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1.
Bull Cancer ; 2024 Sep 05.
Artículo en Francés | MEDLINE | ID: mdl-39242251

RESUMEN

First-line treatments of autoimmune systemic diseases (ARD) are based on the use of various types of immunosuppressive or immunomodulatory drugs, either alone or in association, according to standardized reference protocols. Prolonged use of these drugs in severe or refractory ARD is associated with high morbidity and increased mortality. Innovative cell therapies represent a new promising approach for patients with ARDs, with the recent clinical use of: a) mesenchymal stromal cells (MSCs), based on their immunomodulatory, antifibrotic and pro-angiogenic properties and b) Chimeric Antigen Receptors (CAR) T cell therapies T lymphocytes, where genetically modified expression of a chimeric antigen receptor (CAR-T cells). Therapeutic use of MSC or CAR-T cells, remains indications of exception in patients with severe ARDs resistant to prior standard therapies with new prerequisite and organisation of health-care pathways as compared to traditional drugs, not only for the Cell and Gene Therapy (CGT) product definition and delivery process, but also for the patient clinical management before and after administration of the CGT product. The aim of this workshop under the auspices of the French Speaking Society of Bone Marrow and Cell transplantation (SFGM-TC) working group on autoimmune diseases (MATHEC) is to describe: a) the prerequisite for French hospitals to set-up the specific health-care pathways for MSC or CART therapy in ARDs patients, in accordance with regulatory and safety needs to perform academic or industry sponsored clinical trials, and b) the care-pathway for ARD patients treated with CGT, highlighting the importance of working in tandem between the ARD and the CAR-T cell specialist all along the indication, procedures and follow-up of ARDs. Patient safety considerations are central to guidance on patient selection to be validated collectively at the multidisciplinary team meeting (MDTM) based on recent (less than 3 months) thorough patient evaluation. MSC and CAR-T procedural aspects and follow-up are then carried out within appropriately experienced and SFGM-TC accredited centres in close collaboration with the ADs specialist.

2.
Amyloid ; : 1-7, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255059

RESUMEN

BACKGROUND: To compare the efficacy of modified Ex-PRESS technique (ExP) versus Ahmed Glaucoma Valve (AGV) as primary surgery in hereditary transthyretin amyloidosis (ATTRv) secondary glaucoma. METHODS: Retrospective study at the national amyloidosis centre. Success was defined as an IOP ≥ 6 mmHg and ≤ 21 mmHg with no need for further glaucoma surgery or laser trabeculoplasty and without loss of light perception at the time of the last follow-up. Secondary outcomes included surgical complications, need for hypotensive drugs, and endothelial cell loss. Patients submitted to previous glaucoma surgery were excluded. RESULTS: We included 180 eyes of 150 patients, 121 in AGV and 59 in ExP group. No significant baseline differences were found between groups. At the time of last follow-up, both groups exhibited significant intraocular pressure (IOP) reduction (p < .001) and number of glaucoma medications (p < .001). Kaplan-Meyer analysis showed higher cumulative probability of success for AGV group (80.1% vs. 41.1%, p < .001) and higher mean time to failure (54.5 vs. 36.9 months, respectively, p < 0.001) at 60 months follow-up. AGV showed lower hazard (HR 0.21, 95% CI [0.111-0.407], p < .001) for failure. CONCLUSION: AGV and ExP are safe and effective techniques in the treatment of ATTRv secondary glaucoma. However, AGV's efficacy seems to be more durable.

