bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment resistant schizophrenia
Authors: He Jingqi , Li Jinguang , Wei Yisen , Liu Junyu , Yuan Ning , Zhou Rishen , He Xingtao , Ren Honghong , Liao Yanhui , Gu Lin , Chen Xiaogang , Tang Jinsong
Published: February 2023

Background
Glutamatergic function deficits have been associated with the pathogenesis of treatment resistant schizophrenia (TRS), while the effects of clozapine on the glutamate system may contribute to its superior efficacy. In recent years, evidence emerged supporting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. In this present study, we aimed to investigate multiple anti-glutamate receptor antibody levels in TRS and explored the effects of clozapine on these antibody levels.
Methods
We measured and compared multiple anti-glutamate receptor (NMDAR, AMPAR, mGlur3, mGluR5) antibody levels among clozapine-treated patients with TRS (TRS-C, n = 37), clozapine-naïve patients with TRS (TRS-nC, n = 39), and patients with nTRS (NTRS, n = 35), using enzyme linked immunosorbent assay (ELISA). Severity of clinical symptoms was evaluated with Positive and Negative Symptom Scale (PANSS). Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB).
Results
The four glutamate receptor antibody levels in the TRS-nC were higher than those in the NTRS (p < 0.001). The anti-mGluR3 antibody levels in the TRS-C were similar to those in the NTRS (p = 0.233), and the other three antibody levels were between the NTRS and the TRS-nC. However, in all three groups, no significant associations were found between antibody levels and symptom severity or cognitive function.
Conclusions
Our findings suggest that both glutamatergic function deficits and immune processes may play a role in the pathogenesis of TRS. The effect of clozapine targeting anti-glutamate receptor antibody levels may be an element of its pharmacology that contribute to its therapeutic effects.
Cryopreventive temperatures prior to chemotherapy
Authors: Ibrahim Aram , Camci Emine , Khairallah Lina , Jontell Mats , Walladbegi Java
Published: February 2023

Background: The superiority of oral cryotherapy (OC) for prevention of chemotherapy-induced oral mucositis (OM) has been demonstrated in several trials. In clinical settings, cooling is usually initiated prior to the chemotherapy infusion. It then continues during the infusion, and for a period after the infusion has been completed. While the cooling period post-infusion depends on the half-life of the chemotherapeutic drug, there is no consensus on when cooling should be initiated prior to the infusion. The lowest achieved temperature in the oral mucosa is believed to provide the best conditions to prevent OM. Given this, it was of interest to investigate when along the course of intraoral cooling this temperature is achieved.
Subjects and method: In total, 20 healthy volunteers participated in this randomized crossover trial. Each subject attended three separate cooling sessions of 30 minutes each, with ice chips (IC) and the intraoral cooling device (ICD) set to 8°C and 15°C, respectively. At baseline and following 5, 10, 15, 20 and 30 minutes of cooling, intraoral temperatures were registered using a thermographic camera.
Results: The greatest drop in intraoral temperature was seen after 5 minutes of cooling with both IC, ICD8°C and ICD15°C, respectively. A statistically significant difference, corresponding to 1.4°C was seen between IC and the ICD15°C (p < 0.05). The intraoral temperature further declined throughout the 30 minutes of cooling, showing an additional temperature reduction of 3.1°C, 2.2°C, and 1.7°C for IC, ICD8°C and ICD15°C, respectively.
Conclusion: The greatest drop in intraoral temperature is seen following 5 minutes of cooling.
Necessity of fusion following decompression surgery in patients with single-level lumbar stenosis: study protocol for an open-label multicenter non-inferiority randomized controlled clinical trial
Authors: Grin Andrey , Lvov Ivan , Talypov Aleksandr , Smirnov Vladimir , Kordonskiy Anton , Lebedev Valeriy , Kalandari Alik , Zuev Andrey , Senko Ilya , Pogonchenkova Irena , Krylov Vladimir
Published: February 2023

Background

The necessity of spinal segment fusion after decompression is one of the most controversial and unresolved issues in single-level lumbar spinal stenosis surgery. To date, only one trial carried out 15 years ago focused on this problem. The key purpose of the current trial is to compare the long-term clinical results of the two surgical methods (decompression vs. decompression and fusion) in patients with single-level lumbar stenosis.

Methods

This study is focused on the non-inferior clinical results of decompression compared with the standard fusion procedure. In the decompression group, the spinous process, the interspinous and supraspinous ligaments, part of the facet joints, and corresponding parts of the vertebral arch are to be preserved intact. In the fusion group, decompression is to be supplemented with transforaminal interbody fusion. Participants meeting the inclusion criteria will be randomly divided into two equal groups (1:1), depending on the surgical method. The final analysis will include 86 patients (43 per group). The primary endpoint is Oswestry Disability Index dynamics at the end of the 24-month follow-up compared to the baseline level. Secondary outcomes included those estimated using the SF-36 scale, EQ-5D-5L, and psychological scales. Additional parameters will include sagittal balance of the spine, fusion results, total cost of surgery, and hospital stay followed by two-year treatment. Follow-up examinations will be performed at 3, 6, 12, and 24 months

Discussion

Authors suggest that this study will improve the evidence for application of various surgical techniques for lumbar spine stenosis surgery and verify the existing protocol for surgical management.

