bluuebunny/crossref_metadata_2025 huggingface dataset:
AI-2 Induces Urease Expression Through Downregulation of Orphan Response Regulator HP1021 in Helicobacter pylori
Authors: Yang Huang , Huang Xiaoxing , Zhang Xiaochuan , Zhang Xiaoyan , Xu Xiaohong , She Feifei , Wen Yancheng
Published: April 2022

Helicobacter pylori causes gastric infections in more than half of the world's population. The bacterium's survival in the stomach is mediated by the abundant production of urease to enable acid acclimation. In this study, our transcriptomic analysis demonstrated that the expression of urease structural proteins, UreA and UreB, is induced by the autoinducer AI-2 in H. pylori. We also found that the orphan response regulator HP1021 is downregulated by AI-2, resulting in the induction of urease expression. HP1021 represses the expression of urease by directly binding to the promoter region of ureAB, ranging from −47 to +3 with respect to the transcriptional start site. The study findings suggest that quorum sensing via AI-2 enhances acid acclimation when bacterial density increases, and might enable bacterial dispersal to other sites when entering gastric acid.
Comparison of Two Main Orthokeratology Lens Designs in Efficacy and Safety for Myopia Control
Authors: Lu Weiwei , Ning Rui , Diao Kai , Ding Yang , Chen Ruru , Zhou Lei , Lian Yan , McAlinden Colm , Sanders Francis W. B. , Xia Fangfang , Huang Jinhai , Jin Wanqing
Published: April 2022

Purpose

This study aimed to compare the efficacy and safety of corneal refractive therapy (CRT) lenses and vision shaping treatment (VST) lenses for myopia control in children.

Methods

Medical records of 1,001 children (2,002 eyes) who had been fitted with orthokeratology lenses for over 1.5 years were retrospectively reviewed. We collected the clinical data of four types of orthokeratology (OK) lenses available: one CRT lens (brand: CRT) and three VST lenses (brands: Euclid, Alpha, and Hiline) over 1.5 years. Results were compared and analyzed using a one-way ANOVA and Pearson's chi-square test.

Results

Axial length elongation in the CRT lens group was 0.13 ± 0.02 mm faster than that in the Euclid lens, 0.1 ± 0.02 mm faster in the Alpha lens, and 0.08 ± 0.02 mm faster in the Hiline lens over the 1.5-year period (all P < 0.05). Among the subjects, 37.3% of them using the CRT lens experienced more than 1 D of refractive growth, compared with 20.2–30.8% of subjects wearing the three groups of VST lenses (all P < 0.05). A lower incidence of total adverse events was found with the CRT lenses compared with the VST lenses (P < 0.05), especially corneal staining. No difference was found in axial length elongation, refraction growth, and incidence of adverse events among the three types of VST lenses (all P > 0.05).

Conclusions

Compared with the VST lenses, CRT lenses demonstrated a weaker effect on myopia control but with a better safety profile. Different types of VST lenses had similar efficacy and safety in the context of controlling myopia progression.
Agreement of Potassium, Sodium, Glucose, and Hemoglobin Measured by Blood Gas Analyzer With Dry Chemistry Analyzer and Complete Blood Count Analyzer: A Two-Center Retrospective Analysis
Authors: Xie Hongxiang , Lv Shiyu , Chen Sufeng , Pang Zhenzhen , Ye Deli , Guo Jianzhuang , Xu Wanju , Jin Weidong
Published: April 2022

Background

Blood gas analyzers (BGAs) and dry biochemistry analyzers for potassium and sodium are based on direct electrode methods, and both involve glucose oxidase for glucose detection. However, data are lacking regarding whether the results of the two assay systems can be used interchangeably. In addition, there remains controversy over the consistency between BGA-measured hemoglobin and complete blood count analyzer data. Here, we compared the consistency of sodium, potassium, glucose, and hemoglobin levels measured by BGA and dry chemistry and complete blood count analyzers.

Methods

Data from two teaching hospitals, the Zhejiang Provincial People's Hospital (ZRY) and the Qianfoshan Hospital (QY), were retrospectively analyzed based on dry biochemistry and complete blood count analyzer results as the reference system (X) and BGA as the experimental system (Y). Plasma was used for biochemical analysis at the ZRY Hospital, and serum at the QY Hospital. Paired data from the respective hospitals were evaluated for consistency, and biases between methods were assessed by simple correlation, Passing–Bablok regression, and Bland–Altman analyses.

Results

The correlations of potassium, sodium, glucose, and hemoglobin measured by BGA and dry biochemistry and complete blood count analyzers were high, at 0.9573, 0.8898, 0.9849, and 0.9883 for the ZRY Hospital and 0.9198, 0.8591, 0.9764, and 0.8666, respectively, for the QY Hospital. The results of Passing to Bablok regression analysis showed that the predicted biases at each medical decision level were within clinically acceptable levels for potassium, sodium, glucose, and hemoglobin at the ZRY Hospital. Only the predicted bias of glucose was below the clinically acceptable medical decision levels at the QY Hospital, while potassium, sodium, and hemoglobin were not. Compared with the reference system, the mean bias for BGA measurements at the ZRY Hospital was −0.08 mmol/L (95% confidence interval [CI] −0.091 to −0.069) for potassium, 1.2 mmol/L (95% CI 1.06 to 1.42) for sodium, 0.20 mmol/L (95% CI 0.167 to 0.228) for glucose, and −2.8 g/L for hemoglobin (95% CI −3.14 to −2.49). The mean bias for potassium, sodium, glucose, and hemoglobin at the QY Hospital were −0.46 mmol/L (95% CI −0.475 to −0.452), 3.7 mmol/L (95% CI 3.57 to 3.85), −0.36 mmol/L (95% CI −0.433 to −0.291), and −8.7 g/L (95% CI −9.40 to −8.05), respectively.

