bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mirabegron for overactive bladder in frail patients 80 years or over (HOKUTO study)
Authors: Nakagomi Hiroshi , Mitsui Takahiko , Shimura Hiroshi , Ihara Tatsuya , Kira Satoru , Sawada Norifumi , Takeda Masayuki 
Published: March 2022

Abstract
Background
We assessed the efficacy and safety of mirabegron, a β3-adrenoceptor agonist, in older adults (≥ 80 years old) with overactive bladder (OAB).

Methods
OAB patients aged ≥ 80 years were enrolled in this prospective, single-arm observational study. OAB was diagnosed based on the OAB symptom score (OABSS); i.e., a total score of ≥ 3 points and an urgency score of ≥ 2 points. Patients who received 50 mg mirabegron once daily were evaluated at the baseline and at 4, 8, and 12 weeks. The changes from the baseline in the OABSS, International Prostate Symptom Score (IPSS), OAB questionnaire (OAB-q) score, and Vulnerable Elders Survey (VES-13) score were determined. Adverse events, laboratory tests, 12-lead electrocardiography, the QT interval according to Fridericia’s formula (QTcF), uroflowmetry, the post-void residual urine volume (PVR), and the Mini-Mental State Examination (MMSE) score were used to assess safety.

Results
Forty-three patients (median age: 84 years, range: 80–96 years) were examined. They had high rates of comorbidities and polypharmacy. Mirabegron significantly improved in total score of the OABSS, including urgency and urge incontinence. The total IPSS, IPSS quality-of-life (QOL) index, and OAB-q scores also significantly improved. Mirabegron improved in the VES-13 score. There were no significant changes in laboratory test values, uroflowmetry findings, PVR, the QTcF, or MMSE score. Two patients (4.7%) withdrew from the study after experiencing adverse events.

Conclusions
Mirabegron was well tolerated and significantly improved in OAB symptoms, and QOL in older patients.
Trial registration The present clinical study was approved by University of Yamanashi Institutional Review Board prior to study initiation (ID1447) and was retrospectively registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (UMIN000045996) on Nov 6, 2021.
Women with polycystic ovary syndrome (PCOS) have reduced melatonin concentrations in their follicles and have mild sleep disturbances
Authors: Li Hongwanyu , Liu Mei , Zhang Cong 
Published: March 2022

Abstract
Background
Polycystic ovary syndrome (PCOS) is a common gynecologic disorder related to abnormal circadian rhythm. Therefore, we aimed to find whether the level of melatonin, a rhythm regulating hormone changed in the ovarian microenvironment in this disease.

Methods
The melatonin concentrations in follicular fluid (FF) were measured in 35 PCOS and 36 non-PCOS women undergoing in vitro fertilization (IVF) treatment.

Results
The FF melatonin concentration was significantly lower in PCOS women than non-PCOS women (p = 0.045) and it was found positively correlated with serum basal FSH level (r = 0.308, p = 0.013). In IVF procedures, there was no significant difference in the fertilization rate of oocytes between the two groups, but the high-quality embryogenesis rate on the third day of the PCOS group was significantly lower than that of the control group (p = 0.042), which showed a weak positive correlation with the FF melatonin concentration (rs = 0.240, p = 0.044). Furthermore, there was no significant difference in overall pregnancy outcome. The PSQI questionnaire showed that sleep disorders were more likely to exist in the PCOS group, though there was no significant difference.

Conclusion
The obtained results suggested PCOS women had lower melatonin concentrations in the ovarian microenvironment.
Physical activity and health-related quality of life among high-risk women for type 2 diabetes in the early years after pregnancy
Authors: Sahrakorpi Niina , Engberg Elina , Stach-Lempinen Beata , Tammelin Tuija H. , Kulmala Janne , Roine Risto P. , Koivusalo Saila B. 
Published: March 2022

Abstract
Background
Previous studies have shown that physical activity (PA) correlates positively with health-related quality of life (HRQoL) in the general population. Few studies have investigated associations between device-measured PA and HRQoL among premenopausal women at risk for type 2 diabetes (T2D). In addition to physical well-being, general well-being improved by PA has been suggested to strengthen PA’s benefits in reducing metabolic diseases. The aim of this study was to examine the associations between PA and HRQoL (general and dimensions) among high-risk women in the early post-pregnancy years when T2D risk is highest and to estimate whether current obesity or prior gestational diabetes (GDM) modified these associations.

