bluuebunny/crossref_metadata_2025 huggingface dataset:
A process perspective on the expatriate social capital – knowledge transfer and expatriate adjustment relationships
Authors: Wang Chun-Hsiao , Chen Yu-Ping
Published: March 2024

Purpose

The purpose of this study is to develop a conceptual model explicating the development of expatriate social capital and its influence on expatriate effectiveness in terms of knowledge transfer and adjustment. Drawing upon social capital theory and weak tie theory, we elucidate the process through which expatriate social capital facilitates expatriate knowledge transfer and adjustment via greater access of role information and social support.

Design/methodology/approach

This study reviews and distills research on expatriate social capital development and proposes a conceptual model of expatriate effectiveness and suggests potential research avenues for global mobility scholars.

Findings

This study contributes to the understanding of the development of expatriate social capital in the host country and its impacts on expatriate effectiveness as a process. With regard to expatriates’ social capital accumulation, this study also highlights the important but less-known role of accompanying spouse/family members as expatriates’ weak tie enablers. We articulate a framework that outlines the sources of social capital for expatriates and the processes through which social capital transmits (via expatriates’ access to role information and social support) and then enhances expatriate effectiveness. This conceptual model aims to establish a basic “roadmap” for use by practitioners and researchers.

Research limitations/implications

Before the proposed conceptual model can be theoretically refined or extended by future research, its veracity needs to be tested empirically. Although we do not incorporate “time,” “personal characteristics” and “context” in our model, we recognize their potential importance and urge future researchers to incorporate them in studying the role of social capital on expatriate effectiveness.

Practical implications

A conceptual model is presented that enables multinational corporations (MNCs) to map their current (and future) strategies to enhance expatriate effectiveness by further strengthening the expatriate social capital.

Originality/value

Drawing upon social capital theory and weak tie theory, this paper links various sources of expatriate social capital to expatriates’ access to role information and social support in supporting expatriate effectiveness. From this, several avenues of future research are drawn.
Law enforcement perceptions of job stress and barriers to supportive resources when working child sexual abuse cases in the southern United States
Authors: Nichols Lisa , Bowen Kendra N.
Published: March 2024

Purpose

The purpose of this paper was to examine law enforcement officers' perspectives on job stress and barriers to supportive resources when working child sexual abuse cases in a large southern state. It is well documented in the literature that professionals who work in healthcare, emergency services and law enforcement face tremendous amounts of stress and consequences to their physical and mental health. Little research has been done to examine how child sexual abuse investigations impact law enforcement, and how these specialized officers perceive access to supportive resources.

Design/methodology/approach

This qualitative study was part of a larger quantitative study and included 20 law enforcement officers who participated in anonymous, semi-structured phone interviews.

Findings

Findings included (1) child sexual abuse cases are difficult, specialized and disturbing (2) barriers to supportive resources include law enforcement culture, the stigma of asking for help, awareness and accessibility of resources and leadership as gatekeeper to the resources and (3) officers perceive both formal and informal resources to be helpful and at best should be proactively available to all officers in the state. A model of the findings was developed to illustrate the implications for practitioners and scholars.

Research limitations/implications

This study was not without weaknesses, specifically the small number of participants, volunteer sampling does not represent the general population and the sampling technique means some demographics may have been missed by researchers.

Practical implications

This study adds to the literature on law enforcement mental health, occupational health and mental health resources. It confirms established research in the literature and provides insight into officer perspectives about barriers that prevent access to informal and formal supports that could improve their emotional well-being.

Originality/value

This study is the first of its kind, to our knowledge, that asks detectives and investigators of child abuse cases about mental health resources. These law enforcement officers are at high-risk for traumatic stress, compassion fatigue and burnout due to the specialized cases they investigate.
Phylogeographic incongruence between two related Geranium species with divergent habitat preferences in East Asia
Authors: Kurata Seikan , Sakaguchi Shota , Hirota Shun K. , Kurashima Osamu , Suyama Yoshihisa , Ito Motomi
Published: March 2024

