bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight into Bone Metabolism and Skeletal Mass in Polycystic Ovary Syndrome
Authors: Berberoglu Zehra
Published: March 2023

Polycystic ovary syndrome (PCOS) is a complex, multifaceted disorder that manifests with obesity, hyperandrogenaemia, hyperinsulinaemia, and possibly hyperoestrogenaemia. These clinical features can cause PCOS to positively influence bone mass, and new relationships between obesity, bone remodelling, and energy metabolism have emerged. Bone mass can also be influenced by interrelated metabolic events that are not necessarily mediated by androgens. This article summarises the current literature with respect to the associations between the diverse clinical components of PCOS and bone.
Varicocele in Male Infertility: Current Status of Surgery Techniques
Authors: Üçer Oktay , Gümüş Bilal
Published: March 2023

Varicocele is the most common cause of male infertility and is generally correctable, or at least improvable, through various surgical techniques. Although several different techniques for varicocele repair have been described in the literature, microsurgical subinguinal varicocelectomy is recognised as the gold-standard approach for varicocelectomy due to high success rates with minimal complications. This article reviews the current status of the effects of varicocelectomy techniques on male infertility and the recurrence and complication rates associated with these techniques.
Targeting SCUBE3 in Hepatocellular Carcinoma
Authors: Liu Teng , Yang Xia , Wang Ke , Luo Qiang
Published: March 2023

HCC is one of the most common malignant tumors. The life and health of humans are gravely threatened by HCC because of its hidden onset, high recurrence rate, poor therapeutic effect, and high mortality. It is essential to explore the particular pathological mechanisms of HCC in order to increase the rate of early diagnosis and enhance patient therapy outcomes. Recent research has demonstrated that SCUBE3 can influence HCC cell proliferation by regulating the TGFβ/PI3K/AKT/GSK3β pathway. The molecular regulatory network of HCC proliferation is improved by this research, which also offers a solid theoretical and experimental foundation for SCUBE3 as a potential new therapeutic target for HCC.
PENGARUH VARIASI KONSENTRASI HPMC TERHADAP SIFAT FISIK GEL EKSTRAK KULIT PISANG AGUNG SEMERU (Musa paradisiaca L.)
Authors: Eryani Mikhania Christiningtyas , Siddiq Hadi Barru Hakam Fajar , Rashati Dewi , Safitri Risma Khoiro
Published: March 2023

The aims of this study was to determine the effect of HPMC variation concentration to the physical properties of Semeru Agung banana (Musa paradisiaca L.) skin extract gel. Gel was formulated with various HPMC concentration namely F1 (2%), F2 (3%) and F3 (4%). Gel was evaluated organoleptic, homogeinity, pH, viscosity, spreadbility and adhesion value. The results showed that F2 meet the organoleptic requirements while F1 and F3 did not meet. All formulas are homogeneous. The results of the pH test showed that the pH value of F1 was 5.9 ± 0; F2 of 5.8± 0 ; F3 of 5.9 ± 0. The results of the viscosity test showed that the viscosity value of F1 was 150 ± 0 dPas; F2 of 250 ± 0 dPas; F3 of 300 ± 0 dPas. The results of the dispersion test showed that the dispersion value of F1 was 5.6 ± 0.06 cm; F2 of 5.3 ± 0.29 cm ; F3 is 4.0 ± 0.12 cm. The results of the adhesion test showed that the value of the F1 adhesiveness was 11.04 ± 0.43 seconds; F2 of 17.4 ± 1.47 seconds; F3 is 24.2 ± 2.44 seconds. It is known that variations in HPMC concentration affect gel texture, viscosity, spreadability and adhesion, and have no effect on gel smell, color and pH.
Pengaruh Pijat Efleurage Terhadap Penurunan Nyeri Dismenore Pada Remaja Putri
Authors: Saputri Ika Nur , Lubis Riza Ardila Verawati , Nurianti Irma , Munthe Novita Br Ginting
Published: March 2023

Every woman will always experience menstruation every month, this can cause dysmenorrhea caused by prostaglandin production such as menstrual pain in the form of cramps in the lower abdomen in the pelvic area which results in disruption of activities and quality of life. This study aims to determine the effect of effleurage massage on reducing menstrual pain in young women. This type of research uses a quasi-experimental design with one group pretest and posttest while the sampling technique is purposive sampling. The results showed that the p-value before and after effleurage massage therapy was 0.000 (<0.05). The results of the study concluded that Ha was accepted and Ho was rejected because there was a significant effect before and after being given effleurage massage on reducing dysmenorrhea pain in young women.
The algebraic structure of f(Q) gravity
Authors: CHEN WEN-XIANG
Published: March 2023

In this paper, we focus on investigating the algebraic structure of f(Q) gravity. We introduce the basic concepts of f(Q) gravity and its Lagrangian density to do so. Using the variation principle, we derive the field equations of f(Q) gravity and show that it is a modification of the standard gravity theory, where an arbitrary function of the torsion tensor replaces the torsion scalar.We further explore the algebraic structure of f(Q) gravity and demonstrate that it can be described by a set of algebraic equations. Additionally, we delve into the symmetries of f(Q) gravity and examine their relation to the algebraic structure. This research provides valuable insights into the behavior of the theory and may lead to a better understanding of the nature of gravity and the universe's structure.
Simulation of Certain Quantum Effects
Authors: I. Gurianov Vasyliy
Published: March 2023

