bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, cytogenetic, and genomic analyses of an Ecuadorian subject with Klinefelter syndrome, recessive hemophilia A, and 1;19 chromosomal translocation: a case report
Authors: Gaviria Anibal , Cadena-Ullauri Santiago , Cevallos Francisco , Guevara-Ramirez Patricia , Ruiz-Pozo Viviana , Tamayo-Trujillo Rafael , Paz-Cruz Elius , Zambrano Ana Karina 
Published: September 2022

Abstract
Background
Hemophilia A is considered one of the most common severe hereditary disorders. It is an X-linked recessive disease caused by a deficiency or lack of function of the blood clotting factor VIII. Klinefelter syndrome is a genetic disorder that affects male individuals due to one or more extra X chromosomes, present in all cells or with mosaicism. The aneuploidy is due to either mitotic or meiotic chromosome non-disjunction. Chromosomal translocations are a group of genome abnormalities in which a region or regions of a chromosome break and are transferred to a nonhomologous chromosome or a new location in the same chromosome.

Case presentation
Our subject was born in Ecuador at 36 weeks of gestation by vaginal delivery. At 3 months old, the Factor VIII activity measure showed a 23.7% activity indicating a diagnosis of mild hemophilia A. At 1 year old, the karyotype showed an extra X chromosome, consistent with a diagnosis of Klinefelter syndrome, and a translocation between the long arms of chromosomes 1 and 19, at positions q25 and q13, respectively.

Conclusions
Klinefelter syndrome and hemophilia are a rare combination. In the present case report, the subject presents both, meaning that he has inherited one X chromosome from the father and one X chromosome from the mother. Since the father has severe hemophilia A; and the subject presents a below 40% Factor VIII activity, a skewed X inactivation is suggested. Additionally, the proband presents a translocation with the karyotype 47,XXY,t(1;19)(q25;q13). No similar report with phenotypic consequences of the translocation was found. The present report highlights the importance of a correct diagnosis, based not only on the clinical manifestations of a disease but also on its genetic aspects, identifying the value of integrated diagnostics. The subject presents three different genetic alterations, Klinefelter syndrome, hemophilia A, and a 1;19 chromosomal translocation.
Learning and visualizing chronic latent representations using electronic health records
Authors: Chushig-Muzo David , Soguero-Ruiz Cristina , Miguel Bohoyo Pablo de , Mora-Jiménez Inmaculada 
Published: September 2022

Abstract
Background
Nowadays, patients with chronic diseases such as diabetes and hypertension have reached alarming numbers worldwide. These diseases increase the risk of developing acute complications and involve a substantial economic burden and demand for health resources. The widespread adoption of Electronic Health Records (EHRs) is opening great opportunities for supporting decision-making. Nevertheless, data extracted from EHRs are complex (heterogeneous, high-dimensional and usually noisy), hampering the knowledge extraction with conventional approaches.

Methods
We propose the use of the Denoising Autoencoder (DAE), a Machine Learning (ML) technique allowing to transform high-dimensional data into latent representations (LRs), thus addressing the main challenges with clinical data. We explore in this work how the combination of LRs with a visualization method can be used to map the patient data in a two-dimensional space, gaining knowledge about the distribution of patients with different chronic conditions. Furthermore, this representation can be also used to characterize the patient’s health status evolution, which is of paramount importance in the clinical setting.

Results
To obtain clinical LRs, we considered real-world data extracted from EHRs linked to the University Hospital of Fuenlabrada in Spain. Experimental results showed the great potential of DAEs to identify patients with clinical patterns linked to hypertension, diabetes and multimorbidity. The procedure allowed us to find patients with the same main chronic disease but different clinical characteristics. Thus, we identified two kinds of diabetic patients with differences in their drug therapy (insulin and non-insulin dependant), and also a group of women affected by hypertension and gestational diabetes. We also present a proof of concept for mapping the health status evolution of synthetic patients when considering the most significant diagnoses and drugs associated with chronic patients.

