic factors for the prognosis of VE.

Results

Neutrophil-to-lymphocyte ratio and MLR of the poor prognosis group were significantly higher than that of the good prognosis group. Multivariate logistic regression analysis results showed that NLR [odds ratio (OR): 1.421, 95% confidence interval (CI): 1.105–1.827; P < 0.05] and MLR (OR: 50.423, 95% CI: 2.708–939.001; P < 0.05) were independent risk factors for the poor prognosis of VE. NLR > 4.32 and MLR > 0.44 were suggested as the cutoff threshold for the prediction of the poor prognosis of VE.

Conclusion

Neutrophil-to-lymphocyte ratio and MLR obtained from blood tests done at hospital admission have the potential to predict poor prognosis in patients with VE.
Evolution of postural control assessment: From dynamic posturography to virtual reality
Authors: Keshner Emily A. , Mallinson Arthur I. , Longridge Neil S. , Sinno Solara , Petersen Hannes , Perrin Philippe
Published: January 2023

During the early years of spaceflight it was documented that astronauts were impaired and incapacitated upon return to earth. Computerized Dynamic Posturography (CDP) was devised to investigate and quantify this deficit, and eventually progressed into a clinical assessment tool. The current sprouting of virtual reality (VR) technologies has allowed for the development of an alternative approach that could be more informative. Many low-cost VR systems (including desktop gaming programs designed for rehabilitation) are now available. Continued improvements in this technology indicate a high probability that VR will become an integral component of posturography by replacing present mechanical CDP techniques. We researched the relevant literature to evaluate the strengths and weaknesses of CDP using the Equitest (Neurocom International; Clackamas USA), and the added benefits of incorporating VR to help clinicians assess the complex task of balance maintenance. VR is capable of manipulating task and environmental demands in order to assess functional postural behavior. VR is also a useful tool for clinical testing of postural disorders resulting from sensory mismatch. Although posturography is still a useful clinical tool, VR provides an inherent conflict between the visual and vestibular senses and can elevate the effectiveness of CDP for both assessment and intervention. We conclude that, when initially developed, CDP was innovative and ahead of its time. However, with the advent of VR, we have a chance to modernize CDP and enhance its value as a clinical instrument.
Changes of local microenvironment and systemic immunity after acupuncture stimulation during inflammation: A literature review of animal studies
Authors: Yu Wei-Lien , Park Ji-Yeun , Park Hi-Joon , Kim Seung-Nam
Published: January 2023

An increasing number of studies have demonstrated the underlying mechanisms by which acupuncture therapy mediates both local and systemic immunomodulation. However, the connection between alterations in the local microenvironment and the resulting change in systemic immunity remains unclear. In this review, we focus on cell-specific changes in local immune responses following acupuncture stimulation and their link to systemic immune modulation. We have gathered the most recent evidence for chemo- and mechano-reactive changes in endothelial cells, neutrophils, macrophages, and mast cells in response to acupuncture. Local signaling is then related to the activation of systemic neuro-immunity including the cholinergic, adrenal, and splenic nervous systems and pain-related neuromodulation. This review aims to serve as a reference for further research in this field.
Parkinson's disease constipation effect of electroacupuncture at ST25 through colonic motility and enteric neuropathology
Authors: Song Li-zhe-xiong , Li Yuan , Qian Xu , Xu Na , Yu Zhi , Dai Jing-wen , Xu Bin , Hu Xuan-ming
Published: January 2023

Background

The enteric nervous system (ENS) plays a central role in developing Parkinson's disease (PD) constipation, and the regulation of the ENS may be a key component in treating PD constipation. Electroacupuncture (EA) can effectively treat constipation symptoms in PD, but research on its specific mechanisms, especially in terms of ENS, is relatively lacking. Therefore, we investigated whether EA at ST25 promotes the restoration of ENS structure and colonic motor function in the rotenone-induced PD constipation rat model.

Methods

In this study, we evaluated constipation symptoms by stool characteristics, excretion and water volume, and whole gut transit time and observed colonic motility regulation through colonic motion detection and pathological changes in the colonic myenteric nervous plexus by transmission electron microscopy and immunofluorescence staining.

