bluuebunny/crossref_metadata_2025 huggingface dataset:
Function-structure approach reveals novel insights on the interplay of Immunoglobulin G 1 proteoforms and Fc gamma receptor IIa allotypes
Authors: Lippold Steffen , Mistry Karishma , Lenka Sunidhi , Whang Kevin , Liu Peilu , Pitschi Sebastian , Kuhne Felix , Reusch Dietmar , Cadang Lance , Knaupp Alexander , Izadi Saeed , Dunkle Alexis , Yang Feng , Schlothauer Tilman
Published: September 2023

Human Fc gamma receptor IIa (FcγRIIa) or CD32a has two major allotypes with a single amino acid difference at position 131 (histidine or arginine). Differences in FcγRIIa allotypes are known to impact immunological responses such as the clinical outcome of therapeutic monoclonal antibodies (mAbs). FcγRIIa is involved in antibody-dependent cellular phagocytosis (ADCP), which is an important contributor to the mechanism-of-action of mAbs by driving phagocytic clearance of cancer cells. Hence, understanding the impact of individual mAb proteoforms on the binding to FcγRIIa, and its different allotypes, is crucial for defining meaningful critical quality attributes (CQAs). Here, we report a function-structure based approach guided by novel FcγRIIa affinity chromatography-mass spectrometry (AC-MS) assays to assess individual IgG1 proteoforms. This allowed to unravel allotype-specific differences of IgG1 proteoforms on FcγRIIa binding. FcγRIIa AC-MS confirmed and refined structure-function relationships of IgG1 glycoform interactions. For example, the positive impact of afucosylation was higher than galactosylation for FcγRIIa Arg compared to FcγRIIa His. Moreover, we observed FcγRIIa allotype-opposing and IgG1 proteoform integrity-dependent differences in the binding response of stress-induced IgG1 proteoforms comprising asparagine 325 deamidation. The FcγRIIa-allotype dependent binding differences resolved by AC-MS were in line with functional ADCP-surrogate bioassay models. The molecular basis of the observed allotype specificity and proteoform selectivity upon asparagine 325 deamidation was elucidated using molecular dynamics. The observed differences were attributed to the contributions of an inter-molecular salt bridge between IgG1 and FcγRIIa Arg and the contribution of an intra-molecular hydrophobic pocket in IgG1. Our work highlights the unprecedented structural and functional resolution of AC-MS approaches along with predictive biological significance of observed affinity differences within relevant cell-based methods. This makes FcγRIIa AC-MS an invaluable tool to streamline the CQA assessment of therapeutic mAbs.
Learning from the microbes: exploiting the microbiome to enforce T cell immunotherapy
Authors: Staudt Sarah , Ziegler-Martin Kai , Visekruna Alexander , Slingerland John , Shouval Roni , Hudecek Michael , van den Brink Marcel , Luu Maik
Published: September 2023

The opportunities genetic engineering has created in the field of adoptive cellular therapy for cancer are accelerating the development of novel treatment strategies using chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. The great success in the context of hematologic malignancies has made especially CAR T cell therapy a promising approach capable of achieving long-lasting remission. However, the causalities involved in mediating resistance to treatment or relapse are still barely investigated. Research on T cell exhaustion and dysfunction has drawn attention to host-derived factors that define both the immune and tumor microenvironment (TME) crucially influencing efficacy and toxicity of cellular immunotherapy. The microbiome, as one of the most complex host factors, has become a central topic of investigations due to its ability to impact on health and disease. Recent findings support the hypothesis that commensal bacteria and particularly microbiota-derived metabolites educate and modulate host immunity and TME, thereby contributing to the response to cancer immunotherapy. Hence, the composition of microbial strains as well as their soluble messengers are considered to have predictive value regarding CAR T cell efficacy and toxicity. The diversity of mechanisms underlying both beneficial and detrimental effects of microbiota comprise various epigenetic, metabolic and signaling-related pathways that have the potential to be exploited for the improvement of CAR T cell function. In this review, we will discuss the recent findings in the field of microbiome-cancer interaction, especially with respect to new trajectories that commensal factors can offer to advance cellular immunotherapy.
Differential molecular programs of cutaneous anaplastic large cell lymphoma and CD30-positive transformed mycosis fungoides
Authors: Lai Pan , Liu Fengjie , Liu Xiangjun , Sun Jingru , Wang Yang
Published: September 2023

Background

Discriminating between cutaneous anaplastic large cell lymphoma (cALCL) and CD30-positive transformed mycosis fungoides (CD30+ TMF) is challenging, particularly when they arise in the context of pre-existing mycosis fungoides. The development of molecular diagnostic tools was hampered by the rarity of both diseases and the limited understanding of their pathogenesis.

Methods

In this study, we established a cohort comprising 25 cALCL cases and 25 CD30+ TMF cases, with transcriptomic data obtained from 31 samples. We compared the clinicopathological information and investigated the gene expression profiling between these two entities. Furthermore, we developed an immunohistochemistry (IHC) algorithm to differentiate these two entities clinically.

