bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin remodeler CHD7 targets active enhancer region to regulate cell type-specific gene expression in human neural crest cells
Authors: Sanosaka Tsukasa , Okuno Hironobu , Mizota Noriko , Andoh-Noda Tomoko , Sato Miki , Tomooka Ryo , Banno Satoe , Kohyama Jun , Okano Hideyuki
Published: December 2022

A mutation in the chromatin remodeler chromodomain helicase DNA-binding 7 (CHD7) gene causes the multiple congenital anomaly CHARGE syndrome. The craniofacial anomalies observed in CHARGE syndrome are caused by dysfunctions of neural crest cells (NCCs), which originate from the neural tube. However, the mechanism by which CHD7 regulates the function of human NCCs (hNCCs) remains unclear. We aimed to characterize the cis-regulatory elements governed by CHD7 in hNCCs by analyzing genome-wide ChIP-Seq data and identifying hNCC-specific CHD7-binding profiles. We compared CHD7-binding regions among cell types, including human induced pluripotent stem cells and human neuroepithelial cells, to determine the comprehensive properties of CHD7-binding in hNCCs. Importantly, analysis of the hNCC-specific CHD7-bound region revealed transcription factor AP-2α as a potential co-factor facilitating the cell type-specific transcriptional program in hNCCs. CHD7 was strongly associated with active enhancer regions, permitting the expression of hNCC-specific genes to sustain the function of hNCCs. Our findings reveal the regulatory mechanisms of CHD7 in hNCCs, thus providing additional information regarding the transcriptional programs in hNCCs.
Live probiotic bacteria administered in a pathomimetic Leaky Gut Chip ameliorate impaired epithelial barrier and mucosal inflammation
Authors: Min Soyoun , Than Nam , Shin Yong Cheol , Hu Grace , Shin Woojung , Ambrosini Yoko M. , Kim Hyun Jung
Published: December 2022

Here, we report a pathomimetic Leaky Gut Chip that recapitulates increased epithelial permeability and intestinal inflammation to assess probiotic intervention as live biotherapeutics. We leveraged a mechanodynamic human gut-on-a-chip (Gut Chip) that recreates three-dimensional epithelial layers in a controlled oxygen gradient and biomechanical cues, where the addition of a cocktail of pro-inflammatory cytokines, TNF-α and IL-1β, reproducibly induced impaired epithelial barrier followed by intestinal inflammation. This inflamed leaky epithelium was not recovered for up to 3 days, although the cytokine treatment ceased. However, when probiotic bacteria, either Lactobacillus rhamnosus GG or a multi-species mixture (VSL#3), were respectively administered on the leaky epithelium, bacterial cells colonized mucosal surface and significantly improved barrier function, enhanced the localization of tight junction proteins such as ZO-1 and occludin, and elevated mucus production. In addition, inflammatory markers, including p65, pSTAT3, and MYD88, that were highly expressed in the germ-free control were significantly reduced when probiotic bacteria were co-cultured in a Leaky Gut Chip. Probiotic treatment also significantly reduced the production of secretory pro-inflammatory cytokines. Hence, our pathomimetic Leaky Gut Chip may offer a translational strategy to dissect the therapeutic mechanism of live biotherapeutic products and validate their clinical potential by incorporating patient-derived organoids.
Line impedance compensation control strategy for multiple interlinking converters in hybrid AC/DC microgrid
Authors: Wang Can , Deng Can , Pan Xuewei
Published: December 2022

In a hybrid AC/DC microgrid (MG), the interlinking converter (IC) plays an important role in power flow regulation between subgrids. However, line impedance will cause deviations in the power transmitted by the IC if a communication device is not used. To realize accurate power delivery between subgrids without communication, an IC control method based on line impedance compensation is proposed. A harmonic signal is injected into the IC in this method using converters of distributed generation, which are connected to an AC bus. The specified frequency of the signal indicating the voltage of the AC bus can be acquired by an IC using a filter and phase‐locked‐loop (PLL) so that the IC can obtain line impedance by local information and then compensate for voltage drop to realize accurate power transmission. The entire implementation of this method uses no communication. Moreover, when multiple ICs run in parallel, this method can also be conducted easily and effectively to realize accurate power flow between subgrids and power sharing among ICs in proportion to the ICs’ rated capacity. This strategy is verified by simulation and hardware‐in‐the‐loop tests.
Electrical treeing behaviours in cross‐linked polyethylene cables after thermal ageing
Authors: Zhang Yi , Wu Zaijun , He Jiahong , Zhang Dongdong , Hu Minqiang
Published: December 2022

