bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Italian registry for patients with Prader-Willi syndrome
Authors: Salvatore Marco , Torreri Paola , Rocchetti Adele , Maghnie Mohamad , Patti Giuseppa , Crinò Antonino , Elia Maurizio , Greco Donatella , Romano Corrado , Grugni Graziano , Taruscio Domenica 
Published: December 2022

Abstract
Background
Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools i) to collect clinical and epidemiologic data, ii) to assess the clinical management including the diagnostic delay, iii) to improve patients’ care and iv) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results.
Materials and methods
The Italian PWS registry was established in 2019 with the aims i) to describe the natural history of the disease, ii) to determine clinical effectiveness of health care services, iii) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality.
Results
A total of 165 patients (50,3% female vs 49,7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4,6 years. Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33,3% of patients. Central hypothyroidism was reported in 20% of patients; 94,7% of children and adolescents and 13,3% of adult patients is undergoing GH treatment.
Conclusions
The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.
Dissection of a Cell Atlas of Developing Somatic Embryos in Cotton by Single-cell RNA-sequencing and Spatial Transcriptomic and Metabolomic Analyses
Authors: Ge Xiao-Yang , Yu Xiaole , Liu Zhixin , Yuan Jiachen , Qin Aizhi , Wang Ye , Chen Yanli , Qin Wenqiang , Liu Yumeng , Liu Xingxing , Zhou Yaping , Wang Peng , Yang Jincheng , Liu Hao , Zhao Zihao , Hu Mengke , Zhang Yixin , Sun Susu , Herrera-Estrella Luis , Tran Lam-Son Phan , Sun Xuwu , Li Fuguang 
Published: December 2022

Abstract

Somatic embryogenesis is a major pathway for the regeneration of cotton in tissue culture, and a major technique used for cotton breeding and improvement. The signaling pathway regulating the process of somatic embryogenesis in cotton are extremely complex and still poorly characterized. Little is known about the mechanisms regulating the changes that occur in gene expression and metabolites during somatic embryogenesis at a single-cell resolution. Here, we investigated the spatial and single-cell expression profiles of key genes and metabolic patterns of key metabolites by integrated single-cell RNA-sequencing, spatial transcriptomics, and spatial metabolomics. To evaluate the results of the above analyses, we characterized the potential roles of two representative marker genes AATP1 and DOX2 in the regulation of somatic embryo development. A publicly accessible web-based resource database (http://cottonsomaticembryo.cricaas.com.cn) was generated to facilitate future studies designed to analyze the expression patterns of marker genes at specific developmental stages.
Needs and contents of a customized digital tool for retention in care among breast- feeding and pregnant women living with HIV in Kilimanjaro
Authors: Maro Rehema , Ngowi Kennedy , Martin Haikael , Dillip Angel , Masika Lydia , Mtenga Alan , Mtesha Benson , Boer Marion Sumari-de 
Published: December 2022

