bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin suppresses serum starvation-induced autophagy of ovarian granulosa cells in premature ovarian insufficiency
Authors: Wu Di , Zhao Wenjie , Xu Chengjuan , Zhou Xin , Leng Xia , Li Yanmin 
Published: November 2022

Abstract
Objectives
Premature ovarian insufficiency (POI) refers to the decline and cessation of ovarian functions in women under 40 years of age. Melatonin (MT) acts as a protective for the ovary. This study elucidated the role of MT in autophagy of granulosa cells (GCs) in POI via modulating the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway.

Methods
The expression levels of microRNA (miR)-15a-5p, signal transducer and activator of transcription 3 (Stat3), and relevant hormones in the clinically collected serum samples of POI patients and healthy controls were examined. Human ovarian granulosa-like tumor cells (KGN) underwent serum starvation (SS) treatment to induce POI cell models and then received MT treatment. The expression levels of miR-15a-5p, Stat3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in KGN cells were tested via quantitative real-time polymerase chain reaction and Western blotting. KGN cell viability was assessed by MTT assay and the protein levels of autophagy-related markers Beclin-1, microtubule-associated protein light chain 3 II/I, and p62 were detected by Western blotting. The binding relation between miR-15a-5p and Stat3 was verified via the dual-luciferase reporter gene assay. Functional rescue experiments were performed to probe the underlying role of miR-15a-5p/Stat3/the PI3K-Akt-mTOR pathway in KGN cell autophagy.

Results
miR-15a-5p was increased whilst Stat3 was decreased in the serum of POI patients and SS-induced KGN cells. MT inhibited miR-15a-5p and Stat3, activated the PI3K-Akt-mTOR pathway, and repressed cell autophagy in SS-induced KGN cells. miR-15a-5p targeted and repressed Stat3 expression. Upregulation of miR-15a-5p or downregulation of Stat3 or the PI3K-Akt-mTOR pathway promoted KGN cell autophagy.

Conclusion
MT suppressed miR-15a-5p and activated Stat3 and the PI3K-Akt-mTOR pathway, finally impeding SS-induced autophagy of GCs.
Do the benefits continue? Long term impacts of the Anatomy Education Research Institute (AERI) 2017
Authors: Husmann Polly R. , Brokaw James J. , O’Loughlin Valerie Dean 
Published: November 2022

Abstract
Background
The Anatomy Education Research Institute (AERI) was held in Bloomington, Indiana in July of 2017. Previous research has shown that AERI was successful in meeting Kirkpatrick’s first two levels of evaluation via positive initial reactions and learning gains identified at the end of AERI. This manuscript demonstrates continued success in Kirkpatrick levels two and three via six-month and thirty-month follow-up surveys and nine-month follow-up focus groups and interviews.

Methods
Quantitative analyses were completed using Microsoft Excel (2019) and SPSS version 26 while qualitative analyses were completed for both survey responses and focus groups/interviews using thematic analyses.

Results
Results demonstrate that the learning gains seen immediately post-AERI 2017 were sustained for all participants (accepted applicants and invited speakers). Qualitative results continued to demonstrate positive reactions to AERI 2017. Both quantitative and qualitative results demonstrated that the main obstacle to educational research for most participants is time, while collaboration, IRB, institutional roadblocks, and devaluing of educational research were also identified as obstacles.

Conclusions
The research presented here indicates positive outcomes to Kirkpatrick Levels 1, 2, & 3 of evaluation following AERI 2017. However, substantial obstacles still exist for researchers in medical education. The need for a sustained community of practice for educational researchers was suggested as a potential buffer against these obstacles and multiple options for providing that community are discussed.
Risk factors affecting COVID-19 vaccine effectiveness identified from 290 cross-country observational studies until February 2022: a meta-analysis and meta-regression
Authors: Petráš Marek , Máčalík Roman , Janovská Daniela , Čelko Alexander M. , Dáňová Jana , Selinger Eliška , Doleček Jonáš , Neradová Sylva , Franklová Martina , Dlouhý Pavel , Rosina Jozef , Lesná Ivana Králová 
Published: November 2022

Abstract
Background
Observational studies made it possible to assess the impact of risk factors on the long-term effectiveness of mRNA and adenoviral vector (AdV) vaccines against COVID-19.