Long‐term thermal ageing might have impacts on the physicochemical properties of cross‐linked polyethene (XLPE) cables, thereby influencing their electrical behaviours, such as electrical treeing initiation and growth. The main objective of this work is to report the effects of thermal ageing on the electrical treeing behaviours (initiation and growth) in XLPE cable insulation. For this purpose, the electrical treeing initiation and growth test were performed in accelerated thermal samples. In addition, Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy were utilised to investigate corresponding changes in the microstructures of materials. In addition, a correlation was established between electrical treeing behaviours and physicochemical properties during the thermal ageing process. Test results indicate that the thermal ageing process should be divided into three phases, and the re‐crystallisation reaction is considered the primary reason for the increase of average electrical tree initiation voltage (AETIV). Furthermore, the thermal ageing index Xc is correlated to AETIV and the propagation rate of the electrical tree. As equivalent relationships have been established between the relative decrease value w of indexes AETIV, the propagating rate and Xc, this method can be employed to predict the changing pattern of electrical treeing initiation voltage and the propagating rate in future research.
Knowledge and Practice of Internship Students on the Emergency Crash Cart System in a Selected Tertiary Care Hospital, Mangaluru, Karnataka, India
Authors: Nair Varsha B. , Joseph Shilpa , Thomas Shintu , Sharvana Sharvana , PK Pranav , Mathew Shycil
Published: December 2022

Introduction A crash cart is the trolley for storing lifesaving equipment and drugs in a hospital. During an emergency situation, nurses are left with confusion and hurry in getting the emergency medication and equipment. Typically, the crash cart system remains locked until a code blue triage is initiated by the hospital. This lack of exposure leads to poor competency and confident in performing essential tasks during a code blue. A well-organized crash cart system can save a lot of time and confusion during an emergency, which in turn can save a life.

Aim The aim of this study was to identify the knowledge and practice of internship students on emergency crash cart system and to find the correlation between knowledge and practices of nursing internship students on maintenance of emergency crash cart system.

Materials and Methods A descriptive correlative research study was conducted among 93 nursing internship students tertiary care hospital, Mangaluru, Karnataka, India. The samples were selected by using purposive sampling techniques. Demographic proforma, structured knowledge questionnaire on knowledge regarding emergency crash cart system with 32 items was used to determine the level of knowledge and observation practice checklist with 24 items was used to assess the practice of internship students on maintenances of emergency crash cart system. Descriptive and inferential statistics was used to analyze the collected data.

Results Majority (89; 95.7%) of the internship students are in the age group of 20 to 25 years and most (59; 63.4%) of internship students are working in wards. Of that 79 (84.9%) internship students have average knowledge with mean 18.1, median 19, and standard deviation (SD) 3.2. Majority 90 (96.7%) of the internship students have satisfactory practice on emergency crash carts with mean 22.9, median 23, and SD 1. 11. There is a moderate positive linear relationship between knowledge and practice scores of the internship students on the emergency crash cart system (r = 0.38, df =92, p= 0.05).

Conclusions The study concludes nursing internship students have average knowledge about emergency crash cart system. And the practice of internship students on maintenance of crash cart was satisfactory. The study thus implies the need for frequent reinforcement and training programs, which may help the internship students to improve knowledge on emergency crash cart systems. There should be clear instructions about the arrangement and use of a crash cart in each and every unit.
Knowledge on PCOS among the Nursing Students of a Selected College, Mangaluru
Authors: Ferrao Welcita Ianya , Fernandes Veena Melisha , Thomas Twinkle , Baretto Vineetha Roshni , Sequera Sonia Karen Liz
Published: December 2022

Polycystic ovarian syndrome (PCOS) is an endocrine disorder commonly affecting the adolescent girls. Globally, the prevalence rate is around 4 to 12% and it affects 5 to 10% women in their reproductive age group. The study was conducted to assess the knowledge on PCOS among the student nurses. This was a questionnaire-based cross-sectional study among 350 adolescent girls of a selected nursing college recruited using stratified random sampling. A predesigned, pretested, semistructured 16-item questionnaire containing two components—basic knowledge on PCOS (8) and treatment and prevention of PCOS (8), was used for data collection and the results were analyzed. Results revealed that all the adolescent girls (350; 100%) belonged to the age group of 18 to 20 years. It was noted that 306 (87.4%) of students had inadequate knowledge, whereas 44 (12.6%) students had adequate knowledge on PCOS. Significant association was found between primary source of information (p = 0.012) and knowledge on PCOS at 0.05 level of significance. The study concluded that conduction of planned teaching programs is necessary to increase comprehensive knowledge with regard to detection of presenting symptoms and foster early diagnosis and treatment of the syndrome thereby promoting overall health.
Separation Anxiety in Horses
Authors: Nellist Jenni
Published: December 2022

Although there are no published statistics on the prevalence of separation-related behaviour (SRB) problems, they are likely to be a common issue in horses and constitute around 20% of the author’s caseload. They may present as difficulty catching and leading horses away from their social group, inability to settle (such as box walking or weaving when stabled, walking or pacing the fence when left behind in the pasture), difficulty with loading and travelling, napping when attempting to ride out alone or away from a group, and increased handling or riding difficulty at horse shows and other events. The normal state of the horse is to be in a group of other horses; it is entirely natural and to be expected that horses will become stressed when isolated from others. Horses need to become gradually habituated to isolation from other horses and can be easily sensitized to other fears when first exposed to frightening stimuli in isolation from other horses.
Effects of Er addition and cooling rate on the corrosion resistance of Zn-5Al alloys
Authors: Ge Zhen , Huang Chengcong , Qi Liang , Tang Liang , You Shengyi
Published: December 2022