3.
Eur J Neurosci ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39161111

RESUMEN

The superior colliculus (SC) has been increasingly implicated in the rapid processing of evolutionarily relevant stimuli like faces, but the behavioural relevance of such processing is unclear. The SC has also been implicated in the generation of express visuomotor responses (EVR), which are very short-latency (~80 ms) bursts of muscle activity time-locked to visual target presentation. These observations led us to investigate the influence of faces on EVRs. We recorded upper limb muscle activity from healthy participants as they reached toward targets in the presence of a distractor. In some experiments, faces were used as stimuli. Across blocks of trials, we varied the instruction as to which stimulus served as the target or distractor. Doing so allowed us to assess the impact of instruction on muscle recruitment given identical visual stimuli. We found that responses were uniquely modulated in tasks involving high-contrast faces, promoting reaches toward or away from a face depending on instruction. Follow-up experiments confirmed that the phenomenon required highly salient repeated faces and was not observed to non-facial stimuli nor to faces expressing different affects. This study extends the hypothesis that the SC mediates the EVR by demonstrating that faces impact muscle recruitment at short latencies that precede cortical activity for face perception. Our results constitute direct evidence for the behavioural relevance of face detection in the brainstem, and also implicate a role for top-down cortical pre-setting of the EVR depending on task context.

4.
Plant Methods ; 20(1): 128, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152473

RESUMEN

BACKGROUND: As genomes of many eukaryotic species, especially plants, are large and complex, their de novo sequencing and assembly is still a difficult task despite progress in sequencing technologies. An alternative to genome assembly is the assembly of transcriptome, the set of RNA products of the expressed genes. While a bunch of de novo transcriptome assemblers exists, the challenges of transcriptomes (the existence of isoforms, the uneven expression levels across genes) complicates the generation of high-quality assemblies suitable for downstream analyses. RESULTS: We developed Trans2express - a web-based tool and a pipeline of de novo hybrid transcriptome assembly and postprocessing based on rnaSPAdes with a set of subsequent filtrations. The pipeline was tested on Arabidopsis thaliana cDNA sequencing data obtained using Illumina and Oxford Nanopore Technologies platforms and three non-model plant species. The comparison of structural characteristics of the transcriptome assembly with reference Arabidopsis genome revealed the high quality of assembled transcriptome with 86.1% of Arabidopsis expressed genes assembled as a single contig. We tested the applicability of the transcriptome assembly for gene expression analysis. For both Arabidopsis and non-model species the results showed high congruence of gene expression levels and sets of differentially expressed genes between analyses based on genome and based on the transcriptome assembly. CONCLUSIONS: We present Trans2express - a protocol for de novo hybrid transcriptome assembly aimed at recovering of a single transcript per gene. We expect this protocol to promote the characterization of transcriptomes and gene expression analysis in non-model plants and web-based tool to be of use to a wide range of plant biologists.

5.
Scand J Med Sci Sports ; 34(8): e14713, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39155402

RESUMEN

Evidence has demonstrated that athletes exhibit superior cognitive performance associated with executive control. In the oculomotor system, this function has been examined using the interleaved pro-saccade and anti-saccade task (IPAST), wherein participants, prior to target appearance, are instructed to either automatically look at the peripheral target (pro-saccade) or suppress the automatic response and voluntarily look in the opposite direction (anti-saccade). While the IPAST has provided much insight into sensorimotor and inhibitory processing, it has yet to be performed in athletes. Moreover, limited research has examined saccade metrics in athletes. Here, we examined saccade latency and movement kinematics in the IPAST among athletes (N = 40) and nonathletes (NON) (N = 40). Higher direction error rates were obtained in the anti-saccade compared to the pro-saccade condition, with no differences between athletes and NON noted. Significantly faster saccade latencies were observed in athletes compared to NON in both conditions, in addition to faster pro-saccades compared to anti-saccades. Furthermore, athletes showed significantly higher frequencies and faster latencies of express saccades compared to NON in correct pro-saccades. Additionally, athletes exhibited significantly faster latencies of express saccades compared to NON in erroneous anti-saccades. Differences in saccade metrics between athletes and NON were not seen. Overall, these findings demonstrate that athletes display altered saccade performance likely associated with sensorimotor and preparatory processing, highlighting the potential of using IPAST to objectively investigate sensorimotor and cognitive functions in athletes.


