bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-pharmacological prevention of postoperative delirium by occupational therapy teams: A randomized clinical trial
Authors: Alvarez Evelyn A. , Rojas Veronica A. , Caipo Lorena I. , Galaz Melany M. , Ponce Daniela P. , Gutierrez Rodrigo G. , Salech Felipe , Tobar Eduardo , Reyes Fernando I. , Vergara Rodrigo C. , Egaña Jose I. , Briceño Constanza A. , Penna Antonello
Published: February 2023

Background

Patients who develop postoperative delirium (POD) have several clinical complications, such as increased morbidity, increased hospital stays, higher hospital costs, cognitive and functional impairment, and higher mortality. POD is a clinical condition preventable by standard non-pharmacological measures An intensive Occupational Therapy (OT) intervention has been shown to be highly effective in preventing delirium in critically ill medical patients, but it is unknown the effect in surgical patients. Thus, we designed a prospective clinical study with the aim to determine whether patients undergoing intervention by the OT team have a lower incidence of POD compared to the group treated only with standard measures.

Methods

A multicenter, single-blind, randomized clinical trial was conducted between October 2018 and April 2021, in Santiago of Chile, at a university hospital and at a public hospital. Patients older than 75 years undergoing elective major surgery were eligible for the trial inclusion. Patients with cognitive impairment, severe communication disorder and cultural language limitation, delirium at admission or before surgery, and enrolled in another study were excluded. The intervention consisted of OT therapy twice a day plus standard internationally recommended non-pharmacological prevention intervention during 5 days after surgery. Our primary outcome was development of delirium and postoperative subsyndromal delirium.

Results

In total 160 patients were studied. In the interventional group, treated with an intensive prevention by OT, nine patients (12.9%) developed delirium after surgery and in the control group four patients (5.5%) [p = 0.125, RR 2.34 CI 95 (0.75–7.27)]. Whereas subsyndromal POD was present in 38 patients in the control group (52.1%) and in 34 (48.6%) in the intervention group [p = 0.4, RR 0.93 CI95 (0.67–1.29)]. A post hoc analysis determined that the patient’s comorbidity and cognitive status prior to hospitalization were the main risk factors to develop delirium after surgery.

Discussion

Patients undergoing intervention by the OT team did not have a lower incidence of POD compared to the group treated only with standard non-pharmacological measures in adults older than 75 years who went for major surgery.

Clinical trial registration

www.ClinicalTrials.gov, identifier NCT03704090.
Six-month follow-up after recovery of COVID-19 Delta variant survivors via CT-based deep learning
Authors: Huang Jianliang , Lin Ruikai , Bai Na , Su Zhongrui , Zhu Mingxin , Li Han , Chai Conghai , Xia Mingkai , Shu Ziwei , Qiu Zhaowen , Lei Mingsheng
Published: February 2023

Purpose

Using computer-aided diagnosis (CAD) methods to analyze the discharge and 6-month follow-up data of COVID-19 Delta variant survivors, evaluate and summarize the recovery and prognosis, and improve people's awareness of this disease.

Methods

This study collected clinical data, SGRQ questionnaire results, and lung CT scans (at both discharge and 6-month follow-up) from 41 COVID-19 Delta variant survivors. Two senior radiologists evaluated the CT scans before in-depth analysis. Deep lung parenchyma enhancing (DLPE) method was used to accurately segment conventional lesions and sub-visual lesions in CT images, and then quantitatively analyze lung injury and recovery. Patient recovery was also measured using the SGRQ questionnaire. The follow-up examination results from this study were combined with those of the original COVID-19 for further comparison.

Results

The participants include 13 males (31.7%) and 28 females (68.3%), with an average age of 42.2 ± 17.7 years and an average BMI of 25.2 ± 4.4 kg/m2. Compared discharged CT and follow-up CT, 48.8% of survivors had pulmonary fibrosis, mainly including irregular lines (34.1%), punctuate calcification (12.2%) and nodules (12.2%). Compared with discharged CT, the ground-glass opacity basically dissipates at follow-up. The mean SGRQ score was 0.041 (0–0.104). The sequelae of survivors mainly included impaired sleep quality (17.1%), memory decline (26.8%), and anxiety (21.9%). After DLPE process, the lesion volume ratio decreased from 0.0018 (0.0003, 0.0353) at discharge to 0.0004 (0, 0.0032) at follow-up, p < 0.05, and the absorption ratio of lesion was 0.7147 (–1.0303, 0.9945).

Conclusion

The ground-glass opacity of survivors had dissipated when they were discharged from hospital, and a little fibrosis was seen in CT after 6-month, mainly manifested as irregular lines, punctuate calcification and nodules. After DLPE and quantitative calculations, we found that the degree of fibrosis in the lungs of most survivors was mild, which basically did not affect lung function. However, there are a small number of patients with unabsorbed or increased fibrosis. Survivors mainly had non-pulmonary sequelae such as impaired sleep quality and memory decline. Pulmonary prognosis of Delta variant patients was better than original COVID-19, with fewer and milder sequelae.
Analysis of microbial diversity in the feces of Arborophila rufipectus
Authors: Ma Xiaoping , Li Junshu , Chen Benping , Li Xinni , Ling Zhenwen , Feng Shenglin , Cao Sanjie , Zuo Zhicai , Deng Junliang , Huang Xiaobo , Cai Dongjie , Wen Yiping , Zhao Qin , Wang Ya , Zhong Zhijun , Peng Guangneng , Jiang Yaozhang , Gu Yu
Published: February 2023

Introduction

Intestinal microbiota composition plays a crucial role in modulating the health of the host. This evaluation indicator is very sensitive and profoundly impacts the protection of endangered species. Currently, information on the gut microbiota of wild birds remains scarce. Therefore, this study aimed to describe the gut microbial community structure and potentially, the pathogen composition of wild Arborophila rufipectus.

