bluuebunny/crossref_metadata_2025 huggingface dataset:
Afatinib plus osimertinib in the treatment of osimertinib-resistant non-small cell lung carcinoma: a phase I clinical trial
Authors: Miura Satoru , Koh Yasuhiro , Azuma Koichi , Yoshioka Hiroshige , Koyama Kenichi , Teraoka Shunsuke , Ishii Hidenobu , Kibata Kayoko , Ozawa Yuichi , Tokito Takaaki , Oyanagi Jun , Shimokawa Toshio , Kurata Takayasu , Yamamoto Nobuyuki , Tanaka Hiroshi
Published: January 2023

Background

Conquering acquired resistance to osimertinib remains a major challenge in treating patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Thus, we aimed to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib.

Methods

This open-label phase I study was a feasibility study of the combination of afatinib and osimertinib for patients with advanced EGFR-positive NSCLC who had progressive disease after receiving osimertinib. The primary endpoint was to determine the maximum tolerated dose (MTD). We enrolled patients who received afatinib at three different dose levels (level 1, 20 mg; level 2, 30 mg; level 3, 40 mg) combined with osimertinib at a standard dose of 80 mg once per day.

Results

Thirteen patients were enrolled in this study. The MTD was defined as 30 mg afatinib when combined with daily oral administration of osimertinib (80 mg). The most frequent adverse events were diarrhea (76.9%), anemia (76.9%), and rash (69.2%). Considering the toxicity profiles during all treatment periods, the recommended oral dose of afatinib was determined as 20 mg daily, with an osimertinib dose of 80 mg. For all evaluable patients (n = 12), the response rate was 7.7% and the disease-control rate was 46.2%.

Conclusion

Combination therapy with osimertinib and afatinib was tolerable; however, the synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients.

Trial registration

Japan Registry of Clinical Trials ID: jRCTs051180008, registered date: 08/11/2018.
A comparative analysis of solitary suicides, suicides following homicide, and suicide pacts using the National Violent Death Reporting System
Authors: Ashley Jenna , Kim Kawon Victoria , Russell Cayley , Lange Shannon
Published: January 2023

Background

Incidents of suicide can be categorized into three main types: solitary suicides, suicides following homicide, and suicide pacts. Although these three suicide incidents vary by definition, no studies to-date have simultaneously examined and compared them for potential differences. The objective of the current study was to empirically and descriptively compare solitary suicides, suicides following homicide, and suicide pacts in the United States.

Methods

Restricted-access data from the National Violent Death Report System for 2003–2019 for 262,679 solitary suicides, 4,352 suicides following homicide, and 450 suicide pacts were used. Pairwise comparisons of the three suicide incident types were made for demographic factors, method of suicide, preceding circumstances, mental health status, and toxicology findings.

Results

Solitary suicides, suicides following homicide, and suicide pacts have distinct profiles, with statistically significant (p < 0.05) differences across all pairwise comparisons of sex, race, ethnicity, marital status, education, method of suicide, financial problems, interpersonal relationship problems, physical health problems, mental health problems, mood disorders, suicide attempt history, and opiate use at the time of death.

Conclusion

Despite sharing a few commonalities, solitary suicides, suicides following homicide, and suicide pacts represent distinct phenomena. Each of these suicide incident types likely have their own unique prevention pathways.
Features and effects of computer-based games on cognitive impairments in children with autism spectrum disorder: an evidence-based systematic literature review
Authors: Rezayi Sorayya , Tehrani-Doost Mehdi , Shahmoradi Leila
Published: January 2023

Introduction

Children with Autism Spectrum Disorder (ASD) have different cognitive and intelligence profiles than typical developing individuals. Some of these children need cognitive rehabilitation. This study's main purpose is to provide a systematic review about applying computerized cognitive games for autistic children and to determine the effectiveness of such interventions.

Material and methods

A thorough search of the ISI Web of Science, Medline (through PubMed), Scopus, IEEE Xplore, and APA PsycInfo databases was performed for articles published from inception to May 17, 2022.

Results

Of 1746 papers, 28 studies were found to be eligible in this systematic review. Fifteen studies (53.57%) compared a Control Group (CG) with Experimental Groups (EGs), while 13 papers (46.42%) evaluated only the impact of the applied intervention in an experimental group. Major domains of cognitive functions are divided into five main categories: 1. Executive functions, 2. Social cognition/emotions, 3. Attention/concentration, 4. Learning and memory, and 5. Language. In 42.85% (12 studies) of the screened papers, social cognition and emotions were assessed after cognitive rehabilitation. The highest rate of effects reported by studies were related to social cognition enhancement. Of the total number of included studies, 17 studies reported a positive effect at all scales, of which nine were quasi-experimental, and seven were fully experimental.

