bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional ultrasound imaging of stroke in awake rats
Authors: Brunner Clément , Montaldo Gabriel , Urban Alan
Published: July 2023

Anesthesia is a major confounding factor in preclinical stroke research as stroke rarely occurs in sedated patients. Moreover, anesthesia affects both brain functions and the stroke outcome acting as neurotoxic or protective agents. So far, no approaches were well suited to induce stroke while imaging hemodynamics along with simultaneous large-scale recording of brain functions in awake animals. For this reason, the first critical hours following the stroke insult and associated functional alteration remain poorly understood. Here, we present a strategy to investigate both stroke hemodynamics and stroke-induced functional alterations without the confounding effect of anesthesia, i.e., under awake condition. Functional ultrasound (fUS) imaging was used to continuously monitor variations in cerebral blood volume (CBV) in +65 brain regions/hemispheres for up to 3 hr after stroke onset. The focal cortical ischemia was induced using a chemo-thrombotic agent suited for permanent middle cerebral artery occlusion in awake rats and followed by ipsi- and contralesional whiskers stimulation to investigate on the dynamic of the thalamocortical functions. Early (0–3 hr) and delayed (day 5) fUS recording enabled to characterize the features of the ischemia (location, CBV loss), spreading depolarizations (occurrence, amplitude) and functional alteration of the somatosensory thalamocortical circuits. Post-stroke thalamocortical functions were affected at both early and later time points (0–3 hr and 5 days) after stroke. Overall, our procedure facilitates early, continuous, and chronic assessments of hemodynamics and cerebral functions. When integrated with stroke studies or other pathological analyses, this approach seeks to enhance our comprehension of physiopathologies towards the development of pertinent therapeutic interventions.
Evidence for deliberate burial of the dead by Homo naledi
Authors: Berger Lee R , Makhubela Tebogo , Molopyane Keneiloe , Krüger Ashley , Randolph-Quinney Patrick , Elliott Marina , Peixotto Becca , Fuentes Agustín , Tafforeau Paul , Beyrand Vincent , Dollman Kathleen , Jinnah Zubair , Brewer Gillham Angharad , Broad Kenneth , Brophy Juliet , Chinamatira Gideon , Dirks Paul H. M. , Feuerriegel Elen , Gurtov Alia , Hlophe Nompumelelo , Hunter Lindsay , Hunter Rick , Jakata Kudakwashe , Jaskolski Corey , Morris Hannah , Pryor Ellie , Ramaphela Maropeng , Roberts Eric , Smilg Jacqueline S. , Tsikoane Mathabela , Tucker Steven , van Rooyen Dirk , Warren Kerryn , Wren Colin D. , Kissel Marc , Spikins Penny , Hawks John
Published: July 2023

Recent excavations in the Rising Star Cave System of South Africa have revealed burials of the extinct hominin species
Homo naledi
. A combination of geological and anatomical evidence shows that hominins dug holes that disrupted the subsurface stratigraphy and interred the remains of
H. naledi
individuals, resulting in at least two discrete features within the Dinaledi Chamber and the Hill Antechamber. These are the most ancient interments yet recorded in the hominin record, earlier than evidence of
Homo sapiens
interments by at least 100,000 years. These interments along with other evidence suggest that diverse mortuary practices may have been conducted by
H. naledi
within the cave system. These discoveries show that mortuary practices were not limited to
H. sapiens
or other hominins with large brain sizes.
Burials and engravings in a small-brained hominin, Homo naledi, from the late Pleistocene: contexts and evolutionary implications
Authors: Fuentes Agustin , Kissel Marc , Spikins Penny , Molopyane Keneiloe , Hawks John , Berger Lee R.
Published: July 2023

Data from recent explorations in the Dinaledi subsystem illustrates one of the earliest examples of a mortuary practice in hominins and offers the earliest evidence of multiple interments and funerary actions, as well as evidence of the early creation of meaning making by a hominin. The hominin undertaking these behaviors was the small-brained
Homo naledi
. These data call into question several key assumptions about behavioral and cognitive evolution in Pleistocene hominins. The evidence from Dinaledi push back the temporal origins of mortuary and funerary behaviors and associate the creation of meaning making with a small-brained species and thus challenge key assumptions about the role and importance of encephalization in human evolution. This suggests that the hominin socio-cognitive niche and its relation to meaning-making activities is more diverse than previously thought. The association of these activities in subterranean spaces accessed and modified by the small brained species
Homo naledi
impacts assertations that technological and cognitive advances in human evolution are associated solely with the evolution of larger brains.Burials and related meaning making in a small-brained hominin alter our understandings of human evolution.
Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase
Authors: Colin Léonard , Reyes Céline , Berthezene Julien , Maestroni Laetitia , Modolo Laurent , Toselli Esther , Chanard Nicolas , Schaak Stephane , Cuvier Olivier , Gachet Yannick , Coulon Stéphane , Bernard Pascal , Tournier Sylvie
Published: July 2023

The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome-remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosomes arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.
Personalized movie recommendations based on deep representation learning
Authors: Li Luyao , Huang Hong , Li Qianqian , Man Junfeng
Published: July 2023

