bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic yield and novel candidate genes for neurodevelopmental disorders by exome sequencing in an unselected cohort with microcephaly
Authors: Wang Chunli , Zhou Wei , Zhang Luyan , Fu Luhan , Shi Wei , Qing Yan , Lu Fen , Tang Jian , Gao Xiucheng , Zhang Aihua , Jia Zhanjun , Zhang Yue , Zhao Xiaoke , Zheng Bixia 
Published: July 2023

Abstract
Objectives
Microcephaly is caused by reduced brain volume and most usually associated with a variety of neurodevelopmental disorders (NDDs). To provide an overview of the diagnostic yield of whole exome sequencing (WES) and promote novel candidates in genetically unsolved families, we studied the clinical and genetic landscape of an unselected Chinese cohort of patients with microcephaly.

Methods
We performed WES in an unselected cohort of 103 NDDs patients with microcephaly as one of the features. Full evaluation of potential novel candidate genes was applied in genetically undiagnosed families. Functional validations of selected variants were conducted in cultured cells. To augment the discovery of novel candidates, we queried our genomic sequencing data repository for additional likely disease-causing variants in the identified candidate genes.

Results
In 65 families (63.1%), causative sequence variants (SVs) and clinically relevant copy number variants (CNVs) with a pathogenic or likely pathogenic (P/LP) level were identified. By incorporating coverage analysis to WES, a pathogenic or likely pathogenic CNV was detected in 15 families (16/103, 15.5%). In another eight families (8/103, 7.8%), we identified variants in newly reported gene (CCND2) and potential novel neurodevelopmental disorders /microcephaly candidate genes, which involved in cell cycle and division (PWP2, CCND2), CDC42/RAC signaling related actin cytoskeletal organization (DOCK9, RHOF), neurogenesis (ELAVL3, PPP1R9B, KCNH3) and transcription regulation (IRF2BP1). By looking into our data repository of 5066 families with NDDs, we identified additional two cases with variants in DOCK9 and PPP1R9B, respectively.

Conclusion
Our results expand the morbid genome of monogenic neurodevelopmental disorders and support the adoption of WES as a first-tier test for individuals with microcephaly.
Symptoms and symptom clusters in patients newly diagnosed with inflammatory bowel disease: results from the IBSEN III Study
Authors: Johansen Ingunn , Småstuen Milada Cvancarova , Løkkeberg Stine Torp , Kristensen Vendel Ailin , Høivik Marte Lie , Lund Charlotte , Olsen Bjørn , Strande Vibeke , Huppertz-Hauss Gert , Aabrekk Tone Bergene , Bengtson May-Bente , Ricanek Petr , Detlie Trond Espen , Frigstad Svein Oskar , Jelsness-Jørgensen Lars-Petter , Opheim Randi 
Published: July 2023

Abstract
Background
Patients with inflammatory bowel disease report multiple symptoms, but the relationships among co-occurring symptoms are poorly understood. This study aimed to examine the prevalence of symptoms and explore symptom clusters and possible associations between symptom clusters and socio-demographic and clinical variables in patients newly diagnosed with inflammatory bowel disease.

Methods
The IBSEN III study is a prospective population-based inception cohort of patients with inflammatory bowel disease. This study used patient data from the three largest hospitals in the study catchment area. The Memorial Symptom Assessment Scale was used to assess the prevalence of symptoms. Symptom clusters were identified using principal component analysis. Possible associations between socio-demographic and clinical variables and symptom cluster membership were estimated using regression analysis.

Results
Of the 573 patients (age, ≥18 years) diagnosed with inflammatory bowel disease, 350 (61.1%) completed the questionnaire (responders). Eleven symptoms were reported by >50% of the responders. The three most prevalent symptoms were bloating (84%), drowsiness (81%), and lack of energy (81%). Three symptom clusters were identified: psychological (56% of the patients), impaired energy (28%), and physical (16%) clusters. Multinomial regression analysis revealed that vitamin D deficiency was significantly associated with the impaired energy cluster (odds ratio=2.49, 95% confidence interval [1.00-6.2],
p=0.05).

