bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated synthesis of [68Ga]Ga-FAPI-46 without pre-purification of the generator eluate on three common synthesis modules and two generator types
Authors: Alfteimi Ammar , Lützen Ulf , Helm Alexander , Jüptner Michael , Marx Marlies , Zhao Yi , Zuhayra Maaz
Published: July 2022

Background

The recent development of quinoline-based radiotracers, which act as fibroblast activation protein inhibitors (FAPIs), has shown promising preclinical and clinical advantages. [68Ga]Ga-FAPI-46 is a new radiotracer for in vivo detection of the fibroblast activation protein by positron emission tomography (PET). Recently, the automated synthesis of [68Ga]Ga-FAPI-46 was reported based on pre-concentration and purification of the generator eluate by using a cation exchange-cartridge.

Our aim was to simplify the synthesis and shorten the automated synthesis of [68Ga]Ga-FAPI-46 to make it accessible and thus even more attractive to a broader clinical and scientific community.

Results

We developed and evaluated the GMP compliant automatic synthesis of [68Ga]Ga-FAPI-46 using two different 68Ge/68Ga generators (an Eckert & Ziegler, GalliaPharm generator, 1.85 GBq/50 mCi and an iThemba generator, 1.85 GBq/50 mCi) Somerset West, South Africa) and three different commercial and customized systems: the EasyOne module from Trasis; the GaSy module from Synthra with a customized synthesis template and a customized single use cassette. Additionally, the automatic synthesis of [68Ga]Ga-FAPI-46 was established on a GallElut synthesis module from Scintomics with fixed tubing.

Conclusions

Independent of the synthesis modules or the generators employed we were able to complete the synthesis of [68Ga]Ga-FAPI-46 in 12 min including the process of purification and formulation. In all cases, the final products showed more than 99.5% chemical purity and the radiochemical yield reached around 92.5% (decay corrected). All quality control parameters (e.g. sterility, stability and radiochemical purity) were conform to the European Pharmacopoeia.
Global research trends on the links between insulin resistance and obesity: a visualization analysis
Authors: Zyoud Sa’ed H. , Shakhshir Muna , Abushanab Amani S. , Koni Amer , Shahwan Moyad , Jairoun Ammar A. , Al-Jabi Samah W.
Published: July 2022

Background

Obesity increases the chance of developing insulin resistance. Numerous inflammatory markers have been linked to an increased risk of insulin resistance in obese individuals. Therefore, we performed a bibliometric analysis to determine global research activity and current trends in the field of obesity and insulin resistance.

Methods

Scopus was used between 2002 and 2021 to retrieve publications related to terms related to obesity and insulin resistance. Data were exported to Microsoft Excel. Additionally, we use VOSviewer software to create visualization maps that describe international collaborations and research hotspots.

Results

We identified 6626 publications, including 5754 journal articles, 498 review articles, and 109 letters to the editor. The most productive countries were the United States (n = 995, 30.11%), followed by China (n = 650, 9.81%), Italy (n = 412, 6.22%) and Spain (n = 386, 5.83%). Previously to 2012, this field was mainly focused on ‘adipocyte dysfunctions that link obesity with insulin resistance”; and ‘relationship between obesity, insulin resistance, and risk of cardiovascular disease’. ‘Supplements improve insulin sensitivity‘, and ‘obesity-induced inflammation and insulin resistance’ were found more recently (after 2014), indicating that research in this field has acquired significant interest and emphasis in recent years.

Conclusions

This is the first bibliometric study to focus on publications related to insulin resistance and obesity at the global level. Our reporting of quantifiable knowledge in this field may be useful in providing evidence and direction for future research, clinical practice, and educational initiatives.
Algorithm-based advice taking and clinical judgement: impact of advice distance and algorithm information
Authors: Pálfi Bence , Arora Kavleen , Kostopoulou Olga
Published: July 2022

Evidence-based algorithms can improve both lay and professional judgements and decisions, yet they remain underutilised. Research on advice taking established that humans tend to discount advice—especially when it contradicts their own judgement (“egocentric advice discounting”)—but this can be mitigated by knowledge about the advisor’s past performance. Advice discounting has typically been investigated using tasks with outcomes of low importance (e.g. general knowledge questions) and students as participants. Using the judge-advisor framework, we tested whether the principles of advice discounting apply in the clinical domain. We used realistic patient scenarios, algorithmic advice from a validated cancer risk calculator, and general practitioners (GPs) as participants. GPs could update their risk estimates after receiving algorithmic advice. Half of them received information about the algorithm’s derivation, validation, and accuracy. We measured weight of advice and found that, on average, GPs weighed their estimates and the algorithm equally—but not always: they retained their initial estimates 29% of the time, and fully updated them 27% of the time. Updating did not depend on whether GPs were informed about the algorithm. We found a weak negative quadratic relationship between estimate updating and advice distance: although GPs integrate algorithmic advice on average, they may somewhat discount it, if it is very different from their own estimate. These results present a more complex picture than simple egocentric discounting of advice. They cast a more optimistic view of advice taking, where experts weigh algorithmic advice and their own judgement equally and move towards the advice even when it contradicts their own initial estimates.
Anthropology of tourism: practical and theoretical development in China
Authors: Sun Jiuxia , Luo Yilin
Published: July 2022

