bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population study of the gut microbiome: associations with diet, lifestyle, and cardiometabolic disease
Authors: Walker Rebecca L. , Vlamakis Hera , Lee Jonathan Wei Jie , Besse Luke A. , Xanthakis Vanessa , Vasan Ramachandran S. , Shaw Stanley Y. , Xavier Ramnik J. 
Published: December 2021

Abstract
Background
The human gut harbors trillions of microbes that play dynamic roles in health. While the microbiome contributes to many cardiometabolic traits by modulating host inflammation and metabolism, there is an incomplete understanding regarding the extent that and mechanisms by which individual microbes impact risk and development of cardiovascular disease (CVD). The Framingham Heart Study (FHS) is a multi-generational observational study following participants over decades to identify risk factors for CVD by correlating genetic and phenotypic factors with clinical outcomes. As a large-scale population-based cohort with extensive clinical phenotyping, FHS provides a rich landscape to explore the relationships between the gut microbiome and cardiometabolic traits.

Methods
We performed 16S rRNA gene sequencing on stool from 1423 participants of the FHS Generation 3, OMNI2, and New Offspring Spouse cohorts. Data processing and taxonomic assignment were performed with the 16S bioBakery workflow using the UPARSE pipeline. We conducted statistical analyses to investigate trends in overall microbiome composition and diversity in relation to disease states and systematically examined taxonomic associations with a variety of clinical traits, disease phenotypes, clinical blood markers, and medications.

Results
We demonstrate that overall microbial diversity decreases with increasing 10-year CVD risk and body mass index measures. We link lifestyle factors, especially diet and exercise, to microbial diversity. Our association analyses reveal both known and unreported microbial associations with CVD and diabetes, related prescription medications, as well as many anthropometric and blood test measurements. In particular, we observe a set of microbial species that demonstrate significant associations with CVD risk, metabolic syndrome, and type 2 diabetes as well as a number of shared associations between microbial species and cardiometabolic subphenotypes.

Conclusions
The identification of significant microbial taxa associated with prevalent CVD and diabetes, as well as risk for developing CVD, adds to increasing evidence that the microbiome may contribute to CVD pathogenesis. Our findings support new hypothesis generation around shared microbe-mediated mechanisms that influence metabolic syndrome, diabetes, and CVD risk. Further investigation of the gut microbiomes of CVD patients in a targeted manner may elucidate microbial mechanisms with diagnostic and therapeutic implications.
Pneumatosis cystoides intestinalis in a trauma patient presenting with pneumoperitoneum: a case report
Authors: Lebby Elliott , Hanna Medhat , Bui Thanh-Lan , Rudd Adam , Lee Whayoung , Houshyar Roozbeh 
Published: December 2021

Abstract
Background
Pneumatosis cystoides intestinalis is a rare and usually benign condition in which multiple thin-walled cysts develop in the submucosa or subserosa of the gastrointestinal tract. While usually asymptomatic, severe cases can result in pneumoperitoneum, which can be managed surgically or medically depending on circumstances. We present a case of a patient with pneumatosis cystoides intestinalis, which presented as pneumoperitoneum following trauma. To our knowledge, there are no other published cases in which a trauma patient with pneumoperitoneum was found to have radiologic evidence of pneumatosis cystoides intestinalis.

Case presentation
We present the case of a 37-year-old Hispanic male admitted to the hospital after being involved in a motorcycle accident. Computed tomography imaging of the abdomen and pelvis with oral and intravenous contrast demonstrated trace pneumoperitoneum, possibly originating from the splenic flexure of the colon without evidence of extravasation of oral contrast. Laparoscopy with conversion to exploratory laparotomy revealed bowel abnormalities at the distal transverse colon and splenic flexure, which were identified as pneumatosis cystoides intestinalis by pathology. There was no evidence of bowel perforation. A panel of abdominal radiologists attended the computed tomography interpretation to note that incidental atraumatic or traumatic rupture of the cysts could have caused the pneumoperitoneum. The patient had an uncomplicated postoperative course and was transferred to another facility per insurance request.

