bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon‐γ inducible protein 30 promotes the epithelial–mesenchymal transition‐like phenotype and chemoresistance by activating EGFR/AKT/GSK3β/β‐catenin pathway in glioma
Authors: Chen Ying , Xu Hui , Yu Pei , Wang Qing , Li Shenggang , Ji Fufu , Wu Chunwang , Lan Qing
Published: July 2023

Aims

Previous studies have indicated that IFI30 plays a protective role in human cancers. However, its potential roles in regulating glioma development are not fully understood.

Methods

Public datasets, immunohistochemistry, and western blotting (WB) were used to evaluate the expression of IFI30 in glioma. The potential functions and mechanisms of IFI30 were examined by public dataset analysis; quantitative real‐time PCR; WB; limiting dilution analysis; xenograft tumor assays; CCK‐8, colony formation, wound healing, and transwell assays; and immunofluorescence microscopy and flow cytometry.

Results

IFI30 was significantly upregulated in glioma tissues and cell lines compared with corresponding controls, and the expression level of IFI30 was positively associated with tumor grade. Functionally, both in vivo and in vitro evidence showed that IFI30 regulated the migration and invasion of glioma cells. Mechanistically, we found that IFI30 dramatically promoted the epithelial–mesenchymal transition (EMT)‐like process by activating the EGFR/AKT/GSK3β/β‐catenin pathway. In addition, IFI30 regulated the chemoresistance of glioma cells to temozolomide directly via the expression of the transcription factor Slug, a key regulator of the EMT‐like process.

Conclusion

The present study suggests that IFI30 is a regulator of the EMT‐like phenotype and acts not only as a prognostic marker but also as a potential therapeutic target for temozolomide‐resistant glioma.
Familiar observers attenuate surgery‐induced neuroinflammation and cognitive dysfunction in mice
Authors: Jiang Qun , Guo Mingyan , Zuo Zhiyi
Published: July 2023

Aims

Postoperative cognitive dysfunction (POCD) is a common complication associated with poor outcome. Our previous study has shown that living with familiar observers in the same cage reduces anxiety of mice with surgery. Anxiety can impair learning and memory. Thus, this study was designed to determine whether living with familiar observers attenuated the dysfunction of learning and memory of mice with surgery.

Methods

Six‐ to eight‐week‐old CD‐1 male mice or 18‐month‐old C57BL/6 male mice had left carotid artery exposure under isoflurane anesthesia. They lived with non‐surgery male mice at 2 (number of surgery mice) to 3 (number of non‐surgery mice) ratio or with other surgery mice. Mice were subjected to light and dark box test 3 days after surgery to measure their anxiety levels and novel object recognition and fear conditioning tests from 5 days after surgery to measure their learning and memory. Blood and brain were harvested for biochemical analysis.

Results

Living with familiar observers that lived with surgery mice for at least 2 weeks before the surgery and then after surgery reduced the anxiety and dysfunction of learning and memory in young adult male mice. Living with unfamiliar observers that lived with surgery mice after the surgery but not before the surgery did not have those effects on the mice with surgery. Living with familiar observers attenuated learning and memory dysfunction after surgery also in old male mice. Living with familiar observers attenuated inflammatory response in the blood and brain and the activation of the lateral habenula (LHb)‐ventral tegmental area (VTA) neural circuitry, which has been shown to be important for POCD. Wound infiltration with bupivacaine attenuated the activation of LHb‐VTA.

Conclusion

These results suggest that living with familiar observers attenuates POCD and neuroinflammation, possibly via inhibiting the activation of the LHb‐VTA neural circuitry.
A decade comparison of regulatory decision patterns for oncology products to all other non‐oncology products among Swissmedic, European Medicines Agency, and US Food and Drug Administration
Authors: Rohr Ulrich‐P. , Iovino Mario , Rudofsky Leonie , Li Qiyu , Juritz Stephanie , Gircys Arunas , Wildner Oliver , Bujar Magda , Bolte Claus , Dalla Torre di Sanguinetto Simon , Wolfer Anita
Published: July 2023

Consensus of regulatory decisions on the same Marketing Authorization Application (MAA) are critical for stakeholders. In this context, regulatory decision patterns from the Swissmedic (SMC), the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA) were analyzed for hemato‐oncology products (OP) and non‐oncology products (NOP). We compared 336 SMC regulatory decisions between 2009 and 2018 on new active substances with the EMA and the FDA for OP (n = 77) and NOP (n = 259) regarding approval rates, consensus, and divergent decisions. For OP MAA, we analyzed the underlying reasons for divergent decisions; for consensus decisions, the similarity and strictness of labeling. For OP, the approval rate for the SMC was 88.4%, the EMA 91.3%, and the FDA 95.7%. For NOP, the SMC had an approval rate of 86.2%, the EMA of 93.8%, and the FDA of 88.8%. The consensus decision rate among agencies was 88.4% for OP and 84.4% for NOP. The main clinical driver for divergent decisions for OP was nonrandomized trial design and low patient numbers. Comparing the approved indication wordings, the highest similarity was between the SMC and the EMA, and lowest for the FDA and the EMA. Investigating label strictness, the FDA numerically had the highest but not‐statistically significant number of strict labels. The approval rate stratified by disease area (OP and NOP) differed among the SMC, the EMA, and the FDA. High concordance in regulatory decisions was observed between agencies for OP as well as NOP. Reasons for divergent decisions regarding OP were mainly due to scientific uncertainties. Comparing strictness of indications, numerical but no statistically significant differences were observed between agencies.
Management of the ‘wicked’ combination of heart failure and chronic kidney disease in the patient with diabetes
Authors: Bell David S. H. , McGill Janet B. , Jerkins Terri
Published: July 2023

