bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan
Authors: Takahashi Naoto , Kondo Takeshi , Ikari Yuji , Fukumoto Yoshihiro , Hatake Kiyohiko , Masunari Akira , Nishibayashi Seiji , Kageyama Akiko , Fukuta Yasuhiko , Tojo Arinobu
Published: May 2024

Background

In September 2016, ponatinib was approved in Japan for the treatment of patients with chronic myeloid leukemia with resistance/intolerance to prior tyrosine kinase inhibitors and patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

Methods

We conducted a post-marketing all-case surveillance to study the safety and efficacy of ponatinib in clinical practice, focusing on arterial occlusive events.

Results

Data from 724 patients were collected for 2 years from the initiation of ponatinib. The arterial occlusive events were reported in 6.49% (47/724) with an exposure-adjusted incidence rate of 6.8/100 person-years. The risks associated with arterial occlusive events were age and comorbidities including hypertension and diabetes. At 104 weeks, the cumulative major molecular response rate in patients with chronic-phase chronic myeloid leukemia was 67.2% and the complete cytogenetic response in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was 80.0%. Furthermore, the estimated 1-year overall survival rate was 98.5% for chronic-phase chronic myeloid leukemia and 68.6% for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Conclusions

This surveillance demonstrated that ponatinib has a favorable safety and efficacy profile in Japanese patients and also showed the necessity of closely monitoring arterial occlusive events in older adults and patients with predisposing factors for atherosclerosis.
Cholinesterase as a predictor of skeletal muscle loss after gastrectomy for gastric cancer
Authors: Takano Yasuhiro , Kai Wataru , Kanno Hironori , Hanyu Nobuyoshi
Published: May 2024

Background

Cholinesterase is a classical nutritional and inflammatory marker. The aim of the present study was to evaluate the value of cholinesterase as a predictive marker for postoperative skeletal muscle loss after gastrectomy for gastric cancer.

Methods

The study comprised 68 patients who had undergone gastrectomy for gastric cancer. Skeletal muscle mass was evaluated using skeletal mass index, and major skeletal muscle loss was defined as less than or equal to the median change rate (1-year postoperative/preoperative) of skeletal mass index in all patients. We explored the relationship between postoperative major skeletal muscle loss and disease-free survival and overall survival. Then we investigated the relationship between change rate of skeletal muscle index and serum cholinesterase levels after gastrectomy.

Results

The median value of change rate of skeletal mass index was 0.93. Postoperative major skeletal muscle loss was significantly associated with disease-free survival after gastrectomy (P = 0.003). Although major skeletal muscle loss had worse overall survival, it was not significant (P = 0.058). The change rate of skeletal mass index and cholinesterase had a stronger positive correlation compared with other nutritional indices according to Spearman's rank correlation coefficient (r = 0.438, P ≤ 0.001).

Conclusion

Evaluation of serum cholinesterase levels may be valuable for predicting postoperative skeletal muscle loss after gastrectomy, suggesting the importance of cholinesterase in postoperative nutritional management of patients with gastric cancer.
Treponema pallidum recombinant protein Tp0768 enhances the ability of HUVECs to promote neutrophil chemotaxis through the TLR2/ER stress signaling pathway
Authors: Cao Ting , Li Yue , Zhou Xiangping , Tang Yun , He Bisha , Cao Qian , Hu Yibao , Chen En , Li Yumeng , Xie Xiaoping , Zhao Feijun , Lan Xiaopeng , Liu Shuangquan
Published: May 2024

Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema pallidum remains unknown. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768 (also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1, CXCL2, and CXCL8 (also known as interleukin-8). At the same time, the results show that the Toll-like receptor 2 (TLR2) signaling pathway is activated and that endoplasmic reticulum (ER) stress occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and immunoglobulin-regulated enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress–related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.
Proceedings of the second international meeting on endemic mycoses of the Americas (IMEMA) and first international symposium on implantation mycoses (ISIM)
Authors: Fernandez Norma B , Cáceres Diego H , Serrano Julian A , Bonifaz Alexandro , Canteros Cristina E , Suarez-Alvarez Roberto , Oliveira Rosely Maria Zancope , Cognialli Regielly C R , de Macedo Priscila Marques , Gomez Beatriz L , Tobon Angela M , Taborda Carlos , Chiller Tom , Brunelli Jose Guillermo Pereira , Smith Dallas J , de Melo Teixeira Marcus , Queiroz-Telles Flavio , Garcia-Effron Guillermo , Ardizzoli Karina , Negroni Ricardo , Giusiano Gustavo
Published: May 2024

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25–27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.
The debris of the ‘last major merger’ is dynamically young
Authors: Donlon Thomas , Newberg Heidi Jo , Sanderson Robyn , Bregou Emily , Horta Danny , Arora Arpit , Panithanpaisal Nondh
Published: May 2024