Methods

To guarantee comprehensive data analysis, we collected fecal samples from wild A. rufipectus and Lophura nycthemera in their habitats for two quarters. The 16S rRNA gene was then sequenced using high-throughput sequencing technology to examine the intestinal core microbiota, microbial diversity, and potential pathogens with the aim of determining if the composition of the intestinal microflora varies seasonally.

Results and Discussion

The gut microbiota of A. rufipectus and L. nycthemera primarily comprised four phyla: Proteobacteria (45.98%), Firmicutes (35.65%), Bacteroidetes (11.77%), and Actinobacteria (3.48%), which accounted for 96.88% of the total microbial composition in all samples. At the genus level, core microorganisms were found, including Shigella (10.38%), Clostridium (6.16%), Pseudomonas (3.03%), and Rickettsiella (1.99%). In these genera, certain microbial species have been shown to be pathogenic. This study provides important indicators for analyzing the health status of A. rufipectus and formulating protective measures.
A bibliometric analysis of the role of microbiota in trauma
Authors: Huang Runzhi , Lu Yuwei , Jin Minghao , Liu Yifan , Zhang Mengyi , Xian Shuyuan , Chang Zhengyan , Wang Lei , Zhang Wei , Lu Jianyu , Tong Xirui , Wang Siqiao , Zhu Yushu , Huang Jie , Jiang Luofeng , Gu Minyi , Huang Zongqiang , Wu Minjuan , Ji Shizhao
Published: February 2023

Introduction

Over the last several decades, the gut microbiota has been implicated in the formation and stabilization of health, as well as the development of disease. With basic and clinical experiments, scholars are gradually understanding the important role of gut microbiota in trauma, which may offer novel ideas of treatment for trauma patients. In this study, we purposed to summarize the current state and access future trends in gut microbiota and trauma research.

Methods

We retrieved relevant documents and their published information from the Web of Science Core Collection (WoSCC). Bibliometrix package was responsible for the visualized analysis.

Results

Totally, 625 documents were collected and the number of annual publications kept increasing, especially from 2016. China published the most documents while the USA had the highest local citations. The University of Colorado and Food & Function are respectively the top productive institution and journal, as PLOS One is the most local cited journal. With the maximum number of articles and local citations, Deitch EA is supported to be the most contributive author. Combining visualized analysis of keywords and documents and literature reading, we recognized two key topics: bacteria translocation in trauma and gut microbiota's effect on inflammation in injury, especially in nervous system injury.

Discussion

The impact of gut microbiota on molecular and pathological mechanism of inflammation is the focus now. In addition, the experiments of novel therapies based on gut microbiota's impact on trauma are being carried out. We hope that this study can offer a birds-eye view of this field and promote the gradual improvement of it.
A dark matter in sake brewing: Origin of microbes producing a Kimoto-style fermentation starter
Authors: Ito Kohei , Niwa Ryo , Kobayashi Ken , Nakagawa Tomoyuki , Hoshino Genki , Tsuchida Yuji
Published: February 2023

Introduction

In Kimoto-style fermentation, a fermentation starter is produced before the primary brewing process to stabilize fermentation. Nitrate-reducing bacteria, mainly derived from brewing water, produce nitrite, and lactic acid bacteria such as Leuconostoc can proliferate because of their tolerance toward low temperature and their low nutritional requirements. Later, Lactobacillus becomes the dominant genus, leading to weakly acidic conditions that contribute to control yeasts and undesired bacterial contaminants. However, the sources of these microorganisms that play a pivotal role in Sake brewing have not yet been revealed. Thus, comprehensive elucidation of the microbiome is necessary.

Methods

In this study, we performed 16S rRNA amplicon sequencing analysis after sampling from floor, equipment surfaces, and raw materials for making fermentation starters, including koji, and water in Tsuchida Sake brewery, Gunma, Japan.

Results

Amplicon sequence variants (ASVs) between the external environments and the fermentation starter were compared, and it was verified that the microorganisms in the external environments, such as built environments, equipment surfaces, and raw materials in the sake brewery, were introduced into the fermentation starter. Furthermore, various adventitious microbes present in the fermentation starter of early days and from the external environments were detected in a nonnegligible proportion in the starter, which may impact the taste and flavor.

