Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistence of Immunity Following 2-Dose Priming with a 10-Valent Pneumococcal Conjugate Vaccine at 6 and 10 Weeks or 6 and 14 Weeks of Age in Nepalese Toddlers

Supplemental Digital Content is available in the text. Background: The pneumococcal conjugate vaccine has had a substantial impact on invasive pneumococcal disease. Previously, we compared immunity following vaccination with the 10-valent pneumococcal conjugate vaccine (PCV10) administered at 2 slightly different schedules: at 6 and 10 weeks of age, and at 6 and 14 weeks of age, both followed by a 9-month booster. In this study, we followed up those participants to evaluate the medium-term persistence of serotype-specific pneumococcal immunity at 2-3 years of age. Method: Children from the previous studies were contacted and after taking informed consent from their parents, blood samples and nasopharyngeal swabs were collected. Serotype-specific IgG antibody concentrations were determined by enzyme-linked immunosorbent assay, for the 10 vaccine serotypes, at a WHO pneumococcal serology reference laboratory. Findings: Two hundred twenty of the 287 children who completed the primary study returned at 2–3 years of age to provide a blood sample and nasopharyngeal swab. The nasopharyngeal carriage rate of PCV10 serotypes in the 6 + 14 group was higher than the 6 + 10 group (13.4% vs. 1.9%). Nevertheless, the proportion of toddlers with serum pneumococcal serotype-specific IgG greater than or equal to 0.35 µg/mL was comparable for all PCV10 serotypes between the 6 + 10 week and 6 + 14 week groups. Similarly, the geometric mean concentrations of serum pneumococcal serotype-specific IgG levels were similar in the 2 groups for all serotypes, except for serotype 19F which was 32% lower in the 6 + 10 group than the 6 + 14 group. Conclusion: Immunization with PCV10 at 6 + 10 weeks or 6 + 14 weeks, with a booster at 9 months in each case, results in similar persistence of serotype-specific antibody at 2-3 years of age. Thus, protection from pneumococcal disease is expected to be similar when either schedule is used.
Early detection of metastatic uveal melanoma by the analysis of tumor‐specific mutations in cell‐free plasma DNA

Eye salvaging therapy of malignant melanomas of the uvea can preserve the eye in most cases, but still about half of patients die from metastatic disease. Previous analyses of cell‐free DNA from plasma had shown detectable levels of tumor‐specific GNAQ/GNA11 mutations in patients with the clinical diagnosis of progressive disease. However, data on the time span that elapses from the detection of ctDNA in plasma to the clinical detection of metastases (diagnostic lead time) are missing.
miR‐671‐5p repressed progression of papillary thyroid carcinoma via TRIM14

The pivotal role of dysregulated miRNAs in development of papillary thyroid carcinoma has been emphasized in recent research. miR‐671‐5p was previously documented to function as a tumor suppressor. However, the role and mechanism of miR‐671‐5p in progression of papillary thyroid carcinoma remain to be further studied. Data from functional assays indicated that forced expression of miR‐671‐5p decreased cell viability, repressed cell proliferation, migration, and invasion in papillary thyroid carcinoma cells. In vivo study showed that miR‐671‐5p overexpression inhibited tumor growth, downregulated Ki67, and decreased tumor volume and weight. Tripartite motif containing 14 (TRIM14) was verified as downstream target of miR‐671‐5p. The expression of TRIM14 was suppressed by miR‐671‐5p in papillary thyroid carcinoma. Overexpression of TRIM14 increased cell viability, and promoted the proliferation, migration, and invasion of papillary thyroid carcinoma. Moreover, TRIM14 counteracted the suppressive effect of miR‐671‐5p overexpression on papillary thyroid carcinoma cell growth. In conclusion, miR‐671‐5p repressed progression of papillary thyroid carcinoma through downregulation of TRIM14, providing a promising target for therapy of papillary thyroid carcinoma.
Effects of anticholinergic and sedative medication use on fractures: A self‐controlled design study

Unintentional falls are a leading cause of injury for older adults, and evidence is needed to understand modifiable risk factors. We evaluated 1‐year fall‐related fracture risk and whether dispensing of medications with anticholinergic/sedating properties is temporally associated with an increased odds of these fractures.
Culturally adapting youth mental health first aid training for Asian Americans.

