bluuebunny/crossref_metadata_2025 huggingface dataset:
Sclerostin small-molecule inhibitors promote osteogenesis by activating canonical Wnt and BMP pathways
Authors: Sangadala Sreedhara , Kim Chi Heon , Fernandes Lorenzo M , Makkar Pooja , Beck George R , Boden Scott D , Drissi Hicham , Presciutti Steven M
Published: August 2023

Background:

The clinical healing environment after a posterior spinal arthrodesis surgery is one of the most clinically challenging bone-healing environments across all orthopedic interventions due to the absence of a contained space and the need to form de novo bone. Our group has previously reported that sclerostin in expressed locally at high levels throughout a developing spinal fusion. However, the role of sclerostin in controlling bone fusion remains to be established.

Methods:

We computationally identified two FDA-approved drugs, as well as a single novel small-molecule drug, for their ability to disrupt the interaction between sclerostin and its receptor, LRP5/6. The drugs were tested in several in vitro biochemical assays using murine MC3T3 and MSCs, assessing their ability to (1) enhance canonical Wnt signaling, (2) promote the accumulation of the active (non-phosphorylated) form of β-catenin, and (3) enhance the intensity and signaling duration of BMP signaling. These drugs were then tested subcutaneously in rats as standalone osteoinductive agents on plain collagen sponges. Finally, the top drug candidates (called VA1 and C07) were tested in a rabbit posterolateral spine fusion model for their ability to achieve a successful fusion at 6 wk.

Results:

We show that by controlling GSK3b phosphorylation our three small-molecule inhibitors (SMIs) simultaneously enhance canonical Wnt signaling and potentiate canonical BMP signaling intensity and duration. We also demonstrate that the SMIs produce dose-dependent ectopic mineralization in vivo in rats as well as significantly increase posterolateral spine fusion rates in rabbits in vivo, both as standalone osteogenic drugs and in combination with autologous iliac crest bone graft.

Conclusions:

Few if any osteogenic small molecules possess the osteoinductive potency of BMP itself – that is, the ability to form de novo ectopic bone as a standalone agent. Herein, we describe two such SMIs that have this unique ability and were shown to induce de novo bone in a stringent in vivo environment. These SMIs may have the potential to be used in novel, cost-effective bone graft substitutes for either achieving spinal fusion or in the healing of critical-sized fracture defects.

Funding:

This work was supported by a Veteran Affairs Career Development Award (IK2-BX003845).
Effects of smoking on genome-wide DNA methylation profiles: A study of discordant and concordant monozygotic twin pairs
Authors: van Dongen Jenny , Willemsen Gonneke ,   BIOS Consortium, de Geus Eco JC , Boomsma Dorret I , Neale Michael C
Published: August 2023

Background:

Smoking-associated DNA methylation levels identified through epigenome-wide association studies (EWASs) are generally ascribed to smoking-reactive mechanisms, but the contribution of a shared genetic predisposition to smoking and DNA methylation levels is typically not accounted for.

Methods:

We exploited a strong within-family design, that is, the discordant monozygotic twin design, to study reactiveness of DNA methylation in blood cells to smoking and reversibility of methylation patterns upon quitting smoking. Illumina HumanMethylation450 BeadChip data were available for 769 monozygotic twin pairs (mean age = 36 years, range = 18–78, 70% female), including pairs discordant or concordant for current or former smoking.

Results:

In pairs discordant for current smoking, 13 differentially methylated CpGs were found between current smoking twins and their genetically identical co-twin who never smoked. Top sites include multiple CpGs in CACNA1D and GNG12, which encode subunits of a calcium voltage-gated channel and G protein, respectively. These proteins interact with the nicotinic acetylcholine receptor, suggesting that methylation levels at these CpGs might be reactive to nicotine exposure. All 13 CpGs have been previously associated with smoking in unrelated individuals and data from monozygotic pairs discordant for former smoking indicated that methylation patterns are to a large extent reversible upon smoking cessation. We further showed that differences in smoking level exposure for monozygotic twins who are both current smokers but differ in the number of cigarettes they smoke are reflected in their DNA methylation profiles.

Conclusions:

In conclusion, by analysing data from monozygotic twins, we robustly demonstrate that DNA methylation level in human blood cells is reactive to cigarette smoking.

Funding:

We acknowledge funding from the National Institute on Drug Abuse grant DA049867, the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI-NL, NWO 184.033.111) and the BBRMI-NL-financed BIOS Consortium (NWO 184.021.007), NWO Large Scale infrastructures X-Omics (184.034.019), Genotype/phenotype database for behaviour genetic and genetic epidemiological studies (ZonMw Middelgroot 911-09-032); Netherlands Twin Registry Repository: researching the interplay between genome and environment (NWO-Groot 480-15-001/674); the Avera Institute, Sioux Falls (USA), and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); epigenetic data were generated at the Human Genomics Facility (HuGe-F) at ErasmusMC Rotterdam. Cotinine assaying was sponsored by the Neuroscience Campus Amsterdam. DIB acknowledges the Royal Netherlands Academy of Science Professor Award (PAH/6635).
lncRNA read-through regulates the BX-C insulator Fub-1
Authors: Ibragimov Airat , Bing Xin Yang , Shidlovskii Yulii V , Levine Michael , Georgiev Pavel , Schedl Paul
Published: August 2023

