bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoblast Lineage Cell-derived Sema3A Regulates Bone Homeostasis Independently of Androgens
Authors: Yamashita Yu , Hayashi Mikihito , Saito Mitsuru , Nakashima Tomoki 
Published: August 2022

AbstractSemaphorin 3A (Sema3A) coordinates bone resorption and formation under the control of estrogen signaling. However, the contribution of osteoblast lineage cell–derived Sema3A to vertebral homeostasis has remained unclear. Moreover, it is unknown whether androgen signaling is involved in Sema3A expression in osteoblast lineage cells. In this study, we show that osteoblast lineage cell–derived Sema3A plays a key role in bone homeostasis independent of androgen signaling. Sema3a deletion with Sp7-Cre did not alter the trabecular bone mass in lumbar vertebrae, along with there being no significant difference in Sema3a mRNA expression. In contrast, osteoblast lineage cell–specific deletion of Sema3A with BGLAP-Cre led to decreased bone volume in both long bones and lumbar vertebrae. In addition, osteoblast lineage cell–derived Sema3A was not involved in orchidectomy-induced bone loss because androgen deficiency did not affect Sema3A protein expression. Thus, these results indicate that Sema3A derived from osteoblast lineage cells acts as an osteoprotective factor, even in vertebrae, and its expression is controlled in an androgen-independent manner.
The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty
Authors: Brito Vinicius N , Canton Ana P M , Seraphim Carlos Eduardo , Abreu Ana Paula , Macedo Delanie B , Mendonca Berenice B , Kaiser Ursula B , Argente Jesús , Latronico Ana Claudia 
Published: August 2022

AbstractThe etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.
The uncoating of EV71 in mature late endosomes requires CD-M6PR
Authors: Ohka Seii , Tan Soon Hao , Ishiyama Eri , Ogasawara Katsutoshi , Hanasaka Tomohito , Ishida Kinji , Hagiwara Kyoji , Liu Chia-Chyi , Chong Pele Choi-Sing , Hanaki Ken-ichi , Schiavo Giampietro 
Published: August 2022

ABSTRACT
Enterovirus 71 (EV71) is one of the causative agents of hand-foot-and-mouth disease, which in some circumstances could lead to severe neurological diseases. Despite of its importance for human health, little is known about the early stages of EV71 infection. EV71 starts uncoating with its receptor, human scavenger receptor B2 (hSCARB2), at low pH. We show that EV71 was not targeted to lysosomes in human rhabdomyosarcoma cells overexpressing hSCARB2 and that the autophagic pathway is not essential for EV71 productive uncoating. Instead, EV71 was efficiently uncoated 30 min after infection in late endosomes (LEs) containing hSCARB2, mannose-6-phosphate receptor (M6PR), RAB9, bis(monoacylglycero)phosphate and lysosomal associated membrane protein 2 (LAMP2). Furthering the notion that mature LEs are crucial for EV71 uncoating, cation-dependent (CD)-M6PR knockdown impairs EV71 infection. Since hSCARB2 interacts with cation-independent (CI)-M6PR through M6P-binding sites and CD-M6PR also harbor a M6P-binding site, CD-M6PR is likely to play important roles in EV71 uncoating in LEs.
Practical guide for preparation, computational reconstruction and analysis of 3D human neuronal networks in control and ischaemic conditions
Authors: Räsänen Noora , Harju Venla , Joki Tiina , Narkilahti Susanna 
Published: August 2022

ABSTRACT
To obtain commensurate numerical data of neuronal network morphology in vitro, network analysis needs to follow consistent guidelines. Important factors in successful analysis are sample uniformity, suitability of the analysis method for extracting relevant data and the use of established metrics. However, for the analysis of 3D neuronal cultures, there is little coherence in the analysis methods and metrics used in different studies. Here, we present a framework for the analysis of neuronal networks in 3D. First, we selected a hydrogel that supported the growth of human pluripotent stem cell-derived cortical neurons. Second, we tested and compared two software programs for tracing multi-neuron images in three dimensions and optimized a workflow for neuronal analysis using software that was considered highly suitable for this purpose. Third, as a proof of concept, we exposed 3D neuronal networks to oxygen-glucose deprivation- and ionomycin-induced damage and showed morphological differences between the damaged networks and control samples utilizing the proposed analysis workflow. With the optimized workflow, we present a protocol for preparing, challenging, imaging and analysing 3D human neuronal cultures.
The role of cellular quiescence in cancer – beyond a quiet passenger
Authors: Tomasin Rebeka , Bruni-Cardoso Alexandre 
Published: August 2022

