bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of protein-DNA binding reveals mechanisms of spatiotemporal gene control in early Drosophila embryos
Authors: Syed Sahla , Duan Yifei , Lim Bomyi
Published: November 2023

It is well known that enhancers regulate the spatiotemporal expression of their target genes by recruiting transcription factors (TFs) to the cognate binding sites in the region. However, the role of multiple binding sites for the same TFs and their specific spatial arrangement in determining the overall competency of the enhancer has yet to be fully understood. In this study, we utilized the MS2-MCP live imaging technique to quantitatively analyze the regulatory logic of the snail distal enhancer in early Drosophila embryos. Through systematic modulation of Dorsal and Twist binding motifs in this enhancer, we found that a mutation in any one of these binding sites causes a drastic reduction in transcriptional amplitude, resulting in a reduction in mRNA production of the target gene. We provide evidence of synergy, such that multiple binding sites with moderate affinities cooperatively recruit more TFs to drive stronger transcriptional activity than a single site. Moreover, a Hidden Markov-based stochastic model of transcription reveals that embryos with mutated binding sites have a higher probability of returning to the inactive promoter state. We propose that TF-DNA binding regulates spatial and temporal gene expression and drives robust pattern formation by modulating transcriptional kinetics and tuning bursting rates.
100 years of anthropogenic impact causes changes in freshwater functional biodiversity
Authors: Eastwood Niamh , Zhou Jiarui , Derelle Romain , Abdallah Mohamed Abou-Elwafa , Stubbings William A , Jia Yunlu , Crawford Sarah E , Davidson Thomas A , Colbourne John K , Creer Simon , Bik Holly , Hollert Henner , Orsini Luisa
Published: November 2023

Despite efforts from scientists and regulators, biodiversity is declining at an alarming rate. Unless we find transformative solutions to preserve biodiversity, future generations may not be able to enjoy nature’s services. We have developed a conceptual framework that establishes the links between biodiversity dynamics and abiotic change through time and space using artificial intelligence. Here, we apply this framework to a freshwater ecosystem with a known history of human impact and study 100 years of community-level biodiversity, climate change and chemical pollution trends. We apply explainable network models with multimodal learning to community-level functional biodiversity measured with multilocus metabarcoding, to establish correlations with biocides and climate change records. We observed that the freshwater community assemblage and functionality changed over time without returning to its original state, even if the lake partially recovered in recent times. Insecticides and fungicides, combined with extreme temperature events and precipitation, explained up to 90% of the functional biodiversity changes. The community-level biodiversity approach used here reliably explained freshwater ecosystem shifts. These shifts were not observed when using traditional quality indices (e.g. Trophic Diatom Index). Our study advocates the use of high-throughput systemic approaches on long-term trends over species-focused ecological surveys to identify the environmental factors that cause loss of biodiversity and disrupt ecosystem functions.
Genetic validation of PfFKBP35 as an antimalarial drug target
Authors: Thommen Basil T , Dziekan Jerzy M , Achcar Fiona , Tjia Seth , Passecker Armin , Buczak Katarzyna , Gumpp Christin , Schmidt Alexander , Rottmann Matthias , Grüring Christof , Marti Matthias , Bozdech Zbynek , Brancucci Nicolas MB
Published: November 2023

Plasmodium falciparum accounts for the majority of over 600,000 malaria-associated deaths annually. Parasites resistant to nearly all antimalarials have emerged and the need for drugs with alternative modes of action is thus undoubted. The FK506-binding protein PfFKBP35 has gained attention as a promising drug target due to its high affinity to the macrolide compound FK506 (tacrolimus). Whilst there is considerable interest in targeting PfFKBP35 with small molecules, a genetic validation of this factor as a drug target is missing and its function in parasite biology remains elusive. Here, we show that limiting PfFKBP35 levels are lethal to P. falciparum and result in a delayed death-like phenotype that is characterized by defective ribosome homeostasis and stalled protein synthesis. Our data furthermore suggest that FK506, unlike the action of this drug in model organisms, exerts its antiproliferative activity in a PfFKBP35-independent manner and, using cellular thermal shift assays, we identify putative FK506-targets beyond PfFKBP35. In addition to revealing first insights into the function of PfFKBP35, our results show that FKBP-binding drugs can adopt non-canonical modes of action – with major implications for the development of FK506-derived molecules active against Plasmodium parasites and other eukaryotic pathogens.
Novel axonemal protein ZMYND12 interacts with TTC29 and DNAH1, and is required for male fertility and flagellum function
Authors: Dacheux Denis , Martinez Guillaume , Broster Reix Christine E , Beurois Julie , Lores Patrick , Tounkara Magamba , Dupuy Jean-William , Robinson Derrick Roy , Loeuillet Corinne , Lambert Emeline , Wehbe Zeina , Escoffier Jessica , Amiri-Yekta Amir , Daneshipour Abbas , Hosseini Seyedeh-Hanieh , Zouari Raoudha , Mustapha Selima Fourati Ben , Halouani Lazhar , Jiang Xiaohui , Shen Ying , Liu Chunyu , Thierry-Mieg Nicolas , Septier Amandine , Bidart Marie , Satre Véronique , Cazin Caroline , Kherraf Zine Eddine , Arnoult Christophe , Ray Pierre F , Toure Aminata , Bonhivers Mélanie , Coutton Charles
Published: November 2023