Patients with type 2 diabetes are at an increased risk of developing heart failure and chronic kidney disease. The presence of these co‐morbidities substantially increases the risk of morbidity as well as mortality in patients with diabetes. The clinical focus has historically centred around reducing the risk of cardiovascular disease by targeting hyperglycaemia, hyperlipidaemia and hypertension. Nonetheless, patients with type 2 diabetes who have well‐controlled blood glucose, blood pressure and lipid levels may still go on to develop heart failure, kidney disease or both. Major diabetes and cardiovascular societies are now recommending the use of treatments such as sodium‐glucose co‐transporter‐2 inhibitors and non‐steroidal mineralocorticoid receptor antagonists, in addition to currently recommended therapies, to promote cardiorenal protection through alternative pathways as early as possible in individuals with diabetes and cardiorenal manifestations. This review examines the most recent recommendations for managing the risk of cardiorenal progression in patients with type 2 diabetes.
Development and validation of a real‐world model to predict 1‐year Level 3 (severe) hypoglycaemia risk in adults with diabetes (theiNPHORMstudy, United States)
Authors: Ratzki‐Leewing Alexandria A. , Black Jason E. , Ryan Bridget L. , Zou Guangyong , Klar Neil , Webster‐Bogaert Susan , Timcevska Kristina , Harris Stewart B.
Published: July 2023

Aims

We aimed to develop and internally validate a real‐world prognostic model for Level 3 hypoglycaemia risk compatible with outpatient care in the United States.

Materials and Methods

iNPHORM is a 12‐month, US‐based panel survey. Adults (18‐90 years old) with type 1 diabetes mellitus or insulin‐ and/or secretagogue‐treated type 2 diabetes mellitus were recruited from a nationwide, probability‐based internet panel. Among participants completing 1 follow‐up questionnaire(s), we modelled 1‐year Level 3 hypoglycaemia risk using Andersen and Gill's Cox survival and penalized regression with multiple imputation. Candidate variables were selected for their clinical relevance and ease of capture at point‐of‐care.

Results

In total, 986 participants [type 1 diabetes mellitus: 17%; men: 49.6%; mean age: 51 (SD: 14.3) years] were analysed. Across follow‐up, 035.1 (95% CI: 32.2‐38.1)% reported ≥1 Level 3 event(s), and the rate was 5.0 (95% CI: 4.1‐6.0) events per person‐year. Our final model showed strong discriminative validity and parsimony (optimism corrected c‐statistic: 0.77). Numerous variables were selected: age; sex; body mass index; marital status; level of education; insurance coverage; race; ethnicity; food insecurity; diabetes type; glycated haemoglobin value; glycated haemoglobin variability; number, type and dose of various medications; number of SH events requiring hospital care (past year and over follow‐up); type and number of comorbidities and complications; number of diabetes‐related health care visits (past year); use of continuous/flash glucose monitoring; and general health status.

Conclusions

iNPHORM is the first US‐based primary prognostic study on Level 3 hypoglycaemia. Future model implementation could potentiate risk‐tailored strategies that reduce real‐world event occurrence and overall diabetes burden.
Parental gender preferences in Central and Eastern Europe and differential early life disadvantages
Authors: Myck Michał , Oczkowska Monika , Wowczko Izabela
Published: July 2023

Parental gender preferences may affect partnership decisions and as a result lead to early life disadvantages. We study these preferences in five post‐communist countries of Central and Eastern Europe, a region with strong traditional gender norms and persisting inequalities between women and men in labour market outcomes. Using subsamples of census from Belarus, Hungary, Poland, Romania and Russia around 2000 and 2010, we follow Dahl and Moretti (2008), The demand for sons, to examine the effect of the gender of the first‐born child(ren) on fertility decisions and relationship stability of their parents. We only find strong evidence of ‘boy preferences’ in fertility decisions in the cases of Romania and Russia. However, unlike Dahl and Moretti (2008), The demand for sons, for the US, we cannot confirm a relationship between the children's gender and parental partnership decisions. This is the case for all examined Central and Eastern European countries, as well as for a number of countries from Western Europe. The cases of Romania and Russia raise questions about other potential consequences of the documented gender preferences. We argue that our approach can be applied more broadly to identify other countries characterised by parental gender preferences, and to motivate further examination of different forms of gender driven early life disadvantages.
The political economy triangle of government spending, interest‐group influence, and income inequality: Evidence and implications from the US states
Authors: Cole Ismail M.
Published: July 2023

