bluuebunny/crossref_metadata_2025_split huggingface dataset:
Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study
Authors: Adami Giovanni , Pedrollo Elisa , Rossini Maurizio , Fassio Angelo , Braga Vania , Pasetto Emma , Pollastri Francesco , Benini Camilla , Viapiana Ombretta , Gatti Davide 
Published: February 2024

Abstract

Background
Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).

Methods
We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (&gt;2 years) or continuing ongoing denosumab alone (&gt;2 years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6 months.

Results
Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change.

Conclusion
Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.
Glandular doses and diagnostic reference levels (DRLs) for Saudi breast cancer screening programme (2012–2021)
Authors: Albeshan Salman M , Alhulail Ahmad A , Almuqbil Maha M 
Published: February 2024

Abstract
The aim of this study was to report the diagnostic reference levels (DRLs) corresponding to different compressed breast thickness (CBT) ranges. To achieve this, mammographic examinations with 187,788 exposures were analysed. The mean average glandular (AGD) dose was calculated per view, examination, and center. Moreover, the DRL values corresponding to different CBT ranges were reported. The result of the mean AGD per view was found to be 1.36 mGy for craniocaudal (CC) and 1.54 mGy for Mediolateral oblique (MLO), while the mean AGD per examination for all women was 1.45 mGy. The DRL values corresponding to CBTs between 20 to 79 mm ranges were below 2 mGy. These results were from a population of mean age = 49 ± 8 years and mean CBT = 58 ± 8 mm, and was imaged with mean exposures of 29 ± 1 kVp and 74 ± 31 mAs, and a mean compression force of 135±37 N. In conclusion, good mammography practice has been shown, as DRL values are within the limits suggested by the international organizations.
Measurement of Hp(10), Hp(3) and Hp(0.07) to medical staff in endoscopic retrograde cholangiopancreatography, using thermoluminescence dosimetry
Authors: ZarifSanayei Ava , Sina Sedigheh 
Published: February 2024

Abstract
Endoscopic retrograde cholangiopancreatography (ERCP) is widely used in the diagnosis and treatment of pancreatic and bile duct disorders. The procedure is performed under the guidance of fluoroscopy. This study aims to investigate the dose received by staff in the Endoscopy Department of AbuAli Sina Medicine and Organ Transplant Hospital in Shiraz. The dosimetry was performed using thermoluminescent dosemeters (TLD), type TLD-100. The values of Hp(10), Hp(3) and Hp(0.07) were estimated for the staff for 2 months. According to the results obtained in this study, the equivalent dose of the gastroenterologist’s body, eye lenses and hands was 0.045 ± 0.001 mSv, 0.111 ± 0.014 mSv and 0.357 ± 0.034 $\mathrm{mSv}$, respectively. This study showed that the annual radiation exposure for ERCP department staff of Abu Ali Sinai Hospital is less than the annual dose limit. However, if the principles of proper radiation protection and individual dosimetry are followed, the dose to staff members can be reduced.
Teaching schools to compete: the case of Swedish upper secondary education
Authors: Arora-Jonsson Stefan , Edlund Peter 
Published: February 2024

Abstract
Significant efforts have been made to promote competition in public service sectors, expanding the reach of competition into non-economic fields. Surprisingly little is, however, known about the process by which competition is introduced into such settings. We examine this process, focusing on a Swedish municipality’s efforts to implement competition for students among its schools. By incorporating recent theoretical advancements regarding competition as an organized relationship, and utilizing a combination of qualitative and quantitative data, we shed light on the organizational efforts undertaken by politicians and bureaucrats to teach their schools to compete. We find that introducing competition can be complex, time-consuming and that it requires substantial organizational commitment. We highlight the existence of varying perceptions of competition among different stakeholders following its introduction. These findings suggest the need for future research that addresses questions about the costs of, and interests behind, introducing competition, as well as questions about responsibility for the subsequent effects of competition.
Prisons and Pollution: A Nationwide Analysis of Carceral Environmental Inequality
Authors: Greenberg Pierce , Perdue Robert Todd 
Published: February 2024

