bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consistent brain structural abnormalities and multisite individualised classification of schizophrenia using deep neural networks
Authors: Cui Yue , Li Chao , Liu Bing , Sui Jing , Song Ming , Chen Jun , Chen Yunchun , Guo Hua , Li Peng , Lu Lin , Lv Luxian , Ning Yuping , Wan Ping , Wang Huaning , Wang Huiling , Wu Huawang , Yan Hao , Yan Jun , Yang Yongfeng , Zhang Hongxing , Zhang Dai , Jiang Tianzi 
Published: February 2022

BackgroundPrevious analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.AimsTo identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.MethodWe used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.ResultsWe found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.ConclusionsThese results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Preoperative Thoracic Muscle Mass Predicts Bone Density Change After Parathyroidectomy in Primary Hyperparathyroidism
Authors: Burm Seung Won , Hong Namki , Lee Seunghyun , Kim Gi Jeong , Hwang Sang Hyun , Jeong Jongju , Rhee Yumie 
Published: February 2022

Abstract

Context
Predicting bone mineral density (BMD) gain after parathyroidectomy may influence individualized therapeutic approaches for treating patients with primary hyperparathyroidism (PHPT).

Objective
This study aimed to assess whether skeletal muscle mass data could predict BMD change after parathyroidectomy in patients with PHPT.

Methods
This retrospective study collected data from 2012 to 2021 at Severance Hospital, Seoul, Korea. A total of 130 patients (mean age, 64.7 years; 81.5% women) with PHPT who underwent parathyroidectomy were analyzed. Thoracic muscle volume (T6-T7 level) was estimated using noncontrast parathyroid single photon emission computed tomography/computed tomography (SPECT/CT) scans and an automated deep-learning–based software. The primary outcome assessed was the change in femoral neck BMD (FNBMD, %) 1 year after parathyroidectomy.

Results
The median degree of FNBMD change after parathyroidectomy was + 2.7% (interquartile range: –0.9 to + 7.6%). Elevated preoperative PTH level was associated with lower thoracic muscle mass (adjusted β: –8.51 cm3 per one log-unit PTH increment, P = .045) after adjusting for age, sex, body mass index (BMI), and baseline FNBMD. One SD decrement in thoracic muscle mass was associated with lesser FNBMD (adjusted β: –2.35%, P = .034) gain and lumbar spine BMD gain (adjusted β: –2.51%, P = .044) post surgery after adjusting for covariates.

Conclusion
Lower thoracic skeletal muscle mass was associated with elevated preoperative PTH levels in patients with PHPT. Lower skeletal muscle mass was associated with lesser BMD gain after parathyroidectomy, independent of age, sex, BMI, preoperative BMD, and PTH level.
Insights From Long-term Follow-up of a Girl With Adrenal Insufficiency and Sphingosine-1-Phosphate Lyase Deficiency
Authors: Maharaj Avinaash , Güran Tülay , Buonocore Federica , Achermann John C , Metherell Louise , Prasad Rathi , Çetinkaya Semra 
Published: February 2022

Abstract

Introduction
Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is a multisystemic disorder which, in the main, incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency (PAI).

Case Presentation
We present a young girl with a novel homozygous variant in SGPL1, p.D350G, with PAI in the absence of nephrotic syndrome. In the course of 15 years of follow-up she has further developed primary hypothyroidism and while she has progressed through puberty appropriately, ovarian calcifications were noted on imaging. The p.D350G variant results in reduced protein expression of SGPL1. We demonstrate that CRISPR engineered knockout of SGPL1 in human adrenocortical (H295R) cells abrogates cortisol production. Furthermore, while wild-type SGPL1 is able to rescue cortisol production in this in vitro model of adrenal disease, this is not observed with the p.D350G mutant.