Trial registration

ClinicalTrials.gov NCT05273879. Registered on March 10, 2022, https://clinicaltrials.gov/ct2/show/NCT05273879
Discovering patterns in outpatient neurology appointments using state sequence analysis
Authors: Biggin Fran , Ashcroft Quinta , Howcroft Timothy , Knight Jo , Emsley Hedley
Published: February 2023

Background
Outpatient services in the UK, and in particular outpatient neurology services, are under considerable pressure with an ever-increasing gap between capacity and demand. To improve services, we first need to understand the current situation. This study aims to explore the patterns of appointment type seen in outpatient neurology, in order to identify potential opportunities for change.
Methods
We use State Sequence Analysis (SSA) on routinely collected data from a single neurology outpatient clinic. SSA is an exploratory methodology which allows patterns within sequences of appointments to be discovered. We analyse sequences of appointments for the 18 months following a new appointment. Using SSA we create groups of similar appointment sequence patterns, and then analyse these clusters to determine if there are particular sequences common to different diagnostic categories.
Results
Of 1315 patients 887 patients had only one appointment. Among the 428 patients who had more than one appointment a 6 monthly cycle of appointments was apparent. SSA revealed that there were 11 distinct clusters of appointment sequence patterns. Further analysis showed that there are 3 diagnosis categories which have significant influence over which cluster a patient falls into: seizure/epilepsy, movement disorders, and headache.
Conclusions
Neurology outpatient appointment sequences show great diversity, but there are some patterns which are common to specific diagnostic categories. Information about these common patterns could be used to inform the structure of future outpatient appointments.
Comparison of Freehand Technique and a Novel Laser-Guiding Navigation System in Femoral Neck-Cannulated Screw Fixation: A Randomized Controlled Trial
Authors: Gao Hua , Liu Zhenyu , Bai Xiaodong , Wang Gang , Xu Guoqiang , Ma Ji , Wang Yijun , Wang Jiatian , Chen Wentao , Wang Baojun
Published: February 2023

Cannulated screw fixation is essential in treating femoral neck fractures, and the widely used freehand technique has several limitations. Therefore, we designed a new laser-positioning and navigation system and compared its efficacy with that of the traditional freehand technique in the cannulated screw fixation of femoral neck fractures. This randomized controlled single-blind trial recruited patients with femoral neck fracture, who were treated using either the newly designed laser-navigation device or the freehand technique. In in-vitro experiments, using the femoral neck model, the laser group was better than the freehand group in terms of operation time (P=0.0153) and radiation exposure time (P<0.001). In in-vivoexperiments, involving 30 patients (15 in each group), the laser group was better than the freehand group in terms of operation time (P<0.001), radiation exposure time (P<0.001), blood loss (P<0.001) and first success rate (P=0.03). There was no difference in visual analog scale score, Harris score, and fracture-healing time between the two groups. In conclusion, the novel laser-guiding navigation system resulted in shorter operation time, less radiation exposure, and higher first success rate compared with the freehand technique. Further qualified investigations with a larger number of patients and longer follow-up are required in the future.
Proximity extracellular protein-protein interaction analysis of EGFR using AirID-conjugated fragment of antigen binding
Authors: Yamada Kohdai , Shioya Ryouhei , Nishino Kohei , Furihata Hirotake , Hijikata Atsushi , Kaneko Mika , Kato Yukinari , Shirai Tsuyoshi , Kosako Hidetaka , Sawasaki Tatsuya
Published: February 2023

Receptor proteins, such as epidermal growth factor receptor (EGFR), interact with other proteins in the extracellular region of the cell membrane to drive intracellular signalling. Therefore, analysis of extracellular protein-protein interactions (exPPIs) is important for understanding the biological function of receptor proteins. Here, we demonstrate a new approach using a proximity biotinylation enzyme (AirID) fusion fragment of antigen binding (FabID) to analyse the proximity exPPIs of EGFR. AirID was C-terminally fused to the Fab fragment against EGFR (EGFR-FabID), which could then biotinylate the extracellular region of EGFR in several cell lines. LC-MS/MS analysis indicated that many known EGFR interactors were identified as proximity exPPIs, along with many new candidate interactors, using EGFR-FabID. Interestingly, these proximity exPPIs were influenced by treatment with EGF ligand and its specific kinase inhibitor, gefitinib. These results indicate that FabID provides accurate proximity exPPI analysis of target receptor proteins on cell membranes with ligand and drug responses.
WITHDRAWN: Design of 5G MIMO Aerial With Non-Ionizing Radiation Protection.
Authors: S AJITH A
Published: February 2023

Novel antenna designs that utilise antenna arrays to provide improved coverage, minimise interference, and boost data-carrying capacity are needed to meet 5G targets. This paper provides an approach for designing an inverted-L 5G MIMO antenna with SAR (Specific Absorption Rate) calculation. The designed antenna will be resonating at 5.84GHz, with optimal parameters like reflection coefficient, gain and voltage standing wave ratio (VSWR). The measured bandwidth is in the range of 3.07GHz to 6.6GHz. The simulated human body SAR values are 0.925 W/kg, which is less than the ICNIRP-recommended SAR safety limit of 2 W/kg. The user-friendly CST Microwave Studio Software is used for all simulations and design.
Distance learning and face-to-face learning in medical PBL course during COVID-19 pandemic: an investigation and teaching experience
Authors: Chen Fang Hsu , Wu Bo-Ren , Chi Chih-Hsien
Published: February 2023