Galfan (Zn-5Al-RE) coating is widely used in high-strength steel wires. The effects of cooling rate and the adulteration of erbium (Er) on the microstructure and corrosion resistance of Zn-5Al alloys were investigated in this study. The results show that the Zn-5Al alloy is made up of the primary η-Zn phase and eutectic structure at a high cooling rate. As the cooling rate decreases, the corrosion current firstly increased and then decreased due to decrease of the primary η-Zn content, the appearance and grew of α-Al phase. Moreover, the addition of Er leads to the formation of Er-containing intermetallic compounds in the Zn-5Al alloy, reducing the size of the primary η-Zn and α-Al phase, decreasing the corrosion current density, and improving the density and compactness of the corrosion product.
A Smart Contract-Based Access Control Framework For Smart Healthcare Systems
Authors: Abid Amal , Cheikhrouhou Saoussen , Kallel Slim , Tari Zahir , Jmaiel Mohamed
Published: December 2022

Security faces huge challenges in Internet of Things (IoT) environments. In particular, conventional access control standards and models tend to be less tailored for IoT due to the constrained nature of smart objects. Usually, a powerful third party is used to handle the access control logic. However, this third party is lacking in transparency and could harm user privacy. Therefore, providing a distributed access control solution, while considering transparency and privacy-preserving awareness in IoT smart systems, is of paramount importance. The described issue can be addressed using the emergent Blockchain technology that provides a promising choice to build a new generation of decentralized and transparent access control solutions. This paper proposes a smart contract-based access control framework for IoT smart healthcare systems, which is based on smart contracts to provide a distributed and trustworthy access control, combined with the GTRBAC model to express fine-grained access control policies while considering temporal authorization constraints. To prove the feasibility and validity of the proposed framework, this paper also provides a detailed technical description and an initial implementation and execution. An experimental evaluation shows that security properties’ analyses on smart contracts achieved the best possible evaluation with no vulnerabilities found, and the cost of access control operations increases linearly as the number of policy constraints increases. Besides, a comparative analysis reveals that the proposed approach can achieve good results with low gas costs and latency.
CSEA: A Fine-Grained Framework of Climate-Season-Based Energy-Aware in Cloud Storage Systems
Authors: Yuan Zhu , Lv Xueqiang , Xie Ping , Ge Haojie , You Xindong
Published: December 2022

Continuous data scale growth increases energy consumption and operating cost that cannot be ignored in cloud storage systems. Previous studies have shown that analyzing the characteristics of I/O access and mining data features is effective for reasonable data distribution in storage systems. The granularity and criterion of classification are the key factors in determining the data distribution. To decrease energy consumption and operating cost, this paper puts forward a fine-grained framework of the climatic-season-based energy-aware in cloud storage system called CSEA. The framework concludes the following three aspects: (i) data feature mining. CSEA discovers potential data features by analyzing data access to provide help with data classification. (ii) K-means clustering algorithm. CSEA uses an unsupervised data classification algorithm in machine learning to divide data into categories based on seasonal characteristics by gathering real I/O access. (iii) data distribution of fine-grained. On the basis of seasonal features, CSEA fuses regional features to further refine the data distribution granularity to save on energy consumption and operating cost. Simulation experiments using extended CloudSimDisk and the constructed mathematical models indicate that CSEA reduces the energy consumption and operating cost compared with the single data classification standard and coarse-grained data distribution.
Warranty period of coronary computed tomography angiography and [15O]H2O positron emission tomography in symptomatic patients
Authors: Jukema Ruurt , Maaniitty Teemu , van Diemen Pepijn , Berkhof Hans , Raijmakers Pieter G , Sprengers Ralf , Planken R Nils , Knaapen Paul , Saraste Antti , Danad Ibrahim , Knuuti Juhani
Published: December 2022

Aims

Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET.

Method and results

Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year).

Conclusion

As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD.
Climate change has limited effect on the growth of Afzelia africana Sm. and Anogeissus leiocarpus (DC.) Guill. and Perr. in riparian forests in the savannas of Ghana
Authors: Boakye Emmanuel A , Ceesay Adam , Osemwegie Isimemen , Kapoury Sanogo , Hounkpevi Achille , Matchi Issiaka I , Tetteh Erasmus N
Published: December 2022