Conclusions
When presenting in the context of trauma, pneumatosis cystoides intestinalis can lead to difficult management decisions. To our knowledge, there are no existing evidence-based guidelines for the scenario of concurrent pneumatosis cystoides intestinalis, blunt abdominal trauma, and pneumoperitoneum in a patient with a benign abdominal exam. This patient’s pneumoperitoneum was likely caused by rupture of preexisting cysts rather than frank bowel perforation. Patients who are asymptomatic, lack signs of clinically worrisome disease, and have a low pretest probability will likely not benefit from surgery and can be medically managed. Thorough discussion between surgeons and radiologists can be helpful when evaluating the clinical significance of a patient’s pneumatosis cystoides intestinalis and aid in the decision to perform surgery.
Microinjection of antisense oligonucleotides into living mouse testis enables lncRNA function study
Authors: Chen Zhaohui , Ling Li , Shi Xiaolian , Li Wu , Zhai Huicong , Kang Zhenlong , Zheng Bangjin , Zhu Jiaqi , Ye Suni , Wang Hao , Tong Lingxiu , Ni Juan , Huang Chaoyang , Li Yang , Zheng Ke 
Published: December 2021

AbstractBackgroundLong non-coding RNAs (lncRNAs) have been the focus of ongoing research in a diversity of cellular processes. LncRNAs are abundant in mammalian testis, but their biological function remains poorly known.ResultsHere, we established an antisense oligonucleotides (ASOs)-based targeting approach that can efficiently knock down lncRNA in living mouse testis. We cloned the full-length transcript of lncRNATsx(testis-specific X-linked) and defined its testicular localization pattern. Microinjection of ASOs through seminiferous tubules in vivo significantly lowered theTsxlevels in both nucleus and cytoplasm. This effect lasted no less than 10 days, conducive to the generation and maintenance of phenotype. Importantly, ASOs performed better in depleting the nuclearTsxand sustained longer effect than small interfering RNAs (siRNAs). In addition to the observation of an elevated number of apoptotic germ cells upon ASOs injection, which recapitulates the documented description ofTsxknockout, we also found a specific loss of meiotic spermatocytes despite overall no impact on meiosis and male fertility.ConclusionsOur study detailed the characterization ofTsxand illustrates ASOs as an advantageous tool to functionally interrogate lncRNAs in spermatogenesis.
Global and regional shock transmission: an Asian perspective
Authors: Shrestha Nagendra , Sato Kiyotaka 
Published: December 2021

AbstractThis paper constructs and uses the global input–output (GIO) table with 35 industries, 29 endogenous countries and 59 exogenous countries, and develops new indices to measure the degree of shock transmission in terms of intermediate goods and value-added embodied in production induced by negative global demand shock to finished goods. After the Global Financial Crisis (GFC) in 2008, China did not experience a large decline in economic growth, even though China’s gross exports fell most severely among Asian countries. In contrast, a sharp decrease in Japanese GDP in 2009 is a consequence of a substantial decline in finished goods exports, especially in the transport equipment industry. In Japan, the shock effect tends to be absorbed in its domestic sector and is not transmitted to other foreign countries. An asymmetric pattern of shock transmission between Japan and other Asian countries can explain why Japan was more affected by GFC than other Asian countries.
Activating biophilic design patterns as a sustainable landscape approach
Authors: Hady Sahar Ismail Mohamed Abdel 
Published: December 2021

AbstractBiophilic design elements are found around us in many landscape elements while we do not perceive them as biophilic design patterns. By developing our understanding of biophilic design as a phenomenon, we could discover simple ways to utilize landscape elements and transform them into a good biophilic design that might have positive impacts on a user’s health and well-being. Activating existing biophilic elements as an approach to a sustainable landscape has not been studied yet. Therefore, we rather analyse some international case studies in order to understand how biophilic design patterns can be implemented and see their different forms. Later, we will also go through an Egyptian biophilic design pattern case study and implement it to reach a sustainable landscape model. To summarize, the purpose of this study is to present a new sustainable landscape approach by activating biophilic design patterns in order to increase landscape efficiency.
Can we check serum lithium levels less often without compromising patient safety?
Authors: Heald Adrian H. , Holland David , Stedman Michael , Davies Mark , Duff Chris J. , Parfitt Ceri , Green Lewis , Scargill Jonathan , Taylor David , Fryer Anthony A. 
Published: December 2021

BackgroundLithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.AimsThis study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.MethodWe included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.ResultsFor tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.ConclusionWe propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
Unique Transcriptomic Changes Underlie Hormonal Interactions During Mammary Histomorphogenesis in Female Pigs
Authors: Trott Josephine F , Schennink Anke , Horigan Katherine C , Lemay Danielle G , Cohen Julia R , Famula Thomas R , Dragon Julie A , Hovey Russell C 
Published: December 2021

