bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herbs’ Disease-matched Pharmacological Mechanisms of HuanglianJiedu Decoction in Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease
Authors: Ma Su-Ya , Wang Xu , Shi Jing 
Published: January 2022

Abstract
Along with cognitive deficit, behavioral and psychological symptoms in dementia (BPSD) is another characteration of Alzheimer's disease that hamper clinical management and exacerbate burden for caregivers. However, therapeutic management of BPSD remains challenging. HuanglianJiedu decoction (HLJDD), a traditional Chinese prescription which contains Coptidis rhizome(Huang lian), Scutellariae radix (Huang-qin), Phellodendri chinrnsis cortex (Huang-bai) and Gardeniae fructus (Zhi-zi), is applied to treat BPSD. So elucidating the herbs’ disease-matched pharmacological mechanisms underlying HLJDD, further put forward each herbs’ disease-matched combination are critical to the application of HLJDD. In this study, network pharmacology was used to determine the targets and biological processes regulated by HLJDD in the treatment of BPSD. Moreover, molecular docking was utilized to evaluate the binding activity between the herbs' main active ingredients and neurotransmitter receptors. The results showed that the KEGG signaling pathway of HLJDD in treating BPSD mainly lies in TNF signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Scutellariae radix and Phellodendri chinrnsis cortex exhibited better anti-BPSD effects when compared to Coptidis rhizoma and Gardeniae fructus. Scutellariae radix exhibited superior anti-neuroinflammation functions, with better blood vessel regulation effects. Phellodendri chinrnsis cortex showed a higher binding affinity to the dopamine D2 receptor (DRD2) and 5-hydroxytryptamine receptor 2A (HTR2A). Coptidis rhizoma and Gardeniae fructus were better in neuronal signaling. In conclusion, for treating BPSD, Scutellariae radix and Phellodendri chinrnsis cortex are the principal herbs while Coptidis rhizoma and Gardeniae fructus are the ancillary herbs. Beta-sitosterol, stigmasterol, chelerythrine, campesterol and berberine are the potential effective ingredients in treating BPSD.
Influencing Factors Associated with Delayed Initiation of Insulin Among Patients with Type 2 Diabetes Mellitus at The Diabetes Clinic of a Tertiary Hospital in Ethiopia
Authors: Reshid Elham , Habte Bruck Messele , Kebede Tedla , Fenta Teferi Gedif 
Published: January 2022

Abstract
Background

Guidelines recommend the initiation of insulin in patients with type 2 diabetes mellitus who failed on maximum dose of oral medications. However, time to initiation is inconsistent due to different barriers resulting in delay and thus leads to failure to achieve glycemic control which in turn may lead to different complications. The aim of this study was to explore factors influencing the delayed initiation of insulin among patients with type 2 diabetes being managed at the Diabetes Clinic of Tikur Anbessa Specialized Hospital.
Methods

A qualitative descriptive study design was employed. Data was collected using in-depth interviews with 27 participants, including patients and healthcare providers. Audio-recorded data was transcribed and then thematically analyzed.
Results

Different factors influencing the delayed initiation of insulin in patients with type 2 diabetes mellitus were revealed. Patient factors included beliefs about the necessity of insulin and concerns related to starting insulin. Physician factors included perceived patient’s situation and lack of clinical competency. Health institution factors included inadequate laboratory set up and absence of contextual guidelines for diabetes management including insulin initiation.
Conclusions

The study findings indicated different influencing factors some of which were similar to those reported from other settings while there were others which somehow were unique to study setting. These are indicative of the need to implement interventions such as strengthening the patients’ diabetes health education program that is considerate of the religious, cultural, and social aspects of the society.
Sufficient condition for infinite solutions of Diophantine Equation: n! = P(s)
Authors: SINGH DEVANSH 
Published: January 2022