Conclusion

BGA can be used interchangeably with plasma electrolyte results from dry biochemistry analyzers but does not show sufficient consistency with serum electrolyte results from dry biochemistry analyzers to allow data interchangeability. Good consistency was observed between BGA and plasma or serum glucose results from dry biochemistry analyzers. However, BGA-measured hemoglobin and hematocrit assay results should be treated with caution.
Computed Tomography-Based Texture Features for the Risk Stratification of Portal Hypertension and Prediction of Survival in Patients With Cirrhosis: A Preliminary Study
Authors: Wan Shang , Wei Yi , Zhang Xin , Yang Caiwei , Hu Fubi , Song Bin
Published: April 2022

Objective

Clinical evidence suggests that the risk stratification of portal hypertension (PH) plays a vital role in disease progression and patient outcomes. However, the gold standard for stratifying PH [portal vein pressure (PVP) measurement] is invasive and therefore not suitable for routine clinical practice. This study is aimed to stratify PH and predict patient outcomes using liver or spleen texture features based on computed tomography (CT) images non-invasively.

Methods

A total of 114 patients with PH were included in this retrospective study and divided into high-risk PH (PVP ≥ 20 mm Hg, n = 57) or low-risk PH (PVP < 20 mm Hg, n = 57), a progression-free survival (PFS) group (n = 14), or a non-PFS group (n = 51) based on patients with rebleeding or death after the transjugular intrahepatic portosystemic shunt (TIPS) procedure. All patients underwent contrast-enhanced CT, and the laboratory data were recorded. Texture features of the liver or spleen were obtained by a manual drawing of the region of interest (ROI) and were performed in the portal venous phase. Logistic regression analysis was applied to select the significant features related to high-risk PH, and PFS-related features were determined by the Cox proportional hazards model and Kaplan-Meier analysis. Receiver operating characteristic (ROC) curves were used to test the diagnostic capacity of each feature.

Results

Five texture features (one first-order feature from the liver and four wavelet features from the spleen) and the international normalized ratio (INR) were identified as statistically significant for stratifying PH (p < 0.05). The best performance was achieved by the spleen-derived feature of wavelet.LLH_ngtdm_Busyness, with an AUC of 0.72. The only log.sigma.3.0.mm.3D_firstorder_RobustMeanAbsoluteDeviation feature from the liver was associated with PFS with a C-index of 0.72 (95% CI 0.566–0.885), which could stratify patients with PH into high- or low-risk groups. The 1-, 2-, and 3-year survival probabilities were 66.7, 50, and 33.3% for the high-risk group and 93.2, 91.5, and 84.4% for the low-risk group, respectively (p < 0.05).

Conclusion

CT-based texture features from the liver or spleen may have the potential to stratify PH and predict patient survival.
Immune Cells Characteristics and Their Prognostic Effects in Exertional Heatstroke Patients: A Retrospective Cohort Study
Authors: Ji Jingjing , Su Peng , Lin Wenyi , Ouyang Leifang , Wang Conglin , Jia Jinxin , Liu Zheying , Liu Zhifeng
Published: April 2022

Background

Exertional heatstroke (EHS) remains a major problem for those who take strenuous physical activity. Inflammation and immune dysfunction were thought to be crucial to the pathophysiological process of heatstroke. The present study was aimed to investigate the dynamic changes of the immune cells in patients with EHS and determine their prognostic effects to provide the clinical evidence of the above process.

Methods

This single-center retrospective cohort study collected all patients with EHS admitted to the intensive care unit (ICU) of the General Hospital of Southern Theater Command of PLA from October 2008 to May 2019. The dynamic changes of the main immune cell count and ratio were collected, including white blood cell (WBC), neutrophil, monocyte, and lymphocyte. The neutrophil-to-lymphocyte ratios (NLR) were calculated by the neutrophil count/lymphocyte count × 100%. The main outcome was 90-day mortality.

Results

A total of 189 patients were enrolled. For survivors, after 24 h, the WBC and neutrophil counts began to decrease, and they were back to normal in 72 h. In addition, the lymphocyte counts were within normal limits all the time. For non-survivors, the WBC and neutrophil counts were continuous over the normal range, while the lymphocyte count and the ratio began to decrease after 24 h and were continuously low in the following days. Receiver operating characteristic (ROC) curves analysis showed that increased neutrophils and decreased lymphocytes were associated with the poor prognosis of the patients. A prediction model based on immune cell counts and ratios was constructed, and the lymphocyte count was accounted for the maximum weight.

Conclusions

In patients with EHS, increased neutrophils and decreased lymphocytes were associated with the poor prognosis. The lymphocyte count at 72 h after admission was the most important prognostic factor.
Clinical Analysis of Pediatric Glaucoma in Central China
Authors: Liu Qian , Liu Changgeng , Li Haijun , Yang Xiaoyuan , Dong Yangzeng , Feng Xiaomei , Cheng Wenjun
Published: April 2022

Purpose

We aimed to describe the characteristics, epidemiology, management, and outcomes of glaucoma in pediatric patients in central China.

Methods

This study retrospectively analyzed inpatients with pediatric glaucoma at Henan Provincial People's Hospital, Henan Eye Institute, and Henan Eye Hospital between 2017 and 2020.