Plant species with overlapping distributions are expected to experience the same historical events. In contrast, species with different preferred habitat types may exhibit incongruent phylogeographic patterns because of their habitat‐dependent demographic changes in spite of their overlapping distributions. On the western side of the Japanese Archipelago, boreal forest and non‐forest vegetation were dominant during the last glacial period; subsequently, temperate forests expanded, and open vegetation (e.g., grasslands) decreased. Such vegetation shifts can result in incongruent phylogeographic patterns among temperate forest and grassland species; however, few phylogeographic studies have investigated this hypothesis. Here, we evaluated the phylogeographic structure of two related Geranium species that occur in grassland (Geranium krameri) and temperate forest (Geranium shikokianum) habitats using chloroplast genome sequencing and nuclear genome‐wide single‐nucleotide polymorphisms genotyping. The phylogeographic structure was stronger for the temperate forest species than the grassland species, despite its currently scattered distribution for grassland species. The observed patterns indicate that the phylogeographic histories of these species were influenced by their habitat configurations since the last glacial period. During the ice age, grasslands in Japan were much more widespread than today; this would have enabled the grassland species to form a continuous distribution, leading to low divergence among regional populations. In contrast, the significant genetic divergence within the forest species can be attributed to the glacial isolation of regional populations. Our genetic results suggest that vegetation transitions have variously controlled the population dynamics of two species with overlapping distributions.
The ectomycorrhizal fungus Paxillus ammoniavirescens influences the effects of salinity on loblolly pine in response to potassium availability
Authors: Rose Benjamin D. , Dellinger Marissa A. , Larmour Clancy P. , Polishook Mira I. , Higuita‐Aguirre Maria I. , Dutta Summi , Cook Rachel L. , Zimmermann Sabine D. , Garcia Kevin
Published: March 2024

Salinity is an increasing problem in coastal areas affected by saltwater intrusion, with deleterious effects on tree health and forest growth. Ectomycorrhizal (ECM) fungi may improve the salinity tolerance of host trees, but the impact of external potassium (K+) availability on these effects is still unclear. Here, we performed several experiments with the ECM fungus Paxillus ammoniavirescens and loblolly pine (Pinus taeda L.) in axenic and symbiotic conditions at limited or sufficient K+ and increasing sodium (Na+) concentrations. Growth rate, biomass, nutrient content, and K+ transporter expression levels were recorded for the fungus, and the colonization rate, root development parameters, biomass, and shoot nutrient accumulation were determined for mycorrhizal and non‐mycorrhizal plants. P. ammoniavirescens was tolerant to high salinity, although growth and nutrient concentrations varied with K+ availability and increasing Na+ exposure. While loblolly pine root growth and development decreased with increasing salinity, ECM colonization was unaffected by pine response to salinity. The mycorrhizal influence on loblolly pine salinity response was strongly dependent on external K+ availability. This study reveals that P. ammoniavirescens can reduce Na+ accumulation of salt‐exposed loblolly pine, but this effect depends on external K+ availability.
The backlash against free movement: Does EU‐internal migration fuel public concerns about immigration?
Authors: STOETZER LUKAS F. , KROH MARTIN , DASEY LEONARD
Published: March 2024

The free movement of people is a fundamental principle of the European Union (EU) that has led to an increase in EU‐internal migration. This study investigates the impact of increased immigration to Germany resulting from the 2004 and 2007 eastern enlargement of the EU on concerns about immigration within the German population. By merging 20 years of annual migration statistics with panel data on individual attitudes and exploiting exogenous variation in the gradual enlargement of the free movement policy, we examine the causal effects of EU‐internal migration on immigration concerns. Our findings suggest that the influx of immigrants from new member states did not have a clear average effect on concerns about immigration, but increased concerns among German natives with materialist‐survival values. The study provides insights into the societal division caused by opposition to immigration as part of the European integration process.
Long‐term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre
Authors: Hsieh Michael Ti , Shakespeare Thomas Philip , Winkley Lauren , Goonetilleke Daniel , Yap Shaun Zheng Liang , Tahir Abdul Rahim Mohd
Published: March 2024

Introduction

Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long‐term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines.

Methods

All consecutive patients treated with the VMAT technique for curative‐intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan–Meier estimates of locoregional control, distant metastasis‐free survival, disease‐free survival, anal cancer‐specific survival and overall survival were obtained.

Results

In total, 44 patients were analysed. The median follow‐up was 48.9 months (Range 7.8–107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan–Meier estimates for locoregional control, distant metastasis‐free survival, disease‐free survival, anal cancer‐specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment‐related deaths. The 5 ‐year colostomy‐free survival rate was 86.4%.

Conclusion

Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.
Are multiple projections necessary when assessing umbilical venous catheter placement in neonates? A retrospective study
Authors: Yeoh Melanie , Erickson Jonathan , Desai Saumil , Hazeldine Beth , Thomas Rebecca , Gibson Craig , Powers Neil , Falkner Nathalie
Published: March 2024

Introduction

There is variability in clinical practice regarding the number of radiographic views required to accurately determine umbilical venous catheter (UVC) tip position. Some units prefer performing a single anteroposterior (AP) view and others do both AP and lateral views. The aim of this study was to compare the need for one versus two radiographical views to accurately determine UVC tip position.

