bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Insights of Schizophrenia via Single Cell RNA-Sequencing Analyses
Authors: Wu Yong , Zhang Chu-Yi , Wang Lu , Li Yi , Xiao Xiao 
Published: February 2023

Abstract

Background
Schizophrenia is a complex and heterogeneous disorder involving multiple regions and types of cells in the brain. Despite rapid progress made by genome-wide association studies (GWAS) of schizophrenia, the mechanisms of the illness underlying the GWAS significant loci remain less clear.

Study Design
We investigated schizophrenia risk genes using summary-data-based Mendelian randomization based on single-cell sequencing data, and explored the types of brain cells involved in schizophrenia through the expression weighted cell-type enrichment analysis.

Results
We identified 54 schizophrenia risk genes (two-thirds of these genes were not identified using sequencing data of bulk tissues) using single-cell RNA-sequencing data. Further cell type enrichment analysis showed that schizophrenia risk genes were highly expressed in excitatory neurons and caudal ganglionic eminence interneurons, suggesting putative roles of these cells in the pathogenesis of schizophrenia. We also found that these risk genes identified using single-cell sequencing results could form a large protein-protein interaction network with genes affected by disease-causing rare variants.

Conclusions
Through integrative analyses using expression data at single-cell levels, we identified 54 risk genes associated with schizophrenia. Notably, many of these genes were only identified using single-cell RNA-sequencing data, and their altered expression levels in particular types of cells, rather than in the bulk tissues, were related to the increased risk of schizophrenia. Our results provide novel insight into the biological mechanisms of schizophrenia, and future single-cell studies are necessary to further facilitate the understanding of the disorder.
Altered neuronal response to visual food stimuli in adolescents undergoing chronic sleep restriction
Authors: DiFrancesco Mark W , Alsameen Maryam , St-Onge Marie-Pierre , Duraccio Kara M , Beebe Dean W 
Published: February 2023

Abstract

Study Objectives
Poor sleep in adolescents can increase the risk of obesity, possibly due to changes in dietary patterns. Prior neuroimaging evidence, mostly in adults, suggests that lacking sleep results in increased response to food cues in reward-processing brain regions. Needed is a clarification of the mechanisms by which food reward processing is altered by the kind of chronic sleep restriction (SR) typically experienced by adolescents. This study aimed to elucidate the impact of sleep duration on response to visual food stimuli in healthy adolescents using functional neuroimaging, hypothesizing increased reward processing response after SR compared to a well-rested condition.

Methods
Thirty-nine healthy adolescents, 14–17 years old, completed a 3-week protocol: (1) sleep phase stabilization; (2) SR (~6.5 h nightly); and (3) healthy sleep (HS) duration (~9 h nightly). Participants underwent functional MRI while performing a visual food paradigm. Contrasts of food versus nonfood responses were compared within-subject between conditions of SR and HS.

Results
Under SR, there was a greater response to food stimuli compared to HS in a voxel cluster including the left ventral tegmental area and substantia nigra. No change in food appeal rating due to the sleep manipulation was detected.

Conclusions
Outcomes of this study suggest that SR, as commonly experienced by healthy adolescents, results in the elevated dopaminergic drive of the reward network that may augment motivation to seek food in the context of individual food appeal and inhibitory profiles. Countermeasures that reduce food salience could include promoting consistent HS habits.
Intracellular Reactive Oxygen Species-Aided Localized Cell Death Contributing to Immune Responses Against Wheat Powdery Mildew Pathogen
Authors: Li Yinghui , Roychowdhury Rajib , Govta Liubov , Jaiwar Samidha , Wei Zhen-Zhen , Shams Imad , Fahima Tzion 
Published: February 2023

Reactive oxygen species (ROS)- and hypersensitive response (HR)-mediated cell death have long been known to play critical roles in plant immunity to pathogens. Wheat powdery mildew caused by Blumeria graminis f. sp. tritici ( Bgt) is a destructive wheat pathogen. Here, we report a quantitative analysis of the proportion of infected cells with local apoplastic ROS (apoROS) versus intracellular ROS (intraROS) accumulation in various wheat accessions that carry different disease resistance genes ( R genes) at a series of time points postinfection. The proportion of apoROS accumulation was 70 to 80% of the infected wheat cells detected in both compatible and incompatible host−pathogen interactions. However, intensive intraROS accumulation followed by localized cell death responses was detected in 11 to 15% of the infected wheat cells, mainly in wheat lines that carried nucleotide-binding leucine-rich repeat R genes (e.g., Pm3F, Pm41, TdPm60, MIIW72, and Pm69). The lines that carry unconventional R genes, Pm24 ( Wheat Tandem Kinase 3) and pm42 (a recessive R gene), showed fewer intraROS responses, whereas 11% of Pm24 line-infected epidermis cells still showed HR cell death, suggesting that different resistance pathways are activated there. Here, we also demonstrated that ROS could not act as a strong systemic signal for inducing high resistance to Bgt in wheat, although it induced the expression of pathogenesis-related genes. These results provide new insights into the contribution of intraROS and localized cell death to immune responses against wheat powdery mildew.
Polymorphism of Avirulence Genes and Adaptation to Brassica Resistance Genes Is Gene-Dependent in the Phytopathogenic Fungus Leptosphaeria maculans
Authors: Gautier Angélique , Laval Valérie , Faure Sébastien , Rouxel Thierry , Balesdent Marie-Hélène 
Published: February 2023