Male infertility is common and complex, presenting a wide range of heterogeneous phenotypes. Although about 50% of cases are estimated to have a genetic component, the underlying cause often remains undetermined. Here, from whole-exome sequencing on samples from 168 infertile men with asthenoteratozoospermia due to severe sperm flagellum, we identified homozygous ZMYND12 variants in four unrelated patients. In sperm cells from these individuals, immunofluorescence revealed altered localization of DNAH1, DNALI1, WDR66, and TTC29. Axonemal localization of ZMYND12 ortholog TbTAX-1 was confirmed using the Trypanosoma brucei model. RNAi knock-down of TbTAX-1 dramatically affected flagellar motility, with a phenotype similar to the sperm from men bearing homozygous ZMYND12 variants. Co-immunoprecipitation and ultrastructure expansion microscopy in T. brucei revealed TbTAX-1 to form a complex with TTC29. Comparative proteomics with samples from Trypanosoma and Ttc29 KO mice identified a third member of this complex: DNAH1. The data presented revealed that ZMYND12 is part of the same axonemal complex as TTC29 and DNAH1, which is critical for flagellum function and assembly in humans, and Trypanosoma. ZMYND12 is thus a new asthenoteratozoospermia-associated gene, bi-allelic variants of which cause severe flagellum malformations and primary male infertility.
PI(3,4,5)P3 allosteric regulation of repressor activator protein 1 controls antigenic variation in trypanosomes
Authors: Touray Abdoulie O. , Rajesh Rishi , Isebe Tony , Sternlieb Tamara , Loock Mira , Kutova Oksana , Cestari Igor
Published: November 2023

African trypanosomes evade host immune clearance by antigenic variation, causing persistent infections in humans and animals. These parasites express a homogeneous surface coat of variant surface glycoproteins (VSGs). They transcribe one out of hundreds of VSG genes at a time from telomeric expression sites (ESs) and periodically change the VSG expressed by transcriptional switching or recombination. The mechanisms underlying the control of VSG switching and its developmental silencing remain elusive. We report that telomeric ES activation and silencing entail an on/off genetic switch controlled by a nuclear phosphoinositide signaling system. This system includes a nuclear phosphatidylinositol 5-phosphatase (PIP5Pase), its substrate PI(3,4,5)P3, and the repressor-activator protein 1 (RAP1). RAP1 binds to ES sequences flanking VSG genes via its DNA binding domains and represses VSG transcription. In contrast, PI(3,4,5)P3 binds to the N-terminus of RAP1 and controls its DNA binding activity. Transient inactivation of PIP5Pase results in the accumulation of nuclear PI(3,4,5)P3, which binds RAP1 and displaces it from ESs, activating transcription of silent ESs and VSG switching. The system is also required for the developmental silencing of VSG genes. The data provides a mechanism controlling reversible telomere silencing essential for the periodic switching in VSG expression and its developmental regulation.
The impact of surgery and oncological treatment on risk of type 2 diabetes onset in patients with colorectal cancer: nationwide cohort study in Denmark
Authors: Krag Caroline , Svane Maria Saur , Madsbad Sten , Graversen Susanne Boel , Christensen Jesper Frank , Sørensen Thorkild IA , Lehrskov Louise Lang , Laurberg Tinne
Published: November 2023

Background:

Comorbidity with type 2 diabetes (T2D) results in worsening of cancer-specific and overall prognosis in colorectal cancer (CRC) patients. The treatment of CRC per se may be diabetogenic. We assessed the impact of different types of surgical cancer resections and oncological treatment on risk of T2D development in CRC patients.

Methods:

We developed a population-based cohort study including all Danish CRC patients, who had undergone CRC surgery between 2001 and 2018. Using nationwide register data, we identified and followed patients from date of surgery and until new onset of T2D, death, or end of follow-up.

Results:

In total, 46,373 CRC patients were included and divided into six groups according to type of surgical resection: 10,566 Right-No-Chemo (23%), 4645 Right-Chemo (10%), 10,151 Left-No-Chemo (22%), 5257 Left-Chemo (11%), 9618 Rectal-No-Chemo (21%), and 6136 Rectal-Chemo (13%). During 245,466 person-years of follow-up, 2556 patients developed T2D. The incidence rate (IR) of T2D was highest in the Left-Chemo group 11.3 (95% CI: 10.4–12.2) per 1000 person-years and lowest in the Rectal-No-Chemo group 9.6 (95% CI: 8.8–10.4). Between-group unadjusted hazard ratio (HR) of developing T2D was similar and non-significant. In the adjusted analysis, Rectal-No-Chemo was associated with lower T2D risk (HR 0.86 [95% CI 0.75–0.98]) compared to Right-No-Chemo.

For all six groups, an increased level of body mass index (BMI) resulted in a nearly twofold increased risk of developing T2D.

Conclusions:

This study suggests that postoperative T2D screening should be prioritised in CRC survivors with overweight/obesity regardless of type of CRC treatment applied.