Methods

Radiographs of 382 infants (all gestations) from two level six neonatal units were included in the study. Patients with congenital anomalies and those who had adjustment of UVC position between AP and lateral films being performed were excluded. Six clinicians reviewed anonymized AP only images and documented UVC tip position. Subsequently, they reviewed both AP and lateral views and again documented the UVC tip position. Results were compared to the expert consensus which was taken from the consensus of two paediatric radiologists.

Results

The study population had a mean gestational age of 32.8 weeks and birth weight of 2190 g, with 58% males. The UVC tip positions were accurately determined 76% times by the AP view alone and 82% times by using both the AP and lateral views (P < 0.001). The low placed UVC tip position which is the most inappropriate for use was more accurately determined by two images (78% times) rather than single image (70% times) (P < 0.001).

Conclusions

Utilising both AP and lateral views was superior in accurately determining UVC tip position to AP view alone.
Hydroxychloroquine had neutral effect on long‐term risk of malignancy in rheumatoid arthritis patients: A population‐based retrospective cohort study
Authors: Hou Xiu‐Juan , Chang Renin , Wang Yu‐Hsun , Kang Tian‐Lun , Wei James Cheng‐Chung
Published: March 2024

Background

The cancer risk in rheumatoid arthritis (RA) patients has been discussed. Hydroxychloroquine (HCQ) may exert protective effects against malignancy. The study investigated the association between HCQ use and the risk of subsequent malignancy in RA patients.

Methods

Catastrophic illness certificated RA patients were extracted from the National Health Insurance Research Database. The index date was set 180 days after the RA diagnosis date to avoid immortal time bias. Two groups were matched in a 1‐to‐1 ratio by propensity score regarding age, gender, index date, relevant comorbidities, and comedication. HCQ users prior to the diagnosis of RA were exempted to ensure compliance with the new‐user design. Cancers diagnosed before or less than 180 days after the index date were excluded to mitigate protopathic bias. The study adopted the Kaplan–Meier curve and Cox proportional hazards model to examine the association between HCQ use and cancer risk. The assumption of proportional hazard was also tested.

Results

Based on strict criteria, we included 492 eligible RA patients and divided them into study and control groups (N = 246 in each group). HCQ users exhibited a neutral risk of cancer relative to the controls (adjusted hazard ratio, 0.99; 95% CI, 0.44–2.21, p > .05). The assumption of proportional hazard was not violated.

Conclusion

This study does not observe the effect of using HCQ as a primary regimen to prevent cancer in RA patients. We are assured that HCQ is not associated with an increased risk of subsequent malignancy in RA patients. Further mechanistic research is needed.
Reporting Control Deficiencies in Repeat Internal Audit Engagements*
Authors: Favere‐Marchesi Michael
Published: March 2024

This study examines the reporting of control deficiencies in repeat internal audit engagements. Experienced internal auditors were presented with a hypothetical case in which they were asked about the likelihood of reporting an internal control deficiency discovered last year but which was, “through an oversight,” not reported to company management. The study varies whether the deficiency is an operational control or an internal control over financial reporting and who identified but failed to report the deficiency last year (either the participant, the participant's colleague whom they like and admire, or a colleague whom they neither like nor dislike). The results show that internal auditors are less likely to report an operational deficiency (versus a financial reporting deficiency) in the current year that was not reported last year. Further, internal auditors are less likely to report a control deficiency in the current year when they themselves or a colleague they like and admire (versus a colleague they feel neutral about) failed to report it last year.
Impact of feeding native Caatinga pasture on the rumen histomorphometry of sheep raised in semi‐extensive management
Authors: Leite Eglésia Rodrigues , Conde Júnior Aírton Mendes , Fonseca Clarisse Maria Barbosa , de Almeida Monteiro Hatawa Melo , de Carvalho Maria Acelina Martins , de Melo Wanderson Gabriel Gomes , Teodoro Ana Lúcia , de Jesus Silva Daniel , da Silva Oliveira Larissa Stefany , Ferraz José Cláudio Barros , de Oliveira Bezerra Dayseanny
Published: March 2024