The fungal phytopathogen Leptosphaeria maculans, which causes stem canker (blackleg) of rapeseed ( Brassica napus), is mainly controlled worldwide by genetic resistance, which includes major resistance genes ( Rlm). This model is one of those for which the highest number of avirulence genes ( AvrLm) has been cloned. In many systems, including the L. maculans–B. napus interaction, intense use of resistance genes exerts strong selection pressure on the corresponding avirulent isolates, and the fungi may rapidly escape resistance through various molecular events which modify the avirulence genes. In the literature, the study of polymorphism at avirulence loci is often focused on single genes under selection pressure. In this study, we investigate allelic polymorphism at 11 avirulence loci in a French population of 89 L. maculans isolates collected on a trap cultivar in four geographic locations in the 2017−2018 cropping season. The corresponding Rlm genes have been (i) used for a long time, (ii) recently used, or (iii) unused in agricultural practice. The sequence data generated indicate an extreme diversity of situations. For example, genes submitted to an ancient selection may have either been deleted in populations ( AvrLm1) or replaced by a single-nucleotide mutated virulent version ( AvrLm2, AvrLm5-9). Genes that have never been under selection may either be nearly invariant ( AvrLm6, AvrLm10A, AvrLm10B), exhibit rare deletions ( AvrLm11, AvrLm14), or display a high diversity of alleles and isoforms ( AvrLmS-Lep2). These data suggest that the evolutionary trajectory of avirulence/virulence alleles is gene-dependent and independent of selection pressure in L. maculans. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Development of a Wound Assessment Tool for Use in Adults at End of Life: A Modified Delphi Study
Authors: Latimer Sharon , Harbeck Emma , Walker Rachel M. , Ray-Barruel Gillian , Shaw Joanie , Hunt Tracy , Gillespie Brigid M. 
Published: February 2023

ABSTRACT

BACKGROUND
Some patients at end of life (EOL) develop wounds known as Kennedy terminal ulcers, terminal ulcers, and Skin Changes At Life’s End. However, there is ambiguity around the defining wound characteristics of these conditions and a lack of validated clinical assessment tools available to identify them.

OBJECTIVE
To gain consensus on the definition and characteristics of EOL wounds and establish the face and content validity of a wound assessment tool for use in adults at EOL.

METHODS
Using a reactive online Delphi technique, international wound experts reviewed the 20 items in the tool. Over two iterative rounds, experts assessed item clarity, relevance, and importance using a four-point content validity index. The content validity index scores were calculated for each item, with a level of 0.78 or higher signifying panel consensus.

RESULTS
Round 1 included 16 panelists (100.0%). The agreement for item relevance and importance ranged from 0.54% to 0.94%, and item clarity scored between 0.25% and 0.94%. Following round 1, four items were removed, and seven others reworded. Other suggestions included changing the tool name and including Kennedy terminal ulcer, terminal ulcer, and Skin Changes At Life’s End in the EOL wound definition. In round 2, the now 13 panel members agreed with the final 16 items included and suggested minor wording changes.

CONCLUSIONS
This tool could provide clinicians with an initially validated tool to accurately assess EOL wounds and gather much needed empirical prevalence data. Further research is needed to underpin accurate assessment and the development of evidence-based management strategies.
Comparison of Different Surgical Techniques in Correction of Congenital Vertical Talus Deformity: A Systematic Review and Meta-Analysis of the Literature
Authors: Cummings Jason L. , Rivera Asdrubal E. , Tippabhatla Abhishek , Hosseinzadeh Pooya 
Published: February 2023

Background:
Congenital Vertical Talus (CVT) is a rare form of congenital rigid flatfoot. Numerous surgical techniques have been developed over the years in an attempt to definitively correct this deformity. We performed a systematic review and meta-analysis of the existing literature to compare the outcomes of children with CVT treated with different methods.