Conclusion

Using suitable computerized game-based solutions could enhance cognition indexes in autistic children. Hence, further investigation is needed to determine the real effectiveness of these novel technologies.
Efficiency of the new reciprocating and rotary systems with or without ultrasonics in removing root-canals filling with calcium silicate-based sealer (MTA)
Authors: Madarati Ahmad A. , Sammani Aya M. N. , Alnazzawi Ahmad A. , Alrahlah Ali
Published: January 2023

Background

To compare the efficiency of endodontic rotary and reciprocating systems in removing calcium silicate-sealer based fillings and to investigate the impact of passive ultrasonic irrigation (PUI) on their efficiency.

Materials and methods

160 root-canals were instrumented, filled with gutta-percha and calcium silicate based-sealer and divided into 10 equal groups. Five groups in which the reciprocating systems (WaveOne-Gold, Reciproc-Blue and R-Motion) and rotary systems (Fanta-AF-One and Tango-Endo) were used to remove root-canals’ fillings. In the other five groups the fillings were removed by the same systems then additionally with PUI. The times to complete retreatments procedures were recorded. Micro-computed tomography’s analysis of the root-canals fillings’ volume before and after retreatments was used to determine the remaining filling materials (RFMs) volumes.

Results

The RFMs after using rotary systems (10.1%) was greater than after using reciprocating systems (3.8%) (P < 0.001). The RFMs after using WOG (2%) and RB systems (2.6%) were less than those in the RM (6.8%), TE (9.5%) and FAFO (10.7%) systems [P < 0.05]. The times required to remove the filling materials using the TE (3.7 min), FAFO (4.1 min) and RM (4.1 min) systems were shorter than those required by the RB (5.4 min) and WOG (4.9 min) systems [P < 0.05]. Using PUI resulted in less RFMs (1.44%) when compared to using only rotary or reciprocating systems (6.27%) [P < 0.001].

Conclusions

Endodontic reciprocation systems were more effective, but needed longer times than rotary systems in removing calcium silicate based- sealers fillings. The PUI significantly improved removal of the root-canals’ filling materials.

Clinical relevance: Reciprocating systems and PUI are recommended whenever root-canals retreatment is considered regardless of using calcium silicate-based sealers.
Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana
Authors: Akakpo Patrick Kafui , Imbeah Emmanuel Gustav , Edusei Lawrence , Naporo Simon , Ulzen-Appiah Kofi , Clegg-Lamptey Joe Nat , Dedey Florence , Nsaful Josephine , Affram Nelson , Wiafe Beatrice , Mensah Samuel , Nortey Michael , Sheriff Mohammed , Amponsah-Manu Forster , Agbedinu Kwabena , Jiagge Evelyn Mawunyo
Published: January 2023

Background

Breast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among women younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC).

Methods

A descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Reports of core or incision biopsy, Wide Local Excision or Mastectomy with or without axillary lymph node dissection specimen and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p < 0.05.

Results

A total of 2418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (< 40 years) and 54.29 (IQR: 16.86) in the LOBC group (≥ 40 years). Invasive carcinoma—No Special Type was the commonest tumour type with grade III tumours being the commonest in both categories of patients. Perineural invasion was the only statistically significant pathologic parameter with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67 > 20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80% vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC.

Conclusion

EOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger study is recommended to identify the association between relevant pathological features and early onset breast cancer in Ghana. Again, further molecular and genetic studies to understand the molecular genetic drivers of the general poorer pathological features of EOBCs and its relation to patient outcome in our setting is needed.
Revealing the significant shortcomings in the learning environment at the three largest medical schools in Syria: what’s next?
Authors: Alfakhry Ghaith , Naeem Ahmad , AboHajar M. Bader , Alfakhry Aisha , Mohandes Abdul Fattah , Ali Iyad , Makhoul Ebrahim , Ahmed Nadeem , Abla M. Mhdy , Alhomsi Khaled , Jamous Issam
Published: January 2023

Background

Medical education in Syria still adopts a traditional, teacher-centered curriculum to this day. These elements imply the existence of issues in the learning environment (LE). This study aims to provide the first evaluation of the LE at the largest medical schools in Syria using the DREEM inventory.

Methods

The three largest medical schools in Syria are the ones at Damascus University (DU), University of Aleppo (AU), Tishreen University (TU). The Arabic version of the DREEM questionnaire was used. Students across all years of study except year 1 were approached. Both paper-based and electronic surveys were conducted.