Methods
A computerized literature search was undertaken using the MEDLINE, EMBASE, and MedRxiv databases to identify eligible studies, with no language restrictions, published up to 28 February 2022. Eligible were observational studies assessing vaccine effectiveness (VE) by disease severity with reference groups of unvaccinated participants or participants immunized with one, two, or three vaccine doses. Our study was carried out in compliance with the PRISMA and MOOSE guidelines. The risk of study bias was identified using the Newcastle–Ottawa Quality Assessment Scale. The GRADE guidelines were applied to assess the strength of evidence for the primary outcome. The synthesis was conducted using a meta-analysis and meta-regression.

Results
Out of a total of 14,155 publications, 290 studies were included. Early VE of full vaccination against COVID-19 of any symptomatology and severity decreased from 96% (95% CI, 95–96%) for mRNA and from 86% (95% CI, 83–89%) for AdV vaccines to 67% for both vaccine types in the last 2 months of 2021. A similar 1-year decline from 98 to 86% was found for severe COVID-19 after full immunization with mRNA, but not with AdV vaccines providing persistent 82–87% effectiveness. Variant-reduced VE was only associated with Omicron regardless of disease severity, vaccine type, or vaccination completeness. The level of protection was reduced in participants aged >65 years, with a comorbidity or those in long-term care or residential homes independently of the number of doses received. The booster effect of the third mRNA dose was unclear because incompletely restored effectiveness, regardless of disease severity, declined within a short-term interval of 4 months.

Conclusions
Full vaccination provided an early high, yet waning level of protection against COVID-19 of any severity with a strong impact on the high-risk population. Moreover, the potential risk of new antigenically distinct variants should not be underestimated, and any future immunization strategy should include variant-updated vaccines.
Lipid and metabolic alteration involvement in physiotherapy for chronic nonspecific low back pain
Authors: Zhang Zhou , Zhang Chanjuan , Li Yuelong , Wang Chuhuai , Yu Qiuhua 
Published: November 2022

Abstract
Background
Chronic nonspecific low back pain (cNLBP) is a common health problem worldwide, affecting 65–80% of the population and greatly affecting people’s quality of life and productivity. It also causes huge economic losses. Manual therapy (MT) and therapeutic exercise (TE) are effective treatment options for cNLBP physiotherapy-based treatment. However, the underlying mechanisms that promote cNLBP amelioration by MT or TE are incompletely understood.

Methods
Seventeen recruited subjects were randomly divided into an MT group and a TE group. Subjects in the MT group performed muscular relaxation, myofascial release, and mobilization for 20 min during each treatment session. The treatment lasted for a total of six sessions, once every two days. Subjects in the TE group completed motor control and core stability exercises for 30 min during each treatment session. The motor control exercise included stretching of the trunk and extremity muscles through trunk and hip rotation and flexion training. Stabilization exercises consisted of the (1) bridge exercise, (2) single-leg-lift bridge exercise, (3) side bridge exercise, (4) two-point bird-dog position with an elevated contralateral leg and arm, (5) bear crawl exercise, and (6) dead bug exercise. The treatment lasted for a total of six sessions, with one session every two days. Serum samples were collected from subjects before and after physiotherapy-based treatment for lipidomic and metabolomic measurements.

Results
Through lipidomic analysis, we found that the phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio decreased and the sphingomyelin/ceramide (SM/Cer) ratio increased in cNLBP patients after MT or TE treatment. In addition, eight metabolites enriched in pyrimidine and purine differed significantly in cNLBP patients who received MT treatment. A total of nine metabolites enriched in pyrimidine, tyrosine, and galactose pathways differed significantly in cNLBP patients after TE treatment during metabolomics analysis.

