bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Serum High Sensitivity C-Reactive Protein with Insulin Resistance in Patients with Type-ΙΙ Diabetes Mellitus
Authors: Hossain Nadia , Haque Mahmudul , Karmakar Pijush , Chowdhury Hasan Murad , Barua Prasun , Hoque Asma , Mazhar Aklima
Published: November 2022

Background: Insulin resistance (IR) is the major event in type-ΙΙ diabetes mellitus followed by an increasing degree of β-cell dysfunction. Chronic inflammation is the driving force for IR and type-ΙΙ DM. The process of inflammation induces hepatic synthesis of high sensitivity C-reactive protein (an acute-phase protein) which plays a role in IR. The study was undertaken to find out the association of serum hs-CRP with insulin resistance in patients with type-ΙΙ diabetes mellitus.

Methodology: A hospital-based observational study was carried out in the Outpatient Department of Endocrinology, Chittagong Medical College Hospital and Department of Biochemistry, Chittagong Medical College. A total of 126 patients with type-II diabetes mellitus aged 40-64 years were included by non-probability consecutive sampling technique. Serum hs-CRP, fasting serum insulin was estimated. IR was calculated by using the Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR).

Results: The mean serum hs-CRP level was 9.1 ± 0.36 mg/L in patients with type-II DM. Serum hs-CRP was significantly associated with insulin resistance and positively correlated with HOMA-IR in type-II diabetics. Body mass index (BMI) as one of the key indicators of insulin resistance was also associated with serum hs-CRP in this study population. Additionally serum hs-CRP was correlated positively with BMI and fasting serum insulin in patients with type-II DM.

Conclusion: The results of this study concluded that increased serum hs-CRP was well associated and positively correlated with insulin resistance and its parameters signifying a possible role of subclinical inflammation in IR among patients with type-II diabetes mellitus.

EMCJ. January 2022; 7(1): 15-20
Complete Excision of Nerve Originating Hemangioma: A Case Report
Authors: Mahmud Nasir Uddin , Rahman Patwary Md Shafiqur , Hasan Mohammad Mainul , Tauhidur Rahman Sarker Mohammad , Alam Md Shariful
Published: November 2022

The hemangioma is a hamartomatous malformation and not a true tumorous of the hemangioma occur during childhood. It affects three girls for every boy. Commonest site of involvement is skin. Nerve originating hemangioma refers when it arises from the vessels supplying the nerve (vasa nervosum). It is very rare condition and presents painful, soft, compressible swelling in the course of nerve. Microscopically, hemangioma consist of poorly demarcated, non-capsulated masses and leashes of vascular channels, most of which contain blood. Although diagnosis is clinical; FNAC, Doppler Ultrasonogram study, MRI and EMG all investigations are helpful for confirmation. Surgery is the main stay of treatment but recurrence may occur. Per-operative microsurgical facility and in recurrent cases, administration of corticosteroid can prevent recurrence. We have operated one case with our own circumstances and patient has got uneventful recovery in one year follow up.

EMCJ. January 2022; 7(1): 32-35
Yeni Medyada Barış Gazeteciliği: Rusya-Ukrayna Savaşı'nda Cüneyt Özdemir Örneği
Authors: DEMİREL Yaren , ARIK Muhammed Bilal
Published: November 2022

İnsanlık tarihi kadar eski bir olgu olan savaş, toplumların ve bireylerin yaşamları üzerinde derin ve kalıcı etkiler bırakmaktadır. Modern toplumlarda, demokrasinin teminatı olan basın kuruluşlarının savaş ortamında yaptıkları habercilik, onlara ciddi bir sorumluluk yüklemektedir. Genellikle bulundukları ülkelerin iktidarlarına yakın bir söylem benimseyen ve savaşı çoğu zaman meşru gören geleneksel medyaya karşılık, son yıllarda barış sorumluluğunu merkeze alan barış gazeteciliği, iletişim biliminde sıklıkla tartışılmaya başlanmıştır. Barış gazeteciliği; insan hakları ve eşitliğe odaklanmakta ve çatışmaları gidererek birlikte yaşama kültürüne katkı sağlamayı amaçlamaktadır. Bu makalede, 2022 yılının ilk aylarında patlak veren Rusya’nın Ukrayna’yı işgal sürecinde, ülkemizin popüler gazetecilerinden biri olan Cüneyt Özdemir’in programları, barış gazeteciliği açısından incelenmiştir. Çalışma kapsamında öncelikle barış gazeteciliğinin tarihsel kökenlerine ve temel özelliklerine açıklık getirilmiş, ardından yeni medya ve barış gazeteciliği ilişkisi tartışılmıştır. Daha sonra araştırmanın bağlamsal temellerine işaret etmek amacıyla, Rusya Ukrayna Savaşı’nın arka planı ve Cüneyt Özdemir’in habercilik anlayışı ele alınmıştır. Makalenin araştırma bölümünde Norveçli Barış Profesörü Johan Galtung tarafından ortaya konan barış gazeteciliği ilkeleri üzerinden, söylem analizi yöntemiyle toplam 55 program irdelenmiş ve kurulan söylemin ardındaki ideolojik yaklaşıma açıklık getirilmiştir. Çalışma öncesi temel varsayımımız, Cüneyt Özdemir’in günümüz koşullarında etkin bir barış gazeteciliği yaptığı yönündedir. Yapılan analiz neticesinde varsayımımız doğrulanmış; Özdemir’in savaş ortamında barış gazeteciliği yaptığı; çatışma ve çözümsüzlüğü değil, insani ve uzlaşıdan yana bir söylemi tercih ettiği sonucuna ulaşılmıştır.
Role of Probiotics in Diabetes: A Review of Their Rationale and Efficacy
Authors: Jayesh Shah Neel , Swami Onkar C.
Published: November 2022

