bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovering new peripheral plasma biomarkers to identify cognitive decline in type 2 diabetes
Authors: Yu Haitao , Gao Yang , He Ting , Li Mengzhu , Zhang Yao , Zheng Jie , Jiang Bijun , Chen Chongyang , Ke Dan , Liu Yanchao , Wang Jian-Zhi
Published: November 2022

Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer’s disease (AD), and thus identifying who among the increasing T2DM populations may develop into AD is important for early intervention. By using TMT-labeling coupled high-throughput mass spectrometry, we conducted a comprehensive plasma proteomic analysis in none-T2DM people (Ctrl, n = 30), and the age-/sex-matched T2DM patients with mild cognitive impairment (T2DM-MCI, n = 30) or T2DM without MCI (T2DM-nMCI, n = 25). The candidate biomarkers identified by proteomics and bioinformatics analyses were verified by ELISA, and their diagnostic capabilities were evaluated with machine learning. A total of 53 differentially expressed proteins (DEPs) were identified in T2DM-MCI compared with T2DM-nMCI patients. These DEPs were significantly enriched in multiple biological processes, such as amyloid neuropathies, CNS disorders, and metabolic acidosis. Among the DEPs, alpha-1-antitrypsin (SERPINA1), major viral protein (PRNP), and valosin-containing protein (VCP) showed strong correlation with AD high-risk genes APP, MAPT, APOE, PSEN1, and PSEN2. Also, the levels of PP2A cancer inhibitor (CIP2A), PRNP, corticotropin-releasing factor-binding protein (CRHBP) were significantly increased, while the level of VCP was decreased in T2DM-MCI patients compared with that of the T2DM-nMCI, and these changes were correlated with the Mini-Mental State Examination (MMSE) score. Further machine learning data showed that increases in PRNP, CRHBP, VCP, and rGSK-3β(T/S9) (ratio of total to serine-9-phosphorylated glycogen synthase kinase-3β) had the greatest power to identify mild cognitive decline in T2DM patients.
Structure-based virtual screening identified novel FOXM1 inhibitors as the lead compounds for ovarian cancer
Authors: Zhou Zi-Ying , Han Xiao-Yang , Sun Lian-Qi , Li Si-Yan , Xue Si-Tu , Li Zhuo-Rong
Published: November 2022

Ovarian cancer (OC) is a gynecological tumor with possibly the worst prognosis, its 5-year survival rate being only 47.4%. The first line of therapy prescribed is chemotherapy consisting of platinum and paclitaxel. The primary reason for treatment failure is drug resistance. FOXM1 protein has been found to be closely associated with drug resistance, and inhibition of FOXM1 expression sensitizes cisplatin-resistant ovarian cancer cells. Combining existing first-line chemotherapy drugs with FOXM1 prolongs the overall survival of patients, therefore, FOXM1 is considered a potential therapeutic target in ovarian cancer. Previous research conducted by our team revealed a highly credible conformation of FOXM1 which enables binding by small molecules. Based on this conformation, the current study conducted virtual screening to determine a new structural skeleton for FOXM1 inhibitors which would enhance their medicinal properties. DZY-4 showed the highest affinity towards FOXM1, and its inhibitory effect on proliferation and migration of ovarian cancer at the cellular level was better than or equal to that of cisplatin, while its efficacy was equivalent to that of cisplatin in a nude mouse model. In this study, the anti-tumor effect of DZY-4 is reported for the first time. DZY-4 shows potential as a drug that can be used for ovarian cancer treatment, as well as a drug lead for future research.
Initiation of anti-retroviral/Trimethoprim-Sulfamethoxazole therapy in a longitudinal cohort of HIV-1 positive individuals in Western Kenya rapidly decreases asymptomatic malarial parasitemia
Authors: Kifude Carolyne M. , Roberds Ashleigh , Oyieko Janet , Ocholla Stephen , Otieno Solomon , Waitumbi John N. , Hutter Jack , Smith Hunter , Copeland Nathanial K. , Luckhart Shirley , Stewart V. Ann
Published: November 2022

