bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal diabetes caused by disrupted pancreatic and β‐cell development
Authors: De Franco Elisa 
Published: October 2021

AbstractNeonatal diabetes is diagnosed before the age of 6 months and is usually caused by single‐gene mutations. More than 30 genetic causes of neonatal diabetes have been described to date, resulting in severely reduced β‐cell number or function. Seven of these genes are known to cause neonatal diabetes through disrupted development of the whole pancreas, resulting in diabetes and exocrine pancreatic insufficiency. Pathogenic variants in five transcription factors essential for β‐cell development cause neonatal diabetes without other pancreatic phenotypes. However, additional extra‐pancreatic features are common. This review will focus on the genes causing neonatal diabetes through disrupted β‐cell development, discussing what is currently known about the genetic and phenotypic features of these genetic conditions, and what discoveries may come in the future.
Hematopoietic PBX‐interacting protein is a novel regulator of mammary epithelial cell differentiation
Authors: Dwivedi Anju , Padala Chiranjeevi , Kumari Anita , Khumukcham Saratchandra Singh , Penugurti Vasudevarao , Ghosh Sinjini , Mazumder Aprotim , Goffin Vincent , Manavathi Bramanandam 
Published: October 2021

Hematopoietic PBX‐interacting protein (HPIP, also known as PBXIP1) is an estrogen receptor (ER) interacting protein that regulates estrogen‐mediated breast cancer cell proliferation and tumorigenesis. However, its functional significance in the context of mammary gland development is unexplored. Here, we report that HPIP is required for prolactin (PRL)‐induced lactogenic differentiation in vitro. Molecular analysis of HPIP expression in mice revealed its induced expression at pregnancy and lactation stages of mammary gland. Moreover, PRL is a lactogenic hormone that controls pregnancy as well as lactation and induces Hpip/Pbxip1 expression in a signal transducer and activator of transcription 5a‐dependent manner. Using mammary epithelial and lactogenic‐competent cell lines, we further show that HPIP plays a regulatory role in PRL‐mediated mammary epithelial cell differentiation, which is measured by acini formation, β‐casein synthesis, and lipid droplet formation. Further mechanistic studies using pharmacological inhibitors revealed that HPIP modulates PRL‐induced β‐casein synthesis via phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) activation. This study also identified HPIP as a critical regulator of autocrine PRL signaling as treatment with the PRL receptor antagonist Δ1‐9‐G129R‐hPRL restrained HPIP‐mediated PRL synthesis, AKT activation, and β‐casein synthesis in cultured HC11 cells. Interestingly, we also uncovered that microRNA‐148a (miR‐148a) antagonizes HPIP‐mediated mammary epithelial cell differentiation. Together, our study identified HPIP as a critical regulator of PRL signaling and revealed a novel molecular circuitry involving PRL, HPIP, PI3K/AKT, and miR‐148a that controls mammary epithelial cell differentiation in vitro.
Improving primary health care quality for refugees and asylum seekers: A systematic review of interventional approaches
Authors: P. Iqbal Maha , Walpola Ramesh , Harris‐Roxas Ben , Li Jiadai , Mears Stephen , Hall John , Harrison Reema 
Published: October 2021

AbstractBackgroundIt has been widely acknowledged that refugees are at risk of poorer health outcomes, spanning mental health and general well‐being. A common point of access to health care for the migrant population is via the primary health care network in the country of resettlement. This review aims to synthesize the evidence of primary health care interventions to improve the quality of health care provided to refugees and asylum seekers.MethodsA systematic review was undertaken, and 55 articles were included in the final review. The Preferred Reporting Items for Systematic Reviews was used to guide the reporting of the review, and articles were managed using a reference‐management software (Covidence). The findings were analysed using a narrative empirical synthesis. A quality assessment was conducted for all the studies included.ResultsThe interventions within the broad primary care setting could be organized into four categories, that is, those that focused on developing the skills of individual refugees/asylum seekers and their families; skills of primary health care workers; system and/or service integration models and structures; and lastly, interventions enhancing communication services. Promoting effective health care delivery for refugees, asylum seekers and their families is a complex challenge faced by primary care professionals, the patients themselves and the communication between them.ConclusionThis review highlights the innovative interventions in primary care promoting refugee health. Primary care interventions mostly focused on upskilling doctors, with a paucity of research exploring the involvement of other health care members. Further research can explore the involvement of interprofessional team members in providing effective refugee/migrant health.Patient or Public ContributionPatient and public involvement was explored in terms of interventions designed to improve health care delivery for the humanitarian migrant population, that is, specifically refugees and asylum seekers.
Mass spectrometric study of the laser‐evaporated Fe–Zr–O system up to 3300 K
Authors: Sheindlin Michael , Frolov Alexander , Petukhov Sergei , Bottomley David , Masaki Kurata , Manara Dario , Costa Davide 
Published: October 2021