The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the ‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space, because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago. We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data 1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’ did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within the last few Gyr, consistent with the body of work surrounding the VRM.
ComPACT: combined Atacama Cosmology Telescope + Planck galaxy cluster catalogue
Authors: Voskresenskaia S , Meshcheryakov A , Lyskova N
Published: May 2024

Galaxy clusters are the most massive gravitationally bound systems consisting of dark matter, hot baryonic gas, and stars. They play an important role in observational cosmology and galaxy evolution studies. We develop a deep learning model for segmentation of Sunyaev–Zeldovich (SZ) signal on Atacama Cosmology Telescope (ACT) + Planck intensity maps and construct a pipeline for microwave cluster detection in the ACT footprint. The proposed model allows us to identify previously unknown galaxy clusters, i.e. it is capable of detecting SZ sources below the detection threshold adopted in the published galaxy clusters catalogues [such as ACT DR5 and Planck Sunyaev–Zeldovich 2 (PSZ2)]. In this paper, we use the derived SZ signal map to considerably improve a cluster purity in the extended catalogue of Sunyaev–Zeldovich objects from Planck data (SZcat) in the ACT footprint. From SZcat, we create a new microwave galaxy cluster catalogue (ComPACT), which includes 2962 SZ objects with cluster purity conservatively estimated as ≳74–84 per cent. We categorize objects in the catalogue into three categories, based on their cluster reliability. Within the ComPACT catalogue, there are ≳977 new clusters with respect to the ACT DR5 and PSZ2 catalogues.
Extracellular vesicles secreted by cumulus cells contain microRNAs that are potential regulatory factors of mouse oocyte developmental competence
Authors: Fiorentino Giulia , Merico Valeria , Zanoni Mario , Comincini Sergio , Sproviero Daisy , Garofalo Maria , Gagliardi Stella , Cereda Cristina , Lin Chih-Jen , Innocenti Federica , Taggi Marilena , Vaiarelli Alberto , Ubaldi Filippo Maria , Rienzi Laura , Cimadomo Danilo , Garagna Silvia , Zuccotti Maurizio
Published: May 2024

The role of cumulus cells (CCs) in the acquisition of oocyte developmental competence is not yet fully understood. In a previous study, we matured cumulus-denuded fully-grown mouse oocytes to metaphase II (MII) on a feeder layer of CCs (FL-CCs) isolated from developmentally competent (FL-SN-CCs) or incompetent (FL-NSN-CCs) SN (surrounded nucleolus) or NSN (not surrounding nucleolus) oocytes, respectively. We observed that oocytes cultured on the former could develop into blastocysts, while those matured on the latter arrested at the 2-cell stage. To investigate the CC factors contributing to oocyte developmental competence, here we focused on the CCs' release into the medium of extracellular vesicles (EVs) and on their miRNA content. We found that, during the 15-h transition to MII, both FL-SN-CCs and FL-NSN-CCs release EVs that can be detected, by confocal microscopy, inside the zona pellucida (ZP) or the ooplasm. The majority of EVs are <200 nm in size, which is compatible with their ability to cross the ZP. Next-generation sequencing of the miRNome of FL-SN-CC versus FL-NSN-CC EVs highlighted 74 differentially expressed miRNAs, with 43 up- and 31 down-regulated. Although most of these miRNAs do not have known roles in the ovary, in silico functional analysis showed that seven of these miRNAs regulate 71 target genes with specific roles in meiosis resumption (N = 24), follicle growth (N = 23), fertilization (N = 1), and the acquisition of oocyte developmental competence (N = 23). Overall, our results indicate CC EVs as emerging candidates of the CC-to-oocyte communication axis and uncover a group of miRNAs as potential regulatory factors.
TEENA: an integrated web server for transposable element enrichment analysis in various model and non-model organisms
Authors: Li Yuzhuo , Lyu Renzhe , Chen Shuai , Wang Yejun , Sun Ming-an
Published: May 2024

Transposable elements (TEs) are abundant in the genomes of various eukaryote organisms. Increasing evidence suggests that TEs can play crucial regulatory roles—usually by creating cis-elements (e.g. enhancers and promoters) bound by distinct transcription factors (TFs). TE-derived cis-elements have gained unprecedented attentions recently, and one key step toward their understanding is to identify the enriched TEs in distinct genomic intervals (e.g. a set of enhancers or TF binding sites) as candidates for further study. Nevertheless, such analysis remains challenging for researchers unfamiliar with TEs or lack strong bioinformatic skills. Here, we present TEENA (Transposable Element ENrichment Analyzer) to streamline TE enrichment analysis in various organisms. It implements an optimized pipeline, hosts the genome/gene/TE annotations of almost one hundred species, and provides multiple parameters to enable its flexibility. Taking genomic interval data as the only user-supplied file, it can automatically retrieve the corresponding annotations and finish a routine analysis in a couple minutes. Multiple case studies demonstrate that it can produce highly reliable results matching previous knowledge. TEENA can be freely accessed at: https://sun-lab.yzu.edu.cn/TEENA. Due to its easy-to-use design, we expect it to facilitate the studies of the regulatory function of TEs in various model and non-model organisms.
Neural-net-based cell deconvolution from DNA methylation reveals tumor microenvironment associated with cancer prognosis
Authors: Yasumizu Yoshiaki , Hagiwara Masaki , Umezu Yuto , Fuji Hiroaki , Iwaisako Keiko , Asagiri Masataka , Uemoto Shinji , Nakamura Yamami , Thul Sophia , Ueyama Azumi , Yokoi Kazunori , Tanemura Atsushi , Nose Yohei , Saito Takuro , Wada Hisashi , Kakuda Mamoru , Kohara Masaharu , Nojima Satoshi , Morii Eiichi , Doki Yuichiro , Sakaguchi Shimon , Ohkura Naganari
Published: May 2024