Abstract
In this article I have used method which tells that number of solutions of Diophantine equation: n! = P(s) is infinite if some condition is satisfied. I have applied Inverse Laplace Transform to n! = P(s) and got function f(t) which is easier to deal with. The condition is given in section below contains zero of f(t) or zero of some modified function of f(t): g(t) = f(t) - h(t).
Effects and mechanisms of Portulaca oleracea L. polysaccharides on the activation of dendritic cells derived from mice immunized with FMD vaccine
Authors: Zhao Rui , Zhou Xiechen , Zhao Hui , Jia Guiyan , Li Liyang , Li Tao , Li Yan , Qi Xin 
Published: January 2022

Abstract
Background

Our previous study has showed that Portulaca oleracea L. (POL-P), as an immunoenhancer, could increase the IgG and isotypes antibody titers in mice immunized with foot and mouth disease (FMD) vaccines. However, the structural features and the mechanism of action are still unclear. Enhancing antigen presentation is one of the main ways that immunoenhancer boost immune response. Dendritic cells (DCs) are the most potent antigen presenting cell (APC), which stimulate the initial T cells directly and initiate the specific immune responses. In addition to extracellular factors and intracellular genetic factors, epigenetics plays a major role in the regulation of DCs. In this study, we obtained POL-P, and structural features and monosaccharide composition were analyzed. We evaluated the effect of POL-P on functional maturation of DCs derived from mice immunized with foot and mouth disease (FMD) vaccine and explored the related mechanism responsible for immunoenhancer. The levels of protein and gene related to IL-12p35 and IL-12p40 were determined by western blot and chromatin immunoprecipitation (ChIP) assays. The expressions of TLR2, TLR4 receptors and the downstream molecules of MyD88 and NF-κB were examined using immunohistochemistry.
Results

The average molecular weight (Mw) of the POL-P was 4×104 Da. The monosaccharide composition of the POL-P was mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose with a relative mass of 1.2%, 13.2%, 33.5%, 1.2%, 3.3%, 32.2% and 15.4%, respectively. We concluded that co-administration of POL-P with the FMD vaccine could significantly promote DCs maturation of phenotype and the immune function. In addition, the acetylation level of histone H3 of IL-12 was closely connected with the immune activity of DCs. Moreover, POL-P induced immune response was related to up-regulating protein expression of TLR2, TLR4, MyD88 and NF-κB in DCs.
Conclusions

Our evidence suggested that POL-P could be a potential immunostimulant in the regulation of DCs maturation for FMD vaccine.
A single dose ChAdOx1 nCoV-19 vaccine elicits high antibody responses in individuals with prior SARS-CoV-2 infection comparable to that of double dose vaccinated SARS-CoV-2 infection naïve individuals
Authors: Gelanew Tesfaye , Mulu Andargachew , Abebe Markos , Bates Timothy A , Wassie Liya , Tefer Mekonnen , Fentahun Desalegn , Alemu Aynalem , Tamiru Frehiwot , Assefa Gebeyehu , Bayih Abebe Genetu , Taffesse Fikadu G , Mihret Adane , Abdissa Alemseged 
Published: January 2022

Abstract
Background

A single dose COVID-19 vaccines, mostly mRNA-based vaccines, are shown to induce robust antibody responses in individuals who were previously infected with SARS-CoV-2, suggesting the sufficiency of a single dose to those individuals. However, these important data are limited to developed nations and lacking in resource-limited countries, like Ethiopia.
Methods

We compared receptor-binding domain (RBD)-specific IgG antibodies in 40 SARS-CoV-2 naïve participants and 25 participants previously infected with SARS-CoV-2, who received two doses of ChAdOx1 nCoV-19 vaccine. We measured the antibody response in post-vaccination blood samples from both groups of participants collected at four different post-vaccination time points: 8- and 12-weeks after each dose of the vaccine administration using an in-house developed ELISA.
Results

We observed a high level of anti-RBD IgG antibodies titers 8-weeks after a single dose administration (16/27; 59.3%) among naïve participants, albeit dropped significantly (p<0.05) two months later, suggesting the protective immunity elicited by the first dose ChAdOx1 nCoV-19 vaccine will likely last for a minimum of three months. However, as expected, a significant (p<0.001) increase in the level of anti-RBD IgG antibodies titers was observed after the second dose administration in all naïve participants. By contrast, the ChAdOx1 nCoV-19 vaccine-induced anti-RBD IgG antibody titers produced by the P.I participants at 8- to 12-weeks post-single dose vaccination were found to be similar to the antibody titers seen after a two-dose vaccination course among infection- naïve participants and showed no significant (p>0.05) increment following the second dose administration.
Conclusion