In our opinion, semantic networks can be used to provide a description of scientific models. Such a description is just as effective as a mathematical description. This article presents a description of some quantum effects in the language of frame semantic networks. The following questions are considered: the double-slit experiment, the uncertainty principle, quantum entanglement, and Bell's test. For each topic, a mathematical description is given, a description in the language of semantic networks, and the results of simulation experiments are given. The object-oriented simulation language UML2 SP is used to describe semantic frame networks. Software, related software documentation and experimental results are available on the GitHub service.
Perancangan Dan Implementasi Half Bridge Dc – Dc Converter Dengan Kendali Arus Hysteresis
Authors: Saputra Masramdhani , Yustiawan Gian Fikih , Ridzki Imron , Wiwaha Sigit Setya , Gumilang Binar Surya
Published: March 2023

DC-DC Converter is a direct voltage (DC) power supply device that is produced by converting DC input voltage into a lower or higher DC output voltage. In its development, the application of DC-DC Converter allows an electronic device to function with a small energy source, where the output voltage can be varied as needed. DC-DC Converters have been widely developed because they have various advantages, including: simpler form and has high efficiency. In this thesis, an Arduino Mega 2560-based current controller will be implemented. The type of current controller implemented is hysteresis current control with the well-known, tested and proven considerations. Current control works if the inductor current rises from the lower limit of the hysteresis band to the upper limit then the switch will be turned off (inductor current above the upper reference Ip.Ref) and if this current drops from the upper limit to the lower limit the switch will be turned on (current inductor under low frequency Iv.Ref). This current control also has advantages in overcurrent protection such as when there is a short circuit in the load.
Analisis Penstabilan Tegangan Output Generator Induksi 3 Fasa
Authors: Sucipto Rachmat , Syamsuri Tresna Umar , Epiwardi
Published: March 2023

One of the alternative generators in supplying electrical energy is a 3-phase generator made from a 3-phase slip ring induction motor, after which the rotor winding is supplied with a DC source and rotated using a prime mover. The problem arises because of the large % voltage regulation of a 3-phase generator when it is under load. This is because the induction generator has a relatively larger voltage loss when loaded with a certain load compared to a 3-phase synchronous generator. To overcome these conditions, there are several ways that can be used to stabilize the voltage from the generator, namely: setting the excitation current from the generator, setting the connection on the rotor windings (using 2 windings or using 3 rotor windings) and a combination of the two steps above. . Based on the results of experiments that have been carried out, it is known that the method of stabilizing the output voltage by setting the rotor winding connection is less effective than setting the excitation current because it turns out that the results of changing the output voltage are not too significant compared to changing the generator excitation current. In addition, it is also known that the stabilization of the output voltage from an inductive load will require a DC voltage that is greater than when under a resistive load because of the large difference in losses.
Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7
Authors: Min Jungki , Foo Alexander C. Y. , Gabel Scott A. , Perera Lalith , DeRose Eugene F. , Pomés Anna , Pedersen Lars C. , Mueller Geoffrey A.
Published: March 2023

Introduction

Pet lipocalins are respiratory allergens with a central hydrophobic ligand-binding cavity called a calyx. Molecules carried in the calyx by allergens are suggested to influence allergenicity, but little is known about the native ligands.

Methods

To provide more information on prospective ligands, we report crystal structures, NMR, molecular dynamics, and florescence studies of a dog lipocalin allergen Can f 1 and its closely related (and cross-reactive) cat allergen Fel d 7.

Results

Structural comparisons with reported lipocalins revealed that Can f 1 and Fel d 7 calyxes are open and positively charged while other dog lipocalin allergens are closed and negatively charged. We screened fatty acids as surrogate ligands, and found that Can f 1 and Fel d 7 bind multiple ligands with preferences for palmitic acid (16:0) among saturated fatty acids and oleic acid (18:1 cis-9) among unsaturated ones. NMR analysis of methyl probes reveals that conformational changes occur upon binding of pinolenic acid inside the calyx. Molecular dynamics simulation shows that the carboxylic group of fatty acids shuttles between two positively charged amino acids inside the Can f 1 and Fel d 7 calyx. Consistent with simulations, the stoichiometry of oleic acid-binding is 2:1 (fatty acid: protein) for Can f 1 and Fel d 7.