DNA methylation is a pivotal epigenetic modification that defines cellular identity. While cell deconvolution utilizing this information is considered useful for clinical practice, current methods for deconvolution are limited in their accuracy and resolution. In this study, we collected DNA methylation data from 945 human samples derived from various tissues and tumor-infiltrating immune cells and trained a neural network model with them. The model, termed MEnet, predicted abundance of cell population together with the detailed immune cell status from bulk DNA methylation data, and showed consistency to those of flow cytometry and histochemistry. MEnet was superior to the existing methods in the accuracy, speed, and detectable cell diversity, and could be applicable for peripheral blood, tumors, cell-free DNA, and formalin-fixed paraffin-embedded sections. Furthermore, by applying MEnet to 72 intrahepatic cholangiocarcinoma samples, we identified immune cell profiles associated with cancer prognosis. We believe that cell deconvolution by MEnet has the potential for use in clinical settings.
Reducing Commercial Tobacco Sales to Youth On and Around California Tribal Reservations With a Reward and Reminder Retail Intervention
Authors: Kornacki Chase , Rodriguez Joseph , Rodriguez Justin , Calac Alec J , Calac Daniel , Lee Juliet P , Moore Roland S , Brucks Lisa , Jacques Isabella , Yang Maxine , Almodovar Veronica , Berber Samantha-Starr
Published: May 2024

Introduction

High prevalence of commercial tobacco product (CTP) use among American Indian and Alaska Native (AI/AN) youth is a public health crisis. A multi-level Tribal-community-based participatory research project under Tribal public health authority implemented a retailer-focused intervention to reduce AI/AN youth CTP use.

Aims and Methods

We sought resolutions in support of a retailer-focused CTP intervention from Tribal Nations organized by a Tribally directed research program. We identified tobacco retail outlets operating on and within five miles of nine Tribal reservations, and CTP products sold at these outlets. We conducted a four-wave Reward and Reminder intervention with apparent minor buyers. Clerks who complied with the law received a modest reward and commendation in social media posts to the local Tribal communities, while clerks who sold without age verification were reminded of the laws.

Results

Of 18 retail outlets selling CTP, eight sold e-cigarettes, and all sold combustible cigarettes. The Reward and Reminder intervention showed an approximate 25% reduction in sales of CTP to apparent minors, with a 33% baseline CTP sales rate without age verification and an 8% intervention CTP sales rate without age verification.

Conclusions

The intervention increased awareness of laws prohibiting CTP sales to minors and mandating age verification for young adults seeking to buy CTP. The intervention, which had support from all governing Tribal Nations, builds the evidence base of effective practices which Tribal public health authorities may utilize to reduce youth access to CTP on and around Tribal reservations.

Implications

Sovereign Tribes have authority over commercial businesses operating on their lands. Tobacco 21 laws aiming to restrict commercial tobacco availability to youth are supported by Tribes. A retailer intervention in which apparent minors attempt commercial tobacco purchases can offer accountability feedback to retailers both on and near Tribal reservations. Obtaining Tribal support and publicizing the interventions helps mobilize Tribal communities to support commercial tobacco prevention and promote healthy youth.
Classifying LEO satellite platforms with boosted decision trees
Authors: Shrive Billy , Pollacco Don , Chote Paul , Blake James A , Cooke Benjamin F , McCormac James , West Richard , Airey Robert , MacManus Alex , Allen Phineas
Published: May 2024

As the cost of reaching LEO (low Earth orbit) has diminished we expect, over the next decade, an almost exponential increase in the numbers of LEO spacecraft from established and potentially new agents. Remote characterization of these and the increasing numbers of decommissioned/debris satellites are thus becoming more important, along with identifying unannounced changes in megaconstellations. In this paper we examine the light curves of known LEO platforms with a boosted tree algorithm in order to determine whether spacecraft properties were discernible. A priori we expected little correlation as we expected the large variations in sight-line geometries would mask signs from the spacecraft. Using large numbers of light curves from the MMT-9 data base, we find that this is not the case and most platforms are statistically identifiable in most sight-lines and tentatively associate this correlation with the differences and similarities between downward facing instruments. Pairs of satellite platforms can be distinguished 86.13 per cent ($N=15\, 600$) of the time using this method. Evolutionary changes to the Starlink satellite platform are also distinguished.
Trade unions and the partisan preferences of their members: Sweden 1986–2021
Authors: Ray Ari A , Pontusson Jonas G
Published: May 2024

