bluuebunny/crossref_metadata_2025 huggingface dataset:
Tension Hydropneumothorax Caused by a Ruptured Hydatic Cyst in the Pleural Cavity: Case Report
Authors: Messaoud Ola , El Haddad Siham , Cherraqi Amine , Allali Nazik , Chat Latifa
Published: March 2023

Hydatid disease is a zoonosis caused by a larva of the tapeworm Echinococcus. All organs can be involved, but it is frequently located in liver for adults and lung for children. The clinical features are nonspecific. Imaging findings has an important place in the diagnosis and the follow-up. Rupture is the most common complication of a hydatic cyst and has a variety of imaging findings depending on the ruptured layer, the amount of air within the cyst and the type rupture. We report the case of a 10-year-old boy presenting shortness of breath and fever among other symptoms revealing by chest X-ray and thoracic CT scan, a lung ruptured hydatic cyst to the pleural cavity causing a tension hydro-pneumothorax and a superadded infection.
History, neighborhood, and proximity as factors of land-use change: A dynamic spatial regression model
Authors: Tepe Emre
Published: March 2023

Spatio-temporal land-use change (LUC) modeling provides vital information about land development dynamics. However, accounting for such dynamics faces methodological challenges. This research introduces a Dynamic Spatial Panel Data (DSPD) modeling framework for LUC, incorporating spatial and temporal dependencies. A continuous response variable is introduced to take advantage of traditional spatial regression models. The DSPD model is applied to balanced spatial panel data at the block-group level covering Florida between 2010 and 2019 and incorporating both new and previously used proxy variables. The urban growth impacts of site-specific, proximity, neighborhood, socio-economic, and transportation factors are investigated. This study contributes to the literature by providing extensive insights into spatial autocorrelation, spillover, heterogeneity, and temporal lag effects in urban growth. Also, the study reveals the importance of mobility and mortgage financing in land development. The proposed modeling framework achieves high accuracy. The dynamic structure of this model provides an opportunity to predict future urban growth without the need for a land development scenario. Such predictions provide insights about future land development to practitioners and policymakers.
Patient-Reported Outcome Measures After Surgical Management of Unstable Lisfranc Injuries in Athletes
Authors: Brown Cortez L. , James Nia A. , Onyeukwu Chukwudi , Belayneh Rebekah , Boakye Lorraine , Hogan MaCalus V.
Published: March 2023

Background:

Athletes sustaining Lisfranc joint instability after a low-energy injury often undergo surgical fixation. Limited studies report validated patient-reported outcome measures (PROMs) for this specific patient population. Our purpose was to report PROMs of athletes experiencing instability after a low-energy Lisfranc injury and undergoing surgical fixation.

Methods:

Twenty-nine athletes (23 competitive, 6 recreational) sustained an unstable Lisfranc injury (14 acute, 15 chronic) and met our inclusion criteria. Injuries were classified as acute if surgically managed within 6 weeks. All athletes completed validated PROMs pre- and postoperatively. The cohort underwent various open reduction internal fixation methods. We evaluated outcomes with the Foot and Ankle Ability Measure (FAAM) activities of daily living (ADL) and sports subscales.

Results:

Fourteen of 29 (48%) athletes reported PROMs at ≥2 years with a median follow-up time of 44.5 months. Substantial improvement for both FAAM ADL (50% vs 93%; P < .001) and sports (14.1% vs 80%; P = .002) subscales were found, when comparing preoperative to postoperative scores at ≥2 years.

Conclusion:

This study provides outcomes information for the young athletic population that were treated operatively for low-energy Lisfranc injury with apparent joint instability. Based on the FAAM sports subscale, these patients on average improved between their 6-month evaluation and their final ≥2 years but still scored 80% of the possible 100%, which indicates continued but “slight” difficulty with lower extremity function.

Level of Evidence:

Level IV, case series.
Photoreceptor outer segment layer thinning as a biomarker in acute central serous chorioretinopathy
Authors: Maltsev Dmitrii S. , Kulikov Alexey N. , Burnasheva Maria A. , Chhablani Jay
Published: March 2023

Background:

The photoreceptor outer segment (PROS) layer demonstrates focal thinning above the fluorescein leakage in acute central serous chorioretinopathy (CSC); however, the nature of this phenomenon is not known.

Objectives:

To study the relationship between the PROS layer and thickness of the outer retinal layers above the fluorescein leakage in newly diagnosed acute CSC.

Design:

Single-center retrospective study.

Methods:

All participants received multimodal imaging, including fluorescein angiography and optical coherence tomography. Thickness of PROS, outer nuclear layer (ONL), and ONL-outer plexiform layer (OPL) complex was measured above the leakage and outside the leakage within the area of neurosensory detachment. The number of intraretinal hyperreflective foci of the outer retina was counted. The correlation between PROS thickness and ONL, OPL-ONL complex thickness, and the number of intraretinal hyperreflective foci was calculated.