Results

Our investigation revealed distinct clinicopathological features and unique gene expression programs associated with cALCL and CD30+ TMF. cALCL and CD30+ TMF displayed marked differences in gene expression patterns. Notably, CD30+ TMF demonstrated enrichment of T cell receptor signaling pathways and an exhausted T cell phenotype, accompanied by infiltration of B cells, dendritic cells, and neurons. In contrast, cALCL cells expressed high levels of HLA class II genes, polarized towards a Th17 phenotype, and exhibited neutrophil infiltration. An IHC algorithm with BATF3 and TCF7 staining emerged as potential diagnostic markers for identifying these two entities.

Conclusions

Our findings provide valuable insights into the differential molecular signatures associated with cALCL and CD30+ TMF, which contribute to their distinct clinicopathological behaviors. An appropriate IHC algorithm could be used as a potential diagnostic tool.
Further evidence of humpback whale presence in deep tropical ocean during the breeding season: confirmation and extension of acoustic detections between Hawaii and Mexico
Authors: Darling James D. , Goodwin Beth
Published: September 2023

During winter humpback whales converge on tropical breeding grounds characterized by shallow, warm seas. In the eastern half of the North Pacific two such breeding grounds are located along the shorelines and shallows of Mexico, and in mid-ocean around Hawaii, separated by 4,500-6,000 km of deep ocean basin. A 2018 acoustic survey by an autonomous Wave Glider from Hawaii eastward towards Mexico, at breeding ground latitudes (circa 20°N) and during peak breeding season, discovered singing whales between these locations near continuously out to mid-ocean - the first evidence of this latitudinal, tropical deep-water distribution. We report the results from a 2021 study which replicated the first half of the 2018 route and extended the survey to Isla Clarión, the westernmost breeding ground of Mexico. The portion of the 2021 survey replicating the earlier course resulted in markedly similar, near-continual detection of humpback whales from Hawaii out 2,161 km (over 1,000 nm) to mid-ocean. Detections occurred on 29 of the first 37 days eastbound from South Point Hawaii (vs. 30 of 35 days in 2018), with up to 3,000 calls a day, including multiple simultaneous singers. The 2021 extension (non-replicative portion) from mid-ocean eastward produced intermittent detections to Isla Clarión. The results, combined with recent reports of photo-identified individuals which traveled between Mexico and Hawaii in one winter season, indicate a recurring tropical offshore presence between these traditional breeding grounds - its extent and purpose to be determined.
Large-scale seabird community structure along oceanographic gradients in the Scotia Sea and northern Antarctic Peninsula
Authors: Ollus Victoria Marja Sofia , Biuw Martin , Lowther Andrew , Fauchald Per , Deehr Johannessen John Elling , Martín López Lucía Martina , Gkikopoulou Kalliopi C. , Oosthuizen W. Chris , Lindstrøm Ulf
Published: September 2023

Introduction

The Scotia Sea and Antarctic Peninsula are warming rapidly and changes in species distribution are expected. In predicting habitat shifts and considering appropriate management strategies for marine predators, a community-level understanding of how these predators are distributed is desirable. Acquiring such data, particularly in remote areas, is often problematic given the cost associated with the operation of research vessels. Here we use cruise vessels as sampling platforms to explore seabird distribution relative to habitat characteristics.

Methods

Data on seabird at-sea distribution were collected using strip-transect counts throughout the Antarctic Peninsula and Scotia Sea in the austral summer of 2019-2020. Constrained correspondence analysis (CCA) and generalized additive models (GAM) were used to relate seabird community composition, density, and species richness to environmental covariates.

Results

Species assemblages differed between oceanographic areas, with sea surface temperature and distance to coast being the most important predictors of seabird distribution. Our results further revealed a geographic separation of distinct communities rather than hotspot regions in the study area in summer.

Discussion

These findings highlight the importance of large-scale environmental characteristics in shaping seabird community structure, presumably through underlying prey distribution and interspecific interactions. The present study contributes to the knowledge of seabird distribution and habitat use as well as the baseline for assessing the response of Antarctic seabird communities to climate warming. We argue that cruise vessels, when combined with structured research surveys, can provide a cost-effective additional tool for the monitoring of community and ecosystem level changes.
Hydrogel assistant synthesis of new Ti-MOF cross-linked oxidized pectin and chitosan with anti-breast cancer properties
Authors: Alkhathami Ali G. , Khaled Younis Albahadly Waleed , Jawad Mohammed Abed , Ramadan Montather F. , Alsaraf Khulood Majid , Riyad Muedii Zainab Al-Hawraa , Alsaikhan Fahad , Suliman Muath
Published: September 2023