Despite high rates of mental health challenges, Asian Americans are less likely to seek out and receive school-based mental health services (SBMHSs) than their non-Asian peers. The Youth Mental Health First Aid (YMHFA) training is an 8-hr manualized public education program designed to educate adults on recognizing common mental health challenges among adolescents and intervening. However, no published research has evaluated YMHFA among Asian Americans. We culturally adapted YMHFA for Asian Americans (Asian American parents and youth workers) and used a pretest/posttest design to evaluate its effectiveness. Specifically, we (a) added one 2-hr session before the YMHFA to augment engagement with the curriculum and (b) contextualized the YMHFA curriculum content to ensure cultural sensitivity for Asian American participants. Thirty-one Asian immigrant parents (Mage = 45.55, SD = 3.6) and 24 Asian American youth workers (Mage = 23.17, SD = 3.67) participated in YMHFA. Participants' mental health literacy (MHL) and their confidence in using MHFA skills significantly increased after the training. Participants also participated in four focus groups after the training to share their experiences. Participants stated that they benefited from this training and suggested additional cultural adaptations to make the program more appropriate for Asian Americans. Culturally adapted YMHFA may be an effective way to promote MHL and engage Asian Americans in mental health services. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Variation in Auditory Experience Affects Language and Executive Function Skills in Children Who Are Hard of Hearing

Objective: Children who are hard of hearing (CHH) experience delays in spoken language and executive function, but the mechanisms for these deficits remain unresolved. Differences in auditory experience and language skills have been examined as contributing factors to deficits in executive function, primarily with children who are deaf and children with cochlear implants. The theoretical model of cumulative auditory experience quantifies auditory dosage as how much speech is audible and how often children wear their hearing aids. CHH with higher auditory dosage have better language outcomes than peers with less auditory dosage. However, the effects of auditory experience on executive function have not been studied in CHH. The goal of this study was to examine the influences of auditory experience and language skills on the development of executive function in CHH. Design: We collected measures of aided speech audibility, hearing aid use, executive function, and receptive vocabulary in 177 CHH and 86 children with typical hearing who were 5- to 10 years old and matched for socioeconomic status and nonverbal intelligence. Auditory dosage was calculated by combining each child’s average hours of hearing aid use with their audibility for speech to create a variable that quantifies individual differences in auditory access. Results: CHH had lower receptive vocabulary and deficits in executive function related to working memory and selective attention compared to peers with typical hearing. CHH with greater auditory dosage had higher receptive vocabulary than CHH with lower auditory dosage. Better receptive vocabulary was associated with better scores on executive function measures related to working memory and attention. Auditory dosage was also directly associated with measures of verbal working memory. Conclusions: CHH have deficits in language and some, but not all, areas of executive function related to working memory and attention. Auditory dosage was associated with language abilities and verbal working memory. Language was associated with individual differences in executive function skills related to attention and working memory. These results provide support for systems theories regarding the development of executive function in CHH. Interventions that improve auditory access and language may be effective for improving executive function related to working memory and attention in CHH.
Comparing individual and collective management of referential choices in dialogue

Past research shows that when a discourse referent is mentioned repeatedly, it is usually introduced with a full noun phrase and maintained with a reduced form such as a pronoun. Is this also the case in dialogue, where the same referent may be introduced by one person and maintained by another person? An experiment was conducted in which participants either told entire stories to each other or told stories together, thus enabling us to contrast situations in which characters were introduced and maintained by the same person (control condition) and situations in which the introduction and the maintaining of each character were performed by different people (alternating condition). Story complexity was also manipulated through the introduction of one or two characters in each story. We found that participants were less likely to use reduced forms to maintain referents in the alternating condition. The use of reduced forms also depended on the context in which the referent was maintained (in particular, first or second mention of a character) and on story complexity. These results shed light on how the pressure to signal understanding to one’s conversational partner affects referential choices throughout the interaction.
AID overexpression leads to aggressive murine CLL and non-Ig mutations that mirror human neoplasms.

Most cancers become more dangerous by the outgrowth of malignant subclones with additional DNA mutations that favor proliferation or survival. Using chronic lymphocytic leukemia (CLL), a disease exemplary of this process, and a model for neoplasms in general, we created transgenic mice overexpressing the enzyme, activation-induced deaminase (AID), whose normal function is to induce DNA mutations in B lymphocytes. AID allows normal B lymphocytes to develop more effective immunoglobulin (Ig)-mediated immunity, but also is able to mutate non-Ig genes, predisposing to cancer. In chronic lymphocytic leukemia (CLL), AID expression correlates with poor prognosis suggesting a role for this enzyme in disease progression. Nevertheless, direct experimental evidence identifying the specific genes that are mutated by AID and indicating that those genes are associated with disease progression is not available. To address this point, we overexpressed Aicda in a murine model of CLL (Em-TCL1). Analyses of TCL1/AID mice demonstrate a role for AID in disease kinetics, CLL-cell proliferation, and the development of cancer-related target mutations with canonical AID signatures in non-Igs genes. Notably, our mouse models can accumulate mutations in the same genes that are mutated in human cancers. Moreover, some of these mutations occur at homologous positions, leading to identical or chemically-similar amino acid substitutions as in human CLL and lymphoma.Together, these findings support a direct link between aberrant AID activity and CLL driver mutations that are then selected for their oncogenic effects, whereby AID promotes aggressiveness in CLL and other B-cell neoplasms.
Substance use behavior and its lifestyle-related risk factors in Bangladeshi high school-going adolescents: An exploratory study