Results

A total of 1774 questionnaire forms were completed (DU:941, AU:533, TU: 300). The overall DREEM score at DU, AU, and TU were 100.8 ± 28.7, 101.3 ± 31.7, and 97.8 ± 35.7 respectively with no significant difference (P = 0.254) between the three universities. DREEM subscales concerningLearning, Atmosphere, Academic Self-perception and Social Self-perceptionhad a low score across all universities. Clinical-stage students reported significantly lower perception (P ≤ 0.001) of the LE in comparison to their pre-clinical counterparts across all subscales.

Conclusions

The findings of this study highlight the significant shortcomings of the medical LE in Syria. If not addressed properly, the academic, clinical, and professional competence of the healthcare workforce will continue to deteriorate. Moreover, the negative LE might be a predisposing factor for medical students’ exodus. The Syrian medical education system requires leaders who are willing to defy the status quo to achieve a true educational transformation.
Researching the application of virtual reality in medical education: one-year follow-up of a randomized trial
Authors: Gan Wenyi , Mok Tsz-Ngai , Chen Junyuan , She Guorong , Zha Zhengang , Wang Huajun , Li Hua , Li Jieruo , Zheng Xiaofei
Published: January 2023

Background

Compared with traditional tendon repair teaching methods, using a virtual reality (VR) simulator to teach tendon suturing can significantly improve medical students’ exercise time, operation flow and operation knowledge. At present, the purpose of this study is to explore the long-term influence of VR simulator teaching on the practice performance of medical students.

Method

This is a one-year long-term follow-up study of a randomized controlled study. A total of 117 participants who completed the initial study were invited to participate in the follow-up study. Participants in the VR group and the control group were required to complete a questionnaire developed by the authors and the teachers in the teaching and research department and to provide their surgical internship scores and Objective Structure Clinical Examination(OSCE) graduation scores.

Results

Of the 117 invitees, 108 completed the follow-up. The answers to the questions about career choice and study habits were more positive in the VR group than in the control group (p < 0.05). The total score for clinical practice in the VR group was better than that in the control group, and the difference was statistically significant (p < 0.05). In the OSCE examination, the scores for physical examination, suturing and knotting and image reading were higher in the VR group than in the control group, and the difference was statistically significant (p < 0.05).

Conclusion

The results of the one-year long-term follow-up indicated that compared with medical students experiencing the traditional teaching mode, those experiencing the VR teaching mode had more determined career pursuit and active willingness to learn, better evaluations from teachers in the process of surgical clinical practice, and better scores in physical examination, suturing and knotting and image reading in the OSCE examination. In the study of nonlinear dynamics to cultivate a good learning model for medical students, the VR teaching model is expected to become an effective and stable initial sensitive element.

Trial registration

Chinese Clinical Trial Registry(25/05/2021, ChiCTR2100046648);http://www.chictr.org.cn/hvshowproject.aspx?id=90180.
Trends in carbapenem resistance in Pre-COVID and COVID times in a tertiary care hospital in North India
Authors: Chatterjee Nirupama , Nirwan Pushpa K. , Srivastava Shruti , Rati Ruchi , Sharma Lalit , Sharma Priyanka , Dwivedi Priyambada , Jaggi Namita
Published: January 2023

Background

Carbapenem resistance is endemic in the Indian sub-continent. In this study, carbapenem resistance rates and the prevalence of different carbapenemases were determined in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa during two periods; Pre-COVID (August to October 2019) and COVID (January to February 2021) in a north-Indian tertiary care hospital.

Methods

Details of patient demographics and clinical condition was collated from the Hospital Information System and detection of carbapenemases NDM, OXA-48, VIM, IMP and KPC was done by Polymerase chain reaction (PCR) in 152 and 138 non-consecutive carbapenem resistant isolates during the two study periods respectively. Conjugation assay and sequencing of NDM and OXA-48 gene was done on a few selected isolates.

Results

As compared to Pre-COVID period, co-morbidities and the mortality rates were higher in patients harbouring carbapenem resistant organisms during the COVID period. The overall carbapenem resistance rate for all the four organisms increased from 23 to 41% between the two periods of study; with Pseudomonas aeruginosa and Klebsiella pneumoniae showing significant increase (p < 0.05). OXA-48, NDM and co-expression of NDM and OXA-48 were the most common genotypes detected. NDM-5 and OXA-232 were most common variants of NDM and OXA-48 family respectively during both the study periods.

Conclusion

Higher rate of carbapenem resistance in COVID times could be attributed to increase in number of patients with co-morbidities. However, genetic elements of carbapenem resistance largely remained the same in the two time periods.
Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma
Authors: Zhang Peisen , Cui Yingying , Wang Jian , Cheng Junwei , Zhu Lichong , Liu Chuang , Yue Saisai , Pang Runxin , Guan Jiaoqiong , Xie Bixia , Zhang Ni , Qin Meng , Jing Lihong , Hou Yi , Lan Yue
Published: January 2023

Background

Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects.