Results

EA significantly improved the constipation symptoms and positively adjusted the colonic motility in rotenone-induced PD constipation rats. At the same time, EA reversed the rotenone-induced colonic myenteric nervous plexus injury and regulated the ratio of inhibitory and excitatory neurotransmitters.

Conclusion

Our results indicate that EA treatment of PD constipation may be mediated through the adjustment of ENS.
Executive function and relation to static balance metrics in chronic mild TBI: A LIMBIC-CENC secondary analysis
Authors: van der Veen Susanne M. , Perera Robert A. , Manning-Franke Laura , Agyemang Amma A. , Skop Karen , Sponheim Scott R. , Wilde Elisabeth A. , Stamenkovic Alexander , Thomas James S. , Walker William C.
Published: January 2023

Introduction

Among patients with traumatic brain injury (TBI), postural instability often persists chronically with negative consequences such as higher fall risk. One explanation may be reduced executive function (EF) required to effectively process, interpret and combine, sensory information. In other populations, a decline in higher cognitive functions are associated with a decline in walking and balance skills. Considering the link between EF decline and reduction in functional capacity, we investigated whether specific tests of executive function could predict balance function in a cohort of individuals with a history of chronic mild TBI (mTBI) and compared to individuals with a negative history of mTBI.

Methods

Secondary analysis was performed on the local LIMBIC-CENC cohort (N = 338, 259 mTBI, mean 45 ± STD 10 age). Static balance was assessed with the sensory organization test (SOT). Hierarchical regression was used for each EF test outcome using the following blocks: (1) the number of TBIs sustained, age, and sex; (2) the separate Trail making test (TMT); (3) anti-saccade eye tracking items (error, latency, and accuracy); (4) Oddball distractor stimulus P300 and N200 at PZ and FZ response; and (5) Oddball target stimulus P300 and N200 at PZ and FZ response.

Results

The full model with all predictors accounted for between 15.2% and 21.5% of the variability in the balance measures. The number of TBI's) showed a negative association with the SOT2 score (p = 0.002). Additionally, longer times to complete TMT part B were shown to be related to a worse SOT1 score (p = 0.038). EEG distractors had the most influence on the SOT3 score (p = 0.019). Lastly, the SOT-composite and SOT5 scores were shown to be associated with longer inhibition latencies and errors (anti-saccade latency and error, p = 0.026 and p = 0.043 respectively).

Conclusions

These findings show that integration and re-weighting of sensory input when vision is occluded or corrupted is most related to EF. This indicates that combat-exposed Veterans and Service Members have greater problems when they need to differentiate between cues when vision is not a reliable input. In sum, these findings suggest that EF could be important for interpreting sensory information to identify balance challenges in chronic mTBI.
Sustainability and scalability of egg consumption in Burkina Faso for infant and young child feeding
Authors: Moore Emily V. , Wood Elizabeth , Stark Heather , Wereme N'Diaye Aissata , McKune Sarah L.
Published: January 2023

Introduction

Malnutrition is a significant challenge to the health of women and children in Burkina Faso. Given the critical role of animal source food on the health of infants and young children (IYC), interventions continue to explore the potential for eggs to prevent malnutrition.

Methods

Using data from the Un Oeuf intervention, which significantly increased IYC egg consumption, combined with quantitative and qualitative data from endline and 3-month follow-up, we explore the barriers and facilitating factors to IYC egg consumption and the sustainability and scalability of the intervention.

Results

Child egg consumption was high at follow-up in the Control, Partial, and Full Intervention arms (83.3, 88.2%, and 100, respectively). The Full Intervention arm had the highest mean number of eggs consumed (2.9, 2.6, and 5.7), which reflected a slight reduction from endline (6.2). All participants owned chickens at follow-up (100%), however, flock size varied. The Full Intervention arm had more chickens (mean 8.8) than the Control (5.1) or Partial Intervention (6.2) arms, which was a 50% reduction in below endline (18.5 chickens). Qualitative results indicate that chicken ownership, education about the nutritional value of eggs, and spousal support facilitated IYC egg consumption. Barriers included egg production, cultural taboos, and animal health. Motivational factors reported included the observed improvement in child health, increased availability of mothers' time, and mothers' financial independence. Knowledge sharing within the Full and Partial Intervention groups was widely reported, and the sustainability of IYC egg consumption was reinforced by accountability among mothers and to community leaders, flipbooks distributed during the project, and high motivation.