Methods
This cross-sectional study of high-risk women [body mass index (BMI) ≥ 30 kg/m2 and/or prior GDM)]4–6 years after delivery measured sleep, sedentary time, daily steps, and light (LPA), moderate-to-vigorous (MVPA), and vigorous PA (VPA) with the SenseWear ArmbandTM accelerometer for seven days and HRQoL with the 15D instrument.

Results
The analyses included 204 women with a median (IQR) age of 39 (6.0) years and a median BMI of 31.1 kg/m2 (10.9). 54% were currently obese (BMI ≥ 30 kg/m2), and 70% had prior gestational diabetes (GDM+). Women with obesity had lower PA levels than women with normal weight or overweight (p < 0.001) but there was no difference between the GDM+ or GDM− women. Women with both current obesity and GDM+ had highest sedentary time and lowest PA levels. The whole sample’s median 15D score was 0.934 (IQR 0.092), lower among women with obesity compared to the others (p < 0.001), but not different between GDM+ or GDM−. There was a positive correlation between VPA (adjusted rs = 0.262 p = 0.001) and the 15D score. After grouping according to BMI (< and ≥ 30 kg/m2), the associations remained significant only in women without obesity. Among them, sleep, total steps, MVPA, and VPA were positively associated with 15D.

Conclusions
Higher PA levels are associated with better HRQoL among high-risk women with normal weight and overweight but no differences were found among women affected by obesity in the early years after pregnancy.
Trial registration Ethics committees of Helsinki University Hospital (Dnro 300/e9/06) and South Karelian Central Hospital (Dnro 06/08).
Indicators and criteria of consciousness: ethical implications for the care of behaviourally unresponsive patients
Authors: Farisco Michele , Pennartz Cyriel , Annen Jitka , Cecconi Benedetta , Evers Kathinka 
Published: March 2022

AbstractBackgroundAssessing consciousness in other subjects, particularly in non-verbal and behaviourally disabled subjects (e.g., patients with disorders of consciousness), is notoriously challenging but increasingly urgent. The high rate of misdiagnosis among disorders of consciousness raises the need for new perspectives in order to inspire new technical and clinical approaches.Main bodyWe take as a starting point a recently introduced list of operational indicators of consciousness that facilitates its recognition in challenging cases like non-human animals and Artificial Intelligence to explore their relevance to disorders of consciousness and their potential ethical impact on the diagnosis and healthcare of relevant patients. Indicators of consciousness mean particular capacities that can be deduced from observing the behaviour or cognitive performance of the subject in question (or from neural correlates of such performance) and that do not define a hard threshold in deciding about the presence of consciousness, but can be used to infer a graded measure based on the consistency amongst the different indicators. The indicators of consciousness under consideration offer a potential useful strategy for identifying and assessing residual consciousness in patients with disorders of consciousness, setting the theoretical stage for an operationalization and quantification of relevant brain activity.ConclusionsOur heuristic analysis supports the conclusion that the application of the identified indicators of consciousness to its disorders will likely inspire new strategies for assessing three very urgent issues: the misdiagnosis of disorders of consciousness; the need for a gold standard in detecting consciousness and diagnosing its disorders; and the need for a refined taxonomy of disorders of consciousness.
Safety and efficacy of G2-S16 dendrimer as microbicide in healthy human vaginal tissue explants
Authors: Rodríguez-Izquierdo I. , Serramía M. J. , Gómez R. , Espinosa G. , Genebat M. , Leal M. , Muñoz-Fernandez M. A. 
Published: March 2022

Abstract
Background
The absence of an effective treatment and vaccine in HIV-1 pandemic place preventive strategies such as safety and effective microbicide development as a central therapeutic approach to control HIV-1 pandemic nowadays.

Results
Studies of cytotoxicity, immune population status, inflammation or tissue damage and mainly prophylactic inhibition of HIV-1 infection in vaginal human explants demonstrate the biosafety and effectivity of G2-S16 dendrimer. Human explants treated with G2-S16 dendrimer or treated and HIV-1 infected do not presented signs of irritation, inflammation, immune activation or T cell populations deregulation.

Conclusions
Herein we conclude that G2-S16 dendrimer has demonstrated sufficient efficacy, biosafety, effectivity and behavior in the closest to the real-life condition model represented by the human healthy donor vaginal tissue explants, to raise G2-S16 dendrimer as a promising candidate to clinical trials to develop an effective microbicide against HIV-1 infection.