Focusing on the effects of union membership on partisan preferences, this article explores how changes in Swedish industrial relations and trade-union politics have affected electoral support for Left parties since the mid-1980s. Our analysis shows that unionization among blue-collar workers has declined sharply since the mid-1990 and that this development has contributed to the decline of electoral support for the Social Democrats and for the Swedish Left as a whole. In addition, we find that the association between union membership and voting for Left parties has declined among white-collar employees without tertiary education as well as blue-collar workers over the same period. We argue that sectoral blue-collar and white-collar unions alike have responded to membership losses and intensified competition between unions by engaging in practices that render the partisan preferences of union members less distinctive than what they used to be (less Left-leaning relative to non-unionized counterparts).
‘The Needs of New Communities’: Social Development, the New Towns, and the Case of Milton Keynes, c. 1962–87
Authors: Fair Alistair
Published: May 2024

This article contributes to the emerging history of ‘community’ in post-war Britain by considering what was known as ‘social development’ in Britain’s new towns, with particular reference to Milton Keynes between the late 1960s and the early 1980s. This article traces the roots of social development in the activities and ideas of the voluntary sector during the 1920s and 1930s and notes how they were co-opted by the state during the 1940s and 1950s. The ‘mark 1’ new towns of that period in some cases took steps to promote social development, understood in terms of an active community life and civic engagement, but the practice was particularly promoted in 1967 by a government committee, which called for new towns to be based on clear social plans as well as physical land-use proposals. In making this argument, the committee reflected a wider train of thought, which had already informed the likes of the Parker Morris report on housing; in essence, they scaled up Parker Morris’ approach from the home to the urban level. These ideas were especially influential in Milton Keynes, whose planners and administrators took a broad, even philosophical view of their role. This article considers the extent to which social development was as much about individual aspiration and opportunity as communal activity and also explores the role of the voluntary sector. In so doing, it makes observations about the nature of the post-war state as an enabler, rather than a universal provider.
RPGRIP1L as a new biomarker for prognosis and tumor immune of breast cancer
Authors: Yi Jianing , Liu Luyao , Chen Yongzhi , Ding Tianjinhao , Fan Peizhi , Yu Jie , Zeng Jie
Published: May 2024

The Retinitis pigmentosa GTPase regulator interacting protein 1‐like (RPGRIP1L) gene encodes an important protein that performs various physiological functions. Variants of RPGRIP1L are related to a number of diseases. However, it is currently unknown whether RPGRIP1L is correlated with breast invasive carcinoma (BRCA). In BRCA tissue specimens, the expression of RPGRIP1L was found to be elevated in comparison to its levels in normal breast tissue. A notable decline in survival rates was associated with patients exhibiting heightened RPGRIP1L gene expression. Consistent with these findings, our data also show the above results. Furthermore, elevated expression of RPGRIP1L corresponded with a spectrum of unfavorable clinicopathological features, including the presence of human epidermal growth factor receptor 2 (HER2) positive, estrogen receptor (ER) positive, over 60 years old, T2, N0, and N3. At the same time, our research indicated that 50 genes and 15 proteins were positively related to RPGRIP1L, and that these proteins and genes were mostly involved in T cell proliferation, immune response, cytokine activity, and metabolic regulation. In addition, in the present study, there was a significant correlation between RPGRIP1L expression and immune cell infiltration. Finally, we found that four Chemicals could downregulate the expression of RPGRIP1L. Altogether, our results strongly indicated that RPGRIP1L might serve as a new prognostic biomarker for BRCA.
Impact of heparanase‐2 (Hpa2) on cancer and inflammation: Advances and paradigms
Authors: Vlodavsky Israel , Hilwi Maram , Kayal Yasmin , Soboh Soaad , Ilan Neta
Published: May 2024