Interactions between malaria and HIV-1 have important public health implications. Our previous cross-sectional studies showed significant associations between HIV-1 positivity and malarial parasitemia with an increased risk of gametocytemia. In this follow-up longitudinal study, we evaluated these associations to determine the magnitude of asymptomatic parasitemia over time, and to examine the effects of initiating Antiretroviral Therapy (ART) together with the broad-spectrum antibiotic Trimethoprim Sulfamethoxazole (TS) on asymptomatic parasitemia. 300 adult volunteers in a malaria holoendemic region in Western Kenya were enrolled and followed for six months. The study groups were composed of 102 HIV-1 negatives, 106 newly diagnosed HIV-1 positives and 92 HIV-1 positives who were already stable on ART/TS. Blood samples were collected monthly and asymptomatic malarial parasitemia determined using sensitive18SqPCR. Results showed significantly higher malaria prevalence in the HIV-1 negative group (61.4%) (p=0.0001) compared to HIV-1 positives newly diagnosed (36.5%) and those stable on treatment (31.45%). Further, treatment with ART/TS had an impact on incidence of asymptomatic parasitemia. In volunteers who were malaria PCR-negative at enrollment, the median time to detectable asymptomatic infection was shorter for HIV-1 negatives (149 days) compared to the HIV-1 positives on treatment (171 days) (p=0.00136). Initiation of HIV treatment among the newly diagnosed led to a reduction in malarial parasitemia (expressed as18Scopy numbers/μl) by over 85.8% within one week of treatment and a further reduction by 96% after 2 weeks. We observed that while the impact of ART/TS on parasitemia was long term, treatment with antimalarial Artemether/Lumefantrine (AL) among the malaria RDT positives had a transient effect with individuals getting re-infected after short periods. As was expected, HIV-1 negative individuals had normal CD4+ levels throughout the study. However, CD4+ levels among HIV-1 positives who started treatment were low at enrollment but increased significantly within the first month of treatment. From our association analysis, the decline in parasitemia among the HIV-1 positives on treatment was attributed to TS treatment and not increased CD4+ levelsper se. Overall, this study highlights important interactions between HIV-1 and malaria that may inform future use of TS among HIV-infected patients in malaria endemic regions.
Double sequential external defibrillation versus standard defibrillation in refractory ventricular fibrillation: A systematic review and meta-analysis
Authors: Li Yongkai , He Xiaojing , Li Zhuanyun , Li Dandan , Yuan Xin , Yang Jianzhong
Published: November 2022

Introduction

Double sequential external defibrillation (DSED) in cardiopulmonary resuscitation has shown different results in comparison with standard defibrillation in the treatment of refractory ventricular fibrillation (RVF). This review aims to compare the advantages of DSED with standard defibrillation in the treatment of refractory ventricular fibrillation.

Materials and methods

PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to May 1, 2022. Studies included adult patients who developed RVF. The study used random-effects and fixed-effects models for meta-analysis, which was reported by risk ratio (RR) with 95% confidence interval (CI), mean difference (MD), or standardized mean difference (SMD). The risk of bias in individual studies was assessed using the Robins-I tool for observational studies and the Cochrane Risk of Bias 2 (ROB-2) tool for clinical trials. Primary outcomes included the termination of RVF, prehospital return of spontaneous circulation (ROSC), survival to hospital admission, survival to hospital discharge, and good neurological recovery. Secondary outcomes included age, total defibrillation attempts, emergency medical system arrival time, and dose of epinephrine and amiodarone used.

Results

In this systematic review and meta-analysis, 10 studies containing 1347 patients with available data on treatment outcomes were included. The pooled estimate was (RR 1.03, 95% CI, 0.89 to 1.19; Z = 0.42, P = 0.678 > 0.05) for Termination of RVF, (RR 0.84, 95% CI, 0.63 to 1.11; Z = 1.23, P = 0.219 > 0.05) for ROSC, (RR 0.86, 95% CI, 0.69 to 1.06; Z = 1.4, P = 0.162 > 0.05) for survival to hospital admission, (RR 0.77, 95%CI, 0.52 to 1.15; Z = 1.26, P = 0.206 > 0.05) for survival to hospital discharge, (RR 0.65, 95%CI, 0.35 to 1.22; Z = 1.33, P = 0.184 > 0.05) for good neurologic recovery, (MD −1.01, 95%CI, −3.07 to 1.06; Z = 0.96, P = 0.34 > 0.05) for age, (MD 2.27, 95%CI, 1.80 to 2.73; Z = 9.50, P = 0.001 < 0.05) for total defibrillation attempts, (MD 1.10, 95%CI, −0.45 to 66; Z = 1.39, P = 0.16 > 0.05) for emergency medical system arrival time, (SMD 0.34, 95%CI, 0.17 to 0.50; Z = 4.04, P = 0.001 < 0.05) for epinephrine, and (SMD −0.30, 95%CI, −0.65 to −0.05; Z = 1.66, P = 0.1 > 0.05) for amiodarone.