Breast cancer is one of the most common diseases of the modern age. Although many methods for its treatment have been reported so far, the report and synthesis of new compounds based on new technologies, especially nanotechnology, is important. One of the laboratory methods for evaluating the anticancer properties of compounds is the in vitro MTT method (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide). In this study, the in vitro anti-breast cancer activity of the newly synthesized (Titanium Metal-Organic Framework) Ti-MOF cross-linked oxidized pectin and chitosan hydrogel, which uses biopolymers in its synthesis and structure, was investigated. The anticancer activity results showed that the synthetic nanopolymer had cell proliferation and viability of 27% more than the control and (the half maximal inhibitory concentration) IC50 of 111 μg/mL against breast cancer cells. Before the anticancer evaluation, the structure of the synthesized Ti-MOF cross-linked oxidized pectin, and chitosan hydrogel was confirmed by (X-Ray Diffraction) XRD pattern (Fourier Transform Infrared) FT-IR spectrum (Energy-dispersive X-ray) EDAX spectroscopy, N2 adsorption/desorption isotherm and (Scanning Electron Microscope) Scanning Electron Microscope images. The results of identification and characterization showed that the synthetic nanopolymer was in the range of nanoparticles. The peaks of the expected functional groups and reactant elements were observed in the FT-IR spectrum and energy-dispersive X-ray spectroscopy of the final product. High physicochemical capabilities such as the uniform morphology, crystallization of particles, and high specific surface area from synthesized Ti-MOF cross-linked oxidized pectin, and chitosan hydrogel were observed. The unique properties of the synthesized Ti-MOF cross-linked oxidized pectin and chitosan hydrogel can be attributed to the appropriate method of its synthesis that was carried out in this study.
Increasing incidence and prevalence of metabolic syndrome in people living with HIV during the COVID-19 pandemic
Authors: Papaioannu Borjesson Rebecka , Galli Laura , Muccini Camilla , Poli Andrea , Clemente Tommaso , Bottanelli Martina , Gianotti Nicola , Nozza Silvia , Castagna Antonella , Spagnuolo Vincenzo
Published: September 2023

Introduction

The aim of this study was to analyze the impact of COVID-19 pandemic restrictions on the prevalence and incidence of metabolic syndrome (MS), and to identify predictors of new MS cases in people living with HIV (PLWH).

Methods

This cohort study included PLWH followed at the IRCCS San Raffaele, Milan, Italy, with at least one body mass index (BMI) determination during the pre-pandemic period (1 December 2018 to 29 February 2020) and the pandemic period (1 March 2020 to 31 May 2021). MS diagnosis was based on NCEP ATP III 2005 criteria. Univariable Poisson regression model was used to compare MS incidence rates. Univariable mixed linear models estimated the crude mean change in metabolic parameters during each time period. Multivariable Cox proportional hazards model was used to assess risk factors for MS.

Results

This study included 1,564 PLWH, of whom 460 and 1,104 were with and without a diagnosis of MS, respectively, at the beginning of the pre-pandemic period, with an overall prevalence of MS of 29.4%. During the pre-pandemic period, 528/1,564 PLWH had MS, with a prevalence of 33.8% (95%CI = 31.5%–36.1%), while during the pandemic period, the number of PLWH with a diagnosis of MS increased to 628/1,564, with a prevalence of 40.2% (95%CI 37.8%–42.6%; McNemar’s test: p < 0.0001). Similarly, the MS incidence rate increased from 13.7/100 person-years of follow-up (PYFU; 95%CI = 11.7–16.0) in the pre-pandemic period to 18.5/100 PYFU (95%CI = 16.2–21.1) in the pandemic period (p = 0.004), with 201 subjects developing MS during the pandemic period. In addition, we observed a significant increase in the crude mean change during the pandemic period compared with the pre-pandemic period for: total cholesterol, LDL cholesterol, plasma glucose, blood pressure, and atherosclerotic cardiovascular disease (ASCVD) risk score. Finally, after adjustment for HIV risk factors, HBV, HCV, ART duration, duration of virologic suppression and use of INSTIs, age [adjusted hazard ratio (AHR) per 3 years older = 1.12 (95%CI = 1.08–1.17)], sex [AHR female vs. male = 0.62 (95%CI = 0.44–0.87)] and CD4+ cell count [AHR per 100 cells/μL higher = 1.05 (95%CI = 1.01–1.09)] were associated with the risk of MS.

Conclusion

The COVID-19 pandemic affected the metabolic profile of PLWH and increased the prevalence and incidence of MS.
Bibliometric analysis of the current status and trends on medical hyperspectral imaging
Authors: Jiang Sijia , Ma Ding , Tan Xin , Yang Mingyu , Jiao Qingbin , Xu Liang
Published: September 2023

Hyperspectral imaging (HSI) is a promising technology that can provide valuable support for the advancement of the medical field. Bibliometrics can analyze a vast number of publications on both macroscopic and microscopic levels, providing scholars with essential foundations to shape future directions. The purpose of this study is to comprehensively review the existing literature on medical hyperspectral imaging (MHSI). Based on the Web of Science (WOS) database, this study systematically combs through literature using bibliometric methods and visualization software such as VOSviewer and CiteSpace to draw scientific conclusions. The analysis yielded 2,274 articles from 73 countries/regions, involving 7,401 authors, 2,037 institutions, 1,038 journals/conferences, and a total of 7,522 keywords. The field of MHSI is currently in a positive stage of development and has conducted extensive research worldwide. This research encompasses not only HSI technology but also its application to diverse medical research subjects, such as skin, cancer, tumors, etc., covering a wide range of hardware constructions and software algorithms. In addition to advancements in hardware, the future should focus on the development of algorithm standards for specific medical research targets and cultivate medical professionals of managing vast amounts of technical information.
Genome analysis of a plasmid-bearing myxobacterim Myxococcus sp. strain MxC21 with salt-tolerant property
Authors: Liu Lin , Xu Fengjuan , Lei Jinhui , Wang Peiwen , Zhang Lei , Wang Jihong , Zhao Jingya , Mao Dongmei , Ye Xianfeng , Huang Yan , Hu Gang , Cui Zhongli , Li Zhoukun
Published: September 2023