HPSE2, the gene‐encoding heparanase 2 (Hpa2), is mutated in urofacial syndrome (UFS), a rare autosomal recessive congenital disease attributed to peripheral neuropathy. Hpa2 lacks intrinsic heparan sulfate (HS)‐degrading activity, the hallmark of heparanase (Hpa1), yet it exhibits a high affinity toward HS, thereby inhibiting Hpa1 enzymatic activity. Hpa2 regulates selected genes that promote normal differentiation, tissue homeostasis, and endoplasmic reticulum (ER) stress, resulting in antitumor, antiangiogenic, and anti‐inflammatory effects. Importantly, stress conditions induce the expression of Hpa2, thus establishing a feedback loop, where Hpa2 enhances ER stress which, in turn, induces Hpa2 expression. In most cases, cancer patients who retain high levels of Hpa2 survive longer than patients bearing Hpa2‐low tumors. Experimentally, overexpression of Hpa2 attenuates the growth of tumor xenografts, whereas Hpa2 gene silencing results in aggressive tumors. Studies applying conditional Hpa2 knockout (cHpa2‐KO) mice revealed an essential involvement of Hpa2 contributed by the host in protecting against cancer and inflammation. This was best reflected by the distorted morphology of the Hpa2‐null pancreas, including massive infiltration of immune cells, acinar to adipocyte trans‐differentiation, and acinar to ductal metaplasia. Moreover, orthotopic inoculation of pancreatic ductal adenocarcinoma (PDAC) cells into the pancreas of Hpa2‐null vs. wild‐type mice yielded tumors that were by far more aggressive. Likewise, intravenous inoculation of cancer cells into cHpa2‐KO mice resulted in a dramatically increased lung colonization reflecting the involvement of Hpa2 in restricting the formation of a premetastatic niche. Elucidating Hpa2 structure–activity‐relationships is expected to support the development of Hpa2‐based therapies against cancer and inflammation.
Interaction of age and CYP2C19 genotypes on voriconazole steady-state trough concentration in Chinese patients
Authors: Du Yin-Xiao , Zhu Ying-Xia , Li Liang , Yang Jing , Chen Xiao-Ping
Published: May 2024

Objectives

Both age and CYP2C19 genotypes affect voriconazole plasma concentration; the interaction of age and CYP2C19 genotypes on voriconazole plasma concentration remains unknown. This study aims to investigate the combined effects of age and CYP2C19 genotypes on voriconazole plasma concentration in Chinese patients.

Methods

A total of 480 patients who received voriconazole treatment were recruited. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) polymorphisms were genotyped. Patients were divided into the young and the elderly groups by age of 60 years old. Influence of CYP2C19 genotype on steady-state trough concentration (Css-min) in overall patients and in age subgroups was analyzed.

Results

Voriconazole Css-min correlated positively with age, and mean voriconazole Css-min was significantly higher in the elderly group (P < 0.001). CYP2C19 poor metabolizers showed significantly increased mean voriconazole Css-min in the young but not the elderly group. The percentage of patients with subtherapeutic voriconazole Css-min (<1.0 mg/l) was higher in the young group and that of supratherapeutic voriconazole Css-min (>5.5 mg/l) was higher in the elderly patients. When the average Css-min in the CYP2C19 normal metabolizer genotype was regarded as a reference, CYP2C19 genotypes showed greater impact on voriconazole Css-min in the young group, while the influence of age on voriconazole Css-min exceeded CYP2C19 genotypes in the elderly.

Conclusion

CYP2C19 genotypes affects voriconazole exposure is age dependent. Influence of CYP2C19 poor metabolizer genotype on increased voriconazoleexposure is prominent in the young, while age is a more important determinant factor for increased voriconazole exposure in the elderly patients.
Careful Where You Cut: Strategies for Successful Nerve-preserving Mastectomy
Authors: Coopey Suzanne , Keleher Angela , Daniele Karla , Peled Anne Warren , Gomez Janette , Julian Thomas , Moreira Andrea A.
Published: May 2024

Breast neurotization represents an evolving technique that is not widely practiced in most centers specializing in breast cancer treatment. Recognizing the limited educational resources available for breast and plastic surgeons concerning mastectomy techniques that emphasize nerve preservation, our study sought to bridge this gap. Specifically, we aimed to provide a comprehensive exploration of the surgical applied anatomy of breast sensory innervation and a detailed, step-by-step guide for incorporating nerve-sparing mastectomy and breast neurotization into clinical practice. The significance of this work lies in its potential to enhance the understanding and implementation of nerve-preserving techniques in mastectomy procedures, contributing to improved patient outcomes and quality of life post surgery. We hope that by familiarizing breast and reconstructive surgeons with this procedure, we can gain momentum in our research efforts and ultimately enhance the care provided to mastectomy patients.
Research on the academic thought of distinguished veteran doctors of traditional Chinese medicine based on Mendelian randomization: a case study of the causation between Sjögren’s syndrome and rheumatoid arthritis
Authors: Li Haotian , Hu Sile , Xia Congmin , Liu Yanjun
Published: May 2024

Aim:

This study investigated the causation between Sjögren’s syndrome (SS) and rheumatoid arthritis (RA) based on Mendelian randomization (MR), with the purpose of promoting research on the academic thought of distinguished veteran doctors of traditional Chinese medicine (TCM) via bioinformatics with information technology and providing new basis for better inheriting and carrying forward the valuable experience of a National Master of TCM, Zhizheng Lu.

Methods:

The causation between RA and SS in TCM was inferred from the perspective of coordination between dryness and dampness. For further assessment, MR was performed based on the summary data of genome-wide association studies (GWAS), with genetic loci closely related to SS(instrumental variables (IVs)), RA(research outcome), inverse-variance weighted (IVW) and MR-Egger regression and weighted median (WME) ( main MR methods). Heterogeneity was evaluated by Cochran Q test, pleiotropy by MR-Egger regression, and robustness by the Leave-One-Out method.

