bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterozygous missense variant in GLI2 impairs human endocrine pancreas development
Authors: Mueller Laura M. , Isaacson Abigail , Wilson Heather , Salowka Anna , Tay Isabel , Gong Maolian , Elbarbary Nancy Samir , Raile Klemens , Spagnoli Francesca M. 
Published: March 2024

AbstractMissense variants are the most common type of coding genetic variants. Their functional assessment is fundamental for defining any implication in human diseases and may also uncover genes that are essential for human organ development. Here, we apply CRISPR-Cas9 gene editing on human iPSCs to study a heterozygous missense variant in GLI2 identified in two siblings with early-onset and insulin-dependent diabetes of unknown cause. GLI2 is a primary mediator of the Hedgehog pathway, which regulates pancreatic β-cell development in mice. However, neither mutations in GLI2 nor Hedgehog dysregulation have been reported as cause or predisposition to diabetes. We establish and study a set of isogenic iPSC lines harbouring the missense variant for their ability to differentiate into pancreatic β-like cells. Interestingly, iPSCs carrying the missense variant show altered GLI2 transcriptional activity and impaired differentiation of pancreatic progenitors into endocrine cells. RNASeq and network analyses unveil a crosstalk between Hedgehog and WNT pathways, with the dysregulation of non-canonical WNT signaling in pancreatic progenitors carrying the GLI2 missense variant. Collectively, our findings underscore an essential role for GLI2 in human endocrine development and identify a gene variant that may lead to diabetes.
Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer
Authors: Jiang Yuan , Zheng Yueyuan , Zhang Yuan-Wei , Kong Shuai , Dong Jinxiu , Wang Fei , Ziman Benjamin , Gery Sigal , Hao Jia-Jie , Zhou Dan , Zhou Jianian , Ho Allen S. , Sinha Uttam K. , Chen Jian , Zhang Shuo , Yin Chuntong , Wei Dan-Dan , Hazawa Masaharu , Pan Huaguang , Lu Zhihao , Wei Wen-Qiang , Wang Ming-Rong , Koeffler H. Phillip , Lin De-Chen , Jiang Yan-Yi 
Published: March 2024

AbstractSquamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.
An entanglement association polymer electrolyte for Li-metal batteries
Authors: Wang Hangchao , Yang Yali , Gao Chuan , Chen Tao , Song Jin , Zuo Yuxuan , Fang Qiu , Yang Tonghuan , Xiao Wukun , Zhang Kun , Wang Xuefeng , Xia Dingguo 
Published: March 2024

AbstractTo improve the interface stability between Li-rich Mn-based oxide cathodes and electrolytes, it is necessary to develop new polymer electrolytes. Here, we report an entanglement association polymer electrolyte (PVFH-PVCA) based on a poly (vinylidene fluoride-co-hexafluoropropylene) (PVFH) matrix and a copolymer stabilizer (PVCA) prepared from acrylonitrile, maleic anhydride, and vinylene carbonate. The entangled structure of the PVFH-PVCA electrolyte imparts excellent mechanical properties and eliminates the stress arising from dendrite growth during cycling and forms a stable interface layer, enabling Li//Li symmetric cells to cycle steadily for more than 4500 h at 8 mA cm−2. The PVCA acts as a stabilizer to promote the formation of an electrochemically robust cathode–electrolyte interphase. It delivers a high specific capacity and excellent cycling stability with 84.7% capacity retention after 400 cycles. Li1.2Mn0.56Ni0.16Co0.08O2/PVFH-PVCA/Li full cell achieved 125 cycles at 1 C (4.8 V cut-off) with a stable discharge capacity of ~2.5 mAh cm−2.
Extreme Li-Mg selectivity via precise ion size differentiation of polyamide membrane
Authors: Peng Quan , Wang Ruoyu , Zhao Zilin , Lin Shihong , Liu Ying , Dong Dianyu , Wang Zheng , He Yiman , Zhu Yuzhang , Jin Jian , Jiang Lei 
Published: March 2024