In the northeastern region of Brazil, sheep and goat farming, encompassing around 20 million animals, is predominantly a subsistence activity. Forage quality plays a crucial role in animal productivity, posing a complex interplay between plant and animal aspects. The Caatinga biome, vital for livestock in the region, serves as a significant source for animal diet through pastures. This study aimed to conduct a histomorphometric evaluation of sheep rumens in a semi‐extensive system, comparing those feeding on native Caatinga pastures to those on cultivated pastures. Histological processing followed standard protocols, with morphometry focusing on six viable rumen papillae and the submucosa and muscular layer thickness. Statistical correlation analysis revealed morphological differences in papillae across various rumen regions. Morphometric data indicated no significant difference in papillae area between the groups, with average values in Group A surpassing those in Group B, except for width. This study establishes a morphological and morphometric pattern for rumen regions linked to diet types—native or cultivated. The findings not only enhance understanding of the dietary foundation in the Caatinga's extensive system, but also contribute valuable insights for formulating nutritional strategies to enhance sheep production in the region. This research sheds light on the intricacies of forage‐based animal nutrition, particularly in semi‐extensive systems, offering a foundation for future studies and practices to optimise livestock management in the northeastern Brazilian context.
Complexity of surgery and treatment burden in patients with peritoneal malignancy is not determined by addition of hyperthermic intraperitoneal chemotherapy
Authors: Steffens Daniel , Ansari Nabila , Koh Cherry , Ahmadi Nima , Solomon Michael J. , Hogan Sophie , Karunaratne Sascha , Anderson Teresa , Harvey Kiel , McBride Kate , Moran Brendan
Published: March 2024

Background

This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non‐parametric tests and log‐rank test was used to compare survival curves.

Results

403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed.

Conclusions

The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings ‘intention to treat’ with CRS and HIPEC should be the basis for resource allocation and funding.
Pathogenesis of MASLD and MASH – role of insulin resistance and lipotoxicity
Authors: Bansal Shalini K. , Bansal Meena B.
Published: March 2024

Background

Insulin resistance and lipotoxicity are extremely interconnected but fundamental in setting the stage for the development of MASLD/MASH.

Aim/Methods

A comprehensive literature search was performed and key themes were synthesised to provide insight into the underlying molecular mechanisms of insulin resistance and lipotoxicity in the liver, muscle, pancreas and adipose tissue and how organ cross‐talk is fundamental to driving disease pathogenesis.

Results

Classical thinking postulates that excess FFA load exceeds the storage capacity of adipose tissue, which is predicated upon both genetic and environmental factors. This results in insulin resistance and compensatory hyperinsulinaemia by pancreatic beta cells to overcome target organ insulin resistance. As adipocyte dysfunction worsens, not only are excess FFA delivered to other organs, including skeletal muscle, pancreas and liver but a pro‐inflammatory milieu is established with increases in IL‐6, TNF‐α and changes in adipokine levels (increased leptin and decreased adiponectin). With increased intramuscular lipid accumulation, lipotoxic species decrease insulin signalling, reduce glucose uptake by downregulation of GLUT4 and decrease glycogen synthesis. With this additional reduced capacity, hyperglycaemia is further exacerbated and increased FFA are delivered to the liver. The liver has the largest capacity to oxidise fat and to adapt to these stressors and, therefore, has become the last line of defence for excess lipid storage and utilisation, the capacity of which may be impacted by genetic and environmental factors. However, when the liver can no longer keep up with increasing FFA delivery and DNL, lipotoxic species accumulate with ensuing mitochondrial dysfunction, increased ER stress, oxidant stress and inflammasome activation, all of which drive hepatocyte injury and apoptosis. The resulting wound healing response, marked by stellate cell activation, drives collagen accumulation, progressive fibrosis, and, ultimately, end organ failure and death. This vicious cycle and complex interplay between insulin resistance, hyperinsulinaemia, lipotoxicity and multi‐directional cross‐talk among different target organs are critical drivers of MASLD/MASH.

Conclusions

Targeting tissue‐specific insulin resistance and hyperinsulinaemia while decreasing FFA load (lipotoxicity) through dietary and lifestyle changes remain the best upstream interventions.
Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application
Authors: Thakur Kanika , Telaprolu Krishna Chaitanya , Paterson Daniel , Salem Farzaneh , Arora Sumit , Polak Sebastian
Published: March 2024

Aims

The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations.

Methods

Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation.

Results

For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0‐t and Cmax ratios were well within 2‐fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0‐t and Cmax ratios were well within 2‐fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83).

Conclusion

The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.
Identification of TMZ resistance‐associated histone post‐translational modifications in glioblastoma using multi‐omics data
Authors: Ye Liguo , Gu Lingui , Wang Yaning , Xing Hao , Li Pengtao , Guo Xiaopeng , Wang Yu , Ma Wenbin
Published: March 2024

Backgroud

Glioblastoma multiforme (GBM) is among the most aggressive cancers, with current treatments limited in efficacy. A significant hurdle in the treatment of GBM is the resistance to the chemotherapeutic agent temozolomide (TMZ). The methylation status of the MGMT promoter has been implicated as a critical biomarker of response to TMZ.