Personalized recommendation is a technical means to help users quickly and efficiently obtain interesting content from massive information. However, the traditional recommendation algorithm is difficult to solve the problem of sparse data and cold-start and does not make reasonable use of the user-item rating matrix. In this article, a personalized recommendation method based on deep belief network (DBN) and softmax regression is proposed to address the issues with traditional recommendation algorithms. In this method, the DBN is used to learn the deep representation of users and items, and the user-item rating matrix is maximized. Then softmax regression is used to learn multiple categories in the feature space to predict the probability of interaction between users and items. Finally, the method is applied to the area of movie recommendation. The key to this method is the negative sampling mechanism, which greatly improves the effectiveness of the recommendations, as a result, creates an accurate list of recommendations. This method was verified and evaluated on Douban and several movielens datasets of different sizes. The experimental results demonstrate that the recommended performance of this model, which has high accuracy and generalization ability, is much better than typical baseline models such as singular value decomposition (SVD), and the mean absolute error (MAE) value is 98%, which is lower than the best baseline model.
Gazing left, gazing right: exploring a spatial bias in social attention
Authors: Dalmaso Mario , Fedrigo Giacomo , Vicovaro Michele
Published: July 2023

Faces oriented rightwards are sometimes perceived as more dominant than faces oriented leftwards. In this study, we explored whether faces oriented rightwards can also elicit increased attentional orienting. Participants completed a discrimination task in which they were asked to discriminate, by means of a keypress, a peripheral target. At the same time, a task-irrelevant face oriented leftwards or rightwards appeared at the centre of the screen. The results showed that, while for faces oriented rightwards targets appearing on the right were responded to faster as compared to targets appearing on the left, for faces oriented leftwards no differences emerged between left and right targets. Furthermore, we also found a negative correlation between the magnitude of the orienting response elicited by the faces oriented leftwards and the level of conservatism of the participants. Overall, these findings provide evidence for the existence of a spatial bias reflected in social orienting.
Incentivised School Climate and Teachers’ Productivity in Mission Secondary Schools in Delta State, Nigeria
Authors: Ubah C. , Egwunyenga E. J. , Asiyai R. I.
Published: July 2023

This study examined incentivized school climate and teachers productivity in mission secondary schools in Delta State, Nigeria. The study utilized the Ex-post-facto survey method and focused on teachers in mission secondary schools in Delta State. A total of 537 teachers were selected as the study sample using the simple random sampling technique. Data collection involved the use of a questionnaire on incentivized school climate and teachers' productivity. The collected data were analyzed using mean scores, standard deviations, and Pearson's product moment correlation coefficient. The results indicated that the climate in mission secondary schools in Delta State is positively incentivized and that there is a positive relationship between the school climate in mission secondary schools and teachers' productivity. Based on the findings, it was recommended that teachers in mission secondary schools in Delta state should develop the sense of ownership of the school system and consider themselves as members of an institutional family with a common objectives to be achieved.
Unified Modeling Language for Requirements Engineering, Strategies and Best Practices for FinTech and Beyond
Authors: Challapalli Surendra Reddy
Published: July 2023

Effective requirements management is crucial in the rapidly evolving landscape of Financial Technology (FinTech) to deliver innovative and customer-centric solutions. Unified Modeling Language (UML) has emerged as a powerful tool in the FinTech industry for requirements management, providing a standardized notation and comprehensive set of diagrams. By leveraging UML, FinTech companies can overcome challenges such as miscommunication and inconsistency. UML fosters a common understanding among stakeholders, aligning perspectives and enabling informed decisions. This article explores strategies and best practices in leveraging UML for FinTech requirements management, addressing complexities, utilizing key UML diagram types, and overcoming challenges. Clear communication, collaboration, documentation standards, traceability, tool support, requirement validation, iterative approach, and model-driven development are highlighted as key practices. By adopting these strategies, organizations can streamline requirements engineering, ensure compliance, and deliver high-quality FinTech solutions. These strategies are not limited to the FinTech industry but can be applied in any industry and domain within the realm of software engineering and requirements management.
Reproductive Parameters and Oxidative Stress Marker Impacts Associated with Oral and Inhalation Exposure to Chlorview
Authors: U. Amadi Eustace , J. Nweze Ekene , U. Amalunweze Adaude , S. Ubani Chibuike
Published: July 2023

Aim: Factory workers, pesticide applicators and farmers are the most susceptible group to reproductive problems due to continuous exposure to pesticides. Farmers now increasingly deploy pesticides in their agronomic practices. This research aimed to assess the impact on reproductive markers and stress markers of acute exposure to chlorview, an organophosphate pesticide, through oral and inhalation routes using animal model.

Study Design: A total of 64 male wistar rats were used for the experiment. The animals were divided into two groups for oral (36 rats) and inhalation (28 rats) routes of exposure. Acute toxicity studies and the median lethal dose were carried out using a modified method.

Methodology: Standard methods were used to determine oxidative stress markers of lipid peroxides, catalase activity and glutathione peroxidase activity. Immunoassay test kit was used to determine the reproductive toxicity studies.