Discussion

These findings illuminate the uncharacterized microbial dark matter of sake brewing, the sources of microbes in Kimoto-style fermentation.
Role of immediate early genes in the development of salivary gland organoids in polyisocyanopeptide hydrogels
Authors: Schaafsma Paulien , Kracht Laura , Baanstra Mirjam , Jellema-de Bruin Anne L. , Coppes Robert P.
Published: February 2023

Human salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. Here, we envisage that the use of a fully, synthetic hydrogel based on the oligo (-ethylene glycol) functionalized polymer polyisocyanopeptides (PICs) can provide an environment suitable for the generation and expansion of salivary gland organoids (SGOs) after optimization of PIC polymer properties. We demonstrate that PIC hydrogels decorated with the cell-binding peptide RGD allow SGO formation from salivary gland (SG)-derived stem cells. This self-renewal potential is preserved for only 4 passages. It was found that SGOs differentiated prematurely in PIC hydrogels affecting their self-renewal capacity. Similarly, SGOs show decreased expression of immediate early genes (IEGs) after culture in PIC hydrogels. Activation of multiple signalling pathways involved in IEG expression by β-adrenergic agonist isoproterenol, led to increased stem cell self-renewal capacity as measured by organoid forming efficiency (OFE). These results indicate that PIC hydrogels are promising 3D matrices for SGOs, with the option to be used clinically, after further optimization of the hydrogel and culture conditions.
Testing the extreme male hypothesis in the valproate mouse model; sex-specific effects on plasma testosterone levels and tyrosine hydroxylase expression in the anteroventral periventricular nucleus, but not on parental behavior
Authors: Grgurevic Neza
Published: February 2023

Introduction

Autism is a neurodevelopmental disorder with a strong male bias in prevalence and severity. The extreme male hypothesis proposed that autism is a manifestation of extreme male traits as evidenced by increased masculine behaviors, hypermasculinization of some brain regions, and alterations in androgen metabolism. In the present study, the extreme male hypothesis was tested in the valproate (VPA) mouse model.

Methods

Females of the C57BL/6JOlaHsd mouse strain were treated with 500 mg/kg VPA on gestational day 12. Offspring of both sexes were tested at 3 to 4 months of age in the elevated plus maze (EPM), open field, sociability tests, and for parental behavior. After sacrifice at 5 to 6 months of age, plasma testosterone was measured in males, while the brains of both sexes were examined for tyrosine hydroxylase (TH) expression in the anteroventral periventricular nucleus (AVPV).

Results

VPA treatment significantly increased plasma testosterone levels and decreased AVPV TH expression in males, whereas the expression of TH in females remained at the same level. In parental behavior test none of the pup-oriented behavior was affected by VPA treatment in both sexes, the exception was nest quality which was lower after VPA exposure in males, but not in females.

Discussion

Our results suggest a hypermasculinizing effect of VPA that occurred specifically in males but not in females, and this effect could be related to changes in androgen physiology. Nevertheless, a generalized interpretation of the extreme male hypothesis on brain and behavior should be avoided due to the complex effects of VPA.
Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions
Authors: Swan Julia , Boyer Scott , Westlund Karolina , Bengtsson Camilla , Nordahl Gunnar , Törnqvist Elin
Published: February 2023

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are lacking, and specialized behavioral or biochemical tests are often required. Here, two groups of CD1 mice were exposed to either traditional laboratory handling methods or a training protocol with cup lifting for 3 and 5 weeks. The training protocol was designed to habituate the mice to the procedures involved in subcutaneous injection, e.g., removal from the cage, skin pinch. This protocol was followed by two common research procedures: subcutaneous injection and tail vein blood sampling. Two training sessions and the procedures (subcutaneous injection and blood sampling) were video recorded. The mouse facial expressions were then scored, focusing on the ear and eye categories of the mouse grimace scale. Using this assessment method, trained mice expressed less distress than the control mice during subcutaneous injection. Mice trained for subcutaneous injection also had reduced facial scores during blood sampling. We found a clear sex difference as female mice responded to training faster than the male mice, they also had lower facial scores than the male mice when trained. The ear score appeared to be a more sensitive measure of distress than the eye score, which may be more indicative of pain. In conclusion, training is an important refinement method to reduce distress in mice during common laboratory procedures and this can best be assessed using the ear score of the mouse grimace scale.
Case reports: Central nervous system involvement in patients with newly diagnosed multiple myeloma
Authors: Liu Jinghua , Shen Jing , Liu Daihong
Published: February 2023

Multiple myeloma with central nervous system involvement (CNS-MM) is rare, having a poor outcome and occurring in newly diagnosed or relapsed/refractory patients. The current report concerns 3 cases of newly diagnosed MM patients who presented with skull-derived plasmacytomas. Case 1 was a 54-year-old female patient with immunoglobulin D (IgD) subtype who developed extramedullary lesions from the sphenoid and occipital bones and the sphenoid sinus. Cases 2 and 3 had IgA subtype with left or bilateral frontal area lesions. Case 1 was treated with bortezomib, cyclophosphamide and dexamethasone (VCD) as the initial chemotherapy regimen and with bortezomib, lenalidomide, pegylated liposomal doxorubicin and dexamethasone (DVD-R) as the second line regimen. Whole-brain irradiation and intrathecal injection were given but the patient died within 9 months due to disease progression. Case 2 was treated with bortezomib, lenalidomide and dexamethasone (VRD) and received autologous hematopoietic stem cell transplantation (auto-HSCT) with a conditioning regimen of cyclophosphamide, etoposide and melphalan (CEM). Case 3 received DVD-R initially and auto-HSCT with a conditioning regimen of busulfan, cyclophosphamide, and etoposide (BuCyE). Cases 2 and 3 survived until the last follow-up more than 3 years later. Auto-HSCT with modified conditioning regimen as consolidation therapy improved the prognosis of CNS-MM.
Quantitative IVIM parameters evaluating perfusion changes in brain parenchyma in patients newly diagnosed with acute leukemia: Compared with healthy participants
Authors: Cui Jianing , Zheng Jing , Niu Weiran , Bian Wenjin , Wang Jun , Niu Jinliang
Published: February 2023