Though long non-coding RNAs (lncRNAs) represent a substantial fraction of the Pol II transcripts in multicellular animals, only a few have known functions. Here we report that the blocking activity of the Bithorax complex (BX-C) Fub-1 boundary is segmentally regulated by its own lncRNA. The Fub-1 boundary is located between the Ultrabithorax (Ubx) gene and the bxd/pbx regulatory domain, which is responsible for regulating Ubx expression in parasegment PS6/segment A1. Fub-1 consists of two hypersensitive sites, HS1 and HS2. HS1 is an insulator while HS2 functions primarily as an lncRNA promoter. To activate Ubx expression in PS6/A1, enhancers in the bxd/pbx domain must be able to bypass Fub-1 blocking activity. We show that the expression of the Fub-1 lncRNAs in PS6/A1 from the HS2 promoter inactivates Fub-1 insulating activity. Inactivation is due to read-through as the HS2 promoter must be directed toward HS1 to disrupt blocking.
Understanding disruptions in cancer care to reduce increased cancer burden
Authors: Davis Kia L , Ackermann Nicole , Klesges Lisa M , Leahy Nora , Walsh-Bailey Callie , Humble Sarah , Drake Bettina , Sanders Thompson Vetta L
Published: August 2023

Background:

This study seeks to understand how and for whom COVID-19 disrupted cancer care to understand the potential for cancer health disparities across the cancer prevention and control continuum.

Methods:

In this cross-sectional study, participants age 30+residing in an 82-county region in Missouri and Illinois completed an online survey from June-August 2020. Descriptive statistics were calculated for all variables separately and by care disruption status. Logistic regression modeling was conducted to determine the correlates of care disruption.

Results:

Participants (N=680) reported 21% to 57% of cancer screening or treatment appointments were canceled/postponed from March 2020 through the end of 2020. Approximately 34% of residents stated they would need to know if their doctor’s office is taking the appropriate COVID-related safety precautions to return to care. Higher education (OR = 1.26, 95% CI:1.11–1.43), identifying as female (OR = 1.60, 95% CI:1.12–2.30), experiencing more discrimination in healthcare settings (OR = 1.40, 95% CI:1.13–1.72), and having scheduled a telehealth appointment (OR = 1.51, 95% CI:1.07–2.15) were associated with higher odds of care disruption. Factors associated with care disruption were not consistent across races. Higher odds of care disruption for White residents were associated with higher education, female identity, older age, and having scheduled a telehealth appointment, while higher odds of care disruption for Black residents were associated only with higher education.

Conclusions:

This study provides an understanding of the factors associated with cancer care disruption and what patients need to return to care. Results may inform outreach and engagement strategies to reduce delayed cancer screenings and encourage returning to cancer care.

Funding:

This study was supported by the National Cancer Institute’s Administrative Supplements for P30 Cancer Center Support Grants (P30CA091842-18S2 and P30CA091842-19S4). Kia L. Davis, Lisa Klesges, Sarah Humble, and Bettina Drake were supported by the National Cancer Institute’s P50CA244431 and Kia L. Davis was also supported by the Breast Cancer Research Foundation. Callie Walsh-Bailey was supported by NIMHD T37 MD014218. The content does not necessarily represent the official view of these funding agencies and is solely the responsibility of the authors.
Spatial–temporal order–disorder transition in angiogenic NOTCH signaling controls cell fate specification
Authors: Kang Tae-Yun , Bocci Federico , Nie Qing , Onuchic José N , Levchenko Andre
Published: August 2023

Angiogenesis is a morphogenic process resulting in the formation of new blood vessels from pre-existing ones, usually in hypoxic micro-environments. The initial steps of angiogenesis depend on robust differentiation of oligopotent endothelial cells into the Tip and Stalk phenotypic cell fates, controlled by NOTCH-dependent cell–cell communication. The dynamics of spatial patterning of this cell fate specification are only partially understood. Here, by combining a controlled experimental angiogenesis model with mathematical and computational analyses, we find that the regular spatial Tip–Stalk cell patterning can undergo an order–disorder transition at a relatively high input level of a pro-angiogenic factor VEGF. The resulting differentiation is robust but temporally unstable for most cells, with only a subset of presumptive Tip cells leading sprout extensions. We further find that sprouts form in a manner maximizing their mutual distance, consistent with a Turing-like model that may depend on local enrichment and depletion of fibronectin. Together, our data suggest that NOTCH signaling mediates a robust way of cell differentiation enabling but not instructing subsequent steps in angiogenic morphogenesis, which may require additional cues and self-organization mechanisms. This analysis can assist in further understanding of cell plasticity underlying angiogenesis and other complex morphogenic processes.
Finding structure during incremental speech comprehension
Authors: Lyu Bingjiang , Marslen-Wilson William D , Fang Yuxing , Tyler Lorraine K
Published: August 2023