Results

Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cellsviaCD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstandingT1magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+and CD8+T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them.

Conclusion

The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Graphical Abstract
Total coumarins of Pileostegia tomentella induces cell death in SCLC by reprogramming metabolic patterns, possibly through attenuating β-catenin/AMPK/SIRT1
Authors: Liu Ying , Wu Kun , Li Li , Zhu Fucui , Wang Li , Su Hua , Li Ying , Lu Lu , Lu Guoshou , Hu Xiaoxi
Published: January 2023

Background

Small-cell lung cancer (SCLC) is a high malignant and high energy-consuming type of lung cancer. Total coumarins of Pileostegia tomentella (TCPT) from a traditional folk medicine of Yao minority, is a potential anti-cancer mixture against SCLC, but the pharmacological and molecular mechanism of TCPT remains largely unknown.

Methods

Screening of viability inhibition of TCPT among 7 cell lines were conducted by using CCK-8 assays. Anti-proliferative activities of TCPT in SCLC were observed by using colony formation and flow cytometry assays. Morphological changes were observed by transmission electron microscope and Mito-Tracker staining. High Throughput RNA-seq analysis and bio-informatics analysis were applied to find potential targeted biological and signaling pathways affected by TCPT. The mRNA expression of DEGs and protein expression of signalling proteins and metabolic enzymes were verified by qPCR and Western blot assays. Activity of rate-limiting enzymes and metabolite level were detected by corresponding enzyme activity and metabolites kits. Xenograft nude mice model of SCLC was established to observe the in vivo inhibition, metabolism reprogramming and mechanism of TCPT.

Results

TCPT treatment shows the best inhibition in SCLC cell line H1688 rather than other 5 lung cancer cell lines. Ultrastructural investigation indicates TCPT induces mitochondria damage such as cytoplasm shrinkage, ridges concentration and early sight of autolysosome, as well as decrease of membrane potential. Results of RNA-seq combined bio-informatics analysis find out changes of metabolism progression affected the most by TCPT in SCLC cells, and these changes might be regulated by β-catenin/AMPK/SIRT1 axis. TCPT might mainly decline the activity and expression of rate-limiting enzymes, OGDH, PDHE1, and LDHA/B to reprogram aerobic oxidation pattern, resulting in reduction of ATP production in SCLC cells. Xenograft nude mice model demonstrates TCPT could induce cell death and inhibit growth in vivo. Assimilate to the results of in vitro model, TCPT reprograms metabolism by decreasing the activity and expression of rate-limiting enzymes (OGDH, PDHE1, and LDHA/B), and attenuates the expression of β-catenin, p-β-catenin, AMPK and SIRT1 accordance with in vitro data.

Conclusion

Our results demonstrated TCPT induces cell death of SCLC by reprograming metabolic patterns, possibly through attenuating master metabolic pathway axis β-catenin/AMPK/SIRT1.
Role of GRPR in Acupuncture Intervention in the “Itch-scratch Vicious Cycle” Spinal Circuit of Chronic Pruritus
Authors: Liu Jia-jia , Li Xuemei , Guo Jing , Yu Shuguang , Yang Sha
Published: January 2023

Many previous studies have shown the potential antipruritic effect of acupuncture. This paper reviews the antipruritic mechanisms of acupuncture according to these aspects: sample characteristics, detail of intervention, and effects evaluation. The majority of research on acupuncture’s antipruritic effect has focused on primary afferents of the peripheral mechanism. Relatively few studies, however, have addressed the central mechanisms. Combination the latest research achievements of chronic itch, gastrin-releasing peptide receptor (GRPR) in the dorsal horn of the spinal cord may represent the first molecule identified that is dedicated to mediating the itch response and may provide an important therapeutic target for the treatment of chronic pruritic conditions. Therefore, GRPR may be a new target for acupuncture to relieve itch in the future and provide new ideas for acupuncture intervention in the mechanisms of the spinal level of the “itch-scratch vicious cycle” of chronic itch.
Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol
Authors: Jang Young-Eun , Joo Eun-Young , Lee Ji-Hyun , Kim Eun-Hee , Kang Pyoyoon , Park Jung-Bin , Kim Hee-Soo , Kim Jin-Tae
Published: January 2023

Background

Oral chloral hydrate is widely used in pediatric sedation. Intranasal dexmedetomidine has been increasingly used for pediatric sedation; however, its improvement is warranted. The combination of dexmedetomidine with ketamine can improve onset and hemodynamic stability while maintaining sedative efficacy. This study aims to determine the efficacy and safety of intranasal combination of dexmedetomidine and ketamine compared to oral chloral hydrate.