Abstract
Background: Retention in care and adherence to medication among pregnant and breastfeeding women living with HIV (PBWLH) are crucial for prevention of mother-to-child transmission (PMTCT) of HIV. Due to the comprehensive coverage of mobile phones, digital tools, including the use of internet-enabled medication dispensers and short message service (SMS), have been described as potential interventions to improve adherence. Therefore, the study’s main objective was to understand the needs and contents of a customized digital tool for retention in care and medication adherence among PBWLH.
Method: A mixed-methods study was conducted from September 2021 to March 2022 at five health facilities in Kilimanjaro region. Pregnant and breastfeeding receiving PMTCT services were included in a survey using a semi-structured questionnaire. Among the interviewed, twenty breastfeeding participants were purposively selected, trained, and enrolled to use an internet-enabled medication dispenser for one month. They received different types of SMS reminders for four weeks and feedback on their adherence patterns from a nurse counsellor after one month using an adherence graph from Wisepill. Later, exit interview and an in-depth interview (IDI) were conducted to explore needs and content. We did descriptive analyses for quantitative data and thematic content analyses for qualitative data.
Results: Among 142 women interviewed, 42(29.5%) were pregnant, and 100 (70.5%) were breastfeeding. A majority of 136(95%) had access to mobile phones and used SMS daily. Ninety-six percent were interested in receiving reminder messages. Nearly 86(61%) preferred to be reminded daily before medication intake time. Showing adherence graphs during tailored feedback sessions was highly appreciated. Qualitative findings revealed more insights into the content of reminders and educational SMS. Most people prefer neutral SMS which does not contain the word “medication”. Health educational SMS contents preferred breastfeeding, opportunistic diseases, nutrition, and entrepreneurship education. Overall, SMSs were regarded as helpful in reminding clients of medication time and medication dispenser provided them with privacy and safe storage for their medication.
Conclusion: This study helps to construct useful content for future digital adherence tools to support the health of pregnant and breastfeeding women living with HIV. Digital tools seem to be highly needed.
Routine surveillance of upper urinary tract imaging for diagnosing upper urinary tract urothelial cancer recurrence in patients with non-muscle invasive bladder cancer having a tumor size ≥30 mm and carcinoma in situ.
Authors: Nishimura Nobutaka , Miyake Makito , Miyamoto Tatsuki , Shimizu Takuto , Fujii Tomomi , Morizawa Yosuke , Hori Shunta , Gotoh Daisuke , Nakai Yasushi , Torimoto Kazumasa , Tanaka Nobumichi , Fujimoto Kiyohide 
Published: December 2022

Abstract
Background
Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow-up of non-muscle invasive bladder cancer is recommended, its necessity remains invalidated. We performed a single-institute long-term follow-up cohort study to identify risk factors for upper urinary tract urothelial cancer recurrence after non-muscle invasive bladder cancer treatment, as well as the clinical impact of routine surveillance imaging.
Methods and materials
A retrospective chart review of 864 patients with primary non-muscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. Oncological outcomes included upper urinary tract urothelial cancer recurrence-free survival and overall survival. Moreover, we examined the opportunities to diagnose its recurrence.
Results
Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. On multivariate Fine-Gray proportional regression analyses, a tumor size ≥ 30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence-free survival. Recurrence was associated with shorter overall survival. Among the aforementioned 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in two (10.5%), urine cytology in two (10.5%), presence of gross hematuria in one (5.3%), and unknown methods in two (10.5%).
Conclusion
Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with non-muscle invasive bladder cancer accompanied by a tumor size ≥ 30 mm and carcinoma in situ.
Polymeric curcumin nanospheres for lysozyme aggregation inhibition, antibacterial and wound healing applications
Authors: Rananaware Pranita , Bauri Samir , Keri Rangappa , Mishra Monalisa , Brahmkhatri Varsha 
Published: December 2022

Abstract
Curcumin is a renowned drug for its numerous applications as an anti-inflammatory, anti-oxidant, anti-allergic, and anti-hyperglycemic agent. However, its clinical applications are limited because of its low physicochemical stability, solubility, cellular uptake, and rapid systemic clearance. Various nanoformulations have been proposed and characterized to upsurge curcumin's solubility and bioavailability. Nanomaterials have much potential to modulate the aggregation kinetics of several proteins, which may lead to the treatment option for several neurological disorders and act as a multi-therapeutic agent. The present study reports highly stable polymeric nanoparticles consisting of curcumin and polyvinylpyrrolidone, C-PVP, and further conjugated with gold nanoparticles, C-PVP-Au, were synthesized. The synthesized conjugates C-PVP and C-PVP-Au were investigated for amyloid aggregation inhibition activity, antimicrobial activity, and wound healing applications. The anti-amyloidogenic capacity of nanoconjugates for model protein, hen egg-white lysozyme (HEWL), was examined at pH and temperature-induced aggregation. The ThT binding assay, fibril size measurement, and electron microscopy results revealed that conjugates suppress fibrillogenesis in HEWL. The highest amyloid inhibition activity obtained against C-PVP and C-PVP-Au was 31 µg.mL-1 and 30 µg.mL-1, respectively. The dissociation activity for amyloid aggregation was observed against Q-PVP and Q-PVP-Au at 29 µg.mL-1 and 27 µg.mL-1, respectively. The antibacterial studies show significant antibacterial efficacy against Escherichia coli (E.coli) in the presence of C-PVP and C-PVP-Au. The substantial antibacterial potential of C-PVP@PVA and C-PVP-Au@PVA membranes shows promising wound healing applications. Membranes containing curcumin polymeric nanoparticles, gold nanoparticles, and polyvinyl alcohol (PVA) promote the antibacterial activity and wound healing activity to the wound of Drosophila. C-PVP-Au@PVA membrane healed the wound faster than the C-PVP@PVA, and it can be used for better results in wound healing. Thus, C-PVP-Au NP and C-PVP NP have higher bioavailability and stability and can act as multifunctional therapeutic agents for amyloid-related diseases and wound management systems.
Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion
Authors: Fang Pengfei , Qiao Hang , Xia Mingyu , Cheng Yiyuan , Zhou Jintong , Zheng Li , Li Wei , Wang Jing 
Published: December 2022