Myxobacteria are widely distributed in various habitats of soil and oceanic sediment. However, it is unclear whether soil-dwelling myxobacteria tolerate a saline environment. In this study, a salt-tolerant myxobacterium Myxococcus sp. strain MxC21 was isolated from forest soil with NaCl tolerance >2% concentration. Under 1% salt-contained condition, strain MxC21 could kill and consume bacteria prey and exhibited complex social behaviors such as S-motility, biofilm, and fruiting body formation but adopted an asocial living pattern with the presence of 1.5% NaCl. To investigate the genomic basis of stress tolerance, the complete genome of MxC21 was sequenced and analyzed. Strain MxC21 consists of a circular chromosome with a total length of 9.13 Mbp and a circular plasmid of 64.3 kb. Comparative genomic analysis revealed that the genomes of strain MxC21 and M. xanthus DK1622 share high genome synteny, while no endogenous plasmid was found in DK1622. Further analysis showed that approximately 21% of its coding genes from the genome of strain MxC21 are predominantly associated with signal transduction, transcriptional regulation, and protein folding involved in diverse niche adaptation such as salt tolerance, which enables social behavior such as gliding motility, sporulation, and predation. Meantime, a high number of genes are also found to be involved in defense against oxidative stress and production of antimicrobial compounds. All of these functional genes may be responsible for the potential salt-toleration. Otherwise, strain MxC21 is the second reported myxobacteria containing indigenous plasmid, while only a small proportion of genes was specific to the circular plasmid of strain MxC21, and most of them were annotated as hypothetical proteins, which may have a direct relationship with the habitat adaptation of strain MxC21 under saline environment. This study provides an inspiration of the adaptive evolution of salt-tolerant myxobacterium and facilitates a potential application in the improvement of saline soil in future.
Research progress on using biological cathodes in microbial fuel cells for the treatment of wastewater containing heavy metals
Authors: Wang Hui , Zhai Pengxiang , Long Xizi , Ma Jianghang , Li Yu , Liu Bo , Xu Zhiqiang
Published: September 2023

Various types of electroactive microorganisms can be enriched to form biocathodes that reduce charge-transfer resistance, thereby accelerating electron transfer to heavy metal ions with high redox potentials in microbial fuel cells. Microorganisms acting as biocatalysts on a biocathode can reduce the energy required for heavy metal reduction, thereby enabling the biocathode to achieve a lower reduction onset potential. Thus, when such heavy metals replace oxygen as the electron acceptor, the valence state and morphology of the heavy metals change under the reduction effect of the biocathode, realizing the high-efficiency treatment of heavy metal wastewater. This study reviews the mechanisms, primary influencing factors (e.g., electrode material, initial concentration of heavy metals, pH, and electrode potential), and characteristics of the microbial community of biocathodes and discusses the electron distribution and competition between microbial electrodes and heavy metals (electron acceptors) in biocathodes. Biocathodes reduce the electrochemical overpotential in heavy metal reduction, permitting more electrons to be used. Our study will advance the scientific understanding of the electron transport mechanism of biocathodes and provide theoretical support for the use of biocathodes to purify heavy metal wastewater.
Hierarchical machine learning model predicts antimicrobial peptide activity against Staphylococcus aureus
Authors: Khabaz Hosein , Rahimi-Nasrabadi Mehdi , Keihan Amir Homayoun
Published: September 2023

Introduction:Staphylococcus aureus is a dangerous pathogen which causes a vast selection of infections. Antimicrobial peptides have been demonstrated as a new hope for developing antibiotic agents against multi-drug-resistant bacteria such as S. aureus. Yet, most studies on developing classification tools for antimicrobial peptide activities do not focus on any specific species, and therefore, their applications are limited.

Methods: Here, by using an up-to-date dataset, we have developed a hierarchical machine learning model for classifying peptides with antimicrobial activity against S. aureus. The first-level model classifies peptides into AMPs and non-AMPs. The second-level model classifies AMPs into those active against S. aureus and those not active against this species.

Results: Results from both classifiers demonstrate the effectiveness of the hierarchical approach. A comprehensive set of physicochemical and linguistic-based features has been used, and after feature selection steps, only some physicochemical properties were selected. The final model showed the F1-score of 0.80, recall of 0.86, balanced accuracy of 0.80, and specificity of 0.73 on the test set.

