bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal Encoding of Speech Features in the Human Thalamus in Parkinson's Disease and Essential Tremor Patients
Authors: Tankus Ariel , Lustig-Barzelay Yael , Gurevitch Guy , Faust-Socher Achinoam , Strauss Ido 
Published: September 2023

BACKGROUND AND OBJECTIVES:
The human thalamus is known, from stimulation studies and functional imaging, to participate in high-level language tasks. The goal of this study is to find whether and how speech features, in particular, vowel phonemes, are encoded in the neuronal activity of the thalamus, and specifically of the left ventralis intermediate nucleus (Vim), during speech production, perception, and imagery.

METHODS:
In this cross-sectional study, we intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients with Parkinson's disease (PD) (n = 4) or essential tremor (n = 4) undergoing implantation of deep brain stimulation (n = 3) or radiofrequency lesioning (n = 5) while patients articulated the five monophthongal vowel sounds.

RESULTS:
In this article, we report that single neurons in the left Vim encode individual vowel phonemes mainly during speech production but also during perception and imagery. They mainly use one of two encoding schemes: broad or sharp tuning, with a similar percentage of units each. Sinusoidal tuning has been demonstrated in almost half of the broadly tuned units. Patients with PD had a lower percentage of speech-related units in each aspect of speech (production, perception, and imagery), a significantly lower percentage of broadly tuned units, and significantly lower median firing rates during speech production and perception, but significantly higher rates during imagery, than patients with essential tremor.

CONCLUSION:
The results suggest that the left Vim uses mixed encoding schemes for speech features. Our findings explain, at the single neuron level, why deep brain stimulation and radiofrequency lesioning of the left Vim are likely to cause speech side effects. Moreover, they may indicate that speech-related units in the left Vim of patients with PD may be degraded even in the subclinical phase.
Chondroitin sulfate is required for follicle epithelial integrity and organ shape maintenance in Drosophila
Authors: Knudsen Collin , Woo Seuk Koh  , Izumikawa Tomomi , Nakato Eriko , Akiyama Takuya , Kinoshita-Toyoda Akiko , Haugstad Greg , Yu Guichuan , Toyoda Hidenao , Nakato Hiroshi 
Published: September 2023

ABSTRACT
Heparan sulfate (HS) and chondroitin sulfate (CS) are evolutionarily conserved glycosaminoglycans that are found in most animal species, including the genetically tractable model organism Drosophila. In contrast to extensive in vivo studies elucidating co-receptor functions of Drosophila HS proteoglycans (PGs), only a limited number of studies have been conducted for those of CSPGs. To investigate the global function of CS in development, we generated mutants for Chondroitin sulfate synthase (Chsy), which encodes the Drosophila homolog of mammalian chondroitin synthase 1, a crucial CS biosynthetic enzyme. Our characterizations of the Chsy mutants indicated that a fraction survive to adult stage, which allowed us to analyze the morphology of the adult organs. In the ovary, Chsy mutants exhibited altered stiffness of the basement membrane and muscle dysfunction, leading to a gradual degradation of the gross organ structure as mutant animals aged. Our observations show that normal CS function is required for the maintenance of the structural integrity of the ECM and gross organ architecture.
Modeling a variant of unknown significance in the Drosophila ortholog of the human cardiogenic gene NKX2.5
Authors: Lovato TyAnna L. , Blotz Brenna , Bileckyj Cayleen , Johnston Christopher A. , Cripps Richard M. 
Published: September 2023

ABSTRACT
Sequencing of human genome samples has unearthed genetic variants for which functional testing is necessary to validate their clinical significance. We used the Drosophila system to analyze a variant of unknown significance in the human congenital heart disease gene NKX2.5 (also known as NKX2-5). We generated an R321N allele of the NKX2.5 ortholog tinman (tin) to model a human K158N variant and tested its function in vitro and in vivo. The R321N Tin isoform bound poorly to DNA in vitro and was deficient in activating a Tin-dependent enhancer in tissue culture. Mutant Tin also showed a significantly reduced interaction with a Drosophila T-box cardiac factor named Dorsocross1. We generated a tinR321N allele using CRISPR/Cas9, for which homozygotes were viable and had normal heart specification, but showed defects in the differentiation of the adult heart that were exacerbated by further loss of tin function. We propose that the human K158N variant is pathogenic through causing a deficiency in DNA binding and a reduced ability to interact with a cardiac co-factor, and that cardiac defects might arise later in development or adult life.
Comparative multi-omic analyses of cardiac mitochondrial stress in three mouse models of frataxin deficiency
Authors: Sayles Nicole M. , Napierala Jill S. , Anrather Josef , Diedhiou Nadège , Li Jixue , Napierala Marek , Puccio Hélène , Manfredi Giovanni 
Published: September 2023