Conclusions
We found high symptom prevalence in patients newly diagnosed with inflammatory bowel disease. Three distinct symptom clusters were identified, and the psychological cluster includes >50% of the patients. Vitamin D deficiency is the only factor associated with cluster membership, namely the impaired energy cluster.
The efficacy and safety of patent Foramen Ovale Closure for Refractory Epilepsy (PFOC-RE): a prospectively randomized control trial of an innovative surgical therapy for refractory epilepsy patients with PFO of high-grade right-to-left shunt
Authors: Shuming Ji , Hua Li , Yusha Tang , Lei Chen 
Published: July 2023

Abstract
Background
A significant proportion of patients with epilepsy have an unknown etiology and lack effective targeted therapeutic drugs. Patent Foramen Ovale (PFO) induces hypoxia and microembolism, leading to cerebral neurological dysfunction and increased epilepsy risk. This study aims to assess the efficacy and safety of PFO closure for relieving epileptic seizures in patients with refractory epilepsy associated with PFO.

Methods/design
Recruitment takes place at the West China Hospital of Sichuan University, China, for an open-label, randomized controlled clinical trial. The trial will include 110 patients with refractory epilepsy and PFO. Disease diagnoses will conform to the diagnostic criteria of the International League Against Epilepsy (ILAE) for refractory epilepsy and the American Society of Echocardiography (ASE) for PFO. Refractory epilepsy and high-grade right-to-left shunt (RLS) of the PFO will be further diagnosed using 24-hour video electroencephalogram and transthoracic echocardiography with contrast injection, respectively. Eligible participants require a secondary or higher volume of RLS.

Trial registration
Chinese Clinical Trial Registry (ChiCTR2200065681). Registered on November 11, 2022.
COVID-19 vaccine registry for pregnant women: policy to control complications of vaccination in pregnant women in 2021–2022
Authors: Asadi Farkhondeh , Shakiba Roya , Rabiei Reza , Emami Hassan , Sabahi Azam 
Published: July 2023

Abstract
Background
Data management related to COVID-19 vaccination in pregnant women is vital to improve the treatment process and to establish preventive programs. Implementing a registry to manage data is an essential part of this process. This study aims to design a national model of the COVID-19 vaccination registry for pregnant women in Iran.

Methods
The present study is an applied descriptive study conducted in 2021 and 2022 in two stages. In the first stage, the coordinates of the National Registry of COVID-19 vaccination of pregnant women from related references and articles, as well as the comparative study of the National Registry of COVID-19 vaccination of pregnant women in the United States, Canada, and the United Kingdom was done. In the second stage, the preliminary model was designed. The model was validated using the Delphi technique and questionnaire tools and analyzing the data.

Results
The presented national COVID-19 vaccination registry model of pregnant women’s main components consist of objectives, data sources, structure, minimum data set, standards, and registry processes, all of which received 100% expert consensus.

Conclusion
The vaccination registry of pregnant women has a major role in managing COVID-19 vaccination data of pregnant women and can be one of the Ministry of Health and Medical Education priorities.
Implementing a quality improvement initiative for private healthcare facilities to achieve accreditation: experience from India
Authors: Nair Tapas Sadasivan , Memon Parvez , Tripathi Sanjay , Srivastava Ashish , Sunny Kujur Meshach , Singh Deepti , Bhamare Parag , Yadav Vikas , Kumar Srivastava Vineet , Prasad Pallipamula Suranjeen , Usmanova Gulnoza , Kumar Somesh 
Published: July 2023

Abstract
Background
The Manyata program is a quality improvement initiative for private healthcare facilities in India which provided maternity care services. Under this initiative, technical assistance was provided to selected facilities in the states of Uttar Pradesh, Jharkhand and Maharashtra which were interested in obtaining ‘entry level certification’ under the National Accreditation Board for Hospitals and Healthcare Providers (NABH) for provision of quality services. This paper describes the change in quality at those Manyata-supported facilities when assessed by the NABH standards of care.

Methods
Twenty-eight private-sector facilities underwent NABH assessments in the three states from August 2017 to February 2019. Baseline assessment (by program staff) and NABH assessment (by NABH assessors) findings were compared to assess the change in quality of care as per NABH standards of care. The reported performance gaps from NABH assessments were then also classified by thematic areas and suggested corrective actions based on program implementation experience.

Results
The overall adherence to NABH standards of care improved from 9% in the baseline assessment to 80% in the NABH assessment. A total of 831 performance gaps were identified by the NABH assessments, of which documentation issues accounted for a majority (70%), followed by training (19%). Most performance gaps could be corrected either by revising existing documentation or creating new documentation (62%), or by orienting facility staff on various protocols (35%).