Results

Overall, 239 cases (276 eyes) of pediatric glaucoma in patients, comprising 87 girls (36.40%) and 152 boys (63.60%) were analyzed. The mean age was 6.65 ± 4.46, and 2.93% of the patients had a family history of glaucoma. Primary congenital glaucoma (PCG) was the most common type of glaucoma, followed by traumatic glaucoma in 8.33% of the patients, which was considered secondary glaucoma. The most common signs and symptoms were elevated intraocular pressure (IOP) and eye pain. Trabeculotomy (Trab) and microcatheter-assisted 360° trabeculotomy (MAT) combined with Trab were the most commonly performed surgeries. The IOP of patients with PCG, juvenile open-angle glaucoma (JOAG), and secondary glaucoma were 15.27 ± 7.48 mmHg, 17.16 ± 10.05, and 18.65 ± 8.55, respectively, at the final follow up. The rate of re-operations in patients with PCG, JOAG, and secondary glaucoma were 9.15%, 6.78%, and 4.69%, respectively. The mean visual acuity of the eyes with PCG, JOAG, and secondary glaucoma was 0.79 ± 0.68, 0.51 ± 0.48, and 0.53 ± 0.50, respectively.

Conclusion

PCG, JOAG, and traumatic glaucoma were the most prevalent subtypes in patients with pediatric glaucoma in central China. Trab and MAT combined with Trab were the most common interventions used in this study. Pediatric amblyopia might require full attention during the entire treatment, especially after glaucoma surgery. Effective preventive measures and more public education on glaucoma prevention and the importance of early diagnosis and treatment is necessary.
Geminivirus-Derived Vectors as Tools for Functional Genomics
Authors: Bhattacharjee Bipasha , Hallan Vipin
Published: April 2022

A persistent issue in the agricultural sector worldwide is the intensive damage caused to crops by the geminivirus family of viruses. The diverse types of viruses, rapid virus evolution rate, and broad host range make this group of viruses one of the most devastating in nature, leading to millions of dollars’ worth of crop damage. Geminiviruses have a small genome and can be either monopartite or bipartite, with or without satellites. Their ability to independently replicate within the plant without integration into the host genome and the relatively easy handling make them excellent candidates for plant bioengineering. This aspect is of great importance as geminiviruses can act as natural nanoparticles in plants which can be utilized for a plethora of functions ranging from vaccine development systems to geminivirus-induced gene silencing (GIGS), through deconstructed viral vectors. Thus, the investigation of these plant viruses is pertinent to understanding their crucial roles in nature and subsequently utilizing them as beneficial tools in functional genomics. This review, therefore, highlights some of the characteristics of these viruses that can be deemed significant and the subsequent successful case studies for exploitation of these potentially significant pathogens for role mining in functional biology.
Metabolic Engineering for Valorization of Agri- and Aqua-Culture Sidestreams for Production of Nitrogenous Compounds by Corynebacterium glutamicum
Authors: Wendisch Volker F. , Nampoothiri K. Madhavan , Lee Jin-Ho
Published: April 2022

Graphical Abstract

Strategy to valorize non-utilized nitrogen from sidestreams by producing nitrogen-containing products.
Salient Findings on Host Range, Resistance Screening, and Molecular Studies on Sterility Mosaic Disease of Pigeonpea Induced by Pigeonpea sterility mosaic viruses (PPSMV-I and PPSMV-II)
Authors: Sayiprathap B. R. , Patibanda A. K. , Prasanna Kumari V. , Jayalalitha K. , Ramappa H. K. , Rajeswari E. , Karthiba L. , Saratbabu K. , Sharma Mamta , Sudini H. K.
Published: April 2022

Two distinct emaraviruses, Pigeonpea sterility mosaic virus-I (PPSMV-I) and Pigeonpea sterility mosaic virus-II (PPSMV-II) were found to be associated with sterility mosaic disease (SMD) of pigeonpea [Cajanus cajan (L.) Millsp.]. The host range of both these viruses and their vector are narrow, confined to Nicotiana benthamiana identified through mechanical transmission, and to Phaseolus vulgaris cvs. Top Crop, Kintoki, and Bountiful (F: Fabaceae) through mite transmission. A weed host Chrozophora rottleri (F: Euphorbiaceae) was also infected and tested positive for both the viruses in RT-PCR. Among the wild Cajanus species tested, Cajanus platycarpus accessions 15661, 15668, and 15671, and Cajanus scarabaeoides accessions 15683, 15686, and 15922 were infected by both the viruses and mite vector suggesting possible sources of SMD inoculum. Though accession 15666 of C. platycarpus, 15696 of C. scarabaeoides, and 15639 of Cajanus lanceolatus were infected by both the viruses, no mite infestation was observed on them. Phylogenetic analysis of nucleotide sequences of RNA-1 and RNA-2 of PPSMV-I and PPSMV-II isolates in southern India revealed significant divergence especially PPSMV-II, which is closely related to the Fig mosaic virus (FMV) than PPSMV-I. In multilocation testing of pigeonpea genotypes for their broad-based resistance to SMD for two consecutive years, genotypes ICPL-16086 and ICPL-16087 showed resistance reaction (<10% incidence) in all three locations studied. Overall, the present study gives a clear idea about the host range of PPSMV-I and PPSMV-II, their molecular relationship, and sources of resistance. This information is critical for the development of reliable diagnostic tools and improved disease management strategies.
Dissemination of Resistant Escherichia coli Among Wild Birds, Rodents, Flies, and Calves on Dairy Farms
Authors: Hickman Rachel A. , Agarwal Viktoria , Sjöström Karin , Emanuelson Ulf , Fall Nils , Sternberg-Lewerin Susanna , Järhult Josef D.
Published: April 2022