Methods

This is a prospective, parallel-arm, single-blinded, two-center, superiority randomized controlled trial with 1:1 allocation, designed to compare the effects of intranasal combination of dexmedetomidine and ketamine with those of oral chloral hydrate. We shall enroll 136 patients aged < 7 years old in this study. Prior to the procedure, we shall randomize each patient into the control group (oral chloral hydrate 50 mg/kg) or study group (intranasal dexmedetomidine 2 μg/kg and ketamine 3 mg/kg). The primary outcome will be the rate of achieving an adequate sedation level (6-point Pediatric Sedation State Scale 1, 2, or 3) within 15 min. In addition, we shall measure the sedation time, sedation failure rate, completion of procedure, adverse events, patient acceptance, and physician satisfaction.

Discussion

This study will provide evidence of the efficacy and safety of the intranasal combination of dexmedetomidine and ketamine in comparison with oral chloral hydrate.

Trial registration

ClinicalTrials.gov, NCT04820205. Registered on 19th March 2021
An intermixed method for solving the combination of mixed variational inequality problems and fixed-point problems
Authors: Khuangsatung Wongvisarut , Kangtunyakarn Atid
Published: January 2023

In this paper, we introduce an intermixed algorithm with viscosity technique for finding a common solution of the combination of mixed variational inequality problems and the fixed-point problem of a nonexpansive mapping in a real Hilbert space. Moreover, we propose the mathematical tools related to the combination of mixed variational inequality problems in the second section of this paper. Utilizing our mathematical tools, a strong convergence theorem is established for the proposed algorithm. Furthermore, we establish additional conclusions concerning the split-feasibility problem and the constrained convex-minimization problem utilizing our main result. Finally, we provide numerical experiments to illustrate the convergence behavior of our proposed algorithm.
Low-power multi-cloud deployment of large distributed service applications with response-time constraints
Authors: Singh Babneet , Kaur Ravneet , Woodside Murray , Chinneck John W.
Published: January 2023

Distributed service applications make heavy use of clouds and multi-clouds, and must (i) meet service quality goals (e.g. response time) while (ii) satisfying cloud resource constraints and (iii) conserving power. Deployment algorithms must (iv) provide a solution meeting these requirements within a short time to be useful in practice. Very few existing deployment methods address the first three requirements, and those that do take too long to find a deployment. The Low-Power Multi-Cloud Application Deployment (LPD) algorithm fills this gap with a low-complexity heuristic combination of generalized graph partitioning between clouds, bin-packing within each cloud and queueing approximations to control the response time. LPD has no known competitor that quickly finds a solution that satisfies response time bounds. A host execution time approximation for contention is fundamental to achieving sufficient solution speed. LPD is intended for use by cloud managers who must simultaneously manage hosts and application deployments and plan capacity to offer services such as Serverless Computing.

On 104 test scenarios deploying up to 200 processes with up to 240 replicas (for scaling), LPD always produced a feasible solution within 100 s (within 20 seconds in over three-quarters of cases). Compared to the Mixed Integer Program solution by CPLEX (which took a lot longer and was sometimes not found) LPD solutions gave power consumption equal to MIP in a third of cases and within 6% of MIP in 95% of cases. In 93% of all 104 cases the power consumption is within 20% of an (unachievable) lower bound.

LPD is intended as a stand-alone heuristic to meet solution time restrictions, but could easily be adapted for use as a repair mechanism in a Genetic Algorithm.
Ecological niche shifts affect the potential invasive risk of Phytolacca americana (Phytolaccaceae) in China
Authors: Xu Yifeng , Ye Xingzhuang , Yang Qianyue , Weng Huiying , Liu Yipeng , Ahmad Sagheer , Zhang Guofang , Huang Qiuliang , Zhang Tianyu , Liu Bao
Published: January 2023

Background

Predicting the potential habitat of Phytolacca americana, a high-risk invasive species, can help provide a scientific basis for its quarantine and control strategies. Using the optimized MaxEnt model, we applied the latest climate data, CMIP6, to predict the distribution of potential risk zones and their change patterns for P. americana under current and future (SSP126, SSP245, SSP585) climate conditions, followed by invasion potential analysis.

Results

The predictions of MaxEnt model based on R language optimization were highly accurate. A significantly high area of 0.8703 was observed for working characteristic curve (AUC value) of subject and the kappa value was 0.8074. Under the current climate conditions, the risk zones for P. americana were mainly distributed in Sichuan, Chongqing, Guizhou, Hunan, and Guangxi provinces. The contribution rate of each climatic factor of P. americana was calculated using the jackknife test. The four factors with the highest contribution rate included minimum temperature of coldest month (bio6, 51.4%), the monthly mean diurnal temperature difference (bio2, 27.9%), precipitation of the driest quarter (bio17, 4.9%), and the warmest seasonal precipitation (bio12, 4.3%).