Conclusion
While the adherence of facilities to the NABH standards of care improved considerably, certain performance gaps remained, which were primarily related to documentation of facility policies and protocols and training of staff, and required corrective actions for the facilities to achieve NABH entry level certification.
Resistance of Anopheles stephensi to selected insecticides used for indoor residual spraying and long-lasting insecticidal nets in Ethiopia
Authors: Teshome Abebe , Erko Berhanu , Golassa Lemu , Yohannes Gedeon , Irish Seth R. , Zohdy Sarah , Yoshimizu Melissa , Dugassa Sisay 
Published: July 2023

Abstract
Background
Malaria, transmitted by the bite of infective female Anopheles mosquitoes, remains a global public health problem. The presence of invasive Anopheles stephensi, capable of transmitting Plasmodium vivax and Plasmodium falciparum, was first reported in Ethiopia in 2016. The ecology of this mosquito species differs from that of Anopheles arabiensis, the primary malaria vector in Ethiopia. This study aimed to evaluate the efficacy of selected insecticides, which are used in indoor residual spraying (IRS) and selected long-lasting insecticidal nets (LLINs) for malaria vector control against adult An. stephensi.

Methods
Anopheles stephensi mosquitoes were collected as larvae and pupae from Awash Subah Kilo Town and Haro Adi village, Ethiopia. Adult female An. stephensi, reared from larvae and pupae collected from the field, aged 3–5 days were exposed to impregnated papers of IRS insecticides (propoxur 0.1%, bendiocarb 0.1%, pirimiphos-methyl 0.25%), and insecticides used in LLINs (alpha-cypermethrin 0.05%, deltamethrin 0.05% and permethrin 0.75%), using diagnostic doses and WHO test tubes in a bio-secure insectary at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. For each test and control tube, batches of 25 female An. stephensi were used to test each insecticide used in IRS. Additionally, cone bioassay tests were conducted to expose An. stephensi from the reared population to four brands of LLINs, MAGNet™ (alpha-cypermethrin), PermaNet® 2.0 (deltamethrin), DuraNet© (alpha-cypermethrin) and SafeNet® (alpha-cypermethrin). A batch of ten sugar-fed female mosquitoes aged 2–5 days was exposed to samples taken from five positions/sides of a net. The data from all replicates were pooled and descriptive statistics were used to describe features of the data.

Results
All An. stephensi collected from Awash Subah Kilo Town and Haro Adi village (around Metehara) were resistant to all tested insecticides used in both IRS and LLINs. Of the tested LLINs, only MAGNet™ (alpha-cypermethrin active ingredient) caused 100% knockdown and mortality to An. stephensi at 60 min and 24 h post exposure, while all other net brands caused mortality below the WHO cut-off points (< 90%). All these nets, except SafeNet®, were collected during LLIN distribution for community members through the National Malaria Programme, in December 2020.

Conclusions
Anopheles stephensi is resistant to all tested insecticides used in IRS and in the tested LLIN brands did not cause mosquito mortality as expected, except MAGNet. This suggests that control of this invasive vector using existing adult malaria vector control methods will likely be inadequate and that alternative strategies may be necessary.
'It’s not going to be a one size fits all': a qualitative exploration of the potential utility of three drug checking service models in Scotland
Authors: Carver Hannah , Falzon Danilo , Masterton Wendy , Wallace Bruce , Aston Elizabeth V. , Measham Fiona , Hunter Carole , Sumnall Harry , Gittins Rosalind , Raeburn Fiona , Craik Vicki , Priyadarshi Saket , Rothney Laura , Weir Kira , Parkes Tessa 
Published: July 2023

Abstract
Background
Scotland currently has the highest rates of drug-related deaths in Europe, so drug checking services are being explored due to their potential role in reducing these deaths and related harms. Drug checking services allow individuals to submit presumed psychoactive drug samples for analysis, and then receive individualised feedback and counselling. This paper explores participants’ views on the advantages and challenges of three hypothetical service models, to inform future service delivery in Scotland.

Methods
Semi-structured interviews were conducted with 43 people: 27 professional stakeholders, 11 people with experience of drug use, and five family members across three cities. Vignettes were used to provide short descriptions of three hypothetical service models during the interviews. Interviews were audio-recorded, transcribed and analysed using thematic analysis.

