bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline-related molecular phenotype in Metazoa: conservation and innovation highlighted by comparative transcriptomics
Authors: Piccinini Giovanni , Milani Liliana 
Published: January 2023

Abstract
Background
In Metazoa, the germline represents the cell lineage devoted to the transmission of genetic heredity across generations. Its functions intuitively evoke the crucial roles that it plays in organism development and species evolution, and its establishment is tightly tied to animal multicellularity itself. The molecular toolkit expressed in germ cells has a high degree of conservation between species, and it also shares many components with the molecular phenotype of some animal totipotent cell lineages, like planarian neoblasts and sponge archaeocytes. The present study stems from these observations and represents a transcriptome-wide comparative analysis between germline-related samples of 9 animal species (7 phyla), comprehending also totipotent lineages classically considered somatic.

Results
Differential expression analyses were performed for each species between germline-related and control somatic tissues. We then compared the different germline-related transcriptional profiles across the species without the need for an a priori set of genes. Through a phylostratigraphic analysis, we observed that the proportion of phylum- and Metazoa-specific genes among germline-related upregulated transcripts was lower than expected by chance for almost all species. Moreover, homologous genes related to proper DNA replication resulted the most common when comparing the considered species, while the regulation of transcription and post-transcriptional mechanisms appeared more variable, showing shared upregulated functions and domains, but very few homologous whole-length sequences.

Conclusions
Our wide-scale comparative analysis mostly confirmed previous molecular characterizations of specific germline-related lineages. Additionally, we observed a consistent signal throughout the whole data set, therefore comprehending both canonically defined germline samples (germ cells), and totipotent cell lineages classically considered somatic (neoblasts and archaeocytes). The phylostratigraphic analysis supported the less probable involvement of novel molecular factors in the germline-related transcriptional phenotype and highlighted the early origin of such cell programming and its conservation throughout evolution. Moreover, the fact that the mostly shared molecular factors were involved in DNA replication and repair suggests how fidelity in genetic material inheritance is a strong and conserved driver of germline-related molecular phenotype, while transcriptional and post-transcriptional regulations appear differently tuned among the lineages.
Psychiatric sequelae of thromboangiitis obliterans: a case report and review of the literature
Authors: Awara Mahmoud A. , Downing Laura M. , Elnenaei Manal O. 
Published: January 2023

Abstract
Background
Peripheral manifestations secondary to progressive vascular occlusions are characteristic of the rare condition termed thromboangiitis obliternas (TAO) or Buerger’s disease. The central manifestations of this disease are however poorly characterized, particularly those of psychiatric nature, and their prevalence is largely unknown. Speculations have been made around the polymorphic nature and triggers of observed psychopathology in TAO; much however remains to be unraveled in this area.

Case presentation
We present the case of a 33-year-old Caucasian male who developed first episode of psychosis at the age of 29 years. There was no history of previous mental illness either in the patient, or in any of his family members. He had been a long- term heavy smoker and was experiencing progressive lower limb claudication since the age of 22 years; however, all inflammatory, autoimmune and atherosclerotic markers were negative. His psychosis was characterized by retention of a warm affect, and despite some amelioration, was generally resistant to a fair trial of several anti-psychotic medications including Clozapine.

Conclusion
The pathophysiology of psychosis secondary to Buerger’s is not yet well characterized which adds to the complexity of managing these cases. Recognizing that cerebral manifestations of this disease may evolve several years after the onset of peripheral thromboangiitic features is important for following the natural history and considering measures that may reduce the burden of illness.
Severe skin and soft tissue infection in the left upper limb caused by Aeromonas veronii: a case report
Authors: Li Linhui , Huang Jie , Xu Long , Wang Guangyi , Xiao Shichu , Xia Zhaofan , Qin Qin , Li Yazhou , Ji Shizhao 
Published: January 2023

Abstract
Introduction
Skin and soft tissue infections are common because of exposure to aquatic environment, while severe infections caused by Aeromonas veronii are rare.

Case presentation
We report a case of severe skin and soft tissue infection of the left upper limb caused by Aeromonas veronii. A 50-year-old Chinese woman, who had a history of cardiac disease and type 2 diabetes mellitus, accidentally injured her left thumb while cutting a fish. Early antibiotic therapy and surgical debridement was performed before the result of bacterial culture came back. Whole-genome sequencing was further performed to confirm the pathogen and reveal the drug resistance and virulence genes. The wound was gradually repaired after 1 month of treatment, and the left hand recovered well in appearance and function after 3 months of rehabilitation.