Results:

Fifty eyes of 48 patients (38 males and 10 females, 43.8 ± 10.6 years) with a mean symptom duration of 1.4 ± 1.3 months were included. PROS thickness above the fluorescein leakage showed a statistically significant correlation with ONL thickness, OPL-ONL complex thickness, and the number of hyperreflective foci in the outer retina, 0.57, 0.60, and −0.46, respectively ( p < 0.001). Measuring the extent of PROS thinning above the leakage in newly diagnosed CSC allowed to predict self-resolution of subretinal fluid. The greatest linear dimension of PROS thinning showed an area under the receiver operating curve (ROC) curve of 0.98. The cases without PROS thinning had the fastest resolution of subretinal fluid.

Conclusion:

PROS thinning above the fluorescein leakage in acute CSC is associated with thinning of the outer retinal layers and reveals mild outer retinal atrophy. The absence of PROS thinning predicts faster resolution of CSC.
Gender Differences in Self-Efficacy for Diabetes Self-Management Among Hispanics: The Mediating Role of Perceived Support and Depressive Symptoms
Authors: Mansyur Carol L. , Rustveld Luis O. , Nash Susan G. , Jibaja-Weiss Maria L.
Published: March 2023

Purpose

The purpose of this study is to examine the extent to which perceived support and depressive symptoms might interfere with Hispanic patients’ ability to manage their diabetes and whether these effects vary by gender.

Methods

Data were collected from a cohort of 232 Hispanic men and women with type 2 diabetes mellitus (T2DM). Conditional process analysis was used to test a moderated mediation model of the time-lagged processes associating gender, diabetes support, and depressive symptoms with reported self-efficacy after 3 months.

Results

Increased depressive symptoms were associated with lower self-efficacy, but the conditional effects varied among men and women. The index of moderated mediation was significant, indicating that among women, the indirect effect of depressive symptoms on self-efficacy was contingent on lower levels of perceived support. Among men, increased depressive symptoms were directly associated with declines in self-efficacy and were not conditional on perceived support.

Conclusions

Results of the study have important implications for gender health equity. Mental health screening and an assessment of support needs may be important for determining appropriate complementary therapies when treating Hispanic women with chronic conditions such as diabetes. Attention to possible differences in gender-specific mental health needs could lead to improved self-management, better glycemic control, and more equitable health outcomes.
3D Infant Orthopedic Nasal Molding System for Improved Outcomes in Cleft Nasal Deformity
Authors: Mejia Martha L. , Pablo Gomez Juan , Moon Savannah L. , Wolfe Erin M. , Perlyn Chad A. , Anthony Wolfe S. , Steinberg Jordan P.
Published: March 2023

The cleft nasal deformity is a hallmark feature in infants with cleft lip and palate and includes deviation of the caudal septum, slumping of the ipsilateral lower lateral cartilage, and obstructed nasal breathing. Presurgical orthopedic protocols have been developed and refined over several decades now, with limited evidence supporting their long-term efficacy, particularly with respect to the nasal form. Some limitations relate to variabilities in studies and data outcome measures. We have designed a novel method of presurgical orthopedic molding using separate nasal and intraoral components. The independent nasal device, called the Rhinoplastic Appliance System, is introduced in this technique article and shown to have distinct biomechanical advantages for the unilateral and bilateral cleft nasal deformity, both presurgically before lip repair, and postsurgically for nostril maintenance. As with CAD/CAM technologies for the intraoral plate component of traditional NAMs, we believe digital preparation of RAS devices, combined with separate oral appliances, can allow for more effective and reproducible presurgical infant cleft molding with less operator dependence and family/patient burden.
Ancient lineages of the keratin-associated protein (KRTAP) genes and their co-option in the evolution of the hair follicle
Authors: Litman Thomas , Stein Wilfred D.
Published: March 2023

BLAST searches against the human genome showed that of the 93 keratin-associated proteins (KRTAPs) of Homo sapiens, 53 can be linked by sequence similarity to an H. sapiens metallothionein and 16 others can be linked similarly to occludin, while the remaining KRTAPs can themselves be linked to one or other of those 69 directly-linked proteins. The metallothionein-linked KRTAPs comprise the high-sulphur and ultrahigh-sulphur KRTAPs and are larger than the occludin-linked set, which includes the tyrosine- and glycine-containing KRTAPs. KRTAPs linked to metallothionein appeared in increasing numbers as evolution advanced from the deuterostomia, where KRTAP-like proteins with strong sequence similarity to their mammalian congeners were found in a sea anemone and a starfish. Those linked to occludins arose only with the later-evolved mollusca, where a KRTAP homologous with its mammalian congener was found in snails. The presence of antecedents of the mammalian KRTAPs in a starfish, a sea anemone, snails, fish, amphibia, reptiles and birds, all of them animals that lack hair, suggests that some KRTAPs may have a physiological role beyond that of determining the characteristics of hair fibres. We suggest that homologues of these KRTAPs found in non-hairy animals were co-opted by placodes, formed by the ectodysplasin pathway, to produce the first hair-producing cells, the trichocytes of the hair follicles.
Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques
Authors: Ghandhi Shanaz A. , Morton Shad R. , Shuryak Igor , Lee Younghyun , Soni Rajesh K. , Perrier Jay R. , Bakke James , Gahagan Janet , Bujold Kim , Authier Simon , Amundson Sally A. , Brenner David J. , Nishita Denise , Chang Polly , Turner Helen C.
Published: March 2023

Background

Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation.