Conclusion
Our results highlighted the value of ML techniques to extract clinical knowledge, supporting the identification of patients with certain chronic conditions. Furthermore, the patient’s health status progression on the two-dimensional space might be used as a tool for clinicians aiming to characterize health conditions and identify their more relevant clinical codes.
MeCP2 deficiency impairs motor cortical circuit flexibility associated with motor learning
Authors: Yue Yuanlei , Ash Ryan T. , Boyle Natalie , Kinter Anna , Li Yipeng , Zeng Chen , Lu Hui 
Published: September 2022

AbstractLoss of function mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MECP2) cause Rett syndrome (RTT), a postnatal neurological disorder. The loss of motor function is an important clinical feature of RTT that manifests early during the course of the disease. RTT mouse models with mutations in the murine orthologous Mecp2 gene replicate many human phenotypes, including progressive motor impairments. However, relatively little is known about the changes in circuit function during the progression of motor deficit in this model. As the motor cortex is the key node in the motor system for the control of voluntary movement, we measured firing activity in populations of motor cortical neurons during locomotion on a motorized wheel-treadmill. Different populations of neurons intermingled in the motor cortex signal different aspects of the locomotor state of the animal. The proportion of running selective neurons whose activity positively correlates with locomotion speed gradually decreases with weekly training in wild-type mice, but not in Mecp2-null mice. The fraction of rest-selective neurons whose activity negatively correlates with locomotion speed does not change with training in wild-type mice, but is higher and increases with the progression of locomotion deficit in mutant mice. The synchronization of population activity that occurs in WT mice with training did not occur in Mecp2-null mice, a phenotype most clear during locomotion and observable across all functional cell types. Our results could represent circuit-level biomarkers for motor regression in Rett syndrome.
Henoch-Schönlein purpura following COVID-19 vaccine in a child: a case report
Authors: Casini Francesca , Magenes Vittoria Carlotta , De Sanctis Marina , Gattinara Maurizio , Pandolfi Marco , Cambiaghi Stefano , Zuccotti Gian Vincenzo , Fabiano Valentina 
Published: September 2022

Abstract
Background
Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis, typical of childhood. It’s a self-limiting disease and it affects different systems. HSP is characterized by dermatological, abdominal, joint and renal clinical manifestations. This condition usually occurs upon infections, mainly upper respiratory tract ones, medications, vaccinations and malignancies.

Case presentation
We describe the case of a 11 year-old girl who developed a urticarial rash 12 days after the first dose of Pfizer-BioNTech BNT16B2b2 mRNA vaccine and a clear picture of Henoch Schönlein purpura 5 days after administration of the second dose of the same vaccine.

Conclusion
To our knowledge, this is the first description of a pediatric patient with Henoch-Schönlein purpura occurring in association with vaccination against COVID-19.
Integrating temporal single-cell gene expression modalities for trajectory inference and disease prediction
Authors: Ranek Jolene S. , Stanley Natalie , Purvis Jeremy E. 
Published: September 2022

AbstractBackgroundCurrent methods for analyzing single-cell datasets have relied primarily on static gene expression measurements to characterize the molecular state of individual cells. However, capturing temporal changes in cell state is crucial for the interpretation of dynamic phenotypes such as the cell cycle, development, or disease progression. RNA velocity infers the direction and speed of transcriptional changes in individual cells, yet it is unclear how these temporal gene expression modalities may be leveraged for predictive modeling of cellular dynamics.ResultsHere, we present the first task-oriented benchmarking study that investigates integration of temporal sequencing modalities for dynamic cell state prediction. We benchmark ten integration approaches on ten datasets spanning different biological contexts, sequencing technologies, and species. We find that integrated data more accurately infers biological trajectories and achieves increased performance on classifying cells according to perturbation and disease states. Furthermore, we show that simple concatenation of spliced and unspliced molecules performs consistently well on classification tasks and can be used over more memory intensive and computationally expensive methods.ConclusionsThis work illustrates how integrated temporal gene expression modalities may be leveraged for predicting cellular trajectories and sample-associated perturbation and disease phenotypes. Additionally, this study provides users with practical recommendations for task-specific integration of single-cell gene expression modalities.
Overestimation of benefit when clinical trials stop early: a simulation study
Authors: Liu Sharon , Garrison Scott R. 
Published: September 2022