Purpose

To study the value of quantitative IVIM parameters in evaluating cerebral blood perfusion changes in patients newly diagnosed with acute leukemia (AL) by comparing them with healthy participants.

Materials and methods

This prospective study consecutively recruited 49 participants with newly diagnosed AL and 40 normal controls between July 2020 and September 2022. All participants underwent an MRI of the brain using an axial T1-weighted and an IVIM sequence. The IVIM parameters (water diffusion coefficient, sADC, pseudoperfusion fraction, f; diffusion coefficient, D, pseudodiffusion coefficient, D*, and perfusion-diffusion ratio, PDR) and peripheral white blood cell (WBC) counts were obtained. An unpaired t-test or the Mann–Whitney U-test was performed to compare the differences in gray matter (GM) and white matter (WM) of healthy participants and AL patients and the differences in IVIM parameters between healthy participants and patients with AL. In addition, multivariate (logistic regression) analyses were used to identify independent predictors and then, the receiver operating characteristic curve (ROC) analyses were performed.

Results

40 healthy participants and 49 patients with newly diagnosed AL were evaluated. In healthy participants, sADC, PDR, D and f values of GM were significantly higher than those of WM (t = 5.844, t = 3.838, t = 7.711, z = −2.184, respectively, all P < 0.05). In AL patients, the D, f and sADC values of GM were significantly higher than those of WM (t = 3.450, t = 6.262, t = 4.053, respectively, all P < 0.05). The sADC and f value from AL patients were significantly lower than those from healthy participants in GM (z = −2.537, P = 0.011; and z = −2.583, P = 0.010, respectively) and WM (z = −2.969, P = 0.003; z = −2.923, P = 0.003, respectively). The WBC counts of AL patients were significantly higher than those of healthy participants (t = 3.147, P = 0.002). Multivariate analyses showed that the f values of GM and WM were independent predictors of AL (P = 0.030, and 0.010, respectively), with the optimal cut-off value at 7.08% (AUC ROC curve: 0.661, specificity: 11.4%, sensitivity: 98%) and 13.77% (AUC ROC curve: 0.682, specificity: 79.5%, sensitivity: 59.2%).

Conclusion

The IVIM parameters of brain parenchyma in patients newly diagnosed with AL differed from those of the healthy participants. The changes of cerebral blood flow perfusion are expected to provide new ideas for studying central nervous system infiltration in AL.
General anesthesia vs. non-general anesthesia for vertebrobasilar stroke endovascular therapy
Authors: Lu Yanan , Xu Pengfei , Wang Jinjing , Xiao Lulu , Zhang Pan , Duan Zuowei , Liu Dezhi , Liu Chaolai , Wang Delong , Wang Di , Zhang Chao , Yao Tao , Sun Wen , Cheng Zhaozhao , Li Min
Published: February 2023

Background

The optimal type of anesthesia for acute vertebrobasilar artery occlusion (VBAO) remains controversial. We aimed to assess the influence of anesthetic management on the outcomes in VBAO patients received endovascular treatment (EVT).

Methods

Patients underwent EVT for acute VBAO at 21 stroke centers in China were retrospectively enrolled and compared between the general anesthesia (GA) group and non-GA group. The primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0–3 at 90 days. Secondary outcomes included functional independence (90-day mRS score 0–2), and the rate of successful reperfusion. The safety outcomes included all-cause mortality at 90 days, the occurrence of any procedural complication, and the rate of symptomatic intracranial hemorrhage (sICH). In addition, we performed analyses of the outcomes in subgroups that were defined by Glasgow Coma Scale (GCS) score (≤8 or >8).

Results

In the propensity score matched cohort, there were no difference in the primary outcome, secondary outcomes and safety outcomes between the two groups. Among patients with a GCS score of 8 or less, the proportion of successful reperfusion was significantly higher in the GA group than the non-GA group (aOR, 3.57, 95% CI 1.06–12.50, p = 0.04). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar results were found.

Conclusions

Patients placed under GA during EVT for VBAO appear to be as effective and safe as non-GA. Furthermore, GA might yield better successful reperfusion for worse presenting GCS score (≤8).