Results: The results from the 24 hour acute toxicity studies revealed that oral exposure to pesticide gave a median lethal dose (LD50) of 155 mg/kg b.w. while inhalation exposure gave a median lethal concentration (LC50) of 1414 mg/kg b.w. for 60 min. Oxidative stress markers [glutathione (GSH), Malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx)] show that the pesticide induced appreciable oxidative imbalance in the system. In oral exposure, there was a significant (p<0.05) increase in the activity when compared to control. The reproductive marker toxicity studies revealed that oral exposure to pesticide led to a significant (p<0.05) increase in the Cholesterol (which has a correlation with estradiol) and a significantly (p<0.05) decreased in testosterone and sperm count when compared to control. This research concludes that exposure to pesticides can pose a reasonable risk to reproductive and stress markers through oral and inhalation routes of exposure which affect many biochemical processes.
Türkçe Duygu Haritası Modeli Aracını Kullanarak Çokluortam Öğrenme Materyalinin Duygu Salınımını Belirleme
Authors: ÖZGÜR Adem , SAĞLAM Fatih , GENÇ Burkay , ALTUN Arif
Published: July 2023

Çokluortam öğrenme materyallerinin (ÇÖM) duygusal tasarımı ile öğrenenlerde belirli bir duygu oluşturma (olumlu-olumsuz), öğrenenlerin motivasyonlarını düzenleme, bilişsel özelliklerini ve öğrenme çıktılarını etkileme gibi hedefler güdülmektedir. Bununla birlikte, ÇÖM’lerin duygusal niteliğini sağlamak için belirli yönergelerin geliştirilmesi önemlidir. Bu çalışmada, metinleri açısından olumlu ve olumsuz duygusal tasarıma sahip iki ÇÖM’ün duygu salınımını belirlemek için duygu haritası modeli (DHM) kullanılmıştır. DHM sözlük (lexicon) tabanlı bir metin duygu analizi (sentiment analysis) aracıdır. DHM sürecine göre; öncelikle olumlu ve olumsuz ÇÖM’ler cümle cümle ayrılmış ve her bir cümlenin duygu tonu hesaplanmıştır. Ardından olumlu ve olumsuz ÇÖM’ler için hesaplanan duygu ton değerleri Shewhart Kontrol Diyagramı üzerine yerleştirilerek metinlerin duygu salınımları görselleştirilmiştir. Duygu salınımı içerisinde; istikrarlı, belirgin, baskın, şiddetli duyguların yer aldığı bölgeleri belirlemek için analiz kuralları uygulanmış ve bu bölgeler diyagram üzerinde belirginleştirilmiştir. Sonuç olarak, olumlu ÇÖM’deki duygu salınımlarında olumsuz ÇÖM’e göre daha fazla istikrarlı bölgenin yer aldığı görülmüştür. Bu bağlamda, ÇÖM’lerde yer alan metinlerin DHM ile duygu analizinin yapılması, ÇÖM’lerin duygusal tasarımı ve öğrenme-öğretme süreçlerinde kullanımı tartışılmıştır.
Prevalence of Neuroradiological Abnormalities in First-Episode Psychosis
Authors: Blackman Graham , Neri Giulia , Al-Doori Omar , Teixeira-Dias Maria , Mazumder Asif , Pollak Thomas A. , Hird Emily J. , Koutsouleris Nikolaos , Bell Vaughan , Kempton Matthew J. , McGuire Philip
Published: July 2023

Importance

Individuals presenting with first-episode psychosis (FEP) may have a secondary (“organic”) etiology to their symptoms that can be identified using neuroimaging. Because failure to detect such cases at an early stage can have serious clinical consequences, it has been suggested that brain magnetic resonance imaging (MRI) should be mandatory for all patients presenting with FEP. However, this remains a controversial issue, partly because the prevalence of clinically relevant MRI abnormalities in this group is unclear.

Objective

To derive a meta-analytic estimate of the prevalence of clinically relevant neuroradiological abnormalities in FEP.

Data Sources

Electronic databases Ovid, MEDLINE, PubMed, Embase, PsychINFO, and Global Health were searched up to July 2021. References and citations of included articles and review articles were also searched.

Study Selection

Magnetic resonance imaging studies of patients with FEP were included if they reported the frequency of intracranial radiological abnormalities.

Data Extraction and Synthesis

Independent extraction was undertaken by 3 researchers and a random-effects meta-analysis of pooled proportions was calculated. Moderators were tested using subgroup and meta-regression analyses. Heterogeneity was evaluated using the I2 index. The robustness of results was evaluated using sensitivity analyses. Publication bias was assessed using funnel plots and Egger tests.

Main Outcomes and Measures

Proportion of patients with a clinically relevant radiological abnormality (defined as a change in clinical management or diagnosis); number of patients needed to scan to detect 1 such abnormality (number needed to assess [NNA]).

Results

Twelve independent studies (13 samples) comprising 1613 patients with FEP were included. Of these patients, 26.4% (95% CI, 16.3%-37.9%; NNA of 4) had an intracranial radiological abnormality, and 5.9% (95% CI, 3.2%-9.0%) had a clinically relevant abnormality, yielding an NNA of 18. There were high degrees of heterogeneity among the studies for these outcomes, 95% to 73%, respectively. The most common type of clinically relevant finding was white matter abnormalities, with a prevalence of 0.9% (95% CI, 0%-2.8%), followed by cysts, with a prevalence of 0.5% (95% CI, 0%-1.4%).