To prevent the infection and outbreak of COVID-19, the education method has adjusted the conventional in-person classes to distance learning in recent two years. Most classes were lectures that could go well if the participants were familiar with the online operation and had a stable network environment. Nevertheless, classes such as problem-based learning (PBL) rely on plenty of discussions and still have some limitations for communication and group development. In this research, we surveyed the learning effects of face-to-face (FF) and distance learning (DL) in the medical PBL course at Cheng-Kung University for two individual classes. Tutors and students were requested to give grades for the five key areas (participation, communication, preparation, critical thinking, and group skill). Five factors are used to evaluate the learning effect of face-to-face and distance learning. Compared with FF and DL methods, our research clarified that student learning effects would reduce participation, communication, and group skills by questionnaire survey. The tutors’ perspective regarded participation and communication ability as reduced at distance learning. But for group skills, one of the two classes showed no difference. Our research provides an experience for the PBL class focusing on discussion and communication. In the post-pandemic era, whether face-to-face or distance learning, classes should be adjusted properly to let students conduct effective communication in time.
Acetylglutamine facilitates motor recovery after brachial plexus root avulsion in ratsby promoting motoneuronal survival and axonal remyelination
Authors: Wu Lin , Chen Shuangxi , He Bing , Zhou Guijuan , Xu Yan , Zhu Guanghua , Xie Juan , Deng Limin , Wen Xuanwei , Li Sijing , Xiao Zijian
Published: February 2023

Background: Brachial plexus root avulsion (BPRA) is a disabling peripheral nerve injury that induces substantial death of motoneurons, degeneration of motor axons and de-innervation of biceps muscles, leading toloss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proved to exert neuroprotective and anti-inflammatory effects in various disorders in the nervous system. Hence, the present study focused on the effect of NAG on motor recovery after BPRA in rats and the underlying mechanisms.
Methods: Adult male Sprague Dawley rats were subject to BPRA and reimplantation surgery andsubsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR was utilized to measure the mRNA levels of remyelination and regenerstion indicators on myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the anterior horn of the spinal cord were measured using Western blot analysis.
Results: Our results indicated NAG could significantly accelerate recovery of motor function in the injured forelimbs, enhance motoneuronal survival in the anterior horn of the spinal cord, inhibit the expression of proinflammatory cytokines and pyroptosis pathway, facilitate axonal remyelination in the myocutaneous nerve and alleviate atrophy of biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.
Conclusion: NAG promotes functional motor recovery by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for NAG to be a novel strategy for BPRA treatment.
The prevalence and clinical importance of isolated inverted T wave in precordial leads
Authors: Rad Seyed Hamed Banihashem , Moohebati Mohsen , Ghayour-Mobarhan Majid , Ebrahimi Mahmoud , Zandi Zahra , Esmaily Habibollah
Published: February 2023

Introduction: Isolated precordial inverted T-wave (IPITW) is a challenging finding on electrocardiogram (ECG) due to a wide range of differential diagnoses ranging from a normal finding to coronary heart disease. The aim of this study was to determine the overall prevalence of IPITW and its underlying causes along with ECG mapping.
Materials and methods: The MASHAD cohort study participants (phase II) were screened for the presence of IPITW on the ECG. Demographic and clinical information of patients with IPITW extracted from the cohort study archive. ECG mapping and trans-thoracic echocardiography were performed on randomly selected 40 participants with IPITW. These participants were divided into symptomatic and asymptomatic groups.
Results: The prevalence of IPITW was 1.56%. Of the selected 40 participants (9, 22.5% male and 31, 77.5% female), IPITW was mostly present in V3 and V4 leads (77.5% in each case). There was no significant difference in the number of leads with IPITW between I, M and N patterns (p = 0.051). Hypertension, ischemic heart disease (IHD) and heart failure (HF) were the least prevalent among N pattern group. The prevalence of heart failure was the highest in M pattern group (60%). Pattern I was associated with 525.2-fold increased likelihood of IHD compared to the N pattern. I pattern had the highest sensitivity (68.42%), specificity (90.48%), positive (86.67%) and negative (76.0 %) predictive values in IHD diagnosis.
Conclusions: IPITW in the presence of I pattern in ECG mapping can be an indicator for IHD.
Prevalence of chronic obstructive pulmonary disease and associated risk factors among small-holder fish vendors along coastal areas in Tanzania
Authors: Onesmo Brigitha M. , Mamuya Simon H. , Mwema Mwema Felix , Hella Jerry
Published: February 2023