Conclusion
SGPL1 deficiency should be considered in the differential diagnosis of PAI with close attention paid to evolving disease on follow-up.
Safety and Efficacy of Burosumab in Pediatric Patients With X-Linked Hypophosphatemia: A Phase 3/4 Open-Label Trial
Authors: Namba Noriyuki , Kubota Takuo , Muroya Koji , Tanaka Hiroyuki , Kanematsu Masanori , Kojima Masahiro , Orihara Shunichiro , Kanda Hironori , Seino Yoshiki , Ozono Keiichi 
Published: February 2022

Abstract

Objective
Burosumab, an anti-fibroblast growth factor 23 antibody, was recently approved for the treatment of X-linked hypophosphatemia (XLH).
We evaluated the safety and efficacy of burosumab in pediatric XLH patients.

Methods
This open-label, phase 3/4 trial of ≤ 124 weeks’ duration was conducted at 4 Japanese medical centers. Fifteen children aged 1 to 12 years with XLH were included. All had previously been treated with phosphorus or vitamin D. Subcutaneous burosumab was administered every 2 weeks, starting with 0.8 mg/kg, and adjusted based on serum phosphorus levels and any safety concerns (maximum 2 mg/kg). Safety assessments included the frequency of treatment-emergent adverse events (TEAEs). Efficacy of burosumab on biochemical markers, clinical markers of rickets, motor function, and growth was also evaluated.

Results
The average treatment duration was 121.7 weeks. Frequently reported TEAEs were nasopharyngitis (46.7%), dental caries (40.0%), and influenza (33.3%). At baseline, patients had low serum phosphorus concentrations (2.6 ± 0.3 mg/dL) and low-to-normal 1,25-dihydroxyvitamin D concentrations (24.7 ± 12.7 pg/mL), which increased with burosumab treatment and were maintained during the study period. Alkaline phosphatase decreased continuously. At baseline, the mean ± SD total Thacher Rickets Severity Score (RSS) was 1.3 ± 1.2, and 4 patients (26.7%) had an RSS ≥ 2.0. Mean Radiographic Global Impression of Change and RSS tended to improve, particularly in patients with higher baseline RSS. There was a trend toward increased 6-minute walk test distance. No apparent changes in growth rate were observed.

Conclusion
Burosumab has a good safety profile and is effective in pediatric patients with XLH.
The Utility of Intraoperative Magnetic Resonance Imaging in the Resection of Cerebellar Hemispheric Pilocytic Astrocytomas: A Cohort Study
Authors: Hamilton Kimberly M. , Malcolm James G. , Desai Sona , Reisner Andrew , Chern Joshua J. 
Published: February 2022

BACKGROUND:
The mainstay of treatment for cerebellar pilocytic astrocytomas in the pediatric population is surgery. The use of intraoperative magnetic resonance imaging (iMRI) as a surgical adjunct may lower the likelihood of reoperation. Studies have examined iMRI in heterogenous tumor populations, but few have looked at single pathologies.

OBJECTIVE:
To compare iMRI vs non-iMRI for hemispheric cerebellar pilocystic astrocytomas, specifically looking at revision surgeries and residual disease in follow-up.

METHODS:
Retrospective review of medical records for 60 sequential patients with cerebellar hemispheric pilocytic astrocytoma at a single institution was conducted. Thirty-two patients with cerebellar pilocytic astrocytoma underwent surgery without iMRI, whereas 28 patients underwent surgical resection with iMRI. All patients had at least 3-year follow-up.

RESULTS:
There were no significant differences between the patient populations in age, tumor size, or need for cerebrospinal fluid diversion between groups. Operative time was shorter without iMRI (without iMRI 4.4 ± 1.3 hours, iMRI 6.1 ± 1.5, P = .0001). There was no significant difference in the patients who had repeat surgery within 30 days (9% without iMRI, 0% iMRI, P = .25), residual disease at 3 months (19% without iMRI, 14% iMRI, P = .78), or underwent a second resection beyond 30 days (9% without iMRI, 4% iMRI, P = .61). There were more total reoperations in the group without iMRI, although this did not reach significance (19% vs 4%, P = .11).