This paper introduces the political economy triangle (PET) concept of government spending, special interest groups (SIGs) influence, and income inequality, empirically confirming its existence and unveiling its nature while directly addressing key shortcomings of most prior research on the determinants of such inequality. Using static and dynamic panel techniques and data from the US states, it reports several new results: (i) the findings of previous studies regarding the roles of government spending and interest groups, including labor unions, in income distribution are confirmed, however, their estimated inequality effects grossly underestimate those obtained when endogeneity issues are accounted for explicitly; (ii) a dynamic tripartite relationship between the variables of the PET exists; (iii) government spending and SIGs' influence, including union strength, beyond their direct effects on inequality, have a separate positive impact through their interactions; (iv) the effectiveness of government spending in reducing inequality diminishes as the level of SIGs' influence and union strength increase in the short and long run, (v) the aggregate inequality‐increasing effect of SIGs is strengthened and the inequality‐reducing effects of unions weakened as the spending rises, in the short run and long run. Finally, the broad implications of these findings are discussed.
Critical appraisal of the 2020 IADT Guidelines: A personal commentary
Authors: Philip Nebu , Nazzal Hani , Duggal Mandeep Singh
Published: July 2023

The 2020 International Association of Dental Traumatology (IADT) Guidelines feature several important changes in the treatment recommendations for traumatic dental injuries (TDIs) from the previous 2012 iteration of these Guidelines. This evidence‐based narrative review aims to provide a detailed appraisal of five specific changes incorporated in the 2020 IADT Guidelines, based on the available literature evidence that may have prompted these changes. The paper discusses three excellent additions/changes to the new Guidelines: (i) inclusion of a core outcome set for reporting TDIs; (ii) more conservative management of primary dentition TDIs including the changed recommendations for radiation exposure and managing primary dentition luxation injuries; and (iii) the changes in the treatment recommendations for permanent dentition avulsion injuries. The paper further debates whether two other changes made in the current IADT Guidelines for—(i) intrusion injuries in immature teeth; and (ii) complicated crown‐root fractures in mature teeth—have sufficient evidence to support the changed recommendations.
Deafness induces complete crossmodal plasticity in a belt region of dorsal auditory cortex
Authors: Merrikhi Yaser , Mirzaei Ali , Kok Melanie A. , Meredith M. Alex , Lomber Stephen G.
Published: July 2023

Many neural areas, where patterned activity is lost following deafness, have the capacity to become activated by the remaining sensory systems. This crossmodal plasticity can be measured at perceptual/behavioural as well as physiological levels. The dorsal zone (DZ) of auditory cortex of deaf cats is involved in supranormal visual motion detection, but its physiological level of crossmodal reorganisation is not well understood. The present study of early‐deaf DZ (and hearing controls) used multiple single‐channel recording methods to examine neuronal responses to visual, auditory, somatosensory and combined stimulation. In early‐deaf DZ, no auditory activation was observed, but 100% of the neurons were responsive to visual cues of which 21% were also influenced by somatosensory stimulation. Visual and somatosensory responses were not anatomically organised as they are in hearing cats, and fewer multisensory neurons were present in the deaf condition. These crossmodal physiological results closely correspond with and support the perceptual/behavioural enhancements that occur following hearing loss.
Functional tics: Expanding the phenotypes of functional movement disorders?
Authors: Cavanna Andrea E. , Purpura Giulia , Riva Anna , Nacinovich Renata , Seri Stefano
Published: July 2023

Background and purpose

Until the outbreak reported during the COVID‐19 pandemic, functional tics were considered to be a relatively rare clinical phenotype, as opposed to other functional movement disorders such as functional tremor and dystonia. To better characterize this phenotype, we compared the demographic and clinical characteristics of patients who developed functional tics during the pandemic and those of patients with other functional movement disorders.

Methods

Data from 110 patients were collected at the same neuropsychiatry centre: 66 consecutive patients who developed functional tics without other functional motor symptoms or neurodevelopmental tics and 44 patients with a mix of functional dystonia, tremor, gait, and myoclonus.

Results

Both groups were characterized by female sex preponderance (70%–80%) and (sub)acute onset of functional symptoms (~80%). However, patients with functional tics had a significantly earlier age at onset of functional symptoms (21 vs. 39 years). Exposure to relevant social media content was reported by almost half of the patients with functional tics, but by none of the patients with other functional movement disorders. Comorbidity profiles were similar, with relatively high rates of anxiety/affective symptoms and other functional neurological symptoms (nonepileptic attacks).

Conclusions

Patients who developed functional tics during the pandemic represent a phenotypic variant of the wider group of patients with functional movement disorders, associated with younger age at onset and influenced by pandemic‐related factors, including increased exposure to specific social media content. Diagnostic protocols and treatment interventions should be tailored to address the specific features of this newly defined phenotype.
A new record of an invasive aquatic fern from Türkiye: Salvinia molesta
Authors: Şenol S. G. , Bozyel D. , Pelit N. B.
Published: July 2023

Salvinia molesta D.S. Mitch, which is on the list of harmful invasive species in many countries, is reported from Muğla–Köyceğiz as a new invasive species record for the flora of Türkiye. This species was found by chance on 11 March 2017, during the field work of the date palm project (TUBİTAK 116Z288) carried out by the authors. In the article a description of the species and detailed photographs and information on its distribution are given.
List of aphids (Hemiptera: Aphidoidea) intercepted at South Korean plant quarantine
Authors: Suh Soo‐Jung
Published: July 2023