Results

The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiated earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGFβ and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27–0.33 up to 28 days and declined to 0.1 by day 56.

Conclusions

Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.
Isolation and functional verification of an aspartate aminotransferase gene from Neoporphyra haitanensis
Authors: Li Shuang , Shao Zhanru , Lu Chang , Duan Delin
Published: March 2023

Background

Neoporphyra haitanensis is a commercial laver species in China. Aspartic acid is an important flavor amino acid, and aspartate aminotransferase (AAT) is a crucial enzyme in its biosynthesis. In this study, we cloned one AAT gene (NhAAT) from the red alga N. haitanensis and investigated its sequence structure, transcriptional expression and enzymatic characteristics. The purpose of our research is to obtain a functional AAT responsible for the biosynthesis of aspartic acid from red seaweeds, which has the potential to influence the flavor of N. haitanensis.

Results

Sequence analysis showed that NhAAT contains a conserved domain of Aminotran_1_2, which belongs to the transaminase superfamily. The secondary structure of NhAAT is dominated by α-helix. The results of enzymatic characterization illustrated that the NhAAT has highest catalytic activity at 45 °C and pH 7.5 in both forward and reverse reactions. The calculated Km values of NhAAT was 5.67 and 6.16 mM for L-glutamic acid and L-aspartic acid, respectively. Quantitative analysis showed that the NhAAT expression of N. haitanensis collected in late harvest (Dec) was 4.5 times that of N. haitanensis collected in early harvest (Oct), while the aspartic acid content of N. haitanensis collected in late harvest (Dec) was 1.2 times that of N. haitanensis collected in early harvest (Oct).

Conclusion

The results of enzyme kinetics indicated that NhAAT prefers to catalyze the reaction in the direction of aspartic acid production. Moreover, the trend of NhAAT expression level was consistent with that of aspartic acid content in N. haitanensis in different harvest periods. Our research is helpful to understand the accumulation and regulation of amino acids in N. haitanensis in different habitats and the taste difference of N. haitanensis in different harvest periods.
Effects of dexmedetomidine on postoperative sleep quality: a systematic review and meta-analysis of randomized controlled trials
Authors: Liu Huizi , Wei Hanwei , Qian Shaojie , Liu Jintao , Xu Weicai , Luo Xiaopan , Fang Junbiao , Liu Qiaoyan , Cai Fang
Published: March 2023

Study objectives

To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances.

Methods

An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis.

Results

Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes.

Conclusions

Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.
Brainstem atrophy in dementia with Lewy bodies compared with progressive supranuclear palsy and Parkinson’s disease on MRI
Authors: Müller Sebastian Johannes , Khadhraoui Eya , Hansen Niels , Jamous Ala , Langer Philip , Wiltfang Jens , Riedel Christian Heiner , Bouter Caroline , van Riesen Christoph , Maass Fabian , Bartl Michael , Lange Claudia , Ernst Marielle
Published: March 2023

Background

Although Dementia with Lewy bodies (DLB) is the second most common form of dementia in elderly patients, it remains underdiagnosed compared with Alzheimer's (AD) and Parkinson's diseases (PD). This may be explained by overlapping clinical symptoms, e.g. Parkinsonism. While current MRI research focuses primarily on atrophy patterns of the frontal and temporal lobes, we focus on brainstem characteristics of DLB. In particular, we focused on brainstem atrophy patterns distinguishing DLB from Progressive Supranuclear Palsy (PSP) and PD based as the most common differential diagnoses.

Methods

We identified patients diagnosed with DLB, PD, PSP, and a control group (CTRL) in our psychiatric and neurological archives. All patients with competing diagnoses and without a high-quality T1 MPRAGE 3D dataset were excluded. We assessed atrophy patterns in all patients (1) manually and (2) using FastSurfer’s segmentation algorithm in combination with FreeSurfer’s brainstem volumetric calculations. We compared classical measurement methods and ratios with automated volumetric approaches.

Results

One hundred two patients were enrolled and evaluated in this study. Patients with DLB (n = 37) showed on average less atrophy of the brainstem than patients with PSP (n = 21), but a significantly more pronounced atrophy than patients with PD (n = 36) and the control group (CTRL, n = 8). The mean measured sagittal diameters of the midbrain were 8.17 ± 1.06 mm (mean ± standard deviation) for PSP, 9.45 ± 0.95 mm for DLB, 10.37 ± 0.99 mm for PD and 10.74 ± 0.70 for CTRL. The mean measured areas of the midbrain were 81 ± 18 mm2 for PSP, 105 ± 17 mm2 for DLB, 130 ± 26 mm2 for PD and 135 ± 23 mm2 for CTRL. The mean segmented volumes of the midbrain were 5595 ± 680 mm3 for PSP, 6051 ± 566 mm3 for DLB, 6646 ± 802 mm3 for PD and 6882 ± 844 mm3 for CTRL. The calculated midbrain pons ratios did not show superiority over the absolute measurements of the midbrain for distinguishing PSP from DLB. Because of the relatively uniform atrophy throughout the brainstem, the ratios were not suitable for distinguishing DLB from PD.

