bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural variations of heterosis-related allele-specific expression genes in promoter regions lead to allele-specific expression in maize
Authors: Zhan Weimin , Cui Lianhua , Yang Shuling , Zhang Kangni , Zhang Yanpei , Yang Jianping 
Published: May 2024

Abstract
Background
Heterosis has successfully enhanced maize productivity and quality. Although significant progress has been made in delineating the genetic basis of heterosis, the molecular mechanisms underlying its genetic components remain less explored. Allele-specific expression (ASE), the imbalanced expression between two parental alleles in hybrids, is increasingly being recognized as a factor contributing to heterosis. ASE is a complex process regulated by both epigenetic and genetic variations in response to developmental and environmental conditions.

Results
In this study, we explored the differential characteristics of ASE by analyzing the transcriptome data of two maize hybrids and their parents under four light conditions. On the basis of allele expression patterns in different hybrids under various conditions, ASE genes were divided into three categories: bias-consistent genes involved in basal metabolic processes in a functionally complementary manner, bias-reversal genes adapting to the light environment, and bias-specific genes maintaining cell homeostasis. We observed that 758 ASE genes (ASEGs) were significantly overlapped with heterosis quantitative trait loci (QTLs), and high-frequency variations in the promoter regions of heterosis-related ASEGs were identified between parents. In addition, 10 heterosis-related ASEGs participating in yield heterosis were selected during domestication.

Conclusions
The comprehensive analysis of ASEGs offers a distinctive perspective on how light quality influences gene expression patterns and gene-environment interactions, with implications for the identification of heterosis-related ASEGs to enhance maize yield.
Recurrent neural network for predicting absence of heterozygosity from low pass WGS with ultra-low depth
Authors: Tang Fei , Wang Zhonghua , Sun Yan , Fan Linlin , Yang Yun , Guo Xueqin , Wang Yaoshen , Yan Saiying , Qiao Zhihong , Li Yun , Jiang Ting , Wang Xiaoli , Man Jianfen , Wang Lina , Wang Shunyao , Peng Huanhuan , Peng Zhiyu , Xie Xiaoyuan , Song Lijie 
Published: May 2024

Abstract
Background
The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES).

Results
Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions.

Conclusions
Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.
Evaluation of fortimicin antibiotic combinations against MDR Pseudomonas aeruginosa and resistome analysis of a whole genome sequenced pan-drug resistant isolate
Authors: Kamel Noha A. , Tohamy Sally T. , Alshahrani Mohammad Y. , Aboshanab Khaled M. 
Published: May 2024

Abstract
Background
Multidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate.

Methods
Standard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate.

Results
Out of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with β-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (β-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents.

Conclusion
Fortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.
Development of PCR-based markers for identification of wheat HMW glutenin Glu-1Bx and Glu-1By alleles
Authors: Lee Myoung Hui , Kim Kyeong-Min , Kang Chon-Sik , Yoon Mira , Jang Ki-Chang , Choi Changhyun 
Published: May 2024

Abstract
Background
In common wheat (Triticum aestivum L.), allelic variations in the high-molecular-weight glutenin subunits Glu-B1 locus have important effects on grain end-use quality. The Glu-B1 locus consists of two tightly linked genes encoding x- and y-type subunits that exhibit highly variable frequencies. However, studies on the discriminating markers of the alleles that have been reported are limited. Here, we developed 11 agarose gel-based PCR markers for detecting Glu-1Bx and Glu-1By alleles.

Results
By integrating the newly developed markers with previously published PCR markers, nine Glu-1Bx locus alleles (Glu-1Bx6, Glu-1Bx7, Glu-1Bx7*, Glu-1Bx7OE, Glu-1Bx13, Glu-1Bx14(−), Glu-1Bx14(+)/Bx20, and Glu-1Bx17) and seven Glu-1By locus alleles (Glu-1By8, Glu-1By8*, Glu-1By9, Glu-1By15/By20, Glu-1By16, and Glu-1By18) were distinguished in 25 wheat cultivars. Glu-1Bx6, Glu-1Bx13, Glu-1Bx14(+)/Bx20, Glu-1By16, and Glu-1By18 were distinguished using the newly developed PCR markers. Additionally, the Glu-1Bx13 and Glu-1Bx14(+)/Bx20 were distinguished by insertions and deletions in their promoter regions. The Glu-1Bx6, Glu-1Bx7, Glu-1By9, Glu-1Bx14(−), and Glu-1By15/By20 alleles were distinguished by using insertions and deletions in the gene-coding region. Glu-1By13, Glu-1By16, and Glu-1By18 were dominantly identified in the gene-coding region. We also developed a marker to distinguish between the two Glu-1Bx14 alleles. However, the Glu-1Bx14(+) + Glu-1By15 and Glu-1Bx20 + Glu-1By20 allele combinations could not be distinguished using PCR markers. The high-molecular-weight glutenin subunits of wheat varieties were analyzed by ultra-performance liquid chromatography and sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and the findings were compared with the results of PCR analysis.

