bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of a novel gross deletion in the UNC13D gene ends the diagnostic odyssey for a family with familial hemophagocytic lymphohistiocytosis 3
Authors: Nagaraj Chinmayee B. , Brightman Diana S. , Rea Hannah , Wakefield Emily , Harkavy Nina V. G. , Dyer Lisa , Zhang Wenying 
Published: March 2023

Abstract
Background: Familial hemophagocytic lymphohistiocytosis (FHL) is an immunological disorder characterized by overactivation of macrophages and T lymphocytes. This autosomal recessive condition has been characterized into multiple types depending on the genetic etiology. FHL type 3 is associated with bi-allelic pathogenic variants in the UNC13D gene.
Case presentation: We present a 12-year diagnostic odyssey for a family with FHL that signifies the advances of FHL genetic testing in a diagnostic genetics laboratory with expertise in heritable immunodeficiencies. We describe the first case of a large UNC13D gross deletion in transto a sequence variant in a family with FHL3, which may have been mediated by Alu elements within introns 12 and 25 of the UNC13D gene.
Conclusions: This case highlights the importance of reevaluating past genetic testing for a patient and family as test technology evolves in order to end a diagnostic odyssey.
Frailty Predicts 30-day Mortality in Spine Surgery Patients Classified as Obese and the Risk Analysis Index Exhibits Excellent Discrimination
Authors: Owodunni Oluwafemi , Courville Evan , Okakpu Uchenna , Ricks Christian , Schmidt Meic , Bowers Christian 
Published: March 2023

Abstract
Background/Objectives
Obesity is a global health challenge that affects > 1/3 adults worldwide. Obesity and frailty pose considerable health risks due to their potential to interact and amplify one another’s negative effects. Therefore, we sought to compare the discriminatory thresholds and independent relationship of the risk analysis index (RAI), 5-factor modified frailty index (m-FI-5) and greater patient age for the primary endpoint of 30-day postoperative mortality.
Subjects/Methods
We included spine surgery patients ≥ 18 years old, from the American College of Surgeons National Quality Improvement program database from 2012-2020, that were classified as obese. We performed receiver operating characteristic curve analysis to compare the discrimination threshold of RAI, mFI-5, and patient age for 30-day postoperative mortality. Risk-adjusted analyses were performed.
Results
Overall, there were 149 163 patients evaluated, and in the ROC analysis for 30-day postoperative mortality, RAI showed superior discrimination C-statistic 0.793 (95% CI: 0.773-0.813), compared to mFI-5 C-statistic 0.671 (95% CI 0.650-0.691), and patient age C-statistic 0.686 (95% CI 0.666-0.707). By subgroups for obesity class I-III, consistent results were observed (C-statistics range: RAI 0.767-0.808; mFI-5 0.642-0.693; patient age 0.665-0.706). In the risk-adjusted analyses, frailty had a dose-dependent relationship with 30-day postoperative mortality, and the RAI had a larger effect size (p<0.001). Additionally, obesity and frailty had a synergistic dose-dependent relationship across obesity class I-III (p<0.001).
Conclusion
In this study of 149 163 patients classified as obese and undergoing spine procedures in an international prospective surgical database, the RAI demonstrated superior discrimination compared to the mFI-5 and patient age in predicting 30-day postoperative mortality risk. The deleterious effects of frailty and obesity were synergistic as their combined effect predicted worse outcomes.
Water Can Copy and Reproduce the Size of Its Own Clusters and Other Molecules
Authors: Shevchenko Igor 
Published: March 2023

Abstract
Water dissolved in an organic solvent does not decompose into individual molecules, but forms clusters, the size of which can vary from a few water molecules to several hundreds. If bulk water is added to acetonitrile containing a small amount of water clusters, it will copy the size of these clusters and reproduce them in large numbers. Small clusters are much more reactive than large clusters because they contain more free hydroxyl groups. Therefore, depending on the size of the initial clusters in the solvent, the added water may turn into a large number of small active clusters, or a small number of large passive clusters. As a result, the rate of hydrolytic reactions with the same water added to acetonitrile can differ by a factor of 200. Water can also form clusters upon contact with organic molecules.
Effect of a nutritional intervention associated with different models of physical training on health parameters of adult and elderly women: A Randomized Trial
Authors: Prado Laís Sousa , Rodrigues Karine Pereira , Almeida Mariana Luciano , Rodrigues Guilherme Silva , Finzeto Larissa Chacon , Sobrinho Andressa C. S. , Santos Daniel , Bueno Carlos Roberto 
Published: March 2023