Discussion

Main findings indicate that mothers who received the full Un Oeuf intervention were able to overcome barriers to feeding their child an egg daily, were able to improve their livelihood, were motivated to continue feeding their child eggs, and saw the addition of eggs into the child's diet as sustainable. Future nutrition sensitive agriculture interventions should consider tailoring this approach for other LMIC contexts. Future research is needed to explore a possible threshold in the number of household chickens necessary to continuously feed a child an egg a day.
Global research trends on anti-PD-1/anti-PD-L1 immunotherapy for triple-negative breast cancer: A scientometric analysis
Authors: Wu Jinyao , Chen Yaokun , Chen Lingzhi , Ji Zeqi , Tian Huiting , Zheng Daitian , Yang Qiuping , Liu Yiyuan , Cai Jiehui , Zheng Jiehua , Chen Yexi , Li Zhiyang
Published: January 2023

In recent years, anti-PD-1/anti-PD-L1 has been considered to be a valuable therapeutic target and prognostic indicator for triple-negative breast cancer. We analyzed all publications published in the field from their inception until the present day in order to determine the current research status and hotspots. All related publications were searched on the Web of Science. Our research used R-studio (bibliometrix package), VOSviewer, and CiteSpace to analyze and obtain annual publications and citation information, articles, highest publication countries and affiliations, influential journals and authors, keyword analysis, and keyword bursts. In total, 851 documents were retrieved including 628 articles and 223 review articles. The output of publications increased year by year from 2013 to 2021. However, the average article citation times reached the top in 2014 but generally showed a downward trend from 2014 to 2021. It was an article written by Schmid et al. in 2018 that received the most citations. With regard to publications, citations, and link strength, among the top countries was the United States. Cancers was the most published journal. Schmid and Loi ranked top in total citations and h-index. Schmid has the largest M-index and Loi has the most publication. The keywords that received the most attention were “Immunotherapy”, “PD-L1”, “Triple-negative breast cancer”, “Tumor-infiltrating lymphocytes”, and “Expression”. According to the report, this current research focuses on immunotherapy for triple-negative breast cancer and the expression of PD-L1 and tumor-infiltrating lymphocytes (TILs). Pembrolizumab and Atezolizumab plus chemotherapy have completed the Phase 3 clinical trial. However, the biomarkers were limited in predicting the treatment prognosis. Through the scientometric analysis, we can understand the current research status and potential research points in this filed and provide research direction for researchers.
Initial clinical experience with magnetic resonance-guided radiotherapy in pediatric patients: Lessons learned from a single institution with proton therapy
Authors: Hall Matthew D. , Mittauer Kathryn E. , Herrera Roberto , Von Werne Katherine , Kotecha Rupesh , Kalman Noah S. , McCulloch James , Alvarez Diane , McAllister Nicole C. , Doty Delia G. , Rzepczynski Amy E. , Deere Will , Gutierrez Alonso N. , Chuong Michael D.
Published: January 2023

Purpose/Objectives

Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children.

Materials/Methods

All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments.

Results

Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments.

Conclusions

In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing.
Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
Authors: Allegretti Matteo , Barberi Vittoria , Ercolani Cristiana , Vidiri Antonello , Giordani Elena , Ciliberto Gennaro , Giacomini Patrizio , Fabi Alessandra
Published: January 2023

Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes: punctuated, branched and convergent. Punctuated evolution of the trunk was supported by en bloc inheritance of a large set (19 distinct genes) of copy number alterations. Branched evolution was supported by the distribution of site-specific SNVs. Convergent evolution was characterized by a unique asynchronous expansion of three actionable (OncoKB level 3A) mutations at two consecutive ESR1 codons. Low or undetectable in all the sampled tumor tissues, ESR1 mutations expanded rapidly in blood during HER2/hormone double-blockade, and predicted life-threatening local progression at lung and liver metastatic foci. Dramatic clinical response to Fulvestrant (assigned off-label exclusively based on liquid biopsy) was associated with clearance of all 3 subclones and was in stark contrast to the poor therapeutic efficacy reported in large liquid biopsy-informed interventional trials. Altogether, deconvolution of the tumor phylogenetic tree, as shown herein, may help to customize treatment in breast cancers that rapidly develop refractoriness to multiple drugs.
Immune checkpoint inhibitor-induced myocarditis and myositis in liver cancer patients: A case report and literature review
Authors: Mei Haoran , Wen Wu , Fang Kang , Xiong Yuanpeng , Liu Weiqi , Wang Jie , Wan Renhua
Published: January 2023