Conclusions and Relevance

This systematic review and meta-analysis found that 5.9% of patients presenting with a first episode of psychosis had a clinically relevant finding on MRI. Because the consequences of not detecting these abnormalities can be serious, these findings support the use of MRI as part of the initial clinical assessment of all patients with FEP.
Potential Avoidable Costs of Low-Value Clinical Practices in Acute Injury Care in an Integrated Canadian Provincial Trauma System
Authors: Conombo Blanchard , Guertin Jason R. , Hoch Jeffrey S. , Lauzier François , Turgeon Alexis F. , Stelfox Henry T. , Moore Lynne
Published: July 2023

This economic evaluation estimated the direct health care costs associated with 11 low-value clinical practices in acute trauma care in the integrated health care system of Quebec, Canada.
GPR35‐mediated kynurenic acid sensing contributes to maintenance of gut microbiota homeostasis in ulcerative colitis
Authors: Wang Di , Wang Wenbao , Bing Xue , Xu Chenguang , Qiu Jiahua , Shen Jiangang , Huang Jinwen , Li Junda , Liu Pi , Xie Biao
Published: July 2023

Ulcerative colitis (UC) is a recurrent inflammatory disease related to gut microbiota disorder. Metabolites and their sensors play an important role in the communication between gut microbes and their host. Our previous study revealed that G protein‐coupled receptor 35 (GPR35) is a key guardian of kynurenic acid (KA) and a core element of the defense responses against gut damage. However, the mechanism remains unknown. In this study, a DSS‐induced rat colitis model was established and 16S rRNA sequencing was applied to explore the influence of GPR35‐mediated KA sensing on gut microbiota homeostasis. Our results demonstrated that GPR35‐mediated KA sensing is a necessary component in maintaining gut barrier integrity against DSS‐induced damage. Furthermore, we provide compelling evidence suggesting that GPR35‐mediated KA sensing plays a crucial role in maintaining gut microbiota homeostasis, which contributes to alleviation of DSS‐induced colitis. In addition, five classes (Actinobacteria, Beta‐/Gamma‐proteobacteria, Erysipelotrichi, and Coriobacteriia) and six genera (Corynebacterium, Allobaculum, Parabacteroides, Sutterella, Shigella, and Xenorhabdus) were identified as the marked bacterial taxa that characterized the progression and outcome of colitis and are regulated by GPR35‐mediated KA sensing. Our findings highlight that GPR35‐mediated KA sensing is an essential defense mechanism against disorder of gut microbiota in UC. The results provide insights into the key role of specific metabolites and their monitor in maintaining gut homeostasis.
Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low‐Concentration Collagen‐Based Bioinks
Authors: Shi Wen , Mirza Sameer , Kuss Mitchell , Liu Bo , Hartin Andrew , Wan Shibiao , Kong Yunfan , Mohapatra Bhopal , Krishnan Mena , Band Hamid , Band Vimla , Duan Bin
Published: July 2023

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models challenging. This work produces embedded, bioprinted breast cancer cells and tumor organoid models using low‐concentration collagen I based bioinks. The biocompatible and physically crosslinked silk fibroin hydrogel is used to generate the support bath for the embedded 3D printing. The composition of the collagen I based bioink is optimized with a thermoresponsive hyaluronic acid‐based polymer to maintain the phenotypes of both the noninvasive epithelial and invasive breast cancer cells, as well as cancer‐associated fibroblasts. Mouse breast tumor organoids are bioprinted using optimized collagen bioink to mimic in vivo tumor morphology. A vascularized tumor model is also created using a similar strategy, with significantly enhanced vasculature formation under hypoxia. This study shows the great potential of embedded bioprinted breast tumor models utilizing a low‐concentration collagen‐based bioink for advancing the understanding of tumor cell biology and facilitating drug discovery research.
Aliphatic Alcohol Hydroxyl‐Directed One‐Pot Stepwise Synthesis: A Concise Synthesis of 1H‐pyrrolo[3,4‐b]quinoline‐1,3(2H)‐diones
Authors: Huang Shuntao , Yang Qi , Wan Juan , Wang Zhuoyu , Zhang Zhou , Liu Teng , Huang Chao
Published: July 2023

A concise and flexible protocol to assemble structurally diverse 1H‐pyrrolo[3,4‐b]quinoline‐1,3(2H)‐diones (29 examples, 70–87% yields) has been developed via one‐pot stepwise synthesis. The potentially valuable quinine‐fused heterocycles were synthetized by utilizing aliphatic alcohol hydroxyl as directing group which promoted a sequential transformation to form functionalized aminomaleimides, and then underwent an I2‐oxidized tandem annulations. This route involved the formation of multiple new chemical bonds (C=N, 2C−N, C−C) in a one‐pot fashion under mild conditions.
Synthesis of Tetraazamacrocycles by Sequential Palladium‐Catalyzed Allylic Substitution Reactions
Authors: Lee Seoyoung , Kim Juyeong , Kang Kyungjun , Lee Ansoo , Kim Hyunwoo
Published: July 2023