Discussion: The susceptibility to a single AMP is highly varied among different target species. Therefore, it cannot be concluded that AMP candidates suggested by AMP/non-AMP classifiers are able to show suitable activity against a specific species. Here, we addressed this issue by creating a hierarchical machine learning model which can be used in practical applications for extracting potential antimicrobial peptides against S. aureus from peptide libraries.
Multimodal magnetic resonance imaging on brain structure and function changes in subjective cognitive decline: a mini-review
Authors: Yue Jinhuan , Han Shengwang , Li Ang , Wei Zeyi , Cao Danna , Gao Shenglan , Li Xiaoling , Yang Guanhu , Zhang Qinhong
Published: September 2023

Subjective cognitive decline (SCD) is the initial stage of Alzheimer’s disease (AD). Early identification of SCD and its risk factors is of great importance for targeted interventions and for delaying the onset of AD. We reviewed the relevant literature on structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and other techniques regarding SCD research in recent years. This study applied sMRI and fMRI techniques to explore abnormal brain structures and functions, which may help provide a basis for SCD diagnosis.
Challenges of neural interfaces for stroke motor rehabilitation
Authors: Vidaurre Carmen , Irastorza-Landa Nerea , Sarasola-Sanz Andrea , Insausti-Delgado Ainhoa , Ray Andreas M. , Bibián Carlos , Helmhold Florian , Mahmoud Wala J. , Ortego-Isasa Iñaki , López-Larraz Eduardo , Lozano Peiteado Héctor , Ramos-Murguialday Ander
Published: September 2023

More than 85% of stroke survivors suffer from different degrees of disability for the rest of their lives. They will require support that can vary from occasional to full time assistance. These conditions are also associated to an enormous economic impact for their families and health care systems. Current rehabilitation treatments have limited efficacy and their long-term effect is controversial. Here we review different challenges related to the design and development of neural interfaces for rehabilitative purposes. We analyze current bibliographic evidence of the effect of neuro-feedback in functional motor rehabilitation of stroke patients. We highlight the potential of these systems to reconnect brain and muscles. We also describe all aspects that should be taken into account to restore motor control. Our aim with this work is to help researchers designing interfaces that demonstrate and validate neuromodulation strategies to enforce a contingent and functional neural linkage between the central and the peripheral nervous system. We thus give clues to design systems that can improve or/and re-activate neuroplastic mechanisms and open a new recovery window for stroke patients.
Metalloproteinase-2 in failed back surgery syndrome caused by epidural fibrosis: can it play a role in persistent pain?
Authors: Bielewicz Joanna , Daniluk Beata , Kamieniak Piotr
Published: September 2023

Purpose

Failed Back Surgery Syndrome (FBSS) occurs in 10–40% of patients treated surgically due to disk herniation (DH). There are several factors that can cause a predisposition to FBSS, but the exact pathomechanism has not been elucidated. The aim of this study was to investigate Metalloproteinase-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) activities in a homogeneous group of FBSS patients with epidural fibrosis in comparison to its activity in patients with surgically treated DH.

Methods

DH, FBSS, and control (CG) groups consisted of 30 subjects. The patients were assessed clinically by the Numerical Rating Scale (NRS), McGill Pain Questionnaire (SF -MPQ), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). Serum concentrations of MMP-2 and TIMP-2 were measured by using the immunoenzymatic method.

Results

There was a significantly higher MMP-2 expression (medians: 4797.49 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 166.40 vs. 109.60; p < 0.0001) in the DH compared to the CG. Significantly higher MMP-2 expression (4219.95 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 150.17 vs. 109.60; p = 0.0003) were also found in the FBSS compared to the CG. The activity of MMP-2, measured as MMP-2/TIMP-2, did not significantly change between the DH, FBSS, and CG. MMP2 expression (p < 0.0001) and TIMP-2 concentration (p < 0.0001) were significantly higher in the DH than FBSS.

Conclusion

Results indicate the presence of a contribution of MMP-2 and TIMP-2 in DH and FBSS. Unchanged activity of MMP-2 can indicate an insufficiency in the MMP-2 repair system in both diseases. Lower MMP-2 expression and TIMP-2 concentration in the FBSS group can reflect the chronicity of the process.
After-effects of repetitive transcranial magnetic stimulation with parameter dependence on long-term potentiation-like plasticity and object recognition memory in rats
Authors: Chen Shanjia , He Xiaokuo , Wei XinChen , Huang Jiyi , Zhang Jie
Published: September 2023

Objective

To investigate the after-effects of 25-Hz repetitive transcranial magnetic stimulation (rTMS) at 60, 100, and 120% resting motor threshold (rMT) on long-term potentiation (LTP) in the rat hippocampus, to clarify the intensity dependence of rTMS, and to determine whether it simultaneously affects learning and memory ability.

Methods

Five rats were randomly selected from 70 male Wistar rats, and evoked rMT potentials were recorded in response to magnetic stimulation. The remaining 65 rats were randomly assigned to five groups (n = 13), including sham rTMS, 1 Hz 100% rMT, and 25 Hz rTMS groups with 3 subgroups of 60% rMT, 100% rMT, and 120% rMT. Five rats in each group were anesthetized and induced by a priming TMS-test design for population spike (PS) response of the perforant path-dentate gyrus in the hippocampus; the remaining eight rats in each group were evaluated for object recognition memory in the novel object recognition (NOR) task after the different rTMS protocols.