This paper examines the origins, developments and new trends of anthropology of tourism in China through a comparison between China and the West. Chinese anthropologists have, since the end of the last century, begun to introduce Western academic achievements and tried to conduct domestic research. In the process of development into a big and great power in tourism, Chinese researchers have intensively absorbed new concepts and new theories from abroad, studied local cases in China’s context, and carry out China-West dialogues in various aspects. Anthropology of tourism in China has seen many breakthroughs in terms of topics, theories, disciplines and methods, contributing its own experiences and new theories to the development of anthropology of tourism worldwide.
Assessment of knowledge, perception, attitude, and use of performance-enhancing substances among students of Faculty of Medicine, Alexandria University, Egypt: a pilot study
Authors: Badr el Dine Fatma Mohamed Magdy , Attia MennattAllah Hassan
Published: July 2022

Background

The market for performance enhancement substances (PESs) is currently one of the fastest expanding sectors. Most studies have always concentrated on athletes in terms of PESs’ misuse, ignoring a critical segment of the community: the future health-care workers. Thus, the aim of the study was to probe the knowledge, perception, and attitude of medical students regarding the misuse of PESs in sports and medical academic study. A cross-sectional study was conducted among students of Alexandria Faculty of Medicine, Egypt. Data were collected via self-administered electronic survey from 208 students of both sexes (aged from 18 to 26 years old). Analysis of factors affecting the consumption of PESs like gender differences, and their prior knowledge and perception was performed using logistic regression models.

Results

More than half of the participants have no idea about law concerning the use of doping substances. There were no significant disparities in knowledge and perception between males and females. Female students, on the other hand, consistently reported having a better understanding of the negative impacts of PESs’ misuse. Surprisingly, females are more prone to consume PESs for cognitive enhancement rather than the physical performance.

Conclusions

The study is the first to explore the awareness of the medical students, their attitude, and perception towards different ethical scenarios confronted in the daily practice. This finding pinpoints that the common trend of striving for fitness and an ideal body shape and weight has produced a shift in the prevalence of the PESs use according to gender in Egypt. Moreover, females in medicine academics are more prone to use PESs to improve the cognitive functions albeit it is nonsignificant statistically. Therefore, efforts should be directed to raise the awareness of medical practitioners of diverse categories of these substances, health hazards, laws, and penalties. More importantly, policy measures for their production, marketing, and misuse among university students should be reconsidered by the government.
Efficacy of Metarhizium brunneum and Beauveria bassiana isolates against the European tent caterpillar, Malacosoma neustria Linnaeus, 1758 (Lepidoptera: Lasiocampidae)
Authors: Topkara Elif Fatma , Yanar Oğuzhan , Sahin Funda , Yanar Yusuf , Yanar Dürdane
Published: July 2022

Background

The European tent caterpillar Malacosoma neustria Linnaeus, 1758 (Lepidoptera: Lasiocampidae), a worldwide pest, feeds on a wide variety of woody and shrub-like plants in its larval stage and causes extensive economic losses. In the fight against this species, environmentally friendly biological control methods should be preferred instead of chemical control. The aim of this study was to evaluate the efficacy of entomopathogenic fungi (EPF) Metarhizium brunneum (ORP-13) and Beauveria bassiana (GOPT-301-2) isolates against the fourth instar larvae of M. neustria under laboratory conditions.

Results

M. neustria eggs were collected from the Kızılırmak Delta of Samsun Province, Turkey, and the fourth instar larvae were used in the experiment. Larvae in the control group were fed on sterilized leaves of Eleagnus rhamnoides. Both fungal isolates were applied onto the larvae at 2 ml for each concentration (1 × 106, 1 × 107, and 1 × 108 conidia ml−1). Ten larvae were placed in each group, and sterilized E. rhamnoides leaves were offered to the larvae. The study was carried out in 9 replicates for each group, and the larvae were observed for 14 days. As a result of the study, it was found that the survival rates of the larvae decreased as concentration increased. It was determined that both isolates caused 100% mortality at 1 × 108 conidia ml−1 concentration. The lowest LC50 value was found in larvae exposed to the ORP-13 isolate.

Conclusion

It has been suggested that M. brunneum and B. bassiana isolates were virulent for M. neustria larvae and can be used for biological control of this species.
Vegetation fires along the Czech rail network
Authors: Nezval Vojtěch , Andrášik Richard , Bíl Michal
Published: July 2022

Background

In the past, fires around railways were often associated with steam locomotives. Although steam locomotives have disappeared from everyday rail traffic, fires still occur. A vegetation fire near Bzenec (Czech Republic) on 21 June 2018 affected, for example, 124,110 m2 of forest and grassland. The investigation revealed that the fire was caused by a spark from a passing train. In this study, we analyzed vegetation fires that occurred near Czech railway lines between 2011 and 2019 to investigate their temporal pattern and relation to weather conditions or to identify the most hazardous locations.

Results

Fires were concentrated mainly between March and August in the afternoon. They are also more likely to occur during periods of high air temperature, low rainfall, low relative air humidity, and low wind speed. Using the KDE+ method, we identified 186 hotspots, which contained 510 vegetation fires and represented only 0.3% of the length of the entire Czech rail network. Spatial analysis revealed that there are more than 4 times higher odds that a vegetation fire occurs near an electrified railway line than near a non-electrified line or that additional 10 freight trains per 24 h increases the odds by 5%.