In this study, we focused on the synthesis of tetraazamacrocycles, an essential class of macrocyclic compounds with applications in coordination chemistry, pharmaceuticals, and catalysis. To accomplish this, we developed a ligand‐controlled palladium‐catalyzed allylic substitution approach using bicyclic bridgehead phosphoramidite (briphos) ligands. This approach allowed us to selectively achieve [1+1] and [1+2] allylic aminations between allylic diols and diamines, while avoiding the formation of cyclic [1+1] products. By combining this approach with sequential acetylation and allylic amination, we successfully synthesized tetraazamacrocycles with ring sizes ranging from 16 to 38. These findings demonstrate the potential of a sequential allylation strategy for synthesizing complex molecules with broad applications in the fields of chemistry, pharmaceuticals, and medicine.
Copper‐Catalyzed Olefinic C(sp2)−H Activation/Carbene Insertion/Ester Hydrolysis/Cyclization with Aryl Diazo Esters for the Synthesis of Multisubstituted Furanones
Authors: Wang Yuzhi , Yu Yadong , Yu Yang , Huang Fei , Baell Jonathan B.
Published: July 2023

A copper‐catalyzed olefinic C(sp2)−H activation/carbene insertion/ester hydrolysis/cyclization sequence has been developed for the synthesis of substituted 2(5H)‐furanones employing readily available enaminones and aryl diazo esters as substrates. This method features operationally simple and good functional group tolerance. The transformation could be scaled up to gram quantities and the obtained 2(5H)‐furanone derivatives could be easily converted to a wide range of useful synthetic building blocks, indicative of the applicability of the synthetic strategy. Isotope labeling experiments demonstrated the ester group of diazo esters was hydrolyzed during the reaction.
Palladium‐Catalyzed Chemoselective Mono‐α‐Arylation of O‐Protected Hydroxyacetone with Ortho‐Substituted (Hetero)aryl Electrophiles
Authors: MacMillan Joshua W. M. , Lundrigan Travis , Volpin Giulio , Kaldas Sherif J. , Holstein Philipp M. , Ford Mark James , Guimond Nicolas , Stradiotto Mark
Published: July 2023

The mono‐α‐arylation of 2‐tetrahydropyranyl O‐protection of hydroxyacetone is reported. When using a catalyst system comprised of [Pd(cinnamyl)Cl]2 and the JosiPhos ligands PhPF‐tBu or (4‐CF3Ph)PF‐tBu, such transformations are achieved with ortho‐substituted aryl bromides and triflates in the presence of potentially contending functionalities including chloro groups.
Recent Progress in Transient Energy Storage using Biodegradable Materials
Authors: Yamada Shunsuke
Published: July 2023

With the development of wireless sensor networks, electrical waste that remains in the environment is an inevitable issue in achieving sustainability and progress in electronics. Transient electronics that disappear after a prescribed time are of interest in electronics and material sciences. Such devices comprise naturally sourced materials that degrade without harmful or toxic substances during biodegradation. Although there are reports on transient electronic devices, including transistors, sensors, and radio frequency circuits, insufficient research has been conducted on the energy storage essential for operating transient devices. This review highlights the recent progress in developing transient energy storage. First, materials for transient energy storage, including conductors, electrolytes, and gels, are introduced. Second, transient supercapacitors, pseudocapacitors, primary batteries, and secondary batteries, are described and summarized. Finally, this review concludes and discusses the prospect of transient energy storage. The continuous progress of transient batteries and integration with transient devices are promising for sustainable electronics in the future.
15q26.3 deletions distal to IGF1R cause growth retardation, congenital heart defect and skeletal anomalies: Case report and review of literature
Authors: Sivakumaran Theru A. , Grebe Theresa A.
Published: July 2023

15q26 deletion is a rare genomic disorder characterized by intrauterine and postnatal growth retardation, microcephaly, intellectual disability, and congenital malformations. Here, we report a 4‐month‐old female with intrauterine growth retardation, short stature, pulmonary hypertension, atrial septal defect and congenital bowing of long bones of the legs. Chromosomal microarray analysis showed a de novo deletion of approximately 2.1 Mb at 15q26.3 region that does not include IGF1R. Our analysis of patients documented in the literature and the DECIPHER database with 15q26 deletions distal to IGF1R, including 10 patients with de novo pure deletions, allowed us to define the smallest region of overlap to 686 kb. This region includes ALDH1A3, LRRK1, CHSY1, SELENOS, SNRPA1, and PCSK6. We propose haploinsufficiency of one or more genes, besides IGF1R, within this region may contribute to the clinical findings in patients with 15q26.3 deletion.
The national public health response to Alzheimer's disease and related dementias: Origins, evolution, and recommendations to improve early detection
Authors: Vinze Sanjna , Chodosh Joshua , Lee Matthew , Wright Jacob , Borson Soo
Published: July 2023

Longstanding gaps in the detection of Alzheimer's disease and related dementias (ADRD) and biopsychosocial care call for public health action to improve population health. We aim to broaden the understanding of the iterative role state plans have played over the last 20 years in prioritizing improvements in the detection of ADRD, primary care capacity, and equity for disproportionately affected populations. Informed by national ADRD priorities, state plans convene stakeholders to identify local needs, gaps, and barriers and set the stage for development of a national public health infrastructure that can align clinical practice reform with population health goals. We propose policy and practice actions that would accelerate the collaboration between public health, community organizations, and health systems to improve ADRD detection—the point of entry into care pathways that could ultimately improve outcomes on a national scale.