A core aspect of human speech comprehension is the ability to incrementally integrate consecutive words into a structured and coherent interpretation, aligning with the speaker’s intended meaning. This rapid process is subject to multidimensional probabilistic constraints, including both linguistic knowledge and non-linguistic information within specific contexts, and it is their interpretative coherence that drives successful comprehension. To study the neural substrates of this process, we extract word-by-word measures of sentential structure from BERT, a deep language model, which effectively approximates the coherent outcomes of the dynamic interplay among various types of constraints. Using representational similarity analysis, we tested BERT parse depths and relevant corpus-based measures against the spatiotemporally resolved brain activity recorded by electro-/magnetoencephalography when participants were listening to the same sentences. Our results provide a detailed picture of the neurobiological processes involved in the incremental construction of structured interpretations. These findings show when and where coherent interpretations emerge through the evaluation and integration of multifaceted constraints in the brain, which engages bilateral brain regions extending beyond the classical fronto-temporal language system. Furthermore, this study provides empirical evidence supporting the use of artificial neural networks as computational models for revealing the neural dynamics underpinning complex cognitive processes in the brain.
Mechanical coupling coordinates microtubule growth
Authors: Leeds Bonnibelle K , Kostello Katelyn F , Liu Yuna Y , Nelson Christian R , Biggins Sue , Asbury Charles L
Published: August 2023

During mitosis, kinetochore-attached microtubules form bundles (k-fibers) in which many filaments grow and shorten in near-perfect unison to align and segregate each chromosome. However, individual microtubules grow at intrinsically variable rates, which must be tightly regulated for a k-fiber to behave as a single unit. This exquisite coordination might be achieved biochemically, via selective binding of polymerases and depolymerases, or mechanically, because k-fiber microtubules are coupled through a shared load that influences their growth. Here, we use a novel dual laser trap assay to show that microtubule pairs growing in vitro are coordinated by mechanical coupling. Kinetic analyses show that microtubule growth is interrupted by stochastic, force-dependent pauses and indicate persistent heterogeneity in growth speed during non-pauses. A simple model incorporating both force-dependent pausing and persistent growth speed heterogeneity explains the measured coordination of microtubule pairs without any free fit parameters. Our findings illustrate how microtubule growth may be synchronized during mitosis and provide a basis for modeling k-fiber bundles with three or more microtubules, as found in many eukaryotes.
Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states
Authors: Yao Junjun , Dai Shaoxing , Zhu Ran , Tan Ju , Zhao Qiancheng , Yin Yu , Sun Jiansen , Du Xuewei , Ge Longjiao , Xu Jianhua , Hou Chunli , Li Nan , Li Jun , Ji Weizhi , Zhu Chuhong , Zhang Runrui , Li Tianqing
Published: August 2023

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.
The effects of trunk kinematics and EMG activity of wheelchair racing T54 athletes on wheelchair propulsion speeds
Authors: Guo Wei , Liu Qian , Huang Peng , Wang Dan , Shi Lin , Han Dong
Published: August 2023

Background

The purpose of this study is to examine the impact of trunk kinematic characteristics and trunk muscle electromyography (EMG) activity on propulsion speeds in wheelchair racing T54 athletes.

Method

The Vicon infrared high-speed 3D motion capture system was utilized to acquire kinematic data of the shoulders, elbows, wrists, and trunk from twelve T54 athletes at four different speeds (5.55 m/s, 6.94 m/s, 8.33 m/s, and personal maximum speed). Additionally, the Trigno Wireless EMG system was employed to collect synchronous surface electromyography (EMG) data from the rectus abdominis and erector spinae muscles. The kinematics and EMG data of the trunk were compared across various wheelchair propulsion speeds while also examining the correlation coefficient between wheelchair propulsion speeds and: (1) the range of motion of upper limb joints as well as the trunk; (2) the maximum angular velocities of the upper limbs joints as well as the trunk; and (3) rectus abdominis and erector spinae EMG activity. Two multiple linear stepwise regression models were utilized to examine the impact of variables that had been identified as significant through correlation coefficient tests (1) and (2) on propulsion speed, respectively.

Results

There were significant differences in the range of motion (p<0.01) and angular velocity (p<0.01) of the athlete’s trunk between different propulsion speeds. The range of motion (p<0.01,r = 0.725) and angular speed (p<0.01,r = 0.882) of the trunk showed a stronger correlation with propulsion speed than did upper limb joint movements. The multiple linear stepwise regression model revealed that the standardizedβvalues of trunk motion range and angular velocity in athletes were greater than those of other independent variables in both models. In terms of the EMG variables, four of six variables from the rectus abdominis showed differences at different speeds (p<0.01), one of six variables from the erector spinae showed differences at different speeds (p<0.01). All six variables derived from the rectus abdominis exhibited a significant correlation with propulsion speed (p<0.05,r>0.3), while one variable derived from the erector spinae was found to be significantly correlated with propulsion speed (p<0.01,r = 0.551).