Conclusion

We discovered no differences between DSED and standard defibrillation in termination of RVF, prehospital return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, good neurological outcome, emergency medical system arrival time, and amiodarone doses in patients with RVF. There were some differences in the number of defibrillations and epinephrine doses utilized during resuscitation.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329354], identifier [CRD42022329354].
Mapping research approaches to data practices in schools
Authors: Krein Ulrike , Hartenstein Anna , Schiefner-Rohs Mandy
Published: November 2022

Digital data have a major impact on school practices and play a central role for teachers, including their pedagogical practice. From a research perspective, the question arises how data practices and data-related transformation processes in schools can be studied. Therefore, the aim of this paper is to methodically review research approaches and underlying methodological assumptions about data practices in schools based on a systematic review. The focus is on social science research designs, social science research instruments, and knowledge production methods. The article provides an overview of previous research practice in this area and concludes with possible implications for future research.
Home-based laboratory experiences during COVID-19 pandemic in undergraduate biochemistry students
Authors: Velarde Victoria , Casado-Barragán Felipe , Thamar Michelle , Rands Vicky F. , Gonzalez Alexis A.
Published: November 2022

The coronavirus pandemic (COVID-19) pointed out new challenges to teaching in laboratory-based disciplines, such as chemistry, biology, and biochemistry with on-site practical sessions interrupted or suspended during 2020 and 2021. Observation and experimentation are part of education in science-based disciplines and provide necessary skills for professional and academic careers. In an effort to solve this disruption to experimental observations, we designed a set of home-based experiences related to chemistry and biochemistry. These included visual identification of lipids, sugars, proteins, and DNA in biological samples using materials easily found at home, such as alcohol, soap, and oil, among others. Each activity was documented with smartphones and discussed in a final portfolio. Fifty-two students were part of an introductory cell biochemistry course. The home-based laboratories were organized into 2.5-h sessions that included a lab session, a post lab session, and a period for preparing the experiment at home. Thirty-six (17 men and 19 women) students answered a survey designed to assess three major domains: (1) student’s demographics and home environment, (2) general perceptions of the laboratory activities, and (3) specific perceptions of each laboratory activity. Sixty two percent of the students thought that these activities helped them to understand how to isolate and identify macromolecules. Eleven percent said these home activities did not contribute to their understanding while 27% stated the activities were not significant for the topic. We conclude that, although the addition of in-house experiments provides a complementary tool for understanding the main concepts in biochemistry along with improving skills in scientific thinking, this should be accompanied by a good feedback mechanism from the instructors. In addition, student to student interaction should be part of the at home activities to increase student motivation. A Flipped laboratory methodology plus tools where metacognition is evaluated, appear to be appropriate to promote the understanding of concepts in the context of the laboratory. And although some aspects of the experimental experience can be substitute with online resources and in home experiences, others can only be achieved by the in-person experience.
Intrinsic properties and dopability effects on the thermoelectric performance of binary Sn chalcogenides from first principles
Authors: Bipasha Ferdaushi Alam , Gomes Lídia C. , Qu Jiaxing , Ertekin Elif
Published: November 2022

High-performance thermoelectric (TE) materials rely on semiconductors with suitable intrinsic properties for which carrier concentrations can be controlled and optimized. To demonstrate the insights that can be gained in computational analysis when both intrinsic properties and dopability are considered in tandem, we combine the prediction of TE quality factor (intrinsic properties) with first-principles simulations of native defects and carrier concentrations for the binary Sn chalcogenides SnS, SnSe, and SnTe. The computational predictions are compared to a comprehensive data set of previously reported TE figures-of-merit for each material, for both p-type and n-type carriers. The combined analysis reveals that dopability limits constrain the TE performance of each Sn chalcogenide in a distinct way. In SnS, TE performance for both p-type and n-type carriers is hindered by low carrier concentrations, and improved performance is possible only if higher carrier concentrations can be achieved by suitable extrinsic dopants. For SnSe, the p-type performance of the Cmcm phase appears to have reached its theoretical potential, while improvements in n-type performance may be possible through tuning of electron carrier concentrations in the Pnma phase. Meanwhile, assessment of the defect chemistry of SnTe reveals that p-type TE performance is limited by, and n-type performance is not possible due to, the material’s degenerate p-type nature. This analysis highlights the benefits of accounting for both intrinsic and extrinsic properties in a computation-guided search, an approach that can be applied across diverse sets of semiconductor materials for TE applications.
The effects and mechanism of taxanes on chemotherapy-associated ovarian damage: A review of current evidence
Authors: Wu Chuqing , Wu Tong , Chen Dan , Wei Simin , Tang Weicheng , Xue Liru , Xiong Jiaqiang , Huang Yibao , Guo Yican , Chen Ying , Wu Meng , Wang Shixuan
Published: November 2022

Chemotherapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicles are extremely sensitive to the effects of chemotherapeutic agents. Different chemotherapeutic agents with varying mechanisms of action may damage ovarian function differently. Taxanes are widely used in clinical cancer treatment, but the specific reproductive toxicological information is still controversial. This review described the impact and duration of taxanes on ovarian function in women and analyzed the possible reasons for different conclusions. Furthermore, the toxicity of taxanes on ovarian function and its possible mechanisms were discussed. The potential protective strategies and agents against ovarian damage induced by taxanes are also reviewed.
The positive effect of green agriculture development on environmental optimization: Measurement and impact mechanism
Authors: Wang Shaowen
Published: November 2022