Conclusion

Under future climatic conditions, the change in the habitat pattern of P. americana generally showed a migration toward the Yangtze River Delta region and the southeastern coastal region of China. This migration exhibited an expansion trend, highlighting the strong future invasiveness of the species. Based on the predictions, targeted prevention and control strategies for areas with significant changes in P. americana were developed. Therefore, this study emphasizes the need of an integrated approach to effectively prevent the further spread of invasive plants.
Artificial intelligence models for prediction of monthly rainfall without climatic data for meteorological stations in Ethiopia
Authors: Abebe Wondmagegn Taye , Endalie Demeke
Published: January 2023

Global climate change is affecting water resources and other aspects of life in many countries. Rainfall is the most significant climate element affecting the livelihood and well-being of the majority of Ethiopians. Rainfall variability has a great impact on agricultural production, water supply, transportation, the environment, and urban planning. Because all agricultural activities and subsequent national crop production hinge on the amount and distribution of rainfall, accurate monthly and seasonal predictions of this rainfall are vital for agricultural planning. Rainfall prediction is also useful for governmental, non-governmental, and private agencies in making long-term decisions and planning in numerous areas such as farming, early warning of potential hazards, drought mitigation, disaster prevention, and insurance policy. Artificial Intelligence (AI) has been widely used in almost every area, and rainfall prediction is one of them. In this study, we attempt to investigate the use of AI-based models to predict monthly rainfall at 92 Ethiopian meteorological stations. The applicability of Artificial Neural Networks (ANNs) and Adaptive Neuro-Fuzzy Inference System (ANFIS) models in predicting long-term monthly precipitation was investigated using geographical and periodicity component (longitude, latitude, and altitude) data collected from 2011 to 2021. The experimental results reveal that the ANFIS model outperforms the ANN model in all assessment criteria across all testing stations. The Nash–Sutcliffe efficiency coefficients were 0.995 for ANFIS and 0.935 for ANN over testing stations.
A review on slow earthquakes in the Japan Trench
Authors: Nishikawa Tomoaki , Ide Satoshi , Nishimura Takuya
Published: January 2023

Slow earthquakes are episodic slow fault slips. They form a fundamental component of interplate deformation processes, along with fast, regular earthquakes. Recent seismological and geodetic observations have revealed detailed slow earthquake activity along the Japan Trench—the subduction zone where the March 11, 2011, moment magnitude (Mw) 9.0 Tohoku-Oki earthquake occurred. In this paper, we review observational, experimental, and simulation studies on slow earthquakes along the Japan Trench and their research history. By compiling the observations of slow earthquakes (e.g., tectonic tremors, very-low-frequency earthquakes, and slow slip events) and related fault slip phenomena (e.g., small repeating earthquakes, earthquake swarms, and foreshocks of large interplate earthquakes), we present an integrated slow earthquake distribution along the Japan Trench. Slow and megathrust earthquakes are spatially complementary in distribution, and slow earthquakes sometimes trigger fast earthquakes in their vicinities. An approximately 200-km-long along-strike gap of seismic slow earthquakes (i.e., tectonic tremors and very-low-frequency earthquakes) corresponds with the huge interplate locked zone of the central Japan Trench. The Mw 9.0 Tohoku-Oki earthquake ruptured this locked zone, but the rupture terminated without propagating deep into the slow-earthquake-genic regions in the northern and southern Japan Trench. Slow earthquakes are involved in both the rupture initiation and termination processes of megathrust earthquakes in the Japan Trench. We then compared the integrated slow earthquake distribution with the crustal structure of the Japan Trench (e.g., interplate sedimentary units, subducting seamounts, petit-spot volcanoes, horst and graben structures, residual gravity, seismic velocity structure, and plate boundary reflection intensity) and described the geological environment of the slow-earthquake-genic regions (e.g., water sources, pressure–temperature conditions, and metamorphism). The integrated slow earthquake distribution enabled us to comprehensively discuss the role of slow earthquakes in the occurrence process of the Tohoku-Oki earthquake. The correspondences of the slow earthquake distribution with the crustal structure and geological environment provide insights into the slow-earthquake-genesis in the Japan Trench and imply that highly overpressured fluids are key to understanding the complex slow earthquake distribution. Furthermore, we propose that detailed monitoring of slow earthquake activity can improve the forecasts of interplate seismicity along the Japan Trench.
Comprehensive comparisons of ocular biometry: A network-based big data analysis
Authors: Yu Jinjin , Wen Daizong , Zhao Jing , Wang Yiran , Feng Ke , Wan Ting , Savini Giacomo , McAlinden Colm , Lin Xuanqiao , Niu Lingling , Chen Sisi , Gao Qingyi , Ning Rui , Jin Yili , Zhou Xingtao , Huang Jinhai
Published: January 2023

Purpose

To systematically compare and rank ocular measurements with optical and ultrasound biometers based on big data.