Conclusion

The movement of the trunk plays a pivotal role in determining the propulsion speed of wheelchair racing T54 athletes. Athletes are advised to utilize trunk movements to enhance their wheelchair’s propulsion speed while also being mindful of the potential negative impact on sports performance resulting from excessive trunk elevation. The findings of this study indicate that it would be beneficial for wheelchair racing T54 athletes to incorporate trunk strength training into their overall strength training regimen, with a specific emphasis on enhancing the flexion and extension muscles of the trunk.
Transmissão geracional de mulheres na agricultura familiar e pesca artesanal
Authors: Monteiro Elideth Pacheco , Dos Santos Marcos Antônio Souza , Martins Cyntia Meireles , Brabo Marcos Ferreira , De Araújo Janayna Galvão , Lopes Maria Lúcia Bahia
Published: August 2023

A renovação geracional é uma questão relevante no contexto do futuro da agricultura familiar e pesca artesanal, pois está relacionada com a migração rural e juvenil, e o envelhecimento da população rural. Compreender os fatores por trás da disposição de sucessores em potencial de assumir o controle da entidade familiar é crucial para a continuidade das atividades agropecuárias. Nesse contexto, o estudo tem por objetivo identificar os diversos pontos de vista das filhas de agricultores e pescadores, sobre a possibilidade de assumir o controle das atividades rurais realizadas por seus pais nos municípios de Bragança, Viseu e Augusto Corrêa, no estado do Pará. Os dados foram coletados por meio de uma dinâmica presencial, similar a um jogo de tabuleiro, elaborado a partir de diretrizes da Q-Methodology e de entrevista semiestruturada com 60 filhas destes profissionais, sendo 20 em cada município, sobre os fatores que afetam a possibilidade das mulheres de continuarem os negócios da família. Sete principais pontos de vista foram identificados: condições de trabalho, condições de vida, atratividade de socialização, apoio familiar, organizações associativas, amparo institucional e atratividade do meio rural; e autonomia financeira. Os resultados sugerem que existem diferentes pontos de vista que precisam ser considerados ao se avaliar a probabilidade de sucessão nas comunidades rurais. Esses diferentes pontos de vista devem ser empregados por formuladores de políticas para ajustar os princípios atuais e desenvolver programas para encorajar essas mulheres a assumirem o controle das atividades, buscando sua permanência nas zonas rurais.
Análises do Balanço Patrimonial da cidade de São Paulo (2021-2022) com suporte da Teoria da Divulgação
Authors: Da Silva Maurício Corrêa
Published: August 2023

A adoção de uma nova contabilidade pública teve como um dos objetivos proporcionar transparência e de melhorar a divulgação das demonstrações contábeis e fiscais do setor público brasileiro. Os grupos de contas que compõem o Balanço Patrimonial foram alterados e ficaram parecidos com os do setor privado. Esta investigação tem o objetivo de evidenciar se existem inconsistências contábeis no Balanço Patrimonial da cidade 2de São Paulo, nos anos de 2022 e 2021, com o suporte da Teoria da Divulgação. A Teoria da Divulgação apresenta questionamentos que a divulgação de maior qualidade é eficiente na medida em que leva a uma redução no componente da assimetria da informação, sendo considerada como interessante na luz que lança sobre como interpretar o silêncio, ou seja, na falta de informação. Os dados foram extraídos do Portal de Transparência da cidade São Paulo e da Secretaria do Tesouro Nacional (STN) – Sistema de Informações Contábeis e Fiscais do Setor Público Brasileiro - SICONFI e Visão Integrada das Dívidas da União, dos Estados, do Distrito Federal e dos Municípios. Foi utilizado o método indutivo. Os resultados revelaram que existem inconsistências contábeis na identificação do indicador do superávit financeiro e na verificação das dívidas flutuantes, consolidadas e não integrantes com as registradas no Passivo (endividamento total da entidade). Os achados sinalizam que existe a necessidade de uma revisão da forma de realizar os registros patrimoniais com base no Plano de Contas Aplicado ao Setor Público (PCASP) em contas do Ativo e Passivo Financeiro e Permanente, bem como das contas representativas das dívidas flutuantes, consolidadas e valores não integrantes da dívida consolidada. Além de avançar na literatura contábil aplicada ao setor público brasileiro com as contribuições de como realizar as análises, o estudo contribui do ponto de vista social para minimizar a assimetria informacional e serve como controle social.
Aplicação da inteligência artificial na prevenção de acidentes de trabalho: uma revisão sistemática de literatura
Authors: Da Silva Alexandre Pinto , Dutra Frederico Giffoni de Carvalho , Corrêa Fábio , Ribeiro Jurema Suely de Araújo Nery
Published: August 2023

Os acidentes de trabalho representam um problema não só no Brasil, mas também em todo o mundo. A Organização Internacional do Trabalho estima que 2 milhões de pessoas morrem no mundo a cada ano de causas relacionadas ao trabalho. Empresas, governos e trabalhadores estão sempre em busca de medidas para a prevenção dos riscos nos ambientes laborais. Esta pesquisa apresenta uma revisão sistemática de literatura, com o objetivo de identificar quais as principais publicações internacionais que abordam a aplicação da IA na segurança do trabalho, com o foco na prevenção de acidentes. Após a elaboração do protocolo de pesquisa, e realização de busca nas bases Emerald Insight, IEEE Xplore, Science Direct, Scopus e Web of Science foram encontrados 2.369 artigos que, após a aplicação dos critérios de exclusão, foram selecionados 31 artigos ligados diretamente à temática. Os países com mais pesquisas foram China, EUA e Coreia do Sul, com cerca de 50% do total. Em relação ao tipo de IA utilizada nas pesquisas, 65% usam Deep Learning, enquanto Machine Learning foi usado por 35%. Ficou evidenciado que a IA aplicada a segurança do trabalho ainda é pouco explorada, havendo um bom aumento a partir de 2022.
A review of the taxonomy and distribution of Australia’s endemic Calyptorhynchinae black cockatoos
Authors: Saunders Denis A , Pickup Geoffrey
Published: August 2023

