bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the effect of CRISPR-Cas9-based epigenome editing
Authors: Batra Sanjit Singh , Cabrera Alan , Spence Jeffrey P , Goell Jacob , Anand Selvalakshmi S , Hilton Isaac B , Song Yun S
Published: December 2023

Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models to predict gene expression from histone post-translational modifications (PTMs), achieving transcriptome-wide correlations of ∼ 0.70 − 0.79 for most cell types. Our models recapitulate known associations between histone PTMs and expression patterns, including predicting that acetylation of histone subunit H3 lysine residue 27 (H3K27ac) near the transcription start site (TSS) significantly increases expression levels. To validate this prediction experimentally and investigate how natural vs. engineered deposition of H3K27ac might differentially affect expression, we apply the synthetic dCas9-p300 histone acetyltransferase system to 8 genes in the HEK293T cell line and to 5 genes in the K562 cell line. Further, to facilitate model building, we perform MNase-seq to map genome-wide nucleosome occupancy levels in HEK293T. We observe that our models perform well in accurately ranking relative fold-changes among genes in response to the dCas9-p300 system; however, their ability to rank fold-changes within individual genes is noticeably diminished compared to predicting expression across cell types from their native epigenetic signatures. Our findings highlight the need for more comprehensive genome-scale epigenome editing datasets, better understanding of the actual modifications made by epigenome editing tools, and improved causal models that transfer better from endogenous cellular measurements to perturbation experiments. Together these improvements would facilitate the ability to understand and predictably control the dynamic human epigenome with consequences for human health.
UGGT1/2-mediated reglucosylation of N-glycan competes with ER-associated degradation of unstable and misfolded glycoproteins
Authors: Ninagawa Satoshi , Matsuo Masaki , Ying Deng , Aso Shinya , Matsushita Kazutoshi , Fueki Akane , Saito Shunsuke , Imami Koshi , Kizuka Yasuhiko , Sakuma Tetsushi , Yamamoto Takashi , Yagi Hirokazu , Kato Koichi , Mori Kazutoshi
Published: December 2023

Here we investigated how the fate (folding versus degradation) of glycoproteins is determined in the endoplasmic reticulum (ER). Monoglucosylated glycoproteins are recognized by lectin chaperones to facilitate their folding, whereas glycoproteins with well-trimmed mannoses are subjected to glycoprotein ER-associated degradation (gpERAD). Previously we elucidated how mannoses are trimmed by EDEM family members (George et al., 2020, 2021 eLife). Though reglucosylation by UGGTs (UGGT1 and UGGT2) was reported to have no effect on substrate degradation, here, we directly test this using genetically disrupted UGGTs. Strikingly, the results showed that UGGTs (mainly UGGT1) delayed the degradation of misfolded substrates and unstable glycoproteins including ATF6α. An experiment with a point mutant of UGGT1 indicated that the glucosylation activity of UGGT was required for the inhibition of early glycoprotein degradation. We further demonstrated the physiological importance of UGGT, since ATF6 cannot function properly without UGGTs. The fate of glycoproteins is determined by a tug-of-war between structure formation by UGGTs and degradation by EDEMs. Thus, our work strongly suggests that UGGTs are central factors in ER protein quality control via regulation of both glycoprotein folding and degradation.
Mapping the molecular motions of 5-HT3 serotonin-gated channel by Voltage-Clamp Fluorometry
Authors: Peverini Laurie , Shi Sophie , Medjebeur Karima , Corringer Pierre-Jean
Published: December 2023

The serotonin-gated ion channel (5-HT
3
R) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive antagonists widely used as antiemetics, and is involved in several neurological diseases. Cryo-electron microscopy of the 5-HT
3
R in complex with serotonin or setrons revealed that the protein has access to a wide conformational landscape. However, assigning known high-resolution structures to actual states contributing to the physiological response remains a challenge.In the present study, we used voltage-clamp fluorometry (VCF) to measure simultaneously, for 5-HT
3
R expressed at a cell membrane, conformational changes by fluorescence and channel opening by electrophysiology. Four positions identified by mutational screening report motions around and outside the serotonin-binding site through incorporation of cysteine-tethered rhodamine dyes with or without a nearby quenching tryptophan. VCF recordings show that the 5-HT
3
R has access to four families of conformations endowed with distinct fluorescence signatures: “resting-like” without ligand, “inhibited-like” with setrons, “pre-active-like” with partial agonists and “active-like” (open channel) with partial and strong agonists. Data are remarkably consistent with cryo-EM structures, the fluorescence partners matching respectively Apo, setron-bound, 5-HT bound-closed and 5-HT-bound-open conformations. Data show that strong agonists promote a concerted motion of all sensors during activation, while partial agonists, especially when loss-of-function mutations are engineered, stabilize both active and pre-active conformations.In conclusion, VCF, though the monitoring of electrophysiologically silent conformational changes, illuminates allosteric mechanisms contributing to signal transduction and their differential regulation by important classes of physiological and clinical effectors.High-resolution structures of serotonin-gated receptors (5-HT
3A
R) have evidenced a wide range of conformations that are challenging to annotate to physiologically relevant states. Voltage-clamp fluorometry allows to investigate the activation of 5-HT
3A
R by simultaneously following molecular motions and electrophysiological states at the plasma membrane. Here, we developed four fluorescent sensors reporting conformational changes at the serotonin binding site and at the extracellular domain and transmembrane domain interface. Investigation of a series of agonists, partial agonists and antagonists show that strong agonists promote a concerted motion of the whole protein during activation, while antagonists and partial agonists stabilize distinct closed-channel conformations. Data offer insights into allosteric mechanisms, unravelling the conformational dynamics of the receptors and helping to annotate high-resolution static structures.
Human Serum is a Potent Chemoattractant for Enterobacteriaceae Species Associated with Gastrointestinal Bleeding
Authors: Glenn Siena J. , Gentry-Lear Zealon , Shavlik Michael , Harms Michael J. , Asaki Thomas J. , Baylink Arden
Published: December 2023