Asunto(s)
Atletas , Tiempo de Reacción , Movimientos Sacádicos , Humanos , Movimientos Sacádicos/fisiología , Masculino , Adulto Joven , Femenino , Tiempo de Reacción/fisiología , Adulto , Fenómenos Biomecánicos , Desempeño Psicomotor/fisiología , Función Ejecutiva/fisiología , Adolescente
6.
Med Leg J ; : 258172241252512, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39157991

RESUMEN

The restraint of patients is one of the important aspects of the regime in psychiatric hospitals. It has been an issue in hospitals over the years because it interferes with the personal freedom of patients. Most recently it was one of the matters raised in X NHS Foundation Trust v RH [2024] EWCOP 150. This paper aims to add to the awareness of it by looking at what it means, the forms it may take and the justifications for it. It is concluded that restraint of patients is controversial but reasonable and necessary at times in the interests of the patient's own health/safety or that of others.

7.
Vestn Otorinolaringol ; 89(3): 48-56, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-39104273

RESUMEN

BACKGROUND: Acute bacterial sinusitis is one of the most common causes of prescribing systemic antibacterial drugs in otorhinolaryngology. With bacterial etiology of the disease, beta-lactam antibiotics are prescribed, in particular cefixim. Cefixim in the form of dispersible tablets has high clinical and bacteriological efficiency, as well as good tolerability in patients with acute sinusitis. OBJECTIVE: To study the therapeutic equivalence of two drugs of cefixim (reproduced drug Cefixim Express and reference drug Suprax Solutab) in patients with acute bacterial sinusitis. MATERIAL AND METHODS: 60 adult patients with a diagnosis of acute bacterial sinusitis took part in a randomized open comparative clinical study. Patients of group 1 (n=30) received the drug Cefixim Express in the form of dispersible tablets 400 mg once a day. Group 2 (n=30) received Suprax Solutab in the form of dispersible tablets 400 mg once a day. The duration of treatment course was 7 days. All patients conducted general clinical and otorhinolaryngological examinations, assessment of symptoms of acute sinusitis, assessment of the general clinical impression of the therapy, tolerance of treatment, analysis of the frequency of unwanted phenomena before treatment, 3 days after the beginning of therapy and after the course completion (7 days). RESULTS: Recovery occurred in 63.3% of patients in group 1 according to the inspection on the 7th day of treatment and in 66.67% of patients in group 2. The rate of clinical symptoms regression by the end of therapy was comparable in the comparison groups. Hyperemia of the nasal mucosa, purulent nasal discharge and difficulty in nasal breathing (p<0.01) regressed by the 7th day in patients of both treatment groups. The incidence of adverse reactions on the 7th day of treatment in group 1 was 10%, in group 2 - 6.7% (p>0.05). CONCLUSION: The drug Cefixim Express has high therapeutic effectiveness in the treatment of acute bacterial sinusitis, comparable to Suprax Solutab. Cefixime EXPRESS has demonstrated a good tolerability and a favorable safety profile.


Asunto(s)
Antibacterianos , Cefixima , Sinusitis , Humanos , Masculino , Adulto , Femenino , Cefixima/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Sinusitis/tratamiento farmacológico , Sinusitis/microbiología , Enfermedad Aguda , Resultado del Tratamiento , Persona de Mediana Edad , Equivalencia Terapéutica , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/diagnóstico
8.
Accid Anal Prev ; 207: 107718, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39216287

RESUMEN

The rise of Express Lanes also known as High Occupancy Toll (HOT) Lanes and Managed Lanes, signifies a major leap in traffic management and transportation funding. Despite their increased deployment to ensure reliable travel times through dynamic tolling during peak traffic periods, a comprehensive evaluation of their safety impact is notably lacking. Presently, the Crash Modification Factors Clearinghouse, a vital resource, only lists two case studies related to Express Lanes, one of which is our own research. This lack of data highlights the critical need for more extensive studies to thoroughly assess the safety benefits of Express Lanes and to improve their application. This study aims to rigorously evaluate the safety impact of express lanes on freeways, presenting a first-of-its-kind, in-depth analysis of their specific effects on both Express Lanes and General-Purpose Lanes (GP-Lanes) individually. The analysis utilized data from 55 miles of Express Lanes across various locations in Florida, comparing them to High Occupancy Vehicle (HOV) lanes. The results demonstrate that converting HOV lanes to Express Lanes or introducing new ones does not compromise overall freeway safety. In fact, safety within Express Lanes improves, as evidenced by a decrease in crash occurrence and Crash Modification Factors for Express lanes, which are below "1" across all crash categories. This underscores the effectiveness of Express lanes in enhancing roadway safety. In contrast, incidents in GP-Lanes have increased, indicating a shift of crashes to these lanes, and thus making Express lanes relatively safer. This underlines the importance of continued research into the safety impact of express lanes and calls for further studies to refine traffic management strategies, aiming at enhancing travel efficiency while ensuring traffic safety, especially for the GP-Lanes amid the expansion of express lanes.