HIGHLIGHTS

We systematically reviewed the evolution of state/territory plans for Alzheimer's disease and related dementias (ADRD).

Plan goals improved over time but lacked implementation capacity.

Landmark federal legislation (2018) enabled funding for action and accountability.

The Centers for Disease Control and Prevention (CDC) funds three Public Health Centers of Excellence and many local initiatives.

Four new policy steps would promote sustainable ADRD population health improvement.
Kyoto Collection in The Anatomical Record
Authors: Yamada Shigehito
Published: July 2023

Human embryology began at the end of the 19th century and has developed using valuable human embryo specimens; the Carnegie and Blechshmidt Collections are famous examples. Although established after these two collections, the Kyoto Collection of Human Embryos and Fetuses has become the largest collection worldwide, and its major asset is 1044 serial tissue sections comprising 547 normal and 497 abnormal cases. Morphological changes have been the focus of analysis owing to the absence of fresh embryos in the Kyoto Collection. Furthermore, analysis methods have undergone significant changes. For example, morphometrics has been used to quantitatively analyze shape changes, although it may result in the loss of information on shape changes, which can hinder the visualization of analysis results. However, geometric morphometrics has been recently introduced to the fetal and embryonic stages to circumvent this problem. With the development of DNA analysis kits, several hundred DNA base pairs have been extracted from the Kyoto Collection of studies conducted from the 2000s to the 2010s through genetic analysis. Future technological advances are eagerly awaited.
Unraveling the chemical profile, antioxidant, enzyme inhibitory, cytotoxic potential of different extracts from Astragalus caraganae
Authors: Kurt‐Celep İnci , Zengin Gokhan , Uba Abdullahi I. , Caprioli Giovanni , Mustafa Ahmed M. , Angeloni Simone , Cakilcioglu Ugur , Guler Osman , Kaplan Alevcan , Sharmeen Jugreet , Mahomoodally Mohamad F.
Published: July 2023

Six extracts (water, ethanol, ethanol‐water, ethyl acetate, dichloromethane, and n‐hexane) of Astragalus caraganae were studied for their biological activities and bioactive contents. Based on high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), the ethanol‐water extract yielded the highest total bioactive content (4242.90 µg g−1), followed by the ethanol and water extracts (3721.24 and 3661.37 µg g−1, respectively), while the least total bioactive content was yielded by the hexane extract, followed by the dichloromethane and ethyl acetate extracts (47.44, 274.68, and 688.89 µg g−1, respectively). Rutin, p‐coumaric, chlorogenic, isoquercitrin, and delphindin‐3,5‐diglucoside were among the major components. Unlike the dichloromethane extracts, all the other extracts showed radical scavenging ability in the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay (8.73–52.11 mg Trolox equivalent [TE]/g), while all extracts displayed scavenging property in the 2,2‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) radical scavenging assay (16.18–282.74 mg TE/g). The extracts showed antiacetylcholinesterase (1.27–2.73 mg galantamine equivalent [GALAE]/g), antibutyrylcholinesterase (0.20–5.57 mg GALAE/g) and antityrosinase (9.37–63.56 mg kojic acid equivalent [KAE]/g) effects. The molecular mechanism of the H2O2‐induced oxidative stress pathway was aimed to be elucidated by applying ethanol, ethanol/water and water extracts at 200 µg/mL concentration to human dermal cells (HDFs). A. caraganae in HDF cells had neither a cytotoxic nor genotoxic effect but could have a cytostatic effect in increasing concentrations. The findings have allowed a better insight into the pharmacological potential of the plant, with respect to their chemical entities and bioactive contents, as well as extraction solvents and their polarity.
Identifying new small proteins through a molecular biology course‐based undergraduate research experience laboratory class
Authors: Miranda Rommel J. , Warren Cheryl , Mcdougal Kathryn , Kimble Steven , Sanchez Joseph , Norman Leann , Anderson Virginia , Hemm Matthew
Published: July 2023

We developed a curriculum for an upper‐level molecular biology course‐based undergraduate research laboratory class funded by a National Science Foundation CAREER grant that focuses on identifying new small proteins in the bacterium, Escherichia coli. Our CURE class has been continually offered each semester for the last 10 years, with multiple instructors collaboratively developing and implementing their own pedagogical approach while maintaining the same overall scientific goal and experimental strategy. In this paper, we delineate the experimental strategy for our molecular biology CURE laboratory class, describe a range of pedagogical approaches implemented by multiple instructors, and provide recommendations for teaching the class. The purpose of our paper is to share our experiences both in developing and teaching a molecular biology CURE laboratory class based on small protein identification and in creating a curriculum and support system that allows traditional, non‐traditional, and under‐represented students to participate in authentic research projects.
Establishment of an In Bacterio Assay for the Assessment of Carbon Storage Regulator A (CsrA) Inhibitors
Authors: Wu Yingwen , Zoller Ben G. E. , Kamal Mohamed Ashraf Mostafa , Hotop Sven‐Kevin , Lehr Claus‐Michael , Brönstrup Mark , Dersch Petra , Empting Martin
Published: July 2023