Abstract
Aminoacyl-tRNA synthetases (AARSs), a family of essential protein synthesis enzymes, are attractive targets for drug development. Although several different types of AARS inhibitors have been discovered, AARS covalent inhibitors have not been reported. Here we present five unusual crystal structures showing that threonyl-tRNA synthetase (ThrRS) is covalently inhibited by a natural product, obafluorin (OB). The residue forming a covalent bond with OB is a tyrosine in ThrRS active center, which is not commonly modified by covalent inhibitors. The two hydroxyl groups on the o-diphenol moiety of OB form two coordination bonds with the conserved zinc ion in the active center of ThrRS. Therefore, the beta-lactone structure of OB can undergo ester exchange reaction with the phenolic group of the adjacent tyrosine to form a covalent bond between the compound and the enzyme, and allow its nitrobenzene structure to occupy the binding site of tRNA. In addition, when this tyrosine was replaced by a lysine or even a weakly nucleophilic arginine, similar bonds could also be formed. This work not only reports the mechanism of the first covalent inhibitor of an AARS, but also highlights a powerful warhead of covalent inhibitor that can target multiple different amino acid side chains.
An ARIMA model to quantify the impact of COVID-19 nonpharmaceutical interventions on the epidemiology of varicella in China, 2005–2020
Authors: Wang Miaomiao , Hu Yuehua , Li Xudong , Yin Dapeng , You Meiying , Wang Tianqi 
Published: December 2022

Abstract
Background: Varicella is a common respiratory infectious disease. Since 2020, non-pharmaceutical interventions targeting SARS-CoV-2 greatly affected the activity of other respiratory-transmitted diseases. The aim of our study was to quantify changes of varicella activity in China associated with implementation of COVID-19 non-pharmaceutical interventions (NPIs) and raise awareness of the possibility of an “immunity debt” that may increase risk of varicella outbreaks and activity.
Methods: We developed and fit an autoregressive integrated moving average (ARIMA) model with historical data on monthly varicella outbreak cases in China that were reported between January 2005 and December 2018. The selected, optimal model was used to predict outbreak cases of varicella from January 2019 to June 2020. We evaluated the reliability of the model by comparing the actual and predicted values for 2019. We then used the model to compare the actual and predicted values for first half of 2020 to quantify the impact of the COVID-19-NPIs on varicella.
Results: Four models passed parameter tests (all p<0.05) and the residual tests (all p>0.05): ARIMA（2，1，2)(1，1，0)12, ARIMA（2，1，2)(1，1，1)12, ARIMA（2，1，2)(2，1，0)12, and ARIMA（2，1，2)(0，1，2)12. The model, ARIMA (2,1,2) (1,1,0)12 was determined to be the optimal model, with a high goodness of fit R2 (0.488) and a small, standardized BIC (14.174). We showed that the optimal model fit well because actual outbreak cases in 2019 were within 95% confidence intervals of the model-predicted outbreak cases for 2019. During 2020 however, actual outbreak cases were fewer than the number of cases predicted at the lower limits of the model’s 95% confidence intervals, and actual 2019 cases were 93.37% lower than the number of cases predicted for the first half of 2020 had there been no COVID-19 NPIs.
Conclusions: It is feasible to quantify the impact of COVID-19-targeted NPIs on varicella outbreak cases using a time series model. Our optimal ARIMA model showed that varicella activity was significantly decreased by COVID-19 NPIs. The marked absence of varicella during the first half of 2020 likely led to an immunity debt, thus increasing the likelihood of future varicella outbreaks, off-season varicella activity, and pressure on medical services when COVID-19 NPIs are relaxed.
Cubic nanoparticles as potential carriers for a natural anticancer drug: development, in vitro and in vivo characterization
Authors: Abdou Randa , Mojally Mariam , Dawoud Mohamed 
Published: December 2022