Registration

URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.
Are GABAergic drugs beneficial in providing neuroprotection after traumatic brain injuries? A comprehensive literature review of preclinical studies
Authors: Sudhakar Shyam Kumar
Published: February 2023

Traumatic brain injuries (TBI) caused by physical impact to the brain can adversely impact the welfare and well-being of the affected individuals. One of the leading causes of mortality and dysfunction in the world, TBI is a major public health problem facing the human community. Drugs that target GABAergic neurotransmission are commonly used for sedation in clinical TBI yet their potential to cause neuroprotection is unclear. In this paper, I have performed a rigorous literature review of the neuroprotective effects of drugs that increase GABAergic currents based on the results reported in preclinical literature. The drugs covered in this review include the following: propofol, benzodiazepines, barbiturates, isoflurane, and other drugs that are agonists of GABAAreceptors. A careful review of numerous preclinical studies reveals that these drugs fail to produce any neuroprotection after a primary impact to the brain. In numerous circumstances, they could be detrimental to neuroprotection by increasing the size of the contusional brain tissue and by severely interfering with behavioral and functional recovery. Therefore, anesthetic agents that work by enhancing the effect of neurotransmitter GABA should be administered with caution of TBI patients until a clear and concrete picture of their neuroprotective efficacy emerges in the clinical literature.
Aberrant inter-network functional connectivity in drug-naive Parkinson’s disease patients with tremor dominant and postural instability and gait difficulty
Authors: Wang Qi , Yu Miao , Yan Lei , Xu Jianxia , Wang Yajie , Zhou Gaiyan , Liu Weiguo
Published: February 2023

Background: Insight into neural mechanisms of tremor dominant (TD) and postural instability and gait disorder (PIGD) subtypes in Parkinson’s disease (PD) is vital for understanding pathophysiological hypotheses underlying this phenotype. However, network disturbances and their correlation with motor subtypes of PD remain unclear. We aimed to investigate the alterations of intra- and inter-network functional connectivity (FC) in drug-naive PD patients with different motor subtypes.

Methods: Resting-state functional magnetic resonance imaging was performed on 25 drug-naive PD patients with TD (PD-TD) and 40 drug-naive PD patients with PIGD (PD-PIGD), and 37 healthy controls (HCs) underwent. The following networks were extracted using independent component analysis: sensorimotor network (SMN), left executive control network (LECN), right executive control network, anterior salience network (aSN), posterior salience network (pSN), ventral attention network (VAN), dorsal attention network (DAN), default mode network (DMN), visual network, and auditory network (AN). We measured FC values within and between these networks.

Results: There were no detectable variations in intra-network FC. PD-PIGD group demonstrated lower FC between aSN and pSN, as well as between VAN and DMN, in contrast to PD-TD group. Particularly, the FC strength between VAN and DMN was positively correlated with TD and tremor scores, and the best fitting classification models of TD and PIGD subtypes were based on the FC between aSN and pSN. Compared with HCs, both PD-TD and PD-PIGD patients displayed decreased FC between two SMN subnetworks, while PD-TD patients exhibited increased FC between the SMN subnetwork and pSN, and between LECN and VAN. Furthermore, PD-PIGD patients demonstrated decreased FC between the SMN subnetwork and AN.

Conclusions: The altered FC between aSN and pSN can be an imaging marker to distinguish PD-TD from PD-PIGD. We for the first time disclosed that the PD-TD patients compensated by increasing attention resources and the PD-PIGD patients displayed reduced FC between SMN and AN. Our findings provide a basis for identification and precision treatment of PD motor subtypes.
The clinical relevance of anti-glutamic acid decarboxylase antibodies in children with encephalitis/encephalopathy
Authors: Hou Ju-Yin , Liu Hsin-Uei , Kuo Cheng-Yen , Liu Yi-Hsuan , Lin Jainn-Jim , Hsieh Meng-Ying , Hung Po-Cheng , Cheng Yi-Ting , Su I-Chen , Wang Huei-Shyong , Chou I-Jun , Lin Kuang-Lin
Published: February 2023

Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with different types of syndromes. However, few studies have investigated the correlation between anti-GAD antibody titers with clinical severity and outcomes in children with encephalitis/encephalopathy. In this single-center retrospective cohort study, we consecutively enrolled hospitalized children who had encephalitis and/or encephalopathy with positive anti-GAD antibodies in serum and/or cerebrospinal fluid (CSF) from February 2010 to October 2021. Thirty-seven patients were included and divided into high-titer and low-titer groups. The patients with high anti-GAD antibody titers were associated with initial symptoms of language difficulty and ataxia. The level of titers was not associated with severity or outcomes. Anti-GAD antibody titers decreased after immunotherapy, however, the clinical response to immunotherapy was variable. A transient elevation in anti-GAD antibody titers during immunotherapy was noted. Further studies are warranted to investigate the role of anti-GAD antibodies in the pathogenesis and immune mechanisms of encephalitis/encephalopathy.
Sarcopenia: Molecular regulatory network for loss of muscle mass and function
Authors: Wu Jiaxiang , Ding Ping’an , Wu Haotian , Yang Peigang , Guo Honghai , Tian Yuan , Meng Lingjiao , Zhao Qun
Published: February 2023