Conclusions

As the results show, vegetation fires near railway lines are still relatively common phenomenon, mainly due to favorable weather conditions. Grassy areas with dry or dead vegetation are particularly at risk. These areas can be ignited, for example, by sparks from the brakes of railway vehicles. Due to global warming, vegetation fires can be expected to occur more frequently in the future. The identified hotspots can thus be used to reduce the risk of fires, for example by managing the surrounding vegetation.
STTG-net: a Spatio-temporal network for human motion prediction based on transformer and graph convolution network
Authors: Chen Lujing , Liu Rui , Yang Xin , Zhou Dongsheng , Zhang Qiang , Wei Xiaopeng
Published: July 2022

In recent years, human motion prediction has become an active research topic in computer vision. However, owing to the complexity and stochastic nature of human motion, it remains a challenging problem. In previous works, human motion prediction has always been treated as a typical inter-sequence problem, and most works have aimed to capture the temporal dependence between successive frames. However, although these approaches focused on the effects of the temporal dimension, they rarely considered the correlation between different joints in space. Thus, the spatio-temporal coupling of human joints is considered, to propose a novel spatio-temporal network based on a transformer and a gragh convolutional network (GCN) (STTG-Net). The temporal transformer is used to capture the global temporal dependencies, and the spatial GCN module is used to establish local spatial correlations between the joints for each frame. To overcome the problems of error accumulation and discontinuity in the motion prediction, a revision method based on fusion strategy is also proposed, in which the current prediction frame is fused with the previous frame. The experimental results show that the proposed prediction method has less prediction error and the prediction motion is smoother than previous prediction methods. The effectiveness of the proposed method is also demonstrated comparing it with the state-of-the-art method on the Human3.6 M dataset.
The association between black stain and lower risk of dental caries in children: a systematic review and meta-analysis
Authors: Mousa Haneen Raafat Fathi , Radwan Mohamed Zayed , Wassif Ghada Ossama Mohamed , Wassel Mariem Osama
Published: July 2022

Background

Previous literature shows that children with dental black stain might be less susceptible to dental caries. The aim of this study was to systematically review the available literature to determine whether black stain presence could influence the prevalence or severity of dental caries in primary dentition.

Methods

A systematic search of PubMed, Web of Science, Scopus, Google Scholar, OpenGrey, and Egyptian Universities Libraries Consortium was conducted up to December 2020. Quality assessment was done using a modified version of Down’s and Black checklist. Meta-analyses were performed to assess the association between dental black stain and: (i) Likelihood of developing dental caries/being caries-free (ii) Number of teeth affected by dental caries (iii) Number of tooth surfaces affected.

Results

The database search yielded 2164 results, 14 of which matched the eligibility criteria. The meta-analysis showed that the likelihood of developing caries (Fixed effect model: OR [95% CI]: 0.67 [0.54; 0.82]; I2=37%; τ2=0.05), number of teeth affected (Random effects model: MD [95% CI]: –0.98 [–1.54; -0.42]; I2=79%; τ2 =0.44), and number of surfaces affected (Random-effects model: MD [95% CI]: –2.34 [–4.23; -0.44]; I2=85%; τ2 =2.93), were all lower in children with black stain.

Conclusions

It is suggested that dental black stain is associated with lower dental caries experience in children with primary dentition. However, it is questionable whether black stain has a protective effect against dental caries, or whether children at low risk of dental caries are more likely to develop BS because their oral microbiome favors BS-forming organisms.
Dorsal arachnoid web: the ‘scalpel’ sign—a case report and differential diagnosis
Authors: Arora Vijinder , Verma Himanshu , Kamal Raj , Lone Nasir Ahmed
Published: July 2022

Background

Arachnoid web of the spine is a not so common lesion of the spinal cord. It is a band-like arachnoid tissue in the intradural extramedullary compartment that extends to the surface of the spinal cord, with a tendency to occur in the upper dorsal spine causing focal dorsal indentation of the cord that has been coined the ‘scalpel sign’. Patients usually present with progressive weakening and numbing of bilateral lower limb.

Case presentation

A 58-year-old man presented with difficulty in walking and weakness of right leg for 1 year, aggravated over the previous 2 months. There was no history of trauma or fever. Magnetic resonance imaging (MRI) of the dorsal spine was done which revealed a small syrinx within the cord at D4 vertebral level on right side. There was sharp dorsal indentation of the spinal cord and widening of the arachnoid space below this level. This appearance was similar to a surgical scalpel. The anterior subarachnoid space was preserved. On post-contrast images, no parenchymal or meningeal enhancement was detected. The patient was taken up for surgery as the symptoms further progressed. Laminectomy was done from D3 to D7 under general anesthesia, with release of arachnoid web and adhesions. Histology of the resected specimen revealed epithelial cells and fibrous tissue. No inflammatory or neoplastic cells were observed.