Conclusion
Our study was the first to elucidate the alterations in the lipidomics and metabolomics of cNLBP physiotherapy-based treatment and can expand our knowledge of cNLBP physiotherapy-based treatment.
RRP9 promotes gemcitabine resistance in pancreatic cancer via activating AKT signaling pathway
Authors: Zhang Zhiqi , Yu Haitao , Yao Wenyan , Zhu Na , Miao Ran , Liu Zhiquan , Song Xuwei , Xue Chunhua , Cai Cheng , Cheng Ming , Lin Ke , Qi Dachuan 
Published: November 2022

Abstract
Background
Pancreatic cancer (PC) is a highly lethal malignancy regarding digestive system, which is the fourth leading factor of cancer-related mortalities in the globe. Prognosis is poor due to diagnosis at advanced disease stage, low rates of surgical resection, and resistance to traditional radiotherapy and chemotherapy. In order to develop novel therapeutic strategies, further elucidation of the molecular mechanisms underlying PC chemoresistance is required. Ribosomal RNA biogenesis has been implicated in tumorigenesis. Small nucleolar RNAs (snoRNAs) is responsible for post-transcriptional modifications of ribosomal RNAs during biogenesis, which have been identified as potential markers of various cancers. Here, we investigate the U3 snoRNA-associated protein RRP9/U3-55 K along with its role in the development of PC and gemcitabine resistance.

Methods
qRT-PCR, western blot and immunohistochemical staining assays were employed to detect RRP9 expression in human PC tissue samples and cell lines. RRP9-overexpression and siRNA-RRP9 plasmids were constructed to test the effects of RRP9 overexpression and knockdown on cell viability investigated by MTT assay, colony formation, and apoptosis measured by FACS and western blot assays. Immunoprecipitation and immunofluorescence staining were utilized to demonstrate a relationship between RRP9 and IGF2BP1. A subcutaneous xenograft tumor model was elucidated in BALB/c nude mice to examine the RRP9 role in PC in vivo.

Results
Significantly elevated RRP9 expression was observed in PC tissues than normal tissues, which was negatively correlated with patient prognosis. We found that RRP9 promoted gemcitabine resistance in PC in vivo and in vitro. Mechanistically, RRP9 activated AKT signaling pathway through interacting with DNA binding region of IGF2BP1 in PC cells, thereby promoting PC progression, and inducing gemcitabine resistance through a reduction in DNA damage and inhibition of apoptosis. Treatment with a combination of the AKT inhibitor MK-2206 and gemcitabine significantly inhibited tumor proliferation induced by overexpression of RRP9 in vitro and in vivo.

Conclusions
Our data reveal that RRP9 has a critical function to induce gemcitabine chemoresistance in PC through the IGF2BP1/AKT signaling pathway activation, which might be a candidate to sensitize PC cells to gemcitabine.

Graphical Abstract
PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma
Authors: Corrales Eyleen , Levit-Zerdoun Ella , Metzger Patrick , Mertes Ralf , Lehmann Ariane , Münch Julia , Lemke Steffen , Kowar Silke , Boerries Melanie 
Published: November 2022

Abstract
Background
Current therapeutic management of advanced melanoma patients largely depends on their BRAF mutation status. However, the vast heterogeneity of the tumors hampers the success of therapies targeting the MAPK/ERK pathway alone. Dissecting this heterogeneity will contribute to identifying key players in the oncogenic progression to tailor more effective therapies.

Methods
We performed a comprehensive molecular and phenotypic characterization of a panel of patient-derived BRAFV600E-positive melanoma cell lines. Transcriptional profiling was used to identify groups of coregulated genes whose expression relates to an increased migratory potential and a higher resistance.

Results
A decrease in sensitivity to MAPK/ERK pathway inhibition with vemurafenib or trametinib corresponded with an increasing quiescence and migratory properties of the cells. This was accompanied by the loss of transcriptional signatures of melanocytic differentiation, and the gain of stem cell features that conferred highly-resistant/mesenchymal-like cells with increased xenobiotic efflux capacity. Nevertheless, targeting of the implicated ABC transporters did not improve the response to vemurafenib, indicating that incomplete BRAF inhibition due to reduced drug uptake is not a main driver of resistance. Rather, indifference to MAPK/ERK pathway inhibition arose from the activation of compensatory signaling cascades. The PI3K/AKT pathway in particular showed a higher activity in mesenchymal-like cells, conferring a lower dependency on MAPK/ERK signaling and supporting stem-like properties that could be reverted by dual PI3K/mTOR inhibition with dactolisib.