Background: In Tanzania little is known on how the respiratory system of small-holder fish vendors is affected by occupational exposure to biomass smoke and other associated risk factors. The current study assesses the prevalence of lung obstruction and associated risk factors among small-holder fish vendors along coastal areas in Tanzania.
Methods: A cross-sectional descriptive study was conducted along coastal areas of Tanzania in Bagamoyo and Kunduchi fish markets. Environmental air pollutant levels and composition were measured using a hand-held device. A standardized questionnaire was used to assess respiratory symptoms while EasyOne spirometer was used to test for lung function among small-holder fish vendors. Chronic Obstructive Pulmonary Disease (COPD) was defined as FEV1/FVC below the lower limit of normal. Data were analyzed using STATA Version 17. Descriptive statistics was performed and logistic regression analysis was used to determine factors that are associated with poor lung function presented as crude and adjusted odds ratio and their 95% confidence intervals.
Results: A total of 103 participants were included in the study who were predominantly males (79.6%). The participants’ mean age was 35.47 (±8.77 SD) years. The hourly average concentration levels of PM1, PM2.5, PM10, and CO exposure during fish frying were 653.6 (± 206.3 SD) µg/m3, 748.48 (± 200.6 SD) µg/m3, 798.66 (± 181.71 SD) µg/m3 and 62.6 (± 12.3 SD) ppm respectively which is higher than the WHO recommended limits. The prevalence of COPD was found to be 32.04% (95% CI 0.23-0.42) which was associated with respiratory symptoms like coughing, wheezing, sputum production and breathlessness among participants. The odds for COPD was lower among males (AOR 0.25, 95% CI 0.06-1.16), but intuitively higher among those with history of TB (AOR 1.75, 95% CI 0.2-15.38), underweight (AOR 6.91, 95% CI 0.61-78.53) and those with increased number of days one worked in frying fish.
Conclusion: Findings suggest that three out of ten participants had COPD predominantly due to occupational exposure to biomass smoke being the most risk factor. This calls for effective approaches to reduce exposure and prevent known acute and chronic respiratory diseases that are associated with such exposure to air pollutants.
High sensitive thermoplastic polyurethane/carbon nanotubes strain sensor fitting by a novel optimization empirical model
Authors: Wang Xin , Qu Muchao , Wu Kuangqi , Schubert Dirk W. , Liu Xianhu
Published: February 2023

A variety of high-performance strain sensors for monitoring changes in physical quantities has attracted considerable interest from academia and industry. In this work, a high sensitive flexible strain sensor is fabricated through electrospun thermoplastic polyurethane (TPU) fibrous film with dip-coating ultrasonication treated carbon nanotubes (CNTs). TPU/CNTs strain sensor exhibits an excellent comprehensive performance of high sensitivity (maximum gauge factor of 1571), outstanding tensile strength and toughness (stress > 24 MPa, strain > 400%), brilliant durability (10000 cycles at 10% strain) and a widely workable stretching range (0 ~ 400%). Based on the properties of high sensitivity, wearable and wide workable, TPU/CNTs strain sensor has been prepared as a simple application for intelligent terminals, e-skins and body activity monitoring. More importantly, this work introduces a novel optimization empirical equation provided by our group to describe and predict the conductive response on the stretching of the sensor. Compared with the general optimization model, our novel optimization empirical model presents a better fitting degree and more similar to the benchmark mathematic model from tunnelling theory. Furthermore, this model provides a good description of the changes in the conductive pathways during the operation of different sensors as well.
Predictive Value of Combined Peripheral Inflammatory Markers in Patients with Head and Neck Cancers
Authors: Iuchi Hiroyuki , Ohori Junichiro , Haraguchi Megumi , Ando Yumi , Toge Sakiko , Yamashita Masaru
Published: February 2023

Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide, and patients have low survival and poor quality of life. Combined peripheral inflammatory markers are associated with poor outcomes in patients with malignancies. This study aimed to investigate the prognostic significance of combined peripheral inflammatory markers in patients with HNSCC. Methods Records of 531 patients with histologically confirmed HNSCC between January 2009 and January 2021 were reviewed. The optimal cutoff values of peripheral inflammatory markers were determined by the receiver operating characteristic curve analysis and the Youden test. The neutrophil-to-lymphocyte ratio (NLR)–platelet-to-lymphocyte ratio (PLR) score, NLR–monocyte-to-lymphocyte ratio (MLR) sore, and PLR-MLR score ranged from low to high, i.e., a high score indicated that both inflammation markers are high; mid score, either inflammation marker is high; and low score, both inflammation markers are low. The overall survival (OS) and disease-free survival (DFS) were evaluated. Univariate and multivariate analyses were performed. Results The median follow-up time was 55 (range, 3–148) months. The optimal cutoff values for pretreatment NLR, PLR, MLR, systemic inflammation response index (SIRI), and systemic immune inflammation index (SII) were 2.21, 214.24, 0.33, 0.86, and 472.44, respectively. Univariate analyses revealed that smoking status (P = 0.021), drinking status (P = 0.033), tumor stage (P < 0.001), nodal stage (P < 0.001), tumor node metastasis (TNM) stage (P < 0.001), SIRI (P = 0.031), NLR-PLR score (P = 0.007), NLR-MLR score (P = 0.004), and PLR-MLR score (P < 0.001) were significantly associated with OS. Independent prognostic factors for OS were smoking status, drinking status, tumor stage, and PLR-MLR score. Univariate analyses revealed that smoking status (P = 0.008), tumor stage (P < 0.001), nodal stage (P < 0.001), TNM stage (P < 0.001), SIRI (P = 0.003), SII (P = 0.010), NLR-PLR score (P = 0.002), NLR-MLR score (P = 0.002), and PLR-MLR score (P < 0.001) were significantly associated with DFS. Independent prognostic factors for DFS were smoking status and PLR-MLR score. Conclusions PLR-MLR score may be a valuable inflammatory marker for the prediction of survival in patients with HNSCC.
TREM2 deficiency aggravates NLRP3 inflammasome activation and pyroptosis in MPTP-induced PD mice and LPS-induced BV2 cells
Authors: Huang Peiting , Zhang Zhanyu , Zhang Piao , Feng Jiezhu , Xie Jianwei , Zheng Yinjuan , Liang Xiaomei , Zhu Baoyu , Chen Zhenzhen , Feng Shujun , Lu Jiahong , Liu Yawei , Wang Lijuan , zhang yuhu
Published: February 2023