Enterobacteriaceae bacteria are prone to opportunistic pathogenic behavior during gut dysbiosis, potentially influenced by distinct environmental cues within the compromised gut. Chemosensing systems play a central role in allowing bacteria to perceive and react to physicochemical signals within the gastrointestinal (GI) milieu, influencing their motility, population organization, and colonization site preferences. We investigated the chemosensory behavior of Enterobacteriaceae, a bacterial family associated with gastrointestinal (GI) bleeding and sepsis, to learn whether these bacteria respond to human serum, a chemical stimulus they encounter during GI bleeding. We discover that clinical isolates of diverse non-typhoidal
Salmonella enterica
serovars,
Escherichia coli
, and
Citrobacter koseri
all sense human serum as a potent attractant. Using a custom injection-based microfluidics device we simulated GI bleeding and found that femtoliter volumes of human serum are sufficient to stimulate motile cells to rapidly swim toward, and congregate at, the serum source. With exceptional temporal resolution, we determined that this response is orchestrated through chemotaxis, with a major chemical cue driving chemoattraction being L-serine, an amino acid abundantly present in serum, recognized by the chemoreceptor Tsr. To gain deeper insight into the structural basis of this phenomenon, we successfully elucidated the crystal structure of
Salmonella
Typhimurium Tsr in complex with L-serine. This structure allowed for a precise characterization of the ligand-binding site, thereby correcting prior misconceptions regarding L-serine positioning and accurately defining the chemoreceptor’s ligand-binding interactions. Building upon these structural insights, we identified a conserved amino acid recognition motif for L-serine shared among Tsr orthologues and mapped the phylogenetic distribution of this chemoreceptor. We found that Tsr, which mediates serum chemoattraction, is widely conserved among Enterobacteriaceae and many World Health Organization priority pathogens associated with bloodstream infections. Given that Enterobacteriaceae are a primary cause of bacteremia and sepsis, particularly as a complication of inflammatory bowel diseases, their remarkable sensitivity to serum as a chemoattractant could relate to their proclivity for bloodstream entry.
Investigating the impact of cannabis
Authors: Pierson Smela Merrick
Published: December 2023

The psychoactive component of cannabis, ∆9-THC, affects cell growth and metabolism in early embryonic cell types in mice.
Attribute identification based IoT fog data security control and forwarding
Authors: Xiao Jingxu , Chang Chaowen , Wu Ping , Ma Yingying
Published: December 2023

As Internet of Things (IoT) applications continue to proliferate, traditional cloud computing is increasingly unable to meet the low-latency demands of these applications. The IoT fog architecture solves this limitation by introducing fog servers in the fog layer that are closer to the IoT devices. However, this architecture lacks authentication mechanisms for information sources, security verification for information transmission, and reasonable allocation of fog nodes. To ensure the secure transmission of end-to-end information in the IoT fog architecture, an attribute identification based security control and forwarding method for IoT fog data (AISCF) is proposed. AISCF applies attribute signatures to the IoT fog architecture and uses software defined network (SDN) to control and forward fog layer data flows. Firstly, IoT devices add attribute identifiers to the data they send based on attribute features. The ingress switch then performs fine-grained access control on the data based on these attribute identifiers. Secondly, SDN uses attribute features as flow table matching items to achieve fine-grained control and forwarding of fog layer data flows based on attribute identifiers. Lastly, the egress switch dynamically samples data flows and verifies the attribute signatures of the sampled data packets at the controller end. Experimental validation has demonstrated that AISCF can effectively detect attacks such as data tampering and forged matching items. Moreover, AISCF imposes minimal overhead on network throughput, CPU utilization and packet forwarding latency, and has practicality in IoT fog architecture.
A new species and new records of Hymenopellis and Xerula (Agaricales, Physalacriaceae) from China
Authors: Liu Ya-jie , Qi Zheng-xiang , Li You , Yue Lei , Zhao Gui-ping , Gui Xin-yue , Dong Peng , Wang Yang , Zhang Bo , Li Xiao
Published: December 2023

Hymenopellis is the genus that exhibits the highest number of species within the Xerula/Oudemansiella complex. Numerous species of Hymenopellis demonstrate edibility, and some of these species have been domesticated and cultivated. During an extensive survey carried out in Henan and Jilin Provinces, China, a substantial quantity of Hymenopellis specimens was gathered as a component of the macrofungal resource inventory. Based on the findings of morphological and molecular phylogenetic studies, a new species, Hymenopellis biyangensis, has been identified. A new record species, Hymenopellis altissima, has been discovered in China. Additionally, two new record species, Hymenopellis raphanipes and Xerula strigosa, have been found in Henan Province. Internal transcribed spacer (ITS) and large subunit ribosomal (nrLSU) were used to establish a phylogeny for species identification. Detailed descriptions, field habitat maps and line drawings of these species are presented. The discussion focuses on the relationships between newly discovered species and other related taxa. Additionally, this study provides and a key to the documented species of Hymenopellis and Xerula found in China.
Serum Biochemical Changes among Chronic Kidney Disease Patients in a Rural Cohort of Odisha, India: A Cross-sectional Study
Authors: Dash Pujarini , Nayak Soumya Ranjan , Sahoo Debadutta , Rana Khokan , Nayak Swetalina , Mohanty Kanhu Charan , Pati Sanghamitra , Palo Subrata Kumar
Published: December 2023