Abstract
Successful lactation and the risk for developing breast cancer depend on growth and differentiation of the mammary gland (MG) epithelium that is regulated by ovarian steroids (17β-estradiol [E] and progesterone [P]) and pituitary-derived prolactin (PRL). Given that the MG of pigs share histomorphogenic features present in the normal human breast, we sought to define the transcriptional responses within the MG of pigs following exposure to all combinations of these hormones. Hormone-ablated female pigs were administered combinations of E, medroxyprogesterone 17-acetate (source of P), and either haloperidol (to induce PRL) or 2-bromo-α-ergocryptine. We subsequently monitored phenotypic changes in the MG including mitosis, receptors for E and P (ESR1 and PGR), level of phosphorylated STAT5 (pSTAT5), and the frequency of terminal ductal lobular unit (TDLU) subtypes; these changes were then associated with all transcriptomic changes. Estrogen altered the expression of approximately 20% of all genes that were mostly associated with mitosis, whereas PRL stimulated elements of fatty acid metabolism and an inflammatory response. Several outcomes, including increased pSTAT5, highlighted the ability of E to enhance PRL action. Regression of transcriptomic changes against several MG phenotypes revealed 1669 genes correlated with proliferation, among which 29 were E inducible. Additional gene expression signatures were associated with TDLU formation and the frequency of ESR1 or PGR. These data provide a link between the hormone-regulated genome and phenome of the MG in a species having a complex histoarchitecture like that in the human breast, and highlight an underexplored synergy between the actions of E and PRL during MG development.
What Tears Couples Apart: A Machine Learning Analysis of Union Dissolution in Germany
Authors: Arpino Bruno , Le Moglie Marco , Mencarini Letizia 
Published: December 2021

AbstractThis study contributes to the literature on union dissolution by adopting a machine learning (ML) approach, specifically Random Survival Forests (RSF). We used RSF to analyze data on 2,038 married or cohabiting couples who participated in the German Socio-Economic Panel Survey, and found that RSF had considerably better predictive accuracy than conventional regression models. The man's and the woman's life satisfaction and the woman's percentage of housework were the most important predictors of union dissolution; several other variables (e.g., woman's working hours, being married) also showed substantial predictive power. RSF was able to detect complex patterns of association, and some predictors examined in previous studies showed marginal or null predictive power. Finally, while we found that some personality traits were strongly predictive of union dissolution, no interactions between those traits were evident, possibly reflecting assortative mating by personality traits. From a methodological point of view, the study demonstrates the potential benefits of ML techniques for the analysis of union dissolution and for demographic research in general. Key features of ML include the ability to handle a large number of predictors, the automatic detection of nonlinearities and nonadditivities between predictors and the outcome, generally superior predictive accuracy, and robustness against multicollinearity.
Regulation of retinal amacrine cell generation by miR-216b and Foxn3
Authors: Zhang Huanqing , Zhuang Pei , Welchko Ryan M. , Dai Manhong , Meng Fan , Turner David L. 
Published: December 2021

ABSTRACT
The mammalian retina contains a complex mixture of different types of neurons. We find that microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b directed the formation of additional amacrine cells and reduced bipolar neurons in the developing retina. We identify the Foxn3 mRNA as a retinal target of miR-216b by Argonaute PAR-CLIP and reporter analysis. Inhibition of Foxn3, a transcription factor, in the postnatal developing retina by RNAi increased the formation of amacrine cells and reduced bipolar cell formation. Foxn3 disruption by CRISPR in embryonic retinal explants also increased amacrine cell formation, whereas Foxn3 overexpression inhibited amacrine cell formation prior to Ptf1a expression. Co-expression of Foxn3 partially reversed the effects of ectopic miR-216b on retinal cell formation. Our results identify Foxn3 as a novel regulator of interneuron formation in the developing retina and suggest that miR-216b likely regulates Foxn3 and other genes in amacrine cells.
C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella
Authors: Yang Fang , Gracia Gervasi Maria , Orta Gerardo , Tourzani Darya A. , De la Vega-Beltrán Jose Luis , Ruthel Gordon , Darszon Alberto , Visconti Pablo E. , Wang P. Jeremy 
Published: December 2021

ABSTRACT
The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here, we report identification of an uncharacterized protein, C2CD6, as a subunit of the mouse CatSper complex. C2CD6 contains a calcium-dependent, membrane-targeting C2 domain. C2CD6 associates with the CatSper calcium-selective, core-forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.
Generation and timing of graded responses to morphogen gradients
Authors: Carmon Shari , Jonas Felix , Barkai Naama , Schejter Eyal D. , Shilo Ben-Zion 
Published: December 2021