Abstract
Background
Stopping trials early because of a favourable interim analysis can exaggerate benefit. This study simulated trials typical of those stopping early for benefit in the real world and estimated the degree to which early stopping likely overestimates benefit.

Methods
From 1 million simulated trials, we selected those trials that exceeded interim stopping criteria, and compared apparent benefit when stopped with the true benefit used to generate the data. Each simulation randomly assigned period of observation, number of subjects, and control event rate using normal distributions centred on the same parameters in a template trial typical of real-world “truncated” (i.e. stopped for benefit) trials. The intervention’s true relative risk reduction (RRR) was also randomized, and assumed 1% of drugs have a warfarin-like effect (60% RRR), 5% a statin-like effect (35% RRR), 39% an ASA-like effect (15% RRR), 50% no effect (0% RRR), and that 5% would cause harm (modelled as a 20% relative risk increase). Trials had a single interim analysis and a z-value for stopping of 2.782 (O’Brien-Fleming threshold). We also modelled (1) a large truncated trial based on the SPRINT blood pressure trial (using SPRINT’s parameters and stopping criteria) and (2) the same typical truncated trials if they instead went to completion as planned with no interim analysis.

Results
For typical truncated trials, the true RRR was roughly 2/3 the observed RRR at the time of stopping. RRR was overestimated by an absolute 14.9% (median, IQR 6.4–24.6) in typical truncated trials, by 5.3% (IQR −0.1 to 11.4) in the same trials if instead carried to completion, and by 2.3% (IQR 0.98–1.09) in large SPRINT-like trials. For all models, to keep the absolute RRR overestimate below 5%, 250 events were required.

Conclusion
Simulated trials typical of those stopping early for benefit overestimate the true relative risk reduction by roughly 50% (i.e. the true RRR was 2/3 of the observed value). Overestimation was much smaller, and likely unimportant, when simulating large SPRINT-like trials stopping early. Whether trials were large or small, stopped early or not, a minimum 250 events were needed to avoid overestimating relative risk reduction by an absolute 5% or more.
Higher amoebic and metronidazole resistant forms of Blastocystis sp. seen in schizophrenic patients
Authors: Franklin Freddy , Rajamanikam Arutchelvan , Raju Chandramathi Samudi , Gill Jesjeet Singh , Francis Benedict , Sy-Cherng Luke Woon , Kumar Suresh 
Published: September 2022

Abstract
Background
Blastocystis sp. is one of the most common colonisers of the intestinal tract that demonstrate strong interaction with accompanying gut bacteria. Previously, the protozoan isolated from individuals with irritable bowel syndrome (IBS) showed altered phenotypic features suggesting that it can be triggered to become pathogenic. Previous studies reported altered gut microbiota and high prevalence of Blastocystis sp. in schizophrenia patients. However, the phenotypic characteristics of Blastocystis sp. isolated from individuals with SZ have yet to be described.

Methods
In this study, faecal samples from 50 patients with severe schizophrenia (SZ) and 100 non-schizophrenic (NS) individuals were screened for Blastocystis sp. infection. Positive isolates were subjected to genotypic and phenotypic characterization.