Substance abuse is a major concern worldwide and is increasing rapidly in Bangladesh. However, there are no prior studies concerning lifestyle-related factors that influence adolescents’ substance use behavior. Therefore, the present study investigated the prevalence of substance use and its associated sociodemographic and lifestyle-related risk factors among a total of 424 Bangladeshi high school-going adolescents through a structured questionnaire interview study. The survey questionnaire consisted of socio-demographics, lifestyle-related information, and substance use-related questions. For data analysis, descriptive and inferential statistics were performed using SPSS (Statistical Package for Social Science) version 22.0, and a p-value of <0.05 determined statistical significance. Results showed that 21.2%, 14.4%, and 15.1% of the participants reported smoking, using a drug, and consuming alcohol, respectively, at least once during their lifespan; whereas the current (i.e., past-month) rates were reported to be 10.4%, 2.8%, and 3.1%, respectively. Overall, the current substance use risk factors were identified as being male, not being from science academic background, having less family influence on personal life, irregular teeth brushing, being smartphone users, using a smartphone for a longer time, and being late-night sleepers. From the list of identified risk factors of substance use, those that are modifiable may be targeted to evolve a prevention program to manage this problem in Bangladeshi adolescents.
Response to Gard et al.'s (2021) Comments on the Critical Review “Polychlorinated Biphenyl Tissue‐Concentration Thresholds for Survival, Growth, and Reproduction in Fish”

This response is offered to the critique by Gard et al. (2021) of our meta‐analysis of polychlorinated biphenyl (PCB)‐induced toxicity data in fish (Berninger and Tillitt 2019). Gard et al. (2021) offered numerous comments, the most substantive suggesting that 1) we should have added no‐observable–adverse effect residue (NOAER) data from additional studies and all data points from selected studies, and 2) the uncertainty of aggregating data from different PCB mixtures, different species, and different life stages is too great based on a limited data set. The additional studies Gard et al. suggested either were not designed to produce toxicological data, had experimental design issues, were confounded by co‐contaminants, or did not contain paired exposure–effects data and as such were not appropriate to add to the data set. Lowest‐observable–adverse effect residue (LOAER) values were selected for our analysis because they represent population sensitivities from the central portions of a frequency distribution (the linear portion of dose–response curves). As a consequence, there is less uncertainty in these input data (LOAER values) and greater confidence that they accurately represent the response of fish populations tested. Modeling NOAER values is in the extrapolation portion of a dose–response relationship and subject to enhanced uncertainty. The Gard et al. (2021) critique ignores this fundamental principle of toxicology and adds/deletes data points from our data set without clear selection criteria, which artificially enhances the uncertainty of their models that ultimately are not useful. We reject the premise that it is better to use individual study data as opposed to aggregation of PCB‐induced toxicity thresholds in fish. The scientific process involves critical review to understand strengths and weaknesses of ideas, concepts and models. Vetting ideas to determine a more logical, accurate, conceptual model for predictions that will provide the basis for regulatory decisions is absolutely required for environmental protection. In this regard, we welcome constructive criticism that identifies weaknesses of our approach and offers an even more robust path forward. Unfortunately, the critique by Gard et al. (2021) does not accurately assess our meta‐analysis, nor do they offer a path forward.
Selective auditory attention modulates cortical responses to sound-location change in younger and older adults.

The present study measured scalp potentials in response to low-frequency, narrowband noise bursts changing location in the front, azimuthal plane. At question was whether selective auditory attention has a modulatory effect on the cortical encoding of spatial change, and whether older listeners with normal-hearing thresholds would show depressed cortical representation for spatial changes relative to younger listeners. Young and older normal-hearing listeners were instructed to either passively listen to the stimulus presentation or actively attend to a single location (either 30° left or right of midline) and detect when a noise stream moved to the attended location. Prominent peaks of the electroencephalographic scalp waveforms were compared across groups, location, and attention condition. In addition, an opponent-channel model of spatial coding was performed to capture the effect of attention on spatial-change tuning. Younger listeners not only showed larger responses overall but a greater dynamic range in their response to location changes. Results suggest that younger listeners were acquiring and encoding key spatial cues at early cortical processing areas. On the other hand, each group exhibited modulatory effects of attention to spatial-change tuning, indicating that both younger and older listeners selectively attend to space in a manner that amplifies the available signal.
Colon‐Targeted Adhesive Hydrogel Microsphere for Regulation of Gut Immunity and Flora