Polymicrobial infections involving various combinations of microorganisms, such as Escherichia, Pseudomonas, or Yersinia, can lead to acute and chronic diseases in for example the gastrointestinal and respiratory tracts. Our aim is to modulate microbial communities by targeting the posttranscriptional regulator system called carbon storage regulator A (CsrA) (or also repressor of secondary metabolites (RsmA)). In previous studies, we identified easily accessible CsrA binding scaffolds and macrocyclic CsrA binding peptides through biophysical screening and phage display technology. However, due to the lack of an appropriate in bacterio assay to evaluate the cellular effects of these inhibitor hits, the focus of the present study is to establish an in bacterio assay capable of probing and quantifying the impact on CsrA‐regulated cellular mechanisms. We have successfully developed an assay based on a luciferase reporter gene assay, which in combination with a qPCR expression gene assay, allows for the monitoring of expression levels of different downstream targets of CsrA. The chaperone protein CesT was used as a suitable positive control for the assay, and in time‐dependent experiments, we observed a CesT‐mediated increase in bioluminescence over time. By this means, the cellular on‐target effects of non‐bactericidal/non‐bacteriostatic virulence modulating compounds targeting CsrA/RsmA can be evaluated.
Possible role of translation in unfertilized sea urchin eggs
Authors: Yakovlev Konstantin V.
Published: July 2023

Unfertilized eggs of animals contain maternal messenger RNAs (mRNAs) and proteins, which are required for the maintenance of metabolism and regulation of development during the initial stages of embryogenesis. Unfertilized eggs are transcriptionally and translationally quiescent. After fertilization, activated translation of maternal mRNAs is one of the major forces that direct the early stages of embryogenesis before activation of the zygotic genome. However, a low rate and level of protein synthesis have been detected in unfertilized sea urchin eggs indicating that translation is not completely inhibited. Analysis of translatomes of unfertilized eggs and early embryos detected three sets of maternal mRNAs translated either before or after fertilization, or both before and after fertilization. Proteins encoded by maternal mRNAs, which are translated in unfertilized eggs, perform many different functions required for homeostasis, fertilization, egg activation, and early development. This suggests that translation in unfertilized sea urchin eggs may be required to renew the pool of proteins involved in these processes. Thus, translation may be necessary to maintain the fertility and developmental potential of sea urchin eggs during the long‐term storage of eggs in ovaries until spawning begins.
Role of intraoperative touch imprint cytology and immunohistochemistry in the diagnosis of metastatic malignancies in the central nervous system: Cyto‐histomorphological findings and differential diagnosis
Authors: Koyuncuer Ali
Published: July 2023

Background

Brain metastases (BMs) are intracranial neoplasms that are more common in adults than primary brain tumors, causing significant mortality and morbidity in cancer patients. This study aimed to evaluate the definitive histopathological diagnosis using touch imprint cytology and the importance and use of immunohistochemistry in the diagnosis of primary origin.

Method

Cytological, paraffin section, and immunohistochemical study slides of all metastatic brain tumors consecutively consulted at the pathology department between 2018 and 2023 were evaluated. The sensitivity, specificity, and accuracy of patients' diagnostic results who underwent imprint cytology were compared based on the final diagnosis histopathological report.

Results

A total of 45 patients with and without intraoperative consultation were included in the study. The definitive histopathologic diagnosis and the diagnostic accuracy rate of imprint cytology for distinguishing glial and metastatic tumors on paraffin sections was 100%. Immunohistochemistry was performed in all patients (except one patient; immediate exitus) and histological classification of the primary tumor was performed by analysis of clinical findings and biomarkers. The primary origins of metastatic tumors were often lung and breast, with adenocarcinoma subtype histomorphology, cerebral hemispheres, and discrete foci of metastasis.

Conclusion

TPs is a simple and rapid technique that supports diagnosis in intraoperative neuropathology and is a very cost‐effective procedure. The pathologist's experience is the key factor in the diagnosis and reduces the need for a frozen section. In our series, the final histopathologic correlation of imprint cytology in the diagnosis of primary and metastatic tumors is 100%.
IgG N‐glycans are associated with prevalent and incident complications of type 2 diabetes
Authors: Memarian Elham , Heijmans Ralph , Slieker Roderick C. , Sierra Adriana , Gornik Olga , Beulens Joline W. J. , Hanic Maja , Elders Petra , Pascual Julio , Sijbrands Eric , Lauc Gordan , Dotz Viktoria , Barrios Clara , ’t Hart Leen M. , Wuhrer Manfred , van Hoek Mandy
Published: July 2023

Aims/Hypothesis

Inflammation is important in the development of type 2 diabetes complications. The N‐glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N‐glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N‐glycosylation of IgG may be related to the development of complications of type 2 diabetes.

Methods

In three independent type 2 diabetes cohorts, plasma IgG N‐glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N‐glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox‐ and logistic regression, followed by meta‐analyses. The models were adjusted for age and sex and additionally for clinical risk factors.

Results

IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex.