Graphical Abstract
A four-stage model for murine natural killer cell development in vivo
Authors: Ma Shoubao , Caligiuri Michael A. , Yu Jianhua 
Published: March 2022

AbstractNatural killer (NK) cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. NK cells arise from hematopoietic stem cells in the bone marrow (BM) and undergo lineage specification and maturation. Despite the importance of NK cells for innate immunity and the development of innovative cancer therapy, the detailed steps linking NK progenitor (NKP) cell development through immature NK (iNK) cells to mature NK (mNK) cells are poorly defined. In this study, we found that CD49b, NK1.1, and NKp46 are sequentially acquired during the development of murine Lin−CD122+ NKP cells. Introducing NKp46 allows us to propose a four-stage developmental model, wherein CD122+NK1.1−CD49b−NKp46− defines an NKP population, CD122+NK1.1−CD49b+NKp46− and CD122+NK1.1+CD49b−/+ NKp46− define iNK-a and iNK-b populations, respectively, and CD122+NK1.1+CD49b+NKp46+ defines an mNK population. These four NK cell populations are phenotypically distinct based on their expression of cell surface markers, transcription factors, and effector molecules. Using a differentiation assay ex vivo and adoptive transfer model in vivo, we confirmed that NK cell development follows our predicted four-stage model. Taken together, our findings establish two distinct populations of immature NK cells and define a model for mouse NK cell development.
Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF/miR-192-5p/CYR61/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment
Authors: Yin Shuangshuang , Jin Wenke , Qiu Yuling , Fu Leilei , Wang Tao , Yu Haiyang 
Published: March 2022

AbstractHepatocellular carcinoma (HCC) is well-known to be a highly prevalent malignant tumor, but the treatment of this pathological state has been still challenging. Solamargine (SM), a traditional Chinese herb-derived compound, has been widely reported to possess multiple antitumor properties. However, whether SM plays a vital role in HCC therapy and how it exerts an antitumor effect remains unclear. Thus, in this study, we demonstrated that SM inhibited the proliferation of HCC and effectively induced HCC cell apoptosis and autophagy in vitro and in vivo. Mechanistically, the oncogenic factor LIF was aberrantly elevated in HCC tissues and down-regulated by SM in HCC cells, as well as subsequently the overexpression of LIF could restore the anti-HCC effects of SM via miR-192-5p/CYR61/Akt signaling pathways. Additionally, SM could repolarize tumor associated macrophages by LIF/p-Stat3 to inhibit the growth and epithelial-mesenchymal transition of HCC, and simultaneously affected other immune cell populations in the immune (tumor) microenvironment by regulating macrophages, such as MDSCs, DCs and T cell populations. Together, these findings exploit the potential use of SM against HCC and shed light on exploring SM as a potent candidate drug for the future HCC therapeutics.
Diabetes‐related foot disease research in Aotearoa New Zealand: a bibliometric analysis (1970–2020)
Authors: Carroll Matthew , Al‐Busaidi Ibrahim Saleh , Coppell Kirsten J. , Garrett Michele , Ihaka Belinda , O'Shea Claire , Wu Justina , York Steve 
Published: March 2022

AbstractBackgroundThe aim of this bibliometric study was to examine trends in the quality and quantity of published diabetes‐related foot disease (DRFD) research in Aotearoa/New Zealand (NZ) over the past five decades.MethodIn July 2021, the Scopus® database was searched for DRFD‐related publications (1970–2020) using predetermined search and inclusion criteria. Bibliometric data were extracted from Scopus® and Journal Citation Reports. Retrieved bibliometric indicators were analysed in Biblioshiny, an R Statistical Software interface and reported using descriptive statistics.ResultsForty‐seven DRFD‐related articles were identified. The annual number of publications showed a significant upward trend increasing from one in 1988 to a peak of six in 2018 (P < 0.001). The majority of identified articles (n = 31, 66%) were published in the last decade (2011–2020). Basic/clinical research accounted for 87% (n = 41) of publications and 14 (30%) investigated the screening and/or prevention of DRFD. The average citation per article was 20.23 (range: 0–209) and the median impact factor was 4.31 (range, 1.82–79.32). Over a third of articles (36%) had an international authorship network. Funding was reported in 15 (32%) articles; 12 (26%) were supported by public national grants vs. three (6%) reporting industry‐sponsorship.ConclusionDRFD articles authored by NZ researchers have increased over the past five decades. Despite NZ researchers having increased their global impact through collaborative networks, most of the research was classified as low‐level evidence, with limited focus on Indigenous Māori and limited financial support and funding. Increased funding for interventional research is required to enable a higher level of evidence‐based and practice‐changing research to occur. With rates of diabetes‐related amputations higher in Māori future research must focus on reducing inequalities in diabetes‐related outcomes for Māori by specifically targeting the prevention and screening of DRFD in primary care settings in NZ.
Associations between the size of individual plantar intrinsic and extrinsic foot muscles and toe flexor strength
Authors: Kusagawa Yuki , Kurihara Toshiyuki , Maeo Sumiaki , Sugiyama Takashi , Kanehisa Hiroaki , Isaka Tadao 
Published: March 2022