ABSTRACT
Cardiomyopathy is often fatal in Friedreich ataxia (FA). However, FA hearts maintain adequate function until advanced disease stages, suggesting initial adaptation to the loss of frataxin (FXN). Conditional cardiac knockout mouse models of FXN show transcriptional and metabolic profiles of the mitochondrial integrated stress response (ISRmt), which could play an adaptive role. However, the ISRmt has not been investigated in models with disease-relevant, partial decrease in FXN. We characterized the heart transcriptomes and metabolomes of three mouse models with varying degrees of FXN depletion: YG8-800, KIKO-700 and FXNG127V. Few metabolites were changed in YG8-800 mice, which did not provide a signature of cardiomyopathy or ISRmt; several metabolites were altered in FXNG127V and KIKO-700 hearts. Transcriptional changes were found in all models, but differentially expressed genes consistent with cardiomyopathy and ISRmt were only identified in FXNG127V hearts. However, these changes were surprisingly mild even at advanced age (18 months), despite a severe decrease in FXN levels to 1% of those of wild type. These findings indicate that the mouse heart has low reliance on FXN, highlighting the difficulty in modeling genetically relevant FA cardiomyopathy.
A ubiquitin–proteasome pathway degrades the inner nuclear membrane protein Bqt4 to maintain nuclear membrane homeostasis
Authors: Le Toan Khanh , Hirano Yasuhiro , Asakawa Haruhiko , Okamoto Koji , Fukagawa Tatsuo , Haraguchi Tokuko , Hiraoka Yasushi 
Published: September 2023

ABSTRACT
Aberrant accumulation of inner nuclear membrane (INM) proteins is associated with deformed nuclear morphology and mammalian diseases. However, the mechanisms underlying the maintenance of INM homeostasis remain poorly understood. In this study, we explored the degradation mechanisms of the INM protein Bqt4 in the fission yeast Schizosaccharomyces pombe. We have previously shown that Bqt4 interacts with the transmembrane protein Bqt3 at the INM and is degraded in the absence of Bqt3. Here, we reveal that excess Bqt4, unassociated with Bqt3, is targeted for degradation by the ubiquitin–proteasome system localized in the nucleus and Bqt3 antagonizes this process. The degradation process involves the Doa10 E3 ligase complex at the INM. Bqt4 is a tail-anchored protein and the Cdc48 complex is required for its degradation. The C-terminal transmembrane domain of Bqt4 was necessary and sufficient for proteasome-dependent protein degradation. Accumulation of Bqt4 at the INM impaired cell viability with nuclear envelope deformation, suggesting that quantity control of Bqt4 plays an important role in nuclear membrane homeostasis.
Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants
Authors: Dornan Anthony J. , Halberg Kenneth V. , Beuter Liesa-Kristin , Davies Shireen-Anne , Dow Julian A. T. 
Published: September 2023