Conclusions
Seven Glu-1Bx and four Glu-1By allele detection markers were developed to detect nine Glu-1Bx and seven Glu-1By locus alleles, respectively. Integrating previously reported markers and 11 newly developed PCR markers improves allelic identification of the Glu-B1 locus and facilitates more effective analysis of Glu-B1 alleles molecular variations, which may improve the end-use quality of wheat.
Diabetes mellitus in older persons with neurocognitive disorder: overtreatment prevalence and associated structural brain MRI findings
Authors: Putallaz Pauline , Seematter-Bagnoud Laurence , Draganski Bogdan , Rouaud Olivier , Krief Hélène , Büla Christophe J. 
Published: May 2024

Abstract
Background
Tight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes.

Methods
Retrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated.

Results
Among 161 patients included (median age 76.8 years, range 60.8–93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj β coeff: -0.217, 95%CI: [-0.416 to -0.018], p = .033), the precentral gyri (adj βcoeff:-0.277, 95%CI: [-0.482 to -0.073], p = .009), the superior frontal gyri (adj βcoeff: -0.244, 95%CI: [-0.458 to -0.030], p = .026), the calcarine cortex (adj βcoeff:-0.193, 95%CI: [-0.386 to -0.001], p = .049), the superior occipital gyri (adj βcoeff: -0.291, 95%CI: [-0.521 to -0.061], p = .014) and the inferior occipital gyri (adj βcoeff: -0.236, 95%CI: [-0.456 to – 0.015], p = .036).

Conclusion
A significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample.
Measurement of distances and locations of thoracic and lumbar vertebral bodies from CT scans in cases of spinal deformation
Authors: Grünwald Alexander T. D. , Roy Susmita , Lampe Renée 
Published: May 2024

Abstract
Background
Spinal deformations, except for acute injuries, are among the most frequent reasons for visiting an orthopaedic specialist and musculoskeletal treatment in adults and adolescents. Data on the morphology and anatomical structures of the spine are therefore of interest to orthopaedics, physicians, and medical scientists alike, in the broad field from diagnosis to therapy and in research.

Methods
Along the course of developing supplementary methods that do not require the use of ionizing radiation in the assessment of scoliosis, twenty CT scans from females and males with various severity of spinal deformations and body shape have been analysed with respect to the transverse distances between the vertebral body and the spinous process end tip and the skin, respectively, at thoracic and lumbar vertebral levels. Further, the locations of the vertebral bodies have been analysed in relation to the patient’s individual body shape and shown together with those from other patients by normalization to the area encompassed by the transverse body contour.

Results
While the transverse distance from the vertebral body to the skin varies between patients, the distances from the vertebral body to the spinous processes end tips tend to be rather similar across different patients of the same gender. Tables list the arithmetic mean distances for all thoracic and lumbar vertebral levels and for different regions upon grouping into mild, medium, and strong spinal deformation and according to the range of spinal deformation.

Conclusions
The distances, the clustering of the locations of the vertebral bodies as a function of the vertebral level, and the trends therein could in the future be used in context with biomechanical modeling of a patient’s individual spinal deformation in scoliosis assessment using 3D body scanner images during follow-up examinations.
An unusual case of adult-onset still’s disease complicated with anti-complement factor H antibodies associated atypical haemolytic uraemic syndrome
Authors: Fung Winston Wing-Shing , Chao Amelia Chien-Wei , Pang Wing-Fai , Wong Raymond Siu-Ming , Chow Kai-Ming , Szeto Cheuk-Chun 
Published: May 2024

Abstract
Background
Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still’s disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing.

Case presentation
A 42 years old man was admitted with suspected adult-onset Still’s disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still’s disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml).