Methods

To explore the mechanisms underlying resistance, we developed two TMZ‐resistant GBM cell lines through a gradual increase in TMZ exposure. Transcriptome sequencing of TMZ‐resistant cell lines revealed that alterations in histone post‐translational modifications might be instrumental in conferring TMZ resistance. Subsequently, multi‐omics analysis suggests a strong association between histone H3 lysine 9 acetylation (H3K9ac) levels and TMZ resistance.

Results

We observed a significant correlation between the expression of H3K9ac and MGMT, particularly in the unmethylated MGMT promoter samples. More importantly, our findings suggest that H3K9ac may enhance MGMT transcription by facilitating the recruitment of the SP1 transcription factor to the MGMT transcription factor binding site. Additionally, by analyzing single‐cell transcriptomics data from matched primary and recurrent GBM tumors treated with TMZ, we modeled the molecular shifts occurring upon tumor recurrence. We also noted a reduction in tumor stem cell characteristics, accompanied by an increase in H3K9ac, SP1, and MGMT levels, underscoring the potential role of H3K9ac in tumor relapse following TMZ therapy.

Conclusions

The increase in H3K9ac appears to enhance the recruitment of the transcription factor SP1 to its binding sites within the MGMT locus, consequently upregulating MGMT expression and driving TMZ resistance in GBM.
Effects of agriculture and nature reserves on avian behavior in northwestern Costa Rica
Authors: Ke Alison , Sollmann Rahel , Frishkoff Luke , Echeverri Alejandra , Zook Jim , Karp Daniel S.
Published: March 2024

Behavioral changes are often animals’ first responses to environmental change and may act as a bellwether for population viability. Nonetheless, most studies of habitat conversion focus on changes in species occurrences or abundances. We analyzed >14,000 behavioral observations across 55 bird species in communities in northwestern Costa Rica to determine how land use affects reproductive, foraging, and other passive kinds of behaviors not associated with either foraging or reproduction. Specifically, we quantified differences in behaviors between farms, privately owned forests, and protected areas and implemented a novel modeling framework to account for variation in detection among behaviors. This framework entailed estimating abundances of birds performing different behaviors while allowing detection probabilities of individuals to vary by behavior. Birds were 1.2 times more likely to exhibit reproductive behaviors in forest than in agriculture and 1.5 times more likely to exhibit reproductive behaviors in protected areas than in private forests. Species were not always most abundant in the habitats where they were most likely to exhibit foraging or reproductive behaviors. Finally, species of higher conservation concern were less abundant in agriculture than in forest. Together, our results highlight the importance of behavioral analyses for elucidating the conservation value of different land uses.
Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin‐A receptor antagonist
Authors: Liu Yun , Wang Wei , Qian Hongjie , Gui Yuzhou , Wang Yating , Song Rong , Chen Qian , Rowinsky Eric , Wang Sheng , Liang Xiaoguang , Gu Kaicun , Zhou Bo , Zhang Weiwei , Zhang Liqin , Yu Chen , Jia Jingying
Published: March 2024

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin‐A (ETA) receptor antagonist, in healthy subjects. The primary objectives of this first‐in‐human phase I study, comprised of single‐ascending‐dose, multiple‐ascending‐dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin‐1 (ET‐1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half‐life (t1/2) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET‐1 concentrations were dose‐proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high‐fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.
Deposited sediment influences occurrence of functional traits of stream fishes
Authors: Hirschler Mallory , Villamagna Amy , Angermeier Paul L. , Laflamme Eric
Published: March 2024

To better understand stream‐fish sensitivity to fine sediment, we documented assemblage‐wide responses by selected traits along a sedimentation gradient. We then discuss the management implications of these ‘dose–response’ relations in the contexts of biotic assessments and conservation of sediment‐sensitive species. We identified a spatial gradient in sediment deposition among streams within the upper Piedmont of the Roanoke River basin in North Carolina and Virginia. We assessed fine‐sediment sensitivity of 81 species based on eight species traits stratified by four attributes: food preference, feeding location, spawning substrate and spawning behaviour. We then ranked each trait and scored each species with respect to its sediment sensitivity. Using data from electrofishing surveys during 2018–2019, we calculated proportional abundances of traits observed at 30 sites throughout the study area and grouped species by their aggregate sensitivity scores. We assessed relations between embeddedness and silt cover and occurrences of species and traits using a combination of regression and ordination approaches. All traits tested responded to embeddedness or silt cover, or both. Feeding traits exhibited the strongest responses to embeddedness, while reproductive traits exhibited the strongest responses to silt cover. Our findings indicate that negative responses of the probability of presence for high‐sensitivity traits to embeddedness and silt cover were linear, with no apparent thresholds. Additionally, proportional abundances of species with multiple high‐sensitivity traits were inversely related to embeddedness and silt cover. Overall, our findings regarding population‐level responses to sedimentation were consistent with our findings for trait‐specific responses. Our analysis of species sensitivity to fine sediment corroborated the patterns we saw in our trait‐specific analyses, indicating that population responses to sedimentation can be predicted from combinations of species traits. The ‘dose–response’ relations we documented may be applicable to managing sediment impacts on fishes, especially in the contexts of biotic assessments and conservation of sediment‐sensitive species.
What Mathematics Content Do Teachers Teach? Optimizing Measurement of Opportunities to Learn in the Classroom
Authors: Zhang Jiahui , Schmidt William H.
Published: March 2024

