bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic characterization of two carbapenem-resistant Serratia marcescens isolates causing bacteremia: Emergence of KPC-2-encoding IncR plasmids
Authors: Jia Junli , Huang Lisha , Zhang Long , Sheng Yanbing , Chu Weili , Xu Hao , Xu Aiguo
Published: February 2023

The occurrence and transmission of carbapenemase-producing-Enterobacterales (CPE) on a global scale has become a major issue. Clinical reports are rarely providing information on the genomic and plasmid features of carbapenem-resistant Serratia marcescens. Our objective was to investigate the resistance and transmission dynamics of two carbapenem-resistant S. marcescens that are resistant to carbapenem and have caused bacteremia in China. Blood specimens were taken from two individuals with bacteremia. Multiplex PCR was employed to identify genes that code for carbapenemase. Antimicrobial susceptibility tests and plasmid analysis were conducted on S. marcescens isolates SM768 and SM4145. The genome of SM768 and SM4145 were completely sequenced using NovaSeq 6000-PE150 and PacBio RS II platforms. Antimicrobial resistance genes (ARGs) were predicted using the ResFinder tool. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and southern blotting were employed to analyze plasmids. Two S. marcescens that produced KPC-2 were identified from bloodstream infections. The antimicrobial susceptibility testing demonstrated that both of the isolates had a resistance to various antibiotics. The whole-genome sequence (WGS) and plasmid analysis revealed the presence of blaKPC-2-bearing IncR plasmids and multiple plasmid-borne antimicrobial resistance genes in the isolates. Our comparative plasmid analysis suggested that the two IncR plasmids identified in this study could be derived from a common ancestor. Our findings revealed the emergence of blaKPC-2-bearing IncR plasmid in China, which could be a hindrance to the transmission of KPC-2-producing S. marcescens in clinical settings.
Case report: Persistent ST-segment elevation due to cardiac metastasis from lung cancer
Authors: Zhou Jiawei , Zhan Chengchuang , Zhou Jing , Wei Chao , Zou Cao
Published: February 2023

Patients with secondary cardiac cancer occasionally show ST segment elevation that mimics acute coronary syndrome despite the absence of coronary artery occlusion. We herein describe a rare case of secondary cardiac cancer that presented with ST-segment elevation. An 82-year-old Chinese man was admitted to the hospital with chest discomfort. Electrocardiography (ECG) showed ST segment elevation in the precordial leads and low-voltage QRS complexes in limb leads without the development of Q waves. Unexpectedly, emergency coronary angiography showed no significant stenosis of the coronary arteries. However, fortunately, transthoracic echocardiography (TTE) revealed massive pericardial effusion and a mass at the apex of the ventricular myocardium. Coincidentally, contrast-enhanced chest computed tomography showed primary lung cancer in the left lower lobe, pericardial effusion, and myocardial metastasis at the ventricular apex. The pericardiac fluid contained blood with significantly increased CEA levels and exfoliated tumor cells. The lung histopathological report suggested squamous cell carcinoma. Two months later, the patient died. These findings suggested that the persistent ST-segment without the development of Q waves was associated with ventricular invasion by primary lung cancer and may indicate a poor prognosis. In conclusion, physicians should be aware of persistent ST-segment elevation mimicking myocardial infarction due to cardiac metastasis with a poor prognosis.
Impacts and causative fault of the 2022 magnitude (Mw) 7.0 Northwestern Luzon earthquake, Philippines
Authors: Perez Jeffrey S. , Llamas Deo Carlo E. , Dizon Margarita P. , Buhay Daniel Jose L. , Legaspi Crystel Jade M. , Lagunsad Kristine Dionne B. , Constantino Ryan Christian C. , De Leon Roland Joseph B. , Quimson Marc Marion Y. , Grutas Rhommel N. , Pitapit Ron Stephen D. , Rocamora Cyrah Gale H. , Pedrosa Mike Gabriel G.
Published: February 2023

At 00:43 UTC on 27 July 2022, a 15-km deep major earthquake with magnitude (Mw) 7.0 struck Northwestern Luzon, Philippines. The strongest ground shaking felt was at PHIVOLCS Earthquake Intensity Scale (PEIS) VII (destructive), equivalent to Modified Mercalli Intensity (MMI) VII, in Abra and along the coastal areas of Ilocos Sur. More than a thousand landslides, rockfalls and tension cracks were mapped, near the epicentral region, in the northwestern part of the Central Cordillera. Most of the landslides were shallow-seated, many of which were situated along road cuts. Liquefaction manifested as lateral spreads, sand boils, fissures, ground subsidence, and localized swelling was documented along the coastal areas of Ilocos Sur and river channels in Abra and Ilocos Sur. Sea level disturbance was also observed in some coastal areas of Ilocos Sur and La Union. Damages to buildings and infrastructures were documented in areas that experienced PEIS VI (very strong), equivalent to MMI VI and PEIS VII (destructive). Earthquake data, including hypocentral location, aftershock distribution, focal mechanism solutions and strong motion data, and InSAR observation indicate that the earthquake was generated by an almost north-south striking reverse left-lateral oblique fault that is gently dipping to the east. There is no clear indication of a surface rupture based on InSAR analysis and field investigation. The spatial distribution of geologic impacts, such as earthquake-induced landslides and liquefaction, is strongly controlled by the causative fault, the direction of rupture propagation and geology. Peak ground acceleration (PGA) records show a unidirectional rupture propagation and are congruent with the spatial distribution of earthquake impacts. Although earthquake parameters, deformation analysis and field data suggest that the Abra River Fault is the probable causative fault, the derived geometry and kinematics from the seismotectonic analysis challenge our existing understanding of the nature of the Abra River Fault, as well as the other segments of the Philippine Fault. The need to understand these earthquake sources in the country is needed for a better seismic hazard and risk assessment.
Fracture propagation induced by hydraulic fracturing using microseismic monitoring technology: Field test in CBM wells in Zhengzhuang region, Southern Qinshui Basin, China
Authors: Zhao Jinbin , Liu Peng , Li Junjun , Chen Zhaoying , Li Yang , Li Feng
Published: February 2023