Conclusions

DLB patients exhibit homogenous atrophy of the brainstem and can be distinguished from patients with PSP and PD by both manual measurement methods and automated volume segmentation using absolute values or ratios.
Exploring the psychometric properties of the externalizing spectrum inventory-brief form in a Swedish forensic psychiatric inpatient sample
Authors: Berlin Johan , Wallinius Märta , Nilsson Thomas , Karlén Malin Hildebrand , Delfin Carl
Published: March 2023

Background

The Externalizing Spectrum Inventory-Brief Form (ESI-BF) [1] is a 160-item self-report instrument designed for the assessment of externalizing psychopathology, yet few studies to date have evaluated its psychometric properties, structural fit, and criterion validity in forensic psychiatric settings.

Methods

Here, we investigated these aspects in a sample of forensic psychiatric inpatients (n = 77) from a maximum-security forensic psychiatric hospital in Sweden. We firstly investigated the reliability. Secondly, using confirmatory factor analysis, the structure of the ESI-BF. And thirdly, using a Bayesian approach, assessed how the three ESI-BF subfactors relate to criterion measures of antisocial behaviors, substance use, and lifetime externalizing spectrum diagnoses.

Results

The ESI-BF demonstrated good to adequate reliability and internal consistency, with all but four facet scales exhibiting α and ω values ≥ 0.80. Average inter-item correlations for the facet scales ranged from 0.31 to 0.74. However, all structural models exhibited poor to mediocre fit, with model fit values for the CFI being 0.66, 0.79 and 0.87 and RMSEA values of 0.14, 0.12 and 0.09. for the unidimensional correlated factors and bifactor model, respectively. Regarding criterion validity, all subscales of the item-based ESI-BF three-factor model exhibited robust correlations with the Life History of Aggression total, aggression and antisocial/consequences subscales, with correlations ranging from 0.29 to 0.55. All ESI-BF subfactors demonstrated robust associations, yet with different externalizing outcomes, lending tentative support to its criterion validity.

Conclusion

Despite remaining ambiguities regarding its structural fit, the ESI-BF may be promising for assessing externalizing psychopathology in forensic psychiatric populations. However, further investigation of the ESI-BF is needed before any firm conclusions can be drawn about its appropriateness in forensic psychiatric settings.
Vulvovaginal yeast infections during pregnancy and perinatal outcomes: systematic review and meta-analysis
Authors: Gigi Ranjana M. S. , Buitrago-Garcia Diana , Taghavi Katayoun , Dunaiski Cara-Mia , van de Wijgert Janneke H. H. M. , Peters Remco P. H. , Low Nicola
Published: March 2023

Background

Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast infections are likely to cause more inflammation than asymptomatic. The objective of this study was to investigate associations between symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and perinatal outcomes.

Methods

We did a systematic review and searched eight databases until 01 July 2022. We included studies reporting on pregnant women with and without laboratory confirmed vulvovaginal yeast infection and preterm birth or eight other perinatal outcomes. We used random effects meta-analysis to calculate summary odds ratios (OR), 95% confidence intervals (CI) and prediction intervals for the association between yeast infection and outcomes. We described findings from studies with multivariable analyses. We assessed the risk of bias using published tools.

Results

We screened 3909 references and included 57 studies. Only 22/57 studies reported information about participant vulvovaginal symptoms. Preterm birth was an outcome in 35/57 studies (49,161 women). In 32/35 studies with available data, the summary OR from univariable analyses was 1.01 (95% CI 0.84–1.21, I2 60%, prediction interval 0.45–2.23). In analyses stratified by symptom status, we found ORs of 1.44 (95% CI 0.92–2.26) in two studies with ≥ 50% symptomatic participants, 0.84 (95% CI 0.45–1.58) in seven studies with < 50% symptomatic participants, and 1.12 (95% CI 0.94–1.35) in four studies with asymptomatic participants. In three studies with multivariable analysis, adjusted ORs were greater than one but CIs were compatible with there being no association. We did not find associations between vulvovaginal yeast infection and any secondary outcome. Most studies were at high risk of bias in at least one domain and only three studies controlled for confounding.

Conclusions

We did not find strong statistical evidence of an increased risk for preterm birth or eight other adverse perinatal outcomes, in pregnant women with either symptomatic or asymptomatic vulvovaginal yeast infection. The available evidence is insufficient to make recommendations about testing and treatment of vulvovaginal yeast infection in pregnancy. Future studies should assess vulvovaginal symptoms, yeast organism loads, concomitant vaginal or cervical infections, and microbiota using state-of-the-art diagnostics.

Systematic review registration

PROSPERO CRD42020197564
A snapshot of patient experience of illness control after a hospital readmission in adults with chronic heart failure
Authors: Turrise Stephanie , Hadley Nina , Phillips-Kuhn Denise , Lutz Barbara , Heo Seongkum
Published: March 2023

Background

Approximately 6.5 million adults have chronic heart failure (HF), the number one cause of 30-day hospital readmission. Managing HF and its symptoms is critical for patients. Hospitalization may impact patients’ perceptions of illness control, which can affect illness management. However, how hospital readmissions are perceived as related to one’s ability to control their HF and its symptoms has not been examined.