Funding:

The Novo Nordisk Foundation (NNF17SA0031406); TrygFonden (101390; 20045; 125132).
Modeling corticotroph deficiency with pituitary organoids supports the functional role of NFKB2 in human pituitary differentiation
Authors: Mac Thi Thom , Fauquier Teddy , Jullien Nicolas , Romanet Pauline , Etchevers Heather , Barlier Anne , Castinetti Frederic , Brue Thierry
Published: November 2023

Deficient Anterior pituitary with common Variable Immune Deficiency (DAVID) syndrome results from NFKB2 heterozygous mutations, causing adrenocorticotropic hormone deficiency (ACTHD) and primary hypogammaglobulinemia. While NFKB signaling plays a crucial role in the immune system, its connection to endocrine symptoms is unclear. We established a human disease model to investigate the role of NFKB2 in pituitary development by creating pituitary organoids from CRISPR/Cas9-edited human induced pluripotent stem cells (hiPSCs). Introducing homozygous TBX19K146R/K146R missense pathogenic variant in hiPSC, an allele found in congenital isolated ACTHD, led to a strong reduction of corticotrophs number in pituitary organoids. Then, we characterized the development of organoids harboring NFKB2D865G/D865G mutations found in DAVID patients. NFKB2D865G/D865G mutation acted at different levels of development with mutant organoids displaying changes in the expression of genes involved on pituitary progenitor generation (HESX1, PITX1, LHX3), hypothalamic secreted factors (BMP4, FGF8, FGF10), epithelial-to-mesenchymal transition, lineage precursors development (TBX19, POU1F1) and corticotrophs terminal differentiation (PCSK1, POMC), and showed drastic reduction in the number of corticotrophs. Our results provide strong evidence for the direct role of NFKB2 mutations in the endocrine phenotype observed in patients leading to a new classification of a NFKB2 variant of previously unknown clinical significance as pathogenic in pituitary development.
PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy
Authors: Yoshida Teruhiko , Latt Khun Zaw , Rosenberg Avi Z , Santo Briana A , Myakala Komuraiah , Ishimoto Yu , Zhao Yongmei , Shrivastav Shashi , Jones Bryce A , Yang Xiaoping , Wang Xiaoxin X , Tutino Vincent M , Sarder Pinaki , Levi Moshe , Okamoto Koji , Winkler Cheryl A , Kopp Jeffrey B
Published: November 2023

HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes, and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the pro-fibrogenic PKR-STAT3-platelet-derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN.
The larva and adult of Helicoverpa armigera use differential gustatory receptors to sense sucrose
Authors: Zhang Shuai-Shuai , Wang Pei-Chao , Ning Chao , Yang Ke , Li Guo-Cheng , Cao Lin-Lin , Huang Ling-Qiao , Wang Chen-Zhu
Published: November 2023

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100–1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.
Depletion of SMN protein in mesenchymal progenitors impairs the development of bone and neuromuscular junction in spinal muscular atrophy
Authors: Hann Sang-Hyeon , Kim Seon-Yong , Kim Ye Lynne , Jo Young-Woo , Kang Jong-Seol , Park Hyerim , Choi Se-Young , Kong Young-Yun
Published: November 2023

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cell (MPC)-specific SMN-depleted mouse models, we reveal that SMN reduction in limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ). Specifically, these mice exhibited impaired growth plate homeostasis and reduced insulin-like growth factor (IGF) signaling from chondrocytes, rather than from the liver. Furthermore, the reduction of SMN in fibro-adipogenic progenitors (FAPs) resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis of SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.
FedLGAN: a method for anomaly detection and repair of hydrological telemetry data based on federated learning
Authors: Chen Zheliang , Ni Xianhan , Li Huan , Kong Xiangjie
Published: November 2023

The existing data repair methods primarily focus on addressing missing data issues by utilizing variational autoencoders to learn the underlying distribution and generate content that represents the missing parts, thus achieving data repair. However, this method is only applicable to data missing problems and cannot identify abnormal data. Additionally, as data privacy concerns continue to gain public attention, it poses a challenge to traditional methods. This article proposes a generative adversarial network (GAN) model based on the federated learning framework and a long short-term memory network, namely the FedLGAN model, to achieve anomaly detection and repair of hydrological telemetry data. In this model, the discriminator in the GAN structure is employed for anomaly detection, while the generator is utilized for abnormal data repair. Furthermore, to capture the temporal features of the original data, a bidirectional long short-term memory network with an attention mechanism is embedded into the GAN. The federated learning framework avoids privacy leakage of hydrological telemetry data during the training process. Experimental results based on four real hydrological telemetry devices demonstrate that the FedLGAN model can achieve anomaly detection and repair while preserving privacy.
Molecular signature of the ontogenic development of the prawn Macrobrachium tenellum
Authors: Mateos Guerrero Dulce , Martínez-Cruz Margarito , Pérez-Campos Eduardo , García-Guerrero Marcelo , de los Santos-Romero Rodolfo , Solórzano-Mata Carlos , Sánchez-Salgado José Luís , Pereyra Morales Mohamed Ali , Lugo Agustin , Torres-Rivera Anayetzin , Alpuche Juan
Published: November 2023