The growth of trees in riparian forests in semi-arid savannas is resilient to the natural variations in temperature and precipitation due to the availability of riverine water. Climate change can nevertheless, intensify the evapotranspiration of tree species, altering biodiversity, plant productivity and ecosystem services. Understanding the growth response of riparian tree species to climate change is, therefore, critical for their management and conservation. Here, we used 23 cross-dated stem discs of Anogeissus leiocarpus (DC.) Guill. and Perr. and Afzelia africana Sm. randomly sampled from riparian forests in the humid and dry savanna regions of Ghana to assess their growth response to climate change. A generalized additive mixed model (GAMM) was used to integrate species-specific basal area increments to an array of explanatory variables that may affect growth, including tree size and seasonal temperature and precipitation between 1982 and 2013. We observed significant association between tree size, rainy and dry season temperatures and precipitation variables, and changes in tree growth. Despite the strong fluctuations in tree growth over time, the estimated growth rates of the species from the residuals of the GAMMs showed no significant change in growth. Our findings suggest that these riparian forests are highly resistant to weather extremes and therefore, might persist (up to a certain point) even if climate change continues to intensify.
Incidence and Effect of Heart Rot in Marayur Sandalwood (Santalum albumL.) Reserve, Kerala, and Its Natural Durability Against Fungi
Authors: Sundararaj Ramachandran , Swetha Purushotham , Mondal Soma , Kantha Reddy Mustypally , Raja Rishi Rajappan , Mamatha Narayanaswamy
Published: December 2022

Indian sandalwood (Santalum album L.) is a semi-parasitic tree, well known for its valuable sandalwood oil extracted from heartwood and roots. Extensive loss of heartwood as a result of its decay is observed in living trees and this has inspired the current study, to investigate the health of sandalwood in Marayur sandalwood forest reserves. Located in Kerala, India, the majority of the trees in Marayur are facing high mortality with the loss of heartwood. The current study evaluated the health status and heartwood-rot disease severity of each tree, which revealed that only 16.67 % of the total trees were healthy and 1.5 % of them were dead. Statistical analysis revealed increasing girth class of trees has a significant positive association with increased disease severity at a 0.05 level of significance. Laboratory analysis confirmed the presence of the major wood-rotters Allophoma tropica, Xylaria berteroi, Diaporthe sp., Fomes sp., Ganoderma appalanatum, and Trametes sp., and that they are collectively responsible for the heart rot. A durability assessment revealed sandalwood is highly resistant (durability class I) to white-rot fungi (viz., Trametes hirsutus and T. [Coriolus] versicolor) and moderately resistant (durability class II) to brown-rot fungi (Oligoporous placenta and Fomitopsis meliae).

Study Implications: This study highlights the health status and heart-rot disease severity of sandalwood trees in Marayur Forest Reserves. Of the total trees surveyed, about 1.5% mortality was observed and only 17% of the trees were devoid of any heart-rot symptoms. Allophoma tropica, Ganoderma applanatum, Xylaria berteroi isolate SR52, Diaporthe sp., Fomes sp., G. appalanatum, and Trametes sp. are typical species collectively responsible for the heart rot and this was found to be the case in our study. These findings will sensitize forest managers to the loss of valuable sandalwood and death of the trees due to the heart rot, thereby enabling them to take appropriate preventive measures. Also, the natural durability of sandalwood against brown- and white-rot fungi is reported for the first time, indicating that sandalwood falls in the resistance class I (highly resistant) against white-rot fungi (Trametes hirsutus and T. (Coriolus) versicolor) and resistance class II (resistant) against brown-rot fungi (Oligoporous placenta and Fomitopsis meliae).
Development of gallbladder cancer during follow-up of pancreaticobiliary maljunction: a report of two cases
Authors: Aota Takanori , Tanaka Shogo , Takemura Shigekazu , Amano Ryosuke , Kimura Kenjiro , Shinkawa Hiroji , Ohira Go , Nishio Kohei , Ishizawa Takeaki , Kubo Shoji
Published: December 2022

Pancreaticobiliary maljunction (PBM) is a congenital malformation. The reflux of pancreatic juice into the biliary tract caused by PBM plays a significant role in the development of biliary tract cancers (BTCs), such as gallbladder cancer and cholangiocarcinoma. Previous studies have demonstrated a high incidence of BTC in patients with PBM. However, there are only a few reports of patients who developed BTC after a diagnosis of PBM. We report the cases of two patients who developed gallbladder cancer after being diagnosed with PBM. They had refused treatment and were being managed with follow-up observation alone after the diagnosis of PBM and developed gallbladder cancer after several years of observation. Thus, surgical treatment should be recommended for all patients with PBM in order to prevent the development of BTC. Moreover, long-term, close, regular follow-up is necessary to facilitate the early diagnosis of subsequent BTC in patients with untreated PBM.
Simultaneous nodular lymphocyte-predominant Hodgkin lymphoma with papillary thyroid carcinoma: a case report
Authors: Murayama Daisuke , Hashizume Toko , Hirano Ryosuke , Azuhata Koji , Shimojo Hisashi , Ito Nobuo , Mishima Osamu
Published: December 2022

We herein report the case of a 48-year-old man diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL, Stage IA) and papillary thyroid carcinoma (PTC, Stage I). Total thyroidectomy, left modified neck dissection and biopsy of the right cervical lymph node were performed. Postoperatively, NLPHL treatment was prioritized, and external radiation (30.6 Gy) was applied to the right neck. PTC was considered a high-risk category for recurrence due to extranodal invasion of lymph node metastasis, and radioactive iodine therapy (ablative dose, 1110 MBq) was administered. Both PTC and NLPHL showed no recurrence 18 months after surgery.
Performance of microbiological tests for tuberculosis diagnostic according to the type of respiratory specimen: a 10-year retrospective study
Authors: Boldi Marc-Olivier , Denis-Lessard Justin , Neziri Rina , Brouillet René , von-Garnier Christophe , Chavez Valérie , Mazza-Stalder Jesica , Jaton Katia , Greub Gilbert , Opota Onya
Published: December 2022