AbstractAchieving high selectivity of Li+ and Mg2+ is of paramount importance for effective lithium extraction from brines, and nanofiltration (NF) membrane plays a critical role in this process. The key to achieving high selectivity lies in the on-demand design of NF membrane pores in accordance with the size difference between Li+ and Mg2+ ions, but this poses a huge challenge for traditional NF membranes and difficult to be realized. In this work, we report the fabrication of polyamide (PA) NF membranes with ultra-high Li+/Mg2+ selectivity by modifying the interfacial polymerization (IP) process between piperazine (PIP) and trimesoyl chloride (TMC) with an oil-soluble surfactant that forms a monolayer at oil/water interface, referred to as OSARIP. The OSARIP benefits to regulate the membrane pores so that all of them are smaller than Mg2+ ions. Under the solely size sieving effect, an exceptional Mg2+ rejection rate of over 99.9% is achieved. This results in an exceptionally high Li+/Mg2+ selectivity, which is one to two orders of magnitude higher than all the currently reported pressure-driven membranes, and even higher than the microporous framework materials, including COFs, MOFs, and POPs. The large enhancement of ion separation performance of NF membranes may innovate the current lithium extraction process and greatly improve the lithium extraction efficiency.
Transfection of hypoxia-inducible factor-1α mRNA upregulates the expression of genes encoding angiogenic growth factors
Authors: Wlodarczyk Jakub , Leng Albert , Abadchi Sanaz Nourmohammadi , Shababi Niloufar , Mokhtari-Esbuie Farzad , Gheshlaghi Shayan , Ravari Mohsen Rouhani , Pippenger Emma K. , Afrasiabi Ali , Ha Jinny , Abraham John M. , Harmon John W. 
Published: March 2024

AbstractHypoxia-Inducible Factor-1α (HIF-1α) has presented a new direction for ischemic preconditioning of surgical flaps to promote their survival. In a previous study, we demonstrated the effectiveness of HIF-1a DNA plasmids in this application. In this study, to avoid complications associated with plasmid use, we sought to express HIF-1α through mRNA transfection and determine its biological activity by measuring the upregulation of downstream angiogenic genes. We transfected six different HIF-1a mRNAs–one predominant, three variant, and two novel mutant isoforms–into primary human dermal fibroblasts using Lipofectamine, and assessed mRNA levels using RT-qPCR. At all time points examined after transfection (3, 6, and 10 h), the levels of HIF-1α transcript were significantly higher in all HIF-1α transfected cells relative to the control (all p < 0.05, unpaired Student’s T-test). Importantly, the expression of HIF-1α transcription response genes (VEGF, ANG-1, PGF, FLT1, and EDN1) was significantly higher in the cells transfected with all isoforms than with the control at six and/or ten hours post-transfection. All isoforms were transfected successfully into human fibroblast cells, resulting in the rapid upregulation of all five downstream angiogenic targets tested. These findings support the potential use of HIF-1α mRNA for protecting ischemic dermal flaps.
Enhancing explainable SARS-CoV-2 vaccine development leveraging bee colony optimised Bi-LSTM, Bi-GRU models and bioinformatic analysis
Authors: Ozsahin Dilber Uzun , Ameen Zubaida Said , Hassan Abdurrahman Shuaibu , Mubarak Auwalu Saleh 
Published: March 2024