The prawn Macrobrachium tenellum shows aquaculture potential due to its well-defined reproductive cycle linked to female nutritional requirements. Significant changes occur in egg composition during the 16 to 17-day embryo development. Understanding the ontogenic proteins is crucial for developmental insights and controlled reproduction. We employed free-label quantitative proteomics to analyze egg peptides at the initial and final stages of wild females. Using the emPAI protocol and Proteome Discoverer 2.0, we identified 89 differentially expressed proteins in M. tenellum eggs. Of these, 27 were exclusive to early-stage development and three to late-stage. Abundant proteins included Vitellogenin, glyceraldehyde-3-phosphate dehydrogenase, histone 4, beta-actin, and hemocyanin. Gene Ontology analysis revealed 518 terms across molecular functions, biological processes, and cellular components using the GoRetriever tool of AgBase and the CateGOrizer tool of the Animal Genome Research Program. Carbohydrate metabolism was significant in early-stage development, with glyceraldehyde-3-phosphate dehydrogenase being the second most abundant protein. Proteins involved in ATP synthesis and cytoplasmic proteins associated with catalytic and binding activities related to primary metabolism were also detected. Our study elucidates the role of Vitellogenin in lipid transport activity and its potential involvement in the juvenile hormone feedback pathway. This pathway includes farnesoic acid O-methyltransferase and juvenile hormone epoxide oxidase, regulating protein biosynthesis, molt cycles (including chitinase activity), and potentially influencing controlled reproduction. Our proteomic analysis provides insights into the molecular mechanisms driving Ontogenic development in Macrobrachium tenellum, with implications for controlled reproduction strategies and advancements in aquaculture practices.
Diamonds of the Orgiton Theory
Authors: Heiden Bernhard , Tonino-Heiden Bianca
Published: November 2023

This work addresses the firstly arisen orgiton theory and summarises their key findings in the form of eight diamonds of orgiton theory. We first briefly introduce orgiton theory and focus then on these eight diamonds. We assign them to the first eight prime numbers without dedicating them to any related order, as their interdependency relation: §2 Orgiton. §3 Orgiton Grammar. §5 Directionality. §7 Osmotic Paradigm. §11 Emergence Theorem. §13 Emergence Contraction 1 =n 1. §17 Cybernetic Ethics. §19 Social Dynamics. We further give the prospected relevance of this work and possible applications concerning epistemological, theoretical and practical applications. As a possible practical application field, we will sketch the use in the field of Industrial Engineering and Management. Finally, we give conclusions and an outlook towards the further development of orgiton theory.
Estimation of Lipid Profile, Hepatic Enzymes, Malondialdehyde, and Uric Acid in Preeclampsia: Implications for Early Intervention
Authors: Gera Prem Kumar , Persis Pothala , Battula Sesha Saila , Bera Taposhi , Saripalli Sandhya
Published: November 2023

Introduction: Preeclampsia, a serious pregnancy complication, poses significant risks to both maternal and foetal health, potentially leading to morbidity and mortality. This condition is characterised by changes in lipid profiles, hepatic enzymes, Malondialdehyde (MDA), and uric acid levels. Despite significant medical advancements, identifying precise biomarkers for preeclampsia remains complex. Moreover, there is a lack of epidemiological research on preeclampsia within the southern Indian population. Aim: To estimate the levels of serum lipid profiles, hepatic enzyme levels, MDA, and uric acid levels in pregnant women with preeclampsia. Also, to examine the association between MDA and uric acid levels among women with preeclampsia and those with normal pregnancies. Materials and Methods: This cross-sectional study included 162 pregnant patients aged between 18 and 35 years, who attended the Outpatient Department (OPD) or were admitted to a tertiary care hospital in Visakhapatnam, Andhra Pradesh, India between February 2021 and October 2021. The participants were divided into three groups: Group A (54 normotensive pregnant women), Group B (54 pregnant women with non severe preeclampsia), and Group C (54 pregnant women with severe preeclampsia). Lipid profiles, hepatic enzymes, MDA, and uric acid were evaluated in all subjects, and their relationship with preeclampsia severity was assessed. The data were statistically analysed using one-way Analysis of Variance (ANOVA) followed by the Tukey post-hoc test. Results: The study groups (A, B, and C) had comparable age and gestational periods. However, significant variations were observed in lipid profiles, hepatic enzymes, MDA, and uric acid levels among them, which associated with the severity of preeclampsia. Increasing severity was associated with higher cholesterol and triglyceride levels, as well as a decrease in High Density Lipoprotein (HDL) cholesterol. Furthermore, disease progression led to significant elevations in Alkaline Phosphatase (ALP) , uric acid, and MDA levels. In particular, Group A displayed total cholesterol levels of 138.3±20.32 mg/dL, triglycerides of 109.98±15.22 mg/dL, and a negative association with HDLcholesterol at 30.57±3.65 mg/dL. In contrast, Group C exhibited considerably higher levels of total cholesterol, triglycerides, AST, ALT, uric acid, and MDA compared to Group A. Conclusion: As preeclampsia worsens, cholesterol and triglyceride levels increase, while HDL-cholesterol decreases, indicating a deteriorating metabolic profile. Additionally, ALP, uric acid, and MDA levels rise, indicating increased oxidative stress and liver function impact with the progression of the ailment.
Comparison of Postoperative Outcomes of Laparoscopic Cholecystectomy with or without Abdominal Prophylactic Drainage: A Prospective Interventional Study
Authors: Maurya Naveen Kumar , Hingora Osman Musa , Kumar Manish , Katiyar Ashish
Published: November 2023