The commensal bacteria that are present in our body since infancy are known to play a role in metabolism, in health as well as disease. Diabetes is a growing epidemic, and a long-term solution that targets the disease at the molecular level is yet to be developed. In this article, we have reviewed the link between the body’s microbiota and disturbed glucose metabolism, as well as the reasons for bacterial dysbiosis and the mechanisms by which it causes inflammation. The link between dysbiosis and diabetes is convincing, particularly since probiotics have been shown to be of some benefit in normalising disturbed metabolism in diabetes patients. Probiotics have recently been found to have a wide application in diseases such as autoimmune, inflammatory, and allergic conditions. The efficacy of probiotics in diabetes has been proven by their ability to lower fasting glucose and insulin levels in a preclinical setting as well as in human trials. However, there is heterogeneity in these studies, including the species used, probiotic dosage, and the magnitude of efficacy. Based on the robust understanding of the benefits of probiotics in diabetes at the cellular level, in both animal studies and clinical trials, combined with their excellent tolerability, probiotics should be explored for their application in clinics.
Session One: Basal Insulins: Still Innovating After All These Years
Authors: Michel Lisa
Published: November 2022

Therapeutic basal insulin has evolved considerably over the past 90 years. A series of landmark innovations has led to the availability of therapies that closely mimic the physiological effects of endogenous insulin and serve as an invaluable addition to the treatment armamentarium for diabetes. Advances in basal insulin have led to the development of the newer basal insulin analogues, namely insulin degludec and insulin glargine 300 U/mL (Gla-300). The desirable pharmacokinetic (PK) and pharmacodynamic (PD) properties of these basal insulins, such as a prolonged duration of action (≥24 hours), may translate into a number of clinical benefits for the patient e.g., a simple, once-daily injection schedule and flexible injection timings.

The technologies supporting patients with diabetes have also evolved considerably in recent years. Continuous glucose monitoring (CGM) can provide insights into some of the challenges faced by patients with diabetes, e.g., glycaemic excursions and the impact of injection time, and may become an alternative to the current gold standard glycated haemoglobin (HbA1c). Real-world evidence is also providing fresh perspectives on the effectiveness of basal insulins in clinical practice. Today, innovative methods for real-world evidence collection, analysis, and interpretation are helping to generate robust datasets with external validity. Taken together, these innovative approaches are generating an integrated evidence base that is improving our understanding of how basal insulin therapy can be optimised for the benefit of our patients with diabetes.
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: Efficacy and Safety in the Treatment of Hypercholesterolaemia
Authors: Berberoglu Zehra
Published: November 2022

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9I) are a new class of medication that has recently arisen to combat hypercholesterolaemia. They are targeted towards patients who are unable to achieve low levels of low-density lipoprotein cholesterol despite maximum statin therapy, as well as those who are unable to tolerate maximum statin therapy due to side effects. Two of these medications were released in the summer of 2015: alirocumab and evolocumab. This article provides an overview of this medication class and analyses the clinical data from the numerous studies and trials conducted on both of these medications for their efficacy and safety outcomes. Data indicate that PCSK9I are both a safe and effective means of lowering low-density lipoprotein cholesterol levels of resistant or otherwise currently unmanaged hypercholesterolaemia patients.
Session Three: Innovating Beyond Glucose Control in Diabetes Care
Authors: Michel Lisa
Published: November 2022

Advances in treatment offerings are moving beyond classical considerations around glucose control to focus on other aspects of the disease. Such advances include the development of treatments that address the high cardiovascular (CV) risk in patients with diabetes, or have novel mechanisms of action, and new technologies that will facilitate the future integration of care.

The proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors represent a new therapeutic approach for managing CV risk in patients with diabetes. New clinical data recently generated from dedicated diabetes studies have established PCSK9 inhibitors as an efficacious and well-tolerated treatment option for patients with diabetes and persistently elevated low-density lipoprotein-cholesterol levels, despite optimised lipid-lowering therapy.

Treatments with novel mechanisms of action are also being investigated. Sotagliflozin, a dual inhibitor of the sodium-glucose cotransporter 1 (SGLT1) and sodium-glucose cotransporter 2 (SGLT2), may offer additional clinical benefits beyond those of existing selective SGLT2 inhibitors in patients with Type 1 diabetes mellitus. The sotagliflozin inTandem Phase III programme will provide valuable insights regarding the potential role of dual SGLT1 and SGLT2 inhibitors as an adjunct to insulin therapy in patients with Type 1 diabetes mellitus.

Furthermore, advances in diabetes devices, such as implantable drug delivery systems, non-invasive glucose monitoring, and closed-loop artificial pancreas systems, are fuelling the development of new models of patient care. While there will inevitably be other innovations, three major advances will dramatically change diabetes care over the next 10–20 years: 1) digital diabetes health technologies, 2) artificial intelligence and machine learning, and 3) virtual reality.
KINERJA PEGAWAI DINAS PERHUBUNGAN PADA BIDANG ANGKUTAN DALAM PELAYANAN ANGKUTAN KOTA DI KOTA CIREBON
Authors: Maharani Fani , Sutarjo Moh. , Khumayah Siti , Lestari Aghnia Dian
Published: November 2022