According to the study of the environmental impact of green agricultural development, this paper selects 12 basic indicators from the three dimensions of “ecological agriculture, green production, and output benefits” for the construction of China’s green agricultural development index. There are eight basic indicators used in the construction of the environmental index system, including the area of nature reserves and the level of environmental protection expenditures. It is based on the panel data of 13 provinces in China from 2011 to 2019. For the calculation and analysis of the green agricultural development index and the environmental index, the entropy weight method is used. The calculation results show that there are significant differences in the development level of green agriculture and environmental development among these 13 major provinces; the green agriculture level and environmental development level of Jiangsu Province and Sichuan Province are in the leading position; further using dynamic panel regression, the results show that the development of green agriculture has a significant role in promoting the improvement of the environment, and in the early stage of green agriculture development, the effect of improving the environment is more obvious; the index of green agriculture development can be further divided into ecological agriculture index, green production index and output benefit index. As a result, the improvement of ecological agriculture, green production, and output benefits can contribute to the optimization of the ecological environment. As well, the development of green agriculture has some intermediary effects on the optimization of the environment. It is the intermediary effect of promoting environmental optimization through guiding residents’ green consumption that has the greatest effect, while the intermediary effect of promoting industrial structure upgrading and enterprise technology innovation has a relatively small effect. The empirical results presented in this paper suggest that a variety of measures can be taken to improve the environment, including improving green agriculture development in various regions, increasing government expenditures, and promoting the transformation of economic structures in order to improve the environment.
Green supply chain integration, supply chain agility and green innovation performance: Evidence from Chinese manufacturing enterprises
Authors: Zhang Bochen , Zhao Shukuan , Fan Xueyuan , Wang Shuang , Shao Dong
Published: November 2022

Despite widespread attention on the significance of green supply chain integration (GSCI), there is still limited research on how GSCI can improve firms’ green innovation performance. From the perspective of the natural resource-based view and dynamic capability theory, based on the theoretical logic of “resource-capability-performance”, this study aims to explore the relationship between GSCI and firms’ green innovation performance and its intrinsic mechanism. In order to test the research model, this study collected survey data from 405 Chinese manufacturing firms and tested them by using hierarchical regression and bootstrap analysis. The results show that all three dimensions of GSCI, namely, green internal integration, green supplier integration, and green customer integration, have positive effects on supply chain agility. In addition, supply chain agility has a significant positive impact on green product and process innovation. This study also finds that supply chain agility plays a partially mediating role between all three dimensions of GSCI and green product and process innovation; that is, GSCI can further promote firms’ green innovation performance by improving supply chain agility. The results of this study not only enrich the theoretical research on the driving factors of firms’ green innovation but also provide policy implications for manufacturing firms and government policy-makers regarding the implementation and promotion of green innovation practices.
Diverse cooling effects of green space on urban heat island in tropical megacities
Authors: Li Chunbo , Lu Linlin , Fu Zongtang , Sun Ranhao , Pan Luyang , Han Liying , Guo Huadong , Li Qingting
Published: November 2022

Cities in tropical regions are experiencing high heat risks by overlaying the urban heat island (UHI) effect. Urban green space (UGS) can provide local cooling effect and reduce UHI. However, there still lack a comprehensive exploration of the characteristics of UHI and cooling effect of UGS due to high cloud coverage and limited number of available remote sensing observations. In this study, the enhanced spatial and temporal adaptive reflectance data fusion method was employed to develop an enhanced land surface temperature data in winter seasons in three tropical megacities, Dhaka, Kolkata, and Bangkok. The spatiotemporal variations of surface urban heat island (SUHI) were explored from 2000 to 2020 with a 5-years interval. The optimal size of UGS associated with its cooling effects was assessed by using the threshold value of efficiency (TVoE). The relationship between the intensity and range of urban cooling island (UCI) and four landscape metrics of green space patches, total area (P_Area), shape index (P_SI), normalized difference vegetation index (P_NDVI), and land surface temperature (P_LST), were analyzed. The results show that the average SUHI intensity increased by 0.98°C, 1.42°C, and 0.73°C in Dhaka, Kolkata, and Bangkok, respectively, from 2000 to 2020. The maximum intensity of UCI ranges from 4.83°C in Bangkok to 8.07°C in Kolkata, and the maximum range of UCI varies from 300 m in Bangkok to 420 m in Kolkata. The optimal size of green space is 0.37 ha, 0.77 ha, and 0.42 ha in Dhaka, Kolkata, and Bangkok, respectively. The P_NDVI and P_Area had significant positive effects on UCI intensity and range, while the background temperature had significant negative effects. With higher background temperature, the optimal patch size of UGS is larger. This study provides useful information for developing effective heat mitigation and adaptation strategies to enhance climate resilience in tropical cities.
Profiling the B cell immune response elicited by vaccination against the respiratory virus SARS-CoV-2
Authors: Pettini Elena , Medaglini Donata , Ciabattini Annalisa
Published: November 2022