AbstractMaterial systems such as U–Zr–O, Fe–Zr–O, and Zr–O have been recognized as fundamental for the analysis of in‐vessel nuclear fuel debris behavior during a severe meltdown accident. In the present work, the evaporation behavior of ZrO2 and Zr–Fe–O systems are investigated using heating with laser pulses of millisecond duration and time‐of‐flight mass spectrometry. The relative partial pressures of main species of vapor over ZrO2 and ZrO2–FeO systems were measured at temperatures above 2750 K. The temperature dependence of O/Zr atomic ratio in vapor over zirconia was analyzed: it turned out that evaporation occurs in a noncongruent mode at temperatures above 3000 K. Evaporation of the Zr–Fe–O system was greatly affected by the fast evaporation of FeO, implying that the atomic Zr/Fe ratio, less than 0.1 below 3000 K, significantly increased with temperature. Moreover, the ratios of main vapor components were defined only by the surface temperature, independent of the zirconia sample origin.
Cytokine profiles and the dynamic of gingivitis development in humans
Authors: Leite Fábio R. M. , Nascimento Gustavo G. , Møller Holger J. , Belibasakis Georgios N. , Bostanci Nagihan , Smith Patricio C. , López Rodrigo 
Published: October 2021

AbstractAimTo investigate the relationship between cytokine profiles and “fast” and “slow” patterns of gingival inflammation development.Materials and MethodsForty‐two adults participated in an experimental gingivitis study, comprising a 2‐week hygiene phase (clinical examination and professional cleaning); a 3‐week induction phase (absence of oral hygiene); and a 2‐week resolution phase (re‐establishment of oral hygiene). Plaque and gingival inflammation scores were assessed. Interferon‐gamma (IFN‐γ), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, and tumour necrosis factor‐alpha (TNF‐α) from gingival crevicular fluid were collected and measured by multiplex ELISA. Group‐based‐trajectory‐modelling (GBTM) was used to model cytokine profiles over the induction phase. The effect of gingival inflammation on cytokine levels over time was estimated with mixed‐effects modelling.ResultsGBTM analysis revealed two cytokine profiles, “non‐organized response” (IL‐4, IL‐6, IL‐8, IL‐12, and IL‐13) and “organized response” (IL‐2, IL‐10, and TNF‐α). Among the “slow” responders, neither cytokine profile was associated with gingivitis. In contrast, a “fast” response was associated with a higher “non‐organized response” factor (coef. 0.14) and a lower “organized response” factor (coef. −0.03).ConclusionA “fast” gingivitis development was associated with a higher “non‐organized response” and a lower “organized response”, which may elucidate the role of individual variability in gingivitis susceptibility.
Prenatal androgenization causes expression changes of progesterone and androgen receptor mRNAs in the arcuate nucleus of female mice across development
Authors: Watanabe Yugo , Prescott Melanie , Campbell Rebecca E. , Jasoni Christine L. 
Published: October 2021

AbstractPrenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS). In prenatally androgenised (PNA) mice, a model of PCOS, progesterone receptor (PR) protein expression is reduced in arcuate nucleus (ARC) GABA neurons. This suggests a mechanism for PCOS‐related impaired steroid hormone feedback and implicates androgen excess with respect to inducing transcriptional repression of the PR‐encoding gene Pgr in the ARC. However, the androgen sensitivity of ARC neurons and the relative gene expression of PRs over development and following prenatal androgen exposure remain unknown. Here, we used a quantitative reverse transcriptase‐polymerase chain reaction (RT‐qPCR) of microdissected ARC to determine the relative androgen receptor (Ar) and progesterone receptor (Pgr) gene expression in PNA and control mice at five developmental timepoints. In a two‐way analysis of variance, none of the genes examined showed expression changes with a statistically significant interaction between treatment and age, although PgrA showed a borderline interaction. For all genes, there was a statistically significant main effect of age on expression levels, reflecting a general increase in expression with increasing age, regardless of treatment. For PgrB and Ar, there was a statistically significant main effect of treatment, indicating a change in expression following PNA (increased for PgrB and decreased for Ar), regardless of age. For PgrA, there was a borderline main effect of treatment, suggesting a possible change in expression following PNA, regardless of age. PgrAB gene expression changes showed no significant main effect of treatment. We additionally examined androgen and progesterone responsiveness specifically in P60 ARC GABA neurons using RNAScope® (Advanced Cell Diagnostics, Inc.) in situ hybridization. This analysis revealed that Pgr and Ar were expressed in the majority of ARC GABA neurons in normal adult females. However, our RNAScope® analysis did not show significant changes in Pgr or Ar expression within ARC GABA neurons following PNA. Lastly, because GABA drive to gonadotropin‐releasing hormone neurons is increased in PNA, we hypothesised that PNA mice would show increased expression of glutamic acid decarboxylase (GAD), the rate‐limiting enzyme in GABA production. However, the RT‐qPCR showed that the expression of GAD encoding genes (Gad1 and Gad2) was unchanged in adult PNA mice compared to controls. Our findings indicate that PNA treatment can impact Pgr and Ar mRNA expression in adulthood. This may reflect altered circulating steroid hormones in PNA mice or PNA‐induced epigenetic changes in the regulation of Pgr and Ar gene expression in ARC neurons.
Role of adenosine signaling in preeclampsia
Authors: Iriyama Takayuki , Sayama Seisuke , Osuga Yutaka 
Published: October 2021

AbstractPlacenta‐specific molecular basis that is responsible for the pathophysiology of preeclampsia (PE) remains to be fully understood. Adenosine, an endogenous nucleoside, is a signaling molecule that is induced under pathological conditions such as hypoxia and is involved in various diseases. Recent evidence on humans and animal models has demonstrated that enhanced placental adenosine signaling contributes to the development of PE. This review is to summarize current progress and discuss the significance of adenosine signaling in the pathophysiology of PE and future perspectives of therapeutic possibilities targeting adenosine signaling.
The prognosis of “sandwich” mode of postoperative chemotherapy and radiation in patients with locally advanced cervical cancer
Authors: Geng Yuning , Wang Ming , Yang Shuli , Zhao Hui , Wu Yumei 
Published: October 2021

AbstractObjectiveThis study aims to evaluate the survival outcome between different postoperative radiation and chemotherapy modes in locally advanced cervical cancer (LACC).MethodsThis study is a retrospective cohort study. A total of 150 patients with LACC underwent radical hysterectomy combined with postoperative radiation and /or chemotherapy from October 2009 to October 2019. Of those, 101 patients who received “sandwich” adjuvant chemotherapy and radiation (SCR) were enrolled into group A and 49 patients who received simple radiation were enrolled into group B. The primary outcome was the rates of progression‐free survival (PFS) and overall survival (OS).ResultsOf 150 patients, 95.3% (143/150) patients complete the study. The rates of deep myometrial invasion (92% and 72.9%, p = 0.007), lymph vascular invasion positive (74.3% and 26.5%, p = 2.59 × 10−8), positive surgical margin (11.9% and 0%, p = 0.012), and lymph‐node involvement (40.6% vs. 4.1%, p = 4.0 × 10−6) at baseline were higher in the group A than group B. There was no difference between the follow‐up time of group A and group B (45.81 ± 16.83 vs. 45.81 ± 16.84 months, p = 0.665). After the postoperative adjuvant, group A achieved the comparable PFS to group B [p = 0.40; hazard ratio (HR), 1.45; 95% CI, 0.62–3.38]. The cumulative rate of OS in group A was comparable in group B (p = 0.31; HR, 1.53; 95% CI, 0.68–3.45).ConclusionsPostoperative ‘sandwich’ chemotherapy and radiation could yield a similar survival rate to radiation alone in LACC women with high‐risk factors such as deep interstitial infiltration, lymphatic vascular space infiltration, positive resection margin, and lymph‐node metastasis.
Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells
Authors: Silva Luan César , Borgato Gabriell Bonifácio , Wagner Vivian Petersen , Martins Manoela Domingues , Rocha Guilherme Zweig , Lopes Márcio Ajudarte , Santos‐Silva Alan Roger , de Castro Júnior Gilberto , Kowalski Luiz Paulo , Nor Jacques E. , Squarize Cristiane H. , Castilho Rogerio Moraes , Vargas Pablo Agustin 
Published: October 2021