Banyak gejala-gejala yang belum sesuai terkait optimalnya pelayanan angkot di Kota Cirebon. Penelitian ini diarahkan untuk mengetahui bagaimana Kinerja Pegawai Dinas Perhubungan Pada Bidang Angkutan Dalam Pelayanan Angkutan Kota Di Kota Cirebon. Metode penelitian yang digunakan yaitu deskriptif kualitatif dengan mengambil lokasi penelitian di Dinas Perhubungan Kota Cirebon pada Bidang Angkutan. Informan kunci dalam penelitian ini adalah Seksi Perencanaan Jaringan Trayek. Sedangkan informan pendukungnya yaitu Sopir Angkot dan Penumpang Angkot. Teknik pengumpulan data yang digunakan merupakan studi kepustakaan, studi lapangan (observasi, wawancara dan dokumentasi). Sedangkan teknik penguji keabsahan data menggunakan teknik triangulasi. Hasil Penelitian menunjukan bahwa kinerja pegawai dalam meningkatkan pelayanan angkot di kota cirebon yaitu program peningkatan pelayanan angkot, identifikasi angkot, pengecekan uji kelayakan angkot dan evaluasi trayek angkot, efektivitas dan efisiensi angkot, keterampilan dan semangat kerja dalam pelayanan angkutan kota. Penelitian ini diperoleh hasil bahwa permasalahan terhadap pelayanan angkot di kota Cirebon belum optimal dan bersifat elementer yang masih mampu diatasi melalui pendekatan solusi peningkatan kinerja yang berkelanjutan yang di lakukan oleh Dinas Perhubungan Kota Cirebon. Kata Kunci: Kinerja, Pelayanan, Bidang Angkutan, Transportasi, Uji Berkendara
PENINGKATAN KUALITAS KESEHATAN MASYARAKAT ERA PANDEMIC COVID-19 MELALUI PEMANFAATAN TANAMAN OBAT KELUARGA SEBAGAI SUMBER IMMUNOMODULATOR
Authors: Ihsan Sunandar , Yamin Yamin , Sahumena Muhammad Handoyo , Zubaydah Wa Ode Sitti , Arfan Arfan
Published: November 2022

Coronavirus Diseases 2019 (COVID-19) is a disease caused by a new coronavirus strain (SARS-CoV-2) which then mutates into various variants including the omicron variant, alpha variant, beta variant, and gamma variant. Where, transmission will pose a high risk when the body's immunity is low. The purpose of this activity is to provide information on various "Family Medicine Gardens" that can function as Immunomodulators to the general public, as well as students, both junior high school (SMP) and elementary school (SD) students. The implementation of this activity is carried out face-to-face and is packaged in the form of socializing the benefits of the Family Medicinal Garden (TOGA) as a source of immunomodulators, together with the community practicing making Family Medicinal Plant gardens in the Poasia and Kambuh Districts as well as the School Environment. In addition, this is also done by distributing leaflets containing information on the types of plants that act as immunomodulators and how to make them.
Blood Feud: Carl Schmidt, Karl von Vierordt and the Evolution of Quantitative Blood Methods
Authors: Davis Ian M.
Published: November 2022

This paper will examine the accomplishments and quarrels of two mid-19th Century German physiologists who worked towards characterizing the components of human blood. Between 1848 and 1852, Carl Schmidt and Karl von Vierordt, two accomplished investigators who taught at universities in Tübingen and Dorpat, published research that quantified the organic and inorganic components in human blood (Schmidt) and counted the number of red blood cells in a unit volume of blood (Vierordt). Their work had very little overlap, except in their mutual interest in improving blood fluid analytical techniques. Schmidt’s work attempted to determine how cholera and other diseases affected the amounts of blood components, while Vierordt’s goal intended to improve blood cell microscopy methods, a goal that he accomplished.
Mechanical property degradation of X80 pipeline steel due to microbiologically influenced corrosion caused by Desulfovibrio vulgaris
Authors: Li Zhong , Yang Jike , Guo Huihua , Kumseranee Sith , Punpruk Suchada , Mohamed Magdy E. , Saleh Mazen A. , Gu Tingyue
Published: November 2022

Apart from pinhole leaks, MIC (microbiologically influenced corrosion) can also cause catastrophic failures such as pipe ruptures and support beam collapses due to mechanical property degradation or stress corrosion cracking. In this work, X80 pipeline steel dogbone coupons and square coupons were immersed in 150 ml broths containing Desulfovibrio vulgaris, a common corrosive sulfate reducing bacterium (SRB), for up to 14 days. The headspace volumes in the anaerobic bottles were increased from 150 ml to 200 ml and 300 ml to increase MIC severity. After 14 days of SRB incubation in ATCC 1249 culture medium with X80 coupons at 37°C, the sessile cell counts were 6.5 × 107 cells cm−2 for 150 ml, 2.3 × 108 cells cm−2 for 200 ml and 1.4 × 109 cells cm−2 for 300 ml headspace volumes, respectively owing to reduced H2S cytotoxicity in the broth with a larger headspace because it allowed more biogenic H2S to escape from the broth. Weight losses were 1.7 mg cm−2, 1.9 mg cm−2 and 2.3 mg cm−2 for 150 ml, 200 ml and 300 ml headspace volumes, respectively. The corresponding pit depths were 2.6 μm, 4.2 μm and 6.2 μm for 150 ml, 200 ml and 300 ml headspace volumes, respectively. Electrochemical impedance spectroscopy (EIS), linear polarization resistance (LPR) and potentiodynamic polarization results corroborated the increasing weight loss and pitting data trends as a result of increased headspace. Tensile testing of dogbone coupons after the 14-day SRB immersion test indicated that more severe MIC pitting led to a higher ultimate strain loss by up to 23% (300 ml headspace) compared to the abiotic control, while the ultimate strength losses for all headspace volumes were quite small (3% and lower).
Extracellular vesicle: A magic lamp to treat skin aging, refractory wound, and pigmented dermatosis?
Authors: Wu Haiyan , Zhang Zhenchun , Zhang Yuemeng , Zhao Zhenlin , Zhu Hongming , Yue Changwu
Published: November 2022