Results:

Except for MR-Egger, all other methods showed a clear statistical significance in the association between SS and RA (P<0.05).

Conclusion:

This study, based on the academic thought of distinguished TCM veteran doctor and the thought “moistening dryness” of National Master of TCM, Zhizheng Lu, speculated that there may be a potential association between SS and RA. MR results demonstrated the clear genetic causation between SS and RA, and the guiding role of the academic thought of distinguished TCM veteran doctor in clinical practice genetically.
Associations of serum glucocorticoid levels on hypertension and blood pressure-related indicators: a nested case–control study in rural China
Authors: Chen Zhiwei , Wei Dandan , Zhao Mengzhen , Shi Jiayu , Ma Cuicui , Zhang Caiyun , Lin Hualiang , Huo Wenqian , Wang Chongjian , Fan Caini , Mao Zhenxing
Published: May 2024

Background:

The relationship between glucocorticoids and hypertension has shown inconsistent findings in previous studies. To address this, our study employed a nested case–control design in rural areas to further investigate the association between serum glucocorticoid levels and hypertension, and blood pressure-related indicators.

Methods:

This study employed a nested case–control design, involving 560 pairs of hypertensive cases and matched controls. The concentrations of serum cortisol (F), cortisone (E) and 11-deoxycortisol (S) were determined using liquid chromatography-tandem mass spectrometry. We employed various methods, including generalized linear model (GLM), conditional logistic regression model, restricted cubic spline regression, subgroup analysis, interaction, and joint effects, with adjustments for multiple covariates to analyze the relationships between glucocorticoids, hypertension, and blood pressure-related indicators.

Results:

After multivariable adjustments, ln-F, ln-F/E, and ln-S were positively associated with SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP), while ln-E was negatively associated with DBP and MAP (P < 0.05). Interestingly, ln-S showed no statistically significant association with hypertension prevalence (P > 0.05), whereas ln-F and ln-F/E were positively associated with it (P < 0.05). The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.153 (1.011–1.315) for ln-F and 2.072 (1.622–2.645) for ln-F/E, respectively. In contrast, ln-E exhibited a negative association with hypertension prevalence (adjusted OR = 0.837, 95% CI 0.714–0.982). Moreover, a significant association was observed between the combined use of high-dose F/E and high-dose S with hypertension prevalence (adjusted OR = 3.273, 95% CI 2.013–5.321). Blood pressure indicators and hypertension prevalence significantly increased with elevated serum F and F/E concentrations (P < 0.05). Interaction analysis further revealed that among women, the positive association between F/E and hypertension prevalence was more pronounced than in men (P < 0.05), and S exhibited a more significant positive association with hypertension prevalence in the overweight population (P < 0.05).

Conclusion:

Serum F/E and S levels demonstrated positive associations with hypertension and blood pressure-related indicators, and their combined influence exhibited a synergistic effect on hypertension. Notably, F, F/E, and S were associated with heightened hypertension risk, warranting particular attention in women and overweight populations.
AN UNUSUAL WAY TO INDUCE THE CLOSURE OF A POSTERIOR POLE RETINAL TEAR IN A TRAUMATIC RETINAL DETACHMENT
Authors: Angeli Chiara , Di Leo Laura , Frisina Rino
Published: May 2024

Purpose.

The authors present a case of both traumatic subluxated lens with zonular dialysis and a traumatic retinal detachment with posterior retinal tear.

Methods.

Some fragments have dropped into the vitreous chamber during phaco-emulsification and one of them has even passed through the retinal tear and has been removed from the subretinal space. A 3-piece intraocular lens with a tension ring supporting the capsular bag was implanted. Pars plana vitrectomy with accurate vitreous base shaving was approached by 23-gauge system. Subretinal fluid was removed by a complete fluid-air exchange. A large macular internal limiting membrane (ILM) peeling was performed and the posterior retinal tear was covered by multiple inverted ILM flaps.

Results.

Postoperatively, retinal reattachment was achieved, the retinal break was flat. The ILM flaps were well positioned within the retinal tear and covered the preoperatively bared RPE.

Conclusions.

The surgical treatment of injuries after a blunt ocular trauma are not standardizable. In this case surgical outcomes suggest the effectiveness of the surgeon’s intraoperative unusual maneuvers.
Longitudinal Renal Function Degradation Among Florida Agricultural Workers
Authors: Chicas Roxana C. , Elon Lisa , Xiuhtecutli Nezahualcoyotl , Liang Donghai , Houser Madelyn C. , Mwarumba Tuzo , Berra Liris , Hertzberg Vicki , Sands Jeff M. , McCauley Linda
Published: May 2024

Objective

This longitudinal study evaluated renal function and acute kidney injury (AKI) over time in US agricultural workers.