Our review of the taxonomy of Australia’s endemic Calyptorhynchinae black cockatoos based on morphology, ecology, biology, vocalisations, distributions, and genetic studies concluded that they constitute two genera; those with red subterminal tail bands in the genus Calyptorhynchus Desmarest, 1826 and those with white or yellow subterminal tail bands in the genus Zanda Mathews, 1913. We also concluded that the genus Calyptorhynchus is made up of six monotypic species: Northern Red-tailed Cockatoo C. banksii Latham, 1790; South-eastern Red-tailed Cockatoo C. graptogyne Schodde, Saunders and Homberger, 1988; Forest Red-tailed Cockatoo C. naso Gould, 1837; Inland Red-tailed Cockatoo C. samueli Mathews, 1917; Western Red-tailed Cockatoo C. escondidus Ewart, Joseph and Schodde, 2020; and Glossy Cockatoo C. lathami Temminck, 1807. Formerly, the five red-tailed taxa were regarded as subspecies and the Glossy Cockatoo consisted of three subspecies. In addition, we concluded that the genus Zanda is made up of five monotypic species: two with white subterminal tail bands, Baudin’s Cockatoo Z. baudinii Lear, 1832 and Carnaby’s Cockatoo Z. latirostris Carnaby, 1948; and three with yellow subterminal tail bands, Eastern Yellow-tailed Cockatoo Z. funerea Shaw, 1794, Western Yellow-tailed Cockatoo Z. whiteae Mathews, 1912, and Tasmanian Yellow-tailed Cockatoo Z. xanthanota Gould, 1838. Formerly, the three yellow-tailed taxa were regarded as subspecies. As all cockatoos with coloured subterminal tail bands are black, we recommend deleting the word black from their common names.
Chairux Algorithm for Divisibility Test
Authors: Mwangi Charles Irungu , Ouma Moses Otieno
Published: August 2023

This paper presents a novel Chairux Algorithm for the divisibility test. The test is based on an arbitrary integer via the concepts of Bezout’s identity and the Euclidean algorithm. Examples demonstrating the effectiveness of the proposed algorithm indicate its simplicity, efficiency, and flexibility compared to the existing state-of-the-art algorithms.
Effect of Nitrogen and Foliar Spray of Urea and Nano Urea on Growth and Yield of Rabi Maize (Zea mays L.)
Authors: Srivastava Avantika , Singh Rajesh
Published: August 2023

A field experiment was conducted during Rabi 2022 at Crop Research Farm, Department of Agronomy, SHUATS, Prayagraj (U.P) to study the “Effect of nitrogen and foliar spray of urea and nano urea on growth and yield of rabi maize (Zea mays L.)”, to study treatments consisting of three levels of Nitrogen viz. 50% RDN, 75% RDN and 100% RDN and three foliar sprays of nano urea viz. 2000 ppm (2ml/L), 4000ppm (4ml/L), and foliar spray of urea viz.,  20000 ppm (2%). The soil of experimental plot was sandy loam in texture, nearly neutral in soil reaction (pH 7.1), low in organic carbon (0.28 %), available N (225 kg/ha), available P (19.50 kg/ha) and available K (92 kg/ha). There were 10 treatments each being replicated thrice and laid out in Randomized Block Design. The results revealed that at 60 DAS, treatment combination 100% RDN + 4000 PPM (4ml/L) spray of Nano Urea recorded significantly higher Plant Height (108.10cm), Plant Dry weight (61.20 g), Crop Growth Rate (14.67 g/m2/day), number of cobs per plant (1.60), number of grains per cob (249.67), Seed index (23.55 g), Grain yield (6.41 t/ha), Stover yield (8.65 t/ha) and Harvest Index (42.58 %) as compared to other treatments.
Epidemiology of Candida Species Colonizing Mucosae of HIV-Infected Patients in Two Healthcare Centers of Cameroon During 2018-2020
Authors: Kountchou Cyrille Levis , Iwewe Yves Somo , Kamdem Diane Estelle Modjo , Itor Ekpo Alfred , Dzoyem Jean Paul
Published: August 2023

Aims: This study aimed to investigate Candida species colonizing HIV-infected patients in Bafoussam and Yaounde in Cameroon.

Study Design: Cross-sectional study.

Place and Duration of Study: Yaoundé Central Hospital (YCH) and Bafoussam Regional Hospital (BRH) between October 2018 and December 2020.

Methodology: We included 804 HIV-infected (681 women; 123 men; age range 21-81 years). Vaginal discharge, oral swab, stools, and urine were collected, and mycological diagnosis including direct macroscopic and microscopic analyses, culture on Sabouraud chloramphenicol medium, culture on chromogenic medium, germ tube test, evidence of chlamydospores production, biochemical analysis was performed. Yeast isolates were identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS).

Results: Eight hundred and four patients were recruited, and 2754 samples were collected. The colonization frequency was 17.35%, and 513 yeasts were isolated. Overall, Candida albicans 251 (48.92%) was the most frequently isolated. Non-albicans Candida (NAC) isolates have been classified into 16 species, including Candida krusei (14.23%), Candida glabrata (9.94%), Candida parapsilosis (8.18%), and Candida tropicalis (7.99%) as the major ones. There was a relationship (P-value= 0.00) between antiretroviral therapy and Candida species colonization.