Antimicrobial resistance (AMR) in bacteria in the livestock is a growing problem, partly due to inappropriate use of antimicrobial drugs. Antimicrobial use (AMU) occurs in Swedish dairy farming but is restricted to the treatment of sick animals based on prescription by a veterinary practitioner. Despite these strict rules, calves shedding antimicrobial resistant Enterobacteriaceae have been recorded both in dairy farms and in slaughterhouses. Yet, not much is known how these bacteria disseminate into the local environment around dairy farms. In this study, we collected samples from four animal sources (fecal samples from calves, birds and rodents, and whole flies) and two environmental sources (cow manure drains and manure pits). From the samples, Escherichia coli was isolated and antimicrobial susceptibility testing performed. A subset of isolates was whole genome sequenced to evaluate relatedness between sources and genomic determinants such as antimicrobial resistance genes (ARGs) and the presence of plasmids were assessed. We detected both ARGs, mobile genetic elements and low rates of AMR. In particular, we observed four potential instances of bacterial clonal sharing in two different animal sources. This demonstrates resistant E. coli dissemination potential within the dairy farm, between calves and scavenger animals (rodents and flies). AMR dissemination and the zoonotic AMR risk is generally low in countries with low and restricted AMU. However, we show that interspecies dissemination does occur, and in countries that have little to no AMU restrictions this risk could be under-estimated.
Psychoactive Effects of Lactobacillus johnsonii BS15 on Preventing Memory Dysfunction Induced by Acute Ethanol Exposure Through Modulating Intestinal Microenvironment and Improving Alcohol Metabolic Level
Authors: Sun Ning , Zhu Bin , Xin Jinge , Li Lianxin , Gan Baoxing , Cao Xi , Fang Jing , Pan Kangcheng , Jing Bo , Zeng Yan , Lv Cheng , Zhao Ling , Zeng Dong , Xu Peng , Wang Hesong , Ni Xueqin
Published: April 2022

The negative effects of ethanol (EtOH) abuse on the body have been widely reported in recent years. Building on the microbiota-gut-brain axis hypothesis, our study aimed to demonstrate the potential psychobiotic role of Lactobacillus johnsonii BS15 in the preventive effects of acute EtOH intake on memory impairment. We also determined whether L. johnsonii BS15 intake could effectively improve resistance to acute drinking and alleviate the adverse effects of EtOH. Male mice were fed L. johnsonii BS15 orally with (Probiotic group) or without (Control and Alcohol groups) daily dose of 0.2 × 109 CFU/ml per mouse for 28 days. Gavage with L. johnsonii BS15 significantly modified the ileal microbial ecosystem (assessed by 16S rRNA gene sequencing) in favor of Firmicutes and Lactobacillus, indicating the ability of BS15 to restore the gut microbiota. The acute EtOH exposure model (7 g/kg EtOH per mice) was established by gavage, which was administered to the alcohol and probiotic groups on day 28 of the experiment. The L. johnsonii BS15 intake effectively reduced alcohol unconsciousness time, blood alcohol concentration, and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Meanwhile, the improvement of ethanol resistance time and the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver were shown by BS15 in acute alcohol-induced mice. We found that acute EtOH exposure reduced the exploration ratio (assessed by the novel object recognition test), escape latency, number of errors (assessed by passive avoidance test), and spontaneous exploration (assessed by T-maze test) in mice, which were obviously improved by L. johnsonii BS15. In the hippocampus, L. johnsonii BS15 significantly reversed the decrease in antioxidant capacity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) and mRNA expression of memory-related functional proteins of brain-derived neurotrophic factor (BDNF) and cyclic ampresponse element binding protein (CREB) in the hippocampal tissue after acute EtOH exposure. In conclusion, L. johnsonii BS15 intake appears as a promising psychoactive therapy to ameliorate alcohol-mediated memory impairment by increasing EtOH metabolic levels.
Lactate Albumin Ratio Is Associated With Mortality in Patients With Moderate to Severe Traumatic Brain Injury
Authors: Wang Ruoran , He Min , Qu Fengyi , Zhang Jing , Xu Jianguo
Published: April 2022

Background

Traumatic brain injury (TBI) is a serious public health issue all over the world. This study was designed to evaluate the prognostic value of lactate to albumin ratio (LAR) on patients with moderate to severe TBI.

Methods

Clinical data of 273 moderate to severe TBI patients hospitalized in West China Hospital between May 2015 and January 2018 were collected. Multivariate logistic regression analyses were used to explore risk factors and construct a prognostic model of in-hospital mortality in this cohort. A receiver operating characteristic (ROC) curve was drawn to evaluate the discriminative ability of this model.

Results

Non-survivors had higher LAR than survivors (1.09 vs. 0.53, p < 0.001). Results of multivariate logistic regression analysis showed that Glasgow Coma Scale (GCS; odds ratio [OR] = 0.743, p = 0.001), blood glucose (OR = 1.132, p = 0.005), LAR (OR = 1.698, p = 0.022), subdural hematoma (SDH; OR = 2.889, p = 0.006), intraparenchymal hemorrhage (IPH; OR = 2.395, p = 0.014), and diffuse axonal injury (DAI; OR = 2.183, p = 0.041) were independent risk factors of in-hospital mortality in included patients. These six factors were utilized to construct the prognostic model. The area under the ROC curve (AUC) values of single lactate, albumin, and LAR were 0.733 (95% Cl; 0.673–0.794), 0.740 (95% Cl; 0.683–0.797), and 0.780 (95% Cl; 0.725–0.835), respectively. The AUC value of the prognostic model was 0.857 (95%Cl; 0.812–0.901), which was higher than that of LAR (Z = 2.1250, p < 0.05).

