bluuebunny/crossref_metadata_2025_split huggingface dataset:
Admixture with indigenous people helps local adaptation: admixture-enabled selection in Polynesians
Authors: Isshiki Mariko , Naka Izumi , Kimura Ryosuke , Nishida Nao , Furusawa Takuro , Natsuhara Kazumi , Yamauchi Taro , Nakazawa Minato , Ishida Takafumi , Inaoka Tsukasa , Matsumura Yasuhiro , Ohtsuka Ryutaro , Ohashi Jun 
Published: September 2021

Abstract
Background
Homo sapiens have experienced admixture many times in the last few thousand years. To examine how admixture affects local adaptation, we investigated genomes of modern Polynesians, who are shaped through admixture between Austronesian-speaking people from Southeast Asia (Asian-related ancestors) and indigenous people in Near Oceania (Papuan-related ancestors).

Methods
In this study local ancestry was estimated across the genome in Polynesians (23 Tongan subjects) to find the candidate regions of admixture-enabled selection contributed by Papuan-related ancestors.

Results
The mean proportion of Papuan-related ancestry across the Polynesian genome was estimated as 24.6% (SD = 8.63%), and two genomic regions, the extended major histocompatibility complex (xMHC) region on chromosome 6 and the ATP-binding cassette transporter sub-family C member 11 (ABCC11) gene on chromosome 16, showed proportions of Papuan-related ancestry more than 5 SD greater than the mean (> 67.8%). The coalescent simulation under the assumption of selective neutrality suggested that such signals of Papuan-related ancestry enrichment were caused by positive selection after admixture (false discovery rate = 0.045). The ABCC11 harbors a nonsynonymous SNP, rs17822931, which affects apocrine secretory cell function. The approximate Bayesian computation indicated that, in Polynesian ancestors, a strong positive selection (s = 0.0217) acted on the ancestral allele of rs17822931 derived from Papuan-related ancestors.

Conclusions
Our results suggest that admixture with Papuan-related ancestors contributed to the rapid local adaptation of Polynesian ancestors. Considering frequent admixture events in human evolution history, the acceleration of local adaptation through admixture should be a common event in humans.
Intraspecific differences in plant functional traits are related to urban atmospheric particulate matter
Authors: Zhu Jiyou , Xu Chengyang 
Published: September 2021

Abstract
Background
Functional trait-based ecological research has been instrumental in advancing our understanding of environmental changes. It is still, however, unclear how the functional traits of urban plants respond to atmospheric particulate matter, and which trade-off strategies are shown. In order to explore the variation of plant functional traits with the gradient of urban atmospheric particulate matter, we divided atmospheric particulate matter into three levels according to road distance, and measured the variation of six essential leaf functional traits and their trade-off strategies.

Results
Here, we show that the functional traits of plants can be used as predictors of plant response to urban atmospheric particulate matter. Within the study, leaf thickness, leaf dry matter content, leaf tissue density, stomatal density were positively correlated with atmospheric particulate matter. On the contrary, chlorophyll content index and specific leaf area were negatively correlated with atmospheric particulate matter. Plants can improve the efficiency of gas exchange by optimizing the spatial distribution of leaf stomata. Under the atmospheric particulate matter environment, urban plants show a trade-off relationship of economics spectrum traits at the intraspecific level.

Conclusion
Under the influence of urban atmospheric particulate matter, urban plant shows a “slow investment-return” type in the leaf economics spectrum at the intraspecific level, with lower specific leaf area, lower chlorophyll content index, ticker leaves, higher leaf dry matter content, higher leaf tissue density and higher stomatal density. This finding provides a new perspective for understanding the resource trades-off strategy of plants adapting to atmospheric particulate matter.
Different outcomes after proximal femoral replacement in oncologic and failed revision arthroplasty patients - a retrospective cohort study
Authors: Toepfer Andreas , Straßer Veit , Ladurner Andreas , Calek Anna-Katharina , Potocnik Primoz , von Eisenhart-Rothe Ruediger 
Published: September 2021

Abstract
Background
Proximal femoral replacement (PFR) is a technically demanding procedure commonly performed to restore extensive, oncological or non-oncological bone defects in a severely debilitated patient collective. Depending on different indications, a varying outcome has been reported. The aim of the study was to assess the functional outcomes and complication rates of PFR with the modular Munich-Luebeck (MML) femoral megaprosthesis (ESKA/Orthodynamics, Luebeck, Germany), and to highlight outcome differences in patients treated for failed revision total hip arthroplasty (THA) or malignant bone disease.