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus that caused the outbreak of the coronavirus disease 2019 (COVID-19). The COVID-19 outbreak has led to millions of deaths and economic losses globally. Vaccination is the most practical solution, but finding epitopes (antigenic peptide regions) in the SARS-CoV-2 proteome is challenging, costly, and time-consuming. Here, we proposed a deep learning method based on standalone Recurrent Neural networks to predict epitopes from SARS-CoV-2 proteins easily. We optimised the standalone Bidirectional Long Short-Term Memory (Bi-LSTM) and Bidirectional Gated Recurrent Unit (Bi-GRU) with a bioinspired optimisation algorithm, namely, Bee Colony Optimization (BCO). The study shows that LSTM-based models, particularly BCO-Bi-LSTM, outperform all other models and achieve an accuracy of 0.92 and AUC of 0.944. To overcome the challenge of understanding the model predictions, explainable AI using the Shapely Additive Explanations (SHAP) method was employed to explain how Blackbox models make decisions. Finally, the predicted epitopes led to the development of a multi-epitope vaccine. The multi-epitope vaccine effectiveness evaluation is based on vaccine toxicity, allergic response risk, and antigenic and biochemical characteristics using bioinformatic tools. The developed multi-epitope vaccine is non-toxic and highly antigenic. Codon adaptation, cloning, gel electrophoresis assess genomic sequence, protein composition, expression and purification while docking and IMMSIM servers simulate interactions and immunological response, respectively. These investigations provide a conceptual framework for developing a SARS-CoV-2 vaccine.
Factors influencing delay in malaria treatment seeking at selected public health facilities in South Gonder, Ethiopia
Authors: Alga Adimasu , Wasihun Yitbarek , Ayele Tiruneh , Endawkie Abel , Feleke Sefineh Fenta , Kebede Natnael 
Published: March 2024

AbstractEarly and prompt treatment-seeking for malaria is necessary to reduce the progression of the disease to its severe forms and the associated mortality. Various studies have indicated that treatments sought for malaria were not always within the recommended timeframe. Therefore, this study aims to assess factors influencing delay in malaria treatment seeking at public health facilities in South Gonder, Ethiopia. An unmatched case–control study was conducted among 322 individuals, comprising 161 cases and 161 controls, who were randomly selected malaria patients visiting public health facilities in South Gonder District, Ethiopia, from May 20/2022 to June 25/2022. An interviewer-administered questionnaire was used to collect data, which were subsequently cleaned and entered into Epi data. Descriptive statistics were performed, and variables with a p-value of ≤ 0.25 from the bivariate analysis were included in a multivariable logistic regression model. Significant variables with a p-value of < 0.05 were retained in the multivariable model. Patients who were unable to read and write [AOR = 3.47 (1.01–11.9)], fear of side effects of malaria treatment drugs [AOR = 1.89 (1.04–3.42)], lack of access to health education malaria disease and its treatment [AOR = 1.93 (1.02–3.65)], lack of transportation access [AOR = 4.70 (1.73–12.7)], not membership of community-based health insurance [AOR = 2.5 (1.3–4.82)] and lack of confidence on malaria care health facility providing [AOR = 2.14 (1.06–4.29)], were found to be determinants of treatment-seeking delay among malaria patients. In Summary, this study revealed significant associations between delays in seeking malaria treatment and factors such as educational status (those who were unable to read and write), malaria drug side effects, health education on malaria, transportation access, CBHI membership, and confidence in health malaria care. it is recommended that targeted interventions and awareness campaigns be implemented to address these determinants, promoting prompt and effective malaria treatment-seeking behavior in the studied population.
Acute effects of low-intensity one-legged electrical muscle stimulation on arterial stiffness in experimental and control limbs
Authors: Oda Hiroyuki , Fujibayashi Mami , Kume Daisuke , Matsumoto Naoyuki , Nishiwaki Masato 
Published: March 2024

AbstractThe aim of this study was to examine the acute effects of low-intensity one-legged electrical muscle stimulation (EMS) for skeletal muscle on arterial stiffness in EMS and non-EMS legs. Eighteen healthy subjects received two different protocols (Control (CT) and Experimental (ET) trials) in random order on separate days. EMS was applied to the left lower limb at 4 Hz for 20 min at an intensity corresponding to an elevation in pulse rate of approximately 15 beats/min (10.9 ± 5.1% of heart rate reserve). Before and after the experiment, arterial stiffness parameters in the control right leg (CRL) and control left leg (CLL) in CT and non-EMS leg (NEL) and EMS leg (EL) in ET were assessed by pulse wave velocity (baPWV, faPWV) and cardio-ankle vascular index (CAVI). No significant changes in all parameters were observed in either leg in CT. Conversely, in ET, low-intensity, single-leg EMS significantly reduced CAVI, baPWV, and faPWV in the EL, but not in the NEL. Acute, low-intensity single-leg EMS reduces arterial stiffness only in the EL. These data support our idea that physical movement-related regional factors rather than systematic factors are important for inducing acute reductions in arterial stiffness.
An analysis of case studies for advancing photovoltaic power forecasting through multi-scale fusion techniques
Authors: Guermoui Mawloud , Fezzani Amor , Mohamed Zaiani , Rabehi Abdelaziz , Ferkous Khaled , Bailek Nadjem , Bouallit Sabrina , Riche Abdelkader , Bajaj Mohit , Dost Mohammadi Shir Ahmad , Ali Enas , Ghoneim Sherif S. M. 
Published: March 2024