ABSTRACT
Quiescence, the ability to temporarily halt proliferation, is a conserved process that initially allowed survival of unicellular organisms during inhospitable times and later contributed to the rise of multicellular organisms, becoming key for cell differentiation, size control and tissue homeostasis. In this Review, we explore the concept of cancer as a disease that involves abnormal regulation of cellular quiescence at every step, from malignant transformation to metastatic outgrowth. Indeed, disrupted quiescence regulation can be linked to each of the so-called ‘hallmarks of cancer’. As we argue here, quiescence induction contributes to immune evasion and resistance against cell death. In contrast, loss of quiescence underlies sustained proliferative signalling, evasion of growth suppressors, pro-tumorigenic inflammation, angiogenesis and genomic instability. Finally, both acquisition and loss of quiescence are involved in replicative immortality, metastasis and deregulated cellular energetics. We believe that a viewpoint that considers quiescence abnormalities that occur during oncogenesis might change the way we ask fundamental questions and the experimental approaches we take, potentially contributing to novel discoveries that might help to alter the course of cancer therapy.
Development of dim-light vision in the nocturnal reef fish family Holocentridae. II: Retinal morphology
Authors: Fogg Lily G. , Cortesi Fabio , Lecchini David , Gache Camille , Marshall N. Justin , de Busserolles Fanny 
Published: August 2022

ABSTRACT
Ontogenetic changes in the habitats and lifestyles of animals are often reflected in their visual systems. Coral reef fishes start life in the shallow open ocean but inhabit the reef as juveniles and adults. Alongside this change in habitat, some species also change lifestyles and become nocturnal. However, it is not fully understood how the visual systems of nocturnal reef fishes develop and adapt to these significant ecological shifts over their lives. Therefore, we used a histological approach to examine visual development in the nocturnal coral reef fish family, Holocentridae. We examined 7 representative species spanning both subfamilies, Holocentrinae (squirrelfishes) and Myripristinae (soldierfishes). Pre-settlement larvae showed strong adaptation for photopic vision with high cone densities and had also started to develop a multibank retina (i.e. multiple rod layers), with up to two rod banks present. At reef settlement, holocentrids showed greater adaptation for scotopic vision, with higher rod densities and higher summation of rods onto the ganglion cell layer. By adulthood, they had well-developed scotopic vision with a highly rod-dominated multibank retina comprising 5–17 rod banks and enhanced summation of rods onto the ganglion cell layer. Although the ecological demands of the two subfamilies were similar throughout their lives, their visual systems differed after settlement, with Myripristinae showing more pronounced adaptation for scotopic vision than Holocentrinae. Thus, it is likely that both ecology and phylogeny contribute to the development of the holocentrid visual system.
Stigma-directed services (Stig2Health) to improve ‘linkage to care’ for people living with HIV in rural Tanzania: study protocol for a nested pre-post implementation study within the Kilombero and Ulanga Antiretroviral Cohort
Authors: Magnolini Raphael , Senkoro Elizabeth , Kalinjuma Aneth Vedastus , Kitau Olivia , Kivuma Bernard , Samson Leila , Eichenberger Anna , Mollel Getrud Joseph , Krinke Eileen , Okuma James , Ndege Robert , Glass Tracy , Mapesi Herry , Vanobberghen Fiona , Battegay Manuel , Weisser Maja 
Published: August 2022

Background: HIV-related stigma is a major barrier to the timely linkage and retention of patients in HIV care in sub-Saharan Africa, where most people living with HIV/AIDS reside. In this implementation study we aim to evaluate the effect of stigma-directed services on linkage to care and other health outcomes in newly diagnosed HIV-positive patients. Methods: In a nested project of the Kilombero and Ulanga Antiretroviral Cohort in rural Tanzania, we conduct a prospective observational pre-post study to assess the impact of a bundle of stigma-directed services for newly diagnosed HIV positive patients. Stigma-directed services, delivered by a lay person living with HIV, are i) post-test counseling, ii) post-test video-assisted teaching, iii) group support therapy and group health education, and iv) mobile health. Patients receiving stigma services (enrolled from 1st February 2020 to 31st August 2021) are compared to a historical control receiving the standard of care (enrolled from 1st July 2017 to 1st February 2019). The primary outcome is ‘linkage to care’. Secondary endpoints are retention in care, viral suppression, death and clinical failure at 6-12 months (up to 31st August 2022). Self-reported stigma and depression are assessed using the Berger Stigma scale and the PHQ-9 questionnaire, respectively. The sample size calculation was based on cohort data from 2018. Assuming a pre-intervention cohort of 511 newly diagnosed adults of whom 346 (68%) were in care and on antiretroviral treatment (ART) at 2 months, a 10% increase in linkage (from 70 to 80%), a two-sided type I error rate of 5%, and 90% power, 321 adults are required for the post-implementation group. Discussion: We expect that integration of stigma-directed services leads to an increase of proportions of patients in care and on ART. The findings will provide guidance on how to integrate stigma-directed services into routine care in rural sub-Saharan Africa.
Systematic review of immunogenicity and duration of immunity of currently licensed pertussis wP vaccines in children
Authors: Bagattini Angela M. , Quarti Michelle M. , S. Martinez-Silveira Martha , Policena Gabriela , E. Coelho Lara , M. Luz Paula , B. Russell Louise , M. Toscano Cristiana 
Published: August 2022