Hydraulic fracturing is an important technical measure for coalbed methane (CBM) development, and the propagation of fractures in the target coal seam induced by hydraulic fracturing is related to the stimulation performance in CBM recovery. Therefore, effective monitoring of fracture development during reservoir fracturing is critical for CBM engineering. In this paper, the microseismic technology was used to monitor the spatial and temporal characteristics of the fracture extension in the CBM well during hydraulic fracturing in Zhengzhuang Region, Southern Qinshui Basin, China. Based on the microseismic fracture scanning data and imaging processing, the three-dimensional shape of fractures in vertical wells after fracturing can be quantified, and for the vertical well ZHSY-1, the main fracture direction is identified as NE106°, and the fracture length is 426 m, and the fracture area of coal seam is 1.6 × 105 m2. It is found that fracturing does not develop continuously in time and space with fracturing fluid injection, and the fracture regions are scattered throughout the space, and the formation and development of fracture regions are intermittent. After fracturing with a large amount of fracturing fluid injection in Well ZHSY-1, the fracture area has been significantly increased, and the well gas production has been significantly improved, which is confirmed by the field CBM well data. This study provides a field application case for studying the effect of hydraulic fracturing fracture propagation using microseismic technology, which can be used as a reference for fracturing engineering in CBM development.
The relationship between fat distribution in central region and comorbidities in obese people: Based on NHANES 2011–2018
Authors: Liu Chen-An , Liu Tong , Ruan Guo-Tian , Ge Yi-Zhong , Song Meng-Meng , Xie Hai-Lun , Lin Shi-Qi , Deng Li , Zhang He-Yang , Zhang Qi , Shi Han-Ping
Published: February 2023

Background

Central obesity is closely related to comorbidity, while the relationship between fat accumulation pattern and abnormal distribution in different parts of the central region of obese people and comorbidity is not clear. This study aimed to explore the relationship between fat distribution in central region and comorbidity among obese participants.

Methods

We used observational data of NHANES 2011–2018 to identify 12 obesity-related comorbidities in 7 categories based on questionnaire responses from participants. Fat distribution is expressed by fat ratio, including Android, Gynoid, visceral, subcutaneous, visceral/subcutaneous (V/S), and total abdominal fat ratio. Logistic regression analysis were utilized to elucidate the association between fat distribution and comorbidity.

Results

The comorbidity rate was about 54.1% among 4899 obese participants (weighted 60,180,984, 41.35 ± 11.16 years, 57.5% female). There were differences in fat distribution across the sexes and ages. Among men, Android fat ratio (OR, 4.21, 95% CI, 1.54–11.50, Ptrend=0.007), visceral fat ratio (OR, 2.16, 95% CI, 1.42–3.29, Ptrend<0.001) and V/S (OR, 2.07, 95% CI, 1.43–2.99, Ptrend<0.001) were independent risk factors for comorbidity. Among these, there was a “J” shape correlation between Android fat ratio and comorbidity risk, while visceral fat ratio and V/S exhibited linear relationships with comorbidity risk. The Gynoid fat ratio (OR, 0.87, 95%CI, 0.80–0.95, Ptrend=0.001) and subcutaneous fat ratio (OR, 0.81, 95%CI, 0.67–0.98, Ptrend=0.016) both performed a protective role in the risk of comorbidity. In women, Android fat ratio (OR, 4.65, 95% CI, 2.11–10.24, Ptrend=0.020), visceral fat ratio (OR, 1.83, 95% CI, 1.31–2.56, Ptrend=0.001), and V/S (OR, 1.80, 95% CI, 1.32–2.45, Ptrend=0.020) were also independent risk factors for comorbidity, with a dose-response relationship similar to that of men. Only the Gynoid fat ratio (OR, 0.93, 95% CI, 0.87–0.99, Ptrend=0.016) had a protective effect on female comorbidity. This association was also seen in obese participants of different age groups, comorbidity numbers, and comorbidity types, although it was more statistically significant in older, complex comorbidity, cardiovascular, cerebrovascular, and metabolic diseases.

Conclusions

In the obese population, there were strong correlation between fat distribution in central region and comorbidity, which was affected by sex, age, number of comorbidities, and type of comorbidity.
Impact of land use and land cover change on the landscape pattern and service value of the village ecosystem in the karst desertification control
Authors: Wang Qi , Xiong Kangning , Zhou Jiayi , Xiao Hua , Song Shanhai
Published: February 2023