AbstractThe disproportionate exposure of incarcerated populations to environmental harms is an emerging area of interest among scholars and activists. Existing research has illuminated these intersecting systems of inequality with broad theorization and case study examples of prisons and jails located near environmental hazards. However, there are few nationwide assessments of carceral environmental inequality—studies examining whether prison communities in the United States are disproportionately located near environmental harms. Our paper examines the influence of prison proximity on four measures of environmental harm to test whether carceral environmental inequality exists in the United States at the census tract level. Multi-level regression models—which account for the nested nature of census tracts within both counties and states—find that (1) closer proximity to a prison is associated with higher levels of pollution across all measures of environmental harm, and (2) that trend is mostly driven by proximity to county jails rather than state or federal prisons. We suggest that these trends may be driven by complex prison and pollution siting patterns. Our paper concludes by discussing the implications of these findings for future research on carceral environmental inequality.
Assessing the mitochondrial safety profile of the molnupiravir active metabolite, β-d-N4-hydroxycytidine (NHC), in the physiologically relevant HepaRG model
Authors: Kiy Robyn T , Khoo Saye H , Chadwick Amy E 
Published: February 2024

Abstract

Background
β-d-N4-Hydroxycytidine (NHC) is the active metabolite of molnupiravir, a broad-spectrum antiviral approved by the MHRA for COVID-19 treatment. NHC induces lethal mutagenesis of the SARS-CoV-2 virus, undergoing incorporation into the viral genome and arresting viral replication. It has previously been reported that several nucleoside analogues elicit off-target inhibition of mitochondrial DNA (mtDNA) or RNA replication. Although NHC does not exert these effects in HepG2 cells, HepaRG are proven to be advantageous over HepG2 for modelling nucleoside analogue-induced mitochondrial dysfunction. Therefore, the objective of this work was to assess the mitotoxic potential of NHC in HepaRG cells, a model more closely resembling physiological human liver.

Methods
Differentiated HepaRG cells were exposed to 1–60 μM NHC for 3–14 days to investigate effects of sub-, supra-, and clinically-relevant exposures (in the UK, molnupiravir for COVID-19 is indicated for 5 days and reported Cmax is 16 μM). Following drug incubation, cell viability, mtDNA copy number, mitochondrial protein expression, and mitochondrial respiration were assessed.

Results
NHC induced minor decreases in cell viability at clinically relevant exposures, but did not decrease mitochondrial protein expression. The effects on mtDNA were variable, but typically copy number was increased. At supra-clinical concentrations (60 μM), NHC reduced mitochondrial respiration, but did not appear to induce direct electron transport chain dysfunction.

Conclusions
Overall, NHC does not cause direct mitochondrial toxicity in HepaRG cells at clinically relevant concentrations, but may induce minor cellular perturbations. As HepaRG cells have increased physiological relevance, these findings provide additional assurance of the mitochondrial safety profile of NHC.
G‐protein‐coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1‐mediated redox modulation
Authors: Wu Teng , Ding Ke , Wang Chun , Lin Guoliang , Xie Chengjie , Chen Xianying , Li Quanxin , Yu Fenghai , Mao Yuling , Hong Wei , Lu Lei , Li Shuai 
Published: February 2024

AbstractAdipose tissue is the second most important site of estrogen production, where androgens are converted into estrogen by aromatase. While gastric cancer patients often develop adipocyte‐rich peritoneal metastasis, the underlying mechanism remains unclear. In this study, we identified the G‐protein‐coupled estrogen receptor (GPER1) as a promoter of gastric cancer peritoneal metastasis. Functional in vitro studies revealed that β‐Estradiol (E2) or the GPER1 agonist G1 inhibited anoikis in gastric cancer cells. Additionally, genetic overexpression or knockout of GPER1 significantly inhibited or enhanced gastric cancer cell anoikis in vitro and peritoneal metastasis in vivo, respectively. Mechanically, GPER1 knockout disrupted the NADPH pool and increased reactive oxygen species (ROS) generation. Conversely, overexpression of GPER1 had the opposite effects. GPER1 suppressed nicotinamide adenine dinucleotide kinase 1(NADK1) ubiquitination and promoted its phosphorylation, which were responsible for the elevated expression of NADK1 at protein levels and activity, respectively. Moreover, genetic inhibition of NADK1 disrupted NADPH and redox homeostasis, leading to high levels of ROS and significant anoikis, which inhibited lung and peritoneal metastasis in cell‐based xenograft models. In summary, our study suggests that inhibiting GPER1‐mediated NADK1 activity and its ubiquitination may be a promising therapeutic strategy for peritoneal metastasis of gastric cancer.
Correlations of 2 Novel Inflammation Indexes With the Risk for Early Neurological Deterioration in Acute Ischemic Stroke Patients After Intravenous Thrombolytic Therapy
Authors: Wang Nuo , Wang Ling , Zhang Minmin , Deng Benqiang , Wu Tao 
Published: February 2024

Objectives:
Elevation of the systemic immune inflammation (SII) index and system inflammation response index (SIRI) is known to be associated with higher risk of stroke and all-cause death. However, no study has reported their correlation with early neurological deterioration (END) following recombinant tissue-type plasminogen activator (IV-rtPA) in acute ischemic stroke patients. The aim of this study was to explore the correlation of SII and SIRI with the risk of END after IV-rtPA.