Conclusions

Lactate to albumin ratio is a readily available prognostic marker of moderate to severe TBI patients. A prognostic model incorporating LAR is beneficial for clinicians to evaluate possible progression and make treatment decisions in TBI patients.
Cerebral Blood Flow Disorder in Acute Subdural Hematoma and Acute Intraoperative Brain Bulge
Authors: Xian Liang , Wang Cheng , Wei Liangfeng , Wang Shousen
Published: April 2022

Context

Acute subdural hematoma (ASDH) has a high incidence and high mortality. During surgery for ASDH, brain tissue sometimes rapidly swells and protrudes into the bone window during or after removal of the hematoma. This phenomenon, known as acute intraoperative brain bulge, progresses rapidly and can cause ischemic necrosis of brain tissue or even mortality. The mechanism of this phenomenon remains unclear.

Objective

To investigate the changes in cerebral surface blood flow during ASDH and acute intraoperative brain bulge in rats.

Methods

Adult male Sprague–Dawley rats were selected to establish an ASDH model, and acute intraoperative brain bulge was induced by late-onset intracranial hematoma. The changes in cerebral surface blood flow during ASDH and acute intraoperative brain bulge were observed with a laser speckle imaging system, and intracranial pressure (ICP) was monitored.

Results

ICP in rats increased significantly after ASDH (P < 0.05). The blood perfusion rate (BPR) values of the superior sagittal sinus, collateral vein and artery decreased significantly in rats with subdural hematomas (P < 0.05). There was no significant difference between the preoperative and 90-min postoperative BPR values of rats. ICP was significantly increased in rats with acute intraoperative brain bulge (P < 0.05) and decreased significantly after the removal of delayed hematomas (P < 0.05). The BPR of the superior sagittal sinus, collateral vein and artery decreased significantly during brain bulge (P < 0.05). After the removal of delayed hematomas, BPR increased significantly, but it remained significantly different from the values measured before brain bulge (P < 0.05).

Conclusion

ASDH may cause not only high intracranial pressure but also cerebral blood circulation disorders. Brain bulge resulting from late-onset intracranial hematoma may aggravate these circulation disorders. If the cause of brain bulge in a given patient is late-onset intracranial hematoma, clinicians should promptly perform surgery to remove the hematoma and relieve circulation disorders, thus preventing more serious complications.
Obesity, Psychological Distress, and Resting State Connectivity of the Hippocampus and Amygdala Among Women With Early-Stage Breast Cancer
Authors: Donofry Shannon D. , Lesnovskaya Alina , Drake Jermon A. , Ripperger Hayley S. , Gilmore Alysha D. , Donahue Patrick T. , Crisafio Mary E. , Grove George , Gentry Amanda L. , Sereika Susan M. , Bender Catherine M. , Erickson Kirk I.
Published: April 2022

Objective

Overweight and obesity [body mass index (BMI) ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity (rsFC) among women with breast cancer.

Methods

The sample included 34 post-menopausal women newly diagnosed with Stage 0-IIa breast cancer (Mage = 63.59 ± 5.73) who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety.

Results

Mean BMI was in the obese range (M = 31.83 ± 6.62). For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex (PFC), including ventrolateral PFC (vlPFC), dorsolateral PFC, and superior frontal gyrus (z range = 2.85–4.26). Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety (β = 0.47, p < 0.01).

Conclusion

Higher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted.
Sex-Associated Differences in Neurovascular Dysfunction During Ischemic Stroke
Authors: Tang Tianchi , Hu Libin , Liu Yang , Fu Xiongjie , Li Jianru , Yan Feng , Cao Shenglong , Chen Gao
Published: April 2022

Neurovascular units (NVUs) are basic functional units in the central nervous system and include neurons, astrocytes and vascular compartments. Ischemic stroke triggers not only neuronal damage, but also dissonance of intercellular crosstalk within the NVU. Stroke is sexually dimorphic, but the sex-associated differences involved in stroke-induced neurovascular dysfunction are studied in a limited extend. Preclinical studies have found that in rodent models of stroke, females have less neuronal loss, stronger repairing potential of astrocytes and more stable vascular conjunction; these properties are highly related to the cerebroprotective effects of female hormones. However, in humans, these research findings may be applicable only to premenopausal stroke patients. Women who have had a stroke usually have poorer outcomes compared to men, and because stoke is age-related, hormone replacement therapy for postmenopausal women may exacerbate stroke symptoms, which contradicts the findings of most preclinical studies. This stark contrast between clinical and laboratory findings suggests that understanding of neurovascular differences between the sexes is limited. Actually, apart from gonadal hormones, differences in neuroinflammation as well as genetics and epigenetics promote the sexual dimorphism of NVU functions. In this review, we summarize the confirmed sex-associated differences in NVUs during ischemic stroke and the possible contributing mechanisms. We also describe the gap between clinical and preclinical studies in terms of sexual dimorphism.
Effect of Moderate-to-Severe Iodine Deficiency in Early Pregnancy on Subclinical Hypothyroidism: A Longitudinal Study in an Iodine-Sufficient Region in China
Authors: Wang Taotao , Liu Yanqiu , Kong Qianqian , Cao Xiaoxia , Liu Yuzhou , Xia Song , Zheng Tingting , Yu Li
Published: April 2022

Objective

To investigate iodine status among pregnant women in an iodine-sufficient region in China after the implementation of revised universal salt iodization (USI) standards in 2012 and assess the association between urinary iodine concentrations (UIC) in early pregnancy and the incidence of subclinical hypothyroidism (SCH) in euthyroid women negative for antithyroid Ab during different trimesters.