Methods

We followed Florida agricultural workers from January 2020 to August 2022, collecting blood and urine preworkday and postworkday during five visits.

Results

Preworkday estimated glomerular filtration rate function in all participants was lower in summers but relatively consistent over time. In participants who worked almost exclusively in fernery operations (piece-rate compensation), we observed a high incidence of postworkday AKI in 2020 (21%) that increased to 43% by the end of the study. In comparison, 11% of nursery workers (hourly compensation) had AKI, and this rate was fairly stable.

Conclusion

AKI risk over time differs according to the type of agricultural work. Piece rate workers who are incentivized to forgo rest breaks and hydration to earn higher wages demonstrate steadily increasing rates of AKI.
Artificial intelligence-based classification of breast lesion from contrast enhanced mammography: a multicenter study
Authors: Zhang Haicheng , Lin Fan , Zheng Tiantian , Gao Jing , Wang Zhongyi , Zhang Kun , Zhang Xiang , Xu Cong , Zhao Feng , Xie Haizhu , Li Qin , Cao Kun , Gu Yajia , Mao Ning
Published: May 2024

Purpose:

The authors aimed to establish an artificial intelligence (AI)-based method for preoperative diagnosis of breast lesions from contrast enhanced mammography (CEM) and to explore its biological mechanism.

Materials and methods:

This retrospective study includes 1430 eligible patients who underwent CEM examination from June 2017 to July 2022 and were divided into a construction set (n=1101), an internal test set (n=196), and a pooled external test set (n=133). The AI model adopted RefineNet as a backbone network, and an attention sub-network, named convolutional block attention module (CBAM), was built upon the backbone for adaptive feature refinement. An XGBoost classifier was used to integrate the refined deep learning features with clinical characteristics to differentiate benign and malignant breast lesions. The authors further retrained the AI model to distinguish in situ and invasive carcinoma among breast cancer candidates. RNA-sequencing data from 12 patients were used to explore the underlying biological basis of the AI prediction.

Results:

The AI model achieved an area under the curve of 0.932 in diagnosing benign and malignant breast lesions in the pooled external test set, better than the best-performing deep learning model, radiomics model, and radiologists. Moreover, the AI model has also achieved satisfactory results (an area under the curve from 0.788 to 0.824) for the diagnosis of in situ and invasive carcinoma in the test sets. Further, the biological basis exploration revealed that the high-risk group was associated with the pathways such as extracellular matrix organization.

Conclusions:

The AI model based on CEM and clinical characteristics had good predictive performance in the diagnosis of breast lesions.
Update on the use of long-acting growth hormone in children
Authors: Boguszewski Margaret Cristina da Silva , Boguszewski Cesar Luiz
Published: May 2024

Purpose of review

After extensive research and many years of waiting, long-acting growth hormone (LAGH) formulations have finally become a reality in clinical practice and emerge as a potential solution to address the challenges of daily injections of recombinant human GH (rhGH). In this review, we present a brief history of the development of LAGH and provide a critical analysis of the existing literature on the five LAGH available and approved to date for treatment in children.

Recent findings

In clinical trials, LAGH therapy has shown noninferiority compared with daily rhGH therapy in promoting linear growth in children with GH deficiency, with similar rates of adverse events.

In the real world, many questions still need to be answered, such as whether a specific group of patients will benefit most from the weekly injection, whether compliance will be better compared with daily rhGH, whether long-term efficacy, monitoring and safety profile will be the same for the different LAGH compounds, and whether the cost-effectiveness will justify their use in different settings.
“Minimally symptomatic” congenital cytomegalovirus infection: latest data and emerging concepts
Authors: Howard Ashley , Nishikawa Javier K. , Sánchez Pablo J.
Published: May 2024

Purpose of review

Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with “minimally symptomatic” or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL).

Recent findings

Valganciclovir is being prescribed increasingly in neonates with congenital CMV infection for improvement in hearing outcomes through 2 years of age. Treatment initiated in the first month of age is recommended for clinically apparent disease. A recent study showed hearing improvement at 18–22 months of age when therapy was initiated at age 1–3 months in infants with clinically inapparent CMV infection and isolated SNHL.

Antiviral therapy with either ganciclovir or valganciclovir has shown moderate benefit in prevention of hearing deterioration among infants with clinically apparent CMV infection or isolated SNHL. Sustainability of benefit beyond 2 years of age remains unknown. At present, infants with clinically inapparent CMV infection (normal complete evaluation including hearing) should not receive antiviral therapy. All CMV-infected infants require close audiological and neurodevelopmental follow-up.
Clinical and Immunologic Features of a Patient With Homozygous FNIP1 Variant
Authors: Ulaş Selami , Naiboğlu Sezin , Özyilmaz İsa , Öztürk Demir Asli Güner , Turan Işilay , Yuzkan Sabahattin , Ayaz Akif , Çeliksoy Mehmet Halil
Published: May 2024