Abstract
Natural compounds that elicit anticancer properties are of great interest for cancer therapy. However, the low solubility and bioavailability of these compounds limit their use as efficient anticancer drugs. To avoid these drawbacks, incorporation of these compounds into cubic nanoparticles (cubosomes) was carried out. Cubosomes containing bergapten which is a natural anticancer compound isolated from Ficus carica were prepared by the homogenization technique using monoolein and poloxamer. These cubosomes were characterized for size, zeta potential, entrapment efficiency, small angle X-ray diffraction, In-vitro release, In-vitro cytotoxicity, cellular uptake, and antitumor activity. Particle size of cubosomes was 220 ± 3.6 nm with almost neutral zeta potential -5 ± 1.2 mV and X-ray measurements confirmed the existence of the cubic structure. Additionally, more than 90% of the natural anticancer drug was entrapped within the cubosomes. A sustained release over 30 hours was obtained for these cubosomes. Finally, these cubosomes illustrated higher In-vitro cytotoxicity and In-vivo tumor inhibition compared with the free natural anticancer compound. Thus, cubosomes could be promising carriers for enhancement of antitumor efficiency of this natural compound
Formulation of Calendula officinalis, Glycine max, and Aloe vera extract topical gel ointment attenuates rheumatoid arthritis in rats via inhibition of pro-inflammatory cytokines
Authors: Gutierrez Rosa Martha Pérez , Pérez Julio Tellez 
Published: December 2022

Abstract
Background: Several pharmacological effects have been reported on Calendula officinalis (C), Aloe vera (A) and Glycine max (G) scientific validation of its rheumatoid arthritis property of the combination of these plants in topical gel ointment has not been done so far. Due to its promising therapeutic effects, to improve its efficacy, we designed combined these plants in gel ointment (CAG/gel). This study aimed to investigate special participation of a new topical herbal formulation containing CAG in gel ointment in vitro and in vivo anti-inflammatory models.
Methods: HPLC analysis were performed to investigate the chemical composition of herbal formulation. The efficacy of CAG/gel as potential treatment was supported in CFA-induced-arthritis rats in lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 studies and proliferation of B and T lymphocytes.
Result: In the phytochemical profile, seventeen flavonoids were identified. Results indicated that topical administration of CAG/gel to CFA-induced-arthritis rats showed a significant reduction of paw swelling like those of the diclofenac used as reference. Arthritic joints produce the remission of disease and recovery of the joint structure and regulates the levels of proinflammatory mediators. CAG/gel modulates adjuvant-induced rheumatoid arthritis by regulating inflammatory cytokines. CAG/gel treatment showed that the polyphenolic-rich extract no cytotoxic effect in RAW 264.7 cells and also exhibited significantly inhibition production of tumor necrosis factor (TNF)-α, interleukin 1β (IL-1β), interleukin (IL)-6, nitric oxide (NO),and inducible nitric oxide synthase (iNOS) in LPS-induced inflammation in macrophages RAW 264.7. In addition, CAG/gel significantly decreased the abnormal proliferation of B and T lymphocytes.
Conclusion: Findings demonstrated that treatment with CAG/gel provides satisfactory rheumatoid arthritis property to those in the standard diclofenac. The improved rheumatoid arthritis, especially in the 10% CAG/gel groups, can be attributed to phytochemical content which reveals the presence of anti-inflammatory and antioxidant as the major active components. The mechanism of anti-rheumatoid arthritis associated to decrease of inflammatory mediators and pro-inflammatory cytokines to its immune function. The CAG/gel exhibited a significant anti-inflammatory activity with a synergistic effect between the flavonoids contained in the three plants. Thus, CAG/gel ointment is a reasonable alternative to the topical formulation for the treatment of rheumatoid arthritis conditions.
Evidence of manganese incorporation and distribution at the nanoscale in coccolithophore calcite
Authors: Bottini Cinzia , Dapiaggi Monica , Rotiroti Nicola , Gambacorta Gabriele , Bettoni Chiara , Tucoulou Remi 
Published: December 2022