Methods
A retrospective review of patients treated with PFR for failed THA or malignant tumor disease between 2000 and 2012 was performed. Patient satisfaction, functional outcome (VAS, SF-12, MSTS, WOMAC, TESS), complications and failure types (Henderson’s failure classification) were assessed. A Kaplan-Meier analysis determined implant survival.

Results
Fifty-eight patients (age: 69.9 years, BMI: 26.7 kg/m2, mean follow-up: 66 months) were included. The mean SF-12 (physical / mental) was 37.9 / 48.4. MSTS averaged 68% at final follow-up, while mean WOMAC and TESS scored 37.8 and 59.5. TESS and WOMAC scores demonstrated significantly worse outcomes in the revision group (RG) compared to the tumor group (TG). Overall complication rate was 43.1%, and dislocation was the most common complication (27.6%). Implant survival rates were 83% (RG) and 85% (TG; p = n.s.) at 5 years, while 10-year survival was 57% (RG) and 85% (TG, p < 0.05).

Conclusions
PFR is a salvage procedure for restoration of mechanical integrity and limb preservation after extensive bone loss. Complications rates are considerably high.
Functional outcomes and 10-year implant survival rate were worse in the RG compared to the TG. Strict indications and disease-specific patient education are essential in preoperative planning and prognosis.
Headache and migraine clinical practice guidelines: a systematic review and assessment of complementary and alternative medicine recommendations
Authors: Ng Jeremy Y. , Hanna Christina 
Published: September 2021

Abstract
Background
Globally, 3 billion people suffer from either migraine or tension-type headache disorder over their lifetime. Approximately 50% of American adults suffering from headache or migraine have used complementary and alternative medicine (CAM), however, the quality and quantity of recommendations associated with such therapies across clinical practice guidelines (CPGs) for the treatment and/or management of these conditions are unknown. The purpose of this study was to identify the quantity and assess the quality of such CAM recommendations.

Methods
MEDLINE, EMBASE and CINAHL were systematically searched from 2009 to April 2020; the Guidelines International Network and the National Center for Complementary and Integrative Health websites were also searched for eligible CPGs. CPGs were included if they provided any therapy recommendations. Eligible CPGs included those written for adult patients with headache and migraine; CPGs containing CAM recommendations were assessed twice for quality using the AGREE II instrument, once for the overall CPG and once for the CAM sections.

Results
Of 486 unique search results, 21 CPGs were eligible and quality assessed; fifteen CPGs mentioned CAM, of which 13 CPGs made CAM recommendations. The overall CPG assessment yielded higher scaled domain percentages than the CAM section across all domains. The results from highest to lowest were as follows (overall, CAM): clarity of presentation (66.7% vs. 50.0%), scope and purpose (63.9% vs. 61.1%), stakeholder involvement (22.2% vs. 13.9%), rigour of development (13.5% vs. 9.4%), applicability (6.3% vs. 0.0%), and editorial independence (0.0% vs. 0.0%).

Conclusions
Of the eligible CPGs, the CAM sections were of lower quality compared to the overall recommendations across all domains of the AGREE II instrument. CPGs that scored well could serve as a framework for discussion between patients and healthcare professionals regarding use of CAM therapies in the context of headache and migraine.
Harvard Medical School Department of Global Health and Social Medicine COVID-19 seminar series: COVID and surgical, anesthetic and obstetric care
Authors: Miranda Elizabeth , Meara John G. , Pendleton Alaska , Peters Alexander W. , Santhirapala Vatshalan , Ashraf Nabeel , Alonso Nivaldo , Hakizimana Sadoscar , Bekele Abebe , Park Kee B. , Farmer Paul 
Published: September 2021