Methods

We measured the iodine status of 1,264 pregnant women, and performed follow-up assessment of thyroid function at 20 and 30 weeks of gestation among a cohort of 250 euthyroid women. We assessed the association of UIC in the 1st trimester with the incidence of SCH in subsequent trimesters. UIC and serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured.

Results

The median UIC was 135.95 μg/L among 1,264 women. Serum FT4 level was significantly higher in the group of UIC 150 to 249 μg/L compared with other UIC groups (P < 0.001). TSH was significantly higher in the UIC more than or equal to 250 μg/L group than the UIC 150 to 249 g/L group (P = 0.043). Of the 250 euthyroid women negative for antithyroid Ab (TSH value of 2.5–3.55 mU/L) in the 1st trimester, pregnant women with UIC lower than 100 μg/L in the 1st trimester exhibited a significantly increased risk of SCH (odds ratio [OR] = 2.47; 95% confidence interval [CI] = 1.22–5.71; P = 0.012, according to the Chinese Medical Association criteria; OR = 5.22, 95% CI = 1.73–6.09, P = 0.004, according to ATA criteria) during the latter half of pregnancy compared with the UIC 150 to 249 μg/L group.

Conclusion

Moderate-to-severe iodine deficiency (UIC lower than 100 μg/L) in the 1st trimester was associated with a significantly higher risk of SCH during the 2nd or 3rd trimesters among euthyroid pregnant women who had negative for antithyroid Ab. Women with SCH during pregnancy require regular UIC tests to maintain appropriate iodine status.
Association of Modified Geriatric Nutrition Risk Index and Handgrip Strength With Survival in Cancer: A Multi-Centre Cohort Study
Authors: Xie Hailun , Ruan Guotian , Zhang Heyang , Zhang Qi , Ge Yizhong , Song Mengmeng , Zhang Xi , Lin Shiqi , Liu Xiaoyue , Liu Yuying , Zhang Xiaowei , Li Xiangrui , Zhang Kangping , Yang Ming , Tang Meng , Li Zengning , Shi Hanping
Published: April 2022

Background

This study aimed to explore the value of combining the modified geriatric nutrition risk index (mGNRI) and handgrip strength (HGS) in the prognosis assessment of cancer.

Methods

This multicenter, prospective cohort study, enrolled 5,607 cancer patients from 27 medical centers across 17 provinces in China between June 2012 and December 2019. The primary outcome was overall survival. Secondary outcomes included the Karnofsky Performance Scale (KPS) score, Patient-Generated Subjective Global Assessment (PG-SGA) score, cachexia, and admission 90-day outcome. A composite prognostic score (mGNRI-HGS score) was developed based on the mGNRI and HGS. The Kaplan–Meier method was used to draw the survival curve, and log-rank analysis was used to estimate the survival rate. The Cox proportional hazards model was used to investigate the associations of the mGNRI, HGS or mGNRI-HGS score with risk of mortality among the cancer patients, adjusted for potential confounders.

Results

A low mGNRI (HR = 0.99, 95%CI = 0.98–0.99, p < 0.001) and low HGS (HR = 0.99, 95%CI = 0.98–0.99, p = 0.001) were associated with an increased risk of mortality. A severe mGNRI-HGS score was independently associated with reduced survival. Compared with patients with normal scores, the risk of mortality among the patients with moderate and severe mGNRI-HGS scores was 28.8 and 13.3% higher, respectively. Even within the same pathological stage, it presented significant gradient prognostic stratification. Additionally, a low mGNRI-HGS score was also independently associated with a higher risk of low KPS (p < 0.001), high PGSGA (p < 0.001), cachexia (p < 0.001), and adverse admission 90-day outcome (p < 0.001).

Conclusions

The mGNRI and HGS may be useful predictors of long-term prognosis in cancer patients. The combination of the two methods provides effective prognostic stratification for cancer patients and could predict physical frailty, malnutrition, and cachexia.
Accurate Prediction of Metachronous Liver Metastasis in Stage I-III Colorectal Cancer Patients Using Deep Learning With Digital Pathological Images
Authors: Xiao Chanchan , Zhou Meihua , Yang Xihua , Wang Haoyun , Tang Zhen , Zhou Zheng , Tian Zeyu , Liu Qi , Li Xiaojie , Jiang Wei , Luo Jihui
Published: April 2022

Objectives

Metachronous liver metastasis (LM) significantly impacts the prognosis of stage I-III colorectal cancer (CRC) patients. An effective biomarker to predict LM after surgery is urgently needed. We aimed to develop deep learning-based models to assist in predicting LM in stage I-III CRC patients using digital pathological images.

Methods

Six-hundred eleven patients were retrospectively included in the study and randomly divided into training (428 patients) and validation (183 patients) cohorts according to the 7:3 ratio. Digital HE images from training cohort patients were used to construct the LM risk score based on a 50-layer residual convolutional neural network (ResNet-50). An LM prediction model was established by multivariable Cox analysis and confirmed in the validation cohort. The performance of the integrated nomogram was assessed with respect to its calibration, discrimination, and clinical application value.