Discussion

The results provide valuable insights into the determinants of selectivity and candidate ligands for pet lipocalin allergens Can f 1 and Fel d 7.
Co-infection of hepatitis E virus, Clonorchis sinensis, and Escherichia coli: A case report
Authors: Zhang Lu , Wang Xiaohao , Zhang Jing , Wang Zhongrong , Cai Dachuan
Published: March 2023

Hepatitis E virus (HEV) is a common cause of acute hepatitis that threatens human health worldwide. With the popularization of detection technology, the reports of hepatitis E have gradually increased. Here, we present a rare case of co-infection with hepatitis E viruses, Clonorchis sinensis and Escherichia coli. A 52-year-old man was hospitalized because of fatigue, jaundice, and nausea for more than 2 weeks. Laboratory tests showed elevated bilirubin, aminotransferase (ALT), and aspartate aminotransferase (AST); HEV-IgM was positive, and HEV-RNA could be detected. Moreover, parasites were found in the biliary drainage and the biliary culture, which suggested Escherichia coli. The patient was effectively treated with praziquantel, imipenem, and hepatoprotective drugs and his clinical symptoms were relieved after 2 months; total bilirubin decreased to 85.1 μmol/L, ALT decreased to 92.4 U/L, and AST decreased to 102 U/L.
The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients
Authors: Shen Min , Ding Ping , Luan Guangxin , Du Ting , Deng Shanshan
Published: March 2023

Introduction

With the emergence of SARS-CoV-2 mutant strains, especially the epidemic of Omicron, it continues to evolve to strengthen immune evasion. Omicron BQ. 1 and XBB pose a serious threat to the current COVID-19 vaccine (including bivalent mRNA vaccine for mutant strains) and COVID-19-positive survivors, and all current therapeutic monoclonal antibodies are ineffective against them. Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalization and death after the initial vaccine booster. However, small-molecule drugs for conserved targets remain effective and urgently needed.

Methods

The non-structural protein of SARS-CoV-2 non-structural protein 1(Nsp1) can bind to the host 40S ribosomal subunit and activate the nuclease to hydrolyze the host RNA, while the viral RNA is unaffected, thus hijacking the host system. First, the present study analyzed mutations in the Nsp1 protein and then constructed a maximum-likelihood phylogenetic tree. A virtual drug screening method based on the Nsp1 structure (Protein Data Bank ID: 7K5I) was constructed, 7495 compounds from three databases were collected for molecular docking and virtual screening, and the binding free energy was calculated by the MM/GBSA method.

Results

Our study shows that Nsp1 is relatively conserved and can be used as a comparatively fixed drug target and that therapies against Nsp1 will target all of these variants. Golvatinib, Gliquidone, and Dihydroergotamine were superior to other compounds in the crystal structure of binding conformation and free energy. All effectively interfered with Nsp1 binding to 40S protein, confirming the potential inhibitory effect of these three compounds on SARS-CoV-2.

Discussion

In particular, Golwatinib provides a candidate for treatment and prophylaxis in elderly patients with Omicjon, suggesting further evaluation of the anti-SARS-CoV-2 activity of these compounds in cell culture. Further studies are needed to determine the utility of this finding through prospective clinical trials and identify other meaningful drug combinations.
Ehrlichia effector SLiM-icry: Artifice of cellular subversion
Authors: Pittner Nicholas A. , Solomon Regina N. , Bui Duc-Cuong , McBride Jere W.
Published: March 2023

As an obligately intracellular bacterial pathogen that selectively infects the mononuclear phagocyte, Ehrlichia chaffeensis has evolved sophisticated mechanisms to subvert innate immune defenses. While the bacterium accomplishes this through a variety of mechanisms, a rapidly expanding body of evidence has revealed that E. chaffeensis has evolved survival strategies that are directed by the versatile, intrinsically disordered, 120 kDa tandem repeat protein (TRP120) effector. E. chaffeensis establishes infection by manipulating multiple evolutionarily conserved cellular signaling pathways through effector-host interactions to subvert innate immune defenses. TRP120 activates these pathways using multiple functionally distinct, repetitive, eukaryote-mimicking short linear motifs (SLiMs) located within the tandem repeat domain that have evolved in nihilo. Functionally, the best characterized TRP120 SLiMs mimic eukaryotic ligands (SLiM-icry) to engage pathway-specific host receptors and activate cellular signaling, thereby repurposing these pathways to promote infection. Moreover, E. chaffeensis TRP120 contains SLiMs that are targets of post-translational modifications such as SUMOylation in addition to many other validated SLiMs that are curated in the eukaryotic linear motif (ELM) database. This review will explore the extracellular and intracellular roles TRP120 SLiM-icry plays during infection - mediated through a variety of SLiMs - that enable E. chaffeensis to subvert mononuclear phagocyte innate defenses.
Influence of common palynological extraction treatments on ultraviolet absorbing compounds (UACs) in sub-fossil pollen and spores observed in FTIR spectra
Authors: Wang Tianyuan , Bell Benjamin A. , Fletcher William J. , Ryan Peter A. , Wogelius Roy A.
Published: March 2023

Introduction

Biological life, atmospheric circulation and the Earth’s climate may be influenced by UV-B radiation. In plants, Ultraviolet Absorbing Compounds (UACs) are an indicator of UV-B exposure, and the abundance of UACs in pollen and spores of embryophytes is measurable using Fourier Transform Infrared (FTIR) micro-Spectroscopy. However, understanding the influence of common chemical pre-treatments on sub-fossil pollen and spores with a view to UV-B reconstruction still requires investigation.

Methods

Here, peat samples collected from a Late Holocene raised bog were treated with different chemicals (HCl, KOH, and acetolysis) for varying treatment times (up to 210 min). Pollen or spores of three common taxa (Alnus, Calluna and Sphagnum) were isolated and FTIR spectra obtained on individual grains. The spectra were compared to modern pollen and spore samples collected nearby.