ABSTRACT
Transporting epithelia provide a protective barrier against pathogenic insults while allowing the controlled exchange of ions, solutes and water with the external environment. In invertebrates, these functions depend on formation and maintenance of ‘tight’ septate junctions (SJs). However, the mechanism by which SJs affect transport competence and tissue homeostasis, and how these are modulated by ageing, remain incompletely understood. Here, we demonstrate that the Drosophila renal (Malpighian) tubules undergo an age-dependent decline in secretory capacity, which correlates with mislocalisation of SJ proteins and progressive degeneration in cellular morphology and tissue homeostasis. Acute loss of the SJ protein Snakeskin in adult tubules induced progressive changes in cellular and tissue architecture, including altered expression and localisation of junctional proteins with concomitant loss of cell polarity and barrier integrity, demonstrating that compromised junctional integrity is sufficient to replicate these ageing-related phenotypes. Taken together, our work demonstrates a crucial link between epithelial barrier integrity, tubule transport competence, renal homeostasis and organismal viability, as well as providing novel insights into the mechanisms underpinning ageing and renal disease.
Impact of combining Lenvatinib with Transarterial chemoembolization for unresectable hepatocellular carcinoma
Authors: Long Jianwu , Liu Longfei , Yang Xuefeng , Lu Xianzhou , Qin Lei 
Published: September 2023

Objectives: To investigate the impact of combining lenvatinib with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC).
Methods: This was a retrospective observational study which reviewed the medical records of 103 unresectable HCC patients from January 2017 to June 2020 in The First Affiliated Hospital of Soochow University. It included 46 patients who received TACE plus lenvatinib and 57 patients who received TACE alone. The levels of serum indicators, clinical effect, adverse events, overall survival (OS), and progression-free survival (PFS) were compared between the two groups.
Results: AFP and VEGF levels in the TACE+lenvatinib group post-treatment were significantly lower than the TACE group (P<0.05). The clinical efficacy in the TACE+lenvatinib group (69.57%) was higher than that in the TACE group (40.35%) post-treatment (P<0.05). There were significant differences in hypertension, diarrhea, and bleeding (gingiva) between the two groups (P<0.05). There were no significant differences in one or two year PFS rate or one year OS between groups (P>0.05), while the two years survival rate in the TACE+lenvatinib group was significantly higher than that in the TACE group (P<0.05).
Conclusions: TACE combined with lenvatinib have a high clinical effective rate, with reduced AFP and VEGF levels, higher two year survival rate, and acceptable incidence of adverse events.
doi: https://doi.org/10.12669/pjms.39.6.7944
How to cite this: Long J, Liu L, Yang X, Lu X, Qin L. Impact of combining Lenvatinib with Transarterial chemoembolization for unresectable hepatocellular carcinoma. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.7944
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Role of Human Papilloma Virus 16/18 In Laryngeal Carcinoma with Correlation to the Expression of Cyclin D1, p53, p16 and EGFR
Authors: Tariq Naila , Mirza Talat , Ansari Maqsood , Nazir Sobia 
Published: September 2023

Objective: To investigate the role of Human Papilloma Virus (HPV) (16/18) in relation to the molecular genetic mechanisms of Cyclin D1, p53, p16, and Epidermal growth factor receptor (EGFR) in Laryngeal Squamous Cell Carcinoma (LSSC)
Methods: A cross-sectional study of 88 (Formalin-fixed Paraffin Embedded) FFPE laryngeal biopsies were done at Basic Medical Sciences Institute, Jinnah Postgraduate Centre, Karachi from 2010 to 2019 with the application of Polymerase chain reaction (PCR) for HPV 16/18and Immuno-histochemical staining for molecular genetic expression of proteins, Cyclin D1, p53, p16, and EGFR.
Results: Out of 88 cases of Laryngeal Squamous Cell Carcinoma (LSSC) there was female preponderance. Mean age of the participants was found as 50.7±12.8 years. High risk HPV 16/18 was positive in 28 cases (31.8%), largely related to Grade-II and Grade-III. Immunohistochemically, Cyclin D1 (87.5%) appeared as the most important driver mutation followed by p16 (86.4%), EGFR (65.9%), and, p53 was positive in (61.4%) of cases.
Conclusion: The role of high-risk HPV 16/18 is concurred in the present study strongly in correlation to p16 as a surrogate marker. Moreover, the other driver mutations of Cyclin D1, p53, and EGFR are also implicated as cumulative molecular events in tumor progression as mostly seen in higher Grades.
doi: https://doi.org/10.12669/pjms.39.6.8220
How to cite this: Tariq N, Mirza T, Ansari M, Nazir S. Role of Human Papilloma Virus 16/18 In Laryngeal Carcinoma with Correlation to the Expression of Cyclin D1, p53, p16 and EGFR. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.8220
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effect of feed enriched by products formulated from coconut water, palm sap sugar, and mushroom on the chemical composition of feed and carcass, growth performance, body indices, and gut micromorphology of giant gourami, Osphronemus goramy (Lacepède, 1801), juveniles
Authors: Azrita Azrita , Syandri Hafrijal , Aryani Netti , Mardiah Ainul 
Published: September 2023