Background: Currently recommended whole cell pertussis (wP) vaccination schedule for children includes a 3-dose primary schedule, and at least one booster dose. When estimating the impact of additional strategies to reduce pertussis burden through modelling, duration of immunity conferred by childhood immunization is among the parameters models are most sensitive to. We aim to assess the duration of immunity of currently available wP vaccines in children and the additional protection conferred by booster doses. Methods: We conducted a systematic review of published studies of current commercially available vaccines indexed in Medline, Embase, Web of Science, Lilacs, SciELO and Central until September 2021. We included clinical trials, observational longitudinal, and cross-sectional studies. Citation screening, data extraction, and risk of bias and methodological quality assessment were done in duplicate by independent reviewers, following the study protocol registered in PROSPERO. Studies were included if they reported primary data on the protection, immunity, or duration of immunity conferred by ≥3 doses of wP vaccine in healthy children, without restriction to time or location of the study. Outcomes included clinical events or serological evidence of protection. Results: We included 12 studies conducted from 2007-2020 with heterogeneous methodological quality. Studies report on 5 of the 18 currently available wP vaccines in use. After primary immunization, geometric mean concentration (GMC) of anti-pertussis toxin ranged from 9.1 EU/mL (95% confidence intervals [CI]: 8.1-10.2) to 50.9 (95%CI: 45.9-56.4). Prior to the 1st booster, GMC titers were low ranging from 4.7 to 10 EU/mL, and after the 1st booster averaged around 42 EU/mL. Conclusions: The limited available evidence on immunogenicity of currently available wP vaccines reinforces the need for booster doses and suggests that the duration of wP immunity is short, probably <5 years. This is important information for vaccination policy makers, investigators and modelers. PROSPERO registration: CRD42018107309
Couple Therapists’ States of Mind - thematic analysis of narratives of psychoanalytical couple therapists on experiences of work during the COVID - 19 pandemic
Authors: Małek Karolina , Jurczyk Tomasz 
Published: August 2022

Cel pracyPsychoterapia zdalna stanowiła praktykowaną formę pomocy pacjentom jeszcze przed wybuchem pandemii COVID-19, jednak od marca 2020 roku stała się powszechnym sposobem pracy, stawiając przed wszystkimi uczestnikami procesu poważne wyzwania. Jak wskazują badania, terapeuci pracujący w różnych podejściach i z różnymi grupami pacjentów różnili się w postawach wobec pracy zdalnej, a tym samym gotowością do modyfikowania swojego sposobu pracy. Celem niniejszego badania było zrozumienie subiektywnego doświadczenia terapeutów prowadzenia psychoanalitycznej psychoterapii par podczas pierwszego roku pandemii.MetodaDo badania, przeprowadzonego w paradygmacie jakościowym, zaproszono 10 terapeutów par, pracujących w ujęciu psychoanalitycznym, korzystających z superwizji prowadzonych przez specjalistów z Tavistock Relationship w oparciu o opracowany tam model pracy z parami. Zebrano dziesięć narracji, w których badani terapeuci dzielili się swobodnie swoimi doświadczeniami prowadzenia terapii par podczas pierwszego roku pandemii. Następnie otrzymany materiał został poddany analizie tematycznej przez dwoje badaczy.WynikiW wyniku przeprowadzonej analizy wyłoniono 4 tematy główne (Zmiany powodowane przez pandemię, Praca w warunkach on-line, Przeżycia pacjentów, O terapeucie). Każdy z nich składał się z kilku tematów szczegółowych.WnioskiOtrzymane wyniki w pewnym stopniu spójne są z rezultatami wcześniej przeprowadzonych badań jakościowych z udziałem terapeutów innych modalności i pracujących z inną grupą pacjentów, co wskazywać może na uniwersalność doświadczeń osób pracujących w obszarze psychoterapii. Jednocześnie udało się wyodrębnić tematy specyficzne dla badanej grupy, odnoszące się z jednej strony do doświadczeń trudności prowadzenia terapii psychoanalitycznej zapośredniczonej przez narzędzia pracy zdalnej, z drugiej zaś do kontekstu psychoterapeutycznej pracy z parami.
Perioperative active warming for preventing neonatal hypothermia: the Neohyp trial
Authors: Vilinsky-Redmond Aliona , Brenner Maria , McCaul Conan , McCann Margaret 
Published: August 2022