Background
Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of PD. Triggering receptor expressed on myeloid cells 2(TREM2) confers strong neuroprotective effects in PD by regulating the phenotype of microglia. Recent studies suggest that TREM2 regulates high glucose-induced microglial inflammation through the NLRP3 signaling pathway. This study aimed to investigate the effect of TREM2 on NLRP3 inflammasome activation and neuroinflammation in PD.
Method
The AAV-TREM2-shRNA was injected into the substantia nigra of both sides of the mouse brain using a stereotactic injection method. The chronic PD mouse model was established by intraperitoneal injection of MPTP. Motor behavior test, immunohistochemistry of TREM2 and TH, immunohistochemistry and immunofluorescence Iba1, Western blot of NLRP3 inflammasome and its downstream inflammatory factors IL−1β and IL−18, and the key pyroptosis factors GSDMD and GSDMD-N were performed to explore the effect of TREM2 on NLRP3 inflammasome and neuroinflammation. In vitro experiment, Lentivirus was used to interfere with the expression of TREM2 in BV2 microglia, then LPS and ATP were used to stimulate inflammation to construct a cellular inflammation model. The expression differences of NLRP3 inflammasome and its components were detected by qPCR and western blot.
Result
In vivo, TREM2 expression was decreased, dopaminergic neuron loss was increased, and motor function was decreased, indicating that TREM2 knockdown and PD mouse models were successfully constructed. After TREM2 knockdown, the number of activated microglia was significantly increased, and the expression of cleaved caspase−1, NLRP3 inflammasome, IL−1β, GSDMD, GSDMD-N was increased. In vitro, TREM2 knockdown aggravated the inflammatory response of BV2 cells stimulated by LPS and promoted the activation of NLRP3 inflammasome through the NF-κB pathway. In addition, TREM2 knockdown also promoted the expression of TLRP4/MyD88, an upstream factor of the NF-κB pathway.
Discussion
Our in vivo and in vitro data showed that TREM2 knockdown promoted NLRP3 inflammasome activation and downstream inflammatory response, promoted pyroptosis, and aggravated dopaminergic neuron loss, which extends previous findings and support the notion that TREM2 acts as an important anti-inflammatory factor to ameliorate neuroinflammation in PD.
Engineered MED12 mutations drive uterine fibroid-like transcriptional and metabolic programs by altering the 3D genome compartmentalization
Authors: Buyukcelebi Kadir , Chen Xintong , Abdula Fatih , Duval Alexander , Ozturk Harun , Seker-Polat Fidan , Jin Qiushi , Yin Ping , Feng Yue , Wei Jian-Jun , Bulun Serdar , Yue Feng , Adli Mazhar
Published: February 2023

Uterine fibroid (UF) tumors originate from a mutated smooth muscle cell (SMC). Nearly 70% of these tumors are driven by hotspot recurrent somatic mutations in the MED12 gene; however, there are no tractable genetic models to study the biology of UF tumors because, under culture conditions, the non-mutant fibroblasts outgrow the mutant SMC cells, resulting in the conversion of the population to WT phenotype. The lack of faithful cellular models hampered our ability to delineate the molecular pathways downstream of MED12 mutations and identify therapeutics that may selectively target the mutant cells. To overcome this challenge, we employed CRISPR knock-in with a sensitive PCR-based screening strategy to precisely engineer cells with mutant MED12 Gly44, which constitutes 50% of MED12 exon two mutations. Critically, the engineered myometrial SMC cells recapitulate several UF-like cellular, transcriptional and metabolic alterations, including enhanced proliferation rates in 3D spheres and altered Tryptophan/kynurenine metabolism. Our transcriptomic analysis supported by DNA synthesis tracking reveals that MED12 mutant cells, like UF tumors, have heightened expression of DNA repair genes but reduced DNA synthesis rates. Consequently, these cells accumulate significantly higher rates of DNA damage and are selectively more sensitive to common DNA-damaging chemotherapy, indicating mutation-specific and therapeutically relevant vulnerabilities. Our high-resolution 3D chromatin interaction analysis demonstrates that the engineered MED12 mutations drive aberrant genomic activity due to a genome-wide chromatin compartmentalization switch. These findings indicate that the engineered cellular model faithfully models key features of UF tumors and provides a novel platform for the broader scientific community to characterize genomics of recurrent MED12 mutations and discover potential therapeutic targets.
Predictors Associated With Mental Help Seeking Attitude Among Malaysian College Foundation Students in the Midst of Covid-19 Pandemic: a Cross Sectional Study
Authors: Mesran Nur Nadhirah , Abdul-Razak Suraya , Nikmat Azlina Wati
Published: February 2023