A list of 75 species of aphids which have been intercepted on plants imported into South Korea over the past 27 years (from 1996 to 2022) including information on the number of interceptions, host plants and their distribution is provided. Data on intercepted species were analysed to determine potential invasive species of aphids that could threaten South Korean agroecosystems.
Evidence of hybridization between genetically distinct Baltic cod stocks during peak population abundance(s)
Authors: Helmerson Cecilia , Weist Peggy , Brieuc Marine Servane Ono , Maurstad Marius F. , Schade Franziska Maria , Dierking Jan , Petereit Christoph , Knutsen Halvor , Metcalfe Julian , Righton David , André Carl , Krumme Uwe , Jentoft Sissel , Hanel Reinhold
Published: July 2023

Range expansions can lead to increased contact of divergent populations, thus increasing the potential of hybridization events. Whether viable hybrids are produced will most likely depend on the level of genomic divergence and associated genomic incompatibilities between the different entities as well as environmental conditions. By taking advantage of historical Baltic cod (Gadus morhua) otolith samples combined with genotyping and whole genome sequencing, we here investigate the genetic impact of the increased spawning stock biomass of the eastern Baltic cod stock in the mid 1980s. The eastern Baltic cod is genetically highly differentiated from the adjacent western Baltic cod and locally adapted to the brackish environmental conditions in the deeper Eastern basins of the Baltic Sea unsuitable for its marine counterparts. Our genotyping results show an increased proportion of eastern Baltic cod in western Baltic areas (Mecklenburg Bay and Arkona Basin)—indicative of a range expansion westwards—during the peak population abundance in the 1980s. Additionally, we detect high frequencies of potential hybrids (including F1, F2 and backcrosses), verified by whole genome sequencing data for a subset of individuals. Analysis of mitochondrial genomes further indicates directional gene flow from eastern Baltic cod males to western Baltic cod females. Our findings unravel that increased overlap in distribution can promote hybridization between highly divergent populations and that the hybrids can be viable and survive under specific and favourable environmental conditions. However, the observed hybridization had seemingly no long‐lasting impact on the continuous separation and genetic differentiation between the unique Baltic cod stocks.
Geographies of big water infrastructure: Contemporary insights and future research opportunities
Authors: Birkenholtz Trevor
Published: July 2023

Largescale “big” water infrastructure is once again at the forefront of the global developmentalist agenda and is receiving attendant scholarly attention. Given this parallel growth, now is time to take stock of current scholarly contributions and explore opportunities for future research. In this paper, I review recent developments and insights gained from research on big water infrastructure, and water infrastructure studies, generally, to highlight six key threads of current scholarship. These include the production of big water infrastructure as: (1) a temporal process embedded in colonialism and ecological modernization; (2) infused with infrastructural knowledges, practices and subjectivities; (3) a spatial‐geopolitical process; (4) subject to infrastructural and environmental material characteristics and capacities; (5) producing uneven development and enabling accumulation by dispossession; and (6) a contested process of differentiated socio‐material resistance. In reviewing this literature, I argue that these six research strands form key analytic considerations that could be employed by others studying the nexus between water development, political ecological change, and infrastructure. Before concluding, in the final section of the paper I present additional and ongoing future research directions including big water infrastructure as it intersects with socially differentiated human intimacy and embodiment, indigenous and racialized forms of dispossession, and financialization.
RNA m5C methylation orchestrates BLCA progression via macrophage reprogramming
Authors: Yan Dali , Xie Yongsong , Huang Liyuan , Zhang Yi , Gu Runhuan , Xie Huaibing , Huang Xing , Luo Hao
Published: July 2023

Recently, epigenetics showed essential roles in tumour microenvironment (TME) and immunotherapy response, however, the functions of RNA 5‐methylcytosine (m5C) modification in TME remains unknown. According to 13 m5C regulators, we evaluated 412 BLCA patients from The Cancer Genome Atlas (TCGA) database. The m5C score was constructed by unsupervised clustering analysis and principal component analysis (PCA) algorithms. Gene set variation analysis (GSVA), ESTIMATE algorithm, and immunohistochemical (IHC) staining were performed. Macrophage chemotaxis assay was used to assess the M2 macrophages. Among the 412 patients, the frequency of mutation was 13%. m5C regulators was expressed significantly in BLCA tissue compared with normal tissue. Then, two m5C methylation modification patterns were identified with dissimilar TME cell infiltration patterns. The C1 alteration pattern in the m5C cluster was connected with better survival. In addition, we found that NSUN6 was highly correlated with recruitment of macrophages via bioinformatics and IHC. Further experiment validated that NSUN6 promoted HDAC10 expression by mediating m5C methylation, inhibited the transcription of macrophage‐associated chemokines and thus inhibited the recruitment of M2 macrophages. The m5C score constructed by m5C modification pattern showed that high m5C score group had a better prognosis. This study uncovered the significant roles of m5C modifications in modulating the TME and indicated that NSUN6 could inhibit the recruitment of M2 macrophages via m5C methylation, which provided novel insight into epigenetic regulation of TME and clinical suggestions for immunotherapeutic strategies.
Evaluation of pathogen distribution and antimicrobial resistance in breast plastic surgery infection
Authors: Su Xueshang , Hu Jintian , Jiang Fengli , Wu Yuanyuan , He Jingjing , Jia Ximeng , Zhan Sien
Published: July 2023

Background

The demand for mammaplasty has increased in recent years, and infection remains one of the common and serious post‐operative complications. In this study, we analyzed the pathogen distribution and antibiotic susceptibility of breast plastic surgery infections, and compared the differences in pathogenic species between surgical procedures.