Introduction: Chronic Kidney Disease (CKD) is one of the fastest-growing causes of death worldwide. Monitoring biochemical parameters such as liver function tests, kidney function tests, and lipid profiles is crucial for early identification of health complications, prevention, and prompt management in CKD patients. Aim: To investigate the association of sociodemographic factors and serum biochemical indicators with Glomerular Filtration Rate (GFR) among CKD patients in rural Odisha, India. Materials and Methods: A cross-sectional study was conducted in a rural cohort of the Model Rural Health Research Unit (MRHRU) established in Cuttack district, Odisha, India, from March 2021 to April 2021. A total of 530 registered CKD patients were enrolled in the study. Sociodemographic data and blood samples were collected for lipid profile, kidney function, and liver function analysis. The data were analysed using STATA 15.1 and RStudio 2021.09.0+351. Results: The mean age of the study participants was 51.2±14.1 years, with 330 (62.26%) being male. A total of 74% of the participants showed abnormal Estimated Glomerular Filtration Rate (eGFR). Abnormal eGFR was found to be more common among the older age group (>45 years), those who were literate, and those in private jobs, compared to their counterparts. Both lipid profile and liver function abnormalities were significantly associated with individuals having normal eGFR. Conclusion: The positive association of eGFR with lipid profile and liver function enzymes highlights the importance of regular screening of these parameters among CKD patients for early prevention and control of future complications.
Hepatoid Adenocarcinoma of the Stomach: A Rare Tumour in an Unusual Subserosal Location
Authors: Chatura Kasimsetty Ramakantha , Muniswamyreddy Archana
Published: December 2023

Hepatoid Adenocarcinoma (HAC) is a special type of adenocarcinoma of extrahepatic origin that has overlapping features with Hepatocellular Carcinoma (HCC). Herein, present case is of a 75-year-old man who presented with abdominal pain, bilious vomiting, and constipation for four days, along with a palpable mass in the abdomen for five months. Imaging studies revealed a mass in the subserosal region of the greater curvature of the stomach. Intraoperative findings showed a mass involving the stomach, liver, and omentum, initially suggesting a diagnosis of malignant Gastrointestinal Stromal Tumour (GIST). However, histopathological examination revealed lobules of polygonal cells with abundant eosinophilic to vacuolated cytoplasm and enlarged, moderately pleomorphic nuclei, indicating hepatoid differentiation. The aggressive nature of the lesion, invading the liver and omentum, the absence of risk factors for HCC, negative staining for CD 117 and polyclonal Carcinoembryonic Antigen (pCEA), and positive staining for glypican 3 and CK 19 on immunohistochemistry, confirmed the diagnosis of HAC of the stomach rather than HCC. After surgery, the patient was referred to an Oncology centre. An accurate diagnosis of HAC is crucial due to its aggressive nature and poor prognosis.
Energy Consumption & Economic Growth in Nigeria (1971 - 2021): A Multifaceted Analysis Using Descriptive Statistics, Charts, Logistic Regression, and Neural Networks
Authors: Ikpe Victory , Oyedeji Emmanuel
Published: December 2023

This study examines the intricate interplay between electricity consumption and economic growth, specifically Gross Domestic Product (GDP), in Nigeria. Despite the acknowledged influence of electricity consumption on GDP, the research takes a comprehensive approach by scrutinizing various economic factors that may contribute to Nigeria's remarkable GDP performance within the African context. Utilizing a meticulous methodology, the investigation explores the relationships between GDP and variables such as unemployment, population, lending interest rates, importation costs, and inflation rates across a 50-case observational dataset. The findings highlight the substantial impact of electric power consumption, population, and lending interest rates on Nigeria's GDP, while revealing the relatively minor effects of other predictors.
Comparing Unbalanced and Balanced CNTFET Ternary Adders and Multipliers with the Corresponding Binary Ones
Authors: Etiemble Daniel , Jaber Ramzi
Published: December 2023

This paper compares the performance of the ternary adders and multipliers using balanced and unbalanced set of values. We use the 1-trit adders to evaluate the two versions of a 4-trit propagate adder, which are comparedwith a 6-bit corresponding propagate adder. Similarly, we compare the two types of 2*2 trit multipliers with a3*3 bit multiplier. The simulations with a 32-nm Carbon Nanotuble Field-Effect Transistor (CNTFET) technology show that the binary adders and multipliers are more efficient than the ternary ones that compute the same amount of information
Vulva Candidiasis among HIV Patients and Healthy Female Volunteers in Port Harcourt
Authors: Nwalozie Rhoda , Nnokam Brenda Anyakwe , Onosakponome Evelyn Orevaoghene , Ikpeama Roseanne Adah , Nyenke Clement Ugochukwu
Published: December 2023

Vulvo-rectal the most prevalent species of candida, Candida albicans, is the cause of candidiasis, a fungal infection of the vagina that affects the genital system as an adaptive and opportunistic pathogen.