Exposure of the skin to an external stimulus may lead to a series of irreversible dysfunctions, such as skin aging, refractory wounds, and pigmented dermatosis. Nowadays, many cutaneous treatments have failed to strike a balance between cosmetic needs and medical recovery. Extracellular vesicles (EVs) are one of the most promising therapeutic tools. EVs are cell-derived nanoparticles that can carry a variety of cargoes, such as nucleic acids, lipids, and proteins. They also have the ability to communicate with neighboring or distant cells. A growing body of evidence suggests that EVs play a significant role in skin repair. We summarize the current findings of EV therapy in skin aging, refractory wound, and pigmented dermatosis and also describe the novel engineering strategies for optimizing EV function and therapeutic outcomes.
Repurposing the lineage-determining transcription factor Atoh1 without redistributing its genomic binding sites
Authors: Costa Aida , Powell Lynn M. , Malaguti Mattias , Soufi Abdenour , Lowell Sally , Jarman Andrew P.
Published: November 2022

Although the lineage-determining ability of transcription factors is often modulated according to cellular context, the mechanisms by which such switching occurs are not well known. Using a transcriptional programming model, we found that Atoh1 is repurposed from a neuronal to an inner ear hair cell (HC) determinant by the combined activities of Gfi1 and Pou4f3. In this process, Atoh1 maintains its regulation of neuronal genes but gains ability to regulate HC genes. Pou4f3 enables Atoh1 access to genomic locations controlling the expression of sensory (including HC) genes, but Atoh1 + Pou4f3 are not sufficient for HC differentiation. Gfi1 is key to the Atoh1-induced lineage switch, but surprisingly does not alter Atoh1’s binding profile. Gfi1 acts in two divergent ways. It represses the induction by Atoh1 of genes that antagonise HC differentiation, a function in keeping with its well-known repressor role in haematopoiesis. Remarkably, we find that Gfi1 also acts as a co-activator: it binds directly to Atoh1 at existing target genes to enhance its activity. These findings highlight the diversity of mechanisms by which one TF can redirect the activity of another to enable combinatorial control of cell identity.
Recovery units under the Endangered Species Act should be used more widely
Authors: Evans Michael J. , Malcom Jacob W.
Published: November 2022

Recovering species is the main goal of the Endangered Species Act (ESA). In the face of limited conservation budgets, diverse tools are needed to efficiently recover species. Recovery units may be one such tool - designated portions of a species’ range that must be recovered individually before an entire species can be considered recovered. Recovery units allow for spatial flexibility in developing recovery goals and may be used in regulatory decisions such as ESA section 7 consultation. Despite the advantages, very little information exists on how recovery units have been developed and used. We mined available public data to determine the number and types of species for which recovery units have been designated; evaluated species and geographic characteristics associated with recovery unit designation; and examined how recovery units have been used in implementing the ESA, such as during consultation. We found 49 listed species had designated recovery units through December 2017, and that these species typically had relatively large ranges and were well-studied. We found taxonomic biases in recovery unit designation as well, with fish species being disproportionately likely to have recovery units and plants disproportionately less. These species were also more likely to have their recovery units considered and used in subsequent ESA implementation – a probability that decreased as time since unit designation passed. Improvements in recovery priority numbers among species with recovery units indicate that the theoretical benefits of this tool may have translated to improved status. These data indicate that recovery units could be applied to additional wide-ranging species to improve recovery under the ESA.
Disruption of cardio-pulmonary coupling in myopathies: Pathophysiological and mechanistic characterization with special emphasis on nemaline myopathy
Authors: Ronderos-Botero Diana Maria , Dileep Arundhati , Yapor Laura , Singhal Ravish
Published: November 2022

The heart and lung are in continuous reciprocal interaction that creates a functional and anatomical reserve referred to as cardiopulmonary coupling (CPC). Disruption of CPC can occur due to various cardiac or pulmonary pathologies but also can occur in patients with myopathies. Nemaline myopathy (NM) is a skeletal muscle heterogeneous disorder due to contractile proteins' gene mutations that impact lung and cardiac mechanics and thus is expected to adversely affect CPC in a complex manner. We present a case of NM and we review the literature on cardiac and pulmonary effects of myopathy-related disruption of CPC.
A conceptual graph-based model of creativity in learning
Authors: Paaßen Benjamin , Dehne Julian , Krishnaraja Swathi , Kovalkov Anastasia , Gal Kobi , Pinkwart Niels
Published: November 2022

Teaching creativity is one of the key goals of modern education. Yet, promoting creativity in teaching remains challenging, not least because creative achievement is contingent on multiple factors, such as prior knowledge, the classroom environment, the instruction given, and the affective state of the student. Understanding these factors and their interactions is crucial for successfully integrating creativity in teaching. However, keeping track of all factors and interactions on an individual student level may well exceed the capacity of human teachers. Artificial intelligence techniques may thus prove helpful and necessary to support creativity in teaching. This paper provides a review of the existing literature on creativity. More importantly, the review is distilled into a novel, graph-based model of creativity with three target audiences: Educators, to gain a concise overview of the research and theory of creativity; educational researchers, to use the interactions predicted by theory to guide experimental design; and artificial intelligence researchers, who may use parts of the model as a starting point for tools which measure and facilitate creativity.
Post-vaccination SARS-CoV-2 seroprevalence in children aged 3-11 years and the positivity in unvaccinated children: A retrospective, single-center study
Authors: Li Jing , Ge Menglei , Dai Shuzhi , Song Qinwei , Liu Weijie , Wang Ying , Xu Wenjian , Ma Lijuan
Published: November 2022

Objective

To analyze the positivity and levels of SARS-CoV-2 antibodies in vaccinated children to evaluate the humoral immune response of vaccination on pediatric population. Analysis on the causes of antibody positivity in unvaccinated children.