Background
Globally, the Coronavirus Disease-2019 (COVID-19) pandemic results in major psychological sequalae across age groups including adolescents. Mental illness rates are high, yet mental help seeking attitude (MHSA) among adolescents is evidently low in developed countries during the pandemic. However, data is scarce in developing countries, hence the aim of this study was to determine the MHSA and its predictors including psychological wellbeing of Malaysian college foundation students during the COVID-19 pandemic.
Methods
A cross sectional study was conducted among college foundation students, aged 18 to 19 years old, from a private college in Klang Valley from 1st December 2021 until 30th March 2022. All college foundation students were invited, and eligible students completed self-administered online questionnaires. Data on MHSA, sociodemographic, clinical factors, availability, accessibility and affordability of mental health service, mental health literacy, self-stigma of seeking help and psychological wellbeing were collected. An independent T-test analysis was performed to compare mean of MHSA between psychological distressed and non-psychological distressed. Multiple linear regression analysis was done to identify predictors of MHSA.
Results
345 participants completed the questionnaires and the response rate was 62.9%. The mean age was 18.7 (± 0.75) years old. More than half were female (64.3%, n=222) and a majority had no past history of mental health illness (95.1%, n=328). Almost half had personal history of COVID-19 infection (49.3%, n=170). The mean of MHSA was 50.98 ±10.39. The predictors associated with MHSA were; self-stigma of help seeking (β=-0.59 (95% CI: -0.76, -0.42) p<0.01); mental health literacy (β=0.22 (95% CI: 0.13, 0.30) p<0.01); and affordability of mental health service facility (β=3.29 (95% CI: 1.42, 5.16) p<0.01). The prevalence of psychologically distressed was 23.2%, (95%CI: 20.4, 26.1), in which psychological distressed had a higher mean of MHSA than that of non-psychological distressed (53.29 ±10.48 vs. 50.29 ±10.29, p=0.02)
Conclusion
Mental help seeking attitude among Malaysian college foundation students was low during the COVID-19 pandemic. This may result in lost opportunities for early diagnosis and treatment. Strategies to reduce self-stigma of seeking help for mental illness is vital, while efforts to educate young adults about mental health and make mental health services affordable are warranted.
A global virome of methanogenic archaea highlights novel diversity and adaptations to the gut environment
Authors: Medvedeva Sofia , Borrel Guillaume , Krupovic Mart , Gribaldo Simonetta
Published: February 2023

Mobile genetic elements (MGEs), especially viruses, have a major impact on microbial communities. Methanogenic archaea play key environmental and economical roles, being the main producers of methane -a potent greenhouse gas and an energy source. They are widespread in diverse anoxic artificial and natural environments, including animal gut microbiomes. However, their viruses remain vastly unknown. Here, we carried out a global investigation of MGEs in 3436 genomes and metagenome-assembled genomes covering all known diversity of methanogens and using a newly assembled CRISPR database consisting of 60,000 spacers of methanogens, the most extensive collection to date. We obtained 248 high-quality (pro)viral and 63 plasmid sequences assigned to hosts belonging to nine main orders of methanogenic archaea, including the first MGEs of Methanonatronarchaeales, Methanocellales and Methanoliparales archaea. We found novel CRISPR arrays in ‘Ca. Methanomassiliicoccus intestinalis’ and ‘Ca. Methanomethylophilus’ genomes with spacers targeting small ssDNA viruses of the Smacoviridae, supporting and extending the hypothesis of an interaction between smacoviruses and gut associated Methanomassiliicoccales. Gene network analysis shows that methanogens encompass a unique and interconnected MGE repertoire, including novel viral families belonging to head-tailed Caudoviricetes, but also icosahedral and archaeal-specific pleomorphic, spherical, and spindle (pro)viruses. We reveal well-delineated modules for virus-host interaction, genome replication and virion assembly, and a rich repertoire of defense and counter-defense systems suggesting a highly dynamic and complex network of interactions between methanogens and their MGEs. We also identify potential conjugation systems composed of VirB4, VirB5 and VirB6 proteins encoded on plasmids and (pro)viruses of Methanosarcinales, the first report in Euryarchaeota. We identified 15 new families of viruses infecting Methanobacteriales, the most prominent archaea in the gut microbiome. These encode a large repertoire of protein domains for recognizing and cleaving pseudomurein for viral entry and egress, suggesting convergent adaptation of bacterial and archaeal viruses to the presence of a cell wall. Finally, we highlight an enrichment of glycan-binding domains (immunoglobulin-like (Ig-like)/Flg_new) and diversity-generating retroelements (DGRs) in viruses from gut-associated methanogens, suggesting a role in adaptation to host environments and remarkable convergence with phages infecting gut-associated bacteria. Our work represents an important step toward the characterization of the vast repertoire of MGEs associated with methanogens, including a better understanding of their role in regulating their communities globally and the development of much-needed genetic tools.
Major adverse cardiovascular events and hyperuricemia during tuberculosis treatment
Authors: Shin Hong-Joon , Na Young-Ok , Lee Jae-Kyeong , Kho Bo Gun , Kim Tae-Ok , Kim Yu-Il , Lim Sung-Chul , Jeong Sae-Hee , Kwon Yong-Soo
Published: February 2023