B cells play a fundamental role in host defenses against viral infections. Profiling the B cell response elicited by SARS-CoV-2 vaccination, including the generation and persistence of antigen-specific memory B cells, is essential for improving the knowledge of vaccine immune responsiveness, beyond the antibody response. mRNA-based vaccines have shown to induce a robust class-switched memory B cell response that persists overtime and is boosted by further vaccine administration, suggesting that memory B cells are critical in driving a recall response upon re-exposure to SARS-CoV-2 antigens. Here, we focus on the role of the B cell response in the context of SARS-CoV-2 vaccination, offering an overview of the different technologies that can be used to identify spike-specific B cells, characterize their phenotype using machine learning approaches, measure their capacity to reactivate following antigen encounter, and tracking the maturation of the B cell receptor antigenic affinity.
Antiviral properties of porous graphene, graphene oxide and graphene foam ultrafine fibers against Phi6 bacteriophage
Authors: Gungordu Er Seda , Tabish Tanveer A. , Edirisinghe Mohan , Matharu Rupy Kaur
Published: November 2022

As the world has experienced in the Coronavirus Disease 2019 pandemic, viral infections have devastating effects on public health. Personal protective equipment with high antiviral features has become popular among healthcare staff, researchers, immunocompromised people and more to minimize this effect. Graphene and its derivatives have been included in many antimicrobial studies due to their exceptional physicochemical properties. However, scientific studies on antiviral graphene are much more limited than antibacterial and antifungal studies. The aim of this study was to produce nanocomposite fibers with high antiviral properties that can be used for personal protective equipment and biomedical devices. In this work, 10 wt% polycaprolactone-based fibers were prepared with different concentrations (0.1, 0.5, 1, 2, 4 w/w%) of porous graphene, graphene oxide and graphene foam in acetone by using electrospinning. SEM, FTIR and XRD characterizations were applied to understand the structure of fibers and the presence of materials. According to SEM results, the mean diameters of the porous graphene, graphene oxide and graphene foam nanofibers formed were around 390, 470, and 520 nm, respectively. FTIR and XRD characterization results for 2 w/w% concentration nanofibers demonstrated the presence of graphene oxide, porous graphene and graphene foam nanomaterials in the fiber. The antiviral properties of the formed fibers were tested against Pseudomonas phage Phi6. According to the results, concentration-dependent antiviral activity was observed, and the strongest viral inhibition graphene oxide-loaded nanofibers were 33.08 ± 1.21% at the end of 24 h.
Multicomponent, high-intensity, and patient-centered care intervention for complex patients in transitional care: SPICA program
Authors: García-Hernández Miguel , González de León Beatriz , Barreto-Cruz Silvia , Vázquez-Díaz José Ramón
Published: November 2022

Multimorbidity is increasingly present in our environment. Besides, this is accompanied by a deterioration of social and environmental conditions and affects the self-care ability and access to health resources, worsening health outcomes and determining a greater complexity of care. Different multidisciplinary and multicomponent programs have been proposed for the care of complex patients around hospital discharge, and patient-centered coordination models may lead to better results than the traditional ones for this type of patient. However, programs with these characteristics have not been systematically implemented in our country, despite the positive results obtained. Hospital Universitario de Canarias cares for patients from the northern area of Tenerife and La Palma, Spain. In this hospital, a multicomponent and high-intensity care program is carried out by a multidisciplinary team (made up of family doctors and nurses together with social workers) with complex patients in the transition of care (SPICA program). The aim of this program is to guarantee social and family reintegration and improve the continuity of primary healthcare for discharged patients, following the patient-centered clinical method. Implementing multidisciplinary and high-intensity programs would improve clinical outcomes and would be cost-effective. This kind of program is directly related to the current clinical governance directions. In addition, as the SPICA program is integrated into a Family and Community Care Teaching Unit for the training of both specialist doctors and specialist nurses, it becomes a place where the specific methodology of those specialties can be carried out in transitional care. During these 22 years of implementation, its continuous quality management system has allowed it to generate an important learning curve and incorporate constant improvements in its work processes and procedures. Currently, research projects are planned to reevaluate the effectiveness of individualized care plans and the cost-effectiveness of the program.
Serotype-dependent adhesion of Shiga toxin-producing Escherichia coli to bovine milk fat globule membrane proteins
Authors: Bagel Arthur , Lopez Christelle , David-Briand Elisabeth , Michel Valérie , Douëllou Thomas , Sergentet Delphine
Published: November 2022