AbstractBackgroundThe size of the plantar intrinsic and extrinsic foot muscles has been shown to be associated with toe flexor strength (TFS). Previous studies adopted the size of limited plantar intrinsic foot muscles or a compartment containing several muscles as an independent variable for TFS. Among the plantar intrinsic and extrinsic foot muscles, therefore, it is unclear which muscle(s) primarily contributes to TFS production. The present study aimed to clarify this subject.MethodsIn 17 young adult men, a series of anatomical cross‐sectional area of individual plantar intrinsic and extrinsic foot muscles was obtained along the foot length and the lower leg length, respectively, using magnetic resonance imaging. Maximal anatomical cross‐sectional area (ACSAmax) and muscle volume (MV) for each constituent muscle of the plantar intrinsic foot muscles (flexor hallucis brevis; flexor digitorum brevis, FDB; abductor hallucis; adductor hallucis oblique head, ADDH‐OH; adductor hallucis transverse head, ADDH‐TH; abductor digiti minimi; quadratus plantae) and extrinsic foot muscles (flexor hallucis longus; flexor digitorum longus) were measured. TFS was measured with a toe grip dynamometry.ResultsTFS was significantly associated with the ACSAmax for each of the ADDH‐OH (r = 0.674, p = 0.003), ADDH‐TH (r = 0.523, p = 0.031), and FDB (r = 0.492, p = 0.045), and the MV of the ADDH‐OH (r = 0.582, p = 0.014). As for the ADDH‐OH, the correlation coefficient with TFS was not statistically different between ACSAmax and MV (p = 0.189). Stepwise multiple linear regression analysis indicated that ACSAmax and MV of the ADDH‐OH alone explained 42 and 29%, respectively, of the variance in TFS.ConclusionThe ADDH‐OH is the primary contributor to TFS production among the plantar intrinsic and extrinsic foot muscles as the result of the stepwise multiple linear regression analysis.
Digital PCR applications for the diagnosis and management of infection in critical care medicine
Authors: Merino Irene , de la Fuente Amanda , Domínguez-Gil Marta , Eiros José María , Tedim Ana P. , Bermejo-Martín Jesús F. 
Published: March 2022

AbstractInfection (either community acquired or nosocomial) is a major cause of morbidity and mortality in critical care medicine. Sepsis is present in up to 30% of all ICU patients. A large fraction of sepsis cases is driven by severe community acquired pneumonia (sCAP), which incidence has dramatically increased during COVID-19 pandemics. A frequent complication of ICU patients is ventilator associated pneumonia (VAP), which affects 10–25% of all ventilated patients, and bloodstream infections (BSIs), affecting about 10% of patients. Management of these severe infections poses several challenges, including early diagnosis, severity stratification, prognosis assessment or treatment guidance. Digital PCR (dPCR) is a next-generation PCR method that offers a number of technical advantages to face these challenges: it is less affected than real time PCR by the presence of PCR inhibitors leading to higher sensitivity. In addition, dPCR offers high reproducibility, and provides absolute quantification without the need for a standard curve. In this article we reviewed the existing evidence on the applications of dPCR to the management of infection in critical care medicine. We included thirty-two articles involving critically ill patients. Twenty-three articles focused on the amplification of microbial genes: (1) four articles approached bacterial identification in blood or plasma; (2) one article used dPCR for fungal identification in blood; (3) another article focused on bacterial and fungal identification in other clinical samples; (4) three articles used dPCR for viral identification; (5) twelve articles quantified microbial burden by dPCR to assess severity, prognosis and treatment guidance; (6) two articles used dPCR to determine microbial ecology in ICU patients. The remaining nine articles used dPCR to profile host responses to infection, two of them for severity stratification in sepsis, four focused to improve diagnosis of this disease, one for detecting sCAP, one for detecting VAP, and finally one aimed to predict progression of COVID-19. This review evidences the potential of dPCR as a useful tool that could contribute to improve the detection and clinical management of infection in critical care medicine.
Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society
Authors: Won Hye Sung , Ahn Juneyoung , Kim Yongseon , Kim Jin Sung , Song Jeong-Yoon , Kim Hong-Kyu , Lee Jeeyeon , Park Heung Kyu , Kim Yong-Seok 
Published: March 2022

Abstract
Background
There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody–drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer.

Methods
Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan–Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups.

Results
HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49–0.93; P = 0.019).

Conclusions
These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.