Introduction: With increasing surgeon experience and advancements in instrumentation and equipment, Laparoscopic Cholecystectomy (LC) continues to progress as a safer and less invasive procedure. Drainage should not be regarded as obligatory or standard after elective LC, according to the majority. Aim: To evaluate the efficacy of elective LC with and without abdominal drainage and to compare the postoperative outcomes among the groups. Materials and Methods: This prospective interventional study was carried out among all patients admitted for elective LC at the Department of Surgery, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India from October 2022 to July 2023. A total of 200 patients scheduled for LC were divided into a drain group (n=92) or a no-drain group (n=108). Allocation was non randomised and based on surgeon preference. Along with demographics, surgical details including operation time, estimated blood loss, time to first flatus and tolerance of water and solid nutrition, postoperative hospital stay duration, and postoperative complications were noted and compared. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (SPSS Inc., Chicago, IL, USA) for the Windows program (version 26.0). The continuous and dichotomous variables were evaluated using student’s t-test and Chi-square test. Results: The mean age of patients in the drain and no-drain groups was 57.18±14.39 years and 55.61±14.83 years, respectively, with a female predominance. The no-drain group had a significantly shorter mean operation time than the drain group (93.27±30.81 min vs 124.86±38.64 min). Hospital stays in the no-drain group were substantially shorter (5.47±2.61 days) than those in the drain group (7.56±3.91 days). The postoperative morbidity rates were 14 (15.22%) in the drain group and 10 (9.26%) in the no-drain group. There was no significant difference between the groups in terms of postoperative complications. During the study, no patients in either group required reoperation. The most frequently cited reasons for drain placement were intraoperative haemorrhage (n=11) and difficult operation (n=11). Conclusion: The use of drains after simple, elective, uncomplicated LC could be safely restricted to patients deemed appropriate by the surgeon. Regarding postoperative complications, the no-drain group is superior in its use.
Parasites Observed in Urine Sediments: A Rare but Convincing Truth
Authors: Siagian Forman Erwin
Published: November 2023

Aim: To reveal the urgency to understand and augment the recognizance of the possibility existence of parasitic materials on cytological evaluation of urine.

Discussion: Urine is always contemplated as an ideal diagnostic specimen due to its direct and easiness to collect that surely non-invasive. Three common parasites that can be found in urine are Trichomonas vaginalis, Schistosoma hematobium and microfilaria of Wuchereria bancrofti. Other parasites and parasitic ova may also be seen in urinary sediments as a result of fecal or vaginal contamination. Urine Parasitological analysis embraces a wide expansive areas of tests, which comprise an assortment of physico-macroscopic analysis, microscopic analysis on cells and Parasite-bacterial appearance, parasite and microbe cultures, chemical tests, and even can be extended up to molecular identification. Importantly, from urine samples, a confirmed Parasitological diagnosis (and also Microbiology and other kind of disease) can be made through definite tests.

Conclusion: In the context of allegation of parasite as an etiological agent, thorough morphological detection via careful sediment microscopic analysis helps in making early and correct diagnosis in most cases.
Various Mathematical Models in Agricultural Engineering
Authors: Venu Vaisakh , Sreenath B.  , Ramdas E. R.
Published: November 2023

This paper investigates the important role of mathematics in the solution of complicated issues in the field of agricultural engineering and technology. It shows examples of mathematical modelling and analytical techniques that are used in agriculture, such as Crop Growth, Irrigation Management, Soil Moisture Modeling , Environmental management, Pest and Disease Management, Fertilizer Applications, Watershed Management etc.
Öznel İyi Oluş ile Psikolojik Sahiplenme: Örgütsel Güven ve Psikolojik Dayanıklılığın Durumsal Aracılık Modeli
Authors: VARLIK Savaş
Published: November 2023

Bu çalışmanın amacı, öğretmenlerin öznel iyi oluşlarının örgütsel güven aracılığıyla psikolojik sahiplenme üzerindeki dolaylı etkisinde psikolojik dayanıklılığın düzenleyicilik rolünü belirlemektir. Araştırma, işlevsel paradigma esas alınarak betimsel tarama modelinde yürütülmüştür. Araştırmanın çalışma evrenini, Konya ili Karatay, Meram ve Selçuklu ilçelerinde görev yapan kadrolu öğretmenler oluşturmaktadır. Bu ilçelerde görev yapan öğretmenler, küme ve basit tesadüfi örnekleme alma yöntemiyle seçilmiştir. Araştırmanın verileri, gerekli etik ve yasal izinler alınarak öznel iyi oluş, psikolojik sahiplenme, örgütsel güven ve psikolojik dayanıklılık ölçekleri ile toplanmıştır. Araştırmada kullanılan ölçme araçları için her bir ölçme aracına doğrulayıcı faktör analizi ve güvenirlik analizleri yapılmıştır. Analizler için SPSS 25 ve AMOS 23 paket programları kullanılmıştır. Araştırma genelinde, öznel iyi oluş ile psikolojik sahiplenme arasındaki ilişkide örgütsel güvenin aracı rolünün olduğu, öznel iyi oluş ile örgütsel güven arasındaki ilişkide ve örgütsel güven ile psikolojik dayanıklılık arasındaki ilişkide psikolojik dayanıklılığın düzenleyici rolünün olduğu, model genelinde ise öznel iyi oluşun örgütsel güven aracılığıyla psikolojik sahiplenme üzerindeki dolaylı etkisinde psikolojik dayanıklılığın düzenleyicilik rolünün olduğu bulgusuna ulaşılmıştır. Sonuç olarak öğretmenlerin öznel iyi oluşları, örgütsel güven aracılığıyla psikolojik sahiplenmelerini artırmaktadır. Ayrıca, bu dolaylı ilişki öğretmenlerin psikolojik dayanıklılıklarına bağlıdır. Yani, öğretmenlerin psikolojik dayanıklılıkları yüksek olduğunda psikolojik sahiplenmeleri, örgütsel güven vasıtasıyla öznel iyi oluşlarını daha da artırmaktadır.
Screening, Referral, Behavioral Counseling, and Preventive Interventions for Oral Health in Adults
Authors: Chou Roger , Selph Shelley S. , Bougatsos Christina , Nix Chad , Ahmed Azrah , Griffin Jessica , Schwarz Eli
Published: November 2023

Importance

Dental caries and periodontal disease are common adult oral health conditions and potentially amenable to primary care screening and prevention.