Human activities have had a significant impact on ecosystems. Studying landscape patterns and ecosystem services (ES) at the village scale based on land use and land cover (LULC) is essential in addressing current ecosystem issues. Based on GF images, the paper selects village ecosystems of karst desertification control (KDC) as the research object. It uses the landscape pattern index, topographic position index (TPI), and value equivalent method to conduct a spatial and temporal analysis of the ecosystem service value (ESV) of the karst desertification control cycle (2015–2020). The results show that: 1) forest land, orchard land, and construction land increase, and dryland and grassland decrease. The landscape shows an aggregated state, with spreading and connectivity increasing while fragrant diversity is decreasing. 2) The total ecosystem service value increased by CNY 63.45 × 104, with regulating and cultural services on the rise and supply and support services on the decline. 3) With the rise of the TPI, the value of the supply services is inversely U-shaped, while the value of the remaining services increases. This study provides a case study about karst desertification areas for village-scale ecosystem services research.
Autoantibody profiles in patients with immune checkpoint inhibitor-induced neurological immune related adverse events
Authors: Müller-Jensen Leonie , Knauss Samuel , Ginesta Roque Lorena , Schinke Christian , Maierhof Smilla K. , Bartels Frederik , Finke Carsten , Rentzsch Kristin , Ulrich Claas , Mohr Raphael , Stenzel Werner , Endres Matthias , Boehmerle Wolfgang , Huehnchen Petra
Published: February 2023

Background

Neurological immune-related adverse events (irAE-n) are severe and potentially fatal toxicities of immune checkpoint inhibitors (ICI). To date, the clinical significance of neuronal autoantibodies in irAE-n is poorly understood. Here, we characterize neuronal autoantibody profiles in patients with irAE-n and compare these with ICI-treated cancer patients without irAE-n.

Methods

In this cohort study (DRKS00012668), we consecutively collected clinical data and serum samples of 29 cancer patients with irAE-n (n = 2 pre-ICI, n = 29 post-ICI) and 44 cancer control patients without irAE-n (n = 44 pre- and post-ICI). Using indirect immunofluorescence and immunoblot assays, serum samples were tested for a large panel of neuromuscular and brain-reactive autoantibodies.

Results

IrAE-n patients and controls received ICI treatment targeting programmed death protein (PD-)1 (61% and 62%), programmed death ligand (PD-L)1 (18% and 33%) or PD-1 and cytotoxic T-lymphocyte-associated protein (CTLA-)4 (21% and 5%). Most common malignancies were melanoma (both 55%) and lung cancer (11% and 14%). IrAE-n affected the peripheral nervous system (59%), the central nervous system (21%), or both (21%). Prevalence of neuromuscular autoantibodies was 63% in irAE-n patients, which was higher compared to ICI-treated cancer patients without irAE-n (7%, p <.0001). Brain-reactive autoantibodies targeting surface (anti-GABABR, -NMDAR, -myelin), intracellular (anti-GFAP, -Zic4, -septin complex), or unknown antigens were detected in 13 irAE-n patients (45%). In contrast, only 9 of 44 controls (20%) presented brain-reactive autoantibodies before ICI administration. However, seven controls developed de novo brain-reactive autoantibodies after ICI initiation, therefore, prevalence of brain-reactive autoantibodies was comparable between ICI-treated patients with and without irAE-n (p = .36). While there was no clear association between specific brain-reactive autoantibodies and clinical presentation, presence of at least one of six selected neuromuscular autoantibodies (anti-titin, anti-skeletal muscle, anti-heart muscle, anti-LRP4, anti-RyR, anti-AchR) had a sensitivity of 80% (95% CI 0.52-0.96) and a specificity of 88% (95% CI 0.76-0.95) for the diagnosis of myositis, myocarditis, or myasthenia gravis.

Conclusion

Neuromuscular autoantibodies may serve as a feasible marker to diagnose and potentially predict life-threatening ICI-induced neuromuscular disease. However, brain-reactive autoantibodies are common in both ICI-treated patients with and without irAE-n, hence, their pathogenic significance remains unclear.
Risk factors for persistent tomographic abnormalities at 6 months of follow-up in a cohort of hospitalized patients with moderate and severe COVID-19 living at high altitude
Authors: Rincon-Alvarez Emily , Gonzalez-Garcia Mauricio , Ali-Munive Abraham , Casas Alejandro , Proaños Nadia Juliana , Giraldo-Cadavid Luis Fernando , Moreno Angelica , Pérez Carolina , Rubiano Wendy , Cogollo Mary , Parada-Tovar Patricia , Torres-Duque Carlos A.
Published: February 2023

Introduction

After COVID-19, functional and tomographic lung alterations may occur, but there are no studies at high altitude where, due to lower barometric pressure, there are lower levels of arterial oxygen pressure and saturation in both normal subjects and patients with respiratory disease. In this study, we evaluated the computed tomographic (CT), clinical, and functional involvement at 3 and 6 months post-hospitalization in survivors with moderate-severe COVID-19, as well the risk factors associated with abnormal lung computed tomography (ALCT) at 6 months of follow-up.

Materials and methods

Prospective cohort, after hospitalization for COVID-19, of patients older than 18 years residing at high altitude. Follow-up at 3 and 6 months with lung CT, spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), six-minute walk test (6MWT), and oxygen saturation (SpO2). Comparisons between ALCT and normal lung computed tomography (NLCT) groups with X2 and Mann–Whitney U test, and paired test for changes between 3 and 6 months. A multivariate analysis was performed to evaluate the variables associated with ALCT at 6-month follow-up.

Results

We included 158 patients, 22.2% hospitalized in intensive care unit (ICU), 92.4% with typical COVID CT scan (peripheral, bilateral, or multifocal ground glass, with or without consolidation or findings of organizing pneumonia), and median hospitalization of 7 days. At 6 months, 53 patients (33.5%) had ALCT. There were no differences between ALCT and NLCT groups in symptoms or comorbidities on admission. ALCT patients were older and more frequently men, smokers and hospitalized in ICU. At 3 months, ALCT patients had more frequently a reduced forced vital capacity (< 80%), and lower meters walked (6MWT) and SpO2. At 6 months, all patients improved lung function with no differences between groups, but there were more dyspnea and lower exercise SpO2 in ALCT group. The variables associated with ALCT at 6 months were age, sex, ICU stay, and typical CT scan.