Methods

A retrospective study was conducted on children who were admitted to the Children’s Hospital Affiliated to Capital Institute of Pediatrics. The clinical data of serological testing of SARS-CoV-2 immunoglobulin M (IgM) and IgG antibodies were collected from SARS-CoV-2 vaccinated or unvaccinated children with no evidence of prior novel coronavirus infection. Chemiluminescence immunoassay was utilized for the in vitro determination of SARS-CoV-2 antibodies.

Results

A total of 3,321 healthy children aged 6-11 years received two doses of inactivated SARS-CoV-2 vaccine. At 1 month after the second dose, the positive rate (96.5%) and levels [8.039 (interquartile range (IQR), 6.067-9.098)] of SARS-CoV-2 IgG antibodies reached the peak and remained at a high level for 2-3 months, after which the positive rate and level of vaccine-induced IgG antibody gradually decreased. Compared with 1 month after the second dose of vaccine, the positive rate of IgG antibody decreased to 70.4% at 7 months, and the antibody level decreased by 69.0%. A total of 945 children aged 3-5 years received one or two doses of inactivated vaccine. The positive rate and levels of SARS-CoV-2 IgG antibody in participants remained high for 3 months after vaccination. There was no gender-based difference in positive rate of IgG antibody in children aged 3-11 years old (P>0.05). Among the 5,309 unvaccinated children aged 0 day to 11 years, 105 (2.0%) were positive for SARS-CoV-2 IgG antibody, which was associated with passive infusion. The maternal humoral response to COVID-19 vaccination in noninfected pregnant women was transferred through the placenta to the fetus, and some children obtained SARS-CoV-2-positive antibodies through blood transfusion.

Conclusions

Inactivated SARS-CoV-2 vaccines could induce robust humoral immune response that gradually declined within several months after the second dose. Therefore, it helps to determine whether children receive a booster dose and elicit a long-term memory immune response. Positive SARS-CoV-2 antibodies in unvaccinated children were associated with passive IgG antibody infusion.
Follicular regulatory T cells eliminate HIV-1-infected follicular helper T cells in an IL-2 concentration dependent manner
Authors: Ollerton Matthew T. , Folkvord Joy M. , La Mantia Andriana , Parry David A. , Meditz Amie L. , McCarter Martin D. , D’Aquila Richard T. , Connick Elizabeth
Published: November 2022

Follicular helper CD4+ T cells (TFH) are highly permissive to HIV and major foci of virus expression in both untreated and treated infection. Follicular regulatory CD4+ T cells (TFR) limit TFH numbers and function in vitro and in vivo. We evaluated the hypothesis that TFR suppress HIV replication in TFH using a well-established model of ex vivo HIV infection that employs tonsil cells from HIV uninfected individuals spinoculated with CXCR4- and CCR5-tropic HIV-GFP reporter viruses. Both CXCR4 and CCR5-tropic HIV replication were reduced in TFH cultured with TFR as compared to controls. Blocking antibodies to CD39, CTLA-4, IL-10, and TGF-beta failed to reverse suppression of HIV replication by TFR, and there were no sex differences in TFR suppressive activity. TFR reduced viability of TFH and even more so reduced HIV infected TFH as assessed by total and integrated HIV DNA. Exogenous IL-2 enhanced TFH viability and particularly numbers of GFP+ TFH in a concentration dependent manner. TFR reduced productively infected TFH at low and moderate IL-2 concentrations, and this was associated with decreases in extracellular IL-2. Both IL-2 expressing cells and larger numbers of FoxP3+CD4+ cells were detected in follicles and germinal centers of lymph nodes of people living with HIV. TFR may deplete TFH in vivo through restriction of IL-2 and thereby contribute to decay of HIV expressing cells in B cell follicles during HIV infection.
Immunoregulatory effects of RGMb in gut inflammation
Authors: Pérez-Cruz Magdiel , Iliopoulou Bettina P. , Hsu Katie , Wu Hsin-Hsu , Erkers Tom , Swaminathan Kavya , Tang Sai-Wen , Bader Cameron S. , Kambham Neeraja , Xie Bryan , Dekruyff Rosemarie H. , Freeman Gordon J. , Meyer Everett
Published: November 2022

Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Current strategies to prevent colitis with immunosuppressive drugs carry significant morbidity. Recently, Repulsive Guidance Molecule b (RGMb) has been identified as part of a signaling hub with neogenin and BMP receptors in mice and humans. In addition, RGMb binds BMP-2/4 in mice and humans as well as PD-L2 in mice. RGMb is expressed in the gut epithelium and by antigen presenting cells, and we found significantly increased expression in mouse small intestine after total body irradiation HCT conditioning. We hypothesized that RGMb may play a role in GvHD and IBD pathogenesis by contributing to mucosal inflammation. Using major-mismatched HCT mouse models, treatment with an anti-RGMb monoclonal antibody (mAb) that blocks the interaction with BMP-2/4 and neogenin prevented GvHD and improved survival compared to isotype control (75% versus 30% survival at 60 days after transplantation). The GVT effect was retained in tumor models. Using an inflammatory bowel disease dextran sulfate sodium model, treatment with anti-RGMb blocking monoclonal antibody but not isotype control prevented colitis and improved survival compared to control (73% versus 33% at 21 days after treatment) restoring gut homeostasis. Anti-RGMb mAb (9D1) treatment decreased IFN-γ and significantly increased IL-5 and IL-10 in the gut of the treated mice compared to the isotype control treated mice.
The effect of waves in hydrodynamics, stratification, and salt wedge intrusion in a microtidal estuary
Authors: Higgins Álvarez Aldemar , Otero Luis , Restrepo Juan Camilo , Álvarez Oscar
Published: November 2022