ABSTRACT
Morphogen gradients are known to subdivide a naive cell field into distinct zones of gene expression. Here, we examine whether morphogens can also induce a graded response within such domains. To this end, we explore the role of the Dorsal protein nuclear gradient along the dorsoventral axis in defining the graded pattern of actomyosin constriction that initiates gastrulation in early Drosophila embryos. Two complementary mechanisms for graded accumulation of mRNAs of crucial zygotic Dorsal target genes were identified. First, activation of target-gene expression expands over time from the ventral-most region of high nuclear Dorsal to lateral regions, where the levels are lower, as a result of a Dorsal-dependent activation probability of transcription sites. Thus, sites that are activated earlier will exhibit more mRNA accumulation. Second, once the sites are activated, the rate of RNA Polymerase II loading is also dependent on Dorsal levels. Morphological restrictions require that translation of the graded mRNA be delayed until completion of embryonic cell formation. Such timing is achieved by large introns, which provide a delay in production of the mature mRNAs. Spatio-temporal regulation of key zygotic genes therefore shapes the pattern of gastrulation.
MRI for paediatric flatfoot: is it necessary?
Authors: Bagley Caroline , McIlhone Sean , Singla Nehal , Berkeley Rupert , O’Donnell Paul , Tennant Sally , Saifuddin Asif 
Published: December 2021

Objective:
To determine the additional benefit of MRI for children with flatfoot deformity assessed with weight-bearing radiographs in a specialist paediatric orthopaedic unit.

Methods and materials:
Patient cohort was obtained by searching the Radiology Information System for children referred for investigation of flatfoot. All patients with flatfoot on weight-bearing radiographs who had undergone MRI were included. Radiographs were classified by a consultant musculoskeletal radiologist as showing no underlying abnormality, talo-calcaneal coalition, calcaneonavicular coalition, accessory navicular or other abnormality. MRI studies were classified similarly by a different consultant musculoskeletal radiologist blinded to the radiographic findings.

Results:
33 males and 24 females were included (mean age 12.5 years; range 3–18 years). 24 had bilateral abnormality, so 81 feet were assessed. Radiographs showed no specific abnormality (n = 51), talocalcaneal coalition (n = 6), calcaneonavicular coalition (n = 3), os naviculare (n = 12) or other abnormality (n = 9). MRI showed no specific abnormality (n = 40), talocalcaneal coalition (n = 10), calcaneonavicular coalition (n = 5), os naviculare (n = 12) or other abnormality (n = 14). Assuming MRI as the diagnostic gold-standard, additional relevant diagnostic information was identified in 19 (23.5%) cases, while in the 51 cases for which radiographs provided no specific diagnosis MRI confirmed no underlying abnormality in 31 (60.8%).

Conclusion:
MRI is a valuable adjunct to weight-bearing radiography for investigating paediatric flatfoot deformity.

Advances in knowledge:
MRI is of value in the assessment of paediatric flatfoot, additional diagnostic information to radiography being identified in 23.5% cases, while in 60.8% of cases for which radiographs provided no specific diagnosis MRI confirmed no underlying abnormality.
Understanding the funding characteristics of research impact: A proof-of-concept study linking REF 2014 impact case studies with Researchfish grant agreements
Authors: Reddick Gavin , Malkov Dmitry , Sherbon Beverley , Grant Jonathan 
Published: December 2021

Background: All parts of the research community have an interest in understanding research impact whether that is around the pathways to impact, processes around impact, methods for measurement, describing impact and so on. This proof of concept study explored the relationship between research funding and research impact using the case studies submitted to the UK Research Excellence Framework (REF) exercise in 2014 as a proxy for impact. Methods: The paper describes an approach to link the REF impact case studies with the underpinning research grants present in the Researchfish dataset, primarily using the publications captured in both datasets. Where possible the methodology utilised unique identifiers such as Digital Object Identifiers and PubMed ID’s, and where this was not possible the funding information within each publication was used. Results: Through this automated approach 21% of the non-redacted case studies could be linked to a specific research grant. Additional qualitative analysis was then done for unlinked REF impact case studies, which involved reading the document to identify additional information to make the linkage. This approach was taken on 100 REF impact case studies selected at random and resulted in only seven having no identifiable research grants funding associated. The linked research grants were analysed to identify characteristics that are more frequently associated with these grants, than non-linked ones. Conclusions: This analysis did point to some interesting observations such as the grant funding linked to REF impact case studies are more likely to be longer, higher financial value, have more publications and be more collaborative (amongst other characteristics). These findings should be used with caution at present and not be over interpreted, this is due to the sample size for this proof of concept study and some potential limitations on the data which were not addressed at this stage.