AbstractIntegration renewable energy sources into current power generation systems necessitates accurate forecasting to optimize and preserve supply–demand restrictions in the electrical grids. Due to the highly random nature of environmental conditions, accurate prediction of PV power has limitations, particularly on long and short periods. Thus, this research provides a new hybrid model for forecasting short PV power based on the fusing of multi-frequency information of different decomposition techniques that will allow a forecaster to provide reliable forecasts. We evaluate and provide insights into the performance of five multi-scale decomposition algorithms combined with a deep convolution neural network (CNN). Additionally, we compare the suggested combination approach's performance to that of existing forecast models. An exhaustive assessment is carried out using three grid-connected PV power plants in Algeria with a total installed capacity of 73.1 MW. The developed fusing strategy displayed an outstanding forecasting performance. The comparative analysis of the proposed combination method with the stand-alone forecast model and other hybridization techniques proves its superiority in terms of forecasting precision, with an RMSE varying in the range of [0.454–1.54] for the three studied PV stations.
Shift from income breeding to capital breeding with latitude in the invasive Asian shore crab Hemigrapsus sanguineus
Authors: Reese Tanner C. , Blakeslee April M. H. , Crane Laura C. , Fletcher Laura S. , Repetto Michele F. , Smith Nanette , Stancil Carter , Tepolt Carolyn K. , Toscano Benjamin J. , Griffen Blaine D. 
Published: March 2024

AbstractOrganisms vary in the timing of energy acquisition and use for reproduction. Thus, breeding strategies exist on a continuum, from capital breeding to income breeding. Capital breeders acquire and store energy for breeding before the start of the reproductive season, while income breeders finance reproduction using energy acquired during the reproductive season. Latitude and its associated environmental drivers are expected to heavily influence breeding strategy, potentially leading to latitudinal variation in breeding strategies within a single species. We examined the breeding strategy of the Asian shore crab Hemigrapsus sanguineus at five sites spanning nearly 10° of latitude across its invaded United States range. We hypothesized that the primary breeding strategy of this species would shift from income breeding to capital breeding as latitude increases. We found that though this species’ breeding strategy is dominated by capital breeding throughout much of the range, income breeding increases in importance at lower latitudes. This latitudinal pattern is likely heavily influenced by the duration of the foraging and breeding seasons, which also vary with latitude. We also found that reproductive characteristics at the northern and southern edges of the invaded range were consistent with continued range expansion. We suggest that the reproductive flexibility of the Asian shore crab is a key facilitator of its continued invasion success. Our results highlight the influence of latitude on the breeding strategy of a species and emphasize the need for further research regarding the ecological importance and implications of flexibility in breeding strategies within species.
222 nm far-UVC light markedly reduces the level of infectious airborne virus in an occupied room
Authors: Buonanno Manuela , Kleiman Norman J. , Welch David , Hashmi Raabia , Shuryak Igor , Brenner David J. 
Published: March 2024

