bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroplastic Sec14-like proteins modulate growth and phosphate deficiency responses inArabidopsisand rice
Authors: Yang Mailun , Sakruaba Yasuhito , Ishikawa Toshiki , Ohtsuki Namie , Kawai-Yamada Maki , Yanagisawa Shuichi 
Published: April 2023

AbstractPhosphorus is an essential nutrient acquired from soil as phosphate (Pi), and its deficiency severely reduces plant growth and crop yield. Here, we show that single nucleotide polymorphisms (SNPs) at the PHOSPHATIDYLINOSITOL TRANSFER PROTEIN7 (AtPITP7) locus, which encodes a chloroplastic Sec14-like protein, are associated with genetic diversity regarding Pi uptake activity in Arabidopsis (Arabidopsis thaliana). Inactivation of AtPITP7 and its rice (Oryza sativa) homolog (OsPITP6) through T-DNA insertion and CRISPR/Cas9-mediated gene editing, respectively, decreased Pi uptake and plant growth, regardless of Pi availability. By contrast, overexpression of AtPITP7 and OsPITP6 enhanced Pi uptake and plant growth, especially under limited Pi supply. Importantly, overexpression of OsPITP6 increased the tiller number and grain yield in rice. Targeted metabolome analysis of glycerolipids in leaves and chloroplasts revealed that inactivation of OsPITP6 alters phospholipid contents, independent of Pi availability, diminishing the reduction in phospholipid content and increase in glycolipid content induced by Pi deficiency; meanwhile, overexpression of OsPITP6 enhanced Pi deficiency-induced metabolic alterations. Together with transcriptome analysis of ospitp6 rice plants and phenotypic analysis of grafted Arabidopsis chimeras, these results suggest that chloroplastic Sec14-like proteins play an essential role in growth modulations in response to changes in Pi availability, although their function is critical for plant growth under any Pi condition. The superior traits of OsPITP6-overexpressing rice plants also highlight the potential of OsPITP6 and its homologs in other crops as additional tools for improving Pi uptake and plant growth in low Pi environments.
Early-onset gout and rare deficient variants of the lactate dehydrogenase D gene
Authors: Bardin Thomas , Ducrot Yves-Marie , Nguyen Quang , Letavernier Emmanuel , Zaworski Jeremy , Ea Hang-Korng , Touzain Fréderic , Do Minh Duc , Colot Julien , Barguil Yann , Biron Antoine , Resche-Rigon Matthieu , Richette Pascal , Collet Corinne 
Published: April 2023

Abstract

Objectives
To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout.

Methods
We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d-lactate dosages were analysed using ELISA.

Results
We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C&gt;T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P = 0.02), lower fractional clearance of urate (P = 0.002), and higher levels of d-lactate in blood (P = 0.04) and urine (P = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d-lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C&gt;T, p.(Thr251Met)].

Conclusion
Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d-lactate levels in the blood and/or urine.
Effects of menopausal hormone therapy on the risk of ovarian cancer: Health Insurance Database in South Korea–based cohort study
Authors: Yuk Jin-Sung , Kim Myounghwan 
Published: April 2023

Abstract

Objective
This study aimed to evaluate the risk of ovarian cancer associated with hormone therapy regimens using a Korean population–based study.

Methods
This retrospective cohort study used national health checkup and insurance data from January 1, 2002, to December 31, 2019, provided by Korea's National Health Insurance Service. Women older than 40 years who recorded “menopause” in the questionnaire from 2002 to 2011 were included in this study. Menopausal hormone therapy (MHT) preparations were classified into tibolone, combined estrogen plus progestin by the manufacturer, combined estrogen plus progestin by physician, estrogen, and topical estrogen groups. The number of participants recorded as menopausal during the national health examination between 2002 and 2011 was 2,506,271. The MHT and non-MHT groups consisted of 373,271 and 1,382,653 patients, respectively. The hazard ratios (HR) of ovarian cancer according to MHT type, age at inclusion, body mass index, region, socioeconomic status, Charlson comorbidity index, age at menarche, age at menopause, parity, smoking, alcohol consumption, physical exercise, and period from menopause to inclusion were evaluated.