Measuring opportunities to learn (OTL) is crucial for evaluating education quality and equity, but obtaining accurate and comprehensive OTL data at a large scale remains challenging. We attempt to address this issue by investigating measurement concerns in data collection and sampling. With the primary goal of estimating group‐level OTLs for large populations of classrooms and the secondary goal of estimating classroom‐level OTLs, we propose forming a teacher panel and using an online log‐type survey to collect content and time data on sampled days throughout the school year. We compared various sampling schemes in a simulation study with real daily log data from 66 fourth‐grade math teachers. The findings from this study indicate that sampling 1 day per week or 1 day every other week provided accurate group‐level estimates, while sampling 1 day per week yielded satisfactory classroom‐level estimates. The proposed approach aids in effectively monitoring large‐scale classroom OTL.
Environmental adaptation and genetic variations in geographically isolated Emma field crickets Teleogryllus emma (Orthoptera: Gryllidae)
Authors: Arai Tetsuo , Tanaka (UEDA) Miwa , Arikawa (ANDO) Chiaki , Kiyota Momoko , Masaki Sinzo
Published: March 2024

The Emma field cricket, Teleogryllus emma (Ohmachi & Matsuura), distributed between 43°N and 30°N in the Japanese archipelago, is univoltine and overwinters in the egg stage. Its eggs hatch on the slope of the Oishi Dam (38.03°N, 139.57°E, 160–170 m a.s.l.) in late June, adults begin emerging from late August, and oviposition lasts until early October. Oviposition is limited to the period when the water level of the Oishi Dam is low. The period from egg hatching to adult emergence is approximately 1 month shorter than that of the T. emma population on the Arakawa riverside (38.09°N, 139.57°E, 29 m a.s.l.), which is approximately only 7 km from the Oishi Dam. The egg and body sizes of T. emma on the slope of the Oishi Dam were smaller than those of T. emma on the Arakawa riverside, and the egg and nymphal periods were shorter; these variations were inherited by the next generation of T. emma. The egg period, nymphal period and head width of T. emma on the dam slope correspond to those of the populations near 40°N. Several traits of the T. emma population on the dam slope were naturally selected by adapting to the isolated environment, resulting in the genetic variations. However, their variations were small and the period after isolation is short, suggesting that it is in the early stages of speciation.
Probiotics‐containing beverages and dental caries: A systematic review and meta‐analysis
Authors: Feldmann Alexandra , Eidt Gustavo , Henz Sandra Liana , Arthur Rodrigo Alex
Published: March 2024

The aim was to evaluate the effect of probiotics‐containing beverages on dental caries development by a systematic review and meta‐analysis (PROSPERO CRD42021258010). PubMed, Embase, and Web of Science databases were assessed (up to October 2023) for randomized placebo‐controlled trials that evaluated the consumption of probiotics‐containing beverages having dental caries as endpoint. Risk of bias assessment (Cochrane Handbook) was performed for all studies. Risk ratio (RR), standardized mean difference (SMD) and 95% confidence interval (CI), were calculated for caries prevalence and caries increment, respectively. Meta‐analysis was performed. Qualitative analysis of more than 2000 individuals aged from 1 to 84 years (9 studies) showed inconsistent effects of these probiotics‐containing beverages. Synthesis of more than 1000 children and adolescents did not demonstrate a statistically significant difference in the proportion of individuals with cavitated lesions (RR 0.60 [95 % CI 0.34 to 1.08]; n = 2), but a significantly smaller increment of both cavitated and non‐cavitated carious lesions (SMD −0.23 [95 % CI −0.39 to −0.08]; n = 4) was related to the consumption of probiotics‐containing beverages. Certainty of evidence for caries prevalence and caries increment were moderate and low, respectively. Current evidence is not substantial to strengthen the impact of these beverages on caries development.
Why's it gotta be so complicated: New York's regulation of compensated traditional surrogacy agreements creates a constitutional violation
Authors: Katz Michelle J.
Published: March 2024