Methods:
A detailed systematic search was conducted in accordance with PRISMA guidelines. Radiographic recurrence of the deformity, reoperation rate, ankle arc of motion, and clinical scoring was compared between the following 5 methods: Two-Stage Coleman-Stelling Technique, Direct Medial Approach, Single-Stage Dorsal (Seimon) Approach, Cincinnati Incision, and Dobbs Method. Meta-analyses of proportions were performed, and data were pooled through a random effects model using the DerSimonian and Laird approach. Heterogeneity was assessed using I^2 statistics. The authors used a modified version of the Adelaar scoring system to assess clinical outcomes. An alpha of 0.05 was used for all statistical analysis.

Results:
Thirty-one studies (580 feet) met the inclusion criteria. The reported incidence of radiographic recurrence of talonavicular subluxation was 19.3%, with 7.8% requiring reoperation. Radiographic recurrence of the deformity was highest in the children treated with the direct medial approach (29.3%) and lowest in the Single-Stage Dorsal Approach cohort (11%) (P<0.05). The reoperation rate was significantly lower in the Single-Stage Dorsal Approach cohort (2%) compared with all other methods (P<0.05). There was no significant difference in the reoperation rates between the other methods. The highest clinical score was seen in the Dobbs Method cohort (8.36), followed by the group treated with the Single-Stage Dorsal Approach (7.81). The Dobbs Method resulted in the largest ankle arc of motion.

Conclusion:
We found the lowest radiographic recurrence and reoperation rates in the Single-Stage Dorsal Approach cohort, while the highest rate of radiographic recurrence was seen in those treated with the Direct Medial Approach. The Dobbs Method results in higher clinical scores and ankle arc of motion. Future long-term studies focusing on patient-reported outcomes are needed.

Level of Evidence:
Level III.
Is There a Relationship Between the Functional Level of Juvenile and Adolescent Patients With Down Syndrome and Hip Dysplasia?
Authors: Galán-Olleros María , Palazón-Quevedo Ángel , Egea-Gámez Rosa M. , Ramírez-Barragán Ana , Serrano J. Ignacio , Martínez-Caballero Ignacio 
Published: February 2023

Background:
The prevalence of hip dysplasia among patients with Down syndrome (DS) is higher than in the general population. We hypothesize that a relationship may exist between functional level and hip dysplasia in DS, but this has not been studied to date. The aim of this study is to evaluate whether there is a relationship between functional level and radiographic parameters of hip dysplasia or other measures.

Methods:
Retrospective cross-sectional comparative study of 652 patients with DS from a pediatric referral center database. Patients over 8 years of age with an anteroposterior pelvis radiograph and with no exclusion criteria were selected, totaling 132 patients (264 hips; 54.55% females; mean age 12.96 ± 2.87 y). Several radiographic parameters of the acetabulum [Sharp angle (SA), Tönnis angle (TA), Wiberg center-edge angle (W-CEA), extrusion index (EI), and acetabular retroversion signs], the proximal femur [neck shaft angle (NSA)], and joint congruence [Shenton line (SL)] were assessed. Patients were classified into 2 levels based on functional skills. A multivariate association analysis was performed between radiographic parameters and functional level.

Results:
Sixty-one patients were compatible with a functional level I and 71 with a level II. Forty-six hips were dysplastic and 60 were borderline according to the W-CEA. A statistically significant relationship was found between the categorical distribution of certain radiographic measurements of hip dysplasia (EI, SA, TA, W-CEA, SL, and classification by functional level (P < 0.0005). A significant receiver operating characteristic curve was obtained for W-CEA with a cutt-off point at 26.4 degrees for level I (area under the curve = 0.763; P < 0.005; sensitivity = 0.800 and specificity = 0.644). There was a fairly high correlation between EI and TA (0.749; P < 0.0005), EI and W-CEA (−0.817; P < 0.0005), and TA and W-CEA (−0.748; P < 0.0005). Numerous hips showed signs of acetabular retroversion, with no significant differences found between functional levels or association with hip dysplasia measures.

Conclusions:
The present study reveals a relationship between an increased risk of hip dysplasia and reduced functional levels in DS children older than 8 years. These findings may guide individualized clinical follow-up of hip development in DS children considering their functional level.

Level of Evidence:
Level III, retrospective comparative study.
Indications and Outcomes of a Tibial Turn-up Procedure: A Case Series and Review of the Literature
Authors: Voskuil Ryan T. , Welder Eric , Schulz Steven A. , Mayerson Joel L. , Scharschmidt Thomas J. 
Published: February 2023

Background:
Treatment options for distal femoral bone loss resulting from malignancy, infection, or trauma can be grouped into limb salvage techniques versus amputation. A vascularized osteomyocutaneous flap using the ipsilateral tibia—a tibial turn-up procedure—can be used to restore femoral length for high above-knee amputations in both the primary and revision setting. We report 3 patients treated with this procedure.