Conclusion: The results provide information on the epidemiology of Candida species in HIV-infected patients in Cameroon.
Knowledge, Attitude, and Perception of Nigerians Towards Herbal Contraception: A Questionnaire- Based Study
Authors: Judith John Eloyi , Simisola Oloye Temidayo , Kokonne Ekere , Isaac Ajeh Johnson , Abdullahi Rashida , Olubunmi Olayemi , Sunday Ndiana-Abasi , Yetunde Isimi Christianah , Martins Emeje Ochubiojo
Published: August 2023

Aims: With a population of about 222 million, which is expected to rise to 377 million making Nigeria the 3rd largest country in the world by 2050, a well-planned family will improve the quality of life of mother and child.

Methodology: A non-probability online survey was conducted (October 2021 and November 2021), recruiting 1113 participants across Nigeria. Socio-demographic data and information on contraceptives were obtained, and Pearson’s chi-squared test of independence at a 95% confidence interval (CI) was computed using R 4.2.1.

Results: Significant associations (P < .001) were found between age, marital status, education, and profession of respondents. About 44.65% were 15-29 years, while 41.2% were 30-34 years. No significant association was observed between the age group, gender, and the need for population control. Females (50.04%), 15-29 years old (66.48%) are more likely to approve of the need for population control. Likewise, females (22.01%), with tertiary education (18.78%) are well-informed about contraceptive use (P < .001). Only 19.38% (n = 184; P < .001) of participants used herbal contraceptives, in the form of liquid mixtures (55.98%), teas (17.93%), pills (12.50%), and powders (10.87%), with 26.63% > 7.61% > 6.52% > 5.98% = 5.98% = 5.98% > 4.89% > 3.80% who took Moringa, Alligator Pepper, Neem Plant, Castor Beans, African Star apple Momordica, Rosary Pea, and Horse-eye Bean respectively as contraceptives. Aged parents (32.07%), friends (31.52%), doctors (15.76%), herbalists (5.98%), pharmacists (5.43%), and nurses (3.80%) played a significant (P < .001) role in recommending these herbs. Furthermore, 76.37% recommended the development of indigenous herbal contraceptives in Nigeria, while 23.63% did not.

Conclusion: Although participants have expressed a preference for herbal contraceptives, knowledge of them is lacking, which calls for more awareness campaigns and policy formulations for their promotion, development, and adoption in Nigeria.
Five-Year Trajectories of Prescription Opioid Use
Authors: Gisev Natasa , Buizen Luke , Hopkins Ria E. , Schaffer Andrea L. , Daniels Benjamin , Bharat Chrianna , Dobbins Timothy , Larney Sarah , Blyth Fiona , Currow David C. , Wilson Andrew , Pearson Sallie-Anne , Degenhardt Louisa
Published: August 2023

Importance

There are known risks of using opioids for extended periods. However, less is known about the long-term trajectories of opioid use following initiation.

Objective

To identify 5-year trajectories of prescription opioid use, and to examine the characteristics of each trajectory group.

Design, Setting, and Participants

This population-based cohort study conducted in New South Wales, Australia, linked national pharmaceutical claims data to 10 national and state data sets to determine sociodemographic characteristics, clinical characteristics, drug use, and health services use. The cohort included adult residents (aged ≥18 years) of New South Wales who initiated a prescription opioid between July 1, 2003, and December 31, 2018. Statistical analyses were conducted from February to September 2022.

Exposure

Dispensing of a prescription opioid, with no evidence of opioid dispensing in the preceding 365 days, identified from pharmaceutical claims data.

Main Outcomes and Measures

The main outcome was the trajectories of monthly opioid use over 60 months from opioid initiation. Group-based trajectory modeling was used to classify these trajectories. Linked health care data sets were used to examine characteristics of individuals in different trajectory groups.

Results

Among 3 474 490 individuals who initiated a prescription opioid (1 831 230 females [52.7%]; mean [SD] age, 49.7 [19.3] years), 5 trajectories of long-term opioid use were identified: very low use (75.4%), low use (16.6%), moderate decreasing to low use (2.6%), low increasing to moderate use (2.6%), and sustained use (2.8%). Compared with individuals in the very low use trajectory group, those in the sustained use trajectory group were older (age ≥65 years: 22.0% vs 58.4%); had more comorbidities, including cancer (4.1% vs 22.2%); had increased health services contact, including hospital admissions (36.9% vs 51.6%); had higher use of psychotropic (16.4% vs 42.4%) and other analgesic drugs (22.9% vs 47.3%) prior to opioid initiation, and were initiated on stronger opioids (20.0% vs 50.2%).