This study was aimed at examining the prevalence and risk factors of vulvo-vaginal candidiasis among HIV positive women and healthy volunteers in Port Harcourt. A total of 200 urine and HVS samples, 100 from each of the two groups, were collected. The samples were examined using culture, microscopy, and the germ tube identification method. The overall prevalence of Vulvo-vaginitis in HIV and healthy volunteers using urine and HVS was (32%), (34%), and (76%) and (54%) respectively. HIV recorded a higher of (76%) compared to that of healthy volunteers with (54%). There was no statistically significant difference in the two groups’ prevalence (p>0.05). The age group of 15–25 years old had the highest prevalence of (33%), while the age group of 40–45 had the highest prevalence of 80% for HIV.  HIV-positive workers and retirees had higher rates of vulvo-vaginitis in urine samples (21% and 75%, respectively) than did healthy workers and retirees (15% and 25%, respectively). Individuals with tertiary education had the highest prevalence of (32%) and (14%) in HIV and healthy volunteers respectively. It was also reported that married individuals who are HIV positive had a higher incidence of (50%) while for healthy volunteers, single individuals recorded a higher frequency of (29%). Prevalence of vulvo-vaginal candidiasis was greater in HIV patients in Port Harcourt. To help combat fungal infections, it is proposed that antifungal medications be added to antiretroviral medications prescribed to HIV patients.
Correlation and Path Coefficient Studies of Three Line Rice Hybrids
Authors: Kumar A. Ravi , Kant Ravi , Vennela M. , Varma D. Dinesh
Published: December 2023

Thirty-one three-line rice hybrids and three commercial checks were used in the current study for correlation and path coefficient analysis. In Kharif 2021, the experiment was carried out at the TCA Hybrid Rice field in Dholi, Pusa, Bihar, India. The experimental design adopted was a Randomized Complete Block Design (RBD) with three replications that included 18 quantitative attributes. Plant height, number of tillers per plant, number of panicles per plant, leaf length, leaf area, kernel length, kernel width, root fresh weight, root dry weight, spikelet fertility, and test weight showed a positive significant correlation with grain yield per plant. Hence, selection for any one of these characteristics would ultimately bring improvement in grain yield. The traits number of tillers per plant, plant height, root fresh weight, leaf length, no. of panicles per plant, leaf width, kernel length, and root volume revealed a significant direct impact on grain yield per plant. Thus, breeding for these characteristics could end up resulting in a higher grain yield.
Effect of Pre-harvest Application on Physical Attributes of Guava (Psidium guajava L.) in cv. L–49: Plant Growth Regulators and Bagging
Authors: Deepak  , Pratap Bhanu , Sonkar Abhishek , Patel Brijesh , Kumar Dhananjay , Maurya Aman Kumar
Published: December 2023

The present investigation was conducted to study the Effect of pre-harvest application of plant growth regulators (PGR) and bagging on Physical attributes of Guava (Psidium guajava L.) in cv. L - 49. The research was carried out at the main experiment station Horticulture, Department of Fruit Sciences, Acharya Narendra Deva University of Agriculture and Technology, Narendra Nagar, Kumarganj, Ayodhya 224229 (U.P.) India during the year 2022-23. The experiment was conducted in a Randomized Block Design with three replications and 8 treatments GA3 (50 ppm) and NAA (20 ppm) and GA3 (50 ppm) +NAA (20 ppm), GA3 (50 ppm) with bagging, and NAA (20 ppm) with bagging. GA3 (50 ppm) + NAA (20 ppm) with bagging, bagging (white polythene), and control applied on spray 45 days before harvesting. It is concluded that among the different treatments. T6 GA3 (50 ppm) + NAA (20 ppm) with bagging, was recorded maximum Fruit length (4.90 cm), Fruit width (6.62 cm), Fruit weight (158.20 gram), Fruit volume (161.60 cm3), Specific gravity (0.98 g/cm3) therefore, recommended for application to the Guava tree in the sub-tropical region of Uttar Pradesh in order to obtain better quality fruit.
A Review on Malicious URLs Detection Using Machine Learning Methods
Authors: Tabassum Tasfia , Alam Md. Mahbubul , Ejaz Md. Sabbir , Hasan Mohammad Kamrul
Published: December 2023

Malicious URLs are a serious threat to cybersecurity because they can compromise user security and inflict large financial losses. The extensiveness and adaptability of traditional detection approaches which rely on blacklists are limited when it comes to rapidly emerging threats. In response, machine learning methods have become more popular as a means of improving the detection efficiency of malicious URLs. This paper provides a thorough analysis providing a structured understanding of all aspects and formal formulation of the machine learning job of malicious URL detection. It covers feature representation and algorithm design, classifying and reviewing contributions from literature studies. The survey aims to provide a state-of-the-art understanding and support future research and practical implementations. It targets a diverse audience, including experts, cybersecurity professionals and machine learning researchers. The article provides a comprehensive overview of the field discussing practical system design considerations, ongoing research challenges and future research directions.
Ophthalmia " Adultorum" Secondary to Cytomegalovirus and Candida albicans Isolates from Right Eye Ulcer of an Alcoholic: The Benin City Experience
Authors: Lofor Patrick , Ebeigbe Ejime
Published: December 2023

Background: Eye injuries are more common and have more severe effects when they occur in developing countries. The factors reponsible for these eye injuries can be linked to socioeconomic status, insufficient safety precautions, a lack of ideal treatment facilities, the use of conventional eye medication, and low levels of education. Ocular trauma has been identified in studies from Nigeria and other African countries as a major contributing factor to monocular blindness.

In neonates, conjunctivitis within the first 28 days of life is termed “Ophthalmia neonatorium”. Conjunctivitis arising from either viral, bacteria or fungal causes in an Adult is what we termed as “Ophthalmia Adultorum".