Conclusions
In case of MAPK/ERK independency, therapeutic focus may be shifted to the PI3K/AKT pathway to overcome late-stage resistance in melanoma tumors that have acquired a mesenchymal phenotype.
Are clinical outcomes affected by laminoplasty method and K-line in patients with cervical ossification of posterior longitudinal ligament? A multicenter study
Authors: Li Nan , Ma Sai , Duan Fangfang , Wei Yi , He Da , Nagoshi Narihito , Watanabe Kota , Nakamura Masaya , Matsumoto Morio , Jeon Hyeongseok , Lee J. J. , Kim Keung-Nyun , Ha Yoon , Kwan Kenny , Cheung A. K. P. , Clark Aaron 
Published: November 2022

Abstract
Background
Open-door laminoplasty (ODL) and French-door laminoplasty (FDL) are the main laminoplasty techniques used to treat cervical ossification of the posterior longitudinal ligament (C-OPLL). However, few studies have compared the outcomes of ODL and modified FDL (mFDL) for C-OPLL. We explored the differences in outcomes between ODL and mFDL for C-OPLL and analyzed the technical efficacy of each procedure in patients with K-line (+) or (−) C-OPLL.

Methods
From January 2010 to December 2015, 202 patients with K-line (+) or (−) C-OPLL were retrospectively recruited from 4 institutions. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA score recovery rate, operative time, blood loss, and complications. Univariate analysis and binary logistic regression models were adjusted for confounding factors.

Results
Two hundred patients (mFDL, n = 69; ODL, n = 131) with a median follow-up of 42 months (range 36–54 months) were included. The postoperative JOA score significantly improved in both groups (P < 0.05). After adjusting for confounding factors, there was a statistically significant difference in blood loss (≥ 300 mL) between the two groups (P = 0.005), but there was no significant difference in the postoperative JOA score (≥ 14) (P = 0.062), JOA score recovery rate (≥ 0.82) (P = 0.187), or operative time (≥ 90 min) (P = 0.925). C5 palsy tended to occur more often in the mFDL group, although the difference was not significant (P > 0.05). The stratified analysis of the K-line status showed more blood loss in K-line (+) patients who underwent mFDL, but there was no significant difference in the postoperative JOA score, JOA score recovery rate, or operative time between the ODL and mFDL groups. Additionally, there was no significant difference in blood loss, postoperative JOA score, JOA score recovery rate, or operative time among all patients with K-line (+) or (−) C-OPLL in both groups.

Conclusions
Both ODL and mFDL are effective for patients with C-OPLL. However, more blood loss tends to occur during mFDL. This study showed no significant difference in the operative time or incidence of complications between the two techniques. The efficacy of ODL and mFDL was not affected by the K-line status (+ or −) in patients with C-OPLL.
An investigation into entrepreneurial intentions in Caribbean Small Island Developing States
Authors: Mohan Preeya S. 
Published: November 2022

AbstractThis paper explored entrepreneurial intentions in the Caribbean adult population using a social cognitive approach. It used the Global Entrepreneurship Monitor (GEM) Adult Population Survey (APS), which includes questions about entrepreneurial intentions of potential business owners and entrepreneurial perceptions, namely individual, entrepreneurial opportunities and socio-cultural, along with demographic and socio-economic variables. The effect of perceptions along with socio-economic control variables on entrepreneurial intentions was investigated using probit regression models. The results confirm that even after controlling for demographic and socio-economic and country fixed effects, social cognitive perceptions were indeed relevant in explaining entrepreneurial intentions in the region. This study therefore provides insights into understanding entrepreneurship in particular the decision to form a new business through the individual’s perceptions and intentions.
HT-SIP: a semi-automated stable isotope probing pipeline identifies cross-kingdom interactions in the hyphosphere of arbuscular mycorrhizal fungi
Authors: Nuccio Erin E. , Blazewicz Steven J. , Lafler Marissa , Campbell Ashley N. , Kakouridis Anne , Kimbrel Jeffrey A. , Wollard Jessica , Vyshenska Dariia , Riley Robert , Tomatsu Andy , Hestrin Rachel , Malmstrom Rex R. , Firestone Mary , Pett-Ridge Jennifer 
Published: November 2022