Skeletal muscle is the foundation of human function and plays a key role in producing exercise, bone protection, and energy metabolism. Sarcopenia is a systemic disease, which is characterized by degenerative changes in skeletal muscle mass, strength, and function. Therefore, sarcopenia often causes weakness, prolonged hospitalization, falls and other adverse consequences that reduce the quality of life, and even lead to death. In recent years, sarcopenia has become the focus of in-depth research. Researchers have suggested some molecular mechanisms for sarcopenia according to different muscle physiology. These mechanisms cover neuromuscular junction lesion, imbalance of protein synthesis and breakdown, satellite cells dysfunction, etc. We summarize the latest research progress on the molecular mechanism of sarcopenia in this review in order to provide new ideas for future researchers to find valuable therapeutic targets and develop relevant prevention strategies.
The Kraft Heinz Company global nutrition targets for the innovation and reformulation of food and beverages: Current and future directions
Authors: Yu Lynn , Braesco Véronique , Cooper Sheri L. , Drewnowski Adam , Esteves Bridget Hannon , Budelli Andrea Luigi
Published: February 2023

Reformulating packaged foods has the potential to improve the nutrient density of the global diet. The present perspective illustrates The Kraft Heinz Company’s approach to product (re)formulation to develop healthier product lines that are lower in saturated fats, total sugars, and sodium, and contain health promoting components. Here we present the rationale for The Kraft Heinz Company’s global nutrition targets used for the global innovation and renovation of foods and beverages. The global nutrition targets use a category specific approach to set maximum levels for the main nutrients of public health concern: saturated fat, total sugars and sodium, taking into account product characteristics (typical portion size, eating occasion, role in the diet, etc.) as well as regulatory, technological, sensory and safety constraints. Benchmarking examples illustrate how the nutrition targets are positioned within the United States, France, and Australia. These global nutrition targets serve as part of The Kraft Heinz Company’s environmental, social and governance nutrition commitments and demonstrates how the food industry is improving the nutritional value of packaged foods and beverages both now and into the future.
Primary hepatic angiosarcoma with noncirrhotic portal hypertension: A case report
Authors: Wu Xuwei , Yu Xia , Gan Qiaorong , Wang Bin , Lin Zhaowang , Shi Yu , Huang Zuxiong
Published: February 2023

Background

Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of mesothelial tissue origin in the liver. The diagnosis of PHA relies on pathology, and it is frequently misdiagnosed as multiple hepatic hemangioma. Noncirrhotic portal hypertension is a relatively rare pathological manifestation, and there are few reports of PHA as an uncommon cause of noncirrhotic portal hypertension.

Case summary

A 36-year-old male was admitted with abnormal liver function and suspected drug-induced liver injury (DILI), initially manifesting as multifocal hepatic hemangioma. The liver biopsy revealed features of noncirrhotic portal hypertension (NCPH), and the patient was eventually diagnosed with multifocal hepatic angiosarcoma.

Conclusion

Patients with PHA may present with NCPH in the liver due to injury to hepatic sinusoids; therefore, it is necessary to consider the possibility of unsampled vascular malignancy when hepatic masses are identified, and the histology is consistent with PHA.
Highly expressed CENPL is correlated with breast cancer cell proliferation and immune infiltration
Authors: Gui Zhengwei , Tian Yao , Liu Shiyang , Yu Tianyao , Liu Chenguang , Zhang Lin
Published: February 2023

Background

Centromere protein L (CENPL) is associated with a variety of human diseases. However, its function in breast cancer remains uncertain.

Methods

The Cancer Genome Atlas (TCGA) and genotype-tissue expression across cancer data were used to investigate CENPL expression. Using TCGA clinical survival data, the relationship between CENPL expression and patient prognosis was assessed. Using the cluster profiler R software tool, enrichment analysis of CENPL was carried out. Additionally, by studying the TCGA database, the relationship between CENPL expression and immune cell infiltration was assessed. To evaluate CENPL’s impact on breast cancer cell proliferation, the CCK8 test and colony-formation assay were carried out. Scratch testing and the transwell assay were used to evaluate the effects of CENPL on breast cancer cell migration.

Results

Breast cancer was one of numerous tumor forms with high CENPL expression. Significant relationships between high CENPL expression and the cell cycle, nuclear division, organelle fission, and chromosome segregation were found. Further investigation revealed that minimal infiltration of CD8-positive T cells and natural killer (NK) cells and high levels of Tregs and macrophages were correlated with high levels of CENPL expression. CENPL expression was linked to more than half of the ICP genes. Breast cancer cells’ ability to proliferate and migrate was decreased by CENPL knockdown.

Conclusions

Our findings suggest that CENPL may be an oncogene in breast cancer and a predictor of efficacy of immunotherapy for breast cancer.
Case report: First case of early adenoid cystic carcinoma and squamous cell carcinoma collision cancer treated by endoscopic submucosal dissection
Authors: Liang Zheng , Wei Yongqiu , Li Peng , Xu Rui , Zhou Qiaozhi , Zhang Shutian
Published: February 2023

Background

Collision cancer, a rare tumor, rarely occurs in the esophagus. Most reported cases of esophageal collision cancers are advanced cancers that can only be treated with surgery or palliative chemoradiotherapy. Here, we report a rare case of collisional squamous cell carcinoma (SqCC) and adenoid cystic carcinoma (AdCC) that was detected in the early stages by endoscopy.