Conclusion
Early diagnosis, surgical intervention, and administration of appropriate antibiotics are crucial for patients who are suspected of having skin and soft tissue infection, or septicemia caused by Aeromonas veronii.
Analysis of clinical features and risk factors of peripheral neuropathy in patients with primary Sjögren's syndrome
Authors: Wu Zhihong , Wang Dong , Chen Lirong , Xianyu Kaipu , Yang Huiqing 
Published: January 2023

Abstract
Objective
To observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS.

Methods
Sixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy.

Results
The patients with PN had a longer course of disease than those without PN (z = − 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased.

Conclusion
PN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS.
Radiosynthesis and preclinical evaluation of [11C]SNX-ab as an Hsp90α,β isoform-selective PET probe for in vivo brain and tumour imaging
Authors: Cools Romy , Vermeulen Koen , Narykina Valeria , Leitao Renan C. F. , Bormans Guy 
Published: January 2023

Abstract
Background
The molecular chaperone, Hsp90, is a key player in the protein quality control system that maintains homeostasis under cellular stress conditions. It is a homodimer with ATP-dependent activity, and is a prominent member of the chaperone machinery that stabilizes, matures and (re)folds an extensive list of client proteins. Hsp90 occurs as four isoforms, cytosolic Hsp90α and Hsp90β, mitochondrial TRAP1 and Grp94 present in the endoplasmic reticulum. An aberrant role of Hsp90 has been attributed to several cancers and neurodegenerative disorders. Consequently, Hsp90 has emerged as an attractive therapeutic target. However, pan-Hsp90 inhibition often leads to detrimental dose-limiting toxicities. Novel strategies for Hsp90-targeted therapy intend to avoid this by using isoform-specific Hsp90 inhibition. In this respect, the radiosynthesis of carbon-11 labeled SNX-ab was developed and [11C]SNX-ab was evaluated as a Hsp90α,β isoform-selective PET probe, which could potentially allow to quantify in vivo Hsp90α,β expression.

Results
[11C]SNX-ab was synthesized with excellent radiochemical yields of 45% and high radiochemical purity (> 98%). In vitro autoradiography studies on tissue slices of healthy mouse brain, mouse B16.F10 melanoma and U87 glioblastoma using homologous (SNX-ab, SNX-0723) and heterologous (Onalespib and PU-H71) Hsp90 inhibitors demonstrated only limited reduction of tracer binding, indicating that the binding of [11C]SNX-ab was not fully Hsp90-specific. Similarly, [11C]SNX-ab binding to U87 cells was not efficiently inhibited by Hsp90 inhibitors. Ex vivo biodistribution studies in healthy mice revealed limited brain exposure of [11C]SNX-ab and predominantly hepatobiliary clearance, which was confirmed by in vivo full-body dynamic µPET studies.

Conclusion
Our results suggest that [11C]SNX-ab is not an ideal probe for in vivo visualization and quantification of Hsp90α/β expression levels in tumour and brain. Future research in the development of next-generation Hsp90 isoform-selective PET tracers is warranted to dissect the role played by each isoform towards disease pathology and support the development of subtype-specific Hsp90 therapeutics.
Mapping and gap analysis on antimicrobial resistance surveillance systems in Kenya, Tanzania, Uganda and Zambia
Authors: Matee Mecky , Mshana Stephen E. , Mtebe Majigo , Komba Erick Vitus , Moremi Nyambura , Lutamwa Julius , Kapona Otrida , Sekamatte Musa , Mboera Leonard E. G. 
Published: January 2023

Abstract
Background
Antimicrobial resistance is a global problem and involve pathogens which have the potential to move between food producing animals and humans by direct exposure or through the food chain or the environment. The objective of this study was to determine the performance in addressing antimicrobial resistance in Kenya, Tanzania, Uganda and Zambia. Desk review and in-depth interviews were employed for data collection. Interviews were conducted with national antimicrobial resistance focal officials.