Asunto(s)
Accidentes de Tránsito , Planificación Ambiental , Seguridad , Accidentes de Tránsito/prevención & control , Accidentes de Tránsito/estadística & datos numéricos , Humanos , Florida , Conducción de Automóvil
9.
Int Ophthalmol ; 44(1): 333, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39042198

RESUMEN

PURPOSE: We compared corneal endothelial cell (CED) loss after Ex-Press (EXP) surgery between patients with primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX). PATIENTS AND METHODS: This was a single-facility retrospective study. We included glaucoma patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after (at 12, 24, and 36 months) EXP surgery by noncontact specular microscopy and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test. RESULTS: We included 119 eyes that underwent EXP surgery, including 60 POAG eyes and 59 PEX eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm2 after 3 years. At the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower, at 85.0 ± 19.5%, in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy. CONCLUSIONS: EXP surgery decreased the corneal endothelial cell populations in PEX patients faster than POAG patients.


Asunto(s)
Pérdida de Celulas Endoteliales de la Córnea , Endotelio Corneal , Síndrome de Exfoliación , Glaucoma de Ángulo Abierto , Presión Intraocular , Humanos , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/fisiopatología , Estudios Retrospectivos , Masculino , Femenino , Anciano , Endotelio Corneal/patología , Pérdida de Celulas Endoteliales de la Córnea/etiología , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Recuento de Células , Presión Intraocular/fisiología , Estudios de Seguimiento , Persona de Mediana Edad , Síndrome de Exfoliación/cirugía , Factores de Tiempo , Trabeculectomía/métodos , Anciano de 80 o más Años
10.
Talanta ; 277: 126350, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38843772

RESUMEN

This work reports the development and application of a disposable amperometric sensor built on magnetic microcarriers coupled to an Express PCR strategy to amplify a specific DNA fragment of the chloroplast trnH-psbA. The procedure involves the selective capture of a 68-mer synthetic target DNA (or unmodified PCR products) through sandwich hybridization with RNA capture probe-modified streptavidin MBs and RNA signaling probes, labeled using antibodies specific to the heteroduplexes and secondary antibodies tagged with horseradish peroxidase. Amperometric measurements were performed on screen-printed electrodes using the H2O2/hydroquinone system. Achieving a LOD of 3 pM for the synthetic target, it was possible to detect 2.5 pg of peanut DNA and around 10 mg kg-1 of peanut in binary mixtures (defatted peanut flours prepared in spelt wheat). However, the detectability decreased between 10 and 1000 times in processed samples depending on the treatment. The Express PCR-bioplatform was applied to the detection of peanut traces in foodstuff.


Asunto(s)
Arachis , Arachis/química , Técnicas Electroquímicas/métodos , Cloroplastos/genética , ADN de Plantas/análisis , Técnicas Biosensibles/métodos , Reacción en Cadena de la Polimerasa/métodos , Límite de Detección , Contaminación de Alimentos/análisis , Análisis de los Alimentos/métodos , Alimentos Procesados
11.
J Biol Chem ; 300(6): 107360, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735477