Results

Spectra of modern and sub-fossil samples show several visible differences related to lipid and protoplast contents. The results of chemical treatments on sub-fossil pollen and spores reveal that HCl produced limited changes, while KOH and acetolysis altered several peaks, including the UAC-related aromatic peak at 1516 cm−1. We observe that all treatments modify the FTIR spectra to some degree, from weakest (HCl) to strongest (acetolysis). With respect to reduction of UAC peak area and treatment time, we observe in some cases a significant log-decay relationship, notably for KOH treatment on Calluna pollen and acetolysis on Sphagnum spores. Compared to untreated control samples, UAC peak area in Alnus, Calluna and Sphagnum reduced by 68%, 69% and 60% respectively, after only 3 min of acetolysis treatment. After 60 minutes of acetolysis treatment UAC peaks were reduced by 77%, 84% and 88%.

Discussion

Due to the potential for taxon-specific effects and significant reductions in UAC peak area even within short treatment times, our recommendation for future applications in palaeoecological studies on palynomorph chemistry is to avoid chemical digestions in the pollen extraction process in favour of separation methods including micro-sieving and density separation.
Tumor infiltrating lymphocytes as an endpoint in cancer vaccine trials
Authors: McCarthy Patrick M. , Valdera Franklin A. , Smolinsky Todd R. , Adams Alexandra M. , O’Shea Anne E. , Thomas Katryna K. , Van Decar Spencer , Carpenter Elizabeth L. , Tiwari Ankur , Myers John W. , Hale Diane F. , Vreeland Timothy J. , Peoples George E. , Stojadinovic Alex , Clifton Guy T.
Published: March 2023

Checkpoint inhibitors have invigorated cancer immunotherapy research, including cancer vaccination. Classic early phase trial design and endpoints used in developing chemotherapy are not suited for evaluating all forms of cancer treatment. Peripheral T cell response dynamics have demonstrated inconsistency in assessing the efficacy of cancer vaccination. Tumor infiltrating lymphocytes (TILs), reflect the local tumor microenvironment and may prove a superior endpoint in cancer vaccination trials. Cancer vaccines may also promote success in combination immunotherapy treatment of weakly immunogenic tumors. This review explores the impact of TILs as an endpoint for cancer vaccination in multiple malignancies, summarizes the current literature regarding TILs analysis, and discusses the challenges of providing validity and a standardized implementation of this approach.
Analysis of unsteady thin film flows over the porous and moving surfaces of variable thickness: Unsteady and non-linear kinematics of sheet
Authors: Ullah Naeem , Khan Marwat Dil Nawaz , Khan Zareen A.
Published: March 2023

Thin film flows over porous and moving sheets of variable thickness have been reconsidered here. New and multiple dimensions of classical problems of such type flow are analyzed. Here, we categorically emphasized on the nature and kinds of injection (suction) and moving velocities of the sheet, whereas, variable size of the sheet is also taken into account. We formed and investigated different cases and checked different options for kinematics of sheet, variable sizes of thin film and that of sheet. All possible cases of exact similarities are noticed by which the system of partial differential equations and boundary conditions are exactly transformed into ordinary differential equations. The final systems of exact equations are solved by bvp4c technique. The present simulations are exactly matched with the previously published analyses for special choices of functions and parameters. Strict behavioral changes have been observed in the velocity profiles by changing the nature of sheet’s kinematics.
Data augmentation and multimodal learning for predicting drug response in patient-derived xenografts from gene expressions and histology images
Authors: Partin Alexander , Brettin Thomas , Zhu Yitan , Dolezal James M. , Kochanny Sara , Pearson Alexander T. , Shukla Maulik , Evrard Yvonne A. , Doroshow James H. , Stevens Rick L.
Published: March 2023

Patient-derived xenografts (PDXs) are an appealing platform for preclinical drug studies. A primary challenge in modeling drug response prediction (DRP) with PDXs and neural networks (NNs) is the limited number of drug response samples. We investigate multimodal neural network (MM-Net) and data augmentation for DRP in PDXs. The MM-Net learns to predict response using drug descriptors, gene expressions (GE), and histology whole-slide images (WSIs). We explore whether combining WSIs with GE improves predictions as compared with models that use GE alone. We propose two data augmentation methods which allow us training multimodal and unimodal NNs without changing architectures with a single larger dataset: 1) combine single-drug and drug-pair treatments by homogenizing drug representations, and 2) augment drug-pairs which doubles the sample size of all drug-pair samples. Unimodal NNs which use GE are compared to assess the contribution of data augmentation. The NN that uses the original and the augmented drug-pair treatments as well as single-drug treatments outperforms NNs that ignore either the augmented drug-pairs or the single-drug treatments. In assessing the multimodal learning based on the MCC metric, MM-Net outperforms all the baselines. Our results show that data augmentation and integration of histology images with GE can improve prediction performance of drug response in PDXs.
Environmental factors and gut microbiota: Toward better conservation of deer species
Authors: Wang Yu , Xu Bo , Chen Huan , Yang Fang , Huang Jinlin , Jiao Xin’an , Zhang Yunzeng
Published: March 2023