 In our study the individual was a chronic alcoholic who was already immunosuppressed from his large alcohol intake. This study therefore is case report of a traumatic innoculation causing Ophthalmia Adultorum in a male alcoholic, a university of Benin Teaching Hospital experience.

Methods: This is a case report.

Results: A 57 year old man who  was admitted on 25 September, 2023, as a case of  Cytomegalovirus  (CMV ) and Candida albicans associated  Conjunctivitis ,after a  traumatic  sandball inoculation to his right eye . Conjunctiva swab for microscopy and culture was sent to the medical microbiology laboratory. Gram stain showed yeasts cells, while 10%giemsa staining of the eye swab showed ztanck cells. Culture yielded Candida albicans.

He was placed on chloramphenicol eye drop, steroid eye drops, Acyclovir (patient could not afford gangcyclovir the specific antiviral drug due to high cost) and fluconazole eye drops. Patient was managed by the ophthalmologists and the Medical Microbiology team.

Patient was discharged home on the 5th day  and was asked to come for follow up after one week .On follow up visit , previous symptoms had resolved and right and left eyes were both normal on examination.

Conclusion: We are unaware of any previous reports of Ophthalmia Adultorium involving Cytomegalovirus and Candida albicans in patients with sandball eye accidents. Patients with sandball injuries should be assessed quickly and antibiotic and antifungal therapy should be considered if cultures are positive.
How Do Policymakers Regulate AI and Accommodate Innovation in Research and Medicine?
Authors: Suran Melissa , Hswen Yulin
Published: December 2023

In this Medical News article, JAMA Editor in Chief Kirsten Bibbins-Domingo, PhD, MD, MAS, and Alondra Nelson, PhD, the Harold F. Linder Professor at the Institute for Advanced Study, discuss effective AI regulation frameworks to accommodate innovation.
Despite Safe and Effective Vaccine, Measles Cases and Deaths Increased Worldwide From 2021 to 2022
Authors: Rubin Rita
Published: December 2023

This Medical News story discusses the latest data on measles cases, deaths, and vaccination coverage worldwide.
Adenopathy and an Extensive Skin Patch Overlying a Plasmacytoma Syndrome
Authors: Song Won Ji , Kim Dong Hyo , Mun Je-Ho
Published: December 2023

This case report describes a central cobblestone-like mass and bone lesion on the spinous process of the L3 vertebra underlying the skin mass.
Meaningful Change Thresholds for the Psoriasis Symptoms and Signs Diary
Authors: Papp Kim A. , Gordon Kenneth , Strober Bruce , Zhuo Joe , Becker Brandon , Zhong Yichen , Beaumont Jennifer L. , Pham Tan P. , Kisa Renata , Napoli Andrew A. , Banerjee Subhashis , Armstrong April W.
Published: December 2023

Importance

Change from baseline score on the validated Psoriasis Symptoms and Signs Diary (PSSD) is a widely used, patient-reported end point in clinical trials for psoriasis. Meaningful score change thresholds anchored to patient-reported assessments have not been established in a clinical trial setting.

Objective

To evaluate meaningful within-patient score change thresholds for the PSSD using data from the phase 3 Program to Evaluate the Efficacy and Safety of Deucravacitinib, a Selective TYK2 Inhibitor (POETYK), PSO-1 clinical trial, which compared the efficacy and safety of deucravacitinib vs placebo and apremilast among adults with moderate to severe plaque psoriasis.

Design, Setting, and Participants

In this predefined analysis using data from the POETYK PSO-1 multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, conducted from August 7, 2018, to September 2, 2020, 666 adults with moderate to severe plaque psoriasis completed the PSSD daily throughout the trial. Meaningful change thresholds were derived by anchoring mean PSSD score change from baseline to week 16 to category improvements on the Patient Global Impression of Change (PGI-C) and the Patient Global Impression of Severity (PGI-S).

Interventions

Deucravacitinib, 6 mg, once daily; placebo; or apremilast, 30 mg, twice daily.

Main Outcome and Measures

The main outcome was score change from baseline to week 16 on the PSSD, anchored to the PGI-C and PGI-S.

Results

The trial included 666 patients (mean [SD] age, 46.1 [13.4] years; 453 men [68.0%]). Three thresholds were identified using an analysis set of 609 patients. Score improvement of at least 15 points from baseline reflected meaningful within-patient change anchored to the PGI-C. Score improvements of 25 points were supported by both the PGI-C and the PGI-S, while a 30-point score change identified patients with greater improvements in their psoriasis symptoms and signs.

Conclusions and Relevance

This analysis suggests that PSSD score improvements of 15, 25, or 30 points represent increasing improvements in disease burden that are meaningful to patients with psoriasis.
Esters of Monocarboxylic Acids
Authors: Ziegler‐Skylakakis Kyriakoula
Published: December 2023

This chapter deals with esters of monocarboxylic acids as well as with monoalcohols, di‐, tri‐, or polyalcohols, such as glycerol esters, resorcinol esters, and gallates. The esters of aromatic monocarboxylic acids are benzoates, salicylates, parabens, cinnamates,p‐aminobenzoates, ando‐aminobenzoates. The chemical structures and the physicochemical properties of these chemicals vary considerably. Accordingly, they are widely used in different industrial settings and consumer products. Some of these compounds occur naturally. They exhibit in general a low toxicity.
Development of an optimized, non‐stem cell line for intranasal delivery of therapeutic cargo to the central nervous system
Authors: El‐Ayoubi Ali , Arakelyan Arsen , Klawitter Moritz , Merk Luisa , Hakobyan Siras , Gonzalez‐Menendez Irene , Quintanilla Fend Leticia , Holm Per Sonne , Mikulits Wolfgang , Schwab Matthias , Danielyan Lusine , Naumann Ulrike
Published: December 2023