Methods

The number of each species was counted in the microbial samples of breast plastic surgery infections in Plastic Surgery Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2021. The in vitro antibiotic sensitivity testing data were analyzed using WHONET 5.6 software. The surgical techniques, the period of infection, and other details were gathered in accordance with the clinical data.

Results

There were a total of 42 cases included, and 43 different types of pathogenic bacteria, mostly gram‐positive bacteria, were found. CoNS (13/43) and Staphylococcus aureus (22/43) made up the majority. The most prevalent of the five Gram‐negative bacteria was Pseudomonas aeruginosa. Results of drug sensitivity tests indicate that S. aureus is highly sensitive to vancomycin, cotrimoxazole, and linezolid, whereas CoNS is highly sensitive to vancomycin, linezolid, and chloramphenicol. Both of these bacteria show high resistance to erythromycin and penicillin. Breast augmentation, breast reconstruction, and breast reduction surgery were the most frequently associated breast surgery procedures in this study with infections, with the highest number of infections occurring following breast augmentation with fat grafting, breast reduction surgery, and breast reconstruction with autologous tissue. Various breast plastic surgery procedures have different common pathogens of infection, but the most prevalent are CoNS and S. aureus. Additionally, the majority of the infections in this study were in the early stages.

Conclusions

Gram‐positive bacteria were the predominant cause of breast plastic surgery infections, and the types of infection strains, the period of infection onset, and the antibiotic susceptibility of prevalent strains varied between breast plastic procedures.
Exploring continuity of care for women with prenatal diagnosis of congenital anomaly: A mixed method study
Authors: Psaila Kim M. , Schmied Virginia , Heath Susan
Published: July 2023

Aims

To map the pathway and service provision for pregnant women whose newborns require admission into the surgical neonatal intensive care unit at or soon after birth, and to examine the nature of continuity of care (COC) provided and the facilitators and barriers to woman‐ and family‐centred care from the perspective of women/parents and health professionals.

Background

Limited research exists on current service and care pathways for families whose babies are diagnosed with congenital abnormality requiring surgery.

Design

A mixed method sequential design adhering to EQUATOR guidelines for Good Reporting of a Mixed Methods Study.

Methods

Data collection methods included: (1) a workshop with health professionals (n = 15), (2) retrospective maternal record review (n = 20), prospective maternal record review (17), (3) interviews with pregnant women given a prenatal diagnosis of congenital anomaly (n = 17) and (4) interviews with key health professionals (n = 7).

Results/Findings

Participants perceived care delivered by state‐based services as problematic prior to admission into the high‐risk midwifery COC model. Once admitted to the high‐risk maternity team women described care ‘like a breath of fresh air’ with a ‘contrast in support’, where they felt supported in their decisions.

Conclusion

This study highlights provision of COC, in particular relational continuity between health providers and women as essential to achieve optimal outcomes.

Relevance to Clinical Practice

Provision of individualised COC offers an opportunity for perinatal services to reduce the negative consequences of pregnancy‐related stress associated with diagnosis of foetal anomaly.

Patient or Public Contribution

No patient or public was involved in the design, analysis, preparation or writing of this review.
The effect of the Litcubanine A on the treatment of murine experimental periodontitis by inhibiting monocyte–macrophage chemotaxis and osteoclast differentiation
Authors: Chen Yingyi , Liu Yitong , Xia Huan , Xia Guiyang , Xu Junji , Lin Sheng , Guo Lijia , Liu Yi
Published: July 2023

Background

Periodontal disease is an inflammatory disease of periodontal tissues that is closely connected with systemic diseases. During periodontitis, the inappropriate recruitment and activation of monocytes–macrophages causes an increase in osteoclast activity and disrupts bone homeostasis. Therefore, it is a promising therapeutic strategy to treat periodontitis by regulating the functions of monocytes–macrophages. Litcubanine A (LA) is an isoquinoline alkaloid extracted from the traditional Chinese medicine Litsea cubeba, which was proven to have reproducible anti‐inflammatory effects, but its regulatory role on bone homeostasis in periodontitis is still not clear.

Methods

In this study, zebrafish experiments and a mouse ligature‐induced periodontitis model were performed, and histological analysis was used to investigate the effect of LA on macrophage chemotaxis under the inflammatory environment. Real‐time PCR was used to detect the regulatory effect of LA (100 nM ~ 100 μM) on the chemotaxis function of macrophages induced by LPS. Apoptosis assay and flow cytometry were used to elucidate the influence of LA on macrophage apoptosis and proliferation. To further clarify the regulatory role of LA on macrophage osteoclast differentiation, real‐time PCR, histological analysis, western blot, and micro‐computed tomography (micro‐CT) were performed in vivo and in vitro to verify the impact of LA on bone homeostasis.

Results

Compared with the control group, the chemotaxis function of macrophage was significantly attenuated by LA in vivo. LA could significantly inhibit the expression of genes encoding the chemokine receptors Ccr1 and Cxcr4, and its ligand chemokine Cxcl12 in macrophages, and suppresses the differentiation of osteoclastic precursors to osteoclasts through the MAPK signaling pathway. There were significantly lower osteoclast differentiation and bone loss in the LA group compared with the control in the ligature‐induced periodontitis model.