CONCLUSION:
For hemispheric cerebellar pilocytic astrocytomas, iMRI tended to leave less residual and fewer reoperations; however, neither of these outcomes achieved statistical significance leaving utilization to be determined by the surgeon.
Effect of heterogeneous substrate adhesivity of follower cells on speed and tension profile of leader cells in primary keratocyte collective cell migration
Authors: Chakraborty Madhura , Mukherjee Baishali , Nalinakshan Nanditha , Biswas Arikta , Nayak Rajesh Kumble , Sinha Bidisha 
Published: February 2022

ABSTRACT
In single keratocyte motility, membrane tension is reported to be high at cell-fronts and believed to establish front coherence. To understand role of membrane mechanics in collective cell migration, we study membrane height fluctuations in cell sheets from fish scales using interference reflection microscopy (IRM). We report the monolayer to have cells lacking substrate adhesion and show that such ‘non-sticky’ cells can form bridges between leader cells and far-away follower cells. Do such interactions alter motility and membrane mechanics in such leaders? We find non-significant, but reduced speed for leaders with ‘non-sticky’ followers in comparison to other leaders. Cells show high phenotypic variability in their membrane fluctuation tension profiles. On average, this tension is found to be lower at cell fronts than the mid-section. However, leaders with non-sticky followers are more prone to display higher tension at their front and have a negative correlation between cell speed and front-mid tension difference. Thus, we conclude that intracellular tension gradients are heterogeneous in cell sheets and substrate adhesivity of followers can control the coupling of the gradient to cell speed.
Expression levels and activities of energy-yielding ATPases in the oligohaline neritid snail Theodoxus fluviatilis under changing environmental salinities
Authors: Knobloch Jan , Müller Christian , Hildebrandt Jan-Peter 
Published: February 2022

ABSTRACT
The aquatic gastropod Theodoxus fluviatilis occurs in Europe and adjacent areas of Asia. The snail species has formed two genetically closely related subgroups, the freshwater ecotype (FW) and the brackish water ecotype (BW). Other than individuals of the FW ecotype, those of the BW ecotype survive in salinities of up to 28‰. Coastal aquatic ecosystems may be affected by climate change due to salinization. Thus, we investigated how the two Theodoxus ecotypes adjust to changes in environmental salinity, focusing on the question whether Na+/K+-ATPase or V-ATPase are regulated on the transcriptional, the translational or at the activity level under changing external salinities. Animals were gradually adjusted to extreme salinities in containers under long-day conditions and constant temperature. Whole body RNA- or protein extracts were prepared. Semi-quantitative PCR- and western blot-analyses did not reveal major changes in transcript or protein abundances for the two transporters under low or high salinity conditions. No significant changes in ATPase activities in whole body extracts of animals adjusted to high or low salinity conditions were detected. We conclude that constitutive expression of ATPases is sufficient to support osmotic and ion regulation in this species under changing salinities given the high level of tolerance with respect to changes in body fluid volume.
Effect of microfluidic rectangular microelectrode geometry on bioparticles manipulation in dielectrophoretic application
Authors: Shee Zuriel Da En , Mhd Noor Ervina Efzan Binti , Ahmad Kayani Aminuddin Bin , Abd Rahman Noor Ziela Binti 
Published: February 2022