Hyperuricemia is common during tuberculosis (TB) treatment, mainly pyrazinamide (PZA). This study investigated the relationship between major adverse cardiovascular events (MACEs) and hyperuricemia during TB treatment.
From January 2010–June 2017, this study retrospectively evaluated TB patients treated in a South Korean tertiary hospital. Hyperuricemia was defined as elevated serum uric acid >7.0 mg/dL (men) and >6.0 mg/dL (women).
A total of 1,143 patients were enrolled in this study, and PZA was used in 1081 (94.6%), while hyperuricemia was detected in 941 (84.4%). Eight patients developed MACEs. Multivariate analysis using logistic regression revealed that previous ischemic heart disease was associated with MACE development (OR, 19.071; 95% CI, 4.648–78.249; P < 0.000), while hyperuricemia was not (OR, 1.505; 95% CI, 0.184–12.299; P = 0.703). Among patients without drug-resistant TB, no hyperuricemia was associated with increased deaths (OR, 2.923; 95% CI, 1.119–7.638; P = 0.029), while hyperuricemia was associated with increased favorable outcomes (OR, 3.366; 95% CI, 1.787–6.340; P < 0.001).
In conclusions, most patients who received PZA had hyperuricemia; however, it was not associated with MACE development. Hyperuricemia during TB treatment was associated with better outcomes, possibly due to good compliance with TB treatment.
On the nature of the interlayer magnetic interactions in biphase ferromagnetic films
Authors: Silva E. F. , Gamino M. , Oliveira A. B. , Correa M. A. , Bohn F.
Published: February 2023

We report on the nature of the interlayer magnetic interactions in NiFe/Cu/Co films.By probing the quasi-static and dynamic magnetic properties of biphase ferromagnetic films, with soft and hard ferromagnetic phases intermediated by a non-magnetic layer, we address aspects of the coupling between magnetic layers. Our results demonstrate the nature of the interlayer magnetic coupling in biphase films. We also disclose the asymmetric magnetoimpedance effect as a fingerprint of the nature of the magnetic interlayer interactions playing key role in the magnetization dynamics of the system. We revisit in literature data and ideas on the asymmetric magnetoimpedance and the nature of the magnetic interactions in biphase ferromagnetic systems. Then, we compare our findings with results for biphase ribbons and microwires. Our observations raise the fundamental similarities and differences in the magnetoimpedance response of these structures, hence providing a single framework to interpret the phenomenon of asymmetric magnetoimpedance.
Social Capital and Economic Growth: A Meta-Analysis
Authors: Xue Xindong , Reed W. Robert , Aert Robbie C. M. van
Published: February 2023

This study collects and analyses 993 estimates from 81 studies to generate an overall assessment of the empirical literature on social capital and economic growth. Using a variety of estimation procedures, we reach the following conclusions. First, there is evidence that a meaningful relationship exists between social capital and economic growth. The estimated sizes of the overall mean effect in our specifications range from somewhat larger than “small” to somewhat larger than “medium” depending on the estimation method we use. Second, our analysis does not indicate that the associated empirical literature is distorted by publication bias. Third, there is evidence to indicate that cognitive social capital (e.g., trust) has a larger effect on economic growth than other types of social capital, though the evidence is not strong. Finally, while the coefficient signs of our meta-regression analysis lined up with prior expectations, the associated effect sizes were generally small to negligible. The most noteworthy finding is that social capital is estimated to have a smaller effect on economic growth in the US compared to other parts of the world.
JEL Classifications: B40, O31, O40, O47, R11, Z10
Optimal Intelligent Information Retrieval and Reliable Storage Scheme for Cloud Environment And E-Learning Big Data Analytics
Authors: Venkatachalam Chandrasekar , Venkatachalam Shanmugavalli
Published: February 2023

Currently, online learning systems in the education sector are widely used and have become a new trend, generating large amounts of educational data based on students' activities. In order to improve online learning experiences, sophisticated data analysis techniques are required. Adding value to E-learning platforms through the efficient processing of big learning data is possible with Big Data. With time, the E-learning management system's repository expands and becomes a rich source of learning materials. Subject matter experts may benefit from using E-learning resources to reuse previously created content when creating online content. In addition, it might be beneficial to the students by giving them access to the pertinent documents for achieving their learning objectives effectively. An improved intelligent information retrieval and reliable storage (OIIRS) scheme is proposed for E-learning using hybrid deep learning techniques. Assume that relevant E-learning documents are stored in cloud and dynamically updated according to users' status. First, we present a highly robust and lightweight crypto i.e. optimized CLEFIA, for securely storing data in local repositories that improve the reliability of data loading. We develop an improved butterfly optimization (IBO) algorithm to provide an optimal solution for CLEFIA that selects private keys. In addition, a hybrid deep learning method, i.e., backward diagonal search based deep recurrent neural network (BD-DRNN) is introduced for optimal intelligent information retrieval based on keywords rather than semantics. Here, feature extraction and key feature matching are performed by the modified Hungarian optimization (MHO) algorithm that improves searching accuracy. Finally, we test our proposed OIIRS scheme with different benchmark datasets and use simulation results to test the performance.
An analysis of atmospheric stability indices and parameters under air pollution conditions
Authors: Yavuz Veli
Published: February 2023