Objective

To systematically review the evidence on primary care screening and prevention of dental caries and periodontal disease in adults to inform the US Preventive Services Task Force.

Data Sources

MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to October 3, 2022); surveillance through July 21, 2023.

Study Selection

Diagnostic accuracy studies of primary care screening instruments and oral examination; randomized and nonrandomized trials of screening and preventive interventions; cohort studies on primary care oral health screening and preventive intervention harms.

Data Extraction and Synthesis

One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Diagnostic accuracy data were pooled using a bivariate mixed-effects binary regression model.

Main Outcomes and Measures

Dental caries, periodontal disease, morbidity, quality of life, harms; and diagnostic test accuracy.

Results

Five randomized clinical trials, 5 nonrandomized trials, and 6 observational studies (total 3300 participants) were included. One poor-quality trial (n = 477) found no difference between oral health screening during pregnancy vs no screening in caries, periodontal disease, or birth outcomes. One study (n = 86) found oral health examination by 2 primary care clinicians associated with low sensitivity (0.42 and 0.56) and high specificity (0.84 and 0.87) for periodontal disease and with variable sensitivity (0.33 and 0.83) and high specificity (0.80 and 0.93) for dental caries. Four studies (n = 965) found screening questionnaires associated with a pooled sensitivity of 0.72 (95% CI, 0.57-0.83) and specificity of 0.74 (95% CI, 0.66-0.82) for periodontal disease. For preventive interventions no study evaluated primary care counseling or dental referral, and evidence from 2 poor-quality trials (n = 178) of sealants, and 1 fair-quality and 4 poor-quality trials (n = 971) of topical fluorides, was insufficient. Three fair-quality trials (n = 590) of persons with mean age 72 to 80 years found silver diamine fluoride solution associated with fewer new root caries lesions or fillings vs placebo (mean reduction, −0.33 to −1.3) and decreased likelihood of new root caries lesion (2 trials; adjusted odds ratio, 0.4 [95% CI, 0.3-0.7]). No trial evaluated primary care–administered preventive interventions.

Conclusions and Relevance

Screening questionnaires were associated with moderate diagnostic accuracy for periodontal disease. Research is needed to determine benefits and harms of oral health primary care screening and preventive interventions.
A Highly‐Efficient Boron Interstitially Inserted Ru Anode Catalyst for Anion Exchange Membrane Fuel Cells
Authors: Han Pengyu , Yang Xinyi , Wu Liqing , Jia Hongnan , Chen Jingchao , Shi Wenwen , Cheng Gongzhen , Luo Wei
Published: November 2023

Developing high‐performance electrocatalysts for alkaline hydrogen oxidation reaction (HOR) is crucial for the commercialization of anion exchange membrane fuel cells (AEMFCs). Here, boron interstitially inserted ruthenium (B‐Ru/C) is synthesized and used as an anode catalyst for AEMFC, achieving a peak power density of 1.37 W cm−2, close to the state‐of‐the‐art commercial PtRu catalyst. Unexpectedly, instead of the monotonous decline of HOR kinetics with pH as generally believed, an inflection point behavior in the pH‐dependent HOR kinetics on B‐Ru/C is observed, showing an anomalous behavior that the HOR activity under alkaline electrolyte surpasses acidic electrolyte. Experimental results and density functional theory calculations reveal that the upshifted d‐band center of Ru after the intervention of interstitial boron can lead to enhanced adsorption ability of OH and H2O, which together with the reduced energy barrier of water formation, contributes to the outstanding alkaline HOR performance with a mass activity of 1.716 mA µgPGM−1, which is 13.4‐fold and 5.2‐fold higher than that of Ru/C and commercial Pt/C, respectively.
An “AND” Logic‐Gated Prodrug Micelle Locally Stimulates Antitumor Immunity
Authors: Chen Mengqi , Wang Chunhong , Wang Xuanyu , Tu Zhiyu , Ding Zexuan , Liu Zhibo
Published: November 2023

Materials that can respond to multiple biomarkers simultaneously, acting as an “AND” gate, have the potential to enhance tumor‐targeting for drug delivery. In this study, an “AND” logic‐controlled release prodrug micelle is developed for codelivering the chemotherapeutic and the stimulator of interferon genes (STING) agonist, enabling precise combinatorial therapy. The drug release is programmed by tumor‐enriched boramino acids (BAA) in the tumor microenvironment and intracellular reactive oxygen species (ROS), resulting in enhanced tumor targeting. STING agonist is successfully encapsulated into prodrug micelles through π–π stacking and hydrophobic interactions. These AND logic‐gated prodrug micelles can achieve tumor‐targeted delivery of STING agonist, leading to significantly enhanced immune activation and antitumor efficacy in vivo. It is expected that this clinically relevant nanoplatform will provide a rational design of an effective immunotherapy combination regimen to convert immunologically “cold” tumors to immunogenic “hot” tumors, addressing the major challenges faced by immunotherapies.
Ultrathin, Cationic Covalent Organic Nanosheets for Enhanced CO2 Electroreduction to Methanol
Authors: Song Yun , Guo Peng , Ma Tinghao , Su Jianjun , Huang Libei , Guo Weihua , Liu Yong , Li Geng , Xin Yinger , Zhang Qiang , Zhang Siwei , Shen Hanchen , Feng Xing , Yang Dengtao , Tian Jia , Ravi Sai Kishore , Tang Ben Zhong , Ye Ruquan
Published: November 2023