Results
The risk of ovarian cancer was reduced in the tibolone group (HR, 0.84; 95% confidence interval, 0.75-0.93; P = 0.003) and in patients in rural areas (HR, 0.90; 95% confidence interval, 0.845-0.98; P = 0.013). The risk of ovarian cancer was not related to the other MHT treatments.

Conclusion
Tibolone was associated with a lower risk of ovarian cancer. No other MHT was associated with ovarian cancer.
Endometrial safety of low-dose vaginal estrogens
Authors: Stanczyk Frank Z. , Mandelbaum Rachel S. , Matharu Harpreet , Dancz Christina E. , Sherman Mark E. 
Published: April 2023

Abstract
It is estimated that up to 50% to 90% of postmenopausal women may experience genitourinary syndrome of menopause (GSM), which may have a detrimental impact on quality of life. One of the most effective modes of treatment of GSM is low-dose vaginal estrogens. Numerous studies have addressed the safety of these estrogens using endometrial biopsy and/or endometrial thickness on ultrasound. Based on these studies, the consensus is that low-dose vaginal estrogens do not substantially increase the risk of endometrial hyperplasia or cancer; however, the data are severely limited by short duration of follow-up. Although long-term trials are warranted, they are difficult to carry out, costly, and will not yield data for years. More immediate information regarding endometrial safety may be obtained from studies measuring endometrial tissue and serum concentrations of estradiol, estrone, and relevant equine estrogens after administration of different estrogen formulations and doses. This would allow us to understand better the metabolism of estrogens by the vagina and endometrium, and how much estrogen is reaching the endometrium. Here, we discuss metabolism, receptor binding, and signaling of estrogens in vaginal and endometrial tissue, and summarize the existing studies on the endometrial impact of low-dose vaginal estrogen treatment in postmenopausal women.
Quality of life in Spanish postmenopausal breast cancer patients with localized disease who finish endocrine treatment: a prospective study
Authors: Arraras Juan Ignacio , Illarramendi Jose Juan , Manterola Ana , de la Cruz Susana , Zarandona Uxue , Ibañez Berta , Salgado Esteban , Visus Ignacio , Barrado Marta , Teiejira Lucia , Martinez María Isabel , Martinez Enrique , Vera Ruth 
Published: April 2023

Abstract

Objective
In this article, the quality of life (QOL) of Spanish postmenopausal early-stage breast cancer patients who have finished endocrine therapy (ET), QOL changes after endocrine therapy cessation, and the differences between two endocrine therapy modalities (tamoxifen or aromatase inhibitor [AI]) are studied. More QOL information after endocrine therapy cessation is needed.

Methods
A prospective cohort study was performed. Participating in the study were 158 postmenopausal patients who had received tamoxifen or AI for 5 years. In some cases, endocrine therapy may have changed during those 5 years.
Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR45 questionnaires at baseline, after 6 months, and after 1 year of follow-up. Patients older than 65 years also completed the QLQ-ELD14. Linear mixed-effect models were used to evaluate longitudinal changes in QOL and differences in QOL between endocrine therapy modalities.

Results
QOL scores for the whole sample throughout follow-up were high (>80/100 points) in most QOL areas. Moderate limitations (>30 points) occurred in the QLQ-BR45 in sexual functioning and sexual enjoyment, future perspective, and joint symptoms. Moderate limitations also occurred in the QLQ-ELD14 in worries about others, maintaining purpose, joint stiffness, future worries, and family support. In those who had finished endocrine therapy, pain was reduced in all three assessments conducted during the 1-year follow-up period in both groups. Tamoxifen patients showed better QOL in functioning (role functioning, global QOL, financial impact), symptoms (pain), and emotional areas (future perspective and worries about others) than AI patients but worse QOL in skin mucosis symptoms.

Conclusions
The results of this study show that postmenopausal early-stage breast cancer patients adapted well to their disease and endocrine therapy treatment. QOL improvements in the 1-year follow-up period appeared in one key area: pain. Differences between endocrine therapy modalities suggested QOL was better in the tamoxifen group than in the AI group.
Development and Validation of a Patient-Reported Experience Measure for Gastrointestinal Endoscopy
Authors: Kutyla Marguerite J. , McMaster Jessica J. , Haig Adam , Koloski Natasha , Hourigan Luke , Meeusen Vera , Shah Ayesha , Talley Nicholas J. , Jones Michael P. , Holtmann Gerald J. 
Published: April 2023

Goals:
We aimed to develop and validate a patient-reported experience measure for gastrointestinal (GI) endoscopy, the Comprehensive Endoscopy Satisfaction Tool that captures relevant domains that influence the patient’s experience and identify factors that shape satisfaction.