RESUMEN

The nascent polypeptide chains passing through the ribosome tunnel not only serve as an intermediate of protein synthesis but also, in some cases, act as dynamic genetic information, controlling translation through interaction with the ribosome. One notable example is Escherichia coli SecM, in which translation of the ribosome arresting peptide (RAP) sequence in SecM leads to robust elongation arrest. Translation regulations, including the SecM-induced translation arrest, play regulatory roles such as gene expression control. Recent investigations have indicated that the insertion of a peptide sequence, SKIK (or MSKIK), into the adjacent N-terminus of the RAP sequence of SecM behaves as an "arrest canceler". As the study did not provide a direct assessment of the strength of translation arrest, we conducted detailed biochemical analyses. The results revealed that the effect of SKIK insertion on weakening SecM-induced translation arrest was not specific to the SKIK sequence, that is, other tetrapeptide sequences inserted just before the RAP sequence also attenuated the arrest. Our data suggest that SKIK or other tetrapeptide insertions disrupt the context of the RAP sequence rather than canceling or preventing the translation arrest.


Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Biosíntesis de Proteínas , Ribosomas , Ribosomas/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Biosíntesis de Proteínas/efectos de los fármacos , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Secuencia de Aminoácidos , Oligopéptidos/química , Oligopéptidos/farmacología , Oligopéptidos/metabolismo , Factores de Transcripción
12.
Heliyon ; 10(9): e30120, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707277

RESUMEN

Capital needs transportation channels. Following successful communication and cooperation with Central Asian and European states, the China railway express (CRE) has been built by central and western cities. This new international freight service will greatly enhance the transport conditions in the central and western cities. Therefore, it is necessary to conduct an in-depth analysis of the impact of CRE operations on foreign direct investment (FDI) flows in the central and western regions. For analyses, a panel data of 152 Chinese cities from 2008 to 2020 is used and staggered difference in differences (DID) model is applied as a quasi-natural experiment. The results demonstrated that the operation of the CRE had a positive and significant impact on FDI inflows in the central and western cities, particularly in western cities, large cities, and non-resource based cities in China. Mechanism analysis shows that CRE operations can enhance the ability to attract foreign investment in the central and western regions through the promotion of industrial agglomeration and the expansion of market size. Therefore, the government should actively optimize the layout of CRE transportation routes and establish an inter-regional coordinating mechanism for freight sources, thus allowing the radiating effect of CRE central cities to reach out to peripheral cities.

13.
J Environ Manage ; 360: 121201, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38796870

RESUMEN

The explosive growth of China's express delivery industry has greatly increased plastic waste, with low-value plastics not effectively utilized, such as PE packaging bags, which are often not recycled and end up in landfills or incinerators, causing significant resource waste and severe plastic pollution. A gate -to- grave life cycle assessment was adopted to assess the impacts of express delivery plastic waste (EDPW) management models (S1, landfill; S2, incineration; S3, mechanical pelletization), with Suzhou, China as a case. Results showed that mechanical pelletization, was the most environmentally advantageous, exhibiting a comprehensive environmental impact potential of -215.54 Pt, significantly lower than that of landfill (S1, 78.45 Pt) and incineration (S2, -121.77 Pt). The analysis identified that the end-of-life disposal and sorting stages were the principal contributors to environmental impacts in all three models, with transportation and transfer stages of residual waste having minimal effects. In terms of all environmental impact categories, human carcinogenic toxicity (HTc) emerged as the most significant contributor in all three scenarios. Specifically, S1 exhibited the most detrimental effect on human health, while S2 and S3 showed positive environmental impacts. Based on these findings, it is recommended that the application and innovation in mechanical recycling technologies be enhanced, the promotion of the eco-friendly transformation of packaging materials be pursued, and a sustainable express delivery packaging recycling management system be established. These strategies are essential for achieving more eco-friendly management of EDPW, reducing its environmental pollution, and moving towards more sustainable express delivery management practices.