Objective

The purpose was to explore the experiences of people with HF in managing their illness (i.e., illness control), understand their perceptions of illness control after recent hospital readmission, and clarify the concept of illness control in people with chronic HF.

Methods

A qualitative approach, applied thematic analysis was employed. Purposive sampling was used to identify participants. Semi-structured interviews were conducted in 10 participants’ homes. Ongoing, concurrent, and comparative data analysis was used with ATLASti© data management software.

Results

Two themes were identified, strategies to control HF and barriers to controlling HF. Strategies to control HF included four subthemes: managing dietary intake and medications; self- advocacy; monitoring symptoms; and support. Barriers to control also had four subthemes: healthcare systems issues; health care professional relationships and interactions; personal characteristics; and knowledge deficits.

Conclusion

People use many different strategies to control HF. Control comes from both within and outside of the individual. The desire to control HF and its symptoms was evident, but implementing strategies is challenging and takes time, experience, and trial and error. Individuals did not view readmission negatively but as necessary to help them control their symptoms.
Mesoporous nanodrug delivery system: a powerful tool for a new paradigm of remodeling of the tumor microenvironment
Authors: Hang Yinhui , Liu Yanfang , Teng Zhaogang , Cao Xiongfeng , Zhu Haitao
Published: March 2023

Tumor microenvironment (TME) plays an important role in tumor progression, metastasis and therapy resistance. Remodeling the TME has recently been deemed an attractive tumor therapeutic strategy. Due to its complexity and heterogeneity, remodeling the TME still faces great challenges. With the great advantage of drug loading ability, tumor accumulation, multifactor controllability, and persistent guest molecule release ability, mesoporous nanodrug delivery systems (MNDDSs) have been widely used as effective antitumor drug delivery tools as well as remolding TME. This review summarizes the components and characteristics of the TME, as well as the crosstalk between the TME and cancer cells and focuses on the important role of drug delivery strategies based on MNDDSs in targeted remodeling TME metabolic and synergistic anticancer therapy.

Graphical Abstract
Constructing a seventeen-gene signature model for non-obstructive azoospermia based on integrated transcriptome analyses and WGCNA
Authors: Chen Yinwei , Yuan Penghui , Gu Longjie , Bai Jian , Ouyang Song , Sun Taotao , Liu Kang , Wang Zhao , Liu Chang
Published: March 2023

Background

Non-obstructive azoospermia (NOA) affects approximately 1% of the male population worldwide. The underlying mechanism and gene transcription remain unclear. This study aims to explore the potential pathogenesis for the detection and management of NOA.

Methods

Based on four microarray datasets from the Gene Expression Omnibus database, integrated analysis and weighted correlation network analysis (WGCNA) were used to obtain the intersected common differentially expressed genes (DESs). Differential signaling pathways were identified via GO and GSVA-KEGG analyses. We constructed a seventeen-gene signature model using least absolute shrinkage and selection operation (LASSO) regression, and validated its efficacy in another two GEO datasets. Three patients with NOA and three patients with obstructive azoospermia were recruited. The mRNA levels of seven key genes were measured in testicular samples, and the gene expression profile was evaluated in the Human Protein Atlas (HPA) database.

Results

In total, 388 upregulated and 795 downregulated common DEGs were identified between the NOA and control groups. ATPase activity, tubulin binding, microtubule binding, and metabolism- and immune-associated signaling pathways were significantly enriched. A seventeen-gene signature predictive model was constructed, and receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values were 1.000 (training group), 0.901 (testing group), and 0.940 (validation set). The AUCs of seven key genes (REC8, CPS1, DHX57, RRS1, GSTA4, SI, and COX7B) were all > 0.8 in both the testing group and the validation set. The qRT-PCR results showed that consistent with the sequencing data, the mRNA levels of RRS1, GSTA4, and COX7B were upregulated, while CPS1, DHX57, and SI were downregulated in NOA. Four genes (CPS1, DHX57, RRS1, and SI) showed significant differences. Expression data from the HPA database showed the localization characteristics and trajectories of seven key genes in spermatogenic cells, Sertoli cells, and Leydig cells.

Conclusions

Our findings suggest a novel seventeen-gene signature model with a favorable predictive power, and identify seven key genes with potential as NOA-associated marker genes. Our study provides a new perspective for exploring the underlying pathological mechanism in male infertility.
The short isoform of MS4A7 is a novel player in glioblastoma microenvironment, M2 macrophage polarization, and tumor progression
Authors: Ni Bowen , Huang Guanglong , Yang Runwei , Wang Ziyu , Song Haimin , Li Kaishu , Zhang Yunxiao , Wu Kezhi , Shi Guangwei , Wang Xiran , Shen Jie , Liu Yawei
Published: March 2023

Background

The unique intracranial tumor microenvironment (TME) contributes to the immunotherapy failure for glioblastoma (GBM), thus new functional protein targets are urgently needed. Alternative splicing is a widespread regulatory mechanism by which individual gene can express variant proteins with distinct functions. Moreover, proteins located in the cell plasma membrane facilitate targeted therapies. This study sought to obtain functional membrane protein isoforms from GBM TME.