Conclusion

LA is a promising candidate for the treatment of periodontitis through its reproducible functions of inhibiting monocyte–macrophage chemotaxis and osteoclast differentiation.
Variation in autotrophic and heterotrophic sponge abundance in a shallow water seagrass system
Authors: Bachtiar Ramadian , Madduppa Hawis H. , Bell James J.
Published: July 2023

Sponges are well known to feed heterotrophically through suspension feeding, but their relationships with photosynthetic symbionts mean they also have the potential to utilise or release photosynthetically derived carbon. Here, we determined the nutritional mode of sponges that occurred seagrass meadows at two sites in the Wakatobi National Park (Hoga‐1 and 2), Indonesia from the near‐reef flat (d = 1.9 m), middle‐shore (d = 1.2 m) and high‐shore (d = 0.5 m) zones to assess the role they might play in nutrient fluxes. We measured photosynthetic pigment concentrations and in situ net primary production to dark respiration (P:R) ratios of eight sponge species representing 75%–100% of the total sponge assemblage biomass at the two sites. We found that six of eight sponge species were autotrophic, based on their instantaneous P:R ratios and estimated daily oxygen production/consumption. The proportion of autotrophic sponge biomass in the high and middle shore of the seagrass meadows ranged between 40% and 70%, and accounted for 98% and 81% of the biomass in the near‐flat zones. Our findings that many seagrass sponges are autotrophic challenges the general view that sponges are consumers of organic carbon from the water column.
Building the competency of health professionals in the Kyrgyz Republic for the Baby‐Friendly Hospital Initiative
Authors: Klein Alyssa , Block Charlotte , Mansimov Adil , Okenov Samat , Alvey Jeniece , Abazbekova Nazgul , Mukuria‐Ashe Altrena
Published: July 2023

Health professional competency building is one of nine national responsibilities (to achieve universal coverage and sustainability) described in the 2018 World Health Organization/UNICEF implementation guidance for the Baby‐Friendly Hospital Initiative (BFHI). Skilled breastfeeding support as a standard of newborn care is critical to the establishment of lactation and exclusive breastfeeding. This qualitative case study describes the Kyrgyz Republic's experience with health professional competency building related to breastfeeding counselling and support. We interviewed 38 key informants and reviewed national policies and international guidelines related to BFHI. The study found that although the country has a new policy reflecting BFHI global standards and guidance, the policy has not been disseminated nationally. Additionally, the policy lacks guidance on competency monitoring and verification and does not mention preservice training, even though preservice training on breastfeeding support exists. To achieve universal coverage for health professional competencies, the Kyrgyz Republic uses preservice, in‐service and refresher training. However, the main limitations to aligning with the new guidance are a lack of preservice BFHI‐ and breastfeeding‐specific curricula, experienced trainers and sufficient time and funding to dedicate to practical skill development. Conducted during the COVID‐19 pandemic, this study confirmed disruptions to BFHI training and service delivery but also documents the Kyrgyz Republic's resilient strides to mitigate impacts on breastfeeding support through facility‐level individual champions and adjustments to training such as going online. Opportunities exist for strengthening the competencies of service providers through strengthened preservice training, comprehensive and consistent in‐service training, solutions for overworked service providers and clear and sufficiently funded monitoring guidance.
Moving metals: How microbes deliver metal cofactors to metalloproteins
Authors: Kunkle Dillon E. , Skaar Eric P.
Published: July 2023

First row d‐block metal ions serve as vital cofactors for numerous essential enzymes and are therefore required nutrients for all forms of life. Despite this requirement, excess free transition metals are toxic. Free metal ions participate in the production of noxious reactive oxygen species and mis‐metalate metalloproteins, rendering enzymes catalytically inactive. Thus, bacteria require systems to ensure metalloproteins are properly loaded with cognate metal ions to maintain protein function, while avoiding metal‐mediated cellular toxicity. In this perspective we summarize the current mechanistic understanding of bacterial metallocenter maturation with specific emphasis on metallochaperones; a group of specialized proteins that both shield metal ions from inadvertent reactions and distribute them to cognate target metalloproteins. We highlight several recent advances in the field that have implicated new classes of proteins in the distribution of metal ions within bacterial proteins, while speculating on the future of the field of bacterial metallobiology.
Dietary prevention strategies for childhood asthma
Authors: Brustad Nicklas , Bønnelykke Klaus , Chawes Bo
Published: July 2023

Asthma is the most common chronic disease in childhood and a rise in prevalence has been observed concomitantly with changing dietary habits in the Western world. This change has favored a more Westernized diet characterized by high intake of processed food and fat in contrast to a Mediterranean diet high in fruit, vegetable and fish intake. This has resulted in a decreased intake of several antioxidants and micronutrients including n‐3 long‐chained polyunsaturated fatty acids and vitamin D that are speculated to have anti‐inflammatory effects and hold immunoregulatory properties. Several observational studies have investigated associations between dietary intake and wheeze and asthma but only few large well‐conducted randomized controlled trials (RCTs) have been performed investigating the primary preventive effect of micronutrient supplementations. Currently, the recommendations from the Global Initiative for Asthma (GINA) for primary prevention of asthma in children do not include maternal dietary changes or supplementations during pregnancy, although the most recent report mentions both specific dietary patterns and micronutrients as potential protective supplementation regimes. This review will present the current literature and future research needs focusing on primary and secondary prevention of both early and late childhood asthma from dietary intake during pregnancy and early childhood to highlight potential preventive effects of specific dietary patterns and micronutrient supplements, which may facilitate the planning of future clinical trials in search of a preemptive strategy.
The photophysics of protonated cytidine and hemiprotonated cytidine base pair: A computational study
Authors: Martinez‐Fernandez Lara , Improta Roberto
Published: July 2023