Neural stem cells (NSCs) are considered to be valuable candidates for delivering a variety of anti‐cancer agents, including oncolytic viruses, to brain tumors. However, owing to the previously reported tumorigenic potential of NSC cell lines after intranasal administration (INA), here we identified the human hepatic stellate cell line LX‐2 as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAVs) as a therapeutic cargo, and that is non‐tumorigenic after INA. Our data show that LX‐2 cells can longer withstand the OAV XVir‐N‐31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX‐2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic herpes simplex virus thymidine kinase (HSV‐TK) integration into LX‐2, leading to high vulnerability to ganciclovir (GCV). Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno‐compromised mice 3 months after INA of LX‐2 cells. Our data suggest that LX‐2 is a novel, robust, and safe cell line for delivering anti‐cancer and other therapeutic agents to the brain.
Do Dynamic Plantar Pressures Differ Based on Sonographic Evidence of Metatarsophalangeal Joint Synovitis in People With Rheumatoid Arthritis?
Authors: Anderson Libby , Ihaka Belinda , Bowen Catherine , Dando Charlotte , Stewart Sarah
Published: December 2023

Objective

The metatarsophalangeal joints (MTPJs) are the most common location for synovitis in people with rheumatoid arthritis (RA), yet their association with plantar foot pressures has received very little attention. This study aimed to determine whether plantar pressures differed based on sonographic evidence of MTPJ synovitis in people with RA.

Method

Ultrasound was used to assess synovitis (grey scale synovial hypertrophy and power Doppler signal) in MTPJs 1 to 5 using the combined EULAR/Outcome Measures in Rheumatology scoring system. Peak pressure (PP) and pressure time integrals (PTIs) were assessed during barefoot walking for seven plantar foot regions (heel, midfoot, first metatarsal, second metatarsal, third to fifth metatarsals, hallux, lesser toes). Mixed‐effects linear regression was used to determine the difference in PP and PTI between MTPJs with none/minimal synovitis and MTPJs with moderate/severe synovitis.

Results

Thirty‐five participants with RA were included. Mean age was 66.3 years and mean disease duration was 22.2 years. Participants with sonographic evidence of moderate/severe synovitis at the first MTPJ had reduced PTI at the hallux compared with those with none/minimal synovitis at this joint (P = 0.039). Participants with moderate/severe synovitis at the second MTPJ and fourth MTPJ had reduced PP and reduced PTI at lesser toes compared with those with none/minimal synovitis in these joints (all P ≤ 0.048). No significant differences were observed for synovitis in other joints.

Conclusion

These findings may be suggestive of an inverse relationship between plantar pressure and soft tissue pathology, which is consistent with an offloading strategy and reduced use of the toes during propulsion.
Combining Multifunctional Delivery System with Blood–Brain Barrier Reversible Opening Strategy for the Enhanced Treatment of Alzheimer's Disease
Authors: Ke Jia , Yu Caini , Li Sufen , Hong Yiling , Xu Yichong , Wang Kai , Meng Tingting , Ping Yuan , Fu Qiang , Yuan Hong , Hu Fuqiang
Published: December 2023

Alzheimer's disease (AD) is a neurodegenerative illness characterized by intracellular tau‐phosphorylation, β‐amyloid (Aβ) plaques accumulation, neuroinflammation, and impaired behavioral ability. Owing to the lack of effective brain delivery approaches and the presence of the blood–brain barrier (BBB), current AD therapeutic endeavors are severely limited. Herein, a multifunctional delivery system (RVG‐DDQ/PDP@siBACE1) is elaborately combined with a protein kinase B (AKT) agonist (SC79) for facilitating RVG‐DDQ/PDP@siBACE1 to target and penetrate BBB, enter brain parenchyma, and further accumulate in AD brain lesion. Moreover, compared with the unitary dose of RVG‐DDQ/PDP@siBACE1, this collaborative therapy strategy exhibits a distinctive synergistic function including scavenging reactive oxygen species (ROS), decreasing of Aβ production, alleviating neuroinflammation by promoting the polarized microglia into the anti‐inflammatory M2‐like phenotype and significantly enhancing the cognitive functions of AD mice. More strikingly, according to these results, an innovative signaling pathway “lncRNA MALAT1/miR‐181c/BCL2L11” is found that can mediate the neuronal apoptosis of AD. Taken together, combining the brain targeted delivery system with noninvasive BBB opening can provide a promising strategy and platform for targeting treatment of AD and other neurodegenerative diseases.
2D Methyl Germanane Enhanced 3D Printed Photoelectrodes
Authors: Nittoor‐Veedu Radhika , Ng Siowwoon , Sanna Michela , Pumera Martin
Published: December 2023

3D printing is a cutting‐edge technology, that allows the printing of 3D objects according to the design provided. Nanocarbon electrodes that can be fabricated using 3D printing technology, suffer from a lack of required properties. For enhancing the photoelectrochemical properties of 3D printed electrodes, functionalized germanenes, belonging to the family of 2D materials are used here. Functionalized germananes are becoming popular for application in photoelectrochemical processes, due to their photoactivity in the visible spectral region and their tunable optoelectronic properties, thanks to covalent functionalization. It is shown that 2D methyl germanane has great potential for photoelectrocatalytic enhancement of 3D printed structures, and this potential goes beyond the demonstrated application of water splitting.
Accelerated Augmented Reality Holographic 4k Video Projections Based on Lidar Point Clouds for Automotive Head‐Up Displays
Authors: Skirnewskaja Jana , Montelongo Yunuen , Sha Jinze , Wilkes Phil , Wilkinson Timothy D.
Published: December 2023