Abstract
Objective
This study aimed to investigate the effect of different training models associated with a nutritional intervention program in physically active women aged 50 to 70 years.
Methods
Participants were randomly assigned to four training groups (CT with nutritional intervention, CT without nutritional intervention, MT with nutritional intervention, and MT without nutritional intervention) and evaluated before and after 14 weeks of training for anthropometric measurements, body composition, blood pressure, metabolic parameters, blood analyses, physical capacities, level of physical activity, and quality of life.
Results
The CT group showed a reduction in body mass and improvement in lower limb endurance, agility, lower and upper limb strength, and cardiorespiratory capacity. In the MT group, a positive response was observed in lower limb muscle strength, waist circumference, and the mental domain related to quality of life.
Conclusion
The groups with nutritional intervention showed better performance in sodium, protein, and calcium consumption parameters, as well as improvement in quality of life and level of physical activity. No difference was found between nutritional intervention associated with the two different types of training. These results suggest that a nutritional intervention program associated with different physical training models can be beneficial for physically active women between 50 and 70 years of age.
Statistical machine and deep learning methods for forecasting of Covid-19
Authors: Juneja Mamta , Saini Sumindar Kaur , Kaur Harleen , Jindal Prashant 
Published: March 2023

Abstract

Since the outbreak of the novel coronavirus, Covid-19 has continuously spread across the globe briskly. Countries have undertaken different types of measures to blunt this spread varying from lockdowns to curfews to social distancing to compulsory wearing of protective kits, which has been sporadically fruitful. However, despite these stringent measures, which have their own pitfalls, scientists across the globe have been struggling to develop a suitable mathematical model that could depict the existing disease spreading pattern and also predict a trend of numbers in the forthcoming months or years. In this paper, popularly used mathematical models including Polynomial Regression, Auto Regressive Integrated Moving Average (ARIMA) and Deep learning techniques such as Recurrent Neural Network (RNN) have been explored for 5 countries badly affected by this virus. The models were tested from 16th May, 2020 till 22nd May, 2020 and used for predicting future cases and deaths from 23rd May, 2020 to 30th June, 2020. The current research primarily focuses on forecasting the behaviour of total confirmed cases and deaths in each country and further analysing the performance parameters such as Mean Squared Error (MSE), Root Mean Squared Error (RMSE) and Mean Absolute Percentage Error (MAPE). It has been observed that the polynomial regression model provides a best fit solution at par with actual numbers of confirmed and death cases for India by producing minimum RMSE and MAPE. For South Korea and Italy, the ARIMA and RNN models have shown fidelity with actual numbers. RNN model has shown conformity with US numbers while ARIMA model has found closeness to United Kingdom data. The purpose to perform data analysis is to measure the performance metrics by using different techniques and depict the pattern for each country. Furthermore, the paper also highlights the future predictions for every country to control the spread of disease, save lives, avoid health systems breakdowns and benefit the researchers in this field.
Transcription Factor GmERF105 Negatively Regulates Salt Stress Tolerance in Arabidopsis thaliana
Authors: Li Lu , Guo Na , Xing Han , Zhao Jinming , Zhu Zhen , Liu Juan , Zhang Yu , Lu Yang 
Published: March 2023