Results
The findings indicate that in the four countries there was minimal capacity to conduct AMR surveillance. There were few well-established laboratories in tertiary hospitals, both private and public hospitals. The animal, environment and agricultural sectors in all countries had limited capacity in conducting antimicrobial resistance surveillance. There is limited data on antimicrobial resistance in all the four countries, and regional data sharing was limited. In all the four countries, data from research institutions were not linked using standardized system making difficult to compile the national database. The capacity for microbiological culture, identification and antimicrobial sensitivity testing using standardized protocols was available in the four countries. The interventions adopted by the countries included development of National Action Plans on antimicrobial resistance and setting up of multi-sectoral national coordinating structures.

Conclusions
Based on this findings, the countries need improved National Integrated Antimicrobial Resistance Surveillance systems to include community settings, involving antimicrobial use and resistance in human, animal, food, and environment sectors. In addition, the region requires clear antimicrobial resistance data sharing protocol for quick comparability of the data across the region. This is important in driving antimicrobial resistance agendas at regional level, which will eventually trigger collective actions.
Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study
Authors: Matulonis Ursula A. , Lorusso Domenica , Oaknin Ana , Pignata Sandro , Dean Andrew , Denys Hannelore , Colombo Nicoletta , Van Gorp Toon , Konner Jason A. , Marin Margarita Romeo , Harter Philipp , Murphy Conleth G. , Wang Jiuzhou , Noble Elizabeth , Esteves Brooke , Method Michael , Coleman Robert L. 
Published: January 2023

PURPOSE Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor α (FRα). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC. METHODS SORAYA enrolled FRα-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point. RESULTS One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively. CONCLUSION MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.
The Changing Epidemiology of Adrenal Insufficiency: Iatrogenic Factors Predominate
Authors: Rushworth R Louise , Torpy David J 
Published: January 2023

AbstractContextAdrenal insufficiency (AI)-related morbidity persists despite efforts to minimize its effect. Reasons for this are unknown and warrant examination.ObjectiveThis work aimed to investigate trends in AI hospitalizations and glucocorticoid (GC) replacement therapy use.MethodsData on hospitalizations for a principal diagnosis of AI and prescriptions for short-acting GCs between 2000 and 2019 were extracted from national repositories. Age-standardized admission and prescription rates were calculated using census data. Rates were compared over time overall and according to age, sex, and disease subtype.ResultsAI admissions increased by 62.0%, from 36.78/million to 59.59/million (trend P &lt; .0001). Adrenal crisis (AC) admissions also increased, by 90.1% (from 10.73/million to 20.40/million; trend, P &lt; .00001). These increases were more pronounced in the second decade. Prescriptions for short-acting GCs also increased (by 67.2%, from 2198.36/million in 2000/2001 to 3676.00/million in 2017/2018). Females had higher average admission rates and a greater increase in admission rates than males. Increased AI admissions were found in all age groups among females but only in men aged 70+ yrs. Secondary AI (SAI) admission rates increased by 91.7%, whereas admission rates for primary AI (PAI) remained unchanged.ConclusionThe prevalence of AI and hospitalizations for this disorder (including ACs) have increased since 2000, with a greater increase occurring after 2010. Admission rates for SAI increased but PAI admissions remained stable. Possible causes include immunotherapies for malignancy, increased cranial imaging detecting pituitary tumors and their subsequent treatment, and increased use of low-dose, short-acting GC-replacement therapy.
Paediatric Society and Hyperinsulinism Charity National Surveys on CGM Access for Patients With Recurrent Hypoglycaemia
Authors: Ng Sze May , Dearman Sarah , Fisher Mark , Mushtaq Talat , Randell Tabitha 
Published: January 2023