Conclusions and relevance

Results of this cohort study suggest that most individuals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period. The small proportion of individuals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these individuals.
Final 5-Year Follow-Up Results Evaluating Neoadjuvant Talimogene Laherparepvec Plus Surgery in Advanced Melanoma
Authors: Dummer Reinhard , Gyorki David E. , Hyngstrom John R. , Ning Meng , Lawrence Tatiana , Ross Merrick I.
Published: August 2023

This randomized clinical trial presents the final 5-year follow-up results of neoadjuvant talimogene laherparepvec (T-VEC) plus surgery in patients with advanced melanoma.
Non‐Zero and Open‐Loop Current–Voltage Characteristics in Electronic Memory Devices
Authors: Paul Febin , Nama Manjunatha Krishna , Paul Shashi
Published: August 2023

This work focuses on the non‐zero‐crossing and open‐loop current–voltage (I–V) characteristics of electronic memory devices that are studied and focused on primarily for non‐volatile memory storage applications. Gold nanoparticles‐based devices are fabricated to understand possible non‐crossing zero and open‐loop current–voltage behavior, where a non‐zero current and open loop I–V characteristics are observed at zero voltage. While other studies have attributed this behavior as a “battery effect”, this study presents an alternate perspective for non‐redox‐based charge storage memory devices. The electrical measurements clearly demonstrate that the non‐zero current and open‐loop characteristics are due to the charge trapping of the gold nanoparticles. The charge accumulation within the nanoparticle is observed to create a non‐zero potential within the device and thereby encouraging such behavior, even though the applied external voltage is zero. The longstanding mystery in deciphering if electrical measurements or the charge storage device contributes toward non‐zero property is unfurled in this article. A possible charge storage model is proposed and further verified using liquid crystals‐based two terminal devices. The presence of internal potential leads to an offset within the devices, a non‐zero current and open‐loop I–V even when the external applied voltage is zero.
Artificial intelligence and the impact on medical genetics
Authors: Solomon Benjamin D. , Chung Wendy K.
Published: August 2023

Virtually all areas of biomedicine will be increasingly affected by applications of artificial intelligence (AI). We discuss how AI may affect fields of medical genetics, including both clinicians and laboratorians. In addition to reviewing the anticipated impact, we provide recommendations for ways in which these groups may want to evolve in light of the influence of AI. We also briefly discuss how educational and training programs can play a key role in preparing the future workforce given these anticipated changes.
Synthesis, structural characterization, and in vitro biological activity studies of ternary metal complexes of 1,10‐phenanthroline and the anti‐inflammatory bromhexine drug
Authors: Mahmoud Nessma F. , Omar Norhan R. S. , Mohamed Gehad G. , Sayed Fatma N.
Published: August 2023

The medication bromhexine (BHX) is well‐known for its unique properties and therapeutic advantages, with prospective uses in the prevention and treatment of cancer growth and bacterial infections. The current research describes the synthesis of a unique series of mixed ligand complexes of Cr(III), Fe(III), Ni(II), Mn(II), Cu(II), Co(II), Zn(II), and Cd(II) produced from BHX (1ry ligand) and 1,10‐phenanthroline (Phen; 2ry ligand) and distinguished by spectral. The two ligands' potential for coordination with metal ions has been suggested in view of chemical analysis and spectral (1H‐nuclear magnetic resonance, ultraviolet–visible, and mass spectrometry) and thermal studies. BHX and Phen are neutrally bidentately coupled to the metal ions, according to infrared spectral study. The general formula of [M(BHX)(Phen)(H2O)n.Clm] was suggested using the molar conductivity, elemental analyses, and thermal information of the complexes that were produced. Where M = Fe(III) (n = y = 2, m = 0, and x = 3), Co(II) (n = x = 2, m = 0, and y = 3), Ni(II) (n = x = 2, m = 0, and y = 6), and Cd(II) (n = x = y = 2 and m = 0) with an octahedral geometry was proposed. Thermal analyses revealed that the complexes lost anionic part and organic ligands in continual changes after first losing water molecules of hydration. Compared with their parent BHX ligand, the mixed ligand complexes demonstrated promising microbiological activities against a variety of bacterial species, including Gram‐positive bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram‐negative bacteria (Escherichia coli and Pseudomonas aeruginosa). According to the results, mixed ligand complexes are more efficient than the parent BHX and Phen ligands. The complexes moderately inhibit the development of the MCF‐7 antibreast cancer cell line. The chemistry of the linking energy, H‐bond, and hydrophobic interactions of the BHX ligand and its mixed Cu(II) complex with Phen are revealed by molecular docking investigations with the crystal structure of S. aureus nucleoside (PDB: 3Q8U) and human prostate‐specific antigen (PDB: 3QUM).
Sex differences of the triple network model in children with autism: A resting‐state fMRI investigation of effective connectivity
Authors: Li Cuicui , Li Tong , Chen Ying , Zhang Chunling , Ning Mingmin , Qin Rui , Li Lin , Wang Ximing , Chen Linglong
Published: August 2023

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same‐sex controls. Given its central role, altered structures and functions, and sex‐dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex‐related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8–14 years) and 72 typically developing controls (TCs) (36 females, 8–14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain‐behavior relationships and the effects of age on EC. We found significant diagnosis‐by‐sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain‐behavior correlations and significant effects of age on EC.
Incidence, mechanisms, treatment, and outcomes of donor vessel injury during percutaneous coronary interventions for chronic total occlusion
Authors: Kostantinis Spyridon , Rempakos Athanasios , Simsek Bahadir , Karacsonyi Judit , Allana Salman S. , Alaswad Khaldoon , Basir Mir B. , Krestyaninov Oleg , Khelimskii Dmitrii , Gorgulu Sevket , Davies Rhian E. , Benton Stewart M. , Khatri Jaikirshan J. , Poommipanit Paul , Choi James W. , Jaber Wissam A. , Rinfret Stephane , Nicholson William , Al‐Azizi Karim M. , Potluri Srinivasa , Aygul Nazif , Altunkeser Bulent B. , Koutouzis Michael , Tsiafoutis Ioannis , Milkas Anastasios , ElGuindy Ahmed M. , Abi Rafeh Nidal , Goktekin Omer , Mastrodemos Olga C. , Rangan Bavana V. , Sandoval Yader , Burke M Nicholas , Brilakis Emmanouil S.
Published: August 2023

Background

Donor vessel injury is a potentially life‐threatening complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI).