AbstractAimTo evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands.Material and MethodsUM‐HMC‐1, UM‐HMC‐2, and UM‐HMC‐3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation.ResultsA single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM‐HMC‐1 and UM‐HMC‐3A cell lines, while UM‐HMC‐2 showed a reduced enzymatic activity.ConclusionCephaeline has shown anti‐cancer properties in all MEC cell lines tested by regulating tumor cells’ viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
Serotonin Receptor (HTR2A) Gene Polymorphism Modulates Social Sharing of Happiness in Both American and Japanese Adults
Authors: Matsunaga Masahiro , Ohtsubo Yohsuke , Masuda Takahiko , Noguchi Yasuki , Yamasue Hidenori , Ishii Keiko 
Published: October 2021

AbstractA single nucleotide polymorphism in the serotonin 2A receptor gene (HTR2Ars6311 guanine [G] vs. adenine [A]) appears associated with positive emotional contagion (social sharing of happiness) in Japanese people. However, it remains unknown whether theHTR2Apolymorphism also impacts the social sharing of happiness in Western cultures. The present study thus compared 207 Japanese university students and 200 American adults (including non‐students). Social sharing of happiness was examined using a vignette‐based questionnaire. Participants were asked to imagine that they were experiencing an emotionally neutral event. At the same time, they were asked to imagine that a friend was experiencing a positive valence event (presence condition), whereas in the other condition such information was not presented (absence condition). Results showed that the G allele carriers felt happier in the presence than in the absence of the friend compared with participants with the AA genotype. Although we did not specifically consider comparability between the two samples, the findings suggest that the effect ofHTR2Apolymorphisms on social sharing of happiness observed in Japanese populations may be applicable to American populations.
A review of philopatry and dispersal in felids living in an anthropised world
Authors: de Oliveira Marina E. , Saranholi Bruno H. , Dirzo Rodolfo , Galetti Pedro M. 
Published: October 2021

Abstract

Typically, males of polygamous mammals are responsible for population connectivity and gene flow via dispersal, whereas females, showing stronger philopatry, strengthen local population stability and growth. These expectations can be disrupted by human disturbances; however, this possibility has been poorly examined in wide‐ranging mammals that are important targets for conservation.

By reviewing philopatry and dispersal in felids, we aimed to evaluate: 1) whether the sex‐related patterns of philopatry and dispersal predicted for polygamous mammals are prevalent in felids, 2) possible major causes underlying each of these behaviours, and 3) if, and to what extent, anthropogenic disturbances can alter patterns of philopatry and dispersal in this animal lineage.

We synthesised the available literature (n = 55 papers) comprising 12 species. Puma concolor was the most‐studied species, followed by other large species. Both philopatry and dispersal were heterogeneously defined, depending on the study aim and the method employed (telemetry, camera trapping or molecular tools).