Conclusions

Thoracic arachnoid web is a rare entity, which if not treated can have devastating effects on a patient’s neurological function. Careful evaluation of radiological findings is important to avoid delay in diagnosis. Surgery is the only curative treatment and is known to have a favorable outcome.
An intriguing journey of encapsulated apocrine papillary carcinoma of the breast
Authors: Issar Pratibha , Shah Urshita , Ravindranath M. , Gupta Parag
Published: July 2022

Background

Encapsulated Apocrine Papillary Carcinoma (EAPC) of the breast are very rare tumors. They usually present as a cystic mass with mural nodule in women aged 44–84 years. Affected patients may be asymptomatic or complain of breast swelling, or nipple discharge. Mammographic features are nonspecific. The tumor appears as a high-density round or oval mass with circumscribed or spiculated margins on mammography. On Ultrasonography (US) a classical lesion appears as predominantly cystic mass with intracystic solid papillary projections and area of vascularity within it. Contrast Enhanced Breast MRI helps to further characterize the lesion by showing intense contrast enhancement in early phase along with washout curve. Histological features of these tumors are similar to those of classical encapsulated papillary neoplasm, in that myoepithelial cells are absent within the papillary structures and at the periphery of the cyst. They show variable degree of cytological atypia and mitotic activity. Such tumors consist of abundant granular eosinophilic cytoplasm and large nuclei with prominent nucleoli and are androgen receptor positive. However, a multidisciplinary approach is crucial for diagnosis and tissue histology is essential to suitably formulate treatment guidelines. Surgical excision is the preferred treating option for these tumors. Little consensus is available about local radiation and adjuvant therapy for the treatment of such tumors, yet they have been reported to have good prognosis.

Case presentation

This rare case report describes the intriguing journey towards the diagnosis of an encapsulated intracystic apocrine papillary carcinoma in a 52-year-old premenopausal female who presented with palpable breast swelling in left breast. The patient underwent mammography, breast ultrasound and breast MRI concluding it to be a BIRADS 4A lesion. Then the patient was subjected to trucut core biopsy and finally surgical excision was performed. On Histopathology this lesion was diagnosed as encapsulated apocrine papillary carcinoma with androgen receptor positivity and triple negative hormonal status. At present patient is on regular follow-up.

Conclusions

Encapsulated intracystic apocrine papillary carcinoma has a favorable prognosis with low recurrence rate and excellent long-term survival regardless of its invasive nature. Therefore, we present this rare entity to highlight the importance of radiological and histopathology findings in its diagnosis.
Assessment of nano-iron particles impact on the reproductive health of female Wistar rats
Authors: Magdy Menna-Tullah , EL-Ghareeb Abd EL-Wahab A , Attaby Fawzy A , Abd El-Rahman Heba A
Published: July 2022

Background

Iron oxide nanoparticles, especially nano-magnetite, are promising candidates for use in a variety of applications. The present study aimed to investigate the effect of nano-magnetite on the reproductive health of female Wistar rats. Twenty-one adult female rats were divided into three groups: Group 1 served as the control group, Group 2 received a low dose of 5 mg/kg of nano-magnetite, and Group 3 received a high dose of 10 mg/kg of nano-magnetite. For 30 days, rats were intraperitoneally injected three times per week.

The main findings

Revealed that nano-magnetite did not induce a change in body weight or absolute as well as relative reproductive organs weight. Nano-magnetite nanoparticles influenced the reproductive serum hormone levels as well as imbalanced the ovarian and uterine malondialdehyde and total antioxidant activity. After nano-magnetite nanoparticle injection, the histopathological examination revealed apoptosis of granulosa cells of various types of follicles, degenerated corpora lutea, congested blood vessels, and uterine epithelial cells of uterine tissue showed a high level of apoptosis and inflammation. Immunohistochemistry studies demonstrated a significant increase in activated caspase-3 following nano-magnetite injection, indicating an increase in cell apoptosis.

Conclusion

This study demonstrated the negative effect of magnetite nanoparticle on reproductive health and increased the likelihood of infertility.
Mesenchymal stem cells-based therapy in liver diseases
Authors: Han Heng-Tong , Jin Wei-Lin , Li Xun
Published: July 2022

Multiple immune cells and their products in the liver together form a complex and unique immune microenvironment, and preclinical models have demonstrated the importance of imbalances in the hepatic immune microenvironment in liver inflammatory diseases and immunocompromised liver diseases. Various immunotherapies have been attempted to modulate the hepatic immune microenvironment for the purpose of treating liver diseases. Mesenchymal stem cells (MSCs) have a comprehensive and plastic immunomodulatory capacity. On the one hand, they have been tried for the treatment of inflammatory liver diseases because of their excellent immunosuppressive capacity; On the other hand, MSCs have immune-enhancing properties in immunocompromised settings and can be modified into cellular carriers for targeted transport of immune enhancers by genetic modification, physical and chemical loading, and thus they are also used in the treatment of immunocompromised liver diseases such as chronic viral infections and hepatocellular carcinoma. In this review, we discuss the immunological basis and recent strategies of MSCs for the treatment of the aforementioned liver diseases. Specifically, we update the immune microenvironment of the liver and summarize the distinct mechanisms of immune microenvironment imbalance in inflammatory diseases and immunocompromised liver diseases, and how MSCs can fully exploit their immunotherapeutic role in liver diseases with both immune imbalance patterns.
Pappalysins and Stanniocalcins and Their Relationship With the Peripheral IGF Axis in Newborns and During Development
Authors: Martín-Rivada Álvaro , Guerra-Cantera Santiago , Campillo-Calatayud Ana , Andrés-Esteban Eva María , Sánchez Holgado María , Martos-Moreno Gabriel Á , Pozo Jesús , Güemes María , Soriano-Guillén Leandro , Pellicer Adelina , Oxvig Claus , Frystyk Jan , Chowen Julie A , Barrios Vicente , Argente Jesús
Published: July 2022