AbstractContextRecurrent hypoglycemia can result in significant neurological impairments in children and continuous glucose monitoring (CGM) technology has been shown to reduce recurrent hypoglycemia in conditions such as type 1 diabetes. In the United Kingdom, CGM devices are currently only recommended by the National Institute of Clinical Excellence (NICE) for patients with diabetes and not for other diagnoses.ObjectiveTo examine access to CGM technology for children and young people with recurrent hypoglycemia in the United Kingdom.MethodsIn 2021, the British Society of Paediatric Endocrinology and Diabetes (BSPED) conducted a national health professional survey in England, Wales, Scotland, and Northern Ireland looking at CGM access to funding for children and young people with recurrent hypoglycemia, without the diagnosis of diabetes. The UK Children's Hyperinsulinism Charity (UK CHC) also conducted a national patient survey.ResultsResponses from BSPED were received from 55 units while the UK CHC received 69 responses from individual families, the largest response to a survey carried out by the charity. The results of the BSPED and UK CHC surveys found that funding streams for CGM were highly variable. Only 29% were able to access CGM for recurrent hypoglycemia and from these, 65% were self-funding CGM. Quality of life benefits were evident from the UK CHC survey on the utility of CGM in reducing worry, improving sleep, lessening the burden of frequently finger-pricking and reducing out-of-hours appointments as a result of hypoglycemia. Patient-reported utilization rates of blood glucose test strips per week were significantly reduced.ConclusionBSPED and UK CHC national surveys support a call and a consideration for CGM access to be widened to patients who suffer from recurrent hypoglycemia such as those with hyperinsulinism or metabolic conditions. The prevention of recurrent hypoglycemia and improving quality of life for patients and carers remain a cornerstone management for people who suffer from frequent hypoglycemia. CGM education is critical to support its use and understand its limitations. Further research is warranted to determine the safety and efficacy of CGM in detection and reduction of hypoglycemic events, impact of hospital stay, and long-term neurological outcomes in those who suffer from recurrent hypoglceamia.
Light-sheet microscopy reveals dorsoventral asymmetric membrane dynamics ofAmoeba proteusduring pressure-driven locomotion
Authors: Taniguchi Atsushi , Nishigami Yukinori , Kajiura-Kobayashi Hiroko , Takao Daisuke , Tamaoki Daisuke , Nakagaki Toshiyuki , Nonaka Shigenori , Sonobe Seiji 
Published: January 2023

ABSTRACTAmoebae are found all around the world and play an essential role in the carbon cycle in the environment. Therefore, the behavior of amoebae is a crucial factor when considering the global environment. Amoebae change their distribution through amoeboid locomotion, which are classified into several modes. In the pressure-driven mode, intracellular hydrostatic pressure generated by the contraction of cellular cortex actomyosin causes the pseudopod to extend. During amoeboid locomotion, the cellular surface exhibits dynamic deformation. Therefore, to understand the mechanism of amoeboid locomotion, it is important to characterize cellular membrane dynamics. Here, to clarify membrane dynamics during pressure-driven amoeboid locomotion, we developed a polkadot membrane staining method and performed light-sheet microscopy in Amoeba proteus, which exhibits typical pressure-driven amoeboid locomotion. It was observed that the whole cell membrane moved in the direction of movement, and the dorsal cell membrane in the posterior part of the cell moved more slowly than the other membrane. In addition, membrane complexity varied depending on the focused characteristic size of the membrane structure, and in general, the dorsal side was more complex than the ventral side. In summary, the membrane dynamics of Amoeba proteus during pressure-driven locomotion are asymmetric between the dorsal and ventral sides.This article has an associated interview with the co-first authors of the paper.
Single-cell RNA-based phenotyping reveals a pivotal role of thyroid hormone receptor alpha for hypothalamic development
Authors: Sreenivasan Varun K. A. , Dore Riccardo , Resch Julia , Maier Julia , Dietrich Carola , Henck Jana , Balachandran Saranya , Mittag Jens , Spielmann Malte 
Published: January 2023

ABSTRACT
Thyroid hormone and its receptor TRα1 play an important role in brain development. Several animal models have been used to investigate this function, including mice heterozygous for the TRα1R384C mutation, which confers receptor-mediated hypothyroidism. These mice display abnormalities in several autonomic functions, which was partially attributed to a developmental defect in hypothalamic parvalbumin neurons. However, whether other cell types in the hypothalamus are similarly affected remains unknown. Here, we used single-nucleus RNA sequencing to obtain an unbiased view on the importance of TRα1 for hypothalamic development and cellular diversity. Our data show that defective TRα1 signaling has surprisingly little effect on the development of hypothalamic neuronal populations, but it heavily affects hypothalamic oligodendrocytes. Using selective reactivation of the mutant TRα1 during specific developmental periods, we find that early postnatal thyroid hormone action seems to be crucial for proper hypothalamic oligodendrocyte maturation. Taken together, our findings underline the well-known importance of postnatal thyroid health for brain development and provide an unbiased roadmap for the identification of cellular targets of TRα1 action in mouse hypothalamic development.