Results
We found that 12 out of 50 (24%) SZ and 5 out of 100 (5%) NS individuals were detected Blastocystis sp. positive using both in vitro culture and PCR method with no significant association to age and gender. Out of the 15 sequenced isolates, ST3 was the most prevalent subtype (66.7%) followed by ST1 (20%) and ST6 (13.3%). The isolates from SZ individuals demonstrated significant slower growth rate (34.9 ± 15.6 h) and larger range of cell diameter (3.3–140 µm). We detected higher amoebic forms and metronidazole resistance among SZ isolates with variation in cell surface glycoprotein where 98% of cells from SZ showed consistent medium to high binding affinity (+ 2 to + 3) to Concavalin A staining compared to NS isolates that demonstrated only 76% high lectin (+ 3) binding affinity. Cysteine and serine protease levels were predominantly found among SZ isolates. We also demonstrate the presence of metalloprotease in Blastocystis sp. especially among NS isolates. Introduction of solubilised antigens from SZ isolates increased the cell proliferation of HCT116 cells by two fold when compared to NS isolates.

Conclusion
Our findings demonstrated Blastocystis sp. isolated from SZ individuals showed variation in phenotype specifically in morphology and drug resistance. The findings indicate that the gut environment (SZ and NS) and treatment of SZ could have influenced the phenotype of Blastocystis sp.

Graphical Abstract
Factors secreted by monosodium urate crystal-stimulated macrophages promote a proinflammatory state in osteoblasts: a potential indirect mechanism of bone erosion in gout
Authors: Naot Dorit , Pool Bregina , Chhana Ashika , Gao Ryan , Munro Jacob T. , Cornish Jillian , Dalbeth Nicola 
Published: September 2022

AbstractBackgroundTophi are lesions commonly present at sites of bone erosion in gout-affected joints. The tophus comprises a core of monosodium urate (MSU) crystals surrounded by soft tissue that contains macrophages and other immune cells. Previous studies found that MSU crystals directly reduce osteoblast viability and function. The aim of the current study was to determine the indirect, macrophage-mediated effects of MSU crystals on osteoblasts.MethodsConditioned medium from the RAW264.7 mouse macrophage cell line cultured with MSU crystals was added to the MC3T3-E1 mouse osteoblastic cell line. Conditioned medium from the THP-1 human monocytic cell line cultured with MSU crystals was added to primary human osteoblasts (HOBs). Matrix mineralization was assessed by von Kossa staining. Gene expression was determined by real-time PCR, and concentrations of secreted factors were determined by enzyme-linked immunosorbent assay.ResultsIn MC3T3-E1 cells cultured for 13 days in an osteogenic medium, the expression of the osteoblast marker genesCol1a1,Runx2,Sp7,Bglap,Ibsp, andDmp1was inhibited by a conditioned medium from MSU crystal-stimulated RAW264.7 macrophages. Mineral staining of MC3T3-E1 cultures on day 21 confirmed the inhibition of osteoblast differentiation. In HOB cultures, the effect of 20 h incubation with a conditioned medium from MSU crystal-stimulated THP-1 monocytes on osteoblast gene expression was less consistent. Expression of the genes encoding cyclooxygenase-2 and IL-6 and secretion of the proinflammatory mediators PGE2and IL-6 were induced in MC3T3-E1 and HOBs incubated with conditioned medium from MSU crystal-stimulated macrophages/monocytes. However, inhibition of cyclooxygenase-2 activity and PGE2secretion from HOBs indicated that this pathway does not play a major role in mediating the indirect effects of MSU crystals in HOBs.ConclusionsFactors secreted from macrophages stimulated by MSU crystals attenuate osteoblast differentiation and induce the expression and secretion of proinflammatory mediators from osteoblasts. We suggest that bone erosion in joints affected by gout results from a combination of direct and indirect effects of MSU crystals.
How do responses vary between mothers and their daughters on measuring daughter’s self-rated health (SRH): a study among school-going adolescent girls in the primary setting of Varanasi, India
Authors: Patel Ratna , Bansod Dhananjay W. 
Published: September 2022

Abstract
Objective
How self-rated health (SRH) varies when the response on SRH is recorded from the respondent herself (adolescent girl) and her mother on her behalf. This study examines the prevalence of SRH among adolescent girls from her point of view as well as from her mother’s point of view. This insight could help us interpret the differences in opinion of girls and their mothers while measuring the girls’ self-rated health.