Background: Microfluidic cell manipulation techniques have been continually developed and integrated into miniature chips as a so-called lab-on-a-chip (LOC) platform for high-throughput bioassays. Among the various mechanisms of bioparticles manipulation by electrically induced forces, dielectrophoresis (DEP) has been regarded as the most promising technique utilized in microfluidic systems. Into the micro- to nano-scale level of DEP configuration, the common challenges of undesirable side effects such as electrohydrodynamic effects, joule heating, and electrolysis that may occur in the microfluidic system has always been a hurdle which would severely limit the DEP performance. Methods: A numerical simulation study was performed on a versatile capability of a rectangular type of dielectrophoresis microelectrode with different parametric design configuration variables (channel height: 20-50 µm; electrode width 20-100 µm; electrode spacing 5-50 µm). Results: Numerical study results have shown that the ideal dimension range of design configuration for optimum DEP performance have been identified to be 40µm in channel height, 20-40 µm in electrode width and 5-15µm in electrode spacing, further increasing of the dimensions have shown a decrease in DEP performance consequently abridged the bioparticle manipulation. Conclusion: This investigation of the parametric design of the rectangular geometry microelectrode has provided necessary insight to the microelectrode design information and parametric considerations for optimum DEP device fabrication and enhancement.
Awareness and intention to register halal certification of micro and small-scale food enterprises
Authors: Oemar Hirawati , Prasetyaningsih Endang , Bakar Siti Zakiah Abu , Djamaludin Djamaludin , Septiani Anis 
Published: February 2022

Background: This paper discusses halal awareness of food micro and small-scale enterprises (food MSEs) in West Java Province, Indonesia. Halal awareness is the first step toward obtaining halal certificates, which confirm that the product is lawful according to Islamic Sharia. Unfortunately, most of the food sold on the market do not have halal certificates due to a lack of halal awareness and intention on the part of the entrepreneurs. Methods: This study aims at measuring the level of halal awareness and the intention of food MSE entrepreneurs to register halal certification. Halal awareness is assumed to be influenced by knowledge of halal and MSEs' entrepreneurial perceptions of the benefits of halal certificates. Furthermore, halal awareness, attitudes, and perceptions of ease of procedures will encourage the intention to register halal certification. An electronic Google Form with a cover letter and a set of questionnaires was distributed to collect data. Structural Equation Modelling – Partial Least Square (SEM-PLS) was chosen to evaluate the adopted theoretical models in the exploratory research. Results: The results show that halal awareness is influenced by knowledge of halal and perceptions of benefits. Moreover, halal awareness influences positively the intention to obtain a halal certificate, but the intention is not significantly affected by attitudes and perceptions of procedures for obtaining halal certification. This shows that halal awareness will increase the intention to register halal certification. However, it does not impact attitudes/actions to register for halal certification due to the misconceptions about the procedures for obtaining halal certificates. Conclusions: Micro and small entrepreneurs in West Java Province, Indonesia have a good level of awareness about halal food. However, their products are not halal-certified due to the perceptions of the procedures for obtaining halal certificates, which are relatively complicated and costly for micro and small-scale businesses.
Anticancer activity of Caesalpinia sappan by downregulating mitochondrial genes in A549 lung cancer cell line
Authors: Widodo Nashi , Puspitarini Sapti , Widyananda Muhammad Hermawan , Alamsyah Adzral , Wicaksono Septian Tri , Masruri Masruri , Jatmiko Yoga Dwi 
Published: February 2022

Background: The standardization and mechanism of action of Caesalpinia sappan as an anticancer agent are still lacking. This study aimed to understand the mechanism of action of C,sappan extract as an anticancer agent. Methods: This study was conducted using the A549 lung cancer cell line to understand the mechanism of action of C. sappan extract as an anticancer agent. The cytotoxicity activity, cell cycle progression, apoptosis, protein-related apoptosis (i.e., BCL-2and BAX protein) assays, and RNA sequencing were performed level were measured. Moreover, the antioxidant activity, total flavonoids, and phenolics of C.sappan were also assessed. Results: C.sappan has strong antioxidant activity (22.14 ± 0.93 ppm) total flavonoid content of (529.3 ± 4.56 mgQE/g), and phenolics content of (923.37 ± 5 mgGAE/g). The C.sappan ethanol extract inhibited cancer cell growth and arrested at G0/G1 phase of cell cycle, inducing apoptosis by increasing BAX/BCL-2 protein ratio in A549 lung cancer cell line. Furthermore, results from RNA sequencing analysis showed that C.sappan ethanol extract caused downregulation of genes acting on mitochondrial function including adenosine triphosphate (ATP) production and respiration. Conclusions: This study demonstrated that C.sappan has the ability to inhibit cancer cell growth by inducing apoptosis and mitochondrial dysfunction in A549 cells.
Case Report: The effect of intravenous and oral antibiotics on the gut microbiome and breath volatile organic compounds over one year
Authors: Shahi Farah , Forrester Sarah , Redeker Kelly , Chong James P.J. , Barlow Gavin 
Published: February 2022