Conclusion

At 6-month follow-up, 33.5% of patients with moderate and severe COVID had ALCT. These patients had more dyspnea and lower SpO2 in exercise. Regardless of the persistence of tomographic abnormalities, lung function and 6MWT improved. We identified the variables associated with ALCT.
Outcome prediction in hospitalized COVID-19 patients: Comparison of the performance of five severity scores
Authors: Chung Hsin-Pei , Tang Yen-Hsiang , Chen Chun-Yen , Chen Chao-Hsien , Chang Wen-Kuei , Kuo Kuan-Chih , Chen Yen-Ting , Wu Jou-Chun , Lin Chang-Yi , Wang Chieh-Jen
Published: February 2023

Background

The aim of our study was to externally validate the predictive capability of five developed coronavirus disease 2019 (COVID-19)-specific prognostic tools, including the COVID-19 Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Shang COVID severity score, COVID-intubation risk score-neutrophil/lymphocyte ratio (IRS-NLR), inflammation-based score, and ventilation in COVID estimator (VICE) score.

Methods

The medical records of all patients hospitalized for a laboratory-confirmed COVID-19 diagnosis between May 2021 and June 2021 were retrospectively analyzed. Data were extracted within the first 24 h of admission, and five different scores were calculated. The primary and secondary outcomes were 30-day mortality and mechanical ventilation, respectively.

Results

A total of 285 patients were enrolled in our cohort. Sixty-five patients (22.8%) were intubated with ventilator support, and the 30-day mortality rate was 8.8%. The Shang COVID severity score had the highest numerical area under the receiver operator characteristic (AUC-ROC) (AUC 0.836) curve to predict 30-day mortality, followed by the SEIMC score (AUC 0.807) and VICE score (AUC 0.804). For intubation, both the VICE and COVID-IRS-NLR scores had the highest AUC (AUC 0.82) compared to the inflammation-based score (AUC 0.69). The 30-day mortality increased steadily according to higher Shang COVID severity scores and SEIMC scores. The intubation rate exceeded 50% in the patients stratified by higher VICE scores and COVID-IRS-NLR score quintiles.

Conclusion

The discriminative performances of the SEIMC score and Shang COVID severity score are good for predicting the 30-day mortality of hospitalized COVID-19 patients. The COVID-IRS-NLR and VICE showed good performance for predicting invasive mechanical ventilation (IMV).
Limosilactobacillus reuteri administration alters the gut-brain-behavior axis in a sex-dependent manner in socially monogamous prairie voles
Authors: Donovan Meghan , Mackey Calvin S. , Lynch Michael D. J. , Platt Grayson N. , Brown Amber N. , Washburn Brian K. , Trickey Darryl J. , Curtis J. Thomas , Liu Yan , Charles Trevor C. , Wang Zuoxin , Jones Kathryn M.
Published: February 2023

Research on the role of gut microbiota in behavior has grown dramatically. The probiotic L. reuteri can alter social and stress-related behaviors – yet, the underlying mechanisms remain largely unknown. Although traditional laboratory rodents provide a foundation for examining the role of L. reuteri on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (Microtus ochrogaster), we examined the effects of L. reuteri administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live L. reuteri displayed lower levels of social affiliation compared to those treated with heat-killed L. reuteri. Overall, females displayed a lower level of anxiety-like behaviors than males. Live L. reuteri-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live L. reuteri increased the abundance of several taxa, including Enterobacteriaceae, Lachnospiraceae NK4A136, and Treponema. Interestingly, heat-killed L. reuteri increased abundance of the beneficial taxa Bifidobacteriaceae and Blautia. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that L. reuteri impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.
The potential neuroprotective effects of stingless bee honey
Authors: Zulkifli Nurdarina Ausi , Hassan Zurina , Mustafa Mohd Zulkifli , Azman Wan Norlina Wan , Hadie Siti Nurma Hanim , Ghani Nurhafizah , Mat Zin Anani Aila
Published: February 2023

Tropical Meliponini bees produce stingless bee honey (SBH). Studies have shown beneficial properties, including antibacterial, bacteriostatic, anti-inflammatory, neurotherapeutic, neuroprotective, wound, and sunburn healing capabilities. High phenolic acid and flavonoid concentrations offer SBH its benefits. SBH can include flavonoids, phenolic acids, ascorbic acid, tocopherol, organic acids, amino acids, and protein, depending on its botanical and geographic origins. Ursolic acid, p-coumaric acid, and gallic acid may diminish apoptotic signals in neuronal cells, such as nuclear morphological alterations and DNA fragmentation. Antioxidant activity minimizes reactive oxygen species (ROS) formation and lowers oxidative stress, inhibiting inflammation by decreasing enzymes generated during inflammation. Flavonoids in honey reduce neuroinflammation by decreasing proinflammatory cytokine and free radical production. Phytochemical components in honey, such as luteolin and phenylalanine, may aid neurological problems. A dietary amino acid, phenylalanine, may improve memory by functioning on brain-derived neurotrophic factor (BDNF) pathways. Neurotrophin BDNF binds to its major receptor, TrkB, and stimulates downstream signaling cascades, which are crucial for neurogenesis and synaptic plasticity. Through BDNF, SBH can stimulate synaptic plasticity and synaptogenesis, promoting learning and memory. Moreover, BDNF contributes to the adult brain’s lasting structural and functional changes during limbic epileptogenesis by acting through the cognate receptor tyrosine receptor kinase B (TrkB). Given the higher antioxidants activity of SBH than the Apis sp. honey, it may be more therapeutically helpful. There is minimal research on SBH’s neuroprotective effects, and the related pathways contribute to it is unclear. More research is needed to elucidate the underlying molecular process of SBH on BDNF/TrkB pathways in producing neuroprotective effects.
Case report: Intracranial lesions of cat-scratch disease mimicking an atypical meningioma
Authors: Fang Qiang , Wang Pengju , Qin Shanshan , Liu Shangxin , He Jingzhen
Published: February 2023