Thousands of microbial species inhabiting the animal gut, collectively known as the gut microbiota, play many specific roles related to host nutrient metabolism and absorption, immune regulation, and protection from pathogenic bacteria. Gut microbiota composition is affected by several internal and external factors, such as the host genotype, dietary intake, breeding environment, and antibiotic exposure. As deer species are important members for maintaining ecosystem balance, understanding the effects of multiple factors on the gut microbiota of deer species, particularly endangered ones, is crucial. In this review, we summarize and discuss the factors that significantly affect the gut microbiota of deer and present the impacts of these factors on microbial composition. In particular, we focused on the changes in gut microbiota due to dietary differences under different conditions, including seasonal changes, different geographical locations, and captivity, as well as weaning and pathogen disturbance. Understanding the correlations between gut microbiota composition and its driving factors is important for evaluating and improving the captive breeding environment for better conservation of endangered deer species, and reintroducing wild deer populations in the future.
A novel myeloid cell marker genes related signature can indicate immune infiltration and predict prognosis of hepatocellular carcinoma: Integrated analysis of bulk and single-cell RNA sequencing
Authors: Zheng Su-Su , Wu Yan-Fang , Zhang Bo-Heng , Huang Cheng , Xue Tong-Chun
Published: March 2023

Myeloid cells are physiologically related to innate immunity and inflammation. Tumor-associated myeloid cells gained increasing interest because of their critical roles in tumor progression and anticancer immune responses in human malignancies. However, the associations between tumor-associated myeloid cell-related genes and hepatocellular carcinoma have yet to be revealed. Here, through the integrating analysis of bulk and single-cell RNA (scRNA) sequencing of public HCC samples, we developed a gene signature to investigate the role of HCC-specific myeloid signature genes in HCC patients. We firstly defined 317 myeloid cell marker genes through analyzing scRNA data of HCC from the GEO dataset. After selecting the differentially expressed genes, eleven genes were also proved prognostic. Then we built a gene signature from the TCGA cohort and verified further with the ICGC dataset by applying the LASSO Cox method. An eight genes signature (FABP5, C15orf48, PABPC1, TUBA1B, AKR1C3, NQO1, AKR1B10, SPP1) was achieved finally. Patients in the high risk group correlated with higher tumor stages and poor survival than those in the low-risk group. The risk score was proved to be an independent risk factor for prognosis. The high risk group had higher infiltrations of dendritic cells, macrophages and Tregs. And the APC co-inhibition, T cell co-inhibition pathways were also activated. Besides, the risk score positively correlated with multidrug resistance proteins. In conclusion, our myeloid cell marker genes related signature can predict patients’ survival and may also indicate the levels of immune infiltration and drug resistance.
A simple flash and freeze system for cryogenic time-resolved electron microscopy
Authors: Bhattacharjee Biddut , Rahman Md Mahfuzur , Hibbs Ryan E. , Stowell Michael H. B.
Published: March 2023

As the resolution revolution in CryoEM expands to encompass all manner of macromolecular complexes, an important new frontier is the implementation of cryogenic time resolved EM (cryoTREM). Biological macromolecular complexes are dynamic systems that undergo conformational changes on timescales from microseconds to minutes. Understanding the dynamic nature of biological changes is critical to understanding function. To realize the full potential of CryoEM, time resolved methods will be integral in coupling static structures to dynamic functions. Here, we present an LED-based photo-flash system as a core part of the sample preparation phase in CryoTREM. The plug-and-play system has a wide range of operational parameters, is low cost and ensures uniform irradiation and minimal heating of the sample prior to plunge freezing. The complete design including electronics and optics, manufacturing, control strategies and operating procedures are discussed for the Thermo Scientific™ Vitrobot and Leica™ EM GP2 plunge freezers. Possible adverse heating effects on the biological sample are also addressed through theoretical as well as experimental studies.
Loss of Müller cell glutamine synthetase immunoreactivity is associated with neuronal changes in late-stage retinal degeneration
Authors: Reynisson Hallur , Kalloniatis Michael , Fletcher Erica L. , Shivdasani Mohit N. , Nivison-Smith Lisa
Published: March 2023

Introduction

A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. The exact relationship between neurons and glia remodeling in this late stage of retinal degeneration, however, is unclear. This study assessed this by examining Müller cell dysfunction via glutamine synthetase immunoreactivity and its spatial association with retinal neuron subpopulations through various cell markers.

Methods

Aged Rd1 mice retinae (P150 – P536,n= minimum 5 per age) and control heterozygous rd1 mice retinae (P536,n= 5) were isolated, fixed and cryosectioned. Fluorescent immunolabeling of glutamine synthetase was performed and retinal areas quantified as having low glutamine synthetase immunoreactivity if proportion of labeled pixels in an area was less than two standard deviations of the mean of the total retina. Other Müller cell markers such as Sox9 and Glial fibrillary acidic protein along with neuronal cell markers Calbindin, Calretinin, recoverin, Protein kinase C-α, Glutamic acid decarboxylase 67, and Islet-1 were then quantified within areas of low and normal synthetase immunoreactivity.