Context

Pappalysins (PAPP-A, PAPP-A2) modulate body growth by increasing insulin-like growth factor I (IGF-I) bioavailability through cleavage of insulin-like growth factor binding proteins (IGFBPs) and are inhibited by stanniocalcins (STC1, STC2). Normative data on these novel factors, as well as on free IGF-I and uncleaved fractions of IGFBPs, are not well established.

Objective

This work aimed to determine serum concentrations of PAPP-A, PAPP-A2, STC1, and STC2 in relationship with other growth hormone (GH)-IGF axis parameters during development.

Methods

Full-term newborns (150; gestational age: 39.30 ± 1.10 weeks), 40 preterm newborns (30.87 ± 3.35 weeks), and 1071 healthy individuals (aged 1-30 years) were included in the study and divided according to their Tanner stages (males and females): I:163 males, 154 females; II:100 males, 75 females; III:83 males, 96 females; IV: 77 males, 86 females; and V:109 males,128 females.

Results

Serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were elevated at birth and declined throughout childhood. In postnatal life, PAPP-A2 concentrations decreased progressively in concomitance with the free/total IGF-I ratio; however, stanniocalcin concentrations remained stable. PAPP-A2 concentrations positively correlated with the free/total IGF-I ratio (r = +0.28; P < .001) and negatively with the intact/total IGFBP-3 ratio (r = –0.23; P < .001). PAPP-A concentrations inversely correlated with intact/total IGFBP-4 ratio (r = –0.21; P < .001), with PAPP-A concentrations being lower in females at all ages. Association studies indicate the importance of stanniocalcins and pappalysins in the control of this axis in an age-specific manner.

Conclusion

This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of cleaved and uncleaved IGFBPs.
The Lack of Bmal1, a Core Clock Gene, in the Intestine Decreases Glucose Absorption in Mice
Authors: Onuma Shinsuke , Kinoshita Saori , Shimba Shigeki , Ozono Keiichi , Michigami Toshimi , Kawai Masanobu
Published: July 2022

The circadian clock network is an evolutionarily conserved system that regulates systemic metabolism, such as glucose homeostasis. Intestinal tissue is a pivotal organ for the regulation of glucose metabolism, mainly via glucose absorption into the circulation; however, the significance of the intestinal circadian clock network for glucose metabolism remains largely unclear. We herein utilized a mouse model in which Bmal1, a core clock gene, was deleted in an intestine-specific manner (Bmal1Int–/– mice) and demonstrated a rhythmic expression of Sglt1 with its peak at zeitgeber time (ZT) 10.7 ± 2.8 in control mice, whereas this was lost in Bmal1Int–/– mice. Mechanistically, chromatin immunoprecipitation analysis revealed rhythmic binding of CLOCK to the E-box elements in the Sglt1 gene in control mice; however, this was absent in Bmal1Int–/– mice. Accordingly, SGLT1 protein levels were decreased during the dark phase in Bmal1Int–/– mice and this was associated with impaired glucose absorption, leading to a decline in hepatic glycogen levels at ZT4, which was restored by ingestion of high-sucrose water. Additionally, when mice were starved from ZT0, greater expression of the lipolysis-related gene Pnpla2 was observed in adipose tissue of Bmal1Int–/– mice, and this was not noted when glycogen storage was restored by high-sucrose water prior to fasting, suggesting that higher Pnpla2 expression in Bmal1Int–/– mice was likely caused by lower glycogen storage. These results indicate that disruption of the intestinal circadian clock system impairs glucose absorption in the intestine and affects systemic glucose homeostasis.
GATA6 is a crucial factor for Myocd expression in the visceral smooth muscle cell differentiation program of the murine ureter
Authors: Kurz Jennifer , Weiss Anna-Carina , Lüdtke Timo H.-W. , Deuper Lena , Trowe Mark-Oliver , Thiesler Hauke , Hildebrandt Herbert , Heineke Joerg , Duncan Stephen A. , Kispert Andreas
Published: July 2022

Smooth muscle cells (SMCs) are a crucial component of the mesenchymal wall of the ureter, as they account for the efficient removal of the urine from the renal pelvis to the bladder by means of their contractile activity. Here, we show that the zinc-finger transcription factor gene Gata6 is expressed in mesenchymal precursors of ureteric SMCs under the control of BMP4 signaling. Mice with a conditional loss of Gata6 in these precursors exhibit a delayed onset and reduced level of SMC differentiation and peristaltic activity, as well as dilatation of the ureter and renal pelvis (hydroureternephrosis) at birth and at postnatal stages. Molecular profiling revealed a delayed and reduced expression of the myogenic driver gene Myocd, but the activation of signaling pathways and transcription factors previously implicated in activation of the visceral SMC program in the ureter was unchanged. Additional gain-of-function experiments suggest that GATA6 cooperates with FOXF1 in Myocd activation and SMC differentiation, possibly as pioneer and lineage-determining factors, respectively.
Etv4 regulates nociception by controlling peptidergic sensory neuron development and peripheral tissue innervation
Authors: Ríos Antonella S. , Paula De Vincenti Ana , Casadei Mailin , Aquino Jorge B. , Brumovsky Pablo R. , Paratcha Gustavo , Ledda Fernanda
Published: July 2022