Metalloporphyrins and metallophthalocyanines emerge as popular building blocks to develop covalent organic nanosheets (CONs) for CO2 reduction reaction (CO2RR). However, existing CONs predominantly yield CO, posing a challenge in achieving efficient methanol production through multielectron reduction. Here, ultrathin, cationic, and cobalt‐phthalocyanine‐based CONs (iminium‐CONs) are reported for electrochemical CO2‐to‐CH3OH conversion. The integration of quaternary iminium groups enables the formation of ultrathin morphology with uniformly anchored cobalt active sites, which are pivotal for facilitating rapid multielectron transfer. Moreover, the cationic iminium‐CONs exhibit a lower activity for hydrogen evolution side reaction. Consequently, iminium‐CONs manifest significantly enhanced selectivity for methanol production, as evidenced by a remarkable 711% and 270% improvement in methanol partial current density (jCH3OH) compared to pristine CoTAPc and neutral imine‐CONs, respectively. Under optimized conditions, iminium‐CONs deliver a high jCH3OH of 91.7 mA cm−2 at −0.78 V in a flow cell. Further, iminium‐CONs achieve a global methanol Faradaic efficiency (FECH3OH) of 54% in a tandem device. Thanks to the single‐site feature, the methanol is produced without the concurrent generation of other liquid byproducts. This work underscores the potential of cationic covalent organic nanosheets as a compelling platform for electrochemical six‐electron reduction of CO2 to methanol.
Anhydrous Carbene Insertion Reactions: A Synthetic Platform for DNA‐Encoded Library
Authors: Su Xiao‐can , Shi Wen‐xia , Zhang Yue , Xiao Wen‐jie , Xue Jia‐ying , Zhu Xin‐hai , Yan Ming , Zhang Xue‐jing
Published: November 2023

An operationally simple anhydrous carbene insertion reaction to construct DNA‐encoded libraries (DEL) is reported. The developed reaction employs visible light photolysis of diazo compounds and Reversible Adsorption to Solid Support (RASS) strategy. From readily available amines, alcohols, phenols, and carboxylic acids, a variety of high‐value molecules, including useful unnatural amino acids, ethers, and esters, promising clinical drug derivatives, and bioactive molecules have been constructed.
Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD‐L1 in Cancer Therapy
Authors: Wang Yazhen , Zhou Yang , Yang Lianyi , Lei Lei , He Bin , Cao Jun , Gao Huile
Published: November 2023

Cancer immunotherapy using anti‐programmed death‐ligand 1 (PD‐L1) antibodies has been used in various clinical applications and achieved certain results. However, such limitations as autoimmunity, tumor hyperprogression, and overall low patient response rate impede its further clinical application. Mounting evidence has revealed that PD‐L1 is not only present in tumor cell membrane but also in cytoplasm, exosome, or even nucleus. Among these, the dynamic and spatial heterogeneous expression of PD‐L1 in tumors is mainly responsible for the unsatisfactory efficacy of PD‐L1 antibodies. Hence, numerous studies focus on inhibiting or degrading PD‐L1 to improve immune response, while a comprehensive understanding of the molecular mechanisms underlying spatial heterogeneity of PD‐L1 can fundamentally transform the current status of PD‐L1 antibodies in clinical development. Herein, the concept of spatial heterogeneous expression of PD‐L1 is creatively introduced, encompassing the structure and biological functions of various kinds of PD‐L1 (including mPD‐L1, cPD‐L1, nPD‐L1, and exoPD‐L1). Then an in‐depth analysis of the regulatory mechanisms and potential therapeutic targets of PD‐L1 is provided, seeking to offer a solid basis for future investigation. Moreover, the current status of agents is summarized, especially small molecular modulators development directed at these new targets, offering a novel perspective on potential PD‐L1 therapeutics strategies.
Smart‐Responsive Multifunctional Therapeutic System for Improved Regenerative Microenvironment and Accelerated Bone Regeneration via Mild Photothermal Therapy
Authors: Wu Minhao , Liu Huifan , Li Dan , Zhu Yufan , Wu Ping , Chen Zhe , Chen Feixiang , Chen Yun , Deng Zhouming , Cai Lin
Published: November 2023