Methods

With combined single-cell RNA-seq and bulk RNA-seq analyses, novel candidate membrane proteins generated by prognostic splicing events were screened within GBM TME. The short isoform of MS4A7 (MS4A7-s) was selected for evaluation by RT-PCR and western blotting in clinical specimens. Its clinical relevance was evaluated in a GBM patient cohort. The function of MS4A7-s was identified by in vitro and in vivo experiments. MS4A7-s overexpression introduced transcriptome changes were analyzed to explore the potential molecular mechanism.

Results

The main expression product, isoform MS4A7-s, generated by exon skipping, is an M2-specific plasma membrane protein playing a pro-oncogenic role in GBM TME. Higher expression of MS4A7-s correlates with poor prognosis in a GBM cohort. In vitro cell co-culture experiments, intracranial co-injection tumorigenesis assay, and RNA-seq suggest MS4A7-s promotes activation of glioma-associated macrophages’ (GAMs) PI3K/AKT/GSK3β pathway, leading to M2 polarization, and drives malignant progression of GBM.

Conclusions

MS4A7-s, a novel splicing isoform of MS4A7 located on the surface of GAMs in GBM TME, is a predictor of patient outcome, which contributes to M2 polarization and the malignant phenotype of GBM. Targeting MS4A7-s may constitute a promising treatment for GBM.
Identification of thrombotic biomarkers in orthopedic surgery patients by plasma proteomics
Authors: Liu Cui-Qing , Gao Yu-Jing , Lin Geng-Xiong , Liang Jun-Ze , Li Yan-Fei , Wang Yi-Chun , Chen Wen-Yan , Chen Wei-Ju
Published: March 2023

Background

Due to the poor specificity of D-dimer, more accurate thrombus biomarkers are clinically needed to improve the diagnostic power of VTE.

Methods

The plasma samples were classified into low-risk group (n = 6) and high-risk group (n = 6) according to the Caprini Thrombosis Risk Assessment Scale score. Data-independent acquisition mass spectrometry (DIA-MS) was performed to identify the proteins in the 12 plasma samples. Bioinformatics analysis including volcano plot, heatmap, KEGG pathways and chord diagram analysis were drawn to analyze the significantly differentially expressed proteins (DEPs) between the two groups. Then, another 26 plasma samples were collected to verify the key proteins as potential biomarkers of VTE in orthopedic surgery patients.

Results

A total of 371 proteins were identified by DIA-MS in 12 plasma samples. Volcano plotting showed that there were 30 DEPs. KEGG pathway enrichment analysis revealed that the DEPs were majorly involved in the blood coagulation pathway. The chord diagram analysis demonstrated that proteins SAA1, VWF, FLNA, ACTB, VINC, F13B, F13A and IPSP in the DEPs were significantly related to blood coagulation. VWF and F13B were selected for validation experiments. ELISA test showed that, as compared with those in the low-risk group, the level of VWF in the high-risk sera was significantly increased.

Conclusions

The level of VWF in the high-risk group of thrombosis after orthopedic surgery was significantly higher than that in the low-risk group of preoperative thrombosis, suggesting that VWF may be used as a potential thrombus biomarker in orthopedic surgery patients.
RETRACTED ARTICLE: AMLnet, A deep-learning pipeline for the differential diagnosis of acute myeloid leukemia from bone marrow smears
Authors: Yu Zebin , Li Jianhu , Wen Xiang , Han Yingli , Jiang Penglei , Zhu Meng , Wang Minmin , Gao Xiangli , Shen Dan , Zhang Ting , Zhao Shuqi , Zhu Yijing , Tong Jixiang , Yuan Shuchong , Zhu HongHu , Huang He , Qian Pengxu
Published: March 2023

Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French–American–British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise. Here, we established a comprehensive database encompassing 8245 bone marrow smear images from 651 patients based on a retrospective dual-center study between 2010 and 2021 for the purpose of training and testing. Furthermore, we developed AMLnet, a deep-learning pipeline based on bone marrow smear images, that can discriminate not only between AML patients and healthy individuals but also accurately identify various AML subtypes. AMLnet achieved an AUC of 0.885 at the image level and 0.921 at the patient level in distinguishing nine AML subtypes on the test dataset. Furthermore, AMLnet outperformed junior human experts and was comparable to senior experts on the test dataset at the patient level. Finally, we provided an interactive demo website to visualize the saliency maps and the results of AMLnet for aiding pathologists’ diagnosis. Collectively, AMLnet has the potential to serve as a fast prescreening and decision support tool for cytomorphological pathologists, especially in areas where pathologists are overburdened by medical demands as well as in rural areas where medical resources are scarce.
Multi-omics analysis identifies drivers of protein phosphorylation
Authors: Zhang Tian , Keele Gregory R. , Gyuricza Isabela Gerdes , Vincent Matthew , Brunton Catherine , Bell Timothy A. , Hock Pablo , Shaw Ginger D. , Munger Steven C. , de Villena Fernando Pardo-Manuel , Ferris Martin T. , Paulo Joao A. , Gygi Steven P. , Churchill Gary A.
Published: March 2023

Background

Phosphorylation of proteins is a key step in the regulation of many cellular processes including activation of enzymes and signaling cascades. The abundance of a phosphorylated peptide (phosphopeptide) is determined by the abundance of its parent protein and the proportion of target sites that are phosphorylated.