Abstract
The coccolithophore algae (Calcihaptophycidae) produce an extracellular covering of calcium carbonate plates (coccoliths) and are responsible for up to 10% of global carbon fixation through photosynthesis and biomineralization. Therefore, any alteration in cell functioning and calcification may strongly affect the ocean-atmosphere system. In this regard, the identification of any variation of the element pathways to the cell and their incorporation in the coccolith is important to understand the response of these organisms to changes in (past) environmental conditions and to identify (paleo)ecological proxies. Here, we focus on manganese which is an essential element for coccolithophore functioning: understanding whether manganese is also incorporated in coccolith calcite and if its distribution is species-specific is of seminal importance. In order to obtain ultra-high resolution (50 x 50 nm) spatial elemental distribution maps of Early to mid-Cretaceous (ca. 122 to 110 Ma) coccoliths we used synchrotron-based XRF analyses at the nano scale. The studied nannofossils belong to different taxa preferring low to higher surface-water fertility and were extracted from samples of different ages (from early Aptian to early Albian) collected in distant oceanic settings including the western Tethys, the Pacific and proto-North Atlantic Ocean.
The analyses showed a high correlation in the spatial distribution of calcium and manganese in the coccoliths, suggesting that manganese is present in the coccolith calcite, and it was likely incorporated during coccolith formation. Moreover, the studied species show different Mn/Ca ratios suggesting that there is a species-specific control on the manganese uptake.
Secondary calcite was also identified but it displays higher Mn/Ca ratios compared to biogenic calcite. Only the specimens collected from a black shale displayed secondary calcite crusts probably formed at the sediment-water interface after coccolith precipitation to the seafloor. Suboxic/anoxic conditions promoted manganese remobilization from Mn-oxides and Mn-oxyhydroxides which was incorporated in the secondary calcite. The Mn/Ca ratio in coccolith calcite crusts may therefore be indicator of (past) oxygen variations in bottom waters.
hmc, a cell with previously unknown function couples neuropeptide transmitters with muscle contraction during a rhythmic behavior in C. elegans
Authors: Choi Ukjin , Hu Mingxi , Sieburth Derek 
Published: December 2022

Abstract
Neuropeptides in the brain have both excitatory and inhibitory effects on neuronal activity through paracrine signaling to local circuits. Here, we show that neuropeptides can activate and inhibit calcium responses in a single target cell of previously unknown function, hmc, in C. elegans. We show that hmc controls a discrete muscle contraction during a rhythmic behavior. Live imaging shows that hmc is activated by the neuropeptide like protein FLP-22 in phase with the pacemaker every 50 seconds. FLP-22 is released from a bifunctional motor neuron AVL and activates the frpr-17 G protein-coupled receptor (GPCR), which leads to the activation of a G alpha s-protein kinase A (PKA) signaling pathway in hmc. PKA signaling is not required for hmc activation but instead potentiates hmc activation. hmc activity is inhibited by signaling from the neuropeptide FLP-9, which functions through the GPCR frpr-21 in hmc. Behavioral, calcium imaging, and genetic studies suggest that hmc itself is not contractile but is functionally coupled to muscles through gap junctions composed of UNC-9/innexin. These results indicate that neuropeptides can function as volume neurotransmitters to control the activity state of a target cell and reveal a function for hmc that may be similar to that of endothelial cells.