Identifying road obstacles hidden from the driver's field of view can ensure road safety in transportation. Current driver assistance systems such as 2D head‐up displays are limited to the projection area on the windshield of the car. An augmented reality holographic point cloud video projection system is developed to display objects aligned with real‐life objects in size and distance within the driver's field of view. Light Detection and Ranging (LiDAR) point cloud data collected with a 3D laser scanner is transformed into layered 3D replay field objects consisting of 400 k points. GPU‐accelerated computing generated real‐time holograms 16.6 times faster than the CPU processing time. The holographic projections are obtained with a Spatial Light Modulator (SLM) (3840×2160 px) and virtual Fresnel lenses, which enlarged the driver's eye box to 25 mm × 36 mm. Real‐time scanned road obstacles from different perspectives provide the driver a full view of risk factors such as generated depth in 3D mode and the ability to project any scanned object from different angles in 360°. The 3D holographic projection technology allows for maintaining the driver's focus on the road instead of the windshield and enables assistance by projecting road obstacles hidden from the driver's field of view.
Liquid‐Metal Fabrication of Ultrathin Gallium Oxynitride Layers with Tunable Stoichiometry
Authors: Pedram Panteha , Zavabeti Ali , Syed Nitu , Slassi Amine , Nguyen Chung Kim , Fornacciari Benjamin , Lamirand Anne , Galipaud Jules , Calzolari Arrigo , Orobtchouk Régis , Boes Andreas , Daeneke Torben , Cueff Sébastien , Mitchell Arnan , Monat Christelle
Published: December 2023

The synthesis of nanometer‐thick (≈3 nm) gallium oxynitride (GaOxNy) layers with a variable stoichiometry is reported. The approach primarily exploits the liquid metal chemistry (LMC) technique and promises easier integration of 2D materials onto photonic devices compared to traditional top‐down and bottom‐up methods. The fabrication follows a two‐step process, involving first liquid metal‐based printing of a nanometer‐thick layer of gallium oxide (Ga2O3), followed a plasma‐enhanced nitridation reaction. Control over nitridation parameters (plasma power, exposure time) allows adjustment of the GaOxNy layer's composition, granting access to compounds with distinct optical properties (e.g., a 20% index variation), as demonstrated by ellipsometry and density functional theory (DFT) simulations. DFT provides a microscopic understanding of the effect of the bond polarization and crystallinity on the optical properties of GaOxNy compounds. These findings expand the knowledge of ultrathin GaOxNy alloys, which are poorly studied with respect to their gallium nitride (GaN) and Ga2O3 counterparts. They also represent an essential step toward integrating such 2D materials into photonic chips and offer new opportunities to improve the performance of hybrid optoelectronic devices.
Access to Enantioenriched β‐Hydroxy gem‐Difluorinated Heterocyclic and Acyclic Derivatives through Rh(III)‐Catalyzed Asymmetric Transfer Hydrogenation
Authors: Bacheley Lucas , Ravindra Rathies , Guillamot Gérard , Phansavath Phannarath , Ratovelomanana‐Vidal Virginie
Published: December 2023

We report a process to access a variety of enantioenriched α‐gem‐difluorinated alcohols. A Rh(III)‐catalyzed asymmetric transfer hydrogenation method was developed in 85–98% yields and enantiomeric excesses ranging from 52% to >99%. The reduction proceeds under mild conditions with a range of difluorinated molecules including 3,3‐difluorochromanone, 3,3‐difluorothiochromanone, 3,3‐difluoro‐dihydroquinolinone and α‐difluorinated β‐ketosulfone derivatives to provide the desired enantioenriched difluorinated alcohols which are valuable fluorinated building blocks.
Chiral 1‐Phosphabarrelene‐Pyridines as Suitable Ligands for the Rh/Ir‐Catalyzed Asymmetric Hydrogenation of Olefins
Authors: Saltó Joan , Tarr Daniel , Petrov Andrey , Reich Dorian , Weber Manuela , Biosca Maria , Pàmies Oscar , Müller Christian , Diéguez Montserrat
Published: December 2023

Herein, we report the synthesis of chiral phosphabarrelene‐pyridine ligands. Their synthesis benefit from modified reaction conditions to overcome the low yields normally associated with the [4+2] cycloaddition reaction of phosphinines with hexafluoro‐2‐butyne, which is a key to install the P‐stereocenter in the phosphabarrelene. Their potential as chelating ligands in asymmetric catalysis was assessed in the Rh‐ and Ir‐catalyzed hydrogenation of cyclic β‐enamides and β‐dehydroamino acid derivatives. The catalytic system containing a tert‐butyl substituent at the ortho position of the phosphabarrelene moiety successfully hydrogenates a range of cyclic β‐enamides (ee's between 92% to 94%) and β‐dehydroamino acid derivatives (ee's between 93% to 95%). Moreover, the reactions can be carried out in the environmentally friendly 1,2‐propylene carbonate as solvent with no loss of enantioselectivity. Mechanistic studies with the Rh/P,N catalytic systems agree with the Landis‐Halpern mechanism and explain the influence of the substituent at the phosphabarrelene on enantioselectivity. Finally, the hydrogenation reactions can be carried out at large scale maintaining high enantioselectivities.
Optimization of Transcutaneous Oxygenation Wearable Sensors for Clinical Applications
Authors: Cascales Juan Pedro , Roussakis Emmanuel , Müller Matthias , Witthauer Lilian , Li Xiaolei , Goss Avery , Keshishian Helen , Marks Haley L. , Nguyen John Q. , Kelley Liv , Evans Conor L.
Published: December 2023