AbstractOn May 21, 2020, the Harvard Program in Global Surgery and Social Change (PGSSC) hosted a webinar as part of the Harvard Medical School Department of Global Health and Social Medicine’s COVID-19 webinar series. The goal of PGSSC’s virtual webinar was to share the experiences of surgical, anesthesia, and obstetric (SAO) providers on the frontlines of the COVID pandemic, from both high-income countries (HICs), such as the United States and the United Kingdom, as well as low- and middle-income countries (LMICs). Providers shared not only their experiences delivering SAO care during this global pandemic, but also solutions and innovations they and their colleagues developed to address these new challenges. Additionally, the seminar explored the relationship between surgery and health system strengthening and pandemic preparedness, and outlined the way forward, including a roadmap for prioritization and investment in surgical system strengthening. Throughout the discussion, other themes emerged as well, such as the definition of elective surgery and its implications during a persistent global pandemic, the safe and ethical reintroduction of surgical services, and the social inequities exposed by the stress placed on health systems by COVID-19. These proceedings document the perspectives shared by participants through their invited lectures as well as through the panel discussion at the end of the seminar.
NACK and INTEGRATOR act coordinately to activate Notch-mediated transcription in tumorigenesis
Authors: Shersher Elena , Lahiry Mohini , Alvarez-Trotta Annamil , Diluvio Giulia , Robbins David J. , Shiekhattar Ramin , Capobianco Anthony J. 
Published: September 2021

Abstract
Background
Notch signaling drives many aspects of neoplastic phenotype. Here, we report that the Integrator complex (INT) is a new component of the Notch transcriptional supercomplex. Together with Notch Activation Complex Kinase (NACK), INT activates Notch1 target genes by driving RNA polymerase II (RNAPII)-dependent transcription, leading to tumorigenesis.

Methods
Size exclusion chromatography and CBF-1/RBPJ/Suppressor of Hairless/Lag-1 (CSL)-DNA affinity fast protein liquid chromatography (FPLC) was used to purify Notch/CSL-dependent complexes for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Chromatin immunoprecipitation (ChIP) and quantitative polymerase chain reaction (qPCR) were performed to investigate transcriptional regulation of Notch target genes. Transfection of Notch Ternary Complex components into HEK293T cells was used as a recapitulation assay to study Notch-mediated transcriptional mechanisms. Gene knockdown was achieved via RNA interference and the effects of protein depletion on esophageal adenocarcinoma (EAC) proliferation were determined via a colony formation assay and murine xenografts. Western blotting was used to examine expression of INT subunits in EAC cells and evaluate apoptotic proteins upon INT subunit 11 knockdown (INTS11 KD). Gene KD effects were further explored via flow cytometry.

Results
We identified the INT complex as part of the Notch transcriptional supercomplex. INT, together with NACK, activates Notch-mediated transcription. While NACK is required for the recruitment of RNAPII to a Notch-dependent promoter, the INT complex is essential for RNAPII phosphorylated at serine 5 (RNAPII-S5P), leading to transcriptional activation. Furthermore, INT subunits are overexpressed in EAC cells and INTS11 KD results in G2/M cell cycle arrest, apoptosis, and cell growth arrest in EAC.

Conclusions
This study identifies the INT complex as a novel co-factor in Notch-mediated transcription that together with NACK activates Notch target genes and leads to cancer cell proliferation.
Inhibition of microglial β-glucocerebrosidase hampers the microglia-mediated antioxidant and protective response in neurons
Authors: Brunialti Electra , Villa Alessandro , Mekhaeil Marianna , Mornata Federica , Vegeto Elisabetta , Maggi Adriana , Di Monte Donato A. , Ciana Paolo 
Published: September 2021

Abstract
Background
Homozygotic mutations in the GBA gene cause Gaucher’s disease; moreover, both patients and heterozygotic carriers have been associated with 20- to 30-fold increased risk of developing Parkinson’s disease. In homozygosis, these mutations impair the activity of β-glucocerebrosidase, the enzyme encoded by GBA, and generate a lysosomal disorder in macrophages, which changes morphology towards an engorged phenotype, considered the hallmark of Gaucher’s disease. Notwithstanding the key role of macrophages in this disease, most of the effects in the brain have been attributed to the β-glucocerebrosidase deficit in neurons, while a microglial phenotype for these mutations has never been reported.