Case summary

A 66-year-old man presented with retrosternal pain after swallowing and underwent endoscopy. Pathological biopsy showed high-grade squamous intraepithelial neoplasia. The lesion was removed by endoscopic submucosal dissection (ESD) after magnification and endoscopic ultrasonography. Postoperative pathology proved that the lesion was collision cancer comprising SqCC and AdCC. After six months of postoperative follow-up, there was no recurrence of esophageal cancer.

Conclusions

We provided a case report related to the diagnosis and treatment of esophageal collision cancer, especially early collision cancer. More research is needed to provide insights into the management of collision cancers.
Low expression of HIF1AN accompanied by less immune infiltration is associated with poor prognosis in breast cancer
Authors: Tang Shasha , Liu Dongyang , Fang Yuan , Yong Liyun , Zhang Yi , Guan Mengying , Lin Xiaoyan , Wang Hui , Cai Fengfeng
Published: February 2023

Background

Hypoxia-inducible factor 1-alpha (HIF-1α) stability and transcriptional action are reduced by the hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). Its inappropriate expression is associated with the development of cancer and immune control. It is yet unknown how HIF1AN, clinical outcomes, and immune involvement in breast cancer (BC) are related.

Methods

Using the GEPIA, UALCAN, TIMER, Kaplan-Meier plotter, and TISIDB datasets, a thorough analysis of HIF1AN differential expression, medical prognosis, and the relationship between HIF1AN and tumor-infiltrating immune cells in BC was conducted. Quantitative real-time PCR (qRT−PCR) analysis of BC cells were used for external validation.

Results

The findings revealed that, as compared to standard specimens, BC cells had significantly lower levels of HIF1AN expression. Good overall survival (OS) for BC was associated with higher HIF1AN expression. Additionally, in BC, the expression of HIF1AN was closely associated with the chemokines and immune cell infiltration, including neutrophils, macrophages, T helper cells, B cells, Tregs, monocytes, dendritic cells, and NK cells. A high correlation between HIF1AN expression and several immunological indicators of T-cell exhaustion was particularly revealed by the bioinformatic study.

Conclusions

HIF1AN is a predictive indicator for breast tumors, and it is useful for predicting survival rates.
Tumor−associated macrophage polarization in the inflammatory tumor microenvironment
Authors: Zou Zijuan , Lin Hongfen , Li Mengsen , Lin Bo
Published: February 2023

The chronic inflammation of tumor continues to recruit TAMs (tumor−associated macrophages) to the TME (tumor microenvironment) and promote polarization. Pro-inflammatory signals polarize macrophages to the M1 phenotype to enhance inflammation against pathogens. Tumor inflammatory development changes the pro-inflammatory response to an anti-inflammatory response, resulting in the alteration of macrophages from M1 to M2 to promote tumor progression. Additionally, hypoxia activates HIF (hypoxia-inducible factors) in the TME, which reprograms macrophages to the M2 phenotype to support tumor development. Here, we discuss the factors that drive phenotypic changes in TAMs in the inflammatory TME, which will help in the development of cancer immunotherapy of macrophages.
Geriatric assessment in the older adult with genitourinary cancer: A narrative review
Authors: Singhal Surbhi , Marwell Julianna G. , Khaki Ali Raza
Published: February 2023

Genitourinary (GU) cancers including bladder, prostate, and kidney cancers affect older adults with a higher prevalence compared to younger adults. GU cancer treatment is associated with poorer outcomes in older adults compared to their younger counterparts. To better identify and support older adults receiving cancer care, oncologic societies recommend the use of a geriatric assessment (GA) to guide management. However, little is known about the implementation and usefulness of the GA in older adults with GU cancers. We performed a narrative review to investigate the utility of the GA in older adults with GU cancers and propose strategies to optimize the real-world use of the GA. Here, we describe a framework to incorporate GA into the routine cancer care of older adults with GU cancers and provide several implications for future research.
Case report: Preclinical efficacy of NEDD8 and proteasome inhibitors in patient-derived models of signet ring high-grade mucinous colorectal cancer from a Lynch syndrome patient
Authors: Torchiaro Erica , Petti Consalvo , Arena Sabrina , Sassi Francesco , Migliardi Giorgia , Mellano Alfredo , Porporato Roberta , Basiricò Marco , Gammaitoni Loretta , Berrino Enrico , Montone Monica , Corti Giorgio , Crisafulli Giovanni , Marchiò Caterina , Bardelli Alberto , Medico Enzo
Published: February 2023