Objectives

Cat-scratch disease (CSD) is an infectious disease caused by Bartonella henselae. The most typical symptom of patients with CSD is regional lymphadenopathy, while central nervous system lesions related to CSD are rare. Here, we present a case of an aged woman with CSD involving the dura mater with a manifestation similar to that of an atypical meningioma.

Methods

The patient was followed up by our neurosurgery and radiology teams. Clinical information was recorded, and the pre- and post-operation CT results and magnetic resonance imaging (MRI) changes were collected. The paraffin-embedded tissue was sampled for the polymerase chain reaction (PCR) test.

Results

In this study, we present the details of a 54 year-old Chinese woman admitted to our hospital with a paroxysmal headache for 2 years that had worsened in the past 3 months. Brain CT and MRI showed a meningioma-like lesion below the occipital plate. En bloc resection of the sinus junction area was performed. A pathological examination showed granulation tissue and fibrosis with acute and chronic inflammation, granuloma, and central stellate microabscess, which was suspected as the cat-scratch disease. The paraffin-embedded tissue was sampled for a polymerase chain reaction (PCR) test to amplify the corresponding pathogen gene sequence, which was Bartonella henselae.

Conclusion

The case in our study underscores the fact that the incubation period of CSD may be very long. On the contrary, CSD can involve the meninges, resulting in tumor-like lesions.
ACT-R based human digital twin to enhance operators’ performance in process industries
Authors: Balaji Bharatwaajan , Shahab Mohammed Aatif , Srinivasan Babji , Srinivasan Rajagopalan
Published: February 2023

To ensure safe and efficient operation, operators in process industries have to make timely decisions based on time-varying information. A holistic assessment of operators’ performance is, therefore, challenging. Current approaches to operator performance assessment are subjective and ignore operators’ cognitive behavior. In addition, these cannot be used to predict operators’ expected responses during novel situations that may arise during plant operations. The present study seeks to develop a human digital twin (HDT) that can simulate a control room operator’s behavior, even during various abnormal situations. The HDT has been developed using the ACT-R (Adaptive Control of Thought-Rational) cognitive architecture. It mimics a human operator as they monitor the process and intervene during abnormal situations. We conducted 426 trials to test the HDT’s ability to handle disturbance rejection tasks. In these simulations, we varied the reward and penalty parameters to provide feedback to the HDT. We validated the HDT using the eye gaze behavior of 10 human subjects who completed 110 similar disturbance rejection tasks as that of the HDT. The results indicate that the HDT exhibits similar gaze behaviors as the human subjects, even when dealing with abnormal situations. These indicate that the HDT’s cognitive capabilities are comparable to those of human operators. As possible applications, the proposed HDT can be used to generate a large database of human behavior during abnormalities which can then be used to spot and rectify flaws in novice operator’s mental models. Additionally, the HDT can also enhance operators’ decision-making during real-time operation.
Fast discrimination of fragmentary images: the role of local optimal information
Authors: Castellotti Serena , D’Agostino Ottavia , Del Viva Maria Michela
Published: February 2023

In naturalistic conditions, objects in the scene may be partly occluded and the visual system has to recognize the whole image based on the little information contained in some visible fragments. Previous studies demonstrated that humans can successfully recognize severely occluded images, but the underlying mechanisms occurring in the early stages of visual processing are still poorly understood. The main objective of this work is to investigate the contribution of local information contained in a few visible fragments to image discrimination in fast vision. It has been already shown that a specific set of features, predicted by a constrained maximum-entropy model to be optimal carriers of information (optimal features), are used to build simplified early visual representations (primal sketch) that are sufficient for fast image discrimination. These features are also considered salient by the visual system and can guide visual attention when presented isolated in artificial stimuli. Here, we explore whether these local features also play a significant role in more natural settings, where all existing features are kept, but the overall available information is drastically reduced. Indeed, the task requires discrimination of naturalistic images based on a very brief presentation (25 ms) of a few small visible image fragments. In the main experiment, we reduced the possibility to perform the task based on global-luminance positional cues by presenting randomly inverted-contrast images, and we measured how much observers’ performance relies on the local features contained in the fragments or on global information. The size and the number of fragments were determined in two preliminary experiments. Results show that observers are very skilled in fast image discrimination, even when a drastic occlusion is applied. When observers cannot rely on the position of global-luminance information, the probability of correct discrimination increases when the visible fragments contain a high number of optimal features. These results suggest that such optimal local information contributes to the successful reconstruction of naturalistic images even in challenging conditions.
Acute effects of cochleostomy and electrode-array insertion on compound action potentials in normal-hearing guinea pigs
Authors: Jwair Saad , Ramekers Dyan , Thomeer Hans G. X. M. , Versnel Huib
Published: February 2023

Introduction

Electrocochleography (ECochG) is increasingly used in cochlear implant (CI) surgery, in order to monitor the effect of insertion of the electrode array aiming to preserve residual hearing. However, obtained results are often difficult to interpret. Here we aim to relate changes in ECochG responses to acute trauma induced by different stages of cochlear implantation by performing ECochG at multiple time points during the procedure in normal-hearing guinea pigs.