AbstractAn emerging intervention for control of airborne-mediated pandemics and epidemics is whole-room far-UVC (200–235 nm). Laboratory studies have shown that 222-nm light inactivates airborne pathogens, potentially without harm to exposed occupants. While encouraging results have been reported in benchtop studies and in room-sized bioaerosol chambers, there is a need for quantitative studies of airborne pathogen reduction in occupied rooms. We quantified far-UVC mediated reduction of aerosolized murine norovirus (MNV) in an occupied mouse-cage cleaning room within an animal-care facility. Benchtop studies suggest that MNV is a conservative surrogate for airborne viruses such as influenza and coronavirus. Using four 222-nm fixtures installed in the ceiling, and staying well within current recommended regulatory limits, far-UVC reduced airborne infectious MNV by 99.8% (95% CI: 98.2–99.9%). Similar to previous room-sized bioaerosol chamber studies on far-UVC efficacy, these results suggest that aerosolized virus susceptibility is significantly higher in room-scale tests than in bench-scale laboratory studies. That said, as opposed to controlled laboratory studies, uncertainties in this study related to airflow patterns, virus residence time, and dose to the collected virus introduce uncertainty into the inactivation estimates. This study is the first to directly demonstrate far-UVC anti-microbial efficacy against airborne pathogens in an occupied indoor location.
Speech-Language Pathology in China: An Overview
Authors: Wei Guanyu , Yuan Aiyun , Tian Rujin , Liu Kai 
Published: March 2024

Purpose:
China is a middle-income developing country that is aging rapidly. Speech-language pathology is a developing field in China. The article aims to provide a brief overview of the current status of speech-language pathology in China.

Method:
This article presents the authors' viewpoint, bolstered by insights from nine speech-language pathologists (SLPs) in China. To enrich the depth of the discussion on achievements and challenges within the Chinese speech-language pathology field, the authors also conducted a review of relevant articles in Standard Chinese–based databases.

Result and Discussion:
The authors have delineated both the major achievements and barriers in the field of speech-language pathology in China. Recommendations for improvement are included, emphasizing the importance of sustained efforts from researchers, clinicians, educators, governments, and related organizations within China. Additionally, the authors extend their suggestions to clinicians and researchers in other countries.

Conclusion:
While the field of speech-language pathology has substantially developed in the past 40 years, several challenges confront SLPs in China at both the educational and practical levels.
Introduction
Authors: Wang Elise 
Published: March 2024

Abstract
This Introduction sets up felony’s primary conceptual problem: since its beginnings in the thirteenth and fourteenth centuries, felony has been the quintessential crime, and yet the law has never defined it. This, I suggest, has given us the impression that we know what felony is without providing any concrete vocabulary with which to describe it. In this Introduction, I lay out the central premise of the book’s argument: felony’s concept is inconsistent because it was never a creation of the law. It was created by its practice, which was shaped by the local communities to whom it was left. When they needed guidance, these communities turned not to legal theory, but to cultural concepts. I provide an outline of felony procedure from investigation to conviction, as well as an overview of the historical records that I use in the book. Finally, I describe my methodology and provide an outline for the five chapters of the book.
Death Investigation
Authors: Wang Elise 
Published: March 2024

Abstract
Chapter 1 argues that St. Erkenwald, a Middle English miraculum in which a bishop of London reanimates the long-forgotten corpse of a pagan judge, offers a rare portrait of medieval death investigation. Most scholarship on the poem has focused on its historiographical work, but this chapter argues that the poem meticulously recreates a death inquest by bringing to life the form of a coroner’s enrollment, acting out what was meant to be only a textual form. In doing so, it offers us a vivid glimpse of investigative procedure, particularly of aspects that are absent or only vaguely outlined in legal records, like the investigation of a community after a body is found but before the coroner arrives. The chapter considers the poem next to two coroners’ enrollments in order to see what this new perspective reveals about previously hidden aspects of the procedure.
The Records
Authors: Wang Elise 
Published: March 2024

Abstract
Chapter 4 is about the documentary system of medieval English criminal procedure in the common law, and focuses on robbery as an example to argue that juries used these documents to give nuance to their verdicts. Robbery was hotly condemned in both judicial and social comment, but hazily defined and rarely punished. The chapter considers this phenomenon in the legal record alongside the unpunishable Good Thief, whose unearned salvation plagues the main character in William Langland’s Piers Plowman. Like the robbers that were hauled up repeatedly before the court only to slip the noose, the poem returns again and again to the story but discovers that, however you tell it, the Thief is always saved. The chapter argues that this repetition—in the poem and in the archive—helped the documentation of felony procedure capture the complexity of jury deliberations and express a range of conclusions beyond “guilty” and “acquitted.”