Background:
Patient-reported experience measures are used to capture specific quality aspects of health care services. GI endoscopic services are high-volume services, and there is a lack of specific, validated instruments to capture various domains that shape the patients’ experience with routine clinical endoscopic services.

Study:
After an environmental scan and structured literature review, focus groups with patients were conducted to identify relevant factors influencing the patient experience with GI endoscopic services. After an initial validation in 101 patients undergoing routine GI endoscopies, the instrument was tested in 7800 patients. In addition, the influence of sociodemographic factors on global satisfaction was explored.

Results:
The final version included 26 specific items plus 4 global ratings for preprocedure, experience on day of procedure, postprocedure care, and infrastructure. In addition, a global rating of the overall experience was included. Patient satisfaction was significantly higher in older patients (P<0.001) but not influenced by gender, nationality, marital status, education, or employment status. Interestingly, during periods of coronavirus disease-19-related service interruptions, the Net Promoter Score was significantly reduced (P<0.0001) providing evidence for the responsiveness of the instrument.

Conclusions:
The Comprehensive Endoscopy Satisfaction Tool is a valid measure for the patient experience with the various components of endoscopic services, allows for the identification of domains that impact on the patient experience and is a practical tool to compare patient satisfaction over time and across facilities.
Nocardia pulmonis sp. nov., an actinomycete isolated from a patient with pulmonary infection
Authors: Li Fang , Xu Shuai , Li Zhenpeng , Yue Yuan , Song Jingdong , Du Baozhong , Che Yanlin , Han Lichao , Qiu Xiaotong , Kang Yutong , Liu Xueping , Chen Shenglin , Li Zhenjun 
Published: April 2023

A novel bacterial strain, CDC141T, was isolated from sputum samples of a patient with pulmonary infection in Hainan Province, PR China. We performed a polyphasic study to assess the taxonomic position of the new species. Based on the results of 16S rRNA gene sequence analyses, strain CDC141T belonged to the genus

Nocardia

with the highest sequence similarity to

Nocardia nova

NBRC 15556T (98.84 %) and

Nocardia macrotermiti

s RB20T (98.54 %). The dapb1 gene sequence-based phylogenetic and phylogenomic trees further showed that the novel strain was clustered in a distinct clade adjacent to

Nocardia pseudobrasiliensis

DSM 44290T. The DNA G+C content of strain CDC141T was 68.57 mol%. The genomic diversity analysis revealed low average nucleotide identity and in silico DNA‒DNA hybridization values (<84.7 and <28.9 %, respectively) with its closest relative. Growth occurred at 20–40 °C, pH 6.0–9.0 and with NaCl concentrations of 0.5–2.5 % (w/v). The main fatty acids of strain CDC141T were C16 : 0, C18 : 0 10-methyl, TBSA, C16 : 1
ω6c/C16 : 1
ω7c, C18 : 1
ω9c, C18 : 0, C17 : 1 iso I/anteiso B and C17 : 0. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, unidentified glycolipids, unidentified phospholipids and unidentified lipids. MK8 (H4ω-cycl) and MK8 (H4) were the major respiratory quinones. These characteristics were consistent with the typical chemotaxonomic properties of members of the genus

Nocardia

. Based on the results of phenotypic and genetic analyses, strain CDC141T was identified as representing a new species of the genus

Nocardia

, with the proposed name Nocardia pulmonis sp. nov. (CDC141T=JCM 34955T=GDMCC 4.207T).
Limimaricola litoreus sp. nov., isolated from intertidal sand of the Yellow Sea
Authors: Shao Xuan , Meng Di , Lei Jia-Xuan , Ding Yun-Yun , Su Jing-Yun , Wang Ya-Nan , Li Yi 
Published: April 2023