Materials and methods

Eleven normal-hearing guinea pigs received a gold-ball electrode that was fixed in the round-window niche. ECochG recordings were performed during the four steps of cochlear implantation using the gold-ball electrode: (1) Bullostomy to expose the round window, (2) hand-drilling of 0.5–0.6 mm cochleostomy in the basal turn near the round window, (3) insertion of a short flexible electrode array, and (4) withdrawal of electrode array. Acoustical stimuli were tones varying in frequency (0.25–16 kHz) and sound level. The ECochG signal was primarily analyzed in terms of threshold, amplitude, and latency of the compound action potential (CAP). Midmodiolar sections of the implanted cochleas were analyzed in terms of trauma to hair cells, modiolar wall, osseous spiral lamina (OSL) and lateral wall.

Results

Animals were assigned to cochlear trauma categories: minimal (n = 3), moderate (n = 5), or severe (n = 3). After cochleostomy and array insertion, CAP threshold shifts increased with trauma severity. At each stage a threshold shift at high frequencies (4–16 kHz) was accompanied with a threshold shift at low frequencies (0.25–2 kHz) that was 10–20 dB smaller. Withdrawal of the array led to a further worsening of responses, which probably indicates that insertion and removal trauma affected the responses rather than the mere presence of the array. In two instances, CAP threshold shifts were considerably larger than threshold shifts of cochlear microphonics, which could be explained by neural damage due to OSL fracture. A change in amplitudes at high sound levels was strongly correlated with threshold shifts, which is relevant for clinical ECochG performed at one sound level.

Conclusion

Basal trauma caused by cochleostomy and/or array insertion should be minimized in order to preserve the low-frequency residual hearing of CI recipients.
A bibliometric analysis of Mediterranean diet on cancer from 2012 to 2021
Authors: Liu Yafeng , Lu Jibin
Published: February 2023

Background

Numerous studies have demonstrated the value of the Mediterranean diet (MD) as a nutritious eating regimen for lowering the risk of cancer. This study aims to discuss the research patterns, existing state, and possible hotspots in implementing the MD for the prevention and treatment of cancer using bibliometrics.

Methods

The Web of Science Core Collection (WoSCC) was searched for articles on cancer that were related to the MD. CiteSpace, VOSviewer, Microsoft Excel 2019, and R software were utilized for bibliometric analysis and data visualization.

Results

There were 1,415 articles and reviews published from 2012 to 2021. Annual publication volume showed a continuous upward trend. Italy and Harvard University were the country and institution, respectively, with the highest number of publications on this topic. Nutrients ranked first in the number of documents, number of citations, and the H-index. James R. Hebert was the most productive writer, and Antonia Trichopoulou was the most co-cited author. “Alcohol consumption,” “oleic acid,” and “low density lipoprotein” were keywords used in earlier publications, while more recent hotspots focused on “gut microbiota,” “older adult,” and “polyphenol.”

Conclusion

Over the past decade, research on the MD in the field of cancer has received increasing attention. To improve the level of evidence for the beneficial effects of the MD on a range of cancers, more research on molecular mechanisms and better clinical studies are required.
Risk factors for postoperative myasthenia gravis in patients with thymoma without myasthenia gravis: A systematic review and meta-analysis
Authors: Tang Mingbo , Shao Yifeng , Dong Junxue , Gao Xinliang , Wei Shixiong , Ma Jianzun , Hong Yang , Li Zhiqin , Bi Taiyu , Yin Yipeng , Zhang Wenyu , Liu Wei
Published: February 2023

Introduction

According to the principle, thymomas combined with myasthenia gravis (MG) require surgical treatment. However, patients with non-MG thymoma rarely develop MG and early- or late-onset MG after surgery is called postoperative MG (PMG). Our study used a meta-analysis to examine the incidence of PMG and risk factors.

Methods

Relevant studies were searched for in the PubMed, EMBASE, Web of Science, CNKI,and Wanfang databases. Investigations that directly or indirectly analyzed the risk factors for PMG development in patients with non-MG thymoma were included in this study. Furthermore, risk ratios (RR) with 95% confidence intervals (CI) were pooled using meta-analysis, and fixed-effects or random-effects models were used depending on the heterogeneity of the included studies.

Results

Thirteen cohorts containing 2,448 patients that met the inclusion criteria were included. Metaanalysis revealed that the incidence of PMG in preoperative patients with non-MG thymoma was 8%. Preoperative seropositive acetylcholine receptor antibody (AChR-Ab) (RR = 5.53, 95% CI 2.36 – 12.96, P<0.001), open thymectomy (RR =1.84, 95% CI 1.39 – 2.43, P<0.001), non-R0 resection (RR = 1.87, 95% CI 1.36 – 2.54, P<0.001), world health organization (WHO) type B (RR =1.80, 95% CI 1.07 – 3.04, P= 0.028), and postoperative inflammation (RR = 1.63, 95% CI 1.26 – 2.12, P<0.001) were the risk factors for PMG in patients with thymoma. Masaoka stage (P = 0.151) and sex (P = 0.777) were not significantly associated with PMG.