Methods
We applied the bioluminescence imaging technology, immunohistochemistry and gene expression analysis to investigate the consequences of microglial β-glucocerebrosidase inhibition in the brain of reporter mice, in primary neuron/microglia cocultures and in cell lines. The use of primary cells from reporter mice allowed for the first time, to discriminate in cocultures neuronal from microglial responses consequent to the β-glucocerebrosidase inhibition; results were finally confirmed by pharmacological depletion of microglia from the brain of mice.

Results
Our data demonstrate the existence of a novel neuroprotective mechanism mediated by a direct microglia-to-neuron contact supported by functional actin structures. This cellular contact stimulates the nuclear factor erythroid 2-related factor 2 activity in neurons, a key signal involved in drug detoxification, redox balance, metabolism, autophagy, lysosomal biogenesis, mitochondrial dysfunctions, and neuroinflammation. The central role played by microglia in this neuronal response in vivo was proven by depletion of the lineage in the brain of reporter mice. Pharmacological inhibition of microglial β-glucocerebrosidase was proven to induce morphological changes, to turn on an anti-inflammatory/repairing pathway, and to hinder the microglia ability to activate the nuclear factor erythroid 2-related factor 2 response, thus increasing the neuronal susceptibility to neurotoxins.

Conclusion
This mechanism provides a possible explanation for the increased risk of neurodegeneration observed in carriers of GBA mutations and suggest novel therapeutic strategies designed to revert the microglial phenotype associated with β-glucocerebrosidase inhibition, aimed at resetting the protective microglia-to-neuron communication.
Chiropractic website claims related to non-musculoskeletal conditions: a cross-sectional study
Authors: Goncalves Guillaume , Fleuriau Philippe , Cheron Charlène , Picchiottino Mathieu , Pigeon Sylvain , Jensen Rikke Krüger 
Published: September 2021

Abstract
Background
Chiropractors frequently use spinal manipulation therapy as a treatment modality in the management of musculoskeletal (MSK) conditions such as spinal pain and sometimes in the treatment of non-MSK disorders. The latter is not supported by evidence. This study aimed to investigate the extent of non-MSK website claims from French chiropractors to assess if websites were aligned with current recommendations on evidence-based practice.

Methods
This was a cross-sectional study of a representative sample of French chiropractors. Information on non-MSK conditions was collected from chiropractic professional websites by two independent observers in June 2020. For each non-MSK condition, it was noted whether a clarifying explanation justifying the mentioning of the condition was available. In addition, data on professional association affiliation status, country of education, years since graduation, and special clinical focus (e.g., seniors, children) were collected.

Results
A total of 287 randomly selected websites were included in the study corresponding to 22% of all chiropractors registered in France. One or more of 42 different non-MSK conditions were identified on 231 websites, of which 5 (2.2%) provided a clarifying explanation. 226 (79%) websites mentioned a non-MSK condition without a clarifying explanation. The non-MSK conditions most often mentioned were sleep problems, constipation/digestive problems, unease/discontent in children and menstrual cramps/pains. A larger proportion of the websites advertising treatment for non-MSK disorders was found among those claiming a special clinical focus on infants/children, seniors, pregnant women or athletes compared to those that did not. Also, a larger proportion of chiropractors who were affiliated with a professional association were advertising treatment for non-MSK disorders compared to those who were not affiliated.

Conclusions
Eight out of ten chiropractic websites mentioned one or more non-MSK diagnoses or symptoms. It is unclear if this reflects inaccurate communication or if treatments for non-MSK conditions are provided by the chiropractors.
Nuclear speckle specific hnRNP D-like prevents age- and AD-related cognitive decline by modulating RNA splicing
Authors: Zhang Qingyang , Zhang Juan , Ye Jin , Li Xiaohui , Liu Hongda , Ma Xiaolin , Wang Chao , He Keqiang , Zhang Wei , Yuan Ji , Zhao Yingjun , Xu Huaxi , Liu Qiang 
Published: September 2021