New York's Child–Parent Security Act (CPSA) legalized compensated gestational surrogacy and created a simpler way for parents to establish their parental rights when utilizing assisted reproductive technology (ART). While this was a substantial step forward from past antiquated law, the CPSA continues to heavily regulate compensated genetic, otherwise known as traditional, surrogacy making it challenging to use. The CPSA infringes upon the right to procreate by limiting the ART methods available to those wanting to start a family. This Note proposes an amendment to the current CPSA, including the legalization of compensated traditional surrogacy in New York.
LOXL2‐mediated chromatin compaction is required to maintain the oncogenic properties of triple‐negative breast cancer cells
Authors: Serra‐Bardenys Gemma , Blanco Enrique , Escudero‐Iriarte Carmen , Serra‐Camprubí Queralt , Querol Jessica , Pascual‐Reguant Laura , Morancho Beatriz , Escorihuela Marta , Tissera Natalia Soledad , Sabé Anna , Martín Luna , Segura‐Bayona Sandra , Verde Gaetano , Aiese Cigliano Riccardo , Millanes‐Romero Alba , Jerónimo Celia , Cebrià‐Costa Joan Pau , Nuciforo Paolo , Simonetti Sara , Viaplana Cristina , Dienstmann Rodrigo , Oliveira Mafalda , Peg Vicente , Stracker Travis H. , Arribas Joaquín , Canals Francesc , Villanueva Josep , Di Croce Luciano , García de Herreros Antonio , Tian Tian V. , Peiró Sandra
Published: March 2024

Oxidation of histone H3 at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase homolog 2 (LOXL2). This histone modification is enriched in heterochromatin in triple‐negative breast cancer (TNBC) cells and has been linked to the maintenance of compacted chromatin. However, the molecular mechanism underlying this maintenance is still unknown. Here, we show that LOXL2 interacts with RuvB‐Like 1 (RUVBL1), RuvB‐Like 2 (RUVBL2), Actin‐like protein 6A (ACTL6A), and DNA methyltransferase 1associated protein 1 (DMAP1), a complex involved in the incorporation of the histone variant H2A.Z. Our experiments indicate that this interaction and the active form of RUVBL2 are required to maintain LOXL2‐dependent chromatin compaction. Genome‐wide experiments showed that H2A.Z, RUVBL2, and H3K4ox colocalize in heterochromatin regions. In the absence of LOXL2 or RUVBL2, global levels of the heterochromatin histone mark H3K9me3 were strongly reduced, and the ATAC‐seq signal in the H3K9me3 regions was increased. Finally, we observed that the interplay between these series of events is required to maintain H3K4ox‐enriched heterochromatin regions, which in turn is key for maintaining the oncogenic properties of the TNBC cell line tested (MDA‐MB‐231).
Counteracting effects of “hook avoidance” and “hook habituation” on angler catch rates in a catch‐and‐release fishery
Authors: Mosley Camille L. , Dassow Colin J. , Solomon Christopher T. , Jones Stuart E.
Published: March 2024

Catch‐and‐release (C&R) angling is often used to maintain high catch rates but fish vulnerability to capture may decrease following hooking, thereby decreasing angler catch per unit effort (CPUE) (hyperdepletion). To determine if fish post‐capture response affected recapture probability and population‐level CPUE, individual capture histories of Largemouth Bass in two lakes were compared before and after doubling angling effort in a Before‐After Control‐Impact (BACI) analysis. Previous capture and day‐of‐season both affected recapture probability. Counteracting effects of previous capture and reduced late‐season catch rates caused no hyperdepletion of angler CPUE. Our results highlight the complexity of fish behavioral responses to angling and suggest that hyperdepletion of angling catch rates may not be an issue in C&R fisheries.
Delineating Neighborhoods: An Approach Combining Urban Morphology with Point and Flow Datasets
Authors: Govind Anirudh , Poorthuis Ate , Derudder Ben
Published: March 2024