A novel species of the genus

Limimaricola

, designated ASW11-118T, was isolated from an intertidal sand sample of the Yellow Sea, PR China. Growth of strain ASW11-118T occurred at 10–40 °C (optimum, 28 °C), pH 5.5–8.5 (optimum, pH 7.5) and with 0.5–8.0 % (w/v) NaCl (optimum, 1.5%). Strain ASW11-118T has the highest 16S rRNA gene sequence similarity to

Limimaricola cinnabarinus

LL-001T (98.8%) and 98.6 % to

Limimaricola hongkongensis

DSM 17492T. Phylogenetic analysis based on genomic sequences indicated that strain ASW11-118T belongs to the genus

Limimaricola

. The genome size of strain ASW11-118T was 3.8 Mb and DNA G+C content was 67.8 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain ASW11-118T and other members of the genus

Limimaricola

were below 86.6 and 31.3 %, respectively. The predominant respiratory quinone was ubiquinone-10. The predominant cellular fatty acid was C18 : 1
ω7c. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and one unknown aminolipid. On the basis of the data presented, strain ASW11-118T is considered to represent a novel species of the genus

Limimaricola

, for which the name Limimaricola litoreus sp. nov. is proposed. The type strain is ASW11-118T (=MCCC 1K05581T=KCTC 82494T).
Agreement between the ventilated capsule and the KuduSmart® device for measuring sweating responses to passive heat stress and exercise
Authors: Ravanelli Nicholas , Newhouse Douglas , Foster Fergus , Caldwell Aaron R. 
Published: April 2023

ABSTRACTThe present study assessed agreement between the KuduSmart® device and the ventilated capsule (VC) technique for measuring: i) minute-averaged local sweat rate (LSR); ii) sweating onset; iii) thermosensitivity; and iv) steady-state LSR, during passive heat stress and exercise. On two separate occasions for each heat stress intervention, participants were either passively heated by recirculating hot water (49°C) through a tube-lined garment until rectal temperature increased 1°C over baseline (n=8), or walked on a treadmill for 60 minutes at a fixed rate of heat production (n=9). LSR of the forearm was concurrently measured with a VC and the KuduSmart® device secured within ∼2 cm. Mean body temperature was calculated as the weighted average between rectal (80%) and mean skin (20%) temperature. Using a ratio scale Bland-Altman analysis with the VC as the reference, the KuduSmart® device demonstrated systematic bias for minute-averaged LSR (1.19 [1.09, 1.28]) and steady-state LSR (1.16 [1.09,1.23]), however no bias for thermosensitivity (1.08 [1.00, 1.16]) or sweating onset (1.00 [1.00, 1.00]). Although poor agreement was observed for minute-averaged LSR (CV = 43.3%), more than 73% of all observations with the KuduSmart® device (n=2795) were within an absolute error of < 0.2 mg/cm2/min to the VC. The KuduSmart® device demonstrated acceptable agreement for steady-state LSR (CV = 19.5%) and thermosensitivity (CV = 21.7%), and almost perfect agreement for sweating onset (CV = 0.14%). Collectively, the KuduSmart® device may be a satisfactory in-field solution for assessing the sweating response to heat stress.
Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation
Authors: Tundidor Isabel , Seijo-Vila Marta , Blasco-Benito Sandra , Rubert-Hernández María , Moreno-Bueno Gema , Bindila Laura , Fernández de la Rosa Rubén , Guzmán Manuel , Sánchez Cristina , Pérez-Gómez Eduardo 
Published: April 2023

AbstractMammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined. Endocannabinoid signaling is known to determine cell fate-related events during the development of different organs in the central nervous system and the periphery. Here, we report that the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) plays a pivotal role in adult mammary gland development. Specifically, it is required for luminal lineage specification in the mammary gland, and it promotes hormone-driven secretory differentiation of mammary epithelial cells by controlling the endogenous levels of anandamide and the subsequent activation of cannabinoid CB1receptors. Together, our findings shed light on the role of the endocannabinoid system in breast development and point to FAAH as a therapeutic target in milk-production deficits.
Revealing the Grammar of Small RNA Secretion Using Interpretable Machine Learning
Authors: Zirak Bahar , Naghipourfar Mohsen , Saberi Ali , Pouyabahar Delaram , Zarezadeh Amirhossein , Luo Lixi , Fish Lisa , Huh Doowon , Navickas Albertas , Sharifi-Zarchi Ali , Goodarzi Hani 
Published: April 2023