Methods

PubMed, Embase, the Cochrane Library and the US trial registry (www.ClinicalTrial.gov) were used to systematically search trials published up to October 22nd, 2020. We included comparative studies reporting the following parameters measured by at least two devices: axial length (AL), flattest meridian keratometry (Kf), steepest meridian keratometry (Ks), mean keratometry (Km), astigmatism (AST), astigmatism vectors J0 and J45, anterior chamber depth (ACD), aqueous depth (AQD), central corneal thickness (CCT), corneal diameter (CD) and lens thickness (LT). A network-based big data analysis was conducted using STATA version 13.1.

Results

Across 129 studies involving 17,181 eyes, 12 optical biometers and two ultrasound biometers (with both contact and immersion techniques) were identified. A network meta-analysis for AL and ACD measurements found that statistically significant differences existed when contact ultrasound biometry was compared with the optical biometers. There were no statistically significant differences among the four swept-source optical coherence tomography (SS-OCT) based devices (IOLMaster 700, OA-2000, Argos and ANTERION). As for Ks, Km and CD, statistically significant differences were found when the Pentacam AXL was compared with the IOLMaster and IOLMaster 500. There were statistically significant differences for CCT when the OA-2000 was compared to Pentacam AXL, IOLMaster 700, Lenstar, AL-Scan and Galilei G6.

Conclusion

For AL and ACD, contact ultrasound biometry obtains the lower values compared with optical biometers. The Pentacam AXL achieves the lowest values for keratometry and CD. The smallest value for CCT measurement is found with the OA-2000.
Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis
Authors: Machado Camilla Ribeiro Lima , Dias Felipe Ferraz , Resende Gustavo Gomes , Oliveira Patrícia Gnieslaw de , Xavier Ricardo Machado , Andrade Marcus Vinicius Melo de , Kakehasi Adriana Maria
Published: January 2023

Background

Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA).

Methods

FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β.

Results

RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs.

Conclusion

This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.
Phenolic-protein interactions: insight from in-silico analyses – a review
Authors: Shahidi Fereidoon , Dissanayaka Chandrika Sewwandi
Published: January 2023

Phenolic compounds are ubiquitous plant secondary metabolites that possess various biological activities and are known to interact with proteins, altering their structure and properties. Therefore, interactions between these compounds and proteins has gained increasing attention due to their potential benefits to human health and for exploitation by the food industry. Phenolic compounds and proteins can form complexes via covalent linkages and/or non-covalent interactions through hydrophobic, electrostatic, van der Waals forces and hydrogen bonding. This review describes possible mechanisms of phenol-protein complex formation, their physiological action and activities that are important in the food industry, and possible outcomes in the terms of molecular docking and simulation analysis. The conformational changes of the protein upon binding with polyphenols can lead to the folding or unfolding of the protein molecules, forming insoluble or soluble complexes. The concentration of polyphenols, their molecular weight and structure, ions/cofactors and conditions of the system determine the precipitation or solubilization of the complex, affecting their nutritional and functional properties as well as their bioactivities. In this regard, molecular docking and simulation studies of phenolic-protein interactions allows comprehensive virtual screening of competitive/non-competitive and site-specific/non-specific conjugation of phenolics with different protein targets and facilitates understanding the observed effects. The docking analysis of flavonoids with enzymes and milk proteins has indicated their potential application in producing nutraceuticals and functional foods. Thus, combining molecular docking and simulation studies with experimental techniques is vital for better understanding the reactions that take place during digestion to engineer and manufacture novel food ingredients with desirable pharmacological properties and as potential food additives.

Graphical Abstract
Can triphasic hepatic multislice CT validate the LI-RADS treatment response algorithm after trans-catheter arterial chemoembolization treatment of hepatocellular carcinoma?
Authors: El-Assaly Hany , Abdelwahab Esraa , El Sebai Shady M. , Grace Marie N.
Published: January 2023

Background

Our aim is to evaluate LI-RADS-TR algorithm and its ability to assess the viability of TACE-treated HCC. We prospectively evaluated 100 patients with known HCC, treated with TACE and came for follow-up to assess therapy response and to plan the next step in treatment using triphasic CT study. Imaging response was evaluated according to LI-RADS-TR algorithm and compared to modified Response Evaluation Criteria in Solid Tumors (mRECIST) arterial phase hyperenhancement (APHE) criterion. Reference standard for “viable” tumors in treated observations included presence of strong tumor hyperenhancement in arterial phase and washout in the delayed phase which also shows dense accumulation of iodized oil in the target lesion.