Taken together, our findings show that a single ChAdOx1 nCoV-19 dose in previously SARS-CoV-2 infected individuals elicits similar antibody responses to that of double dose vaccinated naïve individuals. Age and sex were not associated with the level of vaccine-elicited immune responses in both individuals with and without prior SARS-CoV-2 infection. Further studies are required to assess the need for a booster dose to extend the duration and amplitude of the specific protective immune response in Ethiopia settings, especially following the Omicron pandemic.
The Effects From Oral Administration of Recombinant Interferon-alpha on Piglet Daily Care
Authors: Dai Fawen , Liu Yanting , Zhang Meimei , Tao Lin , Huashuo Chu , Gong Ruixue , Zhao Baokai 
Published: January 2022

Abstract
The administration of interferon has improved the antiviral and immunomodulatory abilities of piglets, which is conductive to conductive to the prevention of potential diseases or delay the appearance of clinical symptoms. This study aimed to evaluate the effects from administration of recombinant interferon-alpha (IFN-α) on the daily care of piglets. The results were compared with compound Chinese herbal, which was proved to improve serum interferon level. Further, the administration routes were compared between oral administration and intramuscular injection. Forty (40) piglets with equal age and weight were randomly divided into four groups: Control group (Group C, without treatment), Group H (treated with compound Chinese herbal), Group K (administered orally with recombinant IFN-α, 1500 IU per day per piglet), and Group J (administered intramuscularly with IFN-α, 4× 106 IU per day per piglet). After the treatment of 15 days, both oral and intramuscular treatment of recombinant IFN-α significantly improved the secretion of IFN-gamma (IFN-γ) (P<0.05), and the effects of intramuscular pathway were faster. In addition, the expression levels of IFN-stimulated genes (MX1 and ISG15) were significantly enhanced (P<0.01), independently of IFN-α treatment time and serum IFN-γ level. Different from other studies, compound Chinese herbal showed weaker effects on interferon stimulation in piglets. The results indicated that oral administration of recombinant IFN-α improved interferon-induced response of piglets at both serum and molecular levels, which may be applied for improving autoimmunity of piglets.
Initiating Second-Line Antidiabetic Medication Among Older Adults With Type 2 Diabetes on Metformin
Authors: DeCarlo Kristen , Wallia Amisha , Kang Raymond H. , Cooper Andrew , Cherupally Manisha , Harris Sterling A. , Aikman Cassandra , Liss David T. , Ackermann Ronald T. , O’Brien Matthew J. 
Published: January 2022

Abstract
BACKGROUND: Antidiabetic medications (ADM), especially sulfonylureas (SFU) and basal insulin (BI), are associated with increased risk of hypoglycemia, which is especially concerning among older adults in poor health. The objective of this study was to investigate prescribing patterns of ADM in older adults according to their health status.METHODS: This case control study analyzed administrative claims between 2013-2017 from a large national payer. The study population was derived from a nationwide database of 84,720 U.S. adults aged ≥65, who were enrolled in Medicare Advantage health insurance plans. Participants had type 2 diabetes on metformin monotherapy, and started a second-line ADM during the study period. The exposure was a binary variable for health status, with poor health defined by end-stage medical conditions, dementia, or residence in a long-term nursing facility. The outcome was a variable identifying which second-line ADM class was started, categorized as SFU, BI, or other (i.e. all other ADM classes combined).RESULTS: Over half of participants (54%) received SFU as initial second-line ADM, 14% received BI, and 32% received another ADM. In multivariable models, the odds of filling SFU or BI was higher for participants in poor health than those in good or intermediate health [OR 1.13 (95% CI 1.05-1.21) and OR 2.34 (95% CI 2.14-2.55), respectively]. SFU and BI were also more commonly filled by older adults with poor glycemic control.CONCLUSIONS: Despite clinical consensus to use caution prescribing SFU and BI among older adults in poor health, these medications remain frequently used in this particularly vulnerable population.
Shedding Light On An Undiscovered Aspect That Perfectly Mimics Cosmic Acceleration
Authors: Takkhi Karan R. 
Published: January 2022