With the development of immunotherapy, immune checkpoint inhibitors (ICIs) are widely used in clinical oncology and have achieved good results. ICIs could induce immune-related adverse events (irAEs) in cancer treatment, which warrant sufficient attention. Among them, immune myositis can manifest severe symptoms affecting the whole body, and immune myocarditis occurs with a low incidence but high fatality rate. Here we report a case of grade 3/4 adverse reactions in a patient with partial hepatectomy for malignancy after using ICIs and describe the clinical presentation, laboratory results, treatment, and prognosis. It emphasizes that clinicians should focus on being alert to irAEs in liver cancer patients who have received ICI therapy. The case we present is a 56-year-old male diagnosed with hepatocellular carcinoma. Right hepatic lobectomy was performed in April 2019. Postoperative follow-up showed that transcatheter arterial chemoembolization (TACE) combined with sorafenib (400 mg twice daily) failed to stop the recurrence of the tumor. In December 2020, the patient started to use Camrelizumab injections (200mg/injection every 21 days as a cycle). After 3 cycles, the patient had decreased muscle strength in both lower extremities with chest tightness, dyspnea, and expectoration (whitish sputum). The diagnosis was ICIs injection-induced immune myocarditis and myositis accompanied. The patient’s condition improved considerably by steroid pulse therapy timely. The case emphasizes that clinicians should focus on being alert to irAEs in liver cancer patients who have received ICI therapy.
Case report: NUT carcinoma with MXI1::NUTM1 fusion characterized by abdominopelvic lesions and ovarian masses in a middle-aged female
Authors: Jiang Huahua , Wang Chao , Hou Zheng , Wang Yuxiang , Qiao Jie , Li Huajun
Published: January 2023

Background

Nuclear protein of the testis (NUT) carcinoma is a rare subset of poorly differentiated, highly aggressive malignancy defined by NUTM1 gene rearrangements. Only three NUT cases of probable ovarian origin have been reported.

Case presentation

We report a case of NUT carcinoma in a 53-year-old female who presented with extensive abdominopelvic lesions and bilateral ovarian masses suggestive of advanced ovarian cancer. This patient was admitted to our hospital due to abdominal pain and distension for over two months. Imaging examinations suggested a possible malignancy of bilateral adnexal origin. This patient first underwent diagnostic laparoscopy. After receiving neoadjuvant chemotherapy, she underwent cytoreductive surgery. Surgical pathology showed infiltration of monotonous round tumor cells with no apparent differentiation characteristics. Immunohistochemistry (IHC) revealed nuclear expression of the NUT protein. And MXI1::NUTM1 fusion was identified by next-generation sequencing (NGS). Herein, we introduce an unusual NUT carcinoma and describe the clinical, imaging, and pathological features. In addition, we briefly reviewed the published literature and discussed the possibility of primary gynecological NUT carcinoma.

Conclusions

Identifying a NUT carcinoma arising from the abdominopelvic cavity is essential, and we underscore the need for NUT testing in undifferentiated malignant neoplasms that appear in this clinical setting. Although it is unclear from which origin this tumor arose, proper classification is essential for treatment planning.
Targeting mutant p53-R248W reactivates WT p53 function and alters the onco-metabolic profile
Authors: Brown Kate , Jenkins Lisa M. Miller , Crooks Daniel R. , Surman Deborah R. , Mazur Sharlyn J. , Xu Yuan , Arimilli Bhargav S. , Yang Ye , Lane Andrew N. , Fan Teresa W-M. , Schrump David S. , Linehan W. Marston , Ripley R. Taylor , Appella Ettore
Published: January 2023