Results

We quantified phosphopeptides, proteins, and transcripts in heart, liver, and kidney tissue samples of mice from 58 strains of the Collaborative Cross strain panel. We mapped ~700 phosphorylation quantitative trait loci (phQTL) across the three tissues and applied genetic mediation analysis to identify causal drivers of phosphorylation. We identified kinases, phosphatases, cytokines, and other factors, including both known and potentially novel interactions between target proteins and genes that regulate site-specific phosphorylation. Our analysis highlights multiple targets of pyruvate dehydrogenase kinase 1 (PDK1), a regulator of mitochondrial function that shows reduced activity in the NZO/HILtJ mouse, a polygenic model of obesity and type 2 diabetes.

Conclusions

Together, this integrative multi-omics analysis in genetically diverse CC strains provides a powerful tool to identify regulators of protein phosphorylation. The data generated in this study provides a resource for further exploration.
Mosquito diversity (Diptera: Culicidae) and medical importance in four Cambodian forests
Authors: Rakotonirina Antsa , Maquart Pierre-Olivier , Flamand Claude , Sokha Chea , Boyer Sébastien
Published: March 2023

Background

A total of 290 mosquito species are recorded in Cambodia among which 43 are known vectors of pathogens. As Cambodia is heavily affected by deforestation, a potential change in the dynamic of vector-borne diseases (VDBs) could occur through alteration of the diversity and density of sylvatic vector mosquitoes and induce an increase in their interactions with humans. Understanding mosquito diversity is therefore critical, providing valuable data for risk assessments concerning the (re)emergence of local VBDs. Consequently, this study mainly aimed to understand the spatial and temporal distribution of sylvatic mosquito populations of Cambodia by determining which factors impact on their relative abundance and presence.

Methods

A study was conducted in 12 sites from four forests in Cambodia. All mosquitoes, collected during the dry and rainy seasons, were morphologically identified. The diversity and relative density of mosquito species in each site were calculated along with the influence of meteorological and geographical factors using a quasi-Poisson generalized linear model.

Results

A total of 9392 mosquitoes were collected belonging to 13 genera and 85 species. The most represented genera wereCulex, accounting for 46% of collected mosquitoes, andAedes(42%). Besides being the most abundant species,Culex pseudovishnuiandAedes albopictus, which are known vectors of numerous arboviruses, were present in all sites during both dry and rainy seasons. The presence of mosquito species reported to be zoo-anthropophilic feeders was also observed in both forested and urban areas. Finally, this study demonstrated that altitude, temperature and precipitation impacted the abundance of mosquitoes but also influenced species community composition.

Conclusion

The results indicate an important diversity of mosquitoes in the four forests and an influence of meteorological and geographical factors on their community. Additionally, this work highlights in parallel the abundance of species considered to be of medical importance and therefore underlines the high risk of pathogen emergence/re-emergence in the region.

Graphical Abstract
Clinical and diagnostic characteristics of non-alcoholic fatty liver disease among Egyptian children and adolescents with type1 diabetes
Authors: Abdallah Hanaa Reyad , Youness Eman Refaat , Bedeir Manar Maher , Abouelnaga Marwa W. , Ezzat Wafaa M. , Elhosary Yasser , El-Hariri Hazem Mohamed , Hussein Mona Abd Elmotaleb A. , Ahmed Heba R. , Eladawy Rasha
Published: March 2023

Background

Type 1 diabetes mellitus (T1DM) patients are at an increased risk for non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the clinical criteria associated with the diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) among T1DM Egyptian children and adolescents.

Methods

74 T1DM patients aged 8–18 year were enrolled in this cross sectional study. Assessments of Clinical status, anthropometric measures, lipid profile, glycated haemoglobin (HbA1c) and liver enzymes were done. Abdominal Ultrasound evaluation of hepatic steatosis was done. Accordingly, patients were divided into two groups (NAFLD and normal liver group) and compared together. Assessment of liver fibrosis using acoustic radiation force impulse elastography (ARFI) was done. Statistical analysis included; independent t-test, Chi square and Fisher’s Exact, Pearson and Spearman tests and Logistic regression models for factors associated with fatty liver were used when appropriate.