The perception of noxious environmental stimuli by nociceptive sensory neurons is an essential mechanism for the prevention of tissue damage. Etv4 is a transcriptional factor expressed in most nociceptors in dorsal root ganglia (DRG) during the embryonic development. However, its physiological role remains unclear. Here, we show that Etv4 ablation results in defects in the development of the peripheral peptidergic projections in vivo, and in deficits in axonal elongation and growth cone morphology in cultured sensory neurons in response to NGF. From a mechanistic point of view, our findings reveal that NGF regulates Etv4-dependent gene expression of molecules involved in extracellular matrix (ECM) remodeling. Etv4-null mice were less sensitive to noxious heat stimuli and chemical pain, and this behavioral phenotype correlates with a significant reduction in the expression of the pain-transducing ion channel TRPV1 in mutant mice. Together, our data demonstrate that Etv4 is required for the correct innervation and function of peptidergic sensory neurons, regulating a transcriptional program that involves molecules associated with axonal growth and pain transduction.
Bidirectional regulation between AP-1 and SUMOylation pathway genes modulates inflammatory signaling duringSalmonellainfection
Authors: Kumar Pharvendra , Soory Amarendranath , Mustfa Salman Ahmad , Sarmah Dipanka Tanu , Devvanshi Himadri , Chatterjee Samrat , Bossis Guillaume , Ratnaparkhi Girish S. , Srikanth Chittur V.
Published: July 2022

Post-translational modifications (PTMs), such as SUMOylation, are known to modulate fundamental processes of a cell. Infectious agents such as Salmonella Typhimurium (STm), which causes gastroenteritis, utilize the PTM mechanism SUMOylation to hijack the host cell. STm suppresses host SUMO pathway genes UBC9 (also known as UBE2I) and PIAS1 to perturb SUMOylation for an efficient infection. In the present study, the regulation of SUMO pathway genes during STm infection was investigated. A direct binding of c-Fos (encoded by FOS), a component of activator protein-1 (AP-1), to promoters of both UBC9 and PIAS1 was observed. Experimental perturbation of c-Fos led to changes in the expression of both UBC9 and PIAS1. STm infection of fibroblasts with SUMOylation-deficient c-Fos (c-FOS-KOSUMO-def-FOS) resulted in uncontrolled activation of target genes, leading to massive immune activation. Infection of c-FOS-KOSUMO-def-FOS cells favored STm replication, indicating misdirected immune mechanisms. Finally, chromatin immunoprecipitation assays confirmed a context-dependent differential binding and release of AP-1 to and from target genes due to its phosphorylation and SUMOylation, respectively. Overall, our data point towards the existence of a bidirectional cross-talk between c-Fos and the SUMO pathway and highlight their importance in AP-1 function in STm infection and beyond.

This article has an associated First Person interview with the first author of the paper.
Access to the sky near the horizon and stars does not play a crucial role in compass calibration of European songbird migrants
Authors: Pakhomov Alexander , Prokshina Anisia , Cellarius Fedor , Mouritsen Henrik , Chernetsov Nikita
Published: July 2022

Migratory birds use different global cues including celestial and magnetic information to determine and maintain their seasonally appropriate migratory direction. A hierarchy among different compass systems in songbird migrants is still a matter for discussion owing to highly variable and apparently contradictory results obtained in various experimental studies. How birds decide whether and how they should calibrate their compasses before departure remains unclear. A recent ‘extended unified theory’ suggested that access to both a view of the sky near the horizon and stars during the cue-conflict exposure might be crucial for the results of cue-conflict experiments. In this study, we performed cue-conflict experiments in three European songbird species with different migratory strategies (garden warbler, Sylvia borin; pied flycatcher, Ficedula hypoleuca; and European robin, Erithacus rubecula; juveniles and adults; spring and autumn migrations) using a uniform experimental protocol. We exposed birds to the natural celestial cues in a shifted (120 deg clockwise/counterclockwise) magnetic field from sunset to the end of the nautical twilight and tested them in orientation cages immediately after cue-conflict treatments. None of the species (apart from adult robins) showed any sign of calibration even if they had access to a view of the sky and local surroundings near the horizon and stars during cue-conflict treatments. Based on results of our experiments and data from previous contradictory studies, we suggest that no uniform theory can explain why birds calibrate or do not calibrate their compass systems. Each species (and possibly even different populations) may choose its calibration strategy differently.
Political Parties Do Matter in US Cities … for Their Unfunded Pensions
Authors: Dippel Christian
Published: July 2022