Abstract
The Ethylene Response Factor (ERF) transcription factor is a subfamily of the AP2/ERF family that is instrumental in mediating plant responses to diverse abiotic stressors. Herein, we present the isolation and characterization of theGmERF105 gene from Williams 82 (W82), which is rapidly induced by salt, drought, and abscisic acid (ABA) treatments in soybean. The GmERF105 protein, which contains an AP2 domain, localizes to the nucleus and retains transcriptional activation activity. Furthermore, GmERF105 selectively binds to the GCC-box. Notably, overexpression of GmERF105 in Arabidopsis under salt stress resulted in reduced seed germination rate, fresh weight, and antioxidant enzyme activity; while sodium ion content, reactive oxygen species (ROS) level, and malonic dialdehyde (MDA) content were elevated in comparison to the wild type. Furthermore, the GmERF105 transgenic plants displayed suppressed expression of stress response marker genes, including KIN1, LEA14, NCED3, RD29A, and COR15A/B, under salt treatment. Our findings suggest that GmERF105 can act as a negative regulator in plant salt tolerance pathways by affecting ROS scavenging systems.
Triggering Gel-Sol Transition by Weak Magnetic Field
Authors: Stovbun Sergey , Zanin Anatoly , Skoblin Aleksey , Mikhaleva Mariya , Kuznetsov Dmitry , Zlenko Dmitry 
Published: March 2023

Abstract
The self-assembly of small molecules into fiber-like structures is a mysterious process as the physics underlying such self-assembly is not clear. The energy necessary for this process exceeds the one provided by common dispersion interactions and hydrogen bonding. The recent results obtained by the scientific group of Prof. Naaman for the Weizmann Institute of Science fed light on the nature of the forces providing for the self-assembly of chiral molecules and attributed these forces to the spin exchange interactions. Therefore, the self-assembly of chiral molecules should be magneto-sensitive. We found such sensitivity in solutions of trifluoroacetylated alpha-aminoalcohols, and the process was inhibited by the magnetic field when fibers grew on the surface of the substrate. On the contrary, in the bulk, the self-assembly was enhanced by the magnetic field and led to the formation of the dense gel, while no gelation was observed in the absence of the external magnetic field. The latter observations are the theme of this short report aimed to declare the effect itself but does not pretend to describe it in full.
Evaluating Change in a Degraded Healthcare System: A Cross-Sectional Study of Implementation Outcomes using Routine Data Indicators and Proxies.
Authors: Hanbury Andria , Mafirakureva Nyasha , Chicken Nicola , Bailey Liam 
Published: March 2023

Abstract
Background
Implementation evaluation should focus on implementation success, guided by theories and frameworks, rather than on intervention effectiveness. While implementation evaluations tend to rely on surveys or interviews, it is important to consider alternative methods to avoid adding to healthcare professionals’ burden. This paper presents a cross-sectional rapid evaluation of a handheld medical device designed for remote examinations, which was piloted in Northern England. By using downloaded device data and administrative records mapped to domains from the implementation outcomes framework, this evaluation offers a pragmatic example of assessing implementation success guided by a framework and using readily available data.
Methods
The pilot design was pragmatic: sites volunteered, decided which services to use the device in, and launched the device on a rolling basis. Evaluation lasted one year. Data was downloaded from the devices, and administrative records for the pilot accessed. Variables were mapped to the implementation outcomes framework and reviewed by the device manufacturer and pilot team.
Results
N = 352 care episodes were recorded using the device with 223 patients. Out of 19 sites ‘signed-up’ to the pilot, 5 launched and delivered 10 of 35 proposed projects: a site and project adoption rate of 26% and 29%, respectively. Twenty six of the 71 trained clinicians used the device: a penetration rate of 37%. Six sites signed-up to an extension period; three had launched and three had not during the original timelines, indicating some sustainability. Feasibility was high, with few device error messages. Fidelity of device usage as planned was low for two of the eight available device examinations. Device and staffing costs were high but potential cost savings were attributable to fewer in-person appointments.
Conclusions
Through using device and administrative data, this evaluation minimised burden on busy healthcare staff yet was still guided by an evaluation framework. Six out of the eight implementation outcomes were measured, including sustainability and costs. The findings give insight into implementation challenges, particularly around adoption and penetration. For future research, it is recommended to engage with staff to prioritise outcome measurements and to focus on the interpretation and robustness of indicators.
Molecular basis of TASL recruitment by PHT1
Authors: Custódio Tânia , Killer Maxime , Yu Dingquan , Puente Virginia , Teufel Daniel , Pautsch Alexander , Schnapp Gisela , Grundl Marc , Kosinski Jan , Loew Christian 
Published: March 2023