Asunto(s)
Incineración , Plásticos , Reciclaje , Instalaciones de Eliminación de Residuos , Administración de Residuos , China , Administración de Residuos/métodos , Eliminación de Residuos/métodos , Humanos
14.
Stomatologiia (Mosk) ; 103(2): 32-35, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38741532

RESUMEN

THE AIM OF THE STUDY: Was to evaluate the use of Ketorol Express as a preventive analgesia to increase the effectiveness of local anesthesia in providing emergency dental care to patients with arterial hypertension. MATERIALS AND METHODS: The study was conducted on the basis of the state autonomous healthcare institution of the Moscow region «Royal Dental Clinic¼ with the participation of 83 people. The patients were divided into two groups. In group 1, Ketorol Express was prescribed as a preventive analgesia in a dosage of 20 mg before local anesthesia. Patients of group 2 underwent dental interventions without the use of preventive analgesia. A 3% solution of mepivacaine was used as a local analgesic solution. For a subjective assessment of the effectiveness of anesthesia, use a visual analog scale. All patients had their blood pressure and heart rate measured before and after the interventions and hemodynamic parameters were continuously monitored during emergency dental care. RESULTS: In group 1, the effectiveness of combined anesthesia with the infiltration method of local anesthetic administration was 93±1.17%, according to the patient, 94±1.47%, according to the doctor, with the conductive method of anesthesia at the mandibular orifice - according to the patient it was 91±1.01%, according to the doctor 92± 1.36%. In group 2, when providing emergency dental care with the infiltration method of administration of 3% mepivacaine the anesthesia was effective in 80±1.97% of cases according to the patient and in 80±1.17% of cases according to the doctor, with the conductive method of anesthesia at the mandibular orifice, the effectiveness of anesthesia according to the patient was 82±1.11%, according to the doctor 85±1.23%. CONCLUSION: The results of the study demonstrated a statistically significant increase in the effectiveness of local anesthesia performed with a 3% solution of mepivacaine in patients with arterial hypertension due to the use of preventive analgesia with Ketorol Express at a dosage of 20 mg (2 tablets of 10 mg) in emergency dental care with registration and analysis of changes in hemodynamic parameters.


Asunto(s)
Anestesia Dental , Anestesia Local , Anestésicos Locales , Hipertensión , Mepivacaína , Humanos , Hipertensión/tratamiento farmacológico , Anestesia Local/métodos , Masculino , Mepivacaína/administración & dosificación , Femenino , Anestesia Dental/métodos , Persona de Mediana Edad , Anestésicos Locales/administración & dosificación , Adulto , Atención Odontológica/métodos , Presión Sanguínea/efectos de los fármacos
15.
Biotechnol Prog ; : e3466, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607316

RESUMEN

Monoclonal antibodies (mAbs) are often engineered at the sequence level for improved clinical performance yet are rarely evaluated prior to candidate selection for their "developability" characteristics, namely expression, which can necessitate additional resource investments to improve the manufacturing processes for problematic mAbs. A strong relationship between primary sequence and expression has emerged, with slight differences in amino acid sequence resulting in titers differing by up to an order of magnitude. Previous work on these "difficult-to-express" (DTE) mAbs has shown that these phenotypes are driven by post-translational bottlenecks in antibody folding, assembly, and secretion processes. However, it has been difficult to translate these findings across cell lines and products. This work presents a systematic approach to study the impact of sequence variation on mAb expression at a larger scale and under more industrially relevant conditions. The analysis found 91 mutations that decreased transient expression of an IgG1κ in Chinese hamster ovary (CHO) cells and revealed that mutations at inaccessible residues, especially those leading to decreases in residue hydrophobicity, are not favorable for high expression. This workflow can be used to better understand sequence determinants of mAb expression to improve candidate selection procedures and reduce process development timelines.

16.
J Biotechnol ; 389: 30-42, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38685416

RESUMEN

Ichnos has developed a multi-specific antibody platform based on the BEAT® (Bispecific engagement by antibodies based on the T-cell receptor) interface. The increased complexity of the bi- and multi-specific formats generated with this platform makes these molecules difficult-to-express proteins compared to standard monoclonal antibodies (mAbs). This report describes how expression limitations of a bi-specific bi-paratopic BEAT antibody were improved in a holistic approach. An initial investigation allowed identification of a misbalance in the subunits composing the BEAT antibody as the potential root cause. This misbalance was then addressed by a signal peptide optimization, and the overall expression level was increased by the combination of two vector design elements on a single gene vector. Further improvements were made in the selection of cell populations and an upstream (USP) platform process was applied in combination with a cell culture temperature shift. This allowed titer levels of up to 6 g/L to be reached with these difficult-to-express proteins. Furthermore, a high-density seeding process was developed that allowed titers of around 11 g/L for the BEAT antibody, increasing the initial titer by a factor of 10. The approach was successfully applied to a tri-specific antibody with titer levels reaching 10 g/L. In summary, a platform process for difficult-to-express proteins was developed using molecular biology tools, cell line development, upstream process optimization and process intensification.