This paper studies public sector pension obligations, the biggest fiscal challenge currently facing many US cities. Employing a regression discontinuity design around close elections, benefit payments out of a city’s public sector pensions are shown to grow faster under Democratic party mayors, while contributions into the pensions do not. Previous research showed that parties do not matter for a wide range of cities’ fiscal expenditures and explained this with voters imposing fiscal discipline. This paper replicates previous results but shows that parties can matter for shrouded expenditure types that voters do not pay attention to, especially if they benefit well-organized interest groups. (JEL D72, H72, H75, J32, J45)
How Much Are Public School Teachers Willing to Pay for Their Retirement Benefits? Comment
Authors: Ni Shawn , Podgursky Michael , Wang Fangda
Published: July 2022

In a widely cited study, Fitzpatrick (2015) found that more than one quarter of Illinois teachers were unwilling to pay 19 cents for pension enhancements worth one dollar in present value. We revisit this finding by tracking the same cohort of teachers to retirement, permitting exact measurement of service years and the annuity received. The vast majority of teachers purchased the upgrade. Among those who did not, the net benefit of the upgrade is negative given their retirement timing. The complex relationship between the timing of retirement and potential gain in pension wealth makes drawing inferences about teachers’ willingness to pay for this benefit difficult. (JEL H75, I21, J26, J32, J45)
Replication of alphaviruses requires a pseudoknot that involves the poly(A) tail
Authors: Olsthoorn René C.L.
Published: July 2022

Alphaviruses, such as the Sindbis virus and the Chikungunya virus, are RNA viruses with a positive sense single-stranded RNA genome that infect various vertebrates, including humans. A conserved sequence element (CSE) of ∼19 nt in the 3′ noncoding region is important for replication. Despite extensive mutational analysis of the CSE, no comprehensive model of this element exists to date. Here, it is shown that the CSE can form an RNA pseudoknot with part of the poly(A) tail and is similar to the human telomerase pseudoknot with which it shares 17 nt. Mutants that alter the stability of the pseudoknot were investigated in the context of a replicon of the Sindbis virus and by native gel electrophoresis. These studies reveal that the pseudoknot is required for virus replication and is stabilized by UAU base triples. The new model is discussed in relation to previous data on Sindbis virus mutants and revertants lacking (part of) the CSE.
DPC-Net: Distributed Point Convolution Network for large-scale point clouds semantic segmentation
Authors: Shao Yuyuan , Tong Guofeng , Peng Hao , Ma Mingwei , Zhang Jindong
Published: July 2022

Background: Applying convolution neural networks for large-scale 3D point clouds semantic segmentation is quiet challenging, due to the unordered characteristics of 3D data and the computation burden of large-scale point clouds.

Methods: To solve these problems, we designed DPC-Net (Distributed Point Convolution Network). The input point clouds of DPC-Net are partitioned by the K-nearest neighbor strategy and reordered based on Euclidean distance. For reducing computation and memory consumption while retaining critical features, the random sampling strategy is used and a distributed point convolution operation is designed. Our novel convolution method extracts parallel local geometric information including space distance and angle features, respectively. Furthermore, our proposed method could be easily and efficiently embedded into many networks for point clouds semantic segmentation.

Results: Extensive experimental results on the Semantic3D and CSPC (Complex Scene Point Cloud) datasets indicate that the proposed DPC-Net not only obtains state-of-the-art performances but also reduces semantic segmentation time.

Conclusions: In general, we present an efficient and lightweight deep convolutional network, DPC-Net, which captures local geometric features and local contextual information to predict point labels.
The Neuroimaging Data Model Linear Regression Tool (nidm_linreg): PyNIDM Project
Authors: Kumar Ashmita , Crowley Albert , Queder Nazek , Poline JB , Ghosh Satrajit S. , Kennedy David , Grethe Jeffrey S. , Helmer Karl G. , Keator David B.
Published: July 2022

The Neuroimaging Data Model (NIDM) is a series of specifications for describing all aspects of the neuroimaging data lifecycle from raw data to analyses and provenance. NIDM uses community-driven terminologies along with unambiguous data dictionaries within a Resource Description Framework (RDF) document to describe data and metadata for integration and query. Data from different studies, using locally defined variable names, can be retrieved by linking them to higher-order concepts from established ontologies and terminologies. Through these capabilities, NIDM documents are expected to improve reproducibility and facilitate data discovery and reuse. PyNIDM is a Python toolbox supporting the creation, manipulation, and querying of NIDM documents. Using the query tools available in PyNIDM, users are able interrogate datasets to find studies that have collected variables measuring similar phenotypic properties. This, in turn, facilitates the transformation and combination of data across multiple studies.

