Miracle-dz/UniFAR-FTUs huggingface dataset:
Formulation Approach that Enables the Coating of a Stable Influenza Vaccine on a Transdermal Microneedle Patch

A trivalent influenza split vaccine was formulated at high concentration for coating on the transdermal microneedle system. Monovalent vaccine bulks of three influenza strains, two influenza A strains, and one B strain were diafiltrated, concentrated, and lyophilized. The lyophilized powder of each vaccine strain was separately reconstituted and subsequently combined into a coating formulation of high concentration trivalent vaccine. The formulation process converted the monovalent vaccine bulks with low hemagglutinin (HA) concentrations 0.1 mg/mL into a viscous, emulsion containing HA at ~50 mg/mL. This physically stable emulsion demonstrated viscosity 1 poise and 30° contact angle for effective, homogeneous coating on each microneedle. Evaluation of the vaccine antigen HA by SRID and SDS-PAGE/Western blot showed that HA remained stable throughout the vaccine transdermal microneedle system manufacturing process and 1-year ambient storage (25°C). Anti-influenza antibody responses were evaluated by ELISA and hemagglutination inhibition (HAI) assay after primary and booster immunization with the vaccine-coated transdermal microneedle systems at either 25-μg or 40-μg total HA. The results showed the induction of serum anti-influenza IgG and anti-HA neutralizing antibodies after primary immunization and significant titer rises after booster immunization for both doses, indicating the dry-coated trivalent vaccine delivered by transdermal microneedle system elicited both primary and recall antibody responses against all three antigen strains. The study demonstrates that the transdermal microneedle system provides an attractive alternative for influenza vaccine delivery with key advantages such as preservative-free and room-temperature storage.
For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder

ABSTRACT Clock genes play significant roles in the regulation of circadian rhythms, which are thought to be involved in the pathophysiology of neurodegenerative and psychiatric diseases. We aimed to investigate the association of five gene polymorphisms (PER3 VNTR (rs57875989), PER2 rs2304672, CLOCK rs1801260, CLOCK rs10462028, CLOCK rs11932595) with PCR-based methods as potential risk factors in bipolar disorder (BD). We used a multiple testing methodology in BD patients (n = 121) and healthy control individuals (n = 121) of Turkish descent to analyze the effects of these gene variants both as risk factors for the disorder and for the evaluation of these variants in the patient group with multiple subscales. We evaluated the circadian rhythm disturbances and seasonal variations in mood and behavior in BD patients using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Seasonal Pattern Assessment Questionnaire (SPAQ) to enlighten the possible links between these scores and the studied circadian gene variants. The results of our study revealed significant associations: PER3 VNTR (rs57875989) 5/5 repeat genotype displayed a protective effect against BD when compared with 4/4 repeat genotype. Moreover, patients with PER3 VNTR 5/5 repeat genotype displayed a higher ratio of hypomania. PER2 rs2304672 G allele frequency increased the risk for BD. There was no association in terms of genotype/allele frequency comparisons between patients and controls for CLOCK gene variants. However, significant associations were found in patients in terms of clinical and behavioral patterns such as mean age at disease onset and BRIAN total scores enabling some risk stratifications for patients. Our results indicate the significance of circadian gene variants in BD, which need to be confirmed in different studies with larger samples. Thus, the possible endophenotypes of BD can be enlightened and advanced chronotherapeutics approaches can be manipulated in the future for clinical benefit.
White and Black Differences in Perceived Access to Health and Community Services and Self-Rated Health in an Age-Friendly Community Assessment

Objectives: This study sought to identify the race differences in perceived access to health and community services and self-rated health (SRH) among White and Black older adult participants of an age-friendly community assessment. Methods: Responses (n = 313) to a baseline assessment of Columbus, Ohio, residents aged ≥50 years were analyzed. Results: Significant differences were found between White and Black older adults regarding SRH, with Black older adults reporting lower SRH. Black older adults reported significantly lower perceived access to 11 out of the 13 health and community services. There were no significant differences by race regarding ratings of Columbus and personal neighborhoods as a place for people to live as they age. Regression analyses found income was a significant predictor of SRH for both White and Black older adults. Discussion: Opportunities to increase perceived access and knowledge of health and community services for older adults through targeted, equitable interventions are warranted.
Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation

Supplemental Digital Content is available in the text. Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca2+ release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2R420Q. Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in knock-in mouse cardiomyocytes and by microelectrodes in mutant human induced pluripotent stem cell-derived cardiomyocytes), we observed an increased occurrence of delayed afterdepolarizations under isoproterenol stimulation, associated with increased Ca2+ waves during confocal Ca2+ recording in both mouse and human RyR2R420Q cardiomyocytes. In addition, Ca2+-induced Ca2+-release, as well as a rough indicator of fractional Ca2+ release, were higher and Ca2+ sparks longer in the RyR2R420Q-expressing cells. At the ultrastructural nanodomain level, we observed smaller RyR2 clusters and widened junctional sarcoplasmic reticulum measured by gated stimulated emission depletion super-resolution and electron microscopy, respectively. The increase in junctional sarcoplasmic reticulum width might be due to the impairment of RyR2R420Q binding to JPH2 (junctophilin-2), as there were less junctophilin-2 coimmunoprecipitated with RyR2R420Q. At the single current level, the RyR2R420Q channel dwells longer in the open state at low intracellular Ca2+ ([Ca2+]i), but there is predominance of a subconductance state. The latter might be correlated with an enhanced interaction between the N terminus and the core solenoid, a RyR2 interdomain association that has not been previously implicated in the pathogenesis of arrhythmias and sudden cardiac death. Conclusions: The RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation modifies the interdomain interaction of the channel and weakens its association with JPH2. These defects may underlie both nanoscale disarrangement of the dyad and channel dysfunction. Graphic Abstract: A graphic abstract is available for this article.
Distribution of complete blood count constituents in gestational diabetes mellitus

Abstract Background (Trial Design): The incidence rate of gestational diabetes is high. In the long run, it harms the health of both the mother and child. In order to understand the distribution of hematological cells with gestational diabetes mellitus (GDM), a longitudinal cohort study was conducted from 2012 to 2018. Methods: A longitudinal case control study of 1860 pregnant women was conducted between 2012 and 2018. Data of hematological parameters at 11 time points of gestational stage were obtained from a laboratory database. Repeated measures analysis and independent t-test were used to analyze the effect of the hematological parameters on GDM. Results: The trend of blood cells fluctuated with gestational age in normal controls but was more remarkable in GDM. Compared with the controls, blood neutrophils, lymphocytes, and monocytes augmented in the second trimester but decreased in the third trimester; platelet (PLT) and thrombocytocrit increased throughout the three trimesters, and red blood cell (RBC) was abundant in the last 2 trimesters in GDM. Conclusions: Peripheral blood leukocytes, platelets, and erythrocytes were significantly different during gestation between GDM and normal controls. Inflammation may also be involved in GMD.
CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax by decreasing CXCL12-driven survival cues.

Acute myeloid leukemia (AML) has a poor prognosis under the current standard of care. In recent years, venetoclax, a BCL-2 inhibitor, was approved to treat patients, ineligible for intensive induction chemotherapy. Complete remission rates with venetoclax-based therapies are, however, hampered by minimal residual disease (MRD) in a proportion of patients, leading to relapse. MRD is due to leukemic stem cells retained in bone marrow protective environments; activation of the CXCL12/CXCR4 pathway was shown to be relevant to this process. An important role is also played by cell adhesion molecules such as CD44, which has been shown to be crucial for AML development. Here we show that CD44 is involved in CXCL12 promotion of resistance to venetoclax-induced apoptosis in human AML cell lines and AML patient samples which could be abrogated by CD44 knockdown, knockout or blocking with an anti-CD44 antibody. Split-Venus biomolecular fluorescence complementation showed that CD44 and CXCR4 physically associate at the cell membrane upon CXCL12 induction. In the venetoclax-resistant OCI-AML3 cell line, CXCL12 promoted an increase in the proportion of cells expressing high levels of embryonic-stem-cell core transcription factors (ESC-TFs: Sox2, Oct4, Nanog), abrogated by CD44 knockdown. This ESC-TF-expressing subpopulation which could be selected by venetoclax treatment, exhibited a basally-enhanced resistance to apoptosis, and expressed higher levels of CD44. Finally, we developed a novel AML xenograft model in zebrafish, showing that CD44 knockout sensitizes OCI-AML3 cells to venetoclax treatment in vivo. Our study shows that CD44 is a potential molecular target to sensitize AML cells to venetoclax-based therapies.
Distinctive morphological and molecular features of urothelial carcinoma with an inverted growth pattern

Urothelial carcinoma with an inverted growth pattern (UC-IGP) is a peculiar entity within the spectrum of urothelial lesions. While efforts have been made over the last few decades to unravel its carcinogenesis and relationship with conventional urothelial carcinoma, the exact classification of inverted urothelial lesions is a matter of debate. The morphological features of UC-IGP pose several issues in differential diagnosis with other mostly benign lesions. Various techniques, including immunohistochemistry, UroVysion, and many molecular methods, have been employed to study the exact nature of this lesion. The aim of this review is to provide a comprehensive overview of the morphological and immunophenotypical aspects of UC-IGP. Moreover, we present and discuss the immunohistochemical and molecular markers involved in diagnosis and prognosis of UC-IGP lesions.
In vivo autophagy quantification: Measuring LC3 and P62 puncta in 3D image system from zebrafish larvae