Waves have been found to modulate circulation, stratification, and sediment dynamics in several estuaries, mainly near the mouth. This study analyzes the effects of waves on the hydrodynamics, stratification process, and dynamics of the salt wedge in an estuary with a microtidal range, high fluvial and sediment discharges, and dominated by waves: the Magdalena River estuary (MRE). It is, under low flow conditions, a highly stratified, salt wedge type. Field measurements and the MOHID 3D modeling system, 2D coupled with the SWAN model, were used for this purpose. The low flow seasons of 2018 (February-March) and 2020 (March) were taken as case studies. Results show that when considering wave effects in the numerical simulations, more realistic conditions are reproduced in the circulation patterns and salinity distribution in the outer estuary. Variations in velocity patterns and salinity distribution are found between the mouth and 2 km upstream of the mouth when comparing the simulations with and without waves, especially in the mixing layer. These variations in hydrodynamics and stratification may be associated with increased wave-induced bed shear stress, variations in barotropic and baroclinic acceleration, and increased vertical mixing. At 2 km into the river channel, the reduction in wave height energy of 95% and changes in salinity distribution are already lower than 2%. In addition, it was observed that waves do not generate significant changes in the dynamics of the salt wedge, which is mainly affected by the diurnal tidal cycle, presenting variations in the length of the intrusion of up to 1 km, and in the magnitude of the longitudinal salinity gradient at the salt front, presenting low salinities at high tide when the wedge enters, and high salinities at low tide, in its retreat.
Association of dementia and patient outcomes among COVID-19 patients: A multi-center retrospective case-control study
Authors: Vekaria Pratikkumar H. , Syed Areej , Anderson Jeffrey , Cornett Brendon , Bourbia Amine , Flynn Michael G. , Kashyap Rahul , Shah Asif R.
Published: November 2022

Background

We conducted a retrospective cohort study on COVID-19 patients with and without dementia by extracting data from the HCA Healthcare Enterprise Data Warehouse between January-September 2020.

Aims

To describe the role of patients' baseline characteristics specifically dementia in determining overall health outcomes in COVID-19 patients.

Methods

We grouped in-patients who had ICD-10 codes for dementia (DM) with age and gender-matched (1:2) patients without dementia (ND). Our primary outcome variables were in-hospital mortality, length of stay, Intensive Care Unit (ICU) admission, ICU-free days, mechanical ventilation (MV) use, MV-free days and 90-day re-admission.

Results

Matching provided similar age and sex in DM and ND groups. BMI (median, 25.8 vs. 27.6) and proportion of patients who had smoked (23.3 vs. 31.3%) were lower in DM than in ND patients. The median (IQR) Elixhauser Comorbidity Index was higher in dementia patients 7 (5–10) vs. 5 (3–7, p < 0.01). Higher mortality was observed in DM group (30.8%) vs. ND group (26.4%, p < 0.01) as an unadjusted univariate analysis. The 90-day readmission was not different (32.1 vs. 31.8%, p = 0.8). In logistic regression analysis, the odds of dying were not different between patients in DM and ND groups (OR = 1.0; 95% CI 0.86–1.17), but the odds of ICU admissions were significantly lower for dementia patients (OR = 0.58, 95% CI 0.51–0.66).

Conclusions

Our data showed that COVID-19 patients with dementia did not fare substantially worse, but in fact, fared better when certain metrics were considered.
Endophytic nitrogen-fixing bacteria DX120E inoculation altered the carbon and nitrogen metabolism in sugarcane
Authors: Qin Ying , Xie Xian-Qiu , Khan Qaisar , Wei Jiang-Lu , Sun An-Ni , Su Yi-Mei , Guo Dao-Jun , Li Yang-Rui , Xing Yong-Xiu
Published: November 2022

Endophytic nitrogen-fixing bacteria are versatile and widely distributed in plants. Numerous strains of endophytic nitrogen-fixing bacteria are used as biofertilizers to minimize the utilization of chemical fertilizers, improve nutrient use efficiency, increase crop productivity, and reduce environmental pollution. However, the mechanism underlying the interaction between nitrogen-fixing bacteria and plants is still unclear. So, the present study was planned to assess the effects of endophytic nitrogen-fixing bacteria on sugarcane by analyzing the changes in physiological and biochemical activities. In the current study, Klebsiella variicola DX120E, an endophytic nitrogen-fixing bacterium, was inoculated on sugarcane varieties B8 and ROC22 to evaluate the effects on nitrogen and carbon metabolism-related enzymatic activity and biomass. Results showed that DX120E inoculation improved the enzymatic activities related to gluconeogenesis and nitrogen metabolism increased the sugarcane plant’s height, cane juice Brix, biomass, chlorophyll, and soluble sugar content in sugarcane. Metabolomics analysis revealed that the metabolome modules were highly enriched in carbon and nitrogen metabolic pathways of strain-affected sugarcane than uninoculated control. The identified carbohydrates were associated with the glycolysis or gluconeogenesis and tricarboxylic acid (TCA) cycle in plants. Metabolomic profiling in the present investigation showed that carbohydrate metabolism is coordinated with nitrogen metabolism to provide carbon skeletons and energy to amino acid synthesis, and amino acid degradation results in several metabolites used by the citric acid cycle as an energy source. Moreover, differentially expressed metabolites of non-proteinogenic amino acids have a further complementary role to the action of endophytic nitrogen-fixing bacteria. Meanwhile, a significant difference in metabolites and metabolic pathways present in stems and leaves of B8 and ROC22 varieties was found. This study discovered the potential benefits of DX120E in sugarcane and suggested candidate regulatory elements to enhance interactions between nitrogen-fixing microbes and sugarcane.
Determinants of bacterial and fungal microbiota in Finnish home dust: Impact of environmental biodiversity, pets, and occupants
Authors: Hickman Brandon , Kirjavainen Pirkka V. , Täubel Martin , de Vos Willem M. , Salonen Anne , Korpela Katri
Published: November 2022