Background

The microbial diagnosis of tuberculosis (TB) remains challenging and relies on multiple microbiological tests performed on different clinical specimens. Polymerase chain reactions (PCRs), introduced in the last decades has had a significant impact on the diagnosis of TB. However, questions remain about the use of PCRs in combination with conventional tests for TB, namely microscopy and culture. We aimed to determine the performance of microscopy, culture and PCR for the diagnosis of pulmonary tuberculosis according to the type of clinical specimen in order to improve the diagnostic yield and to avoid unnecessary, time and labor-intensive tests.

Methods

We conducted a retrospective study (2008-2018) on analysis (34’429 specimens, 14’358 patients) performed in our diagnostic laboratory located in the Lausanne University Hospital to compare the performance of microbiological tests on sputum, induced sputum, bronchial aspirate and bronchoalveolar lavage (BAL). We analysed the performance using a classical “per specimen” approach and a “per patient” approach for paired specimens collected from the same patient.

Results

The overall sensitivities of microscopy, PCR and culture were 0.523 (0.489, 0.557), 0.798 (0.755, 0.836) and 0.988 (0.978, 0.994) and the specificity were 0.994 (0.993, 0.995), 1 (0.999, 1) and 1 (1, 1). Microscopy displayed no significant differences in sensitivity according to the type of sample. The sensitivities of PCR for sputum, induced sputum, bronchial aspirate and BAL were, 0.821 (0.762, 0.871), 0.643 (0.480, 0.784), 0.837 (0.748, 0.904) and 0.759 (0.624, 0.865) respectively and the sensitivity of culture were, 0.993 (0.981, 0.998), 0.980 (0.931, 0.998), 0.965 (0.919, 0.988), and 1 (0.961, 1) respectively. Pairwise comparison of specimens collected from the same patient reported a significantly higher sensitivity of PCR on bronchial aspirate over BAL (p < 0.001) and sputum (p < 0.05) and a significantly higher sensitivity of culture on bronchial aspirate over BAL (p < 0.0001).

Conclusions

PCR displayed a higher sensitivity and specificity than microscopy for all respiratory specimens, a rational for a smear-independent PCR-based approach to initiate tuberculosis microbial diagnostic. The diagnosis yield of bronchial aspirate was higher than BAL. Therefore, PCR should be systematically performed also on bronchial aspirates when available.
Neural stress processing, glucocorticoid functioning, and body mass in lean to obese persons with multiple sclerosis
Authors: Meyer-Arndt Lil , Brasanac Jelena , Gamradt Stefanie , Bellmann-Strobl Judith , Maurer Lukas , Mai Knut , Spranger Joachim , Schmitz-Hübsch Tanja , Paul Friedemann , Gold Stefan M. , Weygandt Martin
Published: December 2022

Background and Objectives

Obesity aggravates disease severity in multiple sclerosis (MS). Altered neural processing of food motivation and cognitive control, and the sensitivity of these processes to stress have been recognized as key obesity mechanisms but never been investigated in MS.

Methods

In this cross-sectional observational study, we evaluated the link between body mass and neural, endocrine and immunological stress parameters in persons with MS (PwMS). We conducted an Arterial-Spin-Labeling MRI task comprising a rest and stress stage (mental arithmetic plus evaluative feedback) in 57 PwMS (37 female, 46.4 ± 10.6 years) covering the full spectrum of the Body Mass Index (BMI [kg/m2]; 6 obese, 19 over-, 28 normal-, 4 underweight). We tested whether BMI in MS links to (i) functional connectivity (FC) between stress-reactive brain regions (showing activity differences for stress vs. rest) computed separately for the task’s rest and stress stage, (ii) T cell glucocorticoid sensitivity and (iii) salivary cortisol secretion.

Results

BMI correlated positively with MS relapse rate (t = 3.23, p = 0.003 = pFamily-Wise-Error [FWE]-corrected= 0.012, and f2= 0.22) and rest stage FC between right anterior insula and supramarginal gyrus (t = 4.02, p = 2.5 · 10−4= pFWE= 0.034, f2= 0.51) and negatively with stress stage FC between right superior parietal lobule and cerebellum exterior (t = -3.67, p = 3.3 · 10−4= pFWE= 0.045, f2= 0.30). Further, BMI was negatively associated with the expression of the co-chaperone FKBP4 on CD8+T cells (t = -2.96, p = 0.003 = pFWE= 0.024, f2= 0.13) and positively with that of FKBP5 (t = 1.83, p = 0.003 = pFWE= 0.024, f2= 0.38).