Abstract
The comparison of redshift-distance relationship for high and low-redshift supernovae revealed the surprising transition of the Universe’s expansion from deceleration to acceleration. As compared to local supernovae, remote supernovae appear 10% to 25% dimmer as they are further away than expected. The expansion rate obtained for local supernovae is higher with low redshifts as compared to the expansion rate obtained for remote supernovae with high redshifts. Since observed redshifts in an expanding Universe provide an estimate of recession velocities, therefore, it is very disturbing to find that low recession velocities (just 1% of speed of light) indicate a faster rate of expansion (acceleration), whereas high recession velocities (60% of speed of light) indicate a slower rate of expansion (deceleration). In this paper, I unravel an undiscovered aspect that perfectly mimics cosmic acceleration. Rather than “cosmic deceleration that preceded the current epoch of cosmic acceleration”, I show in this paper, that “consecutive expansion epochs of the Universe that preceded the current epoch of cosmic expansion” were responsible for placing remote supernovae further away than expected. As a consequence of consecutive expansion, expansion began for remote structures in preceding expansion epochs before it did for local structures in the current (or more recent) expansion epoch; remote supernovae, quasars, and gamma-ray bursts are therefore not only further away than expected, but they also happen to yield a slower rate of expansion, thereby suggesting their deceleration even with “superluminal expansion”. As a result of consecutive expansion, preceding expansion epochs appear to be decelerating as compared to the expansion epoch that succeeds them. The analysis is based on the redshift-distance relationship plotted for 580 type Ia supernovae from the Supernova Cosmology Project, 7 additional high-redshift type Ia supernovae discovered through the Advanced Camera for Surveys on the Hubble Space Telescope from the Great Observatories Origins Deep Survey Treasury program, and 1 additional very high-redshift type Ia supernova discovered with Wide Field and Planetary Camera 2 on the Hubble Space Telescope. The results obtained by the High-Z Supernova Search Team through observations of type Ia supernovae have also been analysed. Studies incorporating quasars and gamma-ray bursts to determine how the expansion of the Universe has changed over time have been taken into consideration as well. The results obtained in this paper have been confirmed by plotting velocity-distance relationship, expansion rate vs. time relationship, expansion factor vs. time relationship, scale factor vs. time relationship, scale factor vs. distance relationship, distance-redshift relationship, and distance modulus vs. redshift relationship, moreover, the deceleration parameter (q0) is also found to be negative (q0 < 0).
A robust benchmark for evaluating and improving mosaic variant calling strategies
Authors: Ha Yoo-Jin , Kim Jisoo , Kang Seungseok , Kim Junhan , Jo Se-Young , Kim Sangwoo 
Published: January 2022

Abstract
The rapid advances in sequencing and analysis technologies have enabled the accurate detection of diverse forms of genomic variants, including germline, somatic, and mosaic mutations. However, unlike for the former two mutations, the best practices for mosaic variant calling still remain chaotic due to the technical and conceptual difficulties faced in evaluation. Here, we present our benchmark of nine feasible strategies for mosaic variant detection based on a systematically designed reference standard that mimics mosaic samples, with 390,153 control positive and 35,208,888 negative single-nucleotide variants and insertion–deletion mutations. We identified the condition-dependent strengths and weaknesses of the current strategies, instead of a single winner, regarding variant allele frequencies, variant sharing, and the usage of control samples. Moreover, feature-level investigation directs the way for immediate to prolonged improvements in mosaic variant calling. Our results will guide researchers in selecting suitable calling algorithms and suggest future strategies for developers.
Results of the non-interventional observational program: Influence of Novel COroNavirus on the condition of patients with liver and gastrointestinal Tract diseases and the effect of Ursodeoxycholic acid drugs and Rebamipide on the course of COVID-19 infection (CONTUR)
Authors: Tikhonov I. N. , Ivashkin V. T. , Zharkova M. S. , Maevskaya M. V. , Koloteeva S. N. , Sarsenbaeva A. S. , Tkachenko L I. , Aronova O. V. , Tsvetaeva E. K. , Trofimovskaya N I. 
Published: January 2022