Most species followed the predicted philopatric and dispersal patterns, and most study areas (76%) were under some type of anthropogenic disturbance drivers. Philopatry was linked to females’ higher dependency on the quality and availability of resources, and to their social dynamics, higher reproductive success, inclusive fitness and demographic aspects of population. Dispersal was frequently linked to competition for mates and resources, and inbreeding avoidance. However, some plasticity was observed in both philopatry and dispersal, especially under the presence of anthropogenic drivers. For example, hunting can create open territories, increasing the number of philopatric females and opportunistic philopatric males. Habitat fragmentation can increase population isolation and male dispersal distance, and the presence of anthropogenic or natural barriers can result in unsuccessful dispersal attempts.

We postulate that human activities affect long‐term population persistence in the Felidae, via disruption of sex‐related patterns of spatial dynamics.
Novel use of a Franklin split lens for cycling with hemianopia
Authors: Crossland Michael D , Reuben Mitchel , Bedford Sarah L 
Published: October 2021

AbstractPurposeOptical rehabilitation for hemianopia includes the prescription of partial aperture prismatic lenses. Fresnel lenses for this purpose have poor optical quality, while bonded lenses have poor cosmesis and can only be made in glass, creating a potential hazard. Here we present an alternative lens type, which does not reduce contrast sensitivity and which can be made in plastic materials.MethodsA rotated Franklin split lens was prescribed for the right eye only to provide a full aperture prismatic lens without using a Fresnel prism or bonded lenses. Using different refractive indices in each lens provided a minimal transition in thickness and an acceptable cosmetic appearance. This lens was prescribed to a 34‐year‐old woman with homonymous right hemianopia. Her contemporaneous comments are presented.ResultsThe rotated Franklin split lens provided 18Δ over the temporal edge of the lens. The wearer noticed chromatic aberration with this lens, but was able to cycle comfortably when wearing the lens without any reduction in contrast.ConclusionsA rotated Franklin split lens can be used for the optical rehabilitation of hemianopia. In this case study, cycling was possible with this lens.
Magnetic resonance imaging validation of medial transthyroid ultrasound‐guided stellate ganglion block: A pilot study
Authors: Chung Boo Young , Holfelder Christian , Feldmann Robert E. , Kleinboehl Dieter , Raum Raoul C. , Benrath Justus 
Published: October 2021

AbstractObjectiveUltrasound‐guided stellate ganglion block (usSGB) facilitates improved accuracy of needle position and application of lesser volumes of local anesthetic (LA). Approaches of usSGB, however, have not fully been optimized with respect to efficacy and technical convenience. This pilot study examined the anatomical position and spatial distribution of a small volume of LA injectate dispensed by medial transthyroid usSGB via magnetic resonance imaging (MRI) and assessment of its effect on cervical sympathetic nerves.MethodsTwelve healthy males were tested in a double‐blinded within‐subject design. In a total of 37 usSGB, 3 ml of LA and saline 0.9% solution were injected intramuscularly into the longus colli muscle (LCM) preventing uncontrollable spread of LA within cervical structures. Immediately after injection, distribution of injectate was traced by MRI. Twenty‐four out of the 37 usSGB‐injections with 3 ml ropivacaine 1% (verum) and saline 0.9% (placebo) were compared. Efficacy of usSGB was assessed by the appearance of oculosympathetic paresis and increases in skin temperature.ResultsAll usSGBs were positioned in the proximity of the LCM muscle belly. Most of the axial injectate was distributed within the transversal plane between the middle section of C5 and the upper section of T1 vertebra. Signs of oculosympathetic paresis and skin temperature increase were found exclusively under verum conditions.ConclusionThis pilot study demonstrated the feasibility of medial transthyroid usSGB using an out‐of‐plane technique and a volume of 3 ml of LA. Further studies are required to establish the relative value and safety of this technique compared to other published approaches.
Ginsborg’s Reading of Wittgenstein on Rules and Normativity
Authors: Ebbs Gary 
Published: October 2021

AbstractHannah Ginsborg argues that according to Wittgenstein, a normal human subject can recognise that a new step is correct without grasping any rule with which the step accords. I argue, on the contrary, that according to Wittgenstein, a normal human subject’s understanding of a series and her capacity to take new steps to be correct continuations of the series are, as Wittgenstein says of “rule” and “accord” (PI §224), “related to one another.” Neither is more fundamental than the other.