Conclusion

Our study shows that higher BMI in MS is linked to increased FC between key food motivation and stimulus salience regions and to reduced FC between regions critically involved in cognitive control and generation of stressful states. We further report on correlations between BMI and co-chaperones modulating immune system stress responsivity. Taken together, these results demonstrate that BMI in MS is tied to stress processing across different biological systems.
Study of an age-based Covid-19 outbreak model and the effect of demographic structure of a state on infectious disease dynamics
Authors: Basak Ayanava , Sanyal Tanmay
Published: December 2022

In this paper, our objective was to investigate whether the Covid-19 pandemic disease is more likely to break out in some specific age group or not. We also intended to know whether some specific demographic parameters like birth rate, death rate controls the spreading of the disease. Our investigation showed that the post reproductive population group is more prone to the disease for the countries having population pyramid of stationary or contracting type where as for the countries with expanding population pyramid, the pre reproductive population is more likely to be attacked by the disease. We also found the domains of values of the demographic parameters that result different dynamic phenomena. Further we tried to know whether a country’s population pyramid has an effect in spreading the disease. Our experiment showed that for countries having expanding population pyramid, the total number of cases is expected to be comparatively low whereas for countries having contracting population pyramid, the total number of cases is expected to be comparatively high.
Human neurons lacking amyloid precursor protein exhibit cholesterol-associated developmental and presynaptic deficits
Authors: Mesa Haylee , Zhang Elaine Y. , Wang Yingcai , Zhang Qi
Published: December 2022

Amyloid precursor protein (APP) produces aggregable β-amyloid peptides and its mutations are associated with familial Alzheimer’s disease, which makes it one of the most studied proteins. However, APP’s role in the human brain remains unclear despite years of investigation. One problem is that most studies on APP have been carried out in cell lines or model organisms, which are physiologically different from human neurons in the brain. Recently, human induced neurons (hiNs) derived from induced pluripotent stem cells provide a practical platform for studying the human brainin vitro. Here, we generated APP-null iPSCs using CRISPR/Cas9 genome editing technology and differentiate them to matured human neurons with functional synapses using a two-step procedure. During hiN differentiation and maturation, APP-null cells exhibited less neurite growth and reduced synaptogenesis in serum-free but not serum-containing media. We have found that cholesterol (Chol) remedies those developmental defects in APP-null cells, consistent with Chol’s role in neurodevelopment and synaptogenesis. Phenotypic rescue was also achieved by co-culturing those cells with wildtype mouse astrocytes, suggesting that APP’s developmental role is likely astrocytic. Next, we examined matured hiNs using patch-clamp recording and detected reduced synaptic transmission in APP-null cells. This change was largely due to decreased synaptic vesicle (SV) release and retrieval, which was confirmed by live-cell imaging using two SV-specific fluorescent reporters. Adding Chol shortly before stimulation mitigated the SV deficits in APP-null iNs, indicating that APP facilitates presynaptic membrane Chol turnover during SV exo-/endocytosis cycle. Taken together, our study in hiNs supports the notion that APP contributes to neurodevelopment, synaptogenesis and neurotransmission via maintaining brain Chol homeostasis. Given the vital role of Chol in the central nervous system, the functional connection between APP and Chol bears important implication in the pathogenesis of Alzheimer’s disease.
Estimates of COVID-19 deaths in Mainland China after abandoning zero COVID policy
Authors: Ioannidis John P.A. , Zonta Francesco , Levitt Michael
Published: December 2022

Background

China witnessed a surge of Omicron infections after abandoning zero COVID strategies on December 7, 2022. The authorities report very sparse deaths based on very restricted criteria, but massive deaths are speculated.

Methods

We aimed to estimate the COVID-19 fatalities in Mainland China until summer 2023 using the experiences of Hong Kong and of South Korea in 2022 as prototypes. Both these locations experienced massive Omicron waves after having had very few SARS-CoV-2 infections during 2020-2021. We estimated age-stratified infection fatality rates (IFRs) in Hong Kong and South Korea during 2022 and extrapolated to the population age structure of Mainland China. We also accounted separately for deaths of residents in long-term care facilities in both Hong Kong and South Korea.

Results

IFR estimates in non-elderly strata were modestly higher in Hong Kong than South Korea and projected 987,455 and 619,549 maximal COVID-19 deaths, respectively, if the entire China population was infected. Expected COVID-19 deaths in Mainland China until summer 2023 ranged from 49,962 to 691,219 assuming 25-70% of the non-elderly population being infected and variable protection of elderly (from none to three-quarter reduction in fatalities). The main analysis (45% of non-elderly population infected and fatality impact among elderly reduced by half) estimated 152,886-249,094 COVID-19 deaths until summer 2023. Large uncertainties exist regarding potential changes in dominant variant, health system strain, and impact on non-COVID-19 deaths.