Abstract
PHT1 is a histidine /oligopeptide transporter with an essential role in Toll-like receptor innate immune response. It can act as a receptor by recruiting the adaptor protein TASL which leads to type I interferon production via IRF5. Persistent stimulation of this signalling pathway is known to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Understanding how PHT1 recruits TASL at the molecular level, is therefore clinically important for the development of therapeutics against SLE and other autoimmune diseases. Here we present the Cryo-EM structure of PHT1 stabilized in the outward-open conformation. By combining biochemical and structural modelling techniques we propose a model of the PHT1-TASL complex, in which the first 16 N-terminal TASL residues fold into a helical structure that bind in the central cavity of the inward-open conformation of PHT1. This work provides critical insights into the molecular basis of PHT1-TASL mediated type I interferon production.
Early-stage measurable residual disease dynamics and IGHV repertoire reconstitution during venetoclax and obinutuzumab treatment in chronic lymphocytic leukemia
Authors: Hengeveld Paul , Schilperoord-Vermeulen Joyce , Klift Michèle van der , Dubois Julie , Kolijn P. , Kavelaar François , Rijken Melissa , Dobber Johan , Nasserinejad Kazem , Kersting Sabina , Westerweel Peter , Kater Arnon , Langerak Anton , Levin Mark-David 
Published: March 2023

Abstract
In chronic lymphocytic leukemia, measurable residual disease (MRD) depth following fixed-duration treatment is associated with progression-free survival. MRD is usually reported at the end of treatment as a static parameter, but successive MRD measurements allow more accurately characterization of MRD dynamics, which may reveal additional prognostic information. To study the value of MRD dynamics, we used the IGHV leader-based NGS assay to longitudinally measured MRD in 60 patients treated in the HOVON-139/GIVE trial, in which previously untreated patients received two cycles of pre-induction with obinutuzumab, followed by one year induction treatment with obinutuzumab and venetoclax, followed by randomization to consolidation treatment with venetoclax or MRD-conditional consolidation. Induction treatment resulted in undetectable MRD (uMRD) (<10-5) in 93% of assessed patients, with 85% and 74% of patients retaining uMRD at six and twelve months after randomization. High levels of early-stage MRD, assessed during venetoclax ramp up, were associated with failure of achieving uMRD after induction treatment, whereas low levels of early-stage MRD predicted a low probability of loss of uMRD and disease progression after randomization. Venetoclax consolidation treatment significantly impaired polyclonal IGHV repertoire reconstitution after induction treatment with venetoclax and obinituzumab. In conclusion, very early-stage MRD levels were associated with treatment outcomes.
Successful antibiotic management of Staphylococcus epidermidis endophthalmitis without ICL explantation or vitrectomy.
Authors: Zheng Ke , Zheng Xiaohong , Gan Dekang , Zhou Xingtao 
Published: March 2023

Abstract
Purpose: We report a case of successful medical management of subacute endophthalmitis post implantable collamer lens (ICL) culture-positive of Staphylococcus epidermidis.
Observations: A 18-year-old female presented with decreased visual acuity in the left eye 20 days after ICL implantation. A diagnosis of postoperative endophthalmitis was made based on examination and ultrasonography. A vitreous tap was taken, and intravitreal antibiotics (vancomycin 1mg/0.1ml and ceftazidime 2 mg/0.1 mL) were administered twice (q72h), and para bulbar injection of triamcinolone acetonide on day 8. The vitreous culture was confirmed for Staphylococcus epidermidis. The endophthalmitis was resolved, and BCVA improved from 6/20 to 12/20 on day 7 and 22/20 on day 38. This is the first successful medical resolution of Staphylococcus epidermidis endophthalmitis without ICL explantation and vitrectomy in the V4c model.
Conclusions and importance: In antibiotic therapy, the excellent compliance and close follow-up of this endophthalmitis patient enabled careful postoperative surveillance on the effect of antibiotic therapy, avoiding the removal of the ICL or the loss of the integrity of the eye. The risk of potential infectious endophthalmitis post-ICL surgery should be fully emphasized during preoperative counseling.
Relapse/refractory paediatric B-ALL case with CD19 - phenotype switching indicating the importance of appropriate diagnostics approach and targeted treatment adjustment – case report
Authors: Prażmo Anna , Jawoszek Patryk , Styka Borys , Lejman Monika , Zaucha-Prażmo Agnieszka 
Published: March 2023