We here study the effect that a lowering of the pH has on the excited state processes of cytidine and a cytidine/cytidine pair in solution, by integrating time‐dependent density functional theory and CASSCF/CASPT2 calculations, and including solvent by a mixed discrete/continuum model. Our calculations reproduce the effect of protonation at N3 on the steady‐state infrared and absorption spectra of a protonated cytidine (CH+), and predict that an easily accessible non‐radiative deactivation route exists for the spectroscopic state, explaining its sub‐ps lifetime. Indeed, an extremely small energy barrier separates the minimum of the lowest energy bright state from a crossing region with the ground electronic state, reached by out‐of‐plane motion of the hydrogen substituents of the CC double bond, the so‐called ethylenic conical intersection typical of cytidine and other pyrimidine bases. This deactivation route is operative for the two bases forming an hemiprotonated cytidine base pair, [CH·C]+, the building blocks of I‐motif secondary structures, whereas interbase processes play a minor role. N3 protonation disfavors instead the nπ* transitions, associated with the long‐living components of cytidine photoactivated dynamics.
Highly active antiretroviral therapy discontinuation time is associated with therapeutic failure among human immunodeficiency virus (HIV)‐infected immigrant adults: A cohort study from a Peruvian referral hospital during the Venezuelan exodus
Authors: Rebolledo‐Ponietsky Kirbeliz , Al‐kassab‐Córdova Ali , Lucchetti‐Rodríguez Aldo , Cabieses Baltica , Rodriguez‐Morales Alfonso J. , Mezones‐Holguín Edward
Published: July 2023

Objective

To evaluate the association between Highly Active Antiretroviral Therapy (HAART) discontinuation time and therapeutic failure (TF) in Venezuelan immigrants with HIV that restart HAART.

Methods

We carried out a retrospective cohort study in a large hospital in Peru. We included Venezuelan immigrants who restarted HAART and were followed over at least 6 months. The primary outcome was TF. Secondary outcomes were immunologic (IF), virologic (VF) and clinical (CF) failures. The exposure variable was HAART discontinuation, categorised as no discontinuation, less than 6 months, and 6 months or more. We applied generalised linear models Poisson family with robust standard errors to calculate crude (cRR) and adjusted (aRR) relative risks by statistical and epidemiological criteria.

Results

We included 294 patients, 97.2% were males, and the median age was 32 years. Out of all the patients, 32.7% discontinued HAART for less than 6 months, 15.0% discontinued for more than 6 months and the remaining 52.3% did not discontinue. The cumulative incidence of TF was 27.9%, 24.5% in VF, 6.0% in IF and 6.0% in CF. Compared with non‐discontinued HAART patients, the discontinuation for less than 6 months (aRR = 1.98 [95% CI: 1.27–3.09]) and from 6 months to more (aRR = 3.17 [95% CI: 2.02–4.95]) increased the risk of TF. Likewise, treatment discontinuation of up to 6 months (aRR = 2.32 [95% CI: 1.40–3.84]) and from 6 months to more (aRR = 3.93 [95% CI: 2.39–6.45]) increased the risk of VF.

Conclusions

HAART discontinuation increases the probability of TF and VF in Venezuelan immigrants.
Factors Affecting Employee Turnover in a Small Business in Egypt
Authors: Elsafty Ashraf , Sayed Yasser R.
Published: July 2023

Employee turnover has become a common phenomenon in all organizations. It will cost a lot of money and time because organizations need to hire new employees and train them to fill field open positions. There are many different reasons why they choose to leave the organization. So, organizations need to find out the most important reasons to treat and improve it. There are four categories of factors that affect employee turnover: demographic, work, financial-economic and organizational. The demographic category consists of three factors Age, Tenure and Job designation level. The second category which is personal consists of Job Satisfaction and Organizational commitment. While the third category is the organization which consists of payments and benefits, location of workplace, working environment (i.e., flexible working hours), perceive alternative employment opportunities, career promotion and recognition, supervision and relationship, training and improved skills and the last category consists of work stress, work/life balance and field of study. The research design is descriptive with a correlation type of instrumentation to get the effect of variables positively or negatively with the amount. The data will collect via a structured questionnaire. This study has identified several key factors that contribute to employee turnover, including perceived organizational support, job stress, work-life balance, and available job alternatives. The results suggest that organizations can reduce employee turnover by improving perceived organizational support and work-life balance while also minimizing job stress. These findings have important implications for HR management in developing effective retention strategies to retain valuable employees and improve organizational performance.
Plasma-enhanced atomic layer deposition of silicon nitride for front-end-of-line applications
Authors: Lisker Marco , Kalishettyhalli Mahadevaiah Mamathamba , Dorai Swamy Reddy Keerthi
Published: July 2023