The treatment of bone defects remains a substantial clinical challenge due to the lack of spatiotemporal management of the immune microenvironment, revascularization, and osteogenic differentiation. Herein, deferoxamine (DFO)‐loaded black phosphorus nanosheets decorated by polydopamine layer are prepared (BPPD) and compounded into gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel as a smart‐responsive therapeutic system (GA/BPPD) for accelerated bone regeneration. The BPPD nanocomposites served as bioactive components and near‐infrared (NIR) photothermal agents, which conferred the hydrogel with excellent NIR/pH dual‐responsive properties, realizing the stimuli‐responsive release of DFO and PO43 − during bone regeneration. Under the action of NIR‐triggered mild photothermal therapy, the GA/BPPD hydrogel exhibited a positive effect on promoting osteogenesis and angiogenesis, eliminating excessive reactive oxygen species, and inducing macrophage polarization to the M2 phenotype. More significantly, through macrophage M2 polarization‐induced osteoimmune microenvironment, this hydrogel platform could also drive functional cytokine secretion for enhanced angiogenesis and osteogenesis. In vivo experiments further demonstrated that the GA/BPPD system could facilitate bone healing by attenuating the local inflammatory response, increasing the secretion of pro‐healing factors, stimulating endogenous cell recruitment, and accelerating revascularization. Collectively, the proposed intelligent photothermal hydrogel platform provides a promising strategy to reshape the damaged tissue microenvironment for augmented bone regeneration.
Undifferentiated psychosis or schizophrenia associated with vermis‐predominant cerebellar hypoplasia
Authors: Leslie Alison C. , Ward Mitchell P. , Dobyns William B.
Published: November 2023

Schizophrenia (SCZ) is a well‐studied neuropsychiatric condition that has been shown to have a high degree of genetic heritability. Still, little data on the specific genetic risk variants associated with the disease exists. Classification of the SCZ phenotype into SCZ‐related endophenotypes is a promising methodology to parse out and elucidate the specific genetic risk variants for each. Here, we present a series of 17 previously reported individuals and a new proband with similar SCZ‐related neuropsychiatric characteristics and shared brain imaging findings. Unsurprisingly, these individuals shared classic psychiatric features of SCZ. Interestingly, we also identified shared neuropsychiatric features in this series of individuals that had not been highlighted previously. A consistently decreased IQ, memory impairment, sleep and speech disturbances, and attention deficits were commonly reported findings. The brain imaging findings among these individuals also consistently showed posterior vermis predominant cerebellar hypoplasia (CBLH‐V). Most individuals' diagnoses were initially described as Dandy–Walker malformation; however, our independent review of imaging suggests a more consistent pattern of posterior vermis predominant cerebellar hypoplasia rather than true Dandy–Walker malformation. While the specific genetic risk variants for this endophenotype are yet to be described, the aim of this paper is to present the shared neuropsychiatric features and consistent, symmetrical brain image findings which suggest that this subset of individuals comprises an endophenotype of SCZ with a high genetic solve rate.
Locally Ordered Single‐Atom Catalysts for Electrocatalysis
Authors: Ren Yujing , Wang Jinyong , Zhang Mingyue , Wang Yuqing , Cao Yuan , Kim Dong Ha , Lin Zhiqun
Published: November 2023

Single‐atom catalysts manifest nearly 100 % atom utilization efficiency, well‐defined active sites, and high selectivity. However, their practical applications are hindered by a low atom loading density, uncontrollable location, and ambiguous interaction with the support, thereby posing challenges to maximizing their electrocatalytic performance. To address these limitations, the ability to arrange randomly dispersed single atoms into locally ordered single‐atom catalysts (LO‐SACs) substantially influences the electronic effect between reactive sites and the support, the synergistic interaction among neighboring single atoms, the bonding energy of intermediates with reactive sites and the complexity of the mechanism. As such, it dramatically promotes reaction kinetics, reduces the energy barrier of the reaction, improves the performance of the catalyst and simplifies the reaction mechanism. In this review, firstly, we introduce a variety of compelling characteristics of LO‐SACs as electrocatalysts. Subsequently, the synthetic strategies, characterization methods and applications of LO‐SACs in electrocatalysis are discussed. Finally, the future opportunities and challenges are elaborated to encourage further exploration in this rapidly evolving field.
Diadenosine Tetraphosphate (Ap4A) Serves as a 5′ RNA Cap in Mammalian Cells
Authors: František Potužník Jiří , Nešuta Ondřej , Škríba Anton , Voleníková Barbora , Mititelu Maria‐Bianca , Mancini Flaminia , Serianni Valentina , Fernandez Henri , Spustová Kristína , Trylčová Jana , Vopalensky Pavel , Cahová Hana
Published: November 2023

The recent expansion of the field of RNA chemical modifications has changed our understanding of post‐transcriptional gene regulation. Apart from internal nucleobase modifications, 7‐methylguanosine was long thought to be the only eukaryotic RNA cap. However, the discovery of non‐canonical RNA caps in eukaryotes revealed a new niche of previously undetected RNA chemical modifications. We are the first to report the existence of a new non‐canonical RNA cap, diadenosine tetraphosphate (Ap4A), in human and rat cell lines. Ap4A is the most abundant dinucleoside polyphosphate in eukaryotic cells and can be incorporated into RNA by RNA polymerases as a non‐canonical initiating nucleotide (NCIN). Using liquid chromatography‐mass spectrometry (LC–MS), we show that the amount of capped Ap4A‐RNA is independent of the cellular concentration of Ap4A. A decapping enzyme screen identifies two enzymes cleaving Ap4A‐RNA,NUDT2 and DXO, both of which also cleave other substrate RNAs in vitro. We further assess the translatability and immunogenicity of Ap4A‐RNA and show that although it is not translated, Ap4A‐RNA is recognized as self by the cell and does not elicit an immune response, making it a natural component of the transcriptome. Our findings open a previously unexplored area of eukaryotic RNA regulation.