Shiga toxin-producing Escherichia coli (STEC) are food-borne pathogens that can cause severe symptoms for humans. Raw milk products are often incriminated as vehicule for human STEC infection. However, raw milk naturally contains molecules, such as the milk fat globule membrane and associated proteins, that could inhibit pathogen adhesion by acting as mimetic ligands. This study aimed to: (i) evaluate the capability of STEC cells to adhere to bovine milk fat globule membrane proteins (MFGMPs), (ii) highlight STEC surface proteins associated with adhesion and (iii) evaluate the variation between different STEC serotypes. We evaluated the physicochemical interactions between STEC and milk fat globules (MFGs) by analyzing hydrophobic properties and measuring the ζ-potential. We used a plate adhesion assay to assess adhesion between MFGMPs and 15 Escherichia coli strains belonging to three key serotypes (O157:H7, O26:H11, and O103:H2). A relative quantitative proteomic approach was conducted by mass spectrometry to identify STEC surface proteins that may be involved in STEC-MFG adhesion. The majority of E. coli strains showed a hydrophilic profile. The ζ-potential values were between −3.7 and − 2.9 mV for the strains and between −12.2 ± 0.14 mV for MFGs. Our results suggest that non-specific interactions are not strongly involved in STEC-MFG association and that molecular bonds could form between STEC and MFGs. Plate adhesion assays showed a weak adhesion of O157:H7 E. coli strains to MFGMPs. In contrast, O26:H11 and O103:H2 serotypes attached more to MFGMPs. Relative quantitative proteomic analysis showed that the O26:H11 str. 21,765 differentially expressed five outer membrane-associated proteins or lipoproteins compared with the O157:H7 str. EDL933. This analysis also found strain-specific differentially expressed proteins, including four O26:H11 str. 21,765-specific proteins/lipoproteins and eight O103:H2 str. PMK5-specific proteins. For the first time, we demonstrated STEC adhesion to MFGMPs and discovered a serotype effect. Several outer membrane proteins—OmpC and homologous proteins, intimin, Type 1 Fimbriae, and AIDA-I—that may be involved in STEC-MFG adhesion were highlighted. More research on STEC’s ability to adhere to MFGMs in diverse biological environments, such as raw milk cheeses and the human gastrointestinal tract, is needed to confirm the anti-adhesion properties of the STEC-MFG complex.
Investigating SARS-CoV-2 breakthrough infections per variant and vaccine type
Authors: Dingemans Jozef , van der Veer Brian M. J. W. , Gorgels Koen M. F. , Hackert Volker , den Heijer Casper D. J. , Hoebe Christian J. P. A , Savelkoul Paul H. M. , van Alphen Lieke B.
Published: November 2022

Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Vaxzevria or Jcovden being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Furthermore, the majority of adaptive mutations were concentrated in the N-terminal domain of the Spike protein, highlighting its role in immune evasion. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant were associated with increased viral loads compared to those caused by the Alpha variant. In addition, we investigated the role of the Omicron variant in causing breakthrough infections by analyzing 135 samples that were randomly selected for genomic surveillance during the transition period from Delta to Omicron. We found that the proportion of Omicron vs. Delta infections was significantly higher in individuals who received a booster vaccine compared to both unvaccinated and fully vaccinated individuals. Altogether, these results indicate that the emergence of the Delta variant and in particular Omicron has lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.
C57BL/6N mice show a sub-strain specific resistance to the psychotomimetic effects of ketamine
Authors: Harda Zofia , Misiołek Klaudia , Klimczak Marta , Chrószcz Magdalena , Rodriguez Parkitna Jan
Published: November 2022

Repeated administration of subanesthetic doses of ketamine is a model of psychosis-like state in rodents. In mice, this treatment produces a range of behavioral deficits, including impairment in social interactions and locomotion. To date, these phenotypes were described primarily in the Swiss and C3H/HeHsd mouse strains. A few studies investigated ketamine-induced behaviors in the C57BL/6J strain, but to our knowledge the C57BL/6N strain was not investigated thus far. This is surprising, as both C57BL/6 sub-strains are widely used in behavioral and neuropsychopharmacological research, and are de facto standards for characterization of drug effects. The goal of this study was to determine if C57BL/6N mice are vulnerable to develop social deficits after 5 days withdrawal from sub-chronic ketamine treatment (5 days, 30 mg/kg, i.p.), an experimental schedule shown before to cause deficits in social interactions in C57BL/6J mice. Our results show that sub-chronic administration of ketamine that was reported to cause psychotic-like behavior in C57BL/6J mice does not induce appreciable behavioral alterations in C57BL/6N mice. Thus, we show that the effects of sub-chronic ketamine treatment in mice are sub-strain specific.
Loss of GABA co-transmission from cholinergic neurons impairs behaviors related to hippocampal, striatal, and medial prefrontal cortex functions
Authors: Goral R. Oliver , Harper Kathryn M. , Bernstein Briana J. , Fry Sydney A. , Lamb Patricia W. , Moy Sheryl S. , Cushman Jesse D. , Yakel Jerrel L.
Published: November 2022