Although neighborhoods are a widely used analytical concept in urban geography, they are often proxied using grids or statistical sectors in empirical research. The rationales underlying these proxies are often separated from the theoretical considerations of what makes a neighborhood a neighborhood, casting shadows over their relevance and applicability. In this article, we identify two specific challenges separating empirical operationalizations from theoretical considerations in neighborhood delineations: (1) not incorporating key built environment elements and (2) monodimensional approaches. We develop a method that addresses this double challenge by (1) creating morphological basic spatial units (BSUs) and (2) aggregating them into neighborhoods using multilayer community detection (MLCD) drawing on datasets used in both formal and functional regionalization approaches. We illustrate this method for the case of Leuven, Belgium, by (1) using street blocks as BSUs and (2) focusing on proximity, land use, and social interactions. Through a comparative analysis, we show that our results align with theoretical considerations and perform as well as, and perhaps better, than statistical sectors and grids as neighborhood representations. We therefore argue that this flexible method can bridge formal and functional regionalization approaches making the case for its adoption in neighborhood delineation exercises.
Access Weight Matrix: A Place and Mobility Infused Spatial Weight Matrix
Authors: Janatabadi Fatemeh , Ermagun Alireza
Published: March 2024

This study introduces the Access Weight Matrix (AWM) to capture the spatial dependence of access across a geographical surface. AWM is a nonsymmetry, nonzero diagonal matrix with elements to be a function of (i) the spatial distribution of places, (ii) the number of places, and (iii) the travel‐time threshold to reach places rather than distance, contiguity, or adjacency. AWM is tested and validated to examine the spatial dependence of transit access to employment opportunities in the City of Chicago. Three observations are noticed. First, the degree of spatial dependence between the access of geographical units is not necessarily proportional to their proximity and is better explained by AWM than traditional spatial weight matrices regardless of the travel‐time threshold. Second, the time‐dependence feature of AWM improves the accuracy of capturing spatial dependence, particularly in short travel‐time thresholds. Third, near geographical units are not necessarily more related than distant geographical units even for access that is proved to be spatially highly correlated with neighboring units. With the increased ease of measuring access, research is expanding to explore the socioeconomic, demographic, and built‐environment correlates of access. AWM can be employed in developing more accurate spatial econometrics models.
Dosing lutetium Lu 177‐dotatate for a hemodialysis patient
Authors: Taylor Lindsay , Meades Richard , Quigley Ann‐Marie , Toumpanakis Christos , Goodlad Catriona , Davenport Andrew
Published: March 2024

Lu177‐dotatate (Lutathera™) is a radioactive drug approved for the treatment of adults with gastro‐entero‐pancreatic neuroendocrine tumors and is predominantly renally excreted. Currently all patients receive 7400 MBq (200 mCi), and there are no guidelines for treating hemodialysis patients. We measured radioactivity prior to and post administration of two cycles of Lu177‐dotatate in a hemodialysis patient, and radiation exposure to staff. We reduced the standard 7400 MBq by 33% for the first cycle and patient radioactivity fell by 40% following postdilution hemodiafiltration started 6 h post dosing, and by 45% for the second cycle and radioactivity fell by 47% with postdilution hemodiafiltration started 5 h post administration. By reducing the initial administered radioactivity, coupled with early dialysis, and choosing postdilution hemodiafiltration we were able to achieve radioactivity retention curves similar to those from patients with normal renal function receiving the standard administration of 7400 MBq.
Oviposition preferences and larval survival of the marsh fritillary butterfly: The adverse impact of grazing
Authors: Johansson Victor , Säwenfalk Demieka Seabrook , Bergman Karl‐Olof , Kindvall Oskar , Askling John , Franzén Markus
Published: March 2024

Species‐rich semi‐natural grasslands have been lost during the last century due to agricultural intensification. This has had large negative consequences for many specialised species, including grassland butterflies. To prevent further loss, management regimes in the remaining grasslands must maintain habitat quality over time, and we therefore need to understand the habitat preferences of specialised species and how different management regimes affect their survival.

We studied the egg‐laying preferences of the threatened marsh fritillary butterfly in relation to host plant properties, microclimate and management (grazing) on Gotland, Sweden. Moreover, we followed the survival of eggs and larvae from 27 egg batches during a period of 8 months (from June 2020 to March 2021) in grazed and ungrazed areas.

We found 92 egg batches in total and the average number of eggs was 184.5. Egg‐laying probability increased with increasing host plant size and abundance, and environmental variables associated with a warm microclimate (low grass cover, low vegetation height and south‐facing edges). The 27 egg batches that were followed over time had on average 203 eggs in June. Roughly 28% of the eggs developed into larvae, and about 17% of these survived over the entire study period, resulting in an overall 4.7% survival. Egg survival was higher in ungrazed habitats compared with grazed; in March (post‐hibernation), there were almost nine times more eggs in ungrazed habitats.

This study highlights the complex habitat ecology of specialised butterflies and underscores the detrimental impact of intense grazing, advocating for rotational grazing or mowing regimes.