Conclusions

We showed that IgG N‐glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro‐ and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N‐glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.
Demographic responses of hybridizing cinquefoils to changing climate in the Colorado Rocky Mountains
Authors: Carscadden Kelly A. , Doak Daniel F. , Oldfather Meagan F. , Emery Nancy C.
Published: July 2023

Hybridization between taxa generates new pools of genetic variation that can lead to different environmental responses and demographic trajectories over time than seen in parental lineages. The potential for hybrids to have novel environmental tolerances may be increasingly important in mountainous regions, which are rapidly warming and drying due to climate change. Demographic analysis makes it possible to quantify within‐ and among‐species responses to variation in climate and to predict population growth rates as those conditions change. We estimated vital rates and population growth in 13 natural populations of two cinquefoil taxa (Potentilla hippiana and P. pulcherrima) and their hybrid across elevation gradients in the Southern Rockies. Using three consecutive years of environmental and demographic data, we compared the demographic responses of hybrid and parental taxa to environmental variation across space and time. All three taxa had lower predicted population growth rates under warm, dry conditions. However, the magnitude of these responses varied among taxa and populations. Hybrids had consistently lower predicted population growth rates than P. hippiana. In contrast, hybrid performance relative to P. pulcherrima varied with population and climate, with the hybrid maintaining relatively stable growth rates while populations of P. pulcherrima shrank under warm, dry conditions. Our findings demonstrate that hybrids in this system are neither intrinsically unfit nor universally more vigorous than parents, suggesting that the demographic consequences of hybridization are context‐dependent. Our results also imply that shifts to warmer and drier conditions could have particularly negative repercussions for P. pulcherrima, which is currently the most abundant taxon in the study area, possibly as a legacy of more favorable historical climates. More broadly, the distributions of these long‐lived taxa are lagging behind their demographic trajectories, such that the currently less common P. hippiana could become the most abundant of the Potentilla taxa as this region continues to warm and dry.
Long‐distance gene flow in Acacia senegal: Hope for disturbed and fragmented populations
Authors: Omondi Stephen F. , Githae Eunice W. , Khasa Damase P.
Published: July 2023

Even though pollen and seed dispersals are some of the important factors that determine tree species survival across landscapes, gene dispersal data of important tropical dryland tree species such as Acacia senegal that are undergoing various population disturbances remain scarce. Understanding patterns of gene dispersal in these ecosystems is important for conservation, landscape restoration and tree improvement. We investigated pollen and seed mediated gene flow in two A. senegal populations of contrasting state (less disturbed and heavily disturbed) using nine microsatellites and 128 genotyping‐by‐sequencing single nucleotide polymorphism (SNPs) multilocus genotypes of two growth stages (juvenile and adult trees) and their spatial locations. We performed parentage assignments using likelihood approach and undertook spatial genetic structure (SGS) analyses for the two growth stages through correlation among kinship coefficients and geographical distances between pair of individuals. The SNPs showed higher resolving power and assignment rates than microsatellites; however, a combination of the two marker‐types improved the assignment rate and provided robust parentage assessments. We found evidence of long‐distance (up to 210 m) pollination events for both populations; however, the majority of seed dispersal was found closer to the putative maternal parent. On average, parentage analysis showed high amounts of pollen (40%) and seed (20%) immigration in both populations. Significant positive SGS was found only for the adult cohorts in the less disturbed population for distance classes 20 and 40 m, indicating historical short‐distance seed dispersals. Our results suggest long‐distance gene flow within the species and we recommend conservation of remnant and isolated populations or individual trees to promote genetic connectivity.
Strong Interaction Between Redox Mediators and Defect‐Rich Carbons Enabling Simultaneously Boosted Voltage Windows and Capacitance for Aqueous Supercapacitors
Authors: Guan Lu , Zhu Yifan , Wan Yi , Zhang Mengdi , Li Qiang , Teng Xiaoling , Zhang Yunlong , Yang Hao , Zhang Yan , Hu Han , Wu Mingbo
Published: July 2023

Energy density, the Achilles' heel of aqueous supercapacitors, is simultaneously determined by the voltage window and specific capacitance of the carbon materials, but the strategy of synchronously boosting them has rarely been reported. Herein, we demonstrate that the rational utilization of the interaction between redox mediators (RMs) and carbon electrode materials, especially those with rich intrinsic defects, contributes to extended potential windows and more stored charges concurrently. Using 4‐hydroxy‐2,2,6,6‐tetramethylpiperidinyloxyl (4OH‐TEMPO) and intrinsic defect‐rich carbons as the RMs and electrode materials, respectively, the potential window and capacitance are increased by 67% and sixfold in a neutral electrolyte. Moreover, this strategy could also be applied to alkaline and acid electrolytes. The first‐principle calculation and experimental results demonstrate that the strong interaction between 4OH‐TEMPO and defect‐rich carbons plays a key role as preferential adsorbed RMs may largely prohibit the contact of free water molecules with the electrode materials to terminate the water splitting at elevated potentials. For the RMs offering weaker interaction with the electrode materials, the water splitting still proceeds with a thus sole increase of the stored charges. The results discovered in this work could provide an alternative solution to address the low energy density of aqueous supercapacitors.