Background: Giant gourami, Osphronemus goramy is the most important freshwater fish species produced by aquaculture in Indonesia. This study aimed to the effects of various newly formulated products on the amino acid composition of the diet and whole-body carcass, and to analyse the growth coefficient, body indices, and gut micromorphology. Methods: One hundred gram of palm sap sugar was cooked in 1.1 litre of fresh water for fifteen minutes, to create 1 litre of 11% palm sap sugar solution (after some of it had been boiled off). Two litres of coconut water were then mixed with the litre of palm sugar solution. One litre of this product was added in turn to 2 g of Aspergillus niger (CP2), 2 g of Rhizopus oligosporus (CP3), and 2 g of Saccharomyces cerevisiae (CP4), while freshwater was used as a control (labeled CP1). Aquafeed was added to CP1, CP2, CP3, and CP4, to make diets labeled KP1, KP2, KP3, and KP4. The dosage was 150 ml/kg of feed. Juvenile giant gourami (initial weight 50±0.25 g and length 13.2±0.07 cm) were reared in triplicate net frames (2×1×1 m; water volume 1.5 m 3) in a freshwater concrete pond with a stocking density of 30 juveniles/net. Results: The results supported our hypothesis that different product formulations have a significant effect (P < 0.05) on aquafeed nutrition and the whole-body carcass, growth coefficient, feed utilization, body indices, and gut micromorphology of giant gourami juveniles. The thermal growth coefficient strongly correlated with the daily growth coefficient (r 2 = 92%), condition factor (r2 = 77%), protein efficiency ratio (r2 = 75%), while a moderate relationship with the feed intake ( r2 = 69%). Conclusions: Diet KP3 contains higher total amino acids in diets and carcasses and leads to feed efficiency and better growth for giant gourami.
Investigating the link between frontal sinus morphology and craniofacial characteristics with sex: A 3D CBCT study on the South Indian population
Authors: Denny Ceena , Bhoraskar Mohana , Abdul Aziz Shaikh Sabiha , T S Bastian , Sujir Nanditha , Natarajan Srikant 
Published: September 2023

Background: Measurement of craniofacial parameters plays an important role in sex determination in forensic science. The present study was done using cone beam computed tomography (CBCT) scans to evaluate the morphologic structure of the frontal sinuses and compare it with the width of nasal, cranial, maxillary and mandibular width which might help us in sex determination. Methods: A cross-sectional retrospective study was conducted using 142 full field of view (FOV) scans of patients archived from the department. The width of the nose, cranium, maxilla, and mandibular width was measured and compared with the frontal sinus between the two sexes. Results: A paired t-test was done to compare the linear measurements for both sexes' right and left frontal sinuses. The measurements were higher in males when compared to females. There was a statistically significant asymmetry (larger dimension on the left side) of the anterioposterior (p-value of 0.012) and superior-inferior dimensions in males (p-value of 0.135). Spearman's correlation showed that frontal sinus correlated with other craniofacial parameters like nasal, cranial, maxillary and mandibular width among both sexes. The frontal sinus, nasal, cranial, maxillary and mandibular widths were higher in males when compared to females (independent t-test). Discriminant function scores showed 66-68% accuracy to discriminate sex, using the anteroposterior dimension and mandibular width. Conclusions: The measurement of craniofacial parameters using CBCT can aid in determining the sex of unidentified and decomposed bodies.
Evaluating the reliability of the sickling test and peripheral blood film method for screening of sickle cell disease: a study protocol
Authors: Bawane Tejaswini , Vodithala Sahitya 
Published: September 2023