Conclusions

The most critical factor that can affect total COVID-19 fatalities in China is the extent to which the elderly can be protected.
Nanofluidic Device for Manipulation and Modification of DNA by Proteins
Authors: Dangi Saroj , Liu Ming , Azad Zubair , Countryman Preston , Roushan Maedeh , Livshits Gideon I. , Kaur Parminder , Pan Hai , Shi Zhubing , Detwiler Ariana C. , Opresko Patricia L. , Yu Hongtao , Wang Hong , Riehn Robert
Published: December 2022

Single-molecule techniques provide important details supplementing the framework obtained from traditional bulk experiments. Many cellular processes such as DNA replication, DNA repair, and telomere maintenance involve interaction among multiple proteins, their co-factors, and DNA. To investigate such interactions and to differentiate the function of each component necessitate a technique that allows the combinatorial exposure of DNA to multiple proteins and co-factors as well as manipulation of the DNA configuration. We present a nanofluidic device with the capability of active combinatorial exchange of up to three buffers in real-time and dynamic manipulation of DNA under physiologically relevant conditions. We demonstrate its utility in monitoring compaction of DNA by telomeric proteins, DNA modification by an endonuclease, and DNA loop extrusion by cohesin.
DNA origami 2.0
Authors: Agarwal Nayan P. , Gopinath Ashwin
Published: December 2022

DNA origami is a technique that allows the creation of precise, modular, and programmable nanostructures using DNA. These nanostructures have found use in several fields like biophysics, molecular biology, nanoelectronics, and nanophotonic due to their programmable nature as well as ability to organize other nanomaterials with high accuracy. However, they are fragile and unstable when removed from their optimal aqueous conditions. In contrast, other commonly used bottom-up methods for creating inorganic nanoparticles do not have these issues, but it is difficult to control the shape or spatial organization of ligands on these nanoparticles. In this study, we present a simple, highly controlled method for templated growth of silica on top of DNA origami while preserving all the salient features of DNA origami. Using the polyplex micellization (PM) strategy, we create DNA nanostructures that can withstand salt-free, buffer-free, alcohol-water mixtures, enabling us to control the material growth conditions while maintaining the monodispersity and organization of nanoelements. We demonstrate the growth of silica shells of different thicknesses on brick and ring-shaped DNA origami structures using the standard Stöber process. We also demonstrate the thermostability of the silica-coated nanostructures as well as accessibility of surface sites programmed into the DNA origami after the silica growth in the final inorganic nanostructure.
Atypical B cells mediate poor response to Bacillus Calmette Guérin immunotherapy in non-muscle invasive bladder cancer
Authors: Yolmo Priyanka , Rahimi Sadaf , Chenard Stephen , Conseil Gwenaëlle , Jenkins Danielle , Sachdeva Kartik , Emon Isaac , Hamilton Jake , Xu Minqi , Rangachari Manu , Michaud Eva , Mansure Jose , Kassouf Wassim , Berman David M. , Siemens D. Robert , Koti Madhuri
Published: December 2022

Poor response to Bacillus Calmette-Guérin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle-invasive bladder cancer (NMIBC). Among the multiple factors contributing to poor outcomes, a B cell infiltrated pre-treatment immune microenvironment of NMIBC tumors has emerged as a key determinant of response to BCG. The mechanisms underlying the paradoxical roles of B cells in NMIBC are poorly understood. Here, we show that B cell dominant tertiary lymphoid structures (TLSs), a hallmark feature of chronic mucosal immune response, are abundant and located close to the epithelial compartment in pre-treatment tumors from BCG non-responders. Digital spatial proteomic profiling of whole tumor sections revealed higher expression of immune exhaustion-associated proteins within the TLSs from both responders and non-responders. Chronic local inflammation, induced by the N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen, led to TLS formation with recruitment and differentiation of the immunosuppressive atypical B cell (ABCs) subset within the bladder microenvironment, predominantly in aging female mice compared to their male counterparts. Depletion of ABCs simultaneous to BCG treatment delayed cancer progression in female mice. Our findings provide the first evidence indicating the role of ABCs in BCG response and will inform future development of therapies targeting the B cell exhaustion axis.
An Autoinhibited Conformation of the DnaB-Replicative Helicase – phage λP Helicase Loader Complex
Authors: Brown Dhanjai , Shatarupa Abhipsa , Olinares Paul Dominic B. , Chase Jillian , Isiorho Eta , Chait Brian T. , Jeruzalmi David
Published: December 2022

Replicative helicases require loader proteins for assembly at origins of DNA replication. Multiple copies of the bacteriophage λP loader bind to theE. coliDnaB replicative helicase and trigger its reconfiguration into a right-handed open spiral wherein an internal chamber becomes accessible to physiological single stranded DNA. In the 2.84 Å model of the DnaB – λP complex, the pentameric λP ensemble adopts an asymmetric configuration; one copy of λP, which is visualized in full, binds at the top and bottom of the open DnaB spiral; the presence of a single breach in the DnaB open spiral implies that the remaining four copies of λP must adopt distinct conformations. DnaB’s internal chamber remains accessible to ssDNA, however, the λP protomer whose binding site spans the breach effectively blocks the path into the inner chamber to give rise to an autoinhibited configuration for the complex. Although the path to the inner chamber is blocked, the BP complex, nevertheless, binds ssDNA, and we suggest that the path for ssDNA lies outside the DnaB ring. Comparisons of the λP and DnaC complexes of the DnaB helicase shed new light on how the two loaders, though unrelated in structure, converged on the same ring-opening mechanism. Our structure suggests the conformation changes that accompany recruitment to the initiator protein complex at the replication origin.