Abstract
Background:
The case reported presents a rare CD19− phenotype shift of acute lymphoblastic leukaemia clone during the course of relapse/refractory ALL in a paediatric patient. We explore possible reasons promoting CD19 negative cell selection, including discrete mutations and anti-CD19 treatment, which is gaining importance as targeted therapies such as blinatumomab enter standard treatment protocols.
Case presentation:
A 9-year-old male patient was admitted to the Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Poland with fatigue, anaemia and hepatosplenomegaly, and was subsequently diagnosed with B lymphocyte acute lymphoblastic leukaemia. Initial standard genetic analysis did not show significant chromosomal aberrations, and the patient underwent chemotherapy in line with the intermediate-risk protocol. After initially achieving remission, the disease relapsed, and the patient required hematopoietic stem cell transplantation (HSCT). In-depth retrospective microarray analysis performed at this point revealed additional risk factors including hyperdiploidy. After staying in remission for several months, a second recurrence was diagnosed which prompted targeted treatment application (Blinatumomab) and subsequent HSCT. The third leukemic relapse diagnosed shortly after second HSCT limited treatment options to last-resort CAR T cell therapy in Germany. Subsequent immunophenotyping revealed lack of CD19 expression by ALL clones and disqualified the patient from treatment. The patient died in October 2019 from disease progression.
Conclusions:
The case we report highlights the importance of in-depth molecular diagnostics and monitoring of relapse/recurrent ALL cases in order to identify and manage as many potential risk factors as possible during treatment. This gain importance as selective targeted treatments use increases, as antigenic phenotype and its changes directly influence the efficacy of such treatments, and therefore patients’ prognosis.
Impacts of Pit latrines on Groundwater Quality in Squatter Settlements in Zanzibar
Authors: Bakari Said Suleiman , Suleiman Zeyana Nassor , Ali Hassan Rashid , Kai Kombo Hamad 
Published: March 2023

Abstract
Impacts of Pit latrines on Groundwater Quality in Squatter Settlements in Zanzibar
Said Suleiman Bakari1*, Zeyana Nassor Suleiman1; Hassan Rashid Ali1 and Kombo Hamad Kai2
1School of Social and Natural Science, State University of Zanzibar, P. O. Box 146, Zanzibar, Tanzania.
Zeyyuna2@gmail.com
2Tanzania Meteorological Authority (TMA) Zanzibar office, P. O. Box 340
E mail kombokai68@gmail.com
*E-mail of the corresponding author: sayeed.bakari@gmail.com
Abstract
Groundwater is the major source of drinking water in Zanzibar. Most of the people in squatter settlement rely on shallow groundwater due to insufficient supply of treated water. In these areas, shallow wells are located close to pit latrines, the condition which increasing the risk of contamination. This study aimed to assess the impact of pit latrines on groundwater quality in five sub-urban areas of squatter settlements in Unguja Island. Water samples were collected from twenty shallow wells and analyzed for the microbiological and physio-chemical parameters. The Ordinary Least Square (OLS) regression model was used to assess the influence of distance from pit latrine to the groundwater sources. The data revealed that nitrate and chloride concentrations increases when the distance between the shallow wells and the nearest pit latrine decreases. In contrary, faecal coliform counts shows that for every unit increase in the distance from pit latrine to the shallow wells the counts decreased by 42 CFU/100 ml. However, OLS regression model did not show significant relationship of total coliform and distance from the well. This study suggests that there are other factors that may accelerate the total coliform bacteria in water wells. These results illustrate that public health risks associated with waterborne diseases could be ranked high at densely populated squatter settlement. Thus, the study recommends that routine monitoring of shallow wells is required as well as application of low-cost technologies such as raised and lined pit latrines in order to minimize potential risk of groundwater pollution.
Key words: Groundwater quality; squatter settlement; pit latrines; water wells; Zanzibar