Results

Glutamine synthetase immunoreactivity was lost as a function of age in the rd1 mouse retina (P150 – P536). Immunoreactivity of other Müller cell markers, however, were unaffected suggesting Müller cells were still present in these low glutamine synthetase immunoreactive regions. Glutamine synthetase immunoreactivity loss affected specific neuronal populations: Type 2, Type 8 cone, and rod bipolar cells, as well as AII amacrine cells based on reduced recoverin, protein kinase Ca and parvalbumin immunoreactivity, respectively. The number of cell nuclei within regions of low glutamine synthetase immunoreactivity was also reduced suggesting possible neuronal loss rather than reduced cell marker immunoreactivity.

Conclusion

These findings further support a strong interplay between glia-neuronal alterations in late-stage degeneration and highlight a need for future studies and consideration in intervention development.
Development of a new clinical tool to evaluate the balance abilities of children with bilateral vestibular loss: The Geneva Balance Test
Authors: Monin Emile , Bahim Céline , Baussand Lou , Cugnot Jean-François , Ranieri Maurizio , Guinand Nils , Pérez Fornos Angélica , Cao Van Hélène
Published: March 2023

Introduction

Vestibular deficits are considered rare in children, but the lack of systematic screening leads to underdiagnosis. It has been demonstrated that chronic vestibular dysfunction impacts the normal psychomotor development of children. Early identification is needed to allow for clinical management, ensuring better global development. For this purpose, our research group has developed the Geneva Balance Test (GBT), aiming to objectively quantify the balance capacity of children over a broad age range, to screen for bilateral vestibulopathy (BV), and to quantify the improvement of balance abilities in children.

Methods

To determine the capacity of the GBT to quantify the balance capacity of children with BV, we conducted an observational prospective study with three populations: 11 children with BV, and two age-matched control groups composed of (1) 15 healthy subjects without the vestibular or auditory disorder (HS) and (2) 11 pediatric cochlear implant recipients (CIs) without vestibular disorders. Results of the three populations have been compared in three different age sub- groups (3–5, 6–9, and ≥10 years), and with results of a short, modified version of the Bruininks-Oseretsky test of Motor proficiency Ed. 2 (mBOT-2).

Results

Statistical analyses demonstrated significant differences in the scores of the GBT between children aged 3–5, 6–9, and ≥10 years with BV and in both control populations (HS and CI). BV scores reflected poorer balance capacities at all ages. Children in the youngest CI sub-group (3–5 years) showed intermediate GBT scores but reached HS scores at 6–9 years, reflecting an improvement in their balance capacities. All the results of the GBT were significantly correlated with mBOT-2 results, although only a few BV completed the entire mBOT-2.

Discussion

In this study, the GBT allowed quantifying balance deficits in children with BV. The BOT-2 test is not validated for children <4.5 years of age, and the GBT seems to be better tolerated in all populations than the mBOT-2. Furthermore, mBOT-2 results saturated, reaching maximum values by 6–9 years whereas the GBT did not, suggesting that the GBT could be a useful tool for monitoring the development of balance capacities with age and could be used in the follow-up of children with severe vestibular disorders.
Posttraumatic stress disorder symptoms among Chinese college students following the COVID-19 outbreak
Authors: Wang Jie-Yu , Li Qi , Liu Wei , Yang Yang , Wang Xiao-Guang , Liu Chun-Yan , Shu Xi-Ji , Xue Li , Shi Yan-Wei
Published: March 2023

Objective

This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms in college students 1 month after the lockdown of Wuhan to identify possible risk factors for PTSD symptoms in a cross-sectional study.

Methods

Out of 10,502 who responded, 9,274 students impacted by the COVID-19 pandemic were included in our study. PTSD symptoms was evaluated by the Impact of Event Scale-revised (IES-R). Anxiety/depression symptoms were evaluated by the Kessler Psychological Distress Scale (K10). Personality traits, coping style, and social support were assessed by the Eysenck Personality Questionnaire-Revised Short Scale for Chinese (EPQ-RSC), the Simplified Coping Style Questionnaire (SCSQ), and the Social Support Rating Scale (SSRS). Logistic regression analysis was utilized to further explore risk factors for PTSD symptoms.

Results

More than 1 month after the COVID-19 outbreak, 13.1% of college students developed PTSD symptoms, indicating that COVID-19 associated stressful experiences were connected with PTSD symptoms. After the COVID-19 outbreak, subjects with symptomatologic PTSD symptoms were more likely to experience strained relationships with their family, to have close contact with COVID-19 patients and to drop out of college. The logistic regression model demonstrated the association factors of PTSD symptoms. Neuroticism, psychoticism and an avoidant coping style were associated with increased risk for PTSD symptoms, while an active coping style was protective against PTSD symptoms during this pandemic.

Conclusion

The results showed that PTSD symptoms was prevalent in Chinese college students 1 month after the COVID-19 outbreak. Effective psychological support work should be carried out accordingly.
Transformed common spatial pattern for motor imagery-based brain-computer interfaces
Authors: Ma Zhen , Wang Kun , Xu Minpeng , Yi Weibo , Xu Fangzhou , Ming Dong
Published: March 2023

Objective

The motor imagery (MI)-based brain–computer interface (BCI) is one of the most popular BCI paradigms. Common spatial pattern (CSP) is an effective algorithm for decoding MI-related electroencephalogram (EEG) patterns. However, it highly depends on the selection of EEG frequency bands. To address this problem, previous researchers often used a filter bank to decompose EEG signals into multiple frequency bands before applying the traditional CSP.