Background Perioperative hypothermia for women undergoing elective caesarean section is a common comorbidity, which may result in neonatal hypothermia when at-birth skin-to-skin contact is performed. This trial compared the effectiveness of warm intravenous and room temperature fluids among women performing at birth skin-to-skin contact on perioperative neonatal and maternal heat loss. Methods A double-blind, randomised controlled trial compared warm and room temperature intravenous fluids in 150 healthy women performing at birth skin-to-skin contact while undergoing elective caesarean section. Analysis was based on intention-to-treat. Results Active warming of women significantly reduced neonatal (P=0.02) and maternal (P=0.0027) hypothermia at the end of skin-to-skin contact in the operative theatre, maternal hypothermia on post-anaesthesia care unit admission (P=0.0022) and maternal shivering (P=0.0001). Conclusions Administering warm intravenous fluids during caesarean section when skin-to-skin contact is performed at birth is a safe practice with multiple health benefits for both newborns and their mothers. Consideration should be given to incorporating this intervention into clinical practice procedures promoting skin-to-skin contact in women undergoing elective caesarean section.
Learning about compassion during midwifery education: exploring student midwives' perspectives
Authors: Pearson Maria 
Published: August 2022

Background Although compassionate healthcare is not a new neologism in midwifery, formal study about compassion in undergraduate curricula is relatively unexplored. This research offered an opportunity to explore midwifery students' perspectives of learning about compassion during their course. Methods A mixed-methods approach was used to collect data in three phases. First, 24 first-year student midwives completed a free writing exercise. Second, 81 self-completion questionnaires were given to students from all three years. Third, semi-structured interviews in focus groups were conducted with six first-year students, four second-year students and six third-year students. Thematic analysis was used to interpret qualitative findings. Results The majority of students reported formal study about and for compassion had increased their understanding of the concept. Midwifery practice placements were reported to support students' learning about compassion. Conclusions Formal teaching about compassion during undergraduate midwifery education is recommended. Three distinct, interrelated themes emerged and students' brought their pre-professional life experiences to the classroom and clinical practice; they continued to learn about compassion both formally and informally, depending upon the situations they found themselves in.
FXR deficiency in hepatocytes disrupts the bile acid homeostasis and inhibits autophagy to promote liver injury in Schistosoma japonicum-infected mice
Authors: Zhang Beibei , Li Jing , Zong Xianlong , Wang Jianling , Xin Lianlian , Song Haiyao , Zhang Wenxue , Koda Stephane , Hua Hui , Zhang Bo , Yu Qian , Zheng Kui-Yang , Yan Chao 
Published: August 2022

Background
Schistosomiasis, with 250 million people affected, is characterized by its serious hepatic inflammatory response and fibrosis formation, which could lead to dangerous complications, such as portal hypertension, splenomegaly and even ascites. But until now, the pathogenesis of schistosomiasis remains largely unknown. Farnesoid X Receptor (FXR), a bile acid-activated nuclear transcription factor mainly expresses in hepatocytes in the liver, can regulate liver diseases by controlling bile acid metabolism.

Methodology/Principal findings
In this study, we found that the expression of FXR was decreased in the liver of infected mice as shown by western blot and RT-qPCR assays. Furthermore, hepatocyte-specific FXR-deficient mice (FXRflox/floxAlbCre, FXR-HKO) were generated and infected with ~16 cercariae of S. japonicum for five weeks. We found that FXR deficiency in hepatocytes promoted the progression of liver injury, aggravated weight loss and death caused by infection, and promoted inflammatory cytokines production, such as IL-6, IL-1β, TNF-α, IL-4, IL-10, and IL-13. Surprisingly, hepatic granulomas and fibrosis were not affected. In addition, using UPLC-MS/MS spectrometry, it was found that S. japonicum infection resulted in elevated bile acids in the liver of mice, which was more obvious in FXR-deficient mice. Meanwhile, autophagy was induced in littermate control mice due to the infection, but it was significantly decreased in FXR-HKO mice.

Conclusions/Significance
All these findings suggest that FXR deficiency in hepatocytes disrupts bile acid homeostasis and inhibits autophagy, which may aggravate the damages of hepatocytes caused by S. japonicum infection. It highlights that FXR in hepatocytes plays a regulatory role in the progression of schistosomiasis.