Agammaglobulinemia represents the most profound primary antibody deficiency, stemming from early cessation of B-cell development. Deficiency in folliculin-interacting protein 1 (FNIP1) is a novel inborn error of immunity characterized by a severe defect in B-cell development, agammaglobulinemia, variable neutropenia, and hypertrophic cardiomyopathy. FNIP1 plays a critical role in B-cell development and metabolic homeostasis, establishing a metabolic checkpoint that ensures pre-B cells possess sufficient metabolic capacity to undergo division while concurrently limiting lymphogenesis due to abnormal growth. Disruption of FNIP1 functionality affects the fundamental metabolic regulators adenosine monophosphate-activated protein kinase and mTOR, culminating in a severe B-cell deficiency alongside hypogammaglobulinemia, hypertrophic cardiomyopathy, preexcitation syndrome, and intermittent neutropenia. This case report presents an 11-month-old male patient with FNIP1 deficiency who, in addition to classical features, exhibited posterior cerebellar hypoplasia.
The impact of vitamin D treatment on pregnancy rate among endometriosis patients: a systematic review and meta-analysis
Authors: Shrateh Oadi N. , Siam Haneen A. , Ashhab Yasmeen S. , Sweity Raneen R. , Naasan Mashhour
Published: May 2024

Background:

Vitamin D supplementation is supposed to have an important role in the management of several endometriosis-related aspects, offering potential relief to affected individuals. Herein, the authors aim to evaluate the impact of vitamin D on pregnancy rates and clinical symptoms in women with endometriosis.

Methods:

The authors extensively searched PubMed, Cochrane Library, EMBASE, Ovid MEDLINE, and CINAHL from their inception to 20 July 2023.

Results:

Three randomized controlled trials involving 167 patients were included in this meta-analysis. The findings demonstrated that vitamin D supplementation exhibits efficacy in alleviating dysmenorrhea associated with endometriosis, as evidenced by a meta-analysis showing a significant reduction in dysmenorrhea (mean difference −1.41, 95% CI −2.61 to −0.22, P = 0.02). However, the impact on dyspareunia was inconclusive, with a non-significant mean difference of –0.2 (95% CI −1.62 to 1.22, P = 0.78). In contrast, dyschezia significantly decreased with vitamin D supplementation (mean difference −1.10, 95% CI −2.22 to 0.02, P = 0.05 However, the meta-analysis did not show a significant effect of vitamin D on chronic pelvic pain associated with endometriosis.

Conclusion:

While antioxidant vitamin D supplementation demonstrates general effectiveness in alleviating endometriosis symptoms, such as dysmenorrhea, dyspareunia, and dyschezia, the existing literature lacks direct investigations into the specific impact of vitamin D on enhancing pregnancy rates among endometriosis patients. This observation prompts various hypotheses, suggesting that the positive effects of vitamin D supplementation on endometriosis-related symptoms may indirectly contribute to improved pregnancy outcomes and enhanced fertility.
Retropubic Versus Transobturator Midurethral Slings at Time of Colpocleisis
Authors: Wong Jennifer W.H. , Stram Douglas A. , Patel Minita S.
Published: May 2024

Importance

This study aimed to evaluate if there is a difference between outcomes when retropubic or transobturator midurethral sling surgery is performed at the time of colpocleisis.

Objectives

The purpose of this study was to compare the surgical outcomes of the retropubic midurethral sling (RP-MUS) versus the transobturator midurethral sling (TO-MUS) in women who underwent concomitant colpocleisis, specifically 2-year MUS failure and 1-year lower urinary tract symptoms (LUTSs). A secondary aim was to identify factors associated with these surgical outcomes.

Study Design

All cases of concomitant MUS and colpocleisis within a closed, integrated health care delivery system were reviewed between April 1, 2010, and March 31, 2020. Postoperative MUS failure was defined as (1) postoperative stress urinary incontinence symptoms and/or (2) additional anti-incontinence surgery. Postoperative LUTSs were defined as (1) MUS lysis and/or (2) overactive bladder requiring management with a new treatment.

Results

Of the 558 women included, 454 (81%) received RP-MUS and 104 (19%) received TO-MUS. Cohort demographics were similar. Neither MUS failure (7% RP-MUS and 9% TO-MUS, P = 0.450) nor LUTSs (7% RP-MUS and 12% TO-MUS, P = 0.171) were significantly different between RP-MUS and TO-MUS. In multivariable analysis, age was found to be significantly associated with LUTSs (odds ratio 0.29, 95% confidence interval 0.09–0.93, P = 0.038 among 70–74-year-olds; odds ratio 0.28, 95% confidence interval 0.09–0.83, P = 0.022 among 75–79-year-olds).

Conclusions

At the time of colpocleisis, both RP-MUS and TO-MUS were highly successful and associated with a low incidence of LUTSs, including MUS lysis. The findings of this large study support RP-MUS and TO-MUS as similarly effective anti-incontinence options at time of colpocleisis.