Aims

Our goal was to examine the incidence, mechanisms, treatment, and outcomes of patients with donor vessel injury in a large multicenter CTO PCI registry.

Methods

We analyzed the baseline clinical and angiographic characteristics, and procedural outcomes of 12,349 CTO PCIs performed between 2012 and 2022 at 44 centers.

Results

The incidence of donor vessel injury was 0.35% (n = 43). The baseline clinical characteristics of patients with and without donor vessel injury were similar. Cases complicated by donor vessel injury were more complex with higher Japanese CTO score (2.9 ± 1.1 vs. 2.4 ± 1.3;p = 0.004) and lower procedural success rate (69.8% vs. 85.2%;p = 0.004). The retrograde approach was used more commonly in donor vessel injury cases (68.9% vs. 30.9%;p < 0.001). Most (53.5%) donor vessel injuries were guide catheter‐induced, whereas 20.9% were due to donor vessel thrombosis. Of the 43 patients with donor vessel injury, 36 (83.7%) were treated with stenting and seven (16.3%) received a left ventricular assist device. The incidence of major adverse cardiovascular events (MACEs) was significantly higher in cases with donor vessel injury (23.3% vs. 2.0%;p < 0.001). Of the 43 patients with donor vessel injury, five patients (11.6%) experienced acute myocardial infarction and four patients (9.3%) died.

Conclusions

Donor vessel injury, occurred in 0.35% of CTO PCIs performed by experienced operators, was mainly due to guide catheter‐induced dissection or thrombosis and was associated with lower procedural success and higher MACE.
Practical Aspects Concerning Catalysis with Molecularly Doped Metals**
Authors: Ciriminna Rosaria , Formenti Matteo , Pagliaro Mario , Della Pina Cristina
Published: August 2023

Ranging from silver‐entrapped dyes and gold‐entrapped enzymes through palladium‐entrapped graphene oxide, molecularly doped metals (or metal organic alloys, MORALs) are active, stable and uniquely versatile catalysts in a number of reactions of relevance to the chemical industry. Reactions successfully catalyzed by MORALs concern both industry's main sectors, producing bulk and fine chemicals. Though first reported in 2005, and clearly holding a great applicative potential, their use in catalysis is still surprisingly limited. This study investigates a number of practical aspects concerning molecularly doped metals as heterogeneous catalysts.
Metal‐Catalyzed Carbonylation Reactions with CO2: An Update
Authors: Giovanelli Riccardo , Bertuzzi Giulio , Bandini Marco
Published: August 2023

The utilization of CO2 as an efficient and environmentally friendly chemical analogue of CO is becoming a solid reality in the chemical scenario. CO2‐based carbonylations have started paralleling the more consolidated carboxylation procedures, opening new horizons and perspectives in the utilization of carbon dioxide as an organic C1‐containing building block. The advent of efficient and site‐selective metal‐catalyzed protocols for the fixation of CO2 into organic scaffolds, under controlled reductive conditions, contributed substantially to the development of robust, efficient, and convenient protocols. In the present Review article, a collection of the most recent examples of metal‐catalyzed CO2‐based carbonylations is documented with a particular emphasis on mechanistic aspects.
DFT Study of Imine‐Exchange Reactions in Iron(II)‐Coordinated Pincers
Authors: van Dam Annemieke , van Schendel Robin , Gangarapu Satesh , Zuilhof Han , Smulders Maarten M. J.
Published: August 2023

The imine bond is among the most applied motifs in dynamic covalent chemistry. Although its uses are varied and often involve coordination to a transition metal for stability, mechanistic studies on imine exchange reactions so far have not included metal coordination. Herein, we investigated the condensation and transimination reactions of an Fe2+‐coordinated diimine pyridine pincer, employing wB97XD/6‐311G(2d,2p) DFT calculations in acetonitrile. We first experimentally confirmed that Fe2+ is strongly coordinated by these pincers, and is thus a justified model ion. When considering a four‐membered ring‐shaped transition state for proton transfers, the required activation energies for condensation and transimination reaction exceeded the values expected for reactions known to be spontaneous at room temperature. The nature of the incoming and exiting amines and the substituents on the para‐position of the pincer had no effect on this. Replacing Fe2+ with Zn2+ or removing it altogether did not reduce it either. However, the addition of two ethylamine molecules lowered the energy barriers to be compatible with experiment (19.4 and 23.2 kcal/mol for condensation and transimination, respectively). Lastly, the energy barrier of condensation of a non‐coordinated pincer was significantly higher than found for Fe2+‐coordinating pincers, underlining the catalyzing effect of metal coordination on imine exchange reactions.