AbstractBackgroundAberrant alternative splicing plays critical role in aging and age-related diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) reportedly regulate RNA splicing process. Whether and how hnRNPs contribute to age-related neurodegenerative diseases, especially Alzheimer’s disease (AD), remain elusive.MethodsImmunoblotting and immunostaining were performed to determine expression patterns and cellular/subcellular localization of the long isoform of hnRNP D-like (L-DL), which is a hnRNP family member, in mouse hippocampus. Downregulation of L-DL in WT mice was achieved by AAV-mediated shRNA delivery, followed by memory-related behavioural tests. L-DL interactome was analysed by affinity-precipitation and mass spectrometry. Alternative RNA splicing was measured by RNA-seq and analyzed by bioinformatics-based approaches. Downregulation and upregulation of L-DL in APP/PS1 mice were performed using AAV-mediated transduction.ResultsWe show that L-DL is specifically localized to nuclear speckles. L-DL levels are decreased in the hippocampus of aged mouse brains and downregulation of L-DL impairs cognition in mice. L-DL serves as a structural component to recruit other speckle proteins, and regulates cytoskeleton- and synapse-related gene expression by altering RNA splicing. Mechanistically, these splicing changes are modulated via L-DL-mediated interaction of SF3B3, a core component of U2 snRNP, and U2AF65, a U2 spliceosome protein that guides U2 snRNP’s binding to RNA. In addition, L-DL levels are decreased in APP/PS1 mouse brains. While downregulation of L-DL deteriorates memory deficits and overexpression of L-DL improves cognitive function in AD mice, by regulating the alternative splicing and expression of synaptic geneCAMKV.ConclusionsOur findings define a molecular mechanism by which hnRNP L-DL regulates alternative RNA splicing, and establish a direct role for L-DL in AD-related synaptic dysfunction and memory decline.
RETRACTED ARTICLE: LNCAROD enhances hepatocellular carcinoma malignancy by activating glycolysis through induction of pyruvate kinase isoform PKM2
Authors: Jia Guizhi , Wang Yan , Lin Chengjie , Lai Shihui , Dai Hongliang , Wang Zhiqian , Dai Luo , Su Huizhao , Song Yanjie , Zhang Naiwen , Feng Yukuan , Tang Bo 
Published: September 2021

Abstract
Background
Mounting evidence has suggested the essential role of long non-coding RNAs (lncRNAs) in a plethora of malignant tumors, including hepatocellular carcinoma. However, the underlyling mechanisms of lncRNAs remain unidentified in HCC. The present work was aimed to explore the regulatory functions and mechanisms of LncRNA LNCAROD in HCC progression and chemotherapeutic response.

Methods
The expression of LNCAROD in HCC tissues and cell lines were detected by quantitative reverse transcription PCR (qPCR). Cancer cell proliferation, migration, invasion, and chemoresistance were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and chemosensitivity assays. Methylated RNA immunoprecipitation qRCR (MeRIP-qPCR) was used to determine N6-methyladenosine (m6A) modification level. RNA immunoprecipitation (RIP) and RNA pull down were applied to identify the molecular sponge role of LNCAROD for modulation of miR-145-5p via the competing endogenous RNA (ceRNA) mechanism, as well as the interaction between LNCAROD and serine-and arginine-rich splicing factor 3 (SRSF3). The interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and LNCAROD was also identified by RIP assay. Gain- or-loss-of-function assays were used to identify the function and underlying mechanisms of LNCAROD in HCC.

Results
We found that LNCAROD was significantly upregulated and predicted a poorer prognosis in HCC patients. LNCAROD upregulation was maintained by increased m6A methylation-mediated RNA stability. LNCAROD significantly promoted HCC cell proliferation, migration, invasion, and chemoresistance both in vitro and in vivo. Furthermore, mechanistic studies revealed that pyruvate kinase isoform M2 (PKM2)-mediated glycolysis enhancement is critical for the role of LNACROD in HCC. According to bioinformatics prediction and our experimental data, LNCAROD directly binds to SRSF3 to induce PKM switching towards PKM2 and maintains PKM2 levels in HCC by acting as a ceRNA against miR-145-5p. The oncogenic effects of LNCAROD in HCC were more prominent under hypoxia than normoxia due to the upregulation of hypoxia-triggered hypoxia-inducible factor 1α.

Conclusions
In summary, our present study suggests that LNCAROD induces PKM2 upregulation via simultaneously enhancing SRSF3-mediated PKM switching to PKM2 and sponging miR-145-5p to increase PKM2 level, eventually increasing cancer cell aerobic glycolysis to participate in tumor malignancy and chemoresistance, especially under hypoxic microenvironment. This study provides a promising diagnostic marker and therapeutic target for HCC patients.