In this manuscript, the development of an experimental and mathematical toolset is reported that allows for improved in vivo measurements of optical transcutaneous oxygen tension measurements (TCOM) wearable technology in humans. In addition to optimizing O2‐sensing films for higher sensitivity oxygen detection, calibration algorithms are additionally developed to account for excitation source leakage, as well as algorithms to combine readings of partial pressure of oxygen (pO2), derived from phosphorescence intensity and lifetime, into a single metric. This new iteration of the TCOM wearable device is then tested in a pilot human study. By implementing characterization and calibration algorithms, the data from the pilot study demonstrates the ability to obtain reliable transcutaneous pO2 readings with a TCOM sensor regardless of size and without the need for strict conditions of constant temperature, humidity, or motion that have limited the range of applications of this technology in the past.
The Hypothalamic Epigenetic Landscape in Dietary Obesity
Authors: Ma Kai , Yin Kaili , Li Jiong , Ma Li , Zhou Qun , Lu Xiyuan , Li Bo , Li Juxue , Wei Gang , Zhang Guo
Published: December 2023

The hypothalamus in the brain plays a pivotal role in controlling energy balance in vertebrates. Nutritional excess through high‐fat diet (HFD) feeding can dysregulate hypothalamic signaling at multiple levels. Yet, it remains largely unknown in what magnitude HFD feeding may impact epigenetics in this brain region. Here, it is shown that HFD feeding can significantly alter hypothalamic epigenetic events, including posttranslational histone modifications, DNA methylation, and chromatin accessibility. The authors comprehensively analyze the chromatin immunoprecipitation‐sequencing (ChIP‐seq), methylated DNA immunoprecipitation‐sequencing (MeDIP‐seq), single nucleus assay for transposase‐accessible chromatin using sequencing (snATAC‐seq), and RNA‐seq data of the hypothalamus of C57 BL/6 mice fed with a chow or HFD for 1 to 6 months. The chromatins are categorized into 6 states using the obtained ChIP‐seq data for H3K4me3, H3K27ac, H3K9me3, H3K27me3, and H3K36me3. A 1‐month HFD feeding dysregulates histone modifications and DNA methylation more pronouncedly than that of 3‐ or 6‐month. Besides, HFD feeding differentially impacts chromatin accessibility in hypothalamic cells. Thus, the epigenetic landscape is dysregulated in the hypothalamus of dietary obesity mice.
Hydrophobic Hydrogen‐Bonded Polymer Network for Efficient and Stable Perovskite/Si Tandem Solar Cells
Authors: Liu Lu , Farhadi Bita , Li Jianxun , Liu Siyi , Lu Linfeng , Wang Hui , Du Minyong , Yang Liyou , Bao Shaojuan , Jiang Xiao , Dong Xinrui , Miao Qingqing , Li Dongdong , Wang Kai , Liu Shengzhong Frank
Published: December 2023

The pursuit of highly efficient and stable wide‐band gap (WBG) perovskite solar cells (PSCs), especially for monolithic perovskite/silicon tandem devices, is a key focus in achieving the commercialization of perovskite photovoltaics. In this study, we initially designed poly(ionic liquid)s (PILs) with varying alkyl chain lengths based on density functional theory calculations. Results pinpoint that PILs with longer alkyl chain lengths tend to exhibit more robust binding energy with the perovskite structure. Then we synthesized the PILs to craft a hydrophobic hydrogen‐bonded polymer network (HHPN) that passivates the WBG perovskite/electron transport layer interface, inhibits ion migration and serves as a barrier layer against water and oxygen ingression. Accordingly, the HHPN effectively curbs nonradiative recombination losses while facilitating efficient carrier transport, resulting in substantially enhanced open‐circuit voltage (Voc) and fill factor. As a result, the optimized single‐junction WBG PSC achieves an impressive efficiency of 23.18 %, with Voc as high as 1.25 V, which is the highest reported for WBG (over 1.67 eV) PSCs. These devices also demonstrate outstanding thermostability and humidity resistance. Notably, this versatile strategy can be extended to textured perovskite/silicon tandem cells, reaching a remarkable efficiency of 28.24 % while maintaining exceptional operational stability.
Synthesis of Pyrrole‐Sharing Fused Porphyrinoid Hybrids by Post‐fabrication of Ni(II) Porphyrins
Authors: Zi Lili , Liu Li , Zhou Mingbo , Liu Le , Xiao Boyu , Xu Ling , Rao Yutao , Yin Bangshao , Song Jianxin , Osuka Atsuhiro
Published: December 2023

Pyrrole‐sharing fused hybrids of NiII porphyrin with PdII N‐confused(NC)‐corrole and PdII NC‐oxaporphyrin were synthesized by post‐fabrication of NiII porphyrins. Specifically this consists of Friedel–Crafts type aromatic substitution reaction of meso‐free NiII porphyrin with α,α′‐dibromotripyrrin and Pd(OAc)2 assisted cyclization, and final heating to induce a Pd−C bond formation. NiII porphyrins fused with PdII NC‐corrole and with PdII NC‐oxaporphyrins show coplanar structures with a shared pyrrole unit. In these hybrids, the PdII NC‐oxaporphyrin is aromatic and the PdII NC‐corrole is moderately antiaromatic and these local electronic properties interact to influence the whole network.