Background: Mutations in beta-globin are the cause of a widespread condition known as sickle cell disease (SCD). Sickle cells cause organ damage, hemolysis of blood cells, weakness, and sometimes even death. SCD can be effectively managed and mortality can be reduced through early detection. This protocol’s study aims to evaluate the sensitivity and specificity of the sickling test, peripheral blood smear, and hemoglobin electrophoresis for SCD screening. Methods: In this study,75 cases of SCD will be selected. 5ml blood will be drawn into a dipotassium ethylenediaminetetraacetic acid tube for testing of SCD. Testing will involve: the sickling test, where an equal volume of K2EDTA blood will be mixed with 2% sodium metabisulfite; the peripheral blood smear, where Leishman’s stain will be placed on a thin film of blood for 2 minutes; and Hb electrophoresis, where equal parts of distilled water and packed cells will be combined and then the mixture will be centrifuged. Results: We will be comparing between the sickling test and the peripheral blood film method, and we will conclude depending upon the results as to which test is better. Conclusions: Using peripheral blood smear images, SCD can be quickly diagnosed. A peripheral smear-based differential diagnosis may be possible but requires special tests such as hemoglobin electrophoresis to confirm the diagnosis. Therefore, early diagnosis can help initiate transfusion therapy and create a better prognosis.
Prevalence of health care associated infections and antibiotic use among adult patients: Results of a cross-sectional survey at a tertiary university hospital in Tunisia
Authors: Nouira Mariem , Maatouk Mohamed , Ben Youssef Sarra , Ennigrou Samir 
Published: September 2023

Background: Healthcare-associated infections (HAIs) represent a major public health problem concern with a high attributable morbidity and mortality. This study aimed to estimate the prevalence of HAIs among adult patients at the Charles Nicolle Hospital (CNH) of Tunis and to identify the main associated factors as well as to estimate the frequency of antibiotic use.Methods: This was a cross sectional study at the CNH with a unique passage per department (October-December 2018). All patients present at the wards for more than 48 hours were included. The site definitions of infections proposed by the Centers for Disease Control and Prevention were used.Results: A total of 261 patients were included with a mean age of 52.4 years SD (±16.1) and a sex ratio (Female/Male) of 1.25. Overall, 34 patients having at least one active HAI were identified which represent a prevalence of 13% (95% CI [9.2 %–17.0 %]). The most common type of reported infections were urinary tract infections (33.3%) followed by surgical site infections (19.4%) and pneumonia (19.4%). Independent risk factors of high prevalence of HAIs among adults above 18 years old were: having hypertension (ORadjusted=3.3;p=0.008), alcohol use (ORadjusted=5.2; p=.01), being infected at admission (ORadjusted=2.8;p=0.01), having at least one invasive device inserted during last 7 days prior to the survey date (ORadjusted=3.5;p=0.004) and undergoing a surgery 30 days prior to the study date (ORadjusted=2.6;p=0.03). The antibiotic use prevalence was 32.2%.Conclusions:An infection prevention and control committee, as well as the development of an Antibiotic stewardship program with continuous monitoring using repeated prevalence surveys, must be implemented to limit the frequency of these infections effectively.
Puzzle—Integer Linear Programming: Spreadsheet Solver Excellence Without Excel
Authors: Barlow Evan 
Published: September 2023

Because of the limitations on problem size with the built-in optimization solver in Microsoft Excel, other software applications are required to illustrate the power of integer linear programming in spreadsheets. The built-in linear optimization solver in LibreOffice Calc allows much larger problems. In this paper, we build a spreadsheet in LibreOffice Calc to solve sudoku problems and a simple generalization that further illustrates the power of integer linear programming in spreadsheets. The generalization we consider, n-doku, also introduces an interesting puzzle that includes, as a special case, a union of multiple sudoku puzzles. Besides further demonstrating the power of integer linear programming in spreadsheets, we use the n-doku solutions to develop optimization intuition and to, more generally, foster critical thinking. We use this spreadsheet in the classroom to transition from continuous to categorical decisions, emphasizing the idea of one-hot encoding. We also illustrate multiple optima and add preferences to sudoku puzzles as a way introduce multiobjective optimization. Supplemental Material: The online supplement is available at https://doi.org/10.1287/ited.2022.0068 .