High-grade mucinous colorectal cancer (HGM CRC) is particularly aggressive, prone to metastasis and treatment resistance, frequently accompanied by “signet ring” cancer cells. A sizeable fraction of HGM CRCs (20-40%) arises in the context of the Lynch Syndrome, an autosomal hereditary syndrome that predisposes to microsatellite instable (MSI) CRC. Development of patient-derived preclinical models for this challenging subtype of colorectal cancer represents an unmet need in oncology. We describe here successful propagation of preclinical models from a case of early-onset, MSI-positive metastatic colorectal cancer in a male Lynch syndrome patient, refractory to standard care (FOLFOX6, FOLFIRI-Panitumumab) and, surprisingly, also to immunotherapy. Surgical material from a debulking operation was implanted in NOD/SCID mice, successfully yielding one patient-derived xenograft (PDX). PDX explants were subsequently used to generate 2D and 3D cell cultures. Histologically, all models resembled the tumor of origin, displaying a high-grade mucinous phenotype with signet ring cells. For preclinical exploration of alternative treatments, in light of recent findings, we considered inhibition of the proteasome by bortezomib and of the related NEDD8 pathway by pevonedistat. Indeed, sensitivity to bortezomib was observed in mucinous adenocarcinoma of the lung, and we previously found that HGM CRC is preferentially sensitive to pevonedistat in models with low or absent expression of cadherin 17 (CDH17), a differentiation marker. We therefore performed IHC on the tumor and models, and observed no CDH17 expression, suggesting sensitivity to pevonedistat. Both bortezomib and pevonedistat showed strong activity on 2D cells at 72 hours and on 3D organoids at 7 days, thus providing valid options for in vivo testing. Accordingly, three PDX cohorts were treated for four weeks, respectively with vehicle, bortezomib and pevonedistat. Both drugs significantly reduced tumor growth, as compared to the vehicle group. Interestingly, while bortezomib was more effective in vitro, pevonedistat was more effective in vivo. Drug efficacy was further substantiated by a reduction of cellularity and of Ki67-positive cells in the treated tumors. These results highlight proteasome and NEDD8 inhibition as potentially effective therapeutic approaches against Lynch syndrome-associated HGM CRC, also when the disease is refractory to all available treatment options.
Gadoxetic acid–enhanced MRI with a focus on LI-RADS v2018 imaging features predicts the prognosis after radiofrequency ablation in small hepatocellular carcinoma
Authors: Wang Ruizhi , Xu Hengtian , Chen Wufei , Jin Liang , Ma Zhuangxuan , Wen Lei , Wang Hongwei , Cao Kun , Du Xia , Li Ming
Published: February 2023

Introduction

Gadoxetic acid–enhanced magnetic resonance imaging (MRI) contributes to evaluating the prognosis of small hepatocellular carcinoma (sHCC) following treatment. We have investigated the potential role of gadoxetic acid–enhanced MRI based on LI-RADS (Liver Imaging Reporting and Data System) v2018 imaging features in the prognosis prediction of patients with sHCC treated with radiofrequency ablation (RFA) as the first-line treatment and formulated a predictive nomogram.

Methods

A total of 204 patients with sHCC who all received RFA as the first-line therapy were enrolled. All patients had undergone gadoxetic acid–enhanced MRI examinations before RFA. Uni- and multivariable analyses for RFS were assessing using a Cox proportional hazards model. A novel nomogram was further constructed for predicting RFS. The clinical capacity of the model was validated according to calibration curves, the concordance index (C-index), and decision curve analyses.

Results

Alpha fetoprotein (AFP) > 100 ng/ml (HR, 2.006; 95% CI, 1.111–3.621; P = 0.021), rim arterial phase hyperenhancement (APHE) (HR, 2.751; 95% CI, 1.511–5.011; P = 0.001), and targetoid restriction on diffusion-weighted imaging (DWI) (HR, 3.289; 95% CI, 1.832–5.906; P < 0.001) were considered as the independent risk features for recurrence in patients with sHCC treated with RFA. The calibration curves and C-indexes (C-index values of 0.758 and 0.807) showed the superior predictive performance of the integrated nomogram in both the training and validation groups.

Discussion

The gadoxetic acid–enhanced MRI features based on LI-RADS v2018, including rim APHE, targetoid restriction on DWI, and the AFP level, are the independent risk factors of recurrence in patients with sHCC treated with RFA as the first-line therapy. The predictive clinical-radiological nomogram model was constructed for clinicians to develop individualized treatment and surveillance strategies.
Case Report: A case of recurrent thrombosis in pediatric antiphospholipid syndrome associated with pediatric onset systemic lupus
Authors: Liu Lingjuan , Liu Liqun , Zhang Lu , Huang Peng , Dang Xiqiang , Shuai Lanjun , Li Xingfang , Li Yongzhen , Mao Dingan , Wu Xiaochuan , Cao Yan
Published: February 2023

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-system involvement as the main manifestation, and has complex and diverse clinical features. Studies on large samples have revealed that SLE patients have a significantly increased risk of thrombotic events, which are also one of the important causes of morbidity and mortality in SLE patients. Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by recurrent arterial and venous thrombosis, pregnancy-related complications, and the persistence of antiphospholipid antibodies at a 12-week interval. There are few reports about SLE coexisting with APS in children. This paper reported a school-age patient who started the disease with gross hematuria after bumping into the waist. The initial diagnosis of renal contusion was then confirmed by color Doppler ultrasound as renal vein and inferior vena cava embolism. She suddenly developed severe chest pain and dyspnea 3 days after hospitalization. And imaging supported pulmonary embolism with massive proteinuria, hypoalbuminemia, and hypercholesterolemia. The initial diagnosis was nephrotic syndrome (NS) with arteriovenous embolization, and popliteal vein embolism occurred again 5 years later, and she was thus diagnosed with SLE coexisting with APS. Afterwards, we discussed the possible mechanism and therapeutic strategies of SLE&APS that started with nephrotic syndrome, in order to achieve early identification and treatment of the disease and improve the prognosis of children.