The indoors is where many humans spend most of their time, and are strongly exposed to indoor microbiota, which may have multifaceted effects on health. Therefore, a comprehensive understanding of the determinants of indoor microbiota is necessary. We collected dust samples from 295 homes of families with young children in the Helsinki region of Finland and analyzed the bacterial and fungal composition based on the 16S rRNA and ITS DNA sequences. Microbial profiles were combined with extensive survey data on family structure, daily life, and physical characteristics of the home, as well as additional external environmental information, such as land use, and vegetational biodiversity near the home. Using permutational multivariate analysis of variance we explained 18% of the variation of the relative abundance between samples within bacterial composition, and 17% of the fungal composition with the explanatory variables. The fungal community was dominated by the phyla Basidiomycota, and Ascomycota; the bacterial phyla Proteobacteria, Firmicutes, Cyanobacteria, and Actinobacteria were dominant. The presence of dogs, multiple children, and firewood were significantly associated with both the fungal and bacterial composition. Additionally, fungal communities were associated with land use, biodiversity in the area, and the type of building, while bacterial communities were associated with the human inhabitants and cleaning practices. A distinction emerged between members of Ascomycota and Basidiomycota, Ascomycota being more abundant in homes with greater surrounding natural environment, and potential contact with the environment. The results suggest that the fungal composition is strongly dependent on the transport of outdoor environmental fungi into homes, while bacteria are largely derived from the inhabitants.
Chlorogenic acid improves growth performance of weaned rabbits via modulating the intestinal epithelium functions and intestinal microbiota
Authors: Chen Jiali , Song Zhicheng , Ji Rongmei , Liu Yongxu , Zhao Hong , Liu Lei , Li Fuchang
Published: November 2022

This study was conducted to investigate the impacts of chlorogenic acid (CGA) on growth performance, intestinal permeability, intestinal digestion and absorption-related enzyme activities, immune responses, antioxidant capacity and cecum microbial composition in weaned rabbits. One hundred and sixty weaned rabbits were allotted to four treatment groups and fed with a basal diet or a basal diet supplemented with 400, 800, or 1,600 mg/kg CGA, respectively. After a 35-d trial, rabbits on the 800 mg/kg CGA-supplemented group had higher (p < 0.05) ADG and lower (p < 0.05) F/G than those in control (CON) group. According to the result of growth performance, eight rabbits per group were randomly selected from the CON group and 800 mg/kg CGA group to collect serum, intestinal tissue samples and cecum chyme samples. Results showed that compared with the CON group, supplementation with 800 mg/kg CGA decreased (p < 0.05) levels of D-lactate, diamine oxidase, IL-1β, IL-6, and malondialdehyde (MDA), and increased IL-10 concentration in the serum; increased (p < 0.05) jejunal ratio of villus height to crypt depth, enhanced (p < 0.05) activities of maltase and sucrase, increased (p < 0.05) concentrations of IL-10, T-AOC, MHCII and transforming growth factor-α, and decreased (p < 0.05) levels of TNF-α and MDA in the jejunum of weaned rabbits. In addition, results of high-throughput sequencing showed that CGA supplementation elevated (p < 0.05) microbial diversity and richness, and increased (p < 0.05) the abundances of butyrate-producing bacteria (including genera V9D2013_group, Monoglobus, Papillibacter, UCG-005, and Ruminococcus). These results indicated that dietary supplementation with 800 mg/kg CGA could improve the growth performance of weaned rabbits by enhancing intestinal structural integrity, improving the intestinal epithelium functions, and modulating the composition and diversity of gut microbiota.
Enzymatic properties of CARF-domain proteins in Synechocystis sp. PCC 6803
Authors: Ding Jin , Schuergers Nils , Baehre Heike , Wilde Annegret
Published: November 2022

Prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes) systems provide immunity against invading genetic elements such as bacteriophages and plasmids. In type III CRISPR systems, the recognition of target RNA leads to the synthesis of cyclic oligoadenylate (cOA) second messengers that activate ancillary effector proteins via their CRISPR-associated Rossmann fold (CARF) domains. Commonly, these are ribonucleases (RNases) that unspecifically degrade both invader and host RNA. To mitigate adverse effects on cell growth, ring nucleases can degrade extant cOAs to switch off ancillary nucleases. Here we show that the model organism Synechocystis sp. PCC 6803 harbors functional CARF-domain effector and ring nuclease proteins. We purified and characterized the two ancillary CARF-domain proteins from the III-D type CRISPR system of this cyanobacterium. The Csx1 homolog, SyCsx1, is a cyclic tetraadenylate(cA4)-dependent RNase with a strict specificity for cytosine nucleotides. The second CARF-domain protein with similarity to Csm6 effectors, SyCsm6, did not show RNase activity in vitro but was able to break down cOAs and attenuate SyCsx1 RNase activity. Our data suggest that the CRISPR systems in Synechocystis confer a multilayered cA4-mediated defense mechanism.
Identification of foodborne pathogenic bacteria using confocal Raman microspectroscopy and chemometrics
Authors: Zhang Jin , Gao Pengya , Wu Yuan , Yan Xiaomei , Ye Changyun , Liang Weili , Yan Meiying , Xu Xuefang , Jiang Hong
Published: November 2022