Graphical Abstract

The autoinhibited configuration of the DnaB helicase λP loader complex. Interaction with the loader reconfigures the helicase, depicted in the ribbon format and under a transparent surface, into an open spiral, with its internal chamber exposed to solvent. One copy of the λP loader binds across the single breached interface in DnaB, effectively blocking the path into the inner chamber. The pink cylinder represents the expected path of ssDNA through DnaB.
Self-pressurized rapid freezing at arbitrary cryoprotectant concentrations
Authors: Rolle K. , Okotrub K.A. , Zaytseva I.V. , Babin S.A. , Surovtsev N.V.
Published: December 2022

Self-pressurized rapid freezing (SPRF) has been proposed as a simple alternative to traditional high pressure freezing (HPF) protocols for vitrification of biological samples in electron microscopy and cryopreservation applications. Both methods exploit the circumstance that the melting point of ice reaches a minimum when subjected to pressure of around 210 [MPa], however, in SPRF its precise quantity depends on sample properties and hence, is generally unknown. In particular, cryoprotective agents (CPAs) are expected to be a factor; though eschewed by many SPRF experiments, vitrification of larger samples notably cannot be envisaged without them. Thus, in this study, we address the question of how CPA concentration affects pressure inside sealed capillaries, and how to design SPRF experiments accordingly. By embedding a fiber-optic probe in samples and performing Raman spectroscopy after freezing, we first present a direct assessment of pressure buildup during SPRF, enabled by the large pressure sensitivity of the Raman shift of hexagonal ice. Choosing dimethyl sulfoxide (DMSO) as a model CPA, this approach allows us to demonstrate that average pressure drops to zero when DMSO concentrations of 15 wt % are exceeded. Since a trade-off between pressure and DMSO concentration represents an impasse with regards to vitrification of larger samples, we introduce a sample architecture with two chambers, separated by a partition that allows for equilibration of pressure but not DMSO concentrations. We show that pressure and concentration in the fiber-facing chamber can be tuned independently, and present differential scanning calorimetry (DSC) data supporting the improved vitrification performance of two-chamber designs.
miR-17∼92 Suppresses Proliferation and Invasion of Cervical Cancer Cells by Inhibiting Cell Cycle Regulator Cdt2
Authors: Singh Garima , Sharma Sonika Kumari , Aastha  , Singh Samarendra Kumar
Published: December 2022

Cervical cancer (CC) is 4thlargest killer of women worldwide when diagnosed in late stages the treatment options are almost negligible. 99% of CC is caused by high risk human papilloma viruses (HR-HPV). Upon integration into human genome the encoded viral proteins mis-regulates various onco-suppressor and checkpoint factors including cell cycle regulators. One such factor is cell cycle S phase licensing factor Cdt2, which has been reported to be highly upregulated in various cancers including CC. HPV proteins also suppress several tumor suppressor miRNAs concluding miR-17-92 cluster. In this study we report that miR-17-92 directly recruits to 3’UTR of Cdt2 and downregulates this oncogene which suppresses the proliferation, migration, invasion capabilities of the CC cell lines while normal cells are fine. Suppression of Cdt2 by miR17-92 blocks the cancerous cells in S phase and induces apoptosis eventually leading to their death. Hence, our work for the first time mechanistically shows how miR17-92 could work as tumor suppressor opening up the potential of miR17-92 to be used in developing therapy for cervical cancer treatment.
A newly-recognized population of residual neural crest cells in the adult leptomeninges is re-activated for vascular repair
Authors: Nakamura Yoshihiko , Nakano Takafumi , Park Ji Hyun , Tanaka Masayoshi , Li Wenlu , Esposito Elga , Ahn Bum Ju , Durán-Laforet Violeta , Desai Rakhi , Sencan Ikbal , Sakadžić Sava , Lo Eng H. , Snyder Evan Y. , Tabaka Marcin , Hayakawa Kazuhide
Published: December 2022

The neural crest (NC) is a transient structure in vertebrate embryogenesis comprising highly migratory multipotent stem cells that give rise to a diverse array of cell types in organs throughout the body, including initiating neurovascular patterning. It is assumed that neural crest stem cells (NCSCs) disappear after development. Unexpectedly, using single-nucleus RNA-sequencing, we discovered residual quiescent NCSCs in the adult mouse meninges which are activated by injury and contribute to the brain’s homeostatic response. RNA velocity, pathway, and transcription factor analyses in a murine stroke model (combined with in vivo imaging) show that these adult NCSCs migrate towards the perivascular spaces of the infarct and undergo a perivascular stromal cell transition that is regulated by Ptp1b, Ghr, and Stat3. Loss- and gain-of-function experiments show that these “vestigial” NCSCs are required for restoring vascular endothelial barrier function via β-catenin and Stat3 signaling. These findings suggest that, in the adult, an unexpected reservoir of cells -- once pivotal to embryogenesis and vascular morphogenesis -- are re-invoked for neurovascular repair.