Introduction: Altered signaling or function of acetylcholine (ACh) has been reported in various neurological diseases, including Alzheimer’s disease, Tourette syndrome, epilepsy among others. Many neurons that release ACh also co-transmit the neurotransmitter gamma-aminobutyrate (GABA) at synapses in the hippocampus, striatum, substantia nigra, and medial prefrontal cortex (mPFC). Although ACh transmission is crucial for higher brain functions such as learning and memory, the role of co-transmitted GABA from ACh neurons in brain function remains unknown. Thus, the overarching goal of this study was to investigate how a systemic loss of GABA co-transmission from ACh neurons affected the behavioral performance of mice.

Methods: To do this, we used a conditional knock-out mouse of the vesicular GABA transporter (vGAT) crossed with the ChAT-Cre driver line to selectively ablate GABA co-transmission at ACh synapses. In a comprehensive series of standardized behavioral assays, we compared Cre-negative control mice with Cre-positive vGAT knock-out mice of both sexes.

Results: Loss of GABA co-transmission from ACh neurons did not disrupt the animal’s sociability, motor skills or sensation. However, in the absence of GABA co-transmission, we found significant alterations in social, spatial and fear memory as well as a reduced reliance on striatum-dependent response strategies in a T-maze. In addition, male conditional knockout (CKO) mice showed increased locomotion.

Discussion: Taken together, the loss of GABA co-transmission leads to deficits in higher brain functions and behaviors. Therefore, we propose that ACh/GABA co-transmission modulates neural circuitry involved in the affected behaviors.
Synaptic connectivity amongst components of the locomotor central pattern generator
Authors: Gosgnach Simon
Published: November 2022

In the past two decades we have learned an enormous amount of information regarding the identity of functional components of the neural circuitry responsible for generating locomotor activity in mammals. Molecular techniques, combined with classic electrophysiological and anatomical approaches, have resulted in the identification of a handful of classes of genetically defined interneuronal populations, and a delineation of the specific function of many of these during stepping. What lags behind at this point is a clear picture of the synaptic connectivity of each population, this information is key if we are to understand how the interneuronal components that are responsible for locomotor activity work together to form a functional circuit. In this mini review I will summarize what is, and what is not, known regarding the synaptic connectivity of each genetically defined interneuronal population that is involved in locomotion.
Stroke systems of care in the Philippines: Addressing gaps and developing strategies
Authors: Collantes Maria Epifania , Navarro Jose , Belen Allan , Gan Robert
Published: November 2022

In the Philippines, the mortality from stroke during the last 10 years remains high. This paper aims to describe the gaps in stroke care and the development of stroke systems of care in the Philippines. Gaps in stroke systems of care include low number of neurologist, inadequate CT scan machines, lack of stroke training among health workers, lack of stroke protocols and pathways, poor community stroke awareness, low government insurance coverage with high out of pocket medical expenses, lack of infrastructure for EMS, inadequate acute stroke ready hospitals, stroke units and rehabilitation facilities. Although there are government programs for primary stroke prevention, the strategies are inadequate to address the stroke pandemic. The Stroke Society of the Philippines has worked with the government for nationwide and regional stroke training of health care workers, community stroke awareness, setting up acute stroke ready hospitals and acute stroke units in different areas of the country and adapting stroke protocols and pathways. Stroke registries are now utilized for quality improvement. Thrombolysis rate has improved from 1.4% in 2014–2016 to 11% in 2021 based on RES-Q database. Because of government subsidy, thrombolysis in the government hospitals is higher at 7.4% (range 4.4–16.9) compared to 4.8% (range 0–10.1) rate in private hospitals. Mechanical thrombectomy rate remained low at 0.4% of all acute ischemic stroke patients because of the cost. With limited resources, infrastructures for emergency medical service is lacking. The innovations done by other LMIC can be done in the Philippines including the use of technology to reach out to geographically isolated areas and use of mobile stroke units. Non neurologist can be trained to help treat stroke patients. Upgrading of the Philhealth insurance to cover for reperfusion therapies, adequate stroke infrastructures and network, and increase in community stroke awareness are areas for improvement in the Philippine stroke systems of care.
Interventions for zoster-associated pain: A retrospective study based on the clinical database
Authors: Chen Lu , Li Jun , Liu Hui , Yang Pingliang , Zuo Yunxia , Ye Ling
Published: November 2022

Background

Herpes zoster (HZ)-associated pain can lead to severe pain and reduced quality of life. Exploring effective treatment and the risk factors of zoster-associated pain has become important.