Results
Almost one-fifth (19.4%) of the girls reported poor SRH. In contrast, only one in eight mothers (12.3%) could report their daughters under the category of poor SRH. Nearly one-third (76.5%) of the mothers reported their daughter’s SRH as good when daughters themselves rated poorly on SRH and another one-tenth (9.6%) reported their daughter’s SRH as poor when daughters themselves categorized in the good SRH category [χ2 = 9.900; p < 0.002]. More than 90 percent of the Rich and Middle wealth index women, women in the household with only daughters and no son, women whose husbands had higher education, women with higher secondary education, and non-working women visualized their daughter’s SRH as good when daughters themselves reported poor SRH.
Characterization of the fatty acid profile in the ventral midbrain of mice exposed to dietary imbalance between omega-6 and omega-3 fatty acids during specific life stages
Authors: Sakayori Nobuyuki , Katakura Masanori , Setogawa Susumu , Sugita Makoto , Kobayashi Kazuto 
Published: September 2022

Abstract
Objective
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients. Dietary imbalance between these PUFAs, in particular high in n-6 PUFAs and low in n-3 PUFAs (n-6high/n-3low), is common in modern society. We have previously reported that C57BL/6 mouse male offspring derived from mothers exposed to an n-6high/n-3low diet during the gestation had an augmented ventral midbrain dopamine system in adulthood; however, the fatty acid composition in this brain region has not yet been investigated. This follow-up study aims to characterize the fatty acid profile of the ventral midbrain of mice exposed to the n-6high/n-3low diet during specific life stages.

Results
n-6 PUFAs, especially linoleic acid, were increased in the ventral midbrain of offspring exposed to the n-6high/n-3low diet during the gestation compared to those exposed to a well-balanced control diet throughout life. On the other hand, n-3 PUFAs, especially docosahexaenoic acid, were decreased in the ventral midbrain of offspring exposed to the n-6high/n-3low diet during the gestation, lactation, or postweaning period compared to those exposed to the control diet throughout life. Thus, exposure to the n-6high/n-3low diet in pregnancy increases linoleic acid and that in any life stage decreases docosahexaenoic acid in the offspring's ventral midbrain.
Solar maculopathy secondary to sunlight exposure reflected from the screen of mobile devices: two case reports
Authors: Marticorena Joaquín , Honrubia Ana , Ascaso Javier 
Published: September 2022

Abstract
Background
Solar maculopathy is a well described clinical entity that usually occurs in patients that have gazed directly the sun. In this report we describe the first two cases of solar maculopathy in individuals exposed to sunlight reflected from the screen of mobile devices in the absence of direct sun gaze.

Cases description
Case 1. A 30-year-old Caucasic man presented with bilateral metamorphopsia, central scotoma and decreased visual acuity two days after being reading for four hours with his tablet computer in a terrace of a ski center. Case 2. A 20-year-old Caucasic woman was examined for bilateral decrease of visual acuity and central scotoma after being at the beach the day before and reading with her mobile phone for 3 hours. Both patients denied gazing directly to sunlight at any moment. In each case, exploration revealed fundus and OCT images compatible with the typical features of solar maculopathy. After 2 years of follow-up, in absence of any specific treatment, Case 1 had a complete resolution of the fundus alterations, while Case 2 still presented defects of the outer retinal layers. In both cases, an exposure to sunlight reflected from the screen of their mobile devices was documented in environments where solar radiation is thought to be augmented.

Conclusion
Sunlight reflection from a display screen needs to be considered as a possible risk factor for increased solar radiation and a subsequent risk of solar maculopathy.