Conclusion
Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.
Prevalence, factors associated and management of needle phobia among the general population in Saudi Arabia and Egypt
Authors: Alwafi Hassan , Naser Abdallah Y. , Alsaleh Nada A. , Asiri Jamila Kamal , Almontashri Rawan M. , Alqarni Lujain Mohammed , Salawati Rawan Sulaiman , Alsharif Alaa , Aldhahir Abdulelah M. , Alqarni Abdullah A. , Hafiz Waleed , Alqahtani Jaber S. , Salawati Emad , Almatrafi Mohammed A. , Bahlol Mohamed 
Published: May 2024

Abstract
Objective
This study aims to assess the prevalence of needle phobia among Saudi and Egyptian adult populations. In addition, underlying causes and strategies that can be utilized to address needle fear were investigated.

Methods
A cross-sectional online survey study was conducted in Saudi Arabia and Egypt between 1 May and 30 June 2023. Participants aged 18 years and above and living in Saudi Arabia and Egypt were eligible to complete the survey. Participants were invited to participate in this study through social media platforms (Facebook, X, Snapchat, and Instagram). A convenience sampling technique was used to recruit the study participants. A 21-item questionnaire consisting of four sections including a Likert scale score was used to answer the research objectives. Numeric data were presented as mean ± SD. For categorical variables, percentages were used. Comparison between groups were made by Student’s t-test or Mann Whitney test according to data distribution. Chi squared tests for categorical values were conducted. A binary logistic regression analysis was conducted to investigate factors associated with needle phobia.

Results
A total of 4065 participants were involved in this study (Saudi Arabia: 2628 and Egypt: 1437). Around one-third of the study participants (36.5%) confirmed that they have needle phobia. Most of the study participants (81.1%) reported that they have had needle phobia since they were under 18 years of age. Pain, general anxiety, and fear of making a mistake during the procedure were the most commonly reported contributors for fear of needles during or before a medical procedure. Around 15.8% of the study participants reported that they have tried to get rid of phobia from needles. Non-surgical alternatives (such as oral medications and patches) and using smaller/thinner needles were the most commonly reported interventions that reduced fear of needles. Binary logistic regression analysis identified that females, those who are aged (41–50 years), widowed, those with bachelor’s degrees and higher education, and those unemployed were more likely to have needle phobia compared to others.

Conclusion
Our study highlighted the high prevalence of needle fear within an adult population in Egypt and Saudi Arabia. Females, those who are aged (41–50 years), those widowed, those with higher education degrees, those unemployed, those working in the health sector and people with low income were more likely to have needle phobia compared to others.
Concentrated transdiagnostic and cross-disciplinary micro-choice based group treatment for patients with depression and with anxiety leads to lasting improvements after 12 months: a pilot study
Authors: Wilhelmsen-Langeland Ane , Børtveit Tore , Jürgensen Marte , Søfteland Eirik , Hystad Sigurd William , Kvale Gerd 
Published: May 2024

Abstract
Background
A concentrated transdiagnostic and micro choice-based group treatment for patients with depression and anxiety has previously shown to yield significant reduction in symptoms and increased level of functioning from pre to 3-month follow-up. In the present study, we report the results after 12 months follow-up.

Methods
This was a non-randomized clinical intervention pilot study, conducted in line with a published protocol. Sixty-seven consecutively referred patients, aged 19–47 (mean age 32.5, SD = 8.0) were included and completed treatment. All had a severity of their problems that entitled them to care in the specialist public mental health care. Self-reported age at onset of symptoms was 17.6 (SD = 7.9) years. Mean number of prior treatment courses was 3.5 (SD = 3.3; range 0–20). The main objective was to assess the treatment effectiveness by questionnaires measuring relevant symptoms at pre-treatment, 7 days-, 3 months-, 6 months- and at 12-months follow-up.

Results
Validated measures of functional impairment (WSAS), depression (PHQ9), anxiety (GAD7), worry (PSWQ), fatigue (CFQ), insomnia (BIS) and illness perception (BIPQ) improved significantly (p < .0005) from before treatment to 12 months follow-up, yielding mostly large to extremely large effect sizes (0.89–3.68), whereas some moderate (0.60–0.76). After 12 months, 74% report an overall improvement in problems related to anxiety and depression. Utilization of specialist, public and private mental health care was reported as nonexistent or had decreased for 70% of the patients at 12-month follow up.

Conclusions
The concentrated, micro-choice based group treatment approach yielded a highly clinically significant reduction in a wide range of symptoms already one week after treatment, and the positive results persisted at 12-month follow-up.

Trial registration
ClinicalTrials.gov Identifier: NCT05234281, first posted date 10/02/2022.