Intriduction. The course and outcome of COVID-19 infection in patients with liver and gastrointestinal tract diseases remain poorly understood. The article presents a multicenter non-interventional observational program conducted by the Russian Society for the Study of the Liver.Aim. To study the relationship between COVID-19 and injuries of gastrointestinal tract and liver, to assess the effect of therapy with UDCA and Rebamipide on the course and outcome of COVID-19 infection. Materials and methods. 460 patients were enrolled in the study, of which 46% were patients with gastrointestinal and liver diseases. Some patients received Rebamipide and UDCA at a dose of 15 mg/kg body weight, followed by assessment of the clinical and laboratory parameters.Results. In the study group, more severe lung injury and the course of infection were observed. The investigators detected three phenotypes of gastrointestinal tract injury: dyspeptic, diarrheal and painful. The latter was more common in patients with gastrointestinal diseases. Liver injury occurred in 87% of patients with COVID-19 (of which 44% had a history of liver disease). Increased ALT and AST were more often recorded in patients with obesity and diabetes mellitus and correlated with the severity of the infection. An inverse relationship was found between the albumin level and death and transfer to mechanical ventilation. At least 5-day Rebamipide therapy leads to reduction of diarrhea and abdominal pain (p < 0.00001 and p = 0.002), decrease in the levels of systemic inflammatory markers (CRP and ferritin, p<0.00001). The use of UDCA leads to a decrease of the systemic inflammation markers: ferritin and is associated with a significant decrease/normalization of ALT levels (p < 0.00001).Conclusions. In patients with diseases of the gastrointestinal tract and liver, COVID-19 develops in a more severe form and symptoms of gastrointestinal tract injury may prevail in the clinical picture. The severity of liver injury correlates with the severity of COVID-19 and a poor prognosis. Rebamipide reduces diarrhea and abdominal pain. UDCA prevents or reduces liver injury in COVID-19 infection. Both drugs reduce the level of systemic inflammation markers.
Insulin biosimilars in clinical practice
Authors: Verbovoy A. F. , Dolgikh Yu. A. , Sharonova L. A. 
Published: January 2022

Diabetes mellitus (DM) is an important medical and social problem throughout the world due to its high prevalence. At the same time, the majority of patients have type 2 diabetes. The onset of the disease is gradual, with a prolonged asymptomatic preclinical stage. Therefore, it is necessary to conduct screening among patients at risk. Therapy for type 2 diabetes is carried out with oral hypoglycemic drugs. If it is impossible with their help to achieve adequate glycemic control, it is possible to add basal insulin to therapy, and if the own insulin secretion is depleted, an intensive insulin therapy regimen must be prescribed. Insulin preparations differ in the source of receipt, as well as in the duration of action: background, or basal (insulin of medium duration, long-term or ultra-long-acting) and prandial, or food (ultrashort and short insulin). Currently, along with original insulin preparations, their analogues, or biosimilars (biosimilars), appear on the pharmaceutical market. Biosimilar (biosimilar) is a biological product similar in quality, efficacy and safety parameters to a reference biological medicinal product in the same dosage form and having an identical route of administration. Biosimilars are used all over the world, and this applies not only to insulin preparations, but also to other biological preparations. Proof of bioequivalence is a long-term process that ensures comparability and the absence of clinically significant differences between the study and the reference drug, and includes preclinical and clinical studies. The task of studies of biosimilars of insulin is to confirm the comparability with a reference, previously well-studied biological product. The efficacy and safety of domestically produced biosimilars has been studied in a number of clinical studies, during which the bioequivalence of the drugs was shown. These drugs are of high quality and safe, and their pharmacological characteristics, immunogenicity and effectiveness do not differ from the original drugs.