Approach

This study proposed a novel method, i.e., transformed common spatial pattern (tCSP), to extract the discriminant EEG features from multiple frequency bands after but not before CSP. To verify its effectiveness, we tested tCSP on a dataset collected by our team and a public dataset from BCI competition III. We also performed an online evaluation of the proposed method.

Main results

As a result, for the dataset collected by our team, the classification accuracy of tCSP was significantly higher than CSP by about 8% and filter bank CSP (FBCSP) by about 4.5%. The combination of tCSP and CSP further improved the system performance with an average accuracy of 84.77% and a peak accuracy of 100%. For dataset IVa in BCI competition III, the combination method got an average accuracy of 94.55%, which performed best among all the presented CSP-based methods. In the online evaluation, tCSP and the combination method achieved an average accuracy of 80.00 and 84.00%, respectively.

Significance

The results demonstrate that the frequency band selection after CSP is better than before for MI-based BCIs. This study provides a promising approach for decoding MI EEG patterns, which is significant for the development of BCIs.
Disrupted interhemispheric coordination of sensory-motor networks and insula in major depressive disorder
Authors: Zhang Chunguo , Jing Huan , Yan Haohao , Li Xiaoling , Liang Jiaquan , Zhang Qinqin , Liang Wenting , Ou Yangpan , Peng Can , Yu Yang , Wu Weibin , Xie Guojun , Guo Wenbin
Published: March 2023

Objective

Prior researches have identified distinct differences in neuroimaging characteristics between healthy controls (HCs) and patients with major depressive disorder (MDD). However, the correlations between homotopic connectivity and clinical characteristics in patients with MDD have yet to be fully understood. The present study aimed to investigate common and unique patterns of homotopic connectivity and their relationships with clinical characteristics in patients with MDD.

Methods

We recruited 42 patients diagnosed with MDD and 42 HCs. We collected a range of clinical variables, as well as exploratory eye movement (EEM), event-related potentials (ERPs) and resting-state functional magnetic resonance imaging (rs-fMRI) data. The data were analyzed using correlation analysis, support vector machine (SVM), and voxel-mirrored homotopic connectivity (VMHC).

Results

Compared with HCs, patients with MDD showed decreased VMHC in the insula, and increased VMHC in the cerebellum 8/vermis 8/vermis 9 and superior/middle occipital gyrus. SVM analysis using VMHC values in the cerebellum 8/vermis 8/vermis 9 and insula, or VMHC values in the superior/middle occipital gyrus and insula as inputs can distinguish HCs and patients with MDD with high accuracy, sensitivity, and specificity.

Conclusion

The study demonstrated that decreased VMHC in the insula and increased VMHC values in the sensory-motor networks may be a distinctive neurobiological feature for patients with MDD, which could potentially serve as imaging markers to discriminate HCs and patients with MDD.
Extended and replicated white matter changes in obesity: Voxel-based and region of interest meta-analyses of diffusion tensor imaging studies
Authors: Dietze Lorielle M. F. , McWhinney Sean R. , Radua Joaquim , Hajek Tomas
Published: March 2023

Introduction

Obesity has become a global public health issue, which impacts general health and the brain. Associations between obesity and white matter microstructure measured using diffusion tensor imaging have been under reviewed, despite a relatively large number of individual studies. Our objective was to determine the association between obesity and white matter microstructure in a large general population sample.

Methods

We analyzed location of brain white matter changes in obesity using the Anisotropic Effect Size Seed-based d Mapping (AES-SDM) method in a voxel-based meta-analysis, with validation in a region of interest (ROI) effect size meta-analysis. Our sample included 21 742 individuals from 51 studies.

Results

The voxel-based spatial meta-analysis demonstrated reduced fractional anisotropy (FA) with obesity in the genu and splenium of the corpus callosum, middle cerebellar peduncles, anterior thalamic radiation, cortico-spinal projections, and cerebellum. The ROI effect size meta-analysis replicated associations between obesity and lower FA in the genu and splenium of the corpus callosum, middle cerebellar peduncles. Effect size of obesity related brain changes was small to medium.

Discussion

Our findings demonstrate obesity related brain white matter changes are localized rather than diffuse. Better understanding the brain correlates of obesity could help identify risk factors, and targets for prevention or treatment of brain changes.
Malnutrition and gender disparities in the Eastern Mediterranean Region: The need for action
Authors: Jabbour Jana , Khalil Merette , Ronzoni Anna Rita , Mabry Ruth , Al-Jawaldeh Ayoub , El-Adawy Maha , Sakr Hala
Published: March 2023