Asunto(s)
Anticuerpos Monoclonales , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/biosíntesis , Células CHO , Cricetulus , Humanos
17.
Environ Sci Pollut Res Int ; 31(20): 28939-28949, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38564128

RESUMEN

Encouraging the recycling of plastic packaging materials in express delivery is a necessary step toward environmentally friendly industrial development. In this study, we present a framework for analyzing the flow of materials in express plastic packaging, from production and manufacturing to consumption and recycling. In examining the use of recycled materials in post-consumer express plastic packaging and the destination of consumer packaging waste in 2020 and 2021, we found that 44.4% (1613.6 Gg) of the studied express plastic packaging was incinerated. Additionally, approximately 1296.6 Gg of express plastic packaging flowed into rural areas. Our calculations showed that the ΔRSE in 2020 was 15.1%, and on the condition that 25% separated collection with 80% recycling, ΔRSE would be - 0.5%. Results verified that separated collection is an important step in the recycling strategy for packaging materials. Survey data from universities in Beijing indicate that currently, 26% of college students are participating in the separate collection of packaging.


Asunto(s)
Entropía , Plásticos , Embalaje de Productos , Reciclaje , China
18.
Molecules ; 29(6)2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38542944

RESUMEN

The pollution from waste plastic express packages (WPEPs), especially microplastic (MP) fragments, caused by the blowout development of the express delivery industry has attracted widespread attention. On account of the variety of additives, strong complexity, and high diversity of plastic express packages (PEPs), the multi-class classification of WPEPs is a typical large-class-number classification (LCNC). The traceability and identification of microplastic fragments from WPEPs is very challenging. An effective chemometric method for large-class-number classification would be very beneficial for the comprehensive treatment of WPEP pollution through the recycling and reuse of waste plastic express packages, including microplastic fragments and plastic debris. Rather than using the traditional one-against-one (OAO) and one-against-all (OAA) dichotomies, an exhaustive and parallel half-against-half (EPHAH) decomposition, which overcomes the defects of the OAO's classifier learning limitations and the OAA's data proportion imbalance, is proposed for feature selection. EPHAH analysis, combined with partial least squares discriminant analysis (PLS-DA) for large-class-number classification, was performed on 750 microplastic fragments of polyethylene WPEPs from 10 major courier companies using near-infrared (NIR) spectroscopy. After the removal of abnormal samples through robust principal component analysis (RPCA), the root mean square error of cross-validation (RMSECV) value for the model was reduced to 0.01, which was 21.5% lower than that including the abnormal samples. The best models of PLS-DA were obtained using SNV combined with SG-17 smoothing and 2D (SNV+SG-17+2D); the latent variables (LVs), the error rates of Monte Carlo cross-validation (ERMCCVs), and the final classification accuracies were 6.35, 0.155, and 88.67% for OAO-PLSDA; 5.37, 0.103, and 87.33% for OAA-PLSDA; and 3.12, 0.054, and 96.00% for EPHAH-PLSDA. The results showed that the EPHAH strategy can completely learn the complex LCNC decision boundaries for 10 classes, effectively break the tie problem, and greatly improve the voting resolution, thereby demonstrating significant superiority to both the OAO and OAA strategies in terms of classification accuracy. Meanwhile, PLS-DA further maximized the covariance and data interpretation abilities between the potential variables and categories of microplastic debris, thereby establishing an ideal performance identification model with a recognition rate of 96.00%.