Results

Patients were divided into low- and high-LM risk score groups according to the cutoff value and significant differences were observed in the LM of the different risk score groups in the training and validation cohorts (P<0.001). Multivariable analysis revealed that the LM risk score, VELIPI, pT stage and pN stage were independent predictors of LM. Then, the prediction model was developed and presented as a nomogram to predict the 1-, 2-, and 3-year probability of LM. The integrated nomogram achieved satisfactory discrimination, with C-indexes of 0.807 (95% CI: 0.787, 0.827) and 0.812 (95% CI: 0.773, 0.850) and AUCs of 0.840 (95% CI: 0.795, 0.885) and 0.848 (95% CI: 0.766, 0.931) in the training and validation cohorts, respectively. Favorable calibration of the nomogram was confirmed in the training and validation cohorts. Integrated discrimination improvement and net reclassification index indicated that the integrated nomogram was superior to the traditional clinicopathological model. Decision curve analysis confirmed that the nomogram has clinical application value.

Conclusions

The LM risk score based on ResNet-50 and digital HE images was significantly associated with LM. The integrated nomogram could identify stage I-III CRC patients at high risk of LM after primary colectomy, so it may serve as a potential tool to choose the appropriate treatment to improve the prognosis of stage I-III CRC patients.
All the Routes for Laparoscopic Liver Segment VIII Resection: A Comprehensive Review of Surgical Techniques
Authors: Anselmo Alessandro , Sensi Bruno , Bacchiocchi Giulia , Siragusa Leandro , Tisone Giuseppe
Published: April 2022

Liver surgery is highly demanding for anatomical, physiological and technical reasons, and minimally invasive approaches have been implemented at a slower rate. Today, laparoscopic liver resection is a standard of care in many occasions, yet specific operations remain particularly challenging and generally performed in open surgery. In particular, SVIII resection may be considered one of the most difficult due to anatomical characteristics including its sub-diaphragmatic position, the deep-lying Glissonean pedicle and the close contact with the inferior vena cava and right and middle hepatic veins. Many techniques have risen to overcome technical difficulties, and today laparoscopic SVIII resection has been demonstrated to be feasible. This review provides a complete picture of current approaches, focusing on all techniques reported so far with critical appraisal of each, discussing and explaining benefits and pitfalls.
The Therapeutic Effect and Clinical Outcome of Immune Checkpoint Inhibitors on Bone Metastasis in Advanced Non-Small-Cell Lung Cancer
Authors: Asano Yohei , Yamamoto Norio , Demura Satoru , Hayashi Katsuhiro , Takeuchi Akihiko , Kato Satoshi , Miwa Shinji , Igarashi Kentaro , Higuchi Takashi , Yonezawa Hirotaka , Araki Yoshihiro , Morinaga Sei , Saito Shiro , Sone Takashi , Kasahara Kazuo , Tsuchiya Hiroyuki
Published: April 2022

Introduction

In advanced non-small-cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) have been reported a better treatment outcome on primary lesions, however, the therapeutic effect on bone metastases has not been clarified. This study investigates the therapeutic effect of ICIs on bone metastases in advanced NSCLC.

Methods

The data of patients with advanced NSCLC, treated with ICIs from 2016 to 2019 at our hospital, were analyzed. The therapeutic effects of ICIs on primary lung and metastatic bone lesions, concomitant use of bone modifying agents (BMA), treatment outcomes, and frequency of immune-related adverse events (irAEs) and skeletal-related events (SREs) were investigated.

Results

A total of 29 patients were included (19 men and 10 women; mean age, 64.2 years). Among the ICIs, pembrolizumab was the most used (55.2%), and concomitant use of BMA was prevalent in 21 patients (zoledronic acid=1, denosumab=20). The therapeutic effect was partial response (PR) in 10.3% (n=3) on primary lung lesions by RECIST 1.1, complete response (CR) in 6.9% (n=2) and PR in 17.2% (n=5) on bone metastatic lesions by MDA criteria. ICIs suppressed the progression of bone metastasis in 21 cases (72.4%). All patients in CR and PR were treated with pembrolizumab and denosumab. SREs and irAEs were developed in 3.4% (n=1) and 20.7% (n=6), respectively. The median survival time after treatment with ICIs was 11.0 months. Concomitant therapy with ICIs and denosumab significantly prolonged the overall survival compared to ICI-only therapy (16.0 months vs. 2.5 months, p<0.01).

Conclusions

This study showed that treatment with ICIs may successfully suppress the progression of bone metastasis in advanced NSCLC. Pembrolizumab with denosumab had the highest therapeutic effect on both primary lung lesions and bone metastases. Systemic treatment with this combination and conservative treatment of bone metastasis could be one of the options in the treatment of advanced NSCLC.
Renal Cell Carcinoma Associated With HIV/AIDS: A Review of the Epidemiology, Risk Factors, Diagnosis, and Treatment
Authors: Zhu Zhiqiang , Zhang Yihang , Wang Hu , Jiang Taiyi , Zhang Mengmeng , Zhang Yu , Su Bin , Tian Ye
Published: April 2022