Intestinal immune homeostasis and microbiome structure play a critical role in the pathogenesis and progress of inflammatory bowel disease (IBD), whereas IBD treatment remains a challenge as the first‐line drugs show limited therapeutic efficiency and great side effect. In this study, a colon‐targeted adhesive core–shell hydrogel microsphere is designed and fabricated by the ingenious combination of advanced gas‐shearing technology and ionic diffusion method, which can congregate on colon tissue regulating the gut immune‐microbiota microenvironment in IBD treatment. The degradation experiment indicates the anti‐acid and colon‐targeted property of the alginate hydrogel shell, and the in vivo imaging shows the mucoadhesive ability of the thiolated‐hyaluronic acid hydrogel core of the microsphere, which reduces the systematic exposure and prolongs the local drug dwell time. In addition, both in vitro and in vivo study demonstrate that the microsphere significantly reduces the secretion of pro‐inflammatory cytokines, induces specific type 2 macrophage differentiation, and remarkably alleviates colitis in the mice model. Moreover, 16S ribosomal RNA sequencing reveals an optimized gut flora composition, probiotics including Bifidobacterium and Lactobacillus significantly augment, while the detrimental communities are inhibited, which benefits the intestinal homeostasis. This finding provides an ideal clinical candidate for IBD treatment.
Actigraphy: Metrics reveal it is not a valid tool for determining sleep in neonates

Study of emerging sleep–wake patterns in neonates is important for promptly identifying and treating abnormal sleep behaviours to ensure healthy infant development and neurobehavioral outcomes. Current methods to assess sleep are costly, labour intensive, and particularly difficult to implement in fragile, hospitalised infants requiring intensive medical care. The aim of the present study was to assess the validity of actigraphy as a tool for detecting sleep in preterm infants, using polysomnography (PSG) as the “gold standard”. A total of 10 neonates (mean [SD] 35.8 [1.2] weeks post‐menstrual age; five female) hospitalised since birth for prematurity each participated in one 8–10 hr session during which PSG and actigraphy were recorded simultaneously. Inter‐feed minute‐by‐minute PSG Sleep–Wake scores were compared to concurrent actigraph epochs categorised as either “Sleep” or “Wake” using three separate movement‐per‐minute thresholds (≤20, ≤40, ≤80). Tool validity was assessed using five metrics. A key finding was that for each of the movement thresholds there was high agreement rate, sensitivity, and predictive value of sleep (85.2%–97.2%), whereas specificity and predictive value of wake remained low (12%–46%). Receiver operating characteristic curve analysis also revealed low discriminatory power of actigraphy for estimating sleep (area under the curve = 0.636; Youden’s Index J = 0.2173). Lack of sufficient minutes of autonomous wake periods among infants was identified as a key limitation in actigraphy. Findings from the present study suggest actigraphy cannot be validated for Sleep/Wake discrimination in preterm infants and that proper validation requires sufficient data from periods of both Sleep and Wake.
Long‐term increases in pathogen seroprevalence in polar bears (Ursus maritimus) influenced by climate change

The influence of climate change on wildlife disease dynamics is a burgeoning conservation and human health issue, but few long‐term studies empirically link climate to pathogen prevalence. Polar bears (Ursus maritimus) are vulnerable to the negative impacts of sea ice loss as a result of accelerated Arctic warming. While studies have associated changes in polar bear body condition, reproductive output, survival, and abundance to reductions in sea ice, no long‐term studies have documented the impact of climate change on pathogen exposure. We examined 425 serum samples from 381 adult polar bears, collected in western Hudson Bay (WH), Canada, for antibodies to selected pathogens across three time periods: 1986–1989 (n = 157), 1995–1998 (n = 159) and 2015–2017 (n = 109). We ran serological assays for antibodies to seven pathogens: Toxoplasma gondii, Neospora caninum, Trichinella spp. , Francisella tularensis, Bordetella bronchiseptica, canine morbillivirus (CDV) and canine parvovirus (CPV). Seroprevalence of zoonotic parasites (T. gondii, Trichinella spp.) and bacterial pathogens (F. tularensis, B. bronchiseptica) increased significantly between 1986–1989 and 1995–1998, ranging from +6.2% to +20.8%, with T. gondii continuing to increase into 2015–2017 (+25.8% overall). Seroprevalence of viral pathogens (CDV, CPV) and N. caninum did not change with time. Toxoplasma gondii seroprevalence was higher following wetter summers, while seroprevalences of Trichinella spp. and B. bronchiseptica were positively correlated with hotter summers. Seroprevalence of antibodies to F. tularensis increased following years polar bears spent more days on land, and polar bears previously captured in human settlements were more likely to be seropositive for Trichinella spp. As the Arctic has warmed due to climate change, zoonotic pathogen exposure in WH polar bears has increased, driven by numerous altered ecosystem pathways.