19.
J Infect Public Health ; 17(5): 748-766, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38518681

RESUMEN

BACKGROUND: Long COVID has appeared as a significant global health issue and is an extra burden to the healthcare system. It affects a considerable number of people throughout the globe. However, substantial research gaps have been noted in understanding the mechanism and genomic landscape during the long COVID infection. A study has aimed to identify the differentially expressed genes (DEGs) in long COVID patients to fill the gap. METHODS: We used the RNA-seq GEO dataset acquired through the GPL20301 Illumina HiSeq 4000 platform. The dataset contains 36 human samples derived from PBMC (Peripheral blood mononuclear cells). Thirty-six human samples contain 13 non-long COVID individuals' samples and 23 long COVID individuals' samples, considered the first direction analysis. Here, we performed two-direction analyses. In the second direction analysis, we divided the dataset gender-wise into four groups: the non-long COVID male group, the long COVID male group, the non-long COVID female group, and the long COVID female group. RESULTS: In the first analysis, we found no gene expression. In the second analysis, we identified 250 DEGs. During the DEG profile analysis of the non-long COVID male group and the long COVID male group, we found three upregulated genes: IGHG2, IGHG4, and MIR8071-2. Similarly, the analysis of the non-long COVID female group and the long COVID female group reveals eight top-ranking genes. It also indicates the gender biases of differentially expressed genes among long COVID individuals. We found several DEGs involved in PPI and co-expression network formation. Similarly, cluster enrichment and gene list enrichment analysis were performed, suggesting several genes are involved in different biological pathways or processes. CONCLUSIONS: This study will help better understand the gene expression landscape in long COVID. However, it might help the discovery and development of therapeutics for long COVID.


Asunto(s)
COVID-19 , Perfilación de la Expresión Génica , Humanos , Masculino , Femenino , Leucocitos Mononucleares , Síndrome Post Agudo de COVID-19 , COVID-19/genética , Expresión Génica , Sesgo
20.
Int Ophthalmol ; 44(1): 93, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38367121

RESUMEN

BACKGROUND: The most common retinal complications after glaucoma surgery are choroidal detachment, hypotony maculopathy, malignant glaucoma, vitreous hemorrhage, endophthalmitis and retinal detachment. However, if glaucoma surgery is a risk factor for the ERM development needs to be clarified. This study aims to assess the incidence of epiretinal membrane (ERM) in 2 years of follow-up in patients with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. METHODS: A prospective, consecutive, single-center, case-control study. We enrolled patients affected by POAG and scheduled for Ex-Press device implant with or without concomitant cataract surgery. The control group was the contralateral eyes which continues anti-glaucomatous eyedrops. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography were performed before surgery, at 6 months and 24 months of follow-up. RESULTS: Eighty-two eyes of 41 consecutive patients, 18 males and 23 females with a mean age of 70, 29 ± 8,45, were analyzed at 24 months. 39.1% of eyes developed ERM: 29.3% were cellophane macular reflex (CMR) and 9.8% were pre-macular fibrosis (PMF). In the control group, 19.5% of eyes developed ERM: 17.1% were CMR and 2.4% were PMF. No statistically significant difference was reported (p = 0.121) between treated and control group. ERM development did not affect significantly the central foveal thickness (260.13 ± 35.01 µm at baseline, 265.03 ± 34.90 µm at 6 months and 275.18 ± 33.31 µm at 24 months) and macular volume (7.75 ± 0.43 mm3 at baseline, 7.77 ± 0.48 mm3 at 6 months and 7.77 ± 0.46 mm3 at 24 months), remained comparable to reported average measures in healthy individuals during the follow-up. Concomitant cataract surgery did not increase the ERM incidence. CONCLUSION: Ex-Press implant may increase the ERM incidence regardless concomitant cataract surgery, accelerating or inducing a posterior vitreous detachment, such as other ocular surgical procedure. Nevertheless, the vast majority of ERM are CMR, not affecting the macular profile.


Asunto(s)
Catarata , Membrana Epirretinal , Glaucoma de Ángulo Abierto , Glaucoma , Masculino , Femenino , Humanos , Recién Nacido , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Estudios de Casos y Controles , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Glaucoma/complicaciones , Tomografía de Coherencia Óptica , Catarata/complicaciones
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