TP53 is the most commonly mutated gene in cancer, and gain-of-function mutations have wide-ranging effects. Efforts to reactivate wild-type p53 function and inhibit mutant functions have been complicated by the variety of TP53 mutations. Identified from a screen, the NSC59984 compound has been shown to restore activity to mutant p53 in colorectal cancer cells. Here, we investigated its effects on esophageal adenocarcinoma cells with specific p53 hot-spot mutations. NSC59984 treatment of cells reactivated p53 transcriptional regulation, inducing mitochondrial intrinsic apoptosis. Analysis of its effects on cellular metabolism demonstrated increased utilization of the pentose phosphate pathway and inhibition of glycolysis at the fructose-1,6-bisphosphate to fructose 6-phosphate junction. Furthermore, treatment of cells with NSC59984 increased reactive oxygen species production and decreased glutathione levels; these effects were enhanced by the addition of buthionine sulfoximine and inhibited by N-acetyl cysteine. We found that the effects of NSC59984 were substantially greater in cells harboring the p53 R248W mutation. Overall, these findings demonstrate p53-dependent effects of NSC59984 on cellular metabolism, with increased activity in cells harboring the p53 R248W mutation. This research highlights the importance of defining the mutational status of a particular cancer to create a patient-centric strategy for the treatment of p53-driven cancers.
The role of Hippo pathway in ferroptosis
Authors: Xiang Jiangxia , Jiang Mengmeng , Du Xing
Published: January 2023

The role of Hippo pathway in ferroptosis

The Hippo pathway is mainly composed of mammalian serine/threonine (Ste20)like kinases 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and transcriptional coactivator Yes-associated protein (YAP), and is closely related to cell growth, survival, proliferation, and migration; tissue and organ size control; and tumorigenesis and development. Ferroptosis is a regulated form of cell death characterized by the accumulation of iron-dependent reactive oxygen species (ROS) and the depletion of plasma membrane polyunsaturated fatty acids (PUFAs), which is caused by the imbalance of oxidation and the antioxidant system. This article elaborates the role of Hippo pathway in ferroptosis, providing ideas for the regulation of cell fate and the treatment of tumors.
Effect of GATA3 rs3824662 gene polymorphism in Han Chinese children with pre-B-cell acute lymphoblastic leukemia with 10 years follow-up
Authors: Chu Xinran , Qian Maoxiang , Yang Jin , Wu Dong , Gao Jing , Cao Lu , Fang Fang , Pan Jian , Zhang Hui , Hu Shaoyan
Published: January 2023

Purpose

To evaluate the influence of GATA3 rs3824662 on pre-B-cell acute lymphoblastic leukemia (pre-B-cell ALL) susceptibility and long-term prognosis in Han Chinese children with pre-B-cell ALL treated with the CCLG-2008 protocol at the Children’s Hospital of Soochow University.

Methods

A total of 256 patients with childhood pre-B-cell ALL under the CCLG-2008 protocol were enrolled in this study, and 174 healthy children were used as case controls. GATA3 rs3824662 genotyping was performed using a polymerase chain reaction, followed by Sanger sequencing. The association of genotype with clinical characteristics, treatment response, adverse events, and outcomes were analyzed.

Results

The A allele frequency of GATA3 rs3824662 in patients with pre-B cell ALL was significantly higher than that in healthy children (OR = 1.41, 95% CI = 1.042–1.908; P = 0.026). Among patients with pre-B-cell ALL, the GATA3 rs3824662 AA genotype was associated with poor prednisolone response and high blast cell burden on day 15 of the induction therapy (P = 0.011 and 0.007, respectively). Patients with the rs3824662 AA variant suffered more episodes of sepsis than those with the CC or CA variants (P = 0.021). The GATA3 rs3824662 AA genotype was significantly associated with sepsis [hazard ratio (HR) = 3.375; P = 0.01]. No significant differences were found in the cumulative incidence of relapse, overall survival, and event-free survival among all genotypes.

Conclusion

GATA3 rs3824662 was associated with susceptibility in Han Chinese children with pre-B-cell ALL and could be a possible risk factor for poor early treatment response and treatment-related sepsis.