Results

Forty-five percent (approximately 1.03 T) of the magnetic stimulator output was confirmed as rMT in the biceps femoris muscle. The PS ratio was ranked as follows: 25 Hz 100% rMT (267.78 ± 25.71%) > sham rTMS (182 ± 9.4%) >1 Hz 100% rMT (102.69 ± 6.64%) > 25 Hz 120% rMT (98 ± 11.3%) > 25 Hz 60% rMT (36 ± 8.5%). Significant differences were observed between the groups, except for the difference between the 25 Hz 120% rMT and the 1 Hz 100% rMT groups (p = 0.446). LTP was successfully induced over the 60-min recording period only in the sham rTMS and 25 Hz 100% rMT groups. Moreover, these two groups spent more time exploring a novel object than a familiar object during the NOR task (p < 0.001), suggesting long-term recognition memory retention. In the between-group analysis of the discrimination index, the following ranking was observed: 25 Hz 100% rMT (0.812 ± 0.158) > sham rTMS (0.653 ± 0.111) > 25 Hz 120% rMT (0.583 ± 0.216) >1 Hz 100% rMT (0.581 ± 0.145) > 25 Hz 60% rMT (0.532 ± 0.220).

Conclusion

The after-effect of 25-Hz rTMS was dependent on stimulus intensity and provided an inverted (V-shaped) bidirectional modulation on hippocampal plasticity that involved two forms of metaplasticity. Furthermore, the effects on the recognition memory ability were positively correlated with those on LTP induction in the hippocampus in vivo.
Machine learning-based early diagnosis of autism according to eye movements of real and artificial faces scanning
Authors: Meng Fanchao , Li Fenghua , Wu Shuxian , Yang Tingyu , Xiao Zhou , Zhang Yujian , Liu Zhengkui , Lu Jianping , Luo Xuerong
Published: September 2023

Background

Studies on eye movements found that children with autism spectrum disorder (ASD) had abnormal gaze behavior to social stimuli. The current study aimed to investigate whether their eye movement patterns in relation to cartoon characters or real people could be useful in identifying ASD children.

Methods

Eye-tracking tests based on videos of cartoon characters and real people were performed for ASD and typically developing (TD) children aged between 12 and 60 months. A three-level hierarchical structure including participants, events, and areas of interest was used to arrange the data obtained from eye-tracking tests. Random forest was adopted as the feature selection tool and classifier, and the flattened vectors and diagnostic information were used as features and labels. A logistic regression was used to evaluate the impact of the most important features.

Results

A total of 161 children (117 ASD and 44 TD) with a mean age of 39.70 ± 12.27 months were recruited. The overall accuracy, precision, and recall of the model were 0.73, 0.73, and 0.75, respectively. Attention to human-related elements was positively related to the diagnosis of ASD, while fixation time for cartoons was negatively related to the diagnosis.

Conclusion

Using eye-tracking techniques with machine learning algorithms might be promising for identifying ASD. The value of artificial faces, such as cartoon characters, in the field of ASD diagnosis and intervention is worth further exploring.
The utility of peripheral stereopsis
Authors: Verghese Preeti
Published: September 2023

This perspective article makes the case for evaluating and training peripheral stereopsis, particularly when the central visual field is compromised in one or both eyes. Examples of clinical conditions that preferentially affect the central visual field include macular degeneration, which affects the central macular region in one or both eyes, and amblyopia where the central field is often affected in one eye, but the peripheral field is largely intact. While binocular acuity may be preserved when the monocular central field of one eye is affected, fine stereopsis is compromised because it requires intact vision in corresponding locations in the two eyes. Even in these clinical conditions, recent studies that map stereoacuity at locations across the visual field demonstrate that the periphery supports coarse stereopsis, and that training efforts to use residual stereopsis may have greater benefit if they take this finding into account.
TiN/Ti/HfO2/TiN memristive devices for neuromorphic computing: from synaptic plasticity to stochastic resonance
Authors: Maldonado David , Cantudo Antonio , Perez Eduardo , Romero-Zaliz Rocio , Perez-Bosch Quesada Emilio , Mahadevaiah Mamathamba Kalishettyhalli , Jimenez-Molinos Francisco , Wenger Christian , Roldan Juan Bautista
Published: September 2023

We characterize TiN/Ti/HfO2/TiN memristive devices for neuromorphic computing. We analyze different features that allow the devices to mimic biological synapses and present the models to reproduce analytically some of the data measured. In particular, we have measured the spike timing dependent plasticity behavior in our devices and later on we have modeled it. The spike timing dependent plasticity model was implemented as the learning rule of a spiking neural network that was trained to recognize the MNIST dataset. Variability is implemented and its influence on the network recognition accuracy is considered accounting for the number of neurons in the network and the number of training epochs. Finally, stochastic resonance is studied as another synaptic feature. It is shown that this effect is important and greatly depends on the noise statistical characteristics.
From recreational to income-generating opportunities: assessment of public preferences for non-wood forest products in the Czech Republic
Authors: Purwestri Ratna Chrismiari , Hochmalová Miroslava , Hájek Miroslav , Palátová Petra , Jarský Vilém , Huertas-Bernal Diana Carolina , Perdana Mayang Christy , García-Jácome Sandra Paola , Lusiana Betha , Riedl Marcel
Published: September 2023