Background: Antimicrobial resistance (AMR) is a global concern and better understanding of the gut microbiome, a known ‘amplifier’ of AMR, may allow future clinicians to tailor therapy to minimise this risk and offer a personalised medicine approach. To examine the gut microbiome, patients are required to provide faecal samples; more convenient and cheaper solutions need to be found.Methods: As part of a pilot study looking at how routes of administration affect the gut microbiome in NHS patients undergoing routine clinical management for infections, we hypothesised that effects on the gut microbiome varied with the route and metabolism of antibiotic used, and these changes may be reflected in breath metabolites. We present a case report of a patient with an unusual clinical history, alongside breath metabolite and gut microbiome data taken before, during and after antibiotic therapy over a period of one year.Results: We noted a shift in the dominantBacteroidesstrain in the patient’s gut microbiome between pre- and post-therapy samples, along with an alteration in the composition of breath metabolites.Conclusions: This study provides a framework for similar future work and highlights the need for further research on the relationships between changes in microbial gut communities and antimicrobial exposure, patient clinical status, and the metabolites of human breath.
Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK
Authors: Campbell Cori , Wang Tingyan , Smith David A. , Freeman Oliver , Noble Theresa , Várnai Kinga A , Harris Steve , Salih Hizni , Roadknight Gail , Little Stephanie , Glampson Ben , Mercuri Luca , Papadimitriou Dimitri , Jones Christopher R , Taylor Vince , Chaudhry Afzal , Phan Hang , Borca Florina , Olza Josune , Warricker Frazer , Romão Luis , Ramlakhan David , English Louise , Klenerman Paul , Andersson Monique I. , Collier Jane , Nastouli Eleni , Khakoo Salim I. , Gelson William , Cooke Graham S. , Woods Kerrie , Davies Jim , Barnes Eleanor , Matthews Philippa C. 
Published: February 2022

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts. Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient. Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.
Lymphoplasmacytic Lymphoma with Only Lambda Light Chain Monoclonal Paraprotein Expression
Authors: Cautha Sandhya , Gupta Sorab , Ahnif Ahmad , Morangthem Valentina , Jain Kevin 
Published: February 2022

Introduction: Lymphoplasmacytic lymphoma (LPL) is a rare low-grade B-cell neoplasm that accounts for approximately 2% of all haematological malignancies. Most patients have the clinical syndrome of Waldenstrom macroglobulinemia (WM), which is defined as LPL with an associated immunoglobulin M (IgM) serum monoclonal protein. Roughly 5% of LPL patients secrete non-IgM paraproteins (e.g., IgG, IgA, kappa, lambda) or are non-secretory. Case description: We report the case of a 41-year-old woman who was diagnosed with non-IgM LPL with lambda light chain monoclonal paraprotein production and normal serum immunoglobulin levels. The MYD88 L265P mutation was detected on fluorescence in-situ hybridization (FISH) analysis of the bone marrow. The patient underwent treatment with a combination of ibrutinib and rituximab. There was an initial response but she died 8 months after diagnosis. Discussion: Non-IgM LPL poses diagnostic and therapeutic challenges to clinicians as it is an exceptionally rare malignancy with a heterogeneous clinicopathological presentation and scarce literature. Among non-IgM LPL cases, those with lambda light chain production are even more rare. To the best of our knowledge, none have been reported to date. The addition of MYD88 L265P testing to the diagnostic armamentarium of non-IgM LPL cases is advisable for potential therapeutic reasons.