Autophagy is a central pathway in maintaining cellular homeostasis through the recycling of damaged proteins and organelles. Detection of LC3 protein levels by immunofluorescence or western blot analysis is one of the most common ways to measure autophagy. For quantitative autophagy analysis, LC3 western blot analysis is commonly used, whereas immunostaining is used for qualitative autophagy analysis. However, zebrafish larvae have a lot of proteases that rapidly degrade LC3 protein in samples. P62 is another autophagy marker that bind to damaged proteins and can reflects autophagic status. This study demonstrates a fast and accurate way to quantify autophagy from LC3 and/or P62 immunostaining images. We used a three‐dimensional analysis of whole‐mount LC3 immunostaining images of zebrafish larvae. Counting LC3 and P62 punctate by two dimensions can be used as a qualitative method for the analysis of autophagy. However, here we demonstrate that 3D image analysis can be used as a quantitative, rapid tool for monitoring autophagy in zebrafish larvae and avoiding drawbacks of LC3 western blot analysis.
Search committee diversity and applicant pool representation of women and underrepresented minorities: A quasi-experimental field study.

The diversification of applicant pools constitutes an important step for broadening the participation of women and underrepresented minorities (URMs) in the workforce. The current study focuses on recruiting diverse applicant pools in an academic setting. We test strategies grounded in homophily theory to attract a diverse set of applicants for open faculty positions. Analysis of recruitment data (13,750 job applications) showed that women search committee chairs and greater percentages of women on search committees related to more women applicants and that URMs search chairs and a greater percentage of URM members on search committees related to more URM applicants, resulting in 23% more women applicant pools with a woman chair and over 100% more URM applicants for a URM chair. Furthermore, women and URMs actively engage in ways to reach out to a more diverse set of applicants, whereas men and non-URMs' behavior maintains the status quo. We discuss the implications and advancement of homophily theory that can ultimately increase the representation of women and URM in the workforce. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Pharmacokinetics of Five Alkaloids and their Metabolites in Normal and Diabetic Rats after Oral Administration of Rhizoma coptidis

Abstract Rhizoma coptidis has been clinically used for a long time for the treatment of various diseases in China, such as hypertension, diabetes, and inflammation. Previous studies have shown that alkaloid components of Rhizoma coptidis extract could be extensively metabolized and the metabolites were also considered to be the therapeutic material basis. However, until now, pharmacokinetic studies of the in vivo metabolites have not been revealed yet. The aim of the present study was to characterize the pharmacokinetics and excretions of five main alkaloids (berberine, jatrorrhizine, palmatine, epiberberine, and coptisine) and their seven metabolites (berberrubine, demethyleneberberine, jatrorrhizine-3-O-β-D-glucuronide, thalifendine-10-O-β-D-glucuronide, berberrubine-9-O-β-D-glucuronide, demethyleneberberine-2-O-sulfate, and demethyleneberberine-2-O-β-D-glucuronide) in rats after oral administration of Rhizoma coptidis extract. Meanwhile, comparative pharmacokinetics and excretions of these analytes in diabetic model rats were also investigated, since Rhizoma coptidis is widely used for the treatment of diabetes. Our results showed that the in vivo existing forms of alkaloid components were phase II metabolites, highlighting the glucuronidation metabolic pathway. In diabetic model rats, the utilization of Rhizoma coptidis alkaloids was significantly increased and the biotransformation of berberine into berberrubine was significantly inhibited.
A five amino acids deletion in NKCC2 of C57BL/6 mice affects analysis of NKCC2 phosphorylation but does not impact kidney function

The phosphorylation level of the furosemide‐sensitive Na+‐K+‐2Cl− cotransporter (NKCC2) in the thick ascending limb (TAL) is used as a surrogate marker for NKCC2 activation and TAL function. However, in mice, analyses of NKCC2 phosphorylation with antibodies against phosphorylated threonines 96 and 101 (anti‐pT96/pT101) give inconsistent results. We aimed (a) to elucidate these inconsistencies and (b) to develop a phosphoform‐specific antibody that ensures reliable detection of NKCC2 phosphorylation in mice.
Forty Years of HIV: The Intersection of Laws, Stigma, and Sexual Behavior and Identity.