SiN deposition at low temperatures using the plasma-enhanced atomic layer deposition (PEALD) process is gaining momentum. A high-quality SiN layer deposited using a lower thermal budget and low wet etch rates are desired for front-end-of-line applications in semiconductor industries. In this study, deposition of PEALD SiN is investigated by utilizing a highly reactive trisilylamine silicon precursor and three different reaction partners for a nitrogen precursor. The quality of PEALD SiN layers is compared with the reference standard, low-pressure chemical vapor deposition SiN layers. The properties of different SiN layers are interpreted using FTIR and XPS material characterization techniques. Furthermore, the wet etch rates of as-deposited and annealed PEALD SiN layers are investigated. Finally, the conformality of PEALD SiN layers is assessed in trench and horizontal high aspect ratio structures.
Direct observation of nonlocal fermion pairing in an attractive Fermi-Hubbard gas
Authors: Hartke Thomas , Oreg Botond , Turnbaugh Carter , Jia Ningyuan , Zwierlein Martin
Published: July 2023

The Hubbard model of attractively interacting fermions provides a paradigmatic setting for fermion pairing. It features a crossover between Bose-Einstein condensation of tightly bound pairs and Bardeen-Cooper-Schrieffer superfluidity of long-range Cooper pairs, and a “pseudo-gap” region where pairs form above the superfluid critical temperature. We directly observe the nonlocal nature of fermion pairing in a Hubbard lattice gas, using spin- and density-resolved imaging of

∼

1000 fermionic potassium-40 atoms under a bilayer microscope. Complete fermion pairing is revealed by the vanishing of global spin fluctuations with increasing attraction. In the strongly correlated regime, the fermion pair size is found to be on the order of the average interparticle spacing. Our study informs theories of pseudo-gap behavior in strongly correlated fermion systems.
Paleoenvironments shaped the exchange of terrestrial vertebrates across Wallace’s Line
Authors: Skeels A. , Boschman L. M. , McFadden I. R. , Joyce E. M. , Hagen O. , Jiménez Robles O. , Bach W. , Boussange V. , Keggin T. , Jetz W. , Pellissier L.
Published: July 2023

Faunal turnover in Indo-Australia across Wallace’s Line is one of the most recognizable patterns in biogeography and has catalyzed debate about the role of evolutionary and geoclimatic history in biotic interchanges. Here, analysis of more than 20,000 vertebrate species with a model of geoclimate and biological diversification shows that broad precipitation tolerance and dispersal ability were key for exchange across the deep-time precipitation gradient spanning the region. Sundanian (Southeast Asian) lineages evolved in a climate similar to the humid “stepping stones” of Wallacea, facilitating colonization of the Sahulian (Australian) continental shelf. By contrast, Sahulian lineages predominantly evolved in drier conditions, hampering establishment in Sunda and shaping faunal distinctiveness. We demonstrate how the history of adaptation to past environmental conditions shapes asymmetrical colonization and global biogeographic structure.
Oncogene-like addiction to aneuploidy in human cancers
Authors: Girish Vishruth , Lakhani Asad A. , Thompson Sarah L. , Scaduto Christine M. , Brown Leanne M. , Hagenson Ryan A. , Sausville Erin L. , Mendelson Brianna E. , Kandikuppa Pranav K. , Lukow Devon A. , Yuan Monet Lou , Stevens Eric C. , Lee Sophia N. , Schukken Klaske M. , Akalu Saron M. , Vasudevan Anand , Zou Charles , Salovska Barbora , Li Wenxue , Smith Joan C. , Taylor Alison M. , Martienssen Robert A. , Liu Yansheng , Sun Ruping , Sheltzer Jason M.
Published: July 2023

Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrate that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of
MDM4
and suppresses p53 signaling, and we show that
TP53
mutations are mutually exclusive with 1q aneuploidy in human cancers. Thus, tumor cells can be dependent on specific aneuploidies, raising the possibility that these “aneuploidy addictions” could be targeted as a therapeutic strategy.
Dearomative ring expansion of thiophenes by bicyclobutane insertion
Authors: Wang Huamin , Shao Huiling , Das Ankita , Dutta Subhabrata , Chan Hok Tsun , Daniliuc Constantin , Houk K. N. , Glorius Frank
Published: July 2023

Skeletal ring enlargement is gaining renewed interest in synthetic chemistry and has recently focused on insertion of one or two atoms. Strategies for heterocyclic expansion through small-ring insertion remain elusive, although they would lead to the efficient formation of bicyclic products. Here, we report a photoinduced dearomative ring enlargement of thiophenes by insertion of bicyclo[1.1.0]butanes to produce eight-membered bicyclic rings under mild conditions. The synthetic value, broad functional-group compatibility, and excellent chemo- and regioselectivity were demonstrated by scope evaluation and product derivatization. Experimental and computational studies point toward a photoredox-induced radical pathway.
Altering Earth in our image
Human Footprint
Day’s Edge Productions
PBS, Wednesdays, 5 July to 9 August 2023, 9 p.m. EST (check local listings)
Authors: Hannibal Mary Ellen
Published: July 2023

A new documentary series traces humanity’s profound effects on the world around us