With the alarming increase in dying trees and massive logging in the Czech forests due to bark beetle infestation, the collection of non-wood forest products, a beneficial recreational activity in the Czech Republic, is now being promoted as an alternative to wood provisioning services. This paper aims to present findings on the non-wood forest product preferences in the country as part of a baseline assessment for promoting the usage. This study relied on the 2019 national survey data of public preferences in collecting forest berries, mushrooms, honey, and medicinal herbs. K-means cluster analysis was employed to classify the respondents. A binary logistic regression with a conditional forward approach was employed to identify the potential predictors of the high preference for each non-wood forest product. Data from 1,050 online respondents were included, and two groups of respondents were clustered based on their preferences for the entire non-wood forest, i.e., higher and lower utilization. The regression analysis revealed that frequent forest visitors were the primary predictor of high utilization of all non-wood forest products (between 1.437 to 4.579 odd ratios), in addition to age, gender, and location of the forest property. By clustering the respondents based on the high and low preferences in utilizing non-wood forest products, the promotion of this service, from recreational to potential livelihood activities and economic benefits, can be better targeted, e.g., target customer, infrastructure development in the location with high preferences, scenarios based on the type of owners (municipal or private forest owners), which in accordance to the national forest policy and laws, and, at the same time, maintain the ecological stability.
Nonlinear relationship between dietary calcium and magnesium intake and peripheral neuropathy in the general population of the United States
Authors: Wu Zhe , Yang Xuesong , Ruan Zhishen , Li Lianlian , Wu Jianlin , Wang Bin
Published: September 2023

Background

Calcium and magnesium are essential minerals that have significant roles in nerve function and regulation. There may be a correlation between dietary calcium and magnesium intake and peripheral neuropathy. However, this relationship remains unclear and requires further study.

Methods

Data from 7,726 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 were analyzed in this study. The relationship between total dietary calcium and magnesium intake, as well as each quantile, and peripheral neuropathy was analyzed using a multifactor logistic regression model. To illustrate the dose–response relationship between calcium and magnesium intake and peripheral neuropathy, we utilized a restricted cubic spline (RCS) plot.

Results

Our analysis found a positive correlation between dietary intake of calcium and magnesium and peripheral neuropathy (calcium: OR 1.000, 95% CI 1.000–1.000; magnesium: OR 1.001, 95% CI 1.00–1.002). Participants in the first and third quantiles of dietary calcium intake had a significantly higher incidence of peripheral neuropathy than those in the second quantile (OR 1.333, 95% CI 1.034–1.719, OR 1.497, 95% CI 1.155–1.941). Those in the first and third quantiles of dietary magnesium intake also had a significantly higher incidence of peripheral neuropathy than those in the second quantile (OR 1.275, 95% CI 1.064–1.528, OR 1.525, 95% CI 1.231–1.890). The restricted cubic spline analysis revealed a U-shaped nonlinear relationship between dietary intake of calcium and magnesium and peripheral neuropathy.

Conclusion

The study found a U-shaped non-linear relationship between dietary calcium and magnesium intake levels and peripheral neuropathy, indicating that both excessive and insufficient intake of calcium and magnesium can increase the incidence of peripheral neuropathy.
The potential and challenges of targeting MTAP-negative cancers beyond synthetic lethality
Authors: Bray Chandler , Balcells Cristina , McNeish Iain A. , Keun Hector C.
Published: September 2023

Approximately 15% of cancers exhibit loss of the chromosomal locus 9p21.3 – the genomic location of the tumour suppressor gene CDKN2A and the methionine salvage gene methylthioadenosine phosphorylase (MTAP). A loss of MTAP increases the pool of its substrate methylthioadenosine (MTA), which binds to and inhibits activity of protein arginine methyltransferase 5 (PRMT5). PRMT5 utilises the universal methyl donor S-adenosylmethionine (SAM) to methylate arginine residues of protein substrates and regulate their activity, notably histones to regulate transcription. Recently, targeting PRMT5, or MAT2A that impacts PRMT5 activity by producing SAM, has shown promise as a therapeutic strategy in oncology, generating synthetic lethality in MTAP-negative cancers. However, clinical development of PRMT5 and MAT2A inhibitors has been challenging and highlights the need for further understanding of the downstream mediators of drug effects. Here, we discuss the rationale and methods for targeting the MAT2A/PRMT5 axis for cancer therapy. We evaluate the current limitations in our understanding of the mechanism of MAT2A/PRMT5 inhibitors and identify the challenges that must be addressed to maximise the potential of these drugs. In addition, we review the current literature defining downstream effectors of PRMT5 activity that could determine sensitivity to MAT2A/PRMT5 inhibition and therefore present a rationale for novel combination therapies that may not rely on synthetic lethality with MTAP loss.
Molecular mechanisms of hormones implicated in migraine and the translational implication for transgender patients
Authors: Martinez Cameron I. , Liktor-Busa Erika , Largent-Milnes Tally M.
Published: September 2023