Renal cell carcinoma (RCC), one of the most common genitourinary tumors, is induced by many factors, primarily smoking, obesity, and hypertension. As a non-acquired immunodeficiency syndrome (AIDS)-defining cancer, human immunodeficiency virus (HIV) may also play a critical role in the incidence and progression of RCC. It is evident that individuals who are infected with HIV are more likely than the general population to develop RCC. The age of RCC diagnosis among HIV-positive patients is younger than among HIV-negative individuals. However, many other characteristics remain unknown. With the increase in RCC incidence among HIV-infected patients, more research is being conducted to discover the relationship between RCC and HIV, especially with regard to HIV-induced immunodeficiency, diagnosis, and treatment. Unexpectedly, the majority of the literature suggests that there is no relationship between RCC and HIV-induced immunodeficiency. Nonetheless, differences in pathology, symptoms, or treatment in HIV-positive patients diagnosed with RCC are a focus. In this review, we summarize the association of RCC with HIV in terms of epidemiology, risk factors, diagnosis, and treatment.
Longitudinal Outcomes and Monitoring of Patients With Multisystem Inflammatory Syndrome in Children
Authors: Fremed Michael A. , Farooqi Kanwal M.
Published: April 2022

The acute manifestations and short-term outcomes of multisystem inflammatory syndrome (MIS-C) have been extensively described; however, our understanding of the longitudinal outcomes associated with this condition continue to evolve. Here we review the existing literature on outcomes of MIS-C up to 1 year following diagnosis and summarize current published expert recommendations for management and follow up of these patients.
Access to Insulin Products in Pakistan: A National Scale Cross-Sectional Survey on Prices, Availability, and Affordability
Authors: Saeed Amna , Lambojon Krizzia , Saeed Hamid , Saleem Zikria , Anwer Naveed , Aziz Muhammad Majid , Ji Wenjing , Liu Wenchen , Chen Chen , Yang Caijun , Fang Yu , Babar Zaheer-Ud-Din
Published: April 2022

Background: Diabetes is among the top ten most prevalent diseases in Pakistan, and the availability of medicines to treat the disease is vital for a great percentage of the country’s population. Insulin was discovered a century ago; however, its access in several parts of the globe remains an issue. This study aims to evaluate prices, availability, and affordability (access components) of insulin and five comparator medicine access in Pakistan.

Methods: A nationwide cross-sectional survey was conducted to evaluate the access to insulin and some comparator medicines in eight cities of Pakistan, using a modified WHO/HAI methodology. The survey included 80 medicine outlets, i.e., 40 private pharmacies and 40 public hospitals. Data for every unique insulin product available in the Pakistani market were obtained, including five comparator medicines. Percentage availability, median unit prices (MUPs), and affordability (the number of days’ wages (NDWs) required for a month’s course by the lowest-paid unskilled government worker) of all products were calculated, including originator brands (OBs) and biosimilar (BS) products.

Results: Of all insulin products surveyed (n = 320), 87.5% were manufactured by foreign multinational companies (MNCs). None of the insulin products had an ideal availability of 80% in any of the surveyed health facilities. In the public sector, none of the insulin products had an availability of more than 50%. In the public sector, the overall availability of human insulin was 70% (including OB and BS). While in the private sector, the overall availability of human insulin was 90% and that of analog insulin was 62.5%. The analog insulin products were 72.8% costlier than the human insulin products. The median prices of BS insulin were 25.4% lower than the OB products, indicating that almost one-fourth of the cost could be saved by switching to BS human insulin from OB human insulin. All oral anti-diabetic medicines were found to be affordable, whereas none of the insulin was affordable. The NDWs for human and analog insulin were 1.38 and 5.06.

Conclusion: In Pakistan, the insulin availability falls short of the WHO’s benchmark of 80%. Insulin continues to be unaffordable in both private and government sectors. To increase insulin access, the government should optimize insulin procurement at all levels, promote local production, enforce biosimilar prescribing, and provide financial subsidies for these products.
Precipitation Patterns in Reaction–Diffusion–Reaction Systems of Prussian Blue and Cu–Fe-Based Prussian Blue Analogs
Authors: Hayashi Hisashi
Published: April 2022

In agarose gel containing [Fe(CN)6]3‒ions and sandwiched between two metal rods (Ti, Fe, or Cu) with a voltage of 1‒5 V applied for 20–100 h, reaction–diffusion–reaction (RDR) processes (that is, electrochemical reactions at metal rods to generate reactant ions, diffusion of the reactant ions influenced by the electric field in agarose gel, and reactions of the reactant ions to form/decompose precipitates) were coupled to generate diverse precipitation patterns of Prussian blues (PB) or Cu–Fe-based Prussian blue analogs (Cu–Fe PBA). These patterns strongly depended on the type of metal electrode, applied voltage, initial [Fe(CN)6]3‒concentration, and elapsed time after voltage application. Under the application of 2 V for 20/50 h, the PB/Cu–Fe PBA formed a discrete precipitation band on the anode/cathode side in an agarose gel containing 0.050 M [Fe(CN)6]3‒ions. In the Cu–Fe PBA system, a relatively long precipitation band of Cu(OH)2was also generated on the anode side by OH−ions produced on the cathode as a byproduct. Longer voltage applications promoted propagation of the Cu–Fe PBA band to the anode side and caused the discrete PB band to disappear. Higher initial [Fe(CN)6]3‒concentrations deepened the color of the generated patterns. Higher voltage applications suppressed the propagation of the Cu–Fe PBA band to the anode side and caused the PB band to disappear. Experiments using a Ti cathode suggested that the formation and subsequent decomposition of PB or Cu–Fe PBA at the cathode surface are important for forming precipitation band(s) in the gel near the cathode. The application of cyclic alternating voltages (particularly, 4 V for 1 h and 1 V for 4 h) was effective in generating Liesegang-band-like periodic bands, particularly for the Cu–Fe PBA system.