Rapid and accurate identification of foodborne pathogenic bacteria is of great importance because they are often responsible for the majority of serious foodborne illnesses. The confocal Raman microspectroscopy (CRM) is a fast and easy-to-use method known for its effectiveness in detecting and identifying microorganisms. This study demonstrates that CRM combined with chemometrics can serve as a rapid, reliable, and efficient method for the detection and identification of foodborne pathogenic bacteria without any laborious pre-treatments. Six important foodborne pathogenic bacteria including S. flexneri, L. monocytogenes, V. cholerae, S. aureus, S. typhimurium, and C. botulinum were investigated with CRM. These pathogenic bacteria can be differentiated based on several characteristic peaks and peak intensity ratio. Principal component analysis (PCA) was used for investigating the difference of various samples and reducing the dimensionality of the dataset. Performances of some classical classifiers were compared for bacterial detection and identification including decision tree (DT), artificial neural network (ANN), and Fisher’s discriminant analysis (FDA). Correct recognition ratio (CRR), area under the receiver operating characteristic curve (ROC), cumulative gains, and lift charts were used to evaluate the performance of models. The impact of different pretreatment methods on the models was explored, and pretreatment methods include Savitzky–Golay algorithm smoothing (SG), standard normal variate (SNV), multivariate scatter correction (MSC), and Savitzky–Golay algorithm 1st Derivative (SG 1st Der). In the DT, ANN, and FDA model, FDA is more robust for overfitting problem and offers the highest accuracy. Most pretreatment methods raised the performance of the models except SNV. The results revealed that CRM coupled with chemometrics offers a powerful tool for the discrimination of foodborne pathogenic bacteria.
Relationship between maternal–infant gut microbiota and infant food allergy
Authors: Wang Shuo , Zhang Rui , Li Xinyue , Gao Yajuan , Dai Nini , Wei Yuan , Liu Luyan , Xing Yan , Li Zailing
Published: November 2022

The gut microbiota plays a crucial role in food allergies. We sought to identify characteristics of the maternal gut microbiota in the third trimester and the infant gut microbiota in early life and the association of these microbiotas with infant food allergy. A total of 68 healthy pregnant women and their full-term newborns were selected from a cohort of 202 mother–infant pairs; among them, 24 infants had been diagnosed with food allergy within 1 year of age, whereas 44 infants were healthy without allergic symptoms. We collected 65 maternal fecal samples before delivery and 253 infant fecal samples at five time points following birth. Fecal samples were microbiologically analyzed using 16S rRNA gene sequencing. Holdemania abundance in the maternal gut microbiota in the third trimester was significantly higher in the non-allergy group than in the food allergy group (P = 0.036). In the infant gut microbiota, Holdemania was only found in meconium samples; its abundance did not differ significantly between the two groups. The change in the abundance of Actinobacteria over time differed between the non-allergy and food allergy groups (FA, P = 0.013; NA, P = 9.8 × 10−5), and the change in the abundance of Firmicutes over time differed significantly in the non-allergy group (P = 0.023). The abundances of genera Anaerotruncus, Roseburia, Ruminococcus, and Erysipelotricaceae were significantly different between the non-allergy and food allergy groups at different time points. Our results showed that maternal carriage of Holdemania during the third trimester strongly predicted the absence of food allergies in infants; there was no correlation between the presence of food allergies and the abundance of Holdemania in the infant gut microbiota. More dynamic fluctuations in phyla Actinobacteria and Firmicutes early in life protect against food allergy. Thus, the enrichment of the infant gut microbiota early in life with short-chain fatty acid-producing bacteria may be beneficial in preventing the development of food allergies in infants.
Binding pocket stabilization by high-throughput screening of yeast display libraries
Authors: Lerma Romero Jorge A. , Meyners Christian , Christmann Andreas , Reinbold Lisa M. , Charalampidou Anna , Hausch Felix , Kolmar Harald
Published: November 2022

Protein dynamics have a great influence on the binding pockets of some therapeutic targets. Flexible protein binding sites can result in transient binding pocket formation which might have a negative impact on drug screening efforts. Here, we describe a protein engineering strategy with FK506-binding protein 51 (FKBP51) as a model protein, which is a promising target for stress-related disorders. High-throughput screening of yeast display libraries of FKBP51 resulted in the identification of variants exhibiting higher affinity binding of conformation-specific FKBP51 selective inhibitors. The gene libraries of a random mutagenesis and site saturation mutagenesis of the FK1 domain of FKBP51 encoding sequence were used to create a yeast surface display library. Fluorescence-activated cell sorting for FKBP51 variants that bind conformation-specific fluorescently labeled ligands with high affinity allowed for the identification of 15 different protein variants with improved binding to either, or both FKBP51-specific ligands used in the screening, with improved affinities up to 34-fold compared to the wild type. These variants will pave the way to a better understanding of the conformational flexibility of the FKBP51 binding pocket and may enable the isolation of new selective ligands that preferably and selectively bind the active site of the protein in its open conformation state.