Methods

Interventions including nerve block, radiofrequency, and thermocoagulation were used for zoster-associated pain. The data of 131 patients with HZ and 230 patients with postherpetic neuralgia (PHN) were collected at baseline, 2 weeks, 3, 6, and 12 months after the intervention. Visual analog scale (VAS) and Brief Pain Inventory (BPI) scores at different time points were analyzed by two-way repeated measures ANOVA with Group as the between-subject variable (different pain durations and areas), Time as the within-subject variable (baseline, 2 weeks, 3 months, 6 months, and 12 months), and Group × Time as the two-way interaction. Besides, the effective rate, adverse effects, and medication were also recorded. The risk factors of PHN were analyzed by logistic regression.

Results

A total of 25 (19.08%) patients with HZ continued to have pain in the initially affected area after 3 months. The VAS scores and the BPI quality of life scores of patients with HZ-associated pain were significantly reduced from baseline to 2 weeks, 3, 6, and 12 months after the interventions. There was no significant difference in VAS and BPI scores in different pain areas and pain durations. No significant Group × Time interaction was observed. Age, diabetes mellitus, and immune-related diseases were risk factors of PHN.

Conclusion

Interventions could significantly improve the pain degree and life quality of patients with zoster-associated pain, and the positive effect of intervention did not change with pain duration and area. Advanced age, diabetes, and immune-related diseases are risk factors of PHN.
Iron metabolism patterns in non-anemic patients with myasthenia gravis: A cross-sectional and follow-up study
Authors: Li Ke , Hou Li'an , Tan Ying , Huang Yangyu , Shi Jiayu , Han Jianhua , Yan Jingwen , Guan Yuzhou
Published: November 2022

Background and purpose

Iron metabolism in myasthenia gravis (MG) and factors associated with it are explored by few published studies. Therefore, this study aimed to compare iron metabolism patterns between patients with MG and healthy individuals as well as between the same group of patients before and after immunotherapy, and to identify predictors of iron metabolism disorders in MG.

Materials and methods

For this study, 105 patients and healthy individuals were included at baseline, after which paired parametric and non-parametric tests were adopted to compare their iron metabolism patterns, and multivariate binary logistic regression was used to identify predictors of iron metabolism disorders. Patients with MG were then followed up for 12 ± 3 months to explore alterations in their iron metabolism patterns after starting immunotherapy with the help of paired tests.

Results

Non-anemic immunotherapy-naive patients with MG had significantly lower serum iron (SI) and transferrin saturation (TS) levels than healthy individuals. Premenopausal female was significantly associated with SI < 65 μg/dL and iron deficiency in these patients. However, iron metabolism parameters did not significantly alter after around 12 months of immunotherapy in patients with MG.

Conclusion

Iron inadequacy was present in patients with MG, particularly premenopausal female patients, and it would hardly improve after immunotherapy. Given the significant role of iron in human body, it should be given more attention in patients with MG.
Remote programming for subthalamic deep brain stimulation in Parkinson's disease
Authors: Chen Si , Xu Shu-jun , Li Wei-guo , Chen Teng , Li Chao , Xu Shuo , Yang Ning , Liu Yi-ming
Published: November 2022

Introduction

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of Parkinson's disease (PD). Moreover, remote programming is widely used in Mainland China. This necessitates evaluating the ability of remote programming to achieve the ideal postoperative effect. Therefore, we aimed to retrospectively evaluate the effects of different programming modes on the effectiveness of STN-DBS 12 months postoperatively in patients with PD.

Methods

Clinical data were collected retrospectively, before and 12 months after surgery, in 83 patients with PD. Based on the programming modes voluntarily selected by the patients during 12 months postoperatively, they were divided into three groups, namely remote programming alone, hospital programming alone, and hospital + remote programming. We compared the programming data and the effects of different programming methods on STN-DBS-related improvements 12 months postoperatively among these groups. Furthermore, we analyzed STN-DBS-related improvements at 12 months postoperatively in 76 patients.

Results

The effectiveness of STN-DBS was not influenced by the three programming modes. The postoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale scores did not reveal statistically significant differences between the remote alone and hospital alone programming groups, except for motor examination. The postoperative decline in the levodopa equivalent daily dose was most apparent in the hospital programming alone group. The programming frequency of the hospital + remote programming group was considerably higher than that of the remaining groups. Seventy-six patients with PD displayed good STN-DBS surgical efficacy.

Conclusion

Programming modes do not influence the short-term efficacy of STN-DBS, and remote programming can yield a satisfactory surgical effect.