Results
Participants identified advantages and challenges for each of the three potential service models. The third sector (not-for-profit) model was favoured overall by participants, and the NHS substance use treatment service was the least popular. Participants also noted that multiple drug checking sites within one city, along with outreach models would be advantageous, to meet the diverse needs of different groups of people who use drugs.

Conclusions
Drug checking services need to be tailored to local context and needs, with a range of service models being possible, in order to meet the needs of a heterogeneous group of people who use drugs. Addressing issues around stigma, accessibility, and concerns about the potential impact of accessing drug checking on access to and outcomes of drug treatment, are essential for successful service delivery.
Investigating residual leukemic cells in acute lymphoblastic leukemia: a practical approach using a streamlined interphase fluorescence in situ hybridization method on cerebrospinal fluid
Authors: Karapetyan Knarik , Gizhlaryan Mane , Kalinovskaia Olga , Hovhannisyan Anna , Tadevosyan Gohar , Matinyan Lilit , Tamamyan Gevorg , Ghazaryan Narine 
Published: July 2023

Abstract
Introduction
A precise diagnosis of central nervous system involvement in acute lymphoblastic leukemia (ALL) requires comprehensive knowledge of morphological analysis, with a focus on the quantity and quality of cells being examined. Some research has utilized techniques such as immunocytochemistry, flow cytometry, polymerase chain reaction (PCR), and interphase fluorescence in situ hybridization (iFISH) on cerebrospinal fluid (CSF) cytospin samples to detect any remaining leukemic cells in the CSF. To obtain reliable results using immunocytochemistry and flow cytometry, it is essential to use freshly collected specimens within a limited timeframe. At the same time, PCR requires a sufficient number of cells for DNA extraction. On the other hand, the iFISH procedure on CSF cytospin samples can be challenging and requires practice. Therefore, there is a need for a fast, easy method that will be affordable and marketable in laboratories where the above methods are not available, or the sample is insufficient to use those methods.

Methods
The samples were prepared by centrifugation of 1 mL aliquots of CSF collected into EDTA tubes. The CSF sample was centrifuged at 3000 rpm for 3 min, the supernatant was removed, and the pellet was placed in KCl hypotonic solution for 5 min at 37 °C. Other steps (fixation, hybridization, wash steps, and analysis) were the same as in the standard protocol for blood samples. The BCR-ABL1 rearrangements were performed and evaluated in 200 interphase cells.

Results
90% of Ph(+) cells were found in CSF.

Conclusion
We propose a significantly streamlined iFISH method for detecting blast/residual leukemic cells in acute lymphoblastic leukemia using CSF as a complementary test option.
Ovarian reserve in women with cystic fibrosis: is this a cause of sub-fertility?
Authors: Cohen-Cymberknoh Malena , Garber Keren Marks , Reiter Joel , Shteinberg Michal , Stolovas Aielet , Barghouti Iyad , Adler Lazarovits Chana , Esh Broder Efrat , Hershko Klement Anat 
Published: July 2023

Abstract
Background
Over the past two decades, increasing number of people with cystic fibrosis (CF) survive into adulthood. Compared to the general population, sub-fertility is an obstacle for many women with CF (wwCF). Decreased ovarian reserve has been proposed as a possible cause, but limited data is available to support this. The aim of this study was to evaluate the ovarian reserve in wwCF and to correlate this with patients’ demographic and clinical data.

Methods
Reproductive-aged wwCF were enrolled during their routine medical appointments. Assessment included Anti-Mullerian hormone (AMH) levels, routine blood tests and antral follicular count (AFC) evaluation. Additionally, demographic, and clinical information were collected.

Results
A total of wenty-three wwCF were enrolled, with ages ranging from 19 to 40 years (median 27 years). Among the fourteen wwCF who were considering pregnancy, five (35.7%) disclosed undergoing an infertility assessment and receiving fertility treatments. All but one patient had an Anti-Mullerian hormone (AMH) level between the 5th and 95th % for age. Measurement of the antral follicular count (AFC) was possible in 12 of the 23 patients and was ranging 8–40 with a median of 17. The proportion of wwCF presenting below median AMH values was not different in sub-fertile as compared to fertile wwCF (P value 0.54). There were no correlations between AMH levels and disease severity parameters. AMH seemed to be relatively higher in wwCF with mild class mutations, but this was not shown to have statistical significance.