Migraine is a primary headache disorder recognized by the World Health Organization as one of the most poorly understood and debilitating neurological conditions impacting global disability. Chronic pain disorders are more frequently diagnosed among cisgender women than men, suggesting that female sex hormones could be responsible for mediating chronic pain, including migraine and/or that androgens can be protective. This review discusses the major gonadal hormones, estrogens, progesterone, and testosterone in the context of molecular mechanisms by which they play a role in migraine pathophysiology. In addition, the literature to date describing roles of minor sex hormones including prolactin, luteinizing hormone, follicular stimulating hormone, and gonadotropin releasing hormone in migraine are presented. Because transgender and gender non-conforming (trans*) individuals are an underserved patient population in which gender-affirming sex hormone replacement therapy (HRT) is often medically necessary to align biological sex with gender identity, results from cisgender patient populations are discussed in the context of these major and minor sex hormones on migraine incidence and management in trans* patients.
Improving feeding skills and transition to breastfeeding in early preterm infants: a randomized controlled trial of oromotor intervention
Authors: Comuk Balci Nilay , Takci Sahin , Seren H. Canan
Published: September 2023

Introduction

Oromotor therapy exercises used for preterm infants in the NICU might promote oral-motor skills and shorten discharge day. This study investigates the impact of an oral-motor therapy program on the successful transition to breastfeeding (BF) and the enhancement of feeding skills in preterm infants below 30 weeks of gestational age who experience feeding intolerance.

Methods

The intervention group received oral-motor therapy programme for one month, while the control group did not. The feeding skills were evaluated by Early Feeding Skills Assessment Tool (EFS) and Preterm Oral Feeding Readiness Scales (POFRAS).

Results

There was a significant difference in EFS and POFRAS scores, transition to bottle feeding at discharge and transition to BF after discharge between babies given oral-motor therapy programme and controls (p < 0.05). While the transition time to full enteral feeds did not vary significantly between the groups, noteworthy outcomes were observed in the intervention group, including differences in feeding type at discharge, the nature of feeds at discharge, and the success of transitioning to breastfeeding after discharge.

Discussion

We conclude that the oromotor therapy exercises in NICU improves the quality of sucking, contributes to better oromotor skills and promotes transition to enteral feeding and BF in preterm babies.

Clinical Trial Registration

ClinicalTrials.gov, identifier (NCT05845684).
Cardiovascular adverse effects associated with the use of anti-HER2 in breast cancer treatment
Authors: Valente Patricia Marques Soares , da Silva Paula Nogueira , da Silva Licínio Esmeraldo , Martins Wolney de Andrade , de Castilho Selma Rodrigues
Published: September 2023

Background: Cancer represents an important public health problem with increasing incidence, prevalence, and mortality, affecting the entire Western population, especially in developed and developing countries. The use of monoclonal antibodies has revolutionized the treatment of cancer, but this treatment can cause adverse cardiovascular effects (AE).

Objective: The objective of this paper is to identify and classify AE in breast cancer patients in the use of Trastuzumab in two health institutions.

Methods: Retrospective study of medical records of patients with breast cancer Her 2+ submitted the therapy with trastuzumab in early and advanced stage of the disease. Review conducted in a university hospital and a private clinic, both located in Rio de Janeiro State, Brazil.

Results: Cardiovascular events were late for trastuzumab, with predominance of moderate reactions. There was a predominance of dyspnea, increased blood pressure, fatigue and reduced left ventricular ejection.

Conclusion: The results resemble similarities in the pattern of the institutions’ reactions. Identify possible AE and know the toxicity profile of trastuzumab can contribute to a safer therapy.
Crosstalk between endoplasmic reticulum stress and multidrug-resistant cancers: hope or frustration
Authors: Qing Bowen , Wang Song , Du Yingan , Liu Can , Li Wei
Published: September 2023

Endoplasmic reticulum stress (ERS) is a kind of cell response for coping with hypoxia and other stresses. Pieces of evidence show that continuous stress can promote the occurrence, development, and drug resistance of tumors through the unfolded protein response. Therefore, the abnormal ac-tivation of ERS and its downstream signaling pathways not only can regulate tumor growth and metastasis but also profoundly affect the efficacy of antitumor therapy. Therefore, revealing the molecular mechanism of ERS may be expected to solve the problem of tumor multidrug resistance (MDR) and become a novel strategy for the treatment of refractory and recurrent tumors. This re-view summarized the mechanism of ERS and tumor MDR, reviewed the relationship between ERS and tumor MDR, introduced the research status of tumor tissue and ERS, and previewed the prospect of targeting ERS to improve the therapeutic effect of tumor MDR. This article aims to provide researchers and clinicians with new ideas and inspiration for basic antitumor treatment.
A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy
Authors: Riccardi Federico , Dal Bo Michele , Macor Paolo , Toffoli Giuseppe
Published: September 2023

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tumor toxicity. Based on their beneficial mechanism of action, 15 ADCs have been approved to date by the market approval by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and/or other international governmental agencies for use in clinical oncology, and hundreds are undergoing evaluation in the preclinical and clinical phases. Here, our aim is to provide a comprehensive overview of the key features revolving around ADC therapeutic strategy including their structural and targeting properties, mechanism of action, the role of the tumor microenvironment and review the approved ADCs in clinical oncology, providing discussion regarding their toxicity profile, clinical manifestations and use in novel combination therapies. Finally, we briefly review ADCs in other pathological contexts and provide key information regarding ADC manufacturing and analytical characterization.