AbstractSmall non-coding RNAs can be secreted through a variety of mechanisms, including exosomal sorting, in small extracellular vesicles, and within lipoprotein complexes1,2. However, the mechanisms that govern their sorting and secretion are still not well understood. In this study, we present ExoGRU, a machine learning model that predicts small RNA secretion probabilities from primary RNA sequence. We experimentally validated the performance of this model through ExoGRU-guided mutagenesis and synthetic RNA sequence analysis, and confirmed that primary RNA sequence is a major determinant in small RNA secretion. Additionally, we used ExoGRU to revealcisandtransfactors that underlie small RNA secretion, including known and novel RNA-binding proteins, e.g., YBX1, HNRNPA2B1, and RBM24. We also developed a novel technique called exoCLIP, which reveals the RNA interactome of RBPs within the cell-free space. We used exoCLIP to reveal the RNA interactome of HNRNPA2B1 and RBM24 in extracellular vesicles. Together, our results demonstrate the power of machine learning in revealing novel biological mechanisms. In addition to providing deeper insight into complex processes such as small RNA secretion, this knowledge can be leveraged in therapeutic and synthetic biology applications.
Multiomics Approach to Understanding Olaparib Resistance and Predicting Drug Response
Authors: Lim Won-Jun , Kim Hyunjin M. , Oh YongHo , Pyo Junhee 
Published: April 2023

AbstractWe aimed to uncover genetic factors affecting resistance to the cancer drug olaparib. To do this, we utilized multiomics matrix factorization (MOFA), a multiomics approach, to explore omic-based features that might become biomarker candidates. Our results showed that 17 damaging mutations, 6 gene expression signatures, 17 DNA methylations, and 26 transcription-factor activities can impact the refractory response to olaparib.To verify the potential utility of the identified biomarker candidates, we generated a predictive model to differentiate between olaparib responding and nonresponding cell lines using machine learning techniques, including support vector machine algorithms, random forest algorithms, and Siamese neural networks. The model was centered around six gene-expression biomarker candidates and validated using the Genomics of Drug Sensitivity in Cancer database.Our findings suggest that using a multiomics approach with machine learning methods can lead to a better understanding of the mechanism of drug resistance and identify biomarkers, which will ultimately facilitate the appropriate administration of drugs to patients. The source codes can be found athttps://github.com/wjlim/DrugResistance.
Both CD8 and CD4 T cells contribute to immunosurveillance preventing the development of neoantigen-expressing autochthonous sarcomas
Authors: Himes Jonathon E. , Wisdom Amy J. , Wang Laura , Shepard Sam J. , Daniel Andrea R. , Williams Nerissa , Luo Lixia , Ma Yan , Mowery Yvonne M. , Kirsch David G. 
Published: April 2023

AbstractThe adaptive immune system plays an essential anti-tumor role through immunosurveillance and response to immunotherapies. Characterizing phenotypic features and mechanisms of dysfunction of tumor-specific T cell populations may uncover novel immunotherapeutic targets and biomarkers of response. To study tumor-specific T cell responsesin vivo, a tumor model must express a known neoantigen. While transplant models with known neoantigen expression are widely available, autochthonous tumor models in which the tumor coevolves with the immune system are limited. In this study, we combined CRISPR/Cas9 and sleeping beauty transposase technology to develop an autochthonous orthotopic murine sarcoma model with oncogenic KrasG12D, functionally impaired p53, and expression of known MHCI and MHCII sarcoma neoantigens. Using MHC tetramer flow cytometry, we identified a tumor-specific immune response in the peripheral blood as early as 10 days after tumor induction leading to tumor clearance. Tumors developed at high penetrance after co-depletion of CD8 and CD4 T cells, but depletion of either CD8 or CD4 T cells alone was insufficient to permit tumor growth. These results suggest that CD8 and CD4 T cells can independently contribute to immunosurveillance leading to clearance of sarcomas expressing MHCI and MHCII neoantigens.