Methods:
Included in this study were 466 consecutive patients treated with IV-rtPA. SII and SIRI were calculated according to blood cell counts before IV-rtPA. Patients were divided into 3 groups based on trisectional quantiles according to SII and SIRI values. The risk of END was assessed by multivariate regression. The overall discriminative ability of SII and SIRI in predicting END was assessed by receiver operating characteristic curve analysis.

Results:
Of the 466 included patients, 62 (13.3%) were identified as having END. Compared with the first tertile of SII, multivariable regression analysis demonstrated that patients were more likely to have END (odds ratio 2.54; 95% CI: 1.23-5.23) and poor outcome at 90 days (odds ratio 2.02; 95% CI: 1.06-3.86) in third tertile after adjustment for potential confounders. In addition, a cutoff value of 591.63 for SII was detected in predicting post-thrombolysis END with a sensitivity of 58.1% and a specificity of 64.6% (area under the curve 0.61; 95% CI: 0.54-0.69).

Conclusions:
Higher SII but not SIRI may prove to be a predictor for high risk of END and a poor functional outcome at 90 days after IV-rtPA.
The evolutionary age-range size relationship is modulated by insularity and
dispersal in plants and animals
Authors: Alzate Adriana , Rozzi Roberto , Velasco Julian A. , Robertson D. Ross , Zizka Alexander , Tobias Joseph A. , Hill Adrian , Bacon Christine D. , Janzen Thijs , Pellissier Loïc , van der Plas Fons , Rosindell James , Onstein Renske E. 
Published: February 2024

Abstract
Earth is home to millions of plant and animal species, with more than 40
thousand species facing extinction worldwide (Diaz et al. 2019). Species’ range
size is particularly important in this context because it influences extinction
risk (Purvis et al. 2000, Gaston & Fuller 2009), but the causes underlying
the wide natural variation in range size remain poorly known. Here, we
investigate how evolutionary age is related to present-day range size for over
25,000 species of mammals, birds, reptiles, amphibians, reef fishes, and plants.
We show that, on average, older species have significantly larger ranges, but
the effect of age on range size is modulated by clade, geographical context and
dispersal ability. Specifically, age does not affect range size for island
species, because islands limit dispersal and hence range size, regardless of
species age. Furthermore, species from clades with high dispersal capabilities
obtain large ranges faster, thereby further neutralizing the relationship
between age and range size. Our results can help supporting global conservation
priorities, by showing that species that are young, occupy islands, and/or are
dispersal limited often have small ranges and therefore increased extinction
risk.
Environmental DNA from ethanol eluent of flowers reveals a widespread diversity in cowpea associated animal communities in Hainan Island
Authors: Chen Qi , Yu Huai-Liang , Lv Jun-Xian , Wang Xing , Li Jin , Wu Ming-Yue , Shi Cai-Hua , Xie Wen , Kong Xiang-Yi , Huang Guo-Hua 
Published: February 2024

AbstractCowpea (Vigna unguiculata(L.) Walp.), as an economical crop, is one of the important pillar industries of rural revitalization strategy in China. However, cowpea planting in China is often infested and damaged by many insects during growth, especially in Hainan region with a warm and wet tropical climate. Traditional monitoring methods with technical limitation could only detect a few common significant agricultural pests, how many kinds of species associated with cowpea is unknown. Here, we employed environmental DNA (eDNA) metabarcoding to characterize cowpea associated animal community-level diversity among six planting areas in Hainan. In all, 62 species were detected, of which 99.05% was Arthropoda, suggesting that Arthropods are the main groups interacting with cowpea. Moreover, we also detected 28 pests on cowpea, predominantly belonging to Thysanoptera, Lepidoptera, Diptera and Hemiptera, of which 20 pests were first reported and need more extra attention. Furthermore, clustering results indicated that there is a certain diversity of cowpea associated animals in different regions of Hainan, but the species composition was similar in the large planting areas due to the indiscriminate use of pesticides, which need further develop scientific pesticide applications to ensure adequate species diversity. This study represents the first molecular approach to investigate the cowpea associated animal communities and provides basic information for further scientific pesticide applications.
Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair
Authors: Saul Dominik , Doolittle Madison L. , Rowsey Jennifer L. , Froemming Mitchell N. , Kosinsky Robyn L. , Vos Stephanie J. , Ruan Ming , LeBrasseur Nathan , Chandra Abhishek , Pignolo Robert , Passos João F. , Farr Joshua N. , Monroe David G. , Khosla Sundeep 
Published: February 2024