The focus of this manuscript is the linear regression tool which is a part of the PyNIDM toolbox and works directly on NIDM documents. It provides a high-level statistical analysis that aids researchers in gaining more insight into the data that they are considering combining across studies. This saves researchers valuable time and effort while showing potential relationships between variables. The linear regression tool operates through a command-line interface integrated with the other tools (pynidm linear-regression) and provides the user with the opportunity to specify variables of interest using the rich query techniques available for NIDM documents and then conduct a linear regression with optional contrast and regularization.
Community-driven ELIXIR activities in single-cell omics
Authors: Czarnewski Paulo , Mahfouz Ahmed , Calogero Raffaele A. , Palagi Patricia M. , Portell-Silva Laura , Gonzalez-Uriarte Asier , Soneson Charlotte , Burdett Tony , Szomolay Barbara , Videm Pavankumar , Hotz Hans-Rudolf , Papatheodorou Irene , Hancock John M. , Grüning Björn , Haerty Wilfried , Krause Roland , Capella-Gutierrez Salvador , Leskošek Brane , Alessandri Luca , Arigoni Maddalena , Rezen Tadeja , Botzki Alexander , Ferk Polonca , Lindvall Jessica , Heil Katharina F. , Ishaque Naveed , Korpelainen Eija
Published: July 2022

Single-cell omics (SCO) has revolutionized the way and the level of resolution by which life science research is conducted, not only impacting our understanding of fundamental cell biology but also providing novel solutions in cutting-edge medical research. The rapid development of single-cell technologies has been accompanied by the active development of data analysis methods, resulting in a plethora of new analysis tools and strategies every year. Such a rapid development of SCO methods and tools poses several challenges in standardization, benchmarking, computational resources and training. These challenges are in line with the activities of ELIXIR, the European coordinated infrastructure for life science data. Here, we describe the current landscape of and the main challenges in SCO data, and propose the creation of the ELIXIR SCO Community, to coordinate the efforts in order to best serve SCO researchers in Europe and beyond. The Community will build on top of national experiences and pave the way towards integrated long-term solutions for SCO research.
Prevalence of Fabry disease in Iraq
Authors: Younus Naji Al Atbee Mohammed , Allawi Ali Abdulmajid Dyab , Almukhtar Safa E. , Ibrahim Rasheed Jawad , Hammoudi Faten Abdulghani , Sami Tuama Hala , Esam Mohammed Al Baldawi Mohammed , Al Farhan Hasan , Ali Ala Sh.
Published: July 2022

Background: Fabry disease occurs due to mutations in the α-galactosidase A (GLA) gene present in the X-chromosome, which results in α-galactosidase A (α-GAL A) enzyme deficiency, leading to the intracellular accumulation of glycosphingolipids like globotriaosylceramide (Gb3). It involves multiorgan dysfunction, particularly affecting kidneys, heart, and central and peripheral nervous system. We intended to evaluate the prevalence of Fabry disease in various regions of Iraq along with the clinical manifestations.

Methods: This cross-sectional multi-center study was conducted in Iraq with 1148 patients with variable presentations from January 2018 to June 2022. The demography, patient medical and family history were recorded. Routine clinical investigations were performed along with some specific assessments. Lysosomal α-GAL A enzyme activity was determined using the dried blood spot test followed by tandem mass spectrometry, where values between 200–2000 pmol/spot*20 h were considered normal. Any patient with α-GAL A activity <100 pmol/spot*20h was sent for genetic testing for confirmation of the diagnosis. Statistical analysis of data involved Pearson’s chi-squared test.

Results: In total, 17 patients had Fabry disease, with a 16:1 male:female ratio. The disorder was predominant in the 10–30-year age group. Renal dysfunction was the dominant clinical manifestation (82.3%), followed by peripheral neuropathy (35.3%), angiokeratoma (29.4%), corneal verticillate (23.5%), and left ventricular hypertrophy (17.6%). The prevalence of Fabry disease was highest in north Iraq, followed by middle and south regions.

Conclusions: A prompt and timely diagnosis of Fabry disease is the cornerstone for preventing complications, especially renal and cardiac involvement.
Effects of vaccination against COVID-19 on the emotional health of older adults
Authors: Alarcon-Ruiz Christoper A. , Romero-Albino Zoila , Soto-Becerra Percy , Huarcaya-Victoria Jeff , Runzer-Colmenares Fernando M. , Romani-Huacani Elisa , Villarreal-Zegarra David , Maguiña Jorge L. , Apolaya-Segura Moises , Cuba-Fuentes Sofía
Published: July 2022

Background: The COVID-19 pandemic significantly impacted the mental and emotional health of the elderly, especially those from low to middle-income countries. However, COVID-19 vaccination may reduce this influence. Therefore, we aimed to estimate the effect of vaccination against COVID-19 on the emotional health of older adults.

Methods: We selected a national, random, and stratified sample of non-hospitalized adults aged 60 to 79 years from Peru who intended to receive or had already received the COVID-19 vaccine during recruitment. During June and July 2021, the assessed outcomes were the fear, anxiety, and worry about COVID-19, general anxiety, and depression at baseline and after a month. We estimated the adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for each altered emotional health outcomes in those who had one and two doses, compared with those who were not vaccinated using multilevel logistic regression with mixed effects.

Results: We recruited 861 older adults with 20.8% of loss to follow-up. At baseline, 43.9% had received only one dose of the vaccine, and 49.1% had two doses. In the analysis during follow-up, those who had two doses had less fear (aOR: 0.19; CI 95%: 0.07 to 0.51) and anxiety to COVID-19 (aOR: 0.45; CI 95%: 0.22 to 0.89), compared to unvaccinated. We observed no effects in those with only one dose.

Conclusions: Two doses of COVID-19 vaccination in older adults improves their perception of COVID-19 infection consequences. This information could be integrated into the vaccination campaign as an additional beneficial effect.