Results

When equivocal observations were considered as LR-TR viable, LR-TR viable resulted in 92.31% sensitivity, 83.33% specificity and 88% accuracy. On the other side when equivocal observations were considered as LR-TR nonviable, it resulted in 84.62% while the specificity increased to 100% with increased accuracy (92%). The mRECIST criteria for viable tumors (presence of APHE) showed sensitivity of 84.62% and specificity of 75%. mRECIST and LR-TR sensitivities were the same when equivocal lesions were considered as nonviable and lower mRECIST than LR-TR when equivocal lesions were considered as viable, while specificities were higher in LR-TR viable being 100% when equivocal lesions were considered as nonviable, 83.33% when equivocal lesions were considered as viable and 75% in mRECIST-viable.

Conclusions

LR-TR algorithm showed good diagnostic performance compared to mRECIST, with high specificity and sensitivity when equivocal lesions were considered as nonviable, as well as improved accuracy.
Spectral extrapolation principles and application: Mindoro Island, Philippines, seismic data
Authors: Puryear Charles Ian , Tharimela Raghava , Ray Dhirendra , Egorov Vsevolod , Baille Graeme , Hernandianto Agus Imran
Published: January 2023

Spectral extrapolation is a bandwidth extension technique that we implement by combining spectral inversion with constraints, time-variant wavelet extraction, and targeted broadband filtering. We explain the principles of spectral extrapolation as a valid and effective bandwidth extension method and demonstrate its application to a 2D onshore Philippines legacy seismic data set using a time-variant wavelet extraction, resulting in a tripling of the frequency range of the spectrum. The results indicate significant potential for mapping complex stratigraphy and geomorphological features not evident on the input seismic data images, yielding information about reservoir distribution and connectivity that is often critical for optimal well placement.
When Forests Run Amok
Authors: Ruiz-Serna Daniel
Published: January 2023

Daniel Ruiz-Serna examines how the devastation caused by war impacts nonhuman inhabitants in the forests and rivers in the traditional lands of Indigenous and Afro-Colombian peoples.
Uncomfortable Television
Authors: Hargraves Hunter
Published: January 2023

From The Wire to Intervention to Girls, postmillennial American television has dazzled audiences with novelistic seriality and cinematic aesthetics. Yet this television is also more perverse: it bombards audiences with misogynistic and racialized violence, graphic sex, substance abuse, unlikeable protagonists, and the extraordinary exploitation of ordinary people. In Uncomfortable Television, Hunter Hargraves examines how television makes its audiences find pleasure through feeling disturbed. He shows that this turn to discomfort realigns collective definitions of family and pleasure with the values of neoliberal culture. In viscerally violent dramas, cringeworthy ironic comedies, and trashy reality programs alike, televisual unease trains audiences to survive under late capitalism, which demands that individuals accept a certain amount of discomfort, dread, and irritation into their everyday lives. By highlighting how discomfort has been central to the reorganization and legitimization of television as an art form, Hargraves demonstrates television’s role in assimilating viewers into worlds marked by precarity, perversity, and crisis.
Mitochondrial respiration promotes Cdc37-dependent stability of the Cdk1 homolog Cdc28
Authors: Leite Ana Cláudia , Martins Telma S. , Cesário Rute R. , Teixeira Vitor , Costa Vítor , Pereira Clara
Published: January 2023

Cdc28, the homolog of mammalian Cdk1, is a conserved key regulatory kinase for all major cell cycle transitions in yeast. We have found that defects in mitochondrial respiration (including deletion of ATP2, an ATP synthase subunit) inhibit growth of cells carrying a degron allele of Cdc28 (cdc28td) or Cdc28 temperature-sensitive mutations (cdc28-1 and cdc28-1N) at semi-permissive temperatures. Loss of cell proliferation in the atp2Δcdc28td double mutant is associated with aggravated cell cycle arrest and mitochondrial dysfunction, including mitochondrial hyperpolarization and fragmentation. Unexpectedly, in mutants defective in mitochondrial respiration, steady-state protein levels of mutant cdc28 are strongly reduced, accounting for the aggravated growth defects. Stability of Cdc28 is promoted by the Hsp90–Cdc37 chaperone complex. Our results show that atp2Δcdc28td double-mutant cells, but not single mutants, are sensitive to chemical inhibition of the Hsp90–Cdc37 complex, and exhibit reduced levels of additional Hsp90–Cdc37 client kinases, suggesting an inhibition of this complex. In agreement, overexpression of CDC37 improved atp2Δcdc28td cell growth and Cdc28 levels. Overall, our study shows that simultaneous disturbance of mitochondrial respiration and Cdc28 activity reduces the capacity of Cdc37 to chaperone client kinases, leading to growth arrest.