ABSTRACTCells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells are key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings establish contextual roles of p21+vsp16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.
Visualizing sarcomere and cellular dynamics in skeletal muscle to improve cell therapies
Authors: Hüttemeister Judith , Rudolph Franziska , Radke Michael H. , Fink Claudia , Friedrich Dhana , Preibisch Stephan , Falcke Martin , Wagner Eva , Lehnart Stephan E. , Gotthardt Michael 
Published: February 2024

AbstractThe giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin’s Z-disk to study skeletal muscle development and remodeling. We find titin’s integration into the sarcomere tightly regulated and its unexpected mobility facilitating a homogenous distribution of titin after cell fusion – an integral part of syncytium formation and maturation of skeletal muscle. In adult mCherry-titin mice, treatment of muscle injury by implantation of titin-eGFP myoblasts reveals how myocytes integrate, fuse and contribute to the continuous myofilament system across cell boundaries. Unlike in immature primary cells, titin proteins are retained at the proximal nucleus and do not diffuse across the whole syncytium with implications for future cell-based therapies of skeletal muscle disease.
A Comprehensive Benchmarking Study on Computational Tools for Cross-omics Label Transfer from Single-cell RNA to ATAC Data
Authors: Wang Yuge , Zhao Hongyu 
Published: February 2024

AbstractWith continuous progress of single-cell chromatin accessibility profiling techniques, scATAC-seq has become more commonly used in investigating regulatory genomic regions and their involvement in developmental, evolutionary, and disease-related processes. At the same time, accurate cell type annotation plays a crucial role in comprehending the cellular makeup of complex tissues and uncovering novel cell types. Unfortunately, the majority of existing methods primarily focus on label transfer within scRNA-seq datasets and only a limited number of approaches have been specifically developed for transferring labels from scRNA-seq to scATAC-seq data. Moreover, many methods have been published for the joint embedding of data from the two modalities, which can be used for label transfer by adding a classifier trained on the latent space. Given these available methods, this study presents a comprehensive benchmarking study evaluating 27 computational tools for scATAC-seq label annotations through tasks involving single-cell RNA and ATAC data from various human and mouse tissues. We found that when high quality paired data were available to transfer labels across unpaired data, Bridge and GLUE were the best performers; otherwise, bindSC and GLUE achieved the highest prediction accuracy overall. All these methods were able to use peak-level information instead of purely relying on the gene activities from scATAC-seq. Furthermore, we found that data imbalance, cross-omics dissimilarity on common cell types, data binarization, and the introduction of semi-supervised strategy usually had negative impacts on model performance. In terms of scalability, we found that the most time and memory efficient methods were Bridge and deep-learning-based algorithms like GLUE. Based on the results of this study, we provide several suggestions for future methodology development.
Effects of inbreeding and elevated rearing temperatures on strategic sperm production
Authors: Chung Meng-Han Joseph , Mahmud-Al-Hasan Md , Jennions Michael D. , Head Megan L. 
Published: February 2024

AbstractMales often strategically modify their rate of sperm production based on the social context, but it remains unclear how environmental and genetic factors shape this plasticity. In freshwater ecosystems, high ambient temperatures often lead to isolated pools of hotter water in which inbreeding occurs. Higher water temperatures and inbreeding can impair fish development, potentially disrupting sperm production. We used guppies (Poecilia reticulata) to investigate how developmental temperature (26 °C or 30 °C) and male inbreeding status (inbred, outbred) influence sperm production in the absence or presence of a female (i.e., sperm priming response). We also tested if sperm priming was affected by whether the female was a relative (sister), and whether she was inbred or outbred. A higher rearing temperature had no effect on the rate of sperm production or the priming response. Inbred males produced significantly more sperm in the presence of an unrelated, outbred female than when no female was present. Conversely, outbred males did not alter sperm production in response to female presence or relatedness. In addition, inbred males showed marginally greater sperm production when exposed to an unrelated female that was outbred rather than inbred, but no difference when exposed to an inbred female that was unrelated versus related. Together, only inbred males increased sperm production in response to the presence of a female, but this depended on her being outbred. This suggests stronger sexual selection on inbred males to allocate ejaculate resources, perhaps due to greater benefits when mating with outbred females in better condition.