Discussion

Patients with thymoma but without MG had a high probability of developing PMG. Although the incidence of PMG was very low, thymectomy could not completely prevent the occurrence of MG. Preoperative seropositive AChR-Ab level, open thymectomy, non-R0 resection, WHO type B, and postoperative inflammation were risk factors for PMG.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022360002.
Small hyperattenuating adrenal nodules in patients with lung cancer: Differentiation of metastases from adenomas on biphasic contrast-enhanced computed tomography
Authors: Cao Lixiu , Zhang Libo , Xu Wengui
Published: February 2023

Objective

The objective of this study was to evaluate the value of biphasic contrast-enhanced computed tomography (CECT) in the differential diagnosis of metastasis and lipid-poor adenomas (LPAs) in lung cancer patients with unilateral small hyperattenuating adrenal nodule.

Materials and methods

This retrospective study included 241 lung cancer patients with unilateral small hyperattenuating adrenal nodule (metastases, 123; LPAs, 118). All patients underwent plain chest or abdominal computed tomography (CT) scan and biphasic CECT scan, including arterial and venous phases. Qualitative and quantitative clinical and radiological characteristics of the two groups were compared using univariate analysis. An original diagnostic model was developed using multivariable logistic regression, and then, according to odds ratio (OR) of the risk factors of metastases, a diagnostic scoring model was developed. The areas under the receiver operating characteristic curves (AUCs) of the two diagnostic models were compared by DeLong test.

Results

Compared with LAPs, metastases were older and showed more frequently irregular in shape and cystic degeneration/necrosis (all p < 0.05). Enhancement ratios on venous (ERV) and arterial (ERA) phase of LAPs were noticeably higher than that of metastases, whereas CT values in unenhanced phase (UP) of LPAs were noticeably lower than that of metastases (all p < 0.05). Compared with LAPs, the proportions of male and III/IV clinical stage and small-cell lung cancer (SCLL) were significantly higher for metastases (all p < 0.05). As for peak enhancement phase, LPAs showed relatively faster wash-in and earlier wash-out enhancement pattern than metastases (p < 0.001). Multivariate analysis revealed age ≥ 59.5 years (OR: 2.269; p = 0.04), male (OR: 3.511; p = 0.002), CT values in UP ≥ 27.5 HU (OR: 6.968; p < 0.001), cystic degeneration/necrosis (OR: 3.076; p = 0.031), ERV ≤ 1.44 (OR: 4.835; p < 0.001), venous phase or equally enhanced (OR: 16.907; p < 0.001 or OR: 14.036; p < 0.001), and clinical stage II or III or IV (OR: 3.550; p = 0.208 or OR: 17.535; p = 0.002 or OR: 20.241; p = 0.001) were risk factors for diagnosis of metastases. AUCs of the original diagnostic model and the diagnostic scoring model for metastases were 0.919 (0.883–0.955) and 0.914 (0.880–0.948), respectively. There was no statistical significance of AUC between the two diagnostic model (p = 0.644).

Conclusions

Biphasic CECT performed well diagnostic ability in differentiating metastases from LAPs. The diagnostic scoring model is easy to popularize due to simplicity and convenience.
Non-cancer-specific survival in patients with primary central nervous system lymphoma: A multi-center cohort study
Authors: Chi Kaiyi , Zhou Ruoyun , Luo Zehao , Zhao Hongjun , Jiang Yanting , He Baixin , Li Yemin , Chen Dongting , Feng Manting , Liang Yinglan , Yang Wenting , Liu Ruisi , Yao Dunchen , Lin Xiaozhen , Xu Xiuhong
Published: February 2023

Objective

The study aimed to evaluate the non-cancer-specific death risk and identify the risk factors affecting the non-cancer-specific survival (NCSS) in patients with primary central nervous system lymphoma (PCNSL).

Methods

This multi-center cohort study included 2497 patients with PCNSL in the Surveillance, Epidemiology and End Results (SEER) database from 2007 to 2016, with a mean follow-up of 4.54 years. The non-cancer-specific death risk in patients with PCNSL and primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) was evaluated using the proportion of deaths, standardized mortality ratio (SMR), and absolute excess risk (AER). Univariate and multivariate competing risk regression models were utilized to identify the risk factors of NCSS.

Results

PCNSL was the most frequent cause of death in PCNSL patients (75.03%). Non-cancer-specific causes constituted a non-negligible portion of death (20.61%). Compared with the general population, PCNSL patients had higher risks of death from cardiovascular disease (CVD) (SMR, 2.55; AER, 77.29), Alzheimer’s disease (SMR, 2.71; AER, 8.79), respiratory disease (SMR, 2.12; AER, 15.63), and other non-cancer-specific diseases (SMR, 4.12; AER, 83.12). Male sex, Black race, earlier year of diagnosis (2007–2011), being unmarried, and a lack of chemotherapy were risk factors for NCSS in patients with PCNSL and PCNS-DLBCL (all P < 0.05).

Conclusion

Non-cancer-specific causes were important competing causes of death in PCNSL patients. More attention is recommended to non-cancer-specific causes of death in the management of PCNSL patients.
Potentially inappropriate medication among older patients with diabetic kidney disease
Authors: Wang Yuping , Zhu Jie , Shan Luchen , Wu Ling , Wang Cunchuan , Yang Wah
Published: February 2023

Objective: Potentially inappropriate medications (PIM) contribute to poor outcomes in older patients, making it a widespread health problem. The study explored the occurrence and risk factors of PIM in older diabetic kidney disease (DKD) patients during hospitalization and investigated whether polypharmacy was associated with it.

Methods: Retrospective analysis of the patients ≥ 65 years old diagnosed with DKD from July to December 2020; the PIM was evaluated according to the American Beers Criteria (2019). Factors with statistical significance in univariate analysis were included in Logistic multivariate analysis to explore the potential risk factors related to PIM.