The stability of the atmosphere plays an important role in changes in air pollutant concentrations. Stable atmospheric conditions cause pollutant concentrations to reach high values, which degrades the air quality in a particular region. This study aims to reveal the relationship between atmospheric stability indices/parameters (thermodynamic indices) and changes in air pollutant concentrations. Pollutant concentrations of PM10, PM2.5, SO2, NO2, CO, and O3 were statistically analyzed for a 10-year (2013-2022) period for nine air quality stations located in the megacity Istanbul. Based on national and international air quality standards, 145 episode days were determined for the days when these parameters exceeded the threshold values. Five stability indices (Showalter Index – SI, Lifted Index – LI, Severe Weather Index – SWEAT, K Index – KI, Totals Totals Index – TTI), and three stability parameters (Convective Available Potential Energy – CAPE, Convective Inhibition – CIN, Bulk Richardson Number – BRN) were used to determine the stability of the atmosphere for episode days. It has been found that in cases where air pollutant concentrations are high, the stability parameters reveal the stability of the atmosphere better than the stability indices. It was also found that there was at least one vertical inversion layer on 122 of the 145 episode days, these layers mostly (84%) occurred between the surface and 850 hPa levels, and the layer thicknesses were mostly between 0-250 m (84%).
Landslide susceptibility modeling derived from remote sensing, multi-criteria decision analysis, and GIS techniques: A case study in the Southeast Bohol Province, Philippines
Authors: Tubog Michael Vincent , Villahermosa Ryan Lester , Perong John Glenn
Published: February 2023

The Philippines has conducted several landslide hazard susceptibility mapping over the past years to increase the requirement for vulnerability assessment. As a karstic mountainous region in the country, the southeast Bohol province is accustomed to frequent landslide occurrences, causing hazard risks in adjacent communities. These landslides are generally controlled by both extrinsic (e.g., road network, fault) and intrinsic (e.g., geomorphologic and geologic) factors. Field observation denotes several occurrences along steep slopes and stream banks. However, challenges in updating the landslide hazard susceptibility maps arose from the scarcity of updated field information and high-precision digital elevation models. With data access limitations, this study aims to generate accurate and precise landslide susceptibility models using remote sensing and statistical-based analysis processed in Geographic Information System (GIS). This study uses open-sourced medium-resolution satellite data and digital elevation models to generate and process the eight (8) landslide factor maps such as the geology, slope gradient, aspect, vegetation, proximity to stream and road networks, soil cover, and fault. These maps were analyzed through Analytical Hierarchy Process (AHP) and Fuzzy Logic Overlay. The generated landslide susceptibility models were validated using Forest-based Classification and Regression (FBCR), analysis of variance (ANOVA), and ordinary linear regression. The AHP-based model shows significant accuracy and compatibility with the actual susceptibility of the site since the p-value of the map is 0.031 in ANOVA, while the Fuzzy-based model cannot be considered accurate since it generated a 0.266 p-value result. Moreover, both models were analyzed in FBCR and resulted in a p-value of 2.2x10− 16 in the ordinary linear regression validation, making both as significant landslide prediction models. This result signifies that medium-resolution satellite data can generate accurate and compatible landslide susceptibility and prediction models, and this process will give disaster risk reduction managers an avenue to generate landslide models that are not bounded by data access limitations. It is also noteworthy to indicate the impact of changing climate in the Philippines where extreme cyclones have been frequent for the past years. Such events contribute to the occurrences of slope and river bank erosion and water saturation to the slope causing the periodic distribution of landslides throughout the study area.
MRI Based Fiber Strain Mapping of the Medial Gastrocnemius Muscle at Submaximal Isometric Contractions at Different Ankle Angles.
Authors: Cunnane Brandon , Sinha Usha , Malis Vadim , Hernandez Ryan , Smitaman Edward , Sinha Shantanu
Published: February 2023

Muscle force production is influenced by muscle fiber and aponeurosis architecture. This prospective cohort study utilizes special MR imaging sequences to examine the structure-function in-vivo in the Medial Gastrocnemius (MG) at three-ankle angles (dorsiflexion, neutral, and plantar flexion) and two sub-maximal levels of maximum voluntary contraction (25% and 50% MVC). The study was performed on 6 young male subjects. Muscle fiber and aponeurosis strain, fiber strain normalized to force, fiber length and pennation angle (at rest and peak contraction) were analyzed for statistical differences between ankle positions and %MVC. A two-way repeated measures ANOVA and post hoc Bonferroni-adjusted tests were conducted for normal data. A related samples test with Friedman’s 2-way ANOVA by ranks with corrections for multiple comparisons was conducted for non-normal data. The dorsiflexed ankle position generated significantly higher force with lower fiber strain than neutral and plantarflexed positions. Sarcomere length extracted from muscle fiber length at each ankle angle was used to track the location on the Force-Length curve and showed the MG operates on the curve’s ascending limb. Muscle force changes predicted from the F-L curve going from dorsi- to plantarflexion was less than that experimentally observed suggesting other determinants of force changes with ankle position.