Purpose:
To describe the treatment algorithm and functional outcomes of patients who have undergone a tibial turn-up procedure and to highlight its viability when considering surgical options for the treatment of distal femoral primary bone and soft tissue malignancy and in cases of severe trauma, infection, or implant failure.

Patients and Methods:
Three patients ages 21 to 56 years old treated with tibial turn-up as a salvage procedure for failed limb sparing techniques were followed for 1.5 to 3.5 years postoperatively. One was treated for recalcitrant chronic distal femur osteomyelitis, 1 for aseptic loosening of distal femoral replacement, and 1 for infected distal femoral replacement. Radiographic and functional outcomes including prosthetic use, ambulatory status, and current activity level were reported.

Results:
At a minimum 1.5-year follow-up, all 3 patients achieved bony union and were ambulatory with prosthetics without the use of additional gait aids.

Conclusions:
Tibial turn-up is an effective treatment option in the setting of distal femoral bone loss and/or limb salvage complications, providing good functional outcomes with a single durable surgery.
Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume
Authors: Chen Xiang , Chen Yuxi , Yan Kai , Chen Huiyao , Qin Qian , Yang Lin , Liu Bo , Cheng Guoqiang , Cao Yun , Wu Bingbing , Dong Xinran , Qiao Zhongwei , Zhou Wenhao 
Published: February 2023

Abstract

Background:
Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).

Methods:
We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.

Results:
We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<−2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs.75% [30/40, P = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes (P = 1.656e–9). In seven human brain regions related to motor development, we abserved burden genes had higher expression before 37 weeks gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.

Conclusion:
Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Muscular tissue desaturation and pneumonia in patients receiving lung cancer surgery: a cohort study
Authors: Zhao Wei , Zhang Caijuan , Mu Dongliang , Cui Fan , Jia Huiqun 
Published: February 2023

Abstract

Background:
Post-operative pneumonia (POP) is a common complication of lung cancer surgery, and muscular tissue oxygenation is a root cause of post-operative complications. However, the association between muscular tissue desaturation and POP in patients receiving lung cancer surgery has not been specifically studied. This study aimed to investigate the potential use of intra-operative muscular tissue desaturation as a predictor of POP in patients undergoing lung cancer surgery.

Methods:
This cohort study enrolled patients (≥55 years) who had undergone lobectomy with one-lung ventilation. Muscular tissue oxygen saturation (SmtO2) was monitored in the forearm (over the brachioradialis muscle) and upper thigh (over the quadriceps) using a tissue oximeter. The minimum SmtO2 was the lowest intra-operative measurement at any time point. Muscular tissue desaturation was defined as a minimum baseline SmtO2 of <80% for >15 s. The area under or above the threshold was the product of the magnitude and time of desaturation. The primary outcome was the association between intra-operative muscular tissue desaturation and POP within seven post-operative days using multivariable logistic regression.The secondary outcome was the correlation between SmtO2 in the forearm and that in the thigh.

Results:
We enrolled 174 patients. The overall incidence of muscular desaturation (defined as SmtO2 < 80% in the forearm at baseline) was approximately 47.1% (82/174). The patients with muscular desaturation had a higher incidence of pneumonia than those without desaturation (28.0% [23/82] vs. 12.0% [11/92]; P = 0.008). The multivariable analysis revealed that muscular desaturation was associated with an increased risk of pneumonia (odds ratio: 2.995, 95% confidence interval: 1.080–8.310, P = 0.035) after adjusting for age, American Society of Anesthesiologists status, Assess Respiratory Risk in Surgical Patients in Catalonia score, smoking, use of peripheral nerve block, propofol, and study center.

Conclusion:
Muscular tissue desaturation, defined as a baseline SmtO2 < 80% in the forearm, may be associated with an increased risk of POP.

Trial registration:
No. ChiCTR-ROC-17012627.
Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution
Authors: Liang Yuanzheng , Liu Xindi , Yang Jing , Wang Henan , Piao Yingshi , Wei Liqiang , Wang Liang 
Published: February 2023

Abstract

Background:
To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution.

Methods:
This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS).

Results:
During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan–Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P = 0.025 and P = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4–99.8%) and 95.2% (95% CI: 89.0–100.0%), respectively, and 80.5% (95% CI: 69.3–93.6%) and 90.5% (95% CI: 52.8–99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01–0.88) and 0.042 (HR: 0.19; 95% CI: 0.04–0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups.

Conclusion:
Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.