Results: Included 186 patients, 65.6% of patients had PIM, and 300 items were confirmed. The highest incidence of PIM was 41.7% for drugs that should be carefully used by the older, followed by 35.3% that should be avoided during hospitalization. The incidence of PIM related to diseases or symptoms, drug interactions to avoid, and drugs to avoid or reduce dose for renal insufficiency patients were 6.3%, 4.0% and 12.7%, respectively. The medications with a high incidence of PIM were diuretics (35.0%), benzodiazepines (10.7%) and peripheral ɑ1 blockers (8.7%). Compared with hospitalization, there were 26% of patients had increased PIM at discharge. Multivariate Logistic regression analysis showed that polypharmacy during hospitalization was an independent risk factor for PIM, OR = 4.471 (95% CI: 2.378, 8.406).

Conclusion: The incidence of PIM in hospitalized older DKD patients is high; we should pay more attention to the problem of polypharmacy in these patients. Pharmacists identifying the subtypes and risk factors for PIM may facilitate risk reduction for older DKD patients.
Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota
Authors: Su Yunfang , Liu Ningning , Sun Ruiqin , Ma Jinlian , Li Zhonghua , Wang Pan , Ma Huifen , Sun Yiran , Song Junying , Zhang Zhenqiang
Published: February 2023

Radix Rehmanniae Praeparata (RRP, Shu Dihuang in Cinese) is widely used as primal medicine in Chinese herbal formula for the treatment of Alzheimer’s disease (AD). However, the underlying mechanism of RRP for AD remains unclear. The aim of this study was to investigate the therapeutic effect of RRP on intracerebroventricular injection of streptozotocin (ICV-STZ)-induced AD model mice and its potential mechanism. ICV-STZ mice were continuously gavaged with RRP for 21 days. The pharmacological effects of RRP were evaluated by behavioral tests, brain tissue H&E staining and hippocampal tau protein phosphorylation levels. The expression levels of insulin receptor (INSR), IRS-1, pSer473-AKT/AKT and pSer9-GSK-3β/GSK-3β proteins in hippocampal and cortical tissues were detected by Western-blot method. The 16S rRNA gene sequencing was used to analyze the changes of intestinal microbiota in mice. The compounds in RRP were analyzed by mass spectrometry and their binding ability to INSR proteins was detected by molecular docking. The results showed that RRP ameliorated cognitive dysfunction and neuronal pathological changes of brain tissue in ICV-STZ mice, reduced tau protein hyperphosphorylation, INSR, IRS-1, pSer473-AKT/AKT, and pSer9-GSK-3β/GSK-3β levels in hippocampal and cortical tissues. Meanwhile, RRP reversed ICV-STZ-induced dysregulation of intestinal microbiota in AD mice. Mass spectrometry analysis showed that the RRP consisted mainly of seven compounds, namely Acteoside (Verbascoside), 5-Hydroxymethyl-2-furaldehyde (5-HMF), Apigenin7-O-glucuronide, Icariin, Gallic acid, Quercetin-3β-D-glucoside, and Geniposide. Molecular docking results further indicated that the compounds in RRP have binding ability to INSR protein and potential multiple synergistic effects. RRP ameliorates cognitive dysfunction and brain histopathological changes in AD mice. The mechanism of RRP ameliorating AD may be related to the regulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota. This study supports the potential anti-AD efficacy of RRP and initially reveals the pharmacological mechanism of RRP, providing a theoretical basis for further clinical application of RRP.
Mellein: Production in culture by Macrophomina phaseolina isolates from soybean plants exhibiting symptoms of charcoal rot and its role in pathology
Authors: Khambhati Vivek H. , Abbas Hamed K. , Sulyok Michael , Tomaso-Peterson Maria , Chen Jian , Shier Wayne Thomas
Published: February 2023

Macrophomina phaseolina (Mp) is a fungal pathogen proposed to enter host roots by releasing toxins that induce local necrosis in roots allowing entry of hyphae. Mp is reported to produce several potent phytotoxins, including (-)-botryodiplodin and phaseolinone, but isolates that do not produce these phytotoxins retain virulence. One hypothesis explaining these observations is that some Mp isolates may produce other unidentified phytotoxin(s) responsible for virulence. A previous study of Mp isolates from soybean found 14 previously unreported secondary metabolites using LC-MS/MS, including mellein, which has various reported biological activities. This study was conducted to investigate the frequency and amounts of mellein produced in culture by Mp isolates from soybean plants exhibiting symptoms of charcoal rot and to investigate the role of mellein in any observed phytotoxicity. LC-MS/MS analysis of cell-free culture filtrates (CCFs) from 89 Mp isolates revealed that 28.1% produced mellein (49–2,203 µg/L). In soybean seedlings in hydroponic culture, Mp CCFs diluted to 25% (vol/vol) in hydroponic growth medium induced phytotoxic symptoms with frequencies of 73% chlorosis, 78% necrosis, 7% wilting, and 16% death, and at 50% (vol/vol) induced phytotoxicity with frequencies of 61% chlorosis, 82% necrosis, 9% wilting, and 26% death. Commercially-available mellein (40–100 µg/mL) in hydroponic culture medium induced wilting. However, mellein concentrations in CCFs exhibited only weak, negative, insignificant correlations with phytotoxicity measures in soybean seedlings, suggesting that mellein does not contribute substantially to observed phytotoxic effects. Further investigation is needed to determine if mellein plays any role in root infection.