AbstractBackgroundLinking the identity of wild microbes with their ecophysiological traits and environmental functions is a key ambition for microbial ecologists. Of many techniques that strive for this goal, Stable-isotope probing—SIP—remains among the most comprehensive for studying whole microbial communities in situ. In DNA-SIP, actively growing microorganisms that take up an isotopically heavy substrate build heavier DNA, which can be partitioned by density into multiple fractions and sequenced. However, SIP is relatively low throughput and requires significant hands-on labor. We designed and tested a semi-automated, high-throughput SIP (HT-SIP) pipeline to support well-replicated, temporally resolved amplicon and metagenomics experiments. We applied this pipeline to a soil microhabitat with significant ecological importance—the hyphosphere zone surrounding arbuscular mycorrhizal fungal (AMF) hyphae. AMF form symbiotic relationships with most plant species and play key roles in terrestrial nutrient and carbon cycling.ResultsOur HT-SIP pipeline for fractionation, cleanup, and nucleic acid quantification of density gradients requires one-sixth of the hands-on labor compared to manual SIP and allows 16 samples to be processed simultaneously. Automated density fractionation increased the reproducibility of SIP gradients compared to manual fractionation, and we show adding a non-ionic detergent to the gradient buffer improved SIP DNA recovery. We applied HT-SIP to13C-AMF hyphosphere DNA from a13CO2plant labeling study and created metagenome-assembled genomes (MAGs) using high-resolution SIP metagenomics (14 metagenomes per gradient). SIP confirmed the AMFRhizophagus intraradicesand associated MAGs were highly enriched (10–33 atom%13C), even though the soils’ overall enrichment was low (1.8 atom%13C). We assembled 21213C-hyphosphere MAGs; the hyphosphere taxa that assimilated the most AMF-derived13C were from the phyla Myxococcota, Fibrobacterota, Verrucomicrobiota, and the ammonia-oxidizing archaeon genusNitrososphaera.ConclusionsOur semi-automated HT-SIP approach decreases operator time and improves reproducibility by targeting the most labor-intensive steps of SIP—fraction collection and cleanup. We illustrate this approach in a unique and understudied soil microhabitat—generating MAGs of actively growing microbes living in the AMF hyphosphere (without plant roots). The MAGs’ phylogenetic composition and gene content suggest predation, decomposition, and ammonia oxidation may be key processes in hyphosphere nutrient cycling.
Subcutaneous fat necrosis in newborns: a systematic literature review of case reports and model of pathophysiology
Authors: Frank Leonie , Brandt Stephanie , Wabitsch Martin 
Published: November 2022

Abstract
Background
Subcutaneous fat necrosis of the newborn (SCFN) is a rare disease occurring in the first days of life. Characteristically, the infants show hard nodules in subcutaneous tissue, purple or erythematous in color and appear on the upper back, cheeks, buttocks and limbs. In most cases, SCFN is a self-limiting disease, as the nodules disappear in up to 6 months. A severe complication associated with SCFN is hypercalcaemia. Pathophysiological mechanisms causing SCFN or associated hypercalcaemia are not fully understood yet.

Methods
A systematic literature research including the six biggest databases for medical research has been used to identify all published case reports of SCFN. N = 206 publications has been identified containing n = 320 case reports. All cases have been classified into four subgroups (depending on reported serum-calcium-level): hypercalcaemia, normocalcaemia, hypocalcaemia or no information given. Reported maternal factors, birth characteristics, details about SCFN, diagnostics, therapy and long-term observations have been extracted from publications.

Results
This is the first systematic literature research that summed up all published cases of SCFN from 1948 up to 2018. Information about serum calcium level was given in 64.3% of the cases. From those, the majority showed hypercalcaemia (70.5%) (normocalcaemia 25.1%, hypocalcemia 4.3%). 89.3% of newborns with hypercalcaemia showed suppressed levels of the parathormone. Maternal gestational diabetes, maternal hypertensive diseases during pregnancy, macrosomia (> 4000g), asphyxia and therapeutic hypothermia are risk factors for SCFN. Histological findings showed a granulomatous inflammation in 98% of cases.

Conclusion
We identified that maternal, birth characteristics and therapeutic measures are probably risk factors for SCFN. These risk factors should be taken into account within the care of neonates.