Forty years after the Centers for Disease Control and Prevention's (CDC's) June 1981 Morbidity and Mortality Weekly Report about five gay men with a syndrome that came to be called AIDS, both the impact of HIV and the legal landscape in the United States for the most affected population have changed dramatically. Laws, policies, and how they are enforced reflect the values and prejudices of society, and laws can help or hinder public health efforts, regardless of intent. From the outset, HIV aroused widespread fear and new stigmatizing laws and policies, and the crisis revealed injustices in existing laws that compounded stigma and health disparities among the most affected groups. In the 1980s, HIV engulfed already stigmatized communities of gay and bisexual men and other men who have sex with men (MSM) and people who inject drugs. The CDC's HIV surveillance reports show that, throughout the epidemic, MSM have constituted the majority of annual and prevalent cases, and the burden on racial or ethnic minority MSM has increased disproportionately since the early 1990s.1 It is timely to reflect on the intertwining of HIV, laws, stigma, and inequity in the United States and their intersection with the lives of gay and bisexual men (both cisgender and transgender). (Am J Public Health. Published online ahead of print June 10, 2021: e1-e3. https://doi.org/10.2105/AJPH.2021.306335).
Faith-Based Advocacy for Family Planning Works: Evidence From Kenya and Zambia

Faith-based organizations and religious leaders can be effective family planning advocates for policy change, funding, and services. To do so, they need evidence-based knowledge, training, support within their faith communities, as well as respect for their beliefs and values. Key Messages Although it is often assumed that religion has a negative influence on family planning (FP), virtually all faith traditions support the concept of healthy timing and spacing of pregnancy. Given the growing evidence of the importance of religious leaders and faith-based organizations (FBOs) in shaping policy and reaching communities in support of FP, faith leaders play an important role in advocating for FP and increasing its uptake. FBOs are interested in expanding access to FP and increasing service delivery, yet governments, donors, and nongovernmental organizations give low priority to FBOs for financial, training, and commodity support of FP, resulting in a lack of services for underserved populations. Faith leaders become effective FP advocates with governments and donors through advocacy training, internal discussions to develop church positions on FP, technical information on FP, and evidence-based rationales for FP.
Current Classification of the Bacillus pumilus Group Species, the Rubber-Pathogenic Bacteria Causing Trunk Bulges Disease in Malaysia as Assessed by MLSA and Multi rep-PCR Approaches

Bacillus pumilus is the causal agent of trunk bulges disease affecting rubber and rubberwood quality and yield production. In this study, B. pumilus and other closely related species were included in B. pumilus group, as they shared over 99.5% similarity from 16S rRNA analysis. Multilocus sequence analysis (MLSA) of five housekeeping genes and repetitive elements-based polymerase chain reaction (rep-PCR) using REP, ERIC, and BOX primers conducted to analyze the diversity and systematic relationships of 20 isolates of B. pumilus group from four rubber tree plantations in Peninsular Malaysia (Serdang, Tanah Merah, Baling, and Rawang). Multi rep-PCR results revealed the genetic profiling among the B. pumilus group isolates, while MLSA results showed 98-100% similarity across the 20 isolates of B. pumilus group species. These 20 isolates, formerly established as B. pumilus, were found not to be grouped with B. pumilus. However, being distributed within distinctive groups of the B. pumilus group comprising of two clusters, A and B. Cluster A contained of 17 isolates close to B. altitudinis, whereas Cluster B consisted of three isolates attributed to B. safensis. This is the first MLSA and rep-PCR study on B. pumilus group, which provides an in-depth understanding of the diversity of these rubber-pathogenic isolates in Malaysia.
Abnormal singing can identify patients with right hemisphere cortical strokes at risk for impaired prosody

Abstract Despite lacking aphasia seen with left hemisphere (LH) infarcts involving the middle cerebral artery territory, right hemisphere (RH) strokes can result in significant difficulties in affective prosody. These impairments may be more difficult to identify but lead to significant communication problems. We determine if evaluation of singing can accurately identify stroke patients with cortical RH infarcts at risk for prosodic impairment who may benefit from rehabilitation. A prospective cohort of 36 patients evaluated with acute ischemic stroke was recruited. Participants underwent an experimental battery evaluating their singing, prosody comprehension, and prosody production. Singing samples were rated by 2 independent reviewers as subjectively “normal” or “abnormal,” and analyzed for properties of the fundamental frequency. Relationships between infarct location, singing, and prosody performance were evaluated using t tests and chi-squared analysis. Eighty percent of participants with LH cortical strokes were unable to successfully complete any of the tasks due to severe aphasia. For the remainder, singing ratings corresponded to stroke location for 68% of patients. RH cortical strokes demonstrated a lower mean fundamental frequency while singing than those with subcortical infarcts (176.8 vs 130.4, P = 0.02). They also made more errors on tasks of prosody comprehension (28.6 vs 16.0, P < 0.001) and production (40.4 vs 18.4, P < 0.001). Patients with RH cortical infarcts are more likely to exhibit impaired prosody comprehension and production and demonstrate the poor variation of tone when singing compared to patients with subcortical infarcts. A simple singing screen is able to successfully identify patients with cortical lesions and potential prosodic deficits.