Malnutrition takes a heavy toll on the populations of the Eastern Mediterranean Region (EMR), with gender related socioeconomic risk factors impacting undernutrition and obesity in both women and men. This perspective article, a derivative of a report by the World Health Organization, reviews the scientific literature on the effect of gender on malnutrition related outcomes in the EMR. Results revealed that biological and gender-related socioeconomic risk factors play a role for undernutrition and obesity in both women and men. Malnutrition can be negatively influenced by gender-biased cultural standards, habits, structural determinants, differential exposures, and health system gaps. This can result, for example, in women tending to focus on familial and household related needs, at the expense of their own health and physical mobility and on suffering more food insecurity, undernutrition, micronutrient deficiencies and obesity compared to men in the EMR. Conflict and crisis situations negatively affect both genders, but generally put women at a higher risk of adverse. Women’s socially limited autonomy in mobility is also an obstacle to access to health services in the EMR, including those related to nutrition. Multi-level approaches are needed to address gender issues to enable a more equitable distribution of resources and reduce the impact of malnutrition in the EMR.
Development of artificial blood loss and duration of excision score to evaluate surgical difficulty of total laparoscopic anterior resection in rectal cancer
Authors: Lv Jingfang , Guan Xu , Wei Ran , Yin Yefeng , Liu Enrui , Zhao Zhixun , Chen Haipeng , Liu Zheng , Jiang Zheng , Wang Xishan
Published: March 2023

Purpose

Total laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR.

Methods

RC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score.

Results

A total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set.

Conclusion

This preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.
Targeting c-Met in the treatment of urologic neoplasms: Current status and challenges
Authors: Su Pengxiao , Zhang Ming , Kang Xin
Published: March 2023

At present, studies have found that c-Met is mainly involved in epithelial-mesenchymal transition (EMT) of tumor tissues in urologic neoplasms. Hepatocyte growth factor (HGF) combined with c-Met promotes the mitosis of tumor cells, and then induces motility, angiogenesis, migration, invasion and drug resistance. Therefore, c-Met targeting therapy may have great potential in urologic neoplasms. Many strategies targeting c-Met have been widely used in the study of urologic neoplasms. Although the use of targeting c-Met therapy has a strong biological basis for the treatment of urologic neoplasms, the results of current clinical trials have not yielded significant results. To promote the application of c-Met targeting drugs in the clinical treatment of urologic neoplasms, it is very important to study the detailed mechanism of c-Met in urologic neoplasms and innovate c-Met targeted drugs. This paper firstly discussed the value of c-Met targeted therapy in urologic neoplasms, then summarized the related research progress, and finally explored the potential targets related to the HGF/c-Met signaling pathway. It may provide a new concept for the treatment of middle and late urologic neoplasms.
Correlation of tumor mutational burden with prognosis and immune infiltration in lung adenocarcinoma
Authors: Li Lin , Li Junyu
Published: March 2023

Background

Tumor mutational burden (TMB) plays an important role in the evaluation of immunotherapy efficacy in lung adenocarcinoma (LUAD).

Objective

To improve the clinical management of LUAD by investigating the prognostic value of TMB and the relationship between TMB and immune infiltration.

Methods

TMB scores were calculated from the mutation data of 587 LUAD samples from The Cancer Genome Atlas (TCGA), and patients were divided into low-TMB and high-TMB groups based on the quartiles of the TMB score. Differentially expressed genes (DEGs), immune cell infiltration and survival analysis were compared between the low-TMB and high-TMB groups. We queried the expression of genes in lung cancer tissues through the GEPIA online database and performed experimental validation of the function of aberrant genes expressed in lung cancer tissues.

Results

We obtained sample information from TCGA for 587 LUAD patients, and the results of survival analysis for the high- and low- TMB groups suggested that patients in the high-TMB group had lower survival rates than those in the low-TMB group. A total of 756 DEGs were identified in the study, and gene set enrichment analysis (GSEA) showed that DEGs in the low-TMB group were enriched in immune-related pathways. Among the differentially expressed genes obtained, 15 immune-related key genes were screened with the help of ImmPort database, including 5 prognosis-related genes (CD274, PDCD1, CTLA4, LAG3, TIGIT). No difference in the expression of PDCD1, CTLA4, LAG3, TIGIT in lung cancer tissues and differential expression of CD274 in lung cancer tissues.

Conclusions

The survival rate of LUAD patients with low TMB was better than that of LUAD patients with high TMB. CD274 expression was down regulated in human LUAD cell lines H1299, PC-9, A549 and SPC-A1, which inhibited malignant progression of A549 cells.
Claudin and pancreatic cancer
Authors: Wang Chen , Wu Na , Pei Beibei , Ma Xiaoyan , Yang Wenhui
Published: March 2023

Due to the lack of timely and accurate screening modalities and treatments, most pancreatic cancer (PCa) patients undergo fatal PCa progression within a short period since diagnosis. The claudin(CLDN) family is expressed specifically as tight junction structure in a variety of tumors, including PCa, and affects tumor progression by changing the cell junctions. Thus far, many of the 27 members of the claudin family, including claudin-18.2 and claudin-4, have significantly aberrantly expression in pancreatic tumors. In addition, some studies have confirmed the role of some claudin proteins in the diagnosis and treatment of pancreatic tumors. By targeting different targets of claudin protein and combining chemotherapy, further enhance tumor cell necrosis and inhibit tumor invasion and metastasis. Claudins can either promote or inhibit the development of pancreatic cancer, which indicates that the diagnosis and treatment of different kinds of claudins require to consider different biological characteristics. This literature summarizes the functional characteristics and clinical applications of various claudin proteins in Pca cells, with a focus on claudin-18.2 and claudin-4.