Conclusions
Our results, in contrast with the limited available published data, do not support the hypothesis that decreased ovarian reserve plays a major role in infertility in wwCF.
PAI-1 regulates AT2-mediated re-alveolarization and ion permeability
Authors: Ali Gibran , Zhang Mo , Chang Jianjun , Zhao Runzhen , Jin Yang , Zhang Jiwang , Ji Hong-Long 
Published: July 2023

Abstract
Background
Acute lung injury is characterized by overwhelmingly elevated PAI-1 in both lung edema fluid and the circulating system. The role of increased PAI-1, encoded by Serpine1 gene, in the regeneration of injured lung epithelium has not been understood completely. This study aimed to investigate the role of Serpine1 in the regulation of alveolar type 2 epithelial cell (AT2) fate in a humanized mouse line carrying diseased mutants (Serpine1Tg).

Methods
Wild-type (wt) and Serpine1Tg AT2 cells were either cultured as monolayers or 3D alveolospheres. Colony-forming assay and total surface area of organoids were analyzed. AT1 and AT2 cells in organoids were counted by immunohistochemistry and fluorescence-activated cell sorting (FACS). To test the potential effects of elevated PAI-1 on the permeability in the epithelial monolayers, we digitized the biophysical properties of polarized AT2 monolayers grown at the air–liquid interface.

Results
A significant reduction in total AT2 cells harvested in Serpine1Tg mice was observed compared with wt controls. AT2 cells harvested from Serpine1Tg mice reduced significantly over the wt controls. Spheroids formed by Serpine1Tg AT2 cells were lesser than wt control. Similarly, the corresponding surface area, a readout of re-alveolarization of injured epithelium, was markedly reduced in Serpine1Tg organoids. FACS analysis revealed a significant suppression in the number of AT2 cells, in particular, the CD44+ subpopulation, in Serpine1Tg organoids. A lesser ratio of AT1:AT2 cells in Serpine1Tg organoids was observed compared with wt cultures. There was a significant increase in transepithelial resistance but not amiloride inhibition.

Conclusions
Our study suggests elevated PAI-1 in injured lungs downregulates alveolar epithelial regeneration by reducing the AT2 self-renewal, particularly in the CD44+ cells.
Pan-cancer analysis from multi-omics data reveals AAMP as an unfavourable prognostic marker
Authors: Wang Yang , Liu Ting , Zhang Ke , Huang Rong-hai , Jiang Li 
Published: July 2023

Abstract
Objectives
Angio-associated migratory cell protein (AAMP) is a protein that participates in cell migration and is reported to be involved in cancer progression. However, the molecular mechanism of AAMP in pan-cancer is not known.

Methods
We used multi-omics data, such as TIMER, TCGA, GTEx, CPTAC, HPA, and cBioPortal to analyze AAMP expression, and gene alteration in pan-cancer. Univariate Cox regression and Kaplan–Meier were utilized to explore prognostic significance of AAMP expression level. We applied Spearman analysis to investigate the correlation between AAMP and TMB, MSI, immune cell infiltration, immune checkpoints. Moreover, we mainly studied liver hepatocellular carcinoma(LIHC) to explore AAMP expression, clinical significance, and prognosis. Cox regression analysis was used to study independent factor to predict prognosis for AAMP in LIHC. GSEA was utilized to investigate the biological function for AAMP in LIHC.

Results
AAMP was overexpressed in most cancers, and high AAMP expression was associated with worse overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) for LIHC and adrenocortical carcinoma (ACC). Moreover, AAMP had the highest mutation frequency in uterine corpus endometrial carcinoma (UCEC). AAMP was correlated with TMB and MSI in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), lung squamous cell carcinoma (LUSC), and thyroid carcinoma (THCA). Then, we focus on LIHC to investigate the expression and prognosis of AAMP. AAMP overexpression was related to histological grade and pathological stage in LIHC. Multivariate Cox regression analysis revealed that AAMP overexpression was an independent adverse prognostic marker for LIHC. AAMP expression was correlated with immune cell infiltration and immune checkpoints in LIHC. Function enrichment analysis indicated the participation of AAMP in the cell cycle and DNA replication.

Conclusions
AAMP was a latent prognostic indicator for pan-cancer and had high potential as a biomarker for the diagnosis and prognosis of LIHC.