Results

In this study; 74 patients were enrolled; 37 males (50%) and 37 females with mean age 14.3 ± 3.0 year. The mean insulin dose was 1.1 ± 0.4 U/kg and mean disease duration was 6.3 ± 3.0 year. NAFLD was detected in 46 cases while 28 cases had normal liver as diagnosed by abdominal ultrasound. Cases with NAFLD had statistically significant higher BMI-Z scores, waist/hip, waist/height and sum of skin fold thicknesses compared to those with normal liver (P < 0.05). The mean value of HbA1c % was significantly higher in NAFLD group (P = 0.003). Total cholesterol, triglycerides and LDL serum levels were significantly elevated (p < 0.05), while the HDL level was significantly lower in NAFLD cases (p = 0.001). Although, serum levels of liver enzymes; ALT and AST were significantly higher among cases with NAFLD than in normal liver group (p < 0.05), their means were within normal. Using the ARFI elastography; NAFLD cases exhibited significant fibrosis (F2, 3 and 4). BMI, patient age and female gender were among risk factors for NAFLD.

Conclusions

NAFLD represents a serious consequence in type 1 diabetic children and adolescents that deserves attention especially with poor glycemic control. NAFLD has the potential to evolve to fibrosis. This study demonstrated a very high prevalence of NAFLD in T1D children and adolescents using US which was (62.2%) with the percent of liver fibrosis among the NAFLD cases (F2-F4) using ARFI elastography was 26%. BMI, age of patients and female gender were detected as risk factors for NAFLD.
Gut microbiota and host cytochrome P450 characteristics in the pseudo germ-free model: co-contributors to a diverse metabolic landscape
Authors: Wang Shanshan , Wen Qiuyu , Qin Yan , Xia Quan , Shen Chenlin , Song Shuai
Published: March 2023

Background

The pseudo germ-free (PGF) model has been widely used to research the role of intestinal microbiota in drug metabolism and efficacy, while the modelling methods and the utilization of the PGF model are still not standardized and unified. A comprehensive and systematic research of the PGF model on the composition and function of the intestinal microbiota, changes in host cytochrome P450 (CYP450) enzymes expression and intestinal mucosal permeability in four different modelling cycles of the PGF groups are provided in this paper.

Results

16S rRNA gene amplicon sequencing was employed to compare and analyze the alpha and beta diversity, taxonomic composition, taxonomic indicators and predicted function of gut microbiota in the control and PGF groups. Bacterial richness and diversity decreased significantly in the PGF group beginning after the first week of establishment of the PGF model with antibiotic exposure. The PGF group exposed to antibiotics for 4-week-modelling possessed the fewest indicator genera. Moreover, increased intestinal mucosal permeability occurred in the second week of PGF model establishment, indicating that one week of antibiotic exposure is an appropriate time to establish the PGF model. The results of immunoblots revealed that CYP1A2, CYP2C19 and CYP2E1 expression was significantly upregulated in the PGF group compared with the control group, implying that the metabolic clearance of related drugs would change accordingly. The abundance of functional pathways predicted in the gut microbiota changed dramatically between the control and PGF groups.

Conclusions

This study provides information concerning the microbial and CYP450 enzyme expression profiles as a reference for evaluating drug metabolism differences co-affected by gut microbiota and host CYP450 enzymes in the PGF model.
DNA methylation abnormalities induced by advanced maternal age in villi prime a high-risk state for spontaneous abortion
Authors: Qin Meng , Chen Wei , Hua Lingyue , Meng Yan , Wang Jing , Li Hanna , Yang Rui , Yan Liying , Qiao Jie
Published: March 2023

Background

Advanced maternal age (AMA) has increased in many high-income countries in recent decades. AMA is generally associated with a higher risk of various pregnancy complications, and the underlying molecular mechanisms are largely unknown. In the current study, we profiled the DNA methylome of 24 human chorionic villi samples (CVSs) from early pregnancies in AMA and young maternal age (YMA), 11 CVSs from early spontaneous abortion (SA) cases using reduced representation bisulfite sequencing (RRBS), and the transcriptome of 10 CVSs from AMA and YMA pregnancies with mRNA sequencing(mRNA-seq). Single-cell villous transcriptional atlas presented expression patterns of targeted AMA-/SA-related genes. Trophoblast cellular impairment was investigated through the knockdown of GNE expression in HTR8-S/Vneo cells.

Results

AMA-induced local DNA methylation changes, defined as AMA-related differentially methylated regions (DMRs), may be derived from the abnormal expression of genes involved in DNA demethylation, such as GADD45B. These DNA methylation changes were significantly enriched in the processes involved in NOTCH signaling and extracellular matrix organization and were reflected in the transcriptional alterations in the corresponding biological processes and specific genes. Furthermore, the DNA methylation level of special AMA-related DMRs not only significantly changed in AMA but also showed more excessive defects in CVS from spontaneous abortion (SA), including four AMA-related DMRs whose nearby genes overlapped with AMA-related differentially expressed genes (DEGs) (CDK11A, C19orf71, COL5A1, and GNE). The decreased DNA methylation level of DMR near GNE was positively correlated with the downregulated expression of GNE in AMA. Single-cell atlas further revealed comparatively high expression of GNE in the trophoblast lineage, and knockdown of GNE in HTR8-S/Vneo cells significantly impaired cellular proliferation and migration.

Conclusion

Our study provides valuable resources for investigating AMA-induced epigenetic abnormalities and provides new insights for explaining the increased risks of pregnancy complications in AMA pregnancies.

Graphical Abstract